The largest ever outbreak of monkeypox disease in non-endemic countries began in May 2022. Although no monkeypox case has been reported from India till mid-June, given the rate of its spread in non-endemic countries, it is urgently needed. Better understanding of disease epidemiology to help clinicians, public health experts and policy makers be prepared for any eventuality. The disease is known to cause serious consequences in children, pregnant women, and hosts with weakened immune systems, and this group requires special attention.
Monkeypox in non-endemic countries should be used by India and other low- and middle-income countries as an opportunity to strengthen public health surveillance and health system capacity for outbreak and pandemic preparedness and response.
Monkeypox disease is an infectious zoonotic disease caused by the monkeypox virus (MPXV), which belongs to the orthopoxvirus genus of the family Poxviridae, similar to the smallpox virus. It is a double-stranded deoxy ribonucleic acid (dsDNA) virus. MPXV was first detected in a group of monkeys in a laboratory in Denmark in 1958. The first human case was identified in a nine-month-old baby in 1970 during an intensive search for smallpox cases in the Democratic Republic of Congo (then known as Zaire). Since then, the disease has been endemic in about 11. Countries in the Central and West African regions where thousands of cases are reported every year. Although various animal species have been identified as susceptible to monkeypox virus, uncertainty remains on the natural host of the virus and further studies are needed to identify reservoirs and how virus circulation is maintained in nature. is required.
Mortality rates are 0–11 percent for monkeypox, about 0 to 3 percent for the West African clade and 0 to 11 percent for the Central African (Congo Basin) clade, slightly lower than the higher mortality rate. 30 percent for the smallpox virus. To date, deaths in endemic countries have mainly occurred 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 surge of cases. According to the latest update from WHO, as of June 15, 2022, around 2,039 laboratory confirmed cases of monkeypox disease have been notified from 36 non-endemic countries around the world. The majority of cases (84 percent) have been reported from the WHO European region. However, cases imported from the Americas, the Eastern Mediterranean and the Western Pacific and related to travel history have been reported. Among endemic countries, outbreaks of monkeypox disease have continued in Nigeria since 2017.
Consequences of infection and exposure in children
Monkeypox is usually a self-limiting disease and is mild but severe cases occur in children, pregnant women, comorbid and immunocompromised hosts. Transplacental transmission of monkeypox has resulted in miscarriage and fetal death. However, the relationship between maternal illness severity and these outcomes remains unclear. Over the years, the average age of monkeypox disease in Africa has changed, ranging from four and five-year-olds in the 1970s and 1980s to 10 and 21 years old in 2000 and 2010. During an outbreak in the US in the past, of the confirmed cases, 10 out of 34 (29 percent) were under the age of 18. However, during the first year of the ongoing outbreak in Nigeria, in 2017–2018, children constituted about eight percent of the 91 cases.
A recent longitudinal study from the Democratic Republic of the Congo showed that half of 216 admitted patients with monkeypox from the years 2007 to 2021 were in the age group of 0-12 years.
Available data suggest that the risk of developing the disease in children has decreased over the years; However, they remain a more vulnerable group given the potential for adverse outcomes in this population. Prognosis is related to the extent of exposure to the virus, infection with the Congo Basin clade of viruses, the patient’s health status and the nature of complications.
Treatment of monkeypox disease is mostly symptomatic with management of complications and prevention of long-term sequelae. Fluids and adequate nutrition are essential for improving overall health. A drug called Tecovirimat, originally researched and developed for smallpox, was approved for MPXV in some countries in early 2022; However, it is not widely available yet. Two other antiviral drugs, cidofovir and brincidofovir, also developed to treat smallpox and working by inhibiting viral DNA polymerase, have shown effectiveness in animal studies. However, there is insufficient data on their effectiveness for the treatment of monkeypox disease in humans. Research on monoclonal antibody combinations is also ongoing. Vaccinia immunoglobulin (VIG) has shown some efficacy against other orthopoxviruses and is licensed by the US Food and Drug Administration. , VIG plays a role in postexposure prophylaxis and reducing disease severity, but further studies are needed.
In observational studies, vaccination against smallpox showed up to 85 percent cross protection and reduced the severity of monkeypox disease. However, in the current outbreak, immunity from previous smallpox vaccinations may not be as useful as before, it is limited to those who were vaccinated until or before the 1980s and second, the protective effect is likely to diminish further. Chances are. That population, over the past four decades.
Smallpox vaccines have not been available to the public since its elimination in 1980. It is also believed that vaccination can prevent disease or reduce its severity, given the long incubation period, up to 14 days after exposure and up to four days before symptoms appear.
