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Transmission assessment surveys (TAS) for lymphatic filariasis have been proposed as a platform to assess the impact of mass drug administration (MDA) on soil-transmitted helminths (STHs). This study used computer simulation and field data from pre- and post-MDA settings across Kenya to evaluate the performance and cost-effectiveness of the TAS design for STH assessment compared with alternative survey designs. Variations in the TAS design and different sample sizes and diagnostic methods were also evaluated. The district-level TAS design correctly classified more districts compared with standard STH designs in pre-MDA settings. Aggregating districts into larger evaluation units in a TAS design decreased performance, whereas age group sampled and sample size had minimal impact. The low diagnostic sensitivity of Kato-Katz and mini-FLOTAC methods was found to increase misclassification. We recommend using a district-level TAS among children 8–10 years of age to assess STH but suggest that key consideration is given to evaluation unit size.

Cross-reactions observed in serological assays between Usutu virus (USUV), the USUV outlier subtype strain CAR_1969 and West Nile virus (WNV) suggest that they share antigenic features amongst their structural outer proteins especially envelope (E) proteins. To investigate the molecular background of this observation, we compared the E protein sequences of seven USUV strains, USUV subtype strain CAR_1969 and WNV strain 2471, focusing on the binding site defined by the WNV neutralizing antibody E16. USUV SouthAfrica_1959 differs from WNV 2741 in three of four residues critical for E16 antibody binding and five of the 12 additionally involved residues. In contrast, USUV subtype CAR_1969 differs from WNV 2741 in two critical residues and five additional residues. Furthermore, USUV subtype CAR_1969 differs from other USUV strains in two critical residues. E16 antibody binding has previously been shown to be highly specific for WNV; thus, the observed variation in amino acid residues suggests that the region corresponding to the WNV E16 epitope is probably not responsible for the observed cross-reactions between WNV and USUV. Seroneutralisation assays confirmed these findings for WNV and USUV, however, showed occurring cross-reactivity between WNV and USUV subtype CAR_1969 at high antibody titers. The sequence diversity in this region might also explain some of the observed different antigenic characteristics of USUV strains and USUV subtype CAR_1969. A therapeutic effect of E16 antibody has been described in WNV infected mice; therefore, a USUV specific antibody generated against the region corresponding to the WNV E16 binding site might represent an approach for treating USUV infections.

Usutu virus (USUV), a flavivirus belonging to the Japanese encephalitis serocomplex, was isolated for the first time from a Culex neavei mosquito in 1959 in South Africa. Despite multiple isolations of USUV from Cx. neavei in Africa, its vector competence remains unproven. Therefore, we infected Cx. neavei orally with the USUV reference strain and used reverse transcription-polymerase chain reaction and an indirect immunofluorescence assay to detect virus in bodies, legs, wings, and saliva of mosquitoes. We demonstrated the susceptibility of Cx. neavei mosquitoes for the USUV reference strain, its potential to be transmitted, and infection, dissemination, and transmission rates of 90.9%, 40.0%, and 81.3%, respectively. Also, we showed that infection rates are dependent on the virus titer of the blood meal. Given the bionomics of Cx. neavei, its role as enzootic vector for USUV in Africa in a mosquito-bird transmission cycle or as bridge vector for USUV transmission to humans is discussed.

