Schistosomiasis Research Program

 
Remigio M. Olveda, MD
Research Program Leader

TECHNICAL
GROUP MEMBERS

Luz P. Acosta, MScPH, DrPH
Fe F. Aligui
Gemiliano dL. Aligui, MD, MPH, PhD

Non-TECHNICAL
GROUP MEMBERS

Ernesto A. Abeto
Ricardo A. Reyes III

 

The RITM-Schistosomiasis Study Program has, in the past, spearheaded important research projects funded by local and international grants obtained through competitive funding mechanisms.

Combining both field and laboratory-based researches, the research program objectives are: 1) The development of cost-effective schistosomiasis control measures based on existing technology that can be applied by the Department of Health in schistosomiasis endemic areas in the Philippines; 2) The development of alternative diagnostic tests for determining prevalence and intensity of infection in field settings; and 3) The conduct of studies that will provide new insights in the pathogenesis of disease and resistance to Schistosoma japonicum infection that can include the development of a safe and effective vaccine against establishment of infection.

Schistosomiasis

Schistosomiasis


Acute Respiratory Infections
Dengue
Diarrheal Diseases
Filariasis
Filovirus
Hepatitis
HIV/AIDS
Malaria
Rabies
Tuberculosis
Leprosy

Under a US-NIH grant in 1991, these objectives were further developed into a more comprehensive undertaking for which two projects were obtained. Project 1 focused on the: 1) continuation of the longitudinal follow-up of study villages; 2) effects of praziquantel treatment on child growth and development, 3) determination of the natural history of hepatosplenic disease; 3) the examination of differential susceptibility or resistance to infection using intensive water-contact study; and 4) cost-effective analysis on the impact of chemotherapy to develop an improved strategic plan of disease control. While Project 2 focused on vaccine development: 1) generating a variety of immune sera containing protective antibodies against Schistosoma japonicum and 2) immunoscreening of cDNA expression libraries utilizing monoclonal or human immune antibodies. With a WHO/TDR grant, domestic animal studies (dogs, pigs and water buffaloes) showed that the burden of infection in domestic animals is low, varies with the animal care practices, specifically penning of dogs and pigs. Water buffaloes also have a very low level schistosoma infection. However, it was found that a high fasciola infection exist among non-schistosomiasis infected water buffaloes. This is being investigated further in another WHO/TDR grant that will cover more number of water buffaloes and a study of antigen recognition that could be common to both trematodes. The prospect of a vaccine is also envisioned in this line of study.

Under developmental study is a rapid immunoblot assay in a ‘dipstick’ format that can use urine samples for the diagnosis of S. japonicum infection. The expectation of the field application of this assay would be high population compliance since the bio-sample is not stool and, thus, will be a better technique for screening schistosomiasis in endemic communities. Since a monoclonal, producing anti-circulating antigens have been already developed by RITM under a PCHRD/DOST grant, the group embarked on developing an assay based on enzyme technique. Currently, prototype urine ‘dipstick’ has been developed and is being tested in diagnosis of schistosomiasis.

During the past five years, the investigators’ efforts towards the development of a vaccine have focused on the identification of S. japonicum antigens recognized by specific antibody isotypes implicated in human immunity such as IgE and IgA. Combining the tools of molecular biology, immunology and epidemiology, a direct approach using infected human sera to screen adult worm cDNA library for potential vaccine candidates was used to identify several ‘IgE’ and ‘IgA’ clones. In addition, two WHO/TDR project was recently granted, firstly to investigate cellular and humoral responses to specific S. japonicum recombinant antigens using lymphocytes from individuals living in an endemic area. Cell proliferation, cytokine (IL-5, IFN-g and IL-10) and antibody responses to five candidate vaccine antigens were tested to determine immunological markers of protection among individuals who were characterized as ‘immune’. The second project currently under investigation is looking into the possibility of using monkeys (Macaca fasciuclaris) as vaccine models for schistosomiasis infection.

On-going Researches: (1) Refinement of the immunodot ‘SJ-URIDIP’ kit for the detection of S. japonicum circulating antigens in urine samples. (Institutional/Intra-mural grant) (2) Evaluating the natural course of S. japonicum infection in monkeys (Macaca fascicularis): Future animal model for schistosomiasis vaccine studies. [UNDP/WORLD BANK/WHO Special Program for Research and Training in Tropical Diseases (TDR)] (3) Pathogenesis and immunology of protection of F. gigantica infection for S. japonicum infection in water buffaloes and sheep. [UNDP/WORLD BANK/WHO Special Program for Research and Training in Tropical Diseases (TDR)]

Future research direction of the program will focus on the development of dynamic and predictive models to better understand the ecology of S. japonicum transmission and estimate the effects and costs of putative environmental interventions. The mechanisms of infection will also be investigated in relation to puberty.