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PloS One 2020Plasmodium ovale can infect humans, causing malaria disease. We aimed to investigate the severity and mortality of severe P. ovale infection to increase the awareness of... (Meta-Analysis)
Meta-Analysis
Plasmodium ovale can infect humans, causing malaria disease. We aimed to investigate the severity and mortality of severe P. ovale infection to increase the awareness of physicians regarding the prognosis of this severe disease and outcome-related deaths in countries in which this disease is endemic. Articles that were published in the PubMed, Scopus, and ISI Web of Science databases prior to January 5, 2020 and reported the prevalence of severe P. ovale infection were systematically searched and reviewed. Studies that mainly reported severe P. ovale infection according to the 2014 WHO criteria for the treatment of malaria were included. Two reviewers selected, identified, assessed, and extracted data from studies independently. The pooled prevalence of severe P. ovale mono-infections was estimated using the command "metaprop case population, random/fixed", which yielded the pooled estimate, 95% confidence interval (CI) and the I2 value, indicating the level of heterogeneity. Meta-analyses of the proportions were performed using a random-effects model to explore the different proportions of severity between patients with P. ovale and those with other Plasmodium species infections. Among the eight studies that were included and had a total of 1,365 ovale malaria cases, the pooled prevalence of severe P. ovale was 0.03 (95% CI = 0.03-0.05%, I2 = 54.4%). Jaundice (1.1%), severe anemia (0.88%), and pulmonary impairments (0.59%) were the most common severe complications found in patients infected with P. ovale. The meta-analysis demonstrated that a smaller proportion of patients with P. ovale than of patients with P. falciparum had severe infections (P-value = 0.01, OR = 0.36, 95% CI = 0.16-0.81, I2 = 72%). The mortality rate of severe P. ovale infections was 0.15% (2/1,365 cases). Although severe complications of P. ovale infections in patients are rare, it is very important to increase the awareness of physicians regarding the prognosis of severe P. ovale infections in patients, especially in a high-risk population.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Female; Humans; Infant; Malaria; Male; Middle Aged; Plasmodium falciparum; Plasmodium ovale; Prevalence
PubMed: 32559238
DOI: 10.1371/journal.pone.0235014 -
The American Journal of Tropical... Sep 2020and form dormant liver hypnozoites that can reactivate weeks to months following initial infection. Malaria recurrences caused by relapses are an important cause of... (Meta-Analysis)
Meta-Analysis
and form dormant liver hypnozoites that can reactivate weeks to months following initial infection. Malaria recurrences caused by relapses are an important cause of morbidity and source of transmission. To estimate the proportions of malaria recurrences caused by relapses in different geographical locations, we systematically reviewed clinical efficacy studies of uncomplicated malaria, in which patients were randomized to treatment with or without radical cure primaquine regimens and were followed up for 1 year. The minimum proportion of recurrences caused by relapses was estimated for each study site by assuming primaquine prevented all relapses and did not augment blood-stage efficacy. Of the 261 studies identified, six were eligible enrolling 4,092 patients from 14 treatment arm comparisons across seven countries. Of the 2,735 patients treated with primaquine, 24.3% received low dose (2.5 to < 5.0 mg/kg total) and 75.7% received high-dose primaquine (≥ 5.0 mg/kg total). The overall pooled incidence rate ratio of relapses for patients treated with primaquine versus no primaquine was 0.15 (95% CI: 0.10-0.21; = 83.3%), equating to a minimum of 79% of recurrences attributable to relapse. Country-specific incidence rate ratios ranged from 0.05 (95% CI: 0.01-0.34; one estimate) in Pakistan to 0.34 in Nepal (95% CI: 0.12-0.83; one estimate) and Afghanistan (95% CI: 0.22-0.51; three estimates). Relapses account for a very high proportion of recurrent infections following schizontocidal treatment of acute malaria across diverse geographic locations. This emphasizes the importance of implementing hypnozoitocidal treatment.
