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ObjectivesMuscular strength represents a specific component of health-related fitness. Hand grip strength (HGS) is used as an indicator for musculoskeletal fitness in children. HGS can also be used as a marker of cardiometabolic risk, but most available HGS data are derived from Western high-income countries. Therefore, this study examines whether HGS is associated with body composition and markers of cardiovascular risk in children from three sub-Saharan African countries.DesignCross-sectional study.SettingPublic primary schools (grade 1–4) in Taabo (Côte d’Ivoire), Gqeberha (South Africa) and Ifakara (Tanzania).ParticipantsData from 467 children from Côte d’Ivoire (210 boys, 257 girls), 864 children from South Africa (429 boys, 435 girls) and 695 children from Tanzania (334 boys, 361 girls) were analysed.Primary and secondary outcome measuresBody composition (assessed via bioelectrical impedance analysis) was the primary outcome. Cardiovascular risk markers were considered as secondary outcome. Blood pressure was measured with an oscillometric monitor, and blood markers (cholesterol, triglycerides, glycated haemoglobin) via Afinion point-of-care testing. HGS (independent variable) was assessed with a hydraulic hand dynamometer. Inferential statistics are based on mixed linear regressions and analyses of covariance.ResultsAcross all study sites, higher HGS was associated with lower body fat, higher muscle mass and higher fat-free mass (pConclusionsHGS assessment is popular due to its simplicity, feasibility, practical utility and high reliability of measurements. This is one of the first HGS studies with children from sub-Saharan Africa. There is a great need for further studies to examine whether our findings can be replicated, to develop reference values for African children, to establish links to other health outcomes, and to explore whether HGS is associated with later development of cardiovascular risk markers.Trial registration numberISRCTN29534081.

Background Reliable and field-applicable diagnosis of schistosome infections in non-human animals is important for surveillance, control, and verification of interruption of human schistosomiasis transmission. This study aimed to summarize uses of available diagnostic techniques through a systematic review and meta-analysis. Methods and principal findings We systematically searched the literature and reports comparing two or more diagnostic tests in non-human animals for schistosome infection. Out of 4,909 articles and reports screened, 18 met our inclusion criteria, four of which were considered in the meta-analysis. A total of 14 techniques (parasitologic, immunologic, and molecular) and nine types of non-human animals were involved in the studies. Notably, four studies compared parasitologic tests (miracidium hatching test (MHT), Kato-Katz (KK), the Danish Bilharziasis Laboratory technique (DBL), and formalin-ethyl acetate sedimentation-digestion (FED-SD)) with quantitative polymerase chain reaction (qPCR), and sensitivity estimates (using qPCR as the reference) were extracted and included in the meta-analyses, showing significant heterogeneity across studies and animals hosts. The pooled estimate of sensitivity was 0.21 (95% confidence interval (CI): 0.03 – 0.48) with FED-SD showing highest sensitivity (0.89, 95% CI: 0.65 – 1.00). Conclusions and significance Our findings suggest that the parasitologic technique FEA-SD and the molecular technique, qPCR, are the most promising field-applicable techniques for schistosome diagnosis in non-human animal hosts. Future studies are needed for validation and standardization of the techniques for real-world field applications.

Background Soil-transmitted helminth (STH) infections are widespread in tropical and subtropical regions. While many STH infections are asymptomatic, vulnerable populations such as pregnant women face repercussions such as aggravation of maternal anaemia. However, data on prevalence and the effect of STH infections in pregnancy are limited. The aim of this analysis was to describe the burden of STH infections within and between populations of pregnant women from a local refugee camp to a mobile migrant population, and to explore possible associations between STH infection and pregnancy outcomes. Methodology This is a retrospective review of records from pregnant refugee and migrant women who attended Shoklo Malaria Research Unit antenatal care (ANC) clinics along the Thailand-Myanmar border between July 2013 and December 2017. Inclusion was based on provision of a stool sample during routine antenatal screening. A semi-quantitative formalin concentration method was employed for examination of faecal samples. The associations between STH mono-infections and maternal anaemia and pregnancy outcomes (i.e., miscarriage, stillbirth, preterm birth, and small for gestational age) were estimated using regression analysis. Principal findings Overall, 12,742 pregnant women were included, of whom 2,702 (21.2%) had a confirmed infection with either Ascaris lumbricoides, hookworm, Trichuris trichiura, or a combination of these. The occurrence of STH infections in the refugee population (30.8%; 1,246/4,041) was higher than in the migrant population (16.7%; 1,456/8,701). A. lumbricoides was the predominant STH species in refugees and hookworm in migrants. A. lumbricoides and hookworm infection were associated with maternal anaemia at the first ANC consultation with adjusted odds ratios of 1.37 (95% confidence interval (CI) 1.08–1.72) and 1.65 (95% CI 1.19–2.24), respectively. Pregnant women with A. lumbricoides infection were less likely to miscarry when compared to women with negative stool samples (adjusted hazard ratio 0.63, 95% CI 0.48–0.84). STH infections were not significantly associated with stillbirth, preterm birth or being born too small for gestational age. One in five pregnant women in this cohort had STH infection. Association of STH infection with maternal anaemia, in particular in the event of late ANC enrolment, underlines the importance of early detection and treatment of STH infection. A potential protective effect of A. lumbricoides infection on miscarriage needs confirmation in prospective studies., Author summary Soil-transmitted helminths (STHs) are parasitic worms transmitted through the faecal-oral or transcutaneous route. STHs are ubiquitous in tropical and subtropical regions where access to clean water, improved sanitation, and hygiene are lacking. STH infections are often asymptomatic; however, heavy infections can cause adverse effects such as abdominal discomfort and anaemia. Anaemia in pregnancy can increase the risk of pregnancy problems such as miscarriage, preterm delivery, and poor fetal growth. This retrospective analysis of routinely collected data from more than 12,000 pregnant refugee and migrant women who attended antenatal care clinics along the Thai-Myanmar border shows that one in five pregnant women were infected with STHs. Moreover, pregnant women with a STH infection were more likely to present with anaemia, suggesting that early presentation to antenatal care as well as anthelmintic treatment with subsequent anaemia prophylaxis may reduce the risk of anaemia. Interestingly, our data also indicate that STH infections may have beneficial effects on pregnancy outcomes, as miscarriage was less likely to occur in pregnancies with maternal STH infections. This finding was significant for infection with the roundworm Ascaris lumbricoides. Verification of these findings in prospective studies is warranted.

