Illicium Verum Against Schistomiasis Japonicum
A long history of Schistosomiasis japonica in the Philippines can be traced down as the first case of a Filipino man, who has never left the country, infected with Schistosomiasis was reported way back in 1906. Amoebiasis and bacterial infection were the clinical impressions of his death. Amoebiasis was confirmed by the autopsy. However, Schistosoma ova in sections of the large intestine, liver, and lungs were found. The same case was found in the diagnosis of the feces of some prisoners of the Bilibid Prison in the City of Manila. A few years later, a case of Katayama disease (a toxemic syndrome with fever in the acute, early egg-laying phase of schistosomiasis) was reported. This led to efforts in identifying the intermediate host of the parasite. This was not successful until the discovery of the snail Oncomelania hupensis quadrasi in Palo, Leyte in 1932. S. japonicum cercariae were obtained from the Oncomelania snails and were infected into mice, rabbits, and monkeys for study.
Following the identification of the host, researches and studies were conducted about Schistosomiasis-endemic areas and the clinical and pathological aspects of S. japonica. During the World War I, the research activities were disrupted for a period of time due to its drawbacks but later on continued since an outbreak of the disease infected the Americans and Allied Armed Forces who landed on the island of Leyte in 1945. Large-scale research activities including studies in parasite biology, transmission, and control to clinical and pathological aspects of the disease were carried out after it was recognized to be a public health problem in the Philippines in 1953. In 1975, the S. japonica endemic-regions in the Philippines were determined to be the islands of Leyte, Samar, and Mindanao, which covers 24 provinces of the country. An estimate of more than five million people is subjected to risk, with about one million people infected, a situation which is still prevailing up until now. These schistosomiasis-endemic regions have no distinct dry season and are comprised of predominantly rice growing areas which maximize contact between humans and fresh water snails.
Schistosomiasis Japonicum-Caused Morbidity
In the Philippines, three clinical stages of Schistosomiasis japonicum infection are recognized and classified: the first or early phase, the second or acute phase, and the third or chronic phase.
Early Phase
The first phase includes the period from cercarial penetration to establishment of paired worms in the mesenteric venules. Exposure to cercariae via fresh water contact immediately (but not necessarily) results in pruritus, erythema, and a papular rash known as ‘swimmer's itch’. People living in endemic areas are seldom seen with the erythema and papular rashes. However, in non-immune individuals, the incidence is highly variable. For instance, among 158 American soldiers landing on the island of Leyte during World War II, 9% showed signs and symptoms of swimmer's itch. During the period corresponding to larval migration, infected individuals may have chills, fever, headache, an unproductive cough due to pulmonary involvement, and abdominal cramps. The time of onset and intensity of the above clinical manifestations varies widely.
Acute Phase
Maturation and pairing of adult worms along with the onset of oviposition 42–70 days post-exposure, leads to the second or acute phase of the disease. At this stage, worm metabolic products that are expelled into the systemic circulation contribute to a serum sickness-like condition called Katayama syndrome. This syndrome has been well described among 337 American soldiers who were affected by schistosomiasis during the Leyte campaign. Moderate to severe disease is characterized by marked eosinophilia, malaise, generalized muscle pain, and pulmonary symptoms and lymphadenopathy. Tender hepatomegaly was seen in 92% of the soldiers and splenomegaly occurred in 30% of the cases. Diarrhea or dysentery was seen in about 67% of the men. Neurological symptoms suggestive of meningoencephalitis were seen in 9. 3%. The severity of clinical disease was also noted to be correlated with the intensity of infection.
Chronic Phase
During chronic schistosome infection, a variety of clinical manifestations may result from infection depending on the organ involved, and these range from mild to severe, with several gradations in between. Sequelae are categorized into hepatosplenic, hepatointestinal, pulmonary, cerebral, and ectopic forms. Cardiac and renal localizations of lesions are rarely encountered. In the hepatosplenic form, hemodynamic changes are due to S. japonicum eggs trapped in the presinusoidal areas of the liver. These eggs induce classical pipe-stem fibrosis (PSF) around the intrahepatic radicals of the portal vein, leading to increases in splenic pulp and portal vein pressures and signs of severe portal hypertension. The severity of portal hypertension correlates with the severity of fibrosis as demonstrated by Doppler ultrasonography. Patients with severe periportal thickening have dilated portal and splenic veins, high portal vein velocity, and portal vein collateral formation. Recently we conducted community-based ultrasound examinations in endemic villages in Northern Samar Province to determine the prevalence of schistosomiasis-induced hepatic fibrosis and hepatosplenic disease. Individuals within these villages have been receiving annual mass drug administration (MDA) with praziquantel for more than 10 years.
