Prospects for the Control of Neglected Tropical Diseases by Mass Drug Administration

Henk L. Smits

Disclosures

Expert Rev Anti Infect Ther. 2009;7(1):37-56. 

In This Article

Schistosomiasis

Etiology, Pathology & Treatment of Schistosomiasis

Urinary schistosomiasis is caused by infection with the flukeworm Schistosoma haematobium and intestinal disease is caused by infection with Schistosoma intercalatum, Schistosoma mansoni, Schistosoma japonicum or Schistosoma mekongi. With the exception of S. japonicum , these pathogens have freshwater snails as an intermediate host and cercariea produced by the snails penetrate the human skin when in contact with infested water. The snail that functions as intermediate host for S. japonicum is amphibious. Disease is primarily caused by the deposition of eggs by adult female worms in blood vessels surrounding the bladder and intestines. Hematuria is the main sign of urinary schistosomiasis and major findings are bladder and urethral fibrosis and hydronephrosis in advanced cases. Intestinal schistosomiasis presents with a number of nonspecific findings, including diarrhea and blood in the stool, with liver enlargement and other pathological findings in more-severe cases.[68,69,70] Iron deficiency due to blood loss is the major cause of morbidity in schistosomiasis. The amount of iron lost owing to S. haematobium can be very dramatic as large amounts are lost with the urine from hemoglobulin that passes the bladder and patients will require iron supplementation. The use of PZQ in MDA has proven to be a very effective but, unfortunately, the high cost of this drug prohibits its use in many countries.[71] Despite many years of widespread use, no signs of emerging resistance have yet been observed; even though isolates from Egypt with diminished drug sensitivity have been reported, no evidence has been found for a reduced effectiveness of the drug in MDA programs in Egypt.[72] The drug is safe and no serious side effects have been observed, even when administered to pregnant and lactating women.[73,74] The dose of PZQ is based on bodyweight and is 40 mg/kg for S. haematobium infection and 60 mg/kg for S. japonicum infection, or even more conveniently may be based on height.[75,76]

MDA for Schistosomiasis

Different studies have demonstrated that a single round of community-based PZQ treatment in a high-endemic area results in an extended period of low transmission of S. mansoni and S. haematobobium .[77,78,79,80] A very recent study performed in Uganda showed that two rounds of treatment administered to children and adults in high-risk areas resulted in an overall 83% reduction of the prevalence of S. mansoni and a mean reduction in egg burden of 92%.[81] However, experience in China with the control of S. japonicum has demonstrated that, after termination of the control program, which was based on treatment of humans and animals with PZQ, and depletion of the snail population using the molluscicide niclosamide, the prevalence of infection increased again.[82] Furthermore, although MDA is effective in reducing the prevalence of infection in high-prevalence areas, it is much less effective in low-prevalence areas.[83] The control of S. japonicum was more successful on Bohol Islands in The Philippines where, by high coverage of selective mass treatment based on stool examination accompanied by successful snail control, the prevalence of the infection has been kept low for more than two decades.[84] While such an approach may work in isolated communities it has proven to be less effective elsewhere. Furthermore, snail control is expensive, difficult to sustain and the use of molluscicides has negative effects on the environment. Given the complex lifecycle of these blood flukes, mathematical modeling has been employed to predict the outcome of control strategies. One model has emphasized the importance of environmental and seasonal factors to consider.[85] In addition, it can be foreseen that infrastructural water-management projects may have a huge impact on the habitat of snails (and intermediate hosts and vectors of other infectious diseases) and mathematical modeling may help to predict the effect of changes in water management on the frequency and transmission dynamics of infectious diseases.[86] If through increased contacts any such negative affects are foreseen, control and preventive measures should be taken. Water-management projects may also lead to less contacts and, hence, less risk of disease. Health-impact assessment implemented early in the project development plan may assist in mitigating negative health impacts and enhancing positive effects.[87]

It has been noted that the problem of schistosomiasis is underestimated in sub-Saharan Africa and that national health authorities have been reluctant to develop a commitment toward its control because the required public-health effort is judged disproportional high.[88,89] Therefore, integration with other programs in areas of overlap should be considered. Individuals infected with food-borne trematodes, such as the liver flukes Clonorchis sinensis, Opisthorchis felineus and Opisthorchis viverrini, the lung flukes Paragonimus spp., and the intestinal flukes Fasciolopsis buski, Echinostoma spp., Heterophyes heterophyes and Metagonimus yokogawi , may also benefit from PZQ or ALB treatment,[90] providing another argument for setting up MDA programs based on these drugs.

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