Background Usutu virus (USUV), a flavivirus belonging to the Japanese encephalitis serocomplex, was identified in South Africa in 1959 and reported for the first time in Europe in 2001. To date, full length genome sequences have been available only for the reference strain from South Africa and a single isolate from each of Austria, Hungary, and Italy. Methods We sequenced four USUV isolates from Senegal and the Central African Republic (CAR) between 1974 and 2007 and compared the sequence data to USUV strains from Austria, Hungary, Italy, and South Africa using a Bayesian Markov chain Monte Carlo method. We further clarified the taxonomic status of a USUV strain isolated in CAR in 1969 and proposed earlier as a subtype of USUV due to an asymetric serological cross-reactivity with USUV reference strain. Results A comparison of the four newly obtained USUV sequences with those from SouthAfrica_1959, Vienna_2001, Budapest_2005, and Italy_2009 revealed that they are all 96-99% and 99% similar at the nucleotide and amino acid levels, respectively. The phylogenetic relationships between these sequences indicated that a strain isolated in Senegal in 1993 is most closely related to the USUV strains detected in Europe. Analysis of a strain isolated from a human in CAR in 1981 (CAR_1981) revealed the presence of specific amino acid substitutions and a deletion in the 3′ noncoding region. This is the first fully sequenced human USUV isolate. The putative USUV subtype, CAR_1969, was 81% and 94% identical at the nucleotide and amino acid levels, respectively, compared to the other USUV strains. Our phylogenetic analyses support the serological identification of CAR_1969 as a subtype of USUV. Conclusions In this study, we investigate the genetic diversity of USUV in Africa and the phylogenetic relationship of isolates from Africa and Europe for the first time. The results suggest a low genetic diversity within USUV, the existence of a distinct USUV subtype strain, and support the hypothesis that USUV was introduced to Europe from Africa. Further sequencing and analysis of USUV isolates from other African countries would contribute to a better understanding of its genetic diversity and geographic distribution.

Summary Background Emphasis is being given to the control of neglected tropical diseases, including the possibility of interrupting the transmission of soil-transmitted helminths (STH). We evaluated the feasibility by country of achieving interruption of the transmission of STH. Methods Based on a conceptual framework for the identification of the characteristics of a successful STH control programme, we assembled spatial data for a range of epidemiological, institutional, economic, and political factors. Using four different statistical methods, we developed a composite score of the feasibility of interrupting STH transmission and undertook a sensitivity analysis of the data and methods. Findings The most important determining factors in the analysis were underlying intensity of STH transmission, current implementation of control programmes for neglected tropical diseases, and whether countries receive large-scale external funding and have strong health systems. The composite scores suggested that interrupting STH transmission is most feasible in countries in the Americas and parts of Asia (eg, Argentina [range of composite feasibility scores, depending on scoring method, 9·4–10·0], Brazil [8·7– 9·7], Chile [8·84–10·0], and Thailand [9·1–10·0]; there was perfect agreement between the four methods), and least feasible in countries in sub-Saharan Africa (eg, Congo [0·4–2·7] and Guinea [2·0–5·6]; there was full agreement between methods), but there were important exceptions to these trends (eg, Ghana [7·4–10·0]; there was agreement between three methods). Agreement was highest between the scores derived with the expert opinion and principal component analysis weighting schemes (Pearson correlation coefficient, r =0·98). The largest disagreement was between benefit-of-the-doubt-derived and principal-component-analysis-derived weighting schemes ( r =0·74). Interpretation The interruption of STH transmission is feasible, especially in countries with low intensity of transmission, supportive household environments, strong health systems, and the availability of suitable delivery platforms and in-country funds, but to achieve local elimination of STH an intersectoral approach to STH control will be needed. Funding Bill & Melinda Gates Foundation and Wellcome Trust.