Background The extent to which drug–drug interactions (DDIs) between antiretrovirals (ARVs) and co-medications are recognized and managed has not been thoroughly evaluated in limited-resource settings. Objectives This prospective questionnaire-based study aimed to determine the prevalence and risk factors for unrecognized/incorrectly managed DDIs in people living with HIV followed-up at the Chronic Diseases Clinic of Ifakara (CDCI) and enrolled in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO). Methods We prospectively included ARV-treated adults receiving ≥1 co-medication coming for a follow-up visit at the CDCI between March and July 2017. Using a structured questionnaire, physicians were requested to identify potentially clinically significant DDIs in the prescribed treatment, to provide recommendations for their management and to indicate any hurdles to implement the recommendations. Prescriptions were subsequently screened for DDIs using the Liverpool DDIs database. Identified clinically significant DDIs and their recommended management according to the DDIs database were compared with the information provided in the questionnaires. Results Among 334 participants, the median age was 47 years (IQR = 40–56 years), 69% were female and 82% had ≥1 non-communicable disease (NCD). Overall, 129 participants had ≥1 clinically relevant DDI, which was not recognized and/or incorrectly managed in 56 participants (43%). Of those, 6 (11%) were due to limited monitoring options or medication affordability issues. In the multivariable logistic regression, the presence of ≥1 NCD was associated with an increased risk for unrecognized/incorrect DDI management (OR = 15.8; 95% CI = 1.8–139.6). Conclusions Recognition/appropriate management of DDIs is suboptimal, highlighting the need for educational programmes, pharmacovigilance activities and increased access to medications and monitoring options. This should become a focus of HIV programmes given the increasing burden of NCDs in sub-Saharan Africa.

Background The Service Availability and Readiness Assessment surveys generate data on the readiness of health facility services. We constructed a readiness index related to malaria services and determined the association between health facility malaria readiness and malaria mortality in children under the age of 5 years in Burkina Faso. Methods Data on inpatients visits and malaria-related deaths in under 5-year-old children were extracted from the national Health Management Information System in Burkina Faso. Bayesian geostatistical models with variable selection were fitted to malaria mortality data. The most important facility readiness indicators related to general and malaria-specific services were determined. Multiple correspondence analysis (MCA) was employed to construct a composite facility readiness score based on multiple factorial axes. The analysis was carried out separately for 112 medical centres and 546 peripheral health centres. Results Malaria mortality rate in medical centres was 4.8 times higher than that of peripheral health centres (3.5% vs. 0.7%, p Conclusion Performant health services in Burkina Faso are associated with lower malaria mortality rates. Health system readiness should be strengthened in the regions of Sahel, Sud-Ouest and Boucle du Mouhoun. Emphasis should be placed on improving the management of essential medicines and to reducing delays of emergency transportation between the different levels of the health system.

West African cities face critical societal challenges that are linked to environmental and health changes. These challenges are further exacerbated by urbanization dynamics, climate change, socio-economic mutation and lack of capacity for sustainable urban development, governance and basic services delivery. The deficiency of environmental sanitation and ecosystem services have led to high complexity of urban health risks inequalities, resulting in the need for more research on efficient urban health policies. The purpose of this contribution is to present the main findings on the spatial epidemiology of diarrhaea and malaria, and their associated risks factors in the following select West African cities. Spatial variability of exposure to diarrhaea and malaria transmission is linked to several health risks such as lack of access to water and sanitation, solid wastes management, urban flooding, precarious housing conditions, urban agriculture, socio-economic status and social practices and individual behaviours fluctuating according to the specificity of urban areas. These factors and their interconnections make some groups (differentiated by geography) more vulnerable to poor outcomes due to limited capacity to effectively respond to health risks and poor performance by the health system. We demonstrate the potential for a spatial epidemiology perspective that disaggregates data to, clusters of houses, neighbourhood, sector and municipality scale to support health policies and interventions, and how these results can contribute to achieving SDG 3 (Health and Well-Being for all) in African urban areas.

Background: The Service Availability and Readiness Assessment (SARA) surveys generate data on the readiness of health facility services. We constructed a readiness index related to malaria services and determined the association between health facility malaria readiness and malaria mortality in children under the age of 5 years in Burkina Faso.Methods: Data on inpatients visits and malaria-related deaths in under 5-year-old children were extracted from the national Health Management Information System (HMIS) in Burkina Faso. Bayesian geostatistical models with variable selection were fitted to malaria mortality data. The most important facility readiness indicators related to general and malaria-specific services were determined. Multiple correspondence analysis (MCA) was used to construct a composite facility readiness score based on multiple factorial axes. The analysis was carried out separately for 112 medical centres and 546 peripheral health centres.Results: Malaria mortality rate in medical centres was 4.8 times higher than that of peripheral health centres (3.46% vs. 0.72%, pConclusion: Performant health services in Burkina Faso are associated with lower malaria mortality rates. Health system readiness should be strengthened in the regions of Sahel, Sud-Ouest and Boucle du Mouhoun. Emphasis should be given to improving the management of essential medicines and to reducing delays of emergency transportation between the different levels of the health system.

