[Practices of caregivers and national recommendations for treatment of malaria in Benin in 2009]. / Recommandations nationales et pratiques en matière de traitement du paludisme au Bénin en 2009.

New treatments against malaria (artemisinin-based combination therapies, ACT) resulted in profound changes in the therapeutic behaviours in Africa. This study aims to evaluate the practices adaptation to the new strategies in Benin in 2009. In three southern areas of the country, 14 private pharmacies, 10 public health centers and 10 private health centers were audited. Between July and October 2009, 36 providers and 93 prescribers were interviewed, 127 dispensations for self-medication were observed, 210 prescriptions were analyzed according to the WHO recommendations, 251 patients with complaints of malaria and 50 healthy women were interviewed and 34 physical inventories were conducted in pharmacies. Knowledge and trainings were inadequate, especially in the private sector and for the providers, as 41.6% of requests for antimalarial drugs were without prescription in private pharmacies. Only 28% of prescribers and 47% of providers knew the national recommendations of 1st line treatment for uncomplicated malaria. 53% of prescribers treated patients by ACT without prior parasitological examination in the case of uncomplicated malaria and no Rapid Diagnostic Test (RDT) was carried out or requested during the dispensation. Pharmaceutical advices were absent in 78.7% of cases and population acknowledged a lack of knowledge about use of the treatment. Private pharmacies were structures where the variability of available antimalarial drugs was the largest, up to 70 different specialities and where unit prices were highest, up to 7.7 times those charged in public health centers. In the field, the difficulties of application of recommendations, given at the scientific or political level, show the necessity of accompanying policy change by prior training activities of all health stakeholders and of adapting the previous regulations to facilitate implementation of the new rules. The number of authorizations issued for the ACT should be limited; authorization to chloroquine and oral formulations of artemisinin monotherapy should be removed. Since the private sector is actually involved in the fight against malaria, one should provide in this sector ACT and rapid diagnostic tests at subsidized prices.

Consumers stated and revealed preferences for community health workers and other strategies for the provision of timely and appropriate treatment of malaria in southeast Nigeria.

BACKGROUND: The African Heads of State meeting in Abuja, Nigeria on Roll Back Malaria adopted effective treatment of malaria nearer the home as one of the strategies for malaria control in Africa. A potentially effective strategy for bringing early, appropriate and low cost treatment of malaria closer to the home is through the use of community health workers (CHWs). There is paucity of information about people's actual preferences for CHWs and how stated preferences relates to revealed preferences for both the CHW strategy and other strategies for improving the timeliness of malaria treatment in not only Nigeria but in many malaria endemic countries. OBJECTIVES: To determine peoples' stated and actual preferences for different strategies for improving the timeliness and appropriateness of treatment of malaria before and after the implementation of a community health workers (CHW) strategy in their community. METHODS: A prospective study was undertaken in a rural malaria holo-endemic Nigerian community. A questionnaire was used to collect information on health-seeking from householders before (first survey) and after (second survey) implementation of a CHW malaria treatment strategy. RESULTS: The consumers mostly preferred the CHW strategy over self-treatment in the homes and other strategies of treatment. The use of community health workers (CHWs) increased from 0% to 26.1% (p < 0.05), while self-treatment in the homes decreased from 9.4% to 0% (p < 0.05) after the implementation of the CHW strategy. Use of patent medicine dealers also decreased from 44.8% to 17.9% (p < 0.05) after CHW strategy was implemented. CONCLUSION: Community health workers can be used to improve and ensure timely and appropriate treatment of malaria. The CHW strategy could also be sustained since it was preferred and used by consumers over self-treatment in the homes as well as other strategies for improving treatment. Hence, the CHW strategy is a feasible and promising method of improving home-management of uncomplicated malaria.

Should chloroquine be laid to rest?

