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PubMed2005

Effect of HIV-1 infection on antimalarial treatment outcomes in Uganda: a population-based study.

BACKGROUND: Human immunodeficiency virus (HIV) infection may increase the burden of malaria by increasing susceptibility to infection or by decreasing the response to antimalarial treatment. We investigated the seroprevalence rate of HIV-1 infection and its effect on antimalarial treatment outcomes in adults and children with uncomplicated falciparum malaria in Uganda. METHODS: This retrospective study included 1965 patients > or =18 months old who were randomized to receive 1 of 3 antimalarial regimens at 7 sites in Uganda. HIV-1 testing was performed using 2 enzyme-linked immunosorbent assays and Western blot analysis of stored blood spots. The primary study outcome was clinical treatment failure at 28 days after antimalarial treatment. Molecular genotyping was used to distinguish clinical treatment failures due to new infections from those due to recrudescences. RESULTS: The HIV-1 seroprevalence rate was 2.5% in 1802 patients <18 years old and 31% in 163 patients > or =18 years old presenting with malaria. HIV-1 infection was associated with a >3-fold (hazard ratio [HR], 3.28 [95% confidence interval [CI], 1.25-8.59]) increased risk of clinical treatment failure for adults, but there was no increased risk for HIV-1-infected children. Molecular genotyping revealed that clinical treatment failures were due to new infections (HR, 6.35 [95% CI, 1.64-24.5]) rather than to recrudescences (HR, 1.51 [95% CI, 0.27-8.58]). CONCLUSIONS: The HIV-1 seroprevalence rate was surprisingly high in adults presenting with malaria. This finding supports the implementation of routine HIV counseling and testing for adults with uncomplicated falciparum malaria. HIV-1 infection increased the susceptibility to new malarial infections but did not increase the risk of recrudescences in adults.

Adolescent↗
PubMed2005

How do patients use antimalarial drugs? A review of the evidence.

Patient adherence is a major determinant of the therapeutic response to antimalarial drugs, as most treatments are taken at home without medical supervision. With the introduction of new, effective, but more expensive antimalarials, there is concern that the high levels of efficacy observed in clinical trials may not be translated into effectiveness in the normal context of use. We reviewed available published evidence on adherence to antimalarial drugs and community drug usage; 24 studies were identified of which nine were 'intervention' studies, seven were classified as 'outcome studies', and the remainder were purely descriptive studies of antimalarial adherence. Definitions, methods, and results varied widely. Adherence was generally better when treatments were effective, and was improved by interventions focusing on provider knowledge and behaviour, packaging, and provision of correct dosages. There is insufficient information on this important subject, and current data certainly do not justify extrapolation from results with ineffective drugs to new effective treatments. Research in this area would benefit from of standardization of methodologies and the application of pharmacokinetic modelling.

Antimalarials↗
PubMed2005

The phenothiazinium chromophore and the evolution of antimalarial drugs.

The phenothiazinium salt methylene blue [3,7-bis(dimethylamino)phenothiazinium chloride] is the oldest known synthetic antimalarial drug, its clinical efficacy having been reported in 1891. The role of methylene blue in the evolution of the modern antimalarial armoury is often unappreciated, yet it can be linked directly to standard drugs such as chloroquine and its congeners. Also, in the face of increasing plasmodial resistance to modern antimalarials, phenothiazinium derivatives have again featured as lead compounds in drug research. The precise mode of action of methylene blue and its commercial analogues against Plasmodium spp. remains a cause for conjecture, having been variously described as nucleic acid intercalation, food vacuole basification, parasite redox cycle interference and haem polymerization inhibition. That the activity of the series may be due to more than one route - i.e. a multifactorial activity - underlines the utility of these compounds in antimalarial research either as single drugs or as adjuvants (partners in a drug combination), particularly in the face of resistant parasitic strains.

Animals↗
PubMed2005

Adoption of the new antimalarial drug policy in Tanzania--a cross-sectional study in the community.

