Beyond Lassa Fever: Systemic and structural barriers to disease detection and response in Sierra Leone

BackgroundLassa fever (LF) often presents clinically as undifferentiated febrile illness. Lassa Fever cases in Sierra Leone have been falling since the 2014–2016 Ebola epidemic. Data from other LF endemic countries suggest that this is not a true reflection of local epidemiological decline, but rather a function of either health seeking behaviour or the health/referral system. In Sierra Leone, many other diseases present with a similar early clinical picture, including COVID-19 and Marburg Disease (which has recently emerged in neighbouring Guinea). This empirical study explores the implementation of health system processes associated with International Health Regulations (IHR) requirements for early detection and timely and effective responses to the spread of febrile disease, through the case study of LF in Sierra Leone.Methodology/Principal findingsThis study used a qualitative approach to analyse local policy and guidance documents, key informant interviews with policy and practice actors, and focus group discussions and in-depth interviews with health care workers (HCWs) and community health workers (CHWs) in Kenema District to examine the ways in which undifferentiated fever surveillance and response policies and processes were implemented in the post-Ebola period. Multiple challenges were identified, including: issues with the LF case definition, approaches to differential diagnosis, specimen transport and the provision of results, and ownership of laboratory data. These issues lead to delays in diagnosis, and potentially worse outcomes for individual patients, as well as affecting the system’s ability to respond to outbreak-prone disease.Conclusions/SignificanceIdentification of ways to improve the system requires balancing vertical disease surveillance programmes against other population health needs. Therefore, health system challenges to early identification of LF specifically have implications for the effectiveness of the wider Integrated Disease Surveillance and Response (IDSR) system in Sierra Leone more generally. Sentinel surveillance or improved surveillance at maternity facilities would help improve viral haemorrhagic fever (VHF) surveillance, as well as knowledge of LF epidemiology. Strengthening surveillance for vertical disease programmes, if correctly targeted, could have downstream benefits for COVID-19 surveillance and response as well as the wider health system—and therefore patient outcomes more generally.     

Boosting understanding of Lassa Fever virus epidemiology: Field testing a novel assay to identify past Lassa Fever virus infection in blood and oral fluids of survivors and unexposed controls in Sierra Leone

BackgroundDespite identification 50 years ago, the true burden of Lassa Fever (LF) across Africa remains undefined for reasons including research focus on hospitalised patients, lack of validated field-feasible tools which reliably identify past infection, and the fact that all assays require blood samples making large-scale surveys difficult. Designated a priority pathogen of epidemic potential requiring urgent research by the World Health Organisation, a better understanding of LF sero-epidemiology is essential to developing and evaluating new interventions including vaccines. We describe the first field testing of a novel species-neutral Double Antigen Binding Assay (DABA) designed to detect antibodies to LF in plasma and oral fluid.Methodology/Principal findingsPaired plasma and oral fluid were collected in Sierra Leone from survivors discharged from Kenema Government Hospital Lassa Fever Unit between 1980 and 2018, and from controls recruited in Freetown in 2019. Epidemiological sensitivity and specificity of the DABA measured against historical diagnosis in survivors and self-declared non-exposed controls was 81.7% (95% CI 70.7%– 89.9%) and 83.3% (72.7%- 91.1%) respectively in plasma, and 71.8% (60.0%– 81.9%) and 83.3% (72.7%– 91.1%) respectively in oral fluid. Antibodies were identified in people infected up to 15 years and, in one case, 40 years previously. Participants found oral fluid collection easy and painless with 80% happy to give an oral fluid sample regularly.Conclusions/SignificanceGiven the difficulties of assay validation in a resource-limited setting, including unexpected exposures and diagnostics of varying accuracy, the new assay performed well in both plasma and oral fluid. Sensitivity and specificity are expected to be higher when case/control ascertainment is more definitive and further work is planned to investigate this. Even at the performance levels achieved, the species-neutral DABA has the potential to facilitate the large-scale seroprevalence surveys needed to underpin essential developments in LF control, as well as support zoonotic investigations.     