Topics: Antimalarials; Geography; Humans; Malaria; Malaria, Vivax; Plasmodium vivax; Primaquine; Recurrence
PubMed: 32524950
DOI: 10.4269/ajtmh.20-0186 -
PLoS Medicine May 2020The radical cure of Plasmodium vivax and P. ovale requires treatment with primaquine or tafenoquine to clear dormant liver stages. Either drug can induce haemolysis in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The radical cure of Plasmodium vivax and P. ovale requires treatment with primaquine or tafenoquine to clear dormant liver stages. Either drug can induce haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, necessitating screening. The reference diagnostic method for G6PD activity is ultraviolet (UV) spectrophotometry; however, a universal G6PD activity threshold above which these drugs can be safely administered is not yet defined. Our study aimed to quantify assay-based variation in G6PD spectrophotometry and to explore the diagnostic implications of applying a universal threshold.
METHODS AND FINDINGS
Individual-level data were pooled from studies that used G6PD spectrophotometry. Studies were identified via PubMed search (25 April 2018) and unpublished contributions from contacted authors (PROSPERO: CRD42019121414). Studies were excluded if they assessed only individuals with known haematological conditions, were family studies, or had insufficient details. Studies of malaria patients were included but analysed separately. Included studies were assessed for risk of bias using an adapted form of the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Repeatability and intra- and interlaboratory variability in G6PD activity measurements were compared between studies and pooled across the dataset. A universal threshold for G6PD deficiency was derived, and its diagnostic performance was compared to site-specific thresholds. Study participants (n = 15,811) were aged between 0 and 86 years, and 44.4% (7,083) were women. Median (range) activity of G6PD normal (G6PDn) control samples was 10.0 U/g Hb (6.3-14.0) for the Trinity assay and 8.3 U/g Hb (6.8-15.6) for the Randox assay. G6PD activity distributions varied significantly between studies. For the 13 studies that used the Trinity assay, the adjusted male median (AMM; a standardised metric of 100% G6PD activity) varied from 5.7 to 12.6 U/g Hb (p < 0.001). Assay precision varied between laboratories, as assessed by variance in control measurements (from 0.1 to 1.5 U/g Hb; p < 0.001) and study-wise mean coefficient of variation (CV) of replicate measures (from 1.6% to 14.9%; p < 0.001). A universal threshold of 100% G6PD activity was defined as 9.4 U/g Hb, yielding diagnostic thresholds of 6.6 U/g Hb (70% activity) and 2.8 U/g Hb (30% activity). These thresholds diagnosed individuals with less than 30% G6PD activity with study-wise sensitivity from 89% (95% CI: 81%-94%) to 100% (95% CI: 96%-100%) and specificity from 96% (95% CI: 89%-99%) to 100% (100%-100%). However, when considering intermediate deficiency (<70% G6PD activity), sensitivity fell to a minimum of 64% (95% CI: 52%-75%) and specificity to 35% (95% CI: 24%-46%). Our ability to identify underlying factors associated with study-level heterogeneity was limited by the lack of availability of covariate data and diverse study contexts and methodologies.
CONCLUSIONS
Our findings indicate that there is substantial variation in G6PD measurements by spectrophotometry between sites. This is likely due to variability in laboratory methods, with possible contribution of unmeasured population factors. While an assay-specific, universal quantitative threshold offers robust diagnosis at the 30% level, inter-study variability impedes performance of universal thresholds at the 70% level. Caution is advised in comparing findings based on absolute G6PD activity measurements across studies. Novel handheld quantitative G6PD diagnostics may allow greater standardisation in the future.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antimalarials; Child; Child, Preschool; Female; Glucosephosphate Dehydrogenase; Glucosephosphate Dehydrogenase Deficiency; Humans; Infant; Infant, Newborn; Malaria; Male; Middle Aged; Spectrophotometry; Young Adult
PubMed: 32407380
DOI: 10.1371/journal.pmed.1003084