scholarly journals In vivo efficacy of anti-malarial drugs against clinical Plasmodium vivax malaria in Ethiopia: a systematic review and meta-analysis

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Tsige Ketema ◽  
Ketema Bacha ◽  
Kefelegn Getahun ◽  
Quique Bassat
Keyword(s):  
Plasmodium Vivax ◽  
Publication Bias ◽  
Vivax Malaria ◽  
Meta Analysis ◽  
Treatment Options ◽  
Significant Heterogeneity ◽  
Radical Cure ◽  
In Vivo Efficacy

Abstract Background Ethiopia is one of the few countries in Africa where Plasmodium vivax commonly co-exists with Plasmodium falciparum, and which accounts for ~ 40% of the total number of malaria infections in the country. Regardless of the growing evidence over many decades of decreasing sensitivity of this parasite to different anti-malarial drugs, there has been no comprehensive attempt made to systematically review and meta-analyse the efficacy of different anti-malarial drugs against P. vivax in the country. However, outlining the efficacy of available anti-malarial drugs against this parasite is essential to guide recommendations for the optimal therapeutic strategy to use in clinical practice. The aim of this study was to synthesize evidence on the efficacy of anti-malarial drugs against clinical P. vivax malaria in Ethiopia. Methods All potentially relevant, peer-reviewed articles accessible in PubMed, Scopus, Web of Science, and Clinical Trial.gov electronic databases were retrieved using a search strategy combining keywords and related database-specific subject terms. Randomized controlled trials (RCTs) and non-randomized trials aiming to investigate the efficacy of anti-malarial drugs against P. vivax were included in the review. Data were analysed using Review Manager Software. Cochrane Q (χ2) and the I2 tests were used to assess heterogeneity. The funnel plot and Egger’s test were used to examine risk of publication bias. Results Out of 1294 identified citations, 14 articles that presented data on 29 treatment options were included in the analysis. These studies enrolled 2144 clinical vivax malaria patients. The pooled estimate of in vivo efficacy of anti-malarial drugs against vivax malaria in Ethiopia was 97.91% (95% CI: 97.29–98.52%), with significant heterogeneity (I2 = 86%, p < 0.0001) and publication bias (Egger’s test = -12.86, p < 0.001). Different anti-malarial drugs showed varied efficacies against vivax malaria. The duration of follow-up significantly affected the calculated efficacy of any given anti-malarial drug, with longer duration of the follow-up (42 days) associated with significantly lower efficacy than efficacy reported on day 28. Also, pooled PCR-corrected efficacy and efficacy estimated from altitudinally lower transmission settings were significantly higher than PCR-uncorrected efficacy that estimated for moderate transmission settings, respectively. Conclusion The overall efficacy of anti-malarial drugs evaluated for the treatment of vivax malaria in Ethiopia was generally high, although there was wide-ranging degree of efficacy, which was affected by the treatment options, duration of follow-up, transmission intensity, and the confirmation procedures for recurrent parasitaemia. Regardless of evidence of sporadic efficacy reduction reported in the country, chloroquine (CQ), the first-line regimen in Ethiopia, remained highly efficacious, supporting its continuous utilization for confirmed P. vivax mono-infections. The addition of primaquine (PQ) to CQ is recommended, as this is the only approved way to provide radical cure, and thus ensure sustained efficacy and longer protection against P. vivax. Continuous surveillance of the efficacy of anti-malarial drugs and clinical trials to allow robust conclusions remains necessary to proactively act against possible emergence and spread of drug-resistant P. vivax in Ethiopia.

scholarly journals Monitoring the Efficacy of Chloroquine-Primaquine Therapy for Uncomplicated Plasmodium vivax Malaria in the Main Transmission Hot Spot of Brazil

2019 ◽  
Vol 63 (5) ◽  
Author(s):  
Simone Ladeia-Andrade ◽  
Maria José Menezes ◽  
Taís Nóbrega de Sousa ◽  
Ana Carolina R. Silvino ◽  
Jaques F. de Carvalho ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
Amazon Basin ◽  
Ex Vivo ◽  
Hot Spot ◽  
Radical Cure ◽  
Content Type ◽  
Plasmodium Vivax Malaria

