Infectious Diseases

The Diagnosis: Tinea Corporis Bullosa

At the time of presentation, a potassium hydroxide (KOH) preparation, fungal culture, and punch biopsy of the right ventral wrist was performed. The KOH preparation was positive for fungal hyphae characteristic of dermatophyte infections. Histologically, the biopsy showed intraepidermal and subepidermal blisters with neutrophil- and lymphocyte-rich contents (Figure 1). Fungal hyphae and spores were present within the stratum corneum and superficial epidermis (Figure 2), and fungal cultures grew Microsporum canis. The extent of the rash (upper and lower extremities, chest, and back), positive fungal culture, and KOH preparation all supported the diagnosis of tinea corporis bullosa, which was confirmed with biopsy. Oral prednisone use was discouraged and triamcinolone ointment was discontinued given that inappropriate treatment with steroids in the setting of fungal infection suppresses an inflammatory response and alters clinical appearance, obviating the persistent underlying infection.

Tinea corporis bullosa is a rare superficial dermatophyte fungal infection that often is acquired by close personto- person contact or contact with domestic animals. The infection begins as a circular pruritic plaque, generally with raised borders, which may be erythematous or hyperpigmented. By definition, tinea corporis occurs in sites other than the face, feet, hands, or groin area. Bullae formation is thought to be secondary to a delayed hypersensitivity reaction provoked by the presence of a dermatophyte antigen.¹

Linear IgA bullous dermatosis is an immunemediated disease characterized by IgA deposition at the dermoepidermal junction. Linear IgA bullous dermatosis classically presents as widespread tense vesicles in an arciform or annular pattern. Mucosal involvement is common and typically presents with erosions, ulcerations, and scarring.² Given the absence of mucosal involvement in our patient and a positive KOH preparation, linear IgA bullous dermatosis was an unlikely diagnosis.

Benign inoculation lymphoreticulosis, more commonly known as cat scratch disease (CSD), is a Bartonella henselae infection that results from a cat scratch or bite. Cat scratch disease can present as localized cutaneous and nodal involvement (lymphadenopathy) near the site of inoculation, or it may present as disseminated disease. Cutaneous lesions generally progress through vesicular, erythematous, and papular phases. Regional lymphadenopathy proximal to the inoculation site is the hallmark of CSD.³ Given the absence of lymphadenopathy in our patient as well as the sporadic distribution of lesions, CSD was an unlikely diagnosis.

Dermatitis herpetiformis (DH) is an autoimmune disorder with cutaneous manifestations of gluten sensitivity. Dermatitis herpetiformis presents as extremely pruritic papules and vesicles arranged in groups on areas such as the elbows, dorsal aspects of the forearms, knees, scalp, back, and buttocks. Most patients with DH have celiac disease or small bowel disease related to gluten sensitivity.4 Given our patient’s acute presentation in adulthood and lack of gluten sensitivity, DH was an unlikely diagnosis.

Bullous fixed drug reaction is a cutaneous eruption that typically presents in the setting of exposure to an offending drug/agent. Drug reactions can have various cutaneous presentations, with the most common being pigmented macules that progress into plaques.⁵ Given the isolated nature of our patient’s episode and apparent lack of association with medication, bullous fixed drug reaction was an unlikely diagnosis.

Tinea corporis bullosa is a rare clinical variant of tinea corporis that has only been reported in patients with a history of contact with different animals. There are many causative organisms related to tinea corporis; Trichophyton rubrum is the most common etiology of tinea corporis, while tinea corporis due to close contact with domesticated animals often is caused by M canis.⁶ The immunoinhibitory properties of the mannans in the fungal cell wall allow the organisms to adhere to the skin prior to invasion. Cutaneous invasion into dead cornified layers of the skin is credited to the proteases, subtilisinlike proteases (subtilases), and keratinases produced by the fungus.¹ There are many different clinical presentations of tinea corporis due to the variability of causative organisms. An annular (ring-shaped) lesion with a central plaque and advancing border is the most typical presentation. Tinea corporis bullosa is characterized by the presence of bullae or vesicles in the borders of the scaly plaque. Rupture of the bullae subsequently leads to erosions and crusts over the plaque.

The diagnosis of tinea corporis bullosa often is clinical if the lesion is typical and can be confirmed using KOH preparation and fungal culture. Once the diagnosis is confirmed, topical antifungals are the standard treatment approach for localized superficial tinea corporis. Systemic antifungal treatment can be initiated if the lesion is extensive, recurrent, chronic, or unresponsive to topical treatment.¹ Given our patient’s characteristic presentation, she was managed with an over-the-counter topical antifungal (terbinafine). The patient’s lesions dramatically improved, rendering oral therapy unnecessary. At 1-month follow-up, the rash had nearly resolved.

The Diagnosis: Tinea Corporis Bullosa

At the time of presentation, a potassium hydroxide (KOH) preparation, fungal culture, and punch biopsy of the right ventral wrist was performed. The KOH preparation was positive for fungal hyphae characteristic of dermatophyte infections. Histologically, the biopsy showed intraepidermal and subepidermal blisters with neutrophil- and lymphocyte-rich contents (Figure 1). Fungal hyphae and spores were present within the stratum corneum and superficial epidermis (Figure 2), and fungal cultures grew Microsporum canis. The extent of the rash (upper and lower extremities, chest, and back), positive fungal culture, and KOH preparation all supported the diagnosis of tinea corporis bullosa, which was confirmed with biopsy. Oral prednisone use was discouraged and triamcinolone ointment was discontinued given that inappropriate treatment with steroids in the setting of fungal infection suppresses an inflammatory response and alters clinical appearance, obviating the persistent underlying infection.

Tinea corporis bullosa is a rare superficial dermatophyte fungal infection that often is acquired by close personto- person contact or contact with domestic animals. The infection begins as a circular pruritic plaque, generally with raised borders, which may be erythematous or hyperpigmented. By definition, tinea corporis occurs in sites other than the face, feet, hands, or groin area. Bullae formation is thought to be secondary to a delayed hypersensitivity reaction provoked by the presence of a dermatophyte antigen.¹

Linear IgA bullous dermatosis is an immunemediated disease characterized by IgA deposition at the dermoepidermal junction. Linear IgA bullous dermatosis classically presents as widespread tense vesicles in an arciform or annular pattern. Mucosal involvement is common and typically presents with erosions, ulcerations, and scarring.² Given the absence of mucosal involvement in our patient and a positive KOH preparation, linear IgA bullous dermatosis was an unlikely diagnosis.

Benign inoculation lymphoreticulosis, more commonly known as cat scratch disease (CSD), is a Bartonella henselae infection that results from a cat scratch or bite. Cat scratch disease can present as localized cutaneous and nodal involvement (lymphadenopathy) near the site of inoculation, or it may present as disseminated disease. Cutaneous lesions generally progress through vesicular, erythematous, and papular phases. Regional lymphadenopathy proximal to the inoculation site is the hallmark of CSD.³ Given the absence of lymphadenopathy in our patient as well as the sporadic distribution of lesions, CSD was an unlikely diagnosis.

Dermatitis herpetiformis (DH) is an autoimmune disorder with cutaneous manifestations of gluten sensitivity. Dermatitis herpetiformis presents as extremely pruritic papules and vesicles arranged in groups on areas such as the elbows, dorsal aspects of the forearms, knees, scalp, back, and buttocks. Most patients with DH have celiac disease or small bowel disease related to gluten sensitivity.4 Given our patient’s acute presentation in adulthood and lack of gluten sensitivity, DH was an unlikely diagnosis.

Bullous fixed drug reaction is a cutaneous eruption that typically presents in the setting of exposure to an offending drug/agent. Drug reactions can have various cutaneous presentations, with the most common being pigmented macules that progress into plaques.⁵ Given the isolated nature of our patient’s episode and apparent lack of association with medication, bullous fixed drug reaction was an unlikely diagnosis.

Tinea corporis bullosa is a rare clinical variant of tinea corporis that has only been reported in patients with a history of contact with different animals. There are many causative organisms related to tinea corporis; Trichophyton rubrum is the most common etiology of tinea corporis, while tinea corporis due to close contact with domesticated animals often is caused by M canis.⁶ The immunoinhibitory properties of the mannans in the fungal cell wall allow the organisms to adhere to the skin prior to invasion. Cutaneous invasion into dead cornified layers of the skin is credited to the proteases, subtilisinlike proteases (subtilases), and keratinases produced by the fungus.¹ There are many different clinical presentations of tinea corporis due to the variability of causative organisms. An annular (ring-shaped) lesion with a central plaque and advancing border is the most typical presentation. Tinea corporis bullosa is characterized by the presence of bullae or vesicles in the borders of the scaly plaque. Rupture of the bullae subsequently leads to erosions and crusts over the plaque.

The diagnosis of tinea corporis bullosa often is clinical if the lesion is typical and can be confirmed using KOH preparation and fungal culture. Once the diagnosis is confirmed, topical antifungals are the standard treatment approach for localized superficial tinea corporis. Systemic antifungal treatment can be initiated if the lesion is extensive, recurrent, chronic, or unresponsive to topical treatment.¹ Given our patient’s characteristic presentation, she was managed with an over-the-counter topical antifungal (terbinafine). The patient’s lesions dramatically improved, rendering oral therapy unnecessary. At 1-month follow-up, the rash had nearly resolved.

The Diagnosis: Tinea Corporis Bullosa

At the time of presentation, a potassium hydroxide (KOH) preparation, fungal culture, and punch biopsy of the right ventral wrist was performed. The KOH preparation was positive for fungal hyphae characteristic of dermatophyte infections. Histologically, the biopsy showed intraepidermal and subepidermal blisters with neutrophil- and lymphocyte-rich contents (Figure 1). Fungal hyphae and spores were present within the stratum corneum and superficial epidermis (Figure 2), and fungal cultures grew Microsporum canis. The extent of the rash (upper and lower extremities, chest, and back), positive fungal culture, and KOH preparation all supported the diagnosis of tinea corporis bullosa, which was confirmed with biopsy. Oral prednisone use was discouraged and triamcinolone ointment was discontinued given that inappropriate treatment with steroids in the setting of fungal infection suppresses an inflammatory response and alters clinical appearance, obviating the persistent underlying infection.

Tinea corporis bullosa is a rare superficial dermatophyte fungal infection that often is acquired by close personto- person contact or contact with domestic animals. The infection begins as a circular pruritic plaque, generally with raised borders, which may be erythematous or hyperpigmented. By definition, tinea corporis occurs in sites other than the face, feet, hands, or groin area. Bullae formation is thought to be secondary to a delayed hypersensitivity reaction provoked by the presence of a dermatophyte antigen.¹

Linear IgA bullous dermatosis is an immunemediated disease characterized by IgA deposition at the dermoepidermal junction. Linear IgA bullous dermatosis classically presents as widespread tense vesicles in an arciform or annular pattern. Mucosal involvement is common and typically presents with erosions, ulcerations, and scarring.² Given the absence of mucosal involvement in our patient and a positive KOH preparation, linear IgA bullous dermatosis was an unlikely diagnosis.

Benign inoculation lymphoreticulosis, more commonly known as cat scratch disease (CSD), is a Bartonella henselae infection that results from a cat scratch or bite. Cat scratch disease can present as localized cutaneous and nodal involvement (lymphadenopathy) near the site of inoculation, or it may present as disseminated disease. Cutaneous lesions generally progress through vesicular, erythematous, and papular phases. Regional lymphadenopathy proximal to the inoculation site is the hallmark of CSD.³ Given the absence of lymphadenopathy in our patient as well as the sporadic distribution of lesions, CSD was an unlikely diagnosis.

Dermatitis herpetiformis (DH) is an autoimmune disorder with cutaneous manifestations of gluten sensitivity. Dermatitis herpetiformis presents as extremely pruritic papules and vesicles arranged in groups on areas such as the elbows, dorsal aspects of the forearms, knees, scalp, back, and buttocks. Most patients with DH have celiac disease or small bowel disease related to gluten sensitivity.4 Given our patient’s acute presentation in adulthood and lack of gluten sensitivity, DH was an unlikely diagnosis.

Bullous fixed drug reaction is a cutaneous eruption that typically presents in the setting of exposure to an offending drug/agent. Drug reactions can have various cutaneous presentations, with the most common being pigmented macules that progress into plaques.⁵ Given the isolated nature of our patient’s episode and apparent lack of association with medication, bullous fixed drug reaction was an unlikely diagnosis.

Tinea corporis bullosa is a rare clinical variant of tinea corporis that has only been reported in patients with a history of contact with different animals. There are many causative organisms related to tinea corporis; Trichophyton rubrum is the most common etiology of tinea corporis, while tinea corporis due to close contact with domesticated animals often is caused by M canis.⁶ The immunoinhibitory properties of the mannans in the fungal cell wall allow the organisms to adhere to the skin prior to invasion. Cutaneous invasion into dead cornified layers of the skin is credited to the proteases, subtilisinlike proteases (subtilases), and keratinases produced by the fungus.¹ There are many different clinical presentations of tinea corporis due to the variability of causative organisms. An annular (ring-shaped) lesion with a central plaque and advancing border is the most typical presentation. Tinea corporis bullosa is characterized by the presence of bullae or vesicles in the borders of the scaly plaque. Rupture of the bullae subsequently leads to erosions and crusts over the plaque.

The diagnosis of tinea corporis bullosa often is clinical if the lesion is typical and can be confirmed using KOH preparation and fungal culture. Once the diagnosis is confirmed, topical antifungals are the standard treatment approach for localized superficial tinea corporis. Systemic antifungal treatment can be initiated if the lesion is extensive, recurrent, chronic, or unresponsive to topical treatment.¹ Given our patient’s characteristic presentation, she was managed with an over-the-counter topical antifungal (terbinafine). The patient’s lesions dramatically improved, rendering oral therapy unnecessary. At 1-month follow-up, the rash had nearly resolved.

When Amy Moser had a simple urinary tract infection in her late 20s, her doctor prescribed Cipro, a powerful antibiotic used to treat anthrax and some of the most fearsome bacterial infections.

Nearly 2 weeks after she finished her treatment, her left kneecap dislocated while she was trying on a swimsuit at a retail store. Shortly afterward, she had painful ligament ruptures in her wrists, then her shoulder dislocated, followed by three Achilles tendon tears.

“That’s when I fell apart,” says Ms. Moser, a Phoenix health blogger and book author. “From that moment on, for almost the next 2.5 years consistently, I had new tendon tears every few weeks.”

Ms. Moser’s doctors had no answer for what was causing her injuries, all of which required surgical fixes. A married mother of three, she was otherwise healthy and fit. So, after her third Achilles tear, she turned to the FDA’s website for answers. There, she found many warnings about side effects of Cipro, Levaquin, and other so-called fluoroquinolones, including risks for tendon and ligament injuries.

“When all the ruptures started to happen, my doctor kept asking me if I’d ever taken Levaquin, and every time I was like, ‘No.’ So I did what all doctors don’t want you to do: I Googled ‘Levaquin,’ ” she recalls.

Her search led to FDA warnings and articles about the possibility of tendon and ligament ruptures with fluroquinolones.

“That was the first time I’d ever even heard that word ‘fluroquinolones,’ and I found Cipro on that list ... and I realized that I’d just been prescribed that before everything started,” she says.

That was 12 years ago. Since then, the FDA has issued more warnings about fluoroquinolone risks. In that time, Ms. Moser, now 40, has had more than 30 surgeries to correct tendon ruptures and injuries, including a double-knee replacement this year.

“I am in chronic pain all the time,” she says. “I am chronically injured. I have a lot of tears that I’ve not fixed because they’re very complicated, and I don’t know if the rest of my body can handle the strain of recovering from those surgeries.”

Ms. Moser’s is hardly an isolated case. Since the 1980s, more than 60,000 patients have reported hundreds of thousands of serious events linked to fluoroquinolones to the FDA, including 6,575 reports of deaths.

The most common side effects were tendon rupture, as well as neurological and psychiatric symptoms. But experts estimate only 1%-10% of such events are reported to the FDA. That suggests that fluoroquinolones might have harmed hundreds of thousands of people in the United States alone, says Charles Bennett, MD, a hematologist at the University of South Carolina’s College of Pharmacy, Columbia.

