RESUMEN
BACKGROUND: Malaria in pregnancy can expose the fetus to malaria-infected erythrocytes or their soluble products, thereby stimulating T and B cell immune responses to malaria blood stage antigens. We hypothesized that fetal immune priming, or malaria exposure in the absence of priming (putative tolerance), affects the child's susceptibility to subsequent malaria infections. METHODS AND FINDINGS: We conducted a prospective birth cohort study of 586 newborns residing in a malaria-holoendemic area of Kenya who were examined biannually to age 3 years for malaria infection, and whose malaria-specific cellular and humoral immune responses were assessed. Newborns were classified as (i) sensitized (and thus exposed), as demonstrated by IFNgamma, IL-2, IL-13, and/or IL-5 production by cord blood mononuclear cells (CBMCs) to malaria blood stage antigens, indicative of in utero priming (n = 246), (ii) exposed not sensitized (mother Plasmodium falciparum [Pf]+ and no CBMC production of IFNgamma, IL-2, IL-13, and/or IL-5, n = 120), or (iii) not exposed (mother Pf-, no CBMC reactivity, n = 220). Exposed not sensitized children had evidence for prenatal immune experience demonstrated by increased IL-10 production and partial reversal of malaria antigen-specific hyporesponsiveness with IL-2+IL-15, indicative of immune tolerance. Relative risk data showed that the putatively tolerant children had a 1.61 (95% confidence interval [CI] 1.10-2.43; p = 0.024) and 1.34 (95% CI 0.95-1.87; p = 0.097) greater risk for malaria infection based on light microscopy (LM) or PCR diagnosis, respectively, compared to the not-exposed group, and a 1.41 (95%CI 0.97-2.07, p = 0.074) and 1.39 (95%CI 0.99-2.07, p = 0.053) greater risk of infection based on LM or PCR diagnosis, respectively, compared to the sensitized group. Putatively tolerant children had an average of 0.5 g/dl lower hemoglobin levels (p = 0.01) compared to the other two groups. Exposed not sensitized children also had 2- to 3-fold lower frequency of malaria antigen-driven IFNgamma and/or IL-2 production (p<0.001) and higher IL-10 release (p<0.001) at 6-month follow-ups, when compared to sensitized and not-exposed children. Malaria blood stage-specific IgG antibody levels were similar among the three groups. CONCLUSIONS: These results show that a subset of children exposed to malaria in utero acquire a tolerant phenotype to blood-stage antigens that persists into childhood and is associated with an increased susceptibility to malaria infection and anemia. This finding could have important implications for malaria vaccination of children residing in endemic areas.
Asunto(s)
Tolerancia Inmunológica , Malaria Falciparum/epidemiología , Malaria Falciparum/inmunología , Intercambio Materno-Fetal/inmunología , Plasmodium falciparum , Complicaciones Parasitarias del Embarazo/epidemiología , Complicaciones Parasitarias del Embarazo/inmunología , Adulto , Animales , Anticuerpos Antiprotozoarios/sangre , Antígenos de Protozoos/sangre , Antígenos de Protozoos/inmunología , Antígenos de Protozoos/metabolismo , Células Cultivadas , Citocinas/inmunología , Citocinas/metabolismo , Femenino , Sangre Fetal/inmunología , Humanos , Recién Nacido , Kenia/epidemiología , Masculino , Proteínas de la Membrana/inmunología , Proteínas de la Membrana/metabolismo , Proteína 1 de Superficie de Merozoito/inmunología , Proteína 1 de Superficie de Merozoito/metabolismo , Embarazo , Estudios Prospectivos , Proteínas Protozoarias/inmunología , Proteínas Protozoarias/metabolismo , Linfocitos T/inmunología , Linfocitos T/metabolismo , Linfocitos T/parasitologíaRESUMEN
Hepatosplenomegaly among Kenyan schoolchildren has been shown to be exacerbated where there is transmission of both Schistosoma mansoni and Plasmodium falciparum. This highly prevalent and chronic morbidity often occurs in the absence of ultrasound-detectable periportal fibrosis and may be due to immunological inflammation. For a cohort of school-age children, whole-blood cultures were stimulated with S. mansoni soluble egg antigen (SEA) or soluble worm antigen (SWA). Responses to SWA were found to be predominantly Th2 cytokines; however, they were not significantly associated with either hepatosplenomegaly or infection with S. mansoni or P. falciparum. In comparison, SEA-specific Th2 cytokine responses were low, and the levels were negatively correlated with S. mansoni infection intensities and were lower among children who were coinfected with P. falciparum. Tumor necrosis factor alpha levels in response to stimulation with SEA were high, and a negative association between presentation with hepatomegaly and the levels of the regulatory cytokines interleukin-6 and transforming growth factor beta(1) suggests that a possible mechanism for childhood hepatomegaly in areas where both malaria and schistosomiasis are endemic is poor regulation of an inflammatory response to schistosome eggs.
