Epidemiological description of and response to a large yellow fever outbreak in Edo state Nigeria, September 2018 - January 2019

Yellow fever (YF) is an acute viral haemorrhagic disease characterised by fever, yellowness of the eyes, skin and urine caused by the yellow fever virus which belongs to the genus Flavivirus. It is a vector-borne (arbovirus) disease transmitted to man from the bites of infected Aedes mosquitoes. Humans and non-human primates are the reservoir hosts of yellow fever [1, 2]. There are three basic transmission cycles of yellow fever: i) the jungle (sylvatic) yellow fever virus transmission cycle, is between non-human primates (e.g. monkeys) and mosquito species; ii) The intermediate (savannah) cycle involves the transmission of the virus from infected mosquitoes to humans living or working in jungle border areas; iii) the urban cycle involves transmission of the virus between humans. Transmission occurs when an infected person from the jungle or savannah introduces the disease in human populations with low immunity for fellow fever [3, 4].

Yellow fever remains a public health problem, especially in Africa, despite the availability of an effective vaccine [5]. This is due to several factors including uncontrolled urbanisation with rapid encroachment into natural habitats of the yellow fever vector, low production capacity for yellow fever vaccines and limited enforcement of the International Health Regulations (IHR) by countries in the region [1, 2]. Yellow fever control is guided by the World Health Organization (WHO) coordinated “Elimination of Yellow Fever Epidemic (EYE) Strategy” with three strategic objectives namely: to protect at-risk populations (no epidemics), prevent international spread (no exportation) and contain outbreaks rapidly (no sustained transmission) [6].

The current cycle of yellow fever transmission in Nigeria was detected in September 2017, in Ifelodun Local Government Area (LGA) of Kwara State, 21 years after the last reported confirmed yellow fever case [7]. Since the onset of the outbreak, increasing numbers of cases with increasing geographic spread have been reported. From July 2017 to December 2018, a total of 163 confirmed cases in 46 LGAs in 17 states were reported from the Institut Pasteur (IP Dakar), Ninety deaths were reported (CFR = 2.2%) from all suspected cases and 31 deaths among confirmed cases (CFR = 19.0%) [8, 9].

As a major preventive measure, the yellow fever vaccine was introduced into routine immunization (RI) schedule nationwide in 2004 targeting children 9 months to 2 years. However, since the re-emergence of YF in 2017, yellow fever vaccinations have been accelerated through both preventive and reactive mass vaccination campaigns. As at first quarter of 2021, 11 international coordinating group for vaccine provision (ICG) requests were approved for YF reactive mass vaccination (RMVC) with about 15 million Nigerians vaccinated across 75 LGAs in 16 States. While 88,121,329 were vaccinated through preventive mass vaccination campaigns in 19 states. Planned phase PMVC schedule to cover all the states in Nigeria till 2025 [10].

The first recent confirmed case of yellow fever in Edo State was recorded in May 2018 of a 65-year-old woman from Etsako East LGA. The case presented with fever, jaundice and vomiting with no history of vaccination nor travel to yellow fever affected states. On November 14, 2018, the Epidemiology Unit of the Department of Disease Control, Edo State reported an observed incidence of a disease with “no clear-cut diagnosis” that required urgent attention, to the Nigeria Centre for Disease Control (NCDC). The cases presented with clinical signs and symptoms suggestive of a viral haemorrhagic disease, with dates of onset between September 6 and November 1, 2018. The cases were resident in four LGAs including Esan Central, Esan West, Owan East and Uhunmwode. The state has the highest Lassa fever (LF) burden in Nigeria [11]. Most LGAs with high LF burden were the LGAs that reported the strange disease. This led to a low index of suspicion of yellow fever in the affected communities which consequently increased the mortality experienced in the outbreak.

Preliminary investigations on the samples for Lassa fever at the Institute of Lassa Fever Research and Control (ILFRC), Irrua, Edo State were negative. Further investigations were done using IgM serology in Central Public Health Laboratory Lagos (CPHL) and metagenomic analysis at the African Center of Excellence for Genomics of Infectious Diseases (ACEGID), Redeemer’s University, Ede, Osun State. The results of these investigations were positive for yellow fever [12]. Following the notification of these cases, NCDC deployed a multi-disciplinary team to support the state’s response to the outbreak. The objectives of the deployment were to describe the re-emergence of yellow fever, assess the risk of a larger outbreak occurring, assess the determinants of the outbreak and define short, medium- and long-term control measures.

