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Oxford University Press makes no representation, express or implied, that the drug dosages in this book are correct. Readers must therefore always … More Oxford University Press makes no representation, express or implied, that the drug dosages in this book are correct. Readers must therefore always check the product information and clinical procedures with the most up to date published product information and data sheets provided by the manufacturers and the most recent codes of conduct and safety regulations. The authors and the publishers do not accept responsibility or legal liability for any errors in the text or for the misuse or misapplication of material in this work. Except where otherwise stated, drug dosages and recommendations are for the non-pregnant adult who is not breastfeeding.

Asiatic schistosomosis is a very old disease with Schistosoma japonicum eggs found in human remains >2000 years old from Hunan and Hubei provinces in China (Mao and Shao 1982). The original description of Asiatic schistosomosis was made by Fujii in 1847 (Sasa 1972). The life cycle was first described by Kawanashi (1904) who noted trematode-like eggs in cat faeces. The same year, Katsurada recovered adult worms from a cat from Katayama, Japan (Okabe 1964). Fujinami and Nakamura (1909) first reported skin infection with S. japonicum cercariae of different mammals, and Miyairi and Suzuki (1914) discovered that Oncomelania hupensis served as intermediate host where miracidia developed into sporocysts and further into cercariae (Jordan 2000). The snail hosts of S. japonicum were discovered in China by Faust and Meleney (1923), the Philippines by Tubangui (1932) and in Indonesia by Carvey et al. (1973). In addition to the skin as the principal route of infection, Suda (1924) described oral infection and several authors described the intrauterine route of infection (Okabe 1964; Sasa 1972).

Following the understanding of the lifecycle, control measures including wearing closely woven clothing, composting of faeces with urine for at least 14 days, replacing cattle with horses, killing of rodents especially rats, killing of snails by lime, copper sulphate or salt water, were proven to have some efficacy. In Japan, an effective integrated control programme started after the Second World War with the last human case being reported in 1978 (Jordan 2000). The National Schistosomosis Control Programme in China started in 1955 and at that time more than 10 million people were infected with S. japonicum (Wu 2002). Emetine and antimony potassium tartrate were among the first drugs with proven efficacy against schistosomosis in humans. Later antimony and finally praziquantel and artemether have been introduced as highly effective drugs with only minor adverse effects (Wu 2002).

The zoonotic schistosomes all belong to the genera Schistosoma of the family Schistosomatidae which are dioecious Digenea belonging to the class Trematoda. The main zoonotic schistosomes are found in the S. japonicum species group, which comprises S. japonicum from the People’s Republic of China, Taiwan, Japan, Sulawesi and the Philippines, S. mekongi from Laos and Cambodia, S. malayensis from the Malaysian Peninsula, S. sinensium from Thailand and China (Chilton et al. 1999), and S. ovuncatum from Thailand (Attwood et al. 2002). The former two are zoonotic. Molecular techniques suggest that an ancestral schistosome dispersed from Asia to Africa by mammal migration 12–19 million years ago (Morgan et al. 2001). In Asia, the ancestral Schistosoma branched as the S. japonicum group (Lockyer et al. 2003).

Sexual dimorphism in schistosomes is unique among trematodes. Adult females of S. japonicum and S. mekongi measure 15–30 mm in length whereas males are smaller (Rollingson and Simpson 1987). Both male and female worms have oral and ventral suckers, an oesophagus, a bifurcated intestine joins to form a blind caecum, and an oral mouth opening in the anterior end which also serves as the anus. But the oral suckers are much better developed in males. The male has a gynaecophoric (ventral groove) in which the female permanently resides. The male of S. japonicum has 7 testes located posterior to the ventral sucker. Female worms have a single ovary and a uterus which leads to a genital opening near the ventral sucker (Rollingson and Simpson 1987). All S. japonicum males have tubercules and bosses on the posterior area close to the tail tip, suckers and gynaecophoris canal, but not on their surface and spines (Rollingson and Simpson 1987).

