Household characteristics as predictors of access to paediatric malaria treatment in Homa-Bay County, Kenya.

OBJECTIVE: To investigate the influence of socioeconomic household characteristics on access to paediatric malaria treatment in Homa Bay County, Kenya. RESULTS: From univariate analysis, treatment with analgesics only in a community health center or a faith-based organization, self-employment, urban residence and residing in a sub-county other than Suba or Mbita showed significant association with access to paediatric antimalarial treatment. However, on multivariate analysis, urban residence, education, income of 10,000 to 30,000 and information from peers were the most statistically significant predictors of access to treatment. Urban households were 0.37 times more likely to access treatment than rural ones. Having primary, secondary or post-secondary education conferred 0.25, 0.14 and 0.28 higher chance of access to paediatric malaria treatment respectively compared to those with no formal education. Those with monthly income levels of 10,000 to 30,000 shillings had 0.32 higher chance of accessing treatment compared to those with less than 5000 shillings.

Antimalarial drugs available in the city Cabinda (Angola) in 2016.

Antimalarial drug offerings in the city of Cabinda (Angola) were assessed during the fourth quarter of 2016. Combinations of artemisinin with other effective antimalarial drugs were available free of charge in public health centres, theoretically after a biological validation of the diagnosis of a malaria attack. Private pharmacies offered many products without medical prescription, most of them being ACT (Artemisinin Combined Therapy) but some being Artemisia derivatives alone. The cost of treatment for a presumptive attack varied from 14 to 44 €. The diversity of antimalarial drugs and of their dosages makes it difficult for sellers to provide appropriate recommendations for their use. In the informal sector, sellers offered the same products at similar prices as the formal sector but with the option of purchasing only a part of the treatment. Analgesics and herbal medicine not validated as antimalarial drugs were also available.

Qinghaosu (artemisinin): the price of success.

Artemisinin and its derivatives have become essential components of antimalarial treatment. These plant-derived peroxides are unique among antimalarial drugs in killing the young intraerythrocytic malaria parasites, thereby preventing their development to more pathological mature stages. This results in rapid clinical and parasitological responses to treatment and life-saving benefit in severe malaria. Artemisinin combination treatments (ACTs) are now first-line drugs for uncomplicated falciparum malaria, but access to ACTs is still limited in most malaria-endemic countries. Improved agricultural practices, selection of high-yielding hybrids, microbial production, and the development of synthetic peroxides will lower prices. A global subsidy would make these drugs more affordable and available. ACTs are central to current malaria elimination initiatives, but there are concerns that tolerance to artemisinins may be emerging in Cambodia.

Ensuring sustained ACT production and reliable artemisinin supply.

INTRODUCTION: This paper reviews recent trends in the production, supply and price of the active ingredients as well as finished ACT products. Production and cost data provided in this paper are based on an ongoing project (Artepal). Stability data are derived from a development project on rectal artesunate. DISCUSSION: The artemisinin raw material and its derivatives appear to be very stable compared to the finished products. Supply of artemisinin changed in May 2004 when the Global Fund shifted financial support to qualified countries from chloroquine or sulphadoxine-pyrimethamine to an ACT for treatment of malaria. First, there was a sudden shortage of the starting material, and short term scarcity led to a steep rise in API price: it increased dramatically in 2004, from $350 per kg to more than $1000. Second, there was a parallel increase in the number of companies extracting artemisinin from 10 to 80 between 2003 and 2005 in China, and from 3 to 20 in Vietnam. Commercial cultivation began also in East Africa and Madagascar.A steady and predictable demand for the crop can eliminate such wide fluctuations and indirectly contribute to price stability of the herb, the API and ACT. With appropriate mechanisms to reduce those fluctuations, the cost of artemisinin might decrease sustainably to US$ 250-300 per kg. CONCLUSION: Today the global health community is facing the risk of another cyclical swing with lower demand feeding into reduced planting of A. annua and, thereafter, a new shortage of the raw material and higher API prices. International donors, the largest purchasers for ACTs could better coordinate their activities, in order to guarantee purchase of ACTs and consequently of API with manufacturers. In parallel, the base of quality producers of APIs and finished ACT products needs to be broadened.While the ACT programme is still in its early stages, the consequences of another wave of artemisinin and ACT shortages would permanently discredit it and impede any progress in rolling malaria back.

Effect of artemisinin-based treatment policy on consumption pattern of antimalarials.

