scholarly journals Efficacy of Single-Dose Primaquine With Artemisinin Combination Therapy on Plasmodium falciparum Gametocytes and Transmission: An Individual Patient Meta-Analysis

2020 ◽  
Author(s):  
Kasia Stepniewska ◽  
Georgina S Humphreys ◽  
Bronner P Gonçalves ◽  
Elaine Craig ◽  
Roly Gosling ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Low Dose ◽  
Meta Analysis ◽  
Artemisinin Combination Therapy ◽  
World Health ◽  
Combination Therapies ◽  
Transmission Blocking ◽  
Gametocyte Carriage ◽  
Rate Of Decline ◽  
Health Organization

Abstract Background Since the World Health Organization recommended single low-dose (0.25 mg/kg) primaquine (PQ) in combination with artemisinin-based combination therapies (ACTs) in areas of low transmission or artemisinin-resistant Plasmodium falciparum, several single-site studies have been conducted to assess efficacy. Methods An individual patient meta-analysis to assess gametocytocidal and transmission-blocking efficacy of PQ in combination with different ACTs was conducted. Random effects logistic regression was used to quantify PQ effect on (1) gametocyte carriage in the first 2 weeks post treatment; and (2) the probability of infecting at least 1 mosquito or of a mosquito becoming infected. Results In 2574 participants from 14 studies, PQ reduced PCR-determined gametocyte carriage on days 7 and 14, most apparently in patients presenting with gametocytemia on day 0 (odds ratio [OR], 0.22; 95% confidence interval [CI], .17–.28 and OR, 0.12; 95% CI, .08–.16, respectively). Rate of decline in gametocyte carriage was faster when PQ was combined with artemether-lumefantrine (AL) compared to dihydroartemisinin-piperaquine (DP) (P = .010 for day 7). Addition of 0.25 mg/kg PQ was associated with near complete prevention of transmission to mosquitoes. Conclusions Transmission blocking is achieved with 0.25 mg/kg PQ. Gametocyte persistence and infectivity are lower when PQ is combined with AL compared to DP.

scholarly journals Significant Efficacy of a Single Low Dose of Primaquine Compared to Stand-Alone Artemisinin Combination Therapy in Reducing Gametocyte Carriage in Cambodian Patients with Uncomplicated Multidrug-Resistant Plasmodium falciparum Malaria

2020 ◽  
Vol 64 (6) ◽  
Author(s):  
Amélie Vantaux ◽  
Saorin Kim ◽  
Eakpor Piv ◽  
Sophy Chy ◽  
Laura Berne ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Low Dose ◽  
Negative Impact ◽  
Controlled Trial ◽  
Artemisinin Combination Therapy ◽  
Artemisinin Resistance ◽  
Multidrug Resistant ◽  
Transmission Blocking ◽  
Content Type ◽  
Gametocyte Carriage

ABSTRACT Since 2012, a single low dose of primaquine (SLDPQ; 0.25 mg/kg of body weight) with artemisinin-based combination therapies has been recommended as the first-line treatment of acute uncomplicated Plasmodium falciparum malaria to interrupt its transmission, especially in low-transmission settings of multidrug resistance, including artemisinin resistance. Policy makers in Cambodia have been reluctant to implement this recommendation due to primaquine safety concerns and a lack of data on its efficacy. In this randomized controlled trial, 109 Cambodians with acute uncomplicated P. falciparum malaria received dihydroartemisinin-piperaquine (DP) alone or combined with SLDPQ on the first treatment day. The transmission-blocking efficacy of SLDPQ was evaluated on days 0, 1, 2, 3, 7, 14, 21, and 28, and recrudescence by reverse transcriptase PCR (RT-PCR) (gametocyte prevalence) and membrane feeding assays with Anopheles minimus mosquitoes (gametocyte infectivity). Without the influence of recrudescent infections, DP-SLDPQ reduced gametocyte carriage 3-fold compared to that achieved with DP. Of 48 patients tested on day 0, only 3 patients were infectious to mosquitoes (∼6%). Posttreatment, three patients were infectious on day 14 (3.5%, 1/29) and on the 1st and 7th days of recrudescence (8.3%, 1/12 for each); this overall low infectivity precluded our ability to assess its transmission-blocking efficacy. Our study confirms the effective gametocyte clearance of SLDPQ when combined with DP in multidrug-resistant P. falciparum infections and the negative impact of recrudescent infections due to poor DP efficacy. Artesunate-mefloquine (ASMQ) has replaced DP, and ASMQ-SLDPQ has been deployed to treat all patients with symptomatic P. falciparum infections to further support the elimination of multidrug-resistant P. falciparum in Cambodia. (This study has been registered at ClinicalTrials.gov under identifier NCT02434952.)

