The biggest-ever outbreak of monkeypox disease in non-endemic countries started in May, 2022. Though no monkeypox case has been reported from India till mid-June, considering the rate of its spread in non-endemic countries, there is an urgent need of better understanding of the disease epidemiology to help clinicians, public health specialists and policymakers to be prepared for any eventuality. This disease is known to cause severe outcomes in children, pregnant women, and immunocompromised hosts and this group needs to be given special attention.

The monkeypox in non-endemic countries should be used as an opportunity by India and other low and middle income countries to strengthen public health surveillance and health system capacity for outbreak and epidemic preparedness and response.

The disease map

Monkeypox disease is an infectious zoonotic disease caused by the monkeypox virus (MPXV), which belongs to the Orthopoxvirus genus of the Poxviridae family, the same genus as that of the smallpox virus. It is a double-stranded deoxy ribonucleic acid (dsDNA) virus. The MPXV was first detected in 1958, in a group of monkeys in a laboratory in Denmark. The first human case was identified in a nine-month-old child, during the intensive search for smallpox cases, in the Democratic Republic of the Congo (then known as Zaire) in 1970. Ever since, the disease has been endemic in nearly 11 countries of the Central and Western African regions with thousands of cases being reported annually. Though various animal species have been identified as susceptible to the Monkeypox virus, uncertainty remains on the natural host of the virus and further studies are needed to identify the reservoir(s) and how virus circulation is maintained in nature.

The case fatality rate of Monkeypox ranges from 0-11 per cent, slightly lower at around 0 to 3 per cent for the West African clade and 0 to 11 per cent for the Central African (Congo basin) clade, in comparison to the high fatality of 30 per cent for smallpox virus. To date, deaths in the endemic countries have mainly been reported mostly in young children and people with human immunodeficiency virus/acquired and Immunodeficiency syndrome (HIV/AIDS) or other immunocompromised hosts.

In the ongoing outbreak, the West African clade is responsible for the unprecedented rise of cases. As per the latest WHO update, till June 15, 2022, around 2,039 laboratory confirmed cases of Monkeypox disease have been notified from 36 non-endemic countries worldwide. A majority of the cases (84 per cent) have been reported from WHO European region. However, imported and travel history-related cases have been reported from the Americas, Eastern Mediterranean and Western Pacific Region. Among the endemic countries, an outbreak of monkeypox disease has been ongoing in Nigeria since 2017.

Outcome of infection and risk in children

Monkeypox is usually a self-limiting disease and remains mild but severe cases occur among children, pregnant women, comorbid and immunocompromised hosts. The transplacental transmission of monkeypox has resulted in miscarriages and foetal deaths. However, the association between severity of maternal illness and these outcomes is unclear. Over the years, there has been a shift in the median age of monkeypox disease in Africa, which was four and five-year-old children in the 1970s and 1980s to 10 and 21-year-olds in the 2000s and 2010s. During an outbreak in the US in the past, among the confirmed cases, 10 out of 34 (29 per cent) were below 18 years. However, during the first year of the ongoing outbreak in Nigeria, in 2017-2018, children formed around eight per cent of the 91 cases.

A recent longitudinal study from the Democratic Republic of Congo showed that among 216 admitted patients of monkeypox from the year 2007 till 2021, half were in the age group of 0-12 years.

Available data shows that the risk of children developing disease may have gone down over the years; however, they continue to be a more vulnerable group given the possibility of adverse outcomes in this population. The prognosis is related to the extent of virus exposure, infection with Congo Basin clade of virus, patient’s health status and nature of complications.

Therapeutics

Treatment of Monkeypox disease is mostly symptomatic with management of complications and prevention of long-term sequelae. Fluids and adequate nutrition are necessary to improve overall recovery. A drug named Tecovirimat, originally researched and developed for smallpox, was approved for MPXV in a few countries in early 2022; however, it is not yet widely available. Two other antiviral drugs, Cidofovir and Brincidofovir, also developed to treat smallpox and working by inhibiting the viral DNA polymerase, have shown efficacy in animal studies. However, data is insufficient on their effectiveness for treatment of Monkeypox disease in humans. Research is also in progress on monoclonal antibody combinations. Vaccinia Immunoglobulins (VIG) showed some efficacy against other Orthopoxviruses and is licensed by the US Food and Drug Administration [35]. VIG plays a role in post exposure prophylaxis and reducing the severity of the disease, but further studies are needed.

Vaccination

In observational studies, the vaccination against smallpox had shown up to 85 per cent cross protection and reduced severity of Monkeypox disease. However, in the current outbreak, immunity from the past smallpox vaccination may not be useful as first, it is limited to those who were administered the vaccine by or before the 1980s and second, there is every possibility of further waning of the protective effect in that population, over the last four decades.

Smallpox vaccines have not been available to the public since its eradication in 1980. It is also believed that vaccination, up to 14 days after exposure and four days before appearance of symptoms, may also prevent disease or reduce its severity given the long incubation period.