The purpose of this study was to observe the effect of the 2004 national artemisinin-based malaria treatment policy on consumption pattern of antimalarials. The study was undertaken at the University of Ilorin Teaching Hospital (UITH), Nigeria. Prescription and sales data at our pharmacy outlets were gathered from January to December 2004 and compared with similar data for 2005 after policy introduction in January 2005. Total consumption of antimalarials in 2004 was 23,404 doses, made up of artemisinin-containing medications (ACMs; 18.5%); sulphadoxine-pyrimethamine (SP; 7.1%); chloroquine (CQ; 72.85%); and quinine (QUI; 1.6%), compared with 26,383 doses in 2005, made up of ACMs (50.00%); SP (22.7%); CQ (27.3%); and QUI (0%). Z-tests indicate that these differences in proportions were significant (P < 0.001) for ACMs and SP (increased) and decreased for CQ and QUI. The comparative retail price per dose of these medications was in the order: ACMs > QUI > SP > CQ. These data show increased use of antimalarials, with ACMs overtaking CQ as the dominant antimalarial class purchased from the pharmacies operated by the hospital in the first year of policy implementation. This suggests that cost alone may not be the overriding determinant of specific antimalarial consumption.

Operational response to malaria epidemics: are rapid diagnostic tests cost-effective?

OBJECTIVE: To compare the cost-effectiveness of malaria treatment based on presumptive diagnosis with that of malaria treatment based on rapid diagnostic tests (RDTs). METHODS: We calculated direct costs (based on experience from Ethiopia and southern Sudan) and effectiveness (in terms of reduced over-treatment) of a free, decentralised treatment programme using artesunate plus amodiaquine (AS + AQ) or artemether-lumefantrine (ART-LUM) in a Plasmodium falciparum epidemic. Our main cost-effectiveness measure was the incremental cost per false positive treatment averted by RDTs. RESULTS: As malaria prevalence increases, the difference in cost between presumptive and RDT-based treatment rises. The threshold prevalence above which the RDT-based strategy becomes more expensive is 21% in the AS + AQ scenario and 55% in the ART-LUM scenario, but these thresholds increase to 58 and 70%, respectively, if the financing body tolerates an incremental cost of 1 euro per false positive averted. However, even at a high (90%) prevalence of malaria consistent with an epidemic peak, an RDT-based strategy would only cost moderately more than the presumptive strategy: +29.9% in the AS + AQ scenario and +19.4% in the ART-LUM scenario. The treatment comparison is insensitive to the age and pregnancy distribution of febrile cases, but is strongly affected by variation in non-biomedical costs. If their unit price were halved, RDTs would be more cost-effective at a malaria prevalence up to 45% in case of AS + AQ treatment and at a prevalence up to 68% in case of ART-LUM treatment. CONCLUSION: In most epidemic prevalence scenarios, RDTs would considerably reduce over-treatment for only a moderate increase in costs over presumptive diagnosis. A substantial decrease in RDT unit price would greatly increase their cost-effectiveness, and should thus be advocated. A tolerated incremental cost of 1 euro is probably justified given overall public health and financial benefits. The RDTs should be considered for malaria epidemics if logistics and human resources allow.

[Control of malaria: market for artemisinin and its derivatives]. / La lutte contre le paludisme le marché de l'artémisinine et des dérivés.

Artemisinin compounds derived from the Artemisia annua plant provide the raw material for new artemisinin based combined therapies (ACT) against malaria. The purpose of this report is to present the different steps in production of these compounds from planting to harvesting, extraction, purification, chemical transformation and final formulation. Factors affecting cost are given special focus to gain better insight into ways of holding down the purchasing price. We also describe the consequences that the April 2004 decision by several international organizations (e.g. WHO and Global Fund to fight AIDS, tuberculosis and malaria) to make ACT the reference treatment for malaria has had on the supply of ACT, i.e., shortages with a sharp price increase followed by overinvestment and surpluses with a sharp price decrease. In view of these fluctuations, we discuss whether regulation is necessary and who should intervene.

Artemisinin-based combinations.

