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Amodiaquine alone, amodiaquine+sulfadoxine-pyrimethamine, amodiaquine+artesunate, and artemether-lumefantrine for outpatient treatment of malaria in Tanzanian children: a four-arm randomised effectiveness trial
(2005) Mutabingwa, Theonest K.
Background Many countries in Africa are considering a change to combination treatment for falciparum malaria because of the increase in drug resistance. However, there are few effectiveness data for these combinations. Our aim was to study the effectiveness of three drug combinations that have proven efficacious in east Africa compared with amodiaquine monotherapy. Methods We undertook a randomised trial of antimalarial drug combinations for children (aged 4–59 months) with uncomplicated malaria in Muheza, Tanzania, an area with a high prevalence of resistance to sulfadoxine-pyrimethamine and chloroquine. Children were randomly allocated 3 days of amodiaquine (n=270), amodiaquine +sulfadoxine-pyrimethamine (n=507), or amodiaquine+artesunate (n=515), or a 3-day six-dose regimen of artemether-lumefantrine (n=519). Drugs were taken orally, at home, unobserved by medical staff. The primary endpoint was parasitological failure by day 14 assessed blind to treatment allocation. Secondary endpoints included day 28 follow-up and gametocyte carriage. Analysis was by intention to treat. Findings Of 3158 children screened, 1811 were randomly assigned treatment and 1717 (95%) reached the 14-day follow-up. The amodiaquine group was stopped early by the data and safety monitoring board. By day 14, the parasitological failure rates were 103 of 248 (42%) for amodiaquine, 97 of 476 (20%) for amodiaquine+sulfadoxine-pyrimethamine, 54 of 491 (11%) for amodiaquine+artesunate, and seven of 502 (1%) for artemether-lumefantrine. By day 28, the parasitological failure rates were 182 of 239 (76%), 282 of 476 (61%), 193 of 472 (40%), and 103 of 485 (21%), respectively. The difference between individual treatment groups and the next best treatment combination was significant (p<0·001) in every case. Recrudescence rates by day 28, after correction by genotyping, were 48·4%, 34·5%, 11·2%, and 2·8%, respectively. Interpretation The study shows how few the options are for treating malaria where there is already a high level of resistance to sulfadoxine-pyrimethamine and amodiaquine. The WHO-packaged six-dose regimen of artemether-lumefantrine is effective taken unsupervised, although cost is a major limitation.
Amodiaquine and Artemether-Lumefantrine Select Distinct Alleles of the Plasmodium falciparum mdr1 Gene in Tanzanian Children G. S. Humphreys, Treated for Uncomplicated Malaria
(Antimicrobial agents and chemotherapy, 2007) Mutabingwa, Theonest K.
The artemisinin-based combination therapies artemether-lumefantrine (AL) and amodiaquine (AQ) plus artesunate have been adopted for treatment of Plasmodium falciparum malaria in many African countries. Molecular markers of parasite resistance suitable for surveillance have not been established for any of the component drugs in either of these combinations. We assessed P. falciparum mdr1 (Pfmdr1) alleles present in 300 Tanzanian children presenting with uncomplicated falciparum malaria, who were enrolled in a clinical trial of antimalarial therapy. Pfmdr1 genotype analysis was also performed with isolates from 182 children who failed AQ monotherapy and 54 children who failed AL treatment. Pfmdr1 alleles 86Y, 184Y, and 1246Y were more common among treatment failures in the AQ group than among pretreatment infections. The converse was found in the AL-treated group. Children presenting with the 86Y/184Y/1246Y Pfmdr1 haplotype and treated with AQ were significantly more likely to retain this haplotype if they were parasite positive during posttreatment follow-up than were children treated with AL (odds ratio, 33.25; 95% confidence interval, 4.17 to 1441; P, <0.001). We conclude that AL and AQ exert opposite within-host selective effects on the Pfmdr1 gene of P. falciparum.
Ancillary-care responsibilities in observational research: two cases, two issues
(The Lancet, 2007) Mutabingwa, Theonest K.
