Dataset Information

Anti-bacterial activity of intermittent preventive treatment of malaria in pregnancy: comparative in vitro study of sulphadoxine-pyrimethamine, mefloquine, and azithromycin.

ABSTRACT:

Background

Intermittent preventive treatment of malaria with sulphadoxine-pyrimethamine (SP) is recommended for the prevention of malaria in pregnancy in sub-Saharan Africa. Increasing drug resistance necessitates the urgent evaluation of alternative drugs. Currently, the most promising candidates in clinical development are mefloquine and azithromycin. Besides the anti-malarial activity, SP is also a potent antibiotic and incurs significant anti-microbial activity when given as IPTp - though systematic clinical evaluation of this action is still lacking.

Methods

In this study, the intrinsic anti-bacterial activity of mefloquine and azithromycin was assessed in comparison to sulphadoxine-pyrimethamine against bacterial pathogens with clinical importance in pregnancy in a standard microdilution assay.

Results

SP was highly active against Staphylococcus aureus and Streptococcus pneumoniae. All tested Gram-positive bacteria, except Enterococcus faecalis, were sensitive to azithromycin. Additionally, azithromycin was active against Neisseria gonorrhoeae. Mefloquine showed good activity against pneumococci but lower in vitro action against all other tested pathogens.

Conclusion

These data indicate important differences in the spectrum of anti-bacterial activity for the evaluated anti-malarial drugs. Given the large scale use of IPTp in Africa, the need for prospective clinical trials evaluating the impact of antibiotic activity of anti-malarials on maternal and foetal health and on the risk of promoting specific drug resistance of bacterial pathogens is discussed.

SUBMITTER: Capan M

PROVIDER: S-EPMC2984572 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Publications

Anti-bacterial activity of intermittent preventive treatment of malaria in pregnancy: comparative in vitro study of sulphadoxine-pyrimethamine, mefloquine, and azithromycin.

Capan Mesküre M Mombo-Ngoma Ghyslain G Makristathis Athanasios A Ramharter Michael M

Malaria journal 20101029

<h4>Background</h4>Intermittent preventive treatment of malaria with sulphadoxine-pyrimethamine (SP) is recommended for the prevention of malaria in pregnancy in sub-Saharan Africa. Increasing drug resistance necessitates the urgent evaluation of alternative drugs. Currently, the most promising candidates in clinical development are mefloquine and azithromycin. Besides the anti-malarial activity, SP is also a potent antibiotic and incurs significant anti-microbial activity when given as IPTp - t ...[more]

PMID: 21029476

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Project description:BackgroundAnnually, 125.2 million pregnant women worldwide risk contracting malaria, including 30.3 million and 1.5 million in Sub-Saharan Africa and Kenya respectively. At least three doses of sulphadoxine pyrimethamine for intermittent preventive treatment of malaria in pregnancy (IPTp-SP) is recommended for optimal benefit. Kenya recorded low IPTp-SP optimal uptake in 2015. This study investigated the prevalence of and factors influencing IPTp-SP optimal uptake in Sabatia Sub County, Western Kenya.MethodsA cross-sectional study was conducted in Sabatia Sub County from April to October 2020. Using a validated semi-structured questionnaire, data were obtained from 372 randomly sampled post-delivery women aged 15-49 years with live birth within one year preceding the study. Women on cotrimoxazole prophylaxis during pregnancy were excluded. Pearson Chi-square and Fisher's Exact test were measures of association used. Binary logistic regression analysed predictors of optimal IPTp-SP uptake.ResultsOptimal IPTp-SP uptake was 79.6%, 95% CI 75.5%-83.7%. Predictors of IPTp-SP optimization were gestational age at first antenatal care (ANC) visit (P = 0.04), frequency of ANC visits (P < 0.001), maternal knowledge of IPTp-SP benefits (P < 0.001), maternal knowledge of optimal sulphadoxine pyrimethamine (SP) dose (P = 0.03) and SP administration at ANC clinic (P = 0.03). Late ANC initiators were less likely to receive optimal IPTp-SP (aOR = 0.4, 95% CI 0.2-0.9). Odds of optimizing IPTp-SP increased among women with ≥ 4 ANC visits (aOR = 16.7, 95% CI 7.9-35.3), good knowledge of IPTp-SP benefits (aOR = 2.4, 95% CI 1.3-4.5) and good knowledge of optimal SP dose (aOR = 1.9, 95% CI 1.1-3.4). Women who never missed being administered SP were highly likely to receive optimal IPTp-SP (aOR = 2.9, 95% CI 1.1-7.2) CONCLUSIONS: This study has found high IPTp-SP optimal uptake in the study area. Efforts should be directed towards early and more frequent ANC visits. Intensive and targeted health education is required. It's fundamental to adequately stock and consistently administer SP. Future studies considering larger samples and health workers' perspectives of the health system delivery factors are recommended.