Yet despite the many patient reports and FDA warnings on dangerous side effects, many doctors continue to wrongly prescribe fluoroquinolones for simple urinary tract infections, sinus infections, and respiratory issues better treated with less risky antibiotics.

“There probably is overprescription by primary care doctors for urinary tract infections and respiratory infections, when there could be alternatives that are safer to use,” says Amesh Adalja, MD, an infectious disease specialist and senior scholar with the Johns Hopkins Center for Health Security.

“I would say that’s probably the case in the outpatient setting, not necessarily in the hospital setting or among infectious disease doctors ... but I think it’s important to say there are still some judicious uses of fluoroquinolones,” he says. “However, there probably is a lot of injudicious use of fluoroquinolones along with many other antibiotics in the primary care setting.”
 

FDA warnings on fluoroquinolones

Fluoroquinolones are a class of broad-spectrum antibiotics used for decades to treat certain bacterial infections.

FDA-approved fluoroquinolones include ciprofloxacin (Cipro), ciprofloxacin extended-release tablets, delafloxacin (Baxdela), gemifloxacin (Factive) levofloxacin (Levaquin), moxifloxacin (Avelox), and ofloxacin (Floxin). More than 60 generic versions of these brand-name medicines are also on the market, making them among the most prescribed antibiotics in the U.S.

Over the past 2 decades, a wide range of physical and mental health side effects have been tied to fluoroquinolones. As a result of these “adverse event reports” and research published in medical literature, the FDA has required an escalating series of warnings and safety labeling changes for doctors who prescribe these drugs.

• In 2008, the FDA first added a “black box” warning to fluoroquinolones, citing an increased risk of tendinitis and tendon rupture in patients prescribed these meds.
• In 2011, the agency required the warning label to include risks of worsening symptoms for those with myasthenia gravis, a chronic autoimmune disease that causes muscle weakness, vision problems, and speech problems.
• In 2013, regulators required updated labels noting the potential for irreversible peripheral neuropathy (serious nerve damage).
• In 2016, the FDA issued its strongest warning against the use of such antibiotics for simple bacterial infections – such as uncomplicated urinary tract infections (UTIs), acute sinusitis, and acute bronchitis – saying the “association of fluoroquinolones with disabling and potentially permanent side effects involving tendons, muscles, joints, nerves and the central nervous system ... outweighs the benefits for patients.”
• And in 2018, regulators required safety labeling changes to include warnings about the risks of aortic aneurysm – a life-threatening enlargement of the main vessel that delivers blood to the body – as well as mental health side effects and serious blood sugar disturbances.

But FDA regulators have stopped short of barring fluoroquinolone use in the treatment of bacterial infections, citing the benefits for certain conditions.

“For some patients, the benefits of fluoroquinolones may continue to outweigh the risks for treatment of serious bacterial infections, such as pneumonia or intra-abdominal infections,” said former FDA Commissioner Scott Gottlieb, MD, “but there are other serious, known risks associated with these strong antibiotics that must be carefully weighed when considering their use.”

In December 2021, a study published in the journal JAMA Network Open found the FDA’s warnings may have helped lower prescribing of the drugs in Medicare patients. But not all doctors have been responsive to those warnings, researchers found.

“An overall decline in change over time and an immediate change in fluoroquinolone prescribing was observed after the 2016 FDA warning,” the authors concluded. “Certain physicians, such as primary care physicians, were more responsive to FDA warnings than others. ... Findings of this study suggest that identifying the association of physician and organizational characteristics with fluoroquinolone prescribing practices could help in developing mechanisms for improving de-adoption.”

Some critics say the FDA should do more to spotlight the dangers of fluoroquinolones and require doctors and patients to sign checklist consent forms to show they are aware of the potential side effects of these drugs.

Rachel Brummert, a patient advocate who sits on an FDA consumer advisory board, believes the FDA needs to improve its communication to doctors on fluoroquinolone risks and get tougher with those who continue to inappropriately prescribe the drugs.

“I think there needs to be a system in place, where if something comes down from the FDA about a drug, the physician has to sign off on it, the patient has to sign off on it and mark that they understand that there are these ‘black box’ warnings,” says Ms. Brummert, 52, a representative on the FDA’s Medical Devices Advisory Committee.

As an example, she points to Australia’s medical laws requiring doctors and patients to sign a checklist before any fluoroquinolone prescription is approved.

“When a physician prescribes a fluoroquinolone antibiotic, there’s a checklist – does the patient have an infection, is it a simple infection, do they have allergies?” she notes. “And you can’t even get the prescription out – it won’t even print out, it won’t go into the system – unless you check all of the boxes. But we don’t do that here. We don’t have that type of system right now.”

Ms. Brummert says such a system might have prevented the harm from taking Levaquin her doctor prescribed for a suspected sinus infection in 2006.

Soon after she began taking the antibiotic, she ruptured her Achilles tendon, requiring surgery. By 2009, she’d had three ruptures, each needing surgical fixes. To date, she’s had more than 30 surgeries to correct tendon ruptures. She’s also had seizures, blood pressure issues, depression, chronic pain, and memory problems she attributes to taking Levaquin.

As it turns out, her doctor misdiagnosed her condition – a misstep that would have been averted with a system like Australia’s, which requires doctors to verify the presence of a bacterial infection through a simple test before prescribing a fluoroquinolone.

“When I got the Levaquin, it was for a suspected sinus infection that it turned out I didn’t even have in the first place,” she notes. “So, I took the Levaquin basically for nothing. But what I would have asked my doctor had I known is: ‘Why should I take something so strong for so simple an infection?’

“It seems common sense to me now that you don’t prescribe something that can kill anthrax for a simple sinus infection. It’s like an atom bomb killing a mosquito. I agree that there are uses for these drugs, but they are being overprescribed. And so, here I am 16 years later – I’m still rupturing, I’m still having surgery, and I’m still in pain – all for something I didn’t even need medicine for in the first place.”
 

Should guidelines be stronger?

So, why are so many doctors continuing to prescribe fluoroquinolones for simple infections? Dr. Adalja and other experts say several things are at work.

For one thing, Dr. Adalja notes, fluoroquinolones are broad-spectrum antibiotics that are effective against dangerous germs, including “gram-negative” bacterial infections, and are “100% bioavailable.” That means they are as effective when given in pill form as they are if put directly into a vein. So they can be used in an outpatient setting or to allow a patient to be discharged from a hospital sooner because they don’t need an IV to receive treatment.

“There are still some uses for these drugs because they are so bioavailable, and I think that drives some of the use, and those are legitimate uses, knowing that there are risks when you do it,” he says. “But no drug is without risks, and you have to weigh risks and benefits – that’s what medicine is about: deciding what the best drug is for a patient.”

But Dr. Adalja says the overprescription of fluoroquinolones is part of the larger trend of antibiotic overuse. That is driving up antibiotic resistance, which in turn is another thing leading doctors to turn to Cipro and other fluoroquinolones after other drugs have proven ineffective.

“You can’t separate this from the fact that 80% of antibiotic prescriptions in the outpatient setting are probably illegitimate or not warranted,” he notes. “And because fluoroquinolones are highly effective drugs against certain pathogens, they are the go-to [drug] for many people who are prescribing antibiotics.”

That’s why patients should be wary whenever a doctor prescribes a fluoroquinolone, or any drug to treat a suspected infection, he says.

“Any time a patient is getting prescribed an antibiotic by a physician, they should ask: ‘Do I really need this antibiotic?’ That should be the first question they ask,” he advises. “And if they’re getting a fluoroquinolone, they may want to ask: ‘Is this the best antibiotic for me?’ ”
 

What you can do

Ms. Brummert and Ms. Moser say they are sharing their stories to raise awareness of the dangers of fluoroquinolones.

Ms. Moser has published a book on her experiences, “The Magnificent Story of a Lame Author,” and provides a wealth of consumer resources on her blog: Mountains and Mustard Seeds.

“As much as I hate what has happened to me, it has put me in a place where I am glad that I can inform other patients,” she says.

Ms. Brummert supplements her advocacy work as an FDA adviser with useful materials she provides on her website: Drugwatch.com.

“Pain into purpose – that’s what I call it,” she says. “I can’t change what happened to me, but I can warn others.”

The upshot for patients?

• the FDA’s Drug Safety Communication on Fluoroquinolones online to learn more about the risks and benefits of these powerful antibiotics.
• If you believe you’ve been harmed by fluoroquinolones, MedWatch website to report your experiences.

Ms. Brummert also advises patients to ask 12 critical questions of any doctor who wants to prescribe a fluoroquinolone, including the following listed on her website:

• For what condition is this medication prescribed, and is there another drug specific to my condition?
• What are the risks associated with this medication, and do the benefits outweigh them?
• Will this medication interact with my other drugs and/or other health conditions?
• What are the “boxed” warnings for this medication, and where can I report adverse events?

“I would also do my own research,” she says. “I wouldn’t just take a prescription from a physician and just say, ‘OK, doctor knows best.’ ”

Ms. Moser agrees that you have to be your own patient advocate and not simply take a doctor’s advice on any medical issue without having a deeper conversation.

“I’ve had arguments with doctors who legitimately did not believe me when I told them what happened to me,” she says. “And I actually told them, ‘Go get your Physicians’ Desk Reference [for prescription drugs]’ and they opened the book in front of me and read the warnings. Obviously, they had not been keeping up with the added warnings. So, I do think that doctors do need to be better informed.”

“So, yes, it’s the FDA’s responsibility, but it is also the doctors’ responsibility to make sure that they’re watching out for the side effects and they’re reporting them when their patients come up with them and making those connections.”

A version of this article first appeared on WebMD.com.

When Amy Moser had a simple urinary tract infection in her late 20s, her doctor prescribed Cipro, a powerful antibiotic used to treat anthrax and some of the most fearsome bacterial infections.

Nearly 2 weeks after she finished her treatment, her left kneecap dislocated while she was trying on a swimsuit at a retail store. Shortly afterward, she had painful ligament ruptures in her wrists, then her shoulder dislocated, followed by three Achilles tendon tears.

“That’s when I fell apart,” says Ms. Moser, a Phoenix health blogger and book author. “From that moment on, for almost the next 2.5 years consistently, I had new tendon tears every few weeks.”

Ms. Moser’s doctors had no answer for what was causing her injuries, all of which required surgical fixes. A married mother of three, she was otherwise healthy and fit. So, after her third Achilles tear, she turned to the FDA’s website for answers. There, she found many warnings about side effects of Cipro, Levaquin, and other so-called fluoroquinolones, including risks for tendon and ligament injuries.

“When all the ruptures started to happen, my doctor kept asking me if I’d ever taken Levaquin, and every time I was like, ‘No.’ So I did what all doctors don’t want you to do: I Googled ‘Levaquin,’ ” she recalls.

Her search led to FDA warnings and articles about the possibility of tendon and ligament ruptures with fluroquinolones.

“That was the first time I’d ever even heard that word ‘fluroquinolones,’ and I found Cipro on that list ... and I realized that I’d just been prescribed that before everything started,” she says.

That was 12 years ago. Since then, the FDA has issued more warnings about fluoroquinolone risks. In that time, Ms. Moser, now 40, has had more than 30 surgeries to correct tendon ruptures and injuries, including a double-knee replacement this year.

“I am in chronic pain all the time,” she says. “I am chronically injured. I have a lot of tears that I’ve not fixed because they’re very complicated, and I don’t know if the rest of my body can handle the strain of recovering from those surgeries.”

Ms. Moser’s is hardly an isolated case. Since the 1980s, more than 60,000 patients have reported hundreds of thousands of serious events linked to fluoroquinolones to the FDA, including 6,575 reports of deaths.

The most common side effects were tendon rupture, as well as neurological and psychiatric symptoms. But experts estimate only 1%-10% of such events are reported to the FDA. That suggests that fluoroquinolones might have harmed hundreds of thousands of people in the United States alone, says Charles Bennett, MD, a hematologist at the University of South Carolina’s College of Pharmacy, Columbia.

Yet despite the many patient reports and FDA warnings on dangerous side effects, many doctors continue to wrongly prescribe fluoroquinolones for simple urinary tract infections, sinus infections, and respiratory issues better treated with less risky antibiotics.

“There probably is overprescription by primary care doctors for urinary tract infections and respiratory infections, when there could be alternatives that are safer to use,” says Amesh Adalja, MD, an infectious disease specialist and senior scholar with the Johns Hopkins Center for Health Security.

“I would say that’s probably the case in the outpatient setting, not necessarily in the hospital setting or among infectious disease doctors ... but I think it’s important to say there are still some judicious uses of fluoroquinolones,” he says. “However, there probably is a lot of injudicious use of fluoroquinolones along with many other antibiotics in the primary care setting.”
 

FDA warnings on fluoroquinolones

Fluoroquinolones are a class of broad-spectrum antibiotics used for decades to treat certain bacterial infections.

FDA-approved fluoroquinolones include ciprofloxacin (Cipro), ciprofloxacin extended-release tablets, delafloxacin (Baxdela), gemifloxacin (Factive) levofloxacin (Levaquin), moxifloxacin (Avelox), and ofloxacin (Floxin). More than 60 generic versions of these brand-name medicines are also on the market, making them among the most prescribed antibiotics in the U.S.

Over the past 2 decades, a wide range of physical and mental health side effects have been tied to fluoroquinolones. As a result of these “adverse event reports” and research published in medical literature, the FDA has required an escalating series of warnings and safety labeling changes for doctors who prescribe these drugs.

• In 2008, the FDA first added a “black box” warning to fluoroquinolones, citing an increased risk of tendinitis and tendon rupture in patients prescribed these meds.
• In 2011, the agency required the warning label to include risks of worsening symptoms for those with myasthenia gravis, a chronic autoimmune disease that causes muscle weakness, vision problems, and speech problems.
• In 2013, regulators required updated labels noting the potential for irreversible peripheral neuropathy (serious nerve damage).
• In 2016, the FDA issued its strongest warning against the use of such antibiotics for simple bacterial infections – such as uncomplicated urinary tract infections (UTIs), acute sinusitis, and acute bronchitis – saying the “association of fluoroquinolones with disabling and potentially permanent side effects involving tendons, muscles, joints, nerves and the central nervous system ... outweighs the benefits for patients.”
• And in 2018, regulators required safety labeling changes to include warnings about the risks of aortic aneurysm – a life-threatening enlargement of the main vessel that delivers blood to the body – as well as mental health side effects and serious blood sugar disturbances.

But FDA regulators have stopped short of barring fluoroquinolone use in the treatment of bacterial infections, citing the benefits for certain conditions.

“For some patients, the benefits of fluoroquinolones may continue to outweigh the risks for treatment of serious bacterial infections, such as pneumonia or intra-abdominal infections,” said former FDA Commissioner Scott Gottlieb, MD, “but there are other serious, known risks associated with these strong antibiotics that must be carefully weighed when considering their use.”

In December 2021, a study published in the journal JAMA Network Open found the FDA’s warnings may have helped lower prescribing of the drugs in Medicare patients. But not all doctors have been responsive to those warnings, researchers found.

“An overall decline in change over time and an immediate change in fluoroquinolone prescribing was observed after the 2016 FDA warning,” the authors concluded. “Certain physicians, such as primary care physicians, were more responsive to FDA warnings than others. ... Findings of this study suggest that identifying the association of physician and organizational characteristics with fluoroquinolone prescribing practices could help in developing mechanisms for improving de-adoption.”

Some critics say the FDA should do more to spotlight the dangers of fluoroquinolones and require doctors and patients to sign checklist consent forms to show they are aware of the potential side effects of these drugs.

Rachel Brummert, a patient advocate who sits on an FDA consumer advisory board, believes the FDA needs to improve its communication to doctors on fluoroquinolone risks and get tougher with those who continue to inappropriately prescribe the drugs.

