Endemic Parasitic Disease Research Articles

Toxic Side Effects of Drugs Used to Treat Chagas’ Disease (American Trypanosomiasis)

Chagas' disease (American trypanosomiasis) is an endemic parasitic disease in some areas of Latin America. About 16-18 million persons are infected with the aetiological agent of the disease, Trypanosoma cruzi, and more than 100 million are living at risk of infection. There are different modes of infection: (1) via blood sucking vector insects infected with T. cruzi, accounting for 80-90% of transmission of the disease; (2) via blood transfusion or congenital transmission, accounting for 0.5-8% of transmission; (3) other less common forms of infection, eg, from infected food or drinks or via infected organs used in transplants. The acute phase of the disease can last from weeks to months and typically is asymptomatic or associated with fever and other mild nonspecific manifestations. However, life-threatening myocarditis or meningoencephalitis can occur during the acute phase. The death rate for persons in this phase is about 10%. Approximately 10-50% of the survivors develop chronic Chagas' disease, which is characterized by potentially lethal cardiopathy and megacolon or megaoesophagus. There are two drugs available for the aetiological treatment of Chagas' disease: nifurtimox (Nfx) and benznidazole (Bz). Nfx is a nitrofurane and Bz is a nitroimidazole compound. The use of these drugs to treat the acute phase of the disease is widely accepted. However, their use in the treatment of the chronic phase is controversial. The undesirable side effects of both drugs are a major drawback in their use, frequently forcing the physician to stop treatment. The most frequent adverse effects observed in the use of Nfx are: anorexia, loss of weight, psychic alterations, excitability, sleepiness, digestive manifestations such as nausea or vomiting, and occasionally intestinal colic and diarrhoea. In the case of Bz, skin manifestations are the most notorious (e.g., hypersensitivity, dermatitis with cutaneous eruptions, generalized oedema, fever, lymphoadenopathy, articular and muscular pain), with depression of bone marrow, thrombocytopenic purpura and agranulocytosis being the more severe manifestations. Experimental toxicity studies with Nfx evidenced neurotoxicity, testicular damage, ovarian toxicity, and deleterious effects in adrenal, colon, oesophageal and mammary tissue. In the case of Bz, deleterious effects were observed in adrenals, colon and oesophagus. Bz also inhibits the metabolism of several xenobiotics biotransformed by the cytochrome P450 system and its reactive metabolites react with fetal components in vivo. Both drugs exhibited significant mutagenic effects and were shown to be tumorigenic or carcinogenic in some studies. The toxic side effects of both nitroheterocyclic derivatives require enzymatic reduction of their nitro group. Those processes are fundamentally mediated by cytochrome P450 reductase and cytochrome P450. Other enzymes such as xanthine oxidoreductase or aldehyde oxidase may also be involved.

Care of refugees and recent immigrants from low-income countries

Abstract Recent immigrants from low-income countries are at risk of several distinctive health problems, symptomatic or asymptomatic, medical and psychological. The prevalence of health problems is higher in refugees. Recent immigrants commonly have difficulty obtaining knowledgeable and culturally appropriate care. Routine immigration screening in many countries does not include all of the elements that are medically indicated in this group. Preferably, immigrant families should be assessed and treated together. Efforts should be made to integrate their health care with support in the community. An individual or team sensitive to cultural issues and familiar with prevalent medical problems in the country of origin should perform a comprehensive medical assessment. A translator may be required, potentially introducing specific constraints and difficulties. The assessment should address relatively common and important diseases such as HIV, tuberculosis, hepatitis B and probably endemic parasitic diseases, in addition to psychiatric symptoms, depending on the immigrant's clinical and epidemiologic history. Screening for sexually transmitted infections should be considered. Family planning should be addressed, with other ‘routine' care such as cervical cytology and blood pressure screening. Any problems identified by symptoms, examination or laboratory investigation, such as parasitic infection, latent tuberculosis infection or psychological morbidity, should be addressed. This may entail appropriate referral. Vaccine status should be assessed and updated, particularly in children. Finally, the goal should be to establish the immigrant and his or her family with an appropriate source of ongoing primary care.

