|Year : 2018 | Volume
| Issue : 1 | Page : 1-12
Schistosomiasis: A neglected tropical disease of poverty: A call for intersectoral mitigation strategies for better health
Kaliyaperumal Karunamoorthi, Mohammed Jubran Almalki, Khalid Yaser Ghailan
Department of Environmental Health, Faculty of Public Health and Tropical Medicine, Jazan University, Jazan, Kingdom of Saudi Arabia
|Date of Submission||30-Oct-2017|
|Date of Acceptance||06-Feb-2018|
|Date of Web Publication||30-Apr-2018|
Prof. Kaliyaperumal Karunamoorthi
Faculty of Public Health and Tropical Medicine, Jazan University, Jazan
Kingdom of Saudi Arabia
Source of Support: None, Conflict of Interest: None
Schistosomiasis (SCH) is one of the neglected tropical diseases, and it is endemic over 78 resource-constrained countries. It is one the indicator of poverty as it is often ubiquitous among the poorest of the poor. A total of 172 potential articles were identified through premier academic-scientific databases, and 86 were chosen. Human beings (permanent-host) are often exposed to infested water (urine/stools of infected persons) that harbor susceptible snails during their routine domestic and occupational activities. The cercaria (released by snails [intermediate-host]) infects people by penetrating into their skin. Currently, several multi-faceted interventions are underway to combat the SCH, namely, (a) potable water, (b) environmental diagnostics, (c) prophylactic chemotherapy with praziquantel, and (d) scaling up of snail control. Although in the recent decades tremendous strides have been made to minimize the disease burden, they are so feeble to eliminate the infection in several poverty-stricken settings. Female genital-SCH is also one of the key parasitic cofactors of HIV transmission. However, it remains neglected in terms of priority in allocating sufficient resources to develop next-generation tools, i.e., vaccine. Therefore, there are challenges lying ahead in achieving our ambitious goal of global elimination. Nevertheless, it can be attained through the recent medical-technological advancements as well as by strengthening the ongoing multi-pronged interventions such as (1) generating awareness, (2) continual surveillance, (3) early case-detection, (4) mass deworming, (5) increasing the research funds, (6) developing sensitive diagnostic tools, (7) prophylactic vaccines, and (8) therapeutic agents. Besides, the improved disease surveillance and response systems could pave the way to build an SCH-free world in the near future.
Keywords: Mitigation strategies, neglected tropical disease, poverty, schistosomiasis
|How to cite this article:|
Karunamoorthi K, Almalki MJ, Ghailan KY. Schistosomiasis: A neglected tropical disease of poverty: A call for intersectoral mitigation strategies for better health. J Health Res Rev 2018;5:1-12
|How to cite this URL:|
Karunamoorthi K, Almalki MJ, Ghailan KY. Schistosomiasis: A neglected tropical disease of poverty: A call for intersectoral mitigation strategies for better health. J Health Res Rev [serial online] 2018 [cited 2020 Jun 2];5:1-12. Available from: http://www.jhrr.org/text.asp?2018/5/1/1/231536
| Introduction|| |
Infectious diseases of poverty (IDoP) disproportionately inflict the poorest section of the society worldwide and contribute to a “cycle of poverty” as a result of decreased productivity ensuing from a long-term illness, disability, and social stigma.,,,, Schistosomiasis (SCH) also known as Schisto, Bilharzia, or Snail Fever and it is one of the important IDoP and it is the collective name for infection by one (or more) of five trematodes flatworms, called Schistosoma species adapted to humans, namely, Schistosoma mansoni, Schistosoma japonicum, Schistosoma haematobium, Schistosoma mekongi, and Schistosoma intercalatum, or by species adapted to other mammals which can occasionally infect humans, Streptococcus bovis and S. magrobowei.
There are two types of SCH (1) Intestinal schistosomiasis (SCHi) and (2) Urinary schistosomiasis (SCHu). SCHu progressively damage to the bladder, ureters, and kidneys, whereas SCHi, progressively enlarge the liver and spleen, and cause intestinal damage, and hypertension of the abdominal blood vessels. It is prevalent in tropical and subtropical countries, especially among the marginalized sections of society, those living on 1 dollar a day with the lack of access to safe potable water and inadequate sanitation. It has been reported even among the poor living in the world's leading Group of Twenty countries.
Female genital schistosomiasis (FGS), infection increases the risk of HIV-1 infection in women. Genital lesions caused by the S. haematobium increased the risk of acquiring HIV infection threefold in women living in rural Zimbabwe. It probably increases the risk of HIV infection through both vertical and horizontal routes, as it causes genital lesions and “sandy patches” (areas that bleed easily) in the female genitals. SCH ranks second only to malaria as the most common parasitic disease and is the most deadly neglected tropical disease (NTD). It causes of about 280,000 death annually in the African region alone; an estimated 3.3 million disability-adjusted life years (it is a measure of overall disease burden, expressed as the number of years lost due to ill-health, disability, or early death) are lost annually.
| Global Burden of Neglected Tropical Diseases|| |
NTDs represent a group of seventeen major chronic, debilitating, and mostly parasitic infections among the poorest of the poor, with high endemicity in the developing countries of Africa, Asia, and the Americas. Although mortality rate is low, the NTDs inflict severe disabilities on almost 1 billion people globally. Besides, these diseases, particularly SCH, lymphatic filariasis, and onchocerciasis also impose severe socioeconomic burdens and considerable morbidity too. NTDs not only thrive among the poor, they actually promote poverty by weakening, maiming, stigmatizing, and isolating their victims and destroying their ability to learn, work, and contribute to their families and the nation at large.
Although these diseases have well-known, inexpensive, and effective treatments, their terrible toll only because of the world's neglect and inattention., In 2012, the World Health Organization (WHO) has announced the new goals for 2020, to eliminate several NTDs, so that they no longer pose public health issues. In the current era of intensified and integrated control against SCH and other NTDs, there is a need of rethinking and take into consideration of disease-specific issues pertaining to the diagnosis, prevention, control, and of course local elimination, wherever and whenever possible.
| Epidemiology and the Landscape of Schistosomiasis|| |
SCH remains to be a major public health concern., Currently, over the 200 million people infected with at least one species of Schistosoma globally. There are 78 endemic countries, but the greatest burden (≥1 million infections) occurs in thirty-African countries and Brazil. Nearly, 20–50 million people experience substantive disability, with 732 million people at risk in the known transmission settings. If these WHO values are adjusted for the probable 40%–60% of missed diagnoses, the actual number of active Schistosoma infections in 2007 was more likely between 391 and 587 million people worldwide. The largest numbers of cases of schistosomiasis infection are in Nigeria with 73 million cases, followed by Ethiopia, the Democratic Republic of the Congo, and Kenya, while countries with the highest prevalence of schistosomiasis infection are Angola and Gabon of central sub-Saharan Africa followed by several countries in eastern sub-Saharan Africa.
