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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Objective</p> <p>To compare the efficacy of monthly SP presumptive treatment, versus weekly chloroquine for malaria prophylaxis in children attending the Sickle Cell Clinic, Mulago Hospital.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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</p> <p>Conclusion</p> <p>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.</p> <p>Clinical Trials Registration</p> <p>ClinicalTrials.gov Identifier: NCTOO124267</p

Age and geographic patterns of Plasmodium falciparum malaria infection in a representative sample of children living in Burkitt lymphoma-endemic areas of northern Uganda

BACKGROUND: Falciparum malaria is an important risk factor for African Burkitt lymphoma (BL), but few studies have evaluated malaria patterns in healthy BL-age children in populations where both diseases are endemic. To obtain accurate current data, patterns of asymptomatic malaria were investigated in northern Uganda, where BL is endemic. METHODS: Between 2011 and 2015, 1150 apparently healthy children under 15 years old were sampled from 100 villages in northern Uganda using a stratified, multi-stage, cluster survey design. Falciparum malaria prevalence (pfPR) was assessed by questionnaire, rapid diagnostic test (RDT) and thick film microscopy (TFM). Weighted pfPR and unadjusted and adjusted associations of prevalence with covariates were calculated using logistic models and survey methods. RESULTS: Based on 1143 children successfully tested, weighted pfPR was 54.8% by RDT and 43.4% by TFM. RDT sensitivity and specificity were 97.5 and 77.8%, respectively, as compared to TFM, because RDT detect malaria antigens, which persist in peripheral blood after clinical malaria, thus results based on RDT are reported. Weighted pfPR increased from 40% in children aged under 2 years to 61.8% in children aged 6–8 years (odds ratio 2.42, 95% confidence interval (CI) 1.26–4.65), then fell slightly to 49% in those aged 12–15 years. Geometric mean parasite density was 1805.5 parasites/µL (95% CI 1344.6–2424.3) among TFM-positive participants, and it was higher in children aged <5 years at 5092.9/µL (95% CI 2892.7–8966.8) and lower in those aged ≥10 years at 983.8/µL (95% CI 472.7–2047.4; P = 0.001). Weighted pfPR was lower in children residing in sub-regions employing indoor residual spraying (IRS) than in those residing in non-IRS sub-regions (32.8 versus 65.7%; OR 0.26, 95% CI 0.14, 0.46). However, pfPR varied both within IRS (3.2–55.3%) and non-IRS sub-regions (29.8–75.8%; Pheterogeneity <0.001). pfPR was inversely correlated with a child’s mother’s income (P = 0.011) and positively correlated with being enrolled in the wet season (P = 0.076), but sex was irrelevant. CONCLUSIONS: The study observed high but geographically and demographically heterogenous patterns of asymptomatic malaria prevalence among children living in northern Uganda. These results provide important baseline data that will enable precise evaluation of associations between malaria and BL. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12936-017-1778-z) contains supplementary material, which is available to authorized users

Evaluating the Causal Link Between Malaria Infection and Endemic Burkitt Lymphoma in Northern Uganda: A Mendelian Randomization Study

