Diagnosis and Treatment of Schistosomiasis in Children in the Era of Intensified Control

Stefanie Knopp; Sören L Becker; Katrin J Ingram; Jennifer Keiser; Jürg Utzinger

Disclosures

Expert Rev Anti Infect Ther. 2013;11(11):1237-1258. 

In This Article

Prevention & Control of Schistosomiasis

SAC are at highest risk of infection with Schistosoma worms. Hence, most large-scale control efforts focus on the prevention of morbidity in this age group, which is facilitated by preventive chemotherapy, often through the education sector. Preventive chemotherapy follows a vertical approach and, on the day of drug administration, schoolchildren are encouraged to take a morning meal to enhance bioavailability[93,94] and to lower the odds of adverse events.[95] Additionally, SAC should bring along their nonschool-enrolled siblings, so that all children of this age group are being treated. Praziquantel treatment often goes hand-in-hand with the administration of albendazole or mebendazole against soil-transmitted helminthiasis, vitamin A supplementation, malaria control efforts (e.g., distribution of long-lasting insecticidal nets) and/or with vaccinations targeting measles.[96–98] Obvious advantages of treating children in schools are that they are easily accessible, teachers can assist with the treatment, and drug intake by the children can be directly observed. There are, however, concerns that treatment coverage might not be optimal.[99,100] For example, children who lack knowledge about schistosomiasis transmission and prevention and who were not directly supported by a teacher in taking the drugs had significantly lower odds of taking praziquantel in a Kenyan study. These issues, alongside local perceptions and beliefs toward praziquantel administration need to be explored in greater detail.[100] Community-wide treatment campaigns are considered to achieve higher coverage rates of nonschool-enrolled children than school-based treatment.[101] Nevertheless, coverage strongly depends on local circumstances, including sensitization of the community, relation between the drug distributors and targeted groups, experiences on adverse events and understanding of the need and purpose of periodic treatment without prior diagnosis.[102,103]

Although preventive chemotherapy is able to temporarily reduce the prevalence in the targeted population and is thought to lower transmission by the decrease of infection intensity, and hence egg excretion into the environment, it is unlikely to interrupt transmission. Particularly in high-transmission areas, prevalence and intensity of infection can quickly reach pretreatment levels if no other means of control are applied, even if the coverage is high.[104] To achieve the highest impact of praziquantel treatment, it should be applied when the likelihood for re-infection is lowest, and hence be timed to the beginning of the low-transmission season, if there is any.[105] To clear matured schistosomes in the body that were not targeted by the first praziquantel application due to their juvenile stage and to accelerate a more rapid reduction of infection-related disease, a second treatment 2–8 weeks after the first treatment round is recommended.[106]

Snail control using molluscicides to reduce the infected intermediate host snail population at human water contact sites is an important, well-tried and effective tool to complement preventive chemotherapy against schistosomiasis.[107] The most effective time of application is shortly before or shortly after a preplanned chemotherapy campaign to avoid rapid re-infection of people.[108,109] The molluscicide niclosamide has been recommended by the WHO to control schistosomiasis in humans.[110–112] Niclosamide has been widely and effectively used for snail control in schistosomiasis control programs in different parts of the world, most extensively in the People's Republic of China, but also in Egypt, Kenya and Morocco[109,113–116] and is currently applied and evaluated in a randomized intervention trial that aims at elimination of urogenital schistosomiasis in Zanzibar.[9,23] It must be noted, however, that chemical molluscicides, such as niclosamide, not only kill snails but also are toxic for fish and other organisms, and hence there are significant risks for the environment and biodiversity. New molluscicidal-only formulations or products are highly desirable to remedy the negative impact on species other than snails. Alternatively, indirect snail control measures such as the destruction of the snails' natural habitat, for example, by the removal of vegetation from riverbanks, or biological control with fish, ducks, crayfish or competitor snails have been successfully applied to reduce intermediate host snail populations.[10,117,118]