International collaborative research in developing countries raises difficult ethical issues in the setting of severe diseases and complex costly treatments. Discussion of two matters has characterized the debate on this type of research. First, what standard of care should be provided to participants in intervention studies, particularly those in control groups? 1,2,3,4 Second, what level of benefits should be provided to individuals and communities during a study and after completion, particularly with respect to treatments proven effective through research? 4, 5, 6 Here, we focus on a third issue, investigators' responsibilities for meeting participants' needs for ancillary care.
Antimalarial drugs in pregnancy: a review
(Bentham Science Publishers, 2006) Mutabingwa, Theonest K.
In this review we examine the available information on the safety of antimalarials in pregnancy, from both animal and human studies. The antimalarials that can be used in pregnancy include (1) chloroquine, (2) amodiaquine, (3) quinine, (4) azithromycin, (5) sulfadoxine-pyrimethamine, (6) mefloquine, (7) dapsone-chlorproguanil, (8) artemisinin derivatives, (9) atovaquone-proguanil and (10) lumefantrine. Antimalarial drugs that should not be used in pregnancy including (1) halofantrine, (2) tetracycline/doxycycline, and (3) primaquine. There are few studies in humans on the pharmacokinetics, safety and efficacy of antimalarials in pregnancy. This is because pregnant women are systematically excluded from clinical trials. The absence of adequate safety data, especially in the first trimester, is an important obstacle to developing treatment strategies. The pharmacokinetics of most antimalarial drugs are also modified in pregnancy and dosages will need to be adapted. Other factors, including HIV status, drug interactions with antiretrovirals, the influence of haematinics and host genetic polymorphisms may influence safety and efficacy. For these reasons there is an urgent need to assess the safety and efficacy of antimalarial treatments in pregnancy, including artemisinin based combination therapies.
Antimalarial treatment with artemisinin combination therapy in Africa desirable, achievable, but not easy
(BMJ, 2005) Mutabingwa, Theonest K.
The steady increase of drug resistant malaria across Africa is a crisis for which there are achievable solutions, but no easy ones. The scale of the problem is not in doubt. In Africa malaria remains one of the commonest causes of death and serious morbidity, especially for children and pregnant women.1 Despite a decision in principle by many countries in Africa to use artemisinin based combination therapies (ACTs), most cases of malaria are still treated with monotherapy and in many areas most of these treatments will fail.2 3 Drug combinations, rather than monotherapy, are now seen to be the best solution for treating malaria, and artemisinin based drug combinations are highly effective, with cure rates similar to that of chloroquine 30 years ago. They seem to be a good long term choice for most African countries, being safe and well tolerated (with the caveat that their safety in early pregnancy is not yet clear). Compared with other antimalarials, ACTs can reduce gametocyte carriage and thereby lower the risk of infectiousness in those who take treatment. In areas of relatively low malaria transmission in South East Asia and South Africa, widespread use of ACTs has reduced significantly the burden of malaria.4 This benefit is likely be less marked in areas of very high transmission in Africa, where much of the reservoir of malaria infection is in asymptomatic people who never seek treatment.
Artemisinin combination therapies
(The Lancet, 2006) Mutabingwa, Theonest K.
Global mortality from Plasmodium falciparum malaria has always been enormous, and has increased in recent decades as chloroquine-resistant parasites spread worldwide. Alarms were raised further when parasites developed resistance to sulfadoxine-pyrimethamine soon after it was introduced to replace chloroquine in many areas. To protect the few remaining drugs in the malaria armamentarium, combination therapy is now touted, particularly combinations that include artemisinin derivatives, widely known as artemisinin combination therapies (ACTs).
Artemisinin-based combination therapies (ACTs): Best hope for malaria treatment but inaccessible to the needy!
(Acta tropica, 2005) Mutabingwa, Theonest K.
