Sensitivity of diagnostic tests for human soil-transmitted helminth infections: a meta-analysis in the absence of a true gold standard.

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

Global feasibility assessment of interrupting the transmission of soil-transmitted helminths: a statistical modelling study.

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

Usutu virus in Africa.

Usutu virus (USUV) was discovered in South Africa in 1959. Since then, it has been reported in several African countries including Senegal, Central African Republic, Nigeria, Uganda, Burkina Faso, Cote d'Ivoire, and Morocco. In 2001, USUV has been identified for the first time outside of Africa, namely in Europe, where it caused a significant mortality among blackbirds in Vienna, Austria. In 2009, the first two human cases of USUV infection in Europe have been reported in Italy, causing encephalitis in immunocompromised patients. The host range in Africa includes mainly Culex mosquitoes, birds, and also humans with one benign and one severe case. Given its role as a potential human pathogen and the similar appearance compared with other emerging arboviruses, it is essential to investigate the natural history and ecology of USUV in Africa. In this regard, we review the emergence of USUV in Africa, summarizing data about isolations, host range, and potential vectors, which should help to improve our understanding of the factors underlying the circulation of USUV in Europe and Africa

Factors associated with the performance and cost-effectiveness of using lymphatic filariasis transmission assessment surveys for monitoring soil-transmitted helminths: a case study in Kenya.

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

Epidemiology of coinfection with soil transmitted helminths and Plasmodium falciparum among school children in Bumula District in western Kenya.

BACKGROUND: Many school children living in Africa are infected with plasmodia and helminth species and are consequently at risk of coinfection. However, the epidemiology of such coinfection and the implications of coinfection for children's health remain poorly understood. This study describes the epidemiology of Ascaris lumbricoides-Plasmodium and hookworm-Plasmodium coinfection among school children living in western Kenya and investigates the associated risk factors. METHODS: As part of a randomized trial, a baseline cross-sectional survey was conducted among school children aged 5-18 years in 23 schools in Bumula District. Single stool samples were collected to screen for helminth infections using the Kato-Katz technique and malaria parasitaemia was determined from a finger prick blood sample. Demographic and anthropometric data were also collected. RESULTS: Overall, 46.4% of the children were infected with Plasmodium falciparum while 27.6% of the children were infected with at least one soil transmitted helminth (STH) species, with hookworm being the most common (16.8%) followed by A. lumbricoides (15.3%). Overall 14.3% of the children had STH-Plasmodium coinfection, with hookworm-Plasmodium (9.0%) coinfection being the most common. Geographical variation in the prevalence of coinfection occurred between schools. In multivariable logistic regression analysis, hookworm was positively associated with P. falciparum infection. In stratified analysis, hookworm infection was associated with increased odds of P. falciparum infection among both boys (P < 0.001) and girls (P = 0.01), whereas there was no association between A. lumbricoides and P. falciparum. CONCLUSION: These findings demonstrate STH infections are still prevalent, despite the ongoing national deworming programme in Kenya, and that malaria parasitaemia is widespread, such that coinfection occurs among a proportion of children. A subsequent trial will allow us to investigate the implications of coinfection for the risk of clinical malaria

How temperature and aridity drive lignin decomposition along a latitudinal transect in western Siberia

Climate change drives a northward shift of biomes in high-latitude regions. This might have consequences on the decomposition of plant litter entering the soil, including its lignin component, which is one of the most abundant components of vascular plants. In order to elucidate the combined effect of climate and soil characteristics on the decomposition pattern of lignin, we investigated lignin contents and its degree of oxidative decomposition within soil profiles along a climosequence in western Siberia. Soil samples were collected from organic topsoil to mineral subsoil at six sites along a 1500-km latitudinal transect, stretching from tundra, through taiga and forest steppe to typical steppe. The stage of lignin degradation, as mirrored by decreasing organic carbon-normalized lignin contents and increasing oxidative alteration of the remnant lignin (acid-to-aldehyde ratios of vanillyl- and syringyl-units [(Ac/Al)V and (Ac/Al)S]) within soil horizons, increased from tundra to forest steppe and then decreased to the steppe. Principal component analysis, involving also climatic conditions such as mean annual temperature and aridity index, showed that the different states of lignin degradation between horizons related well to the activity of phenoloxidases and peroxidases, enzymes involved in lignin depolymerization that are produced primarily by fungi and less importantly by bacteria. The low microbial lignin decomposition in the tundra was likely due to low temperature and high soil moisture, which do not favour the fungi. Increasing temperature and decreasing soil moisture, facilitating a higher abundance of fungi, led to increased fungal lignin decomposition towards the forest-steppe biome, while drought and high pH might be responsible for the reduced lignin decomposition in the steppe. We infer that a shift of biomes to the north, driven by climate change, might promote lignin decomposition in the northern parts, whereas in the south a further retardation might be likely