scholarly journals Stavudine dosage reduction: Effect on symptomatic hyperlactataemia and lactic acidosis in patients at Dr George Mukhari Hospital, Pretoria

2013 ◽  
Vol 14 (1) ◽  
pp. 34-35
Author(s):  
M Nlooto ◽  
E Osuch ◽  
W Du Plooy
Keyword(s):  
Side Effects ◽  
Lactic Acidosis ◽  
Low Dose ◽  
Meta Analysis ◽  
World Health ◽  
Resource Limited ◽  
Obese Female ◽  
Reduction Effect ◽  
Health Organization ◽  
Alternative Solutions

A range of studies have demonstrated that symptomatic hyperlactataemia and lactic acidosis are associated with antiretroviral combinations containing stavudine. Following a meta-analysis showing that lower doses of stavudine are safer and as effective, the World Health Organization (WHO) issued a statement that only a low dose of stavudine (30 mg) should be used. We performed a retrospective review of the records of 86 patients (aged 27 - 59 years) initiated on 30 mg or 40 mg stavudine-containing antiretroviral therapy regimens between 2004 and 2006 at the adult HIV clinic at Dr George Mukhari Hospital, Pretoria, South Africa. Our analysis demonstrated that stavudine dose reduction increased the odds of patients being more stable on treatment with fewer reported side-effects. Stavudine-containing regimens should be avoided in obese female patients. Low-dose stavudine (20 mg) may offer alternative solutions in poor or resource-limited settings, with a lower associated risk of toxicity and side-effects; however, virological non-inferiority to the first-line treatment option should be established.

scholarly journals Clinical Efficacy and Safety of Artemisinin-based Combination Therapies in the Treatment of Uncomplicated Plasmodium Falciparum Malaria in Cameroon: A Systematic Review and Meta-Analysis from Individual Patient Data (2004-2020)

2020 ◽  
Author(s):  
Akindeh M. Nji ◽  
Peter Thelma Ngwa Niba ◽  
Palmer Masumbe Netongo ◽  
Innocent M. Ali ◽  
Randolph Ngwafor ◽  
...  
Keyword(s):  
Systematic Review ◽  
Plasmodium Falciparum ◽  
Clinical Efficacy ◽  
Meta Analysis ◽  
Plasmodium Falciparum Malaria ◽  
World Health Organisation ◽  
World Health ◽  
Efficacy And Safety ◽  
Combination Therapies ◽  
Cure Rates

Abstract Background: Cameroon remains a high malaria endemic country. The rapid emergence and spread of Plasmodium falciparum resistant parasites compelled the World Health Organisation (WHO) to recommend the change from monotherapies to artemisinin-based combination therapies (ACTs). This study aimed to assess the clinical efficacy and safety of artemisinin-based combination therapies in the treatment of uncomplicated Plasmodium falciparum malaria in Cameroon from 2004 to 2020.Methods: The preferred reporting items for systematic review and meta-analysis (PRISMA) statement were adopted for the selection of studies. The heterogeneity of the included studies was determined using Cochrane Q and the I2. The random effects model was used as standard to combine studies showing heterogeneity of Cochrane Q with P < 0.10 and I2 > 50.Results: Out of the 4,920 articles and unpublished datasets screened, 16 records with a sample size of 3,737 participants on 8 generic ACTs fulfilled the inclusion criteria. The per protocol (PP) analysis pooled efficacy of the ACTs was 97.9 % (95 % CI, 97.2-98.7, P<0.01). Sub-group analyses were performed for ASAQ, AL and DHAP. The aggregated efficacies of ASAQ, AL and DHAP were 97.5 % (95 % CI, 96.3-98.8, P<0.01), 99.4 % (95 % CI, 98.6-100.0, P=0.39), 98.0 % (95 % CI, 96.3-99.7, P=0.28) respectively. The pooled efficacies were above the WHO minimum benchmark of 90.0%. The ACTs are well tolerated and common adverse events reported were asthenia, diarrhoea, abdominal pain, anorexia, nausea and vomiting, headache and dizziness.Conclusion: This study reported a high pooled efficacy for all ACTs. AL and DHAP were found to have higher cumulative efficacies than ASAQ. The ACTs are still efficacious and well tolerated for the treatment of malaria in Cameroon. However, there is need for continuous monitoring of efficacy of ACTs despite the high cure rates as resistance seems inevitable.

