Decomposition of socioeconomic inequalities in the uptake of intermittent preventive treatment of malaria in pregnancy in Nigeria: evidence from Demographic Health Survey.

BACKGROUND: Although malaria in pregnancy is preventable with the use of intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP), it still causes maternal morbidity and mortality, in sub-Saharan Africa and Nigeria in particular. Socioeconomic inequality leads to limited uptake of IPTp-SP by pregnant women and is, therefore, a public health challenge in Nigeria. This study aimed to measure and identify factors explaining socioeconomic inequality in the uptake of IPTp-SP in Nigeria. METHODS: The study re-analysed dataset of 12,294 women aged 15-49 years from 2018 Nigeria Demographic Health Survey (DHS). The normalized concentration index (Cn) and concentration curve were used to quantify and graphically present socioeconomic inequalities in the uptake of IPTp-SP among pregnant women in Nigeria. The Cn was decomposed to identify key factors contributing to the observed socioeconomic inequality in the uptake of adequate (≥ 3) IPTp-SP. RESULTS: The study showed a higher concentration of the adequate uptake of IPTp-SP among socioeconomically advantaged women (Cn = 0.062; 95% confidence interval [CI] 0.048 to 0.076) in Nigeria. There is a pro-rich inequality in the uptake of IPTp-SP in urban areas (Cn = 0.283; 95%CI 0.279 to 0.288). In contrast, a pro-poor inequality in the uptake of IPTp-SP was observed in rural areas (Cn = - 0.238; 95%CI - 0.242 to - 0.235). The result of the decomposition analysis indicated that geographic zone of residence and antenatal visits were the two main drivers for the concentration of the uptake of IPTp-SP among wealthier pregnant women in Nigeria. CONCLUSION: The pro-rich inequalities in the uptake of IPTp-SP among pregnant women in Nigeria, particularly in urban areas, warrant further attention. Strategies to improve the uptake of IPTp-SP among women residing in socioeconomically disadvantaged geographic zones (North-East and North-West) and improving antenatal visits among the poor women may reduce pro-rich inequality in the uptake of IPTp-SP among pregnant women in Nigeria.

Effectiveness of seasonal malaria chemoprevention at scale in west and central Africa: an observational study.