OBJECTIVE: To assess the diffusion of the change of first line antimalarial drug from chloroquine (CQ) to sulphadoxine/pyrimethamine (SP) at household level in a rural district of Tanzania less than a year after the policy implementation. METHODS: Caretakers in 729 households were interviewed on knowledge of the new policy, home stocking of antimalarials, home-treatment practices of children younger than 5 years with fever, health-seeking behaviour and experience of SP. SP and CQ levels in blood were analysed from 328 children younger than 5 years in the households. Twelve focus group discussions (FGD) were performed with mothers, fathers and health workers. RESULTS: About 51% of the population knew that SP was the first line antimalarial. Only 8% of mothers stocked antimalarials, and only 4% stated self-treatment as the first action. We estimated that 84% of the children who had had fever during the last 4 weeks sought care at public health facilities. SP was detectable in 18% of the total child population and in 32% of those with reported fever, CQ in only 5% and 7%, respectively. The FGDs revealed negative perceptions of SP and fear of severe adverse reactions with mass media reported as key informant. CONCLUSION: The policy had diffused to the communities in the sense that CQ had been changed to SP, which was well known as first line treatment. Moreover, there was a reported dramatic change from self-treatment with CQ to seeking care at public health facilities where SP was given under observation.

Antimalarials↗
PubMed1998

Novel aryl-bis-quinolines with antimalarial activity in-vivo.

Three rationally designed isomeric aryl-bridged bis-quinolines, N1,Nx-bis(7-chloroquinolin-4-yl)phenylene-1,x-diamines, where x=2, 3 or 4, i.e. o-, m- and p-substituted analogues respectively, were synthesized and evaluated against Plasmodium berghei in-vivo. The compound with x=2 had an ID50 of 30 mg kg(-1), whereas the p-substituted analogue (x=4) was not statistically schizonticidal at either of the two dose levels tested in olive oil-dimethylsulphoxide (5 and 25 mg kg(-1), ID50=60 mg kg(-1) approx.). When the delivery vehicle was changed to saline-DMSO, antimalarial potency increased for the p-substituted compound (ID50 17 mg kg(-1)). In contrast, the m-substituted analogue had marked antimalarial activity (ID50 1.2 mg kg(-1)), which compares favourably with that of chloroquine diphosphate (ID50 = 4.3 mg kg(-1)). The data presented show that the aminomethylene side chain in amodiaquine can be successfully replaced by a 7-halo-4-aminoquinoline, establishing that carbon bridges containing less than four contiguous carbon atoms can be present within highly active aryl-substituted 4-aminoquinoline antimalarials. These results confirm that the presence of an OH group in the aryl bridge is not necessary for antimalarial activity and substantiate the view that, despite the appearance of resistant strains, new and existing aminoquinolines still have an important role in treating malaria.

Animals↗
PubMed1990

[Clinical evaluation of antimalarial drugs].

We have analyzed the clinical data of 189 patients with malaria to establish antimalarial regimens in Japan. The causative parasite species were Plasmodium falciparum in 56 cases (30%), P. vivax in 132 (70%) and P. malariae in 1 (1%). The outcomes f malaria cases are as follows: Cure rats in falciparum and vivax malaria are 86% and 91%, respectively. Two patients died of falciparum malaria and recurrence occurred in 6 cases (11%) of falciparum malaria. Relapse was seen in 12 (9%) of vivax malaria. Chloroquine was most frequently used among antimalarial agents (in 123 cases, 65% of the total) for suppressing acute attacks. The efficacy of chloroquine was evaluated by classifying each case into three groups: chloroquine alone in group one, chloroquine in combination with other antimalarials in group two and other antimalarials except chloroquine in group three. The cure rate among each group is about 80% and there is no difference among them. However, it is noticeable that recurrence occurred when patients were treated with a combination of chloroquine and quinine. We have found a similar result as this in another old report in Japan. Primaquine is effective for eliminating hepatic tissue schizonts but in this study, relapse occurred in 12 cases of vivax, although primaquine had been used in 10 out of 12 cases. In primaquine group, relapse occurred at a similar rate between chloroquine and Fansidar cases. Further studies are needed to decide whether a larger dose of primaquine is appropriate for treatment of vivax malaria. Recovery periods from fever and parasitemia were compared between chloroquine and Fansidar cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1979

Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique.

A rapid, semiautomated microdilution method was developed for measuring the activity of potential antimalarial drugs against cultured intraerythrocytic asexual forms of the human malaria parasite Plasmodium falciparum. Microtitration plates were used to prepare serial dilutions of the compounds to be tested. Parasites, obtained from continuous stock cultures, were subcultured in these plates for 42 h. Inhibition of uptake of a radiolabeled nucleic acid precursor by the parasites served as the indicator of antimalarial activity. Results of repeated measurements of activity with chloroquine, quinine, and the investigational new drug mefloquine demonstrated that the method is sensitive and precise. Several additional antimalarial drugs and compounds of interest were tested in vitro, and the results were consistent with available in vivo data. The use of P. falciparum isolates with known susceptibility to antimalarial drugs also permitted evaluation of the cross-resistance potential of each compound tested. The applications and expectations of this new test system within a drug development program are discussed.

