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Home , Ebola, Lassa fever, Monkeypox

Nov 2017 2017

Watching brief

Date of report 30 November 2017

Monkeypox Disease Not yet confirmed. The first human case in was reported to Origin have killed and eaten a monkey with members of his household and neighbours who later showed symptoms of the monkeypox (1).

Not yet confirmed. Probable source of disease from squirrels, Gambian Suspected Source giant , other and .

On 22 September 2017, three cases of suspected monkeypox was reported in Niger Delta University Teaching Hospital in Bayelsa state, Nigeria(1). Samples were sent to the WHO regional laboratory in Dakar Date of outbreak Senegal for confirmation. The outbreak was confirmed by WHO on 16 beginning October 2017 as all three samples were positive for monkeypox(1). Epidemiological linkage confirmed among the first three cases in Bayelsa state(1, 2).

Date outbreak Ongoing declared over

Nigeria. Affected countries Confirmed cases in Akwa Ibom, Bayelsa, Cross River, Imo, Abia, & regions Nasarawa, Benue, Delta, Edo, Ekiti, Enugu, Lagos, Rivers and Federal Capital Territory (FCT) and suspected cases in 21 states(2, 3).

1

Monkeypox – November – 2017

Clustering of cases in some states of Nigeria has been observed but no evidence of epidemiological linkage across states(2). As of 9 October 2017, 33 suspcted cases in 7 states with no deaths reported (4). As of 16 October 2017, 3 laboratory confirmed cases and 74 suspected cases from 10 states(5). As of 2 November 2017, 38 confirmed cases and 116 suspected cases Number of cases from 20 states(3). As of 19 November 2017, 42 confirmed cases and 146 suspected cases from 21 states(6). As of 30 November 2017, 59 confirmed cases in 14 states and 167 suspected cases from 21 states (2, 7) Clinical symptoms similar to but less severe. In this outbreak, most of the suspected cases have been reported to have (1). Monkeypox is a self-limiting disease with symptoms lasting from two to three weeks. Severity is associated with infectious dose exposure, patient health status and is worse among children. The is usually 6 to 16 days. The infectious period can be divided into two periods(1, 8, 9): Clinical features 1. The invasion period: , , swelling of (distinctive feature), back pain, , 2. The skin eruption period (within 1-3 days after appearance of fever): various stages of , spreading from face to palms and soles of the feet are the most affected areas. The rash continues to evolve from maculopapules to vesicles to pustules, and eventually crusts occur in 10 days. It may take three weeks before resolution of crusts. Zoonotic : Exposure to animals such as close contact with infected rodents or primates through bites,scratches or consumption of infected and inadequately cooked animal products. by inoculation though contact with cutaneous or mucosal lesion on animal, especially when breaks in skin barrier. Person to person transmission: Transmission occurs through direct

contact with the , bodily fluids, fluids from cutaneous or mucosal Mode of lesions of infected persons or via the respiratory route through transmission infected respiratory tract secretions. Congenital monkeypox can occur

as the virus is transmitted across the placenta. Observational studies in the mid 1980s showed an infectious period during the first week of the rash similar to smallpox(10). A study conducted in the US 2003 examining health care worker exposure to patients with confirmed monkeypox showed that human to human transmission in an outbreak seting is rare(11). Monkeypox – November – 2017

