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Rift Valley fever virus (RVFV) causes severe disease in both animals and humans, resulting in significant economic and public health damages. The objective of this study was to measure RVFV seroprevalence in six coastal Kenyan villages between 2009 and 2011, and characterize individual-, household-, and community-level risk factors for prior RVFV exposure. Sera were tested for anti-RVFV IgG via enzyme-linked immunosorbent assay. Overall, 51 (1.8%; confidence interval [CI 95 ] 1.3-2.3) of 2,871 samples were seropositive for RVFV. Seroprevalence differed significantly among villages, and was highest in Jego Village (18/300; 6.0%; CI 95 3.6-9.3) and lowest in Magodzoni (0/248). Adults were more likely to be seropositive than children ( P < 0.001). Seropositive subjects were less likely to own land or a motor vehicle ( P < 0.01), suggesting exposure is associated with lower socioeconomic standing ( P = 0.03). RVFV exposure appears to be low in coastal Kenya, although with some variability among villages.

Abstract Schistosoma haematobium infection causes urogenital schistosomiasis, a chronic inflammatory disease that is highly prevalent in many parts of sub-Saharan Africa. Bulinid snails are the obligate intermediate hosts in the transmission of this parasite. In the present study, Bulinus globosus and Bulinus nasutus snails from coastal Kenya were raised in the laboratory and exposed to miracidia derived from sympatric S. haematobium specimens to assess the species-specific impact of parasite contact and infection. The snails' subsequent patterns of survival, cercarial shedding, and reproduction were monitored for up to 3 months postexposure. Schistosoma haematobium exposure significantly decreased the survival of B. globosus , but not of B. nasutus . Although both species were capable of transmitting S. haematobium , the B. globosus study population had a greater cumulative incidence of cercarial shedders and a higher average number of cercariae shed per snail than did the B. nasutus population. The effects of prior parasite exposure on snail reproduction were different between the two species. These included more numerous production of egg masses by exposed B. nasutus (as compared with unexposed snails), contrasted to decreased overall egg mass production by parasite-exposed B. globosus . The interspecies differences in the response to and transmission of S. haematobium reflect clear differences in life histories for the two bulinid species when they interact with the parasite, which should be taken into account when planning control interventions aimed at reducing each host snails' contribution to local transmission of Schistosoma infection.

Dengue virus (DENV) and West Nile virus (WNV) are important reemerging arboviruses that are under-recognized in many parts of Africa due to lack of surveillance. As a part of a study on flavivirus, alphavirus, and parasite exposure in coastal Kenya, we measured neutralizing antibody against DENV and, to evaluate assay specificity, WNV in serum samples that tested positive for serum anti-DENV IgG by enzyme-linked immunosorbent assay. Of 830 anti-DENV IgG-positive samples that were tested for neutralizing activity, 488 (58.8%) neutralized DENV and 94 (11.3%) neutralized WNV. Of children ≤ 10 years of age, 23% and 17% had serum neutralizing antibody to DENV and WNV, respectively, indicating that DENV and WNV transmission has occurred in this region within the past decade. The results suggest that ongoing DENV and WNV transmission continues on the coast of Kenya and supports a need for routine arboviral surveillance in the area to detect and respond to future outbreaks., (© The American Society of Tropical Medicine and Hygiene.)

Background: Parasitic infections, which are among the most common infections worldwide, disproportionately affect children; however, little is known about the impact of parasitic disease on growth in very early childhood. Our objective was to document the prevalence of parasitic infections and examine their association with growth during the first three years of life among children in coastal Kenya., Methodology/principal Findings: Children enrolled in a maternal-child cohort were tested for soil transmitted helminths (STHs: Ascaris, Trichuris, hookworm, Strongyloides), protozoa (malaria, Entamoeba histolytica and Giardia lamblia), filaria, and Schistosoma infection every six months from birth until age three years. Anthropometrics were measured at each visit. We used generalized estimating equation (GEE) models to examine the relationship between parasitic infections experienced in the first three years of life and growth outcomes (weight, length and head circumference). Of 545 children, STHs were the most common infection with 106 infections (19%) by age three years. Malaria followed in period prevalence with 68 infections (12%) by three years of age. Filaria and Schistosoma infection occurred in 26 (4.8%) and 16 (2.9%) children, respectively. Seven percent were infected with multiple parasites by three years of age. Each infection type (when all STHs were combined) was documented by six months of age. Decreases in growth of weight, length and head circumference during the first 36 months of life were associated with hookworm, Ascaris, E. histolytica, malaria and Schistosoma infection. In a subset analysis of 180 children who followed up at every visit through 24 months, infection with any parasite was associated with decelerations in weight, length and head circumference growth velocity. Multiple infections were associated with greater impairment of linear growth., Conclusions/significance: Our results demonstrate an under-recognized burden of parasitism in the first three years of childhood in rural Kenya. Parasitic infection and polyparasitism were common, and were associated with a range of significant growth impairment in terms of weight, length and/or head circumference.

In a study of children having polyparasitic infections in a Schistosoma haematobium-endemic area, we examined the hypothesis that S. haematobium-positive children, compared with S. haematobium-negative children (anti-soluble worm antigen preparation [SWAP] negative and egg negative) have increased systemic production of pro-inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α) and decreased down-regulatory IL-10. A total of 804 children, 2-19 years of age, were surveyed between July and December 2009 and tested for S. haematobium, Plasmodium falciparum, filariasis, and soil-transmitted helminth infections. Plasma levels of IL-6, TNF-α, and IL-10 were compared for S. haematobium-positive and S. haematobium-negative children, adjusting for malaria, filaria, and hookworm co-infections, and for nutritional status, age group, sex, and geographic location. IL-10 was significantly elevated among children infected with S. haematobium, showing bimodal peaks in 7-8 and 13-14 years age groups. IL-10 was also higher among children who were acutely malnourished, whereas IL-10 levels were lower in the presence of S. haematobium-filaria co-infection. After adjustment for co-factors, IL-6 was significantly elevated among children of 5-6 years and among those with P. falciparum infection. Lower levels of IL-6 were found in malaria-hookworm co-infection. High levels of TNF-α were found in children aged 11-12 years regardless of infection status. In addition, village of residence was a strong predictor of IL-6 and IL-10 plasma levels. In adolescent children infected with S. haematobium, there is an associated elevation in circulating IL-10 that may reduce the risk of later morbidity. Although we did not find a direct link between S. haematobium infection and circulating pro-inflammatory IL-6 and TNF-α levels, future T-cell stimulation studies may provide more conclusive linkages between infection and cytokine responses in settings that are endemic for multiple parasites and multiple co-infections., (© The American Society of Tropical Medicine and Hygiene.)

Background: Mosquito-borne Rift Valley fever virus (RVFV) causes acute, often severe, disease in livestock and humans. To determine the exposure factors and range of symptoms associated with human RVF, we performed a population-based cross-sectional survey in six villages across a 40 km transect in northeastern Kenya., Methodology/principal Findings: A systematic survey of the total populations of six Northeastern Kenyan villages was performed. Among 1082 residents tested via anti-RVFV IgG ELISA, seroprevalence was 15% (CI95%, 13-17%). Prevalence did not vary significantly among villages. Subject age was a significant factor, with 31% (154/498) of adults seropositive vs. only 2% of children ≤15 years (12/583). Seroprevalence was higher among men (18%) than women (13%). Factors associated with seropositivity included a history of animal exposure, non-focal fever symptoms, symptoms related to meningoencephalitis, and eye symptoms. Using cluster analysis in RVFV positive participants, a more severe symptom phenotype was empirically defined as having somatic symptoms of acute fever plus eye symptoms, and possibly one or more meningoencephalitic or hemorrhagic symptoms. Associated with this more severe disease phenotype were older age, village, recent illness, and loss of a family member during the last outbreak. In multivariate analysis, sheltering livestock (aOR = 3.5 CI95% 0.93-13.61, P = 0.065), disposing of livestock abortus (aOR = 4.11, CI95% 0.63-26.79, P = 0.14), and village location (P = 0.009) were independently associated with the severe disease phenotype., Conclusions/significance: Our results demonstrate that a significant proportion of the population in northeastern Kenya has been infected with RVFV. Village and certain animal husbandry activities were associated with more severe disease. Older age, male gender, herder occupation, killing and butchering livestock, and poor visual acuity were useful markers for increased RVFV infection. Formal vision testing may therefore prove to be a helpful, low-technology tool for RVF screening during epidemics in high-risk rural settings.

