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Expert Opinion on Drug Safety Mar 2021: A century-long history in 8-aminoquinolines, the only anti-malaria drug class preventing malaria relapse, has resulted in the approval of tafenoquine by the U.S. Food... (Meta-Analysis)
Meta-Analysis
: A century-long history in 8-aminoquinolines, the only anti-malaria drug class preventing malaria relapse, has resulted in the approval of tafenoquine by the U.S. Food and Drug Administration (FDA) and the Australian Therapeutic Goods Administration (TGA) and to date registration in Brazil and Thailand. Tafenoquine is an alternative anti-relapse treatment for vivax malaria and malaria prophylaxis. It should not be given in pregnancy, during lactation of infants with glucose-6-phosphate dehydrogenase (G6PD) unknown or deficient status, and in those with G6PD deficiency or psychiatric illness.: This systematic review assesses tafenoquine associated adverse events in English-language, human clinical trials. Meta-analysis of commonly reported adverse events was conducted and grouped by comparison arms.: Tafenoquine, either for radical cure or prophylaxis, is generally well tolerated in adults. There is no convincing evidence for neurologic, ophthalmic, and cardiac toxicities. Psychotic disorder which has been attributed to higher doses is a contraindication for the chemoprophylaxis indication and psychiatric illness is a warning for the radical cure indication. Pregnancy assessment and quantitative G6PD testing are required. The optimal radical curative regimen including the tafenoquine dose along with its safety for parts of Southeast Asia, South America, and Oceania needs further assessment.
Topics: Adult; Aminoquinolines; Animals; Antimalarials; Dose-Response Relationship, Drug; Glucosephosphate Dehydrogenase Deficiency; Humans; Malaria, Vivax; Mental Disorders
PubMed: 33306921
DOI: 10.1080/14740338.2021.1859476 -
Malaria Journal Nov 2022This review article aims to investigate the genotypic profiles of Plasmodium falciparum and Plasmodium vivax isolates collected across a wide geographic region and their... (Review)
Review
This review article aims to investigate the genotypic profiles of Plasmodium falciparum and Plasmodium vivax isolates collected across a wide geographic region and their association with resistance to anti-malarial drugs used in Indonesia. A systematic review was conducted between 1991 and date. Search engines, such as PubMed, Science Direct, and Google Scholar, were used for articles published in English and Indonesian to search the literature. Of the 471 initially identified studies, 61 were selected for 4316 P. falciparum and 1950 P. vivax individual infections. The studies included 23 molecular studies and 38 therapeutic efficacy studies. K76T was the most common pfcrt mutation. K76N (2.1%) was associated with the haplotype CVMNN. By following dihydroartemisinin-piperaquine (DHA-PPQ) therapy, the mutant pfmdr1 alleles 86Y and 1034C were selected. Low prevalence of haplotype N86Y/Y184/D1246Y pfmdr1 reduces susceptibility to AS-AQ. SNP mutation pvmdr1 Y976F reached 96.1% in Papua and East Nusa Tenggara. Polymorphism analysis in the pfdhfr gene revealed 94/111 (84.7%) double mutants S108N/C59R or S108T/A16V in Central Java. The predominant pfdhfr haplotypes (based on alleles 16, 51, 59,108, 164) found in Indonesia were ANCNI, ANCSI, ANRNI, and ANRNL. Some isolates carried A437G (35.3%) or A437G/K540E SNPs (26.5%) in pfdhps. Two novel pfdhps mutant alleles, I588F/G and K540T, were associated with six pfdhps haplotypes. The highest prevalence of pvdhfr quadruple mutation (F57L/S58R/T61M/S117T) (61.8%) was detected in Papua. In pvdhps, the only polymorphism before and after 2008 was 383G mutation with 19% prevalence. There were no mutations in the pfk13 gene reported with validated and candidate or associated k13 mutation. An increased copy number of pfpm2, associated with piperaquine resistance, was found only in cases of reinfection. Meanwhile, mutation of pvk12 and pvpm4 I165V is unlikely associated with ART and PPQ drug resistance. DHA-PPQ is still effective in treating uncomplicated falciparum and vivax malaria. Serious consideration should be given to interrupt local malaria transmission and dynamic patterns of resistance to anti-malarial drugs to modify chemotherapeutic policy treatment strategies. The presence of several changes in pfk13 in the parasite population is of concern and highlights the importance of further evaluation of parasitic ART susceptibility in Indonesia.
