An annual 20% excess mortality rate is observed in HIV-seropositive patients after treatment for tuberculosis. An affordable secondary prophylaxis against main opportunistic diseases is needed, i.e. against tuberculosis, toxoplasmosis, pneumocystosis and other infections occurring in this target population. This open prospective randomized study assessed morbidity and mortality in 2 cohorts of HIV-seropositive patients having recently recovered from pulmonary tuberculosis: 134 patients assigned to prophylactic treatment with isoniazid (INH, 300 mg once daily) plus sulphadoxine-pyrimethamine (S, 500 mg/P, 25 mg once weekly), and 129 were controls, comparable for sex, age, weight and HIV-serology. Patients were followed-up for up to 2 years: 192 person-years (PY) in the prophylaxis group and 142 PY in the control group. Four patients developed tuberculosis and 20 patients died in the prophylaxis group, compared to 10 and 23 controls, respectively. Sick days were reported by 22 patients in the prophylaxis group and by 77 patients in the control group. This prophylaxis was associated with a moderate decrease of mortality (log rank test: p = 0.1736), a significant decrease of tuberculosis incidence (log rank test: p = 0.0234), a highly significant reduction of adverse events and sick days, and a prevention of wasting (p = 0.008) and anaemia (p = 0.045). No death from toxoplasmosis occurred in the prophylaxis group as compared to 2 possible cases among controls; toxoplasmosis IgG levels declined in treated patients, but increased in controls (p = 0.01). There was no adverse drug reaction due to SP (10,006 doses) or to INH. Compliance with SP intake was good, but moderate as with INH intake. We conclude that a secondary prophylaxis with INH+SP represents a cost-effective measure to improve health conditions of HIV-infected adults in Côte d’Ivoire, following a full treatment course against tuberculosis.

Background: The objectives of this study were (1) to compare the efficacy of Lariam (mefloquine) with that of Fansimef (mefloquine, sulfadoxine, and pyrimethamine), Fansidar (sulfadoxine and pyrimethamine), chloroquine, and placebo in suppressing asexual parasitemia in semi-immune persons living in an area endemic for Plasmodium falciparum malaria; and (2) to compare the tolerance of these drugs when taken over a prolonged period of time. Method: A randomized double-blind comparative placebo-controlled study was undertaken in the village of Biasso, 60 km from Abidjan in the southern part of the Ivory Coast, a region where P. falciparum malaria is endemic. Four hundred and ninety nine male volunteers (five parallel groups), who were inhabitants of Biasso, were involved. The main outcome measures concerned the incidence of malaria breakthroughs (acute malaria attacks) and the incidence of parasitemia. Results: Within this strictly defined epidemiologic context, prophylaxis, taken once weekly, proved to be fully protective (parasitic index: 0) in the Lariam, Fansidar, and Fansimef groups throughout the whole study period. Prophylaxis with chloroquine proved incompletely protective (parasitic index: 2.5) The most frequent side effects were pruritus (5.6%), diarrhea (1.2%) and headache (0.06%). No significant differences in the incidence of side effects in each group (chi-square test) was observed. All side effects were transient and judged to be mild by the investigators. Conclusions: Excellent efficacy was observed in the prophylaxis of P. falciparum malaria with Lariam, Fansidar, and Fansimef as compared to the partial protection provided by chloroquine. Safety and tolerance were comparable in all groups during the whole period of observation (5 months).

Bacl^round Limb activity meters are useful in correlation with subjective measurements for studying the antipruritic effects of drugs against current chloroquine itch among patients with malarial fever, in a tropical environment. Objective To prospectively monitor the palliative effects of drugs, without any presumptively significant antipuritic effects known, against moderate to severe chloroquine-related pruritus among patients with malaria. Methods Using a standard ordinal (0-10) scale questionnaire and limb activity meters on all limbs, 60 subjects (50 malarial patients plus 10 healthy controls; both sexes; aged 16-32 years) were recruited for study. Forty patients and the 10 healthy unmedicated controls completed the study and were used for data analysis. Results Dapsone (50 mg tablets, 8 hourly, orally) significantly reduced pruritus ordinal scores (below 2.5) and limb activity recordings to levels comparable with unmedicated controls by the second or third night of nocturnal monitoring the chloroquine itch among the patients. Clemastine or ketotifen (1 mg tablets, 8 hourly, orally) or prednisolone (5 mg tablets, 12 hourly, for 3 days, then tapered to 5 mg daily for another 2 days, orally), did not significantly exceed the placebo responsiveness to vitamin B-complex tablets (one 8 hourly, orally, for 3 days). Conclusion Dapsone, or sulphapyridine (500 mg tablets, 6 hourly, orally daily for 5 days in another recent investigation) have now emerged as potent symptomatic palliatives against chloroquine pruritus.

Abstract. The efficacy and tolerability of single, low-dose mefloquine, sulfadoxine-pyrimethamine (MSP) combination was compared with chloroquine (CQ) for malaria treatment in a malaria-endemic area of Nigeria with multiple drug-resistant Plasmodium falciparum. The two drug regimens (MSP and CQ) were tested in a 12-month prospective population study. The patients were divided into two groups. Group 1 patients were treated presumptively, based on malaria symptoms. Group 2 patients were treated based on a parasitologic diagnosis using the World Health Organization seven-day in vivo test and extended to a 28-day follow-up period. Tolerability was assessed by the incidence and intensity of adverse events. One thousand nine hundred thirty-five patients visiting 10 health facilities, including the University of Calabar Teaching Hospital, were enrolled. The study showed that the low-dose MSP was efficacious, with day 7 response rates of 95% and 91% for (presumptive) Group 1 and (in vivo) Group 2, respectively, while CQ had day 7 response rates of 82% and 66% in Groups 1 and 2, respectively. The low-dose MSP was significantly (P Ͻ 0.0001) more efficacious, with faster fever and parasite clearance times than CQ in this area of CQ-resistant P. falciparum malaria. Eight patients treated with CQ, including seven severe cases (RII-RIII) were successfully re-treated with MSP. Adverse events were generally more common among those treated with MSP (29%) than those treated with CQ (17%). However, the adverse events caused by both drugs were mild to moderate and self-limited. The MSP combination appears to be a good substitute for CQ, in view of multiple drug resistance, especially in areas with severe (RII-RIII) malaria.

Thirty Mycobacterium tuberculosis strains (8: INH^R/INH^R, 12: INH^R/RIF^S, 10: INH^S/RIF^S) were examined against MICs of epiroprim (EPM) and isoniazid (INH) separately or in association. EPM alone proved to be insufficiently active against the various mycobacterial isolates (MIC ≧256 µg/ml). The observed average sensitivity to the association of EPM plus INH was, in contrast, considerably increased, as reflected by reduced MICs and lower percentages of resistant strains. MICs ranged between 16 and 32 µg/ml EPM and 2 and 4 µg/ml INH for INH^R strains. All INH^S isolates were inhibited by a concentration of 0.125 µg/ml EPM and 0.06 µg/ml INH. The fractional inhibitory concentration indices indicated an additive activity on INH^R/RIF^R strains and a synergistic activity on INH^R/RIF^S and INH^S/RIF^S strains. The synergistic activity of this drug association needs to be confirmed in an animal model.