Animals↗
PubMed1985

In vitro activities of and mechanisms of resistance to antifol antimalarial drugs.

Certain drugs that interfere with folate metabolism (sulfones, sulfonamides, and inhibitors of dihydrofolate reductase) play an important role in the chemotherapy and prophylaxis of malaria. The activities and mechanisms of action of these drugs are regarded as similar in most respects to their activities against procaryotic microorganisms. Believed incapable of utilizing intact exogenous folates, plasmodia have been regarded as dependent on de novo synthesis of required folate cofactors. The present investigation, conducted in pursuit of a method for testing the in vitro susceptibility of Plasmodium falciparum to antifol antimalarial drugs, produced evidence that earlier assumptions about the folate metabolism of this organism are not correct. Three of four isolates of P. falciparum were successfully maintained in a culture medium depleted of folic acid and p-aminobenzoic acid. The antimalarial activities of sulfonamides and dihydrofolate reductase inhibitors were, furthermore, variably antagonized by the presence of folic acid and p-aminobenzoic acid in the culture medium. Optimum conditions for assessment of antifol antimalarial activity in vitro therefore require precise control of these factors in the culture medium. Our results suggest that resistance to antifol antimalarial drugs involves a complex of factors related to both the de novo synthesis of active folate cofactors and the ability to utilize exogenous intact folates in various forms.

4-Aminobenzoic Acid↗
PubMed1997

New quinoline di-Mannich base compounds with greater antimalarial activity than chloroquine, amodiaquine, or pyronaridine.

We have compared the ex vivo antimalarial activity of 12 new quinoline di-Mannich base compounds containing the 7-dichloroquinoline or 7-trifluoromethylquinoline nucleus with amodiaquine, chloroquine, and pyronaridine using the Saimiri-bioassay model. Each compound was administered orally (30 mg/kg of body weight) to three or more noninfected Saimiri sciureus monkeys, and serum samples were collected at various times after drug administration and serially diluted with drug-free (control) serum. In vitro activity against the multidrug-resistant K1 isolate of Plasmodium falciparum was determined in serum samples by measuring the maximum inhibitory dilution at which the treated monkey serum inhibited schizont maturation in vitro. Of the 12 Mannich bases tested, 8 were associated with levels of ex vivo antimalarial activity in serum greater than those of amodiaquine, chloroquine, or pyronaridine 1 to 7 days after drug administration. Further studies were carried out with four of these compounds, and the results showed that the areas under the serum drug concentration-time curves for the four compounds were between 7- and 26-fold greater than that obtained for pyronaridine. Activity against four multidrug-resistant strains of P. falciparum was also much greater in serum samples collected from monkeys after administration of these four compounds than in serum samples collected after administration of pyronaridine or chloroquine. These findings suggest that these four quinoline Mannich base compounds possess a very marked and prolonged antimalarial activity and that further studies should be performed to determine their value as antimalarial drugs.

Amodiaquine↗
PubMed1998

Identification of Saccharomyces cerevisiae genes conferring resistance to quinoline ring-containing antimalarial drugs.

To identify genes that can confer resistance to antimalarial drugs in yeast, we transformed the quinidine-sensitive strain CYX247-9A of Saccharomyces cerevisiae with a yeast genomic library and selected for transformants that grow in the presence of elevated levels of antimalarial drugs. Plasmids were rescued from such clones and were analyzed for the presence of individual open reading frames that can confer drug resistance. Using quinidine as the selective drug, we were able to identify three genes that can cause resistance to antimalarial drugs. Overexpression of the yeast genes CIN5 (a member of the family of bZIP transcription factors), STII (a Hsp90 cochaperone), and YOR273c (a member of the major facilitator superfamily of transmembrane transporters) conferred 3.9-, 7.0-, and 4.3-fold resistance to quinidine, respectively, over that of control yeast. Cross-resistance assays determined that STI1 also conferred resistance to mefloquine (3.4-fold), while CIN5 also conferred resistance to mefloquine (9.6-fold) and chloroquine (5.4-fold). Using mefloquine as the selective drug, we determined that overexpression of YBR233w, a member of the hnRNPK family of nuclear RNA binding proteins, conferred resistance to mefloquine (13.5-fold). Expression of the human hnRNPK homolog of YBR233w in S. cerevisiae also conferred mefloquine resistance, suggesting that homologs of the identified resistance genes may perform similar functions in species other than yeast. Our experiments have identified heretofore unknown pathways of resistance to quinoline ring-containing antimalarial drugs in S. cerevisiae.