Topics: Plasmodium vivax; Plasmodium falciparum; Indonesia; Antimalarials; Artemisinins; Polymorphism, Single Nucleotide; Drug Resistance
PubMed: 36443817
DOI: 10.1186/s12936-022-04385-2 -
The American Journal of Tropical... Sep 2017Malaria, a major global public health problem, is mainly caused by and , and is responsible for nearly half a million deaths annually. Although malaria was not... (Meta-Analysis)
Meta-Analysis Review
Malaria, a major global public health problem, is mainly caused by and , and is responsible for nearly half a million deaths annually. Although malaria was not believed to cause severe disease, recent robust studies have proved otherwise. However, the clinical spectrum and pathogenesis of severe vivax malaria and, especially, its respiratory complications remain poorly understood. A systematic search for articles reporting respiratory complications associated with vivax malaria was performed in Lilacs, Cochrane, Scielo, Web of Science, and Medline databases irrespective of publication date. Prevalence of acute respiratory distress syndrome ARDS) and associated mortality among vivax patients were calculated from cross-sectional and longitudinal studies, whereas factors associated with mortality were calculated from data pooled from case reports and series of cases. A total of 101 studies were included (49 cross-sectional or longitudinal and 52 case reports or series of cases). Prevalence of ARDS was 2.8% and 2.2% in children and adults, respectively, with nearly 50% mortality. Moreover, female sex ( = 0.013), having any comorbidity ( = 0.036), lower body temperature ( = 0.032), lower hemoglobin ( = 0.043), and oxygen saturation ( = 0.053) values were significantly associated with mortality. malaria respiratory complications included ARDS and were associated with high mortality. Demographics and clinical characteristics upon presentation to hospital were associated with mortality among patients with respiratory complications in vivax malaria. This study reaffirms the evidence of severe and fatal complications of malaria and its associated respiratory complications.
Topics: Global Health; Humans; Malaria, Vivax; Respiratory Tract Diseases
PubMed: 28722625
DOI: 10.4269/ajtmh.17-0131 -
PLoS Neglected Tropical Diseases Aug 2014Plasmodium vivax is one of the major species of malaria infecting humans. Although emphasis on P. falciparum is appropriate, the burden of vivax malaria should be given... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Plasmodium vivax is one of the major species of malaria infecting humans. Although emphasis on P. falciparum is appropriate, the burden of vivax malaria should be given due attention. This study aimed to synthesize the evidence on severe malaria in P. vivax infection compared with that in P. falciparum infection.
METHODS/PRINCIPAL FINDINGS
We searched relevant studies in electronic databases. The main outcomes required for inclusion in the review were mortality, severe malaria (SM) and severe anaemia (SA). The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale. Overall, 26 studies were included. The main meta-analysis was restricted to the high quality studies. Eight studies (n = 27490) compared the incidence of SM between P. vivax infection and P. falciparum mono-infection; a comparable incidence was found in infants (OR: 0.45, 95% CI:0.04-5.68, I2:98%), under 5 year age group (OR: 2.06, 95% CI: 0.83-5.1, I2:83%), the 5-15 year-age group (OR: 0.6, 95% CI: 0.31-1.16, I2:81%) and adults (OR: 0.83, 95% CI: 0.67-1.03, I2:25%). Six studies reported the incidences of SA in P. vivax infection and P. falciparum mono-infection; a comparable incidence of SA was found among infants (OR: 3.47, 95%:0.64-18.94, I2: 92%), the 5-15 year-age group (OR:0.71, 95% CI: 0.06-8.57, I2:82%). This was significantly lower in adults (OR:0.75, 95% CI: 0.62-0.92, I2:0%). Five studies (n = 71079) compared the mortality rate between vivax malaria and falciparum malaria. A lower rate of mortality was found in infants with vivax malaria (OR:0.61, 95% CI:0.5-0.76, I2:0%), while this was comparable in the 5-15 year- age group (OR: 0.43, 95% CI:0.06-2.91, I2:84%) and the children of unspecified-age group (OR: 0.77, 95% CI:0.59-1.01, I2:0%).
