Integrated survey of helminthic neglected tropical diseases and comparison of two mosquito sampling methods for lymphatic filariasis molecular xenomonitoring in the River Galana area, Kilifi County, coastal Kenya.

A lymphatic filariasis (LF) endemic focus along the River Galana/ Sabaki in Kilifi County, coastal Kenya, provided a platform to conduct an integrated survey for three helminthic neglected tropical diseases (NTDs), namely soil-transmitted helminthiasis (STH), schistosomiasis (SCH) and LF. Additionally, the study compared the performance of two mosquito trapping methods for LF molecular xenomonitoring (MX). Cross-sectional surveys measuring STH, SCH and LF prevalence were conducted in four villages. Mosquitoes were trapped using the CDC light trap (CDC-LT) and the Ifakara A tent trap (Ifakara-TT) methods and stored in pools which were tested for Wuchereria bancrofti DNA using the real-time polymerase chain reaction assay. A total of 907 people (436 adults; 471 children) participated in the parasitological testing. Among the STH infections, Trichuris trichiura and hookworms were most prevalent among the children and adult populations, respectively. The schistosome worm eggs detected belonged to the species Schistosoma haematobium and the prevalence of the infection was generally higher among the children compared with the adult population. The prevalence of LF infection among the adult population ranged from 1.8% to 7.6% across all 4 villages (P < 0.05). A total of 3,652 mosquitoes, including Anopheles, Culex, Mansonia, and Aedes species were collected. One mosquito pool consisting of Anopheles mosquitoes tested positive for filarial DNA out of 1,055 pools that were tested. The CDC-LT caught significantly more mosquitoes compared with the Ifakara-TT (P < 0.001). This study demonstrated that integrated epidemiological surveys using standard parasitological and entomological methods can provide useful information on co-endemic parasitic diseases which could help direct interventions and surveillance activities.

Monitoring the impact of a national school based deworming programme on soil-transmitted helminths in Kenya: the first three years, 2012 - 2014.

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

Assessing drivers of the IgG4 antibody reactivity to recombinant antigen Bm14 in Wuchereria bancrofti endemic populations in East Africa.

A high proportion of the human population in lymphatic filariasis (LF) endemic areas is positive for filarial specific IgG4 antibodies, including many individuals without microfilariae (mf; circulating larvae in the human blood) or circulating filarial antigens (CFA; marker of adult worm infection). The antibodies are commonly regarded as markers of infection and/or exposure to filarial larvae, but a direct association between the antibodies and these indices has not been well documented. The present study assessed the role and relative effect of potential drivers of the human IgG4 antibody reactivity to the recombinant filarial antigen Bm14 in Wuchereria bancrofti endemic populations in East Africa. Sera collected during previous studies from 395 well characterized individuals with regard to age, sex, mf, CFA, household vector biting and household exposure to infective filarial larvae were tested for IgG4 antibodies to Bm14, and associations between antibody reactivity and the different variables were statistically analyzed. IgG4 reactivity to Bm14 was highly positively associated with CFA, and to a lesser extent with age. However, an expected association with household exposure to infective filarial larvae was not found. Bm14 antibody reactivity thus appeared mainly to reflect actual infection of individuals with adult filarial worms rather than ongoing exposure to transmission. The analyses moreover suggested that many of the CFA negative but Bm14 positive individuals had early or low level infections where antibodies had been induced but where CFA was not (yet?) measurable. Although the study indicated that IgG4 reactivity to Bm14 is a marker of filarial infection, assessment of this reactivity, especially in children, will still be useful for indirect monitoring of changes in transmission intensity, including break of transmission and post-elimination surveillance, in LF control.

Schistosoma haematobium and soil-transmitted Helminths in Tana Delta District of Kenya: infection and morbidity patterns in primary schoolchildren from two isolated villages.

