Studies on human hydatidosis in Kenya

Abstract

This thesis is concerned with studies on the diagnosis and the chemotherapy of human hydatid disease in Kenya. Prior to this work there was no chemotherapy being undertaken in this disease in Kenya and there was only a small amount of work being conducted on the diagnosis of hydatid disease. A literature review revealed that human hydatidosis is a major global economic and health problem. It also revealed that Kenya has the highest endemicity for human hydatidosis, in the Turkana District n the north-westem part of the country. Occasional hydatid cases have also been seen among the Masai, Luo, Kikuyu and Kalenjin people. In Kenya, increasing documentation of human hydatidosis has featured more prominently since the late sixties because of an increased awareness and interest in the disease. Prior to that, hydatidosis was not considered a major health problem as compared to other diseases such as malaria, schistosomiasis, tuberculosis, malnutrition and diarrhoea. This study was made on ISO cases of surgically proven hydatidosis. In these, the immuno electrophoresis test was carried out so as to evaluate its use as a diagnostic tool for human hydatidosis in Kenya as this would be useful in clinical practice. Its specificity for hydatidosis was also assessed (evaluated) by carrying out the tests in 60 controls consisting of normal, kalazar cases and schistosomiasis cases. This was thought necessary since any cross reactivity would reduce the value of this test in clinical practice in Kenya. The test was found to be specific for human hydatidosis with a sensitivity of 62%, with no cross reactions in any of the control sera. The finding of 38% false negatives and the possibility of such factors as circulating immune complexes and circulating Echinococcus granulosus antigens in this group of patients is postulated and discussed. The factors currently known about the causative organism of hydatidosis in Kenya such as its strain characteristics are discussed in the light of the results obtained. The value of the immunoelectrophoresis test in Kenyan patients in this study is compared to the results of this test in Caucasian subjects with hydatidosis and the differences noted. The sensitivity of the immuno electrophoresis test at 62% limits its routine clinical application. However, it many be of special value in specialist centers like Kenyatta National Hospital and Provincial Hospitals for use in the follow up of cases after medical and/or surgical treatment and also for follow up of control measures especially in young people to see if these measures are successful or not. The recently formed Hydatid Control Committee in the Ministry of Health, Kenya, is initiating a pilot control programme in part of the Turkana District and this project will need several parameters for assessing the value of the control measures. In such a situation the immuno electrophoresis test may be useful for the follow up of a selected group of patients. Although ultrasonography has been previously tried on a very small scale prior to this study, it was decided to evaluate it in the 150 cases, as this would enable us to assess its cost effectiveness compared to serology in clinical practice in Kenya. Ultrasonography is noninvasive, cheap, safe with no radiation hazard and is suitable for a developing country with limited financial resources. This study confirms that ultrasound examination is very useful in abdominal hydatidosis. Radiology was included in the work because it was not available in Turkana at the beginning of this study. Prior to the study, a case had died in Turkana following chest aspiration without any x-ray examination of the case because it was assumed to be having pleural effusion. This emphasizes the value of x-ray examination. Moreover mass radiography may also reveal many more cases than can be diagnosed clinically and is therefore useful in prevalence studies. In Uruguay for instance the use of mass miniature radiography revealed a much higher prevalence of hydatidosis than had ever been suspected previously. The development of chemotherapy for human hydatidosis in Kenya did not start until the present study was undertaken. Prior to that there was no properly controlled clinical trial going on and the treatment was entirely surgical. Since inoperable hydatidosis is an important clinical problem in Kenya, as it account for 30% of the cases, it was thought justified to undel1ake the present work. Mebendazole was selected since it had shown promise in human hydatidosis at the time. Later in the study, when Albendazole became available it was included in the study. The initial work on Mebendazole in Kenya was discouraging since none of the cases responded to it. In the preliminary work, a small dose of 40 mg. Per kilogram of body weight was used. However, when it became possible later on in the study to estimate the serum mebendazole levels in Kenya, a preliminary pharmacokinetics study was undertaken to confirm if fat influenced the absorption of this drug in Kenyan hydatidosis patients, and also to estimate the drug level using the radioimmunoassay method since it became known that the optimal drug level is 100 mg/ml. The study also investigated if mebendazole enters hydatid cysts in Kenyan patients as this had not been established in this country previously. The pharmacokinetics study confirmed that fat greatly enhanced the absorption of mebendazole in Kenyan hydatidosis patients. This study also confirmed that mebendazole enters hydatid cysts in Kenyan patients and this is in agreement with previous reports by Morris on British patients. Thus following this pharmacokinetics study, it was decided to treat cases with hydatidosis so as to assess if when the drug level was around 100 nglml, it was effective in this disease. These cases were initially treated medically and then all underwent laparotomy and the protpscoleces removed were all subjected to viability studies, which included flame cell activity studies, evagination tests and the Eosin exclusion test. The results of this work show that in all the patients some of protoscoleces were structurally damaged, probably by the drug mebendazole. In all cases the optimal serum drug level of 100 nglml was achieved at one time or another during the treatment. Thus mebendazole has worked in this study and this could be a useful tool in future for the clinician looking after inoprablehydatid disease. Albendazole is showing early promise SInce the few cases treated so far show cyst regression on ultrasound. However, its clinical evaluation is still going and audit is still too early to draw any firm conclusions. Thus in the absence of a better alternative regime for inoperable human hydatidosis in Kenya, it may be justified to give either mebendazole or albendazole. In using the former drug the serum levels should be monitored. In conclusion, human hydatidosis is a major economic and health problem in Kenya and its diagnosis and the medical treatment for inoperable cases still need further evaluation. Early diagnosis is desirable with a view to appropriate treatment. This study emphasizes the fact that chemotherapy is necessary in Kenya and the results here show that drug treatment can actually be effective and for the present, mebendazole or albendazole should be used until there is a better alternative. There is also a need in Kenya to establish the precise incidence of hydatidosis especially n Nyanza, Central and Rift Valley Provinces since sporadic cases come from those areas. Finally, as a result of this study there is work going on currently in Kenya on circulating antigens in surgically proven cases with false negative immunoelectrophoresis test. Also following this work, it is now possible to do the Radioimmunoassay estimations of mebendazole levels in the Department of Medicine, Kenyatta National Hospital for hydatid patients receiving chemotherapy.