Comparison of the Kato-Katz technique, hatching test and indirect hemagglutination assay (IHA) for the diagnosis of Schistosoma japonicum infection in China.

The Kato-Katz technique (duplicate 41.7 mg fecal smears), hatching test and indirect hemagglutination assay (IHA) were compared for their ability to detect human Schistosoma japonicum infection in two endemic villages (Zhonjiang and Zhuxi) in rural China. The hatching test (using a nylon bag, and based on about 30 g of feces) and IHA are conventional Chinese diagnostic methods. In both villages, the trends of prevalences with age and sex were comparable for the different methods. In Zhuxi, Kato-Katz examinations of stools from 7 different days and hatching were available, which could be used as a reliable gold standard. This resulted for IHA in a sensitivity of 80% and a specificity of 48%. The sensitivity of the Kato-Katz technique using one stool specimen was 68%, twice that of hatching (33%). In Zhonjiang, however, hatching resulted in more positive cases than Kato-Katz (prevalence 31% vs. 24%). Apparently, the result of the hatching test depends on environmental factors such as temperature and water quality. Although imperfect, Kato-Katz is recommended out of the three evaluated techniques as the method of choice for large-scale screening of S. japonicum. Hatching is much more tedious, provides inconsistent and only qualitative results, and is not much more sensitive than Kato-Katz. Its poor specificity makes IHA unsuitable for individual screening, but it may be more effective for community diagnosis.

The challenge of diagnosing atopic diseases: outcomes in Cuban children depend on definition and methodology.

BACKGROUND: Prevalences of childhood asthma and other atopic diseases are increasing worldwide, and so is the number of diagnostic methods and definitions used. We determined the occurrence of atopic diseases in Cuban children with a range of diagnostic approaches commonly used or proposed in epidemiological studies, and compared the different outcome measures. METHODS: A total of 398 Cuban schoolchildren between 5 and 13 years of age were diagnosed by International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, clinical examination, pre- and post-exercise spirometry, and skin prick testing. All results were considered separately, as well as jointly by using scores and definitions as described in the literature. RESULTS: Using questionnaire-based approaches, 21-39% of the children were positive for asthma, 9-19% for atopic dermatitis, and 15-46% for rhinoconjunctivitis. With spirometry, 7% of the children had asthma. Definitions based on a combination of questionnaire and spirometry results yielded asthma rates of 5%. Of all children, 6% wheezed on clinical examination, and only one child showed clinical signs of atopic dermatitis. Eleven percent of the children had a positive skin prick test. In total, 254 children (64%) had an atopic disease as based on the ISAAC questionnaire, and 263 (66%) based on all approaches used. CONCLUSION: Diagnostic outcomes on atopic diseases vary considerably depending on definition and methodology. Our results clearly demonstrate the need for consensus on diagnosing asthma and other atopic diseases in epidemiological studies. Based on the most commonly used ISAAC questionnaire, our data suggest prevalences of atopic diseases in Cuban children that rival those found in some other Latin American countries and developed nations with the highest prevalences in the world.

Social research as an intervention tool in tuberculosis control.

Our multidisciplinary project on TB control in the Free State, South Africa, is targeting two dimensions for intervention: firstly, patients, to facilitate compliance and improve quality of care; secondly, the health care system, to identify weaknesses that require remedying and best practices to promote better TB control. This communication illustrates how social scientists can contribute towards the implementation of interventions related to their research, thus influencing TB policy, programme planning and practice more directly.

Are the cellular immune responses of children and adults with Schistosoma mansoni infection intrinsically different? Cytokines produced ex vivo in response to antigens and mitogens.