BACKGROUND: Seasonal malaria chemoprevention (SMC) aims to prevent malaria in children during the high malaria transmission season. The Achieving Catalytic Expansion of SMC in the Sahel (ACCESS-SMC) project sought to remove barriers to the scale-up of SMC in seven countries in 2015 and 2016. We evaluated the project, including coverage, effectiveness of the intervention, safety, feasibility, drug resistance, and cost-effectiveness. METHODS: For this observational study, we collected data on the delivery, effectiveness, safety, influence on drug resistance, costs of delivery, impact on malaria incidence and mortality, and cost-effectiveness of SMC, during its administration for 4 months each year (2015 and 2016) to children younger than 5 years, in Burkina Faso, Chad, The Gambia, Guinea, Mali, Niger, and Nigeria. SMC was administered monthly by community health workers who visited door-to-door. Drug administration was monitored via tally sheets and via household cluster-sample coverage surveys. Pharmacovigilance was based on targeted spontaneous reporting and monitoring systems were strengthened. Molecular markers of resistance to sulfadoxine-pyrimethamine and amodiaquine in the general population before and 2 years after SMC introduction was assessed from community surveys. Effectiveness of monthly SMC treatments was measured in case-control studies that compared receipt of SMC between patients with confirmed malaria and neighbourhood-matched community controls eligible to receive SMC. Impact on incidence and mortality was assessed from confirmed outpatient cases, hospital admissions, and deaths associated with malaria, as reported in national health management information systems in Burkina Faso and The Gambia, and from data from selected outpatient facilities (all countries). Provider costs of SMC were estimated from financial costs, costs of health-care staff time, and volunteer opportunity costs, and cost-effectiveness ratios were calculated as the total cost of SMC in each country divided by the predicted number of cases averted. FINDINGS: 12 467 933 monthly SMC treatments were administered in 2015 to a target population of 3 650 455 children, and 25 117 480 were administered in 2016 to a target population of 7 551 491. In 2015, among eligible children, mean coverage per month was 76·4% (95% CI 74·0-78·8), and 54·5% children (95% CI 50·4-58·7) received all four treatments. Similar coverage was achieved in 2016 (74·8% [72·2-77·3] treated per month and 53·0% [48·5-57·4] treated four times). In 779 individual case safety reports over 2015-16, 36 serious adverse drug reactions were reported (one child with rash, two with fever, 31 with gastrointestinal disorders, one with extrapyramidal syndrome, and one with Quincke's oedema). No cases of severe skin reactions (Stevens-Johnson or Lyell syndrome) were reported. SMC treatment was associated with a protective effectiveness of 88·2% (95% CI 78·7-93·4) over 28 days in case-control studies (2185 cases of confirmed malaria and 4370 controls). In Burkina Faso and The Gambia, implementation of SMC was associated with reductions in the number of malaria deaths in hospital during the high transmission period, of 42·4% (95% CI 5·9 to 64·7) in Burkina Faso and 56·6% (28·9 to 73·5) in The Gambia. Over 2015-16, the estimated reduction in confirmed malaria cases at outpatient clinics during the high transmission period in the seven countries ranged from 25·5% (95% CI 6·1 to 40·9) in Nigeria to 55·2% (42·0 to 65·3) in The Gambia. Molecular markers of resistance occurred at low frequencies. In individuals aged 10-30 years without SMC, the combined mutations associated with resistance to amodiaquine (pfcrt CVIET haplotype and pfmdr1 mutations [86Tyr and 184Tyr]) had a prevalence of 0·7% (95% CI 0·4-1·2) in 2016 and 0·4% (0·1-0·8) in 2018 (prevalence ratio 0·5 [95% CI 0·2-1·2]), and the quintuple mutation associated with resistance to sulfadoxine-pyrimethamine (triple mutation in pfdhfr and pfdhps mutations [437Gly and 540Glu]) had a prevalence of 0·2% (0·1-0·5) in 2016 and 1·0% (0·6-1·6) in 2018 (prevalence ratio 4·8 [1·7-13·7]). The weighted average economic cost of administering four monthly SMC treatments was US$3·63 per child. INTERPRETATION: SMC at scale was effective in preventing morbidity and mortality from malaria. Serious adverse reactions were rarely reported. Coverage varied, with some areas consistently achieving high levels via door-to-door campaigns. Markers of resistance to sulfadoxine-pyrimethamine and amodiaquine remained uncommon, but with some selection for resistance to sulfadoxine-pyrimethamine, and the situation needs to be carefully monitored. These findings should support efforts to ensure high levels of SMC coverage in west and central Africa. FUNDING: Unitaid.

Access to and use of preventive intermittent treatment for Malaria during pregnancy: A qualitative study in the Chókwè district, Southern Mozambique.

BACKGROUND: Malaria remains a significant health problem in Mozambique, particularly in the case of pregnant women and children less than five years old. Intermittent preventive treatment with sulfadoxine-pyrimethamine (IPT-SP) is recommended for preventing malaria in pregnancy (MiP). Despite the widespread use and cost-effectiveness of IPTp-SP, coverage remains low. In this study, we explored factors limiting access to and use of IPTp-SP in a rural part of Mozambique. METHODS AND FINDINGS: We performed a qualitative study using semi-structured interviews to collect data from 46 pregnant women and four health workers in Chókwè, a rural area of southern Mozambique. Data were transcribed, translated where appropriate, manually coded, and the content analyzed according to key themes. The women interviewed were not aware of the risks of MiP or the benefits of its prevention. Delays in accessing antenatal care, irregular attendance of visits, and insufficient time for proper antenatal care counselling by health workers were driving factors for inadequate IPTp delivery. CONCLUSIONS: Pregnant women face substantial barriers in terms of optimal IPTp-SP uptake. Health system barriers and poor awareness of the risks and consequences of MiP and of the measures available for its prevention were identified as the main factors influencing access to and use of IPTp-SP. Implementation of MiP prevention strategies must be improved through intensive community health education and increased access to other sources of information. Better communication between health workers and ANC clients and better knowledge of national ANC and IPTp policies are important.

Scaling-up the use of sulfadoxine-pyrimethamine for the preventive treatment of malaria in pregnancy: results and lessons on scalability, costs and programme impact from three local government areas in Sokoto State, Nigeria.

