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Studies on Kenyan and Ugandan primary schoolchildren's knowledge of medicines and self-treatment practices show that children aged between 10 and 18 years have a broad knowledge of herbal and biomedical remedies and that they use them frequently, often without adults' involvement. They use pharmaceuticals, including prescription-only drugs, but lack knowledge about indications and dosages. There is a gap between the children's life worlds and the school health education as it is presently designed and taught in Kenya and Uganda. It limits itself to disease prevention and health promotion, and does not teach treatment or medicine-use. Self-treatment based on insufficient knowledge poses a threat to children's health and to the health of the wider community. Therefore, education on the critical and appropriate use of medicines needs to be developed and tested for possible use in Kenya, Uganda and other countries in which home-treatment is common. The proposed education on medicines should go beyond providing information on accurate dosage and indication: it should create critical awareness with regard to medicine-use, enabling children to use them appropriately and cautiously. Kenyan and Ugandan primary schoolchildren are active agents within pluralistic medical fields. By taking the children seriously as competent health care agents, the dangers of self-treatment could be reduced, and the potential of children could be guided to fruitful use. Educational interventions cannot solve the problems of self-treatment, which are related to the wider social and economic context, but they could contribute to increased awareness as a necessary condition for change. [ABSTRACT FROM AUTHOR] more...

This paper reports the detailed results of a study of the impact of the Health Workers for Change (HWFC) workshop series on clients' perceptions of health services, relationships within the health centre and relations between the health facility and the district health system. The study was carried out in three stages: baseline, intervention and evaluation over a period of 20 months. Data, both qualitative and quantitative, were collected at three levels: client, facility and system. Results indicate that relations between health workers and clients improved a great deal after the intervention while those between the facility and the system remained to a large extent unchanged. The paper concludes that, with external support and help, especially from the health system level, health workers can work towards improving health services and their job satisfaction, which can lead to better health worker-client relations. [ABSTRACT FROM AUTHOR] more...

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

We evaluated the impact of praziquantel therapy (40 mg/kg body weight) on indicators of infection with Schistosoma haematobium by following a cohort of infected children from schools located 12 km apart in the Coast province of Kenya, at 0, 2, 4, 6, 12 and 18 months after treatment. Within this period, measurements of infection parameters pertaining to egg counts and haematuria (micro-, macro- and history) were evaluated at all time points. The initial prevalence of 100% dropped significantly 8 weeks after treatment with a similar trend in the intensity of infection. Microhaematuria followed the same trend as observed for egg counts while macrohaematuria remained low after treatment. Reinfection following successful therapy differed significantly between schools; in one school the children were reinfected immediately while those in the other remained uninfected despite similar starting prevalences, intensities of infection and cure rates. Transmission between the two areas looked homogeneous before treatment but when both groups were treated, contrasting transmission patterns became evident. In a regression model we evaluated factors that might be associated with reinfection, and after allowing for pretreatment infection level, age and sex, area (school) remained a highly significant predictor. [ABSTRACT FROM AUTHOR] more...

In areas endemic for schistosomiasis, there is great heterogeneity in antibody isotype responses to parasite antigens amongst infected individuals. At the population level, the isotype composition of antibody responses undergoes dynamic changes which are associated with the age of infected individuals. Here we examine the IgG subclass responses to Schistosoma mansoni eggs (soluble egg antigens; SEA) of infected individuals by immunoblot and ELISA. By controlled treatment of SEA-coated ELISA plates and immunoblot nitrocellular strips with sodium periodate, in order to oxidize terminal carbohydrate residues selectively, we were able to relate individuals subjects' isotype responses to the different antigens that they responded to, and to the presence of putative carbohydrate and peptide epitopes on those antigens. IgG2 responses were restricted strictly to sodium periodate-sensitive carbohydrate epitopes and antigens of relatively high molecular weight. These antigens were not usually recognized by other isotypes and, therefore, they were only recognized by individuals who had high levels of IgG2. IgG1 and IgG3 responses were directed against both carbohydrate and peptide epitopes, whereas IgG4 responses were restricted to periodate-resistant epitopes. This suggests that the fall in IgG2 responses, and reciprocal rise in IgG4 antibodies, seen in young children as their intensities of schistosome infection increase, is not the result of isotype switching, and that, if these two subclasses are involved in blocking immunity to schistosomiasis, they are operating independently. [ABSTRACT FROM AUTHOR] more...

