Treatment and prevention of mpox in pregnant people and young children

Pregnant people, young children (children younger than 8 years), and people who are immunocompromised are considered to be at increased risk of severe mpox (formerly known as monkeypox). There is an urgent need for improved data about the prevention and treatment of mpox in these groups. The 2022 WHO mpox global trends report included 55 pregnant and recently pregnant people, including four people in their first trimester, 11 people in their second trimester, and nine people in their third trimester. The trimester was unknown for 30 people and one person was less than 6 weeks postpartum.1WHO2022 mpox (monkeypox) outbreak: global trends.https://worldhealthorg.shinyapps.io/mpx_global/#32_Trends_in_casesDate: 2023Date accessed: January 24, 2023Google Scholar Their median age was 28 years. 12 people were hospitalised but none required intensive care or died. In the 2023 Brazilian epidemiological bulletin, 22 pregnant people had confirmed or suspected mpox and two people required hospitalisation for isolation and treatment.2Brazil Ministry of HealthEpidemiological bulletin of monkeypox number 17 (COE).https://www.gov.br/saude/pt-br/centrais-de-conteudo/publicacoes/boletins/epidemiologicos/variola-dos-macacos/boletim-epidemiologico-de-monkeypox-no-18-coe/viewDate: 2022Date accessed: January 24, 2023Google Scholar The US Centers for Disease Prevention and Control (CDC) reported 17 confirmed or probable mpox cases among pregnant and recently pregnant people as of Oct 21, 2022, whose pregnancy outcomes were being monitored. Two additional cases were reported in breastfeeding people.3Centers for Disease Control and PreventionTechnical report 4: multi-national mpox outbreak, United States, 2022.https://www.cdc.gov/poxvirus/monkeypox/cases-data/technical-report/report-4.htmlDate: 2022Date accessed: December 1, 2022Google Scholar The latest WHO report included 348 children (189 male children and 159 female children) younger than 10 years with mpox, whereas Brazil reported 117 confirmed or suspected cases of mpox in children younger than 5 years (59 male children and 64 female children). Because of potentially increased risk of severe disease in young children, reports should include more detailed age distribution. Two severe neonatal mpox cases have been reported, including one with adenovirus co-infection.4Ramnarayan P Mitting R Whittaker E et al.Neonatal monkeypox virus infection.N Engl J Med. 2022; 387: 1618-1620Crossref PubMed Scopus (20) Google Scholar Both people had persistent erythematous rash on the extremities that became pustular. Treatment included tecovirimat with cidofovir4Ramnarayan P Mitting R Whittaker E et al.Neonatal monkeypox virus infection.N Engl J Med. 2022; 387: 1618-1620Crossref PubMed Scopus (20) Google Scholar or intravenous immunoglobulin;5Saunders KE Van Horn AN Medlin HK et al.Monkeypox in a young infant—Florida, 2022.MMWR Morb Mortal Wkly Rep. 2022; 71: 1220-1221Crossref PubMed Scopus (6) Google Scholar both individuals recovered. The latest US CDC update included 35 children with mpox younger than 5 years (24 male children and 11 female children).6Centers for Disease Control and PreventionMpox cases by age and gender, race/ethnicity, and symptoms.https://www.cdc.gov/poxvirus/monkeypox/response/2022/demographics.htmlDate: 2023Date accessed: January 8, 2023Google Scholar 17 of these children received tecovirimat. At the start of the mpox outbreak there were no clear guidelines on management during pregnancy or childhood, and available therapeutics and vaccines were not approved for use in pregnancy, for breastfeeding people, or for children. Tecovirimat was approved for treating smallpox but there were no data on effectiveness against human mpox or prevention of congenital or perinatal mpox in pregnant people.7Centres for Disease Control and PreventionClinical considerations for mpox in people who are pregnant or breastfeeding.https://www.cdc.gov/poxvirus/monkeypox/clinicians/pregnancy.htmlDate: 2022Date accessed: September 25, 2022Google Scholar Several phase 3, randomised, placebo-controlled trials of tecovirimat for the treatment of mpox are planned (table). In the Study of Tecovirimat for Human Monkeypox Virus (STOMP), children, pregnant people, and breastfeeding people are eligible for enrolment to receive open-label tecovirimat after a discussion of potential risks and benefits. The Placebo-Controlled Randomised Trial of Tecovirimat in Non-Hospitalised Mpox Patients (PLATINUM) is a multicentre, parallel collaborative phase 3 clinical trial with Canadian (PLATINUM-CAN) and UK (NCT05534165) arms. The UK arm will enrol children, but the Canadian arm will not. Pregnant and breastfeeding people are excluded in the UK arm and are not mentioned in the PLATINUM-CAN protocol. The Assessment of