'Behind walls': a study of HIV risk behaviours and seroprevalence in prisons in Zambia.

Inmate populations include a large number of individuals at risk of HIV infection. However, there is insufficient data about HIV/AIDS epidemiology in prisons. Our study, conducted in Zambia, a sub-Saharan African nation with an estimated HIV prevalence of 19% in adults, was designed to address this shortfall.

Halofantrine and chloroquine inhibit CYP2D6 activity in healthy Zambians.

AIMS: To determine the effect of therapeutic loading doses of halofantrine and chloroquine on CYP2D6 activity in healthy black Zambians. METHODS: Twenty healthy black male Zambians were phenotyped for CYP2D6 activity by measuring the debrisoquine/4-hydroxydebrisoquine ratio in a 0-8 h urine sample after a 10 mg oral dose of debrisoquine hemi-sulphate. The subjects (all 'extensive metabolizer' phenotype with respect to CYP2D6) were randomized into two groups of 10, and 24 h later one group received 1500 mg halofantrine hydrochloride and the other group 1500 mg chloroquine phosphate both orally in divided doses. All subjects were given further 10 mg doses of debrisoquine at 2 h, 1 week and 2 weeks after the last dose of the antimalarial drug, and phenotyped as described above. RESULTS: The median debrisoquine/4-hydroxydebrisoquine 0-8 h urinary ratio was increased by halofantrine (1.39 to 6.05; P<0.01; 95% confidence intervals 4.00-11.7) and chloroquine (1.96 to 3.91; P<0.01; 95% confidence intervals 1.34-2.66) when debrisoquine was given 2 h after treatment. The decrease in CYP2D6 activity remained statistically significant for 1 week after both drugs. Halofantrine was a significantly more potent inhibitor of CYP2D6 than chloroquine (P=0.037). Phenocopying occurred in two subjects taking halofantrine and one taking chloroquine (i.e. the debrisoquine/4-hydroxydebrisoquine ratios became consistent with the poor metabolizer phenotype). CONCLUSIONS: Given in therapeutic loading doses, both halofantrine and chloroquine caused significant inhibition of CYP2D6 activity in healthy black Zambians. With respect to halofantrine, this finding reinforces the recommendation that its combination with other drugs known to prolong the QT interval should be avoided, especially those that are metabolized significantly by CYP2D6.

Circumcision in the control of HIV?

Ken Rankin (AH, Jan '94, p 34) rightly points out that more circumcisions are carried out than are justified on clinical grounds alone. However, the advent of AIDS raises a number of interesting points about the possible role of circumcision as an epidemiological tool for the control of HIV transmission. It has been reported that an absence of circumcision increases susceptibility to acquiring STDs. STDs, especially those that cause genital ulcer disease (such as syphilis, chancroid and genital herpes), are recognized major risk factors for the transmission of HIV. Furthermore, some studies have shown that the distribution of HIV seroprevalence in Africa is closely associated with the geographical pattern of circumcision practices, whilst other workers have shown an association between absence of circumcision and HIV seropositivity. In some societies where circumcision was formerly practiced on religious/cultural grounds, it has now largely been abandoned as a consequence of urbanization and the adoption of Western lifestyles. In such situations, a revival of this ancient custom might supplement other control measures against HIV transmission. The only proviso would be an insistence on sterile procedures. The devastating impact of AIDS, especially in sub-Saharan Africa, necessitates a consideration of all possible interventions.

Debrisoquine and metoprolol oxidation in Zambians: a population study.

The 0-8 h urinary distributions of the metabolic ratios of debrisoquine (10 mg) and metoprolol (100 mg) were measured in 102 healthy, unrelated, black Zambian medical students. There was a statistically significant correlation (rs = 0.60, p < 0.001; n = 88) between the debrisoquine/4-hydroxydebrisoquine (D/HD) and metoprolol/alpha-hydroxymetoprolol (M/HM) ratios. Bimodality in the distribution of the log10D/HD ratio was not evident from visual inspection and following kernel density analysis of the data, although two subjects (ratios 20, 22) would be classified as phenotypic poor metabolizers (PMs) based on the antimode used for Caucasian populations. The distribution of the log10M/HM ratio was skewed and on the basis of kernel density analysis, bimodal. It was clear from visual inspection of the data that the very high M/HM value (> or = 302) of one individual had a profound influence on the population M/HM ratio distribution. No HM was detected in the urine of this subject but he was not one of the two PMs of debrisoquine (D/HD ratio 1.54). H117/04, the major metabolite of metoprolol was also not detected in this sample. Since H117/04 was shown to be present in all samples from previous population studies, the possibility that this subject did not comply with the protocol could not be excluded. All other subjects had M/HM ratios < or = 12.5. These findings suggest that there is a dissociation in the control of debrisoquine and metoprolol oxidation in Zambians as has been observed previously in Nigerians. Furthermore, clear evidence that the metabolism of these drugs exhibits genetic polymorphism in Zambians was not obtained.