Cardiac hydatid cysts: Echocardiographic findings

Cardiac hydatid disease is rare. Many patients are asymptomatic, hence cardiac involvement is often discovered incidentally. Diagnosis is also difficult because of a long period between parasitic infection and the manifestation of disease. Rupture of a cardiac cyst is a serious complication. Diagnosis of cardiac hydatid cysts is often made using transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) provides details of the cysts. We present the cases of 3 patients with nonspecific symptoms of their endemic parasitic disease. The results of sonographic examinations in all patients strongly suggested the presence of cardiac hydatid cysts. One patient had a cyst in the external surface of the left ventricular apical-lateral wall visualized with TTE and TEE. Parasitic serology was negative. She underwent surgery, which confirmed a cyst located in the pericardium, and then was treated with albendazole. Another patient had a cyst in the left ventricle demonstrated by TTE and TEE and confirmed with serology. Color Doppler sonography verified that her cardiac cyst was in communication with the left ventricle. She was not a surgical candidate and was treated with albendazole. The final patient had a septated cyst in the media basilar portion of the interventricular septum demonstrated using TTE, and CT. He refused surgical treatment and albendazole was prescribed. Chest radiographs in 3 patients failed to show the cysts, and serology in 1 patient failed to indicate a hydatid cyst. Follow-up at 1-2 years revealed no recurrence in any patient. In all 3 cases, cysts could be visualized from the subcostal view via echocardiography. Imaging is critical for the early diagnosis, assessment, and follow-up of patients with this disease.

Reactions of nifurtimox with critical sulfhydryl-containing biomolecules: their potential toxicological relevance.

Nifurtimox (Nfx) is a drug used in the treatment of Chagas' disease, an endemic parasitic disease from Latin American countries. It produces undesirable side-effects in patients, frequently forcing the treatment to be stopped. Its toxic mechanism is not fully understood. In this work we describe purely chemical reactions of Nfx with relevant cellular sulfhydryl (SH) compounds. The compounds tested were glutathione (GSH), cysteine (RSH), lipoic acid (LA) and coenzyme A (CoA). All reacted with Nfx to give nitrite (NO(-) (2)). The relative reaction rates were CoA>LA>GSH>RSH. In studies with GSH and RSH the formation of nitrite was accompanied by decreases in Nfx concentration and increases in the formation of a reaction product revealed by HPLC. We failed to show the presence of liver cytosolic GST (GSH transferase activity)-mediated formation of NO2- from Nfx. These NO(-) (2)-releasing processes occurred under in vivo conditions in Nfx-treated Sprague-Dawley male rats (240-260 g body weight) at a dose of 100 mg Nfx kg(-1) p.o. In urine samples NO(-) (2) excretion was accompanied by unchanged drug and two unidentified more polar metabolites detectable by HPLC. The Nfx reactions with critical SH from molecules such as GSH, RSH, LA and CoA, and potentially others containing SH residues (e.g. enzymes or structural proteins), might have toxicological relevance not only for the Nfx side-effects but also for the chemotherapeutic effects on Trypanosoma cruzi. In addition, Nfx reactions with GSH might be crucial in Nfx detoxification.

Unusual locations of hydatid disease and surgical approach.

Hydatid disease is an endemic parasitic disease of the Mediterranean countries. Although the liver is the most commonly involved organ, the disease can be seen anywhere in the body. In the present study, we present our experience with uncommonly located hydatid disease diagnosed and treated between 1983 and 1999 in the Sixth Surgical Department of Ankara Numune Training and Research Hospital, Ankara, Turkey. Forty-nine patients with unusually located hydatid disease were retrospectively analysed. There were 21 men and 28 women in the present series. Of those, 26 patients were harbouring both hepatic and extrahepatic cysts, while 23 had only extrahepatic cysts. Peritoneal cavity, spleen, retroperitoneum, thyroid gland, anterior abdominal wall, thigh, kidney, presacral space and pancreas were the organs or tissues involved in the cases. Spleen and peritoneal cavity were the two most frequent locations in the present series. Partial or total cystectomy with or without tube drainage or omentopexy was the operation of choice for hydatid cyst of the peritoneal cavity. Splenectomy was performed for splenic hydatidosis. Mean postoperative stay was 7 days (4-23). Three diaphragmatic and one inferior vena cava lacerations occurred during operations that were repaired successfully in the same sessions. No mortality occurred in the present series. Hydatid disease can affect any organ or area throughout the body and suspicion of this disease should be justified in patients presenting with a cystic mass in endemic areas.