Background: Multiple recent outbreaks of Rift Valley Fever (RVF) in Africa, Madagascar, and the Arabian Peninsula have resulted in significant morbidity, mortality, and financial loss due to related livestock epizootics. Presentation of human RVF varies from mild febrile illness to meningoencephalitis, hemorrhagic diathesis, and/or ophthalmitis with residual retinal scarring, but the determinants for severe disease are not understood. The aim of the present study was to identify human genes associated with RVF clinical disease in a high-risk population in Northeastern Province, Kenya., Methodology/principal Findings: We conducted a cross-sectional survey among residents (N = 1,080; 1-85 yrs) in 6 villages in the Sangailu Division of Ijara District. Participants completed questionnaires on past symptoms and exposures, physical exam, vision testing, and blood collection. Single nucleotide polymorphism (SNP) genotyping was performed on a subset of individuals who reported past clinical symptoms consistent with RVF and unrelated subjects. Four symptom clusters were defined: meningoencephalitis, hemorrhagic fever, eye disease, and RVF-not otherwise specified. SNPs in 46 viral sensing and response genes were investigated. Association was analyzed between SNP genotype, serology and RVF symptom clusters. The meningoencephalitis symptom phenotype cluster among seropositive patients was associated with polymorphisms in DDX58/RIG-I and TLR8. Having three or more RVF-related symptoms was significantly associated with polymorphisms in TICAM1/TRIF, MAVS, IFNAR1 and DDX58/RIG-I. SNPs significantly associated with eye disease included three different polymorphisms TLR8 and hemorrhagic fever symptoms associated with TLR3, TLR7, TLR8 and MyD88., Conclusions/significance: Of the 46 SNPs tested, TLR3, TLR7, TLR8, MyD88, TRIF, MAVS, and RIG-I were repeatedly associated with severe symptomatology, suggesting that these genes may have a robust association with RVFV-associated clinical outcomes. Studies of these and related genetic polymorphisms are warranted to advance understanding of RVF pathogenesis.

Background: Chikungunya virus (CHIKV) and o'nyong nyong virus (ONNV) are mosquito-borne alphaviruses endemic in East Africa that cause acute febrile illness and arthritis. The objectives of this study were to measure the seroprevalence of CHIKV and ONNV in coastal Kenya and link it to demographics and other risk factors., Methodology: Demographic and exposure questionnaires were administered to 1,848 participants recruited from two village clusters (Milalani-Nganja and Vuga) in 2009. Sera were tested for alphavirus exposure using standardized CHIKV IgG ELISA protocols and confirmed with plaque reduction neutralization tests (PRNT). Logistic regression models were used to determine the variables associated with seropositivity. Weighted K test for global clustering of houses with alphavirus positive participants was performed for distance ranges of 50-1,000 meters, and G* statistic and kernel density mapping were used to identify locations of higher seroprevalence., Principal Findings: 486 (26%) participants were seropositive by IgG ELISA. Of 443 PRNT confirmed positives, 25 samples (6%) were CHIKV+, 250 samples (56%) were ONNV+, and 168 samples (38%) had high titers for both. Age was significantly associated with seropositivity (OR 1.01 per year, 95% C.I. 1.00-1.01); however, younger adults were more likely to be seropositive than older adults. Males were less likely to be seropositive (p<0.05; OR 0.79, 95% C.I. 0.64-0.97). Adults who owned a bicycle (p<0.05; OR 1.37, 95% C.I. 1.00-1.85) or motor vehicle (p<0.05; OR 4.64, 95% C.I. 1.19-18.05) were more likely to be seropositive. Spatial analysis demonstrated hotspots of transmission within each village and clustering among local households in Milalani-Nganja, peaking at the 200-500m range., Conclusions/significance: Alphavirus exposure, particularly ONNV exposure, is common in coastal Kenya with ongoing interepidemic transmission of both ONNV and CHIKV. Women and adults were more likely to be seropositive. Household location may be a defining factor for the ecology of alphaviral transmission in this region.

Few studies have focused on Rift Valley fever virus (RVFV) transmission in less arid, transitional landscapes surrounding known high-risk regions. The objective of this study was to identify evidence of RVFV exposure in Bodhei Village in a forested area at the edge of the RVFV-epidemic Garissa region. In a household cluster-based survey conducted between epidemics in early 2006, 211 participants were enrolled. Overall seroprevalence for anti-RVFV was high (18%) and comparable with rates in the more arid, dense brush regions farther north. Seroprevalence of adults was 28%, whereas that of children was significantly lower (3%; P < 0.001); the youngest positive child was age 3 years. Males were more likely to be seropositive than females (25% versus 11%; P < 0.01), and animal husbandry activities (birthing, sheltering, and butchering) were strongly associated with seropositivity. The results confirm that significant RVFV transmission occurs outside of recognized high-risk areas and independent of known epidemic periods., (© The American Society of Tropical Medicine and Hygiene.)

Background: Parasitic infections are prevalent among pregnant women in sub-Saharan Africa. We investigated whether prenatal exposure to malaria and/or helminths affects the pattern of infant immune responses to standard vaccinations against Haemophilus influenzae (Hib), diphtheria (DT), hepatitis B (Hep B) and tetanus toxoid (TT)., Methods and Findings: 450 Kenyan women were tested for malaria, schistosomiasis, lymphatic filariasis (LF), and intestinal helminths during pregnancy. After three standard vaccinations at 6, 10 and 14 weeks, their newborns were followed biannually to age 36 months and tested for absolute levels of IgG against Hib, DT, Hep B, and TT at each time point. Newborns' cord blood (CB) lymphocyte responses to malaria blood-stage antigens, soluble Schistosoma haematobium worm antigen (SWAP), and filaria antigen (BMA) were also assessed. Three immunophenotype categories were compared: i) tolerant (those having Plasmodium-, Schistosoma-, or Wuchereria-infected mothers but lacking respective Th1/Th2-type recall responses at birth to malaria antigens, SWAP, or BMA); ii) sensitized (those with infected/uninfected mothers and detectable Th1/Th2-type CB recall response to respective parasite antigen); or iii) unexposed (no evidence of maternal infection or CB recall response). Overall, 78.9% of mothers were infected with LF (44.7%), schistosomiasis (32.4%), malaria (27.6%) or hookworm (33.8%). Antenatal maternal malaria, LF, and hookworm were independently associated with significantly lower Hib-specific IgG. Presence of multiple maternal infections was associated with lower infant IgG levels against Hib and DT antigens post-vaccination. Post-vaccination IgG levels were also significantly associated with immunophenotype: malaria-tolerized infants had reduced response to DT, whereas filaria-tolerized infants showed reduced response to Hib., Conclusions: There is an impaired ability to develop IgG antibody responses to key protective antigens of Hib and diphtheria in infants of mothers infected with malaria and/or helminths during pregnancy. These findings highlight the importance of control and prevention of parasitic infections among pregnant women.