Among the schistosomes infecting humans, S. japonicum alone has significant zoonotic transmission. It is unique among helminth zoonoses as the infection is transmitted naturally between man and other mammals and maintained by all species (Nelson 1975). Using microsatellite DNA markers, Wang et al. (2006) were able to demonstrate that the same S. japonicum population was shared among seven different mammalian species living in the same villages. Besides humans, 40 different mammalian species, belonging to 28 genera and seven orders, are considered reservoir hosts for S. japonicum (Chen 1993). However, it is likely that only about ten species play a significant role in transmission (Carabin et al. 2005; Wang et al. 2005, 2006). The epidemiological importance of each host is based on the actual contribution from each host species, which can be determined by number of hosts, prevalence and intensity of infection, amount of faeces produced, egg hatchability and habitat contamination potential (Wang et al. 2005). Transmission in a given area has been shown to be highly dynamic and complex and significantly influenced by local biological and cultural factors (Wang et al. 2005).

S. mansoni has frequently been found in rodents and non-human primates, and S. haematobium has also been detected in non-human primates, but these hosts are believed not to contribute significantly to infection of humans (Taylor 1987). The true zoonotic potential of S. mekongi has yet to be elucidated, but from P.R. Laos a prevalence of 10% in pigs has been reported (Standgaard et al. 2001).

Important geographical variations in S. japonicum species have been found among China, the Philippines, Japan, Taiwan and Indonesia regarding morphological, biological, and immunological aspects and responses to chemotherapy (Cheever et al. 1980; Hsû and Hsû 1962; Kresina et al. 1991; Moloney et al. 1985; Ruff et al. 1973; Sobhon et al. 1986).

S. japonicum differ within mainland China regarding genetics, morphology, pathogenicity, and drug responses (Chilton et al. 1999; Gasser et al. 1996; He et al. 1991, 1994; Wang and Mao 1989). He et al. (1994) reviewed five S. japonicum isolates from China and found significant variation in worm size, testes number, eggs’ size and shape, pre-patent period, snail infectivity, host/parasite compatibility, pathogenesis, immune responses and host response to chemotherapy. They concluded that at least four distinct strains (Yunnan, Guangxi, Sishuan, Anhui-Hubei) exist. These results were confirmed through random amplified polymorphic DNA technique (Gasser et al. 1996) and allozyme electrophoresis (Chilton et al. 1999) using seven isolates from different locations in China, leading Chilton et al. (1999) to suggest that a species complex exist. Strains from PR China are thought to be significantly different from strains found in the Philippines (Rudge et al. 2009).

Adult schistosomes live in pairs in the mesenteric veins of the definitive host, specifically large intestinal veins for large animal hosts and small intestinal veins for rodents (Johansen et al. 2000). S. japonicum females produce 1,000–3,000 eggs per day. Each egg contains an embryo, which matures to a miracidium in 9–12 days and may survive for up to 3 weeks (see Fig. 55.1 for life cycle of S. japonicum). The miracidium excretes histolytic enzymes which facilitates its passage from the venules to the gut lumen. Eggs excreted with faeces may hatch in freshwater if temperature (15–30°C) and light conditions are favourable. Free swimming miracidia must penetrate an Oncomelania spp. snail host within hours to survive. Upon penetration, the miracidium develops to a primary sporocyst which yields fork-tailed cercariae-producing secondary sporocysts. Stimulated by light and water temperatures above 15°C, cercariae are shed from the snail. The pre-patent period in the snail is influenced by water temperature ranging from 48 days at 30°C to 160 days at 17°C. In freshwater, cercaria can survive for up to 2–3 days. Upon water contact cercariae penetrate the skin of a definitive host using proteolytic enzymes. The cercariae, called schistosomula following transformation in the epidermis, lose their tails and migrate via the venous circulation to the lungs and systemic circulation. In about 4 weeks, they reach the liver where males and females mate and finally lodge in the mesenteric vessels. The pre-patent period for S. japonicum is 42 days in humans. The adult worms may survive in the host for many years (Chen and Mott 1980).

 The life cycle of Schistosoma japonicum
Fig. 55.1

The life cycle of Schistosoma japonicum

.

Both oral and congenital infections (natural and experimental) of the definitive hosts are reported from several animal species. Congenital transmission was first described in dogs in 1911 but has since been described in humans, cattle, goats, sheep, mice, guinea pigs, pigs, and rabbits (Okabe 1964; Sasa 1972; Johansen and Ørnbjerg 2005). Experimental infections of sows during mid to late pregnancy results in nearly 100% patent infection in piglets. Infection in early pregnancy results in high percentage of stillbirths and neonatal deaths (Willingham et al. 1999). Congenital infections also change the pathogenesis, and the host response to postnatal infections and to treatment after birth (Johansen and Ørnbjerg 2005).