La bilharziose cérébelleuse: À propos d’un cas

Schistomiasis or bilharziosis remains an endemic parasitic disease in many countries world wide. Urogenital, intestinal and hepatic symptoms are common. The brain is exceptionally involved and very few cases have been described in the literature. We report the case of a 35-Year-old male with a history of hematuria and bladder disorders, who developed signs of intracranial hypertension and a cerebellar syndrome over a period of one Month. Brain MRI disclosed a cerebellar lesion and a pelvic CT scan revealed a bladder tumor. Treatment consisted in a ventriculo-peritoneal shunt and corticosteroid therapy. Cystoscopy was performed for total resection of the bladder lesion. Histopathology confirmed the diagnosis of schistomiasis. Surgery was also performed to approach the cerebellar lesion. Histopathology showed the inflammatory nature of the lesion. The patient was given an antiparasitic treatment. Clinical and radiological radiological manifestations regressed.

Benznidazole-induced ultrastructural and biochemical alterations in rat esophagus.

Benznidazole (Bz) is a drug used in the chemotherapy of the acute and intermediate phases of Chagas' disease (American Trypanosomiasis), an endemic parasitic disease afflicting more than 16 million people in Latin America. Serious toxic side effects of Bz have been reported in treated human beings and in experimental animals. Bz toxicity would be linked to its nitroreductive bioactivation to reactive intermediates and to the corresponding amine known to occur in vivo and mediated by different enzymatic systems. In the present study the presence of Bz nitroreductases in rat esophagus and the occurrence of Bz induced esophageal cell injury are described. Already 1 and 3 h after an intragastric Bz administration to Sprague-Dawley male rats (240-260 g body weight) at a dose of 100 mg/kg esophageal levels of the drug were 66.4+/-4.0 and 149.2+/-14.3 nmol per g tissue, respectively. The esophageal mucosa homogenates exhibited Bz nitroreductase activity attributable to the participation of cytochrome P450 reductase and xanthine oxidoreductase (XOR). The ultrastructural observation of esophageal tissue from Bz treated animals 24 h after its administration evidenced: detachment and conglomeration of polyribosomes, reduction in the presence of desmosomes and of the amount of bacteria on its surface. The potential significance of these alterations is not fully clear at present. However, these deleterious effects might be additive or synergistic with those induced by the evolution of the disease.

The duality of sleeping sickness: focusing on sleep.

Sleeping sickness, once under control, is a re-emergent endemic parasitic disease in intertropical Africa. Its originality resides in its duality. Two trypanosome groups (Trypanososma brucei gambiense vs.rhodesiense ) are transmitted to humans by tsetse flies from two geographical areas (Western and Central Africa humid forest vs. Eastern Africa arboreous savannah), provoking a slowly or a rapidly evolutive disease. The two stage (haemolymphatic vs. neurological invasion) pathogenic evolution leads to the duality of the immune response, depending on the host-parasite inter-relation differences in the blood and the brain. In the blood, the immune processes involved are both specific (anti-variant surface glycoprotein (VSG) antibodies) and non-specific (complement-mediated lysis, opsonification-facilitated phagocytosis and antibody dependent cell-mediated cytotoxicity). Although macrophages are activated in the blood and infiltrate the brain, nitric oxide decreases in the blood and increases in the brain, with a breakage in the blood-brain barrier, leading to brain lesions through the production of deleterious molecules. Prophylactic means are affected by the duality of pathogenic processes. This finally leads to a two stage disease (haemolymphatic vs. neurological) with two different therapeutic strategies. The sleep-wake cycle and other biological rhythms are also marked by the disappearance of circadian rhythmicity demasking basic ultradian activities and relationships, such as the interdependence of endocrine profiles and the sleep-wake alternation. 2001 Harcourt Publishers Ltd

Hydatid disease of the liver with thoracic involvement.

