The public health impact and cost-effectiveness of the R21/Matrix-M malaria vaccine: a mathematical modelling study.

BACKGROUND: The R21/Matrix-M vaccine has demonstrated high efficacy against Plasmodium falciparum clinical malaria in children in sub-Saharan Africa. Using trial data, we aimed to estimate the public health impact and cost-effectiveness of vaccine introduction across sub-Saharan Africa. METHODS: We fitted a semi-mechanistic model of the relationship between anti-circumsporozoite protein antibody titres and vaccine efficacy to data from 3 years of follow-up in the phase 2b trial of R21/Matrix-M in Nanoro, Burkina Faso. We validated the model by comparing predicted vaccine efficacy to that observed over 12-18 months in the phase 3 trial. Integrating this framework within a mathematical transmission model, we estimated the cases, malaria deaths, and disability-adjusted life-years (DALYs) averted and cost-effectiveness over a 15-year time horizon across a range of transmission settings in sub-Saharan Africa. Cost-effectiveness was estimated incorporating the cost of vaccine introduction (dose, consumables, and delivery) relative to existing interventions at baseline. We report estimates at a median of 20% parasite prevalence in children aged 2-10 years (PfPR2-10) and ranges from 3% to 65% PfPR2-10. FINDINGS: Anti-circumsporozoite protein antibody titres were found to satisfy the criteria for a surrogate of protection for vaccine efficacy against clinical malaria. Age-based implementation of a four-dose regimen of R21/Matrix-M vaccine was estimated to avert 181 825 (range 38 815-333 491) clinical cases per 100 000 fully vaccinated children in perennial settings and 202 017 (29 868-405 702) clinical cases per 100 000 fully vaccinated children in seasonal settings. Similar estimates were obtained for seasonal or hybrid implementation. Under an assumed vaccine dose price of US$3, the incremental cost per clinical case averted was $7 (range 4-48) in perennial settings and $6 (3-63) in seasonal settings and the incremental cost per DALY averted was $34 (29-139) in perennial settings and $30 (22-172) in seasonal settings, with lower cost-effectiveness ratios in settings with higher PfPR2-10. INTERPRETATION: Introduction of the R21/Matrix-M malaria vaccine could have a substantial public health benefit across sub-Saharan Africa. FUNDING: The Wellcome Trust, the Bill & Melinda Gates Foundation, the UK Medical Research Council, the European and Developing Countries Clinical Trials Partnership 2 and 3, the NIHR Oxford Biomedical Research Centre, and the Serum Institute of India, Open Philanthropy.

Evaluation of the effectiveness of topical repellent distributed by village health volunteer networks against Plasmodium spp. infection in Myanmar: A stepped-wedge cluster randomised trial.

BACKGROUND: The World Health Organization has yet to endorse deployment of topical repellents for malaria prevention as part of public health campaigns. We aimed to quantify the effectiveness of repellent distributed by the village health volunteer (VHV) network in the Greater Mekong Subregion (GMS) in reducing malaria in order to advance regional malaria elimination. METHODS AND FINDINGS: Between April 2015 and June 2016, a 15-month stepped-wedge cluster randomised trial was conducted in 116 villages in Myanmar (stepped monthly in blocks) to test the effectiveness of 12% N,N-diethylbenzamide w/w cream distributed by VHVs, on Plasmodium spp. infection. The median age of participants was 18 years, approximately half were female, and the majority were either village residents (46%) or forest dwellers (40%). No adverse events were reported during the study. Generalised linear mixed modelling estimated the effect of repellent on infection detected by rapid diagnostic test (RDT) (primary outcome) and polymerase chain reaction (PCR) (secondary outcome). Overall Plasmodium infection detected by RDT was low (0.16%; 50/32,194), but infection detected by PCR was higher (3%; 419/13,157). There was no significant protection against RDT-detectable infection (adjusted odds ratio [AOR] = 0.25, 95% CI 0.004-15.2, p = 0.512). In Plasmodium-species-specific analyses, repellent protected against PCR-detectable P. falciparum (adjusted relative risk ratio [ARRR] = 0.67, 95% CI 0.47-0.95, p = 0.026), but not P. vivax infection (ARRR = 1.41, 95% CI 0.80-2.47, p = 0.233). Repellent effects were similar when delayed effects were modelled, across risk groups, and regardless of village-level and temporal heterogeneity in malaria prevalence. The incremental cost-effectiveness ratio was US$256 per PCR-detectable infection averted. Study limitations were a lower than expected Plasmodium spp. infection rate and potential geographic dilution of the intervention. CONCLUSIONS: In this study, we observed apparent protection against new infections associated with the large-scale distribution of repellent by VHVs. Incorporation of repellent into national strategies, particularly in areas where bed nets are less effective, may contribute to the interruption of malaria transmission. Further studies are warranted across different transmission settings and populations, from the GMS and beyond, to inform WHO public health policy on the deployment of topical repellents for malaria prevention. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ACTRN12616001434482).