ABSTRACT Emerging Plasmodium vivax resistance to chloroquine (CQ) may undermine malaria elimination efforts in South America. CQ-resistant P. vivax has been found in the major port city of Manaus but not in the main malaria hot spots across the Amazon Basin of Brazil, where CQ is routinely coadministered with primaquine (PQ) for radical cure of vivax malaria. Here we randomly assigned 204 uncomplicated vivax malaria patients from Juruá Valley, northwestern Brazil, to receive either sequential (arm 1) or concomitant (arm 2) CQ-PQ treatment. Because PQ may synergize the blood schizontocidal effect of CQ and mask low-level CQ resistance, we monitored CQ-only efficacy in arm 1 subjects, who had PQ administered only at the end of the 28-day follow-up. We found adequate clinical and parasitological responses in all subjects assigned to arm 2. However, 2.2% of arm 1 patients had microscopy-detected parasite recrudescences at day 28. When PCR-detected parasitemias at day 28 were considered, response rates decreased to 92.1% and 98.8% in arms 1 and 2, respectively. Therapeutic CQ levels were documented in 6 of 8 recurrences, consistent with true CQ resistance in vivo. In contrast, ex vivo assays provided no evidence of CQ resistance in 49 local P. vivax isolates analyzed. CQ-PQ coadministration was not found to potentiate the antirelapse efficacy of PQ over 180 days of surveillance; however, we suggest that larger studies are needed to examine whether and how CQ-PQ interactions, e.g., CQ-mediated inhibition of PQ metabolism, modulate radical cure efficacy in different P. vivax-infected populations. (This study has been registered at ClinicalTrials.gov under identifier NCT02691910.)

scholarly journals Correlation between Soluble α-Klotho and Renal Function in Patients with Chronic Kidney Disease: A Review and Meta-Analysis

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Qinglian Wang ◽  
Wenyan Su ◽  
Zhenwei Shen ◽  
Rong Wang
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Correlation Coefficient ◽  
Publication Bias ◽  
Meta Analysis ◽  
Significant Negative Correlation ◽  
Significant Heterogeneity ◽  
Fgf 23

Objective. Over decades, numerous inconsistent studies are reported on the relationship between soluble α-Klotho and renal function in patients with chronic kidney disease (CKD). This study aims to perform a meta-analysis to figure out the correlations between soluble α-Klotho and renal function in patients with CKD. Materials and Methods. We searched medical and scientific literature databases, PubMed and EMBASE (from the inception to October 2017), for publications that reported studies on associations between soluble α-Klotho and renal function in patients with CKD. Only publications in English were extracted. Summary correlation coefficient (r) values were extracted from each study, and 95% confidence intervals (CIs) were calculated. Publication bias was tested, and sensitivity and subgroup analyses were performed to investigate potential heterogeneity. Results. Of 611 studies, 9 publications with 1457 patients were included into the analysis. The following data were extracted from the literature: first author, year of publication, research region, research index, sample size, average age and Pearson or Spearman correlation coefficient, study design, the αKlotho/FGF23 assays utilized, full length, or the C-terminal fragment of FGF23. The pooled r between α-Klotho and estimated glomerular filtration rate (eGFR), FGF-23 were 0.35 (95%CI, 0.23~0.46, and P<0.05), -0.10 (95%CI, -0.19~-0.01, and P<0.05) with remarkable significance, indicating moderate heterogeneity. There was no significant heterogeneity between subgroups in analyses of α-Klotho and eGFR stratified by research region, mean age, and eGFR, but heterogeneity exists in analyses of α-Klotho and FGF-23 stratified by research region. There was no significant correlation between a-klotho and Ca and PTH and PHOS. There was no evidence of publication bias with Egger’s test (p=0.360) or with Begg’s test (p=0.902) and the distribution of funnel plots was symmetrical in all of our analysis. Conclusions. There exists a significant positive correlation between soluble α-Klotho and eGFR in patients with CKD. Also, a significant negative correlation between α-Klotho and FGF23 levels is proven. This raises hope to employ αKlotho and FGF23 as early biomarkers of CKD. However, further large prospective follow-up researches are needed to validate this hypothesis and to explore whether maintaining or elevating the Klotho level could improve renal function and complications in CKD patients.

scholarly journals Efficacy of Primaquine in Preventing Short- and Long-Latency Plasmodium vivax Relapses in Nepal