Highlights • A Bayesian latent class meta-analysis of diagnostic tests for soil-transmitted helminths was performed. • Overall sensitivity of evaluated diagnostic tests was low. • Test performance was strongly influenced by intensity of infection. • FLOTAC method sensitivity was highest overall and in both intensity groups. • The performance of the Kato-Katz method in high intensity settings was acceptable., Reliable, sensitive and practical diagnostic tests are an essential tool in disease control programmes for mapping, impact evaluation and surveillance. To provide a robust global assessment of the relative performance of available diagnostic tools for the detection of soil-transmitted helminths, we conducted a meta-analysis comparing the sensitivities and the quantitative performance of the most commonly used copro-microscopic diagnostic methods for soil-transmitted helminths, namely Kato-Katz, direct microscopy, formol-ether concentration, McMaster, FLOTAC and Mini-FLOTAC. In the absence of a perfect reference standard, we employed a Bayesian latent class analysis to estimate the true, unobserved sensitivity of compared diagnostic tests for each of the soil-transmitted helminth species Ascaris lumbricoides, Trichuris trichiura and the hookworms. To investigate the influence of varying transmission settings we subsequently stratified the analysis by intensity of infection. Overall, sensitivity estimates varied between the different methods, ranging from 42.8% for direct microscopy to 92.7% for FLOTAC. The widely used double slide Kato-Katz method had a sensitivity of 74–95% for the three soil-transmitted helminth species at high infection intensity, however sensitivity dropped to 53–80% in low intensity settings, being lowest for hookworm and A. lumbricoides. The highest sensitivity, overall and in both intensity groups, was observed for the FLOTAC method, whereas the sensitivity of the Mini-FLOTAC method was comparable with the Kato-Katz method. FLOTAC average egg count estimates were significantly lower compared with Kato-Katz, while the compared McMaster counts varied. In conclusion, we demonstrate that the Kato-Katz and Mini-FLOTAC methods had comparable sensitivities. We further show that test sensitivity of the Kato-Katz method is reduced in low transmission settings.

Fiji recently experienced a sharp increase in reported typhoid fever cases. To investigate geographic distribution and environmental risk factors associated with Salmonella enterica serovar Typhi infection, we conducted a cross-sectional cluster survey with associated serologic testing for Vi capsular antigen-specific antibodies (a marker for exposure to Salmonella Typhi in Fiji in 2013. Hotspots with high seroprevalence of Vi-specific antibodies were identified in northeastern mainland Fiji. Risk for Vi seropositivity increased with increased annual rainfall (odds ratio [OR] 1.26/quintile increase, 95% CI 1.12-1.42), and decreased with increased distance from major rivers and creeks (OR 0.89/km increase, 95% CI 0.80-0.99) and distance to modeled flood-risk areas (OR 0.80/quintile increase, 95% CI 0.69-0.92) after being adjusted for age, typhoid fever vaccination, and home toilet type. Risk for exposure to Salmonella Typhi and its spatial distribution in Fiji are driven by environmental factors. Our findings can directly affect typhoid fever control efforts in Fiji.

Background In 2012, the Kenyan Ministries of Health and of Education began a programme to deworm all school-age children living in areas at high risk of soil-transmitted helminths (STH) and schistosome infections. The impact of this school-based mass drug administration (MDA) programme in Kenya is monitored by the Kenya Medical Research Institute (KEMRI) as part of a five-year (2012–2017) study. This article focuses on the impact of MDA on STH infections and presents the overall achieved reductions from baseline to mid-term, as well as yearly patterns of reductions and subsequent re-infections per school community. Methods The study involved a series of pre- and post-intervention, repeat cross-sectional surveys in a representative, stratified, two-stage sample of schools across Kenya. The programme contained two tiers of monitoring; a national baseline and mid-term survey including 200 schools, and surveys conducted among 60 schools pre- and post-intervention. Stool samples were collected from randomly selected school children and tested for helminth infections using Kato-Katz technique. The prevalence and mean intensity of each helminth species were calculated at the school and county levels and 95 % confidence intervals (CIs) were obtained by binomial and negative binomial regression, respectively, taking into account clustering by schools. Results The overall prevalence of STH infection at baseline was 32.3 % (hookworms: 15.4 %; Ascaris lumbricoides: 18.1 %; and Trichuris trichiura: 6.7 %). After two rounds of MDA, the overall prevalence of STH had reduced to 16.4 % (hookworms: 2.3 %; A. lumbricoides: 11.9 %; and T. trichiura: 4.5 %). The relative reductions of moderate to heavy intensity of infections were 33.7 % (STH combined), 77.3 % (hookworms) and 33.9 % (A. lumbricoides). For T. trichiura, however, moderate to heavy intensity of infections increased non-significantly by 18.0 % from baseline to mid-term survey. Conclusion The school-based deworming programme has substantially reduced STH infections, but because of ongoing transmission additional strategies may be required to achieve a sustained interruption of transmission. Electronic supplementary material The online version of this article (doi:10.1186/s13071-016-1679-y) contains supplementary material, which is available to authorized users.

