[Comparison of the efficacy and safety of praziquantel administered in single dose of 40 versus 60 mg/kg for treating urinary schistosomiasis in Mauritania]. / Comparaison de l'efficacité thérapeutique et de la tolérance du praziquantel administré en prise unique à la dose de 40 versus 60 mg/kg pour le traitement de la bilharziose urinaire en Mauritanie.

During the last twenty years, praziquantel (PZQ) was the drug of choice for the treatment of schistosomiasis in the majority of national programs. However, a lower rate of cure had been significantly noted on the left bank of the Senegal River. To explain this unusual rate of cure, the assumption of a possible resistance to the drug as well as under-dosing was considered. With an aim of testing this hypothesis of underdosing, we compared the amount of a single dose of 60 mg/kg of PZQ versus the standardized dose of 40 mg/kg used in curing urinary schistosomiasis in Mauritania. One hundred and fifty-one children aged from 10 to 19 years, including 77 in the group of 60 mg/kg and 74 in the group of 40 mg/ kg, were included in the study. The rates of cure were respectively 64.8% for 60 mg/kg and 67.5% for 40 mg/kg three weeks after the administration of the treatment without statistically significant difference. For the majority of the patients, the drug was well tolerated and no serious adverse events were noted; however, clinical signs in the form of abdominal pain associated or not with diarrhea and vomiting were noted. Praziquantel remains an effective and well-tolerated drug: the amount of 40 mg/kg of body weight can still be maintained for the treatment of schistosomiasis in Mauritania.

Preventive chemotherapy in human helminthiasis: theoretical and operational aspects.

Preventive chemotherapy (PC), the large-scale distribution of anthelminthic drugs to population groups at risk, is the core intervention recommended by the WHO for reducing morbidity and transmission of the four main helminth infections, namely lymphatic filariasis, onchocerciasis, schistosomiasis and soil-transmitted helminthiasis. The strategy is widely implemented worldwide but its general theoretical foundations have not been described so far in a comprehensive and cohesive manner. Starting from the information available on the biological and epidemiological characteristics of helminth infections, as well as from the experience generated by disease control and elimination interventions across the world, we extrapolate the fundamentals and synthesise the principles that regulate PC and justify its implementation as a sound and essential public health intervention. The outline of the theoretical aspects of PC contributes to a thorough understanding of the different facets of this strategy and helps comprehend opportunities and limits of control and elimination interventions directed against helminth infections.

Control of schistosomiasis in sub-Saharan Africa: progress made, new opportunities and remaining challenges.

Several other journal supplements have documented progress made in the control of schistosomiasis in Egypt, China and Brazil, however, with more than 97% of the schistosome infections now estimated to occur in Africa, the relevance of this special issue in Parasitology cannot be overemphasized. In total, 18 articles are presented, inclusive of a lead-editorial from the WHO highlighting a seminal resolution at the 54th World Health Assembly in 2001 that advocated de-worming. Facilitated by a US$ 30 million grant from the Bill and Melinda Gates Foundation in 2002, the Schistosomiasis Control Initiative subsequently fostered implementation of large-scale schistosomiasis (and soil-transmitted helminthiasis) control programmes in six selected African countries. From 2005, CONTRAST, a European union-funded consortium, was formed to conduct multi-disciplinary research pertaining to optimisation of schistosomiasis control. Progress made in schistosomiasis control across sub-Saharan Africa since the turn of the new millennium is reviewed, shedding light on the latest findings stemming from clinical, epidemiological, molecular and social sciences research, inclusive of public health interventions with monitoring and evaluation activities. New opportunities for integrating the control of schistosomiasis and other so-called neglected tropical diseases are highlighted, but more importantly, several opportune questions that arise from it frame the remaining challenges ahead for an enduring solution.

The global epidemiological situation of schistosomiasis and new approaches to control and research.

While the distribution of schistosomiasis has changed over the last 50 years and there have been successful control programmes, the number of people estimated to be infected or at risk of infection has not been reduced. Today, 85% of the number of infected people are estimated to be on the African continent where few control efforts are made. In terms of disease burden, there is therefore a growing discrepancy between sub-Saharan Africa and the rest of the world. WHO has now developed a dual strategy for the control of schistosomiasis: a strategy for morbidity control adapted to the public health context in high burden areas, and a strategy to consolidate control in areas where a low endemic level has been reached and elimination may be feasible. Related to this new vision, some research needs are pointed out.