The most infected people are school-aged children under 14, those living in rural and urban slums settings. It causing growth retardation and anemia, Vitamin-A deficiency as well as possible cognitive and memory impairment, which limits their potential in learning.,,, They often suffer with severe, disabling, and sometimes fatal effects. The WHO (2017) has estimated that at least 206.5 million people required preventive treatment for SCH in 2016, out of which over 88 million were treated. Over decades, stringent efforts were made to eliminate SCH through the implementation of sustainable control strategies. However, available evidence suggesting that, both urinary and SCHi are still a matter of major public health concern and causing significant morbidity and disability in the endemic countries, particularly in SSA region.
In these perspectives, this systematic review becomes more significant and pertinent too. It is an attempt to sheds some light on the various features of SCH, particularly epidemiology, malacology, morbidity, transmission dynamics, pathophysiology, prevention, snail control, mass drug administration, and socioeconomic impact. Besides, it shall also elaborately discuss the existing challenges and emerging opportunities. The outcome of this scrutiny could pave the way for redefining the of existing intervention approaches such as preventive chemotherapy (PC), as well as to formulate the innovative community-based future intervention measures by the public health experts and policymakers through inter-sectoral action for health by involving an integrated multidisciplinary control approaches.
| Methods|| |
Data mining and extraction: Evidence acquisition
Data for this present review were identified and collected using manual and electronic extensive literature search strategies of published and unpublished sources. Electronic databases included PubMed, Google Scholar, Web of Science, EMBASE, and Global health. References of relevant articles were also screened. Manual identification of unpublished literature sources, including unpublished project surveys, university theses, conference papers and public health organization reports was conducted at the library of Jazan University, Kingdom of Saudi Arabia. We sourced English language papers that were fully published mainly between 1990 and April 2017 using appropriate index terms.
To identify relevant studies on SCH, the search initially began with the text string “schistosoma” and a combination of the following words in permutations were used to extract suitable studies “SCH + epidemiology,” “SCH + transmission,” “SCH + prevention and control,” and “SCH + snail control,” “SCH + mass drug administration,” and “SCH + poverty.” The exclusion and inclusion criteria for choosing the appropriate research articles, notes, and reviews were shown in [Figure 1] for this narrative review, and their bibliographic details (authors, title, full source, document type, and addresses) have been downloaded and maintained in a file. As shown in [Figure 1], PRISMA flow diagram shows the exclusion and inclusion of studies for the present scrutiny.
|Figure 1: The exclusion and inclusion criteria, for choosing the appropriate research articles, notes and reviews for this narrative review|
Click here to view
| Results|| |
The study selection process is shown in [Figure 1] as a PRISMA flow diagram. Of the 234 potentially relevant unique citations from all literature searches, 87 studies met the inclusion criteria. Sixty-nine studies were empirical research studies and nine involved meta-analysis, with the rest involving case reports or reviews. Two-third of studies were conducted in the WHO-defined African region (n = 52), and another major studies were conducted in the Southeast Asian region (n = 24); most were published in between 1995 and 2017. We found that about nine out of ten studies describe the prevalence, existing challenges, emerging opportunities and public health impact of SCH in the poverty-stricken settings of Africa and southeast Asia; the remaining studies examined the actual extent of successful SCH intervention and their clinical and socioeconomic impact worldwide, particularly in the resource limited settings.
| Discussions|| |
History of schistosomiasis
In ancient Egypt, S. haematobium was well documented  and archaeological evidence suggests that SCH, plagued residents of the Nile-valley basin since prehistorical era. Ancient Egyptian mummies revealed that humans have been harboring schistosome parasites for over 5000 years. Pharaonic physicians described on bloody urine that is still the disease's most prominent symptom and mummies have yielded the worm eggs too.
Schistosomiasis: An infectious disease of poverty
It is reported to exist in 78 countries in the Middle East, South America, South-East Asia, and particularly in Africa. Senegal has reported highest transmission rate in the world. It affects the poorest of the poor, those living in remote rural areas or deprived urban settings, those limited access to quality health-care services, pipe-lined water, sanitation, and education. In the present day, SCH is considered as an NTD, one of several groups of preventable as well as treatable illnesses that still rapidly spreading in conditions of poverty; and receive far less attention. Therefore, now, it has to be approached as a disease of poverty, and it is conceivable to argue that the presence of SCH can be used as an indicator of poverty.
Urogenital transmission of multiple parasites and their resultant overlapping chronic infections are facts of daily-life in several underdeveloped rural settings. A previous report has documented the increased risk of subfertility, as well as an ecological association between urogenital SCH prevalence and decreased fertility  in sub-Saharan Africa. The chronic SCH contributes anemia and undernutrition, which, in turn, can lead to stunted growth, poor academic performance, poor work productivity, and ultimately unalleviated poverty.
Thus, SCH to be regarded as an equity issue, as the disease is more widespread among impoverished populations. Besides, it is now well-recognized as being associated with nutritional deficiencies. It is important to note that though, helminths diseases are more insidious in nature and do not rapidly cause death, like other killer diseases for instance malaria. Thus, they are often poorly-measured in terms of health and socioeconomic burdens  and seldom given priority by health-care providers. There is strong evidence that wherever the essential financial and other basic resources exist, we can contain the SCH associated-illness markedly such as China, Brazil, and Egypt. Nevertheless, elimination as a public health threat has proved as a quite challenging task.
Schistosome parasites are potentially contaminate freshwater bodies such as lakes and rivers. The tiny white-gray color parasites measure between 7 and 20 mm long. They are adept of burying into human skin and can migrate into other parts of the body, namely, liver or bladder. SCHi caused by infection with the trematodes S. mansoni, S. mekongi, S. japonicum, and S. intercalatum, and whereas SCHu caused by infection with S. haematobium [Table 1].,
|Table 1: Parasite species and geographical distribution of schistosomiasis (WHO, 2017)|
Click here to view
Disease transmission cycle
Transmission often a periodic, inhomogeneous process and even a single untreated infected individual can contaminate a water-body and convert it to a high-risk transmission zone. A infected asymptomatic victim can threaten a whole community for several months to years., The recent WHO report (2017) also reconfirmed the transmission in 78 countries worldwide, and the prominent transmission sites include Lake Malawi, Lake Victoria in Africa, the Poyang and Dongting Lakes in China, and along the Mekong River in Laos.