scholarly journals In VitroActivities of Primaquine-Schizonticide Combinations on Asexual Blood Stages and Gametocytes of Plasmodium falciparum

2015 ◽  
Vol 59 (12) ◽  
pp. 7650-7656 ◽  
Author(s):  
Mynthia Cabrera ◽  
Liwang Cui
Keyword(s):  
Plasmodium Falciparum ◽  
World Health ◽  
Combination Therapies ◽  
Content Type ◽  
Synergistic Interactions ◽  
Health Organization ◽  
Potential Interactions ◽  
Artemisinin Combination Therapies ◽  
Antagonistic Interactions

ABSTRACTCurrently, the World Health Organization recommends addition of a 0.25-mg base/kg single dose of primaquine (PQ) to artemisinin combination therapies (ACTs) forPlasmodium falciparummalaria as a gametocytocidal agent for reducing transmission. Here, we investigated the potential interactions of PQ with the long-lasting components of the ACT drugs for eliminating the asexual blood stages and gametocytes ofin vitro-culturedP. falciparumstrains. Using the SYBR green I assay for asexual parasites and a flow cytometry-based assay for gametocytes, we determined the interactions of PQ with the schizonticides chloroquine, mefloquine, piperaquine, lumefantrine, and naphthoquine. With the sums of fractional inhibitory concentrations and isobolograms, we were able to determine mostly synergistic interactions for the various PQ and schizonticide combinations on the blood stages ofP. falciparumlaboratory strains. The synergism in inhibiting asexual stages and gametocytes was highly evident with PQ-naphthoquine, whereas synergism was moderate for the PQ-piperaquine, PQ-chloroquine, and PQ-mefloquine combinations. We have detected potentially antagonistic interactions between PQ and lumefantrine under certain drug combination ratios, suggesting that precautions might be needed when PQ is added as the gametocytocide to the artemether-lumefantrine ACT (Coartem).

scholarly journals Artemisinin-Based Combination Therapy Versus Quinine or Other Combinations for Treatment of Uncomplicated Plasmodium falciparum Malaria in the Second and Third Trimester of Pregnancy: A Systematic Review and Meta-Analysis

2015 ◽  
Vol 3 (1) ◽  
Author(s):  
Renée J. Burger ◽  
Anna M. van Eijk ◽  
Milena Bussink ◽  
Jenny Hill ◽  
Feiko O. ter Kuile
Keyword(s):  
Falciparum Malaria ◽  
Health Workers ◽  
Meta Analysis ◽  
Plasmodium Falciparum Malaria ◽  
World Health ◽  
Combination Therapies ◽  
Third Trimester ◽  
Health Organization ◽  
Uncomplicated Plasmodium Falciparum Malaria ◽  
Better Than

Abstract The World Health Organization recommends artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated falciparum malaria in the second and third trimesters of pregnancy. We conducted a meta-analysis to compare efficacy, safety and tolerability of ACTs versus quinine and other non-ACT antimalarials. The median PCR-adjusted failure rate by days 28 to 63 in the non-ACT group was 6 (range 0–37) per 100 women, lower in the ACT group overall (pooled risk ratio [PRR] random effects, 0.41; 95% confidence interval [CI], 0.16–1.05; 6 trials), and significantly lower compared with oral quinine (PRR, 0.20; 95% CI, 0.08–0.49; 4 trials). There were no differences in fetal deaths and congenital abnormalities. Compared with quinine, artemisinin-based combinations therapies were associated with less tinnitus (PRR, 0.19; 95% CI, 0.03–1.11; 4 studies), dizziness (PRR, 0.64; 95% CI, 0.44–0.93; 3 trials), and vomiting (PRR, 0.33; 95% CI, 0.15–0.73; 3 trials). Artemisinin-based combination therapies are better than quinine in the second and third trimesters; their use should be encouraged among health workers.

