Economic evaluation of an alternative drug to sulfadoxine-pyrimethamine as intermittent preventive treatment of malaria in pregnancy

Abstract

Background: Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended in HIV-negative women to avert malaria, while this relies on cotrimoxazole prophylaxis (CTXp) in HIV-positive women. Alternative antimalarials are required in areas where parasite resistance to antifolate drugs is high. The cost-effectiveness of IPTp with alternative drugs is needed to inform policy.

Methods: The cost-effectiveness of 2-dose IPTp-mefloquine (MQ) was compared with IPTp-SP in HIV-negative women (Benin, Gabon, Mozambique and Tanzania). In HIV-positive women the cost-effectiveness of 3-dose IPTp-MQ added to CTXp was compared with CTXp alone (Kenya, Mozambique and Tanzania). The outcomes used were maternal clinical malaria, anaemia at delivery and non-obstetric hospital admissions. The poor tolerability to MQ was included as the value of women's loss of working days. Incremental cost-effectiveness ratios (ICERs) were calculated and threshold analysis undertaken.

Results: For HIV-negative women, the ICER for IPTp-MQ versus IPTp-SP was 136.30 US$ (2012 US$) (95%CI 131.41; 141.18) per disability-adjusted life-year (DALY) averted, or 237.78 US$ (95%CI 230.99; 244.57), depending on whether estimates from Gabon were included or not. For HIV-positive women, the ICER per DALY averted for IPTp-MQ added to CTXp, versus CTXp alone was 6.96 US$ (95%CI 4.22; 9.70). In HIV-negative women, moderate shifts of variables such as malaria incidence, drug cost, and IPTp efficacy increased the ICERs above the cost-effectiveness threshold. In HIV-positive women the intervention remained cost-effective for a substantial (up to 21 times) increase in cost per tablet.

Conclusions: Addition of IPTp with an effective antimalarial to CTXp was very cost-effective in HIV-positive women. IPTp with an efficacious antimalarial was more cost-effective than IPTp-SP in HIV-negative women. However, the poor tolerability of MQ does not favour its use as IPTp. Regardless of HIV status, prevention of malaria in pregnancy with a highly efficacious, well tolerated antimalarial would be cost-effective despite its high price.

Trials registration: ClinicalTrials.gov NCT 00811421; Pan African Trials Registry PACTR2010020001429343 and PACTR2010020001813440.

Trial registration: ClinicalTrials.gov NCT00811421.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Design of the Incremental economic evaluation.

HIV = Human Immunodeficiency Virus; LLITNs = Long-Lasting Insecticide Treated Nets; CTX = Cotrimoxazole; IPTp = Intermittent Preventive Treatment of malaria in pregnancy; SP = Sulphadoxine-Pyrimethamine; MQ = Mefloquine. The figure shows that for both Trials the cost of LLITNs was not considered in the economic evaluation performed as women in both arms were administered with this preventative tool. The same applies for CTX in Trial on HIV-positive women. IPTp-placebo in Trial on HIV-positive women was considered as “doing nothing” option with no costs associated. Incremental net costs were calculated, which included the incremental costs of the intervention minus treatment savings due to its efficacy.

Fig 2. Cost effectiveness plane: IPTp-MQ versus IPTp-SP in HIV-negative pregnant women in Benin, Gabon, Mozambique and Tanzania.

IPTp-MQ = Intermittent Preventive Treatment of malaria in pregnancy with Mefloquine; IPTp-SP = Intermittent Preventive Treatment of malaria in pregnancy with Sulphadoxine-Phyrimethamine; HIV = Human Immunodeficiency Virus; DALYs = Disability-adjusted life years. The graph plots 2,000 Monte Carlo simulations of the incremental cost-effectiveness ratio (ICER) with respect to its components: health impact (X-axis) and incremental costs (Y-axis). Average simulation point, ellipse of confidence (95%) and threshold level of the ICER (240 US$/DALY averted) are also depicted. Cost-effective dots are placed below/right the threshold line.