Intensive monitoring of Wuchereria bancrofti vector abundance and transmission intensity was carried out in two communities, one with high-level endemicity for bancroftian filariasis (Masaika, Tanzania) and the other with lowlevel (Kingwede, Kenya), on the East African coast. Mosquitoes were collected in light traps, from 50 randomly selected households in each community, once weekly for 1 year. They were identified, dissected and checked for parity and filarial larvae. Anopheles gambiae s. l., An. funestus and Culex quinquefasciatus transmitted W. bancrofti in the two communities but the importance of each of these taxa differed between the communities and by season. The overall vector densities and transmission intensities were significantly higher in Masaika than in Kingwede (the annual biting rate by 3.7 times and the annual transmission potential by 14.6 times), primarily because of differences in the available breeding sites for the vectors and in the vectorial capacity of the predominant vector species. A marked seasonal variation in vector abundance and transmission potential contributed to the complex transmission pattern in the communities. Generally, these indices were higher during and shortly after the rainy seasons than at other times of the year. Considerable differences in W. bancrofti transmission were thus observed between communities within a relatively small geographical area (mainly because of environmentally-determined differences in vector habitats), and these were reflected in the marked differences in infection level in the human populations. The variation in vector abundance, vector composition and transmission intensity in the two communities is discussed in respect to its cause, its effects, and its significance to those attempting to control bancroftian filariasis. [ABSTRACT FROM AUTHOR] more...

As part of a larger study on the effects of permethrin-impregnated bednets on the transmission of Wucherena bancrofti, subjects from 12 villages in the Coastal province of Kenya, south of Mombasa. were investigated. The aims were to update the epidemiological data and elucidate the spatial distribution of IV hancrofti infection, Samples of night blood from all the villagers aged ⩾ 1 year were checked for the parasite, and all the adult villagers (aged ? 15 years) were clinically examined for elephantiasis and, if male, lot hydrocele. Overall, 16.0% of the 6531 villagers checked for microfilariate (mff) were found microfilaraemic, although the prevalence at microfilaraemia in each village varied from 8. 1 %-27.4%. The geometric mean intensity of infection among the microfilaraemic was 322 mff/ml blood. At village level, intensity of the microfilaraemia was positively correlated with prevalence% indicating that transmission has a major influence on the prevalence of microfilaraemia. Clinical examination of 2481 adults revealed that 2.9% had elephantiasis of the leg and that 19.9% of the adult men (10.8%- 30.1% of the men invest i- gazed in each village) had hydrocele. Although the overall prevalence of microfilaracmia in the study villages had not changed much since earlier studies in the 1970s, both prevalence and intensity varied distinctly between the study villages. Such geographical variation over relatively short distances appears to he a common but seldom demonstrated feature in the epidemiology of bancroftian filariasis, and the focal nature of the geographical distribution should be carefully considered by those mapping the disease. [ABSTRACT FROM AUTHOR] more...

Presents the results of microgeographical studies of human water contact behavior and Schistosoma mansoni transmission levels and intensity of infection in four rural areas in Machakos District, Kenya. Utilization of linear regression and mapping techniques; Parameters considered; Factors responsible for the development of a transmission pattern. more...

Schistosoma mansoni infection, associated morbidity and symptoms were studied in Piida fishing community at Butiaba, along Lake Albert, Uganda, from November 1996 to January 1997. The study revealed that S. mansoni is highly endemic with an overall prevalence of 72%, a mean intensity of 419.4 eggs per gram (epg) faeces (geometric mean for positives only), with 37.8% of males and 33.0% of females excreting over 1000 epg. Prevalence and intensity peaked in the 10-14 year old age group and decreased with increasing age. Females were less heavily infected than males. Differences were also shown between tribes. Diarrhoea and abdominal pain were commonly reported in Piida. However, no clear-cut correlation between intensity of S. mansoni infection and these conditions could be demonstrated, indicating that retrospective questionnaires concerning S. mansoni related-symptomatology are of limited value. Organomegaly, as assessed by ultrasonography, was frequent and hepatomegaly was associated with heavy S. mansoni infection. No correlation was demonstrated between splenomegaly and infection. This study emphasizes that schistosomiasis mansoni is a major public health problem in Piida fishing community and presumably also in many similar fishing communities. These observations call for immediate intervention and can help in planning long-term strategies for sustainable morbidity control. more...