A third-generation smallpox vaccine, MVA-BN (Modified vaccinia Ankara -Bavarian Nordic strain) was approved against Monkeypox in 2019. This vaccine is based on a strain of vaccinia virus and is considered protective against MPXV. As of June 11, 2022 MVA-BN smallpox vaccine is available in many European countries, USA and Nigeria, mostly for ‘off-label’ use. An interim guideline from WHO has recommended that local authorities may consider the use of approved smallpox and/or Monkeypox vaccines in response to the ongoing outbreak. Only second and third generation smallpox vaccines can be used for the ring vaccination in the Monkeypox outbreak, guided and determined at the local level.

For pregnant and breastfeeding women, non-replicating (MVN-BN) and minimally replicating (LC16) are preferred. For children, MVA-BN and LC-16 are preferred. The only approved vaccine for infants and children is LC16. However, MVA-BN, which is approved for adults, can also be administered as off-label use for children in different settings.

Preparedness and response

Considering the pattern of the spread, there is need for every country to be prepared. The outbreak readiness measures such as the designated isolation facilities and dedicated beds, equipment and reagents for laboratory diagnosis, and training of a group of health care workers as members of rapid response team (RRT) in standard elements of care should be prioritised. Early case identification, contact tracing and as and where possible, the ring vaccination (of close contacts and family members), remain to be the mainstay of response.

It also needs to be remembered that while laboratory confirmation of suspected cases is needed, it should not delay the public health measures. Similarly, while awaiting the laboratory confirmation, patients and contacts in the community need to be traced and further investigated (backward contact tracing). The concerned health staff needs to be trained in risk communication. Once one or more MPXV cases are reported, special efforts should be made to raise awareness about clinical symptoms and prevention of spread. However, it should not be overdone, which may result in panic.

The Ministry of Health and Family Welfare (MoHFW) has already released guidelines on the detection and management of Monkeypox disease. There is emphasis on intensified surveillance and early case identification, using standard case definitions. A laboratory at National Institute of Virology (NIV) in Pune has been designated as nodal laboratory for monkeypox virus testing in India.

Due to the COVID-19 pandemic, the capacity in many countries for conducting genomic sequencing has been strengthened. In case of MPXV, genomic sequencing would be useful to identify the clade and the chain of infection. However, considering that MPXV is a DNA virus, which has a slow rate of mutation, the repeated genomic sequencing has limited value. Besides, the MPXV genome has around 200,000 nucleotide bases, six times larger than the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) and thus genomic sequencing is a bit harder, more time consuming and expensive, with limited benefits.

A key question is whether the MPXV is capable of causing a pandemic? There are several points which make MPXV disease unlikely to become a pandemic. First, it is not a new virus and has been present globally for five decades. There is a reasonable understanding of the viral structure, transmission and pathogenicity. Second, the virus causes mostly mild illness, as evident from zero deaths occurring since the onset of the ongoing outbreak. Third, it is less contagious and requires close personal contact in contrast to SARS-CoV-2 that had a respiratory spread and a high proportion of asymptomatic cases. In Monkeypox disease, a person is contagious only when symptoms start appearing. Therefore, chances of transmission going undetected are negligible. Fourth, a few smallpox vaccines are readily available and their “off-label” use can be recommended, and production can be ramped across the globe, if required. Fifth, it is a relatively stable virus with a very slow rate of mutations. It is in this backdrop, most experts on infectious disease believe that monkeypox outbreak would not turn into a pandemic. There is every reason, as of now, to believe that a Monkeypox outbreak can effectively be tackled and the virus contained by isolation of confirmed cases, quarantine of contacts and the use of authorised smallpox vaccines as ‘off-label’ for ‘ring vaccination.” The overall vaccination of the general population is not currently recommended.

The ongoing Monkeypox outbreak also raises questions about broader global public health response and collaboration. Despite the existence of the disease in 11 countries in Africa for more than five decades, the disease is getting global attention now only when high and upper-middle income countries have been affected. This reflects the inherent bias in global public health, where diseases of low and middle income countries do not get commensurate priority for research and policy interventions. There is a need for technical discussion amongst experts, at all levels, regarding possible use of smallpox vaccines for Monkeypox outbreak situations. The national technical advisory group on immunization (NTAGI) in India and the immunization working groups and expert committees of the professional associations should discuss possible target groups as well as come up with technical guidance on possible target groups and to plan, procure, stockpile and if needed deployment of such vaccines.

In India, many viral and zoonotic diseases have emerged and re-emerged in the last two decades. With climate change, there are estimates of increased risks of cross-species viral transmission and zoonotic diseases. The interventions to tackle those diseases are mostly similar. A stronger primary healthcare system, well-functioning disease surveillance systems, trained public health workforce and focus upon ‘One-health’ approach, where interventions are coordinated to protect the health of humans, animals and ecosystem, are essential for any such eventuality.

(The study, Monkeypox Disease Outbreak (2022): Epidemiology, Challenges, and the Way Forward, has been conducted by Foundation for People-Centric Health Systems, New Delhi. The article was published in the prestigious medical journal ‘Indian Pediatrics.’ The full text of article is available at https://indianpediatrics.net/epub062022/RA-00438.pdf )





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