Development and validation of a 'tablet pole' for the administration of praziquantel in sub-Saharan Africa.

A pole estimating, for each individual, the number of praziquantel tablets needed for treatment according to height was tested in 20 data sets (n = 25,688). In more than 98% of the cases the indicated dose was within the range that has proven efficacious and safe (30 and 60 mg/kg).

The global status of schistosomiasis and its control.

Schistosomiasis is being successfully controlled in many countries but remains a major public health problem, with an estimated 200 million people infected, mostly in Africa. Few countries in this region have undertaken successful and sustainable control programmes. The construction of water schemes to meet the power and agricultural requirements for development have lead to increasing transmission, especially of Schistosoma mansoni. Increasing population and movement have contributed to increased transmission and introduction of schistosomiasis to new areas. Most endemic countries are among the least developed whose health systems face difficulties to provide basic care at the primary health level. Constraints to control include, the lack of political commitment and infrastructure for public health interventions. Another constraint is that available anti-schistosomal drugs are expensive and the cost of individual treatment is a high proportion of the per capita drug budgets. There is need for increased support for schistosomiasis control in the most severely affected countries.

Therapeutic and operational profiles of metrifonate and praziquantel in Schistosoma haematobium infection.

A systematic analysis of the existing literature has been undertaken to compare the therapeutic and operational profiles of metrifonate (CAS 52-68-6), and praziquantel (CAS 55-268-74-1), two anti-schistosomal compounds. The criteria evaluated were therapeutic efficacy against Schistosoma haematobium and other helminths, impact on pathology commonly associated with S. haematobium infection, frequency, type and duration of adverse reactions, health risk associated with inadvertent overdosage, applicability and practicality of treatment in various medical settings, tolerance and resistance, pharmacological properties, toxicity and economic aspects. It is concluded that both medical and operational criteria indicate that praziquantel is superior to metrifonate for the treatment of schistosomiasis caused by S. haematobium. Since, compared to praziquantel, metrifonate has a number of disadvantages, future antischistosomal chemotherapy can do without this drug.

Female genital schistosomiasis due to Schistosoma haematobium. Clinical and parasitological findings in women in rural Malawi.

A total of 51 women with urinary schistosomiasis haematobium were examined in order to identify diagnostic indicators for female genital schistosomiasis (FGS). Patients were selected at random from the outpatient department of the Mangochi District Hospital, Malawi. The medical histories were recorded according to a pre-designed questionnaire and the women were subjected to a thorough gynaecological examination including colposcopy and photographic documentation of lesions. Microscopy of genital biopsies revealed that 33 of the 51 women had S. haematobium ova in cervix, vagina and/or vulva in addition to the presence of ova in urine. The most sensitive diagnostic procedure was beside microscopic examination of a wet cervix biopsy crushed between two glass slides, which revealed 25 of the 33 genital infections. There was a significant correlation between the size of genital lesions and the number of ova counted per mm2 of crushed tissue. Women with FGS had significantly more tumours in the vulva than women with schistosomiasis limited to the urinary tract. Most of the observed genital pathology could easily be identified by the naked eye, but colposcopic examination yielded valuable additional information like the demonstration of neovascularisation around cervical sandy patches. Few of the symptoms previously regarded as indicators for FGS could be linked to the presence of schistosome ova in genital tissue. Husbands of infertile women with FGS had children with other women significantly more often than husbands of women who only had urinary schistosomiasis. This, together with the finding that the majority of the divorced women had FGS, indicates that the manifestation of this disease may have implications for the marital and sexual life of the affected women.

Diagnosis of female genital schistosomiasis by indirect disease markers: determination of eosinophil cationic protein, neopterin and IgA in vaginal fluid and swab eluates.