Peri-portal fibrosis can be a serious sequelae of Schistosoma mansoni infection. Age or duration of exposure have been identified as important risk factors, but their relative importance cannot be easily separated. Here, we have compared two cohorts, aged 6-50 years and resident for ten years or since birth, from two neighbouring villages (Booma and Bugoigo) on the eastern shore of Lake Albert, Uganda. Parasitological measurements were similar, whereas the prevalence of peri-portal fibrosis was 5-fold higher in Booma. Data from the cohorts were pooled to assess the relative contribution of age and duration of residency on the risk of disease. Amongst adults, duration of residency was the critical risk factor--individuals aged 17-31 years resident for more 22 years had an almost 12-fold increased risk of fibrosis than those resident for less than 15 years. Height-standardised Splenic Vein Diameter (SVD), Portal Vein Diameter (PVD), Para-sternal Liver Length (PLL) and Spleen Length (SL) values were all higher in Booma, and each organometric parameter except PLL increased with the severity of fibrosis. Our results clearly demonstrate that duration of exposure is a critical risk factor for the development of peri-portal fibrosis and its sequelae in adults. This parameter should therefore be a routine measurement during epidemiological surveys of S. mansoni. more...

Circulating IgG antibody reactivity and excreted egg counts were investigated in 489 Kenyans given chemotherapy for schistosomiasis mansoni. Antibody reactivity was measured in ELISA, using either unfractionated aqueous soluble constituents of Schistosoma mansoni eggs (SEA) or CEF6 (a soluble fraction of S. mansoni eggs containing two cationic antigens) as the antigen source. Antibody reactivity for each antigen source was strongly associated with egg counts, both pre- and post-treatment. Approximately 6 months after chemotherapy, egg counts were zero in 84% of the subjects. The mean optical densities (OD) measured in the post-treatment ELISA were 60% (CEF6) or 45% (SEA) lower than the pre-treatment values, the reduction in the OD with CEF6 as antigen source being significantly greater than that observed with SEA (P <0.001). The usefulness of an assay for antibody reactivity in monitoring the effects of the treatment of schistosomiasis is discussed. more...

Sickle cell genotype prevalence was 26% in a malaria-holoendemic lowland area compared with 3% in a highland area of Kenya. The prevalence of glucose-6-phosphate dehydrogenase deficiency was 7% and 1% in holoendemic lowland and highland areas, respectively. Lack of protective polymorphisms may contribute to morbidity and mortality during outbreaks of malaria in the highlands. more...

The aim of the study was to assess the efficacy and side effects following single and repeated (6 weeks apart) praziquantel treatment (40 mg/kg) in a Schistosoma mansoni-endemic focus with long-standing transmission at Lake Albert in Uganda between December 1996 and January 1997. The results were based on 482 individuals, randomly representing all age and both gender groups. The cure rate following the first and second treatments was 41.9% and 69.1%, respectively. The cure rate was higher in adults than in children, irrespective of intensity of infection. In addition, the cure rate declined markedly with increasing intensity of infection. The reduction in intensity of infection was marked, being 97.7% and 99.6% after the first and second treatments, respectively. A pre- and post-treatment symptom questionnaire revealed a broad range of side effects, including abdominal pain and diarrhoea. However, no serious or long-lasting complications affecting compliance were observed. The marked reductions in faecal egg excretion and the acceptable level of side effects point to a single praziquantel treatment (40mg/kg) as the strategy of choice in such a highly endemic S. mansoni focus. more...