Cost-Effectiveness of Focal Mass Drug Administration and Mass Drug Administration with Dihydroartemisinin-Piperaquine for Malaria Prevention in Southern Province, Zambia: Results of a Community-Randomized Controlled Trial.

Community-wide administration of antimalarial drugs in therapeutic doses is a potential tool to prevent malaria infection and reduce the malaria parasite reservoir. To measure the effectiveness and cost of using the antimalarial drug combination dihydroartemisinin-piperaquine (DHAp) through different community-wide distribution strategies, Zambia's National Malaria Control Centre conducted a three-armed community-randomized controlled trial. The trial arms were as follows: 1) standard of care (SoC) malaria interventions, 2) SoC plus focal mass drug administration (fMDA), and 3) SoC plus MDA. Mass drug administration consisted of offering all eligible individuals DHAP, irrespective of a rapid diagnostic test (RDT) result. Focal mass drug administration consisted of offering DHAP to all eligible individuals who resided in a household where anyone tested positive by RDT. Results indicate that the costs of fMDA and MDA per person targeted and reached are similar (US$9.01 versus US$8.49 per person, respectively, P = 0.87), but that MDA was superior in all cost-effectiveness measures, including cost per infection averted, cost per case averted, cost per death averted, and cost per disability-adjusted life year averted. Subsequent costing of the MDA intervention in a non-trial, operational setting yielded significantly lower costs per person reached (US$2.90). Mass drug administration with DHAp also met the WHO thresholds for "cost-effective interventions" in the Zambian setting in 90% of simulations conducted using a probabilistic sensitivity analysis based on trial costs, whereas fMDA met these criteria in approximately 50% of simulations. A sensitivity analysis using costs from operational deployment and trial effectiveness yielded improved cost-effectiveness estimates. Mass drug administration may be a cost-effective intervention in the Zambian context and can help reduce the parasite reservoir substantially. Mass drug administration was more cost-effective in relatively higher transmission settings. In all scenarios examined, the cost-effectiveness of MDA was superior to that of fMDA.

A Deadly Wait for U.S. Health Insurance Coverage-Sitting on the Couch with Malaria.

Uninsured and unprepared travelers to countries with endemic tropical diseases pose great health-care burdens and financial risks on returning to the United States. We discuss the delayed presentation of an uninsured U.S. traveler returning from West Africa with severe malaria who required intensive care measures to save his life. Despite being critically ill on his return, he sat rigoring on his couch taking antipyretics for 3 days, while he applied for insurance on the Affordable Care Act website and waited for approval because he was fearful of the costs of seeking care. He also had limited access to affordable pretravel consultation and prophylactic medications and did not take them because he had no insurance. Average fees for a malaria hospitalization cost $25,789; however, this patient accumulated fees nearing $300,000-and his care was reimbursed by emergency Medicaid with $39,000, because his newly accepted insurance did not cover his hospitalization. This patients' experience in the U.S. health-care system with a deadly tropical disease exemplifies the need for affordable universal coverage of pretravel consultation and malaria prophylaxis. In this uncertain political time and the recent removal of the health insurance mandate, along with the White House and Congress wanting to reform health care, this case supports the American Society of Tropical Medicine and Hygiene (ASTMH) statements showing the need for funding of tropical medicine education, research, and public health services for travelers, not cuts to important agencies and insurances that keep our country safe from imported deadly tropical diseases.

Burden, pathology, and costs of malaria in pregnancy: new developments for an old problem.

