Cost-effectiveness of community-based distribution of intermittent preventive treatment of malaria in pregnancy in Madagascar, Mozambique, Nigeria, and the Democratic Republic of Congo.

INTRODUCTION: Malaria in pregnancy is a major driver of maternal and infant mortality in sub-Saharan Africa. The WHO recommends the administration of intermittent preventive treatment with sulfadoxine pyrimethamine (IPTp-SP) at antenatal care (ANC) visits. Despite being a highly cost-effective strategy, IPTp-SP coverage and uptake remains low. A pilot project was conducted to assess the cost-effectiveness (CE) of community-based delivery of IPTp (C-IPTp) in addition to ANC delivery to increase IPTp uptake in the Democratic Republic of Congo (DRC), Madagascar (MDG), Mozambique (MOZ) and Nigeria (NGA). METHODS: Costs and CE estimates of C-IPTp were calculated according to two scenarios: (1) costs in 'programmatic mode' (ie, costs if C-IPTp was to be implemented by national health systems) and (2) costs from the pilot project. The effectiveness of C-IPTp was obtained through estimates of the averted disability-adjusted life-years (DALYs) associated with maternal clinical malaria and anaemia, low birth weight and neonatal mortality. RESULTS: Net incremental costs of C-IPTp ranged between US$6138-US$47 177 (DRC), US$5552-US$31 552 (MDG), US$10 202-US$53 221 (MOZ) and US$667-US$28 645 (NGA) per 1000 pregnant women, under scenarios (1) and (2), respectively. Incremental cost-effectiveness ratios (ICERs) ranged between US$15-US$119 in DRC, US$9-US$53 in MDG, US$104-US$543 in MOZ and US$2-US$66 in NGA per DALY averted, under scenarios (1) and (2), respectively. ICERs fall below the WHO recommended CE threshold based on the gross domestic product per capita. CONCLUSION: Findings suggest that C-IPTp is a highly cost-effective intervention. Results can inform policy decisions on adopting and optimising effective interventions for preventing malaria in pregnancy.

The economic costs of malaria in pregnancy: evidence from four sub-Saharan countries.

Background Malaria in pregnancy is a major public health problem in sub-Saharan Africa (SSA), which imposes a significant economic burden. We provide evidence on the costs of malaria care in pregnancy to households and the health system in four high-burden countries in SSA.  Methods Household and health system economic costs associated with malaria control in pregnancy were estimated in selected areas of the Democratic Republic of Congo (DRC), Madagascar (MDG), Mozambique (MOZ) and Nigeria (NGA). An exit survey was administered to 2,031 pregnant women when leaving the antenatal care (ANC) clinic from October 2020 to June 2021. Women reported the direct and indirect costs associated to malaria prevention and treatment in pregnancy. To estimate health system costs, we interviewed health workers from 133 randomly selected health facilities. Costs were estimated using an ingredients-based approach. Results Average household costs of malaria prevention per pregnancy were USD6.33 in DRC, USD10.06 in MDG, USD15.03 in MOZ and USD13.33 in NGA. Household costs of treating an episode of uncomplicated/complicated malaria were USD22.78/USD46 in DRC, USD16.65/USD35.65 in MDG, USD30.54/USD61.25 in MOZ and USD18.92/USD44.71 in NGA, respectively. Average health system costs of malaria prevention per pregnancy were USD10.74 in DRC, USD16.95 in MDG, USD11.17 in MOZ and USD15.64 in NGA. Health system costs associated with treating an episode of uncomplicated/complicated malaria were USD4.69/USD101.41 in DRC, USD3.61/USD63.33 in MDG, USD4.68/USD83.70 in MOZ and USD4.09/USD92.64 in NGA. These estimates resulted in societal costs of malaria prevention and treatment per pregnancy of USD31.72 in DRC, USD29.77 in MDG, USD31.98 in MOZ and USD46.16 in NGA. Conclusions Malaria in pregnancy imposes a high economic burden on households and the health system. Findings emphasize the importance of investing in effective strategies that improve access to malaria control and reduce the burden of the infection in pregnancy.

Minimally Invasive Tissue Sampling: A Tool to Guide Efforts to Reduce AIDS-Related Mortality in Resource-Limited Settings.