Based on assumptions about the pathophysiology of egg-related lesions in the lower reproductive tract, putative indirect disease markers were investigated in vaginal fluids from 54 Malawi adolescent girls and women infected with S. haematobium. These women received a careful gynecological examination during which biopsies were taken from the cervix, and, if present, also from suspicious lesions in the vagina and the vulva. If the biopsies, either in wet crushed preparations or in histological sections, contained eggs the patients were considered to have female genital schistosomiasis (FGS; n = 33). The remainder (n = 21) were classified as having urinary schistosomiasis only. Eosinophil cationic protein (ECP), a cytotoxic granule protein of eosinophils, neopterin, a second messenger molecule generated during the activation of macrophages, and IgA as an indicator of local B-cell activation were quantitatively determined in vaginal fluid. To clarify the origin of ECP, this protein was also looked for in histological sections by an immunohistochemical method. In order to explore whether such disease markers can be detected after absorption to a tampon-like material, ECP and IgA were also assessed after elution from a non-porous, polypropylene fibre web impregnated with vaginal fluid. The concentration of ECP in vaginal fluid and the degree of immunohistochemical staining in histological sections were significantly higher in patients with FGS than in women with urinary schistosomiasis only. The amount of ECP detected in histological sections correlated to the number of eggs/mm2 of compressed genital tissue (rho = 0.36, P = 0.02), and the concentration of ECP in vaginal fluid correlated to the concentration of neopterin as well as to that of IgA (rho = 0.52, P = 0.004 and rho = 0.37, P = 0.02, respectively). Median neopterin concentration in vaginal fluid was also higher in the FGS group, but the difference was not statistically significant. ECP could also be detected in eluates from impregnated fibre webs, but the concentration was approximately one power of 10 less than in the original vaginal fluid. These results demonstrate that indicators of immunological mechanisms related to the egg-granuloma might be useful as indirect disease markers for women with FGS if assessed in vaginal washings or swab eluates.

Female genital schistosomiasis (FGS): relationship between gynecological and histopathological findings.

Schistosomiasis of the lower female reproductive tract manifests itself in a broad spectrum of clinical features. However, clinical and histopathological findings have never been studied in a synoptic manner. Based on the assumption that any type of pathology present in the female reproductive tract is the expression of a complex pathophysiological reaction towards eggs sequestered in the genital tissues, we decided to analyze colposcopic and histopathological findings in a comprehensive manner. Thirty-three women in Malawi with urinary and genital schistosomiasis were examined parasitologically and gynecologically. A thorough colposcopic examination with photodocumentation was performed and biopsies were taken from the cervix, the vagina and/or the vulva for histological sectioning and immunohistochemistry. The predominant colposcopic findings were sandy patches on the cervical surface similar to those seen in the bladder and polypous/papillomatous tumors with irregular surface on the vaginal wall and in the vulvar area. The histopathological sections of sandy-patch-like lesions demonstrated only a small cellular reaction around S. haematobium eggs in various stages of disintegration. In contrast, in the case of polyps the histology revealed a more pronounced immunological reaction characterized by a heavy cellular infiltrate. One case of invasive squamous cell carcinoma of the cervix was diagnosed. We conclude that colposcopy is a useful tool in the detection of FGS related pathology in the lower female reproductive tract and that the synoptic assessment of surface and of corresponding histological sections helped to understand the pathophysiology of S. haematobium associated disease in genital tissue.

Urine reagent strips for diagnosis of schistosomiasis haematobium in women of fertile age.

Hematuria, proteinuria and leukocyturia were semiquantitatively assessed by reagent strips in single morning urine of women of fertile age visiting the outpatient department of the Mangochi district hospital, Malawi. This was part of a diagnostic approach to female genital schistosomiasis (FGS). In 51 women ova of Schistosoma haematobium were detected in urine by a filtration technique. In 33 of these women ova were also present in genital tissue as demonstrated by microscopic examination of biopsies. In 209 women no ova were found in the single urine filtered. There were significantly higher scores for hematuria, proteinuria and leukocyturia as well as of the combined reagent strip index (RSI) in egg-excreting than in egg-negative women. The sensitivity of a single hematuria, proteinuria and leukocyturia reading was 98, 84 and 73%, respectively. However, the respective specificity was only 24, 22 and 23%. The best prediction of urinary schistosomiasis was achieved by a +2 score for hematuria, of which the sensitivity was 94% and the specificity was 61%. The high false-positive rates can probably be explained by contamination of urine by vaginal secretion. Moreover, cases of schistosomiasis have probably been overlooked because only a single morning urine sample was examined. The total absence of hematuria, proteinuria and leukocyturia, however, may be used to rule out heavy infections in community surveys. There was no difference in reagent strip scores between women with genital and urinary schistosomiasis as compared with those with urinary tract lesions alone. Thus urine analysis reagent strip readings do not help to discriminate between S. haematobium infected women with and without FGS.

Reversibility of lower reproductive tract abnormalities in women with Schistosoma haematobium infection after treatment with praziquantel--an interim report.