The was an 11 year old male patient from Agbura, a rural settlement near Yenagoa and later presented to the Niger Delta University Teaching Hospital in Bayelsa state(1). A medical doctor and a 17 year old boy were one of the first suspected cases in Bayelsa Demographics of state(1). Male to female ratio of suspected cases was initially 3:1 and cases reduced to twice as many males as females(2, 4). The most affected group has been those aged 21-30 years old and subsequently widened to 21-40 years old (median age=30) in the most recent situation report(2, 3). No other details are available. From previous outbreaks, the CFR has been between 1-10%, mostly among young children(12). One deaths have been reported among confirmed or suspected cases in the current outbreak in a confirmed case that had background immunosuppression(2). Media reports mentioned one case alleged to have committed suicide due to the of stress of illness and lack of proper counselling previously, and our sources confirm that this was a separate incident in a patient who was admitted to the same hospital as the initial cases were being treated and unrelated to the outbreak(13). Permanent scarring, disfigurement and death. Prognosis may be worse Complications for patients who are younger, have other co-morbidities such as malnutrition or those who are immunocompromised. There is no for monkeypox. against smallpox confers cross protection for monkeypox and has been shown to be 85% effective against monkeypox(14). However, the vaccine is currently not publicly administered in Nigeria. Patients and response activities are being managed by Available authorities and Nigeria Centre for Disease control especially in states prevention with confirmed cases. Recommendations for infection prevention and control measures: • Contact precautions in healthcare setting • Appropriate use of personal protective equipment • Proper hand • Safe handling of meat products • Avoid close contact with possible source of Available Treatment is supportive and based on the patient’s clinical condition. treatment Symptomatic relief is also provided. Two previous outbreaks were reported in Nigeria in 1971 and 1978 Comparison with with 2 cases and 1 case respectively amongst individuals who were not past outbreaks vaccinated against smallpox. Cases were linked to consumption of Monkeypox – November – 2017

meat obtained from tropical rainforests (15). The outbreak in 1971 involved a 4 year old female index case. The secondary case was her 24 year old mother. The ingle case identified in 1978 was a 35 year old man(15). Since then monkeypox has remained a disease of Central and West African countries except in 2003 when 37 confirmed and 10 probable cases were reported across six states in the US, the first reported outbreak outside of Africa where those affected had close contact with pet prairie dogs ( of Cynomys species) imported from the endemic region(16). The largest outbreak ever reported in Africa was in 1996 in the Democratic Republic of Congo with more than 70 cases that lasted for one year(17). This was associated with close contact with squirrels and person to person transmission. The current outbreak has significantly more cases than previous outbreaks when probable and confirmed cases are included(17). • Uncertain source of infection • Rapid spread of infection across multiple states within few weeks, linkage between cases yet to be confirmed, still a possibility of separate clusters outbreaks • Unusual features Mode of transmission unclear, for example, how much is due to human to human transmission • Delayed diagnosis of infections as unable to diagnose the disease with laboratory confirmation in Nigeria • Large susceptible population with no prior immunity to monkeypox following cessation of in 1980 Uncertain source of Monkeypox is a zoonotic disease. The causative agent: is in the genus which is endemic to Central and Western African countries of which Nigeria is a part of. Previous studies have identified two geographically disjunct clades of the virus: Congo Basin and clades(18). Isolates from Nigeria have been obtained on opposite sides of the Niger river and are more genetically divergent than other samples isolated from the West African Clade indicating that rivers could play a role in the differentiation of monkeypox virus (19). All cases in West Africa have occurred in tropical rainforest areas and Critical analysis clustering of cases has been observed within families(15, 20). People living close to forested areas have higher risk of exposure and could have subclinical infections that have gone undetected due to lack of diagnostic capabilities, low risk perception due to rarity of disease and closeness of symptoms with (17). The clinical course of the disease among people infected with Western African strain was observed to be milder with reduced human to human transmission compared to the other strain(18). Although the current outbreak strain is yet to be confirmed it is likely to be closely related to the Western African strain. Preliminary genetic sequencing suggests multiple sources Monkeypox – November – 2017

of introduction of the virus into the population across various states according to the NCDC latest situation report(2). The precise mode of human infection is not known and no animal reservoir has been confirmed. Close association of cases with wild animals such as monkeys, rodents and squirrels leading to bites or through consumption of bush meat is a risk factor for human infection(21). There is a high probability the current outbreak originated from monkeys, with the index case reported to have killed and consumed a monkey prior to exhibiting symptoms(1). In a qualitative study of Nigerian hunters, participants reported having contact with primates more than with any other wildlife either as pets or through hunting for trade, and 87% reported consuming primates. Monkeys were listed among the most desirable animals to consume and also used for medicinal purposes(22). The role of human to human transmission is unclear in this outbreak. The possibility of the virus being used as a agent cannot be ruled out as well(9).

