[Posted 05/Aug/2022]

AUDIENCE: Infectious Disease, Ob/Gyn, Family Medicine

KEY FINDINGS: As of July 29, 2022, the Centers for Disease Control and Prevention (CDC) and state and local public health partners are reporting 5,189 cases of Monkeypox virus infections in the United States across 47 states, Washington, D.C., and Puerto Rico. CDC is also reporting multiple outbreaks of monkeypox that have been reported globally in 71 countries that do not normally report monkeypox activity. On Friday, July 22, CDC reported the first two cases of monkeypox in children in the United States during the current outbreak. This Health Alert Network (HAN) Health Update serves to alert clinicians to clinical considerations for preventing, diagnosing, and managing monkeypox in people with HIV, children, adolescents, and people who are pregnant or breastfeeding.

BACKGROUND: Since May 2022, CDC has been urging healthcare providers in the United States to be on alert for patients who have rash illnesses consistent with monkeypox. People with HIV, individuals who are immunocompromised, children, adolescents, and people who are pregnant or breastfeeding may be at risk for increased disease severity and adverse health outcomes associated with monkeypox infection. Clinicians should be familiar with unique clinical considerations for monkeypox in these patient populations. A broad diagnostic approach is encouraged to distinguish Monkeypox virus infection from other causes of fever and rash illness. Testing should be performed on persons for whom monkeypox is suspected based on clinical presentation or epidemiologic criteria. Clinicians should consult their state or territorial health department (State Contacts) or CDC through the CDC Emergency Operations Center (770-488-7100) as soon as monkeypox is suspected.

DETAILS: CDC has issued clinical considerations for monkeypox infection in multiple populations including: people with HIV, children and adolescents, and people who are pregnant or breastfeeding. These newly released clinical considerations complement existing clinical guidance for managing monkeypox and provide information on signs and symptoms of Monkeypox virus infection; pre- and post-exposure prophylaxis; treatment; and infection control in these populations.

Recommendations and Information for Healthcare Providers on Monkeypox in People with HIV

In the current outbreak, available international summary surveillance data in the CDC-issued clinical considerations for people with HIV indicate 30-51% HIV prevalence among persons with monkeypox for whom HIV status was known. It is currently unknown whether HIV infection affects a person's risk of acquiring Monkeypox virus infection and developing disease after exposure.

Persons with advanced and uncontrolled HIV might be at higher risk for severe or prolonged monkeypox disease. Therefore, prophylaxis (e.g., vaccination), medical treatment and close monitoring are a priority for this population. Compared with other persons with monkeypox, case reports among persons with inadequately treated HIV who have CD4 counts <=350 per mm³ reported higher rates of secondary bacterial infection, more prolonged illness (and thereby also longer period of infectiousness), as well as a higher likelihood of a confluent or partially confluent rash, rather than discrete lesions. In contrast, recent reports of patients with HIV infection and monkeypox who are on effective antiretroviral therapy (ART) have noted no deaths or evident excess hospitalizations to date. Providers should consider both viral suppression and CD4 count in weighing the risk of severe outcomes from monkeypox for any patient with HIV.

The rash of monkeypox can be confused with other rash illnesses that are considered in people with HIV, including herpes zoster (shingles), scabies, molluscum contagiosum, herpes, syphilis, chancroid, lymphogranuloma venereum, allergic skin rashes, and drug eruptions. Immunocompromised persons, including persons with advanced, untreated or inadequately suppressed HIV, may present with an atypical rash, including a disseminated rash that may make diagnosis more challenging.

Prevention of monkeypox and infection control practices in the home or healthcare setting are the same regardless of peoples' HIV status. Post-exposure prophylaxis (PEP) and antiviral treatments, including tecovirimat, are available for persons exposed to monkeypox or with Monkeypox virus infection. The safety and immunogenicity of JYNNEOS, a live, non-replicating viral vaccine, has been specifically established in people with HIV; however, immunogenicity among persons with HIV who have CD4 counts below 100 cells/mm³ or who are not virologically suppressed remains unknown. ACAM2000, a replicating viral vaccine, should not be given to people with HIV (regardless of immune status). Antiviral treatments for monkeypox have few interactions with antiretroviral therapy. ART and opportunistic infection prophylaxis should be continued in all people with HIV who develop monkeypox.