CONCLUSION
Overall, the present analysis identified that the incidence of SM in patients infected with P. vivax was considerable, indicating that P. vivax is a major cause of SM. Awareness of the clinical manifestations of vivax malaria should prompt early detection. Subsequent treatment and monitoring of complications can be life-saving.
Topics: Adolescent; Adult; Anemia; Child; Child, Preschool; Chloroquine; Drug Resistance; Humans; Infant; Malaria, Falciparum; Malaria, Vivax; Respiratory Distress Syndrome
PubMed: 25121491
DOI: 10.1371/journal.pntd.0003071 -
Malaria Journal Sep 2015An accurate estimate of Plasmodium vivax prevalence is essential for the successful implementation of malaria control and elimination programmes. Prevalence estimates... (Comparative Study)
Comparative Study Review
BACKGROUND
An accurate estimate of Plasmodium vivax prevalence is essential for the successful implementation of malaria control and elimination programmes. Prevalence estimates both inform control strategies and are used in their evaluation. Light microscopy is the main method for detecting Plasmodium parasitaemia in the peripheral blood, but compared to molecular diagnostics, such as polymerase chain reaction (PCR), has limited sensitivity.
METHODS
A systematic review and meta-analysis was conducted to assess the effect of detection method on the prevalence of P. vivax and to quantify the extent to which P. vivax infections are undetected by microscopy. Embase, Medline and the Cochrane Database were searched for studies reporting prevalence by PCR and by microscopy and that contained all of the following key words: vivax, PCR, and malaria. Prevalence estimates and study meta-data were extracted systematically from each publication. Combined microscopy:PCR prevalence ratios were estimated by random effects meta-analysis. Sensitivity and specificity of microscopy were calculated using PCR as the gold standard.
RESULTS
Of 874 studies reviewed, 40 met the criteria for inclusion contributing 54 prevalence pairs. The prevalence of P. vivax infection measured by PCR was consistently higher than the prevalence measured by microscopy with sub-patent parasitaemia. The mean prevalence of infection detected by microscopy was 67 % (95 % CI 59-73 %) lower than the prevalence detected by PCR. The detection of sub-patent parasitaemia did not vary according to the microscopy method (thick or, thick and thin smears), the PCR prevalence (as a measure of the true P. vivax prevalence), the type of blood used or DNA extraction method.
CONCLUSIONS
Quantifying P. vivax parasitaemia by PCR rather than microscopy consistently increased prevalence estimates by a factor of 2.3. Whilst the sensitivity of microscopy can be improved by better methods, molecular methods have potential to be scaled up to improve the detection of P. vivax transmission reservoirs.
Topics: Humans; Malaria, Vivax; Microscopy; Molecular Diagnostic Techniques; Prevalence; Sensitivity and Specificity
PubMed: 26390924
DOI: 10.1186/s12936-015-0884-z -
Malaria Research and Treatment 2019Malaria is a protozoan disease caused by the species. Among the five species. Among the five and malaria are by far the most predominant and widely Malaria is one... (Review)
Review
BACKGROUND
Malaria is a protozoan disease caused by the species. Among the five species. Among the five and malaria are by far the most predominant and widely Malaria is one of the leading causes of morbidity and mortality globally, particularly in the sub-Saharan countries including Ethiopia. It is also a major obstacle to socio-economic development in the country.
METHODS
Articles were searched from PubMed, Google Scholar, and Science Direct databases. The pooled prevalence estimates were analyzed using the DerSimonian-Laird random-effects model and the possible sources of heterogeneity were evaluated through subgroup analysis, metaregression, and sensitivity analysis. Publication bias was analyzed using funnel plots and Egger's test statistics. The data management and analysis were done using STATA 15.1 version software.
RESULTS
Among 922 studies initially identified, thirty-five full-text articles fulfilled the inclusion criteria and included in the study. The combined, and malaria are by far the most predominant and widely.
CONCLUSIONS
This systematic review and meta-analysis showed a high malaria prevalence in Ethiopia. Therefore, previous prevention and control measures should be revised and/or strengthened as appropriate and new strategies should be implemented. In addition, technical, financial and material support, and coordination of the regional capacity building and logistics should be adequately implemented.