The 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 known to be protective against MPXV. As of June 11, 2022, the MVA-BN smallpox vaccine is available in several European countries, the United States and Nigeria, mostly for ‘off-label’ use. A WHO interim guideline has recommended that local authorities consider the use of approved smallpox and/or monkeypox vaccines in response to the ongoing outbreak. Only second- and third-generation smallpox vaccines, directed and prescribed locally, can be used for ring vaccination in monkeypox outbreaks.
For pregnant and lactating 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 an off-label use to children in different settings.
preparation and response
Given the pattern of spread, every country needs to be prepared. Prioritized training of a group of health care workers as members of the Rapid Response Team (RRT) in outbreak preparedness measures such as designated isolation facilities and dedicated beds, equipment and reagents for laboratory diagnostics, and standard elements of care Should be known Early case identification, contact tracing and, wherever possible, ring vaccination (of close contacts and family members), remain the mainstays of the response.
It also needs to be remembered that while there is a need for laboratory confirmation of suspected cases, public health measures should not be delayed. Similarly, patients and contacts in the community should be traced and further investigation (backward contact tracing) should be done, while awaiting laboratory confirmation. The health workers concerned need to be trained in risk communication. Once one or more MPXV cases have been reported, special efforts should be made to increase awareness of the clinical symptoms and prevention of spread. However, do not overdo it, which can result in panic.
The Ministry of Health and Family Welfare (MoHFW) has already issued guidelines on the detection and management of monkeypox disease. The emphasis is on intensive monitoring and early case identification using standard case definitions. A laboratory of the National Institute of Virology (NIV) in Pune has been designated as the nodal laboratory for monkeypox virus testing in India.
Due to the COVID-19 pandemic, the ability to perform genomic sequencing has been strengthened in many countries. In the case of MPXV, genomic sequencing would be useful to identify the clade and chain of infection. However, given that MPXV is a DNA virus with a slow rate of mutation, repetitive genomic sequencing has limited value. Furthermore, the MPXV genome has approximately 200,000 nucleotide bases, which is six times larger than that of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) and thus genomic sequencing is slightly more difficult, more time-consuming and costly, with limited benefit. .
An important question is whether MPXV is capable of causing a pandemic? There are several factors that make MPXV disease unlikely to become a pandemic. First, it is not a new virus and has been present globally for over five decades. There is a proper understanding of viral structure, transmission and pathogenicity. Second, the virus causes mostly mild illness, as evidenced by the zero deaths reported since the start of the ongoing outbreak. Third, it is less contagious and requires close personal contact in contrast to SARS-CoV-2 which had respiratory spread and a high proportion of asymptomatic cases. In monkeypox disease, a person is contagious only when he starts showing symptoms. Therefore, the probability of transmission going undetected is negligible. Fourth, some smallpox vaccines are readily available and their “off-label” use may be recommended, and production can be increased worldwide if necessary. Fifth, it is a relatively stable virus with very slow mutation. Against this background, most infectious disease experts believe that the monkeypox outbreak will not turn into a pandemic. So far, there is every reason to believe that monkeypox outbreaks can be effectively tackled and ‘off-label’ for ‘ring vaccination’ by isolation of confirmed cases, quarantining of contacts and the use of authorized smallpox vaccines. ‘ as the virus can be controlled. Overall vaccination of the general population is not currently recommended.
The monkeypox outbreak also raises questions about the wider global public health response and cooperation. Despite the existence of the disease in 11 countries in Africa for more than five decades, the disease is now receiving global attention only when countries with high and upper-middle incomes are affected. This reflects an inherent bias in global public health, where diseases from low- and middle-income countries do not receive priority for research and policy intervention. The potential use of smallpox vaccines for monkeypox outbreak situations requires technical discussion among experts at all levels. The National Technical Advisory Group on Immunization in India (NTAGI) and the Expert Committees of Immunization Working Groups and Professional Associations should discuss the potential target groups as well as come up with technical guidance on the potential target groups and plan, procure, stockpile and if There is a need for deployment of such vaccines.
In India, several viral and zoonotic diseases have emerged and re-emerged in the last two decades. With climate change, there is projected an increased risk of cross-species viral transmission and zoonotic diseases. Interventions to combat those diseases are mostly similar. Focusing on a robust primary health care system, well-functioning disease surveillance systems, trained public health workforce and a ‘one-health’ approach, where interventions are coordinated to protect human, animal and ecosystem health are necessary for any such event.
(The study, Monkeypox Disease Outbreak (2022): Epidemiology, Challenges, and the Way Ahead, is conducted by the Foundation for People-Centric Health Systems, New Delhi. The article was published in the prestigious medical journal ‘Indian Pediatrics’. The full text of the article is available at https://indianpediatrics.net/epub062022/RA-00438.pdf.)