Recommendations and Information for Healthcare Providers on Monkeypox in Children and Adolescents

Limited pediatric data on infection with the Congo Basin clade of Monkeypox virus suggest increased risk of severe disease in children younger than 8 years of age. Rare complications of monkeypox include abscess, airway obstruction due to severe lymphadenopathy, cellulitis, corneal scarring, encephalitis, keratitis, pneumonia, and sepsis. The West African clade of Monkeypox virus involved in the current outbreak typically causes less severe disease than the Congo Basin clade.

Monkeypox virus can spread to children through contact with infectious body fluids (e.g., lesion exudates and respiratory secretions) of people or animals or through contact with fomites, as may occur in households and other close contact settings. The number of monkeypox cases among children in the United States is currently low; however, CDC acknowledges that the expanding U.S. outbreak and the possible risk for transmission in households and other settings may result in additional pediatric cases. Pediatric providers should be familiar with prevention, recognition, and testing considerations for monkeypox in children and adolescents.

Families should be counseled about preventing the spread of Monkeypox virus between children, caregivers, and household members in the home, including avoidance of contact with persons who have monkeypox, the body fluids of an infected person, and fomites (e.g., clothing, towels, bedding); wearing a well-fitting mask or respirator by the person with monkeypox and the contact (for children over 2 years of age) when interaction is unavoidable; and minimizing the number of caregivers for children with monkeypox. Particular attention should be made to keep children with monkeypox from scratching lesions or touching their eyes to prevent auto-inoculation and more severe illness. Caregivers should cover areas of broken skin with bandages to the extent possible and avoid direct skin-to-skin contact with the rash.

Children and adolescents who are close contacts of a person with monkeypox (e.g., household contact, other family member, caregiver, or friend) should be evaluated for illness and offered post-exposure prophylaxis with JYNNEOS or ACAM2000 (for children older than 12 months) or treatment when indicated. Monkeypox should be considered when children or adolescents present with signs or symptoms that could be consistent with the disease, especially if epidemiologic criteria are present. The rash of monkeypox can be confused with other rash illnesses that are commonly considered in children including varicella (chickenpox); hand, foot, and mouth disease; measles; scabies; molluscum contagiosum; herpes; allergic skin rashes and syphilis (including congenital syphilis); and drug eruptions.

Data are limited on the effectiveness of PEP for children who have been exposed to monkeypox or treatment for children with illness, and no vaccines or other products are currently licensed for monkeypox prevention or treatment in children or adolescents. However, PEP should not be withheld from children or adolescents who are otherwise eligible. Decisions about whether to offer PEP should take into account the patient's degree of exposure and the patient's individual risk of severe disease.

Prophylactic therapeutics that can be administered include vaccination, Vaccinia immune globulin, and antiviral medication. For almost all children and adolescents, vaccination is the preventive treatment that should be administered. Immune globulin or antivirals may also be considered for infants under 6 months of age, given their immature immune systems and possible decreased responses to vaccination.

Tecovirimat is currently being used as the first-line treatment for infection with Monkeypox virus, including for children and adolescents with severe disease or underlying medical conditions that may increase risk for severe disease and those with complications from monkeypox. Individual risks and benefits must be considered prior to initiating tecovirimat. Other treatments such as Vaccinia immune globulin may be considered in unusual circumstances.

In pediatric inpatient care settings, infection control procedures for children with monkeypox infection should also consider the child's age and caregiving needs; family and caregiver preferences; the extent, severity, and course of the child's illness; and risks for severe monkeypox disease in exposed caregivers (e.g., pregnancy or immunocompromising conditions).

