First case of monkeypox in Pakistan: WHO’s response and steps to prevent an outbreak

Introduction Monkeypox (Mpox) is a zoonotic virus of the Poxviridae family that belongs to the Orthopoxviral genus1. It is a linear double-stranded DNA virus with a brick shape that invades host cells by fusing with them, replicating inside, and releasing infectious forms. It co-opts host cell complexes and processes while influencing gene expression and histone modifications2,3. It has been added to the WHO’s list of diseases with epidemic or pandemic potential. The virus was identified in 1958 in a Danish laboratory in monkeys suffering from fever and rash4. Poxviruses are primarily found in rodents, rabbits, and nonhuman primates, but they can occasionally be transferred to people, resulting in human-to-human transmission5. In 1970, a 9-month-old infant boy in the Democratic Republic of the Congo was diagnosed with this viral disease for the first time6. From 1 January 2022 to 26 September 2023, 115 countries (hereinafter ‘countries’) in all six WHO regions reported a total of 90 618 laboratory-confirmed cases of Mpox, including 157 casualties7. The 10 most affected countries globally are the United States of America (n=30 353), Brazil (n=10 967), Spain (n=7559), France (n=4147), Colombia (n=4090), Mexico (n=4039), Peru (n=3812), The United Kingdom (n=3761), Germany (n=3691), and Canada (n=1496). Together, these countries account for 83.5% of the cases reported globally8. Table 1 shows total Mpox cases by WHO region from 1 January 2022 till 18 July 2023 Table 1 - Total mpox cases, by WHO region from 1 January 2022. WHO region Total confirmed cases Total probable cases Total deaths Cases in the last 3 weeks Cases in the preceding 3 weeks Region of the Americas 59946 669 127 52 136 European region 26114 0 7 112 28 African region 1969 0 20 7 38 Western pacific region 2070 0 0 574 551 South-east Asia region 427 0 2 83 98 Eastern mediterranean region 92 0 1 1 1 Data as of 26 September 2023, https://worldhealthorg.shinyapps.io/mpx_global/ The most prevalent symptom among those who reported at least one symptom is any rash, followed by fever and generalized or genital rash. In the nations freshly afflicted by the current epidemic, the symptomatology of patients has been extremely constant throughout time https://worldhealthorg.shinyapps.io/mpx_global/. Among the affected population, males are the most affected, particularly those between 18 and 44 years old, who account for 64.3% of cases9. The majority of those afflicted are guys who have intercourse with other men and identify as homosexual or bisexual. When sexual orientation information is unavailable, a high incidence of male cases may indicate transmission among the group of males who have sex with men. Sexual contact including skin and mucosal contact is the most reported mechanism of transmission, followed by non-sexual person-to-person contact https://worldhealthorg.shinyapps.io/mpx_global/10. Suspected cases of Mpox were investigated in 2003, which include individuals who present with an acute illness with a fever greater than 38.3°C, intense headache, lymphadenopathy, back pain, myalgia, and severe asthenia, followed by a progressively developing rash that often begins on the face and then spreads to other parts of the body, including the soles of the feet and palms of the hands11. It has been proposed that transmission occurs by saliva/respiratory excretions or contact with lesion exudate or crust material. Another route of viral exposure might be viral shedding through feces. While the virus has been detected in blood and upper respiratory tract swabs, the significance of viremia is not well understood12. First case of Mpox in Pakistan On 21 April 2023, health officials confirmed the first Mpox case in Islamabad, Pakistan. The patient was a 25-year-old Pakistani man who had recently returned from Saudi Arabia and exhibited disease symptoms. As the patient was quite unwell, he was sent to quarantine in a hospital, and tests were conducted to determine the cause of his symptoms. The health officials did not give any more details about the man. Patient’s relatives were not sick nor had any symptoms, but still, they were asked to stay at home and avoid contact with others, just to be safe and stop the virus from spreading. Following the discovery of the Mpox case in Pakistan and the country, Pakistan has urged officials to expedite the screening of travelers in response to the outbreak of Mpox, measures have been initiated at the Karachi airport. Health teams are conducting examinations of the arms and hands of passengers arriving from abroad and using scanning machines to confirm suspicions of the disease. The aim is to efficiently handle a large number of travelers and identify potential cases of Mpox. However, specific protocols and guidelines may vary across airports and depend on available resources. and deploy health teams at all its international airports. The airports have trained personnel on hand, arranged necessary logistics support such as gloves, disinfectants, and masks, and established isolation units in hospitals. Although most people recover within 2–4 weeks without hospitalization, the mortality rate for Mpox is estimated to range from 1 to 10% of infected individuals13. While severe cases can occur in people of any age, Mpox is reported to be particularly severe in young individuals, with a higher risk observed in children and adolescents. The overall case-fatality ratio was 7.5%, with a higher ratio of 9.6% among children under 1614. The quarantine period for the virus usually lasts 5 days and 3 weeks. Response of WHO The current epidemic of Mpox in Pakistan has pushed the WHO and the Pakistani government to work together actively. Efforts are being made to prevent the virus’s spread and to offer the best clinical treatment possible to those who have been infected. The WHO has agreed to support the Pakistani government in a variety of ways, including lab testing, points of entry, and the distribution of testing kits. In addition, authorities were instructed to put in place measures such as laboratory diagnostics, contact tracking, and early identification of suspected cases and infection clusters and guarantee effective surveillance15. Possible Mpox cases should be evaluated in properly equipped laboratories utilizing nucleic acid amplification testing (NAAT) techniques such as real-time or traditional PCR to discover unique virus DNA sequences. PCR can be used independently or in conjunction with sequencing. The specimen type for laboratory confirmation is skin lesion material, which includes swabs of lesion