Implementation and Evaluation of Strategies for Control of Schistosomiasis and Soil Transmitted Helminthiasis in Pemba Island, Zanzibar.

The context of this work in Pemba was (i) the initial reestablishment of School-Based Treatment (SBT) with praziquantel (PZQ) and albendazole (ALB) for control of urogenital schistosomiasis and soil-transmitted helminths (STH), respectively, and (ii) the subsequent implementation of mass drug administration (MDA) with or without additional snail control or behavioural modification which was aimed at evaluation of the possibility of elimination of schistosomiasis. The prime focus of the work described was to use regular parasitological monitoring to evaluate and compare control strategies with regard to the effects of intervention on transmission or morbidity. Chapters 1 and 2: General Introduction and Material and Methods respectively Chapter 3: Urogenital schistosomiasis. (i) Use of single annual SBT with PZQ: By assessing urine egg output in new-entry standard (Std)-1 children, neither the intensity nor baseline prevalence of 9.5% was lowered over a two year period of intervention. However, prevalences in St-3 children who had received SBT showed lower prevalences than Std-1 children presumably reflecting PZQ-mediated worm reductions. This supports the WHO recommended use of SBT treatment once/year for areas with prevalence snail control>MDA). There was a downward trend in the overall mean intensity across all interventions (from 2.71 1.83 1.71) but no consistent reduction in the proportion of heavy infections among the infected children. Recommendations: Integrated interventions are likely to be necessary for interrupting transmission of schistosomiasis and eventually leading to elimination. In poor resource areas, such as Zanzibar, it would be difficult to implement fully integrated control measures and so focusing on PC in areas with high transmission coupled with behavioural changes and strengthening of diagnostic capability of health facilities could be essential. ii Chapter 4: STH. Faecal examination of the Std-1 children, as above, for the eggs of Ascaris lumbricoides, Trichuris trichiura and hookworm, showed a high frequency of polyparasitism. Neither SBT nor intense MDA significantly reduced prevalence of any STH worm in the communities. The worm specific prevalences were slightly reduced overall, most consistently for Trichuris. However, there were no significant changes in intensity of infection, which remained light in the majority of infected children. Recommendations: No impact of either SBT or MDA on transmission to Std-1 children was observed. Integrated approaches e.g. WASH (water, sanitation and hygiene), education and PC are likely to be essential for reduction in transmission. Chapter 5: The efficiency of drug distribution and associated compliance were monitored during the MDA by individual questionnaire and reports from the community drug distributors (CDDs). Overall coverage rate was high (~80%) but variable between the districts (69.3-88.2%). Based on questionnaire, a significant proportion of individuals were non-compliant with the MDA especially regarding PZQ (10.2%) although this did not associate with knowledge about disease transmission, signs/symptoms or risk factors for schistosomiasis. Only mild adverse effects were reported. Recommendations: For any future MDA careful thought needs to be given to understanding the variation in compliance observed across the different areas of Pemba. There is a need of intensifying sensitization meetings in the communities with focus of discussion on potential side effects which may develop. Engage religious and other influential leaders during sensitization meetings. Chapter 6: Since the intensive enhanced MDA for schistosomiasis was aimed at evaluating the possibility of elimination of transmission, the role in transmission of the preschool (>3<5yr) children, who were not previously included in PC in Pemba, was assessed. A substantial proportion of these children was infected (7.04%), the prevalence steadily increasing with age. By questionnaire to mothers/care-givers, contact with stream/pond water through washing and visiting with the children were significant risk factors for pre-school infection. Recommendations: In view of the preschool prevalence demonstrated, the community MDA was extended to <3yr olds. The government should be ready to register and order paediatric formulation of PZQ once it becomes available. Diagnostic capability of the respective health facilities has to be strengthened in terms of training of laboratory personnel and purchase of essential laboratory equipment. iii Chapter 7: Implementation of snail control in Pemba prompted study of transmission of schistosomiasis by the snail intermediate host, Bulinus spp. Only ~1% of fieldcollected snails shed cercariae but 56% of tested snails were found infected by PCR. DNA sequencing confirmed the presence of B. nasutus and B. globosus, both of which transmitted schistosomes as judged by cercarial shedding and molecular techniques. Recommendations: Further studies are needed to confirm the potential role of the B. nasutus in the transmission of urogenital schistosomiasis in Pemba. For monitoring of schistosomiasis transmission, it would be essential to assess the presence of infection in snail host using molecular techniques especially when elimination is achieved or targeted. Chapter 8: Increasing intensity of PZQ administration raises concerns about possible selection of drug resistance in S. haematobium and prompted studies on the efficacy of PZQ and its effects on parasite genetic diversity in Pemba. It was found that PZQ efficacy was comparable to previous trials. Miracidial samples collected from Std-1 children in 2011 showed diverse, and some novel, haplotypes of the Cox-1 gene of S. haematobium. Clustering of the different haplotypes from different areas indicated the role of internal/external migration in the spread of infection. Recommendations: Praziquantel remains effective and should still be used for the treatment of schistosomiasis at the individual, community or school level in Pemba. More studies are needed to assess susceptibility to PZQ of different S. haematobium haplotypes and of the groups (G1 and G2) with which they associate. Chapter 9: General Discussion: Overall it was concluded that S. haematobium and STH infections remain a public health problem in Pemba and that, although PC using SBT helps control parasite burdens, integrated control measures were more effective and would be required to reduce transmission to approach elimination. Valuable experience in implementation and monitoring of such measures (MDA±snail control/behavioural modification) and application of modern genetic analysis tools was gained during the work and further studies on the snail hosts and population genetics of S. haematobium proposed