BACKGROUND: Available information on the causes of death among people living with human immunodeficiency virus (PLHIV) in low- and middle-income countries (LMICs) remains scarce. We aimed to provide data on causes of death in PLHIV from two LMICs, Brazil and Mozambique, to assess the impact of clinical misdiagnosis on mortality rates and to evaluate the accuracy of minimally invasive tissue sampling (MITS) in determining the cause of death in PLHIV. METHODS: We performed coupled MITS and complete autopsy on 164 deceased PLHIV (18 children, 36 maternal deaths, and 110 adults). HIV antibody levels and HIV RNA viral loads were determined from postmortem serum samples. RESULTS: Tuberculosis (22.7%), toxoplasmosis (13.9%), bacterial infections (13.9%), and cryptococcosis (10.9%) were the leading causes of death in adults. In maternal deaths, tuberculosis (13.9%), bacterial infections (13.9%), cryptococcosis (11.1%), and cerebral malaria (8.3%) were the most frequent infections, whereas viral infections, particularly cytomegalovirus (38.9%), bacterial infections (27.8%), pneumocystosis (11.1%), and HIV-associated malignant neoplasms (11.1%) were the leading cause among children. Agreement between the MITS and the complete autopsy was 100% in children, 91% in adults, and 78% in maternal deaths. The MITS correctly identified the microorganism causing death in 89% of cases. CONCLUSIONS: Postmortem studies provide highly granular data on the causes of death in PLHIV. The inaccuracy of clinical diagnosis may play a significant role in the high mortality rates observed among PLHIV in LMICs. MITS might be helpful in monitoring the causes of death in PLHIV and in highlighting the gaps in the management of the infections.

Costs associated with delivering HPV vaccination in the context of the first year demonstration programme in southern Mozambique.

BACKGROUND: In Mozambique cervical cancer is a public health threat, due to its high incidence and limited access to early diagnosis of precancerous lesions. International organisations are supporting the introduction of human papillomavirus (HPV) vaccines in low- and middle-income countries. Some of these countries recently conducted demonstration programmes, which included evaluation of acceptability, coverage, and practicality of implementation and of integration in existing programmes. Information on costs of delivering the vaccine is needed to overcome the challenges of reaching vaccine potential recipients in rural and remote areas. METHODS: We estimated the financial and economic costs of delivering HPV vaccination to ten-year-old girls at schools for the first vaccination cycle of the demonstration programme in the Manhiça district (southern Mozambique), delivered throughout 2014. We also estimated costs of an alternative scenario with a reduced number of doses and personnel, which was analogous to the second vaccination cycle delivered throughout 2015. Cost estimates followed a micro-costing approach and included interviews with key informants at different administrative levels through the administration of standard questionnaires developed by the World Health Organisation. RESULTS: Considering only data from the first vaccination cycle (2014), which consisted in the administration of three doses, the average economic cost was US$17.59 per dose and US$52.29 per fully-immunised girl (FIG). Financial cost per dose (US$6.07) and per FIG (US$17.95) were substantially lower. The economic cost was US$15.53 per dose and US$31.14 per FIG when estimating an alternative cost scenario with reduced number of doses and personnel. CONCLUSIONS: The average economic cost per dose was lower than the ones recently reported for low- and middle-income countries. However, our estimation of the financial cost per FIG was higher than the ones observed elsewhere (ranging from US$2.49 in India to US$20.36 in Vietnam) due to the high percentage of out-of-school girls which, reduced vaccine coverage and, therefore, reduced the denominator. Due to budget constraints, if Mozambique is to implement nation-wide HPV vaccination targeted to ten-year-old girls at schools, a reduction in personnel costs should be operated either by restricting the outreach vaccinator team or the number of supervision visits.

Setting the scene and generating evidence for malaria elimination in Southern Mozambique.

