By Chinenye Okeke
April 29th 2016
While the battle to end the Ebola epidemic raged on in Sierra Leone, Guinea and Liberia, another viral haemorrhagic fever, Lassa fever, was just beginning to take its roots in other parts of West Africa. Lassa fever (LF) is not new to this terrain and like Ebola has been around too long and probably ignored that long too. First described and isolated in a small town called Lassa in Borno (Northern) Nigeria, LF is a zoonotic disease caused by the single stranded negative sense RNA virus, Lassa fever virus of family Arenaviridae. Its vector, the multi-mammate rat Mastomys natalensis is widely distributed throughout the west African Region and lives in close contact with humans (1). In 2014, CDC estimated the yearly prevalence of LF cases to be between 300,000 to 500,000 cases resulting in about 5000 deaths across West Africa.(1) LF is endemic in most parts of West Africa with sporadic cases occurring in different countries every year. Studies have predicted approximately 80% of Liberia and Sierra Leone, 40 % of Nigeria, and 30% of Benin to be at risk of Lassa fever through spatial analysis(2). In Nigeria, approximately 4883 cases and 277 deaths have been reported from 2012 to date (3). Due to a paucity of data, the actual number of cases in other West African countries to date is still unknown. However, seroprevalence studies in the past have shown a prevalence of Lassa IgG antibodies in 8% to 52% in the general population in Sierra Leone and in Guinea, andas high as 25- 55% among inhabitants of tropical rain forest and 29-40% in hospital staff of Gueckedou and Lola Prefectures(4, 5).
LF has an incubation period of 6 to 21 days with a gradual onset of non-specific signs and symptoms such as fever, general weakness and malaise. As severity of the disease increases, symptoms such as facial swelling, bleeding from body orifices and low blood pressure manifests, eventually leading to complications including coma in its late stages. Deafness occurs in 25% of people who have LF and about half of these patients recover within 1-3 months (6). However, 80% of LF infections remain asymptomatic with a case fatality rate of 1% in the general population and 20% among hospitalised patients (1, 6). Given that LF is mild or asymptomatic in 80% of those infected, one possible explanation of a lower CFR in endemic regions is the probability of immunity conferred on long-term residents of endemic areas. In a recent study, IgG antibodies were detected 40 years after infection, suggesting the potential for long term immunity. (7).
Direct transmission from rodent to humans mainly occurs through inhalation of primary aerosols from infected rodent urine, ingestion of food contaminated with rodent excreta or by direct contact with broken skin. Human-to-human transmission occurs mainly via close contact with exposure to bodily fluids of infected persons or inhalation of aerosols generated from these bodily fluids, a common mode of transmission in health settings. Airborne transmission has also been observed between rodents (8). The recent case of secondary transmission of the virus to a mortician in Germany who reported only one close contact, and wearing a protective gear during preparation of the body of a LF deceased person, as well as a similar case in Katsina State, Nigeria brings the possibility of viral persistence in bodily fluids of deceased persons and the risk of LF transmission through handling of dead bodies(9-11). The persistence of LF virus in the semen during convalescence also suggests the probability of LF spread via sexual route. (12).
The two major outbreaks of LF occurred in 2016 in the two neighbouring West African countries of Nigeria and Benin Republic. Nigeria suffered a larger burden of LF in this recent outbreak and accounts for about 85% of all deaths recorded (a total of 585 suspected cases, 56 confirmed cases and 73 deaths recorded since disease onset in August 2015 (13). This seems a very high case fatality rate (30% of suspected cases and 58% of confirmed cases) compared to previously documented rates of 1-20%. However, it is uncertain if case ascertainment is complete, given conflicting reports from different sources reporting this outbreak and also the possibility of under-reporting, especially in remote rural areas. The recent imported case to Germany from Togo involving 2 healthcare workers (a physician assistant and a nurse) was the first outbreak outside of Africa. More recently a Swedish woman returned with LF from her travels in West Africa, suggesting that there may be unreported cases of LF in other West African countries which only become evident after contacts become ill overseas (14). Gaps in the health care systems in these countries have contributed to rapid spread of disease and have amplified these outbreaks. These gaps include inadequate surveillance systems and delay in diagnosis of most LF cases which can in turn reflect low diagnostic capacity. In Nigeria, for example; although a press statement reports 5 LF diagnostic centres, it appears only one – the Irrua Specialist Hospital, Edo State may be functional as most serology samples are transported to this diagnostic centre for confirmatory tests, including samples from neighbouring Benin Republic which has no existing LF diagnostic facilities at this time. Even with 5 functional laboratories, the laboratory capacity of Nigeria will still be much lower than required to control the outbreak given its large population size (over 140 million) and the endemicity of Lassa in Nigeria. The situation in neighbouring Benin Republic is far worse, with no specialist diagnostic centres for LF.