Submitted by Nuzia Santos ([email protected]) on 2018-03-14T17:44:37Z No. of bitstreams: 1 Evaluating the Causal Link Between Malaria.pdf: 271793 bytes, checksum: 2844c8378094216bfb4d102d6677dd91 (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2018-03-14T18:01:40Z (GMT) No. of bitstreams: 1 Evaluating the Causal Link Between Malaria.pdf: 271793 bytes, checksum: 2844c8378094216bfb4d102d6677dd91 (MD5)Made available in DSpace on 2018-03-14T18:01:40Z (GMT). No. of bitstreams: 1 Evaluating the Causal Link Between Malaria.pdf: 271793 bytes, checksum: 2844c8378094216bfb4d102d6677dd91 (MD5) Previous issue date: 2017African Field Epidemiology Network. EMBLEM Study. Kampala, UgandaNational Institutes of Health. National Cancer Institute. Division of Cancer Epidemiology and Genetics. Bethesda, MD, USANational Institutes of Health. National Cancer Institute. Division of Cancer Epidemiology and Genetics. Laboratory of Translational Genomics. Bethesda, MD, USANational Institutes of Health. National Cancer Institute. Division of Cancer Epidemiology and Genetics. Bethesda, MD, USAFundação Oswaldo Cruz. Instituto Rene Rachou. Belo Horizonte, MG, BrazilMakerere University. College of Health Sciences. Department of Medical Microbiology. Kampala, UgandaAfrican Field Epidemiology Network. EMBLEM Study. Kampala, UgandaNational Institutes of Health. National Cancer Institute. Division of Cancer Epidemiology and Genetics. Bethesda, MD, USAAfrican Field Epidemiology Network. EMBLEM Study. Kampala, UgandaAfrican Field Epidemiology Network. EMBLEM Study. Kampala, UgandaNational Institutes of Health. National Cancer Institute. Division of Cancer Epidemiology and Genetics. Laboratory of Translational Genomics. Bethesda, MD, USAAfrican Field Epidemiology Network. EMBLEM Study. Kampala, Uganda/ University of Maryland School of Medicine. Institute of Human Virology Benjamin Emmanuel. Baltimore, MD, USAAfrican Field Epidemiology Network. EMBLEM Study. Kampala, UgandaWorld Health Organization. Regional Office for Africa. Brazzaville, CongoNational Institutes of Health. National Cancer Institute. Division of Cancer Epidemiology and Genetics. Bethesda, MD, USANational Institutes of Health. National Cancer Institute. Division of Cancer Epidemiology and Genetics. Bethesda, MD, USANational Institutes of Health. National Cancer Institute. Division of Cancer Epidemiology and Genetics. Bethesda, MD, USAOhio State University. Department of Pathology. Columbus, OH, USANational Institutes of Health. National Institute of Allergy and Infectious Diseases. Division of Intramural Research. Bethesda, MD, USANational Institutes of Health. National Cancer Institute. Division of Cancer Epidemiology and Genetics. Bethesda, MD, USASt. Mary's Hospital. EMBLEM Study. Lacor, Gulu, UgandaNational Institutes of Health. National Cancer Institute. Division of Cancer Epidemiology and Genetics. Bethesda, MD, USANational Institutes of Health. National Cancer Institute. Division of Cancer Epidemiology and Genetics. Laboratory of Translational Genomics. Bethesda, MD, USANational Institutes of Health. National Cancer Institute. Division of Cancer Epidemiology and Genetics. Bethesda, MD, USABackground: Plasmodium falciparum (Pf) malaria infection is suspected to cause endemic Burkitt Lymphoma (eBL), but the evidence remains unsettled. An inverse relationship between sickle cell trait (SCT) and eBL, which supports that between malaria and eBL, has been reported before, but in small studies with low power. We investigated this hypothesis in children in a population-based study in northern Uganda using Mendelian Randomization. Methods: Malaria-related polymorphisms (SCT, IL10, IL1A, CD36, SEMA3C, and IFNAR1) were genotyped in 202 eBL cases and 624 controls enrolled during 2010–2015. We modeled associations between genotypes and eBL or malaria using logistic regression. Findings: SCT was associated with decreased risk of eBL (adjusted odds ratio [OR] 0•37, 95% CI 0•21–0•66; p = 0•0003). Decreased risk of eBL was associated with IL10 rs1800896-CT (OR 0•73, 95% CI 0•50–1•07) and -CC genotypes (OR 0•53, 95% CI 0•29–0•95, ptrend = 0•019); IL1A rs2856838-AG (OR 0•56, 95% CI 0•39–0•81) and -AA genotype (OR 0•50, 95% CI 0•28–1•01, ptrend = 0•0016); and SEMA3C rs4461841-CT or -CC genotypes (OR 0•57, 95% CI 0•35–0•93, p = 0•0193). SCT and IL10 rs1800896, IL1A rs2856838, but not SEMA3C rs4461841, polymorphisms were associated with decreased risk of malaria in the controls. Interpretation: Our results support a causal effect of malaria infection on eB

Closing the access barrier for effective anti-malarials in the private sector in rural Uganda: consortium for ACT private sector subsidy (CAPSS) pilot study

