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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]

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.

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.

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.

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.

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.

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.

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.

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.

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

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

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.

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.

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.

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.

Human neonates are generally deficient in their ability to generate humoral immunity. This deficiency is thought to reflect physiologic immaturity of T and B cell function and lack of previous exposure to exogenous Ags. To determine whether neonatal humoral immunity can be modified by maternal helminth infection during pregnancy, we assessed Ig production by cord blood lymphocytes from healthy newborns of mothers living in an area of Kenya where schistosomiasis, bancroftian filariasis, and geohelminth infections are endemic. Twelve of 40 and 17 of 39 cord blood lymphocyte preparations from healthy newborns in Coast Province, Kenya, spontaneously made polyclonal IgE (range, 0.15-21 ng/ml) and IgG (1.6-10.1 ng/ml) in vitro. In vitro IgE synthesis by cord blood lymphocytes (CBL) was, on the average, 10-fold less than that of PBMC of Kenyan mothers (1.1-98 ng/ml) and was undetectable for CBL from newborns delivered in the United States. Schistosome and filarial Ags stimulated a 3- to > 100-fold increase in the production of polyclonal IgE and parasite-specific IgG Abs by lymphocytes from 10 of 40 and 6 of 39 Kenyan newborns, respectively. CBL observed to have helminth Ag-driven B cell responses were more likely to be from newborns of schistosome- or filaria-infected mothers than from uninfected mothers (p < 0.05). These data indicate that the human fetus can be sensitized in utero to produce helminth-specific B cells and that neonatal B cells are intrinsically capable of IgE and IgG production.

In a case-control study based in two areas of Kenya, hepatosplenic schistosomiasis mansoni was shown to be linked with low levels of IL-5 and with correspondingly high IFN-gamma, TNF, and circulating soluble TNF receptor I (sTNFR-I), sTNFR-II, and sICAM-1. PBMC from the hepatosplenic cases responded to in vitro Ag stimulation with significantly higher levels of IFN-gamma and TNF, but lower levels of IL-5, compared with nonhepatosplenic controls matched for age and infection intensity. Most of these correlations were confounded by differences between geographical areas. However, principle component analysis identified a high IFN-gamma and TNF, and low IL-5 axis in the data as the first principle component; this was significantly associated with hepatosplenomegaly (p < 0.0005) even after controlling for area. High plasma levels of sTNFR-I (p < 0.001), sTNFR-II, (p < 0.0001), and sICAM-1 (p < 0.009) were also significantly associated with hepatosplenomegaly, independently of area, in the case of the soluble forms of both TNF receptors. These parameters were negatively related to IL-5. These results suggest that proinflammatory cytokines are involved in the hepatosplenic disease process in infected individuals who have low anti-inflammatory Th2 responses and that sTNFR may be a useful circulating marker for this disease process, perhaps reflecting the level of TNF activity in hepatic tissues.

Malaria prevalence and status among other diseases were assessed in Suba District, Kenya, using data from past parasitological surveys and hospital records of clinically-diagnosed cases. A short prospective survey was also carried out to determine the methods people used for self protection against mosquito bites. Malaria was the leading cause of morbidity, constituting 42-48% of all illnesses clinically diagnosed at two health centres over a two-year period. Other common endemic diseases included infections of the upper respiratory and urinary tracts. The highest monthly number of malaria cases were recorded in July of each year. Malaria parasite rates in blood samples from people examined at 14 screening centres ranged from 24.4% to 99% over a distance of about 25 kilometres. The most popular method of self-protection against mosquitoes was mosquito nets followed by mosquito (pyrethrum-based) coils. Other methods included insecticidal sprays and smoke from plants traditionally associated with mosquito repellence.

The impact of permethrin-impregnated bednets on resting and feeding behaviour of mosquito vectors of Wuchereria bancrofti, causing human lymphatic filariasis was studied in six pairs of villages (treated and untreated) before and after intervention. The study villages were in Kwale District, near the coast of Kenya, where Bancroftian filariasis is highly endemic, transmitted by a combination of both anopheline and culicine mosquito vectors. Mosquitoes were collected weekly in each village, indoors (using pyrethrum spray catches) and outdoors (using pit traps) during 3-4 months following the long rainy season. Of the filariasis vector species of mosquitoes collected in 1994 before intervention. 33.6% were members of the Anopheles gambiae complex, 30% were An. funestus and 36.4% were Culex quinquefasciatus. PCR analysis of the An. gambiae complex species collected in 1995 demonstrated that 98.5% were An. gambiae sensu stricto. 1% An. arabiensis and 0.5% An. merus. Introduction of impregnated bednets in 1995 significantly reduced the number of indoor-resting An. gambiae s.l. by 94.6% and An. funestus by 96.7%, but there was no change in the number of Cx quinquefasciatus collected indoors. The number of outdoor-resting An. gambiae s.l. was significantly reduced, whereas densities of An. funestus and Cx quinquefasciatus remained unaffected outdoors. ELISA analysis of mosquito bloodmeals showed a shift from human to animal feeding after the introduction of treated nets. The human blood index (HBI) for indoor resting Cx quinquefasciatus was reduced from 93.1% to 14.4%. Vector potential based on the HBI and mosquito density was estimated to be reduced by 99% for An. gambiae s.l., 98% for An. funestus and 97% for Cx quinquefasciatus and vectorial capacity would be suppressed even more by the impact on the vector survival rates (not measured). These results suggest that permethrin-impregnated bednets give effective personal protection against transmission of W. bancrofti by An. gambiae, An. funestus and Cx quinquefasciatus in East Africa.