Recommendations and Information for Healthcare Providers on Monkeypox in People who are Pregnant or Breastfeeding

Data regarding Monkeypox virus infection during pregnancy are limited. It is unknown if pregnant people are more susceptible to acquiring Monkeypox virus infection or if illness is more severe during pregnancy. Other poxviruses cause more severe infection during pregnancy. Monkeypox virus can be transmitted to the fetus during pregnancy and to the newborn by close contact during and after birth. There are few case reports of spontaneous pregnancy loss and stillbirth, preterm delivery, and neonatal monkeypox infection; the frequency and circumstances for these outcomes are unknown. Whether Monkeypox virus is present in breast milk is unknown; however, it may be transmitted through close contact during breastfeeding.

Prevention measures for monkeypox infection are similar for pregnant and non-pregnant people. Pre- or post-exposure prophylaxis should be offered to people who are pregnant or breastfeeding. When pre- or post-exposure prophylaxis by vaccination is chosen, JYNNEOS, a live, non-replicating viral vaccine, can be used. ACAM2000, a replicating viral vaccine, should not be used in people who are pregnant or breastfeeding.

During pregnancy, the cause of fever may be difficult to differentiate from other infections, such as intraamniotic infection (chorioamnionitis), until the monkeypox rash appears. Pregnant patients with rashes initially considered characteristic of dermatoses of pregnancy (e.g., polymorphic eruption of pregnancy) or of more common infections (e.g., varicella zoster or sexually transmitted infections) should be carefully evaluated for a monkeypox rash, and submission of specimens of lesions for monkeypox diagnosis should be considered, especially if the person has any epidemiologic risk factors for monkeypox infection.

While most adults with Monkeypox virus infection experience self-limiting infection and recover within 2-4 weeks, pregnant and breastfeeding people should be prioritized for medical treatment, if needed, due to the probable increased risk of severe disease during pregnancy, risk of transmission to the fetus during pregnancy or to the newborn by close contact during and after birth, and risk of severe infection in newborns. Treatment for Monkeypox virus infection should be offered to people who are pregnant or breastfeeding. The risks and benefits of treatment options should be discussed with the patient.

Recommendations for infection prevention and control of monkeypox in healthcare settings are the same for pregnant and non-pregnant patients. Newborns born to people with monkeypox should be placed in isolation, and healthcare personnel should follow infection prevention and control recommendations. Patients with monkeypox should be counseled about measures to prevent risk of transmission of Monkeypox virus to their newborn from close contact and breastfeeding.

Source: Centers for Disease Control and Prevention (U.S.) (2022). Update for Clinicians on Monkeypox in People with HIV, Children and Adolescents, and People who are Pregnant or Breastfeeding. Centers for Disease Control and Prevention. Published: July 30, 2022. DOI: CDCHAN-00472.

[Posted 28/Aug/2025]

AUDIENCE: Neurology, Pediatric, Neurosurgery

KEY FINDINGS: Infants up to 6 weeks of age with genetically diagnosed SMA who were treated with risdiplam before the development of clinical signs or symptoms appeared to have better functional and survival outcomes at 12 and 24 months than untreated infants in natural history studies. Larger, controlled studies with longer follow-up are needed to further understand the relative efficacy and safety of presymptomatic treatment of SMA with risdiplam.

BACKGROUND: Risdiplam, an oral pre–messenger RNA splicing modifier, is an efficacious treatment for persons with symptomatic spinal muscular atrophy (SMA). The safety and efficacy of risdiplam in presymptomatic disease are unclear.

DETAILS: Authors conducted an open-label study of daily oral risdiplam (with the dose adjusted to 0.2 mg per kilogram of body weight) in infants 1 day (birth) to 42 days of age with genetically diagnosed SMA but without strongly suggestive clinical signs or symptoms. The primary outcome, assessed in infants with two SMN2 copies and a baseline ulnar compound muscle action potential (CMAP) amplitude of at least 1.5 mV, was the ability to sit without support at month 12. Natural history studies have shown that the majority of infants with two SMN2 copies who are untreated would have a severe SMA phenotype (type 1), would never sit independently, would receive permanent ventilation and feeding support, or would die by 13 months of age. Secondary outcomes that were assessed over a period of 24 months included survival, ventilatory support, motor milestones, the development of clinically manifested SMA, feeding, and growth. A total of 26 infants with two, three, or four or more copies of SMN2 were enrolled. After 12 months of treatment, 21 infants (81%) could sit unsupported for 30 seconds, 14 (54%) could stand alone, and 11 (42%) could walk alone. A total of 4 of 5 infants (80%; 95% confidence interval, 28 to 100) with two SMN2 copies and a baseline ulnar CMAP amplitude of at least 1.5 mV were able to sit without support for at least 5 seconds. Three infants were withdrawn from the study by a parent or caregiver after the month 12 visit. Of 23 infants who completed 24 months of treatment, all were alive without the use of permanent ventilation or feeding support. Over a period of 24 months, nine treatment-related adverse events were reported in 7 infants; none of these events were serious.