Mozambique has historically been one of the countries with the highest malaria burden in the world. Starting in the 1960s, malaria control efforts were intensified in the southern region of the country, especially in Maputo city and Maputo province, to aid regional initiatives aimed to eliminate malaria in South Africa and eSwatini. Despite significant reductions in malaria prevalence, elimination was never achieved. Following the World Health Organization's renewed vision of a malaria-free-world, and considering the achievements from the past, the Mozambican National Malaria Control Programme (NMCP) embarked on the development and implementation of a strategic plan to accelerate from malaria control to malaria elimination in southern Mozambique. An initial partnership, supported by the Bill and Melinda Gates Foundation and the La Caixa Foundation, led to the creation of the Mozambican Alliance Towards the Elimination of Malaria (MALTEM) and the Malaria Technical and Advisory Committee (MTAC) to promote national ownership and partner coordination to work towards the goal of malaria elimination in local and cross-border initiatives. Surveillance systems to generate epidemiological and entomological intelligence to inform the malaria control strategies were strengthened, and an impact and feasibility assessment of various interventions aimed to interrupt malaria transmission were conducted in Magude district (Maputo Province) through the "Magude Project". The primary aim of this project was to generate evidence to inform malaria elimination strategies for southern Mozambique. The goal of malaria elimination in areas of low transmission intensity is now included in the national malaria strategic plan for 2017-22 and the NMCP and its partners have started to work towards this goal while evidence continues to be generated to move the national elimination agenda forward.

Inequalities in sub-Saharan African women's and girls' health opportunities and outcomes: evidence from the Demographic and Health Surveys.

BACKGROUND: Maternal and reproductive health services are far from universalization and important gaps exist in their distribution across groups of women in sub-Saharan Africa (SSA). The aim of this study is to determine the magnitude of this unequal distribution of maternal and reproductive health-related opportunities and outcomes and to identify the major sources of inequality. METHODS: Demographic and Health Surveys data were used to analyse 15 opportunities for women of reproductive age (15-49), pregnant women and older adolescent girls (15-19), across 29 SSA countries. The tool employed is the Human Opportunity Index (HOI), a composite indicator that combines the availability of an opportunity (the coverage rate) with a measure of how equitably it is distributed among groups of women with different characteristics (or circumstances). Decompositions are used to assess the contribution of each individual circumstance to inequality. RESULTS: The maternity care package of services is found to have lowest average HOI (26%), while exclusive breastfeeding among children aged 0-6 months has the highest HOI (77%). The other indicators show low HOIs, sometimes lower than 50%, indicating low coverage and/or high inequality. Wealth, education and area of residence are the main contributors to inequality for women of reproductive age. Among adolescent girls, marital status is the major contributor. CONCLUSIONS: Reproductive and maternal health opportunities for women in SSA are scarce and far from reaching the global goals set by the post 2015 agenda. Further progress in improving women's and adolescents' health and well-being can only be achieved by a strong expansion of coverage to produce a more equitable and efficient distribution of health care. Failure to do so will compromise the likelihood of achieving the post-2015 Sustainable Development Goals (SDG). New metrics such as the HOI allows better understanding of the nature of challenges to achieving equity in perinatal and reproductive health, and offers a tool for monitoring progress in implementing a strong equity agenda as a part of the SDG initiative.

Patients' costs, socio-economic and health system aspects associated with malaria in pregnancy in an endemic area of Colombia.

Malaria in pregnancy threatens birth outcomes and the health of women and their newborns. This is also the case in low transmission areas, such as Colombia, where Plasmodium vivax is the dominant parasite species. Within the Colombian health system, which underwent major reforms in the 90s, malaria treatment is provided free of charge to patients. However, patients still incur costs, such as transportation and value of time lost due to the disease. We estimated such costs among 40 pregnant women with clinical malaria (30% Plasmodium falciparum, 70% Plasmodium vivax) in the municipality of Tierralta, Northern Colombia. In a cross-sectional study, women were interviewed after an outpatient or inpatient laboratory confirmed malaria episode. Women were asked to report all types of cost incurred before (including prevention), during and immediately after the contact with the health facility. Median total cost was over 16US$ for an outpatient visit, rising to nearly 30US$ if other treatments were sought before reaching the health facility. Median total inpatient cost was 26US$ or 54US$ depending on whether costs incurred prior to admission were excluded or included. For both outpatients and inpatients, direct costs were largely due to transportation and indirect costs constituted the largest share of total costs. Estimated costs are likely to represent only one of the constraints that women face when seeking treatment in an area characterized, at the time of the study, by armed conflict, displacement, and high vulnerability of indigenous women, the group at highest risk of malaria. Importantly, the Colombian peace process, which culminated with the cease-fire in August 2016, may have a positive impact on achieving universal access to healthcare in conflict areas. The current study can inform malaria elimination initiatives in Colombia.