BACKGROUND: Intermittent preventive treatment of malaria in pregnancy with 3+ doses of sulfadoxine-pyrimethamine (IPTp-SP) reduces maternal mortality and stillbirths in malaria endemic areas. Between December 2014 and December 2015, a project to scale up IPTp-SP to all pregnant women was implemented in three local government areas (LGA) of Sokoto State, Nigeria. The intervention included community education and mobilization, household distribution of SP, and community health information systems that reminded mothers of upcoming SP doses. Health facility IPTp-SP distribution continued in three intervention (population 661,606) and one counterfactual (population 167,971) LGAs. During the project lifespan, 31,493 pregnant women were eligible for at least one dose of IPTp-SP. METHODS: Community and facility data on IPTp-SP distribution were collected in all four LGAs. Data from a subset of 9427 pregnant women, who were followed through 42 days postpartum, were analysed to assess associations between SP dosages and newborn status. Nominal cost and expense data in 2015 Nigerian Naira were obtained from expenditure records on the distribution of SP. RESULTS: Eighty-two percent (n = 25,841) of eligible women received one or more doses of IPTp-SP. The SP1 coverage was 95% in the intervention LGAs; 26% in the counterfactual. Measurable SP3+ coverage was 45% in the intervention and 0% in the counterfactual LGAs. The mean number of SP doses in the intervention LGAs was 2.1; 0.4 in the counterfactual. Increased doses of IPTp-SP were associated with linear increases in newborn head circumference and lower odds of stillbirth. Any antenatal care utilization predicted larger newborn head circumference and lower odds of stillbirth. The cost of delivering three doses of SP, inclusive of the cost of medicines, was US$0.93-$1.20. CONCLUSIONS: It is feasible, safe, and affordable to scale up the delivery of high impact IPTp-SP interventions in low resource malaria endemic settings, where few women access facility-based maternal health services. ClinicalTrials.gov Identifier NCT02758353. Registered 29 April 2016, retrospectively registered.

Assessment of the usage and effectiveness of intermittent preventive treatment and insecticide-treated nets on the indicators of malaria among pregnant women attending antenatal care in the Buea Health District, Cameroon.

BACKGROUND: Malaria in pregnancy is an immense public health problem with at least 50 million pregnant women living in malaria endemic areas. To prevent malaria and its complications in pregnancy the World Health Organization recommends the use of intermittent preventive treatment sulfadoxine-pyrimethamine (IPTp-SP), the use of insecticide-treated nets (ITNs), and effective case management. In most malaria endemic countries in Africa, 40% of pregnant women sleep under ITNs. In Cameroon, about 90% of pregnant women receive the first dose of SP, while 64% take the complete dose. Following the 2011 mass-campaign of free distribution of ITNs coupled with routine ANC distribution of ITN and adoption of IPTp in Cameroon, little has been done to assess the effectiveness of both interventions outside of Yaoundé, the capital city. This study sought to assess the usage and effectiveness of IPTp-SP and ITNs on malaria in pregnancy. METHODS: The research was a cross-sectional hospital-based study that included 410 pregnant women attending antenatal clinics in the Buea Health District. Capillary blood samples were collected to check malaria parasite by microscopy and haemoglobin levels by microhaematocrit technique. RESULTS: A prevalence of 13.4 and 41.7% was detected for malaria and anaemia, respectively. The Overall coverage of ITN was 32.4% while that of ITPp was 63.2%. Malaria prevalence was least (7.2%) amongst women using both IPTp-SP and ITN while those with no intervention had the highest malaria prevalence of 18.6% (χ2 = 6.188; P = 0.103). Of the women with malaria, 12.73% were using ITN and had taken at least one dose of SP, 38.18% had taken at least one dose IPTp only, 10.91% were using only ITN and 38.18% were not using any preventive measure. There was a difference in anaemia status within the different intervention groups (χ2 = 8.673; P = 0.034). Pregnant women using both interventions were less associated to malaria (OR = 0.341, 95% CI = 0.138-0.841) compared to those using only one control method. CONCLUSION: Repeated doses of SP in combination with ITN use are effective in reducing malaria parasitaemia and improving haemoglobin level of pregnant women.

