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1.
Trans R Soc Trop Med Hyg ; 117(9): 637-644, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37042291

ABSTRACT

BACKGROUND: Complications of urogenital schistosomiasis include acute inflammatory and chronic fibrotic changes within the urogenital tract. Disease burden of this neglected tropical disease is often underestimated, as only active, urine egg-patent Schistosoma infection is formally considered. Previous studies have focussed on short-term effects of praziquantel treatment on urinary tract pathology, demonstrating that acute inflammation is reversible. However, the reversibility of chronic changes is less well studied. METHODS: Our study compared, at two time points 14 y apart, urine egg-patent infection and urinary tract pathology in a cohort of women living in a highly endemic area having intermittent praziquantel treatment(s). In 2014 we matched 93 women to their findings in a previous study in 2000. RESULTS: Between 2000 and 2014 the rate of egg-patent infection decreased from 34% (95% confidence interval [CI] 25 to 44) to 9% (95% CI 3 to 14). However, urinary tract pathology increased from 15% (95% CI 8 to 22) to 19% (95% CI 11 to 27), with the greatest increase seen in bladder thickening and shape abnormality. CONCLUSIONS: Despite praziquantel treatment, fibrosis from chronic schistosomiasis outlasts the presence of active infection, continuing to cause lasting morbidity. We suggest that future efforts to eliminate persistent morbidity attributable to schistosomiasis should include intensified disease management.


Subject(s)
Schistosomiasis haematobia , Urinary Tract , Humans , Female , Schistosomiasis haematobia/complications , Schistosomiasis haematobia/diagnostic imaging , Schistosomiasis haematobia/drug therapy , Praziquantel/therapeutic use , Follow-Up Studies , Kenya/epidemiology , Urinary Tract/diagnostic imaging
2.
J Immunol ; 202(5): 1465-1478, 2019 03 01.
Article in English | MEDLINE | ID: mdl-30674575

ABSTRACT

Infections during pregnancy can expose the fetus to microbial Ags, leading to inflammation that affects B cell development. Prenatal fetal immune priming may have an important role in infant acquisition of pathogen-specific immunity. We examined plasma proinflammatory biomarkers, the proportions of various B cell subsets, and fetal priming to tetanus vaccination in cord blood from human United States and Kenyan neonates. United States neonates had no identified prenatal infectious exposures, whereas Kenyan neonates examined had congenital CMV or mothers with prenatal HIV or Plasmodium falciparum or no identified infectious exposures. Kenyan neonates had higher levels of IP-10, TNF-α, CRP, sCD14, and BAFF than United States neonates. Among the Kenyan groups, neonates with prenatal infections/infectious exposures had higher levels of cord blood IFN-γ, IL-7, sTNFR1, and sTNFR2 compared with neonates with no infectious exposures. Kenyan neonates had greater proportions of activated memory B cells (MBC) compared with United States neonates. Among the Kenyan groups, HIV-exposed neonates had greater proportions of atypical MBC compared with the other groups. Although HIV-exposed neonates had altered MBC subset distributions, detection of tetanus-specific MBC from cord blood, indicative of fetal priming with tetanus vaccine given to pregnant women, was comparable in HIV-exposed and non-HIV-exposed neonates. These results indicate that the presence of infections during pregnancy induces fetal immune activation with inflammation and increased activated MBC frequencies in neonates. The immunologic significance and long-term health consequences of these differences warrant further investigation.


Subject(s)
B-Lymphocyte Subsets/immunology , Cytomegalovirus/immunology , HIV/immunology , Inflammation/immunology , Malaria/immunology , Adult , Female , Humans , Infant , Infant, Newborn , Kenya , Male , Pregnancy , Young Adult
3.
J Infect Dis ; 217(9): 1426-1434, 2018 04 11.
Article in English | MEDLINE | ID: mdl-29390149