Asunto(s)
Antígenos de Protozoos/inmunología , Hepatomegalia/parasitología , Malaria Falciparum/complicaciones , Malaria Falciparum/patología , Esquistosomiasis/complicaciones , Esquistosomiasis/patología , Esplenomegalia/parasitología , Adolescente , Animales , Células Cultivadas , Niño , Preescolar , Citocinas/biosíntesis , ADN Protozoario/sangre , Hepatomegalia/inmunología , Humanos , Kenia , Leucocitos Mononucleares/inmunología , Malaria Falciparum/inmunología , Parasitemia , Plasmodium falciparum/inmunología , Plasmodium falciparum/aislamiento & purificación , Reacción en Cadena de la Polimerasa , Schistosoma mansoni/inmunología , Schistosoma mansoni/aislamiento & purificación , Esquistosomiasis/inmunología , Esplenomegalia/inmunología , Células Th2/inmunologíaRESUMEN
OBJECTIVES: Chronic exposure to malaria exacerbates Schistosoma mansoni-associated hepatosplenomegaly in school-aged children. However, residual hepatosplenomegaly after treatment of S. mansoni with concurrent mollusciciding suggests malaria could be an underlying cause of hepatosplenomegaly. We investigated the role of chronic malaria in childhood hepatosplenomegaly in the presence and absence of concurrent S. mansoni infection. METHODS: Cross-sectional study of children in an study area where transmission of S. mansoni, but not malaria, is restricted to the eastern end. Clinical and ultrasound examinations were conducted, and parasitological and serological tests used to determine S. mansoni infection intensities and comparative exposure levels to malaria. RESULTS: Chronic exposure to malaria, as determined by Pfs-IgG3 levels, was associated with hepatosplenomegaly even in the absence of S. mansoni infection. Children infected with S. mansoni mostly had light to moderate infection intensities but greater enlargement of the liver and spleen than children who did not have schistosomiasis, and for the left liver lobe this was S. mansoni infection intensity dependent. CONCLUSIONS: Children chronically exposed to malaria but without S. mansoni infection can have hepatosplenomegaly, which even light S. mansoni infections can exacerbate in an intensity-dependent manner. Thus, concurrent chronic exposure to S. mansoni and Plasmodium falciparum can have an additive or synergistic effect on childhood morbidity.