Objective: To determine the relative susceptibility of Schistosoma mansoni infections to treatment with the oxamniquine (OXA) and praziquantel (PZQ)., Design and Setting: Three separate cross sectional studies were performed in six primary schools located in two Schistosoma mansoni endemic areas in Eastern Kenya: Kangundo (low morbidity) and Kibwezi (high morbidity)., Subjects: One thousand two hundred and fourteen infected children aged 6-20 years were involved., Intervention: Each child received either 15-mg OXA/kg body weight twice within an interval of six hours or a single dose of 40 or 60 mg PZQ/kg body weight. Three duplicate Kato stool examinations were done before and four or five weeks after treatment to assess treatment efficacy., Results: The cure rates in different schools with OXA were 71.7-79.7% in Kangundo and 56.7-61.9% in Kibwezi. In children treated with PZQ, the 40-mg/kg-dose regimen achieved cure rates of 77.6-87.2% in Kangundo and 67.1-81.1% in Kibwezi, whereas the 60-mg/kg dose regimen attained cure rates of 93.2% in Kangundo and 76.3% in Kibwezi. Both OXA and PZQ efficacy declined significantly with age in Kangundo, whereas the age effect was not seen in Kibwezi., Conclusion: The poorer cure rates in Kibwezi than in the Kangundo children were not due to known previous drug exposure to either OXA or PZQ. The varying efficacy may be attributed to innate low drug susceptibility, possibly related to schistosome strain differences between the two areas. more...

This study examined the hypothesis that the nature of the host cellular immune response to schistosome ova is a risk factor for urinary tract morbidity in areas in which Schistosoma haematobium is endemic. S. haematobium-infected children and adolescents with bladder pathology assessed by ultrasonography had 54-fold greater tumor necrosis factor (TNF)-alpha production and a 120-fold greater ratio of TNF-alpha to interleukin (IL)-10 release by peripheral blood mononuclear cells in response to egg antigens, in comparison with control children and adolescents matched by age, sex, and infection severity. Mycobacterial antigens also stimulated 7-fold more TNF-alpha among subjects with bladder morbidity than in control subjects, which suggests an innate predisposition to enhanced TNF-alpha production. Levels of egg antigen-induced IL-4 and -5 and interferon-gamma were equivalent in subjects with and without bladder pathology. Thus, children and adolescents predisposed to increased TNF-alpha production to S. haematobium infection are more likely to develop an exaggerated granulomatous response to ova trapped in the bladder wall, with associated urinary tract pathology. more...

Objective: To determine the extent of intestinal schistosomiasis, ascariasis, trichuriasis and hookworm infections among school children of Usigu and Bondo divisions of Bondo District., Design: A cross sectional study., Setting: Fifty out of 130 primary schools in Usigu and Bondo divisions, Bondo District., Subjects: Randomly selected school children (n= 3158) aged five to 20 years, were examined for intestinal helminths and schistosomiasis using Kato thick smear technique., Results: The overall prevalence and geometric mean egg counts per gram/faeces for Schistosoma mansoni were 31.6% and 3.1; hookworm 36.8% and 4.1; Trichuris trichiura 21.8% and 1.5, and Ascaris lumbricoides 16.5% and 2.5. More girls (34.9%) than boys (28.6%) were infected with S. mansoni whereas more boys (39.0%) than girls (34.5%) were infected with hookworm. The prevalence of S. mansoni and hookworm infections increased with age but Ascaris and Trichuris infections decreased with age without any sex differences. Children under ten years of age tended to be more heavily infected with ascariasis, trichuriasis and hookworm than the older ones, while the intensity of S. mansoni increased gradually with age. There were positive relationships between different infections except for a significant negative correlation between Schistosoma mansoni and hookworm infections. Only four cases out of 789 had S. haematobium infection. CONCLUSION. Schistosoma mansoni and geohelminths were endemic in Bondo District, where two thirds of the school children suffered from these parasites. Polyparasitism was also common. There was a little overlap in the distribution of Schistosoma mansoni and hookworm, whereas ascariasis and trichuriasis were fairly distributed in the district. more...