Cost-effectiveness of two versus three or more doses of intermittent preventive treatment for malaria during pregnancy in sub-Saharan Africa: a modelling study of meta-analysis and cost data.

BACKGROUND: In 2012, WHO changed its recommendation for intermittent preventive treatment of malaria during pregnancy (IPTp) from two doses to monthly doses of sulfadoxine-pyrimethamine during the second and third trimesters, but noted the importance of a cost-effectiveness analysis to lend support to the decision of policy makers. We therefore estimated the incremental cost-effectiveness of IPTp with three or more (IPTp-SP3+) versus two doses of sulfadoxine-pyrimethamine (IPTp-SP2). METHODS: For this analysis, we used data from a 2013 meta-analysis of seven studies in sub-Saharan Africa. We developed a decision tree model with a lifetime horizon. We analysed the base case from a societal perspective. We did deterministic and probabilistic sensitivity analyses with appropriate parameter ranges and distributions for settings with low, moderate, and high background risk of low birthweight, and did a separate analysis for HIV-negative women. Parameters in the model were obtained for all countries included in the original meta-analysis. We did simulations in hypothetical cohorts of 1000 pregnant women receiving either IPTp-SP3+ or IPTp-SP2. We calculated disability-adjusted life-years (DALYs) for low birthweight, severe to moderate anaemia, and clinical malaria. We calculated cost estimates from data obtained in observational studies, exit surveys, and from public procurement databases. We give financial and economic costs in constant 2012 US$. The main outcome measure was the incremental cost per DALY averted. FINDINGS: The delivery of IPTp-SP3+ to 1000 pregnant women averted 113·4 DALYs at an incremental cost of $825·67 producing an incremental cost-effectiveness ratio (ICER) of $7·28 per DALY averted. The results remained robust in the deterministic sensitivity analysis. In the probabilistic sensitivity analyses, the ICER was $7·7 per DALY averted for moderate risk of low birthweight, $19·4 per DALY averted for low risk, and $4·0 per DALY averted for high risk. The ICER for HIV-negative women was $6·2 per DALY averted. INTERPRETATION: Our findings lend strong support to the WHO guidelines that recommend a monthly dose of IPTp-SP from the second trimester onwards. FUNDING: Malaria in Pregnancy Consortium and the Bill & Melinda Gates Foundation.

Moving malaria in pregnancy programs from neglect to priority: experience from Malawi, Senegal, and Zambia.

BACKGROUND: Pregnant women and infants are particularly vulnerable to malaria. National malaria in pregnancy (MIP) programs in Malawi, Senegal, and Zambia were reviewed to identify promising strategies that have helped these countries achieve relatively high coverage of MIP interventions as well as ongoing challenges that have inhibited further progress. METHODS: We used a systematic case study methodology to assess health system strengths and challenges in the 3 countries, including desk reviews of available reports and literature and key informant interviews with national stakeholders. Data were collected between 2009 and 2011 and analyzed across 8 MIP health systems components: (1) integration of programs and services, (2) policy, (3) commodities, (4) quality assurance, (5) capacity building, (6) community involvement, (7) monitoring and evaluation, and (8) financing. Within each program area, we ranked degree of scale up across 4 stages and synthesized the findings in a MIP table of analysis to reveal common themes related to better practices, remaining bottlenecks, and opportunities to accelerate MIP coverage, strengthen MIP programs, and improve results. FINDINGS: Each of the 3 countries has malaria policies in place that reflect current MIP guidance from the World Health Organization. The 3 countries successfully integrated MIP interventions into a platform of antenatal care services, but coordination at the national level was disjointed. All 3 countries recognized the importance of having a MIP focal person to ensure collaboration and planning at the national level, but only Malawi had appointed one. Commodity stockouts were frequent due to problems at all levels of the logistics system, from quantification to distribution. Lack of support for quality assurance and weak monitoring and evaluation mechanisms across all 3 countries affected optimal coverage. CONCLUSIONS: MIP programs should address all 8 interconnected MIP health systems areas holistically, in the context of a health systems approach to building successful programs. The MIP table of analysis can be a useful tool for other malaria-endemic countries to review their programs and improve MIP outcomes.

Systemic constraints continue to limit coverage of intermittent preventive treatment for malaria in pregnancy in southeast Tanzania.