Amino Acid Sequence↗
PubMed2000

Hematin polymerization assay as a high-throughput screen for identification of new antimalarial pharmacophores.

Hematin polymerization is a parasite-specific process that enables the detoxification of heme following its release in the lysosomal digestive vacuole during hemoglobin degradation, and represents both an essential and a unique pharmacological drug target. We have developed a high-throughput in vitro microassay of hematin polymerization based on the detection of (14)C-labeled hematin incorporated into polymeric hemozoin (malaria pigment). The assay uses 96-well filtration microplates and requires 12 h and a Wallac 1450 MicroBeta liquid scintillation counter. The robustness of the assay allowed the rapid screening and evaluation of more than 100, 000 compounds. Random screening was complemented by the development of a pharmacophore hypothesis using the "Catalyst" program and a large amount of data available on the inhibitory activity of a large library of 4-aminoquinolines. Using these methods, we identified "hit" compounds belonging to several chemical structural classes that had potential antimalarial activity. Follow-up evaluation of the antimalarial activity of these compounds in culture and in the Plasmodium berghei murine model further identified compounds with actual antimalarial activity. Of particular interest was a triarylcarbinol (Ro 06-9075) and a related benzophenone (Ro 22-8014) that showed oral activity in the murine model. These compounds are chemically accessible and could form the basis of a new antimalarial medicinal chemistry program.

Animals↗
PubMed2000

Antimalarial activities of dermaseptin S4 derivatives.

The hemolytic antimicrobial peptide dermaseptin S4 was recently shown to exert antimalarial activity. In this study, we attempted to understand the underlying mechanism(s) and identify derivatives with improved antimalarial activity. A number of dermaseptin S4 derivatives inhibited parasite growth with a 50% inhibitory concentration (IC(50)) in the micromolar range. Among these, the substituted S4 analog K(4)K(20)-S4 was the most potent (IC(50) = 0.2 microM), while its shorter version, K(4)-S4(1-13)a, retained a considerable potency (IC(50) = 6 microM). Both K(4)K(20)-S4 and K(4)-S4(1-13)a inhibited growth of the parasites more at the trophozoite stage than at the ring stage. Significant growth inhibition was observed after as little as 1 min of exposure to peptides and proceeded with nearly linear kinetics. The peptides selectively lysed infected red blood cells (RBC) while having a weaker effect on noninfected RBC. Thus, K(4)K(20)-S4 lysed trophozoites at concentrations similar to those that inhibited their proliferation, but trophozoites were >30-fold more susceptible than normal RBC to the lytic effect of K(4)K(20)-S4, the most hemolytic dermaseptin. The same trend was observed with K(4)-S4(1-13)a. The D isomers of K(4)K(20)-S4 or K(4)-S4(1-13)a were as active as the L counterparts, indicating that antimalarial activity of these peptides, like their membrane-lytic activity, is not mediated by specific interactions with a chiral center. Moreover, dissipation of transmembrane potential experiments with infected cells indicated that the peptides induce damage in the parasite's plasma membrane. Fluorescence confocal microscopy analysis of treated infected cells also indicated that the peptide is able to find its way through the complex series of membranes and interact directly with the intracellular parasite. Overall, the data showed that dermaseptins exert antimalarial activity by lysis of infected cells. Dermaseptin derivatives are also able to disrupt the parasite plasma membrane without harming that of the host RBC.

Amphibian Proteins↗
PubMed2005

[Antimalarials in systemic diseases].

Antimalarials are drugs known for more than 300 years. Most widely used antimalarials are chloroquine, hydroxychloroquine, and less commonly quinacrine. The mechanisms of action are various and incompletely defined in the present moment. Antimalarials are used in numerous autoimmune diseases, the most frequent of which are rheumatoid arthritis and lupus erythematous. These drugs benefit especially cutaneous and articular disease, and moreover they are helpful for improvement blood glucose, lipids, and platelet aggregation. We discuss the dose and the most common adverse effects, especially those related to retina. Attention is especially directed to the treatment of pregnant women. Antimalarials favorable effectiveness-toxicity proportion advises consider them in the management of autoimmune diseases.