“I think there needs to be a system in place, where if something comes down from the FDA about a drug, the physician has to sign off on it, the patient has to sign off on it and mark that they understand that there are these ‘black box’ warnings,” says Ms. Brummert, 52, a representative on the FDA’s Medical Devices Advisory Committee.

As an example, she points to Australia’s medical laws requiring doctors and patients to sign a checklist before any fluoroquinolone prescription is approved.

“When a physician prescribes a fluoroquinolone antibiotic, there’s a checklist – does the patient have an infection, is it a simple infection, do they have allergies?” she notes. “And you can’t even get the prescription out – it won’t even print out, it won’t go into the system – unless you check all of the boxes. But we don’t do that here. We don’t have that type of system right now.”

Ms. Brummert says such a system might have prevented the harm from taking Levaquin her doctor prescribed for a suspected sinus infection in 2006.

Soon after she began taking the antibiotic, she ruptured her Achilles tendon, requiring surgery. By 2009, she’d had three ruptures, each needing surgical fixes. To date, she’s had more than 30 surgeries to correct tendon ruptures. She’s also had seizures, blood pressure issues, depression, chronic pain, and memory problems she attributes to taking Levaquin.

As it turns out, her doctor misdiagnosed her condition – a misstep that would have been averted with a system like Australia’s, which requires doctors to verify the presence of a bacterial infection through a simple test before prescribing a fluoroquinolone.

“When I got the Levaquin, it was for a suspected sinus infection that it turned out I didn’t even have in the first place,” she notes. “So, I took the Levaquin basically for nothing. But what I would have asked my doctor had I known is: ‘Why should I take something so strong for so simple an infection?’

“It seems common sense to me now that you don’t prescribe something that can kill anthrax for a simple sinus infection. It’s like an atom bomb killing a mosquito. I agree that there are uses for these drugs, but they are being overprescribed. And so, here I am 16 years later – I’m still rupturing, I’m still having surgery, and I’m still in pain – all for something I didn’t even need medicine for in the first place.”
 

Should guidelines be stronger?

So, why are so many doctors continuing to prescribe fluoroquinolones for simple infections? Dr. Adalja and other experts say several things are at work.

For one thing, Dr. Adalja notes, fluoroquinolones are broad-spectrum antibiotics that are effective against dangerous germs, including “gram-negative” bacterial infections, and are “100% bioavailable.” That means they are as effective when given in pill form as they are if put directly into a vein. So they can be used in an outpatient setting or to allow a patient to be discharged from a hospital sooner because they don’t need an IV to receive treatment.

“There are still some uses for these drugs because they are so bioavailable, and I think that drives some of the use, and those are legitimate uses, knowing that there are risks when you do it,” he says. “But no drug is without risks, and you have to weigh risks and benefits – that’s what medicine is about: deciding what the best drug is for a patient.”

But Dr. Adalja says the overprescription of fluoroquinolones is part of the larger trend of antibiotic overuse. That is driving up antibiotic resistance, which in turn is another thing leading doctors to turn to Cipro and other fluoroquinolones after other drugs have proven ineffective.

“You can’t separate this from the fact that 80% of antibiotic prescriptions in the outpatient setting are probably illegitimate or not warranted,” he notes. “And because fluoroquinolones are highly effective drugs against certain pathogens, they are the go-to [drug] for many people who are prescribing antibiotics.”

That’s why patients should be wary whenever a doctor prescribes a fluoroquinolone, or any drug to treat a suspected infection, he says.

“Any time a patient is getting prescribed an antibiotic by a physician, they should ask: ‘Do I really need this antibiotic?’ That should be the first question they ask,” he advises. “And if they’re getting a fluoroquinolone, they may want to ask: ‘Is this the best antibiotic for me?’ ”
 

What you can do

Ms. Brummert and Ms. Moser say they are sharing their stories to raise awareness of the dangers of fluoroquinolones.

Ms. Moser has published a book on her experiences, “The Magnificent Story of a Lame Author,” and provides a wealth of consumer resources on her blog: Mountains and Mustard Seeds.

“As much as I hate what has happened to me, it has put me in a place where I am glad that I can inform other patients,” she says.

Ms. Brummert supplements her advocacy work as an FDA adviser with useful materials she provides on her website: Drugwatch.com.

“Pain into purpose – that’s what I call it,” she says. “I can’t change what happened to me, but I can warn others.”

The upshot for patients?

• the FDA’s Drug Safety Communication on Fluoroquinolones online to learn more about the risks and benefits of these powerful antibiotics.
• If you believe you’ve been harmed by fluoroquinolones, MedWatch website to report your experiences.

Ms. Brummert also advises patients to ask 12 critical questions of any doctor who wants to prescribe a fluoroquinolone, including the following listed on her website:

• For what condition is this medication prescribed, and is there another drug specific to my condition?
• What are the risks associated with this medication, and do the benefits outweigh them?
• Will this medication interact with my other drugs and/or other health conditions?
• What are the “boxed” warnings for this medication, and where can I report adverse events?

“I would also do my own research,” she says. “I wouldn’t just take a prescription from a physician and just say, ‘OK, doctor knows best.’ ”

Ms. Moser agrees that you have to be your own patient advocate and not simply take a doctor’s advice on any medical issue without having a deeper conversation.

“I’ve had arguments with doctors who legitimately did not believe me when I told them what happened to me,” she says. “And I actually told them, ‘Go get your Physicians’ Desk Reference [for prescription drugs]’ and they opened the book in front of me and read the warnings. Obviously, they had not been keeping up with the added warnings. So, I do think that doctors do need to be better informed.”

“So, yes, it’s the FDA’s responsibility, but it is also the doctors’ responsibility to make sure that they’re watching out for the side effects and they’re reporting them when their patients come up with them and making those connections.”

A version of this article first appeared on WebMD.com.

When Amy Moser had a simple urinary tract infection in her late 20s, her doctor prescribed Cipro, a powerful antibiotic used to treat anthrax and some of the most fearsome bacterial infections.

Nearly 2 weeks after she finished her treatment, her left kneecap dislocated while she was trying on a swimsuit at a retail store. Shortly afterward, she had painful ligament ruptures in her wrists, then her shoulder dislocated, followed by three Achilles tendon tears.

“That’s when I fell apart,” says Ms. Moser, a Phoenix health blogger and book author. “From that moment on, for almost the next 2.5 years consistently, I had new tendon tears every few weeks.”

Ms. Moser’s doctors had no answer for what was causing her injuries, all of which required surgical fixes. A married mother of three, she was otherwise healthy and fit. So, after her third Achilles tear, she turned to the FDA’s website for answers. There, she found many warnings about side effects of Cipro, Levaquin, and other so-called fluoroquinolones, including risks for tendon and ligament injuries.

“When all the ruptures started to happen, my doctor kept asking me if I’d ever taken Levaquin, and every time I was like, ‘No.’ So I did what all doctors don’t want you to do: I Googled ‘Levaquin,’ ” she recalls.

Her search led to FDA warnings and articles about the possibility of tendon and ligament ruptures with fluroquinolones.

“That was the first time I’d ever even heard that word ‘fluroquinolones,’ and I found Cipro on that list ... and I realized that I’d just been prescribed that before everything started,” she says.

That was 12 years ago. Since then, the FDA has issued more warnings about fluoroquinolone risks. In that time, Ms. Moser, now 40, has had more than 30 surgeries to correct tendon ruptures and injuries, including a double-knee replacement this year.

“I am in chronic pain all the time,” she says. “I am chronically injured. I have a lot of tears that I’ve not fixed because they’re very complicated, and I don’t know if the rest of my body can handle the strain of recovering from those surgeries.”

Ms. Moser’s is hardly an isolated case. Since the 1980s, more than 60,000 patients have reported hundreds of thousands of serious events linked to fluoroquinolones to the FDA, including 6,575 reports of deaths.

The most common side effects were tendon rupture, as well as neurological and psychiatric symptoms. But experts estimate only 1%-10% of such events are reported to the FDA. That suggests that fluoroquinolones might have harmed hundreds of thousands of people in the United States alone, says Charles Bennett, MD, a hematologist at the University of South Carolina’s College of Pharmacy, Columbia.

Yet despite the many patient reports and FDA warnings on dangerous side effects, many doctors continue to wrongly prescribe fluoroquinolones for simple urinary tract infections, sinus infections, and respiratory issues better treated with less risky antibiotics.

“There probably is overprescription by primary care doctors for urinary tract infections and respiratory infections, when there could be alternatives that are safer to use,” says Amesh Adalja, MD, an infectious disease specialist and senior scholar with the Johns Hopkins Center for Health Security.

“I would say that’s probably the case in the outpatient setting, not necessarily in the hospital setting or among infectious disease doctors ... but I think it’s important to say there are still some judicious uses of fluoroquinolones,” he says. “However, there probably is a lot of injudicious use of fluoroquinolones along with many other antibiotics in the primary care setting.”
 

FDA warnings on fluoroquinolones

Fluoroquinolones are a class of broad-spectrum antibiotics used for decades to treat certain bacterial infections.

FDA-approved fluoroquinolones include ciprofloxacin (Cipro), ciprofloxacin extended-release tablets, delafloxacin (Baxdela), gemifloxacin (Factive) levofloxacin (Levaquin), moxifloxacin (Avelox), and ofloxacin (Floxin). More than 60 generic versions of these brand-name medicines are also on the market, making them among the most prescribed antibiotics in the U.S.

Over the past 2 decades, a wide range of physical and mental health side effects have been tied to fluoroquinolones. As a result of these “adverse event reports” and research published in medical literature, the FDA has required an escalating series of warnings and safety labeling changes for doctors who prescribe these drugs.

• In 2008, the FDA first added a “black box” warning to fluoroquinolones, citing an increased risk of tendinitis and tendon rupture in patients prescribed these meds.
• In 2011, the agency required the warning label to include risks of worsening symptoms for those with myasthenia gravis, a chronic autoimmune disease that causes muscle weakness, vision problems, and speech problems.
• In 2013, regulators required updated labels noting the potential for irreversible peripheral neuropathy (serious nerve damage).
• In 2016, the FDA issued its strongest warning against the use of such antibiotics for simple bacterial infections – such as uncomplicated urinary tract infections (UTIs), acute sinusitis, and acute bronchitis – saying the “association of fluoroquinolones with disabling and potentially permanent side effects involving tendons, muscles, joints, nerves and the central nervous system ... outweighs the benefits for patients.”
• And in 2018, regulators required safety labeling changes to include warnings about the risks of aortic aneurysm – a life-threatening enlargement of the main vessel that delivers blood to the body – as well as mental health side effects and serious blood sugar disturbances.

But FDA regulators have stopped short of barring fluoroquinolone use in the treatment of bacterial infections, citing the benefits for certain conditions.

“For some patients, the benefits of fluoroquinolones may continue to outweigh the risks for treatment of serious bacterial infections, such as pneumonia or intra-abdominal infections,” said former FDA Commissioner Scott Gottlieb, MD, “but there are other serious, known risks associated with these strong antibiotics that must be carefully weighed when considering their use.”

In December 2021, a study published in the journal JAMA Network Open found the FDA’s warnings may have helped lower prescribing of the drugs in Medicare patients. But not all doctors have been responsive to those warnings, researchers found.

“An overall decline in change over time and an immediate change in fluoroquinolone prescribing was observed after the 2016 FDA warning,” the authors concluded. “Certain physicians, such as primary care physicians, were more responsive to FDA warnings than others. ... Findings of this study suggest that identifying the association of physician and organizational characteristics with fluoroquinolone prescribing practices could help in developing mechanisms for improving de-adoption.”

Some critics say the FDA should do more to spotlight the dangers of fluoroquinolones and require doctors and patients to sign checklist consent forms to show they are aware of the potential side effects of these drugs.

Rachel Brummert, a patient advocate who sits on an FDA consumer advisory board, believes the FDA needs to improve its communication to doctors on fluoroquinolone risks and get tougher with those who continue to inappropriately prescribe the drugs.

“I think there needs to be a system in place, where if something comes down from the FDA about a drug, the physician has to sign off on it, the patient has to sign off on it and mark that they understand that there are these ‘black box’ warnings,” says Ms. Brummert, 52, a representative on the FDA’s Medical Devices Advisory Committee.

As an example, she points to Australia’s medical laws requiring doctors and patients to sign a checklist before any fluoroquinolone prescription is approved.

“When a physician prescribes a fluoroquinolone antibiotic, there’s a checklist – does the patient have an infection, is it a simple infection, do they have allergies?” she notes. “And you can’t even get the prescription out – it won’t even print out, it won’t go into the system – unless you check all of the boxes. But we don’t do that here. We don’t have that type of system right now.”

Ms. Brummert says such a system might have prevented the harm from taking Levaquin her doctor prescribed for a suspected sinus infection in 2006.

Soon after she began taking the antibiotic, she ruptured her Achilles tendon, requiring surgery. By 2009, she’d had three ruptures, each needing surgical fixes. To date, she’s had more than 30 surgeries to correct tendon ruptures. She’s also had seizures, blood pressure issues, depression, chronic pain, and memory problems she attributes to taking Levaquin.

As it turns out, her doctor misdiagnosed her condition – a misstep that would have been averted with a system like Australia’s, which requires doctors to verify the presence of a bacterial infection through a simple test before prescribing a fluoroquinolone.

“When I got the Levaquin, it was for a suspected sinus infection that it turned out I didn’t even have in the first place,” she notes. “So, I took the Levaquin basically for nothing. But what I would have asked my doctor had I known is: ‘Why should I take something so strong for so simple an infection?’

“It seems common sense to me now that you don’t prescribe something that can kill anthrax for a simple sinus infection. It’s like an atom bomb killing a mosquito. I agree that there are uses for these drugs, but they are being overprescribed. And so, here I am 16 years later – I’m still rupturing, I’m still having surgery, and I’m still in pain – all for something I didn’t even need medicine for in the first place.”
 

Should guidelines be stronger?

So, why are so many doctors continuing to prescribe fluoroquinolones for simple infections? Dr. Adalja and other experts say several things are at work.

For one thing, Dr. Adalja notes, fluoroquinolones are broad-spectrum antibiotics that are effective against dangerous germs, including “gram-negative” bacterial infections, and are “100% bioavailable.” That means they are as effective when given in pill form as they are if put directly into a vein. So they can be used in an outpatient setting or to allow a patient to be discharged from a hospital sooner because they don’t need an IV to receive treatment.

“There are still some uses for these drugs because they are so bioavailable, and I think that drives some of the use, and those are legitimate uses, knowing that there are risks when you do it,” he says. “But no drug is without risks, and you have to weigh risks and benefits – that’s what medicine is about: deciding what the best drug is for a patient.”

But Dr. Adalja says the overprescription of fluoroquinolones is part of the larger trend of antibiotic overuse. That is driving up antibiotic resistance, which in turn is another thing leading doctors to turn to Cipro and other fluoroquinolones after other drugs have proven ineffective.

“You can’t separate this from the fact that 80% of antibiotic prescriptions in the outpatient setting are probably illegitimate or not warranted,” he notes. “And because fluoroquinolones are highly effective drugs against certain pathogens, they are the go-to [drug] for many people who are prescribing antibiotics.”

That’s why patients should be wary whenever a doctor prescribes a fluoroquinolone, or any drug to treat a suspected infection, he says.

“Any time a patient is getting prescribed an antibiotic by a physician, they should ask: ‘Do I really need this antibiotic?’ That should be the first question they ask,” he advises. “And if they’re getting a fluoroquinolone, they may want to ask: ‘Is this the best antibiotic for me?’ ”
 

What you can do

Ms. Brummert and Ms. Moser say they are sharing their stories to raise awareness of the dangers of fluoroquinolones.

Ms. Moser has published a book on her experiences, “The Magnificent Story of a Lame Author,” and provides a wealth of consumer resources on her blog: Mountains and Mustard Seeds.

“As much as I hate what has happened to me, it has put me in a place where I am glad that I can inform other patients,” she says.

Ms. Brummert supplements her advocacy work as an FDA adviser with useful materials she provides on her website: Drugwatch.com.

“Pain into purpose – that’s what I call it,” she says. “I can’t change what happened to me, but I can warn others.”

