granulomas in the bladder may increase the exposure of the bladder epithelium to environmental carcinogens.13 Alternatively, the recent sequencing of the S. haematobium genome has also allowed scientists to search for carcinogenic molecules released by schistosome eggs.15 Still another important component of the morbidity of S. haematobium infection is involvement of the female reproductive tract. Up to 75% of women with this form of schistosomiasis develop fibrotic lesions known as “sandy patches” in the vulva, vagina, cervix, and uterus.16 Such lesions and sandy patches are associated with genital bleeding, pain on intercourse, infertility, and even clinical depression.16 Given that S. haematobium infection potentially affects hundreds of millions of people in sub-Saharan Africa, female urogenital schistosomiasis may actually be one of the most common gynecologic conditions on the African continent! This is but one way that schistosomiasis, like many neglected tropical diseases, disproportionately affects girls and women. Moreover, genital schistosomiasis lesions have recently been linked to a three-and fourfold increase in the transmission of HIV/AIDS in Zimbabwe and Tanzania, respectively, and presumably elsewhere in sub-Saharan Africa.16 From these and similar studies, there is considerable interest in looking at schistosomiasis control and prevention efforts in terms of their impact on HIV transmission in rural areas of Africa.16 The opportunity of exploring schistosomiasis elimination efforts as a back-door strategy for HIV/AIDS control is examined further in chapter 10.
Figure 3.4 Children in Niger with hematuria. (Photo courtesy of Juerg Utzinger, Swiss Tropical Institute.)
S. mansoni is also a significant cause of intestinal and liver pathology in sub-Saharan Africa and Brazil. The presence of eggs and granulomas in the intestinal wall, usually of the large intestine and rectum, is associated with bleeding and diarrhea, as well as with loss of appetite, while liver granulomas can cause inflammation and liver enlargement (hence the term “big-belly disease”).13 Chronic schistosomiasis of the liver can progress to fibrosis, splenic enlargement, and bleeding from the esophagus. Occasionally, severe bleeding can result in death. An estimated 8.5 million cases of liver disease result from S. mansoni infection in sub-Saharan Africa.11
Although snail control was the major tool used to effect an almost 10-fold reduction in the prevalence of S. japonicum infection in China, this approach has not been an efficient or very effective means for controlling either S. haematobium or S. mansoni in Africa and elsewhere. Failed efforts to control snails environmentally reflect the unique biology of the snail intermediate hosts of S. haematobium and S. mansoni as well as the epidemiology of these forms of schistosomiasis. In addition, the environmental toxicities of molluscicides preclude their constant and widespread use. Even in China, snail control has not been successful in eliminating the last remaining 840,000 cases in the Yangtze River valley.6
We saw previously (in chapter 2) how mass drug administration of benzimidazole anthelmintics is beginning to have an impact on the global burden of disease caused by soil-transmitted helminth infections. Today, the most effective means of controlling schistosome infections is mass drug administration of praziquantel to affected and at-risk human populations. Developed at Bayer, praziquantel was shown to be effective against all forms of schistosomiasis in multicenter trials, as evidenced by schistosome egg reductions or outright cures.10 Treatment of schistosome-infected children with praziquantel results in a number of health benefits similar to those experienced by children with soil-transmitted helminth infections who are treated with either albendazole or mebendazole, including improvements in growth and physical fitness, as well as reductions of anemia. In addition, multiple treatments with praziquantel can sometimes reverse both urinary tract and liver pathology, particularly if children receive these treatments early in their lives. Building on these breakthrough medical observations were the low-cost synthesis and production methods for manufacturing generic praziquantel by the Korean pharmaceutical company Shin Poong. These manufacturing improvements have dramatically reduced the price of the drug, possibly by as much as 90%.10 As a result, by the 1990s, it became possible to launch praziquantel mass treatment programs for schistosomiasis in several middle-income countries, including Brazil, China, Egypt, Morocco, the Philippines, Saudi Arabia, and Tunisia, as well as Puerto Rico.10,13,17 Several of these initiatives were funded by the World Bank. Praziquantel mass drug administration in these countries has been largely successful, particularly in Morocco and Puerto Rico, where the disease is close to being eliminated (zero transmission) partly because of parallel poverty reduction measures that were enacted.10
Despite the promise that praziquantel offers for controlling human schistosomiasis, up until recently it has not been made widely available.17 Previously (in chapter 2), we learned how in 2001, the 54th World Health Assembly adopted a resolution calling for treatment with a benzimidazole anthelmintic drug of at least 75% of school-age children at risk of acquiring schistosomiasis and soil-transmitted helminth infections by 2010. Based on the experiences and successes of mass drug administration of praziquantel, the resolution was written to include this drug along with either albendazole or mebendazole for the treatment of school-age children. In many regions of the developing world, especially in sub-Saharan Africa and Brazil, it is common for children to be polyparasitized with both soil-transmitted helminths (especially hookworm) and schistosomes,18 so that they could benefit from combination therapy with a benzimidazole anthelmintic and praziquantel. Unfortunately, the World Health Organization (WHO) estimates that in 2010 only about 33 million of the 236 million children at risk for schistosomiasis actually received praziquantel, just a little over 10%.19 The low drug coverage results from the absence of political will in expanding mass drug administration, together with limited availability of praziquantel. In response, in January 2012, the Bill & Melinda Gates Foundation partnered with the major pharmaceutical companies, the World Bank, WHO and other international agencies, and key nongovernmental organizations in a London Declaration to reaffirm support for control of neglected tropical drugs through mass drug administration.20 The announcement coincided with a commitment by a German company, Merck KGaA, to dramatically ramp up praziquantel donations.
A key implementing partner that provides technical assistance to the African health ministries in order to facilitate praziquantel administration (usually together with albendazole for soil-transmitted helminth coinfections) through mass drug administration is the Schistosomiasis Control Initiative (SCI), a public-private partnership established by Alan Fenwick at Imperial College London (www3.imperial.ac.uk/schisto). Previously, Fenwick had acquired a wide-ranging experience in large-scale control of schistosomiasis