Praziquantel coverage in schools and communities targeted for the elimination of urogenital schistosomiasis in Zanzibar: a cross-sectional survey

© 2015 Knopp et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. The attached file is the published version of the article

Erratum to: Development of novel multiplex microsatellite polymerase chain reactions to enable high-throughput population genetic studies of Schistosoma haematobium

© Webster et al. 2015. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

External validation and calibration of IVFpredict:A national prospective cohort study of 130,960 in vitro fertilisation Cycles

© 2015 Smith et al. Background Accurately predicting the probability of a live birth after in vitro fertilisation (IVF) is important for patients, healthcare providers and policy makers. Two prediction models (Templeton and IVFpredict) have been previously developed from UK data and are widely used internationally. The more recent of these, IVFpredict, was shown to have greater predictive power in the development dataset. The aim of this study was external validation of the two models and comparison of their predictive ability. Methods and Findings 130,960 IVF cycles undertaken in the UK in 2008-2010 were used to validate and compare the Templeton and IVFpredict models. Discriminatory power was calculated using the area under the receiver-operator curve and calibration assessed using a calibration plot and Hosmer-Lemeshow statistic. The scaled modified Brier score, with measures of reliability and resolution, were calculated to assess overall accuracy. Both models were compared after updating for current live birth rates to ensure that the average observed and predicted live birth rates were equal. The discriminative power of both methods was comparable: the area under the receiver-operator curve was 0.628 (95% confidence interval (CI): 0.625-0.631) for IVFpredict and 0.616 (95% CI: 0.613-0.620) for the Templeton model. IVFpredict had markedly better calibration and higher diagnostic accuracy, with calibration plot intercept of 0.040 (95% CI: 0.017-0.063) and slope of 0.932 (95% CI: 0.839 - 1.025) compared with 0.080 (95% CI: 0.044-0.117) and 1.419 (95% CI: 1.149-1.690) for the Templeton model. Both models underestimated the live birth rate, but this was particularly marked in the Templeton model. Updating the models to reflect improvements in live birth rates since the models were developed enhanced their performance, but IVFpredict remained superior. Conclusion External validation in a large population cohort confirms IVFpredict has superior discrimination and calibration for informing patients, clinicians and healthcare policy makers of the probability of live birth following IVF

Evaluation of the Widal tube agglutination test for the diagnosis of typhoid fever among children admitted to a rural hdospital in Tanzania and a comparison with previous studies

BACKGROUND: The diagnosis of typhoid fever is confirmed by culture of Salmonella enterica serotype Typhi (S. typhi). However, a more rapid, simpler, and cheaper diagnostic method would be very useful especially in developing countries. The Widal test is widely used in Africa but little information exists about its reliability. METHODS: We assessed the performance of the Widal tube agglutination test among febrile hospitalized Tanzanian children. We calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of various anti-TH and -TO titers using culture-confirmed typhoid fever cases as the "true positives" and all other febrile children with blood culture negative for S. typhi as the "true negatives." RESULTS: We found that 16 (1%) of 1,680 children had culture-proven typhoid fever. A single anti-TH titer of 1:80 and higher was the optimal indicator of typhoid fever. This had a sensitivity of 75%, specificity of 98%, NPV of 100%, but PPV was only 26%. We compared our main findings with those from previous studies. CONCLUSION: Among febrile hospitalized Tanzanian children with a low prevalence of typhoid fever, a Widal titer of > or = 1:80 performed well in terms of sensitivity, specificity, and NPV. However a test with improved PPV that is similarly easy to apply and cost-efficient is desirable

Genome-Wide Survey and Expression Profiling of CCCH-Zinc Finger Family Reveals a Functional Module in Macrophage Activation

