F.F. Stelma

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 40u2003mg/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 12u2003weeks 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 (6–8u2003weeks) yielded cure rates of 31–36%. Increasing the dose to 2u2003×u200330u2003mg/kg did not significantly improve cure rates, whereas treatment with oxamniquine at 20u2003mg/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 3u2003weeks 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.

Oxamniquine Cures Schistosoma mansoni Infection in a Focus in Which Cure Rates with Praziquantel Are Unusually Low

An outbreak of Schistosoma mansoni in northern Senegal was observed in 1988, and chemotherapy with praziquantel in this recently established focus resulted in very low parasitologic cure rates. Among other explanations, the emergence of a praziquantel-tolerant parasite strain was feared. To study this hypothesis further, 138 persons with endemic S. mansoni infection were randomly allocated to treatment with either 20 mg/kg oxamniquine or 40 mg/kg praziquantel. Parasitologic cure rates at 6 weeks were significantly higher in the oxamniquine group (79%) compared with those in the praziquantel group (36%; P = .0043). The reduction in egg counts was generally good, but 12% less reduced in the praziquantel group. These results confirm that cure rates with praziquantel were abnormally low, whereas oxamniquine performed satisfactorily, as in other areas in which S. mansoni is endemic. The possibility of a praziquantel-tolerant S. mansoni strain must therefore be studied carefully.

Evaluation of ultrasonographic staging systems for the assessment of Schistosoma mansoni induced hepatic involvement

For the sonographic assessment and grading of hepatosplenic morbidity induced by Schistosoma mansoni infection, several quantitative and qualitative classification systems have been used. In an attempt to evaluate two staging systems, a study was performed as part of a schistosomiasis research and control programme in Richard Toll, Senegal. A total of 700 residents of the township Ndiangué were parasitologically, clinically and sonographically examined in July 1993. Two ultrasound observers (M.D. and E.D.) applied the Cairo and the Managil classification (E.D. only) for the grading of periportal thickening of the liver. In spite of high prevalence and intensity of infection, severe hepatic morbidity was rare. According to the Cairo classification, there was a high percentage of subjects with grade I periportal thickening, with considerable inter-observer variability. In the Cairo classification, which is based on the diameter of peripheral portal vein branches, firm cut-offs are used, independent of body height. We show the relationship between body height and portal vein diameters and recommend the use of body height-dependent reference values to avoid falsely high percentages of periportal thickening, especially in children. To minimize inter-observer variability, a clarification of existing instructions for taking measurements for grading is suggested. These suggestions have been considered during the follow-up expert meeting on the Cairo classification in Niamey under the auspices of the World Health Organization in October 1996.

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 2u2003years 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 (3u2003years). 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 7u2003months, probably less, in this recently emerged, intense S. mansoni focus.

Serum circulating egg antigen levels in two areas endemic for Schistosoma mansoni

A monoclonal antibody-based enzyme-linked immunosorbent assay detecting Schistosoma mansoni circulating soluble egg antigen (CSEA) was applied in epidemiological studies. The serum CSEA levels were determined for 2 populations with a high prevalence (> 95%) and high intensity of infection as determined by faecal egg counts. In one population (Maniema, Zaire) transmission had been occurring for several decades, while in the other population (Ndombo, Senegal) transmission had started only recently. CSEA could be detected in 88% and 70% of the serum samples from Maniema and Ndombo, respectively. The sensitivity of the CSEA assay increased with rising egg count. The age-related CSEA profiles of the Maniema population followed a pattern similar to that of egg counts and of the adult worm antigen CAA (circulating anodic antigen). However, the recently infected Ndombo population showed a clearly different profile: while the CSEA prevalence reached a peak in children and adolescents, the mean CSEA levels did not vary significantly in the different age groups. CSEA levels were significantly lower in Ndombo than in Maniema. As egg antigens in serum are thought to be in part, or even primarily, derived from eggs in the tissues, these findings indicate a relatively smaller tissue egg load in Ndombo than in Maniema.