Rift Valley Fever Seroprevalence in Coastal Kenya.

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 [CI95] 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%; CI95 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.

Dengue and West Nile Virus Transmission in Children and Adults in Coastal Kenya.

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.

Contrasting Patterns of Serologic and Functional Antibody Dynamics to Plasmodium falciparum Antigens in a Kenyan Birth Cohort.

IgG antibodies to Plasmodium falciparum are transferred from the maternal to fetal circulation during pregnancy, wane after birth, and are subsequently acquired in response to natural infection. We examined the dynamics of malaria antibody responses of 84 Kenyan infants from birth to 36 months of age by (i) serology, (ii) variant surface antigen (VSA) assay, (iii) growth inhibitory activity (GIA), and (iv) invasion inhibition assays (IIA) specific for merozoite surface protein 1 (MSP1) and sialic acid-dependent invasion pathway. Maternal antibodies in each of these four categories were detected in cord blood and decreased to their lowest level by approximately 6 months of age. Serologic antibodies to 3 preerythrocytic and 10 blood-stage antigens subsequently increased, reaching peak prevalence by 36 months. In contrast, antibodies measured by VSA, GIA, and IIA remained low even up to 36 months. Infants sensitized to P. falciparum in utero, defined by cord blood lymphocyte recall responses to malaria antigens, acquired antimalarial antibodies at the same rate as those who were not sensitized in utero, indicating that fetal exposure to malaria antigens did not affect subsequent infant antimalarial responses. Infants with detectable serologic antibodies at 12 months of age had an increased risk of P. falciparum infection during the subsequent 24 months. We conclude that serologic measures of antimalarial antibodies in children 36 months of age or younger represent biomarkers of malaria exposure rather than protection and that functional antibodies develop after 36 months of age in this population.

Use of prospective hospital surveillance data to define spatiotemporal heterogeneity of malaria risk in coastal Kenya.

BACKGROUND: Malaria in coastal Kenya shows spatial heterogeneity and seasonality, which are important factors to account for when planning an effective control system. Routinely collected data at health facilities can be used as a cost-effective method to acquire information on malaria risk for large areas. Here, data collected at one specific hospital in coastal Kenya were used to assess the ability of such passive surveillance to capture spatiotemporal heterogeneity of malaria and effectiveness of an augmented control system. METHODS: Fever cases were tested for malaria at Msambweni sub-County Referral Hospital, Kwale County, Kenya, from October 2012 to March 2015. Remote sensing data were used to classify the development level of each monitored community and to identify the presence of rice fields nearby. An entomological study was performed to acquire data on the seasonality of malaria vectors in the study area. Rainfall data were obtained from a weather station located in proximity of the study area. Spatial analysis was applied to investigate spatial patterns of malarial and non-malarial fever cases. A space-time Bayesian model was performed to evaluate risk factors and identify locations at high malaria risk. Vector seasonality was analysed using a generalized additive mixed model (GAMM). RESULTS: Among the 25,779 tested febrile cases, 28.7 % were positive for Plasmodium infection. Malarial and non-malarial fever cases showed a marked spatial heterogeneity. High risk of malaria was linked to patient age, community development level and presence of rice fields. The peak of malaria prevalence was recorded close to rainy seasons, which correspond to periods of high vector abundance. Results from the Bayesian model identified areas with significantly high malaria risk. The model also showed that the low prevalence of malaria recorded during late 2012 and early 2013 was associated with a large-scale bed net distribution initiative in the study area during mid-2012. CONCLUSIONS: The results indicate that the use of passive surveillance was an effective method to detect spatiotemporal patterns of malaria risk in coastal Kenya. Furthermore, it was possible to estimate the impact of extensive bed net distribution on malaria prevalence among local fever cases over time. Passive surveillance based on georeferenced malaria testing is an important tool that control agencies can use to improve the effectiveness of interventions targeting malaria (and other causes of fever) in such high-risk locations.

Anemia Among Children Exposed to Polyparasitism in Coastal Kenya.

Anemia represents a substantial problem for children living in areas with limited resources and significant parasite burden. We performed a cross-sectional study of 254 Kenyan preschool- and early school-age children in a setting endemic for multiple chronic parasitic infections to explore mechanisms of their anemia. Complete venous blood cell counts revealed a high prevalence of local childhood anemia (79%). Evaluating the potential links between low hemoglobin and socioeconomic factors, nutritional status, hemoglobinopathy, and/or parasite infection, we identified age < 9 years (odds ratio [OR]: 12.0, 95% confidence interval [CI]: 4.4, 33) and the presence of asymptomatic malaria infection (OR: 6.8, 95% CI: 2.1, 22) as the strongest independent correlates of having anemia. A total of 130/155 (84%) of anemic children with iron studies had evidence of iron-deficiency anemia (IDA), 16% had non-IDA; 50/52 of additionally tested anemic children met soluble transferrin-receptor (sTfR) criteria for combined anemia of inflammation (AI) with IDA. Children in the youngest age group had the greatest odds of iron deficiency (OR: 10.0, 95% CI: 3.9, 26). Although older children aged 9-11 years had less anemia, they had more detectable malaria, Schistosoma infection, hookworm, and proportionately more non-IDA. Anemia in this setting appears multifactorial such that chronic inflammation and iron deficiency need to be addressed together as part of integrated management of childhood anemia.