The schistosome species in Southeast Asia are transmitted by prosobranch snails belonging to two subfamilies, Pomatiopsinae and the Triculinae, of the family Pomatiopsidae (Caenogastropoda: Rissooidea). Certain subspecies of Oncomelania hupensis (Pomatiopsidae: Pomatiopsinae) are known to transmit S. japonicum (Rollinson and Southgate 1987). Some of these subspecies, however, should be recognized as a full species, i.e. O. quadrasi (Woodruff et al. 1988; Hope and McManus 1994) and O. lindoensis (Woodruff et al. 1999). S. mekongi, which primarily infects humans along the Mekong river of Laos and Cambodia, is transmitted by Neotricula aperta (Pomatiopsidae: Triculinae). Three strains of N. aperta have been identified (Davis et al. 1976). All three strains are able to act as host for S. mekongi but only the γ-strain is known to be epidemiologically significant (Attwood et al. 1997). In Malaysia, S. malayensis infects mainly rodents but can also infect humans and the intermediate hosts are species of Robertsiella (Pomatiopsidae: Triculinae) (Davis and Greer 1980; Attwood et al. 2005).

Oncomelania hupensis ssp. with some variation among subspecies are small, amphibious and dioecious snails. Females tend to be larger than males. Eggs are laid singly on solid objects. Hatching occurs after 10–25 days, depending on temperature, and newly-hatched snails pass through an aquatic stage of 1–2 weeks. Snails reach sexual maturity after 10–16 weeks and may live for 24–35 weeks. Their reproductive potential is low compared to the pulmonate snails and recolonization of sites treated with molluscicide may take 1–2 years. Oncomelania hupensis ssp. inhabit flood plains and especially man-made habitats, resulting from agricultural development, drainage channels, roadside ditches, rice fields, and small canals and drainage canals of irrigation works, are important. Snails are found primarily on the banks but some are also found in very shallow water (i.e. depth less than 20 cm). Habitats preferred by O. hupensis are shaded by vegetation, and the temperature is relatively constant and cool. Water current speeds above 0.14 m/s are generally unfavourable for O. hupensis.

Tricula aperta is found in parts of the Mekong and Mun rivers where it clings to rocks, twigs and other solid objects in running, well-aerated, clear water (Upatham et al. 1980). Population densities appear to be controlled by the annual variation in the water level of the river. During the rainy season the flow is torrential and the species seems to persist as eggs attached to the underside of stones. Female snails live less than a year and apparently lay large numbers of eggs prior to the onset of the rains. Robertsiella kaporensis may be found in small streams attached to rocks, leaves and twigs, but are most abundant in overgrown areas where they attach to roots (Greer et al. 1980).

Schistosoma infections are reported from China, the Philippines and certain areas of Indonesia (King 2009).

Most risk factors for human S. japonicum infection are linked to water contact behaviour. Some studies report an association between the frequency and duration of water contact and infection (Maszle et al. 1998; Ross et al. 1998; Wu et al. 1993), although measurement of water contact is inconsistent (Payne et al. 2006). Occupations involving frequent water contact are thus associated with the highest prevalence of infection (Blas et al. 2004; Spear et al. 2004; Huang and Manderson 2005; Tarafder et al. 2006). The prevalence of infection tends to peak at adolescence (Domingo et al. 1980; Olveda et al. 1996) and is independent of water contact activities (Ross et al. 2001), due to the ubiquitous water contact in these resource-poor subsistence societies. Males generally show higher prevalences than females (Wu et al. 1993; Olveda et al. 1996; Ross et al. 1997; Acosta et al. 2002) and peaks of infection occur earlier in males than females (Olveda et al. 1983; Ross et al. 1997; Tarafder et al. 2006). Preventive factors include high socio-economic status (household wealth and income, and education) (Huang and Manderson 2005; Spear et al. 2004) and a previous history of infection (Ellis et al. 2007; Olds et al. 1996; Olveda et al. 1996). Some large scale, community-based factors have also been found to be associated with the prevalence of infection. These include climate change and water management (Blas et al. 2004; Maszle et al. 1998; Yang et al. 2005; Zheng et al. 2002), and levels of infection in animals (Guo et al. 2006; Jiang et al. 1996; McGarvey et al. 2006; Wang et al. 2005).