PURPOSE OF REVIEW: Artemisinin-based combination treatments have been the mainstay of treatment for falciparum malaria in Southeast Asia for more than 10 years and are now increasingly recommended as first-line treatment throughout the rest of the world. RECENT FINDINGS: A large multicentre randomised trial conducted in East Asia has shown a 35% reduction in mortality from severe malaria following treatment with parenteral artesunate compared with quinine. There is increasing evidence that artemisinin-based combination treatments are safe and rapidly effective. Artemether-lumefantrine (six doses) has been shown to be very effective in large trials reported from Uganda and Tanzania. A once daily three-dose treatment of dihydroartemisinin piperaquine, a newer fixed combination, was a highly efficacious and well tolerated treatment for multi-drug resistant falciparum malaria in Southeast Asia. SUMMARY: Early diagnosis and treatment of uncomplicated malaria with effective drugs remains a priority as part of a comprehensive malaria control strategy. Artemisinin-based combination treatments have consistently been shown to be highly effective and safe. The challenge is to make them accessible in tropical countries.

Artemisinin-based combination therapy reduces expenditure on malaria treatment in KwaZulu Natal, South Africa.

INTRODUCTION: There is growing international evidence that artemisinin-based combination therapy (ACT) is one of the few effective measures available to 'Roll Back Malaria'. However, concerns about the costs and affordability of ACT are obstacles to its widespread implementation. This paper explores some economic aspects of the implementation of artemether-lumefantrine (AL) to replace sulphadoxine-pyrimethamine (SP) in the KwaZulu Natal (KZN) province, South Africa. METHODS: Recurrent and capital costs for malaria treatment were compared at baseline and post-intervention for nine clinics and a sentinel rural district hospital. Changes in the unit costs of, and total expenditure on, malaria services were calculated and the cost effectiveness of AL relative to SP was assessed. RESULTS: The number of outpatient malaria cases and inpatient admissions both declined by 94% between 2000 and 2002. After accounting for the role of concurrent improvements in vector control, it was conservatively estimated that 36% of the decline in outpatient cases and 46% for inpatient admissions was attributable to changing the first-line drug to AL. Although AL is considerably more expensive than SP, its improved cure rate and reduced malaria transmission resulted in an estimated 201,065 US dollars cost saving in 2002 alone for the subdistrict studied. DISCUSSION: In the context of effective vector control and low efficacy of existing monotherapy, ACT can reduce total expenditure on malaria services. However, the relevance of these findings requires careful consideration in countries with currently effective treatment policies and higher intensity malaria transmission.

Antimalarial drug resistance, artemisinin-based combination therapy, and the contribution of modeling to elucidating policy choices.

Increasing resistance of Plasmodium falciparum malaria to antimalarial drugs is posing a major threat to the global effort to "Roll Back Malaria". Chloroquine and sulfadoxine-pyrimethamine (SP) are being rendered increasingly ineffective, resulting in increasing morbidity, mortality, and economic and social costs. One strategy advocated for delaying the development of resistance to the remaining armory of effective drugs is the wide-scale deployment of artemisinin-based combination therapy. However, the cost of these combinations are higher than most of the currently used monotherapies and alternative non-artemisinin-based combinations. In addition, uncertainty about the actual impact in real-life settings has made them a controversial choice for first-line treatment. The difficulties in measuring the burden of drug resistance and predicting the impact of strategies aimed at its reduction are outlined, and a mathematical model is introduced that is being designed to address these issues and to clarify policy options.

A threshold analysis of the cost-effectiveness of artemisinin-based combination therapies in sub-saharan Africa.

Artemisinin-based combination therapies (ACTs) are generally regarded as vital in addressing the growing problem posed by the development of antimalarial resistance across sub-Saharan Africa. However, the costs of the new ACTs are likely to be significantly higher than current therapies. Therefore, it is important to examine formally the cost-effectiveness of the more effective yet more expensive ACTs before advocating a switch in policy. Importantly, any such economic evaluation must consider the temporal dynamics of drug resistance, and not just focus on the static question of whether switching today would be cost-effective at current levels of resistance, particularly since the development of new antimalarials in the future is so uncertain. However, predicting the future changes in drug resistance is a major difficulty in accurately quantifying the relative costs and health outcomes associated with different drug therapies over time. Here, we use a simple decision tree model to estimate the incremental cost-effectiveness of using ACTs, compared with persisting with current therapies, over 5-, 10-, and 15-year periods. We describe the dynamics of drug resistance using a general logistic growth function, in which the starting frequency of resistance and maximum growth may be altered. However, rather than make assumptions about the absolute rate at which resistance to ACTs will progress, we allow the ratio of the growth rate of resistance to ACTs relative to that of current therapies to vary. Defining the growth rate of ACT resistance in this manner allows us to calculate the threshold ratio at which ACTs would no longer appear cost-effective, for any starting conditions of resistance to current therapies and ACTs, and over any time period. The influence of uncertainty in other decision tree parameters on the threshold ratio values is also quantified, using Monte Carlo simulation techniques. This analysis shows that ACTs are more than 95% likely to be cost-effective under most conditions, other than very low levels of initial resistance to sulfadoxine/pyrimethamine and a five-year time frame. These predictions are conservative in that 95% certainty is a stringent decision rule favoring the rejection of new policies. The importance of other variables not included in the analysis for the robustness of the findings are discussed (e.g., consideration of the entire population at risk for malaria, the affordability of ACTs in specific settings, and the growth of resistance modeled according to population genetic parameters).