Recent data from outbreaks of schistosomiasis in immunologically naive populations have refuelled the debate concerning the nature or existence of protective, acquired immunity to schistosomiasis in humans. Data from endemic communities provide some compelling evidence for an abrupt change in reinfection rates that coincides with puberty. We suggest that the hormonal changes of adrenarche may hold the key to understanding the relative resistance to infection found in adults.

The number of salivary gland malaria sporozoites (sporozoite load) was determined by hemacytometer counts for 2,055 field-collected Anopheles mosquitoes from Kilifi District, Kenya. Of 48 gland-positive Anopheles gambiae s.l., sporozoite loads ranged from 125 to 79,875, with a geometric mean of 1,743 sporozoites per infected mosquito. About half of the infected mosquitoes had sporozoite loads < 1,000. Following hemacytometer examination of salivary gland samples, the same samples were subsequently tested for Plasmodium falciparum circumsporozoite (CS) protein by enzyme-linked immunosorbent assay (ELISA). The confirmation by ELISA of CS protein in 89.6% (43/48) of the salivary gland-positive samples compared to only 1.4% (28/2,007) of the dissection-negative mosquitoes indicated that dissection methods with hemacytometer counts of sporozoites were adequate for detecting even low numbers of sporozoites in field-collected mosquitoes. Detection of 17 or fewer sporozoites in blood meals of 7 freshly bloodfed An. gambiae s.l. provides a further indication that the actual number of sporozoites transmitted during bloodfeeding may be quite low.

Pre- and post-treatment antibody isotype responses to Schistosoma mansoni adult worm and soluble egg antigens were compared in a study population previously used to show that IgE against adult worm correlates negatively with intensity of reinfection following chemotherapeutic cure. IgG subclass responses to adult worm were lower after treatment whereas IgM and IgE were higher. The increase in IgE to adult worm was observed with different preparations of adult worm, including the worm tegument, and with both praziquantel and oxamniquine therapy. No significant difference was observed between pre- and post-treatment isotype responses to egg antigens following either praziquantel or oxamniquine therapy.

Persons employed as vehicle washers in the town of Kisumu, Kenya are exposed for several hours each day to water in Lake Victoria that contains Schistosoma mansoni-infected Biomphalaria pherifferi snails. This results in a focus of high endemicity for schistosomiasis and these persons have very high concentrations of eggs in their feces (mean +/- SD = 1,469 +/- 1,581 eggs per gram [EPG] of feces). Fecal egg counts, but not circulating cathodic antigen (CCA) levels, in these schistosomiasis patients differed strikingly based on the patient's seropositivity for human immunodeficiency virus (HIV). Patients who were infected with S. mansoni and were seropositive for HIV had similar levels of CCA but excreted fewer eggs (643 +/- 622 EPG; n = 16) than individuals who were not seropositive for HIV infection (1,891 +/- 1,779 EPG; n = 37) (P = 0.009). Egg excretion ratios (EPG/CCA) of the seronegative group were also significantly higher than those of the seropositive group. Those in the seropositive group showed a significant correlative relationship between egg excretion ratios and CD4+ lymphocyte percentages. These observations are compatible with the hypothesis that schistosome eggs exit the human host through the requisite facilitation of functional immune responses, and that the efficacy of this process decreases in schistosomiasis patients co-infected with HIV as their peripheral blood CD4- cell levels decrease.

In schistosomiasis endemic areas, intensities of reinfection after treatment are greater amongst young children than amongst adults, and high levels of parasite-specific IgE are associated with resistance to reinfection in an age-dependent manner. Previously we have reported that, in Western blots, a 22 kDa band was recognized by human IgE and that the incidence and intensity of S. mansoni reinfection were significantly lower amongst individuals who had IgE against this band, compared with those who did not (Dunne et al. 1992). Here we report the isolation of a 22 kDa SDS-PAGE band, its incorporation into ELISA and the demonstration that levels of human anti-22 kDa IgE had a significant negative correlation with intensities of subsequent reinfection. Rabbit anti-22 kDa band serum recognized the outer tegument, gut tegument, and the collecting ducts and flame cells of adult worms. The 22 kDa band antigen(s) was also present in "lung'- and "post-lung' schistosomula stages of S. mansoni, and in S. haematobium, S. bovis and S. japonicum adult worms. Metabolic labelling of schistosomula and worms demonstrated the in vitro synthesis and release of 22 kDa antigens.