Asunto(s)
Hepatomegalia/epidemiología , Malaria Falciparum/epidemiología , Esquistosomiasis mansoni/epidemiología , Esplenomegalia/epidemiología , Adolescente , Animales , Antihelmínticos/farmacología , Antihelmínticos/uso terapéutico , Niño , Preescolar , Estudios Transversales , Femenino , Hepatomegalia/clasificación , Hepatomegalia/etiología , Humanos , Kenia/epidemiología , Modelos Lineales , Hígado/diagnóstico por imagen , Malaria Falciparum/complicaciones , Masculino , Praziquantel/uso terapéutico , Prevalencia , Schistosoma mansoni/efectos de los fármacos , Esquistosomiasis mansoni/complicaciones , Esquistosomiasis mansoni/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Esplenomegalia/clasificación , Esplenomegalia/etiología , UltrasonografíaRESUMEN
BACKGROUND: Amongst school-aged children living in malaria endemic areas, chronic morbidity and exacerbation of morbidity associated with other infections are often not coincident with the presence or levels of Plasmodium parasitaemia, but may result from long-term exposure to the parasite. Studies of hepatosplenomegaly associated with Schistosoma mansoni infection and exposure to Plasmodium infection indicate that differences that occur over 1-2 km in levels of Plasmodium transmission are related to the degree of exacerbation of hepatosplenomegaly and that Plasmodium falciparum schizont antigen (Pfs)-IgG3 levels may be a marker for the differing levels of exposure. METHODS: To investigate the validity of Pfs-IgG3 measurements as a tool to assess these comparative exposure levels on a microgeographical scale, cross-sectional community surveys were conducted over a 10 x 6 km study site in Makueni District, Kenya, during low and high malaria transmission seasons. During both high and low malaria transmission seasons, thick blood smears were examined microscopically and circulating Pfs-IgG3 levels measured from dried blood spot elute. GIS techniques were used to map prevalence of parasitaemia and Pfs-IgG3 levels. RESULTS: Microgeographical variations in prevalence of parasitaemia were observed during the high but not the low transmission season. Pfs-IgG3 levels were stable between high and low transmission seasons, but increased with age throughout childhood before reaching a plateau in adults. Adjusting Pfs-IgG3 levels of school-aged children for age prior to mapping resulted in spatial patterns that reflected the microgeographical variations observed for high season prevalence of parasitaemia, however, Pfs-IgG3 levels of adults did not. The distances over which age-adjusted Pfs-IgG3 of school-aged children fluctuated were comparable with those distances over which chronic morbidity has previous been shown to vary. CONCLUSION: Age-adjusted Pfs-IgG3 levels of school-aged children are stable and when mapped can provide a tool sensitive enough to detect microgeographical variations in malaria exposure, that would be useful for studying the aetiology of morbidities associated with long-term exposure and co-infections.
Asunto(s)
Anticuerpos Antiprotozoarios/sangre , Malaria Falciparum/epidemiología , Malaria Falciparum/inmunología , Plasmodium falciparum/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Anticuerpos Antihelmínticos/sangre , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Inmunoglobulina G/sangre , Kenia/epidemiología , Malaria Falciparum/parasitología , Masculino , Persona de Mediana Edad , Parasitemia/complicaciones , Parasitemia/epidemiología , Plasmodium falciparum/patogenicidad , Prevalencia , Proteínas Protozoarias/inmunología , Schistosoma mansoni/inmunología , Schistosoma mansoni/patogenicidad , Esquistosomiasis mansoni/epidemiología , Esquistosomiasis mansoni/inmunología , Esquistosomiasis mansoni/parasitologíaRESUMEN
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.
Asunto(s)
Schistosoma haematobium/patogenicidad , Esquistosomiasis Urinaria/epidemiología , Adolescente , Adulto , Animales , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Incidencia , Kenia/epidemiología , Masculino , Morbilidad , Prevalencia , Estudios Prospectivos , Recurrencia , Esquistosomiasis Urinaria/tratamiento farmacológico , Esquistosomiasis Urinaria/mortalidad , Esquistosomicidas/uso terapéutico , Servicios de Salud Escolar , Análisis de Supervivencia , Factores de TiempoRESUMEN
We report multidisciplinary studies on schistosomiasis which have been ongoing in the fishing communities of Piida, Booma, Bugoigo and Walakuba, on Lake Albert, Uganda, since 1996. Schistosomiasis is the major health problem in this area, with high infection intensities and prevalence. In addition to generating basic data on the epidemiology, morbidity and immunology of human schistosomiasis, this research programme is providing important descriptive and methodological information, and has contributed to the increase in operational capacity within Uganda in recent years. Such information and operational capacity are needed to facilitate much needed schistosomiasis control programmes, such as the Schistosomiasis Control Initiative that was launched in Uganda in 2003.