Chloroquine (CQ) has been the front line antimalarial drug due to its efficacy, low cost and scanty side effects, until resistance has evolved. Although its use has been officially discontinued in most malaria-affected countries, it is still widely used. Practical and pharmacological considerations indicate that it could be still used in semi-immune adults and that more efficient treatment protocols could be devised to treat even patients infected with CQ-resistant parasite strains. Since its antimalarial activity is pleiotropic, drug resistance may be due to different mechanisms, each amenable to reversal by drug combination.

Very high risk of therapeutic failure with chloroquine for uncomplicated Plasmodium falciparum and P. vivax malaria in Indonesian Papua.

Chloroquine remains the first-line therapy for uncomplicated malaria in Indonesia. Among a series of trials of chloroquine for malaria on this archipelago conducted since 1990, we now report the highest risk of therapeutic failure yet observed. A clinical trial of standard chloroquine therapy for uncomplicated malaria at Arso PIR V in northeastern Indonesian Papua was conducted during 1995. We enrolled 104 non-immune subjects infected with Plasmodium falciparum (n = 55), P. vivax (n = 29), or P. falciparum plus P. vivax (n = 20) and administered supervised standard chloroquine therapy (10 + 10 + 5 mg/kg at 24-hour intervals). The 28-day cumulative incidence of therapeutic failure was 95% for P. falciparum, 84% for P. vivax, and 100% for mixed infections. Only one subject each for P. falciparum and P. vivax remained free of parasites at day 28. All recurrent parasitemias occurred with whole blood levels of chloroquine plus desethylchloroquine exceeding 100 ng/ml. These findings document almost complete failure of chloroquine against P. falciparum or P. vivax near the northeastern coast of Indonesian Papua.

Economic impact of febrile morbidity and use of permethrin-impregnated bed nets in a malarious area II. Determinants of febrile episodes and the cost of their treatment and malaria prevention.

The objective of this study is to determine the effect of permethrin insecticide-treated bed net (PITN) use on the incidence of febrile episodes and on household malaria expenses in Benin. Over the course of one year, 208 randomly selected PITN user and non-user households were visited weekly to determine expenditures on febrile morbidity and its treatment, and to monitor spending on malaria prevention. Multivariate analyses were performed to distinguish the effects of PITN use from other important determinants of morbidity, such as malaria-related beliefs and practices, income, and other socio-economic variables. Results from the logistic regression analysis show that the use of PITNs decreases the risk of febrile episodes by 34% in children living in the rural zone. Multiple regression analysis reveals that PITN use does not reduce prevention and treatment expenses. These expenses are significantly associated with women's income. This report also discusses other factors associated with febrile morbidity and malaria-related expenditures.

Vendor-to-vendor education to improve malaria treatment by private drug outlets in Bungoma District, Kenya.

BACKGROUND: Private outlets are the main suppliers of uncomplicated malaria treatment in Africa. However, they are so numerous that they are difficult for governments to influence and regulate. This study's objective was to evaluate a low-cost outreach education (vendor-to-vendor) programme to improve the private sector's compliance with malaria guidelines in Bungoma district, Kenya. The cornerstone of the programme was the district's training of 73 wholesalers who were equipped with customized job aids for distribution to small retailers. METHODS: Six months after training the wholesalers, the programme was evaluated using mystery shoppers. The shoppers posed as caretakers of sick children needing medication at 252 drug outlets. Afterwards, supervisors assessed the outlets' knowledge, drug stocks, and prices. RESULTS: The intervention seems to have had a significant impact on stocking patterns, malaria knowledge and prescribing practices of shops/kiosks, but not consistently on other types of outlets. About 32% of shops receiving job aids prescribed to mystery shoppers the approved first-line drug, sulfadoxine-pyremethamine, as compared to only 3% of the control shops. In the first six months, it is estimated that 500 outlets were reached, at a cost of about $8000. CONCLUSIONS: Changing private sector knowledge and practices is widely acknowledged to be slow and difficult. The vendor-to-vendor programme seems a feasible district-level strategy for achieving significant improvements in knowledge and practices of shops/kiosks. However, alternate strategies will be needed to influence pharmacies and clinics. Overall, the impact will be only moderate unless national policies and programmes are also introduced.