Implications of eradication of smallpox An unexpected consequence of smallpox eradication is an observed rise in monkeypox cases in the decades since smallpox eradication. Human infection with monkeypox has not been reported in West Africa since 1978. The Democratic republic of Congo has reported an increase in number of monkeypox cases from <1 case per 10 000 to >14 per 10 000 since the 1980s with the highest number of cases among those <15 years of age (born after 1997), a recent shifting trend towards persons aged 15-30 years old, those born after the 1980s(23). Smallpox vaccine is most likely to have been ceased in Nigeria in 1984 (12). The vaccine against smallpox in humans has been shown to be 85% effective against monkeypox(14) yet sufficient justification to re- introduce the vaccine due to issues with vaccine safety and monkeypox emerging in areas which struggle to maintain adequate vaccine coverage levels for routine against and polio mean it is unlikely to be used for future prevention(24). The highest number of cases in current outbreak Is seen in the 21-30 age group, those born between 1987 and 1996, coinciding with smallpox vaccine cessation period. Life expectancy in Nigeria is low with the median age of 53.05 years as of 2015 compared to 78.74 years in the of America, and about 29.5% of the population is born after the 1980s (25, 26). As most of the current population has not been previously vaccinated against smallpox and there is possibly a large susceptible population to monkeypox virus infection in Nigeria.

Increasing and incidence of zoonotic diseases in recent years In recent years there has been an increasing number of zoonotic diseases reported in Nigeria. In 2013-14 Nigeria was involved in the largest recorded outbreak of which had an unprecedented size and high case fatality rate of 60-70% (27, 28). Since December 2016, a Monkeypox – November – 2017

Lassa fever outbreak affecting 17 states has reached 501 suspected cases including 104 deaths and 175 laboratory confirmed cases as of June 2017(29). Surveillance of zoonotic diseases in Nigeria has not been consistent and lack of public awareness has resulted in sustained transmission during outbreaks and delays in appropriate response activities(12). Surveillance of human monkeypox cases was very active between 1970 and 1986, particularly at the end of smallpox eradication with more than 400 cases reported during this period(12, 15). Since then, monkeypox surveillance has been limited to outbreak investigations with clusters of cases reported in areas such as the DRC(30). Increasing and civil unrest mean people travel deeper into the jungle to hunt for food, increasing the risk of exposure(30). Factors such as young age, low education level andlarge household size have been drivers of zoonotic disease risk(22, 24). Market surveys in Nigeria estimate that more than 900 000 kilograms of bush meat are sold annually and large profit margins create incentives for trade even at the international level(31). Frequent contact with wildlife through bush meat trade puts people at risk of infection with zoonotic such as monkeypox(22). With the emergence of multiple zoonotic diseases such as Ebola, , and currently monkeypox, there is a need to invest in control measures to educate people on reservoir animal species and training healthcare workers to recognise disease and initiate appropriate response activities like contact precautions when a suspected case presents.

Unusual epidemic pattern Rapid spread of monkeypox infection across Nigeria from one state to 20 states and an increasing number of suspected cases from three to more than a hundred within a month has not been seen before in Nigeria(1, 3, 4). Other than the index case and his family who ate the contaminated , the rest of the confirmed cases have come from close contacts of infected persons, suggesting human to human transmission. There is no further information on the number of cases through close contact with animals(1). Another factor that increases the spread of zoonotic diseases is industrialization and urbanisation. Trade and travel in Nigeria has improved significantly since the 1970s(32). Nigeria has the largest road network in West Africa and the second largest south of the Sahara(33). Although poorly maintained, there is also a large number of highways to neighbouring countries such as the Trans-Sahara highway to Algeria which is almost complete(33, 34). The number of airports has increased to 30 and an increase of domestic airlines since privatisation of domestic carriers was allowed by the government in 2004(35). The increased connectivity and travel routes across the state may have contributed to the increase in number of cases involving more than one state in just a few weeks. Although, some experts believe the incidence of monkeypox is equal in males and females(8) varying ratios have nbeen observed in recent Monkeypox – November – 2017

oubreaks: in a 2013 outbreak in DRC 57.1% were male(36), and the male to female ration was 1.0 in a 2015 outbreak in the (37). However, these outbreaks were relatively small in size with a 104 suspected cases and 12 confirmed cases respectively. Consistent with reported patterns of hunting behaviour, male gender is also associated with increased risk of infection. Similarly in this current outbreak there have been three times as many cases in males than in females(3).