Background: In coastal Kenya, infection of human populations by a variety of parasites often results in co-infection or poly-parasitism. These parasitic infections, separately and in conjunction, are a major cause of chronic clinical and sub-clinical human disease and exert a long-term toll on economic welfare of affected populations. Risk factors for these infections are often shared and overlap in space, resulting in interrelated patterns of transmission that need to be considered at different spatial scales. Integration of novel quantitative tools and qualitative approaches is needed to analyze transmission dynamics and design effective interventions., Methodology: Our study was focused on detecting spatial and demographic patterns of single- and co-infection in six villages in coastal Kenya. Individual and household level data were acquired using cross-sectional, socio-economic, and entomological surveys. Generalized additive models (GAMs and GAMMs) were applied to determine risk factors for infection and co-infections. Spatial analysis techniques were used to detect local clusters of single and multiple infections., Principal Findings: Of the 5,713 tested individuals, more than 50% were infected with at least one parasite and nearly 20% showed co-infections. Infections with Schistosoma haematobium (26.0%) and hookworm (21.4%) were most common, as was co-infection by both (6.3%). Single and co-infections shared similar environmental and socio-demographic risk factors. The prevalence of single and multiple infections was heterogeneous among and within communities. Clusters of single and co-infections were detected in each village, often spatially overlapped, and were associated with lower SES and household crowding., Conclusion: Parasitic infections and co-infections are widespread in coastal Kenya, and their distributions are heterogeneous across landscapes, but inter-related. We highlighted how shared risk factors are associated with high prevalence of single infections and can result in spatial clustering of co-infections. Spatial heterogeneity and synergistic risk factors for polyparasitism need to be considered when designing surveillance and intervention strategies.

To better delineate the impact of parasitic coinfection in coastal Kenya, we developed a novel specimen-sparing bead assay using multiplex flow immunoassay (MFI) technology to simultaneously measure serum or plasma immunoglobulin G4 (IgG4) against Brugia malayi antigen (BMA) and Schistosoma haematobium soluble worm antigen (SWAP). Properties of the bead assay were estimated by latent class analysis using data from S. haematobium egg counts/filarial rapid diagnostic cards (RDTs), parasite-specific enzyme-linked immunosorbent assays (ELISAs), and the multichannel IgG4 assay. For schistosomiasis, the bead assay had an estimated sensitivity of 81% and a specificity of 45%, and it was more sensitive than ELISA or urine egg counts for diagnosing infection. For filariasis, it had a sensitivity of 86% and a specificity of 39%, and it was more sensitive than ELISA or RDT. Measuring antibody by MFI is feasible and may provide more accurate epidemiological information than current parasitological tests, especially in the setting of low-intensity infections.

Long-term success of ongoing malaria control efforts based on mosquito bed nets (long-lasting insecticidal net) and indoor residual spraying is dependent on continuous monitoring of mosquito vectors, and thus on effective mosquito sampling tools. The objective of our study was to identify the most efficient mosquito sampling tool(s) for routine vector surveillance for malaria and lymphatic filariasis transmission in coastal Kenya. We evaluated relative efficacy of five collection methods--light traps associated with a person sleeping under a net, pyrethrum spray catches, Prokopack aspirator, clay pots, and urine-baited traps--in four villages representing three ecological settings along the south coast of Kenya. Of the five methods, light traps were the most efficient for collecting female Anopheles gambiae s.l. (Giles) (Diptera: Culicidae) and Anopheles funestus (Giles) (Diptera: Culicidae) mosquitoes, whereas the Prokopack aspirator was most efficient in collecting Culex quinquefasciatus (Say) (Diptera: Culicidae) and other culicines. With the low vector densities here, and across much of sub-Saharan Africa, wherever malaria interventions, long-lasting insecticidal nets, and/or indoor residual spraying are in place, the use of a single mosquito collection method will not be sufficient to achieve a representative sample of mosquito population structure. Light traps will remain a relevant tool for host-seeking mosquitoes, especially in the absence of human landing catches. For a fair representation of the indoor mosquito population, light traps will have to be supplemented with aspirator use, which has potential for routine monitoring of indoor resting mosquitoes, and can substitute the more labor-intensive and intrusive pyrethrum spray catches. There are still no sufficiently efficient mosquito collection methods for sampling outdoor mosquitoes, particularly those that are bloodfed.

We measured prevalence of Schistosoma haematobium, Wuchereria bancrofti, Plasmodium falciparum, hookworm, and other geohelminths among school-aged children in four endemic villages in Kwale County, Kenya and explored the relationship between multiparasite burden, undernutrition, and anemia. In 2009-2010 surveys, cross-sectional data were obtained for 2,030 children 5-18 years old. Infections were most prevalent for S. haematobium (25-62%), hookworm (11-28%), and falciparum malaria (8-24%). Over one-half of children were anemic, with high rates of acute and chronic malnutrition. Associations with infection status showed significant age and sex differences. For boys, young age, low socioeconomic standing (SES), S. haematobium, and/or malaria infections were associated with greater odds of anemia, wasting, and/or stunting; for girls, heavy S. haematobium infection and age were the significant cofactors for anemia, whereas low SES and older age were linked to stunting. The broad overlap of infection-related causes for anemia and malnutrition and the high frequency of polyparasitic infections suggest that there will be significant advantages to integrated parasite control in this area.

Background: Despite the extensive ownership and use of insecticide-treated nets (ITNs) over the last decade, the effective lifespan of these nets, especially their physical integrity, under true operational conditions is not well-understood. Usefulness of nets declines primarily due to physical damage or loss of insecticidal activity., Methods: A community based cross-sectional survey was used to determine the physical condition and to identify predictors of poor physical condition for bed nets owned by individuals from communities in Kwale County, coastal Kenya. A proportionate hole index (pHI) was used as a standard measure, and the cut-offs for an 'effective net' (offer substantial protection against mosquito bites) and 'ineffective nets' (offer little or no protection against mosquito bites) were determined (pHI ≤88 (about ≤500 cm2 of holes surface area) and pHI of >88 (≥500 cm2 of holes surface area), respectively)., Results: The vast majority (78%) of the surveyed nets had some holes. The median pHI was 92 (range: 1-2,980). Overall, half of the nets were categorized as 'effective nets' or 'serviceable nets'. Physical deterioration of nets was associated with higher use and washing frequency. Young children and older children were found to use ineffective bed nets significantly more often than infants, while the physical integrity of nets owned by pregnant women was similar to those owned by infants. Estuarine environment inhabitants owned nets with the worst physical condition, while nets owned by the coastal slope inhabitants were in fairly good physical condition. The results suggest that bed nets are optimally utilized when they are new and physically intact. Thereafter, bed net utilization decreases gradually with increasing physical deterioration, with most net owners withdrawing physically damaged nets from routine use.This withdrawal commonly happens following 1.5 years of use, making bed net use the most important predictor of physical integrity. On average, the nets were washed twice within six months prior to the survey. Washing frequency was significantly influenced by the bed net colour and bed net age. Lack of knowledge on reasons for net retreatment and the retreatment procedure was evident, while net repair was minimal and did not seem to improve the physical condition of the nets. The "catch-up" bed net distribution strategies are sufficient for ensuring adequate ownership and utilization of 'effective nets' in the targeted groups, but bi-annual mass distribution is necessary to provide similar ownership and utilization for the other groups not targeted by "catch-up" strategies., Conclusions: Monitoring and maintenance strategies that will deliver locally appropriate education messages on net washing and repair will enhance the effectiveness of malaria control programmes, and further research to assess ineffective nets need is needed.

