S. J. De Vlas

Underestimation of Schistosoma mansoni prevalences

Field methods used for detecting Schistosoma mansoni infection miss a certain proportion of the infections. Prevalences of infection appear to be far under-estimated by faecal screening, with important consequences for control and research. Sake de Vlos and Bruno Gryseels investigate how the number of undetected infections can be statistically inferred from population surveys.

Are poor responses to praziquantel for the treatment of Schistosoma mansoni infections in Senegal due to resistance? An overview of the evidence

This paper summarizes and concludes in‐depth field investigations on suspected resistance of Schistosoma mansoni to praziquantel in northern Senegal. Praziquantel at 40 mg/kg usually cures 70–90% of S. mansoni infections. In an initial trial in an epidemic S. mansoni focus in northern Senegal, only 18% of the cases became parasitologically negative 12 weeks after treatment, although the reduction in mean egg counts was within normal ranges (86%). Among other hypotheses to explain the observed low cure rate in this focus, the possibility of drug resistance or tolerance had to be considered. Subsequent field trials with a shorter follow‐up period (6–8 weeks) yielded cure rates of 31–36%. Increasing the dose to 2 × 30 mg/kg did not significantly improve cure rates, whereas treatment with oxamniquine at 20 mg/kg resulted in a normal cure rate of 79%. The efficacy of praziquantel in this focus could be related to age and pre‐treatment intensity but not to other host factors, including immune profiles and water contact patterns. Treatment with praziquantel of individuals from the area residing temporarily in an urban region with no transmission, and re‐treatment after 3 weeks of non‐cured individuals within the area resulted in normal cure rates (78–88%). The application of an epidemiological model taking into account the relation between egg counts and actual worm numbers indicated that the low cure rates in this Senegalese focus could be explained by assuming a 90% worm reduction after treatment with praziquantel; in average endemic situations, such a drug efficacy would result in normal cure rates. Laboratory studies by others on the presence or absence of praziquantel resistance in Senegalese schistosome strains have so far been inconclusive. We conclude that there is no convincing evidence for praziquantel‐resistant S. mansoni in Senegal, and that the low cure rates can be attributed to high initial worm loads and intense transmission in this area.

A model for variations in single and repeated egg counts in Schistosoma mansoni infections

Faecal egg counts are often used to measure Schistosoma mansoni infection, but the considerable variation between successive counts complicates their interpretation. The stochastic model described in this paper gives a description of observed egg counts in a population and can be used as a tool to gain an insight into the underlying worm load distribution. The model distinguishes between two sources of variation in egg counts: (1) variation caused by the difference in worm load between individuals, and (2) the variability of egg counts for an individual with a given worm load. Empirical data, single and repeated measurements, from surveys in five villages in Burundi and Zaire have been used to fit and validate the model. We have discussed possible mechanisms that explain the differences in estimated values between the villages. The model indicates that the expected number of eggs in a stool sample per S. mansoni worm pair is lower than suggested by autopsy data and that, possibly as a consequence of immunity, the inter-individual variation in worm loads decreases with age.

Effects of meteorological factors on epidemic malaria in Ethiopia: a statistical modelling approach based on theoretical reasoning.

This study was conducted to quantify the association between meteorological variables and incidence of Plasmodium falciparum in areas with unstable malaria transmission in Ethiopia. We used morbidity data pertaining to microscopically confirmed cases reported from 35 sites throughout Ethiopia over a period of approximately 6-7 years. A model was developed reflecting biological relationships between meteorological and morbidity variables. A model that included rainfall 2 and 3 months earlier, mean minimum temperature of the previous month and P. falciparum case incidence during the previous month was fitted to morbidity data from the various areas. The model produced similar percentages of over-estimation (19.7% of predictions exceeded twice the observed values) and under-estimation (18.6%, were less than half the observed values). Inclusion of maximum temperature did not improve the model. The model performed better in areas with relatively high or low incidence (>85% of the total variance explained) than those with moderate incidence (55-85% of the total variance explained). The study indicated that a dynamic immunity mechanism is needed in a prediction model. The potential usefulness and drawbacks of the modelling approach in studying the weather-malaria relationship are discussed, including a need for mechanisms that can adequately handle temporal variations in immunity to malaria.

Worm burdens in schistosome infections

Schistosomiasis, caused by fluke worms of Schistosoma spp, is one of the most common tropical diseases. Despite decades of research and progress towards the control of the disease, many aspects of the dynamics of infection and immunity remain unresolved. There is, in fact, not even an approximate measure of how many worms are harboured by infected humans. Epidemiological, mathematical and biomedical arguments indicate that individual worm burdens in endemic areas number hundreds to thousands of adult schistosomes, instead of the few to dozens generally assumed on the basis of available autopsy data. As Bruno Gryseels and Sake de Vlas here discuss, this hypothesis has important consequences for research and control, as many constants in schistosomiasis research have to be reconsidered.