The study of Iranian children and adolescents’ physical activity: a systematic review and meta-analysis

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Adel Alizadeh ◽  
Reza Negarandeh ◽  
Fahimehe Bagheri Amiri ◽  
Zahra Yazdani
Keyword(s):  
Physical Activity ◽  
Children And Adolescents ◽  
Meta Analysis ◽  
World Health ◽  
Chi Square ◽  
The Status ◽  
Newcastle Ottawa Scale ◽  
Health Organization ◽  
Iranian Children

Abstract Objectives This systematic and meta-analysis review was conducted to determine the status of Iranian children and adolescents’ physical activity. Content All the related articles which were published in the major databases, including Pubmed, Scopus, Web of Science, Embase, Magiran, SID from the beginning of 2010 to the end of 2019, were reviewed by researchers. The Newcastle-Ottawa scale was also used to evaluate the quality of articles. Moreover, I 2 index and chi-square were used to assess the heterogeneity between the results. Summary 490 articles were found as a result of the search in the selected international and local databases, where finally, 10 articles were included into the meta-analysis after the elimination of the duplicated articles and applying inclusion and exclusion criteria. The results indicated that 29.5% of the girls were considered active according to WHO criteria (16.1–42.8: 95% CI) and also 20.5% of the boys (7.3–33.7: 95% CI). Outlook Overall, this study’s findings showed that a large percentage of Iranian children and adolescents do not achieve the level of physical activity recommended by the World Health Organization. This can lead to undesirable consequences for this group of population that is considered as the human capital of any country; consequently, it seems necessary to take basic measures at the micro and macro levels in order to reduce such problems in the society.

scholarly journals Treatment of COVID-19 with Chloroquine: Implication for Malaria Chemotherapy Using ACTs in Disease Endemic Countries

2020 ◽  
Author(s):  
Neils Ben Quashie ◽  
Nancy Odurowah Duah-Quashie
Keyword(s):  
Intermittent Preventive Treatment ◽  
Preventive Treatment ◽  
World Health ◽  
Cross Resistance ◽  
Drug Resistant ◽  
Combination Therapies ◽  
Parasite Resistance ◽  
Demand And Supply ◽  
First Choice ◽  
Health Organization

Abstract Based on reports of parasite resistance and on World Health Organization recommendation, chloroquine was replaced with the artemisinin-based combination therapies (ACTs) as the first choice of drugs for the treatment of uncomplicated malaria. Disuse of chloroquine led to restoration of drug-sensitive parasite to some extent in certain countries. Ever since chloroquine and hydroxychloroquine were touted as potential treatment for coronavirus disease 2019 (COVID-19), there has been a dramatic surge in demand for the drugs. Even in areas where chloroquine is proscribed, there has been an unexpected increase in demand and supply of the drug. This situation is quite worrying as the indiscriminate use of chloroquine may produce drug-resistant parasites which may impact negatively on the efficacy of amodiaquine due to cross-resistance. Amodiaquine is a partner drug in one of the ACTs and in some of the drugs used for intermittent preventive treatment. We herein discuss the consequences of the escalated use of chloroquine in the management of COVID-19 on chemotherapy or chemoprevention of malaria and offer an advice. We speculate that parasite strains resistant to chloroquine will escalate due to the increased and indiscriminate use of the drug and consequently lead to cross-resistance with amodiaquine which is present in some drug schemes aforementioned. Under the circumstance, the anticipated hope of reverting to the use of the ‘resurrected chloroquine’ to manage malaria in future is likely to diminish. The use of chloroquine and its derivatives for the management of COVID-19 should be controlled.

scholarly journals A living WHO guideline on drugs to prevent covid-19

BMJ ◽  
2021 ◽  
pp. n526
Author(s):  
François Lamontagne ◽  
Thomas Agoritsas ◽  
Reed Siemieniuk ◽  
Bram Rochwerg ◽  
Jessica Bartoszko ◽  
...  
Keyword(s):  
Systematic Review ◽  
Guideline Development ◽  
Meta Analysis ◽  
World Health ◽  
Policy And Practice ◽  
Assessment Development ◽  
Research Priority ◽  
Health Organization ◽  
Almost All ◽  
Drug Interventions

