Presumptive treatment with sulphadoxine-pyrimethamine versus weekly chloroquine for malaria prophylaxis in children with sickle cell anaemia in Uganda: a randomized controlled trial

Nakibuuka, Victoria; Ndeezi, Grace; Nakiboneka, Deborah; Ndugwa, Christopher M.; Tumwine, James

doi:10.1186/1475-2875-8-237

Cited by 19 publications

(22 citation statements)

References 16 publications

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“…The CQ remains available in Uganda, and in fact it continues to be recommended for regular chemoprophylaxis in children with sickle cell disease. 42 Very recently, the prevalence of parasites with the CQ-sensitive pfcrt K76 genotype increased markedly in Tororo, suggesting a decrease in community use of CQ.…”

Section: Discussionmentioning

confidence: 99%

Temporal Changes in Prevalence of Molecular Markers Mediating Antimalarial Drug Resistance in a High Malaria Transmission Setting in Uganda

Mbogo¹,

Nankoberanyi²,

Tukwasibwe³

et al. 2014

The American Society of Tropical Medicine and Hygiene

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Abstract. Standard therapy for malaria in Uganda changed from chloroquine to chloroquine + sulfadoxine-pyrimethamine in 2000, and artemether-lumefantrine in 2004, although implementation of each change was slow. Plasmodium falciparum genetic polymorphisms are associated with alterations in drug sensitivity. We followed the prevalence of drug resistancemediating P. falciparum polymorphisms in 982 samples from Tororo, a region of high transmission intensity, collected from three successive treatment trials conducted during 2003-2012, excluding samples with known recent prior treatment. Considering transporter mutations, prevalence of the mutant pfcrt 76T, pfmdr1 86Y, and pfmdr1 1246Y alleles decreased over time. Considering antifolate mutations, the prevalence of pfdhfr 51I, 59R, and 108N, and pfdhps 437G and 540E were consistently high; pfdhfr 164L and pfdhps 581G were uncommon, but most prevalent during 2008-2010. Our data suggest sequential selective pressures as different treatments were implemented, and they highlight the importance of genetic surveillance as treatment policies change over time.

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Section: Discussionmentioning

confidence: 99%

Temporal Changes in Prevalence of Molecular Markers Mediating Antimalarial Drug Resistance in a High Malaria Transmission Setting in Uganda

Mbogo¹,

Nankoberanyi²,

Tukwasibwe³

et al. 2014

The American Society of Tropical Medicine and Hygiene

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“… Massaga 2003 Anaemia not part of the inclusion criteria. Nakibuuka 2009 No control group ‐ comparing two malaria treatment regimes. Rohner 2010 Anaemia not part of the inclusion criteria.…”

Section: Characteristics Of Excluded Studies [Ordered By Study Id]mentioning

confidence: 99%

Intermittent preventive antimalarial treatment for children with anaemia

Athuman

Kabanywanyi

Rohwer

2015

Cochrane Database of Systematic Reviews

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BackgroundAnaemia is a global public health problem. Children under five years of age living in developing countries (mostly Africa and South-East Asia) are highly affected. Although the causes for anaemia are multifactorial, malaria has been linked to anaemia in children living in malaria-endemic areas. Administering intermittent preventive antimalarial treatment (IPT) to children might reduce anaemia, since it could protect children from new Plasmodium parasite infection (the parasites that cause malaria) and allow their haemoglobin levels to recover.ObjectivesTo assess the effect of IPT for children with anaemia living in malaria-endemic areas.Search methodsWe searched the Cochrane Infectious Diseases Group Specialized Register, Cochrane Central of Controlled Trials (CENTRAL), published in The Cochrane Library; MEDLINE; EMBASE; and LILACS. We also searched the World Health Organization (WHO) International Clinical Trial Registry Platform and metaRegister of Controlled Trials (mRCT) for ongoing trials up to 4 December 2014.Selection criteriaRandomized controlled trials (RCTs) evaluating the effect of IPT on children with anaemia.Data collection and analysisTwo review authors independently extracted data and assessed risk of bias. We analysed data by conducting meta-analyses, stratifying data according to whether participants received iron supplements or not. We used GRADE to assess the quality of evidence.Main resultsSix trials with 3847 participants met our inclusion criteria. Trials were conducted in areas of low malaria endemicity (three trials), and moderate to high endemicity (three trials). Four trials were in areas of seasonal malaria transmission. Iron was given to all children in two trials, and evaluated in a factorial design in a further two trials.IPT for children with anaemia probably has little or no effect on the proportion anaemic at 12 weeks follow-up (four trials, 2237 participants, (moderate quality evidence).IPT in anaemic children probably increases the mean change in haemoglobin levels from baseline to follow-up at 12 weeks on average by 0.32 g/dL (MD 0.32, 95% CI 0.19 to 0.45; four trials, 1672 participants, moderate quality evidence); and may improve haemoglobin levels at 12 weeks (MD 0.35, 95% CI 0.06 to 0.64; four trials, 1672 participants, low quality evidence). For both of these outcomes, subgroup analysis did not demonstrate a difference between children receiving iron and those that did not.IPT for children with anaemia probably has little or no effect on mortality or hospital admissions at six months (three trials, 3160 participants moderate quality evidence). Subgroup analysis did not show a difference between those children receiving iron supplements and those that did not.Authors' conclusionsTrials did show a small effect on average haemoglobin levels but this did not appear to translate into an effect on mortality and hospital admissions. Three of the six trials were conducted in low endemicity areas where transmission is low and thus any protective effect is likely to be mode...