The upshot for patients?

• the FDA’s Drug Safety Communication on Fluoroquinolones online to learn more about the risks and benefits of these powerful antibiotics.
• If you believe you’ve been harmed by fluoroquinolones, MedWatch website to report your experiences.

Ms. Brummert also advises patients to ask 12 critical questions of any doctor who wants to prescribe a fluoroquinolone, including the following listed on her website:

• For what condition is this medication prescribed, and is there another drug specific to my condition?
• What are the risks associated with this medication, and do the benefits outweigh them?
• Will this medication interact with my other drugs and/or other health conditions?
• What are the “boxed” warnings for this medication, and where can I report adverse events?

“I would also do my own research,” she says. “I wouldn’t just take a prescription from a physician and just say, ‘OK, doctor knows best.’ ”

Ms. Moser agrees that you have to be your own patient advocate and not simply take a doctor’s advice on any medical issue without having a deeper conversation.

“I’ve had arguments with doctors who legitimately did not believe me when I told them what happened to me,” she says. “And I actually told them, ‘Go get your Physicians’ Desk Reference [for prescription drugs]’ and they opened the book in front of me and read the warnings. Obviously, they had not been keeping up with the added warnings. So, I do think that doctors do need to be better informed.”

“So, yes, it’s the FDA’s responsibility, but it is also the doctors’ responsibility to make sure that they’re watching out for the side effects and they’re reporting them when their patients come up with them and making those connections.”

A version of this article first appeared on WebMD.com.

The Centers for Disease Control and Prevention (CDC) and the World Health Organization are investigating an outbreak of monkeypox cases that have occurred around the world in countries that do not have endemic monkeypox virus.^1,2 As of July 5, there have been 6924 cases documented in 52 countries, including 560 cases that have occurred in the United States.² In the United States, as well as globally, a large proportion of cases have been in men who have sex with men.

First, what is monkeypox? Monkeypox is an orthopox virus that is closely related to variola (smallpox) and vaccinia (the virus used in the smallpox vaccine). It is endemic in western and central Africa and is contracted by contact with an infected mammal (including humans). Transmission can occur through direct contact with infected body fluids or lesions, via infectious fomites, or through respiratory secretions (although this usually requires prolonged exposure).

What is the disease course? The incubation period is 4 to 17 days. The initial symptoms include fever, malaise, headache, sore throat, and lymphadenopathy. A rash erupts 1 to 4 days after the prodrome and progresses synchronously from macules to papules to vesicles and then to pustules, which eventually scab over and fall off. In some cases reported in the United States, the rash started in the groin and genital area.

Don’t be fooled by other exanthems. Monkeypox can be confused with chickenpox and molluscum contagiosum (MC). However, the lesions in chickenpox appear asynchronously (all 4 stages present at the same time) and the papules of MC contain a central pit.

Can monkeypox be prevented? There are currently 2 vaccines against orthopox viruses: ACAM2000 and Jynneos. Currently, these vaccines are routinely recommended only for those at occupational risk of orthopox exposure.³

What you should know—and do. Be alert for any patient who presents with a suspicious rash; if there is a possibility of monkeypox, the local public health department should be contacted. They will investigate and collect samples for laboratory testing and will elicit contact names and locations. If monkeypox is confirmed, they may offer close contacts 1 of the 2 vaccines, which if administered within 4 days of exposure can prevent infection.

Advise all patients confirmed to have monkeypox to self-isolate until all skin lesions have healed. Good infection control practices in the clinical setting will prevent spread to staff and other patients.

More information about monkeypox, including images of typical lesions—as well as an update on the current investigation in the United States and worldwide—can be found on the CDC website.⁴

The Centers for Disease Control and Prevention (CDC) and the World Health Organization are investigating an outbreak of monkeypox cases that have occurred around the world in countries that do not have endemic monkeypox virus.^1,2 As of July 5, there have been 6924 cases documented in 52 countries, including 560 cases that have occurred in the United States.² In the United States, as well as globally, a large proportion of cases have been in men who have sex with men.

First, what is monkeypox? Monkeypox is an orthopox virus that is closely related to variola (smallpox) and vaccinia (the virus used in the smallpox vaccine). It is endemic in western and central Africa and is contracted by contact with an infected mammal (including humans). Transmission can occur through direct contact with infected body fluids or lesions, via infectious fomites, or through respiratory secretions (although this usually requires prolonged exposure).

What is the disease course? The incubation period is 4 to 17 days. The initial symptoms include fever, malaise, headache, sore throat, and lymphadenopathy. A rash erupts 1 to 4 days after the prodrome and progresses synchronously from macules to papules to vesicles and then to pustules, which eventually scab over and fall off. In some cases reported in the United States, the rash started in the groin and genital area.

Don’t be fooled by other exanthems. Monkeypox can be confused with chickenpox and molluscum contagiosum (MC). However, the lesions in chickenpox appear asynchronously (all 4 stages present at the same time) and the papules of MC contain a central pit.

Can monkeypox be prevented? There are currently 2 vaccines against orthopox viruses: ACAM2000 and Jynneos. Currently, these vaccines are routinely recommended only for those at occupational risk of orthopox exposure.³

What you should know—and do. Be alert for any patient who presents with a suspicious rash; if there is a possibility of monkeypox, the local public health department should be contacted. They will investigate and collect samples for laboratory testing and will elicit contact names and locations. If monkeypox is confirmed, they may offer close contacts 1 of the 2 vaccines, which if administered within 4 days of exposure can prevent infection.

Advise all patients confirmed to have monkeypox to self-isolate until all skin lesions have healed. Good infection control practices in the clinical setting will prevent spread to staff and other patients.

More information about monkeypox, including images of typical lesions—as well as an update on the current investigation in the United States and worldwide—can be found on the CDC website.⁴

The Centers for Disease Control and Prevention (CDC) and the World Health Organization are investigating an outbreak of monkeypox cases that have occurred around the world in countries that do not have endemic monkeypox virus.^1,2 As of July 5, there have been 6924 cases documented in 52 countries, including 560 cases that have occurred in the United States.² In the United States, as well as globally, a large proportion of cases have been in men who have sex with men.

First, what is monkeypox? Monkeypox is an orthopox virus that is closely related to variola (smallpox) and vaccinia (the virus used in the smallpox vaccine). It is endemic in western and central Africa and is contracted by contact with an infected mammal (including humans). Transmission can occur through direct contact with infected body fluids or lesions, via infectious fomites, or through respiratory secretions (although this usually requires prolonged exposure).

What is the disease course? The incubation period is 4 to 17 days. The initial symptoms include fever, malaise, headache, sore throat, and lymphadenopathy. A rash erupts 1 to 4 days after the prodrome and progresses synchronously from macules to papules to vesicles and then to pustules, which eventually scab over and fall off. In some cases reported in the United States, the rash started in the groin and genital area.

Don’t be fooled by other exanthems. Monkeypox can be confused with chickenpox and molluscum contagiosum (MC). However, the lesions in chickenpox appear asynchronously (all 4 stages present at the same time) and the papules of MC contain a central pit.

Can monkeypox be prevented? There are currently 2 vaccines against orthopox viruses: ACAM2000 and Jynneos. Currently, these vaccines are routinely recommended only for those at occupational risk of orthopox exposure.³

What you should know—and do. Be alert for any patient who presents with a suspicious rash; if there is a possibility of monkeypox, the local public health department should be contacted. They will investigate and collect samples for laboratory testing and will elicit contact names and locations. If monkeypox is confirmed, they may offer close contacts 1 of the 2 vaccines, which if administered within 4 days of exposure can prevent infection.

Advise all patients confirmed to have monkeypox to self-isolate until all skin lesions have healed. Good infection control practices in the clinical setting will prevent spread to staff and other patients.

More information about monkeypox, including images of typical lesions—as well as an update on the current investigation in the United States and worldwide—can be found on the CDC website.⁴

The Diagnosis: Molluscum Contagiosum

A tangential shave removal with electrocautery was performed. Histopathology demonstrated numerous eosinophilic intracytoplasmic inclusion bodies (Figure), confirming a diagnosis of molluscum contagiosum (MC).

Molluscum contagiosum is a common poxvirus infection that is transmitted through fomites, contact, or self-inoculation.1 This infection most frequently occurs in school-aged children younger than 8 years^1-3; peak incidence is 6 years of age.^2,3 The worldwide estimated prevalence in children is 5.1% to 11.5%.^1,3 In children cohabitating with others infected by MC, approximately 40% of households experienced a spread of infection; the risk of transmission is not associated with greater number of lesions.⁴ In adults, infection most commonly occurs in the setting of immunodeficiency or as a sexually transmitted infection in immunocompetent patients.³ Molluscum contagiosum infection classically presents as 1- to 3-mm, flesh- or white-colored, dome-shaped, smooth papules with central umbilication.¹ Lesions often occur in clusters or lines, indicating local spread. The trunk, extremities, and face are areas that frequently are involved.^2,3

Atypical presentations of MC infection can occur, as demonstrated by our case. Involvement of hair follicles by the infection can result in follicular induction.^1,5 Secondary infection can mimic abscess formation.¹ Inflamed MC lesions demonstrating the “beginning of the end” sign often are mistaken for primary infection, which is thought to be an inflammatory immune response to the virus.⁶ Lesions located on the eye or eyelid can present as unilateral conjunctivitis, conjunctival or corneal nodules, eyelid abscesses, or chalazions.¹ Giant MC is a nodular variant of this infection measuring larger than 1 cm in size that can present similar to epidermoid cysts, condyloma acuminatum, or verruca vulgaris.^1,7 Other reported mimicked conditions include basal cell carcinoma, trichoepithelioma, appendageal tumors, keratoacanthoma, foreign body granulomas, nevus sebaceous, or ecthyma.^1,3 Molluscum contagiosum also has been reported to present as large ulcerative growths.⁸ In immunocompromised patients, deep fungal infection is another mimicker.1 Lesions on the plantar surfaces of the feet often are misdiagnosed as plantar verruca and present with pain during ambulation.⁹

The diagnosis of MC is clinical, with additional diagnostic tools reserved for more challenging situations.¹ In cases with atypical presentations, dermoscopy may aid diagnosis through visualization of orifices and vascular patterns including crown, radial, and punctiform vessels.¹⁰ Biopsy or fine-needle aspiration also can be utilized as a diagnostic tool. Histopathology often reveals pathognomonic intracytoplasmic inclusions or Henderson-Paterson bodies.^8,10 The appearance of MC can mimic other conditions that should be included in the differential diagnosis. Pyogenic granuloma often presents as a benign red papule that may grow rapidly and become pedunculated, sometimes with bleeding and crusting, though histology reveals groups of proliferating capillaries.¹¹ More than half of amelanotic melanomas present in the papulonodular form as vascular or ulcerated nodules, and others may appear as erythematous macules. Diagnosis of amelanotic melanoma is made through histologic examination, which reveals atypical melanocytes in nests or cords, in conjunction with immunohistochemical stains such as S-100.12 Spitz nevi often appear as round, dome-shaped papules that most commonly are red, pink, or fleshcolored. They appear histologically similar to melanoma with nests of atypical melanocytes and nuclear atypia.¹³

A variety of treatment modalities can be used for MC including cantharidin, curettage, and cryotherapy.¹⁴ Imiquimod no longer is recommended due to a lack of demonstrated superiority over placebo in recent studies as well as its adverse effects.³ Topical retinoids have been recommended; however, their use frequently is limited by local irritation.^3,14 Cantharidin is the most frequently utilized treatment by pediatric dermatologists. Most health care providers report subjective satisfaction with its results and efficacy, though some side effects may occur including discomfort and temporary changes in pigmentation. Treatment for MC is not required, as the condition is self-limiting.¹⁴ Therapy often is reserved for those with extensive disease, complications from lesions, cosmetic or psychological concerns, or genital involvement given the potential for sexual transmission.³ Time to resolution without treatment varies and is more prolonged in immunocompromised patients. Mean time to resolution in immunocompetent hosts has been reported as 13.3 months, but most infections are noted to clear within 2 to 4 years.^1,4 Although resolution without treatment occurs, transmission to others and negative impact on quality of life (QOL) can occur and support the need for treatment. Greater impact on QOL was observed in females, those with more lesions, and patients with a longer duration of symptoms. Moderate impact on QOL was reported in 28% of patients (n=301), and severe effects were reported in 11%.⁴

In conclusion, MC is a common, benign, treatable cutaneous viral infection that often presents as small, flesh-colored papules in children. Its appearance can mimic a variety of other conditions. In cases with abnormal presentations, definitive diagnosis with pathology can be important to differentiate MC from more dangerous etiologies that may require further treatment.

The Diagnosis: Molluscum Contagiosum

A tangential shave removal with electrocautery was performed. Histopathology demonstrated numerous eosinophilic intracytoplasmic inclusion bodies (Figure), confirming a diagnosis of molluscum contagiosum (MC).

Molluscum contagiosum is a common poxvirus infection that is transmitted through fomites, contact, or self-inoculation.1 This infection most frequently occurs in school-aged children younger than 8 years^1-3; peak incidence is 6 years of age.^2,3 The worldwide estimated prevalence in children is 5.1% to 11.5%.^1,3 In children cohabitating with others infected by MC, approximately 40% of households experienced a spread of infection; the risk of transmission is not associated with greater number of lesions.⁴ In adults, infection most commonly occurs in the setting of immunodeficiency or as a sexually transmitted infection in immunocompetent patients.³ Molluscum contagiosum infection classically presents as 1- to 3-mm, flesh- or white-colored, dome-shaped, smooth papules with central umbilication.¹ Lesions often occur in clusters or lines, indicating local spread. The trunk, extremities, and face are areas that frequently are involved.^2,3

Atypical presentations of MC infection can occur, as demonstrated by our case. Involvement of hair follicles by the infection can result in follicular induction.^1,5 Secondary infection can mimic abscess formation.¹ Inflamed MC lesions demonstrating the “beginning of the end” sign often are mistaken for primary infection, which is thought to be an inflammatory immune response to the virus.⁶ Lesions located on the eye or eyelid can present as unilateral conjunctivitis, conjunctival or corneal nodules, eyelid abscesses, or chalazions.¹ Giant MC is a nodular variant of this infection measuring larger than 1 cm in size that can present similar to epidermoid cysts, condyloma acuminatum, or verruca vulgaris.^1,7 Other reported mimicked conditions include basal cell carcinoma, trichoepithelioma, appendageal tumors, keratoacanthoma, foreign body granulomas, nevus sebaceous, or ecthyma.^1,3 Molluscum contagiosum also has been reported to present as large ulcerative growths.⁸ In immunocompromised patients, deep fungal infection is another mimicker.1 Lesions on the plantar surfaces of the feet often are misdiagnosed as plantar verruca and present with pain during ambulation.⁹

The diagnosis of MC is clinical, with additional diagnostic tools reserved for more challenging situations.¹ In cases with atypical presentations, dermoscopy may aid diagnosis through visualization of orifices and vascular patterns including crown, radial, and punctiform vessels.¹⁰ Biopsy or fine-needle aspiration also can be utilized as a diagnostic tool. Histopathology often reveals pathognomonic intracytoplasmic inclusions or Henderson-Paterson bodies.^8,10 The appearance of MC can mimic other conditions that should be included in the differential diagnosis. Pyogenic granuloma often presents as a benign red papule that may grow rapidly and become pedunculated, sometimes with bleeding and crusting, though histology reveals groups of proliferating capillaries.¹¹ More than half of amelanotic melanomas present in the papulonodular form as vascular or ulcerated nodules, and others may appear as erythematous macules. Diagnosis of amelanotic melanoma is made through histologic examination, which reveals atypical melanocytes in nests or cords, in conjunction with immunohistochemical stains such as S-100.12 Spitz nevi often appear as round, dome-shaped papules that most commonly are red, pink, or fleshcolored. They appear histologically similar to melanoma with nests of atypical melanocytes and nuclear atypia.¹³

A variety of treatment modalities can be used for MC including cantharidin, curettage, and cryotherapy.¹⁴ Imiquimod no longer is recommended due to a lack of demonstrated superiority over placebo in recent studies as well as its adverse effects.³ Topical retinoids have been recommended; however, their use frequently is limited by local irritation.^3,14 Cantharidin is the most frequently utilized treatment by pediatric dermatologists. Most health care providers report subjective satisfaction with its results and efficacy, though some side effects may occur including discomfort and temporary changes in pigmentation. Treatment for MC is not required, as the condition is self-limiting.¹⁴ Therapy often is reserved for those with extensive disease, complications from lesions, cosmetic or psychological concerns, or genital involvement given the potential for sexual transmission.³ Time to resolution without treatment varies and is more prolonged in immunocompromised patients. Mean time to resolution in immunocompetent hosts has been reported as 13.3 months, but most infections are noted to clear within 2 to 4 years.^1,4 Although resolution without treatment occurs, transmission to others and negative impact on quality of life (QOL) can occur and support the need for treatment. Greater impact on QOL was observed in females, those with more lesions, and patients with a longer duration of symptoms. Moderate impact on QOL was reported in 28% of patients (n=301), and severe effects were reported in 11%.⁴

In conclusion, MC is a common, benign, treatable cutaneous viral infection that often presents as small, flesh-colored papules in children. Its appearance can mimic a variety of other conditions. In cases with abnormal presentations, definitive diagnosis with pathology can be important to differentiate MC from more dangerous etiologies that may require further treatment.