Artemisinin-based combination therapies (ACTs) are the best anti-malarial drugs available now. Artemisinin enhances efficacy and has the potential of lowering the rate at which resistance emerges and spreads. Under low transmission intensity, ACTs have an additional public health benefit of reducing the overall malaria transmission and studies are urgently needed to investigate modalities of attaining similar benefits under high transmission. Despite being recommended by WHO since 2001, overall deployment of ACT has been slow. Limiting factors are high cost, limited knowledge and public awareness on the concept of combination therapy (CT) and ACT in particular, limited knowledge on safety of ACTs in pregnancy, operational issue such as inappropriate drug use, lack of suitable drug formulations, lack of post-marketing surveillance (PMS) systems, and the imbalance between demand and supply. Through concerted efforts of multilateral organizations, the local scientific community with involvement of policy-makers progress has been on several fonts leading to improved ACT uptake rates in the last 2 years. Of 43 countries that had adopted ACT by February 2005, 18 (42%) adopted the policy in 2004. Preference to co-formulated Coartem has led to a surge in its demand with consequent shortage. Alternative ways for increased production of ACTs are urgently needed otherwise most policies will remain adopted on paper. Despite limitations, opportunities are opening up for effective malaria control. Insecticides, insecticide-treated nets (ITNs) and ACTs are proven efficacious controls available that should be accessed by many. Substantial funding is now available for biomedical malaria research and for policy implementation. While the Global Fund is the financial engine behind the scaling up of ACT uptake, delays in cash flow after grant approval has led to many countries adopting ACT in 2004 but only few (nine) implementing it. Clear policies on granted funds and minimal politics within funding agencies might improve the situation. Increased interest in drug development together with the public and private sector partnership have led to new anti-malarials, some less expensive and therefore affordable by poor malaria endemic countries. Dihydroartemisinin-piperaquine (Artekin) has a cost advantage over other ACTs (US$ 1 for an adult treatment) making it a potential best candidate for deployment in Africa. Part of available funds should be invested into capacity building and strengthening (personnel, resources and infrastructure) of institutions in malaria endemic countries. This will create enabling environment and a critical mass of scientists and public health experts to spearhead ACT policy implementation. Active involvement of scientists from malaria endemic countries in recent International Scientific Forums like the Malaria in Pregnancy Working Group and the Consortium on ACT Implementation is the best way forward to emulate.
Averting a malaria disaster in Africa where does the buck stop?
(Bulletin of the World Health Organization, 2004) Mutabingwa, Theonest K.
The serious threat posed by the spread of drug-resistant malaria in Africa has been widely acknowledged. Chloroquine resistance is now almost universal, and resistance to the successor drug, sulfadoxine-pyrimethamine (SP), is growing rapidly. Combination therapy has been suggested as being an available and potentially lasting solution to this impending crisis. However, the current cost of combination therapy, and especially that of artemisinin combination therapy (ACT), is potentially a serious drawback, even if a significant part of its cost is passed on to the end-user. If the question of cost is not successfully addressed this could lead to adverse results from the deployment of combination therapy as first-line treatment. These adverse effects range from an increase in potentially fatal delays in infected individuals presenting to medical services, to exclusion of the poorest malaria sufferers from receiving treatment altogether. Urgent steps are needed to reduce the cost of combination therapy to the end-user in a sustainable way if it is to be usable, and some possible approaches are discussed.
Capacity and capability of Tanzania health facilities to diagnose and manage diabetes mellitus in pregnancy
(Diabetes research and clinical practice, 2018) Mutabingwa, Theonest K.
ABSTRACT Aims Gestational Diabetes Mellitus (GDM) remains a neglected cause of maternal and foetal morbidity and mortality in developing countries exacerbated by limited screening and management strategies. This study aimed to understanding how the RCH health system works in Tanzania, so as to provide opportunity for improving GDM screening and management. Methods A questionnaire was administered to facility staff and physical performance observed in 30 randomly selected public RCH facilities. Results Deficiencies identified included limited understaffing, late booking at ANC, and limited screening for GDM due to lack of equipment and supplies. Most women (96%) attending ANCs and postnatal care (87%) were managed at respective facilities with only 12% and 22% respectively being referred to higher levels of care. Facility staff were less trained or received fewer refresher courses in diabetes (0–5%), hypertension (4–6%), and other NCDs (0–16%) compared to training in PMCTC (39%), management of postpartum bleeding (31%) and HIV/AIDs (31%). Conclusion Diabetes during pregnancy is rarely sought in public health facilities and its management is suboptimal. Training and refresher courses of staff in diabetes and hypertension should be uplifted and health systems should be strengthened to improve capacity and capability of facilities for better quality of care.
