Monkeypox Virus: Transmission Pathway, Clinical Manifestation, Predisposing Factors Responsible for the Re-Emergence and Spread in Nigeria‎ ‎

INTRODUCTION

Monkeypox (MPX) is a Zoonotic viral disease of public health concern, occurring in many countries, resulted in mortality and morbidity especially in Central and Western Africa, Nigeria inclusive. On 23rd July 2022, World Health Organization (WHO) officially placed MPX in the list of “disease of public health emergency of international concern”. The causative agent of the disease is the Monkeypox virus (MPXV), which belongs to the family Poxviridae, subfamily Chordopoxvirinae, and genus Orthopoxvirus [1, 2]. Viriola virus, Vicinia virus, and Cowpox are also members of the genus Orthopoxvirus [3, 4]. The MPXV possess linear double-stranded DNA of approximately 197 kb and it resemble brick in shape or oval in structures measuring 200–300nm under an electron microscope [5, 6, 7]. MPX in human was initially reported in the Democratic Republic of the Congo in 1970 [8, 9]. regulation and programming [7, 8]. MPXV can be transmitted through handling bush meat, suspected reservoir animal bite, bodily fluids, contaminated objects, or intimate contact with an infected human [10].  Its symptoms usually begin with headaches, fever, swollen lymph nodes, muscle pain, and tiredness.

Clinical manifestation:

There are numerous nonspecific symptoms that is shared among an individual infected with MPX. Symptoms begin to develop 7 to 14 days after an individual has been exposed to the Monkeypox virus [26, 20]. Initially, during the prodromal stage, nonspecific symptoms such as fever, headache, backache, exhaustion, chills, rashes, mouth and throat ulcers, lymphadenopathy as well as myalgia manifest, stimulating the infected individual’s immune system. As a result of nonspecific nature of these early symptoms, an infected individual may consider these symptoms to other infections such as seasonal flu or the common cold. The activation of the immune system will always cause changes in lymph nodes (enlargement), including maxillary, cervical and inguinal, occurring in synchrony with the onset of fever [23]. In cases before 2022 outbreak in Nigeria, rashes were observed and appeared between 1-3 days after development of fever and lymphadenopathy. In the emergence of these new cases, Harris states “that for some patients, those prodromal symptoms might be mild, or not even noticed at all, suggesting that some individuals may not be aware of any symptom at all, until the appearance of the rashes” [20]. Fever in typical cases often disappears between the ranges of 1-3days post onset of the rashes [20]. The facial rashes will and concomitantly spread and appear across the entire body [21, 20]. There are lesions usually noticed in the mouth and consequently, these lesions cause difficulties with eating and drinking and thus, affects the feeding habit/nutritional intake of an infected individual. The skin lesions cause an extensive perturbation of the skin, and this creates a chance for secondary bacterial infection of the skin, and this complication has been observed in 19% of unvaccinated Monkeypox-infected individuals [21, 8].

Re-Emergence and spread of Monkeybox in Nigeria:

The re-emergence has global potential health threat as trade in suspected reservoir animal have exported MPX to the United State of America in 2003 [17, 27], while human travelers from the epicenter (Africa) have also exported the disease to several other countries [28, 29, 30]. The most devastating part is that; researchers observed transmission from one individual to another and vise- versa of West African strain of MPXV in other countries [31, 18]. The re-emergence of MPX after many years of zero case report may be linked to the fact that significant portion of the population is susceptible to Orthopoxvirus infection as they did not receive smallpox vaccination, which cross-protects against MPXV, or smallpox vaccine-induced immunity has been reduced in vaccinated individuals as well as accumulation of young population [32, 16, 33, 34, 35]. There are quite a number of factors that may facilitate the re-emergence and spread of MPX. This article attempted to explored some of them as:

a)Lack of Smallpox Vaccination Coverage

Studies have shown that smallpox vaccination protects against MPX infection [36, 37, 39, 6, 40, 34]. A number of studies and reports from health institutions from different countries reported a significant number of cases from the disease outbreak. Consequently, no single individual among the reported cases received smallpox vaccination, which cross-protects by 85% against MPXV [41, 9, 42, 43, 18, 9]. Likewise, reports from outbreaks in the Democratic Republic of the Congo (1981–2013) [44, 45, 46, 47] and the US [48] showed that the majority of MPX cases was low in vaccinated individuals and ranged between 4–21% [49, 9] indicating that the majority of cases reported, approximately 80–96%, occurred in unvaccinated individuals. A study conducted in Central African Republic on confirmed and suspected cases showed that 19.2% (5/26) received smallpox vaccination, and the overall secondary attack rate was lower among individual who previously received Smallpox vaccination (0.95/1000) compared to unvaccinated individuals (3.6/1000) [50, 9].