Background: Schistosomiasis remains a global public health challenge, with 93% of the ~237 million infections occurring in sub-Saharan Africa. Though rarely fatal, its recurring nature makes it a lifetime disorder with significant chronic health burdens. Much of its negative health impact is due to non-specific conditions such as anemia, undernutrition, pain, exercise intolerance, poor school performance, and decreased work capacity. This makes it difficult to estimate the disease burden specific to schistosomiasis using the standard DALY metric., Methodology/principal Findings: In our study, we used Pediatric Quality of Life Inventory (PedsQL), a modular instrument available for ages 2-18 years, to assess health-related quality of life (HrQoL) among children living in a Schistosoma haematobium-endemic area in coastal Kenya. The PedsQL questionnaires were administered by interview to children aged 5-18 years (and their parents) in five villages spread across three districts. HrQoL (total score) was significantly lower in villages with high prevalence of S. haematobium (-4.0%, p<0.001) and among the lower socioeconomic quartiles (-2.0%, p<0.05). A greater effect was seen in the psychosocial scales as compared to the physical function scale. In moderate prevalence villages, detection of any parasite eggs in the urine was associated with a significant 2.1% (p<0.05) reduction in total score. The PedsQL reliabilities were generally high (Cronbach alphas ≥0.70), floor effects were acceptable, and identification of children from low socioeconomic standing was valid., Conclusions/significance: We conclude that exposure to urogenital schistosomiasis is associated with a 2-4% reduction in HrQoL. Further research is warranted to determine the reproducibility and responsiveness properties of QoL testing in relation to schistosomiasis. We anticipate that a case definition based on more sensitive parasitological diagnosis among younger children will better define the immediate and long-term HrQoL impact of Schistosoma infection.

In schistosomiasis elimination programs, successful discrimination of Schistosoma haematobium from the related animal Schistosoma parasites will be essential for accurate detection of human parasite transmission. Polymerase chain reaction assays employing primers from two newly selected repeated sequences, named Sh73 and Sh77, did not discriminate S. haematobium when amplifying Sh73-77 intra- or inter-repeats. However, amplification between Sh73 and the previously described DraI repeat exhibited discriminative banding patterns for S. haematobium and Schistosoma bovis (sensitivity 1 pg and 10 pg, respectively). It also enabled banding pattern discrimination of Schistosoma curassoni and Schistosoma intercalatum, but Schistosoma mattheei and Schistosoma margrebowiei did not yield amplicons. Similar inter-repeat amplification between Sh77 and DraI yielded amplicons with discriminative banding for S. haematobium, and S. bovis; however, S. mattheei was detected only at low sensitivity (1 ng). The Sh73/DraI assay detected snails infected with S. haematobium, S. bovis, or both, and should prove useful for screening snails where discrimination of S. haematobium from related schistosomes is required.

Worldwide, lack of access to safe drinking water together with inadequate sanitation and hygiene is an overwhelming contributor to approximately 4 billion cases of illness annually. This study was set out to understand the effects of hygiene and sanitation interventions on targeted health outcomes including diarrhoeal prevalence in children's of Turkana District, Kenya. The interventions undertaken included capacity building and empowerment approach to trigger communities to demand hygiene and sanitation facilities. Three hundred mothers were randomly sampled in a baseline survey carried out in 2007 and in a post-intervention survey carried out in 2008 (a repeat cross-sectional study design). Specimens were collected for microbiological tests of key diarrhoea related pathogens. Overall, Faecal coliform counts per 100 ml sample had significant variations between 2007 and 2008; in Kakuma, reduced from 88 to 30.2 colony units (P = 0.005), Lodwar Central where the number reduced from 91 to 17.3 units (P = 0.003), and in Lokichogio Division, the number reduced from 63.8 to 23.6 units (P = 0.006). From the 230 stool samples examined, the proportion of children from whom infectious pathogens of Proteus spp. was isolated reduced from 16 to 7 % while Escherichia coli reduced from 54 to 41 %. Overall, prevalence of diarrhoea related microbes in children aged <5 years reduced from 91.3 % in 2007 to 78.3 % after intervention (2008). It is notable that sanitation and hygiene promotion leads to significant reduction of diarrhoea prevalence in children aged <5 years. Its application should therefore be up-scaled in resource constrained areas.

Lack of adequate sanitation, hygiene and safe portable water are serious global health problems that contribute to deaths of many children under the age of 5 years annually, mainly due to diarrhoeal diseases. This study was set out to determine the extent to which sanitation and hygiene promotion influenced mothers' and children's health in Turkana District; one of the arid Northern frontier Districts of Kenya. A repeat cross-sectional study design with multi-stage sampling method was used. A total of 300 mothers were randomly sampled for interviews in a baseline survey carried out in 2007 and in a post-intervention survey carried out in 2008. Data were collected using questionnaires and analyzed using SPSS for frequencies, cross tabulations and regression amongst other tests. Significant improvements were observed in hand washing practice, presence of hand washing soap at household and refuse pit ownership. In Kakuma Division the proportion of those who washed hands regularly increased from 48.8 to 91.3 % (χ(2) = 7.28, P = 0.122), in Lodwar Central, those who wash hands regularly increased from 85.5 to 89.9 % (χ² = 10.85, P = 0.028) while in Lokichogio, the proportions increased from 77.5 to 93.8 % (χ² = 15.56, P = 0.004). For hand washing soap at household, there was an increase in proportion of those who wash hands with soap from 65 to 78 % (χ² = 3.87, P = 0.049) within the group with no formal education. There was significant reduction of diarrhoea prevalence in children aged less than 5 years. Sanitation and hygiene promotion based on community participatory approaches can lead to significant reduction of diarrhoea in children.

Background: Schistosome and soil-transmitted helminth (STH) infections are recognized as major global public health problems, causing severe and subtle morbidity, including significant educational and nutritional effects in children. Although effective and safe drugs are available, ensuring access to these drugs by all those at risk of schistosomiasis and STHs is still a challenge. Community-directed intervention (CDI) has been used successfully for mass distribution of drugs for other diseases such as onchocerciasis and lymphatic filariasis. A national control programme is yet to be instituted in Kenya and evidence for cost-effective strategies for reaching most affected communities is needed. This study evaluated the effectiveness and feasibility of the CDI strategy in the control of schistosomiasis and STHs, in East Uyoma location, Rarieda district, a community of western Kenya that is highly endemic for both infections., Results: Pre-treatment prevalence of S. mansoni averaged 17.4% (range 5-43%) in the entire location. Treatment coverage in different villages ranged from 54.19 to 96.6% by community drug distributor (CDD) records. Assessment from a household survey showed coverage of 52.3 -91.9% while the proportion of homesteads (home compounds) covered ranged from 54.9-98.5%. Six months after one round of drug distribution, the prevalence levels of S. mansoni, hookworm and Trichuris trichura infections were reduced by 33.2%, 69.4% and 42.6% respectively., Conclusions: This study shows that CDI is an accepted and effective strategy in the mass treatment of schistosomiasis and STH infections in resource constrained communities in Kenya and may be useful in similar communities elsewhere. A controlled trial comparing CDI and school based mass drug administration to demonstrate their relative advantages is ongoing.

In utero priming to malaria antigens renders cord blood mononuclear cells (CBMC) more susceptible to productive HIV infection in vitro in the absence of exogenous stimulation. This provides a unique model to better understand mechanisms affecting lymphocyte susceptibility to HIV infection in vivo. Effector memory CD3(+)CD4(+) T cells (T(EM)) were the exclusive initial targets of HIV with rapid spread to central memory cells. HIV susceptibility correlated with increased expression of CD25 and HLA-DR on T(EM). Virus entered all samples equally, however gag/pol RNA was only detected in HIV susceptible samples, suggesting regulation of proviral gene transcription. Targeted analysis of human genes in memory T cells showed greater expression of IFNG, NFATc1, IRF1, FOS, and PPIA and decreased expression YY1 and TFCP2 in HIV susceptible samples. Thus fetal priming to exogenous antigens enhances specific proviral gene transcription pathways in effector memory cells that may increase risk of vertical transmission of HIV., (Published by Elsevier Inc.)