In recently exposed communities, intensity of schistosomiasis infection increases as children age and then drops again in adulthood, indicating that host maturity is an important aspect of resistance to schistosomiasis. We investigated whether the cellular immune response to the parasite was correlated with age in subjects with similar daily patterns of exposure, current intensities of infection and number of years of exposure. The cellular immune response of subjects with either 'low' (under 200 eggs per gram (EPG)) or 'high' (over 400 EPG) intensities of infection was investigated, in a recently established focus where subjects had similar histories of exposure and number of years of experience with Schistosoma mansoni. Subject's whole blood was cultured with adult worm antigen (AWA), a mixture of phytohaemagglutinin (PHA) and lipopolysaccharide (LPS), or left unstimulated, and culture supernatants were tested for IL-4, IL-5, IL-10 and IFN-gamma. Children and adults tended to respond differently to schistosome antigen. The most statistically significant illustration of this was the negative correlation between age and IL-5 produced by samples from people with low intensities of infection cultured with AWA (P < 0.003, P < 0.05 after Bonferroni correction). IL-10 produced by samples cultured with PHA and LPS was also notably lower in children than in adults, although not formally significant after Bonferroni correction. This indicates that it is possible for age, independently of intensity of infection or experience with the parasite, to influence the immune response to schistosomiasis.

[Hygiene practices and contamination risks of surface waters by schistosome eggs: the case of an infested village in Northern Senegal]. / Pratiques hygiéniques et risques de contamination des eaux de surface par des oeufs de schistosomes: le cas d'un village infesté dans le nord du Sénégal.

The transmission of intestinal schistosomiasis presumes that faecal materials containing viable schistosome eggs reach natural water bodies infested with snail intermediate host. So far there is little knowledge about the contamination dynamics of streams with schistosome eggs. We conducted a pilot study on defecating behaviour and hygienic practices in an Schistosoma mansoni endemic focus in Northern Senegal. Questionnaires were used to obtain quantitative data on hygienic practices and the use of latrines in 59 children. Although the community was well endowed with pit latrines, most of the children declared that they usually defecated somewhere else, in particular near the streams where the vegetation offers hideouts. Observations based on mapping of defecation sites showed that a considerable number of stools were left just a few meters from the riverbank, thus bearing a high risk of being washed off into the water. All these practices can easily lead to contamination of water bodies with schistosomae eggs. In order to improve hygienic practices and reduce fecal pollution of the environment, a health education model respecting local beliefs and customs would be indispensable.

On the calculation of intestinal schistosome infection intensity.

The effects of using different methods to calculate individual infection intensities on the age-infection distribution of Schistosoma mansoni field data are demonstrated. Methods are tested on a maximum of three stool samples per person collected on three consecutive days; the methods considered for the calculation of individual infection intensities are the geometric mean (GM), arithmetic mean (AM) and pseudo geometric mean (GM of stool samples instead of replicates). In addition, the effects of calculating the infection intensity for each age group using either AMs or GMs are compared. Differences occur in the shape of the age-infection profiles obtained by using either the arithmetic or geometric group mean. When using the AM, peak infection intensity occurs in a younger age group compared to using the GM, and all three methods of calculating individual infection intensity give the first peak of infection in the same age group. However, differences occur in the position of the second peak which occurs earlier with the two GMs than with the AM. Bootstrapping procedures show that the individual AM, gives a different age group for the first peak of infection at least 25% of the time when compared to either of the GMs, and 31% of the time for the second peak, while the two GMs give the same peak age groups around 90-92% of the time for both peaks. When using the GM, to calculate infection intensity for each age group, there are no differences between the three methods used to calculate individual infection intensity. This is confirmed by bootstrapping procedures. The results are discussed in relation to the distribution of parasites and levels of parasite aggregation. The implications of the results for field studies are also discussed.

Human water contacts patterns in Schistosoma mansoni epidemic foci in northern Senegal change according to age, sex and place of residence, but are not related to intensity of infection.

