Interrupting transmission of soil-transmitted helminths : a study protocol for cluster randomised trials evaluating alternative treatment strategies and delivery systems in Kenya

Introduction: In recent years, an unprecedented emphasis has been given to the control of neglected tropical diseases, including soil-transmitted helminths (STHs). The mainstay of STH control is school-based deworming (SBD), but mathematical modelling has shown that in all but very low transmission settings, SBD is unlikely to interrupt transmission, and that new treatment strategies are required. This study seeks to answer the question: is it possible to interrupt the transmission of STH, and, if so, what is the most costeffective treatment strategy and delivery system to achieve this goal? Methods and analysis: Two cluster randomised trials are being implemented in contrasting settings in Kenya. The interventions are annual mass anthelmintic treatment delivered to preschool- and school-aged children, as part of a national SBD programme, or to entire communities, delivered by community health workers. Allocation to study group is by cluster, using predefined units used in public health provision—termed community units (CUs). CUs are randomised to one of three groups: receiving either (1) annual SBD; (2) annual community-based deworming (CBD); or (3) biannual CBD. The primary outcome measure is the prevalence of hookworm infection, assessed by four cross-sectional surveys. Secondary outcomes are prevalence of Ascaris lumbricoides and Trichuris trichiura, intensity of species infections and treatment coverage. Costs and cost-effectiveness will be evaluated. Among a random subsample of participants, worm burden and proportion of unfertilised eggs will be assessed longitudinally. A nested process evaluation, using semistructured interviews, focus group discussions and a stakeholder analysis, will investigate the community acceptability, feasibility and scale-up of each delivery system. Ethics and dissemination: Study protocols have been reviewed and approved by the ethics committees of the Kenya Medical Research Institute and National Ethics Review Committee, and London School of Hygiene and Tropical Medicine. The study has a dedicated web site. Trial registration number: NCT0239777

Spatial distribution and risk factors of Schistosoma haematobium and hookworm infections among schoolchildren in Kwale, Kenya

Background: Large-scale schistosomiasis control programs are implemented in regions with diverse social and economic environments. A key epidemiological feature of schistosomiasis is its small-scale heterogeneity. Locally profiling disease dynamics including risk factors associated with its transmission is essential for designing appropriate control programs. To determine spatial distribution of schistosomiasis and its drivers, we examined schoolchildren in Kwale, Kenya. Methodology/Principal findings: We conducted a cross-sectional study of 368 schoolchildren from six primary schools. Soil-transmitted helminths and Schistosoma mansoni eggs in stool were evaluated by the Kato-Katz method. We measured the intensity of Schistosoma haematobium infection by urine filtration. The geometrical mean intensity of S. haematobium was 3.1 eggs/10 ml urine (school range, 1.4?9.2). The hookworm geometric mean intensity was 3.2 eggs/g feces (school range, 0?17.4). Heterogeneity in the intensity of S. haematobium and hookworm infections was evident in the study area. To identify factors associated with the intensity of helminth infections, we utilized negative binomial generalized linear mixed models. The intensity of S. haematobium infection was associated with religion and socioeconomic status (SES), while that of hookworm infection was related to SES, sex, distance to river and history of anthelmintic treatment. Conclusions/Significance: Both S. haematobium and hookworm infections showed micro-geographical heterogeneities in this Kwale community. To confirm and explain our observation of high S. haematobium risk among Muslims, further extensive investigations are necessary. The observed small scale clustering of the S. haematobium and hookworm infections might imply less uniform strategies even at finer scale for efficient utilization of limited resources

Serological Surveillance Development for Tropical Infectious Diseases Using Simultaneous Microsphere-Based Multiplex Assays and Finite Mixture Models