b)Increase in Susceptible Population over Time

Over time, an increase in number of individual susceptible to MPXV infection plays a role in the re-emergence and person to person transmission of the virus [51, 52], as the number of people susceptible to smallpox infection has increased significantly since the cessation of routine smallpox vaccination in 1978, and a threshold has been declined where presently human-to-human transmission of MPXV is observed. And also, the accumulation of young children who were born during the post-smallpox vaccination era [45, 40, 7] has substantially reduced the overall population immunity level within the past 45 years. The former was evidenced using statistical modeling by Nguyen et al. (2021); they reported that, in 2016, a year before the re-emergence of the MPXV in Nigeria, only 10.1% of the present population were vaccinated, and the population immunity was substantially waned down from 65.6% in 1970 to 2.6% in 2016 [33, 34]. By 2018, the vaccinated population had decreased to 9.3%, and the estimated population immunity had declined to 2.2% [33]. And the level of serologic immunity to MPXV for the vaccinated population would continue to decline at a constant rate until it reached 0%, at which point all previously vaccinated populations would be fully susceptible to MPXV [33, 34]. While the latter was evidenced by a higher increase in the number of young people who were born after stoppage of smallpox vaccination in 1980, when smallpox vaccination was ceased as a result of a declaration by the WHO that smallpox was eradicated [45, 53, 47],

c)Inadequate Health and Research Infrastructures

Initially, there was a diagnostic challenge as many individuals, including physicians, had no knowledge of the etiology of the disease condition. This makes laboratory diagnosis, treatment, and prevention of MPX disease difficult [15]. This is because in developing countries’ health care settings, especially at the basic health care level, are challenged with limited facilities, staff technical skills, and training needed to diagnose Monkeypox [54]. However, delays in detection, treatment, and management of infection caused by unavailable standard laboratories, especially at the basic health care level, contributed greatly to the re-emergence of the disease [54]. In Africa (especially Nigeria), before the re-emergence of MPXV, it had already been considered a neglected pathogen [54, 31], and a lack of research on it has recently been demonstrated. The relatively scarcity of the disease after smallpox vaccination as well as lack of political willpower in health care concerns might be the reasons [19].

d) Increased Bush Meat Trade and Consumption

A number of ecological and behavioral factors contribute to the increased risk of exposure to MPXV through the bush meat trade [55]. Increased human contact with wild animals through hunting, butchering, and consumption of bush meat has led to the cross-species transmission of numerous infectious diseases, several of which have led to devastating outcomes across the globe [56, 1]. Transmission across species through bush meat hunting and butchering has been connected to the outbreaks of MPXV [56]. Monkeypox outbreaks are usually common among residents of small communities who engage in hunting and trade in animals suspected as reservoir of MPX rodents [49], facilitated by the increased demand for and indiscriminate consumption of such animals in Africa [57, 7]. Hunting activities and trade in animals suspected of being reservoirs of MPXV infection lead to excessive bush meat consumption, which in turn might contribute to the re-emergence and spread of MPXV [58]. This evidence is further supported by the higher prevalence observed among men and individuals of higher age groups in majority of the previous outbreaks, because predominantly, men and individuals of higher age groups carry out most high-risk occupations dealing with suspected animals compared to their counterpart women and children [58, 33].

e) Climate Change and Deforestation

Climate change is assumed to result in changes in the geographic ranges and local prevalence of infectious diseases, including MPX, either through direct effects on the pathogen or indirectly through range shifts in vector and reservoir animals [53, 59]. Environmental stress such as heavy rainfall and flooding, as well as deforestation in the name of clearing bush and forest for urbanization or farming, could expose individuals and also drive the transmission of MPXV [7, 16]. However, extension of developed areas could also increase the possibility of reservoir animals to displaced from their natural habitat and moving to live with humans, thus increasing interspecies contact [57, 60, 59]. These allow the transmission of the virus from reservoir host animals to a susceptible human, which consequently hastens the re-emergence and spread of MPX virus [33, 16].

f) Limited Public Health Awareness

The limited public awareness of the disease in endemic areas has greatly contributed toward its re-emergence [15]. This was evidenced by indiscriminate and caution-less handling and dealing with animals suspected as reservoirs of the Monkeypox [61, 62], with the perception that monkeys are the reservoir of MPXV as the name implies. Other behavioral activities that speed up the risk of exposure to suspected reservoir animals and subsequent risk for zoonotic transmission as a result of limited awareness of the disease and in turn fuel the re-emergence of Monkeypox are:  indiscriminate eating of meat from a dead animal from unknown causes of death or eating under- cooked meat [55,47, 54].

Other predisposing factors may include: Social activities; the current outbreak of the MPXV virus is being reported with sustained transmission between men who have engaged in sexual intercourse with men [25]; social gatherings such as clubs and group sex [7]; tourism, migration, and war, among others, have also been agents for the spread of the virus.

Conclusion:

Monkeypox virus is a very serious emerging and re-emerging pathogen with complex mode of transmission and broad clinical signs and symptoms as well as potential global outreach, it requires critical understanding for improved prevention diagnosis and management/treatment of this viral infection. The re-emergence is beyond a public health threat for Nigeria or other historically MPXV reported countries alone but has global health implications as trade in suspected reservoir animals and travelers have facilitated the exportation of MPX to other countries. However, it is re-emergence after several years of no case report, further justify the need for the scientific community to extend their research work on this virus, especially for the development of specific preventive measures, therapies, and control strategies.

Abbreviations:NA= Deoxyribonucleic acid, kb= Kilo-base, MPX=Monkeypox, MPXV=Monkeypox virus, USA = United State of America, WHO=World Health Organization.