BACKGROUND: Factors limiting coverage of intermittent preventive treatment for malaria in pregnancy (IPTp) in Tanzania were explored from the perspective of health workers, in order to make recommendations to improve service delivery. Recent data estimates coverage of the recommended two doses of IPTp at 26.3%, far short of the national target of 80%. METHODS: Semistructured interviews were conducted with 13 health workers and 2 health managers during June 2011 in Ikwiriri, southeast Tanzania. RESULTS: Delivery of sulfadoxine-pyrimethamine (SP) was severely constrained by drug shortages and widespread stock-outs, indicative of ongoing difficulties in the wider health system. While SP was well known and attitudes towards IPTp were positive, health workers were often not informed of up-to-date dosing schedules, limiting coverage. Recent literature suggests this could be due to inconsistent and conflicting national guidelines. In addition, it was found that two pills, instead of the recommended three pills, per dose of IPTp were frequently given to pregnant women, a finding previously unreported. CONCLUSION: To maximize IPTp coverage, sufficient and consistent supplies of SP to both public and private health facilities are a necessity, combined with effective communication of revised dosing schedules. Further research is warranted to investigate the aberrant administration of two pills per dose, as it may exacerbate drug resistance.

Malaria Policy Advisory Committee to the WHO: conclusions and recommendations of September 2012 meeting.

The Malaria Policy Advisory Committee to the World Health Organization met in Geneva, Switzerland from 11 to 13 September, 2012. This article provides a summary of the discussions, conclusions and recommendations from that meeting.Meeting sessions included: updated policy recommendations on the use of sulphadoxine-pyrimethamine for Intermittent Preventive Treatment of malaria in pregnancy, as well as the use of single dose primaquine as a Plasmodium falciparum gametocytocide; the need to develop a Global Technical Strategy for Malaria Control and Elimination 2016- 2025 and a global strategy for control of Plasmodium vivax; the Affordable Medicines Facility for malaria independent evaluation and promoting malaria case management in the private sector; updates from the Technical Expert Group on drug resistance and containment and the Evidence Review Group on malaria burden estimation; update on the RTS,S/AS01 malaria vaccine; progress on the policy setting process for malaria vector control; and the process for updating the WHO Guidelines for the Treatment of Malaria.Policy statements, position statements, and guidelines that arise from the MPAC meeting conclusions and recommendations will be formally issued and disseminated to World Health Organization Member States by the World Health Organization Global Malaria Programme.

Pharmacokinetic properties and bioequivalence of two sulfadoxine/pyrimethamine fixed-dose combination tablets: a parallel-design study in healthy Chinese male volunteers.

BACKGROUND: Sulfadoxine/pyrimethamine fixed-dose combination (FDC) tablet is the long-acting portion of the antimalaria product Artecospe(®), coblister containing artesunate tablets plus sulfadoxine/pyrimethamine FDC tablets. This study was conducted to support the efficacy and tolerability of the sulfadoxine/pyrimethamine FDC tablet in the World Health Organization's (WHO) Prequalification of Medicines Programme, as well as to obtain marketing authorization in China. OBJECTIVE: The aim of the present study was to compare the pharmacokinetic profiles between a new generic and the branded reference formulation of sulfadoxine/pyrimethamine FDC tablets, and to assess the bioequivalence of the 2 products in healthy Chinese volunteers. METHODS: This single-dose, open-label, randomized, parallel-group study was conducted in healthy Chinese male volunteers who were randomly assigned (1:1) to receive a single 1500/75-mg dose (3 × 500/25-mg tablets) of either the test or reference formulation after a 12-hour overnight fast. Seventeen blood samples were obtained over a 168-hour interval, and plasma concentrations of sulfadoxine and pyrimethamine were determined by 2 separate validated liquid chromatography-isotopic dilution mass spectrometry methods. Pharmacokinetic properties (C(max), AUC(0-72), AUC(0-168), and T(max)) were calculated and analyzed statistically. The 2 formulations were to be considered bioequivalent if 90% CIs for the log-transformed ratios of C(max) and AUC(0-72) were within the predetermined bioequivalence range of 80% to 125%, in accordance with the guidelines of WHO and China's Food and Drug Administration (FDA). Tolerability was evaluated throughout the study by vital signs, physical examinations, clinical laboratory tests, 12-lead ECGs, and subject interviews on adverse events (AEs). RESULTS: Forty-six healthy subjects completed the study. The mean values of sulfadoxine C(max) (183.07 and 165.15 mg/L), AUC(0-72) (11,036.52 and 10,536.78 mg/L/h), and AUC(0-168) (22,247.05 and 21,761.02 mg/L/h) were not significantly different between the test and reference formulations, respectively. The same was true for pyrimethamine (0.55 and 0.58 mg/L, 29.85 and 31.44 mg/L/h, and 56.18 and 59.27 mg/L/h, respectively). The 90% CIs for the log-transformed ratios of C(max), AUC(0-72), and AUC(0-168) of both sulfadoxine (105.4%-116.6%, 99.3%-110.6%, and 96.4%-108.1%) and pyrimethamine (88.8%-100.9%, 89.5%-101.0%, and 88.3%-101.6%) were within the acceptance limits for bioequivalence. A total of 7 mild AEs were reported in 7 subjects (15.2%). CONCLUSIONS: The findings from this single-dose (1500/75-mg) study suggest that the test and reference formulations of sulfadoxine/pyrimethamine FDC 500/25-mg tablet have similar pharmacokinetic profiles both in terms of rate and extent of absorption. The formulations met WHO's and China's FDA regulatory criteria for bioequivalence in these healthy Chinese volunteers under fasting conditions. Both formulations were generally well-tolerated.