Background: The Service Availability and Readiness Assessment (SARA) surveys generate data on the readiness of health facility services. We constructed a readiness index related to malaria services and determined the association between health facility malaria readiness and malaria mortality in children under the age of 5 years in Burkina Faso. Methods: Data on malaria-related visits and deaths in under 5-year-old children were extracted from the national Health Management Information System (HMIS) in Burkina Faso. Bayesian geostatistical models with variable selection were fitted to malaria mortality data. The most important facility readiness indicators related to general and malaria-specific services were determined. Multiple correspondence analysis (MCA) was used to construct a composite facility readiness score based on multiple factorial axes. The analysis was carried out separately for 112 medical centers and 546 peripheral health centers. Results: Malaria mortality rate in medical centres was 4.8 times higher than that of peripheral health centres (3.46 vs 0.72%, p

This paper introduces the three stages of development of the Regional Network on Asian Schistosomiasis and other Helminthic Zoonoses (RNAS

From the time it was conceptualized in 1998 to the present, RNAS

For the Regional Network on Asian Schistosomiasis and Other Helminth Zoonosis (RNAS

Schistosomiasis, helminthic zoonoses and NTDs constitute a considerable majority of the diseases of poverty in the world. The RNAS

In 2005, the network decided to increase its number of target diseases to include other helminthic zoonoses such as fascioliasis, clonorchiasis, opisthorchiasis, paragonimiasis and cysticercosis and in the process expanding membership to include South Korea, Vietnam, Thailand and Japan. NTDs were eventually included as awareness is heightened on these diseases affecting poor and developing countries. Researches on clonorchiasis and opisthorchiasis unravel the mechanism by which these diseases eventually predispose to cholangiocarcinoma. The liver cancer associated with these liver fluke infections necessitate the need to clarify the global burden of disease of these infections. The magnitude of these liver fluke diseases in endemic countries like China, Vietnam, Laos, Cambodia and Thailand is described. Success in elimination of lymphatic filariasis in PR China and Cambodia is highlighted to show how intensified multisectoral collaboration and strong political become strong ingredients in elimination of parasitic diseases like LF. New advances are presented that clarify species and strain differences in Fasciola spp., Paragonimus spp., Taenia spp. and Echinococcocus spp. Conventional diagnostic techniques are compared with new serologic techniques that are being developed. New control strategies such as the Lawa model are presented.

Over the past 20 years, RNAS

From the time it was conceptualized in 1998 to the present, RNAS+ has largely concentrated on research that will generate results to facilitate control, prevention and elimination of its target diseases. Diagnostics has remained an active field of research in order to develop tools that are appropriate for each stage from the first efforts until attempts to block transmission. For example, with regard to schistosomiasis, chemotherapy has excellent impact on morbidity, while better diagnostics and vaccine research have been promoted to complement the other components of the control programme. The need for surveillance in areas where the prevalence has been brought down to very low levels necessitated development of spatio-temporal tools and ecological models based on geographical information systems (GIS) to produce risk and distribution maps for monitoring and evaluation of programme success. New knowledge and experiences in management of the diseases contribute to the formulation of new schemes in management and treatment. Ways of drawing attention to the disease, such as determining disability weights for use in computation of burden of disease, updating epidemiological profile and unravelling new aspects of the disease provide bases for modifying the operation of control programmes as we move forward. Programme evaluation based on reports of actual implementation of activities brought to the fore problems related to the distribution of chemotherapy as well as social, cultural and behavioural aspects of endemic communities. Importantly, this highlighted the necessity of adapting control activities to specific situations of the endemic areas. New models evolving from reviews of this kind and success stories, such us the elimination of lymphatic filariasis (LF) in PR China and Cambodia are presented.

This paper introduces the three stages of development of the Regional Network on Asian Schistosomiasis and other Helminthic Zoonoses (RNAS+), namely the preparatory stage, the strengthening stage and the expanding stage. Significant achievements have been made through the help of RNAS+, particularly on research on helminthiases. As scientists, researchers, academics work closer with control authorities, elimination of these diseases is slowly getting nearer and within reach. RNAS+, at present can boast of the following strengths: (i) strong collaboration in the regional research area with support from experts on research and control; (ii) presence of experts in various areas who can improve and promote both research and control; (iii) RNAS+ has been successful in translating research output to field application; (iv) setting up a platform that is capable of advancing the mechanisms of sharing information through its website, databases, publications and meetings; (v) RNAS+ has proved that it is capable of undertaking joint collaborative projects on operational research through multi-country, multi-disease using multi-disciplinary approach and involving different academic and research institutions in the region. Most importantly, experts who are members of RNAS+ are also linked with control programmes of the endemic member countries in the region.

Schistosomiasis, helminthic zoonoses and NTDs constitute a considerable majority of the diseases of poverty in the world. The RNAS+ targeted zoonoses are not only problems to human and animal health, but also cause poverty in 1 billion poor livestock keepers as well as result in 2.3 billion cases of human illness and 1.7 million human deaths a year. The gaps in research of those targeted zoonoses are urgently addressed by identifying the research priority, fulfilled by improving the multisectoral cooperation and strengthening the interventions in the control programme.

IntroductionPreterm birth (PTB) results from heterogeneous influences and is a major contributor to neonatal mortality and morbidity that continues to have adverse effects on infants beyond the neonatal period. This protocol describes the procedures to determine molecular signatures predictive of PTB through high-frequency sampling during pregnancy, at delivery and the postpartum period.Methods and analysisFour hundred first trimester pregnant women from either Myanmar or Thailand of either Karen or Burman ethnicity, with a viable, singleton pregnancy will be enrolled in this non-interventional, prospective pregnancy birth cohort study and will be followed through to the postpartum period. Fortnightly finger prick capillary blood sampling will allow the monitoring of genome-wide transcript abundance in whole blood. Collection of stool samples and vaginal swabs each trimester, at delivery and postpartum will allow monitoring of intestinal and vaginal microbial composition. In a nested case–control analysis, perturbations of transcript abundance in capillary blood as well as longitudinal changes of the gut, vaginal and oral microbiome will be compared between mothers giving birth to preterm and matched cases giving birth to term neonates. Placenta tissue of preterm and term neonates will be used to determine bacterial colonisation as well as for the establishment of coding and non-coding RNA profiles. In addition, RNA profiles of circulating, non-coding RNA in cord blood serum will be compared with those of maternal peripheral blood serum at time of delivery.Ethics and disseminationThis research protocol that aims to detect perturbations in molecular trajectories preceding adverse pregnancy outcomes was approved by the ethics committee of the Faculty of Tropical Medicine, Mahidol University in Bangkok, Thailand (Ethics Reference: TMEC 15–062), the Oxford Tropical Research Ethics Committee (Ethics Reference: OxTREC: 33–15) and the local Tak Province Community Ethics Advisory Board. The results of this cooperative project will be disseminated in multiple publications staggered over time in international peer-reviewed scientific journals.Trial registration numberNCT02797327; Pre-results.