Although preventive chemotherapy and snail control are measures that need to continuously be applied to reduce morbidity and transmission, more sustainable and long-lasting efforts to prevent infection and reinfection include health education and behavior change interventions as well as improvements in the water and sanitation infrastructure in at-risk communities.[9,12,119–122] Behavior change interventions have been described earlier on in the current review, but one needs to be aware that increased knowledge about how to prevent infection and how to reduce transmission and the motivation for behavioral change in deprived communities need to go hand-in-hand with the accessibility of safe water sources and improved sanitation. Transmission of schistosomiasis is closely linked with human practices related to water contact and sanitation.[2,102] Ceasing urination into open water bodies can inhibit the transmission of S. haematobium. While also refraining from open defecation in or near water bodies can lower the transmission of S. guineensis, S. intercalatum, S. japonicum, S. mansoni and S. mekongi, there remains the risk that eggs are trapped in the perianal folds and are released into water while people take a (hygienic) bath and hence contributes considerably to transmission.[123] There is, however, a paucity of studies assessing or showing any clear impact of improved sanitation on schistosomiasis endemicity.[122,124–126] On the other hand, multiple studies have shown that people who lack safe water supply, use water from natural freshwater bodies for washing purposes or children spending time playing in open water bodies are at a higher risk of acquiring schistosomiasis than their less exposed counterparts.[23,25,124] Improving access to safe water in endemic populations has been shown to have a positive effect in reducing the prevalence and intensity of schistosomiasis a long time ago.[127,128] In 2001, WHA resolution 54.19 urged Member States to promote access to safe water, sanitation and health education through intersectoral collaboration to sustain the control of schistosomiasis (and soil-transmitted helminthiasis), and this has been re-emphasized in 2012 in WHA resolution 65.21,[6,8] but more action in this regard must be taken. Additional, well-designed studies to assess the impact of improved sanitation and safe water on schistosomiasis, including information about user uptake, maintenance, sustainability and affordability, are warranted.[122]

Finally, a vaccine would be the key to sustainably control and eliminate schistosomiasis. A vaccine could reduce worm fecundity and/or prevent Schistosoma infection and re-infection not only in humans but also in reservoir hosts (e.g., water buffaloes) that significantly contribute to the transmission of S. japonicum.[129] Over the past 20–30 years, multiple vaccine candidates based on, for example, recombinant-derived schistosome proteins,[130,131] radiation-attenuated schistosome larval stages[132,133] or DNA-delivered proteins have been identified.[129] Although protection against various schistosome species was achieved in a wide range of host reservoir animals, there are currently only very few vaccine candidates (e.g., recombinant Sm14/FABP antigen, rSh28GST antigen), which are studied in clinical trials.[134–138] The identification of the whole S. haematobium, S. japonicum and S. mansoni genomes and the rich resources of genomic data of other Schistosoma species,[139–142] as well as the availability of high-quality outcomes of the additional '-omics' sciences will contribute to the development of a human antischistosome vaccine and novel antischistosomal drugs.[137]

Discussion Point

Since SAC are the main spreaders of schistosomiasis, it will be very important to tailor behavioral change and health education interventions to children's understanding, so that the goal of modifying their behavior to not urinating or defecating into open water, or be in contact with this water while playing or washing, to interrupt transmission can be met. Behavioral interventions should also target children's peers (parents, older siblings and teachers) so that they can exemplify adequate behavior through their own life. Sensitizing children, parents and teachers to the importance and benefit of periodic deworming might increase the coverage of drug intake. When constructing latrines or urinals, it is important to design them in a way that favors the use by children. It should be considered that children might not use latrines because they do not like the smell or are afraid of darkness or of falling into too big holes.[143]

It is clear that for sustainable control, interruption of transmission and finally elimination of schistosomiasis, integrated control approaches that are tailored to the local situation are necessary. The People's Republic of China is a trailblazer in integrated and intersectoral schistosomiasis control demonstrating that transmission can be effectively interrupted by combining preventive chemotherapy with snail control, health education, improved sanitation and environmental and reservoir host management.[144] Lessons from the multifaceted schistosomiasis control program implemented in the People's Republic of China's over the past 60 years can guide the progression from schistosomiasis control to elimination in other endemic areas.[145,146]

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