Background:A strategy to combat infectious diseases, including neglected tropical diseases (NTDs), will depend on the development of reliable epidemiological surveillance methods. To establish a simple and practical seroprevalence detection system, we developed a microsphere-based multiplex immunoassay system and evaluated utility using samples obtained in Kenya.Methods:We developed a microsphere-based immuno-assay system to simultaneously measure the individual levels of plasma antibody (IgG) against 8 antigens derived from 6 pathogens: Entamoeba histolytica (C-IgL), Leishmania donovani (KRP42), Toxoplasma gondii (SAG1), Wuchereria bancrofti (SXP1), HIV (gag, gp120 and gp41), and Vibrio cholerae (cholera toxin). The assay system was validated using appropriate control samples. The assay system was applied for 3411 blood samples collected from the general population randomly selected from two health and demographic surveillance system (HDSS) cohorts in the coastal and western regions of Kenya. The immunoassay values distribution for each antigen was mathematically defined by a finite mixture model, and cut-off values were optimized.Findings:Sensitivities and specificities for each antigen ranged between 71 and 100%. Seroprevalences for each pathogen from the Kwale and Mbita HDSS sites (respectively) were as follows: HIV, 3.0% and 20.1%; L. donovani, 12.6% and 17.3%; E. histolytica, 12.8% and 16.6%; and T. gondii, 30.9% and 28.2%. Seroprevalences of W. bancrofti and V. cholerae showed relatively high figures, especially among children. The results might be affected by immunological cross reactions between W. bancrofti-SXP1 and other parasitic infections; and cholera toxin and the enterotoxigenic E. coli (ETEC), respectively.Interpretation:A microsphere-based multi-serological assay system can provide an opportunity to comprehensively grasp epidemiological features for NTDs. By adding pathogens and antigens of interest, optimized made-to-order high-quality programs can be established to utilize limited resources to effectively control NTDs in Africa

Evaluation of the phenotypic performance of a Red Maasai and Dorper double backcross resource population: Indoor trickle challenge with Haemonchus contortus

Six F1 Dorper (D) x Red Maasai (R) rams were mated to both D and R ewes to produce backcross lambs. These six double backcross resource families are being analysed to identify quantitative trait loci that may be controlling resistance to gastro-intestinal (GI) nematode parasites, mainly Haemonchus contortus. After assessing the phenotypic performance of the lambs following exposure to natural infections, the surviving lambs were drenched and moved indoors for an artificial challenge with H. contortus along with straightbred D and R lambs. A total of 1317 lambs were included in the analyses consisting of 523 3/4D, 580 3/4R, 87 D and 127 R. The D lambs were significantly and consistently heavier than R lambs and 3/4D were significantly heavier than the 3/4R lambs. The difference between the backcrosses was about half of that between the straightbreds. Resistance was assessed in terms of faecal egg counts (FEC) and total worm counts (TWC) at necropsy while packed cell volume (PCV) was used to assess resilience to weekly oral doses of 2500 infective larvae of H. contortus. No significant breed differences were observed for log transformed FEC (LFEC). A significant breed difference in PCV was recorded. The backcrosses had the higher values and while no differences were observed between the straightbreds, 3/4D had significantly higher PCV than the 3/4R. Despite the absence of breed differences in FEC the R and the 3/4R had significantly fewer worms than the D and the 3/4D. The D had significantly longer worms than the R and the 3/4D had significantly longer worms than the 3/4R. Worms recovered from D had more eggs than those recovered from R. Similarly worms from 3/4D contained more eggs than those from 3/4R. Thus, on a breed basis the breed with more worms had longer worms. In contrast, when, in a small part of the experiment two doses of larvae were used to check for any breed by dose interactions, worms from the low dose (and hence fewer worms) animals were longer. We postulate that in fast growing hosts like the D, worms also have a better potential for growth and reproduction than in hosts that have less potential for growth. The overall correlation coefficient between PCV and LFEC was -0.67 while that between LFEC and LTWC was 0.72. From these results it is clear that the R do not respond to the artificial challenge the way they do to natural infection suggesting that phenotyping of R and R cross lambs for purpose of selecting those that are resistant or susceptible is best done under natural challenge

Chronic clinical manifestations related to Wucherieria bancrofti infection in a highly endemic area in Kenya