Asunto(s)
Esquistosomiasis mansoni , Animales , Antihelmínticos/uso terapéutico , Estudios de Cohortes , Resistencia a Medicamentos , Femenino , Explotaciones Pesqueras , Agua Dulce , Humanos , Cirrosis Hepática/epidemiología , Cirrosis Hepática/parasitología , Masculino , Morbilidad , Praziquantel/uso terapéutico , Prevalencia , Schistosoma mansoni/inmunología , Esquistosomiasis mansoni/complicaciones , Esquistosomiasis mansoni/epidemiología , Esquistosomiasis mansoni/inmunología , Esquistosomiasis mansoni/prevención & control , Uganda/epidemiologíaRESUMEN
OBJECTIVE: To investigate the effect of helminth and/or malaria infection on the risk of HIV infection in pregnant women and its transmission to their offspring. DESIGN: A retrospective cohort study of pregnant Kenyan women and their offspring from term, uncomplicated vaginal deliveries (n = 936) with a nested case-control study. METHODS: We determined the presence of HIV, malaria, schistosomiasis, lymphatic filariasis, and intestinal helminthes in mothers and tested for HIV antibodies in 12-24 month-old offspring of HIV-positive women. We related these findings to the presence of cord blood lymphocyte activation and cytokine production in response to helminth antigens. RESULTS: HIV-positive women (n = 83, 8.9% of all women tested) were 2-fold more likely to have peripheral blood and/or placental malaria (P < 0.025) and a 2.1-fold greater likelihood of lymphatic filariasis infection (P < 0.001) compared to location-and-parity matched HIV-negative women. Women with HIV and malaria tended to show an increased risk for mother-to-child-transmission (MTCT) of HIV, although this difference was not significant. MTCT of HIV, however, was significantly higher in women co-infected with one or more helminthes (48%) verses women without helminth infections (10%, P < 0.01; adjusted odds ratio, 7.3; 95% confidence interval, 2.4-33.7). This increased risk for MTCT of HIV correlated with cord blood lymphocytes production of interleukin-5/interleukin-13 in response to helminth antigens (P < 0.001). CONCLUSION: Helminth co-infection is associated with increased risk for MTCT of HIV, possibly by a mechanism in which parasite antigens activates lymphocytes in utero. Treatment of helminthic infections during pregnancy may reduce the risk of MTCT of HIV.
Asunto(s)
Infecciones por VIH/complicaciones , Helmintiasis/complicaciones , Complicaciones Infecciosas del Embarazo , Adulto , Preescolar , Estudios de Cohortes , Citocinas/metabolismo , Filariasis Linfática , Ensayo de Inmunoadsorción Enzimática , Femenino , Sangre Fetal/metabolismo , Humanos , Lactante , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , Kenia , Embarazo , Complicaciones Infecciosas del Embarazo/parasitología , Complicaciones Infecciosas del Embarazo/virología , Complicaciones Parasitarias del Embarazo/parasitología , Complicaciones Parasitarias del Embarazo/virología , Estudios Retrospectivos , Factores de Riesgo , EsquistosomiasisRESUMEN
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.
Asunto(s)
Antihelmínticos/uso terapéutico , Esquistosomiasis Urinaria/tratamiento farmacológico , Esquistosomiasis Urinaria/fisiopatología , Adulto , Animales , Antihelmínticos/administración & dosificación , Femenino , Estudios de Seguimiento , Hematuria/epidemiología , Humanos , Kenia/epidemiología , Enfermedades Renales/epidemiología , Masculino , Prevalencia , Schistosoma haematobium/efectos de los fármacos , Esquistosomiasis Urinaria/epidemiología , Esquistosomiasis Urinaria/parasitología , Factores de Tiempo , Resultado del Tratamiento , Enfermedades de la Vejiga Urinaria/epidemiologíaRESUMEN
Evaluating regression of morbidity associated with parasitic infections is an important component of community-based control programmes. We performed an intervention against Schistosoma mansoni infection, focusing on hepatosplenomegaly in the absence of periportal fibrosis, in a cohort of 67 Kenyan children aged 7-18 years from Makueni District, selected on the basis of hepatosplenomegaly detected by ultrasonography. Clinical and ultrasound examinations were conducted annually for three years after treatment, and the source of infection (a river) was regularly treated with molluscicide, thereby severely reducing exposure to schistosomiasis. Malaria transmission was uninterrupted. The prevalence of hard spleens, and the magnitude of clinically assessed splenomegaly along the mid-axillary and mid-clavicular lines decreased monotonically over time, independently of age, whereas clinically measured hepatomegaly along the mid-sternal line and the prevalence of firm livers decreased in an age-specific manner, being more pronounced amongst children aged 14 years or older at enrolment. Ultrasound data were less informative, and did not concur with clinical observations. These results demonstrate that praziquantel treatment reduces hepatosplenomegaly in the absence of exposure to S. mansoni, even with continuing exposure to malaria. The lack of complete resolution of hepatosplenomegaly in most children suggests, among other things, a residual organomegaly attributable to malaria.