A total of 19 annual or biannual audits were performed over a 12-year period by an independent microscopist on randomized subsamples of Kato slides examined for Schistosoma mansoni eggs by Kenyan microscopists from the Division of Vector-borne Diseases (DVBD). The recounts were invariably lower than the originals owing to some deterioration of the preparations between counts, but the two were strongly correlated: significant regressions of recounts on counts taking up 80-90% of the observed variance. Observer bias differed significantly between microscopists but remained stable over time, whereas repeatability of recounts on counts dropped slightly in periods of maximum work load but did not vary systematically with time. Approximately 7% of the counts and recounts disagreed on the presence or absence of eggs, but less than a third of these were negatives that were found positive on recount. False negatives dropped to 1.3% if duplicate counts were considered. The performance of the Kenyan microscopists was remarkably high and consistent throughout the 12-year period. This form of quality control is suitable for projects where limited funds preclude full-time supervisors using more sophisticated systems.

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

Understanding the dynamics of schistosome infections is problematic because direct measurements of worm burden are not possible. Hitherto, the relative intensity of infection has been estimated by the number of parasite eggs excreted. Egg excretion is assumed to have a consistent relationship with worm burden with duration of infection. We have tested this assumption in Schistosoma mansoni- and S. haematobium-infected populations by looking at the relationships between a circulating parasite antigen, egg excretion level, host age, and parasite density. The study was carried out in two populations because experimental models suggested that S. haematobium but not S. mansoni suffers immune-mediated reduction of fecundity. The results were consistent with this observation, showing that S. mansoni egg output remains stable irrespective of host age or infection intensity while S. haematobium has a substantially reduced egg production with host age. This information is fundamental to understanding the immunology and epidemiology of human schistosomiasis and thus practical approaches to disease control.

Haematological surveys were carried out in 3 schools in 2 areas where Schistosoma mansoni is endemic in Machakos District, Kenya, before and after a treatment campaign using praziquantel. Earlier clinical impressions of differences in the levels of anaemia between the 2 areas were not confirmed. Although individual haemoglobin levels and haematocrits often fell below international norms, significant anaemia with abnormal red blood cell morphology was rare (< 5%), but varied between schools. Altitude could have accounted for some of these differences, but other factors, including diet and parasitism, were involved. Anaemia was associated with splenomegaly and, to a lesser extent, hepatosplenomegaly. Epidemic malaria (mainly Plasmodium falciparum) appeared to be the main cause of parasite-induced anaemia. There was no significant association with the scarce hookworm infections (mainly Necator americanus); nor did the much commoner S. mansoni cause severe anaemia at the community level, but haemoglobin levels dropped as its intensity increased. Treatment with praziquantel eliminated this trend except in a few subjects with splenomegaly alone (probably due to malaria) or with schistosomal hepatosplenic disease. Possible pathogenic mechanisms are reviewed, including the consumption of red blood cells by adult schistosomes as a possible cause of anaemia.

Formol-ether concentration supplemented by fresh saline smears was used to study intestinal parasites in two communities, Miu and Kitengei, in Machakos District, Kenya. These communities differed markedly in schistosome associated morbidity, in spite of similar prevalence and intensities of infection as revealed by Kato examination, Seven helminth and nine protozoan species were detected among 1011 samples examined. More than 60% of the subjects were infected with more than one parasite: one had nine. Age-prevalence curves were typical for the different species, and overall prevalence of some protozoa, including Entamoeba spp. and Blastocystis hominis, exceeded that of the commonest helminth, Schistosoma mansoni. However, the observed prevalence of S. mansoni was barely 40% of that detected by Kato examinations. Strong associations were found between some pairs of protozoan species, but not with or among the helminths. The differences in the abundance and age-specific distribution of the other intestinal parasites at Miu and Kitengei were so small that it is unlikely that interactions between them and S. mansoni would account for the differences in schistosomal morbidity.

The transmission of Plasmodium falciparum was studied in relation to the incidence of severe malaria infections at nine sites in the Kilifi District in Kenya. Intensive mosquito sampling during a one-year period yielded Anopheles gambiae s. l., An. funestus, An. coustani, An. squamosus, An. nili, and An. pharoensis. Anopheles gambiae s.l. was the predominant vector, comprising 98.4% of the total anophelines collected. Overall, 3.5% of 2,868 An. gambiae s.l. collected indoors and 0.8% of 261 collected outdoors contained P. falciparum sporozoites. Transmission was detected during 10 months, with peak periods from June to August and December to January. In eight of the nine sites, entomologic inoculation rates (EIRs) averaged only four infective bites per year (range 0-18); an annual EIR of 60 was measured for the site with the highest intensity of transmission. The incidence of severe malaria infections, ranging from 8.6 to 38.1 per 1,000 children (0-4 years), was not associated with EIRs. At these sites on the coast of Kenya, a high incidence of severe disease occurs under conditions of very low levels of transmission by vector populations. With respect to conventional approaches for vector control in Africa, decreases in transmission, even to levels barely detectable by standard approaches, may not yield corresponding long-term reductions in the incidence of severe disease.