For the Regional Network on Asian Schistosomiasis and Other Helminth Zoonosis (RNAS+), capacity building with emphasis on modern technology with correspondence to traditional techniques was found to be a priority. This article summarized the actual needs of capacity building among RNAS+ member countries and the working mechanism of capacity building during the last 20 years. The needs with respect to the RNAS+ target diseases are highly correlated with the research priorities, since most problems with regard to the performance of the national disease control programme in the member countries are connected with inadequate capacity in relation to implementation of innovative research, epidemiological investigations, laboratory performance; and sociological investigations. The capacity building arranged through RNAS+ platform includes short training courses, individual training in member institutions, e.g., supervision of Ph.D./Masters students; postdoctoral training; and internship training in institutions of southeast Asia as well as in famous institutions of Europe and the United States. In the future, capacity building will focus on platform design and technical standardization aiming at fostering research capacity in the future. Moreover, new training projects, such as massive online courses (MOOC) will be explored under RNAS+ platform.

In 2005, the network decided to increase its number of target diseases to include other helminthic zoonoses such as fascioliasis, clonorchiasis, opisthorchiasis, paragonimiasis and cysticercosis and in the process expanding membership to include South Korea, Vietnam, Thailand and Japan. NTDs were eventually included as awareness is heightened on these diseases affecting poor and developing countries. Researches on clonorchiasis and opisthorchiasis unravel the mechanism by which these diseases eventually predispose to cholangiocarcinoma. The liver cancer associated with these liver fluke infections necessitate the need to clarify the global burden of disease of these infections. The magnitude of these liver fluke diseases in endemic countries like China, Vietnam, Laos, Cambodia and Thailand is described. Success in elimination of lymphatic filariasis in PR China and Cambodia is highlighted to show how intensified multisectoral collaboration and strong political become strong ingredients in elimination of parasitic diseases like LF. New advances are presented that clarify species and strain differences in Fasciola spp., Paragonimus spp., Taenia spp. and Echinococcocus spp. Conventional diagnostic techniques are compared with new serologic techniques that are being developed. New control strategies such as the Lawa model are presented.

We evaluated the Newton Nm1, a commercially available handheld light microscope and compared it with conventional light microscopy for the diagnosis of soil-transmitted helminth infections. A total of 91 Kato-Katz thick smears were examined by experienced microscopists and helminth eggs were counted and expressed as eggs per gram of stool (EPG). Mean egg counts were significantly higher with the conventional light microscope (5,190 EPG versus 2,386 EPG for Ascaris lumbricoides; 826 versus 456 for Trichuris trichiura; both P < 0.05). Using regression coefficients and accounting for intensity of infection, we found that the agreement between the two devices was excellent for both species (κ = 0.90, 95% confidence interval = 0.82–0.99 for A. lumbricoides and κ = 0.96, 95% CI = 0.91–1.00 for T. trichiura). The Newton Nm1 microscope may be a useful tool for the detection and quantification of soil-transmitted helminth infection in clinical, epidemiologic, and public health settings.

In order to determine reported signs and symptoms that may predict an intestinal parasitic infection, 241 schoolchildren in western Cote d'Ivoire were interviewed with a simple questionnaire and their stool specimens were examined over several consecutive days. Special emphasis was placed on (i) assessing infections by Entamoeba histolytica / E. dispar , Giardia duodenalis and by intestinal worms, (ii) looking for associations between these parasites, and (iii) looking for associations between these parasites and commonly perceived intestinal signs and symptoms. Complete questionnaire results, intestinal helminth infections derived from 4 Kato-Katz thick smears, and intestinal protozoa infections assessed on a single day by a formalin-ether concentration procedure were obtained from 209 children (87%). A logistic regression modelling approach showed that an infection with E. histolytica / E. dispar was significantly associated with an Entamoeba coli infection. However, for G. duodenalis , hookworm and Ascaris lumbricoides , no association was found between any of these parasites and other intestinal parasites. In a multivariate analysis reported diarrhoea was the only symptom positively associated with an E. histolytica / E. dispar infection ( P = 0·028). Its diagnostic performance showed a low sensitivity (28%), a high specificity (85%) and moderate positive and negative predictive values (52% and 67%, respectively). Surprisingly, reported ‘turning stomach’ was less often reported by children infected with G. duodenalis (borderline significance, P = 0·057). It is concluded that reported diarrhoea could be a symptom worth exploring further for the rapid identification of schoolchildren infected with E. histolytica / E. dispar .