Leiper  first established the life-cycle of S. japonicum, and it requires alternate development between an intermediate-host (snail) and the final mammalian host, both are obligatory to maintain the parasite. The complex Schistosoma infection requires, three key components: (1) contaminated water bodies with feces or urine containing schistosome eggs, (2) a specific freshwater snail, and (3) human contact with infested water that harbor the larval forms (cercariae; [infective stage]) of schistosomes.,
Transmission mechanism as follows CDC (2016); (1) infected person releases Schistosoma-eggs in the freshwater bodies, (2) eggs hatch and release miracidia, (3) subsequently, the miracidia penetrate into the snail (intermediate host), (4) development of sporocysts in snail (successive generation), (5) freshwater snails release the larval forms (cercariae), (6) they penetrate the skin of people, and locate in the intestines (S. mansoni generally) or the urinary tract (S. haematobium), (7) cercariae lose tail during penetration (turned into schistosomule), (8) through circulation migrate whole human body, and (10) the larvae develop into adult (live in the blood vessels), and the female worms release eggs (some of them passed out of the body through urine/feces, while others trapped within the body tissues, causing an immune response; [diagnostic stage]), and continue their life cycle [Figure 2].
Three high-risk groups have been identified Watts (2006):
- Pregnant and lactating women while exposed to infested water during domestic activities
- Preschool and school-aged children 
- Adults from special groups – (occupations involving contact with infested water, viz., fishermen, farmers, irrigation workers, or women in their domestic tasks), to entire communities living in SCH-endemic settings.
Notably, since women and children (under the age of fourteen) are spend their most of time in water bodies to wash their clothes, dishes, fetching water and bathing, thus make them at the highest risk.
Schistosomiasis and HIV/AIDS transmission
It is one of the important parasitic co-factors of HIV transmission, as S. haematobium species colonize the genitourinary tracts of infected female victims. First, Feldmeier et al. evidently exhibited that the FGS increases the vulnerability to HIV risk and subsequently it has been confirmed by other researcher too. FGS promotes the HIV transmission not only because of general effects such as parasitic load, nutritional deficiency, and immune activation but also through its direct effect on the immune system barriers (skin and mucosa) and the cell-mediated response. Lesions are generally located in the vulva and vagina among the young girls, however, at sexual maturity, they become more numerous and cluster in the cervix in young women. Nevertheless, only limited number of studies were performed to prove genital SCH among the men, but there are indications that it can also promote HIV transmission.
Symptoms, pathophysiology, and the clinical disease
SCH progresses in three distinct phases: (a) acute, (b) chronic, and (c) advanced condition. Initially, rash (a maculopapular eruption) occur at the site of percutaneous penetration of cercariae. Katayama syndrome (acute-SCH) present with the following clinical manifestations, namely, fever, malaise, myalgia, fatigue, non-productive cough, diarrhea (with or without blood), and right upper quadrant pain. However, whereas the chronic condition exists due to lack of appropriate treatment results from the host's immune response to schistosome eggs deposited in the tissues and the granulomatous reaction evoked by the antigens secrete by the schistosome parasites, rather than excreted with the feces or urine. Severe chronic intestinal infection result in colonic or rectal stenosis  and an inflammatory masses in the colon and even now and then mimic cancer too.,
Fibrosis of the bladder ureters, kidney and liver damage often recognized during the advanced stage.,, SCHi can result in colicky hypogastric pain or pain in the left iliac fossa, that may alternate with constipation, dyspareunia (painful intercourse), dysuria (painful urination), and hematochezia (blood in the feces), while the classic sign of urogenital SCH is hematuria (blood in the urine).,, Besides, the chronic parasitic infections can impair protective responses against numerous unrelated acute bacterial and viral infections, including impaired responses to various childhood vaccines., Neuroschistosomiasis is considered as a most severe clinical syndrome of SCH.
Diagnostic tools and techniques
Since many of the complications are correlated with the parasite burden, the determination of the intensity of infection is extremely imperative in the SCH endemic regions. It can be diagnosed by means of quantitative sampling of 20–50 g of stool (Kato-Katz technique) or a standardized volume of urine through a Nuclepore membrane test. However, Kato-Katz remains considered to be a gold-standard for quantification of egg burden, and it must be calculated by collecting 24 h stool sample. Since the urinary excretion of eggs is not uniform, the urine sample must be collected for S. haematobium from 10 AM to 2 PM to acquire the accurate result. Since Kato-technique needed adult worms to produce eggs, just 40–60% of sensitivity has been observed when performing on a single stool specimen.,
Importance of serological screenings
Although parasitological methods are widely performed for the diagnosis, they are often insensitive, particularly in low-endemic areas, and labor intensive. Therefore, detection of parasite antigens could indicate the real status of infection. Accordingly, it demands numerous serological tests/immunoassays to diagnose initial phases of infections. It has been reported that urine analysis by polymerase chain reaction assay could provide 94.4% sensitive and 99.9% specific for SCH. Besides, the following serological assays have also often been performed (1) Falcon Assay Screening Test, (2) Enzyme-Linked Immunosorbent Assay (ELISA), and immunoblot assays [Western blot (used to detect protein); Northern Blot (used to detect RNA); and whereas Southern Blot (used to detect DNA)] because of their high sensitivity and accuracy. The sensitivity and specificity of ELISA tests reported to be >90% and 95%, respectively. The western blot often performed to reconfirm the ELISA results. Egg viability test used to assess the effectiveness of the therapeutic agents.
Control of SCH with the single intervention is a quite challenging task to achieve our ambitious goal of global elimination because of the complex disease transmission mechanism. Thus, calls for a sustainable and cost-effective integrated approaches and currently, the following four major intervention strategies have been adopted in the various endemic settings:
- Snail (intermediate host) control by application both chemical molluscicidal and introduction of biocontrol agents
- Morbidity control strategy through mass-chemotherapy (elimination of the parasite from the definitive host; [human])
- Health education and promotion campaigns
- Integrated SCH control strategy to interrupt transmission and the eventual proper vaccine administration with the reliable one.