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“…A Cochrane review of malaria prophylaxis for patients with SCD concluded that prophylaxis is beneficial, with fewer episodes of malaria, higher mean hemoglobin concentrations, fewer transfusions, fewer hospital admissions, and fewer sickle cell crises in patients receiving prophylaxis [ 6 ], but the review included only 2 small studies, one from Kampala in 1965, which involved administration of chloroquine plus benzathine penicillin for 12 months [ 7 ], and one from Nigeria in 2003, in which 97 patients were randomized to receive daily proguanil therapy, weekly pyrimethamine therapy, or placebo for 9 months [ 8 ]. Studies not in the review included a placebo-controlled trial of 60 patients in Senegal that showed that monthly sulfadoxine-pyrimethamine (SP) treatment during the transmission season was well tolerated and reduced morbidity [ 9 ]; a study in Uganda, with just 1 month of follow-up, that suggested that weekly chloroquine therapy was less effective than monthly SP therapy [ 10 ]; and a study in Nigeria that indicated that weekly mefloquine (MQ) was well tolerated and more effective than daily proguanil [ 11 ]. Several small surveys of patients with SCD in Nigeria who received daily proguanil or weekly pyrimethamine prophylaxis have found that malaria parasitemia is common and attributed this finding to poor compliance and resistance [ 12 – 14 ].…”

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confidence: 99%

A Randomized Trial to Compare the Safety, Tolerability, and Effectiveness of 3 Antimalarial Regimens for the Prevention of Malaria in Nigerian Patients With Sickle Cell Disease

Olaosebikan¹,

Ernest²,

Bojang³

et al. 2015

J Infect Dis.

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BackgroundMalaria prophylaxis is recommended for persons with sickle cell disease (SCD), but the value of this has been questioned. The aim of this study was to find out whether intermittent preventive treatment (IPT) with a fixed-dose combination of mefloquine-artesunate (MQAS) or sulfadoxine-pyrimethamine plus amodiaquine (SPAQ) was more effective than daily proguanil for malaria prevention in subjects with SCD.MethodsPatients with SCD were randomized to receive daily treatment with proguanil or IPT with either MQAS or SPAQ once every 2 months at routine clinic visits. Patients were followed up for 14 months.FindingsA total of 270 patients with SCD were studied, with 90 in each group. Adherence to the IPT regimens was excellent, but 57% of patients took <75% of their daily doses of proguanil. IPT was well tolerated; the most common side effects were vomiting and abdominal pain. Protective efficacy against malaria, compared with daily proguanil, was 61% (95% confidence interval, 3%–84%) for MQAS and 36% (40%–70%) for SPAQ. There were fewer outpatient illness episodes in children who received IPT than those who received proguanil.ConclusionsIPT with MQAS administered to patients with SCD during routine clinic visits was well tolerated and more effective in preventing malaria than daily prophylaxis with proguanil.Clinical Trials RegistrationNCT01319448 and ISRCTN46158146.

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Presumptive treatment with sulphadoxine-pyrimethamine versus weekly chloroquine for malaria prophylaxis in children with sickle cell anaemia in Uganda: a randomized controlled trial

Cited by 19 publications

References 16 publications

Temporal Changes in Prevalence of Molecular Markers Mediating Antimalarial Drug Resistance in a High Malaria Transmission Setting in Uganda

Temporal Changes in Prevalence of Molecular Markers Mediating Antimalarial Drug Resistance in a High Malaria Transmission Setting in Uganda

Intermittent preventive antimalarial treatment for children with anaemia

A Randomized Trial to Compare the Safety, Tolerability, and Effectiveness of 3 Antimalarial Regimens for the Prevention of Malaria in Nigerian Patients With Sickle Cell Disease

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