The Diagnosis: Molluscum Contagiosum

A tangential shave removal with electrocautery was performed. Histopathology demonstrated numerous eosinophilic intracytoplasmic inclusion bodies (Figure), confirming a diagnosis of molluscum contagiosum (MC).

Molluscum contagiosum is a common poxvirus infection that is transmitted through fomites, contact, or self-inoculation.1 This infection most frequently occurs in school-aged children younger than 8 years^1-3; peak incidence is 6 years of age.^2,3 The worldwide estimated prevalence in children is 5.1% to 11.5%.^1,3 In children cohabitating with others infected by MC, approximately 40% of households experienced a spread of infection; the risk of transmission is not associated with greater number of lesions.⁴ In adults, infection most commonly occurs in the setting of immunodeficiency or as a sexually transmitted infection in immunocompetent patients.³ Molluscum contagiosum infection classically presents as 1- to 3-mm, flesh- or white-colored, dome-shaped, smooth papules with central umbilication.¹ Lesions often occur in clusters or lines, indicating local spread. The trunk, extremities, and face are areas that frequently are involved.^2,3

Atypical presentations of MC infection can occur, as demonstrated by our case. Involvement of hair follicles by the infection can result in follicular induction.^1,5 Secondary infection can mimic abscess formation.¹ Inflamed MC lesions demonstrating the “beginning of the end” sign often are mistaken for primary infection, which is thought to be an inflammatory immune response to the virus.⁶ Lesions located on the eye or eyelid can present as unilateral conjunctivitis, conjunctival or corneal nodules, eyelid abscesses, or chalazions.¹ Giant MC is a nodular variant of this infection measuring larger than 1 cm in size that can present similar to epidermoid cysts, condyloma acuminatum, or verruca vulgaris.^1,7 Other reported mimicked conditions include basal cell carcinoma, trichoepithelioma, appendageal tumors, keratoacanthoma, foreign body granulomas, nevus sebaceous, or ecthyma.^1,3 Molluscum contagiosum also has been reported to present as large ulcerative growths.⁸ In immunocompromised patients, deep fungal infection is another mimicker.1 Lesions on the plantar surfaces of the feet often are misdiagnosed as plantar verruca and present with pain during ambulation.⁹

The diagnosis of MC is clinical, with additional diagnostic tools reserved for more challenging situations.¹ In cases with atypical presentations, dermoscopy may aid diagnosis through visualization of orifices and vascular patterns including crown, radial, and punctiform vessels.¹⁰ Biopsy or fine-needle aspiration also can be utilized as a diagnostic tool. Histopathology often reveals pathognomonic intracytoplasmic inclusions or Henderson-Paterson bodies.^8,10 The appearance of MC can mimic other conditions that should be included in the differential diagnosis. Pyogenic granuloma often presents as a benign red papule that may grow rapidly and become pedunculated, sometimes with bleeding and crusting, though histology reveals groups of proliferating capillaries.¹¹ More than half of amelanotic melanomas present in the papulonodular form as vascular or ulcerated nodules, and others may appear as erythematous macules. Diagnosis of amelanotic melanoma is made through histologic examination, which reveals atypical melanocytes in nests or cords, in conjunction with immunohistochemical stains such as S-100.12 Spitz nevi often appear as round, dome-shaped papules that most commonly are red, pink, or fleshcolored. They appear histologically similar to melanoma with nests of atypical melanocytes and nuclear atypia.¹³

A variety of treatment modalities can be used for MC including cantharidin, curettage, and cryotherapy.¹⁴ Imiquimod no longer is recommended due to a lack of demonstrated superiority over placebo in recent studies as well as its adverse effects.³ Topical retinoids have been recommended; however, their use frequently is limited by local irritation.^3,14 Cantharidin is the most frequently utilized treatment by pediatric dermatologists. Most health care providers report subjective satisfaction with its results and efficacy, though some side effects may occur including discomfort and temporary changes in pigmentation. Treatment for MC is not required, as the condition is self-limiting.¹⁴ Therapy often is reserved for those with extensive disease, complications from lesions, cosmetic or psychological concerns, or genital involvement given the potential for sexual transmission.³ Time to resolution without treatment varies and is more prolonged in immunocompromised patients. Mean time to resolution in immunocompetent hosts has been reported as 13.3 months, but most infections are noted to clear within 2 to 4 years.^1,4 Although resolution without treatment occurs, transmission to others and negative impact on quality of life (QOL) can occur and support the need for treatment. Greater impact on QOL was observed in females, those with more lesions, and patients with a longer duration of symptoms. Moderate impact on QOL was reported in 28% of patients (n=301), and severe effects were reported in 11%.⁴

In conclusion, MC is a common, benign, treatable cutaneous viral infection that often presents as small, flesh-colored papules in children. Its appearance can mimic a variety of other conditions. In cases with abnormal presentations, definitive diagnosis with pathology can be important to differentiate MC from more dangerous etiologies that may require further treatment.

This patient was given a diagnosis of Gianotti Crosti syndrome (GCS; also called infantile acrodermatitis of childhood), which is a self-resolving (often dramatic) dermatosis triggered by a viral infection or immunization. Patients with this syndrome develop papules, vesicles, and plaques on their face, hands, feet, and extremities a week (or more) after having a viral illness or receiving an immunization. In patients with darker skin types, lesions may appear purple to brown rather than bright red to red/orange. The syndrome typically occurs in children between the ages of 1 to 4 years, but almost all patients are under the age of 15.¹ Scratching and sleep disturbance are common. The condition typically resolves on its own after 3 or 4 weeks.

Globally, the hepatitis B virus (HBV) is the most common cause of GCS.¹ Other reported triggering viruses include hepatitis A and C, cytomegalovirus, Epstein-Barr virus, enteroviruses, HIV, parainfluenza viruses, parvoviruses, rubella, and COVID-19.²

Since the cause of this patient’s case of GCS was likely linked to a viral infection that produced the loose stools in a population with low-HBV risk, no further serologic testing was performed. Serologic testing may have been necessary if other infections, disease risks, or symptoms were identified. To relieve itching, topical triamcinolone 0.1% cream was prescribed for use once to twice daily on the extremities and hydrocortisone 1% cream was prescribed once to twice daily for use on the child’s face. At the 6-week follow-up visit, the lesions had resolved; light pink discoloration remained but was expected to further fade. In patients with darker skin, post-inflammatory hyperpigmentation may take several months to resolve.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

This patient was given a diagnosis of Gianotti Crosti syndrome (GCS; also called infantile acrodermatitis of childhood), which is a self-resolving (often dramatic) dermatosis triggered by a viral infection or immunization. Patients with this syndrome develop papules, vesicles, and plaques on their face, hands, feet, and extremities a week (or more) after having a viral illness or receiving an immunization. In patients with darker skin types, lesions may appear purple to brown rather than bright red to red/orange. The syndrome typically occurs in children between the ages of 1 to 4 years, but almost all patients are under the age of 15.¹ Scratching and sleep disturbance are common. The condition typically resolves on its own after 3 or 4 weeks.

Globally, the hepatitis B virus (HBV) is the most common cause of GCS.¹ Other reported triggering viruses include hepatitis A and C, cytomegalovirus, Epstein-Barr virus, enteroviruses, HIV, parainfluenza viruses, parvoviruses, rubella, and COVID-19.²

Since the cause of this patient’s case of GCS was likely linked to a viral infection that produced the loose stools in a population with low-HBV risk, no further serologic testing was performed. Serologic testing may have been necessary if other infections, disease risks, or symptoms were identified. To relieve itching, topical triamcinolone 0.1% cream was prescribed for use once to twice daily on the extremities and hydrocortisone 1% cream was prescribed once to twice daily for use on the child’s face. At the 6-week follow-up visit, the lesions had resolved; light pink discoloration remained but was expected to further fade. In patients with darker skin, post-inflammatory hyperpigmentation may take several months to resolve.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

This patient was given a diagnosis of Gianotti Crosti syndrome (GCS; also called infantile acrodermatitis of childhood), which is a self-resolving (often dramatic) dermatosis triggered by a viral infection or immunization. Patients with this syndrome develop papules, vesicles, and plaques on their face, hands, feet, and extremities a week (or more) after having a viral illness or receiving an immunization. In patients with darker skin types, lesions may appear purple to brown rather than bright red to red/orange. The syndrome typically occurs in children between the ages of 1 to 4 years, but almost all patients are under the age of 15.¹ Scratching and sleep disturbance are common. The condition typically resolves on its own after 3 or 4 weeks.

Globally, the hepatitis B virus (HBV) is the most common cause of GCS.¹ Other reported triggering viruses include hepatitis A and C, cytomegalovirus, Epstein-Barr virus, enteroviruses, HIV, parainfluenza viruses, parvoviruses, rubella, and COVID-19.²

Since the cause of this patient’s case of GCS was likely linked to a viral infection that produced the loose stools in a population with low-HBV risk, no further serologic testing was performed. Serologic testing may have been necessary if other infections, disease risks, or symptoms were identified. To relieve itching, topical triamcinolone 0.1% cream was prescribed for use once to twice daily on the extremities and hydrocortisone 1% cream was prescribed once to twice daily for use on the child’s face. At the 6-week follow-up visit, the lesions had resolved; light pink discoloration remained but was expected to further fade. In patients with darker skin, post-inflammatory hyperpigmentation may take several months to resolve.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

The White House is scaling up its response to the monkeypox outbreak, expanding access to vaccines to more at-risk individuals, officials said in a press call. More than 56,000 doses of the monkeypox vaccine JYNNEOS will be made available immediately, and more than 240,000 doses will be allocated in the coming weeks.

“The administration’s current strategy is focused on containing the outbreak by providing vaccines to those most in need to prevent further spread of monkeypox in the communities most impacted,” CDC Director Rochelle Walensky, MD, MPH, said on a June 28 press call. “As additional supply becomes available, we will further expand our efforts making vaccines available to a wider population.”

As of June 28, there were 4,700 detected cases of monkeypox globally in 49 countries. Since the first U.S. case of monkeypox was identified on May 17, there have been 306 confirmed cases across 28 jurisdictions.

Prior to this announcement, vaccination against monkeypox was recommended only for people with known exposures to the virus. Now, the vaccine is available to people who are likely to be exposed to the virus, including:

• People who have had close physical contact with someone diagnosed with monkeypox.
• People with a sexual partner diagnosed with monkeypox.
• Men who have sex with men who have had multiple sex partners in a venue where monkeypox was identified.

The JYNNEOS vaccine is administered in two doses, delivered 28 days apart. People will have maximum immunity 2 weeks after the second dose. People should be vaccinated within 2 weeks of a possible monkeypox exposure, Dr. Walensky said, adding, “The sooner you can get vaccinated after exposure, the better.”

The U.S. Department of Health and Human Services will immediately allocate the 56,000 JYNNEOS doses across the country, prioritizing jurisdictions to areas of high transmission. A second vaccine, ACAM2000, can also be requested, but it has a greater risk for serious side effects and is not appropriate for immunocompromised individuals or people with heart disease. In the coming weeks, 240,000 JYNNEOS doses will be made available for second doses as well as first doses “as the vaccine strategy broadens,” said David Boucher, director of infectious disease preparedness and response for HHS. There are currently 800,000 JYNNEOS doses that have been manufactured and approved for release, he said, and awaiting inspection by the Food and Drug Administration, which should be completed in the beginning of July.

At the same time, the administration is focusing on increasing access to testing. Monkeypox testing is now available in 78 state public health labs in 48 states that can collectively conduct 10,000 tests per week. In addition, the administration announced on June 23 that HHS began shipping monkeypox tests to five commercial lab companies to expand testing capacity as well as make testing more accessible.

“We continue to work very closely with the community and with public health partners and clinicians to increase awareness of the monkey pox outbreak and to facilitate adequate capacity and equitable access to testing,” Dr. Walensky said. “I strongly encourage all health care providers to have a high clinical suspicion for monkeypox among their patients. Patients presenting with a suspicious rash should be tested.”

A version of this article first appeared on Medscape.com.

The White House is scaling up its response to the monkeypox outbreak, expanding access to vaccines to more at-risk individuals, officials said in a press call. More than 56,000 doses of the monkeypox vaccine JYNNEOS will be made available immediately, and more than 240,000 doses will be allocated in the coming weeks.

“The administration’s current strategy is focused on containing the outbreak by providing vaccines to those most in need to prevent further spread of monkeypox in the communities most impacted,” CDC Director Rochelle Walensky, MD, MPH, said on a June 28 press call. “As additional supply becomes available, we will further expand our efforts making vaccines available to a wider population.”

As of June 28, there were 4,700 detected cases of monkeypox globally in 49 countries. Since the first U.S. case of monkeypox was identified on May 17, there have been 306 confirmed cases across 28 jurisdictions.

Prior to this announcement, vaccination against monkeypox was recommended only for people with known exposures to the virus. Now, the vaccine is available to people who are likely to be exposed to the virus, including:

• People who have had close physical contact with someone diagnosed with monkeypox.
• People with a sexual partner diagnosed with monkeypox.
• Men who have sex with men who have had multiple sex partners in a venue where monkeypox was identified.

The JYNNEOS vaccine is administered in two doses, delivered 28 days apart. People will have maximum immunity 2 weeks after the second dose. People should be vaccinated within 2 weeks of a possible monkeypox exposure, Dr. Walensky said, adding, “The sooner you can get vaccinated after exposure, the better.”

The U.S. Department of Health and Human Services will immediately allocate the 56,000 JYNNEOS doses across the country, prioritizing jurisdictions to areas of high transmission. A second vaccine, ACAM2000, can also be requested, but it has a greater risk for serious side effects and is not appropriate for immunocompromised individuals or people with heart disease. In the coming weeks, 240,000 JYNNEOS doses will be made available for second doses as well as first doses “as the vaccine strategy broadens,” said David Boucher, director of infectious disease preparedness and response for HHS. There are currently 800,000 JYNNEOS doses that have been manufactured and approved for release, he said, and awaiting inspection by the Food and Drug Administration, which should be completed in the beginning of July.

At the same time, the administration is focusing on increasing access to testing. Monkeypox testing is now available in 78 state public health labs in 48 states that can collectively conduct 10,000 tests per week. In addition, the administration announced on June 23 that HHS began shipping monkeypox tests to five commercial lab companies to expand testing capacity as well as make testing more accessible.

“We continue to work very closely with the community and with public health partners and clinicians to increase awareness of the monkey pox outbreak and to facilitate adequate capacity and equitable access to testing,” Dr. Walensky said. “I strongly encourage all health care providers to have a high clinical suspicion for monkeypox among their patients. Patients presenting with a suspicious rash should be tested.”

A version of this article first appeared on Medscape.com.