Aim To determine the genetic diversity of invasive snails (Pomacea spp.) that are implicated in crop damage, environmental degradation and human disease, and to determine their distribution pattern in a large part of eastern Asia. Location People’s Republic of China (P.R. China). Methods We collected Pomacea snails in a national survey using a grid sampling approach. Overall, 544 snails from 54 sites were used for the present investigation. The mitochondrial cox1 gene was amplified and sequenced from all the snails. We determined and classified the haplotypes using network analyses and mapped them within P.R. China. Haplotypes from this study, together with sequences available from GenBank, were used to reveal the global distribution of Pomacea canaliculata and P. insularum. Results We obtained 521 cox1 sequences and identified 24 unique haplotypes. Six haplotypes were commonly found in P.R. China. Two species, P. canaliculata and P. insularum, and one cryptic group were observed. The distribution of the 24 haplotypes across P.R. China shows a mosaic pattern. Globally, only six of 112 haplotypes of P. canaliculata, P. insularum, P. dolioides, P. lineata and P. paludosa are shared between introduced and native snail populations. We found 16 haplotype clusters, five of which occur in mainland P.R. China. Three of the five clusters could be traced back to South America. The remaining two clusters were unique to P.R. China. Main conclusions Phylogenetic analyses indicate that P. canaliculata, P. insularum and two cryptic groups, discovered by the present and previous studies, coexist in the mainland of P.R. China. The mosaic distribution and the high diversity found in the collection sites suggests multiple and secondary introductions. The findings indicate the importance of preventing further intentional

Anemia affects one-quarter of the world's population, but its etiology remains poorly understood. We determined the prevalence of anemia and studied underlying risk factors in infants (6–23 months), young school-aged children (6–8 years), and young non-pregnant women (15–25 years) in south-central Côte d'Ivoire. Blood, stool, and urine samples were subjected to standardized, quality-controlled methods. We found high prevalence of anemia, malaria, inflammation, and deficiencies of iron, riboflavin, and vitamin A but low prevalence and intensities of soil-transmitted helminth and schistosome infections. Multivariate regression analysis revealed significant associations between anemia and Plasmodium falciparum for infants, inflammation for school-aged children, and cellular iron deficiency for both school-aged children and non-pregnant women. Women with riboflavin deficiency had significantly lower odds of anemia. Our findings call for interventions to protect infants from malaria, improved intake of dietary iron, better access to health care, and health education.

Parasitic infections cause a myriad of responses in their mammalian hosts, on immune as well as on metabolic level. A multiplex panel of cytokines and metabolites derived from four parasite-rodent models, namely, Plasmodium berghei−mouse, Trypanosoma brucei brucei−mouse, Schistosoma mansoni−mouse, and Fasciola hepatica−rat were statistically coanalyzed. 1H NMR spectroscopy and multivariate statistical analysis were used to characterize the urine and plasma metabolite profiles in infected and noninfected animals. Each parasite generated a unique metabolic signature in the host. Plasma cytokine concentrations were obtained using the ‘Meso Scale Discovery’ multi cytokine assay platform. Multivariate data integration methods were subsequently used to elucidate the component of the metabolic signature which is associated with inflammation and to determine specific metabolic correlates with parasite-induced changes in plasma cytokine levels. For example, the relative levels of acetyl glycoproteins extracted from the plasma metabolite profile in the P. berghei-infected mice were statistically correlated with IFN-γ, whereas the same cytokine was anticorrelated with glucose levels. Both the metabolic and the cytokine data showed a similar spatial distribution in principal component analysis scores plots constructed for the combined murine data, with samples from all infected animals clustering according to the parasite species and whereby the protozoan infections (P. berghei and T. b. brucei) grouped separately from the helminth infection (S. mansoni). For S. mansoni, the main infection-responsive cytokines were IL-4 and IL-5, which covaried with lactate, choline, and d-3-hydroxybutyrate. This study demonstrates that the inherently differential immune response to single- and multicellular parasites not only manifests in the cytokine expression, but also consequently imprints on the metabolic signature, and calls for in-depth analysis to further explore direct links between immune features and biochemical pathways., Parasitic infections cause a myriad of responses in their mammalian hosts, including a range of immune reactions and metabolic perturbations. Here, a multiplex panel of cytokines and metabolites derived from four parasite-rodent models, namely, Plasmodium berghei−mouse, Trypanosoma brucei brucei−mouse, Schistosoma mansoni−mouse, and Fasciola hepatica−rat were statistically coanalyzed. 1H NMR spectroscopy and multivariate statistical analysis were used to characterize the urine and plasma metabolite profiles in infected and noninfected control animals.

Hookworms (Ancylostoma duodenale and Necator americanus) are blood-feeding intestinal nematodes that infect approximately 700 million people worldwide. To further our understanding of the systems metabolic response of the mammalian host to hookworm infection, we employed a metabolic profiling strategy involving the combination of (1)H NMR spectroscopic analysis of urine and serum and multivariate data analysis techniques to investigate the biochemical consequences of a N. americanus infection in the hamster. The infection was characterized by altered energy metabolism, consistent with hookworm-induced anemia. Additionally, disturbance of gut microbiotal activity was associated with a N. americanus infection, manifested in the alterations of microbial-mammalian cometabolites, including phenylacetylglycine, p-cresol glucuronide, 4-hydroxy-3-methyl-phenylpropionic acid, hippurate, 4-hydroxyphenylactate, and dimethylamine. The correlation between worm burden and metabolite concentrations also reflected a changed energy metabolism and gut microbial state. Furthermore, elevated levels of urinary 2-aminoadipate was a characteristic feature of the infection, which may be associated with the documented neurological consequences of hookworm infection.

In order to enhance our understanding of physiological and pathological consequences of a patent Schistosoma mansoni infection in the mouse, we examined the metabolic responses of different tissue samples recovered from the host animal using a metabolic profiling strategy. Ten female NMRI mice were infected with approximately 80 S. mansoni cercariae each, and 10 uninfected age- and sex-matched animals served as controls. At day 74 post infection (p.i.), mice were killed and jejunum, ileum, colon, liver, spleen and kidney samples were removed. We employed (1)H magic angle spinning-nuclear magnetic resonance spectroscopy to generate tissue-specific metabolic profiles. The spectral data were analyzed using multivariate modelling methods including an orthogonal signal corrected-projection to latent structure analysis and hierarchical principal component analysis to assess the differences and/or similarities in metabolic responses between infected and non-infected control mice. Most tissues obtained from S. mansoni-infected mice were characterized by high levels of amino acids, such as leucine, isoleucine, lysine, glutamine and asparagine. High levels of membrane phospholipid metabolites, including glycerophosphoryl choline and phosphoryl choline were found in the ileum, colon, liver and spleen of infected mice. Additionally, low levels of energy-related metabolites, including lipids, glucose and glycogen were observed in ileum, spleen and liver samples of infected mice. Energy-related metabolites in the jejunum, liver and renal medulla were found to be positively correlated with S. mansoni worm burden upon dissection. These findings show that a patent S. mansoni infection causes clear disruption of metabolism in a range of tissues at a molecular level, which can be interpreted in relation to the previously reported signature in a biofluid (i.e. urine), giving further evidence of the global effect of the infection.

