Sulfadoxine/pyrimethamine alone or with amodiaquine or artesunate for treatment of uncomplicated malaria: a longitudinal randomised trial

Dorsey, Grant; Njama, Denise; Kamya, Moses R.; Cattamanchi, Adithya; Kyabayinze, Daniel J; Staedke, Sarah G.; Gasasira, Anne; Rosenthal, Philip J.

doi:10.1016/s0140-6736(02)12021-6

Cited by 131 publications

(137 citation statements)

References 23 publications

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“…41 African countries with high pre-existing levels of SP resistance have achieved poor cure rates using AS-SP. 42,43 Although AS-SP was shown to be highly efficacious at the start of ACT roll out, 16 the high pre-existing dhfr triple mutation prevalence at the time of AS-SP implementation, together with the rather sharp increase in both the dhps double and "quintuple" mutations following ACT implementation, is cause for concern. Allen and colleagues 16 showed the presence of the "quintuple" mutation resulted in a 3-fold increased risk of treatment failure in Maputo Province, after adjusting for treatment arm, age, and temperature.…”

Section: Discussionmentioning

confidence: 99%

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

Raman¹,

Little²,

Roper³

et al. 2010

The American Society of Tropical Medicine and Hygiene

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Abstract. 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.

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Section: Discussionmentioning

confidence: 99%

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

Raman¹,

Little²,

Roper³

et al. 2010

The American Society of Tropical Medicine and Hygiene

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“…In Uganda, sensitivity rates of P falciparum to sulphadoxine-pyrimethamine range between 80% and 99%, 25 although failure rates were higher when recrudescence during 42 days of follow-up was evaluated. 29 Assessment of whether sulphadoxinepyrimethamine remains an effective treatment for individuals receiving co-trimoxazole prophylaxis 30 and whether its use increases sulphadoxine-pyrimethamine resistance in the broader community will be important. 31 Compliance with co-trimoxazole treatment was excellent and, as in other studies in Africa, 3,4,6 the treatment was very well tolerated.…”

Section: Discussionmentioning

confidence: 99%

Effect of co-trimoxazole prophylaxis on morbidity, mortality, CD4-cell count, and viral load in HIV infection in rural Uganda

et al. 2004

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SummaryBackground Prophylaxis with co-trimoxazole (trimethoprim-sulphamethoxazole) is recommended for people with HIV infection or AIDS but is rarely used in Africa. We assessed the effect of such prophylaxis on morbidity, mortality, CD4-cell count, and viral load among people with HIV infection living in rural Uganda, an area with high rates of bacterial resistance to co-trimoxazole.Methods Between April, 2001, and March, 2003, we enrolled, and followed up with weekly home visits, 509 individuals with HIV-1 infection and their 1522 HIV-negative household members. After 5 months of follow-up, HIV-positive participants were offered daily co-trimoxazole prophylaxis (800 mg trimethoprim, 160 mg sulphamethoxazole) and followed up for a further 1·5 years. We assessed rates of malaria, diarrhoea, hospital admission, and death. Findings Co-trimoxazole was well tolerated with rare (<2% per person-year) adverse reactions. Even though rates of resistance in diarrhoeal pathogens were high (76%), co-trimoxazole prophylaxis was associated with a 46% reduction in mortality (hazard ratio 0·54 [95% CI 0·35-0·84], p=0·006) and lower rates of malaria (multivariate incidence rate ratio 0·28 [0·19-0·40], p<0·0001), diarrhoea (0·65 [0·53-0·81], p<0·0001), and hospital admission (0·69 [0·48-0·98], p=0·04). The annual rate of decline in CD4-cell count was less during prophylaxis than before (77 vs 203 cells per µL, p<0·0001), and the annual rate of increase in viral load was lower (0·08 vs 0·90 log 10 copies per mL, p=0·01).Interpretation Daily co-trimoxazole prophylaxis was associated with reduced morbidity and mortality and had beneficial effects on CD4-cell count and viral load. Co-trimoxazole prophylaxis is a readily available, effective intervention for people with HIV infection in Africa.

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“…The details of these studies have been previously published. [6][7][8] These samples were selected randomly for our study after stratifying based on parasite density, which was determined by thick smear.…”

Section: Methodsmentioning

confidence: 99%

The Effect of Storage and Extraction Methods on Amplification of Plasmodium falciparum DNA from Dried Blood Spots

Schwartz

Baidjoe

Rosenthal

et al. 2015

The American Society of Tropical Medicine and Hygiene

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Abstract. Extraction and amplification of DNA from dried blood spots (DBS) collected in field studies is commonly used for detection of Plasmodium falciparum. However, there have been few systematic efforts to determine the effects of storage and extraction methods on the sensitivity of DNA amplification. We investigated the effects of storage conditions, length of storage, and DNA extraction methods on amplification via three PCR-based assays using field samples and laboratory controls. Samples stored as DBS for 2 or more years at ambient temperature showed a significant loss of sensitivity that increased with time; after 10 years only 10% samples with parasite densities 1,000 parasites/μL were detectable by nested polymerase chain reaction (PCR). Conversely, DBS and extracted DNA stored at −20 C showed no loss of sensitivity with time. Samples with low parasite densities amplified more successfully with saponin/Chelex compared with spin-column-based extraction, though the latter method performed better on samples with higher parasite densities stored for 2 years at ambient temperature. DNA extracted via both methods was stable after 20 freeze-thaw cycles. Our results suggest that DBS should be stored at −20 C or extracted immediately, especially if anticipating 2 or more years of storage.

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Sulfadoxine/pyrimethamine alone or with amodiaquine or artesunate for treatment of uncomplicated malaria: a longitudinal randomised trial

Cited by 131 publications

References 23 publications

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

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

Effect of co-trimoxazole prophylaxis on morbidity, mortality, CD4-cell count, and viral load in HIV infection in rural Uganda

The Effect of Storage and Extraction Methods on Amplification of Plasmodium falciparum DNA from Dried Blood Spots

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