Case management of malaria in pregnancy
(The Lancet infectious diseases, 2007) Mutabingwa, Theonest K.
In all malarious areas, infection by any of the main human plasmodial species during pregnancy is detrimental to the mother and the fetus. These potentially fatal infections must be prevented, but when they develop they require prompt diagnosis and treatment. Current tools to detect malaria parasites in pregnant women are often not used and remain too insensitive to detect a low parasitaemia. The kinetics, safety, and efficacy of available antimalarial drugs are poorly documented because pregnant women are systematically excluded from clinical trials. A considerable effort, involving clinical trials, is urgently required to improve the diagnosis and case management of malaria during pregnancy if the morbidity and mortality of maternal malaria is to be reduced.
Chloroguanide metabolism in relation to the efficacy in malaria prophylaxis and the S‐mephenytoin oxidation in Tanzanians
(Clinical Pharmacology & Therapeutics, 1996) Mutabingwa, Theonest K.
S‐Mephenytoin and chloroguanide (proguanil) oxidation was studied in 216 Tanzanians. The mephenytoin S/R ratio in urine ranged from <0.1 to 1.16. The distribution was skewed to the right, without evidence of a bimodal distribution. Ten subjects (4.6%, 2.2% to 8.3%, 95% CI) with an S/R mephenytoin ratio >0.9, were arbitrarily defined as poor metabolizers of mephenytoin. The chloroguanide/cycloguanil ratio ranged from 0.82 to 249. There was a significant correlation between the mephenytoin S/R ratio and the chloroguanide/cycloguanil ratios (rs = 0.73; p < 0.00001). This indicates that cytochrome P4502C19 or CYP2C19 is a major enzyme that catalyzes the bioactivation of chloroguanide to cycloguanil. Chloroguanide is a pro‐drug, and hence a low CYP2C19 activity may lead to prophylactic failure caused by inadequate formation of cycloguanil. Fifty‐eight women who previously took either 200 mg chloroguanide daily (n = 26) or 200 mg chloroguanide daily plus 300 mg chloroquine weekly (n = 32) in a malaria chemoprophylaxis study showed that there was a significant correlation between the number of earlier breakthrough parasitemia episodes and the chloroguanide/cycloguanil ratio (rs = 0.30; p = 0.02). The breakthrough rate did not correlate with the S/R mephenytoin ratio. However, other factors, such as exposure to mosquitoes and sensitivity of the plasmodium to cycloguanil, are probably more important.
Chloroquine therapy still useful in the management of malaria during pregnancy in Muheza, Tanzania
(Tropical and geographical medicine, 1991) Mutabingwa, Theonest K.
In searching for effective malaria chemosuppressives during pregnancy in Muheza District--Tanzania, pregnant women are randomly given either 300 mg base chloroquine once weekly or 200 mg daily proguanil. Breakthroughs presenting with clinical malaria are treated with 25 mg base chloroquine/kg (25 CQ) over three days. Due to loss of malaria immunity during pregnancy and Muheza moderate levels and degrees of chloroquine resistance, the in vivo response to 25 CQ was monitored. Between March and May 1989, 49 women were treated resulting into 32 (65%) parasitological clearances and 17 (35%) failures within 7 days. Two of 17 failures (12%) exhibited RIII response and the remaining 15 (88%) had a favourable clinical response. Only 6 (19%) of 32 cleared patients either recrudesced or got reinfected during the three weeks follow up period. In addition to its safety and affordability, the observed drug efficacy during peak malaria transmission and inspite of prevailing resistance makes 25 CQ an ideal first line drug for the management of malaria during pregnancy.
Chloroquine-resistant plasmodium falciparum at the Tanganyika planting company(TPC) sugar estate,moshi,Tanzania.
(World Health Organization, 1985) Mutabingwa, Theonest K.