[Evaluation of the use of insecticide-treated nets and intermittent preventive treatment in three health zones in Benin]. / Évaluation de l'utilisation des moustiquaires imprégnées d'insecticide et du traitement préventif intermittent dans trois zones sanitaires au Bénin.

This study aims to evaluate the results of the Project to Support the Fight against Malaria in the departments of Mono and Couffo in Benin on insecticide-treated nets (ITNs) use by children under 5 years and pregnant women and the coverage by Intermittent Preventive Treatment (IPT) with Sulfadoxin-Pyrimethamin (SP). This assessment is made from two household surveys. The first at the start up and the second after fifteen months of implementation. The availability of ITN in households and their use by pregnant women and children under 5 years have increased respectively from 8, 5 and 4% in 2005 to 24, 31 and 16 % in 2006. The percentage of pregnant women under IPT with sulfadoxine-pyrimethamine (SP) is 10% while 21% of pregnant women received at least one dose of SP. The availability of ITN in households and their use by children under 5 years and the prevention of malaria during pregnancy remains a concern in these health areas. The promotion of long lasting insecticide treated nets with effective communication strategies for behavior change could improve the results. Research on causes of poor compliance of IPT should be emphasized as well as strengthening management of drugs in health centers.

The cost-effectiveness of intermittent preventive treatment for malaria in infants in Sub-Saharan Africa.

BACKGROUND: Intermittent preventive treatment in infants (IPTi) has been shown to decrease clinical malaria by approximately 30% in the first year of life and is a promising malaria control strategy for Sub-Saharan Africa which can be delivered alongside the Expanded Programme on Immunisation (EPI). To date, there have been limited data on the cost-effectiveness of this strategy using sulfadoxine pyrimethamine (SP) and no published data on cost-effectiveness using other antimalarials. METHODS: We analysed data from 5 countries in sub-Saharan Africa using a total of 5 different IPTi drug regimens; SP, mefloquine (MQ), 3 days of chlorproguanil-dapsone (CD), SP plus 3 days of artesunate (SP-AS3) and 3 days of amodiaquine-artesunate (AQ3-AS3).The cost per malaria episode averted and cost per Disability-Adjusted Life-Year (DALY) averted were modeled using both trial specific protective efficacy (PE) for all IPTi drugs and a pooled PE for IPTi with SP, malaria incidence, an estimated malaria case fatality rate of 1.57%, IPTi delivery costs and country specific provider and household malaria treatment costs. FINDINGS: In sites where IPTi had a significant effect on reducing malaria, the cost per episode averted for IPTi-SP was very low, USD 1.36-4.03 based on trial specific data and USD 0.68-2.27 based on the pooled analysis. For IPTi using alternative antimalarials, the lowest cost per case averted was for AQ3-AS3 in western Kenya (USD 4.62) and the highest was for MQ in Korowge, Tanzania (USD 18.56). Where efficacious, based only on intervention costs, IPTi was shown to be cost effective in all the sites and highly cost-effective in all but one of the sites, ranging from USD 2.90 (Ifakara, Tanzania with SP) to USD 39.63 (Korogwe, Tanzania with MQ) per DALY averted. In addition, IPTi reduced health system costs and showed significant savings to households from malaria cases averted. A threshold analysis showed that there is room for the IPTi-efficacy to fall and still remain highly cost effective in all sites where IPTi had a statistically significant effect on clinical malaria. CONCLUSIONS: IPTi delivered alongside the EPI is a highly cost effective intervention against clinical malaria with a range of drugs in a range of malaria transmission settings. Where IPTi did not have a statistically significant impact on malaria, generally in low transmission sites, it was not cost effective.