ABSTRACT

Background: Antenatal exposure to parasites can affect infants' subsequent responses to vaccination. The present study investigated how maternal prenatal infections and newborns' antiparasite cytokine profiles relate to immunoglobulin G (IgG) responses to standard vaccination during infancy. Methods: A total of 450 Kenyan women were tested for parasitic infections during pregnancy. Their newborns' responses to Plasmodium falciparum, schistosome, and filaria antigens were assessed in cord blood lymphocytes. Following standard neonatal vaccination, this infant cohort was followed biannually to age 30 months for measurement of circulating IgG levels against Haemophilus influenzae b (Hib), diphtheria toxoid (DT), hepatitis B virus (HBV), and tetanus toxoid. Results: Trajectories of postvaccination IgG levels were classified by functional principal component (PC) analysis to assess each child's response profile. Two main components, PC1, reflecting height of response over time, and PC2, reflecting crossover from high to low responses or from low to high responses, were identified. Cord blood cytokine responses to schistosome and filarial antigens showed a significant association between augmented antihelminth interleukin 10 and reduced antibody levels, particularly to DT and HBV, and a more rapid postvaccination decline in circulating IgG levels against Hib. Conclusion: Antenatal sensitization to schistosomiasis or filariasis and related production of antiparasite interleukin 10 at birth are associated with reduced antivaccine IgG levels in infancy, with possibly impaired protection.


Subject(s)
Fetal Blood , Immunoglobulin G/blood , Interleukin-10/blood , Pregnancy Complications, Parasitic , Vaccines/immunology , Adult , Aging , Antibodies, Bacterial/blood , Antibodies, Viral/blood , Biomarkers , Cytokines/genetics , Cytokines/metabolism , Female , Gene Expression Regulation , Humans , Infant , Infant, Newborn , Kenya , Pregnancy , Principal Component Analysis , Risk Factors
4.
Am J Trop Med Hyg ; 97(1): 115-120, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28719329

ABSTRACT

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.


Subject(s)
Antibodies, Viral/administration & dosage , Antibodies, Viral/immunology , Rift Valley Fever/immunology , Rift Valley Fever/virology , Rift Valley fever virus/immunology , Seroepidemiologic Studies , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , Child , Child, Preschool , Female , Humans , Infant , Kenya/epidemiology , Male , Middle Aged , Prevalence , Rift Valley Fever/epidemiology , Risk Factors , Socioeconomic Factors , Young Adult
5.
Am J Trop Med Hyg ; 96(1): 141-143, 2017 Jan 11.
Article in English | MEDLINE | ID: mdl-27821697

ABSTRACT

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.


Subject(s)
Dengue/epidemiology , Dengue/transmission , West Nile Fever/epidemiology , West Nile Fever/transmission , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Child , Child, Preschool , Humans , Infant , Kenya/epidemiology , Middle Aged , West Nile Fever/virology , Young Adult
6.
Clin Vaccine Immunol ; 23(2): 104-16, 2016 02.
Article in English | MEDLINE | ID: mdl-26656119

ABSTRACT

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.


Subject(s)
Antibodies, Protozoan/blood , Antigens, Protozoan/immunology , Malaria, Falciparum/epidemiology , Plasmodium falciparum/immunology , Age Factors , Antibodies, Protozoan/immunology , Biomarkers/blood , Child, Preschool , Female , Fetal Blood/immunology , Humans , Immunity, Maternally-Acquired , Immunoglobulin G/blood , Immunoglobulin M/blood , Infant , Infant, Newborn , Kenya , Malaria, Falciparum/immunology , Malaria, Falciparum/prevention & control , Male , Merozoite Surface Protein 1/immunology , Plasmodium falciparum/growth & development , Pregnancy , Pregnancy Complications, Parasitic/epidemiology , Pregnancy Complications, Parasitic/immunology , Protozoan Proteins/immunology , Serologic Tests
7.
Malar J ; 14: 482, 2015 Dec 01.
Article in English | MEDLINE | ID: mdl-26625721

ABSTRACT

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.


Subject(s)
Epidemiological Monitoring , Hospitals , Malaria/epidemiology , Topography, Medical , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Kenya , Male , Middle Aged , Prospective Studies , Risk Assessment , Seasons , Spatio-Temporal Analysis , Young Adult
8.
Am J Trop Med Hyg ; 93(5): 1099-105, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26324733

ABSTRACT

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.


Subject(s)
Anemia/etiology , Hemoglobins/analysis , Parasitic Diseases/complications , Anemia/epidemiology , Anemia/prevention & control , Animals , Child , Child, Preschool , Cross-Sectional Studies , Female , Filariasis/complications , Filariasis/epidemiology , Hookworm Infections/complications , Hookworm Infections/epidemiology , Humans , Kenya/epidemiology , Malaria/complications , Malaria/epidemiology , Male , Nutritional Status , Odds Ratio , Parasitic Diseases/epidemiology , Prevalence , Risk Factors , Schistosomiasis haematobia/complications , Schistosomiasis haematobia/epidemiology , Socioeconomic Factors , Wuchereria bancrofti
9.
PLoS Negl Trop Dis ; 9(5): e0003721, 2015 May.
Article in English | MEDLINE | ID: mdl-25996157

ABSTRACT

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.