Over the past 10 years, knowledge of the burden, economic costs, and consequences of malaria in pregnancy has improved, and the prevalence of malaria caused by Plasmodium falciparum has declined substantially in some geographical areas. In particular, studies outside of Africa have increased the evidence base of Plasmodium vivax in pregnancy. Rapid diagnostic tests have been poor at detecting malaria in pregnant women, while PCR has shown a high prevalence of low density infection, the clinical importance of which is unknown. Erythrocytes infected with P falciparum that express the surface protein VAR2CSA accumulate in the placenta, and VAR2CSA is an important target of protective immunity. Clinical trials for a VAR2CSA vaccine are ongoing, but sequence variation needs to be carefully studied. Health system and household costs still limit access to prevention and treatment services. Within the context of malaria elimination, pregnant women could be used to monitor malaria transmission. This Series paper summarises recent progress and highlights unresolved issues related to the burden of malaria in pregnancy.

Impact of insecticide resistance in Anopheles arabiensis on malaria incidence and prevalence in Sudan and the costs of mitigation.

Insecticide-based interventions have contributed to ∼78% of the reduction in the malaria burden in sub-Saharan Africa since 2000. Insecticide resistance in malaria vectors could presage a catastrophic rebound in disease incidence and mortality. A major impediment to the implementation of insecticide resistance management strategies is that evidence of the impact of resistance on malaria disease burden is limited. A cluster randomized trial was conducted in Sudan with pyrethroid-resistant and carbamate-susceptible malaria vectors. Clusters were randomly allocated to receive either long-lasting insecticidal nets (LLINs) alone or LLINs in combination with indoor residual spraying (IRS) with a pyrethroid (deltamethrin) insecticide in the first year and a carbamate (bendiocarb) insecticide in the two subsequent years. Malaria incidence was monitored for 3 y through active case detection in cohorts of children aged 1 to <10 y. When deltamethrin was used for IRS, incidence rates in the LLIN + IRS arm and the LLIN-only arm were similar, with the IRS providing no additional protection [incidence rate ratio (IRR) = 1.0 (95% confidence interval [CI]: 0.36-3.0; P = 0.96)]. When bendiocarb was used for IRS, there was some evidence of additional protection [interaction IRR = 0.55 (95% CI: 0.40-0.76; P < 0.001)]. In conclusion, pyrethroid resistance may have had an impact on pyrethroid-based IRS. The study was not designed to assess whether resistance had an impact on LLINs. These data alone should not be used as the basis for any policy change in vector control interventions.

Cost-effectiveness of artemisinin-naphthoquine versus artemether-lumefantrine for the treatment of uncomplicated malaria in Papua New Guinean children.

BACKGROUND: A recent randomized trial showed that artemisinin-naphthoquine (AN) was non-inferior to artemether-lumefantrine (AL) for falciparum malaria and superior for vivax malaria in young Papua New Guinean children. The aim of this study was to compare the cost-effectiveness of these two regimens. METHODS: An incremental cost-effectiveness analysis was performed using data from 231 children with Plasmodium falciparum and/or Plasmodium vivax infections in an open-label, randomized, parallel-group trial. Recruited children were randomized 1:1 to receive once daily AN for 3 days with water or twice daily AL for 3 days given with fat. World Health Organisation (WHO) definitions were used to determine clinical/parasitological outcomes. The cost of transport between the home and clinic, plus direct health-care costs, served as a basis for determining each regimen's incremental cost per incremental treatment success relative to AL by Day 42 and its cost per life year saved. RESULTS: In the usual care setting, AN was more effective for the treatment of uncomplicated malaria in children aged 0.5-5.9 years. AL and AN were equally efficacious for the treatment of falciparum malaria, however AN had increased anti-malarial treatment costs per patient of $10.46, compared with AL. AN was the most effective regimen for treatment of vivax malaria, but had increased treatment costs of $14.83 per treatment success compared with AL. CONCLUSIONS: Whilst AN has superior overall efficacy for the treatment of uncomplicated malaria in PNG children, AL was the less costly regimen. An indicative extrapolation estimated the cost per life year saved by using AN instead of AL to treat uncomplicated malaria to be $12,165 for girls and $12,469 for boys (discounted), which means AN may not be cost-effective and affordable for PNG at current cost. However, AN may become acceptable should it become WHO prequalified and/or should donated/subsidized drug supply become available.