An economic comparison of chloroquine and sulfadoxine-pyrimethamine as first-line treatment for malaria in South Africa: development of a model for estimating recurrent direct costs.

The relative cost-effectiveness of chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) as first-line antimalarial therapy in southern Africa is of great interest to policymakers, clinicians and researchers in the subregion. A model was developed to access the cost-effectiveness of replacing CQ with SP as first-line treatment in Mpumalanga, South Africa, where malaria is seasonal and the population is non-immune. In-vivo drug resistance levels were used to derive a 'resistance variable' for each drug, which was used to compare the costs to the public healthcare provider associated with either therapeutic option. Costs including drugs, staff time, transport, maintenance, utilities, training and consumables were determined and subjected to Monte Carlo simulation and subsequent analysis to generate an average cost-effectiveness ratio (ACER) with confidence intervals for each drug. SP was found to be 4.8 (95% CI 3.3-6.7) times more cost-effective than CQ in Mpumalanga at 1997 resistance levels and costs, despite the far greater cost per treatment course of SP (US$ 4.02 as opposed to US$ 0.22 for CQ) in South Africa. At the price of SP in Kenya and Uganda (US$ 0.47-4.80 per treatment course), the ACER for SP does not change materially, increasing to between 5.1 and 5.6. Resistance emerged as the factor that most influenced the ACER of a specific drug. Indirect costs, compliance, changes in effectiveness and costs over time and costs of adverse events were not included in the model owing to paucity of data and logistical difficulties. Since most of these are likely to be similar in both drug models, the relative ACER is unlikely to be significantly altered by their inclusion.

A trial of Fansidar plus chloroquine or Fansidar alone for the treatment of uncomplicated malaria in Gambian children.

Chloroquine can no longer be recommended as the first-line treatment for uncomplicated malaria in several parts of Africa because of the increasing prevalence of chloroquine resistance. However, chloroquine was a highly effective treatment for malaria not only because of its ability to kill parasites quickly but also because it is an anti-inflammatory drug. Therefore, we have investigated whether Fansidar (pyrimethamine/sulfadoxine) plus chloroquine is a more effective treatment for uncomplicated malaria than Fansidar alone. Four hundred and five Gambian children with uncomplicated Plasmodium falciparum malaria were studied in a randomized controlled trial. Significantly more children treated with Fansidar alone, compared to those treated with Fansidar plus chloroquine (19/203 vs. 2/202; P < 0.001), returned to the clinic with persistent symptoms during the first 3 d after treatment. Three children who had received Fansidar alone had fits, but none of the children treated with Fansidar plus chloroquine did so. At the day 7 follow-up, the parasite failure rate in the Fansidar alone group was 3/198 (1.5%), whilst in the Fansidar plus chloroquine group it was 3/201 (1.5%). At the day 28 follow-up, there was still no significant difference between the parasite failure rate in the Fansidar alone group (15/150; 10.0%) and the Fansidar plus chloroquine group (7/141; 5.0%) and the mean packed cell volume (PCV) in the 2 groups was similar. Thus, a combination of Fansidar plus chloroquine was a more effective symptomatic treatment than Fansidar given alone, but neither the parasite cure rate nor the PCV was enhanced by use of the combination.

A comparison of amodiaquine and chloroquine in the treatment therapy of falciparum malaria in Kenya.

During June to August 1989, 158 symptomatic outpatients with P. falciparum malaria were randomly treated with either amodiaquine or chloroquine 25 mg/kg, divided over three days. Amodiaquine (Camoquin, Parke-Davis) was significantly more effective in terms of the rate of parasite clearance, 2.4 versus 3.1 days; parasite clearance day 7; 87% versus 41%; and clinical amelioration, 98% versus 68%. Moreover, this study demonstrates the lack of therapeutic toxicity of amodiaquine. Globally, tolerance was better with amodiaquine than with chloroquine; in particular, cutaneous side effects were less frequent with amodiaquine. There was no evidence of granulocyte or gross hepatic toxicity. These results suggest that WHO recommendations concerning amodiaquine should be questioned. In view of its low cost, demonstrated efficacy and lack of proven therapeutic toxicity, amodiaquine should be considered as a viable replacement for chloroquine in areas with high levels of clinical chloroquine failure.