It is believed that human contribution to schistosomosis transmission has been greatly reduced in China over the past decades, which has increased the relative contribution of primarily domestic animals. In China, cattle and water buffaloes play a major role in transmission due to the high number of animals, high prevalence, frequent contact with infested waters and large volume of faeces produced (Wang et al. 2005). In contrast, the prevalence of infection in water buffaloes was found to be very low in Samar Province of the Philippines (Fernandez et al. 2007), where there was a cross-sectional association between the village-level intensity of infection in cats and dogs and the intensity of infection in humans (McGarvey et al. 2006). In China, cattle are generally found with significantly higher prevalences compared to water buffaloes in areas where they are grazing together despite the fact that buffaloes have much more water contact than cattle (Dai et al. 2004). Age-related resistance is seen in mainly water buffaloes after repeated exposure in the second grazing season (Wang et al. 2005). However, it is possible that the role that these draught animals play in transmission will change as they are being replaced by tractors. Pigs are also important reservoirs in certain regions due to their numbers and size, relatively high prevalence and often free grazing in infested habitats (Shi et al. 1992). After approximately 3 months of an acute infection, pigs tend to undergo self-cure (Hurst et al. 2000). Goats are highly susceptible to S. japonicum and with an increase in goat farming, especially in China their importance for transmission of schistosomosis needs to be assessed (Zhang et al. 1998). In Samar province of the Philippines, Fernandez et al. (2007) found that the prevalence of infection in animals, when adjusted for misclassification error, was extremely variable from village to village. This suggests that there may be clustering of different strains in villages within the same province. In 29 of 50 villages studies, the prevalence was highest in rats, followed by dogs, and then by pigs and cats. The prevalence was highest in dogs in 18 villages. In China, Wang et al. (1998) found low prevalences of infection in cats and dogs. Although horses, mules and donkeys have been found naturally infected with S. japonicum, they are among the least susceptible livestock (Mao 1990).

More than 20 species of wild mammals have been found infected with S. japonicum of which the rat (Rattus norvegicus) has been found with the highest prevalence; 88% in China (Xu and Li 1992) and 29.5% in 50 villages of the Samar province of the Philippines (Fernandez et al. 2007).

Mathematical transmission models have helped us to improve our understanding of schistosomosis epidemiology (Anderson and May 1992) and of the relative effectiveness of control programmes, by giving greater insight into available data. The structure of models used and the degree of inference used with the models has varied widely for S. japonicum. Complex models of transmission have been produced using data from China (Spear et al. 2004), the Philippines (Ishikawa et al. 2006) and Cambodia for S. mekongi (Hisakane et al. 2008), producing useful region-specific results.

Three studies have assessed the role of non-human definitive hosts in transmission. Williams et al. (2002) used data from bovine and human infections in China to compare four control strategies. Initial human treatment combined with a 45% efficacious bovine vaccine and improvement in human sanitation or reduction in water contact was found to lead to the elimination of the parasite. In the Philippines, Riley et al. (2005) developed an initial transmission model using community data from 1981, before widespread praziquantel use, to provide an estimate of endemic equilibrium. This model suggested that differences in infection intensity between villages were caused by differences in both the infection and recovery processes in humans. In a more recent model, data from 50 villages in the Philippines on humans and other animals, and adjusted for specificities and sensitivities of the measurement techniques were used (Riley et al. 2008). The results suggested that human to human transmission was more important than transmission from other mammals to humans. Also, the process of infection from snails to mammals was found to drive differences in transmission between villages, rather than the process of infection from mammals to snails.

The adult worms of S. japonicum live in the mesenteric veins. Pathology is mainly due to eggs that are swept up into the liver and eggs that damage the intestinal sub-mucosa as they migrate through the intestinal wall to be passed in stool.

Over half of the thousands of eggs released by mature female worms remain trapped in host tissues (Smith and Christie 1986). Eggs swept up into the liver cause the most significant pathology, inducing a granulomatous response that ultimately progresses to focal areas of fibrosis or scarring. Many host-specific factors including age, gender, and type of host immune response to egg antigens modify this risk (Coutinho et al. 2007; Booth et al. 2004). Though early stage liver fibrosis can be modified with treatment, late stage fibrosis is not reversible. Progressive liver fibrosis results in portal hypertension, which leads to splenomegaly, esophageal varices, and upper gastrointestinal bleeding, the latter being the most common cause of death. Even eggs that successfully leave the mesenteric veins en route to the gut lumen may cause organ pathology. Secretions of the miracidium contain proteolytic enzymes that lyse tissue, aiding migration to the sub-mucosa of the intestinal wall. Occasionally, eggs become trapped, leading to granulomatous inflammation and colonic and rectal polyposis, which can result in significant blood loss (Warren 1982).