Cost-effectiveness of adding indoor residual spraying to case management in Afghan refugee settlements in Northwest Pakistan during a prolonged malaria epidemic.

INTRODUCTION: Financing of malaria control for displaced populations is limited in scope and duration, making cost-effectiveness analyses relevant but difficult. This study analyses cost-effectiveness of adding prevention through targeted indoor residual spraying (IRS) to case management in Afghan refugee settlements in Pakistan during a prolonged malaria epidemic. METHODS/FINDINGS: An intervention study design was selected, taking a societal perspective. Provider and household costs of vector control and case management were collected from provider records and community survey. Health outcomes (e.g. cases and DALYs averted) were derived and incremental cost-effectiveness ratios (ICERs) for cases prevented and DALYs averted calculated. Population, treatment cost, women's time, days of productivity lost, case fatality rate, cases prevented, and DALY assumptions were tested in sensitivity analysis. Malaria incidence peaked at 44/1,000 population in year 2, declining to 14/1,000 in year 5. In total, 370,000 malaria cases, 80% vivax, were diagnosed and treated and an estimated 67,988 vivax cases and 18,578 falciparum and mixed cases prevented. Mean annual programme cost per capita was US$0.56. The additional cost of including IRS over five years per case prevented was US$39; US$50 for vivax (US$43 in years 1-3, US$80 in years 4-5) and US$182 for falciparum (US$139 in years 1-3 and US$680 in years 4-5). Per DALY averted this was US$266 (US$220 in years 1-3 and US$486 in years 4-5) and thus 'highly cost-effective' or cost-effective using WHO and comparison thresholds. CONCLUSIONS: Adding IRS was cost-effective in this moderate endemicity, low mortality setting. It was more cost-effective when transmission was highest, becoming less so as transmission reduced. Because vivax was three times more common than falciparum and the case fatality rate was low, cost-effectiveness estimations for cases prevented appear reliable and more definitive for vivax malaria.

Country specific predictions of the cost-effectiveness of malaria vaccine RTS,S/AS01 in endemic Africa.

BACKGROUND: RTS,S/AS01 is a safe and moderately efficacious vaccine considered for implementation in endemic Africa. Model predictions of impact and cost-effectiveness of this new intervention could aid in country adoption decisions. METHODS: The impact of RTS,S was assessed in 43 countries using an ensemble of models of Plasmodium falciparum epidemiology. Informed by the 32months follow-up data from the phase 3 trial, vaccine effectiveness was evaluated at country levels of malaria parasite prevalence, coverage of control interventions and immunization. Benefits and costs of the program incremental to routine malaria control were evaluated for a four dose schedule: first dose administered at six months, second and third - before 9months, and fourth dose at 27months of age. Sensitivity analyses around vaccine properties, transmission, and economic inputs were conducted. RESULTS: If implemented in all 43 countries the vaccine has the potential to avert 123 (117;129) million malaria episodes over the first 10years. Burden averted averages 18,413 (range of country median estimates 156-40,054) DALYs per 100,000 fully vaccinated children with much variation across settings primarily driven by differences in transmission intensity. At a price of $5 per dose program costs average $39.8 per fully vaccinated child with a median cost-effectiveness ratio of $188 (range $78-$22,448) per DALY averted; the ratio is lower by one third - $136 (range $116-$220) - in settings where parasite prevalence in children aged 2-10years is at or above 10%. CONCLUSION: RTS,S/AS01has the potential to substantially reduce malaria burden in children across Africa. Conditional on assumptions on price, coverage, and vaccine properties, adding RTS,S to routine malaria control interventions would be highly cost-effective. Implementation decisions will need to further consider feasibility of scaling up existing control programs, and operational constraints in reaching children at risk with the schedule.

Treatment-seeking behaviour and associated costs for malaria in Papua, Indonesia.