Subject(s)
Helminthiasis/epidemiology , Intestinal Diseases, Parasitic/epidemiology , Malaria/epidemiology , Ancylostomatoidea/isolation & purification , Animals , Ascaris/isolation & purification , Body Weight , Child, Preschool , Entamoeba histolytica/isolation & purification , Female , Filarioidea/isolation & purification , Giardia lamblia/isolation & purification , Helminths/isolation & purification , Humans , Infant , Kenya/epidemiology , Male , Prevalence , Rural Population , Schistosoma/isolation & purification , Strongyloides/isolation & purification , Trichuris/isolation & purification
10.
Am J Trop Med Hyg ; 92(5): 945-51, 2015 May.
Article in English | MEDLINE | ID: mdl-25758654

ABSTRACT

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.


Subject(s)
Cytokines/blood , Hookworm Infections/immunology , Malaria, Falciparum/immunology , Plasmodium falciparum/immunology , Schistosoma haematobium/immunology , Schistosomiasis haematobia/immunology , Adolescent , Age Distribution , Animals , Antibodies, Helminth/blood , Antibodies, Protozoan/blood , Child , Child, Preschool , Coinfection , Female , Geography , Hookworm Infections/epidemiology , Hookworm Infections/parasitology , Humans , Interleukin-10/blood , Interleukin-6/blood , Kenya/epidemiology , Malaria, Falciparum/epidemiology , Malaria, Falciparum/parasitology , Male , Schistosomiasis haematobia/epidemiology , Schistosomiasis haematobia/parasitology , Tumor Necrosis Factor-alpha/blood , Young Adult
11.
PLoS Negl Trop Dis ; 9(2): e0003436, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25658762

ABSTRACT

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.


Subject(s)
Alphavirus Infections/epidemiology , Chikungunya Fever/epidemiology , Chikungunya virus/immunology , O'nyong-nyong Virus/immunology , Adult , Africa, Eastern , Aged , Alphavirus Infections/transmission , Animals , Chikungunya Fever/transmission , Child , Female , Humans , Insect Vectors/virology , Kenya/epidemiology , Male , Middle Aged , Neutralization Tests , Seroepidemiologic Studies , Surveys and Questionnaires
12.
PLoS Negl Trop Dis ; 9(1): e0003466, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25590337

ABSTRACT

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.


Subject(s)
Immunoglobulin G/blood , Pregnancy Complications, Parasitic/immunology , Vaccines/immunology , Adolescent , Adult , Cohort Studies , Female , Haemophilus influenzae type b/immunology , Hepatitis B virus/immunology , Humans , Infant , Infant, Newborn , Kenya , Pregnancy , Prospective Studies , Tetanus Toxoid/immunology , Vaccination
13.
PLoS Negl Trop Dis ; 8(7): e2992, 2014 Jul.
Article in English | MEDLINE | ID: mdl-25057825

ABSTRACT

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.


Subject(s)
Coinfection , Parasitic Diseases , Rural Population/statistics & numerical data , Adolescent , Adult , Ancylostomatoidea , Animals , Child , Child, Preschool , Coinfection/epidemiology , Coinfection/parasitology , Cross-Sectional Studies , Female , Hookworm Infections/epidemiology , Hookworm Infections/parasitology , Humans , Infant , Infant, Newborn , Kenya/epidemiology , Male , Parasitic Diseases/epidemiology , Parasitic Diseases/parasitology , Risk Factors , Schistosoma haematobium , Schistosomiasis haematobia/epidemiology , Schistosomiasis haematobia/parasitology , Spatio-Temporal Analysis , Young Adult
14.
Int J Gynaecol Obstet ; 126(1): 78-82, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24792408