Asunto(s)
Antihelmínticos/uso terapéutico , Hepatomegalia/epidemiología , Praziquantel/uso terapéutico , Esquistosomiasis mansoni/tratamiento farmacológico , Esplenomegalia/epidemiología , Adolescente , Distribución por Edad , Niño , Estudios de Cohortes , Femenino , Hepatomegalia/prevención & control , Humanos , Kenia/epidemiología , Hígado/diagnóstico por imagen , Hígado/parasitología , Masculino , Recuento de Huevos de Parásitos/métodos , Prevalencia , Esquistosomiasis mansoni/epidemiología , Bazo/diagnóstico por imagen , Bazo/parasitología , Esplenomegalia/prevención & control , Resultado del Tratamiento , UltrasonografíaRESUMEN
BACKGROUND: Parasite-specific IgE levels correlate with human resistance to reinfection with Schistosoma spp. after chemotherapy. Although the role of eosinophils in schistosomiasis has been the focus of a great deal of important research, the involvement of other Fcepsilon receptor-bearing cells, such as mast cells and basophils, has not been investigated in relation to human immunity to schistosomes. Chemotherapy with praziquantel (PZQ) kills schistosomes living in an in vivo blood environment rich in IgE, eosinophils and basophils. This releases parasite Ags that have the potential to cross-link cell-bound IgE. However, systemic hypersensitivity reactions are not induced by treatment. Here, we describe the effects of schistosomiasis, and its treatment, on human basophil function by following changes in total cellular histamine and in vitro histamine-release induced by schistosome Ags or anti-IgE, in blood samples from infected Ugandan fishermen, who are continuously exposed to S. mansoni infection, before and 1-day and 21-days after PZQ treatment. RESULTS: There was a significant increase in the total cellular histamine in blood samples at 1-day post-treatment, followed by a very significant further increase by 21-days post-treatment. In vitro histamine-release induced by S. mansoni egg (SEA) or worm (SWA) Ags or anti-IgE antibody, was significantly reduced 1-day post-treatment. The degree of this reduction correlated with pre-treatment infection intensity. Twenty-1-days post-treatment, SEA-induced histamine-release was still significantly lower than at pretreatment. Histamine-release was not correlated to plasma concentrations of total or parasite-specific IgE, nor to specific IgG4 plasma concentrations. CONCLUSION: The biology of human blood basophils is modulated by S. mansoni infection and praziquantel treatment. Infection intensity-dependent suppression of basophil histamine-release, histamine-dependent resistance to infection, and similarities with allergen desensitisation are discussed as possible explanations of these observations.