BACKGROUND: Schistosomes and soil-transmitted helminths (STH) (hookworm, Trichuris trichiura and Ascaris lumbricoides) are widely distributed in developing countries where they infect over 230 million and 1.5 billion people, respectively. The parasites are frequently co-endemic and many individuals are co-infected with two or more of the species, but information on how the parasites interact in co-infected individuals is scarce. The present study assessed Schistosoma haematobium and STH infection and morbidity patterns among school children in a hyper-endemic focus in the Tana River delta of coastal Kenya. METHODS: Two hundred and sixty-two children aged 5-12 years from two primary schools were enrolled in the study. For each child, urine was examined for S. haematobium eggs and haematuria, stool was examined for STH eggs, peripheral blood was examined for eosinophilia and haemoglobin level, the urinary tract was ultrasound-examined for S. haematobium-related pathology, and the height and weight was measured and used to calculate the body mass index (BMI). RESULTS: Prevalences of S. haematobium, hookworm, T. trichiura and A. lumbricoides infection were 94, 81, 88 and 46 %, respectively. There was no significant association between S. haematobium and STH infection but intensity of hookworm infection significantly increased with that of T. trichiura. Lower BMI scores were associated with high intensity of S. haematobium (difference =-0.48, p > 0.05) and A. lumbricoides (difference =-0.67, p < 0.05). Haematuria (both macro and micro) was common and associated with S. haematobium infection, while anaemia was associated with high intensity of S. haematobium (OR = 2.08, p < 0.05) and high hookworm infections OR = 4.75; p < 0.001). The majority of children had eosinophilia, which was significantly associated with high intensity of hookworm infection (OR = 5.34, p < 0.05). Overall 38 % of the children had ultrasound-detectable urinary tract morbidity, which was associated with high intensity of S. haematobium infection (OR = 3.13, p < 0.05). CONCLUSION: Prevalences of S. haematobium and STH infections among the primary school children were high and the parasites were responsible for significant morbidity. A clear synergistic interaction was observed between hookworm and T. trichiura infections. Increased coverage in administration of praziquantel and albendazole in the area is recommended to control morbidity due to these infections.

Urinary cytokines in Schistosoma haematobium-infected schoolchildren from Tana Delta District of Kenya.

BACKGROUND: Pathological changes due to infection with Schistosoma haematobium include cytokine-mediated urinary tract inflammation. The involved cytokines may be excreted in urine and their presence in urine may therefore reflect S. haematobium-related urinary tract pathology. The present study, for the first time, reports on the relationship between selected cytokines in urine and infection with S. haematobium in children from an area highly affected by this parasite. METHODS: Children aged 5-12 years from two primary schools in Tana Delta District of Kenya were examined for S. haematobium eggs using urine filtration technique, for haematuria using dipstix and for eosinophil cationic protein (ECP), IL-6, IFN- γ, TNF-α and IL-10 levels using ELISA, and for S. haematobium-related urinary tract pathology using ultrasonography. In addition, venous blood was examined for serum IL-6, IFN- γ, TNF-α and IL-10 levels using ELISA. RESULTS: There was no significant correlation between urinary and serum levels of IL-6, IFN- γ, TNF-α or IL-10. There was no significant difference in geometric mean intensity (GMI) in any of the serum cytokines, or in urinary TNF-α or IFN-γ, between children with light and heavy S. haematobium infections. However, children with heavy S. haematobium infections had significantly higher GMI of urinary IL-6 (p < 0.001) and lower GMI of urinary IL-10 (p = 0.002) than children with light infections. There was also a significant positive correlation between urinary IL-6 and urinary ECP (p < 0.001) and a significant negative correlation between urinary IL-10 and urinary ECP (p = 0.012). CONCLUSION: Urinary IL-6 was positively correlated to and IL-10 was negatively correlated to infection intensity and urinary tract inflammation in S. haematobium-infected children. Urinary IL-6 and IL-10 ELISA may be a useful non-invasive tool to complement the already available tools for studying S. haematobium-related urinary tract pathology in children.

Increasing coverage in mass drug administration for lymphatic filariasis elimination in an urban setting: a study of Malindi Town, Kenya.

INTRODUCTION: Implementation of Mass Drug Administration (MDA) in urban settings is an obstacle to Lymphatic Filariasis (LF) elimination. No urban-specific guidelines on MDA in urban areas exist. Malindi district urban area had received 4 MDA rounds by the time the current study was implemented. Programme data showed average treatment coverage of 28.4% (2011 MDA), far below recommended minimum of 65-80%. METHODS: To identify, design and test strategies for increased treatment coverage in urban areas, a quasi-experimental study was conducted in Malindi urban area. Three sub-locations with lowest treatment coverage in 2011 MDA were purposively selected. In the pre-test phase, 947 household heads sampled using systematic random method were interviewed for quantitative data. For qualitative data, 12 Focus Group Discussions (FGDs) with single sex adult and youth male and female groups and 3 with community drug distributors (CDDs) were conducted. Forty in-depth interviews with opinion leaders and self-administered questionnaires with District Public Health officers purposively selected were carried out. The quantitative data were analyzed using SPSS version 16 and statistical significance assessed by χ(2) test.The qualitative data were analyzed manually according to study's themes. RESULTS AND DISCUSSION: The identified strategies were implemented prior to and during 2012 MDA in two sub-locations (experimental) while in the third (control), usual MDA strategies were applied. In the post-test phase, 2012 MDA coverage in experimental and control sub-locations was comparatively assessed for effect of the newly designed strategies on urban MDA. Results indicated improved treatment coverage in experimental sub-locations, 77.1% in Shella and 66.0% in Barani. Central (control) sub-location also attained high coverage, 70.4% indicating average treatment coverage of 71%. CONCLUSION: The identified strategies contributed to increased treatment coverage in experimental sites and should be applied in urban areas. Due to closeness of sites, spillover effects may have contributed to increased coverage in the control site.

