Project description:Intermittent preventive antimalarial treatment in infants (IPTi) is currently evaluated as a malaria control strategy. Among the factors influencing the extent of protection that is provided by IPTi are the transmission intensity, seasonality, drug resistance patterns, and the schedule of IPTi administrations. The aim of this study was to determine how far the protective efficacy of IPTi depends on spatio-temporal variations of the prevailing incidence of malaria.One thousand seventy infants were enrolled in a registered controlled trial on the efficacy of IPTi with sulphadoxine-pyrimethamine (SP) in the Ashanti Region, Ghana, West Africa (ClinicalTrial.gov: NCT00206739). Stratification for the village of residence and the month of birth of study participants demonstrated that the malaria incidence was dependent on spatial (range of incidence rates in different villages 0.6-2.0 episodes/year) and temporal (range of incidence rates in children of different birth months 0.8-1.2 episodes/year) factors. The range of spatio-temporal variation allowed ecological analyses of the correlation between malaria incidence rates, anti-Plasmodium falciparum lysate IgG antibody levels and protective efficacies provided by IPTi.Protective efficacy of the first SP administration was positively correlated with malaria incidences in children living in a distinct village or born in a distinct month (R2 0.48, p < 0.04 and R2 0.63, p < 0.003, respectively). Corresponding trends were seen after the second and third study drug administration. Accordingly, IgG levels against parasite lysate increased with malaria incidence. This correlation was stronger in children who received IPTi, indicating an effect modification of the intervention.The spatial and temporal variations of malaria incidences in a geographically and meteorologically homogeneous study area exemplify the need for close monitoring of local incidence rates in all types of intervention studies. The increase of the protective efficacy of IPTi with malaria incidences may be relevant for IPTi implementation strategies and, possibly, for other malaria control measures.

Project description:BackgroundTrials of intermittent preventive treatment against malaria in infants (IPTi) using sulphadoxine-pyrimethamine (SP) have shown a positive, albeit variable, protective efficacy against clinical malaria episodes. The impact of IPTi in different epidemiological settings and over time is unknown and predictions are hampered by the lack of knowledge about how IPTi works. We investigated mechanisms proposed for the action of IPTi and made predictions of the likely impact on morbidity and mortality.Methods/principal findingsWe used a comprehensive, individual-based, stochastic model of malaria epidemiology to simulate recently published trials of IPTi using SP with site-specific characteristics as inputs. This baseline model was then modified to represent hypotheses concerning the duration of action of SP, the temporal pattern of fevers caused by individual infections, potential benefits of avoiding fevers on immunity and the effect of sub-therapeutic levels of SP on parasite dynamics. The baseline model reproduced the pattern of results reasonably well. None of the models based on alternative hypotheses improved the fit between the model predictions and observed data. Predictions suggest that IPTi would have a beneficial effect across a range of transmission intensities. IPTi was predicted to avert a greater number of episodes where IPTi coverage was higher, the health system treatment coverage lower, and for drugs which were more efficacious and had longer prophylactic periods. The predicted cumulative benefits were proportionately slightly greater for severe malaria episodes and malaria-attributable mortality than for acute episodes in the settings modelled. Modest increased susceptibility was predicted between doses and following the last dose, but these were outweighed by the cumulative benefits. The impact on transmission intensity was negligible.ConclusionsThe pattern of trial results can be accounted for by differences between the trial sites together with known features of malaria epidemiology and the action of SP. Predictions suggest that IPTi would have a beneficial impact across a variety of epidemiological settings.

Project description: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.

Project description:BACKGROUND: Achieving the Millennium Development Goals for health requires a massive scaling-up of interventions in Sub Saharan Africa. Intermittent Preventive Treatment in infants (IPTi) is a promising new tool for malaria control. Although efficacy information is available for many interventions, there is a dearth of data on the resources required for scaling up of health interventions. METHOD: We worked in partnership with the Ministry of Health and Social Welfare (MoHSW) to develop an IPTi strategy that could be implemented and managed by routine health services. We tracked health system and other costs of (1) developing the strategy and (2) maintaining routine implementation of the strategy in five districts in southern Tanzania. Financial costs were extracted and summarized from a costing template and semi-structured interviews were conducted with key informants to record time and resources spent on IPTi activities. RESULTS: The estimated financial cost to start-up and run IPTi in the whole of Tanzania in 2005 was US$1,486,284. Start-up costs of US$36,363 were incurred at the national level, mainly on the development of Behaviour Change Communication (BCC) materials, stakeholders' meetings and other consultations. The annual running cost at national level for intervention management and monitoring and drug purchase was estimated at US$459,096. Start-up costs at the district level were US$7,885 per district, mainly expenditure on training. Annual running costs were US$170 per district, mainly for printing of BCC materials. There was no incremental financial expenditure needed to deliver the intervention in health facilities as supplies were delivered alongside routine vaccinations and available health workers performed the activities without working overtime. The economic cost was estimated at 23 US cents per IPTi dose delivered. CONCLUSION: The costs presented here show the order of magnitude of expenditures needed to initiate and to implement IPTi at national scale in settings with high Expanded Programme on Immunization (EPI) coverage. The IPTi intervention appears to be affordable even within the budget constraints of Ministries of Health of most sub-Saharan African countries.