Current major challenges and future prospects
In recent decades, we have attained remarkable progress in respect to declining the number of new cases and its associated morbidity substantially. However, there are enormous challenges that lie ahead to achieve global elimination, namely, (1) existence of extensive snail habitats, (2) alteration of ecosystem, (3) anthropogenic activity on biophysical environments, (4) the concomitant impacts of climate change coupled with the key geoclimatic factors,, (5) limited access to quality health-care facilities, (6) poor surveillance and response system, and (7) lack of specific monitoring and evaluation mechanism. Besides, the man-made sustainable development projects such as (a) new water-management and development projects, (b) dam constructions, (c) unplanned urbanization, and (d) unchecked population spurts have engendered wide range of snail habitats thus created new endemic foci of SCH infections.
Evidently, new dam construction projects have triggered high prevalence (nearly threefold) of SCH in a number of African settings. Since, SCH transmission is greatly reliant on ecological factors global warming also attributed the emergence of SCH in the previously unknown settings. It highly influences the several water-borne diseases transmission patterns and distribution too., Indeed, preventing the spread of infection is a critical phase to lessen the morbidity but the existing inventions often fall short to contain new and high rate of reinfection, even after the implementation of preventive mass chemotherapeutic intervention with praziquantel (PZQ). However, the emerging opportunities are discussed in greater detail below to scaling-up SCH control activities worldwide.
Growing opportunities: Tools for improving health and transforming future
Perhaps, there are several challenges existing to achieve our long-term ambitious goal of SCH elimination. However, the recent technological and bio-computational advancement in terms of novel techniques and tools have offered an ideal platform to combat the SCH successfully than ever before. Since, it is one of the most complex diseases, attaining the goal of elimination is quite challenging and it demands novel integrated-control initiatives for targeting SCH.
Risk profiling by predictive modeling
Remote sensing and geographic information systems
Since 1970s, the potential use of remote sensing (RS) and geographic information systems (GIS) techniques has noticeably enhanced our knowledge and understanding on the eco-epidemiology of SCH. Subsequently, adequate progress has been made in mapping the prevalence and the distribution of intermediate host (snails). Furthermore, RS-GIS also extremely useful to detect environmental alteration that may neither directly nor indirectly influences on the occurrences of a disease. Thus, indicates both the control of transmission and monitoring of the high-risk areas through knowledge of (a) changes in the plant coverage, (b) topography, and (c) water courses, before and after an episode of flooding, through the spatial models of GIS and RS.
Several studies emphasized the potential use of RS-technique to predict the risk of infection, thereby understanding on the large-scale ecology and distribution patterns of SCH. It also highlighted the direct and indirect impact of various determining factors within the microenvironment (parasite and snail) in relation to disease transmission. Bayesian geostatistical modeling techniques have been successfully performed by Simoonga et al. for predicting the prevalence and intensity of infection at different scales in Africa.
Major challenges to make risk profiling by predictive modeling
Nevertheless, the implementation of predictive modeling for the risk profiling a number of challenges remain ahead, namely, (1) spatial and temporal resolution is quite imperative to develop high-risk mapping for understanding the transmission dynamics at the local scale, (2) more realistic risk profile mapping can be constructed by feeding the local residents socioeconomic associated information, (3) adequate efforts must be made to incorporate data on easy-access to clean water, adequate sanitation, education and behavioral issues, (4) intermediate host (snail) distribution, and (5) prediction of multiple species parasitic infections could facilitate validation of infection risk maps and modeling of transmission dynamics, to enhance the sustainability and cost-effectiveness of the existing interventions. Besides, further research must be conducted to overcome the above-cited limitations.
Snail control strategies
Zero-infection can be achieved by adopting appropriate interventions to eliminate the intermediate host (snail) and it can be done through the application of molluscicidal agents. It is one of the key intervention strategies to control SCH. However, there are demerits to implement the snail control strategy, namely, (1) expensiveness and (2) toxicity of the chemicals, which could adversely affects other aquatic beneficial organisms such as fish and the eco-system too.
Alteration of the aquatic environment
Altering the rate of water-flow, clearance of vegetation, and drainage (canals) at certain times of the year could substantially minimize the fresh-water snail population considerably. However, it may not be practical in terms of economical or environmental reasons. It may be harmful to fish populations and even sometimes it could create conducive environment for other disease causing and transmitting agents. Alternatively, increasing rate of water flow may inhibit snail populations, but may then be suitable for colonization by Simulium larvae, the vectors for river blindness.
Biological control of snails
Introduction of competitor snail species like Marisa cornuarietis will compete with Biomphalaria snails for food, and eat its eggs, and has been used in Puerto Rico as a potential biocontrol agent. Other method like introduction of snail eating fish has also been suggested. However, the use of molluscivorous fish as a snail biocontrol agent has not yet been well-demonstrated. The cichlid fish (Astatoreochromis alluaudi) has been introduced in Kenya and Cameroon for field trials. Although initially it was successful in the long-run, it becomes ineffective.
Cultivation of certain plants on the sides of waterways has been used to control snail. The berries of Endod (vernacular name [local native language, Amharic]; Phytolacca dodecandra) have been proved as a natural molluscicidal agent when they fall into the river and streams. This plant often existence on the both sides of rivers in Ethiopia. Berries of Endod have been used as a detergent soap for washing clothes and to control fresh water snails by the Ethiopian rural community even today. It has been shown to be associated with a reduction in local snail population. However, in Ethiopia a study conducted by Karunamoorthi et al. demonstrated that the release of Endod berries extract could adversely affect the aquatic ecosystem, particularly food chain in the streams and rivers.
Duval et al. reported a bacterial pathogen of snails (Paenibacillus glabratella) that causes high snail mortality. The pathogen may transmit from adults to eggs (transovarial), and the infected eggs are less likely to hatch successfully. However, further studies are warranted to understand their impact on the other invertebrates in the aquatic ecosystem too.
Morbidity control strategy through preventive chemotherapy
In endemic areas, every resident is considered to be at risk of the infection and its sequelae. Therefore, large-scale chemoprophylaxis must targets all the eligible individuals in the communities. Besides, there is also a necessity for recurrent retreatment thus limits the success of control efforts, particularly in sub-Saharan Africa, which harbors about 90% of infection worldwide. WHO (2013) documented that though transmission occurs in 78 countries; the mass drug administration is directed to high-risk population groups, those living in 52 endemic countries only.
PZQ remains the drug of choice, and it can cure the infection, often in a single dose. In the 1980s, PZQ was introduced and targeted the high risk-groups through the primary healthcare system. The doses of PZQ varies according to the species of Schistosoma infections (60 mg/kg in three doses per day [S. japonicum and S. mekongi]; while 40 mg/kg in doses per day [S. mansoni, S. haematobium, S. intercalatum]) The cost of a single 600 mg tablet is about US$ 0.08 and an average treatment is estimated to be between US$ 0.20 and 0.30. The WHO recommended dose of PZQ, more effective for all types of SCH and oxamniquine is a valid alternative, but only effective against S. mansoni.