BACKGROUND: Malaria remains a significant public health issue in Eastern Indonesia, where multidrug resistant Plasmodium falciparum and Plasmodium vivax are highly prevalent. The objective of this study was to describe treatment-seeking behaviour and household costs prior to a change to a unified treatment policy of dihydroartemisinin-piperaquine in Mimika district, Papua province in 2006. METHODS: In 2005 a randomized cross-sectional household survey was conducted to collect data on demographics, socio-economic status (SES), treatment-seeking, case management, and household costs. Information on the cost of illness was also collected from patients exiting health facilities, in order to compare the cost of episodes diagnosed as P. vivax compared with those diagnosed as P. falciparum. RESULTS: 825 households were included in the survey. Of the 764 individuals who sought treatment for fever outside the home in the last month, 46% (349/764) went to a public health facility. Of the 894 reported visits to healthcare providers, 48% (433) resulted in a blood test, of which 78% (337) were reportedly positive. Only 10% (17/177) of individuals who reported testing positive for P. falciparum or mixed infection received the first-line treatment of chloroquine with SP, and 38% (61/159) of those with a diagnosis of P. vivax reportedly received the first-line treatment of chloroquine and primaquine. Overall, public facilities were more likely to prescribe the correct prevailing first-line drug combinations than private providers (OR = 3.77 [95% CI 2.31-6.14], p < 0.001). The mean cost to the household of an episode of P. vivax was similar to the cost of P. falciparum [US$44.50 (SD: 46.23) vs US$48.58 (SD: 64.65)]. CONCLUSIONS: Private providers were a popular source of treatment for malaria, but adherence to the national guidelines was low and the economic burden of malaria for both P. falciparum and P. vivax infections was substantial. Engagement with the private sector is needed to ensure that patients have access to affordable good quality, effective diagnostics and anti-malarials for both P. falciparum and P. vivax.

The RooPfs study to assess whether improved housing provides additional protection against clinical malaria over current best practice in The Gambia: study protocol for a randomized controlled study and ancillary studies.

BACKGROUND: In malaria-endemic areas, residents of modern houses have less malaria than those living in traditional houses. This study will determine if modern housing provides incremental protection against clinical malaria over the current best practice of long-lasting insecticidal nets (LLINs) and prompt treatment in The Gambia, determine the incremental cost-effectiveness of the interventions, and analyze the housing market in The Gambia. METHODS/DESIGN: A two-armed, household, cluster-randomized, controlled study will be conducted to assess whether improved housing and LLINs combine to provide better protection against clinical malaria in children than LLINs alone in The Gambia. The unit of randomization will be the household, defined as a house and its occupants. A total of 800 households will be enrolled and will receive LLINs, and 400 will receive improved housing before clinical follow-up. One child aged 6 months to 13 years will be enrolled from each household and followed for clinical malaria using active case detection to estimate malaria incidence for two malaria transmission seasons. Episodes of clinical malaria will be the primary endpoint. Study children will be surveyed at the end of each transmission season to estimate the prevalence of Plasmodium falciparum infection, parasite density, and the prevalence of anemia. Exposure to malaria parasites will be assessed using light traps, followed by detection of Anopheles gambiae species and sporozoite infection. Ancillary economic and social science studies will undertake a cost-effectiveness analysis and use qualitative and participatory methods to explore the acceptability of the housing modifications and to design strategies for scaling-up housing interventions. DISCUSSION: The study is the first of its kind to measure the efficacy of housing on reducing clinical malaria, assess the incremental cost-effectiveness of improved housing, and identify mechanisms for scaling up housing interventions. Trial findings will help inform policy makers on improved housing for malaria control in sub-Saharan Africa. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN02622179 . Registered on 23 September 2014.

The Future of the RTS,S/AS01 Malaria Vaccine: An Alternative Development Plan.

Roly Gosling and Lorenz von Seidlein consider a potential future development plan for the RTS,S/AS01 malaria vaccine.

Public health impact and cost-effectiveness of the RTS,S/AS01 malaria vaccine: a systematic comparison of predictions from four mathematical models.