Efficacy of artesunate in the treatment of urinary schistosomiasis, in an endemic community in Nigeria.

The efficacy and tolerability of oral artesunate for the treatment of urinary schistosomiasis was assessed among schoolchildren aged 5-18 years in Adim community, Nigeria. Overall, 500 children, randomly selected from those attending the Presbyterian primary school, were each invited to provide two consecutive urine samples. Using standard parasitological procedures, Schistosoma haematobium ova were found in the samples from 145 (29.0%) of the subjects. Most (87) of the infected subjects were then treated orally with artesunate, using two doses, each of 6 mg/kg, given 2 weeks apart. When the treated children were re-examined 4 weeks after the second dose of artesunate, 61 (70.1%) appeared egg-negative and were therefore considered cured. Post-treatment, the geometric mean egg count (GMEC) for the treated subjects who were not cured was significantly lower than the pre-treatment GMEC for all the treated subjects, with log10[(eggs/10 ml urine) + 1] values of 0.9 v. 1.75 (t = 4.45; P < 0.05). The cure 'rate' for the subjects aged > or = 10 years was slightly higher than that among the younger subjects. It was lowest for the heavier subjects (70% for those weighing 41-50 kg) and highest (79%) for the subjects who weighed 31-40 kg. The artesunate was well tolerated. This observation of a therapeutic effect of artesunate against S. haematobium in Nigeria confirms recent observations from Senegal. In the Adim community at least, it would be more cost-effective to treat urinary schistosomiasis with artesunate than with praziquantel. The wide-spread use of artesunate against schistosomiasis has to be considered carefully, however, if it is not to compromise the efficacy of the drug as an antimalarial, by increasing the risk of resistance developing in local Plasmodium.

Is combination therapy for malaria based on user-fees worthwhile and equitable to consumers? Assessment of costs and willingness to pay in Southeast Nigeria.

OBJECTIVES: To examine the equity implications of the costs of an episode of malaria, the benefit/cost ratios of using two artemisinin-based combination therapy (CT) from the consumers' view and inequities in willingness to pay (WTP) for CT. METHODS: A cross-sectional survey was conducted in Southeast Nigeria, where there is a moderate to high level of malaria resistance to chloroquine and sulfadoxine-pyrimethamine formulations. WTP was elicited from respondents using the bidding game (BG) and the structured haggling technique (SH). A socio-economic status (SES) index was used to examine the level of inequity in the key variables. In the benefit/cost ratios, the average cost of CT in Nigeria and price of Coartem were, respectively, used as the cost inputs while the mean WTP was the measure of benefit. Multiple regression analyses were used to determine the validity of the WTP estimates. RESULTS: More than 90% of the respondents were willing to pay for CT. The mean WTP in the BG was 301.1 Naira while it was 438.0 Naira in the SH. People in the highest SES quartile (Q4) were more willing to pay for CT than the lowest SES quartile (Q1). In the regression models, the SES quartiles were significantly related to levels of WTP. The benefit/cost ratios were higher in the SH group, and the ratio was only more than 1 using Coartem in only the SH group. The Q1 groups had the least benefit cost-ratios but the trend of SES differentials in benefit/cost ratios were not statistically significant in the BG group but was in the SH group. CONCLUSION: CT based on user-fees may not be worthwhile and equitable because there are economic and equity constraints to its wide-scale use. Benefit/cost ratios depend on the type of questions that were used to elicit WTP. Governments and donors should be willing to commit funds to make CT affordable to the poor consumers for the intervention to be used to significantly reduce the burden of malaria.