An investigation of the disparity in estimates of microfilaraemia and antigenaemia in lymphatic filariasis surveys

The diagnosis of lymphatic filariasis (LF) is based typically on either microfilaraemia as assessed by microscopy or filarial antigenaemia using an immuno-chromatographic test. While it is known that estimates of antigenaemia are generally higher than estimates of microfilaraemia, the extent of the difference is not known. This dataset was produced as part of a literature review of surveys that estimate microfilaraemia and antigenaemia

Effect of Repeated Anthelminthic Treatment on Malaria in School Children in Kenya: A Randomized, Open-Label, Equivalence Trial.

BACKGROUND: School children living in the tropics are often concurrently infected with plasmodium and helminth parasites. It has been hypothesized that immune responses evoked by helminths may modify malaria-specific immune responses and increase the risk of malaria. METHODS: We performed a randomized, open-label, equivalence trial among 2436 school children in western Kenya. Eligible children were randomized to receive either 4 repeated doses or a single dose of albendazole and were followed up during 13 months to assess the incidence of clinical malaria. Secondary outcomes were Plasmodium prevalence and density, assessed by repeat cross-sectional surveys over 15 months. Analysis was conducted on an intention-to-treat basis with a prespecified equivalence range of 20%. RESULTS: During 13 months of follow-up, the incidence rate of malaria was 0.27 episodes/person-year in the repeated treatment group and 0.26 episodes/person-year in the annual treatment group (incidence difference, 0.01; 95% confidence interval, -.03 to .06). The prevalence and density of malaria parasitemia did not differ by treatment group at any of the cross-sectional surveys. CONCLUSIONS: Our findings suggest that repeated deworming does not alter risks of clinical malaria or malaria parasitemia among school children and that school-based deworming in Africa may have no adverse consequences for malaria. CLINICAL TRIALS REGISTRATION: NCT01658774

Comparative full length genome sequence analysis of usutu virus isolates from Africa

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

Ascaris lumbricoides Infection Following School-Based Deworming in Western Kenya: Assessing the Role of Pupils' School and Home Water, Sanitation, and Hygiene Exposures.

Water, sanitation, and hygiene (WaSH) technologies and behaviors can prevent infection by soil-transmitted helminth species independently, but may also interact in complex ways. However, these interactions are poorly understood. The purpose of this study was to characterize how school and home WaSH exposures were associated with Ascaris lumbricoides infection and to identify relevant interactions between separate WaSH technologies and behaviors. A study was conducted among 4,404 children attending 51 primary schools in western Kenya. We used multivariable mixed effects logistic regression to characterize how various WaSH exposures were associated with A. lumbricoides infection after annual school-based deworming. Few WaSH behaviors and technologies were independently associated with A. lumbricoides infection. However, by considering relevant interdependencies between variables, important associations were elucidated. The association between handwashing and A. lumbricoides depended largely upon the pupils' access to an improved water source. Among pupils who had access to improved water sources, A. lumbricoides prevalence was lower for those who handwashed both at school and home compared with neither place (odds ratio: 0.38, 95% confidence interval: 0.18-0.83; P = 0.01). This study contributes to a further understanding of the impact of WaSH on A. lumbricoides infection and shows the importance of accounting for interactions between WaSH technologies and behaviors