Monkeypox infection and pregnancy in lower and middle-income countries: Precautions & recommendations.

Monkeypox (MPX), an orthopoxviral disease endemic in Africa, is now a public health emergency of international concern (PHEIC) as declared by the World Health Organization in July 2023. Although it is generally mild, the overall case fatality rate was reported to be 3%, and the basic reproduction number (R0) is > 1 in men who have sex with men (MSM, i.e., Portugal (1.4), the United Kingdom (1.6), and Spain (1.8)). However, R0 is < 1 in other settings. In concordance with the smallpox virus, it is also expected to increase the risk of adverse outcomes for both the mother and the fetus. The outcomes of the disease in an immunocompromised state of pregnancy are scary, showing high mortality and morbidity of both mother and fetus, with up to a 75% risk of fetal side effects and a 25% risk of severe maternal diseases. Therefore, it warrants timely diagnosis and intervention. The reverse transcription polymerase chain reaction (RT PCR) test is the standard approach to diagnosis. We summarized the recent findings of MPX on pregnancy, and the associated risk factors. We also give recommendations for active fetal surveillance, perinatal care, and good reporting to improve outcomes. The available vaccines have shown promise for primary disease prevention.

Pan-microscopic examination of monkeypox virus in trophoblasts cells reveals new insights into virions release through filopodia-like projections.

Vertical transmission has been described following monkeypox virus (MPXV) infection in pregnant women. The presence of MPXV has been reported in the placenta from infected women, but whether pathogens colonize placenta remains unexplored. We identify trophoblasts as a target cell for MPXV replication. In a pan-microscopy approach, we decipher the specific infectious cycle of MPXV and inner cellular structures in trophoblasts. We identified the formation of a specialized region for viral morphogenesis and replication in placental cells. We also reported infection-induced cellular remodeling. We found that MPXV stimulates cytoskeleton reorganization with intercellular extensions for MPXV cell spreading specifically to trophoblastic cells. Altogether, the specific infectious cycle of MPXV in trophoblast cells and these protrusions that were structurally and morphologically similar to filopodia reveal new insights into the infection of MPXV.

Epidemiological and Clinical Characteristics of Mpox in Cisgender and Transgender Women and Non-Binary Individuals Assigned to the Female Sex at Birth: A Comprehensive, Critical Global Perspective.

The 2022-2023 Mpox multi-country outbreak, identified in over 110 WHO Member States, revealed a predominant impact on cisgender men, particularly those engaging in sex with men, while less frequently affecting women. This disparity prompted a focused investigation into the gender-specific characteristics of Mpox infections, particularly among women, to address a notable knowledge gap. This review systematically gathers and analyzes the scientific literature and case reports concerning Mpox infections in women, covering a broad geographical spectrum including regions such as Argentina, Brazil, Colombia, Nigeria, Europe, Vietnam, and the United States. The analysis delves into various aspects of Mpox in women, including clinical features, epidemiology, psychological impacts, preparedness strategies, and case studies, with particular attention to pregnant women and those with underlying health conditions. Empirical data from multiple studies underscore the unique epidemiological and clinical patterns of Mpox in women. In the United States, a small percentage of Mpox cases were reported among cisgender women, with a notable portion involving non-Hispanic Black or African American, non-Hispanic White, and Hispanic or Latino ethnicities. The primary transmission route was identified as sexual or close intimate contact, with the virus predominantly manifesting on the legs, arms, and genital areas. Further, a study in Spain highlighted significant disparities in diagnosis delays, transmission modes, and clinical manifestations between genders, indicating a different risk profile and disease progression in women. Additionally, a case from Vietnam, linked to a new Mpox sub-lineage in women, emphasized the role of women in the transmission dynamics and the importance of genomic monitoring. This review emphasizes the necessity for inclusive surveillance and research to fully understand Mpox dynamics across diverse population groups, including women. Highlighting gender and sexual orientation in public health responses is crucial for an effective approach to managing the spread and impact of this disease. The findings advocate for a gender-diverse assessment in health services and further research to explore the nuances of Mpox transmission, behavior, and progression among different groups, thereby enhancing the global response to Mpox and similar public health challenges.

Monkeypox Virus Immune Evasion and Eye Manifestation: Beyond Eyelid Implications.