Background: Schistosomiasis remains a significant health burden in many areas of the world. Morbidity control, focused on limiting infection intensity through periodic delivery of anti-schistosomal medicines, is the thrust of current World Health Organization guidelines (2006) for reduction of Schistosoma-related disease. A new appreciation of the lifetime impact of repeated Schistosoma infection has directed attention toward strategies for greater suppression of parasite infection per se, with the goal of transmission interruption. Variations in drug schedules involving increased population coverage and/or treatment frequency are now undergoing field trials. However, their relative effectiveness in long-term infection suppression is presently unknown., Methodology/principal Findings: Our study used available field data to calibrate advanced network models of village-level Schistosoma transmission to project outcomes of six different community- or school age-based programs, as compared to the impact of current 2006 W.H.O. recommended control strategies. We then scored the number of years each of 10 typical villages would remain below 10% infection prevalence (a practicable level associated with minimal prevalence of disease). All strategies that included four annual treatments effectively reduced community prevalence to less than 10%, while programs having yearly gaps ('holidays') failed to reach this objective in half of the communities. Effective post-program suppression of infection prevalence persisted in half of the 10 villages for 7-10 years, whereas in five high-risk villages, program effects on prevalence lasted zero to four years only., Conclusions/significance: At typical levels of treatment adherence (60 to 70%), current WHO recommendations will likely not achieve effective suppression of Schistosoma prevalence unless implemented for ≥6 years. Following more aggressive 4 year annual intervention, some communities may be able to continue without further intervention for 8-10 years, while in higher-risk communities, annual treatment may prove necessary until eco-social factors fostering transmission are removed. Effective ongoing surveillance and locally targeted annual intervention must then become their mainstays of control.

Background: Residents of resource-poor tropical countries carry heavy burdens of concurrent parasitic infections, leading to high rates of morbidity and mortality. This study was undertaken to help identify the social and environmental determinants of multiple parasite infection in one such community., Methodology/principal Findings: Residents of Kingwede, Kenya aged 8 years and older were tested for presence and intensity of S. haematobium and Plasmodium spp. infections in a cross-sectional, household-based, community survey. Using General Estimating Equation (GEE) models, social and environmental determinants associated with patterns of co-infection were identified, with age being one of the most important factors. Children had 9.3 times the odds of co-infection compared to adults (95%CI=5.3-16.3). Even after controlling for age, socio-economic position, and other correlates of co-infection, intense concomitant infections with the two parasites were found to cluster in a subset of individuals: the odds of heavy vs. light S. haematobium infection increased with increasing Plasmodium infection intensity suggesting the importance of unmeasured biological factors in determining intensity of co-infection., Conclusions/significance: Children in this community are more likely to be infected with multiple parasites than are adults and should therefore be targeted for prevention and control interventions. More importantly, heavy infections with multiple parasite species appear to cluster within a subset of individuals. Further studies focusing on these most vulnerable people are warranted.

Background: Besides significantly reducing malaria vector densities, prolonged usage of bed nets has been linked to decline of Anopheles gambiae s.s. relative to Anopheles arabiensis, changes in host feeding preference of malaria vectors, and behavioural shifts to exophagy (outdoor biting) for the two important malaria vectors in Africa, An. gambiae s.l. and Anopheles funestus. In southern coastal Kenya, bed net use was negligible in 1997-1998 when Anopheles funestus and An. gambiae s.s. were the primary malaria vectors, with An. arabiensis and Anopheles merus playing a secondary role. Since 2001, bed net use has increased progressively and reached high levels by 2009-2010 with corresponding decline in malaria transmission., Methods: To evaluate the impact of the substantial increase in household bed net use within this area on vector density, vector composition, and human-vector contact, indoor and outdoor resting mosquitoes were collected in the same region during 2009-2010 using pyrethrum spray catches and clay pots for indoor and outdoor collections respectively. Information on bed net use per sleeping spaces and factors influencing mosquito density were determined in the same houses using Poisson regression analysis. Species distribution was determined, and number of mosquitoes per house, human-biting rates (HBR), and entomological inoculation rate (EIR) were compared to those reported for the same area during 1997-1998, when bed net coverage had been minimal., Results: Compared to 1997-1998, a significant decline in the relative proportion of An. gambiae s.s. among collected mosquitoes was noted, coupled with a proportionate increase of An. arabiensis. Following > 5 years of 60-86% coverage with bed nets, the density, human biting rate and EIR of indoor resting mosquitoes were reduced by more than 92% for An. funestus and by 75% for An. gambiae s.l. In addition, the host feeding choice of both vectors shifted more toward non-human vertebrates. Besides bed net use, malaria vector abundance was also influenced by type of house construction and according to whether one sleeps on a bed or a mat (both of these are associated with household wealth). Mosquito density was positively associated with presence of domestic animals., Conclusions: These entomological indices indicate a much reduced human biting rate and a diminishing role of An. gambiae s.s. in malaria transmission following high bed net coverage. While increasing bed net coverage beyond the current levels may not significantly reduce the transmission potential of An. arabiensis, it is anticipated that increasing or at least sustaining high bed net coverage will result in a diminished role for An. funestus in malaria transmission.

We analyzed temporal changes in spatial patterns of active Schistosoma haematobium infection in different age groups and associated them with ponds infested with Bulinus snails. A major drought between 2001 and 2009 resulted in drying of ponds that were known sources of infection, and we detected very few or no snails in ponds that were infested in the past. The household-level spatial pattern of infection for children of various age groups in 2009 was contrasted with historical data from 2000. The significant local clustering of high- and low-infection levels among school-aged children that occurred in 2000 was absent in 2009. We attribute the disappearance of significant clustering around historical transmission hot spots to a decade-long drought in our study area. The implications of extreme weather and climate conditions on risk and transmission of S. haematobium and their relevance to control strategies are discussed.

Background: In endemic areas, Rift Valley fever virus (RVFV) is a significant threat to both human and animal health. Goals of this study were to measure human anti-RVFV seroprevalence in a high-risk area following the 2006-2007 Kenyan Rift Valley Fever (RVF) epidemic, to identify risk factors for interval seroconversion, and to monitor individuals previously exposed to RVFV in order to document the persistence of their anti-RVFV antibodies., Methodology/findings: We conducted a village cohort study in Ijara District, Northeastern Province, Kenya. One hundred two individuals tested for RVFV exposure before the 2006-2007 RVF outbreak were restudied to determine interval anti-RVFV seroconversion and persistence of humoral immunity since 2006. Ninety-two additional subjects were enrolled from randomly selected households to help identify risk factors for current seropositivity. Overall, 44/194 or 23% (CI(95%):17%-29%) of local residents were RVFV seropositive. 1/85 at-risk individuals restudied in the follow-up cohort had seroconverted since early 2006. 27/92 (29%, CI(95%): 20%-39%) of newly tested individuals were seropositive. All 13 individuals with positive titers (by plaque reduction neutralization testing (PRNT₈₀) in 2006 remained positive in 2009. After adjustment in multivariable logistic models, age, village, and drinking raw milk were significantly associated with RVFV seropositivity. Visual impairment (defined as ≤ 20/80) was much more likely in the RVFV-seropositive group (P<0.0001)., Conclusions: Our results highlight significant variability in RVFV exposure in two neighboring villages having very similar climate, terrain, and insect density. Among those with previous exposure, RVFV titers remained at > 1∶40 for more than 3 years. In concordance with previous studies, residents of the more rural village were more likely to be seropositive and RVFV seropositivity was associated with poor visual acuity. Raw milk consumption was strongly associated with RVFV exposure, which may represent an important new focus for public health education during future RVF outbreaks.