Individual, facility and policy level influences on national coverage estimates for intermittent preventive treatment of malaria in pregnancy in Tanzania.

BACKGROUND: Delivery of two doses of intermittent preventive treatment of malaria during pregnancy (IPTp) is a key strategy to reduce the burden of malaria in pregnancy in sub-Saharan Africa. However, different settings have reported coverage levels well below the target 80%. Antenatal implementation guidelines in Tanzania recommend IPTp first dose to be given at the second antenatal visit, and second dose at the third visit. This investigation measured coverage of IPTp at national level in Tanzania and examined the role of individual, facility, and policy level influences on achieved coverage. METHODS: Three national household and linked reproductive and child health (RCH) facility surveys were conducted July-August 2005, 2006, and 2007 in 210 clusters sampled using two-stage cluster sampling from 21 randomly selected districts. Female residents who reported a livebirth in the previous year were asked questions about malaria prevention during that pregnancy and individual characteristics including education, pregnancy history, and marital status. The RCH facility serving each cluster was also surveyed, and information collected about drug stocks, health education delivery, and the timing of antenatal care delivery by clinic users. RESULTS: The national IPTp coverage had declined over the survey period being 71% for first dose in 2005 falling to 65% in 2007 (chi2 2.9, p = 0.05), and 38% for second dose in 2005 but 30% in 2007 (chi2 4.4, p = 0.01). There was no evidence of any individual factors being associated with second dose coverage beyond living in an urban area. Availability of sulphadoxine-pyrimethamine at RCH had decreased year on year from 85% of clinics in stock in 2005 to 60% in 2007 (chi2 20.6, p < 0.001). This reduction was evident in rural but not urban clinics. If safety recommendations and national antenatal care guidelines for IPTp delivery were followed, in 2007 only 76% of pregnant women could have received IPTp first dose and only 46% could have received second dose. CONCLUSION: There is scope to improve IPTp first and second dose coverage at national scale within existing systems by improving stock at RCH, and by revising the existing guidelines to recommend delivery of IPTp after quickening, rather than at a pre-defined antenatal visit.

Adherence and effectiveness of drug combination in curative treatment among children suffering uncomplicated malaria in rural Senegal.

Increased Plasmodium falciparum resistance to chloroquine has prompted national malaria programs to develop new policies in several African countries. Less than a year after the introduction of amodiaquine/sulfadoxine-pyrimethamine (AQ/SP) as first-line treatment in Senegal, we examined adherence rates to therapy and its efficacy among children. The study was conducted in five dispensaries in rural Senegal. Children aged 2-10 years with a presumptive diagnosis of malaria were prescribed AQ/SP. Thick blood film analyses were carried out on days 0, 3, 7, 14 and 28. Blood and urine samples were collected on day 3 for drug level measurements. The principal caregivers were questioned on treatment adherence. Among the 289 recruited children, 144 had a parasitemia >2500/microl. The results demonstrated markedly good efficacy for the treatment, as no detectable parasitemia was observed on day 28 for 97.9% of the children. However, we noticed that 35.3% of children did not comply with the recommended doses and 62.3% did not exactly adhere to the drug schedule. Despite the good efficacy of the drugs, adherence to the therapeutic scheme was poor. Strategies to promote patient adherence would improve drug performance and thus might help to prevent the rapid emergence of drug resistance.