ABSTRACT

OBJECTIVE: To use ultrasound to explore the impact of malaria in pregnancy on fetal growth and newborn outcomes among a cohort of women enrolled in an intermittent presumptive treatment in pregnancy (IPTp) with sulfadoxine/pyrimethamine (SP) program in coastal Kenya. METHODS: Enrolled women were tested for malaria at first prenatal care visit, and physical and ultrasound examinations were performed. In total, 477 women who had term, live births had malaria tested at delivery and their birth outcomes assessed, and were included in the study. RESULTS: Peripheral malaria was detected via polymerase chain reaction among 10.9% (n=87) at first prenatal care visit and 8.8% (n=36) at delivery. Insecticide-treated bed nets (ITNs) were used by 73.6% (n=583) and were associated with decreased malaria risk. There was a trend for impaired fetal growth and placental blood flow in malaria-infected women in the second trimester, but not later in pregnancy. Among women with low body mass index (BMI), malaria was associated with reduced birth weight (P=0.04); anthropometric measures were similar otherwise. CONCLUSION: With IPTp-SP and ITNs, malaria in pregnancy was associated with transient differences in utero, and reduced birth weight was restricted to those with low BMI.


Subject(s)
Fetal Development , Malaria, Falciparum/physiopathology , Placental Circulation , Pregnancy Complications, Parasitic/physiopathology , Adult , Anthropometry , Antimalarials/administration & dosage , Cohort Studies , Drug Combinations , Female , Humans , Infant, Newborn , Kenya , Malaria, Falciparum/prevention & control , Male , Middle Aged , Pregnancy , Pregnancy Complications, Parasitic/prevention & control , Pyrimethamine/administration & dosage , Sulfadoxine/administration & dosage , Young Adult
15.
PLoS Negl Trop Dis ; 8(2): e2724, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24587473

ABSTRACT

BACKGROUND: Relative contribution of these infections on anemia in pregnancy is not certain. While measures to protect pregnant women against malaria have been scaling up, interventions against helminthes have received much less attention. In this study, we determine the relative impact of helminthes and malaria on maternal anemia. METHODS: A prospective observational study was conducted in coastal Kenya among a cohort of pregnant women who were recruited at their first antenatal care (ANC) visit and tested for malaria, hookworm, and other parasitic infections and anemia at enrollment. All women enrolled in the study received presumptive treatment with sulfadoxine-pyrimethamine, iron and multi-vitamins and women diagnosed with helminthic infections were treated with albendazole. Women delivering a live, term birth, were also tested for maternal anemia, fetal anemia and presence of infection at delivery. PRINCIPAL FINDINGS: Of the 706 women studied, at the first ANC visit, 27% had moderate/severe anemia and 71% of women were anemic overall. The infections with highest prevalence were hookworm (24%), urogenital schistosomiasis (17%), trichuria (10%), and malaria (9%). In adjusted and unadjusted analyses, moderate/severe anemia at first ANC visit was associated with the higher intensities of hookworm and P. falciparum microscopy-malaria infections. At delivery, 34% of women had moderate/severe anemia and 18% of infants' cord hemoglobin was consistent with fetal anemia. While none of the maternal infections were significantly associated with fetal anemia, moderate/severe maternal anemia was associated with fetal anemia. CONCLUSIONS: More than one quarter of women receiving standard ANC with IPTp for malaria had moderate/severe anemia in pregnancy and high rates of parasitic infection. Thus, addressing the role of co-infections, such as hookworm, as well as under-nutrition, and their contribution to anemia is needed.


Subject(s)
Anemia/complications , Anemia/epidemiology , Pregnancy Complications, Parasitic/epidemiology , Adult , Ancylostomiasis/complications , Ancylostomiasis/epidemiology , Animals , Female , Fetal Blood/chemistry , Hemoglobins/analysis , Humans , Kenya/epidemiology , Malaria/complications , Malaria/epidemiology , Pregnancy , Prospective Studies , Schistosomiasis/complications , Schistosomiasis/epidemiology , Young Adult
16.
Am J Trop Med Hyg ; 90(4): 638-45, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24515945

ABSTRACT

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.


Subject(s)
Antibodies, Helminth/blood , Brugia malayi/immunology , Filariasis/immunology , Fluoroimmunoassay/methods , Immunoglobulin G/blood , Schistosoma haematobium/immunology , Schistosomiasis haematobia/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Animals , Child , Child, Preschool , Enzyme-Linked Immunosorbent Assay/methods , Female , Filariasis/diagnosis , Humans , Infant , Kenya , Male , Middle Aged , Schistosomiasis haematobia/diagnosis , Specimen Handling/methods , Young Adult
17.
J Med Entomol ; 50(5): 1140-51, 2013 Sep.
Article in English | MEDLINE | ID: mdl-24180120

ABSTRACT

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.


