Measuring morbidity in schistosomiasis mansoni: relationship between image pattern,portal vein diameter and portal branch thickness in large-scale surveys using new WHO coding guidelines for ultrasound in schistosomiasis

OBJECTIVE: World Health Organization consensus meetings on 'Ultrasound in Schistosomiasis' in 1996 and 1997 anticipated further challenges in the global implementation of a standardized protocol for morbidity assessment in schistosomiasis mansoni. We evaluated the performance of the qualitative and quantitative components of the new Niamey criteria. METHOD: Use of the Niamey protocol among 3954 subjects in two linked, cross-sectional ultrasound surveys of Schistosoma mansoni-endemic populations in Egypt and Kenya. RESULTS: There were significant differences between Egyptian and Kenyan sites in prevalence and age distribution of S. mansoni-related hepatic fibrosis (36%vs. 3%, P < 0.001). Protocol image pattern scoring could be performed quickly and was stable to interobserver variation. However, there were unintended but systematic differences between study sites in the measurement of portal vein diameter (PVD) and wall thickness. By Niamey criteria, a high prevalence of portal dilation was scored for normal Egyptian subjects, which reduced the predictive value of image pattern for portal hypertension. Using alternative height-indexing of PVD, image pattern plus PVD findings predicted 15% of Egyptians and 2.5% of Kenyans were at risk for variceal bleeding, whereas locally derived PVD norms estimated 25% of Egyptians and 12% of Kenyans to be at possible risk. CONCLUSION: Niamey scoring criteria performed acceptably as a relative grading system for disease in schistosomiasis mansoni, but failed to account fully for site-to-site variation in test performance and morbidity prevalence. Consequently, standardized image pattern scoring appears to provide the most useful tool for detection and comparison of S. mansoni-associated morbidity in large-scale surveys.     

Dopamine precursors and brain function in phenylalanine hydroxylase deficiency

Phenylalanine and tyrosine constitute the two initial steps in the biosynthesis of dopamine, which, in its turn, is the metabolic precursor of noradrenaline and adrenaline. The extracellular phenylalanine concentration influences brain function in phenylalanine deficiency (PHD) by decreased dopamine synthesis. It has been shown to induce EEG slowing, and prolonged the performance time on neuropsychological tests. The tyrosine concentration in the CNS is reduced in PHD, possibly implying insufficient substrate (= tyrosine) for catecholamine synthesis due to competition inhibition, for instance across the blood brain barrier. In experimental studies it has been shown that the synthesis and release of dopamine can be influenced by an increase in the availability of tyrosine. In PHD an extra dietary intake of three doses of tyrosine (160mg/kg/24h) induced a shortsning of reaction time and decreased variability, and in a double-blind crossover study a similar dose has been reported to induce an improvement on psychological tests. In a study with lower doses of tyrosine (110mg/kg/24h) no effect was found on reaction time tests. These findings need to be substantiated, and more detailed information should be obtained.     

Relation between the response to iron supplementation and sickle cell hemoglobin phenotype in preschool children in western Kenya

BACKGROUND: Iron supplementation has been associated with greater susceptibility to malaria and lower hematologic responses in pregnant Gambian women with sickle cell trait (HbAS) than in similar women with the normal (HbAA) phenotype. It is not known whether a similar interaction exists in children. OBJECTIVE: Our aim was to determine the influence of the HbAS phenotype on hematologic responses and malaria after iron supplementation in anemic (hemoglobin: 70-109 g/L) children aged 2-35 mo. DESIGN: We conducted a double-blind, randomized, placebo-controlled trial (HbAS, n = 115; HbAA, n = 408) of intermittent preventive treatment with sulfadoxine pyrimethamine (IPT-SP) at 4 and 8 wk and daily supervised iron for 12 wk. RESULTS: The mean difference in hemoglobin concentrations at 12 wk between children assigned iron and placebo iron, after adjustment for the effect of IPT-SP, was 9.1 g/L (95% CI: 6.4, 11.8) and 8.2 g/L (4.0, 12.4) in HbAA and HbAS children, respectively (P for interaction = 0.68). Although malaria parasitemia and clinical malaria occurred more often in HbAS children in the iron group than in those in the placebo iron group, this difference was not significant; incidence rate ratios were 1.23 (95% CI: 0.64, 2.34) and 1.41 (0.39, 5.00), respectively. The corresponding incidence rate ratios in HbAA children in the same groups were 1.07 (95% CI: 0.77, 1.48) and 0.59 (0.35, 1.01), respectively. The corresponding interactions between the effects of iron and hemoglobin phenotype were not significant. CONCLUSIONS: There was no evidence for a clinically relevant modification by the hemoglobin S phenotype of the effects of iron supplementation in the treatment of mild anemia. The benefits of iron supplementation are likely to outweigh possible risks associated with malaria in children with the HbAA or HbAS phenotype.     

Epidemiology and morbidity of Schistosoma mansoni infection in a fishing community along Lake Albert in Uganda

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.     

Hepatosplenic morbidity in two neighbouring communities in Uganda with high levels of Schistosoma mansoni infection but very different durations of residence

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.     

Low heritable component of risk for infection intensity and infection-associated disease in urinary schistosomiasis among Wadigo village populations in Coast Province, Kenya

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.     

Serological responses among individuals in areas where both schistosomiasis and malaria are endemic: cross-reactivity between Schistosoma mansoni and Plasmodium falciparum

We examined specific immunoglobulin G1 (IgG1) and IgG3 responses to Plasmodium falciparum schizont and Schistosoma mansoni egg and worm antigens in individuals from Kenya, Uganda, and the Sudan who had been exposed to malaria and schistosomiasis. A strong correlation between malaria- and schistosome-specific IgG3 responses was observed. This association appears to result from the presence of cross-reactive components of the 2 parasites that bind IgG3 antibodies, rather than to be mediated by immunological cross-regulation or specific regulatory mechanisms induced by either parasite. Cross-reactivity of IgG3 antibodies was confirmed in a Brazilian cohort of individuals living in an area where schistosomiasis is endemic but no malaria occurs and in a Pakistani cohort from an area where malaria is endemic but no schistosomiasis occurs. An IgG3 interaction with antigens from both parasites was observed in individuals from both cohorts, but not in uninfected European control subjects. The immunological and biological implications of this observation require further exploration.