2019 ◽  
Vol 220 (3) ◽  
pp. 448-456 ◽  
Author(s):  
Komal Raj Rijal ◽  
Bipin Adhikari ◽  
Prakash Ghimire ◽  
Megha Raj Banjara ◽  
Garib Das Thakur ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
Standard Dose ◽  
Radical Cure ◽  
Multiplicity Of Infection ◽  
Microsatellite Genotyping ◽  
Long Latency ◽  
To Receive ◽  
Relapse Patterns

Abstract Background Plasmodium vivax is the main cause of malaria in Nepal. Relapse patterns have not been characterized previously. Methods Patients with P. vivax malaria were randomized to receive chloroquine (CQ; 25 mg base/kg given over 3 days) alone or together with primaquine (PQ; 0.25 mg base/kg/day for 14 days) and followed intensively for 1 month, then at 1- to 2-month intervals for 1 year. Parasite isolates were genotyped. Results One hundred and one (49%) patients received CQ and 105 (51%) received CQ + PQ. In the CQ + PQ arm, there were 3 (4.1%) recurrences in the 73 patients who completed 1 year of follow-up compared with 22 of 78 (28.2%) in the CQ-only arm (risk ratio, 0.146 [95% confidence interval, .046–.467]; P &lt; .0001). Microsatellite genotyping showed relatively high P. vivax genetic diversity (mean heterozygosity, 0.843 [range 0.570–0.989] with low multiplicity of infection (mean, 1.05) reflecting a low transmission preelimination setting. Of the 12 genetically homologous relapses, 5 (42%) occurred in a cluster after 9 months, indicating long latency. Conclusions Although there may be emerging CQ resistance, the combination of CQ and the standard-dose 14-day PQ regimen is highly efficacious in providing radical cure of short- and long-latency P. vivax malaria in Nepal.

scholarly journals Plasmodium vivax epidemiology in Ethiopia 2000-2020: A systematic review and meta-analysis

2021 ◽  
Vol 15 (9) ◽  
pp. e0009781
Author(s):  
Tsige Ketema ◽  
Ketema Bacha ◽  
Kefelegn Getahun ◽  
Hernando A. del Portillo ◽  
Quique Bassat
Keyword(s):  
Systematic Review ◽  
Plasmodium Vivax ◽  
Publication Bias ◽  
Systematic Reviews ◽  
Meta Analysis ◽  
Infection Prevalence ◽  
Clear Understanding ◽  
Significant Heterogeneity ◽  
Funnel Plot ◽  
Study Setting

Background Ethiopia is one of the scarce rare African countries where Plasmodium vivax and P. falciparum co-exist. There has been no attempt to derive a robust prevalence estimate of P. vivax in the country although a clear understanding of the epidemiology of this parasite is essential for informed decisions. This systematic review and meta-analysis, therefore, is aimed to synthesize the available evidences on the distribution of P. vivax infection by different locations/regions, study years, eco-epidemiological zones, and study settings in Ethiopia. Methods This study was conducted in accordance with Preferred Reposting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. Studies conducted and published over the last two decades (2000 to 2020) that reported an estimate of P. vivax prevalence in Ethiopia were included. The Cochrane Q (χ2) and the I2 tests were used to assess heterogeneity, and the funnel plot and Egger’s test were used to examine publication bias. A p-value of the χ2 test <0.05 and an I2 value >75% were considered presence of considerable heterogeneity. Random effect models were used to obtain pooled estimate of P. vivax infection prevalence. This study is registered with PROSPERO (International Prospective Register of Systematic Reviews): ID CRD42020201761. Results We screened 4,932 records and included 79 studies that enrolled 1,676,659 confirmed malaria cases, from which 548,214 (32.69%) were P. vivax infections and 1,116,581 (66.59%) were due to P. falciparum. The rest (11,864 or 0.7%) were due to mixed infections. The pooled estimate of P. vivax prevalence rate was 8.93% (95% CI: 7.98–9.88%) with significant heterogeneity (I2 = 100%, p<0.0001). Regional differences showed significant effects (p<0.0001, and I2 = 99.4%) on the pooled prevalence of P. vivax, while study years (before and after the scaling up of interventional activities) did not show significant differences (p = 0.9, I2 = 0%). Eco-epidemiological zones considered in the analysis did show a significant statistical effect (p<0.001, I2 = 78.5%) on the overall pooled estimate prevalence. Also, the study setting showed significant differences (p = 0.001, and I2 = 90.3%) on the overall prevalence, where significant reduction of P. vivax prevalence (4.67%, 95%CI: 1.41–7.93%, p<0.0001) was observed in studies conducted at the community level. The studies included in the review demonstrated lack of publication bias qualitatively (symmetrical funnel plot) and quantitatively [Egger’s test (coefficient) = -2.97, 95% CI: -15.06–9.13, p = 0.62]. Conclusion The estimated prevalence of P. vivax malaria in Ethiopia was 8.93% with P. vivax prevailing in the central west region of Ethiopia, but steadily extending to the western part of the country. Its distribution across the nation varies according to geographical location, study setting and study years.

