David U. Olveda

Can Mass Drug Administration Lead to the Sustainable Control of Schistosomiasis

BACKGROUND In the Philippines, the current national control strategy for schistosomiasis is annual mass drug administration (MDA) with 40 mg/kg of praziquantel in all schistosomiasis-endemic villages with a prevalence ≥10%. METHODS A cross-sectional survey of schistosomiasis was conducted in 2012 on 18 221 individuals residing in 22 schistosomiasis-endemic villages in the province of Northern Samar. The prevalence of schistosomiasis, intensity of Schistosoma infection, and morbidity of disease were assessed. RESULTS Despite an active schistosomiasis-control program in Northern Samar for >30 years, which included a MDA campaign in the last 5 years, the mean prevalence of schistosomiasis among 10 435 evaluated subjects was 27.1% (95% confidence interval [CI], 26.3%-28.0%), and the geometric mean intensity of infection among 2832 evaluated subjects was 17.2 eggs per gram of feces (95% CI, 16.4-18.1). Ultrasonography revealed high levels of schistosomiasis-induced morbidity in the schistosomiasis-endemic communities. Left lobe liver enlargement (≥70 mm) was evident in 89.3% of subjects. Twenty-five percent of the study population had grade II/III liver parenchyma fibrosis, and 13.3% had splenomegaly (≥100 mm). CONCLUSIONS MDA on its own was insufficient to control the prevalence of schistosomiasis, intensity of Schistosoma infection, or morbidity of the disease. Alternative control measures will be needed to complement the existing national MDA program.

Bilharzia in the Philippines: past, present, and future

Schistosomiasis japonica has a long history in the Philippines. In 1975, 24 endemic provinces were identified in the northern, central, and southern islands of the Philippines. More than five million people were at risk, with approximately one million infected. In 2003, new foci of infection were found in two provinces in the north and central areas. For the past 30 years, human mass drug administration (MDA), utilizing the drug praziquantel, has been the mainstay of control in the country. Recent studies have shown that the schistosomiasis prevalence ranges from 1% to 50% within different endemic zones. Severe end-organ morbidity is still present in many endemic areas, particularly in remote villages with poor treatment coverage. Moreover, subtle morbidities such as growth retardation, malnutrition, anemia, and poor cognitive function in infected children persist. There is now strong evidence that large mammals (e.g. water buffaloes, cattle) contribute significantly to disease transmission, complicating control efforts. Given the zoonotic nature of schistosomiasis in the Philippines, it is evident that the incidence, prevalence, and morbidity of the disease will not be controlled by MDA alone. There is a need for innovative cost-effective strategies to control schistosomiasis in the long term.

The chronic enteropathogenic disease schistosomiasis

Schistosomiasis is a chronic enteropathogenic disease caused by blood flukes of the genus Schistosoma. The disease afflicts approximately 240 million individuals globally, causing approximately 70 million disability-adjusted life years lost. Chronic infections with morbidity and mortality occur as a result of granuloma formation in the intestine, liver, or in the case of Schistosoma haematobium, the bladder. Various methods are utilized to diagnose and evaluate liver fibrosis due to schistosomiasis. Liver biopsy is still considered the gold standard, but it is invasive. Diagnostic imaging has proven to be an invaluable method in assessing hepatic morbidity in the hospital setting, but has practical limitations in the field. The potential of non-invasive biological markers, serum antibodies, cytokines, and circulating host microRNAs to diagnose hepatic fibrosis is presently undergoing evaluation. This review provides an update on the recent advances made with respect to gastrointestinal disease associated with chronic schistosomiasis.

Utility of Diagnostic Imaging in the Diagnosis and Management of Schistosomiasis

Diagnosis of schistosomiasis is made by demonstration of the parasite ova in stools, urine,and biopsy specimens from affected organs, or presence of antibodies to the different stages of the parasite or antigens circulating in body fluids by serologic techniques. DNA of schistosomes can now also be detected in serum and stool specimens by molecular technique.However, these tests are unable to determine the severity of target organ pathology and resultant complications. Accurate assessment of schistosome-induced morbidities is now made with the use of imaging techniques like ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI). US has made major contributions in the diagnosis of hepatosplenic and urinary form of disease. This imaging method provides real time results, is portable (can be carried to the bed side and the field) and is lower in cost than other imaging techniques. Typical findings in hepatosplenic schistosomiasis by US include: hyperechoic fibrotic bands along the portal vessels (Symmer’s fibrosis), reduction in the size of the right lobe, hypertrophy of the left lobe, splenomegaly, and ascites. More advanced ultrasound equipment like the colour Doppler ultrasound can characterize portal vein perfusion, a procedure that is critical for the prediction of disease prognosis and for treatment options for complicated portal hypertension. Although CT and MRI are more expensive, are hospital based, and require highly additional specially-trained personnel, they provide more accurate description of the pathology, not only in hepatosplenic and urinary forms of schistosomiasis, but also in the diagnosis of ectopic forms of the disease,particularly involving thebrain and spinal cord. MRI demonstrates better tissue differentiation and lack of exposure to ionizing radiation compared with CT.

