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Effect of seasonal malaria chemoprevention plus azithromycin on Plasmodium falciparum transmission: gametocyte infectivity and mosquito fitness

July 28, 2021 - 15:09 -- Open Access
Koudraogo Bienvenue Yaméogo, Rakiswendé Serge Yerbanga, Jean Bosco Ouédraogo, et al.
Malaria Journal 2021 20:326, 27 July 2021

Seasonal malaria chemoprevention (SMC) consists of administration of sulfadoxine-pyrimethamine (SP) + amodiaquine (AQ) at monthly intervals to children during the malaria transmission period. Whether the addition of azithromycin (AZ) to SMC could potentiate the benefit of the intervention was tested through a double-blind, randomized, placebo-controlled trial. The effect of SMC and the addition of AZ, on malaria transmission and on the life history traits of Anopheles gambiae mosquitoes have been investigated.

Cardiotoxic Potential of Hydroxychloroquine, Chloroquine and Azithromycin in Adult Human Primary Cardiomyocytes

January 26, 2021 - 15:24 -- Open Access
Jordaan P, Dumotier B, Traebert M, Miller PE, Ghetti A, Urban L, Abi-Gerges N
Toxicol Sci. 2021 Jan 23:kfaa194

Substantial efforts have been recently committed to develop COVID-19 medications, and Hydroxychloroquine alone or in combination with Azithromycin has been promoted as a repurposed treatment. While these drugs may increase cardiac toxicity risk, cardiomyocyte mechanisms underlying this risk remain poorly understood in humans. Therefore, we evaluated the pro-arrhythmia risk and inotropic effects of these drugs in the cardiomyocyte contractility-based model of the human heart. We found Hydroxychloroquine to have a low pro-arrhythmia risk, while Chloroquine and Azithromycin were associated with high risk.

Retargeting azithromycin analogues to have dual-modality antimalarial activity

October 1, 2020 - 15:25 -- Open Access
Burns AL, Sleebs BE, Wilson DW, et al.
BMC Biol. 2020 Sep 29;18(1):133

Resistance to front-line antimalarials (artemisinin combination therapies) is spreading, and development of new drug treatment strategies to rapidly kill Plasmodium spp. malaria parasites is urgently needed. Azithromycin is a clinically used macrolide antibiotic proposed as a partner drug for combination therapy in malaria, which has also been tested as monotherapy. However, its slow-killing ‘delayed-death’ activity against the parasite’s apicoplast organelle and suboptimal activity as monotherapy limit its application as a potential malaria treatment. Here, we explore a panel of azithromycin analogues and demonstrate that chemical modifications can be used to greatly improve the speed and potency of antimalarial action.

An open label study of the safety and efficacy of a single dose of weekly chloroquine and azithromycin administered for malaria prophylaxis in healthy adults challenged with 7G8 chloroquine-resistant Plasmodium falciparum in...

September 16, 2020 - 12:48 -- Open Access
Jeffrey Livezey, Patrick Twomey, Paige Waterman, et al.
Malaria Journal 2020 19:336, 16 September 2020

Malaria remains the top infectious disease threat facing the U.S. military in many forward operating environments. Compliance with malaria chemoprophylaxis remains a critical component in preventing malaria in the deployed Service Member. Studies of previous military operations show that compliance is consistently higher with weekly versus daily dosing regimens. Current FDA approved weekly chemoprophylaxis options have contraindications that can limit prescribing. The combination of chloroquine (CQ) with azithromycin (AZ) has previously been shown to be an efficacious treatment option for malaria, has pharmacokinetics compatible with weekly dosing, and has shown synergy when combined in vitro.

NOT Open Access | Evaluation of the combination of azithromycin and naphthoquine in animal malaria models

August 26, 2020 - 14:41 -- NOT Open Access
Bei ZC, Li GF, Zhao JH, Zhang M, Ji XG, Wang JY
Antimicrob Agents Chemother. 2020 Aug 24

Combination therapy using drugs with different mechanisms of action is the current state of the art in antimalarial treatment. However, except for artemisinin-based combination therapies, only few other combinations are available now. The increasing concern on the emergence and spread of artemisinin resistance in Plasmodium falciparum has evoked a need for the development of new antimalarials.

Effects of Biannual Azithromycin Mass Drug Administration on Malaria in Malawian Children: A Cluster-Randomized Trial

April 29, 2020 - 09:13 -- Open Access
Hart JD, Samikwa L, Sikina F, Kalua K, Keenan JD, Lietman TM, Burr SE, Bailey RL
Am J Trop Med Hyg. 2020 Apr 27

Reductions in malaria morbidity have been reported following azithromycin mass drug administration (MDA) for trachoma. The recent MORDOR trial reported a reduction in child mortality following biannual azithromycin MDA. Here, we investigate the effects of azithromycin MDA on malaria at the MORDOR-Malawi study site. A cluster-randomized double-blind placebo-controlled trial, with 15 clusters per arm, was conducted. House-to-house census was updated biannually, and azithromycin or placebo syrup was distributed to children aged 1–59 months for a total of four biannual distributions.

NOT Open Access | Effect of Adding Azithromycin to the Antimalarials used for Seasonal Malaria Chemoprevention on the Nutritional Status of African Children

March 18, 2020 - 14:37 -- NOT Open Access
Gore-Langton GR, Cairns M, Ouedraogo JB, et al.
Trop Med Int Health. 2020 Mar 12

Mass administration of azithromycin has reduced mortality in children in sub‐Saharan Africa but its mode of action is not well characterised. A recent trial found that azithromycin given alongside seasonal malaria chemoprevention was not associated with a reduction in mortality or hospital admissions in young children. We investigated the effect of azithromycin on the nutritional status of children enrolled in this study.

Malaria Parasitemia and Nutritional Status during the Low Transmission Season in the Presence of Azithromycin Distribution among Preschool Children in Niger

February 24, 2020 - 13:45 -- Open Access
Arzika AM, Maliki R, Boubacar N, Kane S, Cook CA, Lebas E, Lin Y, O'Brien KS, Austin A, Keenan JD, Lietman TM, Oldenburg CE, For The Mordor Study Group
Am J Trop Med Hyg. 2020 Feb 17

The relationship between malaria and malnutrition is complicated, and existence of one may predispose or exacerbate the other. We evaluated the relationship between malaria parasitemia and nutritional status in children living in communities participating in a cluster-randomized trial of biannual azithromycin compared with placebo for prevention of childhood mortality. Data were collected during the low malaria transmission and low food insecurity season.

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