The White House is scaling up its response to the monkeypox outbreak, expanding access to vaccines to more at-risk individuals, officials said in a press call. More than 56,000 doses of the monkeypox vaccine JYNNEOS will be made available immediately, and more than 240,000 doses will be allocated in the coming weeks.

“The administration’s current strategy is focused on containing the outbreak by providing vaccines to those most in need to prevent further spread of monkeypox in the communities most impacted,” CDC Director Rochelle Walensky, MD, MPH, said on a June 28 press call. “As additional supply becomes available, we will further expand our efforts making vaccines available to a wider population.”

As of June 28, there were 4,700 detected cases of monkeypox globally in 49 countries. Since the first U.S. case of monkeypox was identified on May 17, there have been 306 confirmed cases across 28 jurisdictions.

Prior to this announcement, vaccination against monkeypox was recommended only for people with known exposures to the virus. Now, the vaccine is available to people who are likely to be exposed to the virus, including:

• People who have had close physical contact with someone diagnosed with monkeypox.
• People with a sexual partner diagnosed with monkeypox.
• Men who have sex with men who have had multiple sex partners in a venue where monkeypox was identified.

The JYNNEOS vaccine is administered in two doses, delivered 28 days apart. People will have maximum immunity 2 weeks after the second dose. People should be vaccinated within 2 weeks of a possible monkeypox exposure, Dr. Walensky said, adding, “The sooner you can get vaccinated after exposure, the better.”

The U.S. Department of Health and Human Services will immediately allocate the 56,000 JYNNEOS doses across the country, prioritizing jurisdictions to areas of high transmission. A second vaccine, ACAM2000, can also be requested, but it has a greater risk for serious side effects and is not appropriate for immunocompromised individuals or people with heart disease. In the coming weeks, 240,000 JYNNEOS doses will be made available for second doses as well as first doses “as the vaccine strategy broadens,” said David Boucher, director of infectious disease preparedness and response for HHS. There are currently 800,000 JYNNEOS doses that have been manufactured and approved for release, he said, and awaiting inspection by the Food and Drug Administration, which should be completed in the beginning of July.

At the same time, the administration is focusing on increasing access to testing. Monkeypox testing is now available in 78 state public health labs in 48 states that can collectively conduct 10,000 tests per week. In addition, the administration announced on June 23 that HHS began shipping monkeypox tests to five commercial lab companies to expand testing capacity as well as make testing more accessible.

“We continue to work very closely with the community and with public health partners and clinicians to increase awareness of the monkey pox outbreak and to facilitate adequate capacity and equitable access to testing,” Dr. Walensky said. “I strongly encourage all health care providers to have a high clinical suspicion for monkeypox among their patients. Patients presenting with a suspicious rash should be tested.”

A version of this article first appeared on Medscape.com.

New cases of COVID-19 continue to drop among children, but the vaccination effort in those under age 5 years began with something less than a bang.

Data are available only for the first 2 weekdays after the final approval on Saturday, June 18, but they show that just 1,245 children aged 4 years and younger received the COVID vaccine on June 20 and June 21. In the first 2 days after their respective approvals, almost 99,000 children aged 5-11 years and over 675,000 children aged 12-15 were vaccinated, according to data from the Centers for Disease Control and Prevention. Children aged 0-4 years represent almost 6% of the overall population, compared with 8.7% for the 5- to 11-year-olds and 5.1% for those aged 12-15.

The recent decline in new cases over the past 4 weeks and the substantial decline since the Omicron surge could be a factor in the lack of response, but it is worth noting that the almost 68,000 new child cases reported in the past week, June 17-23, are “far higher than 1 year ago, June 24, 2021, when 8,400 child cases were reported,” the American Academy of Pediatrics and the Children’s Hospital Association said in their weekly COVID report.

That total for June 17-23 was 19% lower than the previous week and down by 40% since new cases hit a spring peak of 112,000 in late May. Regionally, new cases were down in the Midwest, the South, and the West, the AAP/CHA report showed, but the Northeast saw a small increase, which could be a signal of things to come for the summer.

The decline in new cases, however, has not been accompanied by decreases in hospitalizations or emergency department visits. New admissions of children aged 0-17 with confirmed COVID were at 0.31 per 100,000 population on June 24 after reaching that level on June 15, so no drop-off has occurred yet but there are signs of leveling off, based on CDC data.

The ED visit rates have been fairly steady through June, although COVID-related visits were up to 3.4% of all ED visits on June 22 for children aged 0-11 years, after being below 3% for the first 2 weeks of the month. The rate for children aged 12-15 has been between 1.6% and 1.9% for the past 3 weeks and the rate for 16- and 17-year-olds has been hovering between 1.7% and 2.2% for most of June, after going as high as 2.7% in late May, the CDC said on its COVID Data Tracker.

rfranki@mdedge.com

New cases of COVID-19 continue to drop among children, but the vaccination effort in those under age 5 years began with something less than a bang.

Data are available only for the first 2 weekdays after the final approval on Saturday, June 18, but they show that just 1,245 children aged 4 years and younger received the COVID vaccine on June 20 and June 21. In the first 2 days after their respective approvals, almost 99,000 children aged 5-11 years and over 675,000 children aged 12-15 were vaccinated, according to data from the Centers for Disease Control and Prevention. Children aged 0-4 years represent almost 6% of the overall population, compared with 8.7% for the 5- to 11-year-olds and 5.1% for those aged 12-15.

The recent decline in new cases over the past 4 weeks and the substantial decline since the Omicron surge could be a factor in the lack of response, but it is worth noting that the almost 68,000 new child cases reported in the past week, June 17-23, are “far higher than 1 year ago, June 24, 2021, when 8,400 child cases were reported,” the American Academy of Pediatrics and the Children’s Hospital Association said in their weekly COVID report.

That total for June 17-23 was 19% lower than the previous week and down by 40% since new cases hit a spring peak of 112,000 in late May. Regionally, new cases were down in the Midwest, the South, and the West, the AAP/CHA report showed, but the Northeast saw a small increase, which could be a signal of things to come for the summer.

The decline in new cases, however, has not been accompanied by decreases in hospitalizations or emergency department visits. New admissions of children aged 0-17 with confirmed COVID were at 0.31 per 100,000 population on June 24 after reaching that level on June 15, so no drop-off has occurred yet but there are signs of leveling off, based on CDC data.

The ED visit rates have been fairly steady through June, although COVID-related visits were up to 3.4% of all ED visits on June 22 for children aged 0-11 years, after being below 3% for the first 2 weeks of the month. The rate for children aged 12-15 has been between 1.6% and 1.9% for the past 3 weeks and the rate for 16- and 17-year-olds has been hovering between 1.7% and 2.2% for most of June, after going as high as 2.7% in late May, the CDC said on its COVID Data Tracker.

rfranki@mdedge.com

New cases of COVID-19 continue to drop among children, but the vaccination effort in those under age 5 years began with something less than a bang.

Data are available only for the first 2 weekdays after the final approval on Saturday, June 18, but they show that just 1,245 children aged 4 years and younger received the COVID vaccine on June 20 and June 21. In the first 2 days after their respective approvals, almost 99,000 children aged 5-11 years and over 675,000 children aged 12-15 were vaccinated, according to data from the Centers for Disease Control and Prevention. Children aged 0-4 years represent almost 6% of the overall population, compared with 8.7% for the 5- to 11-year-olds and 5.1% for those aged 12-15.

The recent decline in new cases over the past 4 weeks and the substantial decline since the Omicron surge could be a factor in the lack of response, but it is worth noting that the almost 68,000 new child cases reported in the past week, June 17-23, are “far higher than 1 year ago, June 24, 2021, when 8,400 child cases were reported,” the American Academy of Pediatrics and the Children’s Hospital Association said in their weekly COVID report.

That total for June 17-23 was 19% lower than the previous week and down by 40% since new cases hit a spring peak of 112,000 in late May. Regionally, new cases were down in the Midwest, the South, and the West, the AAP/CHA report showed, but the Northeast saw a small increase, which could be a signal of things to come for the summer.

The decline in new cases, however, has not been accompanied by decreases in hospitalizations or emergency department visits. New admissions of children aged 0-17 with confirmed COVID were at 0.31 per 100,000 population on June 24 after reaching that level on June 15, so no drop-off has occurred yet but there are signs of leveling off, based on CDC data.

The ED visit rates have been fairly steady through June, although COVID-related visits were up to 3.4% of all ED visits on June 22 for children aged 0-11 years, after being below 3% for the first 2 weeks of the month. The rate for children aged 12-15 has been between 1.6% and 1.9% for the past 3 weeks and the rate for 16- and 17-year-olds has been hovering between 1.7% and 2.2% for most of June, after going as high as 2.7% in late May, the CDC said on its COVID Data Tracker.

rfranki@mdedge.com

U.S. maternal deaths – those during pregnancy or within 42 days of pregnancy – increased substantially by 33.3% after March 2020 corresponding to the COVID-19 pandemic onset, according to new research published in JAMA Network Open.

Data from the National Center for Health Statistics (NCHS) revealed this rise in maternal deaths was higher than the 22% overall excess death estimate associated with the pandemic in 2020.

Increases were highest for Hispanic and non-Hispanic Black women, exacerbating already high rates of disparity in comparison with White women, wrote Marie E. Thoma, PhD, an associate professor at the University of Maryland, College Park, and Eugene R. Declercq, PhD, a professor at Boston University.

The authors noted that this spike in maternal deaths might be caused either by conditions directly related to COVID-19, such as respiratory or viral infections, or by conditions worsened by pandemic-associated health care disruptions including those for diabetes or cardiovascular disease.

The precise causes, however, could not be discerned from the data, the authors noted.

The NCHS reported an 18.4% increase in U.S. maternal mortality from 2019 to 2020. The relative increase was 44.4% among Hispanic, 25.7% among non-Hispanic Black, and 6.1% among non-Hispanic White women.

“The rise in maternal mortality among Hispanic women was unprecedented,” Dr. Thoma said in an interview. Given a 16.8% increase in overall U.S. mortality in 2020, largely attributed to the COVID-19 pandemic, the authors examined the pandemic’s role in [the higher] maternal death rates for 2020.

“Prior to this report, the NCHS released an e-report that there had been a rise in maternal mortality in 2020, but questions remained about the role of the pandemic in this rise that their report hadn’t addressed,” Dr. Thoma said in an interview “So we decided to look at the data further to assess whether the rise coincided with the pandemic and how this differed by race/ethnicity, whether there were changes in the causes of maternal death, and how often COVID-19 was listed as a contributory factor in those deaths.”

A total of 1,588 maternal deaths (18.8 per 100,000 live births) occurred before the pandemic versus 684 deaths (25.1 per 100,000 live births) during the 2020 phase of the pandemic, for a relative increase of 33.3%.

Direct obstetrical causes of death included diabetes, hypertensive and liver disorders, pregnancy-related infections, and obstetrical hemorrhage and embolism. Indirect causes comprised, among others, nonobstetrical infections and diseases of the circulatory and respiratory systems as well as mental and nervous disorders.

Relative increases in direct causes (27.7%) were mostly associated with diabetes (95.9%), hypertensive disorders (39.0%), and other specified pregnancy-related conditions (48.0%).

COVID-19 was commonly listed as a lethal condition along with other viral diseases (16 of 16 deaths and diseases of the respiratory system (11 of 19 deaths).

Late maternal mortality – defined as more than 42 days but less than 1 year after pregnancy – increased by 41%. “This was surprising as we might anticipate risk being higher during pregnancy given that pregnant women may be more susceptible, but we see that this rise was also found among people in the later postpartum period,” Dr. Thoma said.

Absolute and relative changes were highest for Hispanic women (8.9 per 100,000 live births and 74.2%, respectively) and non-Hispanic Black women (16.8 per 100,000 live births and 40.2%). In contrast, non-Hispanic White women saw increases of just 2.9 per 100,000 live births and 17.2%.

“Overall, we found the rise in maternal mortality in 2020 was concentrated after the start of pandemic, particularly for non-Hispanic Black and Hispanic women, and we saw a dramatic rise in respiratory-related conditions,” Dr. Thoma said.

In a comment, Steven Woolf, MD, MPH, director emeritus of the Center on Society and Health at Virginia Commonwealth University, Richmond, said the findings are very consistent with his and others research showing dramatic increases in overall death rates from many causes during the pandemic, with these ranging from COVID-19 leading conditions such as diabetes, cardiovascular and Alzheimer’s disease to less-studied causes such as drug overdoses and alcoholism caused by the stresses of the pandemic. Again, deaths were likely caused by both COVID-19 infections and disruptions in diagnosis and care.

“So a rise in maternal mortality would unfortunately also be expected, and these researchers have shown that,” he said in an interview. In addition, they have confirmed “the pattern of stark health disparities in the Hispanic and Black populations relative to the White. Our group has shown marked decreases in the life expectancies of the Black and Hispanic populations relative to the White population.”

While he might take issue with the study’s research methodology, Dr. Woolf said, “The work is useful partly because we need to work out the best research methods to do this kind of analysis because we really need to understand the effects on maternal mortality.”

He said sorting out the best way to do this type of research will be important for looking at excess deaths and maternal mortality following other events, for example, in the wake of the Supreme Court’s recent decision to reverse Roe v. Wade.

The authors acknowledged certain study limitations, including the large percentage of COVID-19 cases with a nonspecific underlying cause. According to Dr. Thoma and Dr. Declercq, that reflects a maternal death coding problem that needs to be addressed, as well as a partitioning of data. The latter resulted in small numbers for some categories, with rates suppressed for fewer than 16 deaths because of reduced reliability.

“We found that more specific information is often available on death certificates but is lost in the process of coding,” said Dr. Thoma. “We were able to reclassify many of these causes to a more specific cause that we attributed to be the primary cause of death.”

The authors said future studies of maternal death should examine the contribution of the pandemic to racial and ethnic disparities and should identify specific causes of maternal deaths overall and associated with COVID-19.

In earlier research, the authors previously warned of possible misclassifications of maternal deaths.

They found evidence of both underreporting and overreporting of deaths, with possible overreporting predominant, whereas accurate data are essential for measuring the effectiveness of maternal mortality reduction programs.

Dr. Thoma’s group will continue to monitor mortality trends with the release of 2021 data. “We hope we will see improvements in 2021 given greater access to vaccines, treatments, and fewer health care disruptions,” Dr. Thoma said. “It will be important to continue to stress the importance of COVID-19 vaccines for pregnant and postpartum people.”

This study had no external funding. The authors disclosed no competing interests. Dr. Woolf declared no conflicts of interest.

U.S. maternal deaths – those during pregnancy or within 42 days of pregnancy – increased substantially by 33.3% after March 2020 corresponding to the COVID-19 pandemic onset, according to new research published in JAMA Network Open.

Data from the National Center for Health Statistics (NCHS) revealed this rise in maternal deaths was higher than the 22% overall excess death estimate associated with the pandemic in 2020.

Increases were highest for Hispanic and non-Hispanic Black women, exacerbating already high rates of disparity in comparison with White women, wrote Marie E. Thoma, PhD, an associate professor at the University of Maryland, College Park, and Eugene R. Declercq, PhD, a professor at Boston University.

The authors noted that this spike in maternal deaths might be caused either by conditions directly related to COVID-19, such as respiratory or viral infections, or by conditions worsened by pandemic-associated health care disruptions including those for diabetes or cardiovascular disease.

The precise causes, however, could not be discerned from the data, the authors noted.

The NCHS reported an 18.4% increase in U.S. maternal mortality from 2019 to 2020. The relative increase was 44.4% among Hispanic, 25.7% among non-Hispanic Black, and 6.1% among non-Hispanic White women.

“The rise in maternal mortality among Hispanic women was unprecedented,” Dr. Thoma said in an interview. Given a 16.8% increase in overall U.S. mortality in 2020, largely attributed to the COVID-19 pandemic, the authors examined the pandemic’s role in [the higher] maternal death rates for 2020.

