Impact of Trimethoprim‐Sulfamethoxazole Prophylaxis on Falciparum Malaria Infection and Disease

Thera, Mahamadou A.; Sehdev, Paul S.; Coulibaly, Drissa; Traore, Karim; Garba, Mamane Nassirou; Cissoko, Yacouba; Koné, Abdoulaye K.; Guindo, Abdoulaye; Dicko, Alassane; Béavogui, Abdoul Habib; Djimdé, Abdoulaye; Lyke, Kirsten E.; Diallo, Dapa A.; Doumbo, Ogobara K.; Plowe, Christopher V.

doi:10.1086/498249

Cited by 117 publications

(105 citation statements)

References 26 publications

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“…Our results thus showed that trimethoprim and streptomycin/spectimonycin resistant gene cassettes were highly encountered in Senegalese Shigella isolates. In sub-Saharan Africa, trimethoprim is widely used, in combination with sulfonamides, to treat diarrhoeal illnesses and urinary tract infections as well as to prevent opportunistic infections in HIV-infected and malarial patients [29,30]. Streptomycin is intensively used to treat tuberculosis, in combination with other drugs.…”

Section: Discussionmentioning

confidence: 99%

High prevalence of trimethoprim-resistance cassettes in class 1 and 2 integrons in Senegalese Shigella spp isolates

Sow

Aı̈dara-Kane

Barraud

et al. 2010

J Infect Dev Ctries

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Background: Integrons have a well-established role in the dissemination of resistance among Gram-negative pathogens and are thus a useful marker of antibiotic resistance. Shigellae are noteworthy for their multiple drug resistance, having gradually acquired resistance to most widely use and inexpensive antimicrobial drugs. Methodology: A total of 32 Shigella strains belonging to serotypes flexneri, dysenteriae, and boydii 20, a new Shigella serovar, resistant to at least four antibiotics were analyzed by molecular techniques. Results: Class 1 integrons were the most prevalent (92.8%); class 2 integrons were found in 16 strains (57.1%). Fifty percent of the strains harboured both class 1 and 2 integrons (intI1 and intI2 genes); this combination of integrase genes was most prevalent in S. boydii 20 and S. dysenteriae strains. The class 1 integrons detected contained dfr and aadA cassettes, alone or in combination (dfrA5/dfrA15, or dfrA15-aadA1, dfrA1-aadA2), and an atypical cassette array with an insertion sequence (oxa30-aadA1-IS1). For class 2 integrons, we detected either the same cassettes as those found in Tn7 (dfrA1-sat1-aadA1-orfX) or truncated class 2 integrons without aadA1 or orfX. The tns genes were absent from all class 2 integrons. The distribution of integrons among RAPD profiles and serotypes revealed a clonal spread of integrons into serotypes and a transfer of integrons between different serotypes. Conclusions: The detection of integrons in a new Shigella serovar, in addition with a high integron prevalence among Shigella strains, confirms the propensity of shigellae to acquire and disseminate resistance determinants.

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Section: Discussionmentioning

confidence: 99%

High prevalence of trimethoprim-resistance cassettes in class 1 and 2 integrons in Senegalese Shigella spp isolates

Sow

Aı̈dara-Kane

Barraud

et al. 2010

J Infect Dev Ctries

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“…At this point, cumulative studies in sub-Saharan Africa indicate that cotrimoxazole prophylaxis does not contribute to increased prevalence of antifolateresistant markers, 24,33,34 although the efficacy of cotrimoxazole prophylaxis in decreasing the incidence of malaria in some of these studies limits the power to detect a difference in these markers between those samples from participants taking cotrimoxazole prophylaxis and those samples from participants not taking this prophylaxis. 33,34 We have directly observed the increasing prevalence of mutations associated with antifolate resistance in P. falciparum over time in Tororo ( Figure 1 ). One of several theories addressing the cause of increasing antifolate resistance hypothesizes that weak selection of antifolate-resistant parasites may be catalyzed through cotrimoxazole prophylaxis.…”

