Adverse reactions in expatriates treated with ivermectin.
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Biomedical subjects
Publications and source records attributed to A D Bryceson.
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The development of visceral leishmaniasis with atypical features in an AIDS patient, and the recent flurry of reports of visceral leishmaniasis in HIV-infected individuals prompted the review of its manifestations in the 47 reported cases. Splenomegaly, which is almost always a feature of visceral leishmaniasis in the immunocompetent host, was absent in eight. Antibodies to Leishmania donovani, which are present in approximately 95 per cent of immunocompetent patients with visceral leishmaniasis, were absent in 29 of 45 (66 per cent) of HIV-infected patients tested. Nine HIV-positive patients with visceral leishmaniasis did not exhibit a primary clinical response to therapy with antimonials and of those who did show a response, relapse occurred in 13, at a mean 4.5 months after stopping therapy. Seventeen patients are known to have died often in association with respiratory disease; Leishmania was seen in one bronchial lavage specimen and in lung tissue in one post-mortem performed. In order to improve the prognosis of visceral leishmaniasis in HIV-infected patients diagnosis will have to be made earlier, taking account of the atypical features, and treatment will need to be improved, both initially and perhaps also by the use of long-term maintenance therapy.
A patient with HIV infection presented with multiple cutaneous Kaposi's sarcomata. Biopsy of one of these showed the presence of amastigotes within an otherwise typical Kaposi's sarcoma. Further investigations proved the patient to have visceral leishmaniasis (kala azar). Visceral leishmaniasis has been reported in HIV infection but it is rare and this presentation is unique. The patient made a good response to a prolonged course of treatment with sodium stibogluconate and allopurinol.
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Clinical features in 173 white expatriates returning to Britain with the sole diagnosis of schistosomiasis were compared with those in non-infected control subjects, matched for age and sex, returning from similar endemic areas. Infection was, with one exception, acquired in Africa. Schistosoma mansoni was found in 135 patients, S haematobium in 29, and mixed infection in 9. 79% of patients with S haematobium had symptoms, compared with 47% of patients with S mansoni. Tiredness, headache, and gastrointestinal disturbance were no more frequent in symptomatic patients than in control subjects. In over 50% of patients with schistosomiasis the diagnosis was established from snips of rectal mucosa, and this raises the question of how best to look for infection in those who have been exposed. Urine examination and schistosomal serology appear to be the best screening methods; patients with haematuria or seropositivity should be investigated further.
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Ten Kenyan patients with visceral leishmaniasis, unresponsive to sodium stibogluconate at a dose of 16 to 20 mg Sb/kg/day given for 30 to 98 days, have been studied clinically and immunologically and compared with 57 antimony-responsive patients. Pulmonary tuberculosis and previous treatment with antimonial drugs were the only factors which were more common in unresponsive patients. The degree of immunosuppression and rate of recovery of immunoreactivity did not differ between antimony-responsive and -unresponsive patients. Only one patient had never been treated before (primary unresponsiveness). In the other nine patients secondary unresponsiveness occurred after one or more treatment courses, suggesting that the parasite developed resistance to antimony. Antimony-unresponsiveness in visceral leishmaniasis is a serious problem numerically, clinically and economically. A plea is made that the initial treatment of visceral leishmaniasis should be adequate in dose and duration.
Ten Kenyan patients with visceral leishmaniasis unresponsive to sodium stibogluconate, at a dose of 16 to 20 mg Sb/kg body-weight/day given for 30 to 98 days, were treated with 20 mg Sb/kg bw given every eight hours. This regimen was modified or abandoned in six patients because of suspected toxicity, although toxicity was difficult to assess because of intercurrent illness. Toxic effects included lethargy, anorexia, vomiting, electrocardiographic changes, fall in haemoglobin and rise in liver enzymes. One patient died, probably from a cardiac arrhythmia. Two patients were cured, four responded partially and four showed no response. Pentamidine, at a dose of 4 mg/kg body-weight given one to 3 times per week for 5 to 39 weeks, was given as initial treatment in one patient and after failure of sodium stibogluconate in seven. Toxic effects included nephritis, hepatitis, transient diabetes and subcutaneous abscesses. Two patients were cured, two responded partially, three showed no response and one, after apparent cure, relapsed and was unresponsive to additional pentamidine treatment. Low-frequency, long-duration pentamidine was often useful in maintaining any improvement made during treatment with the less well tolerated high-dose, high frequency sodium stibogluconate. We observed the step-wise development of resistance to both sodium stibogluconate and pentamidine. The problems of managing patients with visceral leishmaniasis which is unresponsive to conventional doses of pentavalent antimonials are discussed and some tentative suggestions put forward.
Five patients with long-standing visceral leishmaniasis who were unresponsive to sodium stibogluconate, 20 mg antimony/kg body-weight once or twice daily, were treated for 14 to 54 days with a combination of sodium stibogluconate at the same dose plus allopurinol at a dose of 20 mg/kg body-weight per day in three divided doses. This combination was safe and effective. Negative splenic aspirate smears were obtained from all patients within 19 days, and none has relapsed in at least 12 months of follow-up.
A patient with a previous history of an infection with Leishmania b. braziliensis contracted zoonotic cutaneous leishmaniasis (ZCL) in the Al-Hassa oasis, Eastern Province, Saudi Arabia. Five lesions healed spontaneously over a period of 40 weeks without treatment. A year after acquiring ZCL he became infected again in the same focus. Isolates of parasites at both episodes were identified as L. major, zymodeme LON-4. Compared with the first infection of ZCL, parasites were fewer in the lesions on the second occasion, the lesions were smaller and healing was quicker (10 weeks). This work and a previous report of patients with active lesions and leishmanial scars suggest that second infections of L. major are not uncommon in the oasis where no autochthonous infections of other species of Leishmania have yet been recorded in man and only one species of Phlebotomus (P. papatasi) is known.
Small-intestinal function was studied in 10 patients with visceral leishmaniasis. Vitamin-A absorption was impaired in 7 and d-xylose in 1. In 5 of the 10 patients Leishmania were demonstrated in biopsy specimens of intestinal mucosa. Parasitised macrophages were present in villous tips and less commonly in the lamina propria and submucosa; a moderate inflammatory infiltrate was composed of lymphocytes and plasma cells. 2 patients had partial villous atrophy. There was no correlation between intensity of parasitisation and severity of malabsorption. After treatment with sodium stibogluconate there was a significant improvement in absorption of vitamin A and d-xylose, and biopsy specimens became normal. In 1 patient visceral leishmaniasis was thought to be the cause of chronic diarrhoea.
The efficacy and safety of a single daily dose of sodium stibogluconate, 20 mg/kg body weight, given by deep intramuscular injection was compared with the conventional dose of 10 mg Sb/kg body weight in a randomised trial in Kenyan children and adults with visceral leishmaniasis. Splenic aspiration proved a safe and simple method for assessing parasitological response to treatment. In children the higher dose was associated with a faster clinical and parasitological response, and 100% were cured within 4 weeks, compared with 60% receiving the lower dosage. This difference is statistically significant by life-table analysis (x2 = 4.41, p less than 0.05). The superiority of the higher dose was not, however, seen in adults. In both children and adults the higher dose given daily for 2--4 weeks and in one patient for up to 7 weeks was found to be safe and well tolerated. It is likely, but not proven, that the use of sodium stibogluconate in a dose of 20 mg/kg bw daily for 4 weeks will reduce the relapse-rate in Kenyan children with visceral leishmaniasis.