In 2012, alone more than 42 million people, nearly 83% of whom are in sub-Saharan Africa, were successfully treated. The major objectives were prioritizing high-risk individuals, particularly school-age children, who exposed to largest number of infections and shed the largest number of schistosome worms  owing to their frequent water contact behavior. The recent international support to control the NTDs, as well as increased access to PZQ, led to a significant improvement to combat the disease successfully. Mass drug administration in endemic areas resulted to decline in disease severity and intensity too.
It is recommended that preschool-aged children (PSAC) should be treated within child-health services where their weight is monitored; they are immunized, dewormed, and given micronutrient supplements. PZQ is now available free-of-cost to high-disease burden countries in Sub-Saharan Africa, through a donation from Merck Serono to the WHO. PSAC are often excluded from existing control initiatives because of limited evidence of infections burden among the age group. Although there is a low-level of SCH, high prevalence of intestinal helminthiasis and poor nutritional status prevailing that calls for inclusion of PSAC in control programs.
In the low-endemic settings, only children were screened and treated, if they found positive for infection. Infected cattle were also treated under the World Bank project. Miller-Fellows et al. have documented that the urogenital SCH is linked with a high prevalence of subfertility rate. It demands appropriate and adequate early antischistosomal modalities to avert and treat pelvic infections in their initial stages itself. The existing evidence suggesting that early treatment could substantially preclude subfertility and reproductive tract impairment in the S. haematobium endemic settings. In highly endemic areas, severe morbidity can be minimized by regular treatment to the risk groups.
In general, chemoprophylaxis administered with a single oral dose of PZQ 40 mg/kg. The experience learned from China and Egypt indicates that the high coverage of preventive mass chemotherapy, without individual diagnosis, could result on significant impacts on indices of infection and also reduced requirements for PZQ. Since, it is safe even during the pregnancy, it is recommended to include the women, and adolescent girls of child-bearing age in public health intervention campaigns. The implementation of large-scale Preventive Chemotherapy and Transmission Control is considered to be a mainstay of SCH control., WHO (2016) recommended to estimate the population requiring PC for SCH annually using the following model [Table 2].
|Table 2: WHO recommended population requiring preventive chemotherapy in the various endemic settings (WHO, 2016)|
Click here to view
Integration with other anthelminthic drugs
The WHO strategy on the use of antihelminthic drugs now makes it possible to control SCH, in conjunction with other interventions against lymphatic filariasis, onchocerciasis, and soil-transmitted helminthiasis. PZQ has been safely co-administered with albendazole and ivermectin, in areas where these drugs have been used separately for PC.
Changing the mindsets: Inform and involve residents
Currently, all endemic countries are encouraged to increase control efforts and move toward elimination as required by the WHO roadmap for the global control of the NTDs. The following intervention measures are implemented in various endemic settings.
Health education and promotion campaigns
The major objective is to promote the health behavior among the high risk-population, and it has tremendous potential in health promotion campaigns, largely from an individual perspective to reduce the burdens of disease through preventive measures. This behavioral change is heavily relies on the motivation of the at-risk individual to accept treatment as well as on the health-care provider or community volunteer adequately informing and motivating the community. Health education and promotion program managers often advised to seek the assistance of social scientists and communication experts in planning and evaluating such strategies.
It is quite inevitable to succeed the local elimination of SCH, and it can be achieved through active community-based health education campaigns by changing the people mindsets toward the disease by means of novel print and electronic media. There is a universal concurrence that the media, particularly social media is vital tool in the dissemination and publicization of the key research findings. In recent decades, the Information and Communication Technologies has shown unprecedented upswing in the emerging economies, particularly in the SCH endemic countries. Therefore, it is offered a new platform to change the people mindsets through active health education to combat the SCH more competently by confiscating the people misconception  on SCH.
Investment in social mobilization strategies is critical to sustaining high drug coverage throughout the disease control program. Indeed, there is a major gap exists between the development of new health intervention tools and their delivery to communities in the developing world. Similarly, many new interventions miserably fail to produce results when transferred to communities in developing countries, largely because their implementation is untested, unsuitable or incomplete. Health education mass movements were developed to mobilize community resources to contribute to the control of snail hosts of bilharziasis and fascioliasis, through free labor, and local-driven innovative models for snail elimination. It is handy not only to control the disease but also helpful to create a supportive populace in the society to improve the overall health of affected communities in the endemic areas.
In health development, there are three distinct forms of community participation. These have been defined as marginal, substantive, and structural Marsden and Oakley  WHO (2008):
- Marginal participation is limited in scope and implies a very limited influence on the development process
- Substantive participation affords community members the opportunity of determining their needs, contributing to the activities and receiving the benefits. Nevertheless, they have no role in decision-making
- Structural participation is the third and perhaps most broadly-based expression of the community participation concept members of disease-endemic communities play an active and direct role in project development.
Poverty alleviation programs
Both the Millennium Declaration and its eight Millennium Development Goals for sustainable poverty reduction were instrumental in shaping global health policy. The WHO recently put forward an ambitious goal for the year 2020 to control SCH globally and it demands multifaceted approaches. Since the SCH considered as a disease of poverty and it must be rationally addressed through Poverty Reduction Strategies via uplifting the economic and financial status of the weaker and vulnerable sections of the society in the SCH endemic countries.
Development of schistosomiasis vaccine
Despite the availability of potent drug (PZQ), millions of people still suffer from severe morbidity worldwide due to lack of reliable vaccine against schistosome. Accordingly, it demands next-generation alternative intervention tools such as propholytic vaccine to minimize the disease burden in the endemic settings. In spite of several decades of persistent international commitment toward the development of critically needed new tool, namely, functional vaccine has not yet been achieved. It has been reported that immunization with defined antigens is generally less effective than vaccination with attenuated infective cercariae , and majority of the scientists persuaded that potent vaccines can be developed via irradiated cercariae as they induce over 70% protection.
In past decade, several promising candidates have been formulated and scrupulously investigated; the findings were validated in various laboratories worldwide. Nevertheless, many of them have suffered in terms of successive challenges such as scaling-up production, and notably, technical feasibility is one of the important criterions in assessing the candidacy of vaccine. Majority of the candidate vaccines are targeting to contain the infection alone (except Sh28-GST and Sm28-GST; [target both infection and parasite fecundity]). Therefore, adequate research must be focused to develop vaccine that addresses both antimorbidity and transmission blocking. The vaccination should be implemented as a complementary intervention tool with the existing chemotherapy to sustain the infection  in the future.