Asunto(s)
Antihelmínticos/uso terapéutico , Antígenos Helmínticos/sangre , Liberación de Histamina/efectos de los fármacos , Inmunoglobulina E/sangre , Praziquantel/uso terapéutico , Esquistosomiasis mansoni/tratamiento farmacológico , Animales , Anticuerpos Antiidiotipos/sangre , Estudios de Cohortes , Ensayo de Inmunoadsorción Enzimática , Explotaciones Pesqueras , Histamina/sangre , Liberación de Histamina/inmunología , Humanos , Masculino , Schistosoma mansoni/efectos de los fármacos , Schistosoma mansoni/inmunología , Esquistosomiasis mansoni/sangre , Esquistosomiasis mansoni/inmunología , Espectrometría de Fluorescencia , Factores de Tiempo , UgandaRESUMEN
BACKGROUND: Schistosoma mansoni and malaria infections are often endemic in the same communities in sub-Saharan Africa, and both have pathological effects on the liver and the spleen. Hepatosplenomegaly associated with S. mansoni is exacerbated in children with relatively high exposure to malaria. Treatment with praziquantel reduces the degree of hepatosplenomegaly, but the condition does not completely resolve in some cases. The present analysis focused on the possibility that exposure to malaria infection may have limited the resolution of hepatosplenomegaly in a cohort of Kenyan schoolchildren. METHODS: Ninety-six children aged 6-16, from one community in Makueni district, Kenya, were treated with praziquantel. At baseline, all children had hepatomegaly and most had splenomegaly. The source of S. mansoni infection, a river, was molluscicided regularly over the following three years to limit S. mansoni re-infection, whereas malaria exposure was uninterrupted. Hepatic and splenic enlargement was assessed annually outside the malaria transmission season. RESULTS: Children living in an area of relatively high exposure to both infections presented with the largest spleens before treatment and at each follow-up. Spleens of firm consistency were associated with proximity to the river. The regression of hepatomegaly was also affected by location, being minimal in an area with relatively low S. mansoni exposure but high exposure to malaria, and maximal in an area with relatively low exposure to both infections. CONCLUSIONS: The outcome of treating cases of hepatosplenomegaly with praziquantel in this cohort of Kenyan children depended strongly on their level of exposure to malaria infection. Furthermore, a residual burden of hepatosplenic morbidity was observed, which was possibly attributable to the level of exposure to malaria. The results suggest that exposure to malaria infection may be a significant factor affecting the outcome of praziquantel treatment to reduce the level of hepatosplenic morbidity.
Asunto(s)
Hepatomegalia/parasitología , Malaria/complicaciones , Esquistosomiasis mansoni/complicaciones , Esplenomegalia/parasitología , Adolescente , Animales , Niño , Hepatomegalia/tratamiento farmacológico , Humanos , Kenia , Schistosoma mansoni , Esquistosomiasis mansoni/tratamiento farmacológico , Esplenomegalia/tratamiento farmacológicoRESUMEN
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.
Asunto(s)
Bulinus/crecimiento & desarrollo , Schistosoma haematobium/crecimiento & desarrollo , Esquistosomiasis Urinaria/epidemiología , Agua/parasitología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Animales , Bulinus/parasitología , Niño , Preescolar , Análisis por Conglomerados , Composición Familiar , Femenino , Humanos , Lactante , Kenia/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Población Rural , Comunicaciones por Satélite , Esquistosomiasis Urinaria/parasitología , Factores SexualesRESUMEN
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.
Asunto(s)
Bulinus/parasitología , ADN Protozoario/análisis , Reacción en Cadena de la Polimerasa/métodos , Schistosoma haematobium/aislamiento & purificación , Animales , Vectores de Enfermedades , Kenia , Schistosoma haematobium/genéticaRESUMEN
Lymphocyte proliferation and antibody responses to five peptides corresponding to the N- and C-terminal non-repeat and central repeat regions of Plasmodium falciparum liver-stage antigen-1 (LSA-1) were examined in residents of a highland area of Kenya where malaria transmission is episodic and varies with rainfall. The frequency of lymphocyte proliferation responses (stimulation index > 2) by children (persons > or = 6 years old) and adults (persons > or = 18 years old) was similar and did not differ significantly across seasons. In contrast, the proportion of individuals with IgG antibodies to LSA-1 peptides was higher in the rainy than dry season, and the frequency of these responses was greater for adults than children (39.4% versus 18.7% during the period of high transmission; P = 0.009). Antibodies to LSA-1 were primarily of the IgG1 and IgG3 subclasses, and these also varied with season (30.1% and 32.5% of individuals had IgG1 and IgG3 in the rainy season versus none and 10.9% in the dry season). There was no significant difference in the time to re-infection between groups of persons with or without IgG antibody or lymphocyte proliferation responses to LSA-1 peptides. These data indicate that age and transmission intensity independently affect IgG antibody responses to LSA-1 but do not influence lymphocyte proliferation in this highland area where malaria transmission is highly variable.