This passage of eggs through the gut wall, even without development of significant polyps, is thought to contribute to schistosomosis-related anaemia from chronic, occult, gastrointestinal blood loss. However, extra-corporal blood loss, with attendant iron loss, likely contributes to anaemia among those with high egg burdens (Kanzaria et al. 2005; Ndamba et al. 1991). Recent studies have shown that increased inflammatory response to egg antigens increases the risk of anaemia, which suggest anaemia of inflammation (Leenstra et al. 2006a; Leenstra et al. 2006b), rather than gastrointestinal blood loss or other potential mechanisms (Friedman et al. 2005). Regardless of the etiology, S. japonicum-associated anaemia is an important contributor to disability weights, as it is one of the main causes of schistosomosis-related disability (Finklestein et al. 2008; King et al. 2005).

The chronic inflammatory state driven by adult worms and eggs also contribute to under-nutrition. There are two primary ways in which cytokines may impact nutritional status. The first is through appetite suppression or anorexia induced by TNF-α and IL-6 (Arnalich et al. 1997; Mantovani et al. 1998). The second way in which these cytokines may impact nutritional status is through their potent catabolic effects, leading to weight loss and tissue wasting (Kotler 2000).

The three major schistosome species that infect humans have all been related to protein energy malnutrition in human populations (Stephenson 1993). A randomized clinical trial in Leyte, the Philippines, demonstrated a causal link between S. japonicum infection and decreased adiposity (McGarvey et al. 1996). Finally, longitudinal studies at the same site demonstrated improvement in body mass index Z-scores (BMIZ) following treatment after adjustment for confounders (Coutinho et al. 2006). High intensity reinfection at 18 months was associated with significantly less absolute growth from baseline compared to lower intensity and no reinfection.

A final important clinical manifestation of schistosomosis infection is decreased cognitive function. A randomized controlled trial of praziquantel among S. japonicum infected children in China found that younger children in the treatment group showed significant improvement in tests of cognitive function only three months after chemotherapeutic cure (Nokes et al. 1999). A separate, cross-sectional study conducted in the Philippines demonstrated that S. japonicum infection was associated with poor performance on tests of learning, after controlling for confounders (Ezeamama et al. 2005).

Schistosomosis japonica is a disease with a wide range of manifestations depending primarily on the host species, intensity of infection, time of first exposure, and acquired immunity. Cattle, sheep and goats are generally more susceptible than water buffaloes whereas horses and some rodent species are almost refractory (Mao 1990).

The main clinical symptoms are related to the early egg excretion phase and include fever, diarrhoea, anorexia, eosinophilia and anaemia. In heavy infections coughing, bloody diarrhoea, growth reduction, emaciation and death can be seen especially in young animals (Dumag et al. 1980; Hurst et al. 2000; Johansen et al. 2000). Gross pathological lesions, which are primarily associated with the tissue-deposited eggs, are seen in both the intestine and in the liver, correlate with intensity of infection, and peak around time of maximum egg excretion (Johansen et al. 2000). Lesions in the intestines include haemorrhages occasionally with ulcerations and thrombophlebitis in the mesenteric vessels (Hurst et al. 2000). In the liver, hepatomegaly, enlargement of lymph nodes, and disseminated small grey-white nodules are common findings as is portal and interlobular fibrosis. Ascites is another common chronic manifestation. Egg induced lesions may also be found in lungs, brain, spleen, kidney and lymph nodes (Cheever 1985).

There is no gold standard for the diagnosis of schistosomosis in humans or animals.