scholarly journals Protective effect of Mediterranean-type glucose-6-phosphate dehydrogenase deficiency against Plasmodium vivax malaria

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Ghulam R Awab ◽  
Fahima Aaram ◽  
Natsuda Jamornthanyawat ◽  
Kanokon Suwannasin ◽  
Watcharee Pagornrat ◽  
...  
Keyword(s):  
Protective Effect ◽  
Plasmodium Vivax ◽  
G6pd Deficiency ◽  
Vivax Malaria ◽  
Malaria Incidence ◽  
Large Population ◽  
Credible Interval ◽  
Radical Cure ◽  
Plasmodium Vivax Malaria ◽  
Glucose 6 Phosphate Dehydrogenase

X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzymopathy. The severe Mediterranean variant (G6PD Med) found across Europe and Asia is thought to confer protection against malaria, but its effect is unclear. We fitted a Bayesian statistical model to observed G6PD Med allele frequencies in 999 Pashtun patients presenting with acute Plasmodium vivax malaria and 1408 population controls. G6PD Med was associated with reductions in symptomatic P. vivax malaria incidence of 76% (95% credible interval [CI], 58–88) in hemizygous males and homozygous females combined and 55% (95% CI, 38–68) in heterozygous females. Unless there is very large population stratification within the Pashtun (confounding these results), the G6PD Med genotype confers a very large and gene-dose proportional protective effect against acute vivax malaria. The proportion of patients with vivax malaria at risk of haemolysis following 8-aminoquinoline radical cure is substantially overestimated by studies measuring G6PD deficiency prevalence in healthy subjects.

Abstract 14339: Nonalcoholic Fatty Liver Disease and the Risk of Clinical Cardiovascular Events: A Meta-Analysis

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Toufik Mahfood Haddad ◽  
Shadi Hamdeh ◽  
Mahesh Anantha Narayanan ◽  
Arun Kanmanthareddy ◽  
Venkata M Alla
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Publication Bias ◽  
Fatty Liver Disease ◽  
Cardiovascular Events ◽  
Meta Analysis ◽  
Significant Heterogeneity ◽  
Cross Sectional ◽  
Nonalcoholic Fatty Liver

Background: Numerous studies have assessed the association of Nonalcoholic fatty liver disease (NAFLD) withcardiovascular disease (CVD). However, results have been conflicting due to variability in definitionsof NAFLD and ascertainment of CVD, often combining clinical and surrogate endpoints. We therefore systematically reviewed published literature to assess the association between NAFLD and clinical cardiovascular events. Methods: We searched Medline, Cochrane, google scholar, CINAHL, and Web of Sciencedatabasesusing terms “nonalcoholic fatty liver disease”, “cardiovascular disease”, and their combinations to identify studies published through March 2015. Data from selected studies was extracted and meta-analysis was then performed using Random effects model following the PRISMA guidelines. Publication bias and heterogeneity wereassessed. The main outcome measure was Odds ratio (OR) with 95% CI. Clinical CVD was defined as symptomatic coronary artery disease, myocardial infarction, coronary or peripheral intervention, ischemic stroke, and symptomatic peripheral vascular disease. Results: A total of 7 studies with 14634 patients (NAFLD: 4204; controls: 10430) were included in the final analysis. 3 studies were cross- sectional reporting prevalence, while 4 studies were prospective cohort studies reporting incidence. Patients with NAFLD had a significantly higher risk of clinical CVD compared to controls [OR: 3.17; 95% CI: 1.89-5.30, P<0.01) (figure 1A). There was significant heterogeneity (I2=93%). Funnel plot and Begg’s test did not reveal significant publication bias. Separate analyses of the cohort and cross sectional studies and exclusion sensitivity analysis did not alter the findings (figure 1B). Conclusion: NAFLD is associated with a three fold increase in the risk of clinical CVD compared to controls without NAFLD. These results need to be conformed in large prospective studies.