PubMed: 32089818
DOI: 10.1155/2019/7065064 -
PLoS Neglected Tropical Diseases Sep 2021Ethiopia is one of the scarce African countries where Plasmodium vivax and P. falciparum co-exist. There has been no attempt to derive a robust prevalence estimate of P.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ethiopia is one of the scarce 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 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.
Topics: Ethiopia; Humans; Malaria, Vivax; Plasmodium vivax
PubMed: 34525091
DOI: 10.1371/journal.pntd.0009781 -
International Journal For Parasitology.... Aug 2017Recurrent P. vivax infections are associated with significant morbidity and mortality. Although radical cure can reduce recurrent infection, it is confounded by... (Review)
Review
INTRODUCTION
Recurrent P. vivax infections are associated with significant morbidity and mortality. Although radical cure can reduce recurrent infection, it is confounded by antimalarial resistance and the lack of safe and effective hypnozoitocidal treatment. This study documents the available literature of published clinical trials of P. vivax, providing an up to date, online, open access tool to view and download available information.
METHODS
A systematic review was conducted according to PRISMA guidelines to identify prospective P. vivax therapeutic clinical trials with at least 28 days follow-up published between 1st January 1960 and 12th October 2016. Treatment arms and evidence of chloroquine resistance were mapped to trial sites.
RESULTS
Since 1960, a total of 1152 antimalarial clinical trials with a minimum 28 days follow-up have been published, of which 230 (20.0%) enrolled patients with P. vivax and were included. Trials were conducted in 38 countries: 168 (73.0%) in the Asia-Pacific, 13 (5.7%) in Africa and 43 (18.7%) in the Americas. The proportion of antimalarial trials assessing P. vivax rose from 10.7% (12/112) in 1991-1995, to 24.9% (56/225) in 2011-2015. Overall, 188 (81.7%) P. vivax trials included a chloroquine treatment arm, either alone or in combination with primaquine, and 107 (46.5%) trials included a chloroquine treatment arm with early primaquine to assess radical cure. There has been a recent increase in treatment arms with artemisinin derivatives. Of the 131 sites in which chloroquine resistance could be quantified, resistance was present in 59 (45.0%) sites in 15 endemic countries.
CONCLUSIONS
Over the last 20 years there has been a substantial increase in clinical research on the treatment of P. vivax, which has generated a greater awareness of the global extent of chloroquine resistance. The WWARN open access, online interactive map provides up to date information of areas where drug resistant P. vivax is emerging.
Topics: Africa; Americas; Antimalarials; Asia; Chloroquine; Clinical Trials as Topic; Databases, Factual; Drug Resistance; Humans; Malaria, Vivax; Online Systems
PubMed: 28384505
DOI: 10.1016/j.ijpddr.2017.03.003 -
PLoS Medicine Jan 2022Plasmodium vivax infects an estimated 7 million people every year. Previously, vivax malaria was perceived as a benign condition, particularly when compared to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Plasmodium vivax infects an estimated 7 million people every year. Previously, vivax malaria was perceived as a benign condition, particularly when compared to falciparum malaria. Reports of the severe clinical impacts of vivax malaria have been increasing over the last decade.
METHODS AND FINDINGS
We describe the main clinical impacts of vivax malaria, incorporating a rapid systematic review of severe disease with meta-analysis of data from studies with clearly defined denominators, stratified by hospitalization status. Severe anemia is a serious consequence of relapsing infections in children in endemic areas, in whom vivax malaria causes increased morbidity and mortality and impaired school performance. P. vivax infection in pregnancy is associated with maternal anemia, prematurity, fetal loss, and low birth weight. More than 11,658 patients with severe vivax malaria have been reported since 1929, with 15,954 manifestations of severe malaria, of which only 7,157 (45%) conformed to the World Health Organization (WHO) diagnostic criteria. Out of 423 articles, 311 (74%) were published since 2010. In a random-effects meta-analysis of 85 studies, 68 of which were in hospitalized patients with vivax malaria, we estimated the proportion of patients with WHO-defined severe disease as 0.7% [95% confidence interval (CI) 0.19% to 2.57%] in all patients with vivax malaria and 7.11% [95% CI 4.30% to 11.55%] in hospitalized patients. We estimated the mortality from vivax malaria as 0.01% [95% CI 0.00% to 0.07%] in all patients and 0.56% [95% CI 0.35% to 0.92%] in hospital settings. WHO-defined cerebral, respiratory, and renal severe complications were generally estimated to occur in fewer than 0.5% patients in all included studies. Limitations of this review include the observational nature and small size of most of the studies of severe vivax malaria, high heterogeneity of included studies which were predominantly in hospitalized patients (who were therefore more likely to be severely unwell), and high risk of bias including small study effects.