Importance of integrated control strategies
There is considerable evidence suggest that the following integrated SCH control approaches must be included to sustain existing interventions as well as to achieve elimination, namely, (a) provision of potable, (b) improved sanitation, (c) snail control, (d) behavioral change, and (e) availability of safe and potent drugs., Besides, political will and support from national governments, institutions, and the local population coupled with inter-sectoral collaboration between the health, water and sanitation, as well as education sectors are key features to achieve sustainable control of SCH.,,,
Furthermore, appropriate fecal management, some engineering related interventions, such as agriculture irrigation system modification, altering the crops planting, and biogas station could be considerably useful. In addition, novel molecular tools could enable rapid surveillance and monitoring of schistosome transmission over extended areas. Subsequently, effective integrated transmission control approaches could be implemented to optimize the design of the next generation SCH morbidity control and prevention programs, and tailor intervention strategies to specific settings. Otherwise, sustainability of interventions is certainly critical issues.
| Conclusions|| |
Indeed, SCH is the second most common disease caused by parasites after malaria and is one of the most deadly NTDs. Despite several decades control initiatives, SCH continues to impose severe subtle morbidities among the underprivileged poorest-section of the rural and urban communities. Although it is a chronic and debilitating disease; it is poorly noticed within the global public-health agenda; ultimately it often neglected or underestimated miserably. Although currently there are active efforts are made to build research capacity and interventions to combat the disease-burden across diverse endemic settings, but they are incompetent to eliminate the disease due to inadequate resources. Therefore, it requiring stringent efforts and concrete actions.
The present scrutiny has identified a number of challenges as the major barrier that needs to be addressed effectively by exploiting locally-available resources and targeting millions of impoverished people. They are also deserves to access quality healthcare and inclusive socioeconomic development like their mainstream society, as their fundamental basic rights. Indeed, it demands clear and sustained political commitments by all pertinent stakeholders to effectively plan, implement, and deliver through prioritizing tailored interventions. Besides, it also requisites adequate attention from the global health community to pipeline front-line resources by considering the prevailing sociodemographic and health status of infected people to prevail over the identified barriers.
Global public health perspective, effective communication strategies such as training, radio adverts, and community-based meetings are crucial for the successful implementation of change initiatives to interrupt disease transmission and boost socioeconomic development in the poverty-stricken SCH-endemic settings. Conclusively, strong multifaceted intersectoral collaboration for strengthening the linkage of research to policies and practices among the all key stakeholders are extremely important to move into positive and active subsequently to build an SCH free world in the near future.
We sincerely thank Mrs. L Melita for her assistance in editing this manuscript. We acknowledge Dr. Rajathilagar, Dr. Embialle, and Mr. Kumar, of Jimma University, Ethiopia for their assistance in independently assessing and screening the search results by title and abstract for potential eligibility. My heartfelt thanks go to colleagues from the Department of Environmental Health, Faculty of Public Health and Tropical Medicine, Jazan University, Jazan, Kingdom of Saudi Arabia, for their kind constant support and cooperation.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Molyneux DH, Hotez PJ, Fenwick A. Rapid-impact interventions: How a policy of integrated control for Africa's neglected tropical diseases could benefit the poor. PLoS Med 2005;2:e336.
Manderson L, Aagaard-Hansen J, Allotey P, Gyapong M, Sommerfeld J. Social research on neglected diseases of poverty: Continuing and emerging themes. PLoS Negl Trop Dis 2009;3:e332.
Karunamoorthi K. Global malaria burden: Socialomics implications. J Soc 2012;1:e108.
Karunamoorthi K. Malaria vaccine: A future hope to curtail the global malaria burden. Int J Prev Med 2014;5:529-38.
Karunamoorthi K. The counterfeit anti-malarial is a crime against humanity: A systematic review of the scientific evidence. Malar J 2014;13:209.
WHO. Preventive Chemotherapy in Human Helminthiasis. Coordinated use of Anthelminthic Drugs in Control Interventions: A Manual for Health Professionals and Program Managers. Geneva, Switzerland: World Health Organization; 2006. Available from: http://apps.who.int/iris/bitstream/10665/43545/1/9241547103_eng.pd
. [Last accessed on 2018 March 19].
Kjetland EF, Kurewa EN, Ndhlovu PD, Midzi N, Gwanzura L, Mason PR, et al.
Female genital schistosomiasis – A differential diagnosis to sexually transmitted disease: Genital itch and vaginal discharge as indicators of genital Schistosoma haematobium
morbidity in a cross-sectional study in endemic rural Zimbabwe. Trop Med Int Health 2008;13:1509-17.
Wang B, Collins JJ 3rd
, Newmark PA. Functional genomic characterization of neoblast-like stem cells in larval Schistosoma mansoni
. Elife 2013;2:e00768.
Hotez PJ, Alvarado M, Basáñez MG, Bolliger I, Bourne R, Boussinesq M, et al
. The global burden of disease study 2010: Interpretation and implications for the neglected tropical diseases. PLoS Negl Trop Dis 2014;8:e2865.
Hunt P. The human right to the highest attainable standard of health: New opportunities and challenges. Trans R Soc Trop Med Hyg 2006;100:603-7.
Karunamoorthi K, Kassa E, Endale A. Knowledge and beliefs about causes, transmission, prevention and control of onchocerciasis among the rural inhabitants in an endemic area of Ethiopia. Int Health 2009;2:59-64.
Benderly BL. Ending Schistosomiasis. Disease Control Priorities Project (DCPP), 02 April, 2009. Available from: http://www.dcp2.org/features/81
. [Last accessed on 2017 Feb 23].
Karunamoorthi K. Tungiasis: A neglected epidermal parasitic skin disease of marginalized populations – A call for global science and policy. Parasitol Res 2013;112:3635-43.
Knopp S, Becker SL, Ingram KJ, Keiser J, Utzinger J. Diagnosis and treatment of schistosomiasis in children in the era of intensified control. Expert Rev Anti Infect Ther 2013;11:1237-58.
Knopp S, Mohammed KA, Ali SM, Khamis IS, Ame SM, Albonico M, et al.
Study and implementation of urogenital schistosomiasis elimination in Zanzibar (Unguja and Pemba islands) using an integrated multidisciplinary approach. BMC Public Health 2012;12:930.
King CH. Parasites and poverty: The case of schistosomiasis. Acta Trop 2010;113:95-104.