Monkeypox virus (MPXV), belonging to the Poxviridae family and Orthopoxvirus genus, is closely related to the smallpox virus. Initial prodromal symptoms typically include headache, fever, and lymphadenopathy. This review aims to detail various ocular manifestations and immune evasion associated with the monkeypox viral infection and its complications, making it appropriate as a narrative review. Common external ocular manifestations of MPXV typically involve a generalized pustular rash, keratitis, discharges, and dried secretions related to conjunctival pustules, photophobia, and lacrimation. Orthopoxviruses can evade host immune responses by secreting proteins that antagonize the functions of host IFNγ, CC and CXC chemokines, IL-1ß, and the complement system. One of the most important transcription factors downstream of pattern recognition receptors binding is IRF3, which controls the expression of the crucial antiviral molecules IFNα and IFNß. We strongly recommend that ophthalmologists include MPXV as part of their differential diagnosis when they encounter similar cases presenting with ophthalmic manifestations such as conjunctivitis, blepharitis, or corneal lesions. Furthermore, because non-vaccinated individuals are more likely to exhibit these symptoms, it is recommended that healthcare administrators prioritize smallpox vaccination for at-risk groups, including very young children, pregnant women, older adults, and immunocompromised individuals, especially those in close contact with MPXV cases.

Monkeypox Virus: A comprehensive narrative review.

Monkeypox virus, now known as Mpox virus is a large, enveloped, double stranded deoxyribonucleic acid (DNA) virus belonging to the Orthopox viridae genus of the Poxviridae family. Though, Mpox, have earlier been endemic to only African countries, the 2022 outbreak has shown its rapid spread throughout the world. The May 2022 outbreak have shown primarily human to human transmission in contrast to animal to human transmission that had been seen previously. Recent data also suggest a possibility of a pre symptomatic spread. After an incubation period of 9 days, patients with Mpox can present with a prodrome of symptoms followed by a rash. If untreated, severe complications develop in the high-risk groups especially children and pregnant woman. Such groups of people will benefit from antiviral treatments. The current approach to prevent against it is pre-exposure and post exposure prophylaxis with vaccines. The vaccines that have been approved by Food and Drug Administration to date is ACAM2000 and JYNNEOS. Several diagnostic methods exist, among which polymerase chain reaction has proven to be the most specific and sensitive. In this review, we will discuss its epidemiology, the clinical manifestations, diagnostic modalities, complications, treatment approaches and preventive measures.

Clinical review of human mpox.

BACKGROUND: Historically, human mpox was predominantly a zoonotic disease occurring more frequently in rural children in Africa and characterized by a largely self-limiting febrile centrifugal monomorphic rash illness. However, the 2022 mpox global outbreak has shown that the disease is changing in many ways, including sustained human-to-human transmission via sexual contact, novel clinical presentations, and adverse associations between mpox and advanced HIV. OBJECTIVES: The aim of this paper is to review the traditional and emerging clinical aspects of human mpox and provide updated information on the clinical course and outcome of the disease. SOURCES: We searched electronic databases including PubMed and Google Scholar and identified relevant published literature on mpox. CONTENT: The clinical presentation of human mpox is influenced by the route of infectious exposure, the strain and dose of the infecting virus, and the host immune system. Exposure to the virus can result in sub-clinical or clinical diseases of variable severity. Infections caused by clade I viral strains are more severe than class IIa and IIb strains, which are associated with a milder febrile rash illness, and with anogenital skin lesions in clade IIb infections. Most cases of mpox recover entirely within 2-4 weeks after onset of illness and a few develop skin-related sequelae. Overall, people with advanced HIV infection, children <5 years of age, and pregnant women may present with more severe disease and higher case fatalities. IMPLICATIONS: The continued endemicity of the classical mpox in Africa, the emergence of a new clinical form of the disease during the 2022 global outbreak, and the adverse associations between advanced HIV and mpox have implications for the surveillance, clinical diagnosis, and management of human mpox.

Congenital Mpox Syndrome (Clade I) in Stillborn Fetus after Placental Infection and Intrauterine Transmission, Democratic Republic of the Congo, 2008.

We report the autopsy pathology findings of a 21-week stillborn fetus with congenital mpox syndrome that occurred in the Democratic Republic of the Congo in 2008. The fetus acquired mpox from the mother after intrauterine transplacental monkeypox virus transmission. We confirmed monkeypox virus infection in the mother, fetus, and placenta by using a monkeypox virus-specific quantitative PCR. Subtyping of the virus was not performed, but the mother and fetus were almost certainly infected with the clade I variant that was endemic in the Democratic Republic of the Congo at the time. Risk for intrauterine infection appears to differ between virus clades, but clinicians should be aware of potential for intrauterine monkeypox virus transmission among pregnant persons during ongoing and future mpox outbreaks.