Une enquete epidemiologique transversale a ete menee dans la region de Man, a l’ouest de la Cote-d’Ivoire. Les objectifs etaient de determiner les prevalences des protozoaires intestinaux, d’evaluer le polyparasitisme et d’etablir la repartition spatiale des especes de protozoaires pathogenes, Entamoeba histolytica et Giardia intestinalis. Au total, 4 466 echantillons de selles preleves chez des eleves âges de 6 a 16 ans de 57 ecoles primaires ont ete analyses au microscope optique apres concentration par formol-ether, suite a une conservation dans le liquide d’acetate de sodium-acide acetique-formol (SAF). Les especes de protozoaires intestinaux predominantes dans notre echantillon ont ete Endolimax nanus (83,8 %) et Entamoeba coli (74,7 %). Les prevalences regionales de G. intestinalis et d’E. histolytica/Entamoeba dispar ont ete de 17,5 et 11,3 % respectivement, et ces deux especes ont ete retrouvees dans chacune des 57 ecoles. Des prevalences de plus de 15 % ont ete observees dans six villages pour E. histolytica/E. dispar dont une disparite a ete observee dans la repartition geographique. En revanche, trois grands foyers de transmission de G. intestinalis ont ete identifies. Le polyparasitisme a protozoaires intestinaux est tres frequent dans cette region avec 80,2 % d’individus portant au moins deux especes. Nos travaux confirment la presence et l’ampleur des protozoaires intestinaux dans la region de Man. La carte de distribution spatiale des principaux foyers de transmission de ces protozoaires pourrait contribuer a l’elaboration d’un programme de lutte ciblee, integrant les mesures chimiotherapiques et preventives.

The aim of this review was to compare the effects of different dengue vector control interventions (i.e. biological control, chemical control, environmental management and integrated vector management) with respect to the following entomological parameters: Breteau index (BI), container index (CI), and house index (HI). We systematically searched PubMed, ISI Web of Science, Science Direct, the Dengue Bulletin of the World Health Organization and reference lists of retrieved articles on dengue vector control interventions in developing countries. We extracted data on the effectiveness of different dengue vector control interventions (defined as the relative reduction of an entomological measure caused by the intervention compared with the control or pre-intervention phase) and calculated a measure of combined relative effectiveness, with 95% confidence intervals (95% c.i.). We identified 56 publications covering 61 dengue vector control interventions. Integrated vector management was found to be the most effective method to reduce the CI, HI and BI, resulting in random combined relative effectiveness values of 0.12 (95% c.i. 0.02-0.62), 0.17 (95% c.i. 0.02-1.28) and 0.33 (95% c.i. 0.22-0.48), respectively. Environmental management showed a relatively low effectiveness of 0.71 (95% c.i. 0.55-0.90) for the BI, 0.49 (95% c.i. 0.30-0.79) for the CI and 0.43 (95% c.i. 0.31-0.59) for the HI. Biological control (relative effectiveness for the CI: 0.18) usually targeted a small number of people (median population size: 200; range 20-2500), whereas integrated vector management focused on larger populations (median: 12 450; range: 210-9 600 000). In conclusion, dengue vector control is effective in reducing vector populations, particularly when interventions use a community-based, integrated approach, which is tailored to local eco-epidemiological and sociocultural settings and combined with educational programmes to increase knowledge and understanding of best practice. New research should assess the density-dependent effectiveness of each control measure in order to estimate whether reducing vector numbers has an impact on dengue transmission when populations are at a critical threshold.

Background : As the HIV/AIDS pandemic has evolved over recent decades, Africa has been the most affected region, even though a large proportion of HIV/AIDS deaths have not been documented at the individual level. Systematic application of verbal autopsy (VA) methods in defined populations provides an opportunity to assess the mortality burden of the pandemic from individual data. Objective : To present standardised comparisons of HIV/AIDS-related mortality at sites across Africa and Asia, including closely related causes of death such as pulmonary tuberculosis (PTB) and pneumonia. Design : Deaths related to HIV/AIDS were extracted from individual demographic and VA data from 22 INDEPTH sites across Africa and Asia. VA data were standardised to WHO 2012 standard causes of death assigned using the InterVA-4 model. Between-site comparisons of mortality rates were standardised using the INDEPTH 2013 standard population. Results : The dataset covered a total of 10,773 deaths attributed to HIV/AIDS, observed over 12,204,043 person-years. HIV/AIDS-related mortality fractions and mortality rates varied widely across Africa and Asia, with highest burdens in eastern and southern Africa, and lowest burdens in Asia. There was evidence of rapidly declining rates at the sites with the heaviest burdens. HIV/AIDS mortality was also strongly related to PTB mortality. On a country basis, there were strong similarities between HIV/AIDS mortality rates at INDEPTH sites and those derived from modelled estimates. Conclusions : Measuring HIV/AIDS-related mortality continues to be a challenging issue, all the more so as anti-retroviral treatment programmes alleviate mortality risks. The congruence between these results and other estimates adds plausibility to both approaches. These data, covering some of the highest mortality observed during the pandemic, will be an important baseline for understanding the future decline of HIV/AIDS. Keywords : HIV/AIDS; tuberculosis; Africa; Asia; Mortality; INDEPTH Network; Verbal Autopsy; InterVA (Published: 29 October 2014) Citation: Glob Health Action 2014, 7 : 25370 - http://dx.doi.org/10.3402/gha.v7.25370 SPECIAL ISSUE : This paper is part of the Special Issue: INDEPTH Network Cause-Specific Mortality . More papers from this issue can be found at http://www.globalhealthaction.net