Abstract Clinical question What is the role of drugs in preventing covid-19? Why does this matter? There is widespread interest in whether drug interventions can be used for the prevention of covid-19, but there is uncertainty about which drugs, if any, are effective. The first version of this living guideline focuses on the evidence for hydroxychloroquine. Subsequent updates will cover other drugs being investigated for their role in the prevention of covid-19. Recommendation The guideline development panel made a strong recommendation against the use of hydroxychloroquine for individuals who do not have covid-19 (high certainty). How this guideline was created This living guideline is from the World Health Organization (WHO) and provides up to date covid-19 guidance to inform policy and practice worldwide. Magic Evidence Ecosystem Foundation (MAGIC) provided methodological support. A living systematic review with network analysis informed the recommendations. An international guideline development panel of content experts, clinicians, patients, an ethicist and methodologists produced recommendations following standards for trustworthy guideline development using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Understanding the new recommendation The linked systematic review and network meta-analysis (6 trials and 6059 participants) found that hydroxychloroquine had a small or no effect on mortality and admission to hospital (high certainty evidence). There was a small or no effect on laboratory confirmed SARS-CoV-2 infection (moderate certainty evidence) but probably increased adverse events leading to discontinuation (moderate certainty evidence). The panel judged that almost all people would not consider this drug worthwhile. In addition, the panel decided that contextual factors such as resources, feasibility, acceptability, and equity for countries and healthcare systems were unlikely to alter the recommendation. The panel considers that this drug is no longer a research priority and that resources should rather be oriented to evaluate other more promising drugs to prevent covid-19. Updates This is a living guideline. New recommendations will be published in this article and signposted by update notices to this guideline. Readers note This is the first version of the living guideline for drugs to prevent covid-19. It complements the WHO living guideline on drugs to treat covid-19. When citing this article, please consider adding the update number and date of access for clarity.

scholarly journals Low-dose amikacin in the treatment of Multidrug-resistant Tuberculosis (MDR-TB)

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Natasha F. Sabur ◽  
Mantaj S. Brar ◽  
Lisa Wu ◽  
Sarah K. Brode
Keyword(s):  
Hearing Loss ◽  
Adverse Events ◽  
Low Dose ◽  
Multidrug Resistant ◽  
Significant Rise ◽  
World Health ◽  
Therapeutic Drug ◽  
Successful Treatment Outcome ◽  
Mdr Tb ◽  
Health Organization

Abstract Background The World Health Organization recommends intravenous amikacin for the treatment of MDR-TB at a dose of 15 mg/kg. However, higher doses are associated with significant toxicity. Methods Patients with MDR-TB treated at our institution receive amikacin at 8–10 mg/kg, with dose adjustment based on therapeutic drug monitoring. We conducted a retrospective cohort study of patients with MDR-TB who received amikacin between 2010 and 2016. Results Forty-nine patients were included in the study. The median starting dose of amikacin was 8.9 mg/kg (IQR 8, 10), and target therapeutic drug levels were achieved at a median of 12 days (IQR 5, 26). The median duration of amikacin treatment was 7.2 months (IQR 5.7, 8), and median time to sputum culture conversion was 1 month (IQR 1,2). Six patients (12.2%) experienced hearing loss based on formal audiometry testing (95% CI 4.6–24.8%); 22.2% had subjective hearing loss (95% CI 11.2–37.1%) and 31.9% subjective tinnitus (95% CI 19.1–47.1%). Ten patients (23%) had a significant rise in serum creatinine (95% CI 11.8–38.6%), but only 5 patients had a GFR < 60 at treatment completion. 84% of patients had a successful treatment outcome (95% CI 84–99%). Conclusions Low dose amikacin is associated with relatively low rates of aminoglycoside-related adverse events. We hypothesize that low-dose amikacin can be used as a safe and effective treatment for MDR-TB in situations where an adequate regimen cannot be constructed with Group A and B drugs, and where careful monitoring for adverse events is feasible.

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