In humans, the most widely used method of diagnosis for large-scale epidemiological studies and surveillance is the Kato-Katz, which involves clearing a measured volume (weight) of faeces using a glycerine-impregnated cellophane coverslip (Feldmeier and Poggensee 1993). This technique detects current infection but presents obvious identification problems due to the uncharacteristic shape of the eggs resembling protozoan cysts, air bubbles, pollen and debris. Furthermore, the sensitivity of the test declines with decreasing intensity of infection (Yu et al. 1998; Lin et al. 2008; Tarafder et al. 2006). To overcome this problem, antibody detection in serum has been extensively used, especially indirect haemagglutination assay (IHA) and ELISA with soluble egg antigen (Wu 2002). The issue with this approach is that it detects both past and present infection and presents cross reactions with other helminth infections. A commonly used diagnostic strategy has therefore been to screen for antibodies and subsequently examine the stool of seropositive individuals using Kato-Katz or hatching test (Zhou et al. 2007). Polymerase Chain Reaction (PCR) test has the potential for high sensitivity and specificity. Lier et al. (2006) first published the development of a PCR for detection of S. japonicum and determined that the seroprevalence using an IHA was much higher (26.1%) than the prevalence in stool-based tests which were 5.3%, 3.2% and 3.0% for PCR, hatching test and Kato-Katz thick smear, respectively.

In animals, the hatching test for S. japonicum is exclusively used in China. The method has potentially high sensitivity as large samples are used but the method is difficult to standardize as hatching is influenced by a range of abiotic and biotic factors and immature eggs are not likely to hatch and eggs excreted from different host species have different hatching rates (Yu et al. 2007). The method has primarily been used for cattle and water buffaloes but Wang et al. (2005) applied the method to a range of domestic animals and found that prevalence and intensity of the infection varied significantly between species and areas, highlighting the importance of more accurate data to determine cost-effective control strategies. Sedimentation tests are numerous, but are most often only qualitative, lack sensitivity and precision, are too time-consuming and not at all standardized. The tedious microscopy of the sediment makes this approach subject to tremendous potential reader-bias. Willingham et al. (1999) developed a combined filtration, sedimentation and centrifugation technique (DBL-method) for counting S. japonicum in pig faeces. The method is quantitative, uses no hazardous chemicals, is simple and as eggs remain alive, viability is easily assessed.

In all definitive hosts, it has been shown that the sensitivity of the stool examination increases with the number of stool samples provided over consecutive days while the specificity decreases (Table 55.1). This is because Schistosoma eggs are not shed regularly from day to day (Yu et al. 1998). The sensitivity of the test is particularly poor among subject providing one stool sample and with low intensity of infection (Zhang et al. 2009). The sensitivity and specificity of the Kato-Katz for S. japonicum with different numbers of stool samples has not been determined.

Table 55.1
The sensitivity of the stool examination increases with the number of stool samples provided over consecutive days while the specificity decreases
Species
Water buffaloes Cats Dogs Pigs Rats

Sensitivity

1 stool sample

78.0 (47.6–95.7)

65.0 (48.3–79.6)

75.0 (67.1–82.3)

77.1 (56.6–95.7)

76.8 (62.1–88.7)

2 stool samples

95.2 (72.5–99.8)

87.7 (73.2–95.8)

93.8 (89.2–96.9)

94.8 (81.2–99.8)

94.6 (85.6–98.7)

3 stool samples

98.9 (85.6–100)

95.7 (86.2–99.2)

98.4 (96.5–99.5)

98.8 (91.8–100)

98.7 (94.5–99.9)

4 stool samples

99.8 (92.4–100)

99.5 (96.3–100)

99.6 (98.8–99.9)

99.9 (98.5–100)

99.7 (97.9–100)

5 stool samples

100 (96.0–100)

99.5 (96.3–100)

100 (99.6–100)

99.9 (98.5–100)

100 (99.2–100)

Specificity

1 stool sample

98.7 (96.8–99.7)

97.2 (95.2–98.8)

97.0 (95.2–98.3)

99.1 (98.4–99.6)

92.6 (87.0–97.2)

2 stool samples

97.4 (93.7–99.4)

94.4 (90.6–97.6)

94.1 (90.6–96.6)

98.2 (96.8–99.2)

85.7 (75.7–94.5)

3 stool samples

96.2 (90.7–99.1)

91.8 (86.2–96.4)

91.3 (86.3–95.0)

97.3 (95.2–98.8)

79.4 (65.9–91.8)

4 stool samples

94.9 (87.8–98.8)

89.3 (82.1–95.3)

88.5 (82.1–93.4)

96.4 (93.8–98.4)

73.5 (57.3–89.3)

5 stool samples

93.7 (85.0–98.5)

86.8 (78.2–94.1)