CONCLUSIONS
Young children and pregnant women are particularly vulnerable to adverse clinical impacts of vivax malaria, and preventing infections and relapse in this groups is a priority. Substantial evidence of severe presentations of vivax malaria has accrued over the last 10 years, but reporting is inconsistent. There are major knowledge gaps, for example, limited understanding of the underlying pathophysiology and the reason for the heterogenous geographical distribution of reported complications. An adapted case definition of severe vivax malaria would facilitate surveillance and future research to better understand this condition.
Topics: Anemia; Humans; Malaria, Vivax; Prevalence
PubMed: 35041650
DOI: 10.1371/journal.pmed.1003890 -
The Lancet. Global Health Jul 2023Malaria infections during pregnancy can cause adverse birth outcomes, yet many infections are undetected by microscopy. We aimed to describe the epidemiology of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Malaria infections during pregnancy can cause adverse birth outcomes, yet many infections are undetected by microscopy. We aimed to describe the epidemiology of submicroscopic malaria infections in pregnant women in Asia, the Americas, and Africa using aggregated and individual participant data (IPD).
METHODS
For this systematic review and meta-analysis, studies (published Jan 1, 1997 to Nov 10, 2021) with information on both microscopic and submicroscopic infections during pregnancy from Asia, the Americas, or Africa, identified in the Malaria-in-Pregnancy Library, were eligible. Studies (or subgroups or study groups) that selected participants on the basis of the presence of fever or a positive blood smear were excluded to avoid selection bias. We obtained IPD (when available) and aggregated data. Estimates of malaria transmission intensity and sulfadoxine-pyrimethamine resistance, matched by study location and year, were obtained using publicly available data. One-stage multivariable logit and multinomial models with random intercepts for study site were used in meta-analysis to assess prevalence of and risk factors for submicroscopic infections during pregnancy and at delivery. This study is registered with PROSPERO, number CRD42015027342.
FINDINGS
The search identified 87 eligible studies, 68 (78%) of which contributed to the analyses. Of these 68 studies, 45 (66%) studies contributed IPD (48 869 participants) and 23 (34%) studies contributed aggregated data (11 863 participants). During pregnancy, median prevalence estimates were 13·5% (range 0·0-55·9, 66 substudies) for submicroscopic and 8·0% (0·0-50·6, 66 substudies) for microscopic malaria. Among women with positive Plasmodium nucleic acid amplification tests (NAATs), the median proportion of submicroscopic infections was 58·7% (range 0·0-100); this proportion was highest in the Americas (73·3%, 0·0-100), followed by Asia (67·2%, 36·4-100) and Africa (56·5%, 20·5-97·7). In individual patient data analysis, compared with women with no malaria infections, those with submicroscopic infections were more likely to present with fever in Africa (adjusted odds ratio 1·32, 95% CI 1·02-1·72; p=0·038) but not in other regions. Among women with NAAT-positive infections in Asia and the Americas, Plasmodium vivax infections were more likely to be submicroscopic than Plasmodium falciparum infections (3·69, 2·45-5·54; p<0·0001). Risk factors for submicroscopic infections among women with NAAT-positive infections in Africa included older age (age ≥30 years), multigravidity, and no HIV infection.
INTERPRETATION
During pregnancy, submicroscopic infections are more common than microscopic infections and are associated with fever in Africa. Malaria control in pregnancy should target both microscopic and submicroscopic infections.
FUNDING
Bill & Melinda Gates Foundation through the Worldwide Antimalarial Resistance Network.
Topics: Female; Humans; Pregnancy; Adult; Prevalence; Malaria; Antimalarials; Malaria, Falciparum; Risk Factors
PubMed: 37276878
DOI: 10.1016/S2214-109X(23)00194-8