Management of malaria before and after introduction of a treatment protocol at the Eldoret District Hospital.

A prospective study on the management of suspected malaria using a protocol on a general medical ward during the months of February and March, 1992 was done and the results compared with those of a retrospective study covering the months of November and December, 1991. The retrospective analysis showed that 78 (65%) from a total of 120 patients received antimalarial drugs despite negative or absent blood smears for malarial parasites. In 41 (34%) of the 120 patients, the first line treatment given was quinine. In the prospective study the overall quinine use dropped sharply to 19% from 54% in the retrospective study. 94 (49%) from a total of 193 patients with suspected malaria had negative blood smears of whom only 8 (4%) received quinine while 63 (33%) did not receive any antimalarial therapy and 38 of these 63 patients ended up with different final diagnoses; the remaining 25 were observed on no antimalarial treatment and discharged home feeling well. These results emphasize the need for proper diagnosis of malaria and suggest that chloroquine is still acceptable and effective as a first line drug for proven cases of malaria in adult patients in Eldoret. Unnecessary quinine use is discouraged as the drug is more expensive with more toxic effects compared to chloroquine.

PIP: In Kenya, health professionals compared prospective data on 193 suspected malaria patients at the Eldoret District Hospital during February-March, 1992, with retrospective data on 120 suspected malaria cases at the same hospital during November-December, 1991, to examine the protocol on the management of suspected malaria cases. Between these 2 periods, physicians introduced a simple algorithm to follow in suspected malaria cases. The use of quinine as the 1st choice drug fell considerably between the 2 periods (54.2-19%). There was an increase in the use of chloroquine as the 1st choice drug for uncomplicated malaria (38.4-63.9%). The proportion of blood smear positive patients increased (27.5-51.3%), probably because the department technician was more careful conducting repeat blood smears than were technicians at the busy hospital laboratory. Blood smear negative patients were less likely to automatically receive any antimalarial treatment or quinine in 1992 than in 1991 (14.6% vs. 47.5% and 4.1% vs. 30.9%, respectively). The proportion of patients whose final diagnosis was an illness other than malaria was higher in 1992 than in 1991 (19.7% vs. 15.8%). No clear diagnosis other than flu-like illness was the case for 28 (14.5%) of the prospective patients. The tendency for clinicians to accept a diagnosis of malaria without enough evidence to confirm it can have the damaging effect of masking other serious diagnoses (e.g., dysentery [8 cases], meningitis [6 cases], and HIV infection [2 case]). These findings show that hospital physicians should develop simple protocols for inpatient management of suspected malaria cases, a properly quantified blood smear should be done of all suspected malaria cases to confirm or refute the diagnosis, and chloroquine should be the 1st line of treatment in the Kenyan highlands, until considerable parasite resistance is confirmed.

Comparative efficacy and safety of chloroquine and alternative antimalarial drugs: a meta-analysis from six African countries.

OBJECTIVE: To evaluate the safety and efficacy of the currently used antimalarial drugs in six African countries. DESIGN: A meta-analysis. MAIN OUTCOME MEASURES: The role of efficacy, safety and cost on the selection of antimalarial drugs. RESULTS: The comparative efficacy study showed that amodiaquine (with > 90% cure rate) was superior to chloroquine and sulphadoxine-pyrimethamine at seven days schedule. The efficacy of amodiaquine was also observed to be comparable to that of mefloquine and halofantrine. The parasite clearance time (PCT) of these drugs ranged between two days and a week and the fever clearance time (FCT) was within 48 hours. The recrudescence rate at D14-D21 was found to be 12-17% in chloroquine and amodiaquine, while sulphadoxine-pyrimethamine showed a trend similar to halofantrine and mefloquine (0-12% recrudescence rate). Similarly, a big difference was also noted in the cost of the different antimalarial drugs. The pharmacokinetic data, however, showed that they are of similar profile, except in adverse features and contraindications, and values like their half-life (t1/2) where the long (t1/2) in drugs like sulphadoxine-pyrimethamine endows them with suppressive-cure feature, especially against recrudescent strains. Nevertheless, as these data are obtained from resident population in Africa, who however naive are exposed to few malaria challenges in their life, the results should not be directly extrapolated to total non immunes such as visitors from Europe. CONCLUSION: The choice of alternative antimalarial drugs should be mainly based on their relative efficacy, safety and cost.