From 1966 to 1978 the TPC maintained a mass malaria chemoprophylactic programme based on chloroquine.However after reports of treatment failure to 25 mg chloroquine base per kg body weight,the sensitivity of plasmodium falciparum to chloroquine at the TPC sugar estate near Moshi,northern Tanzania,was determined.In Vivo and In vitro test utilizing standard methods were carried out on semi-immune asymptomatic primary-school children whose ages ranged from 8 to 18 years,with a mean age of 12 years.These children were selected from a total of 746 school children who had been screen for malaria parasites and of whom 245(32.8%)were found to be to be positive.
Chlorproguanil-dapsone for treatment of drug-resistant falciparum malaria in Tanzania.
(The Lancet., 2001) Mutabingwa, Theonest K.
Background Resistance to the affordable malaria treatments chloroquine and pyrimethamine-sulfadoxine is seriously impeding malaria control through treatment in east Africa. We did an open, alternate drug allocation study to assess the efficacy of chlorproguanil-dapsone in the treatment of falciparum malaria clinically resistant to pyrimethamine-sulfadoxine. Methods Children younger than 5 years with non-severe falciparum malaria, attending Muheza district hospital in Tanzania, were treated with the standard regimen of pyrimethamine-sulfadoxine. Patients whose clinical symptoms resolved but who remained parasitaemic 7 days after pyrimethamine-sulfadoxine were followed up for 1 month. Clinical malaria episodes were retreated with either single dose pyrimethamine-sulfadoxine or a 3-day regimen of chlorproguanil-dapsone. Those with parasitaemia after 7 days were treated with chlorproguanil-dapsone. Parasite DNA was collected on day 7 after first treatment with pyrimethamine-sulfadoxine and we looked for point mutations in the genes encoding dihydrofolate reductase (dhfr) and dyhydropteroate synthetase (dhps). Findings 360 children were enrolled and treated with pyrimethamine-sulfadoxine. On day 7, 192 (55%) of 348 had cleared parasitaemia. Of the remaining 156 parasitaemic children, 140 (90%) were followed up to day 28, and 92 (66%) of 140 developed clinical malaria. These 92 patients were alternately retreated with either pyrimethamine-sulfadoxine (46) or chlorproguanil-dapsone (46). 28 (61%) of 46 children retreated with pyrimethamine-sulfadoxine were still parasitaemic at day 7, compared with three (15%) of 46 children retreated with chlorproguanil-dapsone. Resistance to pyrimethamine-sulfadoxine increased from 45% (156/348) at the first treatment to 61% (28/46) after retreatment. 83 of 85 parasite isolates collected after the first pyrimethamine-sulfadoxine treatment, and before and after the second treatments with pyrimethamine-sulfadoxine and chlorproguanil-dapsone showed triple-mutant dhfr alleles, associated with a variety of dhps mutations. Interpretation Most patients treated with pyrimethamine-sulfadoxine, who remain parasitaemic at day 7, develop new malaria symptoms within 1 month. Chlorproguanil-dapsone was a practicable therapy under these circumstances. Analysis of parasite dhfr and dhps before and after treatment supports the view that pyrimethamine-sulfadoxine resistance in this part of Africa is primarily due to parasites with three mutations in the dhfr domain.
Combination of probenecid-sulphadoxine-pyrimethamine for intermittent preventive treatment in pregnancy
(Malaria journal, 2012) Mutabingwa, Theonest K.
The antifolate sulphadoxine-pyrimethamine (SP) has been used in the intermittent prevention of malaria in pregnancy (IPTp). SP is an ideal choice for IPTp, however, as resistance of Plasmodium falciparum to SP increases, data are accumulating that SP may no longer provide benefit in areas of high-level resistance. Probenecid was initially used as an adjunctive therapy to increase the blood concentration of penicillin; it has since been used to augment concentrations of other drugs, including antifolates. The addition of probenecid has been shown to increase the treatment efficacy of SP against malaria, suggesting that the combination of probenecid plus SP may prolong the useful lifespan of SP as an effective agent for IPTp. Here, the literature on the pharmacokinetics, adverse reactions, interactions and available data on the use of these drugs in pregnancy is reviewed, and the possible utility of an SP-probenecid combination is discussed. This article concludes by calling for further research into this potentially useful combination.
Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria: a WorldWide Antimalarial Resistance Network individual participant data meta-analysis
(Malaria journal, 2019) Mutabingwa, Theonest K.
Background Therapeutic efficacy studies in uncomplicated Plasmodium falciparum malaria are confounded by new infections, which constitute competing risk events since they can potentially preclude/pre-empt the detection of subsequent recrudescence of persistent, sub-microscopic primary infections. Methods Antimalarial studies typically report the risk of recrudescence derived using the Kaplan–Meier (K–M) method, which considers new infections acquired during the follow-up period as censored. Cumulative Incidence Function (CIF) provides an alternative approach for handling new infections, which accounts for them as a competing risk event. The complement of the estimate derived using the K–M method (1 minus K–M), and the CIF were used to derive the risk of recrudescence at the end of the follow-up period using data from studies collated in the WorldWide Antimalarial Resistance Network data repository. Absolute differences in the failure estimates derived using these two methods were quantified. In comparative studies, the equality of two K–M curves was assessed using the log-rank test, and the equality of CIFs using Gray’s k-sample test (both at 5% level of significance). Two different regression modelling strategies for recrudescence were considered: cause-specific Cox model and Fine and Gray’s sub-distributional hazard model. Results Data were available from 92 studies (233 treatment arms, 31,379 patients) conducted between 1996 and 2014. At the end of follow-up, the median absolute overestimation in the estimated risk of cumulative recrudescence by using 1 minus K–M approach was 0.04% (interquartile range (IQR): 0.00–0.27%, Range: 0.00–3.60%). The overestimation was correlated positively with the proportion of patients with recrudescence [Pearson’s correlation coefficient (ρ): 0.38, 95% Confidence Interval (CI) 0.30–0.46] or new infection [ρ: 0.43; 95% CI 0.35–0.54]. In three study arms, the point estimates of failure were greater than 10% (the WHO threshold for withdrawing antimalarials) when the K–M method was used, but remained below 10% when using the CIF approach, but the 95% confidence interval included this threshold. Conclusions The 1 minus K–M method resulted in a marginal overestimation of recrudescence that became increasingly pronounced as antimalarial efficacy declined, particularly when the observed proportion of new infection was high. The CIF approach provides an alternative approach for derivation of failure estimates in antimalarial trials, particularly in high transmission settings.
Competitive facilitation of drug-resistant Plasmodium falciparum malaria parasites in pregnant women who receive preventive treatment
(Proceedings of the National Academy of Sciences, 2009) Mutabingwa, Theonest K.
Abstract: Intermittent preventive treatment in pregnancy (IPTp) is used to prevent Plasmodium falciparum malaria. However, parasites resistant to the IPTp drug sulfadoxine-pyrimethamine (SP) have emerged worldwide, and infections with mixed resistant and susceptible parasites are exacerbated by pyrimethamine in mice. In a prospective delivery cohort in Muheza, Tanzania, we examined the effects of SP IPTp on parasite resistance alleles, parasite diversity, level of parasitemia, and inflammation in the placenta. IPTp use was associated with an increased fraction of parasites carrying the resistance allele at DHPS codon 581, an increase in the level of parasitemia, and more intense placental inflammation. The lowest mean level of parasite diversity and highest mean level of parasitemia occurred in women after recent IPTp use. These findings support a model of parasite release and facilitation, whereby the most highly resistant parasites out-compete less fit parasite populations and overgrow under drug pressure. Use of partially effective anti-malarial agents for IPTp may exacerbate malaria infections in the setting of widespread drug resistance.
Cost-Effectiveness Study of Three Antimalarial Drug Combinations in Tanzania
(PLoS Medicine., 2006) Mutabingwa, Theonest K.