Haemonchosis in sheep and goats in Sierra Leone

The incidence of haemonchosis in sheep and goats in Sierra Leone showed a seasonal variation with a high peak in the dry season (October to January) and a low one from March to May. Mean relative densities were significantly higher in young hosts and showed two peaks, a high one from August to December and a low one from April to June while the mean relative densities of old hosts were low and exhibited an irregular seasonal pattern with no defined peaks. The peak seasons in young hosts coincided approximately with the dry and rainy seasons. Male hosts showed an overall higher but not a significant mean relative density than females but for most of the months mean relative densities of infection of female hosts were not significantly higher than those of males. The roles of climatic conditions and arrested development (hypobiosis) and self-cure and host age immunity on Haemonchus contortus worm burdens are discussed.     

T Cell-Dependence of Lassa Fever Pathogenesis

Lassa virus (LASV), the causative agent of Lassa fever (LF), is endemic in West Africa, accounting for substantial morbidity and mortality. In spite of ongoing research efforts, LF pathogenesis and mechanisms of LASV immune control remain poorly understood. While normal laboratory mice are resistant to LASV, we report that mice expressing humanized instead of murine MHC class I (MHC-I) failed to control LASV infection and develop severe LF. Infection of MHC-I knockout mice confirmed a key role for MHC-I-restricted T cell responses in controlling LASV. Intriguingly we found that T cell depletion in LASV-infected HHD mice prevented disease, irrespective of high-level viremia. Widespread activation of monocyte/macrophage lineage cells, manifest through inducible NO synthase expression, and elevated IL-12p40 serum levels indicated a systemic inflammatory condition. The absence of extensive monocyte/macrophage activation in T cell-depleted mice suggested that T cell responses contribute to deleterious innate inflammatory reactions and LF pathogenesis. Our observations in mice indicate a dual role for T cells, not only protecting from LASV, but also enhancing LF pathogenesis. The possibility of T cell-driven enhancement and immunopathogenesis should be given consideration in future LF vaccine development.     

Treatment of onchocerciasis with ivermectin in Sierra Leone

Ivermectin chemotherapy is proving to be a major advance in the management of onchocerciasis. In this article, James Whitworth reviews the work done on onchocerciasis and ivermectin in Sierra Leone and examines the evidence that mass treatment might control the clinical features of the disease and its transmission in West Africa. Ivermectin is safe and effectively reduces microfilarial (mf) loads, with major improvement in some ocular manifestations o f disease. This alone makes mass distribution to communities at risk of blindness worthwhile, even though the impact on other clinical features is less clear cut. Repeated doses have a cumulative effect on adult worms, which may cause more reduction in transmission than hitherto thought likely.     

Fungi associated with selected fermented foods in Sierra Leone

Summary The mycoflora of two popular fermented foodstuffs of Sierra Leone, ogi from maize (Zea mays L.) and foofoo from cassava (Manihot esculenta Crantz), were determined before, during and after fermentation. Maize kernels containedAspergillus flavus, A. ochraceus, A. tamarii andPenicillium citrinum. Aflatoxins B₁ and G₁ and ochratoxin A were extracted from these kernels. Fresh cassava tubers had no mycoflora but the stored fermented product, dry ball foofoo, containedA. flavus, A. ochraceus andP. citrinum. The participation of fungi in either fermentation process was not observed. Ogi and dry ball foofoo also contained trace amounts of aflatoxin G₁. In ogi, while the amount of ochratoxin A was much the same as on the maize kernels, significantly low amounts of aflatoxin B₁ were detected. In addition to the known mycotoxins, a number of unidentified fluorescent compounds were isolated only in maize and dry ball foofoo.