PIP: A meta-analysis study evaluating the efficacy and safety of chloroquine and alternative antimalarial drugs used in six African countries including Ethiopia, Kenya, Uganda, Cote D'Ivoire, Gambia and Nigeria is presented. Findings from the six countries showed a higher efficacy of amodiaquine and quinine (over 90%) in malaria treatment compared to chloroquine, which was found to be 70% or more effective. The efficacy of amodiaquine can also be compared to other antimalarial drugs such as mefloquine and halofantrine. Data showed that fever clearance time of these drugs was less than 2 days, but parasite clearance time ranged from 2.5 days to 1 week. Recrudescence rate also varied among the different drugs. This is a very important indicator in determining which drug can be used for prophylactic or suppressive treatment of malaria. Pharmacokinetic profile demonstrates that all these drugs have similar therapeutic effects, but differ in their adverse reactions, contraindications, and half-life. A significant difference was also noted in the cost of these antimalarial drugs; chloroquine was the cheapest, while halofantrine was the most expensive among the drugs. Based on these results, the study recommends that different aspects of antimalarial drugs have to be considered before deciding which drug is the best alternative treatment.

A cost-effectiveness analysis of three antimalarial treatments for acute, uncomplicated Plasmodium falciparum malaria in Mumbai, India.

BACKGROUND: Malaria is a major public health problem representing 2.3% of the overall global disease burden. The cost of treatment of malaria continues to rise as older drugs and insecticides become less effective and are replaced by more effective, but also more expensive products. METHODS: A post-hoc pharmacoeconomic analysis (direct and indirect costs only) of three antimalarials, chloroquine, mefloquine and co-artemether, was carried out to address the problem of switch to a more expensive first-line antimalarial in the face of growing chloroquine resistance. RESULTS: From the perspective of a large public hospital, it was seen that in an area of high grade chloroquine resistance, the total expenditure on patients who fail chloroquine would exceed the excess expenditure on mefloquine when the RII + RIII resistance exceeded 9%. CONCLUSIONS: Switch to a more expensive drug like mefloquine as a first-line option would be cost-effective when the moderate-severe chloroquine resistance exceeded 9%.

Therapeutic efficacy of chloroquine or amodiaquine in combination with sulfadoxine-pyrimethamine for uncomplicated falciparum malaria in Papua New Guinea.

Resistance of Plasmodium falciparum to chloroquine is widespread in Papua New Guinea. At a meeting in Port Moresby in October 1997, it was decided to explore a possible change of the current first-line treatment of uncomplicated malaria with chloroquine alone (amodiaquine for children under five years) to chloroquine or amodiaquine in combination with sulfadoxine-pyrimethamine (S-P). To assess the therapeutic efficacy of the new drug combination in Papua New Guinea, a study was carried out in 1998-1999 at five hospital outpatient departments. From the 513 patients enrolled for the study, 95 defaulted from follow-up. Of the remaining 418, 399 (95.5%) had an adequate clinical response (ACR). Out of the 19 patients who did not have an ACR, 3 (0.7% of the total) developed severe signs in the first 24 hours and were treated in hospital; they were regarded as early treatment failures. The remaining 16 did not complete the study on the basis of various exclusion criteria but were not excluded from the analysis. From these results it was concluded that the combination was effective and a decision was taken in May 2000 to introduce the two-drug combination regimens as the standard first-line treatment of uncomplicated malaria, including falciparum malaria, in Papua New Guinea.