Monitoring the efficacy of different doses of praziquantel by quantification of circulating antigens in serum and urine of schistosomiasis patients

Lieshout, Lisette van; Jonge, Niels de; El-Masry, N. A.; Mansour, Moustafa; Bassily, S.; Krijger, F. W.; Deelder, André M.

doi:10.1017/s0031182000077386

Cited by 41 publications

(16 citation statements)

References 28 publications

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“…19 Serum levels of CAA have shown to be more stable than fecal egg counts and following successful treatment, CAA is cleared from the circulation within a period of 6 weeks. 20,21 So far, only 10% of the treated subjects in cohort 1 and a small group of schoolchildren became CAA-negative 6-12 weeks after 40 mg of praziquantel treatment. 2,3 This indicates actual cure rates to be even lower than the percentages found by parasitologic diagnosis.…”

Section: Discussionmentioning

confidence: 99%

The contribution of host-related factors to low cure rates of praziquantel for the treatment of Schistosoma mansoni in Senegal.

Lieshout¹,

Stelma²,

Guisse³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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Abstract. Surprisingly low cure rates were repeatedly observed after treatment with a standard dosage of praziquantel in a recently established Schistosoma mansoni focus in northern Senegal. In 4 discrete cohorts from the same population, cure rates were 18-36% and egg count reduction rates were 77-88%. Data and material of 920 compliant subjects from all 4 cohorts were further analyzed to identify possible host-related factors associated with low cure rates. The lowest cure rates were found in the highest egg count groups. However, in low and moderate egg count groups, drug efficacy was also below normal values. Cure rates were similar in males and females, showed no seasonal variation, and were independent of previous praziquantel treatment. They were significantly higher in adults than in children, also after allowing for intensity of infection. Individual water contact behavior and specific humoral immune responses were examined in 2 extreme subgroups, either without significant egg count reduction or showing complete parasitologic cure. There was no significant difference in frequency and duration of water contact between those individuals with complete cure and those that showed little effect of praziquantel treatment. Levels of IgG, IgG1, IgG3, IgG4, IgM, and IgE against adult worm antigen were not different between the 2 subgroups. Thus, the abnormally frequent failure of treatment observed in this focus could not be associated with any host-related factor, other than age and pretreatment egg counts.In a recently established focus of Schistosoma mansoni in the Senegal River Basin, praziquantel treatment apparently showed a lower efficacy and induced more side effects than usually reported. 1,2 In an initial cohort of 400 subjects, only 18% was found to be parasitologically negative 12 weeks after treatment with the standard single oral dosage of 40 mg/kg. However, egg reduction rates were substantial (86%) in those remaining positive. Results were confirmed by determination of circulating antigens excreted by metabolically active adult worms.2 Similar low cure rates were found in 3 subsequent cohorts from the same focus (Stelma FF, unpublished data). An increased dosage of praziquantel, given at the same day, showed no significant improvement, 3 while normal cure rates were found after treatment with oxamniquine, 4 or after repeated treatment with praziquantel within a period of 40 days. 5Possible explanations for these findings can be divided into 3 main categories: 1) parasite-related, including reduced strain susceptibility to praziquantel, 2) drug-related, including drug quality or bioavailability, and 3) host-related, including high initial intensity of infection, prepatent infections, rapid reinfection, and still under-developed pharmacosynergistic humoral immune responses. 2 This paper focuses on the third category of hypotheses. We use data from all four cohorts to analyze the contribution of host-related factors on the efficacy of praziquantel treatment in this area, with emphasis on the variabl...

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Section: Discussionmentioning

confidence: 99%

The contribution of host-related factors to low cure rates of praziquantel for the treatment of Schistosoma mansoni in Senegal.

Lieshout¹,

Stelma²,

Guisse³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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“…[4][5][6] The high specificity is the main advantage that the detection of circulating antigens offers as compared with the antibodies determination and the disadvantages are low sensitivity in light infections and dependence on the production of monoclonal antibodies. 7,8 Polymerase chain reaction (PCR) has shown its usefulness in the clinical approach of a wide variety of pathogenic infections, such as human immunodeficiency virus, 9,10 Legionella pneumophila, 11 Plasmodium falciparum, 12,13 and Trypanosoma cruzi. 14,15 In the study of Schistosoma sp., it has also been successfully used for sex determination of the cercariae, 16 for the cloning and sequencing of specific genes, 17,18 in the determination of genetic variability and population structure of Schistosoma sp.…”

Section: Introductionmentioning

confidence: 99%

Detection by polymerase chain reaction of Schistosoma mansoni DNA in human serum and feces.

Pontes¹,

Dias‐Neto²,

Rabello³

2002

The American Journal of Tropical Medicine and Hygiene

191

172

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Abstract. A novel method for the detection of Schistosoma mansoni in human samples that is based on the amplification of a highly repeated DNA sequence has been developed. By use of simple DNA extraction techniques and a rapid 2-step polymerase chain reaction (PCR), it was possible to amplify S. mansoni DNA in human fecal and serum samples. The high sensitivity of the approach enabled the detection of the parasite DNA in fecal samples containing as few as 2.4 eggs per gram of feces, which makes it 10 times more sensitive than the Kato-Katz examination. A detection limit of 1 fg of Schistosoma sp. DNA was determined when pure DNA was used as PCR template. The amplification reaction showed to be specific giving no cross-reaction with DNA from other helminths. The PCR assay developed in this study may constitute a valuable alternative for the diagnosis of the Schistosoma sp. infection.

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“…PZQ, 2 -(cyclohexylcarbonyl) -1,2,3,6,7,11␤-hexahydro-4H-pyrazino- [2,1a]-isoquinolin-4-one, is an effective anthelmintic agent that exhibits broad activity against trematodes and cestodes, particularly for Schistosoma and Taenia infections [16][17][18]. After oral administration to humans, drug absorption is very rapid and is followed by a fast and extensive metabolism by the cytochrome P-450 monooxygenases, producing mainly trans-4 -monohydroxypraziquantel (trans-4 -OH) [19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Biomimetic oxidation of praziquantel catalysed by metalloporphyrins

Melo

Iamamoto²,

Maestrin³

et al. 2005

Journal of Molecular Catalysis A: Chemical

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Monitoring the efficacy of different doses of praziquantel by quantification of circulating antigens in serum and urine of schistosomiasis patients

Cited by 41 publications

References 28 publications

The contribution of host-related factors to low cure rates of praziquantel for the treatment of Schistosoma mansoni in Senegal.

The contribution of host-related factors to low cure rates of praziquantel for the treatment of Schistosoma mansoni in Senegal.

Detection by polymerase chain reaction of Schistosoma mansoni DNA in human serum and feces.

Biomimetic oxidation of praziquantel catalysed by metalloporphyrins

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