Antimalarials↗
PubMedDate not supplied

Effect of self-medication with antimalarial drugs on malaria infection in pregnant women in South-Western Nigeria.

OBJECTIVE: To determine the effect of self-medication with chloroquine and pyrimethamine on malaria infection and anaemia during pregnancy. SUBJECTS AND METHODS: The study involved 210 women who attended Ade Oyo Maternity State Hospital, Ibadan, Nigeria. Of these, 156 were pregnant women while 54 were not pregnant (controls). Of the pregnant women, 66 were primigravidae, while 90 were multigravidae. History of treatment of malaria with antimalarial drugs was obtained from the subjects. Gravidity and gestation period were also documented. Two millilitres of blood was withdrawn from each subject, for haematological parameters. Thin and thick films were prepared for malaria parasite identification and quantification. RESULTS: Of the primigravidae and multigravidae 68 and 16.4%, respectively, had taken antimalarial drugs prior to booking. Among primigravidae, only 18% of those with drugs compared with 32% without drugs were malaria-positive. The parasite density was significantly lower among those who took antimalarial drugs than among those who did not (976 +/- 60 versus 2,421 +/- 78, p < 0.05). Similarly, among multigravidae, only 16.4% of those who took antimalarial drugs compared with 34% of those who were not malaria-positive. The parasite density was also significantly lower in multigravidae with drugs than among those without drugs (350 +/- 45 versus 1,000 +/- 65, p < 0.05). The prevalence of anaemia (packed cell volume, PCV < 33) was high, 89% in primigravidae and 70% in multigravidae. Severe anaemia (PCV < 21) was more common in malaria-positive primigravidae and multigravidae than in malaria-negative women. CONCLUSION: The findings indicate that self-medication with chloroquine and pyrimethamine at booking was able to reduce the prevalence of malaria and anaemia in pregnancy.

Anemia↗
PubMed2005

Antimalarial activities and toxicities of three plants used as traditional remedies for malaria in the Democratic Republic of Congo: Croton mubango , Nauclea pobeguinii and Pyrenacantha staudtii.

The antimalarial activities of crude extracts and 17 fractions from the partition of 80%-methanolic extracts of three plants (the stem bark of Croton mubango, the stem bark of Nauclea pobeguinii and the leaves of Pyrenacantha staudtii) used as antimalarial remedies in the Democratic Republic of Congo were studied both in vitro (against Plasmodium falciparum) and in mice infected with Pl. berghei berghei. The toxic effects of dried aqueous extracts of the plants were also investigated, in uninfected mice. The most active crude extracts in vitro, with median inhibitory concentrations (IC(50)) of <1 microg/ml, were found to be the methanolic and dichloromethane extracts of C. mubango, and the dichloromethane extracts of N. pobeguinii and Py. staudtii. The aqueous extract with the most antimalarial activity in vitro was that of C. mubango (IC(50) = 3.2 microg/ml), followed by that of N. probeguinii (IC(50) = 5.3 microg/ml) and then that of Py. staudii (IC(50) = 15.2 microg/ml). Results from the in-vivo tests of antimalarial activity showed that, at a daily oral dose of 200 mg/kg, all the dichloromethane extracts, the petroleum-ether, chloroformic, ethyl-acetate and residual water-soluble fractions from C. mubango, and the chloroformic, ethyl-acetate and n-butanolic fractions from Py. staudtii produced >80% chemosuppression of the parasitaemias by day 4. The aqueous extracts of C. mubango and N. probeguinii produced a slightly lower but still significant inhibition of parasitaemia (60%-80%) whereas that of Py. staudtii only suppressed the day-4 parasitaemias by 37%. The dried aqueous extract of the stem bark of C. mubango showed some signs of toxicity in mice, with median lethal doses (LD(50)) of 350 mg/kg in the female mice and 900 mg/kg in the male. The extract significantly increased the serum concentrations of glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) in mice of both sexes, but had no effect on the blood levels of creatinine or urea. No significant toxic effect was observed for the dried aqueous extracts of N. pobeguinii and Py. staudtii (LD(50) >5 g/kg). Neither of these extracts affected the serum concentrations of GPT or the blood concentrations of creatinine and urea, although the N. pobeguinii extract did increase the serum concentration of GOT.

Animals↗
PubMed2006

The in-vivo antimalarial activities of Uvaria chamae and Hippocratea africana.