85.9 (78.2–91.8)

95.6 (92.3–98.0)

68.0 (49.8–86.8)

Species
Water buffaloes Cats Dogs Pigs Rats

Sensitivity

1 stool sample

78.0 (47.6–95.7)

65.0 (48.3–79.6)

75.0 (67.1–82.3)

77.1 (56.6–95.7)

76.8 (62.1–88.7)

2 stool samples

95.2 (72.5–99.8)

87.7 (73.2–95.8)

93.8 (89.2–96.9)

94.8 (81.2–99.8)

94.6 (85.6–98.7)

3 stool samples

98.9 (85.6–100)

95.7 (86.2–99.2)

98.4 (96.5–99.5)

98.8 (91.8–100)

98.7 (94.5–99.9)

4 stool samples

99.8 (92.4–100)

99.5 (96.3–100)

99.6 (98.8–99.9)

99.9 (98.5–100)

99.7 (97.9–100)

5 stool samples

100 (96.0–100)

99.5 (96.3–100)

100 (99.6–100)

99.9 (98.5–100)

100 (99.2–100)

Specificity

1 stool sample

98.7 (96.8–99.7)

97.2 (95.2–98.8)

97.0 (95.2–98.3)

99.1 (98.4–99.6)

92.6 (87.0–97.2)

2 stool samples

97.4 (93.7–99.4)

94.4 (90.6–97.6)

94.1 (90.6–96.6)

98.2 (96.8–99.2)

85.7 (75.7–94.5)

3 stool samples

96.2 (90.7–99.1)

91.8 (86.2–96.4)

91.3 (86.3–95.0)

97.3 (95.2–98.8)

79.4 (65.9–91.8)

4 stool samples

94.9 (87.8–98.8)

89.3 (82.1–95.3)

88.5 (82.1–93.4)

96.4 (93.8–98.4)

73.5 (57.3–89.3)

5 stool samples

93.7 (85.0–98.5)

86.8 (78.2–94.1)

85.9 (78.2–91.8)

95.6 (92.3–98.0)

68.0 (49.8–86.8)

Reproduced from Carabin et al. (2005), with permission from Elsevier.

Praziquantel remains the mainstay of treatment for human schistosomosis globally. Praziquantel was released in 1979 and ultimately proved to be more efficacious and safer than its predecessors. Interestingly, praziquantel’s mechanism of action against schistosomes remains poorly understood.

Two special populations warrant further consideration. First, praziquantel was never studied in pregnant or lactating women, thus necessitating its designation as a Pregnancy Class B drug, which has led to withholding treatment in these women in most schistosomosis endemic countries. In 2002, WHO suggested that all schistosomosis infected pregnant and lactating women should be considered as a high-risk group and be offered treatment individually or during treatment campaigns (Allen et al. 2002). However, many nations have not adopted this strategy, and await results of ongoing studies in sub-Saharan Africa and the Philippines. Another group often excluded from treatment is young children. Most school based programs will miss children under the age of six, despite the growing realization that young children are infected and likely contribute to transmission (Stothard and Gabrielli 2007).

Despite evidence that animals transmit and seriously suffer from zoonotic schistosomosis, only few examples of integration of animal treatment in schistosomosis control programmes exist (Chen 1971; Chen 2005; Jiang et al. 2002). Using a mathematical model, Williams et al. (2002) suggested a combination of human and bovine treatment as it would significantly reduce human prevalence and maintain the reduction for an extended period of time. Praziquantel has been shown to be highly effective against all zoonotic scistosomes in a range of animal species (King and Mahmoud 1989). The recommended dose of praziquantel varies depending on the animal host. Effective doses for water buffaloes are 25 mg/kg, cattle 30 mg/kg, pigs 40 mg/kg and goats require 60 mg/kg due to their very fast metabolism (King and Mahmoud 1989; Johansen 1996; Wang et al. 2006). Effectiveness of a single dose of praziquantel applied orally wrapped in tree leaves was assessed in lowland China. The drug efficacy was 97% but as reinfection after treatment was high and occurred throughout the year in both cattle and water buffaloes, the strategy did not effectively prevent transmission (Wang et al. 2006). New evidence-based strategies for integrated control of animal schistosomosis are needed to reduce transmission and improve the health and productivity of the animals. Promising DNA-based vaccines have recently been developed and tested showing reduction in both worm load and an anti-fecundity effect in cattle, water buffaloes and pigs (Shi et al. 2002; Wu et al. 2004).