Mpox (Monkeypox) in Pregnancy: Viral Clade Differences and Their Associations with Varying Obstetrical and Fetal Outcomes.

In African countries where mpox (monkeypox) is endemic, infection is caused by two genetically related clades-Clade I (formerly Congo Basin), and Clade IIa (formerly West Africa), both of which are potentially life-threatening infections. Prior to the 2022-2023 global outbreak, mpox infections among pregnant women caused by Clade I were reported to have a 75% perinatal case fatality rate in the Democratic Republic of Congo, including the only documented case of placental infection and stillbirth from the Congenital Mpox Syndrome, and the Clade IIa mpox infection was associated with stillbirths in Nigeria. The 2022-2023 global mpox outbreak, caused by a genetically distinct strain, Clade IIb, has focused attention on the effects of mpox on pregnant women and fetal outcomes. There have been at least 58 cases of mpox infection occurring in pregnant women during the 2022-2023 outbreak. No confirmed cases of adverse perinatal outcome, including stillbirth, have been reported. The absence of perinatal morbidity and mortality from Clade IIb corresponds to the overall case fatality rate among non-pregnant women of <0.1%, as this clade has been demonstrated to produce a less-severe disease than the mpox Clade I or IIa variants. Thus, there are apparently important differences between mpox clades affecting pregnant women and perinatal outcomes.

Unveiling the Mpox menace: exploring the intricacies of a zoonotic virus and clinical implications.

Mpox (formerly known as monkeypox) is an orthopoxvirus based zoonotic infection that induces a smallpox-like human illness. Since the Democratic Republic of the Congo reported the first human case of mpox in 1970, the disease has proliferated to other areas of Africa, predominantly the West, and Central, with instances recently confirmed outside of Africa. Reports of cases of mpox in 2022 have brought into light its re-emergence. Even though the smallpox vaccine protects against the mpox virus, new nonimmune generations contribute to the rising prevalence of the cases. People are coming into contact with potential hosts as a result of environmental factors, raising the probability of animal-to-human transmission. Mpox poses a more serious threat to previously unaffected nations as it is showing up in data provided by governmental bodies due to increased transmission risk brought on by globalization, armed conflict, and environmental factors. In this article, we have extensively covered the virology, etiology, and epidemiology of the disease. Various gene studies, recent drugs studied, and clinical trials pertaining to mpox have been incorporated in this review. Additionally, we have compiled a comprehensive analysis of various systematic reviews and meta-analyses concerning pregnancies complicated by mpox, retrospective studies examining mpox and HIV-coinfection, mpox in conjuction with SARS-CoV-2, and HIV coinfection, as well as case studies exploring the implications of mpox manifestations in conjunction with syphilis, gonorrhoea, myocarditis, and neuroinflammatory implications.

Mpox in pregnancy: Management, risks and challenges in Africa and lessons from the COVID-19 pandemic.

Data on mpox in pregnancy are currently limited. Historically, only 65 cases in pregnancy have been reported globally since mpox was discovered in 1958. This includes 59 cases in the current outbreak. Vertical transmission was confirmed in one patient. Pregnant women are at high risk of severe disease owing to immunological and hormonal changes that increase susceptibility to infections in pregnancy. African women appear to be at higher risk of mpox infection and adverse outcomes in pregnancy for epidemiological and immunologic reasons, in addition to the background high rates of adverse feto-maternal outcomes in the region. This risk is potentially heightened during the COVID-19 pandemic due to the possibility of mpox virus exportation/importation as a result of the lifting of movement restrictions and trans-border travels between countries affected by the current outbreak. Furthermore, coinfection with mpox and COVID-19 in pregnancy is possible, and the clinical features of both conditions may overlap. Challenges of diagnosis and management of mpox in pregnancy in Africa include patients concealing their travel history from healthcare providers and absconding from/evading isolation after diagnosis, shortage of personal protective equipment and polymerase chain reaction testing facilities for diagnosis, vaccine hesitancy/resistance, and poor disease notification systems. There is a need for local, regional and global support to strengthen the capacity of African countries to address these challenges and potentially reduce the disease burden among pregnant women in the continent.

Prevalence of Mpox (Monkeypox) in patients undergoing STI screening in northern California, April-September 2022.