Fig 3. Cost effectiveness plane: IPTp-MQ versus IPTp-SP in HIV-negative pregnant women in Benin, Mozambique and Tanzania.

IPTp-MQ = Intermittent Preventive Treatment of malaria in pregnancy with Mefloquine; IPTp-SP = Intermittent Preventive Treatment of malaria in pregnancy with Sulphadoxine-Phyrimethamine; HIV = Human Immunodeficiency Virus; DALYs = Disability-adjusted life years. The graph plots N = 2,000 Monte Carlo simulations of the incremental cost-effectiveness ratio (ICER) with respect to its components: health impact (X-axis) and incremental costs (Y-axis). Average simulation point, ellipse of confidence (95%) and threshold level of the ICER (240 US$/DALY averted) are also depicted. Cost-effective dots are placed below/right the threshold line.

Fig 4. Cost effectiveness plane: IPTp-MQ versus IPTp-Placebo in HIV-positive pregnant women in Kenya, Mozambique and Tanzania.

IPTp-MQ = Intermittent Preventive Treatment of malaria in pregnancy with Mefloquine; HIV = Human Immunodeficiency Virus; DALYs = Disability-adjusted life years. The graph plots 2,000 Monte Carlo simulations of the incremental cost-effectiveness ratio (ICER) with respect to its components: health impact (X-axis) and incremental costs (Y-axis). Average simulation point, ellipse of confidence (95%) and threshold level of the ICER (240 US$/DALY averted) are also depicted.

Fig 5. Cost-effectiveness of IPTp-MQ versus IPTp-SP in HIV-negative pregnant women in Benin, Gabon, Mozambique and Tanzania: acceptability curves.

IPTp-MQ = Intermittent Preventive Treatment of malaria in pregnancy with Mefloquine; IPTp-SP = Intermittent Preventive Treatment of malaria in pregnancy with Sulphadoxine-Phyrimethamine; HIV = Human Immunodeficiency Virus; DALYs = Disability-adjusted life years. Acceptability curves were constructed by plotting the cumulative distribution of the incremental cost-effectiveness ratios (ICERs) of IPTp-MQ compared with IPTp-SP per DALYs averted. The Y axis is interpreted as probability that the intervention is cost-effective for every level of policy makers’ willingness to pay for each DALY averted (X axis). US$ 136.30 per DALY averted (CI95% 131.41–141.18) is the ICER for the scenario including Benin, Gabon, Mozambique and Tanzania. US$ 237.99 (CI95% 230.99–244.57) per DALY averted is the ICER for the scenario excluding Gabon.

Fig 6. Cost-effectiveness of IPTp-MQ versus IPTp-Placebo in HIV-positive pregnant women in Kenya, Mozambique and Tanzania: acceptability curve.

IPTp-MQ = Intermittent Preventive Treatment of malaria in pregnancy with Mefloquine; HIV = Human Immunodeficiency Virus; DALYs = Disability-adjusted life years. The acceptability curve was constructed by plotting the cumulative distribution of the incremental cost-effectiveness ratio (ICER) of IPTp-MQ compared with IPTp-Placebo per DALYs averted. The Y axis is interpreted as probability that the intervention is cost-effective for every level of policy makers’ willingness to pay for each DALY averted (X axis). US$ 6.96 per DALY averted (CI95% 4.22–9.70) is the ICER resulting from the analysis.

Fig 7. Results of the threshold analysis of IPTp-MQ among HIV-negative and HIV-positive pregnant women.

IPTp = Intermittent Preventive Treatment of malaria in pregnancy; HIV = Human Immunodeficiency Virus; MQ = Mefloquine; SP = Sulphadoxine-Phyrimethamine; PYAR = Person-year at risk; RR = Relative Risk. The graph depicts up to which level (threshold level) several variables can increase or decrease from their current level for the interventions to remain cost-effective.