Hydatidosis, caused by Echinococcus granulosus, is an endemic parasitic disease in Mediterranean countries. The most frequent anatomic locations are liver and lung. Intrathoracic rupture of hydatid cysts situated in the hepatic dome is a serious complication resulting in damage to the pleura, pulmonary parenchyma, and bronchi. From January 1984 to December 1997 we operated on 40 patients with intrathoracic rupture of a hepatic hydatid cyst. Chest roentgenograms showed a shadow of varying size at the base of the hemithorax. Hepatic and thoracic ultrasonography was performed in all cases. The diagnosis of intrathoracic rupture of a liver cyst was confirmed preoperatively in 30 of the 40 cases. Posterolateral thoracotomy was performed in all patients. This transthoracic approach allowed adhesiolysis and treatment of the pleural lesions, pulmonary lesions, and hepatic cyst. Treatment of the diaphragmatic gap is easily done. We performed 15 lobectomies, 10 wedge resections, 16 decortications, and in one patient simple drainage of a voluminous pleuropulmonary and hepatic purulent hydatic collection. The postoperative course was uneventful in 26 cases, but 14 patients had complications, from which 3 patients died. The therapeutic approach depends on ultrasonographic findings. We believe ultrasonography to be the best examination for assessing biliary, hepatic, diaphragmatic, and pleuropulmonary lesions. When an intrathoracic collection is present, thoracotomy must be performed and is sufficient if the biliary tract is safe. An abdominal approach is necessary when biliary duct drainage is required, and it may be sufficient in cases of direct rupture into the bronchi.

Critical analysis of the estimated number of Schistosomiasis mansoni carriers in Brazil

The number of carriers of Schistosoma mansoni infection in Brazil was estimated based on the results of parasitological examinations of feces carried out by the Fundação Nacional de Saúde (FNS - National Health Foundation) in 1996 and 1997, as well as population data from 18 states collected by the Instituto Brasileiro de Geografia e Estatística (IBGE - Brazilian Institute of Geography and Statistics). This information allowed the number of carriers of schistosomiasis mansoni to be estimated at 7.1 million in 1996 and 6. 3 million in 1997. These figures may not reflect the true situation since the population sample used was not originally selected for this purpose. The absence of precise data indicates the need for an adequate national survey of the prevalence of schistosomiasis, which continues to be an important endemic parasitic disease, justifying greater efforts for its control in Brazil.

Prevalencia de anemia en gestantes, Hospital Regional de Pucallpa, Perú

Population based health surveys in Peru show that the general fertility rates, proportion of pregnant adolescents, and maternal and child morbidity are higher in the jungle regions than in other parts of the country. Endemic intestinal parasitic diseases increase the risk of anemia in pregnant women already suffering from iron, folic acid, and other nutritional deficiencies. This is the most common complication of pregnancy in many Latin American countries and is often associated with premature labor, low birthweight, and perinatal mortality. There are very few studies on this subject based on jungle populations and no reliable estimates of the prevalence of anemia in local pregnant women. The present study was designed to determine the prevalence of anemia in pregnant women attending the Regional Hospital in Pucallpa, located in the Peruvian jungle, from January 1993 to June 1995. This cross-sectional study, which was based on the registries of prenatal and childbirth services encompassing 1,015 pregnant women, looked into the potential association between anemia and such variables as the mother's chronological age, schooling, previous pregnancies, and weight at the beginning of pregnancy. Maternal hemoglobin levels were compared with the newborns' weight at birth. The prevalence of anemia in this population sample was 70.1%. This value was not modified when adjusted for maternal age, schooling, or interval between births. Anemia prevalence was directly related to the number of previous pregnancies and inversely related to weight gain during pregnancy. The perinatal mortality rate was 37.7 per 1,000 births. Neither this rate nor the birthweights were associated with the mother's degree of anemia. A multivariate regression analysis showed that maternal body weight at the start of pregnancy (P = 0.0001), weight gain during pregnancy (P = 0.0001), and the number of pregnancies (P = 0.008) are predictors of birthweight. Results showed that the high prevalence of anemia in Pucallpa's pregnant women is not associated with low birthweight or a high perinatal mortality rate. Future studies should investigate the principal causes of anemia in the pregnant women of Pucallpa and how the disease affects the psychomotor development of their offspring.