BACKGROUND: Despite the sharp increase in mpox (formerly monkeypox) incidence and the wide geographic spread of mpox during the 2022 outbreak, the community prevalence of infection remains poorly characterized. This study is a retrospective epidemiologic survey to estimate mpox prevalence. METHODS: Samples obtained for sexually transmitted infection (STI) testing from April to September 2022 in the public hospital and clinic system of San Mateo County, California were screened for mpox virus (MPXV) using polymerase chain reaction. RESULTS: 16/1,848 samples from 11/1,645 individuals were positive for MPXV by qPCR. 4/11 individuals with positive MPXV testing were cisgender women, 2 of whom were pregnant at the time of sample collection. Both deliveries were complicated by chorioamnionitis. Anorectal and oropharyngeal samples were the most likely to be positive for MPXV (4/60 anorectal samples and 4/66 oropharyngeal samples compared with 5/1,264 urine samples and 3/445 vaginal samples). CONCLUSIONS: Our study is one of the first epidemiologic surveys for MPXV infection outside of sexual health/STI clinic settings. Relatively high rates of MPXV from oropharyngeal and anorectal samples reinforces the importance of MPXV testing at various anatomic sites, particularly if patients are presenting with non-lesional symptoms (pharyngitis, proctitis). However, the United States Food and Drug Administration (FDA) has not yet authorized non-lesional MPXV testing. The identification of MPXV in women in our cohort suggests that the rates of mpox in women may have previously been underestimated and highlights the risk of pregnancy complications associated with mpox.

Monkeypox (Mpox) requires continued surveillance, vaccines, therapeutics and mitigating strategies.

The widespread outbreak of the monkeypox virus (MPXV) recognized in 2022 poses new challenges for public healthcare systems worldwide. With more than 86,000 people infected, there is concern that MPXV may become endemic outside of its original geographical area leading to repeated human spillover infections or continue to be spread person-to-person. Fortunately, classical public health measures (e.g., isolation, contact tracing and quarantine) and vaccination have blunted the spread of the virus, but cases are continuing to be reported in 28 countries in March 2023. We describe here the vaccines and drugs available for the prevention and treatment of MPXV infections. However, although their efficacy against monkeypox (mpox) has been established in animal models, little is known about their efficacy in the current outbreak setting. The continuing opportunity for transmission raises concerns about the potential for evolution of the virus and for expansion beyond the current risk groups. The priorities for action are clear: 1) more data on the efficacy of vaccines and drugs in infected humans must be gathered; 2) global collaborations are necessary to ensure that government authorities work with the private sector in developed and low and middle income countries (LMICs) to provide the availability of treatments and vaccines, especially in historically endemic/enzootic areas; 3) diagnostic and surveillance capacity must be increased to identify areas and populations where the virus is present and may seed resurgence; 4) those at high risk of severe outcomes (e.g., immunocompromised, untreated HIV, pregnant women, and inflammatory skin conditions) must be informed of the risk of infection and be protected from community transmission of MPXV; 5) engagement with the hardest hit communities in a non-stigmatizing way is needed to increase the understanding and acceptance of public health measures; and 6) repositories of monkeypox clinical samples, including blood, fluids, tissues and lesion material must be established for researchers. This MPXV outbreak is a warning that pandemic preparedness plans need additional coordination and resources. We must prepare for continuing transmission, resurgence, and repeated spillovers of MPXV.

Clinical characterization and placental pathology of mpox infection in hospitalized patients in the Democratic Republic of the Congo.

We describe the results of a prospective observational study of the clinical natural history of human monkeypox (mpox) virus (MPXV) infections at the remote L'Hopital General de Reference de Kole (Kole hospital), the rainforest of the Congo River basin of the Democratic Republic of the Congo (DRC) from March 2007 until August 2011. The research was conducted jointly by the Institute National de Recherche Biomedical (INRB) and the US Army Medical Research Institute of Infectious Diseases (USAMRIID). The Kole hospital was one of the two previous WHO Mpox study sites (1981-1986). The hospital is staffed by a Spanish Order of Catholic Nuns from La Congregation Des Soeurs Missionnaires Du Christ Jesus including two Spanish physicians, who were members of the Order as well, were part of the WHO study on human mpox. Of 244 patients admitted with a clinical diagnosis of MPXV infection, 216 were positive in both the Pan-Orthopox and MPXV specific PCR. The cardinal observations of these 216 patients are summarized in this report. There were three deaths (3/216) among these hospitalized patients; fetal death occurred in 3 of 4 patients who were pregnant at admission, with the placenta of one fetus demonstrating prominent MPXV infection of the chorionic villi. The most common complaints were rash (96.8%), malaise (85.2%), sore throat (78.2%), and lymphadenopathy/adenopathy (57.4%). The most common physical exam findings were mpox rash (99.5%) and lymphadenopathy (98.6%). The single patient without the classic mpox rash had been previously vaccinated against smallpox. Age group of less than 5 years had the highest lesion count. Primary household cases tended to have higher lesion counts than secondary or later same household cases. Of the 216 patients, 200 were tested for IgM & IgG antibodies (Abs) to Orthopoxviruses. All 200 patients had anti-orthopoxvirus IgG Abs; whereas 189/200 were positive for IgM. Patients with hypoalbuminemia had a high risk of severe disease. Patients with fatal disease had higher maximum geometric mean values than survivors for the following variables, respectively: viral DNA in blood (DNAemia); maximum lesion count; day of admission mean AST and ALT.