Project description:BackgroundIntermittent preventive treatment in infants (IPTi) is a new malaria control tool. However, it is uncertain whether IPTi works mainly through chemoprophylaxis or treatment of existing infections. Understanding the mechanism is essential for development of replacements for sulfadoxine-pyrimethamine (SP) where it is no longer effective. This study investigated how protection against malaria given by SP, chlorproguanil-dapsone (CD) and mefloquine (MQ), varied with time since administration of IPTi.Methods and findingsA secondary analysis of data from a randomised, placebo-controlled trial in an area of high antifolate resistance in Tanzania was conducted. IPTi using SP, CD, MQ or placebo was given to 1280 infants at 2, 3 and 9 months of age. Poisson regression with random effects to adjust for potential clustering of malaria episodes within children was used to calculate incidence rate ratios for clinical malaria in defined time strata following IPTi. The short-acting antimalarial CD gave no protection against clinical malaria, whereas long-acting MQ gave two months of substantial protection (protective efficacy (PE) 73.1% (95% CI: 23.9, 90.5) and 73.3% (95% CI: 0, 92.9) in the first and second month respectively). SP gave some protection in the first month after treatment (PE 64.5% (95% CI: 10.6, 85.9)) although it did not reduce the incidence of malaria up to 12 months of age. There was no evidence of either long-term protection or increased risk of malaria for any of the regimens.ConclusionPost-treatment chemoprophylaxis appears to be the main mechanism by which IPTi protects children against malaria. Long-acting antimalarials are therefore likely to be the most effective drugs for IPTi, but as monotherapies could be vulnerable to development of drug resistance. Due to concerns about tolerability, the mefloquine formulation used in this study is not suitable for IPTi. Further investigation of combinations of long-acting antimalarials for IPTi is needed.Trial registrationClinicaltrials.gov NCT00158574.

Project description:BackgroundIntermittent Preventive Treatment of malaria in infants (IPTi) is a malaria control strategy consisting of the administration of an anti-malarial drug alongside routine immunizations. So far, this is being implemented nationwide in Sierra Leone only. IPTi has been renamed as Perennial Malaria Chemoprevention -PMC-, accounting for its recently recommended expansion into the second year of life. Before starting a pilot implementation on PMC, the currently implemented strategy and malaria prevalence were assessed in young children in selected areas of Sierra Leone.MethodsA cross-sectional, community-based, multi-stage cluster household survey was conducted from November to December 2021 in selected districts of the Northern and northwestern provinces of Sierra Leone among 10-23 months old children, whose caretakers gave written informed consent to participate in the survey. Coverage of IPTi and malaria prevalence-assessed with rapid diagnostic tests-were calculated using percentages and 95% confidence intervals weighted for the sampling design and adjusted for non-response within clusters. Factors associated with RDT + and iPTi coverage were also assessed.ResultsA total of 720 children were recruited. Coverage of three IPTi doses was 50.57% (368/707; 95% CI 45.38-55.75), while prevalence of malaria infection was 28.19% (95% CI 24.81-31.84). Most children had received IPTi1 (80.26%, 574/707; 95% CI 75.30-84.44), and IPTi2 (80.09%, 577/707; 95% CI 76.30-83.40) and over half of the children also received IPTi3 (57.72%, 420/707; 95% CI 53.20-62.11). The uptake of each IPTi dose was lower than that of the vaccines administered at the same timepoint at all contacts.ConclusionIn Sierra Leone, half of the children received the three recommended doses of IPTi indicating an increase in its uptake compared to previous data of just a third of children receiving the intervention. However, efforts need to be made in improving IPTi coverage, especially in the planned expansion of the strategy into the second year of life following recent WHO guidelines.

Project description:Malaria in pregnancy (MiP) is associated with increased risks of maternal and foetal complications. The WHO recommends a package of interventions including intermittent preventive treatment (IPT) with sulphadoxine-pyrimethamine (SP), insecticide-treated nets and effective case management. However, with increasing SP resistance, the effectiveness of SP-IPT has been questioned. Intermittent screening and treatment (IST) has recently been shown in Ghana to be as efficacious as SP-IPT. This study investigates two important requirements for effective delivery of IST and SP-IPT: antenatal care (ANC) provider knowledge, and acceptance of the different strategies. Structured interviews with 134 ANC providers at 67 public health facilities in Ashanti Region, Ghana collected information on knowledge of the risks and preventative and curative interventions against MiP. Composite indicators of knowledge of SP-IPT, and case management of MiP were developed. Log binomial regression of predictors of provider knowledge was explored. Qualitative data were collected through in-depth interviews with fourteen ANC providers with some knowledge of IST to gain an indication of the factors influencing acceptance of the IST approach. 88.1% of providers knew all elements of the SP-IPT policy, compared to 20.1% and 41.8% who knew the treatment policy for malaria in the first or second/third trimesters, respectively. Workshop attendance was a univariate predictor of each knowledge indicator. Qualitative findings suggest preference for prevention over cure, and increased workload may be barriers to IST implementation. However, a change in strategy in the face of SP resistance is likely to be supported; health of pregnant women is a strong motivation for ANC provider practice. If IST was to be introduced as part of routine ANC activities, attention would need to be given to improving the knowledge and practices of ANC staff in relation to appropriate treatment of MiP. Health worker support for any MiP intervention delivered through ANC clinics is critical.

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Intermittent preventive treatment for malaria in infants.

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