Abstract Background Artemisinin-based combination therapy (ACT), the treatment of choice for uncomplicated falciparum malaria, is unaffordable and generally inaccessible in the private sector, the first port of call for most malaria treatment across rural Africa. Between August 2007 and May 2010, the Uganda Ministry of Health and the Medicines for Malaria Venture conducted the Consortium for ACT Private Sector Subsidy (CAPSS) pilot study to test whether access to ACT in the private sector could be improved through the provision of a high level supply chain subsidy. Methods Four intervention districts were purposefully selected to receive branded subsidized medicines - “ACT with a leaf”, while the fifth district acted as the control. Baseline and evaluation outlet exit surveys and retail audits were conducted at licensed and unlicensed drug outlets in the intervention and control districts. A survey-adjusted, multivariate logistic regression model was used to analyse the intervention’s impact on: ACT uptake and price; purchase of ACT within 24 hours of symptom onset; ACT availability and displacement of sub-optimal anti-malarial. Results At baseline, ACT accounted for less than 1% of anti-malarials purchased from licensed drug shops for children less than five years old. However, at evaluation, “ACT with a leaf” accounted for 69% of anti-malarial purchased in the interventions districts. Purchase of ACT within 24 hours of symptom onset for children under five years rose from 0.8% at baseline to 26.2% (95% CI: 23.2-29.2%) at evaluation in the intervention districts. In the control district, it rose modestly from 1.8% to 5.6% (95% CI: 4.0-7.3%). The odds of purchasing ACT within 24 hours in the intervention districts compared to the control was 0.46 (95% CI: 0.08-2.68, p=0.4) at baseline and significant increased to 6.11 (95% CI: 4.32-8.62, p Conclusions These data demonstrate that a supply-side subsidy and an intensive communications campaign significantly increased the uptake and use of ACT in the private sector in Uganda.</p

Closing the access barrier for effective anti-malarials in the private sector in rural Uganda: consortium for ACT private sector subsidy (CAPSS) pilot study

The study examined closing the access barrier for effective anti-malarials in the private sector in rural UgandaBackground: Artemisinin-based combination therapy (ACT), the treatment of choice for uncomplicated falciparum malaria, is unaffordable and generally inaccessible in the private sector, the first port of call for most malaria treatment across rural Africa. Between August 2007 and May 2010, the Uganda Ministry of Health and the Medicines for Malaria Venture conducted the Consortium for ACT Private Sector Subsidy (CAPSS) pilot study to test whether access to ACT in the private sector could be improved through the provision of a high level supply chain subsidy. Methods: Four intervention districts were purposefully selected to receive branded subsidized medicines - “ACT with a leaf”, while the fifth district acted as the control. Baseline and evaluation outlet exit surveys and retail audits were conducted at licensed and unlicensed drug outlets in the intervention and control districts. A survey-adjusted, multivariate logistic regression model was used to analyse the intervention’s impact on: ACT uptake and price; purchase of ACT within 24 hours of symptom onset; ACT availability and displacement of sub-optimal anti-malarial. Results: At baseline, ACT accounted for less than 1% of anti-malarials purchased from licensed drug shops for children less than five years old. However, at evaluation, “ACT with a leaf” accounted for 69% of anti-malarial purchased in the interventions districts. Purchase of ACT within 24 hours of symptom onset for children under five years rose from 0.8% at baseline to 26.2% (95% CI: 23.2-29.2%) at evaluation in the intervention districts. In the control district, it rose modestly from 1.8% to 5.6% (95% CI: 4.0-7.3%). The odds of purchasing ACT within 24 hours in the intervention districts compared to the control was 0.46 (95% CI: 0.08-2.68, p=0.4) at baseline and significant increased to 6.11 (95% CI: 4.32-8.62, p<0.0001) at evaluation. Children less than five years of age had “ACT with a leaf” purchased for them more often than those aged above five years. There was no evidence of price gouging. Conclusions: These data demonstrate that a supply-side subsidy and an intensive communications campaign significantly increased the uptake and use of ACT in the private sector in Uganda

MOESM1 of Age and geographic patterns of Plasmodium falciparum malaria infection in a representative sample of children living in Burkitt lymphoma-endemic areas of northern Uganda

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