Background: To date, there has been no standardized approach to the assessment of aerobic fitness among children who harbor parasites. In quantifying the disability associated with individual or multiple chronic infections, accurate measures of physical fitness are important metrics. This is because exercise intolerance, as seen with anemia and many other chronic disorders, reflects the body's inability to maintain adequate oxygen supply (VO(2) max) to the motor tissues, which is frequently linked to reduced quality-of-life in terms of physical and job performance. The objective of our study was to examine the associations between polyparasitism, anemia, and reduced fitness in a high risk Kenyan population using novel implementation of the 20-meter shuttle run test (20mSRT), a well-standardized, low-technology physical fitness test., Methodology/principal Findings: Four villages in coastal Kenya were surveyed during 2009-2010. Children 5-18 years were tested for infection with Schistosoma haematobium (Sh), malaria, filaria, and geohelminth infections by standard methods. After anthropometric and hemoglobin testing, fitness was assessed with the 20 mSRT. The 20 mSRT proved easy to perform, requiring only minimal staff training. Parasitology revealed high prevalence of single and multiple parasitic infections in all villages, with Sh being the most common (25-62%). Anemia prevalence was 45-58%. Using multiply-adjusted linear modeling that accounted for household clustering, decreased aerobic capacity was significantly associated with anemia, stunting, and wasting, with some gender differences., Conclusions/significance: The 20 mSRT, which has excellent correlation with VO(2), is a highly feasible fitness test for low-resource settings. Our results indicate impaired fitness is common in areas endemic for parasites, where, at least in part, low fitness scores are likely to result from anemia and stunting associated with chronic infection. The 20 mSRT should be used as a common metric to quantify physical fitness and compare sub-clinical disability across many different disorders and community settings.

Few studies have investigated the many mosquito species that harbor arboviruses in Kenya. During the 2006-2007 Rift Valley fever outbreak in North Eastern Province, Kenya, exophilic mosquitoes were collected from homesteads within 2 affected areas: Gumarey (rural) and Sogan-Godud (urban). Mosquitoes (n = 920) were pooled by trap location and tested for Rift Valley fever virus and West Nile virus. The most common mosquitoes trapped belonged to the genus Culex (75%). Of 105 mosquito pools tested, 22% were positive for Rift Valley fever virus, 18% were positive for West Nile virus, and 3% were positive for both. Estimated mosquito minimum infection rates did not differ between locations. Our data demonstrate the local abundance of mosquitoes that could propagate arboviral infections in Kenya and the high prevalence of vector arbovirus positivity during a Rift Valley fever outbreak.

Monitoring post-control transmission of schistosomes by examining humans becomes less effective as infection rates among humans decrease. Molecular monitoring of prepatent schistosome infection in snails by the polymerase chain reaction (PCR) has been used for studying human-to-snail transmission, and snail prepatent infection rates were found to correspond to infection prevalence and average intensity in human populations contacting the sites studied. We have now developed loop-mediated isothermal amplification (LAMP) assays for identifying Schistosoma mansoni and S. haematobium to facilitate large-scale evaluation of post-intervention transmission potential. LAMP primers were designed based on the Sm1-7 and DraI repeated sequences of the corresponding schistosomes, and amplification by LAMP of these 121-basepair highly abundant sequences provided a detection sensitivity of 0.1 fg of genomic DNA. When these LAMP assays were applied for examining infected laboratory snails, it was possible to identify infection from the first day after exposure to miracidia. The potential advantages of these assays are discussed.

Rift Valley fever (RVF) virus is an emerging pathogen that is transmitted in many regions of sub-Saharan Africa, parts of Egypt, and the Arabian peninsula. Outbreaks of RVF, like other diseases caused by hemorrhagic fever viruses, typically present in locations with very limited health resources, where initial diagnosis must be based only on history and physical examination. Although general signs and symptoms of human RVF have been documented, a specific clinical syndrome has not been described. In 2007, a Kenyan outbreak of RVF provided opportunity to assess acutely ill RVF patients and better delineate its presentation and clinical course. Our data reveal an identifiable clinical syndrome suggestive of severe RVF, characterized by fever, large-joint arthralgia, and gastrointestinal complaints and later followed by jaundice, right upper-quadrant pain, and delirium, often coinciding with hemorrhagic manifestations. Further characterization of a distinct RVF clinical syndrome will aid earlier detection of RVF outbreaks and should allow more rapid implementation of control.

Objectives: To establish modifiable factors associated with active pulmonary tuberculosis (PTB) among prisoners., Design: Retrospective matched case-control study., Setting: Nakuru GK prison in Kenya., Subjects: A total of 144 subjects (48 cases and 96 controls) were recruited into the study. Cases were adult prisoners who had at least two initial sputum specimens being Acid Fast Bacilli-positive (AFB+) on direct smear microscopy and hence recruited to PTB WHO DOTS Programme. Controls were adults with no chronic cough and not on PTB treatment six months prior to the study., Results: Independent factors significantly associated with active PTB disease were: self reported HIV+ status (OR=11; 95% CI = 2.42-47.77), evidence of BCG vaccination (OR = 0.20; 95% CI = 0.05-0.60), contact with PTB case (OR = 7.0; 95% CI = 1.17-38.23), unemployment (OR = 9.0; 95% CI = 1.84-43.97) and sharing linen (OR = 4.32; 95%CI = 1.08-17.29)., Conclusions: Modifiable factors associated with active PTB in Nakuru G.K prison are: HIV status, BCG vaccination, PTB case contact, poverty and poor personal hygiene. We recommend HIV counselling and testing of all PTB patients, screening for TB upon prison entry and TB contact investigation and improving personal hygiene of prisoners.

Most outbreaks of Rift Valley fever (RVF) occur in remote locations after floods. To determine environmental risk factors and long-term sequelae of human RVF, we examined rates of previous Rift Valley fever virus (RVFV) exposure by age and location during an interepidemic period in 2006. In a randomized household cluster survey in 2 areas of Ijara District, Kenya, we examined 248 residents of 2 sublocations, Gumarey (village) and Sogan-Godud (town). Overall, the RVFV seropositivity rate was 13% according to immunoglobulin G ELISA; evidence of interepidemic RVFV transmission was detected. Increased seropositivity was found among older persons, those who were male, those who lived in the rural village (Gumarey), and those who had disposed of animal abortus. Rural Gumarey reported more mosquito and animal exposure than Sogan-Godud. Seropositive persons were more likely to have visual impairment and retinal lesions; other physical findings did not differ.

Urinary schistosomiasis is an important source of human morbidity in Msambweni, Kenya, where the intermediate host snail, Bulinus nasutus is found in ponds and water pools. In the past, aquatic habitats in the area have been studied separately; however, recent collections of B. nasutus snails and shells indicated that many of these ponds are in fact connected during and following sufficient rains. Satellite imagery and a geographical information system (GIS) were used to survey the main water courses and potential drainage routes, to locate potential source populations of snails and to determine probable snail dispersal routes. The 2 water bodies implicated as being the most important Schistosoma haematobium transmission foci in the area were found to differ in their degree of connectivity to other B. nasutus source habitats. One pond becomes connected even after normal rains, while the other pond requires prolonged rains or flooding to become connected with source habitats. Consequently, the transmission foci differ in their susceptibility to snail population control measures. Spatially explicit dispersal models that consider the spatial and temporal patterns of connectivity between aquatic habitats will contribute to improved snail surveillance and more focused control for urinary schistosomiasis at a local level.

Rift Valley fever virus (RVFV) is an emerging pathogen that maintains high biodefense priority based on its threat to livestock, its ability to cause human hemorrhagic fever, and its potential for aerosol spread. To define the range of human transmission during inter-epidemic and epidemic periods in Kenya, we tested archived sera from defined populations (N = 1,263) for anti-RVFV IgG by ELISA and plaque reduction neutralization testing. RVFV seroprevalence was 10.8% overall and varied significantly by location, sex, and age. In NW Kenya, high seroprevalence among those born before 1980 indicates that an undetected epidemic may have occurred then. Seroconversion documented in highland areas suggests previously unsuspected inter-epidemic transmission. RVFV seroprevalence is strikingly high in certain Kenyan areas, suggesting endemic transmission patterns that may preclude accurate estimation of regional acute outbreak incidence. The extent of both epidemic and inter-epidemic RVFV transmission in Kenya is greater than previously documented.

