EFFICACY OF MIRAZID IN COMPARISON WITH PRAZIQUANTEL IN EGYPTIAN SCHISTOSOMA MANSONI–INFECTED SCHOOL CHILDREN AND HOUSEHOLDS

SANAA BOTROS 0 HANAN SAYED 0 HOWAIDA EL-DUSOKI 0 HODA SABRY 0 IBRAHIM RABIE 0 MAGED EL-GHANNAM 0 MOATAZ HASSANEIN 0 YEHIA ABD EL-WAHAB 0 DIRK ENGELS 0 0 Theodor Bilharz Research Institute , Warrak El-Hadar, Giza, Egypt ; Ministry of Health and Population , Cairo, Egypt ; World Health Organization , Geneva, Switzerland This trial investigated the anti-schistosomal activity of mirazid in comparison with that of praziquantel in Schistosoma mansoniinfected Egyptian patients. The sample population was composed of 1,131 individuals (459 school children and 672 household members). Screening for S. mansoni was conducted using the standard Kato Katz technique. Four slides from a single stool sample were examined before treatment, and four slides per sample from stool samples obtained on three consecutive days were examined post-treatment. All positive eligible subjects were randomly assigned into two groups, the first received mirazid at a dose of 300 mg/day for three consecutive days, and the second received praziquantel at a single dose of 40 mg/kg. All treated subjects were examined 4-6 weeks post-treatment. Mirazid showed low cure rates of 9.1% and 8.9% in S. mansoni-infected school children and household members, respectively, compared with cure rates of 62.5% and 79.7%, respectively, in those treated with praziquantel. Therefore, we do not recommend mirazid as an agent to control schistosomiasis. - Schistosomiasis remains one of the most prevalent parasitic infections in the world. It is estimated that more than 200 million people in 76 countries are infected and approximately 600 million people are at risk of infection. The majority (85%) of those infected and at risk live in Africa.1 In Egypt, there is extensive documentation that the governments efforts have been successful in reducing both the prevalence and morbidity of this disease.2 However, schistosomiasis is still endemic in rural areas of Egypt and in spite of the low endemicity level, transmission still occurs. Chemotherapy is the most widely advocated method of schistosomiasis control.3 Praziquantel is still the ideal drug for implementation of schistosomiasis control programs.4 The drug is safe and has a high efficacy against both trematodes and cestodes.5 Moreover, the drug has become significantly less expensive. According to the World Health Organization, the cost of an average treatment with this drug has decreased to less than 0.30 $US.2,3 However, the extensive reliance on just one drug is of concern, due to the possible development of drug-resistant parasites. In view of concern about the possible emergence of resistance to praziquantel, there is a need for developing novel antischistosomal drugs. The antischistosomal drug Mirazid has been available in the local Egyptian market since 2001. Although Mirazid is not used by the Ministry of Health and Population (MOHP) for schistosomiasis control in national control programs, yet the extensive advertising efforts have encouraged physicians in private clinics to use it. Mirazid is a commercial preparation made from myrrh by Pharco Pharmaceuticals (Alexandria, Egypt). Myrrh is collected from trees in Somalia and the Arabian peninsula.6 For several decades, it has been used in a number of medical contexts, as well as in the perfume and incense industries.7 It is an oleo-gum resin obtained from the stem of Commiphora molmol Engier and probably other species of Bursearacae.6 The experimental activity of Mirazid has been demonstrated. In this respect, Sheir and others8 reported that the drug showed a 91.7% cure rate after a dose of 10 mg/kg/day for three days. Badria and others9 reported significant parasite reductions of 76% and 75% after treatment of Schistosoma mansoniinfected mice with 250 mg/kg and 500 mg/kg of myrrh extract twice a day for three days. They also reported that the chemistry of the resin is not fully elucidated and that myrrh is generally classified into etherinsoluble and ether-soluble portions. Moreover, nothing has been reported concerning the exact species, source, and season of collection of myrrh when Mirazid is prepared, although these can determine the activity of any compound of plant origin. Independent studies concerning the antischistosomal activity of Mirazid are limited. This study investigated the antischistosomal activity of Mirazid in S. mansoni-infected school children and household members in comparison with the classic antischistosomal drug praziquantel. MATERIALS AND METHODS The study protocol and patient consent procedure were reviewed and approved by the Institutional Review Board of the Theodor Bilharz Research Institute. The head of the family provided formal consent for household members, while for school children, consent was provided by the school principal, prior to participating in the study. General study design. The study was conducted at ElGezira El-Shakra village, El-Saf district, Giza governorate of Egypt. The village was selected for logistic reasons. It is relatively near the Theodor Bilharz Research Institute, and is a focus of S. mansoni infection.10 The study was conducted in collaboration with the MOHP. The sample size was determined assuming that the two treatments (Mirazid and praziquantel) have equivocal effects. A one-sided upper confidence interval (CI) with a power of 90% was also assumed. A sample size of 1,131 was considered adequate, of which 459 were school children and 672 were household members. School children were composed of those in primary (fifth school year), preparatory, and secondary schools. All students in the randomly selected classes were included in the study. Their ages ranged from 12 to 18 years. Household members were sampled at random. All inhabitants of the houses selected were included in the study. Parasitologic examination. To screen for S. mansoni infection, all subjects participating in the study were asked to provide stool samples. Four slides were examined per subject. For post-treatment examination, three stool samples were collected on different days and four slides per sample were examined. i.e., a total of 12 slides/patient. The Kato Katz technique using the standard weight of 41.7 mg of stool per slide was used. The local health authorities at the village were informed to stop praziquantel treatment six months before beginning the study and any of the patients giving a history of treatment of less than six months were excluded from the study. Drug administration. All positive eligible subjects were stratified into low (<100 egg per gram [epg] of feces), moderate (100400 epg), and heavy (>400 epg) infection strata. Each stratum was then randomly assigned into two groups. One group received Mirazid while the second group received praziquantel. All patients receiving Mirazid were asked to fast the night before treatment (300 mg/day for three consecutive days, irrespective of age and sex) and for one hour post-treatment, as recommended by the manufactur (...truncated)