Are Infants Less than 6 Months of Age a Neglected Group for Anemia Prevention in Low-Income Countries?

Anemia is a major public health problem that affects mainly children, predominantly in low-income countries and most often due to iron deficiency (ID). Administration of iron supplements to prevent and treat ID anemia in malaria endemic areas has been controversial for decades; however, recent World Health Organization guidelines recommend universal iron supplementation for children in highly prevalent anemia settings, including those where malaria is endemic. However, infants younger than 6 months of age have been exempted from this recommendation because ID is not considered prevalent at this age and because of assumptions-without evidence-that they are protected from ID through breast milk. To achieve full impact of anemia prevention targeting infants less than 6 months of age who are at highest risk of ID, operational studies that conclusively demonstrate the effectiveness and safety of delivering iron supplements to young infants in settings with a high burden of infectious diseases, including malaria, are needed.

Barriers and facilitators to health care seeking behaviours in pregnancy in rural communities of southern Mozambique.

BACKGROUND: In countries, such as Mozambique, where maternal mortality remains high, the greatest contribution of mortality comes from the poor and vulnerable communities, who frequently reside in remote and rural areas with limited access to health care services. This study aimed to understand women's health care seeking practices during pregnancy, taking into account the underlying social, cultural and structural barriers to accessing timely appropriate care in Maputo and Gaza Provinces, southern Mozambique. METHODS: This ethnographic study collected data through in-depth interviews and focus group discussions with women of reproductive age, including pregnant women, as well as household-level decision makers (partners, mothers and mothers-in-law), traditional healers, matrons, and primary health care providers. Data was analysed thematically using NVivo 10. RESULTS: Antenatal care was sought at the heath facility for the purpose of opening the antenatal record. Women without antenatal cards feared mistreatment during labour. Antenatal care was also sought to resolve discomforts, such as headaches, flu-like symptoms, body pain and backache. However, partners and husbands considered lower abdominal pain as the only symptom requiring care and discouraged women from revealing their pregnancy early in gestation. Health care providers for pregnant women often included those at the health facility, matrons, elders, traditional birth attendants, and community health workers. Although seeking care from traditional healers was discouraged during the antenatal period, they did provide services during pregnancy and after delivery. Besides household-level decision-makers, matrons, community health workers, and neighbours were key actors in the referral of pregnant women. The decision-making process may be delayed and particularly complex if an emergency occurs in their absence. Limited access to transport and money makes the decision-making process to seek care at the health facility even more complex. CONCLUSIONS: Women do seek antenatal care at health facilities, despite the presence of other health care providers in the community. There are important factors that prevent timely care-seeking for obstetric emergencies and delivery. Unfamiliarity with warning signs, especially among partners, discouragement from revealing pregnancy early in gestation, complex and untimely decision-making processes, fear of mistreatment by health-care providers, lack of transport and financial constraints were the most commonly cited barriers. Women of reproductive age would benefit from community saving schemes for transport and medication, which in turn would improve their birth preparedness and emergency readiness; in addition, pregnancy follow-up should include key family members, and community-based health care providers should encourage prompt referrals to health facilities, when appropriate. TRIAL REGISTRATION: NCT01911494.

Costs Associated with Malaria in Pregnancy in the Brazilian Amazon, a Low Endemic Area Where Plasmodium vivax Predominates.