The antimalarial activities of ethanolic root extracts of two plants used traditionally as malarial remedies in southern Nigeria, Uvaria chamae (Annonaceae) and Hippocratea africana (Hippocrateaceae), were studied in vivo, in mice infected with Plasmodium berghei berghei. The extract of U. chamae, when given orally at 300-900 mg/kg.day, exhibited significant antimalarial activity against both early and established infections. When established infections were treated, the mean survival time of the mice observed with this extract at 900 mg/kg.day was similar to that seen with the positive control: chloroquine at 5 mg/kg.day. The extract of H. africana, tested at oral doses of 200-600 mg/kg.day, also demonstrated promising blood schizontocidal activity, both in early and established infections. Although the question of their toxicities has still to be fully addressed, it is clear that both U. chamae and H. africana possess considerable antimalarial activity and they, or drugs based on their antimalarial constituents, may prove useful in the treatment of human malaria.

Administration, Oral↗
PubMed2005

In vitro antimalarial drug susceptibility in Thai border areas from 1998-2003.

BACKGROUND: The Thai-Myanmar and Thai-Cambodia borders have been historically linked with the emergence and spread of Plasmodium falciparum parasites resistant to antimalarial drugs. Indeed, the areas are often described as harbouring multi-drug resistant parasites. These areas of Thailand have experienced significant changes in antimalarial drug exposure patterns over the past decade. This study describes the in vitro antimalarial susceptibility patterns of 95 laboratory-adapted P. falciparum isolates, collected between 1998 and 2003. METHODS: Ninety five P. falciparum isolates were collected from five sites in Thailand between 1998 and 2003. After laboratory adaptation to in vitro culture, the susceptibility of these parasites to a range of established antimalarial drugs (chloroquine [CQ], mefloquine [MQ], quinine [QN] and dihydroartemisinin [DHA]) was determined by the isotopic microtest. RESULTS: Mefloquine (MQ) sensitivity remained poorest in areas previously described as MQ-resistant areas. Sensitivity to MQ of parasites from this area was significantly lower than those from areas reported to harbour moderate (p = 0.002) of low level MQ resistance (p = 000001). Importantly for all drugs tested, there was a considerable range in absolute parasite sensitivities. There was a weak, but statistically positive correlation between parasite sensitivity to CQ and sensitivity to both QN and MQ and a positive correlation between MQ and QN. In terms of geographical distribution, parasites from the Thai-Cambodia were tended to be less sensitive to all drugs tested compared to the Thai-Myanmar border. Parasite sensitivity to all drugs was stable over the 6-year collection period with the exception of QN. CONCLUSION: This study highlights the high degree of variability in parasite drug sensitivity in Thailand. There were geographical differences in the pattern of resistance which might reflect differences in drug usage in each area. In contrast to many other studies there were weak, but statistically significant positive, correlations between sensitivity to CQ and sensitivity to MQ and QN. Over the six years of sample collection, parasite sensitivity appears to have stabilized to these drugs in these sites.

Animals↗
PubMed2006

The contribution of microscopy to targeting antimalarial treatment in a low transmission area of Tanzania.

BACKGROUND: There is a need for improved targeting of antimalarial treatment if artemisinin combination therapy is to be successfully introduced in Africa. This study aimed to explore why malaria slides are requested and how their results guide treatment decisions in an area of low transmission of P. falciparum. METHODS: Outpatients attending a district hospital in a highland area of Tanzania were studied over a 3-week period. Clinical and social data were collected from patients who had been prescribed an antimalarial or sent for a malaria slide. Hospital slides were re-read later by research methods. RESULTS: Of 1,273 consultations 132(10%) were treated presumptively for malaria and 214(17%) were sent for a malaria slide; only 13(6%) of these were reported positive for P. falciparum but 96(48%) of the 201 slide-negative cases were treated for malaria anyway. In a logistic regression model, adults (OR 3.86, P < 0.01), a history of fever (OR1.72, P = 0.03) and a longer travel time to the clinic (OR 1.77 per hour travelled, P < 0.01) independently predicted the request for a malaria slide. Only a history of a cough predicted (negatively) the prescription of an antimalarial with a negative slide result (OR 0.44, P < 0.01). The sensitivity and specificity of hospital slide results were 50% and 96% respectively. CONCLUSION: Progress in targeting of antimalarials in low malaria transmission settings is likely to depend on consistent use of malaria microscopy and on the willingness of health workers to be guided by negative slide results. Further studies are needed to identify how this can be achieved.

Adolescent↗