Prevention and control of schistosomiasis: a current perspective

Abstract Schistosomiasis is a neglected tropical disease that ranks second only to malaria in terms of human suffering in the tropics and subtropics. Five species are known to infect man and there are currently over 240 million people infected worldwide. The cornerstone of control to date has been mass drug administration with 40 mg/kg of praziquantel but there are problems with this approach. Human and bovine vaccines are in various stages of development. Integrated control, targeting the life cycle, is the only approach that will lead to sustainability and future elimination.

Bilharzia: Pathology, Diagnosis, Management and Control

More than one billion people travel internationally each year and approximately 100 million to the tropics. Schistosomiasis is a neglected tropical disease caused by trematode blood flukes of the genus Schistosoma. It currently infects over 250 million people worldwide and results in approximately 25 million disability adjusted life years lost. Clinical manifestations depend on the affected organ. Subtle morbidities have also been documented including: growth retardation, anaemia and poor cognitive function in children. While schistosomiasis has been eradicated from Japan and significantly reduced in parts of China and Egypt, transmission in many other regions remains ongoing due to the wide-spread distribution of the intermediate snail host, poor sanitation, lack of health education and decreasing compliance to mass drug administration. Integrated control has significantly reduced the burden of disease in China but considerable financial capital is needed if similar results are to be duplicated elsewhere. Human vaccination is in various stages of development, and once found, will become an integral part of future control. This comprehensive review examines the epidemiology, pathology, diagnosis, clinical management, prevention and control of the disease.

Schistosomiasis mass drug administration in the Philippines: lessons learnt and the global implications.

Schistosomiasis was first reported in the Philippines in 1906. A variety of treatments have been deployed to cure infection and to control the disease in the long-term. We discuss the journey to combat the disease in the Philippines and the lessons learnt which have implications for schistosomiasis control globally.

Mass drug administration and the global control of schistosomiasis: successes, limitations and clinical outcomes.

Purpose of review Preventive chemotherapy is advocated for the global control and elimination of schistosomiasis. Despite the well known short-term benefits of treating patients for schistosomiasis, the impact of mass drug administration (MDA) campaigns to control the disease in the long term remains unresolved. Recent findings Many studies have advocated the success of MDA programs in order to attract donor funds for elimination efforts but such successes are often short-lived given the drug does not alter the life cycle of the organism or prevent reinfection. Within a matter of months to years after halting treatment, the prevalence, intensity of infection and morbidity of disease return to baseline levels. Other mitigating factors contribute to the failings of MDA campaigns namely: poverty, poor drug coverage, poor drug compliance, and, in the case of Asiatic schistosomiasis, zoonotic transmission. Genetic and innate and acquired immunologic mechanisms complicate the epidemiologic picture of schistosomiasis globally, and may contribute indirectly to MDA shortcomings. The possibility of drug resistance is an ever present concern because of the sole reliance on one drug, praziquantel. Summary Preventive chemotherapy is advocated for the global control and elimination of schistosomiasis. The short-term benefits of MDA campaigns are well documented but the long-term benefits are questionable.

A Parallel Comparison of Antigen Candidates for Development of an Optimized Serological Diagnosis of Schistosomiasis Japonica in the Philippines

Schistosoma japonicum is stubbornly persistent in China and the Philippines. Fast and accurate diagnostic tools are required to monitor effective control measures against schistosomiasis japonica. Promising antigen candidates for the serological diagnosis of schistosomiasis japonica have generally been identified from the Chinese strain of S. japonicum. However, the Chinese (SjC) and Philippine (SjP) strains of S. japonicum express a number of clear phenotypic differences, including aspects of host immune responses. This feature thereby emphasized the requirement to determine whether antigens identified as having diagnostic value for SjC infection are also suitable for the diagnosis of SjP infection. In the current study, 10 antigens were selected for comparison of diagnostic performance of the SjP infection using ELISA. On testing of sera from 180 subjects in the Philippines, SjSAP4 exhibited the best diagnostic performance with 94.03% sensitivity and 98.33% specificity using an optimized serum dilution. In another large scale testing with 412 serum samples, a combination (SjSAP4 + Sj23-LHD (large hydrophilic domain)) provided the best diagnostic outcome with 87.04% sensitivity and 96.67% specificity. This combination could be used in future for serological diagnosis of schistosomiasis in the Philippines, thereby representing an important component for monitoring integrated control measures.

National survey data for zoonotic schistosomiasis in the Philippines grossly underestimates the true burden of disease within endemic zones: implications for future control

Zoonotic schistosomiasis has a long endemic history in the Philippines. Human mass drug administration has been the cornerstone of schistosomiasis control in the country for the past three decades. Recent publications utilizing retrospective national survey data have indicated that the national human prevalence of the disease is <1%, hence the disease is now close to elimination. However, the evidence for such a claim is weak, given that less than a third of the human population is currently being treated annually within endemic zones and only a third of those treated actually swallow the tablets. For those who consume the drug at the single oral dose of 40mg/kg, the estimated cure rate is 52% based on a recent meta-analysis. Thus, approximately 5% of the endemic human population is in reality receiving the appropriate treatment. To compound this public health problem, most of the bovines in the endemic communities are concurrently infected but are not treated under the current national control programme. Given this evidence, it is believed that the human prevalence of schistosomiasis within endemic regions has been grossly underestimated. Inherent flaws in the reporting of national schistosomiasis prevalence data are reported here, and the problems of utilizing national retrospective data in making geographic information system (GIS) risk maps and advising policy makers of the outcomes are highlighted.