HIV infection in newly diagnosed tuberculosis patients in Ndola, Zambia.

Between June and December 1987, 131 patients newly admitted to the tuberculosis wards of the Ndola Central Hospital, underwent a history and examination, chest radiography, sputum examination and an enzyme linked immuno sorbent assay (ELISA) (Wellcome), for human immuno deficiency virus (HIV) antibodies. For all sera testing positive, the ELISA was repeated on two different occasions before HIV seropositivity was confirmed. Eighty-three patients (67 pc) had tubercle bacilli on microscopy, whilst 76 patients (58 pc) were HIV positive (7 patients had no sputum on admission). Nine patients (7 pc) had signs of disseminated tuberculosis while the rest had evidence of pulmonary tuberculosis. Four patients (3 pc) had normal chest radiography, whereas the remainder had intrapulmonary lesions in their films. No association was found between presence or absence of bacilli and HIV seropositivity (P greater than 0.05). HIV seropositive tuberculosis patients were more likely to be younger and female when compared to HIV seronegative tuberculosis patients (P less than 0.05). It was concluded that HIV infection is common in newly diagnosed tuberculosis patients and that young and female patients are more likely to be HIV seropositive than their male counterparts.

PIP: Between June-December 1987, 131 patients newly admitted to the tuberculosis wards of the Ndola Central Hospital underwent a history and examination, chest radiography, sputum examination, and an enzyme linked immunosorbent assay (ELISA, Wellcome) to test for human immunodeficiency virus (HIV) antibodies. For all sera testing positive, the ELISA was repeated on 2 different occasions before HIV seropositivity was confirmed. 83 patients (67%) had tubercule bacilli on microscopy while 76 (58%) were HIV positive (7 patients had no sputum on admission). 9 patients (7%) had signs of disseminated tuberculosis while the remainder had evidence of pulmonary tuberculosis. 4 patients (3%) had normal chest radiography, whereas the rest of the group had intrapulmonary lesions on their films. No association was seen between presence or absence of bacilli and HIV seropositivity (;0.05). HIV seropositive tuberculosis patients were more likely to be younger and female as compared with the HIV seronegative tuberculosis patients (p0.05). It was concluded that HIV infection is common in newly diagnosed tuberculosis patients and that young female patients are more likely to be HIV seropositive than their male counterparts.

Inhibition of metoprolol metabolism by chloroquine and other antimalarial drugs.

The ability of a series of antimalarial drugs to impair the metabolism of metoprolol in rat and man has been examined. Chloroquine was a potent inhibitor in rat liver microsomes (Ki value for metoprolol alpha-hydroxylation = 0.18 microM and for O-demethylation = 0.36 microM). The other antimalarial drugs also inhibited metoprolol oxidation. Quinine was similar to chloroquine in potency, while quinidine, primaquine and mefloquine were slightly less potent. Chloroquine also inhibited metoprolol oxidation in human liver microsomes, although it was about two orders of magnitude less potent than in the rat and the extent of impairment varied greatly between individual livers. Intraperitoneal administration of chloroquine to anaesthetized rats decreased the clearance of metoprolol (40 mg tartrate salt kg-1 i.p.) to 54, 34, 20 and 26% of the control value at doses of 2.5, 4.0, 25 and 40 mg kg-1, respectively. We conclude that antimalarial treatment might have contributed to a previously reported difference in the metabolic pattern of metoprolol between Caucasians and Nigerians.

Relation between falciparum malaria and HIV seropositivity in Ndola, Zambia.