Mpox: Risks and approaches to prevention.

Since early May 2022, an outbreak due to Mpox virus (formerly called monkeypox) has occurred in many countries around the world. On July 23, the World Health Organization declared the outbreak 'Public Health Emergency of International Concern'. In order to combat the outbreak, it is important to have effective infection prevention and control plans. The first step is to qualitatively and quantitatively determine the risks of infections, followed by the design and implementation of infection prevention and control measures. Mpox is transmitted through direct, indirect, and prolonged contact, through sexual transmission, and via the respiratory route. Men who have sex with men are identified as the most vulnerable population. Home pet-raisers, and health care workers are at risk of catching the disease. The outcome of infection is catastrophic among the elderly, immunocompromised individuals, pregnant female and children. The spillover to animals is of great concern. It is important to communicate the risks and have community engagement in the control of this outbreak. The availability of vaccines will add to the capability of containing the outbreak. It is critical to prevent the virus from spreading further. Hence, we review the recent findings on the risk management of Mpox along with the preventive strategies.

Mpox Virus in Pregnancy, the Placenta, and Newborn.

CONTEXT.­: Before its eradication, the smallpox virus was a significant cause of poor obstetric outcomes, including maternal and fetal morbidity and mortality. The mpox (monkeypox) virus is now the most pathogenic member of the Orthopoxvirus genus infecting humans. The 2022 global mpox outbreak has focused attention on its potential effects during pregnancy. OBJECTIVE.­: To understand the comparative effects of different poxvirus infections on pregnancy, including mpox virus, variola virus, vaccinia virus, and cowpox virus. The impact on the pregnant individual, fetus, and placenta will be examined, with particular attention to the occurrence of intrauterine vertical transmission and congenital infection. DATA SOURCES.­: The data are obtained from the authors' cases and from various published sources, including early historical information and contemporary publications. CONCLUSIONS.­: Smallpox caused maternal and perinatal death, with numerous cases reported of intrauterine transmission. In endemic African countries, mpox has also affected pregnant individuals, with up to a 75% perinatal case fatality rate. Since the start of the 2022 mpox outbreak, increasing numbers of pregnant women have been infected with the virus. A detailed description is given of the congenital mpox syndrome in a stillborn fetus, resulting from maternal-fetal transmission and placental infection, and the potential mechanisms of intrauterine infection are discussed. Other poxviruses, notably vaccinia virus and, in 1 case, cowpox virus, can also cause perinatal infection. Based on the historical evidence of poxvirus infections, mpox remains a threat to the pregnant population, and it can be expected that additional cases will occur in the future.

[Monkeypox: Proposals for care in pregnancy]. / Variole du singe : propositions de conduite à tenir chez les femmes enceintes.

Although the 2022 Monkeypox virus epidemic mostly affects males, particularly men having sex with men, transmission to women may also occur. In case of MPXV infection in pregnancy, transmission to the fetus can result in very severe disease. Thus, caregivers should be aware of the measures to be taken according to the available evidence, in case of exposure or in case of symptoms particularly skin rash compatible with this diagnosis in a pregnant woman. Pregnant women should have access to vaccination, vaccinia immunoglobulin or antiviral medications as required.

Mpox (Monkeypox) Infection During Pregnancy.

BACKGROUND: An mpox (formerly "monkeypox") outbreak began in 2022, leading to infection in special populations, including pregnant individuals. CASE: We present a case of an individual who presented with a labial ulcer and subsequent papular rash at 31 weeks of gestation. She was diagnosed with mpox infection and was treated with tecovirimat. She had an uncomplicated induction of labor at 39 2/7 weeks of gestation and delivered a healthy neonate. The neonate had a positive immunoglobulin G test result for orthopoxvirus but did not have skin lesions or positive molecular test results suggestive of infection. CONCLUSION: Transplacental transmission of mpox is possible, but, in this case, the neonate did not have clinical findings suggestive of active or antenatal mpox infection. Treatment with tecovirimat in gestational cases of mpox may be beneficial.