The promise and potential challenges of intermittent preventive treatment for malaria in infants (IPTi)

Division of Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA.
Malaria Journal (Impact Factor: 3.11). 02/2005; 4(1):33. DOI: 10.1186/1475-2875-4-33
Source: PubMed


Intermittent preventive treatment (IPT) administers a full therapeutic course of an anti-malarial drug at predetermined intervals, regardless of infection or disease status. It is recommended by the World Health Organization (WHO) for protecting pregnant women from the adverse effects of malaria (IPTp) and shows great potential as a strategy for reducing illness from malaria during infancy (IPTi). Administered concurrently with standard immunizations, IPTi is expected to reduce the frequency of clinical disease, but to allow blood-stage infections to occur between treatments, thus allowing parasite-specific immunity to develop. While wide deployment of IPTi is being considered, it is important to assess other potential effects. Transmission conditions, drug choice and administration schedule will likely affect the possibility of post-treatment rebound in child morbidity and mortality and the increased spread of parasite drug resistance and should be considered when implementing IPTi.

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Available from: Joel Breman, Jun 24, 2015
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    • "While SP may have failed as a treatment drug it is still effective for prophylaxis [22]. Several studies from Ghana, Mozambique and Tanzania have documented its usefulness in prophylaxis and particularly in reducing malaria episodes even in areas where resistance is high [16,22]. "
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    ABSTRACT: Malaria carries high case fatality among children with sickle cell anaemia. In Uganda, chloroquine is used for prophylaxis in these children despite unacceptably high levels of resistance. Intermittent presumptive treatment with sulphadoxine-pyrimethamine (SP) has shown great potential for reducing prevalence of malaria and anaemia among pregnant women and infants. To compare the efficacy of monthly SP presumptive treatment, versus weekly chloroquine for malaria prophylaxis in children attending the Sickle Cell Clinic, Mulago Hospital. Two hundred and forty two children with sickle cell anaemia were randomized to presumptive treatment with SP or weekly chloroquine for malaria prophylaxis. Active detection of malaria was made at each weekly visit to the clinic over one month. The primary outcome measure was the proportion of children with one malaria episode at one month follow-up. The secondary outcome measures included malaria-related admissions and adverse effects of the drugs. Ninety-three percent (114/122) of the children in the chloroquine group and 94% (113/120) in the SP group completed one month follow up. SP reduced prevalence of malaria by 50% compared to chloroquine [OR = 0.50, (95% CI 0.26-0.97)]; p = 0.042. Six percent (7/122) of the children receiving weekly chloroquine had malaria related admissions compared to 2.5% (3/120) on presumptive treatment with SP. No serious drug effects were reported in both treatment groups Presumptive treatment with SP was more efficacious than weekly chloroquine in reducing prevalence of malaria in children with sickle cell anaemia. Continued use of chloroquine for malaria chemoprophylaxis in children with sickle cell anaemia in Uganda does not seem to be justified.
    Malaria Journal 10/2009; 8(1):237. DOI:10.1186/1475-2875-8-237 · 3.11 Impact Factor
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    • "The concept of IPTi is to combine both therapeutic and prophylactic effects of an anti-malaria drug administered in intervals short enough to prevent the onset of disease and long enough to enable the development of protective immunity [7]. However, it is unclear which factors contribute to the effects of IPTi and whether an exceeding impact exists. "
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    ABSTRACT: Intermittent preventive treatment in infants (IPTi) with sulphadoxine-pyrimethamine (SP) reduces the incidence of malaria episodes in young children. The exact mechanism by which the protective effect is mediated needs to be defined. This study aimed to investigate therapeutic, prophylactic, and possible exceeding effects of SP-based IPTi in two clinical trials. Protective efficacies from two IPTi trials performed in Kumasi, Ghana, and Lambaréné, Gabon, were assessed for overlapping time series of 61 days. For six-months periods after each of three IPTi doses a multivariate Poisson regression model with the respective cohort as co-variate was generated and effect modification of protective efficacy with time strata was evaluated by log-likelihood tests. Protective efficacies were not significantly different between the two study cohorts. Study-cohort corrected protective efficacy was highest for the first 61 days after each IPTi application and decreased continuously. For the first 61 days after IPTi-1, IPTi-2, and IPTi-3 the protective efficacy was 71%, 44%, and 43%, respectively. A reduction of the malaria incidence rate was detectable for the first 60, 30 and 40 days after IPTi-1, IPTi-2 and IPTi-3 drug application, respectively. After IPTi-3 a higher risk for malaria could be seen after day 60. This effect was mainly based on the overwhelming influence of the Kumasi cohort. The results suggest that SP-based IPTi mainly works through a therapeutic and prophylactic effect over 30 to 60 days after drug application and that a sustained effect beyond post-treatment prophylaxis might be very low. Data analysis from clinical trials NCT ID # 00206739 (Kumasi Trial) and NCT ID # 00167843 (Lambaréné Trial),
    Malaria Journal 11/2008; 7(1):198. DOI:10.1186/1475-2875-7-198 · 3.11 Impact Factor
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    • "For candidate IPTp combinations there is the added complication that there is still some debate as to how IPTp actually works: repeated short courses of antimalarials may act mainly by intermittent suppressive chemotherapy ('prophylactic effect'); by intermittent treatment of repeated infections ('treatment effect'); or by some combination of these effects[36,55]. Similar issues are also being debated about IPTi [124]. Given the early success of SP-IPTp in high transmission areas, the slow parasite clearance times and long elimination half-lives of each of the component drugs[125], it seems likely that the 'prophylactic effect' is the predominant mode of action, at least in this combination. "
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    ABSTRACT: Falciparum malaria is an important cause of maternal, perinatal and neonatal morbidity in high transmission settings in Sub-Saharan Africa. Intermittent preventive treatment with sulphadoxine-pyrimethamine (SP-IPT) has proven efficacious in reducing the burden of pregnancy-associated malaria but increasing levels of parasite resistance mean that the benefits of national SP-IPT programmes may soon be seriously undermined in much of the region. Hence, there is an urgent need to develop alternative drug regimens for IPT in pregnancy. This paper reviews published safety and efficacy data on various antimalarials and proposes several candidate combination regimens for assessment in phase II/III clinical trials.
    Malaria Journal 02/2007; 6(1):16. DOI:10.1186/1475-2875-6-16 · 3.11 Impact Factor
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