Background As a result of rising levels of drug resistance to conventional monotherapy, the World Health Organization (WHO) and other international organisations have recommended that malaria endemic countries move to combination therapy, ideally with artemisinin-based combinations (ACTs). Cost is a major barrier to deployment. There is little evidence from field trials on the cost-effectiveness of these new combinations. Methods and Findings An economic evaluation of drug combinations was designed around a randomised effectiveness trial of combinations recommended by the WHO, used to treat Tanzanian children with non-severe slide-proven malaria. Drug combinations were: amodiaquine (AQ), AQ with sulfadoxine-pyrimethamine (AQ+SP), AQ with artesunate (AQ+AS), and artemether-lumefantrine (AL) in a six-dose regimen. Effectiveness was measured in terms of resource savings and cases of malaria averted (based on parasitological failure rates at days 14 and 28). All costs to providers and to patients and their families were estimated and uncertain variables were subjected to univariate sensitivity analysis. Incremental analysis comparing each combination to monotherapy (AQ) revealed that from a societal perspective AL was most cost-effective at day 14. At day 28 the difference between AL and AQ+AS was negligible; both resulted in a gross savings of approximately US$1.70 or a net saving of US$22.40 per case averted. Varying the accuracy of diagnosis and the subsistence wage rate used to value unpaid work had a significant effect on the number of cases averted and on programme costs, respectively, but this did not change the finding that AL and AQ+AS dominate monotherapy. Conclusions In an area of high drug resistance, there is evidence that AL and AQ+AS are the most cost-effective drugs despite being the most expensive, because they are significantly more effective than other options and therefore reduce the need for further treatment. This is not necessarily the case in parts of Africa where recrudescence following SP and AQ treatment (and their combination) is lower so that the relative advantage of ACTs is smaller, or where diagnostic services are not accurate and as a result much of the drug goes to those who do not have malaria.
Decreased susceptibility to Plasmodium falciparum infection in pregnant women with iron deficiency
(The Journal of infectious diseases, 2008) Mutabingwa, Theonest K.
Abstract Iron plus folate supplementation increases mortality and morbidity among children in areas of malaria endemicity in Africa, but the effects of supplementation on pregnant women in malaria-endemic areas remain unclear. In northeastern Tanzania, where malaria and iron deficiency are common, we found that placental malaria was less prevalent (8.5% vs. 47.3% of women; P < .0001) and less severe (median parasite density, 4.2% vs. 6.3% of placental red blood cells; P = .04) among women with iron deficiency than among women with sufficient iron stores, especially during the first pregnancy. Multivariate analysis revealed that iron deficiency (P < .0001) and multigravidity (P = .002) significantly decreased the risk of placental malaria. Interventional trials of iron and folate supplementation during pregnancy in malaria-endemic regions in Africa are urgently needed to ascertain the benefits and risks of this intervention.
Differences in willingness to pay for artemisinin-based combinations or monotherapy: experiences from the United Republic of Tanzania
(Bulletin of the World Health Organization, 2005) Mutabingwa, Theonest K.
OBJECTIVE: The cost of combination treatment is thought to be one of the greatest barriers to their deployment, but this has not been tested directly. Estimates of willingness to pay were compared across four drug combinations used to treat Tanzanian children with uncomplicated malaria. The reasons behind respondents' valuations and the effect of socioeconomic status on willingness to pay were explored. METHODS: One hundred and eighty mothers whose children had been recruited into a recently completed randomized effectiveness trial of amodiaquine + artesunate (AQ+AS), amodiaquine + sulfadoxine pyrimethamine (AQ+SP), artemether lumefantrine (coartemether) and amodiaquine monotherapy (AQ) were interviewed about their willingness to pay for these drugs two weeks after treatment. Estimates of willingness to pay were elicited with the bidding game technique. FINDINGS: A significant difference was detected in the mean amounts respondents were willing to pay, with those who received AQ+AS willing to pay the most, followed by co-artemether, AQ+SP and finally AQ. The amounts patients' mothers were willing to pay for the artemisinin-based combinations, however, fell well short of the market costs. Socioeconomic status was not found to have a statistically significant effect on mean willingness to pay scores for any treatment group. CONCLUSION: This study shows that families who live in an area in which drug resistance to monotherapy is very high are willing to pay more for more effective artemisinin-based combination therapies. These amounts, however, are nowhere near the real costs of delivering the new drugs. Only with subsidies will artemisinin-based combination therapies realistically have any impact.

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