Despite the notoriety of Ebola virus disease (EVD) as one of the world’s most deadly infections, EVD has a wide range of outcomes, where asymptomatic infection may be almost as common as fatality. With increasingly sensitive EVD diagnosis, there is a need for more accurate prognostic tools that objectively stratify clinical severity to better allocate limited resources and identify those most in need of intensive treatment. This retrospective cohort study analyses the clinical characteristics of 158 EVD(+) patients at the GOAL-Mathaska Ebola Treatment Centre, Sierra Leone. The prognostic potential of each characteristic was assessed and incorporated into a statistically weighted disease score. The mortality rate among EVD(+) patients was 60.8% and highest in those aged 25 years (p<0.05). Death was significantly associated with malaria co-infection (OR = 2.5, p = 0.01). However, this observation was abrogated after adjustment to Ebola viral load (p = 0.1), potentially indicating a pathologic synergy between the infections. Similarly, referral-time interacted with viral load, and adjustment revealed referral-time as a significant determinant of mortality, thus quantifying the benefits of early reporting as a 12% mortality risk reduction per day (p = 0.012). Disorientation was the strongest unadjusted predictor of death (OR = 13.1, p = 0.014) followed by hiccups, diarrhoea, conjunctivitis, dyspnoea and myalgia. Including these characteristics in multivariate prognostic scores, we obtained a 91% and 97% ability to discriminate death at or after triage respectively (area under ROC curve). This study proposes highly predictive and easy-to-use prognostic tools, which stratify the risk of EVD mortality at or after EVD triage. The unprecedented spread of EVD across the fragile healthcare systems of West Africa during the 2013–2015 outbreak infected over 28,600 patients and established it as a disease for which low-income countries are at disproportionate risk. In order to improve the standard of patient care, it is essential to better allocate scarce resources amongst the heterogeneous symptomatic presentations of EVD. This retrospective cohort study on 158 EVD(+) patients in Sierra Leone constructs 2 easy-to-use scoring systems that accurately stratify EVD severity and thus objectively identify the patients in most need of intensive therapy. Using statistically weighted symptoms and demographic characteristics, we obtained scores with a 91% and 97% ability to discriminate death at or after triage respectively. These scores included Ebola viral load, patient age and referral time as well as the symptoms of disorientation, haemorrhage and myalgia. Further univariate analysis revealed several independent predictors of mortality, where patients aged between 5 and 25 years were most likely to survive, while malaria co-infection increased the risk of death by 2.5-fold (p = 0.01). Correcting referral-time for viral load, we also quantify the benefits of early reporting as a 12% mortality risk reduction per day (p = 0.012). Mortality in this cohort was 3-fold more than patients treated in resource-rich settings (60.8% vs. 18%) and we propose that focused patient care is a feasible and low-cost effort that may begin to close this gap.

Wolbachia infection in Anopheles albimanus mosquitoes can render mosquitoes less capable of spreading malaria. We developed and analyzed a mechanistic compartmental ordinary differential equation model to evaluate the effectiveness of Wolbachia-based vector control strategies among wild Anopheles mosquitoes in Haiti. The model tracks the mosquito life stages, including egg, larva, and adult (male and female). It also accounts for critical biological effects, such as the maternal transmission of Wolbachia through infected females and cytoplasmic incompatibility, which effectively sterilizes uninfected females when they mate with infected males. We derive and interpret dimensionless numbers, including the basic reproductive number and next-generation numbers. The proposed system presents a backward bifurcation, which indicates a threshold infection that needs to be exceeded to establish a stable Wolbachia infection. The sensitivity analysis ranks the relative importance of the epidemiological parameters at baseline. We simulate different intervention scenarios, including prerelease mitigation using larviciding and thermal fogging before the release, multiple releases of infected populations, and different release times of the year. Our simulations show that the most efficient approach to establishing Wolbachia is to release all the infected mosquitoes immediately after the prerelease mitigation process. Moreover, the model predicts that it is more efficient to release during the dry season than the wet season.