Great control efforts have been made in all endemic countries to control and eliminate infection. Schistosomosis’ elimination in Japan was achieved throught snail control strategy combined with social-economic development during the 1960s and 1970s (Tanaka and Tsuji 1997; WHO 2001). The snail control strategy involved environmental modification in isolated endemic areas, which was also applied to the Bohol island in the southern Philippines (Ebisawa 1998; Yasuraoka et al. 1989).

Schistosomosis control in China could be considered as exemplary (Wang et al. 2008a). The national control programme has achieved elimination of the disease from five out of 12 formerly endemic provinces by using several resources and approaches. Substantial progress has also been made in most of the remaining endemic areas (Wu et al. 2006) and the estimated total number of infected people has reduced by over 90% since 1950 (Wang et al. 2008b). A 2004 nationwide survey estimated that 720, 000 people are infected (Zhou et al. 2007), while a 2008 study estimated that 412, 000 people are infected (Hao et al. 2009). There is hope of future national elimination through treatment of water buffaloes in marshland and lake regions (Wang et al. 2009a; King 2009; Wang et al. 2009b).

Schistosomosis is believed to be endemic in 28 provinces in the Philippines, including most of the Mindanao region, the eastern part of the Visayas and a few provinces in Luzon. Before the 1980s, the government focused on health education, limiting human exposure to the infective form of the parasite, and efforts to break the parasite life cycle through control of the intermediate host snail using agro-engineering methods and environmental modification (Leonardo et al. 2002). Environmental modifications in combination with molluscicides were found to be too expensive. In 1978, community-based praziquantel treatment became the main approach to control schistosomosis. This period saw dramatic decreases in the national prevalence of S. japonicum infection (Olveda 2006). The most impressive impact was attributed to the implementation of the Philippines Health Development Plan in 1990–95. The National Schistosomosis Control Service was able to intensify case finding and treatment in all endemic areas and reduced the national prevalence from more than 10% before 1990 to less than 5% after 1995 (Hernandez 2003). However, the presence of animal reservoirs was believed to limit the effectiveness of chemotherapy alone at eliminating schistosomosis. Interruption of treatment for more than two years resulted in rebound morbidity and intensity of S. japonicum infection (Leonardo et al. 2002).

Only two isolated areas are endemic in Indonesia, namely Lindu valley and Napu valley, both located in the Province of Central Sulawesi (Hadidjaja 1985). Over the past six decades, schistosomosis control has been implemented and the average prevalence is now much lower. In 2006, the prevalences were 0.5% in seven villages in Lindu valley and 1.1% in 17 villages of Napu valley, respectively. The corresponding prevalence of infection in snails ranged from 0–13.4% and 0–9.1%, respectively (Garjito et al. 2008). The present data indicate that transmission of schistosomosis is ongoing despite regular surveillance and control activities covering the whole endemic area.

Strong political commitment is a key element in successful control, which requires persistent efforts and a systematic step-by-step approach with increasingly ambitious targets to reach elimination (Wang et al. 2009b). There are several limitations to the above-mentioned achievements. First, the successful snail control programmes in Japan were not duplicated elsewhere (Leonardo et al. 2008). Second, the case-detection and praziquantel treatment approach renewed hopes of achieving control with limited resources. Third, the poor sensitivity of the Kato-Katz analysis using a single stool sample underestimates the true prevalence of infection (Lin et al. 2008a; Zhou et al. 2008; Zhang et al. 2009). Fourth, a reduction in coverage of the treatment (Tallo et al. 2008) strongly suggests that chemotherapy-based programmes must be combined with other control measures until an alternative, more effective approach, has been developed (e.g. vaccination) (Utzinger et al. 2005). Fifth, schistosomosis japonica have re-emerged, in terms of the total number of infected cases, in areas where transmission control and interruption had been declared previously (Liang et al. 2006) following the termination of chemotherapy programmes (Utzinger et al. 2005). The ongoing transmission in other endemic areas, albeit at a lower level, is also of considerable concern as the situation is likely to deteriorate as soon as control efforts are scaled down (Utzinger et al. 2005; Wang et al. 2008b). It is crucial for continued success to maintain and sustain the current efforts to further reduce transmission, through integration with other diseases control programmes.

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