A new tool for an old disease

We may be blessed with beautiful tropical islands and a whole year round of warm weather. Unfortunately, however, the tropical islands of the Philippines are also haven for many deadly tropical infectious diseases afflicting many of our fellow Filipinos. We have malaria, still the number one killer parasite that threatens the lives of young children in practically all provinces where there are mountain streams and malaria mosquitoes. And schistosomiasis, a blood fluke infection, ranks second to malaria in terms of public health importance. Most of us who are from the city have probably never heard of schistosomiasis, which is still affecting thousands in the remote rice-farming villages of Sorsogon, Leyte, Samar, Bohol and Mindanao. Like malaria, schistosomiasis has probably been afflicting man since ancient times. There is archeological evidence of the disease from schistosome eggs found inside mummies of ancient Egypt.

It is now almost 100 years since the first case of schistosomiasis was accidentally discovered in the Philippines in 1906 among "Waray" (originating from Samar) inmates of the Bilibid prison in Manila. After a routine course of intestinal parasite screening, eggs were found in stools, later to be identified as Schistosoma japonicum eggs. Popularly called "snail fever" among the local folk in Leyte, the disease is caused by flukes that infect man and other mammals, including dogs and carabaos, feed on their blood and reside as adult worms in the blood vessels of the liver and intestines.

The disease creeps in very slowly. Early symptoms such as paleness and malnutrition may be mistaken for ordinary symptoms of roundworm or hookworm infections common among kids in the rural and urban areas alike. One female worm can lay thousands of eggs, majority lodged in tissues causing inflammation of the liver and intestines, disrupting intestinal blood flow, later to manifest as the "big protruding belly" syndrome in severe intestinal schistosomiasis.

The parasite initially develops into different forms inside the Oncomelania quadrasi snail. These are minute snails, smaller than a grain of rice, found thriving in swampy rice-farming ecosystems of endemic municipalities. The parasite’s infective form can penetrate the bare skin of its targets, thus farmers and their families who are in frequent contact with water and rice paddies where the snails are found are the ones who are ready prey for these blood-feeding parasites.

Vicious as they may seem, schistosome worms are no match to the drug Praziquantel (Biltricide). Discovered by Bayer to treat animal parasites in 1975, Praziquantel was shown to be very effective in killing all types of human schistosome worms in one single dose. While large-scale community-based treatment made a major impact in decreasing infection and disease worldwide, sad to say, it is clear that the control of schistosomiasis was never an easy task. Schistosomiasis remains a public health nuisance in many endemic villages in the country where the snails still abound. In fact, a new endemic focus was recently discovered north of Luzon in Cagayan Valley. Even if treated regularly, due to extensive occupational exposure and the presence of infected animals continuously contaminating the environment with eggs, many continue to get re-infected, thus requiring repeated treatments (yearly treatment), which is often very expensive for many resource-poor endemic communities.

The detection of infection relies on finding eggs in stools of infected patients. This technique, however, is not 100-percent accurate in detecting all infections. A trained microscopist will not find eggs in as many as 35 percent of cases after examining duplicate slides (stool smears) from a single collection of stool sample. Far better techniques (e.g., DNA tests or the use of antibody targeting specific antigens) are available than simply demonstrating the presence of eggs from a very small amount of fecal material. For schistosomiasis, a sensitive test that is simple and affordable, one that can be used in the field for community-based control programs, is a better alternative diagnostic tool.

In our effort to contribute to and uphold sustainable development in our country, the Research Institute for Tropical Medicine (RITM), in Alabang, Muntinlupa, currently headed by Dr. Remigio M. Olveda, continues to enhance tools in biotechnology to upgrade its research and development program. Mandated as the research arm of the Department of Health, the RITM focuses on carrying out high-quality, multi-disciplinary research activities to contribute to the fight against tropical and infectious diseases.

With research funds provided by the Department of Science and Technology through the Philippine Center for Health Research and Development (PCHRD), the RITM developed an immunodiagnostic "dipstick" kit, called the SJ-URIDIP, for diagnosis of Schistosoma japonicum infection. The technique makes use of a locally produced monoclonal antibody to specifically bind or target the S. japonicum circulating cathodic antigen (CCA). CCA is a highly glycosylated proteoglycan molecule largely secreted by cells lining the intestines of adult worms. It is just one of the many antigenic molecules secreted by the parasite which are released in the blood. The good thing is, CCA is also found in the urine and therefore, the use of urine instead of blood or stool for diagnosis makes the collection of samples easier for community-based screening in schistosomiasis.

Antibodies are not only for the immune system. These molecules are now widely used in developing diagnostic kits for various infectious and systemic diseases. Many of these techniques rely on the strong binding affinity of antibodies to its specific antigen, addressing problems of sensitivity and specificity in many detection systems. Monoclonal antibodies are produced by fusing antibody secreting B cells of mice with mutant myeloma cells to allow the continuous propagation of these cells in cell cultures. There is no need for growing them inside the body. From a single cell, these are propagated and grown in large amount, secreting one type of antibody, and therefore the use of the term "monoclonal" antibody.

The SJ-URIDIP kit was tested in the field and gave promising results. Urine samples collected from several endemic barangays in Samar and Leyte were tested for the presence of CCA in urine and compared with the results of multiple stool examinations for the presence of eggs in stools. We demonstrated that the URIDIP test is very sensitive in detecting moderate and heavy infections. However, it is not much better than a stool examination in detecting very light infections, but still it is better than the results of examining a single stool sample. We also collected urine from infected individuals after they received Praziquantel treatment. The test results showed that one month after treatment, almost all CCA-positive individuals became negative in the urine. Since other parasitic infections are very common in these populations, and were not killed with Praziquantel treatment, this shows us that the URIDIP test specifically targets the schistosome antigen and not the other parasites. The ease of collecting a urine specimen for the test instead of stool or blood would result in high compliance for screening and treatment in many endemic communities nationwide.

Clearly, we now have in our hands a new tool for an old disease. But getting this where it is needed is another challenge to hurdle. The Philippines is now lagging far behind its neighbors in Asia in the field of biotechnology. It is high time that we promote biotechnology and contribute to the nation’s sustainable development. As for RITM’s concerns, we still have other diseases to target – malaria, TB, rabies, dengue and many other deadly infections. Developmental research may be a long and painful path, but it is worth pursuing and it can result in significant benefits to our countrymen.

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Luz P. Acosta, DrPH, is the head of the Department of Immunology of the Research Institute for Tropical Medicine, Department of Health, Alabang, Muntinlupa City. E-mail her at [email protected].