Previously, we have identified a novel CCCH zinc finger protein family as negative regulators of macrophage activation. To gain an overall insight into the entire CCCH zinc finger gene family and to evaluate their potential role in macrophage activation, here we performed a genome-wide survey of CCCH zinc finger genes in mouse and human. Totally 58 CCCH zinc finger genes in mouse and 55 in human were identified and most of them have not been reported previously. Phylogenetic analysis revealed that the mouse CCCH family was divided into 6 groups. Meanwhile, we employed quantitative real-time PCR to profile their tissue expression patterns in adult mice. Clustering analysis showed that most of CCCH genes were broadly expressed in all of tissues examined with various levels. Interestingly, several CCCH genes Mbnl3, Zfp36l2, Zfp36, Zc3h12a, Zc3h12d, Zc3h7a and Leng9 were enriched in macrophage-related organs such as thymus, spleen, lung, intestine and adipose. Consistently, a comprehensive assessment of changes in expression of the 58 members of the mouse CCCH family during macrophage activation also revealed that these CCCH zinc finger genes were associated with the activation of bone marrow-derived macrophages by lipopolysaccharide. Taken together, this study not only identified a functional module of CCCH zinc finger genes in the regulation of macrophage activation but also provided the framework for future studies to dissect the function of this emerging gene family

Prostate cancer disparities in Black men of African descent: a comparative literature review of prostate cancer burden among Black men in the United States, Caribbean, United Kingdom, and West Africa

<p>Abstract</p> <p>Background</p> <p>African American men have the highest prostate cancer morbidity and mortality rates than any other racial or ethnic group in the US. Although the overall incidence of and mortality from prostate cancer has been declining in White men since 1991, the decline in African American men lags behind White men. Of particular concern is the growing literature on the disproportionate burden of prostate cancer among other Black men of West African ancestry in the Caribbean Islands, United Kingdom and West Africa. This higher incidence of prostate cancer observed in populations of African descent may be attributed to the fact that these populations share ancestral genetic factors. To better understand the burden of prostate cancer among men of West African Ancestry, we conducted a review of the literature on prostate cancer incidence, prevalence, and mortality in the countries connected by the Transatlantic Slave Trade.</p> <p>Results</p> <p>Several published studies indicate high prostate cancer burden in Nigeria and Ghana. There was no published literature for the countries Benin, Gambia and Senegal that met our review criteria. Prostate cancer morbidity and/or mortality data from the Caribbean Islands and the United Kingdom also provided comparable or worse prostate cancer burden to that of US Blacks.</p> <p>Conclusion</p> <p>The growing literature on the disproportionate burden of prostate cancer among other Black men of West African ancestry follows the path of the Transatlantic Slave Trade. To better understand and address the global prostate cancer disparities seen in Black men of West African ancestry, future studies should explore the genetic and environmental risk factors for prostate cancer among this group.</p

Early Exposure of Infants to GI Nematodes Induces Th2 Dominant Immune Responses Which Are Unaffected by Periodic Anthelminthic Treatment

We have previously shown a reduction in anaemia and wasting malnutrition in infants <3 years old in Pemba Island, Zanzibar, following repeated anthelminthic treatment for the endemic gastrointestinal (GI) nematodes Ascaris lumbricoides, hookworm and Trichuris trichiura. In view of the low intensity of worm infections in this age group, this was unexpected, and it was proposed that immune responses to the worms rather than their direct effects may play a significant role in morbidity in infants and that anthelminthic treatment may alleviate such effects. Therefore, the primary aims of this study were to characterise the immune response to initial/early GI nematode infections in infants and the effects of anthelminthic treatment on such immune responses. The frequency and levels of Th1/Th2 cytokines (IL-5, IL-13, IFN-γ and IL-10) induced by the worms were evaluated in 666 infants aged 6–24 months using the Whole Blood Assay. Ascaris and hookworm antigens induced predominantly Th2 cytokine responses, and levels of IL-5 and IL-13 were significantly correlated. The frequencies and levels of responses were higher for both Ascaris positive and hookworm positive infants compared with worm negative individuals, but very few infants made Trichuris-specific cytokine responses. Infants treated every 3 months with mebendazole showed a significantly lower prevalence of infection compared with placebo-treated controls at one year following baseline. At follow-up, cytokine responses to Ascaris and hookworm antigens, which remained Th2 biased, were increased compared with baseline but were not significantly affected by treatment. However, blood eosinophil levels, which were elevated in worm-infected children, were significantly lower in treated children. Thus the effect of deworming in this age group on anaemia and wasting malnutrition, which were replicated in this study, could not be explained by modification of cytokine responses but may be related to eosinophil function