Asunto(s)
Anticuerpos Antiprotozoarios/sangre , Antígenos de Protozoos/inmunología , Activación de Linfocitos/inmunología , Malaria Falciparum/transmisión , Plasmodium falciparum/inmunología , Estaciones del Año , Adulto , Animales , Antígenos de Protozoos/química , Niño , Preescolar , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/clasificación , Kenia , Leucocitos Mononucleares/inmunología , Hígado/parasitología , Malaria Falciparum/inmunología , Malaria Falciparum/parasitología , Péptidos/química , Péptidos/inmunologíaRESUMEN
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.
Asunto(s)
Hematuria/etiología , Praziquantel/uso terapéutico , Esquistosomiasis Urinaria/tratamiento farmacológico , Enfermedades Urológicas/parasitología , Adolescente , Adulto , Animales , Antihelmínticos/efectos adversos , Antihelmínticos/uso terapéutico , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Geografía , Hematuria/tratamiento farmacológico , Humanos , Kenia , Masculino , Morbilidad , Recuento de Huevos de Parásitos , Praziquantel/efectos adversos , Población Rural , Schistosoma haematobium , Factores de Tiempo , Resultado del Tratamiento , Enfermedades Urológicas/epidemiología , Enfermedades Urológicas/prevención & controlRESUMEN
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.
Asunto(s)
Enfermedades Endémicas , Schistosoma haematobium/crecimiento & desarrollo , Esquistosomiasis Urinaria/genética , Infecciones Urinarias/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Niño , Preescolar , Femenino , Predisposición Genética a la Enfermedad , Humanos , Kenia , Masculino , Persona de Mediana Edad , Recuento de Huevos de Parásitos , Prevalencia , Esquistosomiasis Urinaria/parasitología , Infecciones Urinarias/parasitología , Orina/parasitologíaRESUMEN
The effect of repeated half-yearly mass treatment with diethylcarbamazine (DEC, 6 mg/kg body weight) on infection and transmission of Wuchereria bancrofti was assessed and compared in communities with high and low endemicity in eastern Africa, with pretreatment microfilaria (mf) and circulating filarial antigen (CFA) prevalences of 29.4% and 53.2% in the high endemicity community and 3.1% and 18.7% in the low endemicity community, respectively. Human infection was monitored by repeated cross-sectional surveys, and transmission by weekly light trap collection of vector mosquitoes in selected houses in each community. Treatments resulted in a progressive decrease in microfilaremia and circulating antigenemia in both communities, with relative reductions being considerably higher for mf than for CFA. Among pretreatment mf-positive individuals, more than 60% were diagnosed as mf negative and mean mf intensities were reduced by 99% in both communities after two treatment rounds. In contrast, only moderate reductions were seen in circulating antigenemia among pretreatment CFA-positive individuals, with mean intensities still being 24-39% of pretreatment values after two treatment rounds. Among the pretreatment mf/CFA-positive individuals, clearance to a CFA-negative status was negligible. Complete CFA clearance was only observed among pretreatment CFA-positive but mf negative individuals who also had much lower initial mean CFA levels than the mf-positive individuals. After treatment, the intensity of transmission decreased in the high-endemicity community, but this appeared mainly to be a consequence of a drought-induced reduction in vector density rather than to reduced mf load in the human population, since the proportion of mosquitoes carrying infective larvae was not reduced. No change in transmission or mosquito infectivity was observed after treatment in the low-endemicity community. Implications of these observations for the control of Bancroftian filariasis are discussed.