Section: Discussionmentioning

confidence: 99%

Plasmodium falciparum Dihydrofolate Reductase and Dihyropteroate Synthase Mutations and the Use of Trimethoprim-Sulfamethoxazole Prophylaxis among Persons Infected with Human Immunodeficiency Virus

Malamba

Sandison²,

Lule³

et al. 2010

The American Journal of Tropical Medicine and Hygiene

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Abstract. A prospective cohort design was used to measure the association between daily cotrimoxazole-prophylaxis and infection with Plasmodium falciparum containing mutations associated with antifolate resistance among persons infected with human immunodeficiency virus (HIV) in Tororo and Busia District, in eastern Uganda. Of 149 cases of P. falciparum parasitemia diagnosed, 147 (99%) (smears from participants taking prophylaxis = 91 and smears from those not taking cotrimoxazole prophylaxis = 56) were successfully assessed for mutations in the dihydrofolate reductase ( dhfr ) and dihydropteroate synthase ( dhps ) mutations associated with antifolate resistance. Prevalences of the dhfr pure triple mutant (74% and 70%; P = 0.71), the dhps pure double mutant (95% and 88%; P = 0.21), and the dhfr/dhps pure quintuple mutant (73% and 64%; P = 0.36), were not significantly different between those taking and those not taking cotrimoxazole-prophylaxis, respectively. The overall prevalence of the pure quintuple mutant in this study was 69%, which is among the highest in Africa. Although resistance rates of P. falciparum to antifolate drugs are high, cotrimoxazole-prophylaxis in HIV-infected persons was not associated with a higher prevalence of mutations associated with antifolate resistance.

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“…However, an RCT in children aged 5-15 years in Mali showed that co-trimoxazole prophylaxis does not appear to select for sulfadoxine-pyrimethamine-resistant P falciparum. 31 Furthermore, since sulfadoxinepyrimethamine is being phased out and replaced by more eff ective artemisinin-based combination therapies in most countries, concerns about antimicrobial resistance to sulfadoxine-pyrimethamine might become less relevant.…”

Section: Barriers Preventing Scale-up Of Co-trimoxazole Prophylaxis Imentioning

confidence: 99%

Scaling-up co-trimoxazole prophylaxis in HIV-exposed and HIV-infected children in high HIV-prevalence countries

Zachariah

Harries

Luo

et al. 2007

The Lancet Infectious Diseases

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Co-trimoxazole (trimethoprim-sulfamethoxazole) is a widely available antibiotic that substantially reduces HIV-related morbidity and mortality in both adults and children. Prophylaxis with co-trimoxazole is a recommended intervention of proven benefi t that could serve not only as an initial step towards improving paediatric care in young children with limited access to antiretroviral treatment, but also as an important complement to antiretroviral therapy in resourcelimited settings. Despite co-trimoxazole's known clinical benefi ts, the potential operational benefi ts, and favourable recommendations by WHO, UNAIDS, and UNICEF, its routine use in developing countries-particularly subSaharan Africa-has remained limited. Out of an estimated 4 million children in need of co-trimoxazole prophylaxis (HIV-exposed and HIV-infected), only 4% are currently receiving this intervention. We discuss some of the major barriers preventing the scale-up of co-trimoxazole prophylaxis for children in countries with a high prevalence of HIV and propose specifi c actions required to tackle these challenges.

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Impact of Trimethoprim‐Sulfamethoxazole Prophylaxis on Falciparum Malaria Infection and Disease

Abstract: In this setting of low antifolate resistance, TS was highly effective in preventing falciparum malaria infection and disease and did not appear to select for SP-resistant parasites.

Cited by 117 publications

References 26 publications

High prevalence of trimethoprim-resistance cassettes in class 1 and 2 integrons in Senegalese Shigella spp isolates

High prevalence of trimethoprim-resistance cassettes in class 1 and 2 integrons in Senegalese Shigella spp isolates

Plasmodium falciparum Dihydrofolate Reductase and Dihyropteroate Synthase Mutations and the Use of Trimethoprim-Sulfamethoxazole Prophylaxis among Persons Infected with Human Immunodeficiency Virus

Scaling-up co-trimoxazole prophylaxis in HIV-exposed and HIV-infected children in high HIV-prevalence countries

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