Comparison of STD prevalences in the Mwanza, Rakai, and Masaka trial populations: the role of selection bias and diagnostic errors

Objectives: To assess bias in estimates of STD prevalence in population based surveys resulting from diagnostic error and selection bias. To evaluate the effects of such biases on STD prevalence estimates from three community randomised trials of STD treatment for HIV prevention in Masaka and Rakai, Uganda and Mwanza, Tanzania. Methods: Age and sex stratified prevalences of gonorrhoea, chlamydia, syphilis, HSV-2 infection, and trichomoniasis observed at baseline in the three trials were adjusted for sensitivity and specificity of diagnostic tests and for sample selection criteria. Results: STD prevalences were underestimated in all three populations because of diagnostic errors and selection bias. After adjustment, gonorrhoea prevalence was higher in men and women in Mwanza (2.8% and 2.3%) compared to Rakai (1.1% and 1.9%) and Masaka (0.9% and 1.8%). Chlamydia prevalence was higher in women in Mwanza (13.0%) compared to Rakai (3.2%) and Masaka (1.6%) but similar in men (2.3% in Mwanza, 2.7% in Rakai, and 2.2% in Masaka). Prevalence of trichomoniasis was higher in women in Mwanza compared to women in Rakai (41.9% versus 30.8%). Herpes simplex virus type 2 (HSV-2) seroprevalence and prevalence of serological syphilis (TPHA+/RPR+) were similar in the three populations but the prevalence of high titre syphilis (TPHA+/RPR ≥1:8) in men and women was higher in Mwanza (5.6% and 6.3%) than in Rakai (2.3% and 1.4%) and Masaka (1.2% and 0.7%). Conclusions: Limited sensitivity of diagnostic and screening tests led to underestimation of STD prevalence in all three trials but especially in Mwanza. Adjusted prevalences of curable STD were higher in Mwanza than in Rakai and Masaka.

Water-related disease patterns before and after the construction of the Diama dam in northern Senegal

Abstract The ecological changes caused by projects for the development of water resources are known to affect the epidemiology of water-related diseases. The effects of the construction of the Diama dam (completed in 1986) in the Senegal River on the epidemiology of malaria, urinary and intestinal schistosomiasis, diarrhoea and dysentery were investigated in four districts in northern Senegal. To make allowance for any general trend in reported morbidity (caused by changes in demography or the healthcare system), the numbers of cases of these illnesses reported by the basic healthcare facilities before and after the completion of the dam were compared with those of respiratory disease. Prior to the construction of the dam, malaria was the most encountered water-related disease in the medical records of all districts, followed by diarrhoea, dysentery and urinary schistosomiasis. This order remained the same after the completion of the dam. Despite the optimism of health-assessment reports prepared prior to the construction of the Diama dam, the unexpected appearance and spread of intestinal schistosomiasis as well as an increase in the incidence of urinary schistosomiasis have aggravated public health in the Senegal River basin. It remains to be judged whether the economic benefits of the dam will counterbalance its adverse effects.

Variation in weight of stool samples prepared by the Kato–Katz method and its implications

We investigated both the extent of the variation in weight of stool samples prepared by the Kato–Katz method and its influence on egg counts and commonly used group parameters of infection derived from them. In a first study group of 795 people, the total mean weight of stool aliquots, prepared with templates designed to contain 28.3 mm3, was 23.0 mg with 95% of the individual values lying between 12.0 and 34.0 mg. Minimum and maximum values were 2.4 and 49.5 mg, respectively. Frequency distributions of the individual weights, in series of slides prepared by different laboratory assistants, showed significant differences. In a second study group of 199 people, duplicate series of slides were prepared and variations in the weight of examined stool were related to variations in egg count. The correlation between repeated individual sample weights in this series was poor, but the correlation between egg counts was good. This was translated, at aggregate level, in very similar classifications in egg count categories. This classification was also hardly influenced by the choice of the conversion factor to transform egg counts per slide into eggs per gram. At the individual level, the variability in egg counts far outweighed the variability in sample weight and was not clearly related to it. We therefore concluded that variations in weight of examined stool are considerable, but account for only a minimal part of the important egg count fluctuations generally observed.

Meta-analysis of age-prevalence patterns in lymphatic filariasis: no decline in microfilaraemia prevalence in older age groups as predicted by models with acquired immunity

The role of acquired immunity in lymphatic filariasis is uncertain. Assuming that immunity against new infections develops gradually with accumulated experience of infection, models predict a decline in prevalence after teenage or early adulthood. A strong indication for acquired immunity was found in longitudinal data from Pondicherry, India, where Mf prevalence was highest around the age of 20 and declined thereafter. We reviewed published studies from India and Subsaharan Africa to investigate whether their age-prevalence patterns support the models with acquired immunity. By comparing prevalence levels in 2 adult age groups we tested whether prevalence declined at older age. For India, comparison of age groups 20-39 and 40+ revealed a significant decline in only 6 out of 53 sites, whereas a significant increase occurred more often (10 sites). Comparison of older age groups provided no indication that a decline would start at a later age. Results from Africa were even more striking, with many more significant increases than declines, irrespective of the age groups compared. The occurrence of a decline was not related to the overall Mf prevalence and seems to be a chance finding. We conclude that there is no evidence of a general age-prevalence pattern that would correspond to the acquired immunity models. The Pondicherry study is an exceptional situation that may have guided us in the wrong direction.

Evidence for scaling up HIV treatment in sub-Saharan Africa: A call for incorporating health system constraints

Jan Hontelez and colleagues argue that the cost-effectiveness studies of HIV treatment scale-up need to include health system constraints to be more informative.