Viral hemorrhagic fevers (VHFs) refer to a group of illnesses that are caused by several distinct families of viruses: arenaviruses, filoviruses, Bunyaviruses and Flaviviruses. These viruses share a number of features:

• they are all enveloped RNA viruses

• their survival is dependent on an animal or insect host (natural reservoir).

• humans are not the natural reservoir but are infected when they come into contact with infected hosts

• after transmission from the animal host,humans can transmit the virus to one another

• outbreaks occur sporadically and irregularly and

with a few exceptions, there is no cure or established drug treatment for VHFs1,2, 3,4. In

Nigeria, VHFs of concern include Lassa fever, Ebola, Dengue fever and Yellow fever.

Dengue and Yellow fever viruses are mosquito-borne of the family Flaviridae. Globally, 2.5 billion individuals at risk are at risk of Dengue fever (DENV), with 40-80 million infected each year causing thousands of deaths5. Evidence shows that the four serotypes of DENV (1-4) exist in Africa; antibody prevalence of 38% for DENV-, 45% for DENV-2 and 10% for DENV-3 infections have been documented in northern Nigeria6–8. Increase in prevalence of antibodies against DENV with age has also been detected, suggesting endemicity7. Dengue infection is asymptomatic in >80% of cases while its haemorrhagic form occurs in about 5 % of cases9. Regarding yellow fever infections, 200,000 cases of yellow fever with about 30,000 deaths are reported annually in Africa and America10.Nigeria is one of 12 countries with large non-immune populations at high risk of a yellow fever,due to low vaccine coverages especially among children under 14 years old11.

Lassa fever infection is caused by Arenavirus and is the most exported VHF. Lassa fever is endemic in parts of West Africa; it is responsible for an estimated 300,000 – 500,000 infections annually, with 5,000 deaths4. In Nigeria, Lassa virus antibody levels of up to 21% have been reported12. The Ebola virus is of the genus Filoviridae. Recent widespread outbreaks of the Ebola virus have occurred, involving several countries including Nigeria. The largest of such outbreak occurred between 2014 and 2015; 28,646 Ebola cases were reported with 11,323 deaths as of March 2016 (8 deaths in Nigeria)13.

• Animal/vector to human

Lassa fever infection has a rodent reservoir; Mastomys species (“multimammate rat”). Ebola infection have been linked to infections from monkey and “bush meat”. Spread occurs when following ingestion of food contaminated with bodily fluids, direct consumption or bite; or through aerosol inhalation of excretions in air. Dengue and Yellow fever infections are arboviruses transmitted by Aedesspp mosquito. Aedes mosquito is a daytime biting mosquito, which breeds in stagnant water usually stored in used automobile tires.

• Human-to-human

Ebola and Lassa fever viruses are transmitted in several ways via direct contact with the blood and/or secretions of an infected person or, following contact with objects, such as needles, that have been contaminated with infected secretions.

Dengue and Yellow fever viruses are also transmissible via blood transfusions but not via secretions or direct blood contact.

Incubation period

Incubation periods vary for different VHFs: it ranges from 4 to 10 days for Dengue fever infection and 2 to 21 days for Ebola fever. Lassa fever IP ranges 6 to 21 days. For Yellow fever, the intrinsic phase of the infection ranges 3to 6 dayswhile the extrinsic phase ranges from 1to 2 weeks.

• Acute febrile illnesses characterized by fever, headache, chills, musculoskeletal pain, malaise, abdominal pains, rash, purpura, nausea, vomiting, conjuctivitisetc.

• Sometimes accompanied by bleeding manifestations e.g.bleeding from the gums, nose or in the stool, hematuria.

• Yellow fever cases in the toxic phase often present with jaundice.

• Signs include lymphadenopathy, leucopaenia, thrombocytopaenia, positive tourniquet test, hepatomegaly, splenomagaly, petechiae, ecchymosis, capillary permeability etc.

• The estimated case fatality rate for VHF is as high as 50% for severe cases

• Isolation of virus (PCR).

• Presence of specific IgM (ELISA).

• Detection of VHF antigens in tissues by immunochemistry.

• Virus isolation.

• Mainstay is supportive e.g. antipyretics for fever, replace fluids due to capillary hyper-permeability states, treat dehydration and fever, avoid shock and metabolic acidosis

• Ribavirin: it is indicated for post-exposure prophylaxis and treatment of Lassa fever. Its efficacy is demonstrated if given during the first 6 days of illness. However, it is used with caution in pregnant women.