Significantly lower annual rates of neoplastic progression in short- compared to long-segment non-dysplastic Barrett’s esophagus: a systematic review and meta-analysis

Endoscopy ◽  
2019 ◽  
Vol 51 (07) ◽  
pp. 665-672 ◽  
Author(s):  
Viveksandeep Thoguluva Chandrasekar ◽  
Nour Hamade ◽  
Madhav Desai ◽  
Tarun Rai ◽  
Venkata Subhash Gorrepati ◽  
...  
Keyword(s):  
Systematic Review ◽  
Barrett’S Esophagus ◽  
Barrett's Esophagus ◽  
Meta Analysis ◽  
Significant Heterogeneity ◽  
Neoplastic Progression ◽  
Number Of Patients ◽  
The Mean ◽  
Surveillance Endoscopy

Abstract Background Although shorter lengths of Barrett’s esophagus (BE) have been associated with a lower risk of neoplastic progression, precise estimates have varied, especially for non-dysplastic BE (NDBE) only. Therefore, current US guidelines do not provide specific recommendations on surveillance intervals based on BE length. We performed a systematic review and meta-analysis of the published literature to examine neoplastic progression rates of NDBE based on BE length. Methods PubMed, Cochrane, Google Scholar, and Embase were comprehensively searched. Studies reporting progression rates in patients with NDBE and > 1 year of follow-up were included. The number of patients progressing to esophageal adenocarcinoma (EAC) and high grade dysplasia (HGD)/EAC in individual studies and the mean follow-up were recorded to derive person-years of follow-up. Pooled rates of progression to EAC and HGD/EAC based on BE length (< 3 cm vs. ≥ 3 cm) were calculated. Results Of the 486 initial studies identified, 10 met the inclusion/exclusion criteria. These included a total of 4097 NDBE patients; 1979 with short-segment BE (SSBE; 10 773 person-years of follow-up) and 2118 with long-segment BE (LSBE; 12 868 person-years). The annual rates of progression to EAC were significantly lower for SSBE compared with LSBE: 0.06 % (95 % confidence interval 0.01 % – 0.10 %) vs. 0.31 % (0.21 % – 0.40 %), respectively; odds ratio (OR) 0.25 (0.11 – 0.56); P < 0.001, as were the rates for the combined endpoint (HGD/EAC): 0.24 % (0.09 % – 0.32 %) vs. 0.76 % (0.43 % – 0.89 %), respectively; OR 0.35 (0.21 – 0.58); P < 0.001. There was no significant heterogeneity among studies. Conclusion The results demonstrate significantly lower rates of neoplastic progression in NDBE patients with SSBE compared with LSBE. BE length can easily be used for risk stratification purposes for NDBE patients undergoing surveillance endoscopy and consideration should be given to tailoring surveillance intervals based on BE length in future US guidelines.

Efficacy of Internet-Delivered Psychodynamic Therapy: Systematic Review and Meta-Analysis

2020 ◽  
Vol 48 (4) ◽  
pp. 437-454
Author(s):  
Tomas Lindegaard ◽  
Matilda Berg ◽  
Gerhard Andersson
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Psychodynamic Therapy ◽  
Significant Heterogeneity ◽  
Psychodynamic Treatment ◽  
Literature Searches ◽  
Treatment Models ◽  
Promising Treatment

Recent years have seen an increase of internet-delivered interventions based on psychodynamic treatment models. To test the efficacy of internet-delivered psychodynamic therapy (IPDT), we conducted a systematic review and meta-analysis of randomized controlled trials. Following literature searches, we identified seven studies meeting inclusion criteria. The total number of participants was 528 in the treatment group and 552 in the control conditions. We found small effects favoring IPDT compared to inactive control conditions for main outcomes (g = 0.44), depression (g = 0.46), anxiety (g = 0.20), and quality of life (g = 0.40). There was significant heterogeneity between studies for main outcomes and depression. Within-group effects ranged from Hedges's g = 0.32–0.99. The effects of IPDT were maintained or increased at follow-up. Study quality varied but was generally high. No indications of publication bias were found. In conclusion, IPDT is a promising treatment alternative, especially for depression, although the small number of studies limits the generalizability of the findings.

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