Monitoring and evaluating the impact of national school-based deworming in Kenya: study design and baseline results.

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

Sustained reduction in prevalence of lymphatic filariasis infection in spite of missed rounds of mass drug administration in an area under mosquito nets for malaria control.

BACKGROUND: The Global Programme to Eliminate Lymphatic Filariasis (GPELF) was established by the World Health Organisation (WHO) in 2000 with the goal of eliminating lymphatic filariasis (LF) as a public health problem globally by 2020. Mass drug administration (MDA) of antifilarial drugs is the principal strategy recommended for global elimination. Kenya launched a National Programme for Elimination of Lymphatic Filariasis (NPELF) in Coast Region in 2002. During the same year a longitudinal research project to monitor trends of LF infection during MDA started in a highly endemic area in Malindi District. High coverage of insecticide treated nets (ITNs) in the coastal region has been associated with dramatic decline in hospital admissions due to malaria; high usage of ITNs is also expected to have an impact on LF infection, also transmitted by mosquitoes. RESULTS: Four rounds of MDA with diethylcarbamazine citrate (DEC) and albendazole were given to 8 study villages over an 8-year period. Although annual MDA was not administered for several years the overall prevalence of microfilariae declined significantly from 20.9% in 2002 to 0.9% in 2009. Similarly, the prevalence of filarial antigenaemia declined from 34.6% in 2002 to 10.8% in 2009. All the examined children born since the start of the programme were negative for filarial antigen in 2009. CONCLUSIONS: Despite the fact that the study villages missed MDA in some of the years, significant reductions in infection prevalence and intensity were observed at each survey. More importantly, there were no rebounds in infection prevalence between treatment rounds. However, because of confounding variables such as insecticide-treated bed nets (ITNs), it is difficult to attribute the reduction to MDA alone as ITNs can lead to a significant reduction in exposure to filariasis vectors. The results indicate that national LF elimination programmes should be encouraged to continue provision of MDA albeit constraints that may lead to missing of MDA in some years.

The effect of repeated half-yearly diethylcarbamazine mass treatment on Wuchereria bancrofti infection and transmission in two East African communities with different levels of endemicity.

The effect of repeated half-yearly mass treatment with diethylcarbamazine (DEC, 6 mg/kg body weight) on infection and transmission of Wuchereria bancrofti was assessed and compared in communities with high and low endemicity in eastern Africa, with pretreatment microfilaria (mf) and circulating filarial antigen (CFA) prevalences of 29.4% and 53.2% in the high endemicity community and 3.1% and 18.7% in the low endemicity community, respectively. Human infection was monitored by repeated cross-sectional surveys, and transmission by weekly light trap collection of vector mosquitoes in selected houses in each community. Treatments resulted in a progressive decrease in microfilaremia and circulating antigenemia in both communities, with relative reductions being considerably higher for mf than for CFA. Among pretreatment mf-positive individuals, more than 60% were diagnosed as mf negative and mean mf intensities were reduced by 99% in both communities after two treatment rounds. In contrast, only moderate reductions were seen in circulating antigenemia among pretreatment CFA-positive individuals, with mean intensities still being 24-39% of pretreatment values after two treatment rounds. Among the pretreatment mf/CFA-positive individuals, clearance to a CFA-negative status was negligible. Complete CFA clearance was only observed among pretreatment CFA-positive but mf negative individuals who also had much lower initial mean CFA levels than the mf-positive individuals. After treatment, the intensity of transmission decreased in the high-endemicity community, but this appeared mainly to be a consequence of a drought-induced reduction in vector density rather than to reduced mf load in the human population, since the proportion of mosquitoes carrying infective larvae was not reduced. No change in transmission or mosquito infectivity was observed after treatment in the low-endemicity community. Implications of these observations for the control of Bancroftian filariasis are discussed.