The non-specific symptoms of Ebola Virus Disease (EVD) pose a major problem to triage and isolation efforts at Ebola Treatment Centres (ETCs). Under the current triage protocol, half the patients allocated to high-risk “probable” wards were EVD(-): a misclassification speculated to predispose nosocomial EVD infection. A better understanding of the statistical relevance of individual triage symptoms is essential in resource-poor settings where rapid, laboratory-confirmed diagnostics are often unavailable. This retrospective cohort study analyses the clinical characteristics of 566 patients admitted to the GOAL-Mathaska ETC in Sierra Leone. The diagnostic potential of each characteristic was assessed by multivariate analysis and incorporated into a statistically weighted predictive score, designed to detect EVD as well as discriminate malaria. Of the 566 patients, 28% were EVD(+) and 35% were malaria(+). Malaria was 2-fold more common in EVD(-) patients (p<0.05), and thus an important differential diagnosis. Univariate analyses comparing EVD(+) vs. EVD(-) and EVD(+)/malaria(-) vs. EVD(-)/malaria(+) cohorts revealed 7 characteristics with the highest odds for EVD infection, namely: reported sick-contact, conjunctivitis, diarrhoea, referral-time of 4–9 days, pyrexia, dysphagia and haemorrhage. Oppositely, myalgia was more predictive of EVD(-) or EVD(-)/malaria(+). Including these 8 characteristics in a triage score, we obtained an 89% ability to discriminate EVD(+) from either EVD(-) or EVD(-)/malaria(+). This study proposes a highly predictive and easy-to-use triage tool, which stratifies the risk of EVD infection with 89% discriminative power for both EVD(-) and EVD(-)/malaria(+) differential diagnoses. Improved triage could preserve resources by identifying those in need of more specific differential diagnostics as well as bolster infection prevention/control measures by better compartmentalizing the risk of nosocomial infection. Four decades after the discovery of Ebola virus disease (EVD), the sources, reservoirs and dynamics of infection are still largely unknown and thus the threat of re-emergence remains ever present. As EVD thrives on fragile healthcare systems in the developing world, it is essential that triage tools are low-cost and easy-to-use in order to best allocate limited resources and ensure sustainability of EVD surveillance. From a public health perspective, sensitivity is paramount when screening for highly contagious and fatal diseases such as Ebola. However, once these suspect patients arrive at the treatment centres, specificity becomes far more important in order to accurately allocate them to risk-appropriate wards and better distribute limited resources. Currently, pre-test triage to identify “suspect” Ebola patients consists of a binary evaluation of non-specific symptoms that are shared by the much more prevalent disease: Malaria. Using these guidelines, over 70% of patients selected for admission to the potentially contagious environment of an ETC did not have Ebola. Within the ETC, patients may be further triaged into a higher risk “probable” ward on the basis of a clinically subjective assessment known as the “Ebola look”: since proven to have comparable accuracy to flipping a coin. While compartmentalising risk by stratification is an essential component to infection prevention and control measures, patient triage should be sufficiently accurate to justify to its benefit. This study constructs an easy-to-use and highly accurate (90%) triage scoring system that discriminates EVD infection risk in a malaria-sensitive manner: a strategy, which not only significantly improves the predictive accuracy for EVD but may also identify the (more deadly) infection of malaria.

Background: The use of data in targeting malaria control efforts is essential for optimal use of resources. This work provides a practical mechanism for prioritizing geographic areas for insecticide-treated net (ITN) distribution campaigns in settings with limited resources.Methods: A GIS-based weighted approach was adopted to categorize and rank administrative units based on data that can be applied in various country contexts wherePlasmodium falciparumtransmission is reported. Malaria intervention and risk factors were used to rank local government areas (LGAs) in Nigeria for prioritization during mass ITN distribution campaigns. Each factor was assigned a unique weight that was obtained through application of the analytic hierarchy process (AHP). The weight was then multiplied by a value based on natural groupings inherent in the data, or the presence or absence of a given intervention. Risk scores for each factor were then summated to generate a composite unique risk score for each LGA. This risk score was translated into a prioritization map which ranks each LGA from low to high priority in terms of timing of ITN distributions.Results: A case study using data from Nigeria showed that a major component that influenced the prioritization scheme was ITN access. Sensitivity analysis results indicate that changes to the methodology used to quantify ITN access did not modify outputs substantially. Some 120 LGAs were categorized as ‘extremely high’ or ‘high’ priority when a spatially interpolated ITN access layer was used. When prioritization scores were calculated using DHS-reported state level ITN access, 108 (90.0%) of the 120 LGAs were also categorized as being extremely high or high priority. The geospatial heterogeneity found among input risk factors suggests that a range of variables and covariates should be considered when using data to inform ITN distributions.Conclusion: The authors provide a tool for prioritizing regions in terms of timing of ITN distributions. It serves as a base upon which a wider range of vector control interventions could be targeted. Its value added can be found in its potential for application in multiple country contexts, expediated timeframe for producing outputs, and its use of systematically collected malaria indicators in informing prioritization.

For a malaria elimination strategy, Haiti’s National Malaria Control Program piloted a mass drug administration (MDA) with indoor residual spraying (IRS) in 12 high-transmission areas across five communes after implementing community case management and strengthened surveillance. The MDA distributed sulfadoxine–pyrimethamine and single low-dose primaquine to eligible residents during house visits. The IRS campaign applied pirimiphos–methyl insecticide on walls of eligible houses. Pre- and post-campaign cross-sectional surveys were conducted to assess acceptability, feasibility, drug safety, and effectiveness of the combined interventions. Stated acceptability for MDA before the campaign was 99.2%; MDA coverage estimated at 10 weeks post-campaign was 89.6%. Similarly, stated acceptability of IRS at baseline was 99.9%; however, household IRS coverage was 48.9% because of the high number of ineligible houses. Effectiveness measured by Plasmodium falciparum prevalence at baseline and 10 weeks post-campaign were similar: 1.31% versus 1.43%, respectively. Prevalence of serological markers were similar at 10 weeks post-campaign compared with baseline, and increased at 6 months. No severe adverse events associated with the MDA were identified in the pilot; there were severe adverse events in a separate, subsequent campaign. Both MDA and IRS are acceptable and feasible interventions in Haiti. Although a significant impact of a single round of MDA/IRS on malaria transmission was not found using a standard pre- and post-intervention comparison, it is possible there was blunting of the peak transmission. Seasonal malaria transmission patterns, suboptimal IRS coverage, and low baseline parasitemia may have limited the effectiveness or the ability to measure effectiveness.