the Efficacy and Safety of Tecovirimat in Patients With Monkeypox Virus Disease (UNITY) trial of tecovirimat in patients with mpox also does not mention pregnant or breastfeeding people.TableProposed clinical trials of the efficacy of tecovirimat for the treatment of people with laboratory-confirmed or presumed mpox and current mpox vaccine clinical trialsNumber of participantsPhaseEnrolment criteria of pregnant peopleEnrolment criteria of childrenTrial protocolAntiviralsPLATINUM-UK5003Excluded≥13 kgISRCTN17461766STOMP5303Discuss risks and benefits before receiving open-label tecovirimat≥2·5 kgNCT05534984UNITY1503Not specified in the exclusion criteria≥25 kg and aged 14 years or olderNCT05597735PLATINUM-CAN1203Not specified in the exclusion criteria≥40 kg and aged 18 years or olderNCT05534165Tecovirimat arm of PALM4502Eligible≥3 kgNCT05559099VaccinesMVA-BN (Feb 23, 2017)16002ExcludedExcludedNCT02977715; open-label prospective cohort study in health-care personnelMVA-BN (July 12, 2022)226NANot specified in the exclusion criteriaExcludedNCT05438953; open labelMVA-BN (Sept 7, 2022)2102ExcludedExcludedNCT05512949; open label, randomisedMVA-BN (Sept 14, 2022)1003Not specified in the exclusion criteriaExcludedNCT05562323; vaccine effectiveness in people living with HIVNA=not available. Open table in a new tab NA=not available. In Africa, where mpox is endemic, there is slow improvement because of the current outbreak. Tecovirimat is not authorised, mpox vaccines are not available, and testing capacity is low. In 2022, 1176 cases of mpox and 219 deaths from mpox (case fatality 18·6%) were reported in Africa.8African Centres for Disease Control and PreventionOutbreak brief 21: mpox in Africa Union member states.https://africacdc.org/disease-outbreak/outbreak-brief-23-mpox-in-africa-union-member-states/Date: 2022Date accessed: January 8, 2023Google Scholar Most deaths (n=198) were in the Democratic Republic of the Congo, where samples are tested only at the National Laboratory and can take up to 3 weeks to be reported. A phase 2 tecovirimat clinical trial including pregnant people and children was announced in the DR Congo in 2022 as part of the Pamoja Tulinde Maisha (PALM) partnership between the US National Institute of Allergy and Infectious Diseases and the DR Congo's National Institute for Biomedical Research. Moreover, Africa CDC announced the donation of 50 000 mpox vaccines by Korea that will be prioritised for administration to health-care workers and people living in the areas with the highest number of cases of mpox.9Africa NewsAfrican continent finally to receive 1st monkeypox vaccine.https://www.africanews.com/2022/12/01/african-continent-finally-to-receive-1st-monkeypox-vaccines//Date: 2022Date accessed: December 3, 2022Google Scholar A new mpox vaccine (TNX-801, Tonix Pharmaceuticals, New York, NY, USA) conferred full protection against intratracheal mpox challenge in non-human primates.10Tonix PharmaceuticalsTonix pharmaceuticals presents development update on potential smallpox and monkeypox vaccine TNX-801 in an oral presentation at the World Vaccine and Immunotherapy Congress.https://ir.tonixpharma.com/news-events/press-releases/detail/1352/tonix-pharmaceuticals-presents-development-update-onDate: 2022Date accessed: December 3, 2022Google Scholar Tonix Pharmaceuticals is planning a phase 1 clinical trial in collaboration with Kenya Medical Research Institute.10Tonix PharmaceuticalsTonix pharmaceuticals presents development update on potential smallpox and monkeypox vaccine TNX-801 in an oral presentation at the World Vaccine and Immunotherapy Congress.https://ir.tonixpharma.com/news-events/press-releases/detail/1352/tonix-pharmaceuticals-presents-development-update-onDate: 2022Date accessed: December 3, 2022Google Scholar Current reports indicate a low risk of severe disease in the current global mpox clade IIb outbreak, even in groups that were previously considered to be at increased risk of severe mpox, such as pregnant people and young children. There is, however, a need for a systematic approach to data collection to inform clinical guidance and public health policies on prevention, risks, management, and outcomes. In addition to the ongoing mpox vaccine trials (table), we strongly support the timing of both the PLATINUM and UNITY trials and applaud the horizontal enrolment criteria, defined as the inclusion of pregnant and breastfeeding people, of the STOMP trial and the phase 2 tecovirimat arm of the PALM partnership. Pregnancy-specific outcomes are crucial to include in these trials, which are a unique opportunity to collect safety and efficacy data for vaccines against mpox and treatments for mpox disease in pregnant and breastfeeding people, infants younger than 1 year, and children, particularly those younger than 8 years. We declare no competing interests.