• Vaccination for yellow fever: Health facilities should be supported during routine childhood immunization schedule and immunization supplies should be made available for routine yellow fever activities. Mass vaccination campaigns should be conducted during epidemics.

• Case-based surveillance and management: Analyze data for trends; investigate mild febrile illnesses and unexplained deaths that suggest VHF outbreaks.Ensure that personnel at health facilities in the district know how to identify suspected cases of VHF and that health facilities use a standard case definition for reporting.Report to the nearest local health authority immediately. All cases should be reported as universally required by IHR (2005). Place all suspected cases in isolation (dedicated wards) and health workers should take Infection Prevention and Control measures (use of PPEs, handwashingetc). Cases should be ccounselled not to engage in sexual intercourse for 2 months following treatment for Lassa fever and Ebola. Safe burial practices should be ensured.

• Vector control: Living quarters should be sprayed with residual insecticide and insecticide-treated bednets’ use intensified. Stagnant waters around the house should be emptied and potential mosquito breeding sites eliminated by applying larvicides.Entomological surveillance is important in tracking vectors of arboviral VHFs. Rodent populations should be controlled. Homes should have screen guards and food supplies stored in rodent-proof containers.

• Points of entry: Standard Operating Procedures for VHF screening at points of entry should be available. Persons arriving from countries with confirmed VHF outbreaks should be screened for symptoms consistent with VHF case definition. Safe and secure holding areas with capacity for temporarily quarantine must be available. Aerosol spraying of prescribed insecticides of aircrafts and ships arriving from arboviral VHF endemic areas should be intensified and kept free from breeding of insect vectors (at least 400 meters around their perimeters).

References

1. Center for Disease Control and Prevention. Viral Hemorrhagic Fevers Fact Sheet [Internet]. Available from: http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/Fact_Sheets/Viral_Hemorrhagic_Fevers_Fact_Sheet.pdf

2. GOV.UK. VHFs in Africa: areas of known risk [Internet]. 2014. Available from: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/365845/VHF_Africa_960_640.png

3. Chakrabarti D, Banik S. Viral hemorrhagic fever. Med Updat. 2012;22:54–8.

4. GOV.UK. Lassa fever: origins, reservoirs, transmission and guidelines [Internet]. Guidance. 2014 [cited 2015 Aug 11]. p. 8–12. Available from: https://www.gov.uk/lassa-fever-origins-reservoirs-transmission-and-guidelines

5. World Health Organization. Dengue and severe dengue [Internet]. Media Center. 2014. p. 4–7. Available from: http://www.who.int/mediacentre/factsheets/fs117/en/

6. Adekolu-John E, Fagbami A. Arthropod-borne virus antibodies in sera of residents of Kainji Lake Basin, Nigeria 1980. Trans R Soc Trop Med Hyg. 1983;77(2):149–51.

7. Fagbami AH, Monath TP, Fabiyi A. Dengue virus infections in Nigeria: a survey for antibodies in monkeys and humans. Trans R Soc Trop Med Hyg. 1977;71(1):60–5.

8. Idris AN, Baba MM, Thairu Y, Bamidele O. Sero-prevalence of dengue type-3 Virus among patients with febrile illnesses attending a tertiary hospital in Maiduguri, Nigeria. Int J Med. 2013;5(December):560–3.

9. Heilman JM, De Wolff J, Beards GM, Basden BJ. Dengue fever: A Wikipedia clinical review. Open Med. 2014;8(4):e105–15.

10. Robertson SE, Hull BP, Tomori O, Bele O, LeDuc JW, Esteves K. Yellow fever: a decade of reemergence. JAMA [Internet]. 1996;276(14):1157–62. Available from: http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med4&AN=8827969 http://digitaal.uba.uva.nl:9003/uva-linker?sid=OVID:medline&id=pmid:8827969&id=doi:&issn=0098-7484&isbn=&volume=276&issue=14&spage=1157&pages=1157-62&date=1996&title=JAMA

11. World Health Organization. Increased risk of urban yellow fever outbreaks in Africa [Internet]. Emergencies preparedness, response. 2016 [cited 2016 Sep 14]. p. 1–4. Available from: http://www.who.int/csr/disease/yellowfev/urbanoutbreaks/en/

12. Tomori O, Fabiyi A, Sorungbe A, Smith A, McCormick J. Viral Hemorrhagic Fever Antibodies in Nigerian Populations. Am J Trop Med Hyg. 1988;38(2):407–10.

13. World Health Organization. Ebola Situation Report [Internet]. Ebola - Current Situation. 2016. p. 2. Available from: http://apps.who.int/ebola/current-situation/ebola-situation-report-30-march-2016