Copyright © Massachusetts Medical Society. All rights reserved.

Source: Finkel, R. S., Servais, L., Vlodavets, D., et al. (2024). Risdiplam in Presymptomatic Spinal Muscular Atrophy. N Engl J Med. 2025; 393(7): 671-682. Published: August 13, 2025. DOI: 10.1056/NEJMoa2410120.

[Posted 22/Aug/2025]

AUDIENCE: All Healthcare Professionals

KEY FINDINGS:

BACKGROUND: Recurrent Respiratory Papillomatosis (RRP) is a rare and chronic condition caused by human papillomavirus (HPV) types 6 and 11. The disease leads to the formation of benign tumors in the respiratory tract, most often in the larynx, which can cause significant symptoms like voice changes and difficulty breathing. Historically, the primary treatment for RRP has been repeated surgical removal of the tumors, as there have been no approved medical therapies to address the underlying cause.

DETAILS: The U.S. Food and Drug Administration (FDA) has approved Papzimeos (zopapogene imadenovec-drba), a groundbreaking immunotherapy, for the treatment of adult patients with RRP. This therapy is a non-replicating adenoviral vector that works by stimulating a targeted immune response against the HPV-infected cells. It is administered via a subcutaneous injection and represents the first non-surgical therapeutic option for this rare disease, offering a new approach beyond traditional surgical management.

The approval of Papzimeos was based on data from a single-arm, open-label trial. The study demonstrated that 51.4% of patients who received the treatment achieved a complete response, defined as not needing any further surgical intervention for 12 months following the treatment. The clinical benefits were shown to be durable for most patients over a two-year period and correlated with the development of specific T-cells targeting HPV 6 and 11. The therapy had a favorable safety profile with no serious treatment-related adverse events.

Key information:

• First-of-its-kind Approval: Papzimeos is the first approved medical therapy for RRP.
• Novel Mechanism: It is an immunotherapy that targets the root cause of the disease, HPV-infected cells.
• Approval Pathway: The product received Orphan Drug and Breakthrough Therapy designations and was approved under Priority Review, reflecting the significant unmet medical need for RRP patients.

Source: FDA Approves First Immunotherapy for Recurrent Respiratory Papillomatosis. FDA. 2025; Published: August 14, 2025.

[Posted 21/Aug/2025]

AUDIENCE: Infectious Disease, Family Medicine

KEY FINDINGS: Authors first revealed the plasma metabolomic characteristics of H7N9 patients and found that a machine-learning model based on plasma metabolites could predict the risk of death for H7N9 in the early stage of admission.

BACKGROUND: Avian influenza such as H7N9 is currently a major global public health risk, and at present, there is a lack of relevant diagnostic and treatment markers.

DETAILS: Authors collected plasma samples from 104 confirmed H7N9 patients, 31 of whom died. Plasma metabolites were detected by UHPLC-HRMS, and a survival prediction model based on metabolites was constructed by machine-learning models. A total of 1536 metabolites were identified in the plasma samples of H7N9 patients, of which 64 metabolites were up-regulated and 35 metabolites were down-regulated in the death group. The enrichment analysis of tryptophan metabolism, porphyrin metabolism, and riboflavin metabolism were significantly up-regulated in the death group. We found that most lipids and lipid–like molecules were down-regulated in the death group, and organoheterocyclic compounds were significantly up-regulated in the death group. A machine-learning model was constructed for predicting mortality based on porphobilinogen, 5-hydroxyindole-3-acetic acid, L-kynurenine, Biliverdin, and D-dimer. The AUC on the test set was 0.929.