PIP: A study was conducted at the Ndola Central Hospital, Zambia, in 1987 to determine whether human immunodeficiency virus (HIV) infection increases the risk or severity of infection with falciparum malaria in patients aged 12 years and over. The 170 patients examined all presented with symptoms suggestive of malaria, including fever, chills, rigors, headaches, joint pains, myalgia, acute diarrhea, and vomiting. 67 (39%) were diagnosed as having falciparum malaria and 28 (17%) were positive for the HIV antibody. The prevalence of malarial parasitemia in patients with HIV antibodies was lower than that in patients without such antibodies (29% versus 42%, respectively), and differences in densities of parasites also failed to provide evidence of increased susceptibility to malaria in patients infected in HIV. There were no significant differences in antibody titers to P falciparum in patients who were positive for HIV antibody and in those who were negative, whether or not they had parasitemia. The earlier finding of a significant association between malaria and HIV infection is now believed attributable to false positive results with the 1st enzyme linked immunosorbent assays and to interpretation difficulties with the Western blot test. Of interest is the fact that 20 patients in this study had symptoms suggestive of malaria, but had negative results for parasites and positive results for HIV antibody. This indicates that many patients with HIV infection may be presenting with an illness clinically similar to malaria before acquired immunodeficiency syndrome (AIDS)-related complex or AIDS is recognizable.^ieng

Sensitivity of Plasmodium falciparum to chloroquine, amodiaquine and mefloquine in Ibadan, Nigeria.

The schizontocidal effect of chloroquine was compared to that of amodiaquine in vivo and mefloquine in vitro. In the in-vivo study, 32 patients were randomly given chloroquine whilst 29 received amodiaquine. The mean parasite clearance time was 2.5 days for chloroquine and 2.4 days for amodiaquine. These times were not significantly different. The cure rate in both groups up to day 14 was 100%. In the in-vitro study, three isolates of Plasmodium falciparum were compared for their sensitivity to chloroquine and mefloquine. In all three isolates schizogony was inhibited at a concentration of 0.8 x 10(-6) mol/l of either drug. It was concluded that chloroquine is still an effective schizontocide and should remain the drug of choice for the treatment of P. falciparum in the Ibadan area.

Adult cerebral malaria in Zambia: preliminary report of clinical findings and treatment response.

Fifty-six adult patients diagnosed as having 'cerebral malaria' were admitted and treated over a 4 month period. The presenting symptoms were similar to those of control patients with malaria without cerebral manifestations except that vomiting and convulsions were significantly more frequent and joint pains were less frequent in the cases than in the controls. Physical examination revealed significantly more frequent occurrence of nuchal rigidity, positive Kernig's sign, confusion, muteness, pallor and jaundice in the cases than controls, while splenomegaly was significantly more common in controls than cases. Laboratory data showed that cerebral malaria cases had significantly lower haemoglobin and significantly higher reticulocyte count and erythrocyte sedimentation rate than controls. There was no significant difference in the parasite density between the cases and controls. All patients were treated with 200 mg base of intravenous chloroquine in 250 ml of isotonic saline infused over 2 h and repeated 12 hourly till oral therapy was possible. This proved to be efficacious and the recovery rate was over 90%. Five patients died and the diagnosis was confirmed in three in whom autopsy was permitted. A simple staging system is proposed which retrospectively seems to have prognostic value. It is recommended that the validity of this system be tested prospectively.

A double-blind clinical trial of a combination of mefloquine, sulfadoxine and pyrimethamine in symptomatic falciparum malaria.

Fansimef is a combination of 250 mg of mefloquine, 500 mg of sulfadoxine, and 25 mg of pyrimethamine per tablet. A total of 150 adult male Zambian patients who had symptomatic Plasmodium falciparum parasitaemia were treated in a double-blind randomized fashion with either one, two or three tablets of Fansimef. All patients in the three treatment groups showed an S-type response. The rates of clearance of parasitaemia and fever were similar in all treatment groups. Tolerance was good at all dose levels. The main side-effects were abdominal discomfort, weakness and lassitude, dizziness, and pruritus, but these were mild, transient and required no specific treatment. Vomiting occurred only in 4% of patients given the highest dose of three tablets. The results of various haematological and biochemical investigations and urinalysis were not adversely altered by the administration of Fansimef.