BACKGROUND: An increasing number of countries in Africa and elsewhere are developing national plans for the control of neglected tropical diseases. A key component of such plans is school-based deworming (SBD) for the control of soil-transmitted helminths (STHs) and schistosomiasis. Monitoring and evaluation (M&E) of national programmes is essential to ensure they are achieving their stated aims and to evaluate when to reduce the frequency of treatment or when to halt it altogether. The article describes the M&E design of the Kenya national SBD programme and presents results from the baseline survey conducted in early 2012. METHODS: The M&E design involves a stratified series of pre- and post-intervention, repeat cross-sectional surveys in a representative sample of 200 schools (over 20,000 children) across Kenya. Schools were sampled based on previous knowledge of STH endemicity and were proportional to population size. Stool (and where relevant urine) samples were obtained for microscopic examination and in a subset of schools; finger-prick blood samples were collected to estimate haemoglobin concentration. Descriptive and spatial analyses were conducted. The evaluation measured both prevalence and intensity of infection. RESULTS: Overall, 32.4% of children were infected with at least one STH species, with Ascaris lumbricoides as the most common species detected. The overall prevalence of Schistosoma mansoni was 2.1%, while in the Coast Province the prevalence of S. haematobium was 14.8%. There was marked geographical variation in the prevalence of species infection at school, district and province levels. The prevalence of hookworm infection was highest in Western Province (25.1%), while A. lumbricoides and T. trichiura prevalence was highest in the Rift Valley (27.1% and 11.9%). The lowest prevalence was observed in the Rift Valley for hookworm (3.5%), in the Coast for A. lumbricoides (1.0%), and in Nyanza for T. trichiura (3.6%). The prevalence of S. mansoni was most common in Western Province (4.1%). CONCLUSIONS: The current findings are consistent with the known spatial ecology of STH and schistosome infections and provide an important empirical basis on which to evaluate the impact of regular mass treatment through the school system in Kenya.

Yersinia pestis, the bacterial causative agent of plague, remains an important threat to human health. Plague is a rodent-borne disease that has historically shown an outstanding ability to colonize and persist across different species, habitats, and environments while provoking sporadic cases, outbreaks, and deadly global epidemics among humans. Between September and November 2017, an outbreak of urban pneumonic plague was declared in Madagascar, which refocused the attention of the scientific community on this ancient human scourge. Given recent trends and plague’s resilience to control in the wild, its high fatality rate in humans without early treatment, and its capacity to disrupt social and healthcare systems, human plague should be considered as a neglected threat. A workshop was held in Paris in July 2018 to review current knowledge about plague and to identify the scientific research priorities to eradicate plague as a human threat. It was concluded that an urgent commitment is needed to develop and fund a strong research agenda aiming to fill the current knowledge gaps structured around 4 main axes: (i) an improved understanding of the ecological interactions among the reservoir, vector, pathogen, and environment; (ii) human and societal responses; (iii) improved diagnostic tools and case management; and (iv) vaccine development. These axes should be cross-cutting, translational, and focused on delivering context-specific strategies. Results of this research should feed a global control and prevention strategy within a “One Health” approach., Author summary The historical aspect of plague makes for fascinating reading, due to its capacity to disrupt human society and its socioeconomic and cultural impacts throughout human history. We argue that the Madagascar outbreak in 2017 is a tipping point in human plague epidemiology and a call to elevate research priorities on plague as a matter of some urgency. In contrast with what occurred with the Ebola virus disease crisis in West Africa between 2013 and 2015 and the new coronaviruses (the emergence of severe acute respiratory syndrome coronavirus [SARS-CoV] and Middle East respiratory syndrome coronavirus [MERS-CoV] as early warnings of the current severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] pandemic), we have an opportunity to act preventively and enable evidence-based measures to avoid major health crises due to plague outbreaks in the near future.