Intermittent preventive treatment of malaria in pregnancy: the incremental cost-effectiveness of a new delivery system in Uganda.

The main objective of this study was to assess whether traditional birth attendants, drug-shop vendors, community reproductive health workers and adolescent peer mobilisers could administer intermittent preventive treatment (IPTp) with sulfadoxine-pyrimethamine (SP) to pregnant women. The study was implemented in 21 community clusters (intervention) and four clusters where health centres provided routine IPTp (control). The primary outcome measures were the proportion of women who completed two doses of SP; the effect on anaemia, parasitaemia and low birth weight; and the incremental cost-effectiveness of the intervention. The study enrolled 2785 pregnant women. The majority, 1404/2081 (67.5%) receiving community-based care, received SP early and adhered to the two recommended doses compared with 281/704 (39.9%) at health centres (P<0.001). In addition, women receiving community-based care had fewer episodes of anaemia or severe anaemia and fewer low birth weight babies. The cost per woman receiving the full course of IPTp was, however, higher when delivered via community care at US$2.60 compared with US$2.30 at health centres, due to the additional training costs. The incremental cost-effectiveness ratio of the community delivery system was Uganda shillings 1869 (US$1.10) per lost disability-adjusted life-year (DALY) averted. In conclusion, community-based delivery increased access and adherence to IPTp and was cost-effective.

Assessment of the therapeutic efficacy of chloroquine in the treatment of uncomplicated Plasmodium falciparum malaria in a tribal block of the Kalahandi district of Orissa, India.

The study on therapeutic efficacy of chloroquine was carried out in a tribal dominated block of Kalahandi district of Orissa, India. It revealed 94% treatment failure with standard dose of chloroquine in the treatment of uncomplicated P. falciparum malaria cases. The study warrants the change to alternate antimalarials in this region.

Effect of a community-based delivery of intermittent preventive treatment of malaria in pregnancy on treatment seeking for malaria at health units in Uganda.

BACKGROUND: The impact of intermittent preventive treatment (IPTp) on malaria in pregnancy is well known. However, in countries where this policy is implemented, poor access and low compliance have been widely reported. Novel approaches are needed to deliver this intervention. OBJECTIVE: To assess whether traditional birth attendants, drug-shop vendors, community reproductive health workers and adolescent peer mobilizers can administer IPTp with sulphadoxine-pyrimethamine (SP) to pregnant women, reach those at greatest risk of malaria, and increase access and compliance with IPTp. STUDY DESIGN: An intervention study compared the delivery of IPTp in the community with routine delivery of IPTp at health units. The primary outcome measures were the proportion of adolescents and primigravidae accessed, and the proportion of women who received two doses of SP. The study also assessed the effect of the intervention on access to malaria treatment, antenatal care, other services and related costs. RESULTS: More women (67.5%) received two doses of SP through the community approach compared with health units (39.9%; P<0.0001). Women who accessed IPTp in the community were at an earlier stage of pregnancy (21.0 weeks of gestation) than women who accessed IPTp at health units (23.1 weeks of gestation; P<0.0001). However, health units were visited by a higher proportion of primigravidae (23.6% vs 20.0%; P<0.04) and adolescents (28.4% vs 25.0%; P<0.03). Generally, women who accessed IPTp at health units made more visits for malaria treatment (2.6 (1.0-4.7) vs 1.8 (1.4-2.2); P<0.03). At recruitment, more women who accessed IPTp at health units sought malaria treatment compared with those who accessed IPTp in the community (56.9% vs 49.2%). However, at delivery, a high proportion of women who accessed IPTp in the community had sought malaria treatment (70.3%), suggesting the possibility that the novel approach had a positive impact on care seeking for malaria. Similarly, utilization of antenatal care, insecticide-treated nets and delivery care by women in the community was high. The total costs per woman receiving two doses of SP for IPTp were 4093 Uganda shillings (US$ 2.3) for women who accessed IPTp at health units, and 4491 Uganda shillings (US$ 2.6) for women who accessed IPTp in the community. CONCLUSION: The community approach was effective for the delivery of IPTp, although women still accessed and benefited from malaria treatment and other services at health units. However, the costs for accessing malaria treatment and other services are high and could be a limiting factor in mitigating the burden of malaria in Uganda.