In an epidemic focus in northern Senegal, adults had lower intensities of infection than adolescents, a phenomenon that could not be attributed to immunity acquired over the previous 10-15 years of exposure to the parasite because all age groups had had the same number of years' experience of the worm. This article considers whether this pattern could have been because of higher levels of exposure to the parasite in younger age groups. Personal contact with infected water was recorded using a questionnaire in Schistosoma mansoni foci not more than 3 years old and in another, 10-year-old focus. Many aspects of contact (e.g. frequency, duration or time of day of contact) may contribute to the number of encounters with infective cercariae (true exposure), so various assumptions regarding the relationship between water contact and true exposure were tested resulting in a range of exposure indices. People reported a mean of 4.4 separate contacts, and spent a median of 57 min per day in water. Patterns of water contact differed depending on the exposure index used, e.g. considering duration, males spent a longer time in water than females (P < 0.001). But using frequency, females had more contacts with water than males in most villages (P < 0.001). Generally, exposure levels dropped as people become aged (P < 0.001) and residents of the older focus were more exposed than residents of other foci (P < 0.002). Intensity of (re)infection was not related to exposure either alone or in models incorporating age, sex and/or village irrespective of the index used. There is therefore evidence that age, sex and place of residence determine exposure but none to suggest that exposure had an influence on the relationship between these factors and intensity of infection. We propose therefore that in this population other factors have principal importance in determining intensity of infection.

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

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.

Evaluation of the patterns of Schistosoma mansoni infection and re-infection in Senegal, from faecal egg counts and serum concentrations of circulating anodic antigen.

Infection and re-infection patterns were evaluated in a recent Schistosoma mansoni focus in northern Senegal, by determining concentrations of serum circulating anodic antigen (CAA), as a measure of worm burden, and counting eggs in faeces before, 6 or 12 weeks and 1 year after praziquantel treatment in two subsequent cohorts (cohort A and B). No differences in egg counts and CAA concentrations or their relationship were found between the cohorts, which were examined 2 years apart. Within both cohorts, CAA concentrations showed the same, typical, age-related patterns as egg counts, with a peak in children and a strong decline in adults. These trends were apparent both before and 1 year after treatment. The results indicate that an age-related resistance to infection and to re-infection has been firmly established, at a steady level, in the recent S. mansoni focus investigated, with no indication of a gradual development of immunity or anti-fecundity immunity over a period of 2 years. Both shortly and 1 year after treatment, the decrease in egg counts was stronger than that in CAA concentrations, indicating that that there had been a reduction in worm fecundity after treatment. The possibility that praziquantel may induce anti-fecundity immunity has important implications for the use and interpretation of the results of (egg-count-based) re-infection studies designed to follow the development of naturally acquired immunity.

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 x 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.

Anthelmintic resistance in human helminths: a review.

We briefly review reports on drug resistance in human helminths and compare the factors which contribute to the development of anthelmintic resistance in livestock and man, i.e. high treatment frequency, single-drug regimens, targeting and timing of mass treatments and underdosing. Conclusions are drawn from the mistakes in the treatment and control of livestock helminths. The advantages and inconveniences of current methods for the detection of drug resistance in helminths of livestock are discussed and some suggestions are put forward to standardize the tests for the detection of resistance in human helminths. Finally, based on veterinary experience, some recommendations are made to reduce the risks of development of drug resistance in human helminths. The dramatic and rapid spread of resistance to all major classes of veterinary anthelmintics should be a warning against too strong a reliance on drugs in helminth control programmes.

Studies on the biology of schistosomiasis with emphasis on the Senegal river basin.

The construction of the Diama dam on the Senegal river, the Manantali dam on the Bafing river, Mali and the ensuing ecological changes have led to a massive outbreak of Schistosoma mansoni in Northern Senegal, associated with high intensity of infections, due to intense transmission, and the creation of new foci of S. haematobium. Data on the vectorial capacity of Biomphalaria pfeifferi from Ndombo, near Richard Toll, Senegal are presented with sympatric and allopatric (Cameroon) S. mansoni. Comparisons are made on infectivity, cercarial production, chronobiology of cercarial emergence and longevity of infected snails. Recent data on the intermediate host specificity of different isolates of S. haematobium from the Lower and Middle Valley of the Senegal river basin (SRB) demonstrate the existence of at least two strains of S. haematobium. The role of Bulinus truncatus in the transmission of S. haematobium in the Lower and Middle Valleys of the SRB is reviewed. Both S. haematobium and S. mansoni are transmitted in the same foci in some areas of the SRB.