Clinical examinations were conducted in an effort to provide baseline data for a pilot filariasis elimination programme implemented in a Wuchereria bancrofti-endemic focus in Malindi district, Kenya. Of 186 mates aged 15 years and above examined, 64 individuals (34.4%) had hydrocele, and the prevalence of the manifestation in those above 40 years old was 55.3%. The prevalence of Leg lymphoedema in persons aged 15 years and above was 8.5%, with a higher rate in mates (12.6%) than in females (5.7%). The overall prevalence of inguinal adenopathy was 8.6%, and mates had a significantly higher (12.9%) prevalence of adenopathy than females (5.1%) (P < 0.001). The data in the present study provided support for consideration of filarial infection as a possible cause of inguinal lymphadenopathy in bancroftian filariasis-endemic areas. The results of this study also indicate that Lymphatic filariasis is a serious public health problem in the northern coastal areas and morbidity control programmes should be implemented to alleviate the suffering of those affected. (c) 2006 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved

Impact of two rounds of mass treatment with diethylcarbamazine plus albendazole on Wuchereria bancrofti infection and the sensitivity of immunochromatographic test in Malindi, Kenya

Annual single-dose mass treatment of endemic populations with a combination of either diethylcarbamazine (DEC) or ivermectin plus albendazole is recommended as the mainstay of lymphatic filariasis elimination programmes. We evaluated the impact of two rounds of annual mass drug administration (MDA) of DEC and albendazole on bancroftian filariasis in a pilot elimination programme in an endemic area of Kenya. Overall prevalence of microfilaraemia decreased by 65.4%, whereas community microfilarial load decreased by 84% after the two MDAs. The prevalence of parasite antigenaemia determined by immunochromatographic test (ICT) declined significantly by 43.5% after the two MDAs. We also studied the effect of mass treatment on the sensitivity of the ICT. Although the sensitivity of the test before treatment was high (89.9%; K =0.909) sensitivity was lower after two MDAs (59.3%; K = 0.644). The finding raises concern about the reliability of the ICT in long-term monitoring of infection and for establishing programmatic endpoints. The results of the present study indicate a relatively high effectiveness of MDA using a DEC/albendazole combination against Wuchereria bancrofti infection and, therefore, it may be a useful strategy to eliminate lymphatic filariasis in onchocerciasis-free areas. (c) 2008 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved

The adverse effects of albendazole and praziquantel in mass drug administration by trained schoolteachers

Eastern and Southern Africa Centre of International Parasite Control (ESACIPAC) conducted stool examinations for soil transmitted helminthiases (STH) and Schistosoma mansoni , among school children in Mwea Division, Central Kenya where both infections are endemic. Mass drug administrations (MDAs) were then conducted in 2004 and 2005 using schoolteachers trained on how to administer treatment, physically and psychologically prepare the children to take the medication, have them eat before treatment, handle minor and refer serious side effects to local health facilities. Local health workers were on standby to help manage severe side effects. This study examined side effects of the drugs and the teachers’ preparedness to handle the children when such effects occurred. No serious side effects requiring referral to the health centre occurred and the minor ones observed were temporal. In 2005 children in Mwea schools were treated with albendazole 400mg and praziquantel 40mg/kg body weight while those of Ndia, a neighboring division treated with only albendazole 400mg since there was low S.mansoni prevalence. Monitoring of side effects was done in two schools of Ndia and in three of Mwea through a questionnaire distributed to grade three pupils a week after treatment. Of 73 pupils from Mwea, 49.7% reported incidences of stomachache, vomiting/nausea, headache and dizziness whereas 39.2% of 186 from Ndia experienced incidences of cough, stomachache and headache. This shows that more pupils from Mwea, (albendazole and praziquantel) than from Ndia (albendazole alone) experienced minor side effects. These results show that both drugs have temporary, minor side effects, which can be managed by trained schoolteachers by ensuring that the school children do not swallow the drugs on an empty stomach and rest immediately after swallowing the drugs but should be closely monitored by health personnel. In this study, one trained schoolteacher could administer treatment to three hundred children in one day, which makes the approach cost effective and should be adopted nationally