Études et publications

Gryseels B, Mbaye A, De Vlas SJ, Stelma FF, Guissé F, Van Lieshout L, Faye D, Diop M, Ly A, Tchuem-Tchuenté LA, Engels D, Polman K.

Tropical Medicine and International Health, 2001, 6(11):864-73 (PMID : 11703840)

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.

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Southgate V, Tchuem Tchuenté LA, Sène M, De Clercq D, Théron A, Jourdane J, Webster BL, Rollinson D, Gryseels B, Vercruysse J.

Memorias do instituto Oswaldo Cruz, 2001, 96 Suppl:75-8 (PMID : 11586429)

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.

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Polman K, Stelma FF, De Vlas SJ, Sow S, Fathers L, Le Cessie S, Talla I, Deelder AM, Gryseels B.

Tropical Medicine and International Health, 2001, 6(7):538-44 (PMID : 11469948)

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.

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Remoué F, To Van D, Schacht AM, Picquet M, Garraud O, Vercruysse J, Ly A, Capron A, Riveau G.

Clinical and Experimental Immunology, 2001, 124(1):62-8 (PMID : 11359443)

The cellular and humoral acquired immune responses to Schistosoma haematobium 28 kD gluthathione S-Transferase (Sh28GST) antigen were evaluated in a Senegalese population chronically infected with S. haematobium parasite. We show a gender-dependent immune response in adult individuals presenting similar intensities of infection. Indeed, the specific IgA response and production of TGF-beta and IL-10 were found significantly higher in females compared to males. In addition, we showed that this profile was combined with a weak production of Th1-related cytokines (TNFalpha and IFNgamma) and was associated with an absence of proliferation to the antigen. A significantly higher Nuclear Matrix Protein 41/7 secretion, an apoptosis marker, was specifically observed in mononuclear blood cell cultures of females suggesting that a specific cell death process was engaged in a gender-dependent manner. This specific profile could be associated with the so-called T helper type-3 (Th3) immune response specifically promoting the production of IgA and would be developed upon the down-regulation of the specific Type-1 response by a probable cell death mechanism. This gender-dependent immune regulation, which may be under the influence of nonimmunological factors like sexual hormones, may be related to the chronicity of the infection.

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