Background Treatment and morbidity control of schistosomiasis relies on a single drug, praziquantel. Hence, there is a pressing need to develop additional therapeutics against schistosomiasis. The antimalarial drug mefloquine shows antischistosomal activity in animal models and clinical trials, which calls for further investigations. Methodology We comparatively assessed the efficacy and tolerability of the following treatments against Schistosoma haematobium in school-aged children in Côte d'Ivoire: (i) praziquantel (40 mg/kg; standard treatment); (ii) mefloquine (25 mg/kg) combined with praziquantel (40 mg/kg); and (iii) mefloquine-artesunate (3× (100 mg artesunate +250 mg mefloquine)) combined with praziquantel (40 mg/kg) (treatments administered on subsequent days). Two urine samples were collected before, and on days 21–22 and 78–79 after the first dosing. Principal Findings Sixty-one children were present on all examination time points and had complete datasets. No difference in efficacy was observed between the three treatment groups on either follow-up. On the 21–22 day posttreatment follow-up, based on available case analysis, cure rates of 33% (95% confidence interval (CI) 11–55%), 29% (95% CI 8–50%), and 26% (95% CI 5–48%) were observed for praziquantel, mefloquine-artesunate-praziquantel, and mefloquine-praziquantel, respectively. The corresponding egg reduction rates were 94% and above. On the second follow-up, observed cure rates ranged from 19% (praziquantel) to 33% (mefloquine-artesunate-praziquantel), and egg reduction rates were above 90%. Praziquantel monotherapy was the best tolerated treatment. In the mefloquine-artesunate-praziquantel group, adverse events were reported by 91% of the participants, and in the mefloquine-praziquantel group, 95% experienced adverse events. With the exception of abdominal pain at moderate severity, adverse events were mild. Conclusions/Significance The addition of mefloquine or mefloquine-artesunate does not increase the efficacy of praziquantel against chronic S. haematobium infection. Additional studies are necessary to elucidate the effect of the combinations against acute schistosomiasis., Author Summary The antimalarial drug mefloquine shows activity against blood flukes that cause the disease schistosomiasis. In animal studies it has been found that a mefloquine-praziquantel combination kills blood flukes more effectively than praziquantel alone. Combining praziquantel with another drug might therefore increase efficacy, broaden the spectrum of activity, and delay the development of drug resistance. We designed a study in Ivorian school children to assess the efficacy and tolerability of mefloquine and mefloquine-artesunate combined with praziquantel against the blood fluke Schistosoma haematobium. The administration of the antimalarials and praziquantel was spaced by a day. Treatment outcomes were assessed twice, on days 21–22 and 78–79 after the first dosing to determine the effect against adult and juvenile S. haematobium, respectively. At both follow-ups, high reduction in the intensity of infection (egg reduction rates of 94–96%), but low cure rates (26–33%) were observed in the three treatment groups. Adverse events were common, particularly in children treated with mefloquine-praziquantel and mefloquine-artesunate-praziquantel. Our study suggests that the addition of mefloquine and mefloquine-artesunate to praziquantel has no benefit in the treatment of chronic S. haematobium infection. However, further investigations are warranted to evaluate the effect of combination therapy on juvenile flukes and longer-term morbidity profiles.

Background : Mortality from external causes, of all kinds, is an important component of overall mortality on a global basis. However, these deaths, like others in Africa and Asia, are often not counted or documented on an individual basis. Overviews of the state of external cause mortality in Africa and Asia are therefore based on uncertain information. The INDEPTH Network maintains longitudinal surveillance, including cause of death, at population sites across Africa and Asia, which offers important opportunities to document external cause mortality at the population level across a range of settings. Objective : To describe patterns of mortality from external causes at INDEPTH Network sites across Africa and Asia, according to the WHO 2012 verbal autopsy (VA) cause categories. Design : All deaths at INDEPTH sites are routinely registered and followed up with VA interviews. For this study, VA archives were transformed into the WHO 2012 VA standard format and processed using the InterVA-4 model to assign cause of death. Routine surveillance data also provide person-time denominators for mortality rates. Results : A total of 5,884 deaths due to external causes were documented over 11,828,253 person-years. Approximately one-quarter of those deaths were to children younger than 15 years. Causes of death were dominated by childhood drowning in Bangladesh, and by transport-related deaths and intentional injuries elsewhere. Detailed mortality rates are presented by cause of death, age group, and sex. Conclusions : The patterns of external cause mortality found here generally corresponded with expectations and other sources of information, but they fill some important gaps in population-based mortality data. They provide an important source of information to inform potentially preventive intervention designs. Keywords: external causes; accidents; suicide; assault; transport; drowning; Africa; Asia; mortality; INDEPTH Network; verbal autopsy; InterVA (Published: 29 October 2014) Citation: Glob Health Action 2014, 7 : 25366 - http://dx.doi.org/10.3402/gha.v7.25366 SPECIAL ISSUE : This paper is part of the Special Issue: INDEPTH Network Cause-Specific Mortality . More papers from this issue can be found at http://www.globalhealthaction.net

There is evidence that faecal egg counts ofSchistosoma mansonivary considerably from day to day, which results in poor sensitivity of single stool readings. Intra-specimen variation ofS. mansoniegg counts may also be considerable, but has previously been considered as the less important component. We quantified the relative contribution of these two sources of variation among 96 schoolchildren from an area in Côte d'Ivoire highly endemic forS. mansoni. Stool specimens were collected over 5 consecutive days, and 5 egg-counts were made in each specimen by the Kato–Katz technique. The point prevalence of the first sample was 42.7% and the cumulative prevalence after the maximum sampling effort was 88.5%. Using generalized linear mixed models we found that the presence ofS. mansonieggs in a stool sample varied much more between days than within specimens, indicating that stool sample examination over multiple days is required for accurate prevalence estimates. However, using the same approach, we found that among infected children intra-specimen variation in egg counts was 4.3 times higher than day-to-day variation. After praziquantel administration, day-to-day variation was more important than before, since most infections were very light and thus likely to be missed altogether by stool examination on a single day. We conclude that diagnostic sensitivity in high transmission areas is maximized by making several stool readings on several days, but examining 1 stool specimen several times can make reasonable estimates of infection intensity.