As part of an extensive study of the eco-epidemiology of urinary schistosomiasis along the southern coast of Kenya, spatial and temporal transmission patterns were associated with various ponds infested with Bulinus snails. The household-level spatial pattern of infection for children of various age groups in 2000 was contrasted with historical data from 1984. Significant local clustering of high and low infection levels among school age children was detected, and the spatial extent of clusters and their direction from specific water sources were measured. High infection levels were clustered around ponds known to contain Bulinus nasutus snails that shed Schistosoma haematobium cercariae, and low infection levels were concentrated near a river where intermediate host snails were rarely found. The spatial patterns of infection varied between 2000 and 1984 and between age groups. High levels of infection were clustered around different transmission foci in the two study periods, and, for younger children in 2000, were clustered nearer to the transmission foci than for the older children. Simultaneous consideration of the effects of different foci on transmission will allow for targeted application of control measures aimed at interrupting S. haematobium transmission at a local level.

Urinary schistosomiasis remains a significant burden for Africa and the Middle East. Success of regional control strategies will depend, in part, on what influence local environmental and behavioral factors have on individual risk for primary infection and/or reinfection. Based on experience in a multi-year (1984-1992), school-based Schistosoma haematobium control program in Coast Province, Kenya, we examined risk for infection outcomes as a function of age, sex, pretreatment morbidity, treatment regimen, water contact, and residence location, with the use of life tables and Cox proportional-hazards analysis. After adjustment, location of residence, age less than 12 years, pretreatment hematuria, and incomplete treatment were the significant independent predictors of infection, whereas sex and frequency of water contact were not. We conclude that local physical features and age-related factors play a predominant role in S. haematobium transmission in this setting. In large population-based control programs, treatment allocation strategies may need to be tailored to local conditions on a village-by-village basis.

Late benefits of remote antischistosomal therapy were estimated among long-term residents of an area with high transmission of Schistosoma haematobium (Msambweni, Kenya) by comparing infection and disease prevalence in two local adult cohorts. We compared 132 formerly treated adults (given treatment in childhood or adolescence > or = 10 years previously) compared with 132 age- and sex-matched adults from the same villages who had not received prior treatment. The prevalence of current infection, hematuria, and ultrasound bladder abnormalities were significantly lower among the previously treated group, who were found to be free of severe bladder disease. Nevertheless, heavy infection was equally prevalent (2-3%) in both study groups, and present rates of hydronephrosis were not significantly different. Therapy given in childhood or adolescence appears to improve risk for some but not all manifestations of S. haematobium infection in later adult life. Future prospective studies of continued treatment into adulthood will better define means to obtain optimal, community-based control of S. haematobium-related disease in high-risk locations.

Bladder and kidney disease, which affect approximately 25%-30% of subjects infected with Schistosoma haematobium, are mediated by T cell-dependent granulomatous responses to schistosome eggs. To determine why only some infected subjects develop disease, we examined the hypothesis that infected Kenyan subjects with ultrasound-detected urinary-tract morbidity (n=49) had dysregulated cytokine production leading to enhanced granulomatous responses, compared with subjects of similar age and intensity of infection without morbidity (n=100). Peripheral blood mononuclear cells from subjects with morbidity produced 8-fold greater levels of egg antigen-driven tumor necrosis factor (TNF)-alpha and had a 99-fold greater mean TNF-alpha:interleukin (IL)-10 ratio, compared with subjects without disease. No differences in cytokine response to non-egg-derived schistosome antigens were observed between groups. Subjects with morbidity had increased TNF-alpha production in response to endotoxin, suggesting an innate hyperresponsiveness. These results indicate that increased TNF-alpha production, relative to that of IL-10, is associated with developing bladder-wall morbidity with S. haematobium infection.

Levels of prepatent Schistosoma haematobium infection were monitored in intermediate host snails (Bulinus nasutus) collected from transmission sites in coastal Kenya, using a polymerase chain reaction (PCR) assay amplifying the Dra I repeated sequence of S. haematobium. The timing and number of prepatent and patent infections were determined for each site and, where the time of first appearance was clear, the minimal prepatent period was estimated to be five weeks. High, persistent, prepatency rates (range = 28-54%), indicated a significant degree of repeated area contamination with parasite ova. In contrast, rates of cercarial shedding proved locally variable, and were either low (range = 0.14-3.4%) or altogether absent, indicating that only a small proportion of infected snails reach the stage of cercarial shedding. Given the apparently strong focal effects of environmental conditions, implications of these new data are discussed regarding the estimation of local force of transmission and the design of control activities.

Objective: To establish the prevalence of congenital urinary tract abnormalities in a full population-based ultrasound survey of an area of coastal Kenya., Methods: Ultrasound examination of 3118 residents of 912 households, including all available subjects over 2 years of age, residing in five contiguous rural villages 50 km south of Mombasa., Results: Survey findings indicated simple renal ectopia in 11 of 3118 subjects (0.35%) and renal agenesis in three (0.096%). No cases of horseshoe kidney or complex urinary anomaly were detected, and no cases of multiple congenital anomaly were found. Ectopia cases were evenly distributed between men and women, and across the five study villages. None of the individuals affected by renal ectopia were closely related (i.e. <5th-degree relations)., Conclusion: There is an unusually high prevalence of ectopia among unrelated subjects in this area. In this setting, the findings suggest either a common exposure to teratogenetic factors, or a hereditary condition with variable penetrance, where more severely affected individuals are not observed because of foetal/infant mortality.

In the Msambweni area of the Kwale District in Kenya, an area endemic for Schistosoma haematobium, potential intermediate-host snails were systematically surveyed in water bodies associated with human contact that were previously surveyed in the 1980s. Bulinus (africanus) nasutus, which accounted for 67% of the snails collected, was the only snail shedding S. haematobium cercariae. Lanistes purpureus was the second most common snail (25%); lower numbers of Bulinus forskalii and Melanoides tuberculata were also recovered. Infection with non-S. haematobium trematodes was found among all snail species. Rainfall was significantly associated with the temporal distribution of all snail species: high numbers of Bulinus nasutus developed after extensive rainfall, followed, in turn, by increased S. haematobium shedding. Spatial distribution of snails was significantly clustered over a range of up to 1 km, with peak clustering observed at a distance of 400 meters. Water lily (Nymphaea spp.) and several aquatic grass species appeared necessary for local colonization by B. nasutus or L. purpureus.

Urinary schistosomiasis remains a major contributor to the disease burden along the southern coast of Kenya. Selective identification of transmission hot spots offers the potential for more effective, highly-focal snail control and human chemotherapy to reduce Schistosoma haematobium transmission. In the present study, a geographic information system was used to integrate demographic, parasitologic, and household location data for an endemic village and neighboring households with the biotic, abiotic, and location data for snail collection/water contact sites. A global spatial statistic was used to detect area-wide trends of clustering for human infection at the household level. Local spatial statistics were then applied to detect specific household clusters of infection, and, as a focal spatial statistic, to evaluate clustering of infection around a putative transmission site. High infection intensities were clustered significantly around a water contact site with high numbers of snails shedding S. haematobium cercariae. When age was considered, clustering was found to be significant at different distances for different age groups.