Copyright © The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. All rights reserved.

Source: Wang, Y., Ni, J., Huanga, M., et al. Metabolomic Profiling of Plasma Reveals Differential Disease Severity Markers in Avian Influenza A(H7N9) Infection Patients. International Journal of Infectious Diseases. 2025; 158: 107957. Published: September, 2025. DOI: 10.1016/j.ijid.2025.107957.

Immunogenicity, Safety, and Efficacy of the Vaccine H56:IC31 In Reducing the Rate of Tuberculosis Disease Recurrence In HIV-negative Adults Successfully Treated for Drug-Susceptible Pulmonary Tuberculosis: A Double-Blind, Randomised, Placebo-Controlled, Phase 2b Trial

[Posted 2/Jul/2025]

AUDIENCE: Infectious Disease, Family Medicine

KEY FINDINGS: Vaccination with H56:IC31 at treatment completion for pulmonary tuberculosis did not reduce the risk of recurrent disease. H56:IC31 was well tolerated and immunogenic but might have increased the risk of relapses by endogenous strains.

BACKGROUND: People with tuberculosis who complete treatment remain at risk of recurrent disease. The vaccine H56:IC31 has been shown to be safe and immunogenic in phase 1 and 2 studies, but whether it can reduce the risk of tuberculosis recurrence is unknown.

DETAILS: In a double-blind, randomised, placebo-controlled, phase 2b trial in South Africa (five clinical trial sites) and Tanzania (one clinical trial site), we enrolled participants aged 18-60 years, without HIV, who had completed more than 5 months (22 weeks) of treatment for drug-susceptible pulmonary tuberculosis. During trial screening (<=7 days after starting treatment), two sputum samples were obtained and frozen for later comparison to recurrent isolates by whole-genome sequencing (WGS). Eligible participants were randomly assigned (1:1; block size of four) to receive two intramuscular doses in the deltoid, 56 days apart, of H56:IC31 or placebo. After the first dose of H56:IC31 or placebo, participants were followed up until study day 421 (1 year after the second dose) and checked at each visit for tuberculosis signs and symptoms. If tuberculosis was suspected, two sputum samples were obtained: one sample was tested by automated molecular test (Xpert MTB/RIF Ultra) and sent for liquid culture; and the other sample was stored frozen for later analysis by whole-genome sequencing (WGS). At the last visit (day 421), two sputum samples were obtained from all sputum-productive participants, regardless of symptoms, to detect cases of asymptomatic tuberculosis. The primary endpoint was culture-confirmed recurrent pulmonary tuberculosis (due to relapse with the same strain, reinfection by a different strain, or indeterminate) occuring during the period starting at day 70 (14 days after the second dose) and ending on day 421 (1 year after the second dose). Vaccine efficacy against recurrent tuberculosis was derived from Cox proportional hazards models. Secondary endpoints included vaccine efficacy to prevent tuberculosis relapse or reinfection independently, as differentiated by WGS, and safety and immunogenicity outcomes (H56-specific CD4 T-cell responses and humoral anti-H56 IgG responses). Primary analysis of vaccine efficacy was based on modified intention-to-treat (mITT), in all randomly assigned participants except those with tuberculosis disease recurrence or who withdrew before day 70 (or 14 days after the second dose for those who received both doses). Safety was assessed in all randomly assigned participants who received at least one dose of vaccine or placebo. The trial was registered with ClinicalTrials.gov, NCT03512249, and is complete. 831 participants (mean age 34.7 years [SD 11.1]; 229 [28%] female and 602 [72%] male; 549 [66%] Black) were enrolled from Jan 31, 2019, to Jan 20, 2022; 415 participants were randomly assigned to receive H56:IC31 and 416 to receive placebo. Follow-up was completed by March 20, 2023 (mean follow-up duration 410.1 days [SD 82.8]). In the primary mITT analysis, recurrent tuberculosis occurred in 23 of 400 participants in the H56:IC31 group (12 relapses, eight reinfections, and three indeterminate); and in 14 of 406 in the placebo group (six relapses, seven reinfections, and one indeterminate). Vaccine efficacy for prevention of recurrence was -73.8% (95% CI -246.9 to 9.8; p=0.10). Vaccine efficacy for prevention of relapse was -116.1% (-522.2 to 16.3; p=0.11) and for prevention of reinfection was -21.1% (-245.3 to 56.5; p=0.71). 2 weeks after the planned second dose, H56:IC31 had significantly increased the frequencies of H56-specific CD4 T cells expressing interferon-γ, tumour necrosis factor, interleukin (IL)-2, or IL-17 in vaccinees (median percentage of CD4 T cells, 0.35% [IQR 0.19 to 0.57]) compared with placebo (0.11% [0.09 to 0.23]; p < 0.0001). H56-specific IgG responses were significantly higher in H56:IC31 recipients (median arbitrary units per mL, 6.84 [IQR 1.64 to 32.8]) than in placebo recipients (1.94 [1.05 to 3.86]; p < 0.0001). A greater proportion of H56:IC31 recipients had mild-to-moderate injection site reactions than placebo recipients (165 [40%] of 415 vs 78 [19%] of 416). No treatment-related serious adverse events were reported. Two participants who received H56:IC31 and six who received placebo died.