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Moisissures associées avec certains aliments fermentés au Sierra Leone

Résumé La mycoflore de deux aliments fermentés, populaires au Sierra Leone, l'ogi de maïs (Zea mays Linn) et le foofoo de manioc (Manihot esculenta Crantz) est déterminée avant, pendant et après fermentation. Les grains de maïs contiennentAspergellus flavus, A. ochraceus, A. tamarii etPernicillium citrinum. On a extrait les aflatoxines B₁ et G₁ ainsi que l'ochratoxine A de ces grains. Les tubercules frais de manioc n'ont pas de mycoflore mais le produit fermenté conservé, le foofoo dry ball, contientA. flavus, A. ochraceus etP. citrinum. La participation des moisissures n'a été observée dans aucun des deux processus de fermentation. L'ogi et le foofoo dry ball contiennent aussi des traces d'aflatoxine G₁. Dans l'ogi, la quantité d'ochratoxine A est quasi la même que dans les grains de maïs, tandis que l'aflatoxine B₁ est déteetée en quantité significativement moindre. En plus des mycotoxines connues, un certain nombre de composés fluorescents non-identifiés ont pu être isolés mais seulement du maïs et du foofoo dry ball.

     

Sulphur oxidation in tidal mangrove soils of Sierra Leone

Summary Tidal mangrove soil contained about 17-mg/g (oven-dry soil) of oxidisable sulphur, of which about 9 mg was insoluble in acetone. Samples showed considerable variability and this was shown to be due to the fact that decayed wood in the soil was heavily impregnated with oxidisable sulphur, a high proportion of which was insoluble in acetone. It is suggested that this proportion was the polysulphide fraction.When the soil was dried, its pH value fell to 3.0 to 2.4 due to the activity of sulphur-oxidising bacteria. When the pH value of the soil fell below 3 a rapid decline in the number of the organisms present occurred, and it is suggested that this was due to the increase in the availability of ferric iron which also occurred below this pH value.CaCO₃ had two main effects on sulphur oxidation; one on the sulphur-oxidising bacteria, increasing or decreasing sulphur oxidation according to whether the pH value was moved into or out of their range of activity, and an inhibitory effect on pyrites oxidation. The results indicate that the pyrites fraction was not oxidised above pH 3 and that it was not involved in acid-formation. It is suggested that pyrites oxidation under the experimental conditions was a chemical reaction possibly involving ferric ions.The possible application of the results to the reclamation of saline mangrove swamps is discussed.     

Risk Maps of Lassa Fever in West Africa

Background

Lassa fever is caused by a viral haemorrhagic arenavirus that affects two to three million people in West Africa, causing a mortality of between 5,000 and 10,000 each year. The natural reservoir of Lassa virus is the multi-mammate rat Mastomys natalensis, which lives in houses and surrounding fields. With the aim of gaining more information to control this disease, we here carry out a spatial analysis of Lassa fever data from human cases and infected rodent hosts covering the period 1965–2007. Information on contemporary environmental conditions (temperature, rainfall, vegetation) was derived from NASA Terra MODIS satellite sensor data and other sources and for elevation from the GTOPO30 surface for the region from Senegal to the Congo. All multi-temporal data were analysed using temporal Fourier techniques to generate images of means, amplitudes and phases which were used as the predictor variables in the models. In addition, meteorological rainfall data collected between 1951 and 1989 were used to generate a synoptic rainfall surface for the same region.

Methodology/Principal Findings

Three different analyses (models) are presented, one superimposing Lassa fever outbreaks on the mean rainfall surface (Model 1) and the other two using non-linear discriminant analytical techniques. Model 2 selected variables in a step-wise inclusive fashion, and Model 3 used an information-theoretic approach in which many different random combinations of 10 variables were fitted to the Lassa fever data. Three combinations of absence∶presence clusters were used in each of Models 2 and 3, the 2 absence∶1 presence cluster combination giving what appeared to be the best result. Model 1 showed that the recorded outbreaks of Lassa fever in human populations occurred in zones receiving between 1,500 and 3,000 mm rainfall annually. Rainfall, and to a much lesser extent temperature variables, were most strongly selected in both Models 2 and 3, and neither vegetation nor altitude seemed particularly important. Both Models 2 and 3 produced mean kappa values in excess of 0.91 (Model 2) or 0.86 (Model 3), making them ‘Excellent’.

Conclusion/Significance

The Lassa fever areas predicted by the models cover approximately 80% of each of Sierra Leone and Liberia, 50% of Guinea, 40% of Nigeria, 30% of each of Côte d''Ivoire, Togo and Benin, and 10% of Ghana.