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

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

Seasonal epidemics of malaria occur in highland areas of western Kenya where transmission intensity varies according to rainfall. This study describes the seasonal changes in cytokine responses to Plasmodium falciparum liver-stage antigen 1 (LSA-1) by children (< or =17 years old) and adults (> or =18 years old) living in such a highland area. Fourteen- to 24-mer peptides corresponding to the N- and C-terminal nonrepeat regions of LSA-1 stimulated production of interleukin-5 (IL-5), interleukin-10 (IL-10), gamma interferon (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha) by peripheral blood mononuclear cells (PBMC) from 17 to 73% of individuals in both age groups in both seasons. IL-10 and TNF-alpha responses were more frequent during the high-transmission, rainy season than during the low-transmission, dry season (73 and 67% versus 17 and 25% response rates, respectively). In contrast, there was no seasonal change in the proportion of LSA-1-driven IFN-gamma and IL-5 responses. Children produced less IFN-gamma than adults, but IL-5, IL-10, and TNF-alpha levels were similar for both age groups. Depletion of CD8(+) cells from PBMC decreased IFN-gamma but increased IL-10 production. Individuals with LSA-1-stimulated IL-10 responses in the dry season were less likely to become reinfected in the subsequent rainy season than those without IL-10 responses (25% versus 49%; P = 0.083). These data support the notion that maintenance of LSA-1-driven IL-10 and TNF-alpha responses requires repeated and sustained exposure to liver-stage P. falciparum. In contrast, IFN-gamma responses increase slowly with age but persist once acquired. CD8(+) T cells are the major source of IFN-gamma but may suppress production or secretion of IL-10. more...

Although there is strong epidemiologic evidence linking Schistosoma haematobium infection with carcinoma of the bladder, the utility of cytologic screening for urinary tract cancer has not been critically evaluated in S. haematobium-endemic populations. The present cross-sectional study examined urine cytology findings among 1,014 residents (ages 1 to 91) of the S. haematobium-endemic Msambweni area of Coast Province, Kenya. Among 705 evaluable cytology specimens, prevalence of inflammation (39%), hyperkeratosis (30%), metaplasia (33%), and frank atypia (0.4%) was notably higher than in previously studied, non-endemic populations. Overall, S. haematobium infection was strongly associated with increased risk for cytologic abnormality (> 2.8-fold relative risk of metaplasia or hyperkeratosis; P < 0.001). Age-group analysis confirmed parallel increases in metaplasia and S. haematobium infection prevalence early in life (from age I to 15 for both boys and girls). However, above age 20, metaplasia prevalence persisted at 33-45% prevalence despite a decline in infection prevalence and intensity. Prevalence of advanced (moderate or severe) metaplasia showed two age-related peaks: the first at 10-14 years of age (at the time of peak infection), and the second among subjects > or = 60 years old. No cancers were detected in the study population either on cytology or on follow-up ultrasound examination. These data suggest an age-dependent progression of cellular abnormalities in the urinary epithelium that is associated with chronic S. haematobium infection, which becomes independent of concurrent infection intensity as subjects grow older. Implications for cancer screening are discussed. more...

In a rural area of western Kenya, primary schoolchildren's health seeking behaviour in response to common illnesses was investigated. 57 primary schoolchildren (age 11-17 years, median 13 years) were interviewed weekly about their health status and health seeking activities for 30 weeks. The children each experienced on average 25 illness episodes during this period. Most episodes could be categorised into 4 groups: 'cold', 'headache', 'abdominal complaints' and 'injuries'. One fifth (21%) of the illness episodes were serious enough to keep the children from school. In 28% of them, an adult was consulted, while 72% were not reported to an adult caretaker. Of the episodes without adult involvement, 81% remained untreated, while 19% were treated by the children themselves with either herbal or Western medicines. Of all the medicines taken by the children, two thirds were provided or facilitated by adults (assisted treatment) and one third taken by the children themselves without adult involvement (self-treatment). Among boys, the proportion of illnesses, which were self-treated increased with age from 12% in the youngest age group (< 13 years) to 34% in the oldest (> 14 years). In girls, the proportion of illnesses which were self-treated was consistently lower than among boys and remained constant around 9% for all age groups. The proportion of Western pharmaceuticals used for self-treatment increased with age from 44% in the youngest age group to 63% in the oldest (average 52% Western pharmaceuticals). Again, there were differences between boys and girls: among the youngest age group, boys were twice as likely to use pharmaceuticals than girls (62 versus 32% of the self-treatments, respectively) and in the oldest age group they were nearly three times more likely (75 versus 25%, respectively). These differences in self-treatment practices and choice of medicines between girls and boys may reflect the higher income potential of boys, who can earn money by fishing. Pharmaceuticals were generally preferred for the treatment of headache and fevers, or colds, while herbal remedies were the preferred choice for the treatment of abdominal complaints and wounds. The most commonly used pharmaceuticals were antimalarials (mainly chloroquine), painkillers and antipyretics (mainly aspirin and paracetamol), which were stocked in most small shops in the village at low prices and readily sold to children. Throughout primary school age Kenyan children are growing into a pluralistic medical practice, integrating Western pharmaceuticals into the local herbal medical system, and gradually become autonomous agents in their health care. more...