The aim of this study is to provide the descriptive epidemiology of and response to a large yellow fever (YF) outbreak in Edo State.

The Edo State YF outbreak is the most severe outbreak since the re-emergence of YF in Nigeria in 2017, defined in terms of number of cases, geographic spread, and mortality. The burden of the disease was higher than initially reported and the risk of transmission in the state was high as shown in the rapid risk assessment. In 2017, Kwara State had a similar occurrence of a YF outbreak [7, 20]. The transmission could be described to be of sylvatic origin because of the presence of forests and non-human primates (NHPs) which later spread to semi-urban and urban areas. We have observed that majority of yellow fever outbreaks in Nigeria could be of sylvatic transmission as observed in Kwara, Kogi and Zamfara and other affected states. However, the Edo State yellow fever outbreak transited from sylvatic to urban transmission.

An important consideration which influences the transition cycle from sylvatic to urban is internal migration. The most affected areas in Edo State are rural and peri-urban areas with distances between 40 km to 90 km to urban areas of Benin City, with substantial daily traffic. WHO has observed that with increased virus circulation and intense population migration from infected forest areas to urban settings, many large cities were burdened by yellow fever epidemics in West African countries and simultaneously, many smaller cities are still exposed to the disease [21]. This serves as a critical indicator to intensify efforts in controlling outbreaks in rural areas, to avoid wider urban yellow fever transmission which has more devastating effects.

There was a delay in reporting the outbreak due to poor index of suspicion of yellow fever among clinicians. Edo State is one of the states with the highest burden of Lassa fever in Nigeria [11]. This may have contributed to the delay in diagnosis as most of the initial YF cases had similar presentations with Lassa fever which has higher index of suspicion among clinicians in the state. Similar presentations were seen in Kwara [7] and Kogi yellow fever outbreaks. Again, with high burden of both Lassa fever and yellow fever in the state, the concept of co-circulation of multiple viral haemorrhagic fever (VHF) diseases needs further investigation [22]. This necessitates the need for training of health care providers on the epidemiology and surveillance of yellow fever at all levels of health care system to improve early detection and underscores the need for the introduction of multi-pathogen kits for the diagnosis of VHFs [23].

From our study, the male gender is more in number than the female and the predominant age group affected is 11 – 30 years. The gender and age groups implicated are the most productive and adventurous set in the population. They are more involved in out-door activities and occupations. Control programmes should target this population group.

Table 3 presented most of the symptoms observed among confirmed cases of yellow fever during this outbreak. In line with Simon, Hashmi and Torp observation, in their documentation on complications of YF, identified multiorgan failure, acute respiratory distress syndrome (ARDS), sepsis, respiratory failure, myocarditis, encephalitis, heamorrhage, disseminated intravascular coagulation (DIC) [24]. Most of our confirmed cases registered some of these complications.

Case-based surveillance is an important strategy in the control of YF. It helps to identify high risk areas for preventive mass vaccination campaigns, promptly detects outbreaks for emergency vaccination response required by the IHR and must be reported to the WHO within 24 hours [25, 26]. There are targets set to monitor the efficiency and effectiveness of the yellow fever surveillance system. In this study, most of the surveillance performance monitoring indicators surpassed the target when compared with the Kwara State yellow fever outbreak [7]. Upon confirmation of yellow fever, a RRT was deployed to support the state with the response. There was intensive active case search, quick blood sample collection from active cases, improved communication, sample shipment and testing in the laboratories. Both national and state multi-agency public health Emergency Operation Centres (EOCs) were activated to effectively coordinate the responses. All these timely responses contributed to improve surveillance performance indicators for the outbreak.

The yellow fever vector which transmits the virus is the Aedes mosquito. They are diurnal (active during the day), bite both humans and animals alike, with early mornings and evenings marking their peak biting periods. Aedes species normally breed in transient water collections. These include collections in tree cavities, leaf axils, bamboo stumps, rock pools and artificial containers (including tin cans, coconut shells, domestic water storage containers, discarded vehicle tyres, broken earthen and ceramic wares). These breeding habitats were common in locations affected by yellow fever in Edo State and most of the larvae samples drawn from them were positive for different developmental stages of the Aedes mosquito, facilitating disease transmission.