Asunto(s)
Dietilcarbamazina/administración & dosificación , Enfermedades Endémicas/prevención & control , Filariasis/tratamiento farmacológico , Filaricidas/administración & dosificación , Wuchereria bancrofti/crecimiento & desarrollo , Animales , Antígenos Helmínticos/sangre , Estudios Transversales , Culicidae/parasitología , Esquema de Medicación , Femenino , Filariasis/epidemiología , Filariasis/parasitología , Filariasis/transmisión , Humanos , Insectos Vectores/parasitología , Kenia , Masculino , Microfilarias/aislamiento & purificación , Microfilarias/parasitología , Prevalencia , TanzaníaRESUMEN
Bancroftian filariasis infection, disease and specific antibody response patterns in a high and a low endemicity community in East Africa were analyzed and compared to assess the relationship between these parameters and community transmission intensity. Overall prevalences of microfilaremia and circulating filarial antigenemia were 24.9% and 52.2% in the high and 2.7% and 16.5% in the low endemicity community, respectively. A positive history of acute attacks of adenolymphangitis was given by 12.2% and 7.1% of the populations, 4.0% and 0.9% of the adult (> or = 20 years old) individuals presented with limb lymphedema, and 25.3% and 5.3% of the adult males had hydrocele, in the high and the low endemicity community, respectively. Both infection and disease appeared earlier and reached much higher levels in the high than in the low endemicity community. The observed overall and age-specific infection and disease patterns in the two communities were in agreement with the view that these are primarily shaped by transmission intensity. No statistically significant relationships between infection status of fathers and mothers and that of their children were observed in any of the communities for either microfilaremia or for circulating filarial antigenemia. The overall levels (prevalence and geometric mean intensity) of filarial-specific IgG1, IgG2, IgG4, and IgE were significantly higher in the high endemicity community than in the low endemicity dommunity. Surprisingly, the opposite pattern was found for IgG3. Community transmission intensity thus appears to be an important determinant of observed inter-community variation in infection, disease, and host response patterns in Bancroftian filariasis.
Asunto(s)
Anticuerpos Antihelmínticos/sangre , Filariasis/diagnóstico , Wuchereria bancrofti/aislamiento & purificación , Adolescente , Adulto , Distribución por Edad , Anciano , Animales , Formación de Anticuerpos , Antígenos Helmínticos/análisis , Niño , Preescolar , Femenino , Filariasis/epidemiología , Filariasis/inmunología , Humanos , Inmunoglobulina G/sangre , Isotipos de Inmunoglobulinas/sangre , Lactante , Kenia/epidemiología , Masculino , Persona de Mediana Edad , Tanzanía/epidemiología , Wuchereria bancrofti/inmunologíaRESUMEN
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.
Asunto(s)
Bulinus/crecimiento & desarrollo , Bulinus/parasitología , Schistosoma haematobium/crecimiento & desarrollo , Esquistosomiasis Urinaria/transmisión , Agua/parasitología , Animales , Análisis por Conglomerados , Vectores de Enfermedades , Humanos , Concentración de Iones de Hidrógeno , Kenia , Comunicaciones por Satélite , Esquistosomiasis Urinaria/parasitología , Agua/químicaRESUMEN
Geophagy was studied among 827 pregnant women in western Kenya, during and after pregnancy. The women were recruited at a gestational age of 14-24 weeks and followed-up to 6 months post-partum. The median age (range) of the women was 23 years and median parity 2. At recruitment, 378 were eating earth, of which most (65%) reported earth-eating before pregnancy. The preferred type of earth eaten was soft stone, known locally as odowa (54.2%) and earth from termite mounds (42.8%). The prevalence remained high during pregnancy, and then declined to 34.5% and 29.6% at 3 and 6 months post-partum respectively (P < 0.001). The mean daily earth intake was 44.5 g during pregnancy, which declined to 25.5 g during lactation (P < 0.001). A random sample of 204 stools was collected from the women and analysed for silica content as a tracer for earth-eating. The mean silica content was 2.1% of the dry weight of stool. Geophagous women had a higher mean silica content than the non-geophagous ones (3.1% vs. 1.4%, P < 0.001). Faecal silica and reported geophagy were strongly correlated (P < 0.001).