The Louisiana red swamp crayfish, Procambarus clarkii, which was introduced into east Africa in the 1950s or 1960s, has since widely dispersed. Previous work by our group has shown that P. clarkii can reduce populations of the molluscan intermediate hosts of human schistosomes through predatory and competitive interactions. Here, we investigate whether crayfish can reduce populations of Bulinus africanus and consequently, Schistosoma haematobium prevalence in school children. Children from 6 primary schools in the Machakos and Kitui Districts of Kenya were selected for study. Schools were divided into 3 experimental-control pairs. At experimental schools, crayfish were introduced into nearby aquatic habitats harboring Bulinus africanus snails and serving as S. haematobium transmission sites. Snail habitats near control schools did not receive crayfish. Six months after crayfish introduction, all infected children were treated with praziquantel. Children were then monitored quarterly for 2 years, at which time infection and reinfection rates were compared statistically between the paired schools. In one such pair, crayfish failed to establish, resulting in neither snail control nor a reduction in transmission. At the second pair of schools, the numbers of snails were decreased by the presence of crayfish, but a clear difference in infection rates in children could not be detected, primarily because drought conditions kept overall transmission rates low. At the third school pair, crayfish established well in experimental habitats, snail numbers decreased precipitously, and children at the experimental school were significantly less likely to acquire S. haematobium infections than children at the control school. Our results indicate that under certain environmental circumstances, P. clarkii exerts a significant impact on the transmission of human schistosomiasis in Kenya. Important questions remain regarding the impact of P. clarkii on Kenyan freshwater ecosystems, not the least of which is its potential to significantly influence the epidemiology of schistosomiasis in east Africa. more...

Repeated selective population chemotherapy of school age children reduces infection and morbidity associated with Schistosoma haematobium infection. To examine the long-term effect of this treatment on susceptibility to re-infection and late disease, a cohort of Kenyans (n = 194) were re-examined for infection and urinary tract morbidity 7-13 years after they underwent annual ultrasonography and treatment for an average of 5 years beginning in 1984 as children. Controls were previously untreated age-matched individuals residing in the same or adjacent villages. The overall prevalence and intensity of infection were equivalent between the 2 groups. In contrast, the prevalence of bladder wall pathology was 11-fold lower in previously treated (1.5%) versus untreated subjects (17%). Severe hydronephrosis was completely reversed. These data demonstrate that treatment significantly reduced urinary tract morbidity despite re-infection, and suggest that the important risk factors for urinary tract morbidity in adulthood are cumulative intensity and duration of infection during early adolescence. more...

A cohort of 117 school children infected with Schistosoma haematobium was followed-up after therapy with praziquantel (0, 2, 4, 6, 12, and 18 months) and various infection and morbidity parameters (egg counts, hematuria, soluble egg antigen [SEA] in urine, and ultrasonography-detectable pathology) were quantified. At the onset of the study, 97% of the children were positive for S. haematobium with a geometric mean egg count of 45.7 eggs/10 ml of urine. Eighty-one percent of the children were positive for SEA in urine with a geometric mean SEA concentration of 218.8 ng/ml of urine. Ninety-two percent and 56% of the children were microhematuria positive and macrohematuria positive, respectively. Two months after treatment, all infection and morbidity indicators had significantly decreased. Reinfection after treatment as determined by detection of eggs in urine was observed by four months post-treatment while the other parameters remained low. The clearance of SEA was slower than that of egg counts while pathology resolved at an even slower pace. Levels of SEA and egg output showed similar correlations with ultrasound detectable pathology; these correlations were better than the correlation between hematuria and pathology. more...