Most of the Ovitraps set in some locations were positive for Aedes eggs. This is particularly significant and indicates high risk of transmission because infected Aedes mosquitoes are capable of spreading the yellow fever virus via transovarial transmission to the offspring [27] The risk of transmission is heightened by the fact that their eggs can remain viable for a maximum of 8 months [28].

The immature stages of Aedes mosquitoes were collected mainly in abandoned domestic water containers and in leaf axils of banana plantation in all the communities sampled. The findings from larval survey in all the locations where immature stages were collected revealed the presence of Aedes albopictus and Aedes aegypti which are both peri-domestic and domestic breeders and Aedes simpsoni a peri domestic breeder, commonly breeding in leaf axils around homes [29]. They are also known to be competent vectors for yellow fever virus [30]. The survey was conducted during dry season in which case most domestic and peri-domestic containers were without water, precipitating leaf axils to be the most common breeding sites. This is not unexpected as it is common for community members to surround their homes with banana plantations, the leaf axils of which contains water. The presence of canopy breeders whose active period is late at night was not established because of security reasons.

In our study, high larval index was observed with House Index ≥5% and/or Breteau Index ≥20 in all locations except in Ehor where the house index was low. This is a clear indication that all the communities are at high risk of yellow fever outbreak. The presence of yellow fever virus and competent vectors in the communities is a source of concern in Nigeria due to low vaccination coverage in the state; the proximity of a yellow fever cases to Benin City (an urban area in the state) and the potential spread to new LGAs and contiguous states in which case, all unimmunized individuals may be at high risk. We therefore advocate for enhanced YF vector surveillance and control.

The yellow fever rapid vaccination coverage was low in the LGAs visited and majority of the cases had zero dose vaccination status. This may account for the high number of cases with increased mortality due to low herd immunity for yellow fever in the state. Unlike the Kwara State outbreak that affected the nomadic population with known history of poor immunisation uptake [7], Edo State outbreak started among the indigenous population. Our findings revealed poor card retention for routine immunisation where only 81 (33.7%) of those with history of yellow fever vaccination could produce yellow fever vaccination cards. The implication of this is a gap in the routine immunisation services which needs to be strengthened. The poor yellow fever vaccination card retention among care-givers could account for the low vaccine coverage assessment observed.

The importance of effective leadership and communication during health emergencies was evident in this response. On notification of the outbreak to NCDC, there were timely coordinated response activities through the activation of Level Two Incident Management System (IMS) at both the national and state levels. Through the IMS, deployment of RRT, resource mobilisation and partners’ support were all intensified. Yellow fever blood sample management and transport were efficient and timely; request for yellow fever vaccines through the International Coordinating Group for vaccine provision (ICG) was successful with a swift approval coordinated by the National Primary Healthcare Development Agency (NPHCDA). Upon approval of the ICG request, available doses of yellow fever vaccines from other states that recently implemented YF preventive mass vaccination campaign were mopped-up before release and shipment of the ICG approved yellow fever vaccines to Nigeria. Consequently, the reactive mass vaccination campaign in the thirteen most affected/contiguous LGAs was implemented. And we recommended the provision of additional vaccines to support the implementation of YF vaccination campaign in the remaining 5 LGAs in accordance with the EYE Strategy [31, 32].

Edo State had the highest burden of yellow fever cases in Nigeria since the 2017 when Nigeria recorded the first confirmed case of yellow fever after 21 years. More males were affected among the confirmed. Major symptoms include fever, jaundice, weakness, and bleeding. Majority of surveillance performance indicators were above WHO set target. There is a high risk of transmission of the disease in the state. Low yellow fever vaccination coverage, and presence of yellow fever vectors (Ae.aegypti, Ae.albopictus and Ae.simpsoni) were responsible for cases in affected communities. Enhanced surveillance, improved laboratory sample management, reactive mass vaccination campaign, improved yellow fever case management and increased risk communication/awareness were very important mitigation strategies to be sustained in Edo state to prevent further spread and mortality from yellow fever.