Herricks JR, Hotez PJ, Wanga V, Coffeng LE, Haagsma JA, Basáñez MG, et al
. The global burden of disease study 2013: What does it mean for the NTDs? PLoS Negl Trop Dis 2017;11:e0005424.
Ross AG, Bartley PB, Sleigh AC, Olds GR, Li Y, Williams GM, et al
. Schistosomiasis. N
Eng J Med 2002;346:1212-9.
McManus DP, Gray DJ, Li YS, Feng Z, Williams GM, Stewart D, et al
. Schistosomiasis in the peoples' republic of China: The era of the three gorges dam. Clinic Microbiol Rev 2010;23:442-66.
Gryseels B, Polman K, Clerinx J, Kestens L. Human schistosomiasis. Lancet 2006;368:1106-18.
WHO Schistosomiasis. World Health Organization Fact Sheet. (b) Watts, Susan 2007. “The Social Determinants of Schistosomiasis. Working Paper 11.” Report of the Scientific Working Group Meeting on Schistosomiasis – Geneva 14-16 November, 2005. Geneva: World Health Organization; 2007. Available from: http://apps.who.int/iris/bitstream/10665/69482/1/TDR_SWG_07_eng.pdf
. [Last accessed on 2017 Dec 14].
WHO. Schistosomiasis. Fact Sheet No. 115. October 2017. Estimates Show that at Least 206.5 Million People Required Preventive Treatment for Schistosomiasis in 2016, Out of Which More than 88 Million People were Reported to Have Been Treated. Available from: http://www.who.int/mediacentre/factsheets/fs115/en/
. [Last accessed on 2017 Dec 14].
Barakat RM. Epidemiology of schistosomiasis in Egypt: Travel through time: Review. J Adv Res 2013;4:425-32.
Tan SY, Ahana A. Theodor bilharz (1825-1862): Discoverer of schistosomiasis. Singapore Med J 2007;48:184-5.
Hotez PJ, Engels D, Fenwick A, Savioli L. Africa is desperate for praziquantel. Lancet 2010;376:496-8.
Miller-Fellows SC, Howard L, Kramer R, Hildebrand V, Furin J, Mutuku FM, et al.
Cross-sectional interview study of fertility, pregnancy, and urogenital schistosomiasis in coastal Kenya: Documented treatment in childhood is associated with reduced odds of subfertility among adult women. PLoS Negl Trop Dis 2017;11:e0006101.
King C, Mahmouud AA. Schistosomiasis. In: Guerrant R, Walker DH, Weller PF, editors. Tropical Infectious Diseases. Principles, Pathogens and Practice. Vol. 2. Philadelphia, PA: Churchill Livingstone; 1999. p. 1031.
Gray DJ, Ross AG, Li YS, McManus DP. Diagnosis and management of schistosomiasis. BMJ 2011;342:d2651.
Leiper R. Report on the results of the Bilharzia mission in Egypt: Part I. Transmission. J R Army Med Corps 1915;25:1-55.
Adeniran AA, Mogaji HO, Aladesida AA, Olayiwola IO, Oluwole AS, Abe EM, et al.
Schistosomiasis, intestinal helminthiasis and nutritional status among preschool-aged children in sub-urban communities of Abeokuta, southwest, Nigeria. BMC Res Notes 2017;10:637.
Stillwaggon E. The Ecology of Poverty: Nutrition, Parasites, and Vulnerability to HIV/AIDS. In: Gillespie S, editors. AIDS, Poverty, and Hunger: Challenges and Responses. Durban, South Africa: Highlights of the International Conference on HIV/AIDS and Food and Nutrition Security; 2005. p. 14-6.
Feldmeier H, Poggensee G, Krantz I, Helling-Giese G. Female genital schistosomiasis. Trop Geograph Med 1995;47:2-15.
Harms G, Feldmeier H. HIV infection and tropical parasitic diseases-Deleterious interactions in both directions? Trop Med Int Health 2002;7:479-88.
Marble M, Key K. Clinical facets of a disease neglected too long. AIDS Wkly Plus 1995;7:16-19.
Gray DJ, McManus DP, Li Y, Williams GM, Bergquist R, Ross AG, et al.
Schistosomiasis elimination: Lessons from the past guide the future. Lancet Infect Dis 2010;10:733-6.
Ndhlovu PD, Mduluza T, Kjetland EF, Midzi N, Nyanga L, Gundersen SG, et al.
Prevalence of urinary schistosomiasis and HIV in females living in a rural community of Zimbabwe: Does age matter? Trans R Soc Trop Med Hyg 2007;101:433-8.
Malhotra I, Mungai P, Wamachi A, Kioko J, Ouma JH, Kazura JW, et al.
Helminth- and bacillus calmette-guérin-induced immunity in children sensitized in utero
to filariasis and schistosomiasis. J Immunol 1999;162:6843-8.
Labeaud AD, Malhotra I, King MJ, King CL, King CH. Do antenatal parasite infections devalue childhood vaccination? PLoS Negl Trop Dis 2009;3:e442.
Peters P, Kazura JW. Update on diagnostic methods for schistosomiasis. Baillere's Clin Trop Med Commun Dis 1987;2:419.
De Vlas SJ, Gryseels B, van Oortmarssen GJ, Polderman AM, Habbema JD. A pocket chart to estimate true Schistosoma mansoni
prevalences. Parasitol Today 1993;9:305-7.
Carabin H, Marshall CM, Joseph L, Riley S, Olveda R, McGarvey ST, et al.
Estimating the intensity of infection with Schistosoma japonicum
in villagers of Leyte, Philippines. Part I: A Bayesian cumulative logit model. The schistosomiasis transmission and ecology project (STEP). Am J Trop Med Hyg 2005;72:745-53.
Coulibaly JT, N'Goran EK, Utzinger J, Doenhoff MJ, Dawson EM. A new rapid diagnostic test for detection of anti Schistosoma mansoni
and anti Schistosoma haematobium
antibodies. Parasit Vectors 2013;6:29. doi: 10.1186/1756-3305-6-29.
Macalanda AM, Angeles JM, Moendeg KJ, Dang AT, Higuchi L, Inoue N,et al
. Evaluation of Schistosoma japonicum thioredoxin peroxidase-1 as a potential circulating antigen target for the diagnosis of Asian schistosomiasis. J Vet Med Sci 2018; 80:156-163. doi: 10.1292/jvms.17-0579.
Sandoval N, Siles-Lucas M, Pérez-Arellano JL, Carranza C, Puente S, López-Abán J, et al.
