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

BACKGROUND: Edo State Surveillance Unit observed the emergence of a disease with "no clear-cut-diagnosis", which affected peri-urban Local Government Areas (LGAs) from September 6 to November 1, 2018. On notification, the Nigeria Centre for Disease Control deployed a Rapid Response Team (RRT) to support outbreak investigation and response activities in the State. This study describes the epidemiology of and response to a large yellow fever (YF) outbreak in Edo State. METHODS: A cross-sectional descriptive outbreak investigation of YF outbreak in Edo State. A suspected case of YF was defined as "Any person residing in Edo State with acute onset of fever and jaundice appearing within 14 days of onset of the first symptoms from September 2018 to January 2019". Our response involved active case search in health facilities and communities, retrospective review of patients' records, rapid risk assessment, entomological survey, rapid YF vaccination coverage assessment, blood sample collection, case management and risk communication. Descriptive data analysis using percentages, proportions, frequencies were made. RESULTS: A total of 209 suspected cases were line-listed. Sixty-seven (67) confirmed in 12 LGAs with 15 deaths [Case fatality rate (CFR 22.4%)]. Among confirmed cases, median age was 24.8, (range 64 (1-64) years; Fifty-one (76.1%) were males; and only 13 (19.4%) had a history of YF vaccination. Vaccination coverage survey involving 241 children revealed low YF vaccine uptake, with 44.6% providing routine immunisation cards for sighting. Risk of YF transmission was 71.4%. Presence of Aedes with high-larval indices (House Index ≥5% and/or Breteau Index ≥20) were established in all the seven locations visited. YF reactive mass vaccination campaign was implemented. CONCLUSION: Edo State is one of the states in Nigeria with the highest burden of yellow fever. More males were affected among the confirmed. Major symptoms include fever, jaundice, weakness, and bleeding. Majority of surveillance performance indicators were above 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) are responsible for cases in affected communities. Enhanced surveillance, improved laboratory sample management, reactive vaccination campaign, improved yellow fever case management and increased risk communication/awareness are very important mitigation strategies to be sustained in Edo state to prevent further spread and mortality from yellow fever.

In silico modeling revealed phytomolecules derived from Cymbopogon citratus (DC.) leaf extract as promising candidates for malaria therapy.

The emergence of varying levels of resistance to currently available antimalarial drugs significantly threatens global health. This factor heightens the urgency to explore bioactive compounds from natural products with a view to discovering and developing newer antimalarial drugs with novel mode of actions. Therefore, we evaluated the inhibitory effects of sixteen phytocompounds from Cymbopogon citratus leaf extract against Plasmodium falciparum drug targets such as P. falciparum circumsporozoite protein (PfCSP), P. falciparum merozoite surface protein 1 (PfMSP1) and P. falciparum erythrocyte membrane protein 1 (PfEMP1). In silico approaches including molecular docking, pharmacophore modeling and 3D-QSAR were adopted to analyze the inhibitory activity of the compounds under consideration. The molecular docking results indicated that a compound swertiajaponin from C. citratus exhibited a higher binding affinity (-7.8 kcal/mol) to PfMSP1 as against the standard artesunate-amodiaquine (-6.6 kcal/mol). Swertiajaponin also formed strong hydrogen bond interactions with LYS29, CYS30, TYR34, ASN52, GLY55 and CYS28 amino acid residues. In addition, quercetin another compound from C. citratus exhibited significant binding energies -6.8 and -8.3 kcal/mol with PfCSP and PfEMP1, respectively but slightly lower than the standard artemether-lumefantrine with binding energies of -7.4 kcal/mol against PfCSP and -8.7 kcal/mol against PfEMP1. Overall, the present study provides evidence that swertiajaponin and other phytomolecules from C. citratus have modulatory properties toward P. falciparum drug targets and thus may warrant further exploration in early drug discovery efforts against malaria. Furthermore, these findings lend credence to the folkloric use of C. citratus for malaria treatment.Communicated by Ramaswamy H. Sarma.

Nationwide surveillance identifies yellow fever and chikungunya viruses transmitted by various species of Aedes mosquitoes in Nigeria.