Synthesis and in Vitro Evaluation of Potential Antichagasic Dipeptide Prodrugs of Primaquine

□ American trypanosomiasis (Chagas’ disease) is an endemic parasitic disease afflicting more than 20 million people in Latin America. Currently , therapy is unsatisfactory and only two drugs are available. Primaquine, an antimalarial drug, has trypanocidal activity. Dipeptide derivatives of primaquine, Phe-Arg-PQ, Lys-Arg-PQ, and Phe-Ala-PQ, were synthesized. The choice of the peptides was based on the primary specificity of cruzipain, the major cysteine proteinase from T cruzi. The prodrugs obtained were tested on the LLC-MK2 cell culture infected with trypomastigotes forms of T. cruzi Phe-Arg-PQ, Lys-Arg-PQ, and Phe-Ala-PQ were active in all stages.

Epidemiology of alveolar echinococcosis in southern Germany (Bavaria).

Alveolar echinococcosis is considered to be the most dangerous endemic parasitic disease for man in Central Europe. In Germany, unlike the neighbouring countries of Switzerland, Austria and France, only limited data on the prevalence and incidence of echinococcosis are available. Therefore, a retrospective cross-sectional study was conducted in order to investigate the epidemiology of echinococcosis in Bavaria, one of the two southern states of Germany. A standardised questionnaire was sent to all hospitals in Bavaria requesting information about patients seen from 1985 to 1989. In a second step a team of reviewers was sent to all relevant hospitals for active case finding in hospital statistics and medical records. A total of 216 patients with echinococcosis were detected of whom 58 had alveolar echinococcosis. According to these data, the prevalence in Bavaria was calculated to be 0.5 per 100,000 inhabitants with peak values in the counties of Swabia (2.4) and Upper Bavaria (0.6). The annual mean incidence of newly diagnosed cases amounted to 0.03 per 100,000. The distribution of prevalence in man was closely correlated to the infection rates in foxes throughout Bavaria (p < 0.05). Farmers are the occupational group with the highest risk to acquire echinococcosis with a prevalence/odds ratio of 14.6 for Swabia and 8.8 for Upper Bavaria, when compared to the general rural population.

Activité antiparasitaire d'alcaloïdes bisbenzylisoquinoleiques. I: activité in vitro sur des promastigotes de trois souches de Leishmania

Leishmaniasis caused by protozoan Leishmania ssp., is an endemic parasitic disease in Central and South America. The Chemotherapic agents against Leishmania ssp. (pentavalent antimony compounds, pentamidine and amphothericine B) are toxic and expensive products. Basing on the Bolivian folk medicine, we tried to find new active principles. Fourteen isoquinoline alkaloids, especially bisbenzylisoquinoline alkaloids extracted from Annonaceae, Berberidaceae, Hernandiaceae and Menispermaceae, demonstrate highly effective activity against this protozoan. Among them gyrocarpine, daphnandrine and obaberine seem to be of particular interest. The therapeutic effect was studied by biological assays on culture forms in vitro three strains of Leishmania, L. donovani, L. braziliensis (cutaneous and mucocutaneous lieshmaniasis), L. mexicana amazonensis (cutaneous) and L. donovani (visceral leishmaniasis).

Activité antiparasit aire d'alcaloïdes bisbenzylisoquinoléiques. II: Activité in vitro sur des epimastigotes de trois souches typifiees de Trypanosoma cruzi

Chagas disease caused by the protozoan Trypanosoma cruzi is an endemic parasitic disease in Central and South America. The chemotherapic agents against Trypnosoma cruzi (imidazol compounds, lampit and benznidazol) are not very convenient products. Since it is known that protozoan Trypanosoma are close to Leishmania we studied the action of 14 bisbenzylisoquinoline alkaloids, in vitro, on three strains of T. cruzi (Tulahuen, C8C11, and 1979 CL1). As in the case of Leishmania, gyrocarpine, daphnandrine and obaberine showed an interesting activity and we judge them to be worthy of in vivo assays.