surface and/or exudate, roofs from numerous lesions, or lesion crusts16. In addition to aiding WHO response in Pakistan comprises several other essential steps such as establishing a robust surveillance system to track the spread of Mpox, raising public awareness through education campaigns, improving healthcare capacity for diagnosis and treatment, implementing infection prevention and control measures in healthcare settings, and fostering collaboration and coordination among various stakeholders are all part of these measures. The WHO response is governed by international norms and attempts to address Pakistan’s particular requirements and priorities in managing the Mpox epidemic successfully17. Steps to prevent an outbreak in Pakistan The Pakistani government has decided to increase surveillance and take effective measures to prevent a Mpox outbreak in the country. The health minister has instructed national and provincial health authorities to remain on high alert and issued instructions to border health services for strict monitoring at all points of entry. The government will follow WHO guidelines and implement recommendations based on international health regulations. Screening of incoming passengers, particularly those coming from African countries, will be ensured at border health services. The situation is being closely monitored by health authorities18. Mpox outbreak preparation requires developing and distributing reliable diagnostic assays worldwide to quickly identify cases and prevent further transmission19. It is essential to distinguish Mpox from other infections such as varicella zoster, molluscum contagiosum, syphilis, smallpox, or scabies that may present with similar symptoms such as fever, rash (macules, papules, vesicles, and pustules), headache, fatigue, muscle aches, chills and sweats, swollen lymph nodes, and, in some cases, respiratory symptoms20. Active surveillance is crucial to detect unnoticed cases, and it is necessary to track issues and notify contacts to provide postexposure prophylaxis. Monitoring MPXV nucleic acids in sewer water and on surfaces may help detect the virus early21. An internationally accepted case definition for Mpox is needed, and testing must be widely available, especially in low-income countries and middle-income countries. Additionally, it is essential to perform surveillance on animals in close contact with infected patients to prevent the establishment of animal reservoirs22. Currently, there is no specific vaccine available for Mpox. However, the smallpox vaccine is effective in preventing Mpox in previous outbreaks. The smallpox vaccine, including MVA and Dryvax, has proven highly effective in preventing Mpox. In a study using a monkey model, animals vaccinated with MVA or MVA followed by Dryvax remained healthy with minimal skin lesions, while unvaccinated animals experienced severe illness and numerous pustular skin lesions23. These results demonstrate the smallpox vaccine’s efficacy in protecting against Mpox, and it is recommended for individuals at high risk of exposure, such as healthcare workers and laboratory personnel working with Mpox samples24,25. Public awareness about the risks of contracting Mpox and the measures that can be taken to prevent its spread. This includes educating people on the importance of avoiding contacts with wild animals, especially rodents and primates, and practicing good hygiene, such as washing hands regularly and covering wounds or sores26. It is also essential to prepare health facilities and personnel to identify, isolate, and treat cases of Mpox, as early detection and prompt treatment can help reduce the severity of the disease and prevent its spread. By increasing public awareness and preparedness, we can contribute to controlling and preventing Mpox outbreaks, ultimately protecting the health and well-being of individuals and communities27–29. Wastewater surveillance also plays a vital role in establishing robust surveillance systems necessary for the effective and timely prevention and control of emerging and seasonal infectious diseases, including Mpox. Combining clinical surveillance with Wastewater-Based Surveillance (WBS) can help determine the actual societal impact of the targeted contagious agent. WBS is a valuable tool for environmentally monitoring MPXV30. The Pharmaceutical interventions for Mpox, such as NMCT, Rutaecarpine, Nilotinib, Simeprevir, Hypericin, Naldemedine, Fosdagrocorat, and Lixivaptan, show potential as treatment options, but further research and clinical trials are necessary to determine their efficacy and safety31. The most effective nonpharmaceutical measure to prevent the spread of Mpox is to avoid close contact with infected individuals32. Patients and their households should be advised on proper hygiene and disinfection protocols. Surface disinfectants with proven ʽvirucidal activity against enveloped virusesʼ can be used for disinfection33. Chemothermal reprocessing with a virus-effective, VAH-listed or RKI-listed procedure is required for laundry reprocessing in the clinical and nursing environment34. Conclusion Mpox is a zoonotic virus that poses a significant threat to global public health. The potential for this pathogen to cause epidemics or pandemics, compounded by its ability to spread from animals to humans and between people, underscores the critical need for effective prevention and control measures. Although there is presently no dedicated vaccine for Mpox, the administration of the smallpox vaccine has shown efficacy in preventing the disease. To contain and mitigate outbreaks, diligent surveillance, accurate diagnosis, and dissemination of public health messaging regarding effective protective measures are imperative. Through collaborative efforts at both individual and community levels, we can attenuate the transmission of this viral disease and prevent the emergence of an outbreak. Ethical approval This paper did not involve patients; therefore, no ethical approval was required. Consent This paper did not involve patients; therefore, no consent was required. Sources of funding No funding was acquired for this paper. Author contribution All authors contributed equally to the paper. Conflicts of interest disclosure The authors declare that there is no conflicts of interest. Research registration unique identifying number (UIN) Name of the registry: not applicable. Unique identifying number or registration ID: not applicable. Hyperlink to your specific registration (must be publicly accessible and will be checked): not applicable. Guarantor Hussain Haider Shah.

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