Age-Stratified Profiles of Serum IL-6, IL-10, and TNF-α Cytokines Among Kenyan Children with Schistosoma haematobium, Plasmodium falciparum, and Other Chronic Parasitic Co-Infections.

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.

High rates of o'nyong nyong and Chikungunya virus transmission in coastal Kenya.

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.

Cross-sectional study of the burden of vector-borne and soil-transmitted polyparasitism in rural communities of Coast Province, Kenya.

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.

Development of a specimen-sparing multichannel bead assay to detect antiparasite IgG4 for the diagnosis of Schistosoma and Wuchereria infections on the coast of Kenya.

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.

Evaluation of the health-related quality of life of children in Schistosoma haematobium-endemic communities in Kenya: a cross-sectional study.

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.

Impact of polyparasitic infections on anemia and undernutrition among Kenyan children living in a Schistosoma haematobium-endemic area.

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.

Projecting the long-term impact of school- or community-based mass-treatment interventions for control of Schistosoma infection.

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.

Differentiating Schistosoma haematobium from related animal schistosomes by PCR amplifying inter-repeat sequences flanking newly selected repeated sequences.

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.

Partnering parasites: evidence of synergism between heavy Schistosoma haematobium and Plasmodium species infections in Kenyan children.

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.

In utero activation of fetal memory T cells alters host regulatory gene expression and affects HIV susceptibility.

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.

Impact of drought on the spatial pattern of transmission of Schistosoma haematobium in coastal Kenya.

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.

Measuring fitness of Kenyan children with polyparasitic infections using the 20-meter shuttle run test as a morbidity metric.

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.

Fine specificity of neonatal lymphocytes to an abundant malaria blood-stage antigen: epitope mapping of Plasmodium falciparum MSP1(33).

Cord blood T cells have been reported to respond to a variety of exogenous Ags, including environmental allergens and various viruses and parasites, as demonstrated by enhanced proliferation and cytokine secretion. This finding is evidence that Ags in the maternal environment transplacentally prime and result in fetal development of memory T cells. Some studies suggest these neonatal T cell responses may arise by nonspecific activation of T cells that express TCRs with low binding affinity, thus lacking fine lymphocyte specificity. To address this question, we examined malaria Ag stimulation of human cord and adult blood mononuclear cells in samples from residents of a malaria endemic area in Kenya. We constructed overlapping 18-mer peptides derived from sequences contained in dimorphic alleles of the C-terminal 33-kDa fragment of Plasmodium falciparum merozoite protein 1. This study identified a dominant T cell epitope for one MSP1(33) allele (MAD20) and two T cell epitopes for the second allele (K1); these epitopes were nonoverlapping and allele specific. In a given donor, peptide-specific proliferation and IFN-gamma secretion were highly concordant. However, IL-10 and IL-13 secretion were not correlated. Importantly, the fine specificity of lymphocyte proliferation and cytokine secretion in cord and adult blood mononuclear cells was similar. Cord blood cells obtained from malaria-infected pregnant women were 4-fold more likely to acquire a peptide-specific immune response. We conclude that the fetal malaria response functions in a fully adaptive manner and that this response may serve to help protect the infant from severe malaria during infancy.

Spatial and temporal variations in local transmission of Schistosoma haematobium in Msambweni, Kenya.

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.

Prenatal T cell immunity to Wuchereria bancrofti and its effect on filarial immunity and infection susceptibility during childhood.

BACKGROUND: Antenatal immune experience with Wuchereria bancrofti due to maternal filariasis may influence susceptibility to infection. We tested the hypothesis that filarial-specific T cell responses at birth that are indicative of in utero tolerance or sensitization affect the evolution of filarial-specific immunity and susceptibility to W. bancrofti infection during childhood. METHODS: A birth-cohort study of 159 Kenyan newborns was performed. Cord blood and peripheral blood were obtained annually to age 7 years and were assayed for filarial infection and filarial antigen-driven interferon (IFN)- gamma , interleukin (IL)-2, IL-5, and IL-13 production by lymphocytes. RESULTS: There was a 12.9-fold (95% confidence interval [CI], 2.5-107.2-fold) and a 4.8-fold (95% CI, 1.7-12.9-fold) increased risk of infection for immune-tolerant newborns (maternal infection present during gestation, with no filarial antigen-driven cord blood T cell response [n = 25]), compared with immune-sensitized (maternal infection present with cord blood T cell response [n = 24]) and unexposed (maternal infection absent [n = 110]) newborns. Cytokine responses developed at a later age in tolerant newborns, were characterized by impaired IFN-gamma responses, and contrasted with those of filarial-sensitized newborns, who had sustained and elevated IL-5 and IL-13 responses to age 7 years. CONCLUSION: Prenatal immune experience, as determined by whether in utero priming to filarial antigen occurs, is a major determinant of childhood susceptibility to W. bancrofti infection.