Copyright © Elsevier Ltd. All rights reserved.

Source: Borges, A. H., Russell, M., Tait, D., et al. Immunogenicity, Safety, and Efficacy of the Vaccine H56:IC31 In Reducing the Rate of Tuberculosis Disease Recurrence In HIV-negative Adults Successfully Treated for Drug-Susceptible Pulmonary Tuberculosis: A Double-Blind, Randomised, Placebo-Controlled, Phase 2b Trial. The Lancet Infectious Diseases. 2025; 25(7): 751-763. Published: July, 2025. DOI: 10.1016/S1473-3099(24)00814-4.

[Posted 6/Nov/2024]

AUDIENCE: Gastroenterology, Infectious Disease, Internal Medicine

KEY FINDINGS: The results show that CRISPR-Cas13b can be programmed to specifically target and degrade HBV RNAs to reduce HBV replication and protein expression, demonstrating its potential as a novel therapeutic option for chronic HBV infection.

BACKGROUND: New antiviral approaches that target multiple aspects of the HBV replication cycle to improve rates of functional cure are urgently required. HBV RNA represents a novel therapeutic target. Here, we programmed CRISPR-Cas13b endonuclease to specifically target the HBV pregenomic RNA and viral mRNAs in a novel approach to reduce HBV replication and protein expression.

DETAILS: Cas13b CRISPR RNAs (crRNAs) were designed to target multiple regions of HBV pregenomic RNA. Mammalian cells transfected with replication competent wild-type HBV DNA of different genotypes, a HBV-expressing stable cell line, a HBV infection model and a hepatitis B surface antigen (HBsAg)-expressing stable cell line were transfected with PspCas13b-BFP (blue fluorescent protein) and crRNA plasmids, and the impact on HBV replication and protein expression was measured. Wild-type HBV DNA, PspCas13b-BFP and crRNA plasmids were simultaneously hydrodynamically injected into mice, and serum HBsAg was measured. PspCas13b mRNA and crRNA were also delivered to a HBsAg-expressing stable cell line via lipid nanoparticles and the impact on secreted HBsAg determined. The HBV-targeting crRNAs strongly suppressed HBV replication and protein expression in mammalian cells by up to 96% (p <0.0001). HBV protein expression was also reduced in a HBV-expressing stable cell line and in the HBV infection model. CRISPR-Cas13b crRNAs reduced HBsAg expression by 50% (p <0.0001) in vivo. Lipid nanoparticle-encapsulated PspCas13b mRNA reduced secreted HBsAg by 87% (p = 0.0168) in a HBsAg-expressing stable cell line.

Copyright © Elsevier Inc. All rights reserved.

Source: McCoullough, L. C., Fareh, M., Hu, W., et al. (2024). CRISPR-Cas13b-mediated Suppression of HBV Replication and Protein Expression. Journal of Hepatology. 2024; 81(5): 794-805. Published: November, 2024. DOI: 10.1016/j.jhep.2024.05.025.