To estimate their heritable component of risk for Schistosoma haematobium infection intensity and disease, we performed a community-based family study among an endemic population in coastal Kenya. Demography and family linkages were defined by house-to-house interviews, and infection prevalence and disease severity were assessed by standard parasitologic testing and by ultrasound. The total population was 4,408 among 912 households, with 241 identified pedigree-household groups. Although age- and sex-adjusted risk for greater infection intensity was clustered within households (odds ratio = 2.7), analysis of extended pedigree-household groups indicated a relatively low heritability score for this trait (h2 = 0.199), particularly after adjustment for common household exposure effects (adjusted h2 = 0.086). Statistical evidence was slightly stronger (h2 = 0.353) for familial clustering of bladder morbidity, with an adjusted h2 = 0.142 after accounting for household exposure factors. We conclude that among long-established populations of coastal Kenya, heritable variation in host susceptibility is low, and likely plays a minimal role in determining individual risk for infection or disease.

At present, anthelmintic therapy with praziquantel at a dose of 40 mg/kg of body weight is the recommended treatment for control of urinary tract morbidity caused by Schistosoma haematobium. Although this standard regimen is effective, drug cost may represent a significant barrier to implementation of large-scale schistosomiasis control programs in developing areas. Previous comparison trials have established that low-dose (20-30 mg/kg) praziquantel regimens can effectively suppress the intensity of S. haematobium infection in endemic settings. However, the efficacy of these low-dose regimens in controlling infection-related morbidity has not been determined in a randomized field trial. The present random allocation study examined the relative efficacy of a 20 mg/kg dose versus a 40 mg/kg dose of praziquantel in control of hematuria and bladder and renal abnormalities associated with S. haematobium infection in an endemic area of Coast Province, Kenya. After a nine-month observation period, the results indicated an advantage to the standard 40 mg/kg praziquantel dose in terms of reduction of infection prevalence and hematuria after therapy (P < 0.01 and P < 0.005, respectively). However, the two treatment groups were equally effective in reducing structural urinary tract morbidity detected on ultrasound examination. We conclude that in certain settings, a 20 mg/kg dose of praziquantel may be sufficient in providing control of morbidity due to urinary schistosomiasis in population-based treatment programs.

Two populations with differing histories of Schistosoma mansoni and hepatitis C infection were compared directly for severity of disease and extent of comorbidity. Demographic, parasitologic, and ultrasound surveys were conducted on 2038 Egyptians and on 2120 Kenyans. Hepatitis B and C serologies and transaminase levels were obtained from a subset at each site. Despite significantly lower prevalence and intensity of infection, Egyptians had a higher prevalence of severe schistosomal fibrosis than Kenyans (36.8% vs. 4.6%). Hepatitis C infection was 3 times more prevalent among Egyptians, and evidence of hepatocellular damage was significantly greater among Egyptians. There was no interaction between S. mansoni infection or disease and the prevalence or severity of hepatitis C. For both infections, the intensity or prevalence of infection was a poor predictor of morbidity. The prevalence of disease in the Egyptian population from different pathogens suggests a generalized susceptibility to inflammatory liver disease.

A clinical trial to compare the effectiveness of 4- and 6-mo repeated treatment with albendazole 600 mg (Zentel, SmithKline Beecham) or mebendazole 600 mg (Vermox, Janssen) on geohelminth infections was carried out on children in 6 primary schools; the study included 1,186 children, ages 4 to 19 yr. Kato-Katz examination was performed on stool samples before and after treatment. Overall, albendazole produced better cure rates and egg reduction rates for geohelminths. The cure rates for albendazole were 92.4% for hookworm infection, 83.5% for Ascaris lumbricoides, and 67.8% for Trichuris trichiura. Mebendazole given either 2 or 3 times in a year had cure rates of 50 and 55.0% (respectively) for hookworm, 79.6 and 97.5% for A. lumbricoides, and 60.6 and 68.3% for T. trichiura infection. The geometric mean intensity of hookworm eggs per gram (epg) of stool decreased by 96.7% after albendazole treatment compared with 66.3 and 85.1%, respectively, for 2 or 3 doses of mebendazole (P < 0.05) over the same period. Reductions in epg for A. lumbricoides and T. trichiura were comparable for both drugs. Our results indicate that treatment with albendazole at a 6-mo interval was more effective than mebendazole regimens and may be the best choice for use in the control of the 3 geohelminths.

Severe periportal fibrosis is not an inevitable consequence of infection with Schistosoma mansoni. Genetic predisposition may be a deciding factor in the development of disease. To assess the contribution of genetic factors in the severity of hepatic fibrosis, the degree of familial aggregation was determined in a Kenyan population. Schistosomal fibrosis was identified with hepatic ultrasound and newly proposed World Health Organization criteria, which include both qualitative and quantitative observations. These 2 aspects of the criteria correlated well with one another. The peak prevalence of ultrasound proven fibrosis trailed 5-10 years behind peak prevalence of infection and declined sharply after age 50 years. This pattern was consistent with either resolution of severe fibrosis over 10-20 years or early death of those severely affected. Genetic predisposition appears to be a weak factor in the development of severe disease in this population, since no household or familial aggregation could be identified.

We examined the long-term efficacy of praziquantel against Schistosoma haematobium, the causative agent of urinary schistosomiasis, during a school-based treatment program in the Msambweni area of Coast Province, Kenya, where the disease is highly endemic. Our results, derived from treating 4,031 of 7,641 children from 1984 to 1993, indicate substantial year-to- year variation in drug efficacy. However, the pattern of this variation was not consistent with primary or progressive emergence of praziquantel resistance. Mathematical modeling indicated that, at current treatment rates, praziquantel resistance will likely take 10 or more years to emerge.

Ecologic modeling of Schistosoma transmission in endemic communities has suggested that antiparasite therapy targeted at the most heavily infected segment of the human population (i.e., school-age children) should have a significant impact on local parasite transmission. Our 1984-1991 experience with age-targeted therapy in the Msambweni area of Kenya has shown an overall decrease in area transmission within 1-2 years following initiation of annual treatment of school-age groups. Snail monitoring confirmed a continuing but variable reduction of vector infection rates. However, subgroup analysis showed significant differences in transmission suppression between more developed coastal villages with piped-water kiosks and villages with only limited access to safe water supplies. Villages without piped water were marked by higher initial prevalences of S. haematobium infection, greater prevalence among adults, longer and more frequent contact with high-risk water sources, and persistently high transmission despite compliance with parasitologic screening or drug therapy. We conclude that targeted therapy had a significant impact on S. haematobium transmission in some areas, but that more extensive or more prolonged coverage is necessary to reduce the rate of new infection in high-risk villages. Defining field-use algorithms, based on decision analysis of economic and ecologic parameters, should provide effective guidelines for selective versus mass treatment in expanded control areas.

Severity of urinary tract morbidity increases with intensity and duration of Schistosoma haematobium infection. We assessed the ability of yearly drug therapy to control infection intensity and reduce S. haematobium-associated disease in children 5-21 years old in an endemic area of Kenya. In year 1, therapy resulted in reduced prevalence (66% to 22%, P < 0.001) and intensity of S. haematobium infection (20 to 2 eggs/10 mL urine), with corresponding reductions in the prevalence of hematuria (52% to 19%, P < 0.001). There was not, however, a significant first-year effect on prevalence of urinary tract abnormalities detected by ultrasound. Repeat therapy in years 2 and 3 resulted in significant regression of hydronephrosis and bladder abnormalities (41% to 6% prevalence, P < 0.01), and further reductions in proteinuria. Repeat age-targeted therapy was associated with decreased prevalence of infection among young children (< 5 yr) entering into the targeted age group. Two years after discontinuation of therapy, intensity of S. haematobium infection and ultrasound abnormalities remained suppressed, but hematuria prevalence began to increase (to 33% in 1989). Reinstitution of annual therapy in 1989 and 1990 reversed this trend. We conclude that annual oral therapy provides an effective strategy for control of morbidity due to S. haematobium on a population basis, both through regression of disease in treated individuals, and prevention of infection in untreated subjects.