Schistosomiasis is a public health problem in Nigeria. Although there is a national programme for its control, there is the need for reliable and simple means of rapidly diagnosing communities to provide a detailed map on the distribution of the disease in the country, in order to prioritize control activities, as well as to monitor the effectiveness of control operations. A rapid assessment technique using school questionnaires was tested in Borgu Local Government Area (LGA), Niger State, north-western Nigeria. Following a series of focus group discussions, the questionnaires were adapted before they were administered through the school system to 60 primary schools in Borgu LGA. Correctly completed questionnaires were returned from 58 schools (97%) within 4 weeks. Questionnaires were validated by reagent stick tests performed by trained teachers. Their results proved to be reliable compared to those obtained by our research team in 20 randomly selected schools. Overall prevalences of microhaematuria at 1+ and 2+ levels were 45.7% and 27. 1%, respectively. Highly significant correlations were obtained between school prevalence of microhaematuria and reported schistosomiasis, as well as reported blood in urine. The diagnostic performance of the questionnaires at the 2+ level of microhaematuria was very good. The design of our study also allowed data analysis on an individual level, and multivariate analysis revealed highly significant odds ratios for reported schistosomiasis and reported blood in urine to detect an individual with urinary schistosomiasis. Our results are in good agreement with reports from other African countries, and questionnaires can be recommended for rapid identification of communities at highest risk of urinary schistosomiasis in Nigeria, so that scarce resources of the national control programme can be used most effectively.

Co-infection is ubiquitous in people in the developing world but little is known regarding the potential for one parasite to act as a risk factor for another. Using generalized linear mixed modelling approaches applied to data from school-aged children from Zanzibar, Tanzania, we determined the strength of association between four focal infections (i.e. Ascaris lumbricoides , Trichuris trichiura , hookworm and self-reported fever, the latter used as a proxy for viral, bacterial or protozoal infections) and the prevalence or intensity of each of the helminth infections. We compared these potential co-infections with additional risk factors, specifically, host sex and age, socioeconomic status and physical environment, and determined what the relative contribution of each risk factor was. We found that the risk of infection with all four focal infections was strongly associated with at least one other infection, and that this was frequently dependent on the intensity of that other infection. In comparison, no other incorporated risk factor was associated with all focal infections. Successful control of infectious diseases requires identification of infection risk factors. This study demonstrates that co-infection is likely to be one of these principal risk factors and should therefore be given greater consideration when designing disease-control strategies. Future work should also incorporate other potential risk factors, including host genetics which were not available in this study and, ideally, assess the risks via experimental manipulation.

Improvements of water, sanitation, and hygiene (WASH) infrastructure and appropriate health-seeking behavior are necessary for achieving sustained control, elimination, or eradication of many neglected tropical diseases (NTDs). Indeed, the global strategies to fight NTDs include provision of WASH, but few programs have specific WASH targets and approaches. Collaboration between disease control programs and stakeholders in WASH is a critical next step. A group of stakeholders from the NTD control, child health, and WASH sectors convened in late 2012 to discuss opportunities for, and barriers to, collaboration. The group agreed on a common vision, namely "Disease-free communities that have adequate and equitable access to water and sanitation, and that practice good hygiene." Four key areas of collaboration were identified, including (i) advocacy, policy, and communication; (ii) capacity building and training; (iii) mapping, data collection, and monitoring; and (iv) research. We discuss strategic opportunities and ways forward for enhanced collaboration between the WASH and the NTD sectors.

The transmission of the parasites that cause human malaria is influenced by myriad environmental factors, including changes in agricultural practices, deforestation, and waterresources development and management (Ijumba and Lindsay, 2001; Ijumba et al., 2002; Keiser et al., 2005; Guerra et al., 2006), climatic factors such as rainfall, humidity and temperature (Reiter, 2008), and various cultural, economic, political and social factors, including health-seeking behaviour, urbanization, armed conflict and war (Esse et al., 2008; Baragatti et al., 2009). Drug resistance in the causative parasites and insecticide resistance in the mosquito vectors are also important factors that now influence malaria transmission (Reiter, 2008). Each year, in many parts of Africa, the local populations of anopheline mosquitoes build up rapidly and peak shortly after the onset of the rainy season (Mbogo et al., 1995). In two studies on the relationships between mosquito abundance, malaria transmission and rainfall in West Africa, 70%–90% of the children investigated were found infected with Plasmodium spp. after the rainy season (Bonnet et al., 2002; Koudou et al., 2009). It is particularly during and at the end of the rainy season that malaria becomes one of the leading causes of mortality and health-seeking at dispensaries and hospitals in this region (Rey et al., 1987). Not only season but also changing patterns of agriculture, particularly irrigated rice farming, influence malaria transmission in Africa (Ijumba & Lindsay, 2001; Diuk-Wasser et al., 2007; Sogoba et al., 2007). Additionally, malaria transmission, Plasmodium prevalence rates, the proportion of presumptive and clinically-confirmed malaria episodes have been studied in two villages of central Cote d’Ivoire: one with irrigated rice farming (Zatta) and one without (Tiemelekro) (Koudou et al., 2009). Due to a farmers’ conflict over land and socio-political issues, irrigated rice farming was interrupted in Zatta in 2003. The goal of this contribution to a book chapter is to evaluate the relationship between Plasmodium transmission, seasonality and agriculture practices.