Nosocomial outbreaks of LF are commonplace in LF endemic countries and played a major role in this year’s outbreak. In Nigeria, the 2016 LF outbreak has been estimated to have an overall case fatality rate of 48% and 60% in confirmed cases (15), however, the case fatality rate in healthcare workers is yet to be estimated due to a dearth of data on actual number of LF cases reported among health care workers to date. The recent outbreak in Benin also was first identified among a cluster of health workers who attended to the index case (a pregnant woman with a probable history of travel). Causes of exposure in hospitals have been attributed to inadequately equipped and staffed facilities with poor medical practices. This situation can be compared to the Ebola outbreak, with a similarly high attack rate in hospital settings and isolation centres, which fuelled the spread of the virus. A well-functioning health system may significantly improve epidemic control efforts.
In the past, there has been a few exported cases of LF from endemic regions to developed countries, but until 2016, there had not been any recorded local transmissions in any of the countries to which LF cases had been imported. The case of a mortician in Germany involved in the preparation of the body of the deceased (the index case), who despite limited contact with the corpse and infection control measures such as wearing of gloves , was sero-positive for LF, is the first local transmission reported outside the African continent (16).
The 2016 LF outbreak far exceeds the previous years in numbers and spread (see Fig. 1 below). In Nigeria, the reported cases and deaths stands at a total of 585 and 73 respectively as at week 14 of the outbreak, exceeding the estimated number of cases and deaths within the same period in 2013 (232 cases, 15 deaths in 9 states), 2014 (208 cases, 17 deaths in 12 states, and 2015( 87 cases, 3 deaths) (17-20). The recent outbreak in Benin, the second ever in its history, recorded a total of 71 cases (6 confirmed, 10 probable and 55 suspected) reported from seven departments over a period of 2 weeks (4) compared to the first outbreak in 2014 which ended in January, 2015 with only 16 cases and 9 fatalities reported in one Department. The pattern of spread suggests person-to-person transmission rather than sporadic cases. It is however uncertain if the higher mortality and disease incidence is a function of a more virulent circulating strain of LFV or of inaccurate surveillance data. Politics may also be playing a role in the underreporting of cases, as the outbreak occurred during the period of Presidential elections of March 6 in Benin - a common scenario in most of the Endemic countries, where these outbreaks are seen by politicians as a source of embarrassment to their Government. This compounds the problem of underreporting of cases already faced by most African countries, hence the true burden, severity or consequences of an outbreak are difficult to gauge.
While there is no known vaccine for Lassa fever, early supportive care and treatment with Ribavirin, a guanosine analogue usually given 800mg stat, then 400mg twice per day has been found to improve disease outcome. Treatment with intravenous ribavirin within the first 6 day of illness can greatly improve the prognosis of cases (21). Prevention efforts include isolation of cases, implementing infection control measures such as barrier nursing techniques, rodent control and practicing adequate food hygiene (storing grain and other foodstuffs in rodent –proof containers) and personal hygiene. Although treatment for Lassa fever is available, early diagnosis still remains a challenge in most Nigerian hospitals (22). Delays in reporting cases leads to poor prognosis as Ribavirin, the drug of choice for Lassa fever treatment is more effective early in the disease. Due to the non-specificity of the symptoms observed in LF, it can be mistaken for other endemic fevers such as malaria. Clinical diagnosis presents a challenge to clinicians; hence trial and error methods of differentials before diagnosis may result in delay in diagnosis, treatment and infection control.
The apparently higher risk of infection through human- to human transmission than previously estimated, and the role of nosocomial spread in the recent outbreak points out the need for a change in strategy from rodent control to more focused interventions at reducing human to human transmission in health and non- health settings . A study reviewing the cases of nosocomial outbreaks in Nigeria revealed that parenteral drug rounds with sharing of syringes conducted by minimally educated and poorly supervised staff fuelled previous epidemics, with attack rates in patients in one hospital as high as 55%(23). This highlights the need of educating health care workers in these countries on appropriate triaging skills and infection control methods to reduce the risk of nosocomial spread and also spread to non-endemic regions. This may also necessitate a review of the country’s infection control guidelines in health care settings and guidelines for handling corpses in funeral homes. Early diagnosis, treatment and infection control remains the mainstay of control efforts and can drastically reduce both the incidence and high mortality rates of Lassa fever in endemic countries.
Chinenye Okeke is currently an intern at the Integrated Systems for Epidemic Response (ISER), School of Public Health and Community Medicine (SPHCM) , UNSW and is studying for a Masters in International Public Health/ Health Management at SPHCM, UNSW.
She graduated as a pharmacist in 2011 from Madonna University, Nigeria and has worked for 2 years as a Pharmacist both in Community Practice and in the Infectious Disease Hospital, Zambuk Gombe State. Her interests include- Infectious Diseases, Neglected tropical disease, Vaccines and Drug development .
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