Subject(s)
Culicidae/parasitology , Insect Vectors/parasitology , Malaria, Falciparum/parasitology , Mosquito Control/methods , Plasmodium falciparum/physiology , Animals , Culicidae/classification , Elephantiasis, Filarial/parasitology , Environment , Enzyme-Linked Immunosorbent Assay , Female , Insect Vectors/classification , Kenya/epidemiology , Malaria, Falciparum/epidemiology , Male , Species Specificity
18.
Am J Trop Med Hyg ; 89(6): 1129-34, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24080635

ABSTRACT

Expanded malaria control in Kenya since the early 2000s has resulted in marked reduction in hospital admissions for malaria; however, no studies have reported changes in malaria infection rates in the same population over this period. Randomly selected archived blood samples from four cohorts of pregnant women and their children from 1996 to 2010 in Kwale District, Coast Province, Kenya, were examined for Plasmodium falciparum (Pf), P. malariae, P. ovale, and Plasmodium vivax by quantitative polymerase chain reaction (PCR) and microscopy. Maternal delivery Pf prevalence by PCR declined from 40% in 2000-2005 to 1% in 2009-2010, concordant with increased bed net and malaria chemoprophylaxis use. Individual risk of Pf infection in children from birth to 3 years in serial longitudinal cohort studies declined from almost 100% in 1996-1999 to 15% in 2006-2010. Declines in P. malariae and P. ovale infections rates were also observed. These results show a profound reduction in malaria transmission in coastal Kenya.


Subject(s)
Antimalarials/therapeutic use , Malaria/epidemiology , Plasmodium/isolation & purification , Adolescent , Adult , Child, Preschool , Cohort Studies , DNA, Protozoan/genetics , DNA, Protozoan/isolation & purification , Female , Humans , Infant , Kenya/epidemiology , Longitudinal Studies , Malaria/drug therapy , Malaria/parasitology , Malaria/transmission , Middle Aged , Mosquito Nets/statistics & numerical data , Plasmodium/classification , Plasmodium/drug effects , Plasmodium/genetics , Polymerase Chain Reaction , Pregnancy , Prevalence , Risk Factors , Species Specificity , Young Adult
19.
Acta Trop ; 128(1): 149-53, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23911334

ABSTRACT

Transplacental transfer of antibodies from clinically malaria immune pregnant women to their fetuses is thought to provide passive protection against malaria during infancy. However, the presences and duration of functional antibodies against Plasmodium falciparum (Pf) in newborns has not been described. We used growth inhibition assays (GIA) to measure total anti-malaria functional antibodies present at birth and over the following year. Samples were drawn from cord blood (n=86) and in infants at six and 12 months of life (n=86 and 65 respectively). Three laboratory Pf strains (D10, W2mef, 3D7) and a field isolate (Msambweni 2006) were used in the assays. Median (ranges) GIA levels for cord plasma differed between laboratory parasite strains: D10, 0% (0-81); W2mef, 6% (0-80); 3D7, 18% (0-88); Msambweni 2006, 6% (0-43) (P<0.001, Wilcoxon signed-rank test). GIA levels against all Pf strains were found to decline in infants from birth to six months (P<0.01, Wilcoxon, signed-rank test). Functional antibodies as measured by GIA are transferred to the fetus and wane in the infants over time. Infant protection from clinical malaria disease may in part be mediated by these functional anti-malaria antibodies.


Subject(s)
Antibodies, Protozoan/blood , Immunity, Maternally-Acquired , Malaria/immunology , Plasmodium falciparum/immunology , Adult , Age Factors , Female , Humans , Infant, Newborn , Longitudinal Studies , Pregnancy , Young Adult
20.
PLoS Negl Trop Dis ; 7(3): e2106, 2013.
Article in English | MEDLINE | ID: mdl-23505590

ABSTRACT

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.


Subject(s)
Quality of Life/psychology , Schistosomiasis haematobia/pathology , Schistosomiasis haematobia/psychology , Adolescent , Animals , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Kenya , Male , Schistosoma haematobium/isolation & purification , Surveys and Questionnaires
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