BACKGROUND: The phase 3 trial of the RTS,S/AS01 malaria vaccine candidate showed modest efficacy of the vaccine against Plasmodium falciparum malaria, but was not powered to assess mortality endpoints. Impact projections and cost-effectiveness estimates for longer timeframes than the trial follow-up and across a range of settings are needed to inform policy recommendations. We aimed to assess the public health impact and cost-effectiveness of routine use of the RTS,S/AS01 vaccine in African settings. METHODS: We compared four malaria transmission models and their predictions to assess vaccine cost-effectiveness and impact. We used trial data for follow-up of 32 months or longer to parameterise vaccine protection in the group aged 5-17 months. Estimates of cases, deaths, and disability-adjusted life-years (DALYs) averted were calculated over a 15 year time horizon for a range of levels of Plasmodium falciparum parasite prevalence in 2-10 year olds (PfPR2-10; range 3-65%). We considered two vaccine schedules: three doses at ages 6, 7·5, and 9 months (three-dose schedule, 90% coverage) and including a fourth dose at age 27 months (four-dose schedule, 72% coverage). We estimated cost-effectiveness in the presence of existing malaria interventions for vaccine prices of US$2-10 per dose. FINDINGS: In regions with a PfPR2-10 of 10-65%, RTS,S/AS01 is predicted to avert a median of 93,940 (range 20,490-126,540) clinical cases and 394 (127-708) deaths for the three-dose schedule, or 116,480 (31,450-160,410) clinical cases and 484 (189-859) deaths for the four-dose schedule, per 100,000 fully vaccinated children. A positive impact is also predicted at a PfPR2-10 of 5-10%, but there is little impact at a prevalence of lower than 3%. At $5 per dose and a PfPR2-10 of 10-65%, we estimated a median incremental cost-effectiveness ratio compared with current interventions of $30 (range 18-211) per clinical case averted and $80 (44-279) per DALY averted for the three-dose schedule, and of $25 (16-222) and $87 (48-244), respectively, for the four-dose schedule. Higher ICERs were estimated at low PfPR2-10 levels. INTERPRETATION: We predict a significant public health impact and high cost-effectiveness of the RTS,S/AS01 vaccine across a wide range of settings. Decisions about implementation will need to consider levels of malaria burden, the cost-effectiveness and coverage of other malaria interventions, health priorities, financing, and the capacity of the health system to deliver the vaccine. FUNDING: PATH Malaria Vaccine Initiative; Bill & Melinda Gates Foundation; Global Good Fund; Medical Research Council; UK Department for International Development; GAVI, the Vaccine Alliance; WHO.

A Cost-Effectiveness Analysis of Plasmodium falciparum Malaria Elimination in Hainan Province, 2002-2012.

In Hainan Province, China, great achievements in elimination of falciparum malaria have been made since 2010. There have been no locally acquired falciparum malaria cases since that time. The cost-effectiveness of elimination of falciparum malaria has been analyzed in Hainan Province. There were 4,422 falciparum malaria cases reported from 2002 to 2012, more cases occurred in males than in females. From 2002 to 2012, a total of 98.5 disability-adjusted life years (DALYs) were reported because of falciparum malaria. Populations in the age ranges of 15-25 and 30-44 years had higher incidences and DALYs than other age groups. From 2002 to 2012, malaria-related costs for salaries of staff, funds from the provincial government, national government, and the GFATM were US$3.02, US$2.24, US$1.44, and US$5.08 million, respectively. An estimated 9,504 falciparum malaria cases were averted during the period 2003-2012. The estimated cost per falciparum malaria case averted was US$116.5. The falciparum malaria elimination program in Hainan was highly effective and successful. However, funding for maintenance is still needed because of imported cases.

Cost effectiveness and resource allocation of Plasmodium falciparum malaria control in Myanmar: a modelling analysis of bed nets and community health workers.

BACKGROUND: Funding for malaria control and elimination in Myanmar has increased markedly in recent years. While there are various malaria control tools currently available, two interventions receive the majority of malaria control funding in Myanmar: (1) insecticide-treated bed nets and (2) early diagnosis and treatment through malaria community health workers. This study aims to provide practical recommendations on how to maximize impact from investment in these interventions. METHODS: A simple decision tree is used to model intervention costs and effects in terms of years of life lost. The evaluation is from the perspective of the service provider and costs and effects are calculated in line with standard methodology. Sensitivity and scenario analysis are undertaken to identify key drivers of cost effectiveness. Standard cost effectiveness analysis is then extended via a spatially explicit resource allocation model. FINDINGS: Community health workers have the potential for high impact on malaria, particularly where there are few alternatives to access malaria treatment, but are relatively costly. Insecticide-treated bed nets are comparatively inexpensive and modestly effective in Myanmar, representing a low risk but modest return intervention. Unlike some healthcare interventions, bed nets and community health workers are not mutually exclusive nor are they necessarily at their most efficient when universally applied. Modelled resource allocation scenarios highlight that in this case there is no "one size fits all" cost effectiveness result. Health gains will be maximized by effective targeting of both interventions.