“Prior to this report, the NCHS released an e-report that there had been a rise in maternal mortality in 2020, but questions remained about the role of the pandemic in this rise that their report hadn’t addressed,” Dr. Thoma said in an interview “So we decided to look at the data further to assess whether the rise coincided with the pandemic and how this differed by race/ethnicity, whether there were changes in the causes of maternal death, and how often COVID-19 was listed as a contributory factor in those deaths.”

A total of 1,588 maternal deaths (18.8 per 100,000 live births) occurred before the pandemic versus 684 deaths (25.1 per 100,000 live births) during the 2020 phase of the pandemic, for a relative increase of 33.3%.

Direct obstetrical causes of death included diabetes, hypertensive and liver disorders, pregnancy-related infections, and obstetrical hemorrhage and embolism. Indirect causes comprised, among others, nonobstetrical infections and diseases of the circulatory and respiratory systems as well as mental and nervous disorders.

Relative increases in direct causes (27.7%) were mostly associated with diabetes (95.9%), hypertensive disorders (39.0%), and other specified pregnancy-related conditions (48.0%).

COVID-19 was commonly listed as a lethal condition along with other viral diseases (16 of 16 deaths and diseases of the respiratory system (11 of 19 deaths).

Late maternal mortality – defined as more than 42 days but less than 1 year after pregnancy – increased by 41%. “This was surprising as we might anticipate risk being higher during pregnancy given that pregnant women may be more susceptible, but we see that this rise was also found among people in the later postpartum period,” Dr. Thoma said.

Absolute and relative changes were highest for Hispanic women (8.9 per 100,000 live births and 74.2%, respectively) and non-Hispanic Black women (16.8 per 100,000 live births and 40.2%). In contrast, non-Hispanic White women saw increases of just 2.9 per 100,000 live births and 17.2%.

“Overall, we found the rise in maternal mortality in 2020 was concentrated after the start of pandemic, particularly for non-Hispanic Black and Hispanic women, and we saw a dramatic rise in respiratory-related conditions,” Dr. Thoma said.

In a comment, Steven Woolf, MD, MPH, director emeritus of the Center on Society and Health at Virginia Commonwealth University, Richmond, said the findings are very consistent with his and others research showing dramatic increases in overall death rates from many causes during the pandemic, with these ranging from COVID-19 leading conditions such as diabetes, cardiovascular and Alzheimer’s disease to less-studied causes such as drug overdoses and alcoholism caused by the stresses of the pandemic. Again, deaths were likely caused by both COVID-19 infections and disruptions in diagnosis and care.

“So a rise in maternal mortality would unfortunately also be expected, and these researchers have shown that,” he said in an interview. In addition, they have confirmed “the pattern of stark health disparities in the Hispanic and Black populations relative to the White. Our group has shown marked decreases in the life expectancies of the Black and Hispanic populations relative to the White population.”

While he might take issue with the study’s research methodology, Dr. Woolf said, “The work is useful partly because we need to work out the best research methods to do this kind of analysis because we really need to understand the effects on maternal mortality.”

He said sorting out the best way to do this type of research will be important for looking at excess deaths and maternal mortality following other events, for example, in the wake of the Supreme Court’s recent decision to reverse Roe v. Wade.

The authors acknowledged certain study limitations, including the large percentage of COVID-19 cases with a nonspecific underlying cause. According to Dr. Thoma and Dr. Declercq, that reflects a maternal death coding problem that needs to be addressed, as well as a partitioning of data. The latter resulted in small numbers for some categories, with rates suppressed for fewer than 16 deaths because of reduced reliability.

“We found that more specific information is often available on death certificates but is lost in the process of coding,” said Dr. Thoma. “We were able to reclassify many of these causes to a more specific cause that we attributed to be the primary cause of death.”

The authors said future studies of maternal death should examine the contribution of the pandemic to racial and ethnic disparities and should identify specific causes of maternal deaths overall and associated with COVID-19.

In earlier research, the authors previously warned of possible misclassifications of maternal deaths.

They found evidence of both underreporting and overreporting of deaths, with possible overreporting predominant, whereas accurate data are essential for measuring the effectiveness of maternal mortality reduction programs.

Dr. Thoma’s group will continue to monitor mortality trends with the release of 2021 data. “We hope we will see improvements in 2021 given greater access to vaccines, treatments, and fewer health care disruptions,” Dr. Thoma said. “It will be important to continue to stress the importance of COVID-19 vaccines for pregnant and postpartum people.”

This study had no external funding. The authors disclosed no competing interests. Dr. Woolf declared no conflicts of interest.

U.S. maternal deaths – those during pregnancy or within 42 days of pregnancy – increased substantially by 33.3% after March 2020 corresponding to the COVID-19 pandemic onset, according to new research published in JAMA Network Open.

Data from the National Center for Health Statistics (NCHS) revealed this rise in maternal deaths was higher than the 22% overall excess death estimate associated with the pandemic in 2020.

Increases were highest for Hispanic and non-Hispanic Black women, exacerbating already high rates of disparity in comparison with White women, wrote Marie E. Thoma, PhD, an associate professor at the University of Maryland, College Park, and Eugene R. Declercq, PhD, a professor at Boston University.

The authors noted that this spike in maternal deaths might be caused either by conditions directly related to COVID-19, such as respiratory or viral infections, or by conditions worsened by pandemic-associated health care disruptions including those for diabetes or cardiovascular disease.

The precise causes, however, could not be discerned from the data, the authors noted.

The NCHS reported an 18.4% increase in U.S. maternal mortality from 2019 to 2020. The relative increase was 44.4% among Hispanic, 25.7% among non-Hispanic Black, and 6.1% among non-Hispanic White women.

“The rise in maternal mortality among Hispanic women was unprecedented,” Dr. Thoma said in an interview. Given a 16.8% increase in overall U.S. mortality in 2020, largely attributed to the COVID-19 pandemic, the authors examined the pandemic’s role in [the higher] maternal death rates for 2020.

“Prior to this report, the NCHS released an e-report that there had been a rise in maternal mortality in 2020, but questions remained about the role of the pandemic in this rise that their report hadn’t addressed,” Dr. Thoma said in an interview “So we decided to look at the data further to assess whether the rise coincided with the pandemic and how this differed by race/ethnicity, whether there were changes in the causes of maternal death, and how often COVID-19 was listed as a contributory factor in those deaths.”

A total of 1,588 maternal deaths (18.8 per 100,000 live births) occurred before the pandemic versus 684 deaths (25.1 per 100,000 live births) during the 2020 phase of the pandemic, for a relative increase of 33.3%.

Direct obstetrical causes of death included diabetes, hypertensive and liver disorders, pregnancy-related infections, and obstetrical hemorrhage and embolism. Indirect causes comprised, among others, nonobstetrical infections and diseases of the circulatory and respiratory systems as well as mental and nervous disorders.

Relative increases in direct causes (27.7%) were mostly associated with diabetes (95.9%), hypertensive disorders (39.0%), and other specified pregnancy-related conditions (48.0%).

COVID-19 was commonly listed as a lethal condition along with other viral diseases (16 of 16 deaths and diseases of the respiratory system (11 of 19 deaths).

Late maternal mortality – defined as more than 42 days but less than 1 year after pregnancy – increased by 41%. “This was surprising as we might anticipate risk being higher during pregnancy given that pregnant women may be more susceptible, but we see that this rise was also found among people in the later postpartum period,” Dr. Thoma said.

Absolute and relative changes were highest for Hispanic women (8.9 per 100,000 live births and 74.2%, respectively) and non-Hispanic Black women (16.8 per 100,000 live births and 40.2%). In contrast, non-Hispanic White women saw increases of just 2.9 per 100,000 live births and 17.2%.

“Overall, we found the rise in maternal mortality in 2020 was concentrated after the start of pandemic, particularly for non-Hispanic Black and Hispanic women, and we saw a dramatic rise in respiratory-related conditions,” Dr. Thoma said.

In a comment, Steven Woolf, MD, MPH, director emeritus of the Center on Society and Health at Virginia Commonwealth University, Richmond, said the findings are very consistent with his and others research showing dramatic increases in overall death rates from many causes during the pandemic, with these ranging from COVID-19 leading conditions such as diabetes, cardiovascular and Alzheimer’s disease to less-studied causes such as drug overdoses and alcoholism caused by the stresses of the pandemic. Again, deaths were likely caused by both COVID-19 infections and disruptions in diagnosis and care.

“So a rise in maternal mortality would unfortunately also be expected, and these researchers have shown that,” he said in an interview. In addition, they have confirmed “the pattern of stark health disparities in the Hispanic and Black populations relative to the White. Our group has shown marked decreases in the life expectancies of the Black and Hispanic populations relative to the White population.”

While he might take issue with the study’s research methodology, Dr. Woolf said, “The work is useful partly because we need to work out the best research methods to do this kind of analysis because we really need to understand the effects on maternal mortality.”

He said sorting out the best way to do this type of research will be important for looking at excess deaths and maternal mortality following other events, for example, in the wake of the Supreme Court’s recent decision to reverse Roe v. Wade.

The authors acknowledged certain study limitations, including the large percentage of COVID-19 cases with a nonspecific underlying cause. According to Dr. Thoma and Dr. Declercq, that reflects a maternal death coding problem that needs to be addressed, as well as a partitioning of data. The latter resulted in small numbers for some categories, with rates suppressed for fewer than 16 deaths because of reduced reliability.

“We found that more specific information is often available on death certificates but is lost in the process of coding,” said Dr. Thoma. “We were able to reclassify many of these causes to a more specific cause that we attributed to be the primary cause of death.”

The authors said future studies of maternal death should examine the contribution of the pandemic to racial and ethnic disparities and should identify specific causes of maternal deaths overall and associated with COVID-19.

In earlier research, the authors previously warned of possible misclassifications of maternal deaths.

They found evidence of both underreporting and overreporting of deaths, with possible overreporting predominant, whereas accurate data are essential for measuring the effectiveness of maternal mortality reduction programs.

Dr. Thoma’s group will continue to monitor mortality trends with the release of 2021 data. “We hope we will see improvements in 2021 given greater access to vaccines, treatments, and fewer health care disruptions,” Dr. Thoma said. “It will be important to continue to stress the importance of COVID-19 vaccines for pregnant and postpartum people.”

This study had no external funding. The authors disclosed no competing interests. Dr. Woolf declared no conflicts of interest.

A new analysis from the Centers for Disease Control and Prevention provides further details on mysterious cases of pediatric hepatitis identified across the United States. While 45% of patients have tested positive for adenovirus infection, it is likely that these children “represent a heterogenous group of hepatitis etiologies,” the CDC authors wrote.

Of the 296 children diagnosed between Oct. 1, 2021, and June 15, 2022, in the United States, 18 have required liver transplants and 11 have died.

On April 21, 2022, the CDC issued an alert to providers to report pediatric hepatitis cases of unknown etiology in children under 10 after similar cases had been identified in Europe and the United States. While the United Kingdom has found an uptick in cases over the past year, researchers from the CDC published data on June 14 that suggested pediatric hepatitis cases had not increased from 2017 to 2021.

This newest analysis, published Morbidity and Mortality Weekly Report, provides additional demographic data on affected patients and explores possible causes, including previous infection with COVID-19. Investigators had earlier ruled out COVID-19 vaccination as a potential factor in these cases, as most children were unvaccinated or not yet eligible to receive the vaccine. According to the analysis, only five patients had received at least one dose of a COVID-19 vaccine.

The 296 cases included in the analysis occurred in 42 U.S. states and territories, and the median age for patients was 2 years and 2 months. Nearly 60% of patients were male (58.1%) and 40.9% were female. The largest percentage of cases occurred in Hispanic or Latino children (37.8%), followed by non-Hispanic White (32.4%) children. Black patients made up 9.8% of all cases, and 3.7% of affected children were of Asian descent. Vomiting, fatigue, and jaundice were all common symptoms, and about 90% (89.9%) of children required hospitalization..

Of 224 children tested for adenovirus, 44.6% were positive. The analysis also included information on 123 of these hepatitis patients tested for other various pathogens. Nearly 80% (98/123) received a COVID-19 test and just 10.2% were positive. About 26% of patients had previously had COVID-19, and hepatitis onset occurred, on average, 133 days after the reported SARS-CoV-2 infection.

Other viruses detected included rhinovirus/enterovirus (24.5%), rotavirus (14.0%), and acute Epstein-Barr virus (11.4%)

Simultaneous infection with SARS-CoV-2 and adenovirus occurred in three patients.

There was no evidence of viral inclusions in the 36 patients who had pathological evaluation liver biopsies, explants, or autopsied tissue.

The findings suggest that there may be many different causes behind these severe hepatitis cases, and it is estimated that about one-third of hepatitis cases in children do not have a known cause. However, the identification of adenovirus infection in many cases “raises the question whether a new pattern of disease is emerging in this population or if adenovirus might be an underrecognized cause or cofactor in previously indeterminate cases of pediatric hepatitis,” the authors wrote. As the investigation continues, “further clinical data are needed to understand the cause of these cases and to assess the potential association with adenovirus.”

A version of this article first appeared on Medscape.com.

A new analysis from the Centers for Disease Control and Prevention provides further details on mysterious cases of pediatric hepatitis identified across the United States. While 45% of patients have tested positive for adenovirus infection, it is likely that these children “represent a heterogenous group of hepatitis etiologies,” the CDC authors wrote.

Of the 296 children diagnosed between Oct. 1, 2021, and June 15, 2022, in the United States, 18 have required liver transplants and 11 have died.

On April 21, 2022, the CDC issued an alert to providers to report pediatric hepatitis cases of unknown etiology in children under 10 after similar cases had been identified in Europe and the United States. While the United Kingdom has found an uptick in cases over the past year, researchers from the CDC published data on June 14 that suggested pediatric hepatitis cases had not increased from 2017 to 2021.

This newest analysis, published Morbidity and Mortality Weekly Report, provides additional demographic data on affected patients and explores possible causes, including previous infection with COVID-19. Investigators had earlier ruled out COVID-19 vaccination as a potential factor in these cases, as most children were unvaccinated or not yet eligible to receive the vaccine. According to the analysis, only five patients had received at least one dose of a COVID-19 vaccine.

The 296 cases included in the analysis occurred in 42 U.S. states and territories, and the median age for patients was 2 years and 2 months. Nearly 60% of patients were male (58.1%) and 40.9% were female. The largest percentage of cases occurred in Hispanic or Latino children (37.8%), followed by non-Hispanic White (32.4%) children. Black patients made up 9.8% of all cases, and 3.7% of affected children were of Asian descent. Vomiting, fatigue, and jaundice were all common symptoms, and about 90% (89.9%) of children required hospitalization..

Of 224 children tested for adenovirus, 44.6% were positive. The analysis also included information on 123 of these hepatitis patients tested for other various pathogens. Nearly 80% (98/123) received a COVID-19 test and just 10.2% were positive. About 26% of patients had previously had COVID-19, and hepatitis onset occurred, on average, 133 days after the reported SARS-CoV-2 infection.

Other viruses detected included rhinovirus/enterovirus (24.5%), rotavirus (14.0%), and acute Epstein-Barr virus (11.4%)

Simultaneous infection with SARS-CoV-2 and adenovirus occurred in three patients.

There was no evidence of viral inclusions in the 36 patients who had pathological evaluation liver biopsies, explants, or autopsied tissue.

The findings suggest that there may be many different causes behind these severe hepatitis cases, and it is estimated that about one-third of hepatitis cases in children do not have a known cause. However, the identification of adenovirus infection in many cases “raises the question whether a new pattern of disease is emerging in this population or if adenovirus might be an underrecognized cause or cofactor in previously indeterminate cases of pediatric hepatitis,” the authors wrote. As the investigation continues, “further clinical data are needed to understand the cause of these cases and to assess the potential association with adenovirus.”

A version of this article first appeared on Medscape.com.

A new analysis from the Centers for Disease Control and Prevention provides further details on mysterious cases of pediatric hepatitis identified across the United States. While 45% of patients have tested positive for adenovirus infection, it is likely that these children “represent a heterogenous group of hepatitis etiologies,” the CDC authors wrote.

Of the 296 children diagnosed between Oct. 1, 2021, and June 15, 2022, in the United States, 18 have required liver transplants and 11 have died.