Project description:Background In sub-Saharan Africa, the efficacy of intermittent preventive therapy in pregnancy with sulphadoxine-pyrimethamine (IPTp-SP) for malaria in pregnancy is threatened by parasite resistance. We conducted an individual-participant data (IPD) meta-analysis to assess the efficacy of intermittent screening with malaria rapid diagnostic tests (RDTs) and treatment of RDT-positive women with artemisinin-based combination therapy (ISTp-ACT) compared to IPTp-SP, and understand the importance of subpatent infections. Methods We searched MEDLINE and the Malaria-in-Pregnancy Library on May 6, 2021 for trials comparing ISTp-ACT and IPTp-SP. Generalised linear regression was used to compare adverse pregnancy outcomes (composite of small-for-gestational-age, low birthweight (LBW), or preterm delivery) and peripheral or placental Plasmodium falciparum at delivery. The effects of subpatent (PCR-positive, RDT/microscopy-negative) infections were assessed in both arms pooled using multi-variable fixed-effect models adjusting for the number of patent infections. PROSPERO registration: CRD42016043789. Findings Five trials conducted between 2007 and 2014 contributed (10,821 pregnancies), two from high SP-resistance areas where dhfr/dhps quintuple mutant parasites are saturated, but sextuple mutants are still rare (Kenya and Malawi), and three from low-resistance areas (West-Africa). Four trials contributed IPD data (N=10,362). At delivery, the prevalence of any malaria infection (relative risk [RR]=1.08, 95% CI 1.00-1.16, I2=67.0 %) and patent infection (RR=1.02, 0.61-1.16, I2=0.0%) were similar. Subpatent infections were more common in ISTp recipients (RR=1.31, 1.05-1.62, I2=0.0%). There was no difference in adverse pregnancy outcome (RR=1.00, 0.96-1.05; studies=4, N=9,191, I2=54.5%). Subpatent infections were associated with LBW (adjusted RR=1.13, 1.07-1.19), lower mean birthweight (adjusted mean difference=32g, 15-49), and preterm delivery (aRR=1.35, 1.15-1.57). Interpretation ISTp-ACT was not superior to IPTp-SP and may result in more subpatent infections than the existing IPTp-SP policy. Subpatent infections were associated with increased LBW and preterm delivery. More sensitive diagnostic tests are needed to detect and treat low-grade infections. Funding Centers for Disease Control and Prevention and Worldwide Antimalarial Resistance Network.

Project description:Intermittent preventive treatment for malaria in children (IPTc) involves the administration of a full course of an anti-malarial treatment to children under 5 years old at specified time points regardless of whether or not they are known to be infected, in areas where malaria transmission is seasonal. It is important to determine the costs associated with IPTc delivery via community based volunteers and also the potential savings to health care providers and caretakers due to malaria episodes averted as a consequence of IPTc.Two thousand four hundred and fifty-one children aged 3-59 months were randomly allocated to four groups to receive: three days of artesunate plus amodiaquine (AS+AQ) monthly, three days of AS+AQ bimonthly, one dose of sulphadoxine-pyrimethamine (SP) bi-monthly or placebo. This paper focuses on incremental cost effectiveness ratios (ICERs) of the three IPTc drug regimens as delivered by community based volunteers (CBV) in Hohoe, Ghana compared to current practice, i.e. case management in the absence of IPTc. Financial and economic costs from the publicly funded health system perspective are presented. Treatment costs borne by patients and their caretakers are also estimated to present societal costs. The costs and effects of IPTc during the intervention period were considered with and without a one year follow up. Probabilistic sensitivity analysis was undertaken to account for uncertainty.Economic costs per child receiving at least the first dose of each course of IPTc show SP bimonthly, at US$8.19, is the cheapest to deliver, followed by AS+AQ bimonthly at US$10.67 and then by AS+AQ monthly at US$14.79. Training, drug delivery and supervision accounted for approximately 20-30% each of total unit costs. During the intervention period AS & AQ monthly was the most cost effective IPTc drug regimen at US$67.77 (61.71-74.75, CI 95%) per malaria case averted based on intervention costs only, US$64.93 (58.92-71.92, CI 95%) per malaria case averted once the provider cost savings are included and US$61.00 (54.98, 67.99, CI 95%) when direct household cost savings are also taken into account. SP bimonthly was US$105.35 (75.01-157.31, CI 95%) and AS & AQ bimonthly US$211.80 (127.05-399.14, CI 95%) per malaria case averted based on intervention costs only. The incidence of malaria in the post intervention period was higher in children who were <1 year old when they received AS+AQ monthly compared to the placebo group leading to higher cost effectiveness ratios when one year follow up is included. The cost per child enrolled fell considerably when modelled to district level as compared to those encountered under trial conditions.We demonstrate how cost-effective IPTc is using three different drug regimens and the possibilities for reducing costs further if the intervention was to be scaled up to the district level. The need for effective training, drug delivery channels and supervision to support a strong network of community based volunteers is emphasised.

Dataset Information

Anti-bacterial activity of intermittent preventive treatment of malaria in pregnancy: comparative in vitro study of sulphadoxine-pyrimethamine, mefloquine, and azithromycin.

Background

Methods

Results

Conclusion

Publications

Anti-bacterial activity of intermittent preventive treatment of malaria in pregnancy: comparative in vitro study of sulphadoxine-pyrimethamine, mefloquine, and azithromycin.

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