Anew PCR-based approach for the specific amplification of DNA from different Schistosoma
species applicable to human urine samples. Parasitology 2006;133:581-7.
Al-Sherbiny MM, Osman AM, Hancock K, Deelder AM, Tsang VC. Application of immunodiagnostic assays: Detection of antibodies and circulating antigens in human schistosomiasis and correlation with clinical findings. Am J Trop Med Hyg 1999;60:960-6.
Sulahian A, Garin YJ, Izri A, Verret C, Delaunay P, van Gool T, et al.
Development and evaluation of a western blot kit for diagnosis of schistosomiasis. Clin Diagn Lab Immunol 2005;12:548-51.
Karunamoorthi K, Ilango K, Murugan K. Laboratory evaluation of traditionally used plant-based insect repellent against the malaria vector anopheles arabiensis patton (Diptera
). Parasitol Res 2010;106:1217-23.
Karunamoorthi K. Impact of global warming on vector-borne diseases: Implications for future integrated vector management. J Socialomics 2013;1:e113.
Collins C, Xu J, Tang S. Schistosomiasis control and the health system in P.R. China. Infect Dis Poverty 2012;1:8.
Sharp D. Dam medicine. Lancet 2003;362:184.
Mas-Coma S, Valero MA, Bargues MD. Climate change effects on trematodiases, with emphasis on zoonotic fascioliasis and schistosomiasis. Vet Parasitol 2009;163:264-80.
Simoonga C, Utzinger J, Brooker S, Vounatsou P, Appleton CC, Stensgaard AS, et al.
Remote sensing, geographical information system and spatial analysis for schistosomiasis epidemiology and ecology in africa. Parasitology 2009;136:1683-93.
De Souza Gomes EC, Leal-Neto OB, Albuquerque J, Pereira da Silva H, Barbosa CS. Schistosomiasis transmission and environmental change: A spatio-temporal analysis in Porto de galinhas, Pernambuco – brazil. Int J Health Geogr 2012;11:51.
Zhou XN, Lin DD, Yang HM, Chen HG, Sun LP, Yang GJ, et al
. Use of Landsat TM satellite surveillance data to measure the impact of the 1998 flood on snail intermediate host dispersal in the lower Yangtze River Basin. Acta Trop 2002;82:199-205.
Brooker S. Schistosomes, snails and satellites. Acta Trop 2002;82:207-14.
Slootweg R, Malek EA, McCullough FS. The biological control of snail intermediate hosts of schistosomiasis by fish. Rev Fish Biol Fisheries 1994;4:67.
Karunamoorthi K, Bishaw D, Mulat T. Laboratory evaluation of Ethiopian local plant Phytolacca dodecandra
extract for its toxicity effectiveness against aquatic macro invertebrates. Eur Rev Med Pharmacol Sci 2008;12:381-6.
Deniel K, Seblework M, Argaw A, Karunamoorthi K. Laboratory evaluation of insecticidal activity of Phytolacca dodecandra
L.'Herit leaves extracts against bedbug, (Heteroptera
). ARC J Pub Health Commun Med 2016;1:1-9.
Duval D, Galinier R, Mouahid G, Toulza E, Allienne JF, Portela J, et al.
A novel bacterial pathogen of Biomphalaria glabrata: A potential weapon for schistosomiasis control? PLoS Negl Trop Dis 2015;9:e0003815. doi: 10.1371/journal.pntd.0003815.
Xianyi C, Liying W, Jiming C, Xiaonong Z, Jiang Z, Jiagang G, et al.
Schistosomiasis control in China: the impact of a 10-year World Bank Loan Project (1992-2001). Bull World Health Organ 2005;83:43-8.
Fenwick A. New initiatives against Africa's worms. Trans R Soc Trop Med Hyg 2006;100:200-7.
Fenwick A, Webster JP, Bosque-Oliva E, Blair L, Fleming FM, Zhang Y, et al.
The schistosomiasis control initiative (SCI): Rationale, development and implementation from 2002-2008. Parasitology 2009;136:1719-30. doi: 10.1017/S0031182009990400.
Bergquist R, Zhou XN, Rollinson D, Reinhard-Rupp J, Klohe K. Elimination of schistosomiasis: The tools required. Infect Dis Poverty 2017;6:158.
Grilli ST, Watts P. Development of a 3D numerical wave tank for modeling tsunami generation by underwater landslides. Eng Anal Bound Elem 2002;26:301-13.
Madon T, Hofman KJ, Kupfer L, Glass RI. Public health. Implementation science. Science 2007;318:1728-9.
Marsden D, Oakley P. Evaluating Social Development Projects. Oxford: Oxfam; 1990.
WHO. Community-Directed Interventions for Major Health Problems in Africa. A Multi-Country Study. Final Report; 2008.
Siddiqui AA, Siddiqui BA, Ganley-Leal L. Schistosomiasis vaccines. Hum Vaccin 2011;7:1192-7.
Ganley-Leal LM, Guarner J, Todd CW, Da'Dara AA, Freeman GL Jr., Boyer AE, et al.
Comparison of Schistosoma mansoni
irradiated cercariae and sm23 DNA vaccines. Parasite Immunol 2005;27:341-9.
Utzinger J, Bergquist R, Xiao SH, Singer BH, Tanner M. Sustainable schistosomiasis control–the way forward. Lancet 2003;362:1932-4.
Rollinson D, Knopp S, Levitz S, Stothard JR, Tchuem Tchuenté LA, Garba A, et al.
Time to set the agenda for schistosomiasis elimination. Acta Trop 2013;128:423-40.
Singer BH, de Castro MC. Bridges to sustainable tropical health. Proc Natl Acad Sci U S A 2007;104:16038-43.
Freeman MC, Ogden S, Jacobson J, Abbott D, Addiss DG, Amnie AG, et al
. Integration of water, sanitation, and hygiene for the prevention and control of neglected tropical diseases: A rationale forinter-sectoral collaboration. PLoS Negl Trop Dis 2013;7:e2439.
Spiegel JM, Dharamsi S, Wasan KM, Yassi A, Singer B, Hotez PJ, et al.
Which new approaches to tackling neglected tropical diseases show promise? PLoS Med 2010;7:e1000255.
Alan Wilson R, van Dam GJ, Kariuki TM, Farah IO, Deelder AM, Coulson PS, et al.
The detection limits for estimates of infection intensity in schistosomiasis mansoni established by a study in non-human primates. Int J Parasitol 2006;36:1241-4.
[Figure 1], [Figure 2]
[Table 1], [Table 2]