BACKGROUND: Information on costs associated with malaria in pregnancy (MiP) in low transmission areas where Plasmodium vivax predominates is so far missing. This study estimates health system and patient costs of MiP in the Brazilian Amazon. METHODS/PRINCIPAL FINDINGS: Between January 2011 and March 2012 patient costs for the treatment of MiP were collected through an exit survey at a tertiary referral hospital and at a primary health care centre in the Manaus metropolitan area, Amazonas state. Pregnant and post-partum women diagnosed with malaria were interviewed after an outpatient consultation or at discharge after admission. Seventy-three interviews were included in the analysis. Ninety-six percent of episodes were due to P. vivax and 4% to Plasmodium falciparum. In 2010, the total median costs from the patient perspective were estimated at US $45.91 and US $216.29 for an outpatient consultation and an admission, respectively. When multiple P. vivax infections during the same pregnancy were considered, patient costs increased up to US $335.85, representing the costs of an admission plus an outpatient consultation. Provider direct and overhead cost data were obtained from several sources. The provider cost associated with an outpatient case, which includes several consultations at the tertiary hospital was US $103.51 for a P. vivax malaria episode and US $83.59 for a P. falciparum malaria episode. The cost of an inpatient day and average admission of 3 days was US $118.51 and US $355.53, respectively. Total provider costs for the diagnosis and treatment of all malaria cases reported in pregnant women in Manaus in 2010 (N = 364) were US $17,038.50, of which 92.4% (US$ 15,741.14) due to P. vivax infection. CONCLUSION: Despite being an area of low risk malaria transmission, MiP is responsible for a significant economic burden in Manaus. Especially when multiple infections are considered, costs associated with P. vivax are higher than costs associated with P. falciparum. The information generated may help health policy decisions for the current control and future elimination of malaria in the area.

Assessment of the safety of antimalarial drug use during early pregnancy (ASAP): protocol for a multicenter prospective cohort study in Burkina Faso, Kenya and Mozambique.

BACKGROUND: A major unresolved safety concern for malaria case management is the use of artemisinin combination therapies (ACTs) in the first trimester of pregnancy. There is a need for human data to inform policy makers and treatment guidelines on the safety of artemisinin combination therapies (ACT) when used during early pregnancy. METHODS: The overall goal of this paper is to describe the methods and implementation of a study aimed at developing surveillance systems for identifying exposures to antimalarials during early pregnancy and for monitoring pregnancy outcomes using health and demographic surveillance platforms. This was a multi-center prospective observational cohort study involving women at health and demographic surveillance sites in three countries in Africa: Burkina Faso, Kenya and Mozambique [(ClinicalTrials.gov Identifier: NCT01232530)]. The study was designed to identify pregnant women with artemisinin exposure in the first trimester and compare them to: 1) pregnant women without malaria, 2) pregnant women treated for malaria, but exposed to other antimalarials, and 3) pregnant women with malaria and treated with artemisinins in the 2nd or 3rd trimesters from the same settings. Pregnant women were recruited through community-based surveys and attendance at health facilities, including antenatal care clinics and followed until delivery. Data from the three sites will be pooled for analysis at the end of the study. Results are forthcoming. DISCUSSION: Despite few limitations, the methods described here are relevant to the development of sustainable pharmacovigilance systems for drugs used by pregnant women in the tropics using health and demographic surveillance sites to prospectively ascertain drug safety in early pregnancy. TRIAL REGISTRATION: NCT01232530.

Changing Trends in P. falciparum Burden, Immunity, and Disease in Pregnancy.

BACKGROUND: Prevention of reinfection and resurgence is an integral component of the goal to eradicate malaria. However, the adverse effects of malaria resurgences are not known. METHODS: We assessed the prevalence of Plasmodium falciparum infection among 1819 Mozambican women who delivered infants between 2003 and 2012. We used microscopic and histologic examination and a quantitative polymerase-chain-reaction (qPCR) assay, as well as flow-cytometric analysis of IgG antibody responses against two parasite lines. RESULTS: Positive qPCR tests for P. falciparum decreased from 33% in 2003 to 2% in 2010 and increased to 6% in 2012, with antimalarial IgG antibody responses mirroring these trends. Parasite densities in peripheral blood on qPCR assay were higher in 2010-2012 (geometric mean [±SD], 409±1569 genomes per microliter) than in 2003-2005 (44±169 genomes per microliter, P=0.02), as were parasite densities in placental blood on histologic assessment (50±39% of infected erythrocytes vs. 4±6%, P<0.001). The malaria-associated reduction in maternal hemoglobin levels was larger in 2010-2012 (10.1±1.8 g per deciliter in infected women vs. 10.9±1.7 g per deciliter in uninfected women; mean difference, -0.82 g per deciliter; 95% confidence interval [CI], -1.39 to -0.25) than in 2003-2005 (10.5±1.1 g per deciliter vs. 10.6±1.5 g per deciliter; difference, -0.12 g per deciliter; 95% CI, -0.67 to 0.43), as was the reduction in birth weight (2863±440 g in women with past or chronic infections vs. 3070±482 g in uninfected women in 2010-2012; mean difference, -164.5 g; 95% CI, -289.7 to -39.4; and 2994±487 g vs. 3117±455 g in 2003-2005; difference, -44.8 g; 95% CI, -139.1 to 49.5). CONCLUSIONS: Antimalarial antibodies were reduced and the adverse consequences of P. falciparum infections were increased in pregnant women after 5 years of a decline in the prevalence of malaria. (Funded by Malaria Eradication Scientific Alliance and others.).