An Economic Evaluation of the Posttreatment Prophylactic Effect of Dihydroartemisinin-Piperaquine Versus Artemether-Lumefantrine for First-Line Treatment of Plasmodium falciparum Malaria Across Different Transmission Settings in Africa.

Malaria disproportionately affects young children. Clinical trials in African children showed that dihydroartemisinin-piperaquine (DP) is an effective antimalarial and has a longer posttreatment prophylactic (PTP) effect against reinfections than other artemisinin-based combination therapies, including artemether-lumefantrine (AL). Using a previously developed Markov model and individual patient data from a multicenter African drug efficacy trial, we assessed the economic value of the PTP effect of DP versus AL in pediatric malaria patients from health-care provider's perspective in low-to-moderate and moderate-to-high transmission settings under different drug co-payment scenarios. In low-to-moderate transmission settings, first-line treatment with DP was highly cost-effective with an incremental cost-effectiveness ratio of US$5 (95% confidence interval [CI] = -76 to 196) per disability-adjusted life year (DALY) averted. In moderate-to-high transmission settings, DP first-line treatment led to a mean cost saving of US$1.09 (95% CI = -0.88 to 3.85) and averted 0.05 (95% CI = -0.08 to 0.22) DALYs per child per year. Our results suggested that DP might be superior to AL for first-line treatment of uncomplicated childhood malaria across a range of transmission settings in Africa.

Economic evaluation of a cluster randomized trial of interventions to improve health workers' practice in diagnosing and treating uncomplicated malaria in Cameroon.

BACKGROUND: Malaria rapid diagnostic tests (RDTs) are a valid alternative to malaria testing with microscopy and are recommended for the testing of febrile patients before prescribing an antimalarial. There is a need for interventions to support the uptake of RDTs by health workers. OBJECTIVE: To evaluate the cost-effectiveness of introducing RDTs with basic or enhanced training in health facilities in which microscopy was available, compared with current practice. METHODS: A three-arm cluster randomized trial was conducted in 46 facilities in central and northwest Cameroon. Basic training had a practical session on RDTs and lectures on malaria treatment guidelines. Enhanced training included small-group activities designed to change health workers' practice and reduce the consumption of antimalarials among test-negative patients. The primary outcome was the proportion of febrile patients correctly treated: febrile patients should be tested for malaria, artemisinin combination therapy should be prescribed for confirmed cases, and no antimalarial should be prescribed for patients who are test-negative. Individual patient data were obtained from facility records and an exit survey. Costs were estimated from a societal perspective using project reports and patient exit data. The analysis used bivariate multilevel modeling and adjusted for imbalance in baseline covariates. RESULTS: Incremental cost per febrile patient correctly treated was $8.40 for the basic arm and $3.71 for the enhanced arm. On scale-up, it was estimated that RDTs with enhanced training would save $0.75 per additional febrile patient correctly treated. CONCLUSIONS: Introducing RDTs with enhanced training was more cost-effective than RDTs with basic training when each was compared with current practice.

Contrasting benefits of different artemisinin combination therapies as first-line malaria treatments using model-based cost-effectiveness analysis.

There are currently several recommended drug regimens for uncomplicated falciparum malaria in Africa. Each has different properties that determine its impact on disease burden. Two major antimalarial policy options are artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA-PQP). Clinical trial data show that DHA-PQP provides longer protection against reinfection, while AL is better at reducing patient infectiousness. Here we incorporate pharmacokinetic-pharmacodynamic factors, transmission-reducing effects and cost into a mathematical model and simulate malaria transmission and treatment in Africa, using geographically explicit data on transmission intensity and seasonality, population density, treatment access and outpatient costs. DHA-PQP has a modestly higher estimated impact than AL in 64% of the population at risk. Given current higher cost estimates for DHA-PQP, there is a slightly greater cost per case averted, except in areas with high, seasonally varying transmission where the impact is particularly large. We find that a locally optimized treatment policy can be highly cost effective for reducing clinical malaria burden.