The effect of falciparum malaria prevalence on the effectiveness of intermittent preventive treatment with Sulfadoxine-Pyrimethamine during pregnancy in reducing low birth weight in southern Mozambique

Malaria infection is a major cause of morbidity and mortality in tropical countries, and particularly in Mozambique. Recently substantial resources have been used to reduce the burden of malaria in Mozambique. These include the distribution of insecticide treated bed-nets, indoor residual insecticide spraying, access to artemisinin-based combination treatment (ACT), and intermittent preventive treatment of pregnant women with sulfadoxine-pyrimetamine (SP-IPTp). The most important benefit of SP-IPTp in malaria endemic areas has been the increase in birth weight, thus increasing the probability of child survival. The SP-IPTp policy was based on evidence of its effectiveness in areas of high intensity malaria transmission. The effect of SP-IPTp has been less evident in the presence of high coverage with insecticide treated bed-nets. It is not know whether reducing the risk of malaria through effective vector control using indoor residual insecticide spraying and large-scale deployment of ACTs has a similar effect in reducing the impact of SP-IPTp on birth weight. At the same time, increasing resistance of SP could be compromising the effect of SP-IPTp on birth weight, as could co-infection with HIV. The aim of this study was to determine if the effect of SP-IPTp on reduction in risk of low birth weight is modified by Plasmodium falciparum malaria prevalence. This retrospective antenatal record review, analyzed 20867 antenatal records from 2005 to 2007 from public health facilities in Maputo and Gaza provinces, southern Mozambique. One or two doses of SP-IPTp does not have any effect on reducing the risk of low birth weight, while women who had at least three doses of SP-IPTp had a 15% lower risk of their babies being born with low birth weigh compared with fewer doses, (OR=0.85; 95% CI 0.73 – 1.00; p=0.053). The risk of babies being born with low birth weight was reduced by 28% when both malaria prevalence and dhfr / dhps mutation prevalence are low, (OR=0.72; 95% CI 0.51 – 1.00), but this effect was no longer significant with higher malaria prevalence and or mutation prevalence. SP-IPTp has an effect on reducing low birth weight with three or more doses, and in areas where malaria prevalence and mutation prevalence are low.  CopyrightDissertation (MSc)--University of Pretoria, 2013.Clinical Epidemiologyunrestricte

Efficacy of sulphadoxine-pyrimethamine with or without artesunate for the treatment of uncomplicated Plasmodium falciparum malaria in southern Mozambique: a randomized controlled trial

BACKGROUND: An artemisinin-based combination therapy, artesunate (AS) plus sulphadoxine-pyrimethamine (SP), was compared to SP monotherapy to provide evidence of further treatment options in southern Mozambique. METHODS: Between 2003 and 2005, 411 patients over one year and 10 kg with uncomplicated Plasmodium falciparum malaria were randomly allocated SP (25/1.25 mg per kg day 0) or AS/SP (as above plus 4 mg/kg artesunate days 0, 1 and 2). Allocation was concealed, but treatment was open-label except to microscopists. The primary objective was the relative risk of treatment failure, which was assessed using World Health Organization response definitions modified to a 42-day follow-up. RESULTS: Of the 411 subjects enrolled, 359 (87.3%) completed the follow up period (SP n = 175, AS/SP n = 184). A survival analysis including 408 subjects showed that the polymerase chain reaction-adjusted cure rates were 90.4% (95% confidence interval [CI] 84.9%-93.9%) and 98.0% (95% CI 94.8%-99.3%) for SP and AS/SP respectively. Multivariable analysis showed that treatment with AS/SP decreased the relative hazard of treatment failure by 80% compared to SP (hazard ratio [HR] 0.2; 95% CI 0.1-0.6) and age over seven years decreased the relative hazard of failure by 70% (HR 0.3; 95% CI 0.1-0.9), when compared to younger age. However, having a quintuple dhfr/dhps mutation increased the relative hazard of failure compared to fewer mutations (HR 3.2; 95% CI 1.3-7.5) and baseline axillary temperature increased the relative hazard of failure by 50% for each degreesC increase (HR 1.5; 95% CI 1.1-2.2). CONCLUSION: While both treatments were efficacious, AS plus SP significantly decreased the relative hazard of treatment failure compared to SP monotherapy Artesunate plus sulphadoxine-pyrimethamine, but not sulphadoxine-pyrimethamine monotherapy, met the current WHO criteria of >95% efficacy for policy implementation.TRIAL REGISTRATION:NCT00203736 and NCT0020381

Five Years of Large-Scale dhfr and dhps Mutation Surveillance Following the Phased Implementation of Artesunate Plus Sulfadoxine-Pyrimethamine in Maputo Province, Southern Mozambique

Accumulation of mutations in dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) is strongly associated with sulfadoxine-pyrimethamine (SP) treatment failure. Routine surveillance for these resistance markers was conducted annually at 26 sentinel sites in Maputo Province, Mozambique, before and after the phased deployment of artesunate plus SP (AS-SP), with 15,758 children sampled between 2004 and 2008. Mean asexual parasite prevalence, polymerase chain reaction (PCR) corrected, decreased from 44.2% in 2004 to 3.8% in 2008 (P < 0.0001). Among the 2,012 PCR-confirmed falciparum samples, the dhfr triple mutation remained close to fixation, whereas both dhps double and dhfr/dhps “quintuple” mutations increased from 11.0% in 2004, to 75.0% by 2008 (P < 0.0001). Adding artesunate to SP did not retard the spread of SP-resistant parasites. The high “quintuple” mutation prevalence suggests a limited useful therapeutic lifespan of AS-SP for treating uncomplicated malaria, and may curb efficacy of SP-monotherapy for intermittent preventive treatment in Mozambique