We have identified the influence of host and parasite factors that give rise to characteristic antibody isotype profiles with age seen in human populations living in different areas of schistosomiasis endemicity. This is important in the immunobiology of this disease. It is also of interest in the context of human responses to chronic antigen stimulation, vaccines, allergens, and other pathogens. In populations exposed to endemic schistosomiasis, factors such as intensity and duration of infection are age dependent. They therefore confound the influence of host age on antiparasite responses. Here, we resolved these confounding factors by comparing the developing antibody responses of an immunologically naive immigrant population as they acquired the infection for the first time with those of chronically infected resident inhabitants of the same region of Schistosoma mansoni endemicity in Kenya. Recent arrival in the area strongly favored immunoglobulin G3 (IgG3) responses against the parasite. The antibody isotype responses associated with human susceptibility to reinfection after chemotherapy were elevated in those suffering high intensities of infection (IgG4 responses against worm and egg antigens) or were characteristic responses of young children irrespective of the intensity or duration of infection (IgG2 responses against egg antigen). IgE responses against the adult worm, a response associated with resistance to reinfection after chemotherapy, increased with the ages of infected individuals and were also favored in those currently suffering higher intensities of infection. more...

Infants and children are routinely vaccinated with bacillus Calmette-Guérin (BCG) in areas of the world where worm infections are common. Because maternal helminth infection during pregnancy can sensitize the developing fetus, we studied whether this prenatal immunity persists in childhood and modifies the immune response to BCG. Children and newborns living in rural Kenya, where BCG is administered at birth and filariasis and schistosomiasis are endemic, were examined. T cells from 2- to 10-year-old children of mothers without filariasis or schistosomiasis produced 10-fold more IFN-gamma in response to mycobacterial purified protein derivative than children of helminth-infected mothers (p < 0.01). This relationship was restricted to purified protein derivative because maternal infection status did not correlate with filarial Ag-driven IL-2, IFN-gamma, IL-4, or IL-5 responses by children. Prospective studies initiated at birth showed that helminth-specific T cell immunity acquired in utero is maintained until at least 10-14 mo of age in the absence of infection with either Wuchereria bancrofti or Schistosoma haematobium. Purified protein derivative-driven T cell IFN-gamma production evaluated 10-14 mo after BCG vaccination was 26-fold higher for infants who were not sensitized to filariae or schistosomes in utero relative to subjects who experienced prenatal sensitization (p < 0.01). These data indicate that helminth-specific immune responses acquired during gestation persist into childhood and that this prenatal sensitization biases T cell immunity induced by BCG vaccination away from type 1 IFN-gamma responses associated with protection against mycobacterial infection. more...

A case-control study examined vector-related and environmental parameters associated with severe malaria in Kilifi District along the coast of Kenya. Over an 11-month period, 119 children identified with severe malaria infections at the Kilifi District Hospital were matched by age with control children who reported to the outpatient clinic with nonsevere infections. Intensive mosquito sampling was done in each of the case-control houses over a four-day period, beginning within a week of index case admission. A total of 109 environmental, demographic, behavioral, and animal husbandry variables were characterized for each household. Vector species (Anopheles gambiae s.l. and An. funestus) were detected in 40.1% and 36.1% of case and control houses, respectively. The relative abundance of vectors in individual houses was stable over the two-week resampling periods (r = 0.9). Both the overall abundance of anopheline mosquitoes (odds ratio [OR] = 1.5) and P. falciparum sporozoite rates (OR = 1.5) were not significantly different between case and control houses. In a matched analysis, 11 of 109 house variables associated significantly with severe malaria were also associated with vector abundance, as determined by chi-square linear trend analysis. Under conditions of year-round, low-level transmission on the coast of Kenya, the risk of severe disease in children is multifactorial and not governed strictly by transmission intensity or environmental heterogeneity affecting vector abundance and distributions. This suggests that current interventions that appear to be achievable only in areas where transmission is already low to moderate should be appropriate. However, such interventions should be monitored so that inappropriate and possibly disastrous control activities can be avoided in Africa. more...

Kenyan subjects with visceral leishmaniasis were examined for evidence of increased production of soluble interleukin-4 receptor (sIL-4R). Soluble IL-4R regulates the bioactivity of IL-4, a cytokine important in mediating progressive forms of leishmaniasis. Persons with visceral leishmaniasis sustained 8- to 10-fold more circulating sIL-4R compared with Papua New Guinea residents with documented filariasis or uninfected Kenyan and North American subjects. Soluble IL-2R concentrations were elevated nonspecifically in both visceral leishmaniasis and filariasis patients. These findings are significant given that IL-4 induces sIL-4R in mice, and treatment with recombinant sIL-4R cures progressive murine leishmaniasis dependent on IL-4 bioactivity. Further studies are indicated to determine whether the immunologic detection of IL-4 produced in human visceral leishmaniasis is obscured because of sequestration by soluble receptor and whether the production of sIL-4R is relevant to the pathogenesis of visceral leishmaniasis. more...