Lymphocyte enzyme activities in East African blacks: decrease in 5′nucleotidase and possible relation to immunosuppression

Microanalysis of subcellular organelle marker enzymes was applied to cryopreserved lymphocytes (obtained and processed in the field) from East African blacks with moderate to severe malnutrition and subject to locally endemic parasitic and infectious diseases. An initial study demonstrated that activities of these enzymes, with the partial exception of catalase, were stable to cryopreservation. Cryopreserved and thawed lymphocyte specimens (1 to 3 × 10 6 viable cells) from 26 Africans and 20 Caucasian controls were studied. There was a highly significant decrease in 5′nucleotidase activity in these African subjects. Activity of another plasma membrane enzyme, γ-glutamyl transferase, and of marker enzymes for other intracellular organelles, was not significantly different between the two groups, indicating that the nucleotidase alteration is highly specific. 5′Nucleotidase activity in a group of 17 East African blacks of high socio-economic status lay between the values obtained in the other two groups and was not significantly different from either. Further studies on 5′nucleotidase showed no evidence that the enzyme is functionally different in Africans. The differences in activity of this enzyme in Africans may reflect the known immuno-suppressive effects of infectious disease and malnutrition or may have a genetic basis which may in turn be associated with the pathogenesis of secondary immunodeficiency.

A Histopathologic Study Of The Lungs Infected With Paragonimus Westermani In The Dog

Pulmonary paragonimiasis is one of the most important endemic parasitic disease in Korea. Although it is well known that Paragonimus westermani invades into the lung tissue eventually resulting respiratory failure, the pathogenesis of inducing lung lesions is not fully elucidated. It is still debatable on the nature of morphological component of 'cyst' which is known to be the most consistent change in lung paragonimiasis. For the purpose of clarification of morphological changes associated with pulmonary paragonimiasis, an experimental study was carried out by giving metacercariae of P. westermani to 10 dogs. These dogs were sacrificed 2 months and 6 months after infection respectively, and light microscopic and electron microscopic observations were made. Following conclusions were obtained. 1. Paragonimus lung lesions could basically be classified into two categories, i.e., direct mechanical effects by the worms and eggs, and the changes secondary to the worm infection. The relative importance of these two appeared almost same. 2. Adult worms of P. westermani reside inside the lumina of the dilated bronchi in great majority of the cases. Only exceptions were secondary abscess formation and subsequent scar where no epithelial lining was detected around the worms. In 6 months group almost all P. westermani worms were found inside the bronchial lumina. 3. Obliterative endobronchiolitis was another prominent feature among changes that were not directly associated with worms or eggs. This finding was more prominent in the distal segments of the bronchial trees that harbor the Paragonimus worms. 4. P. westermani eggs were found as isolated and aggregated fashions, provoking characteristic granulomatous inflammation. Some of the egg granulomas were seen in the areas apart from the locations where the worms were physically located. 5. Ultrastructural observations of the cyst wall showed fair numbers of plasma cells and mast cells. Some of the cystlining epithelial cells showed increased deposit of glycogen granules, suggestive of early metabolic alteration of the respiratory epithelium.

Rural health and disease in five continents.

Three-quarters of the world’s peoples live in rural areas, where ill-health and disease are the tacitly accepted norms. Inequalities and disparities are being accentuated by the burgeoning towns of the Third World which claim an overlarge proportion of available finance, doctors and curative medical services. Undernutrition and a rapidly increasing population augment the problems of endemic parasitic and infectious disease in the context of socio-environmental factors militating against healthy living. Food production cannot keep pace with population growth; and leaching, erosion, depletion of topsoil from overcropping and overgrazing result in protein-energy deficiencies and widespread undernourishment. Loss of harvested crops from fungi, insects, vermin and bacterial decomposition tip the precarious balance. Too much water, or too little, and unpredictable major climatic changes add to the hazards of rural existence. The disease-pattern of water-borne intestinal infections, and of parasites whose vectors or intermediate hosts are water-dependent, throws into relief the importance of water in a rural economy: domestically, bringing clean water to, and taking soiled water from, the households would be the most important hygienic innovation conceivable. Total vector control on a large scale is often practically impossible or prohibitively expensive, but much could be done to minimize the prevalence of disease by judicious preventive measures. These measures are dependent upon community acceptance, mass education, the deployment of health auxiliaries, wide use of intermediate technology, and family limitation, coupled with a fundamental rethinking of the training, curricula and functions of doctors and ancillary medical workers. The topsy-turvy world of organ transplantation and research into rare conditions, of the concentration on individual curative medicine to the neglect of the real causes of widespread morbidity, and of the increasing inequalities between the West and 'the others’, makes a reappraisal not only opportune but urgent.