Lack of diagnostic capabilities In the absence of laboratory technologies and delayed laboratory confirmation of cases, identification of suspected cases has been through recognising symptoms and . Implementation of contact precautions such as and supportive treatment of suspected cases have been done pre-emptively while awaiting confirmation to prevent spread(7). Risk factors such as geographical location of patient, extent of closeness of patient to rainforest areas and contact with suspected reservoirs such as monkeys have been used to identify additional cases (1). Monkeypox has been easily confused with other rash-like illnesses and commonly misdiagnosed as chickenpox since the eradication of smallpox(30, 38). In the DRC, varicella coinfection can also occur with monkeypox(38). Public health officials have been worried about fear and panic(39) amongst the public, and report challenges in mitigate this with a lack of accurate and timely information on case rates, linking of clusters and sources of transmission. Definitive diagnosis is done through laboratory confirmation by analysing samples from skin lesions to differentiate it from varicella(8). Electron microscopy(40), tissue culture, DNA restriction analysis and PCR techniques can be used to identify monkeypox but these are expensive and time consuming (41). ELISA for can be used but samples need to be collected and transported to laboratories in time. Previously samples have been reported to be missing and not available for testing. IgM can be detected in serum collected for more than 5 days after symptom onset and IgG antibodies can be detected in serum collected more than 8 days after rash onset(39). The development of an on-site laboratory diagnostic test based on an immune infiltration technique: Immuno Column for Analytical Processes that can be used in humans and animals has been reported recently(42). However, the possibility of novel technologies to be used in Nigeria is highly unlikely(43) due to high implementation costs and need for technical expertise to collect samples and run tests. For the current outbreak, confirmation of cases has been done by sending samples to WHO reference laboratory in Dakar, Senegal. Confirmation of the first three cases took up to three weeks (1, 39). Plans have also been made to send additional samples to laboratories with WHO collaborating centres working on smallpox and other Monkeypox – November – 2017

poxvirus strains such as the US Centre for Disease Control and Prevention(39). The current outbreak is being used to leverage capacity building of local laboratories which has been a high priority (39) for disease control acknowledging the increased circulation of zoonotic virus strains of pathogenic potential in the country. The push for a local laboratory with the capacity to test for monkeypox has had a successful outcome. According to the most recent NCDC situation report, National Reference Laboratory Abuja has commenced monkeypox diagnostic activities and has improved the turnaround time for laboratory confirmation of cases(2). The laboratory testing protocol has been developed by the National Veterinary Research Institute of Nigeria(2)

Poor risk communication There is an atmosphere of public distrust in government and a lack of transparency and accuracy with respect to outbreak-related information. In the Nigerian Centre of Disease Control latest situation report, the number of cases confirmed were reported as 36 and 38 in the same report(3). Nigeria has a history of diluting the seriousness of outbreaks, delayed reporting of outbreaks to the international community and poor risk communication to the public. This has resulted in delayed response activities and contributed to the increase in cases and spread of outbreaks across states. During previous outbreaks, numerous news reports used terms such as acute watery diarrhoea during the initial months and Nigeria only acknowledged an outbreak of cholera after the WHO had announced it(44). With the current outbreak, prior to confirmation of cases, local health departments have been quoted to mention that the cases could be chickenpox and it is not possible for monkeypox to be present in the state(39, 45, 46). Rumours that the government has been the cause of the outbreak and the military has been involved in spreading the virus through vaccination have been reported(13). The rumours have posed a serious challenge to implementation of response and control activities. The alleged reasons for the suicide of one of the confirmed monkeypox cases were lack of counselling and support(13). Effective risk communication has been shown to increase acceptance of control measures such as cancellation of mass gatherings(47) and improve uptake of behavioural interventions(48) such as contact precautions in the public(49, 50). Improved risk communication is necessary to mitigate the impact of the current outbreak. In the most recent situation report of the NCDC, Information Education and Communication (IEC) materials are in development in collaboration with UNICEF and the government is closely monitoring discussions related to monkeypox to deal with unfounded rumours appropriately and in a timely manner(2). What is the risk of cross border transmission? Key questions Is there human to human transmission? Monkeypox – November – 2017

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