Invasive Salmonella Infections Among Children From Rural Mozambique, 2001-2014.

BACKGROUND: Invasive nontyphoidal Salmonella (iNTS) has emerged as a cause of bacteremia in African children and HIV-infected adults, which is associated with high mortality. Epidemiological data and burden of iNTS infections in resource-constrained settings are needed to better define preventive and curative strategies. METHODS: Blood and, if appropriate, cerebrospinal fluid, were collected from children <15 years of age with fever or severe disease admitted to the Manhiça District Hospital and cultured for NTS; isolates were then characterized. RESULTS: From January 2001 to December 2014, 41,668 of the 51,878 admitted children had a blood culture performed. Invasive NTS was isolated from 670 (1.6%) specimens collected from 41,668 patients; 69 (10.3% died). Salmonella enterica subspecies enterica serovar Typhi or Salmonella enterica subspecies enterica serovar Paratyphi A or C were only isolated in 14 (0.03%) patients. A total of 460 of 620 (74.2%) NTS isolates serotyped were Salmonella enterica subspecies enterica serovar Typhimurium (45% [116/258] of which were multilocus sequence type 313). The incidence of iNTS was 61.8 (95% confidence interval, 55.4-68.9) cases per 100,000 child-years, being highest among infants (217.7 cases/100,000 child-years). The incidence of iNTS declined significantly (P < .0001) over time, but the case fatality ratio remained constant at approximately 10%. Antimicrobial resistance of iNTS against most available antimicrobials has steadily increased, with a predominance of multidrug-resistant strains. CONCLUSIONS: The decreasing but still high incidence of iNTS, its high associated case fatality ratio, and the common detection of multidrug-resistant strains call for a need to improve treatment and prevention strategies for iNTS.

Pathological Methods Applied to the Investigation of Causes of Death in Developing Countries: Minimally Invasive Autopsy Approach.

BACKGROUND AND AIMS: Complete diagnostic autopsies (CDA) remain the gold standard in the determination of cause of death (CoD). However, performing CDAs in developing countries is challenging due to limited facilities and human resources, and poor acceptability. We aimed to develop and test a simplified minimally invasive autopsy (MIA) procedure involving organ-directed sampling with microbiology and pathology analyses implementable by trained technicians in low- income settings. METHODS: A standardized scheme for the MIA has been developed and tested in a series of 30 autopsies performed at the Maputo Central Hospital, Mozambique. The procedure involves the collection of 20 mL of blood and cerebrospinal fluid (CSF) and puncture of liver, lungs, heart, spleen, kidneys, bone marrow and brain in all cases plus uterus in women of childbearing age, using biopsy needles. RESULTS: The sampling success ranged from 67% for the kidney to 100% for blood, CSF, lung, liver and brain. The amount of tissue obtained in the procedure varied from less than 10 mm2 for the lung, spleen and kidney, to over 35 mm2 for the liver and brain. A CoD was identified in the histological and/or the microbiological analysis in 83% of the MIAs. CONCLUSIONS: A simplified MIA technique allows obtaining adequate material from body fluids and major organs leading to accurate diagnoses. This procedure could improve the determination of CoD in developing countries.

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

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.