Background: Since its reemergence in 2017, yellow fever (YF) has been active in Nigeria. The Nigeria Centre for Disease Control (NCDC) has coordinated responses to the outbreaks with the support of the World Health Organization (WHO). The National Arbovirus and Vectors Research Centre (NAVRC) handles the vector component of these responses. This study sought to identify the vectors driving YF transmission and any of the targeted arboviruses and their distribution across states. Methods: Eggs, larvae and pupae as well as adult mosquitoes were collected in observational, analytical, and cross-sectional surveys conducted in sixteen YF outbreak states between 2017 and 2020. Adult mosquitoes (field-collected or reared from immature stages) were morphologically identified, and arboviruses were detected using RT-qPCR at the African Centre of Excellence for Genomics of Infectious Diseases (ACEGID). Results: Aedes mosquitoes were collected in eleven of the sixteen states surveyed and the mosquitoes in nine states were found infected with arboviruses. A total of seven Aedes species were collected from different parts of the country. Aedes aegypti was the most dominant (51%) species, whereas Aedes africanus was the least (0.2%). Yellow fever virus (YFV) was discovered in 33 (~26%) out of the 127 Aedes mosquito pools. In addition to YFV, the Chikungunya virus (CHIKV) was found in nine pools. Except for Ae. africanus, all the Aedes species tested positive for at least one arbovirus. YFV-positive pools were found in six (6) Aedes species while CHIKV-positive pools were only recorded in two Aedes species. Edo State had the most positive pools (16), while Nasarawa, Imo, and Anambra states had the least (1 positive pool). Breteau and house indices were higher than normal transmission thresholds in all but one state. Conclusion: In Nigeria, there is a substantial risk of arbovirus transmission by Aedes mosquitoes, with YFV posing the largest threat at the moment. This risk is heightened by the fact that YFV and CHIKV have been detected in vectors across outbreak locations. Hence, there is an urgent need to step up arbovirus surveillance and control activities in the country.

Metagenomic sequencing characterizes a wide diversity of viruses in field mosquito samples in Nigeria.

Mosquito vectors are a tremendous public health threat. One in six diseases worldwide is vector-borne transmitted mainly by mosquitoes. In the last couple of years, there have been active Yellow fever virus (YFV) outbreaks in many settings in Nigeria, and nationwide, entomological surveillance has been a significant effort geared towards understanding these outbreaks. In this study, we used a metagenomic sequencing approach to characterize viruses present in vector samples collected during various outbreaks of Yellow fever (YF) in Nigeria between 2017 and 2020. Mosquito samples were grouped into pools of 1 to 50 mosquitoes, each based on species, sex and location. Twenty-five pools of Aedes spp and one pool of Anopheles spp collected from nine states were sequenced and metagenomic analysis was carried out. We identified a wide diversity of viruses belonging to various families in this sample set. Seven different viruses detected included: Fako virus, Phasi Charoen-like virus, Verdadero virus, Chaq like-virus, Aedes aegypti totivirus, cell fusing agent virus and Tesano Aedes virus. Although there are no reports of these viruses being pathogenic, they are an understudied group in the same families and closely related to known pathogenic arboviruses. Our study highlights the power of next generation sequencing in identifying Insect specific viruses (ISVs), and provide insight into mosquito vectors virome in Nigeria.

Resistance status of Anopheles gambiae (s.l.) to four commonly used insecticides for malaria vector control in South-East Nigeria.

BACKGROUND: Progress made in the control of malaria vectors globally is largely due to the use of insecticides. However, success in the fight against malaria has slowed down or even stalled due to a host of factors including insecticide resistance. The greatest burden of the disease is felt in Africa, particularly Nigeria. Unfortunately, adequate information on insecticide resistance is lacking in many parts of the country, particularly the South-East Zone. Hence, this study aims to bridge the information gap in the Zone. METHODS: The study was conducted from April to December 2016. Anopheles gambiae (s.l.) larvae and pupae were collected from one community each, in the five states of the South-East Zone and reared to the adult stage. The adults were subjected to bioassays for insecticide resistance in accordance with the World Health Organization test procedures, across the four classes of insecticides used in public health. The mosquitoes were also subjected to molecular identification to the species level, and genotyped for West African knockdown resistance mutation (L1014F) and insensitive acetylcholinesterase-1 resistance mutation (G119S). RESULTS: The mosquitoes were susceptible (100%) to bendiocarb but resistant to pirimiphos-methyl (39.6%), deltamethrin (57%) and dichlorodiphenyltrichloroethane (DDT) (13%). Molecular analysis revealed that only An. gambiae (sensu stricto) was found in all the states except for Ebonyi, where only Anopheles coluzzii was present. High frequencies (0.6-0.9) of the L1014F mutation were found across the zone. The L1014F mutation was significantly higher in An. gambiae (s.s.) than in An. coluzzii (P < 0.0001). A relatively low frequency (0.2) of the G119S mutation was found in An. coluzzii, and only in Ebonyi State. CONCLUSION: The results show that mosquitoes collected from the South-East Zone of Nigeria were resistant to all insecticides used, except for bendiocarb. The presence of L1014F and G119S resistance mutations reported in this study calls for urgent attention to stop the growing threat of insecticide resistance in the country.