Studies on the biology of schistosomiasis with emphasis on the Senegal river basin

The construction of the Diama dam on the Senegal river, the Manantali dam on the Bafing river, Mali and the ensuing ecological changes have led to a massive outbreak of Schistosoma mansoni in Northern Senegal, associated with high intensity of infections, due to intense transmission, and the creation of new foci of S. haematobium. Data on the vectorial capacity of Biomphalaria pfeifferi from Ndombo, near Richard Toll, Senegal are presented with sympatric and allopatric (Cameroon) S. mansoni. Comparisons are made on infectivity, cercarial production, chronobiology of cercarial emergence and longevity of infected snails. Recent data on the intermediate host specificity of different isolates of S. haematobium from the Lower and Middle Valley of the Senegal river basin (SRB) demonstrate the existence of at least two strains of S. haematobium. The role of Bulinus truncatus in the transmission of S. haematobium in the Lower and Middle Valleys of the SRB is reviewed. Both S. haematobium and S. mansoni are transmitted in the same foci in some areas of the SRB

Dynamics of egg counts and circulating antigen levels in a recent Schistosoma mansoni focus in northern Senegal.

Serum circulating anodic antigen (CAA) levels were compared with faecal egg counts in four subsequent population samples, randomly selected at 8-month intervals, in a recent Schistosoma mansoni focus in northern Senegal. In all four samples, antigen levels showed the same age-intensity profiles as egg counts, with a strong decline in adults. Also across population samples, a consistent relationship was found between egg counts and antigen levels. Assuming the level of CAA to be a direct reflection of worm burden, these findings support the idea that the observed egg count patterns and levels indeed reflect dynamics of worm burdens, and not of egg excretion or worm fecundity. Remarkably similar levels of both egg counts and CAA were observed in the first and last sample, collected in the same season (August--September), but 2 years apart. This suggests that a steady state of S. mansoni infection had already been reached shortly after the onset of the epidemic in this focus (3 years). Significantly lower infection levels were found in the intermediate population samples collected in January and April. The differences in infection levels across the four population samples may be because of seasonal transmission patterns. They would indicate a substantial turnover of worm populations, with an estimated average life span of only 7 months, probably less, in this recently emerged, intense S. mansoni focus.

Evaluation of density-dependent fecundity in human Schistosoma mansoni infections by relating egg counts to circulating antigens through Deming regression.

Regression analysis of the relationship of serum circulating anodic and cathodic antigens (CAA and CCA), as a possible direct measure of worm burden, and fecal egg counts allows the study of phenomena like density-dependent fecundity in human Schistosoma mansoni infections. For a reliable analysis, variations in egg count measurements as well as in circulating antigen levels have to be taken into account, and an accurate estimation of these variations (represented by parameter lambda in the so-called Deming regression) is of great importance. From a new, extensive data set of repeated measurements of fecal egg counts and CAA and CCA concentrations we determined the respective values for parameter lambda, and (re)analysed the relationship between circulating antigens and egg counts in 3 data sets from Burundi, Senegal and Zaire by Deming regression. For comparison, ordinary linear regression was performed as well, which considerably biased the regression lines for CCA, but not for CAA. The analyses resulted in a clearly non-proportional relationship between egg counts and CAA, and, to a lesser extent, CCA. Assuming that egg counts and antigen measurements directly reflect egg production and worm burdens, respectively, our findings reinforce the indication of density-dependent fecundity in schistosomiasis mansoni, as suggested by others.

Compatibility of Schistosoma mansoni Cameroon and Biomphalaria pfeifferi Senegal.