Little is known whether and to what extent antiparasitic treatment cures female genital schistosomiasis (FGS). Using a standard protocol, of twenty-one women with FGS nine were re-examined at two to nine weeks after they had been treated with praziquantel at a single dose of 40 mg/kg. Symptoms related to pathology of the urinary tract and to a lesser extent of genital pathology subsided in most patients. Schistosoma haematobium ova were no longer detectable in urine of any of the patients post-treatment. Efficiency of chemotherapy against adult worms was confirmed by the disappearance of circulating anodic antigen (CAA) in serum. Sandy patches showed resolution in two of four cases after chemotherapy. Papillomata due to schistosomiasis alone improved, but persisted in mixed infection with human papilloma virus (HPV) or when HPV was the only underlying cause. In one patient ulcera could not be related with certainty to schistosomiasis at admission, but resolved after treatment with parziquantel. Leukoplakia (two cases) was not influenced by chemotherapy, or even increased during follow-up, regardless of whether ova had been detected or not. Although the follow-up period was rather short, time intervals were not standardized, and a relatively small number of patients was investigated, it could be shown that genital pathology due to sequestered S. haematobium ova is, at least partially, reversible already two to nine weeks after killing the adult worms by praziquantel. This is paralleled by a normalization of inflammatory immune responses detectable in histological sections and vaginal lavage.

Schistosomiasis in Lake Malawi.

BACKGROUND: In 1992 two US Peace Corps volunteers (PCVs) developed central nervous system schistosomiasis due to infection with Schistosoma haematobium following recreational water exposure at Cape Maclear on Lake Malawi, an African lake considered by many to be free of schistosomiasis. To determine the transmission potential and risk for aquiring schistosomiasis in Lake Malawi, a cross-sectional survey of resident expatriates and visitors to Malawi was done during March and April, 1993. METHODS: A volunteer cohort of expatriates and visitors representing a cross-section of Malawi's foregn population answered detailed questions about freshwater contact and provided blood specimens to determine the seroprevalence of S haematobium and S mansoni by ELISA and immunoblot analyses. A survey for vector snails was conducted along Lake Malawi's southwestern shore. FINDINGS: The study population of 955 included 305 US citizens and 650 non-US foreign nationals. 303 of the study population had serological evidence of current or past schistosome infection. Seroprevalence was 32% (141/440) among expatriates whose freshwater exposure was limited to Lake Malawi; S haematobium antibodies were found in 135 of 141 (96%) seropositive specimens. Risk of seropositivity increased with the number of freshwater exposures at Lake Malawi resorts. Although many resort areas in the southwestern lake region posed a significant risk, Cape Maclear was the location most strongly associated with seropositivity (OR 2.9, 95% Cl 1.6-5.1). Schistosome-infected Bulinus globosus, the snail vector of S haematobium in Malawi, were found at Cape Maclear and other locations along the lakeshore. INTERPRETATION: S haematobium infection is highly prevalent among expatriates and tourists in Malawi. Recreational water contact at popular resorts on Lake Malawi is the most likely source of infection. Transmission of schistosomiasis is occurring in Lake Malawi, a previously under-recognised site of transmission.

PIP: Schistosomiasis is a parasitic infection caused by trematodes. Humans are infected through skin contact with free-swimming cercariae which develop in freshwater snails. Schistosomiasis has been endemic to Malawi for several decades, but the open waters and shores of Lake Malawi have long been thought to be risk-free with regard to schistosomiasis transmission. However, in 1992, two US Peace Corps volunteers developed central nervous system schistosomiasis due to infection with Schistosoma haematobium following recreational water exposure at Cape Maclear on Lake Malawi. In light of these infections, a cross-sectional survey of resident expatriates and visitors to Malawi was subsequently conducted during March-April 1993 to determine the transmission potential and risk for acquiring schistosomiasis in the lake. 305 US citizens and 650 non-US foreign nationals participated in the study. Serological evidence of current or past schistosome infection was identified in 303 subjects. Indeed, seroprevalence was 32% among expatriates whose freshwater exposure was limited to Lake Malawi; S. haematobium antibodies were found in 135 of 141 seropositive specimens. The risk of seropositivity increased with the number of freshwater exposures at Lake Malawi resorts. While many resort areas in the southwestern lake region posed a significant risk, Cape Maclear was the location most strongly associated with seropositivity. Schistosome-infected Bulinus globosus, the snail vector of S. haematobium in Malawi, were found at Cape Maclear and other locations along the lakeshore.