While research on alternative diagnostic and morbidity markers for infection with Schistosoma haematobium has been going on for a long time, egg counts continue to be used as the gold standard, and infection intensity is thought to reflect the severity of the disease. However, this relationship is not always clear and fluctuation in egg output makes it difficult to classify prevalence correctly. The use of circulating adult worm antigen detection as an alternative diagnostic technique has been applied with varying success. However, this is a measure of worm burden and does not reflect the tissue egg load(s). In the present study we have used an assay that detects soluble egg antigen (SEA) in urine of S. haematobium-infected children, and we have evaluated the applicability of the assay as a diagnostic and morbidity indicator. To evaluate this assay, we have studied a group of 470 children from two schools (Tsunguni and Kibaokiche) in the Coast province of Kenya; 84.8% and 77% were egg-positive while the percentage positive as determined by the SEA-ELISA were 78.8% and 76.2% in Tsunguni and Kibaokiche, respectively. In both schools, SEA levels in urine of S. haematobium-infected children significantly correlated with egg counts (Pearson's r=0.73, P < 0.0001) and with hematuria (Spearman's r=0.65, P < 0.0001). In addition, urinary tract pathology as determined by ultrasound significantly correlated with the SEA levels in urine (Spearman's r=0.3, P < 0.001). The SEA-ELISA compared well with microhematuria within egg count classes and with egg counts within hematuria classes. more...

A cross-sectional study of 729 children and adults in western Kenya investigated the impact of infection with hookworm, Ascaris lumbricoides, Trichuris trichiura, Schistosoma mansoni and malaria on iron status. In bivariate analyses, hookworm intensities as low as 300 eggs/g of faeces were negatively related to levels of haemoglobin (Hb) and serum ferritin (SF). Malaria parasitaemia was negatively related to Hb and positively related to SF, while S. mansoni intensities were negatively related to SF. Multivariate regression analysis was done to identify predictors of Hb and SF levels. In children, age (in years) was the only predictor for Hb (B = 1.7 g/L) and only malaria parasitaemia (negative, light, moderate, heavy) was retained in the model for log10 SF (B = 0.097 microgram/L). In adults, hookworm infection and malaria parasitaemia together with age, sex, pregnancy, SF levels < 12 micrograms/L and elevated body temperature were significant predictors of low Hb. The regression coefficient for hookworm egg count (for increments of 100 eggs/g) was -1.3 g/L. Significant interactions between sex and age and between sex and malaria parasitaemia were revealed. Age and malaria parasitaemia were significant predictors only among females, with a regression coefficient for malaria parasitaemia of -6.9 g/L. The regression coefficient for hookworm did not change when SF < 12 micrograms/L was taken out of the model, indicating that the effect of hookworm cannot be explained by low iron stores alone. Using SF as the dependent variable, hookworm and S. mansoni intensities together with age and sex were retained in the model. The regression coefficients for hookworm egg count (increments of 100 eggs/g) and S. mansoni egg count (increments of 10 eggs/g) were -0.011 microgram/L and -0.012 microgram/L, respectively. Iron deficiency was a problem in this population and hookworm infections contributed significantly to this situation. more...

Praziquantel is the drug of choice for schistosomiasis chemotherapy. Although the exact mechanism of how praziquantel kills schistosomes remains poorly understood, the immune response of the host is an important factor in drug efficacy. It is thus possible that disease states of humans that lead to immunodeficiencies, such as infection with human immunodeficiency virus-1 (HIV-1), may render praziquantel less effective in treating schistosomiasis. To test this hypothesis, persons with high levels of Schistosoma mansoni infection who were or were not also infected with HIV-1 were treated with a standard regimen of praziquantel and monitored by quantitative fecal examination and plasma circulating cathodic antigen. Both groups responded to praziquantel therapy equally and individuals with low percentages (< 20%) of CD4+ T cells did not differ from individuals with higher CD4 cell percentages. These data demonstrate that persons with HIV-1 infection can be treated effectively for schistosomiasis with praziquantel. more...