On April 21, 2022, the CDC issued an alert to providers to report pediatric hepatitis cases of unknown etiology in children under 10 after similar cases had been identified in Europe and the United States. While the United Kingdom has found an uptick in cases over the past year, researchers from the CDC published data on June 14 that suggested pediatric hepatitis cases had not increased from 2017 to 2021.

This newest analysis, published Morbidity and Mortality Weekly Report, provides additional demographic data on affected patients and explores possible causes, including previous infection with COVID-19. Investigators had earlier ruled out COVID-19 vaccination as a potential factor in these cases, as most children were unvaccinated or not yet eligible to receive the vaccine. According to the analysis, only five patients had received at least one dose of a COVID-19 vaccine.

The 296 cases included in the analysis occurred in 42 U.S. states and territories, and the median age for patients was 2 years and 2 months. Nearly 60% of patients were male (58.1%) and 40.9% were female. The largest percentage of cases occurred in Hispanic or Latino children (37.8%), followed by non-Hispanic White (32.4%) children. Black patients made up 9.8% of all cases, and 3.7% of affected children were of Asian descent. Vomiting, fatigue, and jaundice were all common symptoms, and about 90% (89.9%) of children required hospitalization..

Of 224 children tested for adenovirus, 44.6% were positive. The analysis also included information on 123 of these hepatitis patients tested for other various pathogens. Nearly 80% (98/123) received a COVID-19 test and just 10.2% were positive. About 26% of patients had previously had COVID-19, and hepatitis onset occurred, on average, 133 days after the reported SARS-CoV-2 infection.

Other viruses detected included rhinovirus/enterovirus (24.5%), rotavirus (14.0%), and acute Epstein-Barr virus (11.4%)

Simultaneous infection with SARS-CoV-2 and adenovirus occurred in three patients.

There was no evidence of viral inclusions in the 36 patients who had pathological evaluation liver biopsies, explants, or autopsied tissue.

The findings suggest that there may be many different causes behind these severe hepatitis cases, and it is estimated that about one-third of hepatitis cases in children do not have a known cause. However, the identification of adenovirus infection in many cases “raises the question whether a new pattern of disease is emerging in this population or if adenovirus might be an underrecognized cause or cofactor in previously indeterminate cases of pediatric hepatitis,” the authors wrote. As the investigation continues, “further clinical data are needed to understand the cause of these cases and to assess the potential association with adenovirus.”

A version of this article first appeared on Medscape.com.

Bacteria that cause typhoid fever are becoming increasingly resistant to common antibiotics worldwide, a new analysis indicates.

Resistant strains of Salmonella enterica serovar typhi – almost all originating in South Asia – have spread across borders nearly 200 times since 1990.

Until now, analysis has been limited by small samples. This genome analysis is the largest to date and included 3,489 newly sequenced isolates (collected between 2014 and 2019) from prospective surveillance studies in four of the countries with the highest typhoid burden: Bangladesh, Nepal, Pakistan, and India.

Findings of the study, led by Kesia Esther da Silva, PhD, with the division of infectious diseases and geographic medicine at Stanford (Calif.) University, were published online in The Lancet Microbe.
 

Global deaths: 100,000 annually

Typhoid fever remains a global public health threat, causing 11 million infections and more than 100,000 deaths each year. Most cases (70%) are in South Asia, but typhoid also has significant presence in sub-Saharan Africa, Southeast Asia, and Oceania.

The findings are further evidence of the need for a global response, the authors write.

Jason Andrews, MD, a coauthor and associate professor in the division of infectious diseases and geographic medicine at Stanford University, said in an interview that the research helps pinpoint where the highest burden is and where the biggest need is for the two highly effective typhoid vaccines.

“We’re seeing higher levels of resistance than we’ve ever seen before against our latest and greatest antibiotics,” he said.

He said so far, strategies for tackling typhoid have involved country-level decisions and local funding and that needs to be shifted to a global priority. “Given contemporary travel migration patterns, what we see is that when antimicrobial resistance develops in one country, it quickly spreads to other countries.”

Dr. Andrews said the United States sees about 300-500 typhoid cases a year. “About 80% of those cases involve people traveling from South Asia,” he said.

Infections also come from people from the United States visiting high-burden countries, especially to see family. Often they don’t perceive the risk and skip vaccination, he said. U.S. clinicians can help with educating patients traveling to typhoid-endemic regions on pretravel vaccination.

Physician awareness is also important when patients have recently returned from such regions. Data from this study show a need to carefully consider which antibiotics will be effective with the growing resistance.
 

Only one oral option left in Pakistan

“We are running low on treatment options for typhoid,” Dr. Andrews said. The resistance pattern in Pakistan, for example, has left only one oral option, azithromycin, and resistance is building to that.

Without that option, “we’ll have to hospitalize patients and give intravenous antibiotics,” he said. “That’s concerning.”

Moreover, some resistant strains from Pakistan have been turning up in the United States.

“There are actually some cases that have not been tracked at all to travelers going to Pakistan and are thought to be from local transmission in the United States,” he said.

Valida Bajrovic, MD, assistant professor of medicine in infectious diseases at the Icahn School of Medicine at Mount Sinai, New York, said in an interview that, in addition to vaccinating travelers before they head to typhoid-endemic areas, physicians should educate patients on avoiding fecal transmission of typhoid with vigilant hand washing, drinking bottled water, and avoiding foods that may have been prepared in unsanitary conditions.

Dr. Bajrovic, who directs the antimicrobial stewardship efforts at the Mount Sinai Morningside and Mount Sinai West Hospitals, said stricter antimicrobial stewardship efforts are needed, particularly in Europe and South Asia, but also in the United States.

“Restriction of antibiotic use is the way to prevent antibiotic resistance,” she said, adding that such restrictions need to be part of a global effort.

Strains in the study were classified as multidrug resistant (MDR) if they contained genes resistant to ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole. The authors also traced the presence of genes demonstrating resistance to macrolides and quinolones.

At first, fluoroquinolones were effective against MDR S. typhi and in the 1990s became the primary therapy. By the 2010s, however, the majority of S. typhi in south Asia contained mutations in the quinolone resistance-determining regions.

The authors wrote: “We found evidence of frequent international (n = 138) and intercontinental transfers (n = 59) of antimicrobial-resistant S. typhi.”

According to the analysis, since 2000, MDR S. typhi has declined steadily in Bangladesh and India and remained at less than 5% of typhoid strains in Nepal, though it has increased slightly in Pakistan.

However, these are being replaced “with strains containing ceftriaxone resistance (extensively drug resistant), high-level fluoroquinolone resistance, or azithromycin resistance, which are reversing declines in the effective population size of S. typhi,” the authors wrote.

The analysis supports urgency for prevention measures, including use of typhoid conjugate vaccines in typhoid-endemic countries, the authors said.

But given the rise in international spread of increasingly resistant strains, they said, preventive measures should not be limited to those countries.

The study was funded by the Bill & Melinda Gates Foundation. Dr. Da Silva, Dr. Andrews, and Dr. Bajrovic have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Bacteria that cause typhoid fever are becoming increasingly resistant to common antibiotics worldwide, a new analysis indicates.

Resistant strains of Salmonella enterica serovar typhi – almost all originating in South Asia – have spread across borders nearly 200 times since 1990.

Until now, analysis has been limited by small samples. This genome analysis is the largest to date and included 3,489 newly sequenced isolates (collected between 2014 and 2019) from prospective surveillance studies in four of the countries with the highest typhoid burden: Bangladesh, Nepal, Pakistan, and India.

Findings of the study, led by Kesia Esther da Silva, PhD, with the division of infectious diseases and geographic medicine at Stanford (Calif.) University, were published online in The Lancet Microbe.
 

Global deaths: 100,000 annually

Typhoid fever remains a global public health threat, causing 11 million infections and more than 100,000 deaths each year. Most cases (70%) are in South Asia, but typhoid also has significant presence in sub-Saharan Africa, Southeast Asia, and Oceania.

The findings are further evidence of the need for a global response, the authors write.

Jason Andrews, MD, a coauthor and associate professor in the division of infectious diseases and geographic medicine at Stanford University, said in an interview that the research helps pinpoint where the highest burden is and where the biggest need is for the two highly effective typhoid vaccines.

“We’re seeing higher levels of resistance than we’ve ever seen before against our latest and greatest antibiotics,” he said.

He said so far, strategies for tackling typhoid have involved country-level decisions and local funding and that needs to be shifted to a global priority. “Given contemporary travel migration patterns, what we see is that when antimicrobial resistance develops in one country, it quickly spreads to other countries.”

Dr. Andrews said the United States sees about 300-500 typhoid cases a year. “About 80% of those cases involve people traveling from South Asia,” he said.

Infections also come from people from the United States visiting high-burden countries, especially to see family. Often they don’t perceive the risk and skip vaccination, he said. U.S. clinicians can help with educating patients traveling to typhoid-endemic regions on pretravel vaccination.

Physician awareness is also important when patients have recently returned from such regions. Data from this study show a need to carefully consider which antibiotics will be effective with the growing resistance.
 

Only one oral option left in Pakistan

“We are running low on treatment options for typhoid,” Dr. Andrews said. The resistance pattern in Pakistan, for example, has left only one oral option, azithromycin, and resistance is building to that.

Without that option, “we’ll have to hospitalize patients and give intravenous antibiotics,” he said. “That’s concerning.”

Moreover, some resistant strains from Pakistan have been turning up in the United States.

“There are actually some cases that have not been tracked at all to travelers going to Pakistan and are thought to be from local transmission in the United States,” he said.

Valida Bajrovic, MD, assistant professor of medicine in infectious diseases at the Icahn School of Medicine at Mount Sinai, New York, said in an interview that, in addition to vaccinating travelers before they head to typhoid-endemic areas, physicians should educate patients on avoiding fecal transmission of typhoid with vigilant hand washing, drinking bottled water, and avoiding foods that may have been prepared in unsanitary conditions.

Dr. Bajrovic, who directs the antimicrobial stewardship efforts at the Mount Sinai Morningside and Mount Sinai West Hospitals, said stricter antimicrobial stewardship efforts are needed, particularly in Europe and South Asia, but also in the United States.

“Restriction of antibiotic use is the way to prevent antibiotic resistance,” she said, adding that such restrictions need to be part of a global effort.

Strains in the study were classified as multidrug resistant (MDR) if they contained genes resistant to ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole. The authors also traced the presence of genes demonstrating resistance to macrolides and quinolones.

At first, fluoroquinolones were effective against MDR S. typhi and in the 1990s became the primary therapy. By the 2010s, however, the majority of S. typhi in south Asia contained mutations in the quinolone resistance-determining regions.

The authors wrote: “We found evidence of frequent international (n = 138) and intercontinental transfers (n = 59) of antimicrobial-resistant S. typhi.”

According to the analysis, since 2000, MDR S. typhi has declined steadily in Bangladesh and India and remained at less than 5% of typhoid strains in Nepal, though it has increased slightly in Pakistan.

However, these are being replaced “with strains containing ceftriaxone resistance (extensively drug resistant), high-level fluoroquinolone resistance, or azithromycin resistance, which are reversing declines in the effective population size of S. typhi,” the authors wrote.

The analysis supports urgency for prevention measures, including use of typhoid conjugate vaccines in typhoid-endemic countries, the authors said.

But given the rise in international spread of increasingly resistant strains, they said, preventive measures should not be limited to those countries.

The study was funded by the Bill & Melinda Gates Foundation. Dr. Da Silva, Dr. Andrews, and Dr. Bajrovic have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Bacteria that cause typhoid fever are becoming increasingly resistant to common antibiotics worldwide, a new analysis indicates.

Resistant strains of Salmonella enterica serovar typhi – almost all originating in South Asia – have spread across borders nearly 200 times since 1990.

Until now, analysis has been limited by small samples. This genome analysis is the largest to date and included 3,489 newly sequenced isolates (collected between 2014 and 2019) from prospective surveillance studies in four of the countries with the highest typhoid burden: Bangladesh, Nepal, Pakistan, and India.

Findings of the study, led by Kesia Esther da Silva, PhD, with the division of infectious diseases and geographic medicine at Stanford (Calif.) University, were published online in The Lancet Microbe.
 

Global deaths: 100,000 annually

Typhoid fever remains a global public health threat, causing 11 million infections and more than 100,000 deaths each year. Most cases (70%) are in South Asia, but typhoid also has significant presence in sub-Saharan Africa, Southeast Asia, and Oceania.

The findings are further evidence of the need for a global response, the authors write.

Jason Andrews, MD, a coauthor and associate professor in the division of infectious diseases and geographic medicine at Stanford University, said in an interview that the research helps pinpoint where the highest burden is and where the biggest need is for the two highly effective typhoid vaccines.

“We’re seeing higher levels of resistance than we’ve ever seen before against our latest and greatest antibiotics,” he said.

He said so far, strategies for tackling typhoid have involved country-level decisions and local funding and that needs to be shifted to a global priority. “Given contemporary travel migration patterns, what we see is that when antimicrobial resistance develops in one country, it quickly spreads to other countries.”

Dr. Andrews said the United States sees about 300-500 typhoid cases a year. “About 80% of those cases involve people traveling from South Asia,” he said.

Infections also come from people from the United States visiting high-burden countries, especially to see family. Often they don’t perceive the risk and skip vaccination, he said. U.S. clinicians can help with educating patients traveling to typhoid-endemic regions on pretravel vaccination.

Physician awareness is also important when patients have recently returned from such regions. Data from this study show a need to carefully consider which antibiotics will be effective with the growing resistance.
 

Only one oral option left in Pakistan

“We are running low on treatment options for typhoid,” Dr. Andrews said. The resistance pattern in Pakistan, for example, has left only one oral option, azithromycin, and resistance is building to that.

Without that option, “we’ll have to hospitalize patients and give intravenous antibiotics,” he said. “That’s concerning.”

Moreover, some resistant strains from Pakistan have been turning up in the United States.

“There are actually some cases that have not been tracked at all to travelers going to Pakistan and are thought to be from local transmission in the United States,” he said.

Valida Bajrovic, MD, assistant professor of medicine in infectious diseases at the Icahn School of Medicine at Mount Sinai, New York, said in an interview that, in addition to vaccinating travelers before they head to typhoid-endemic areas, physicians should educate patients on avoiding fecal transmission of typhoid with vigilant hand washing, drinking bottled water, and avoiding foods that may have been prepared in unsanitary conditions.

Dr. Bajrovic, who directs the antimicrobial stewardship efforts at the Mount Sinai Morningside and Mount Sinai West Hospitals, said stricter antimicrobial stewardship efforts are needed, particularly in Europe and South Asia, but also in the United States.

“Restriction of antibiotic use is the way to prevent antibiotic resistance,” she said, adding that such restrictions need to be part of a global effort.

Strains in the study were classified as multidrug resistant (MDR) if they contained genes resistant to ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole. The authors also traced the presence of genes demonstrating resistance to macrolides and quinolones.

At first, fluoroquinolones were effective against MDR S. typhi and in the 1990s became the primary therapy. By the 2010s, however, the majority of S. typhi in south Asia contained mutations in the quinolone resistance-determining regions.

The authors wrote: “We found evidence of frequent international (n = 138) and intercontinental transfers (n = 59) of antimicrobial-resistant S. typhi.”

According to the analysis, since 2000, MDR S. typhi has declined steadily in Bangladesh and India and remained at less than 5% of typhoid strains in Nepal, though it has increased slightly in Pakistan.

However, these are being replaced “with strains containing ceftriaxone resistance (extensively drug resistant), high-level fluoroquinolone resistance, or azithromycin resistance, which are reversing declines in the effective population size of S. typhi,” the authors wrote.

The analysis supports urgency for prevention measures, including use of typhoid conjugate vaccines in typhoid-endemic countries, the authors said.

But given the rise in international spread of increasingly resistant strains, they said, preventive measures should not be limited to those countries.

The study was funded by the Bill & Melinda Gates Foundation. Dr. Da Silva, Dr. Andrews, and Dr. Bajrovic have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.