Approximately 50% of the individuals have some form of hepatic fibrosis, with 20% having grade III fibrosis (severe fibrosis) according to the World Health Organization (WHO) staging criteria (unpublished data). The chronic pulmonary form is due to eggs that have reached the pulmonary circulation as emboli via the portosystemic collaterals. The eggs obstruct the arterioles or pass through the walls and lie in the parenchyma just outside the vessels, giving rise to two types of lesions, namely arterial and parenchymatous lesions, and this can lead to pulmonary hypertension or cor pulmonale. Bronchial asthma, bronchitis, bronchiectasis, and pulmonary emphysema have also been associated with schistosomiasis. Chronic schistosomiasis of the central nervous system can present clinically with a wide spectrum of signs and symptoms including: headache, nausea, vertigo, visual and speech defects, rigidity, spasm, mental confusion, and hemiplegia. Focal epilepsy due to schistosomiasis in the Philippines has been estimated to be from 2% to 5% among S. japonicum-infected individuals. Ectopic forms of schistosomiasis have been demonstrated in many organs, including the heart, appendix, ovary, fallopian tubes, and uterus.
Other Manifestations
Over the past 20 years, many studies have examined the impact of S. japonicum infection on growth, nutrition, hemoglobin levels, and cognitive functions in Filipino children. For example, in 1990 it was demonstrated that the intensity of infection was associated with decreased fat, muscle, and long bone growth in adolescents; males aged 16 to 18 years were 7. 8 cm shorter and 5. 8 kg lighter than non-infected adolescents in the same community. The effects were greater in villages not yet receiving annual screening and treatment. In other studies, S. japonicum infection in children was associated with malnutrition, anemia, and lower cognitive performance, such as learning, memory, and verbal fluency. Studies in infected women have shown that maternal schistosomiasis has adverse effects on pregnancy outcomes. Babies born from mothers with schistosomiasis have markedly decreased birth weights. Circulating mediators of inflammation are elevated in the peripheral blood, placental blood, and placental tissues of S. japonicum-infected pregnant women. In addition, placental interferon gamma is associated with both S. japonicum infection status and markedly decreased birth weight.
Strategies in Controlling Schistosomiasis Japonica
Studies and efforts have been done to widen the knowledge in making the morbidity caused by Schistosomiasis japonicum significantly low. Four distinct points are emphasized in order to control schistosomiasis infection: (1) Sanitation-- prevention of human excretes from reaching fresh bodies of water which will inhibit the interaction of free-swimming larval stages of schistosomes. Improved sanitation was also an essential component of the control program, but was difficult to sustain in communities, as no more than one third of the population had satisfactory latrines; (2) Snail Control-- prevention of interaction between the host and the parasite. Decades of research and control efforts have tested an astounding array of chemical, biological and physical weapons with which to reduce snail populations below the level, which would permit transmission. Molluscicides such as N–tritylmorpholine and sodium pentachlorophenate (NaPCP) have been used to control snail’s populations in dams, drains, rice paddies and canals. However, the use of inorganic molluscicides is not suitable for application into water bodies where aquatic snail hosts are abundant and on which people’s daily life depend.
The application of molluscicides must be carefully planned to take advantage of focal and seasonal pattern of transmission; (3) Reduction of water contact-- prevention of the exposure of susceptible humans to the infective free-swimming Cercariae. The Philippines, however, is a tropical country making it difficult to conduct snail control due to its climatic conditions and rice farming methods. Filipinos residing within schistosomiasis-endemic areas are typically very poor rice farmers with family incomes far below the national average. Improved farming methods such as irrigations are unattainable for most of these farmers whose population in the rural endemic areas is growing exponentially; thus more and more individuals are becoming at risk of contracting schistosomiasis; (4) Mass or targeted chemotherapy-- chemotherapeutic attack on the parasite population living within human host. An 8-year longitudinal study was conducted in the Philippines to determine the impact of chemotherapy with praziquantel, an anthelminthic medication. In a span of 3-4 years, the treatment was shown to be effective. The use of chemotherapy with praziquantel became one of the major advances we have achieved over the years since it was able to decrease the prevalence and intensity of Schistosomiasis which causes complications aforementioned above.
However, the efficiency of this treatment is dependent on its dose. In order to achieve high optimization of praziquantel treatment, the WHO Special Program for Research and Training in Tropical Diseases launched a series of multi-country trials, comparing the efficacy and safety of 40 mg/kg and 60 mg/kg in schistosome-infected patients in Asia, Africa, and the Americas. In the clinical trial in the Philippines, the 40 mg/kg dose was effective and better tolerated than the higher 60 mg/kg dose. With the introduction of praziquantel in the Philippines in 1980, schistosomiasis control shifted to a chemotherapy-based program. Unfortunately, the funds ceased in 1995. Subsequent marked budget reductions resulted in significantly decreased financial support and a loss of schistosomiasis control teams in each of the endemic municipalities. After 1995 the chemotherapy-based control program shifted from case finding and treatment to MDA.
Despite the marked reduction in financial and manpower support for the control program, the annual national prevalence data on schistosomiasis in the Philippines reported by the PNSCP has been maintained at less than 5%. This reported low national prevalence data has given the mistaken impression that schistosomiasis is no longer a major public health problem there and can even be eliminated in some endemic areas by MDA. However, bodies of evidence generated from endemic areas in the country are suggesting that elimination of schistosomiasis in the Philippines using MDA as the major approach will not be sustainable in the long run. This is why there is a cheap innovative control strategy to combat the disease is needed.