The vectorial capacity of Biomphalaria pfeifferi from Ndiangue, Senegal, was investigated with an allopatric isolate of Schistosoma mansoni from Nkolbisson, Cameroon. The snail infection rate after exposure to a single miracidium per snail (MD1) was 56. 3 %, and 91.6%, for snails exposed to 5 miracidia per snail (MD5). The minimum pre-patent period was 21 days. The mean total cercarial production for the MDI group was 18,511 cercariae per snail, and 9757 cercariae for the MD5 group. The maximum production of cercariae for 1 day was 4892 observed in a snail from the MDI group at day 43 post-infection. The mean longevity of snails was higher in group MD1 (88 days p.i.) than in group MD5 (65 days p.i.). The chronobiological emergence pattern revealed a circadian rhythm with one shedding peak at mid-day. Comparisons are made with the vectorial capacity of the sympatric combination of B. pfeifferi Senegal/S. mansoni Senegal.

Specificity of circulating antigen detection for schistosomiasis mansoni in Senegal and Burundi.

The specificity of schistosome circulating antigen detection was determined in negative individuals from two S. mansoni- endemic countries, Senegal and Burundi, and compared with results from Dutch control individuals. A nearly absolute specificity was achieved for circulating anodic antigen (CAA) detection in serum, irrespective of the target population or sample pretreatment method. Circulating cathodic antigen (CCA) detection in serum and urine resulted in a lower specificity than serum CAA detection. Apparent large differences in specificity of CCA detection between countries were mainly due to pretreatment methods. Apparently, the alkaline/heating pretreatment method is not as effective as trichloroacetic acid (TCA)-pretreatment in removing (certain) interfering components, which may vary between populations. In view of the development of the urine CCA assay into a noninvasive screening test, a slightly lower specificity may still be acceptable. For precise epidemiological analyses the highly specific serum CAA assay remains the method of choice.

Evaluation of environmental methods to control snails in an irrigation system in Central Morocco.

The Moroccan Ministry of Public Health has launched a programme to eliminate schistosomiasis. One of the components in this process is the control of Bulinus truncatus, the intermediate host snail of Schistosoma haematobium. We evaluated three environmentally safe measures to control B. truncatus in siphon boxes, the main breeding sites for these snails in the Tessaout Amont irrigation system. The first method involved covering the siphon boxes to exclude light and reduce algal growth, the second consisted of increasing the frequency of emptying and cleaning the siphon boxes, and the third method increased water velocity to hinder the establishment of the intermediate hosts. The results showed that covering had a pronounced effect on snail and egg mass density, was accepted by the local community and prevented water contact. Cleaning the siphons three times during the irrigation season led to a reduction in snail density although it was not statistically significant and recolonization was rapid. Increasing water velocity by reducing the dimensions of siphon boxes delayed recolonization, but such a control measure can be applied only in specific situations where it does not pose hydraulic problems. The three interventions were selectively effective against B. truncatus, whereas other snails such as Physa acuta and Lymnaea peregra were hardly affected. Covering, the most promising control measure, could be useful in the Moroccan schistosomiasis eradication programme. However, further investigations are needed to assess its impact on water quality.

New challenges in schistosomiasis control in Morocco.

Cases of schistosomiasis were first detected in 1914. However, there is strong evidence that it was prevailing in the southern part of Morocco long before then. As reported from different African countries, over the last three decades, the development of irrigation has led to the spread of the disease to the north and centre of the country. Thereafter, a national programme of schistosomiasis control was launched by the Ministry of Health in 1983. The programme was based on case detection and treatment, snail control using chemicals, and health education. It has succeeded in reducing the prevalence and intensity of infection to a level low enough to allow an elimination programme to be launched in 1994. The aim is to reach a complete elimination of the disease by the year 2004 in all provinces affected. Though substantial progress was made since the programme started, there is a potential risk of outbreaks in many affected provinces. Therefore, an integrated approach including measures against the intermediate host is needed to reach the goal of elimination. The present paper sheds some light on the features of schistosomiasis in Morocco and presents an evaluation of environmental methods of control of Bulinus truncatus in Tessaout Amont and Akka oasis irrigation schemes. The role of community involvement in planning and implementing environmental measures against the snail intermediate host in modern and traditional irrigation schemes is also discussed.