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Nutrients Oct 2023Despite several studies examining the relationship between calcium levels and malaria, inconsistencies and varied results remain in the literature. This study aimed to... (Meta-Analysis)
Meta-Analysis
Despite several studies examining the relationship between calcium levels and malaria, inconsistencies and varied results remain in the literature. This study aimed to synthesize the evidence on the association between blood calcium levels and malaria severity. A systematic literature search was conducted in the Embase, Scopus, PubMed, Ovid, and Google Scholar databases. The studies that investigated calcium levels in participants with malaria were reviewed and included for synthesis. The quality of included studies was assessed based on a standardized checklist by the Joanna Briggs Institute (JBI) critical appraisal checklists. The thematic synthesis had been used for qualitative synthesis. For the quantitative synthesis, the meta-analysis was performed to estimate the pooled effect sizes for differences in calcium levels between groups of participants using a random effect model using Hedge's g as a measure of effect size. Out of the 4574 identified records, 14 studies were reviewed. The thematic synthesis across these studies noted a consistent theme: reduced calcium levels in malaria patients compared to uninfected controls. However, the meta-analysis encompassing three specific analyses-comparing calcium levels between malaria patients and controls, severe and non-severe malaria cases, and fatal cases versus survivors-showed no significant difference in calcium levels. The statistics were as follows: (1) = 0.15, Hedge's g: -1.00, 95% CI: -2.37-0.38, : 98.97, 9 studies; (2) = 0.35, Hedge's g: -0.33, 95% CI: -1.02-0.36, : 81.61, 3 studies; and (3) = 0.71, Hedge's g: -0.14, 95% CI: -0.91-0.62, : 87.05, 3 studies. Subgroup analyses indicated that regional disparities, especially between Africa and Asia, and participant age groups may influence these outcomes. While a trend of decreased calcium levels in malaria patients was observed, the meta-analytical results suggest regional and age-related variations. Further investigations should emphasize these differences to better guide clinical management, prognostic applications, and the crafting of policies concerning malaria's metabolic effects.
Topics: Humans; Malaria, Vivax; Plasmodium falciparum; Calcium; Malaria; Africa
PubMed: 37960176
DOI: 10.3390/nu15214522 -
Travel Medicine and Infectious Disease 2017With increased international travel over the world the need for safe and effective chemoprophylaxis for malaria is as great as ever. The choice of regimen is difficult,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
With increased international travel over the world the need for safe and effective chemoprophylaxis for malaria is as great as ever. The choice of regimen is difficult, as effectiveness should be weighted against potential adverse effects. Although, some studies have reported high prophylactic efficacy of primaquine, there is no comprehensive evidence comparing its prophylactic effectiveness as well as toxicity. To fill the gap, this systematic review and meta-analysis study was carried out.
METHODS
Using MeSH terms, 756 records were detected through searching "Pubmed", "Embase","Web of Science"and "Cochrane" databases. From these,7 relevant full-text articles with 14 comparisons for final quantitative meta-analysis were included in our review. In order to make a comparison between the studies, Risk Ratios(RRs) and their 95% confidence intervals(CIs) were estimated.
RESULTS
Overall,74% reduction in the incidence of parasitaemia by primaquine versus other prophylactic regimens was estimated(RRoverall = 0.26, CI 95%:0.16-0.41--RRvivax = 0.16, CI 95%:0.07-0.36--RRfalciparum = 0.31, CI 95%:0.18-0.55). The incidence rate ratios for adverse effects showed no statistically significant difference between primaquine and control groups (p > 0.05).
CONCLUSIONS
For persons without G6PD deficiency, who are not pregnant, primaquine is the most effective presently available prophylactic for P. vivax malaria and comparable to such regimens as doxycycline, mefloquine and atovaquone-proguanil for the prevention of P. falciparum malaria.
Topics: Antibiotic Prophylaxis; Antimalarials; Humans; Malaria, Falciparum; Malaria, Vivax; Parasitemia; Plasmodium falciparum; Plasmodium vivax; Primaquine; Travel
PubMed: 28450185
DOI: 10.1016/j.tmaid.2017.04.005 -
Antioxidants (Basel, Switzerland) Jul 2023Several studies have evaluated the relationship between malondialdehyde (MDA) concentrations and infections; however, the findings remain inconclusive. This study... (Review)
Review
Several studies have evaluated the relationship between malondialdehyde (MDA) concentrations and infections; however, the findings remain inconclusive. This study synthesized differences in MDA concentrations among patients with different levels of clinical severity, uninfected controls, and different species. The research protocol was registered in PROSPERO (CRD42023393540). Systematic literature searches for relevant studies were performed using the Embase, MEDLINE, Ovid, ProQuest, PubMed, Scopus, and Google Scholar databases. Qualitative and quantitative syntheses (meta-analyses) of distinct MDA concentrations between the disease groups were performed. Twenty-three studies met the eligibility criteria and were included in the systematic review. Overall, MDA concentrations were significantly elevated in participants with malaria relative to uninfected controls ( < 0.01, Cohen d: 2.51, 95% confidence interval (CI): 1.88-3.14, I: 96.22%, 14 studies). Increased MDA concentrations in participants with malaria compared with uninfected controls were found in studies that enrolled patients with malaria ( < 0.01, Cohen d: 2.50, 95% CI: 1.90-3.10, I: 89.7%, 7 studies) and malaria ( < 0.01, Cohen d: 3.70, 95% CI: 2.48-4.92, I: 90.11%, 3 studies). Our findings confirm that MDA concentrations increase during infection, indicating a rise in oxidative stress and lipid peroxidation. Thus, MDA levels can be a valuable biomarker for evaluating these processes in individuals with malaria. However, further research is necessary to fully elucidate the intricate relationship between malaria, antioxidants, oxidative stress, and the specific role of MDA in the progression of malaria.
PubMed: 37627497
DOI: 10.3390/antiox12081502 -
Journal of Vector Borne Diseases Mar 2007This study aimed to quantify the interaction between Plasmodium falciparum and R vivax and the sources of heterogeneity between studies. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This study aimed to quantify the interaction between Plasmodium falciparum and R vivax and the sources of heterogeneity between studies.
METHODS
We systematically reviewed three databases: Medline (1966-2001), Embase (1980-2001) and CAB-health (1976-2001). Random effects meta-analysis was applied to the data of 62 selected populations. Meta-regression was used to assess the following potential sources of heterogeneity: age-group, presence of fever, continent, temporal and spatial span of studies, and endemicity level.
RESULTS
The summary odds ratio (OR) between P. falciparum and P. vivax was 0.6 (95% CI: 0.49-0.79). The minimum and maximum observed ORs were 0.01 and 10.9, respectively, and the heterogeneity test was highly significant (tau2 = 0.92, p < 0.0001)--the ORs varied over a very wide range. The ORs in longer studies and in those from areas with higher prevalence yielded smaller, more strongly negative association. This is consistent with the idea that any difference in the species' temporal patterns should decrease the OR, and more so over longer periods of time.
INTERPRETATION & CONCLUSION
Although such odds ratios between Plasmodium species may be partly due to missed mixed infections when reading blood slides, the negative association between the OR and prevalence supports the existence of biological interactions such as suppression or cross-immunity between species.
Topics: Animals; Humans; Malaria, Falciparum; Malaria, Vivax; Odds Ratio; Plasmodium falciparum; Plasmodium vivax
PubMed: 17378215
DOI: No ID Found -
BMC Medicine Aug 2019Malaria causes a reduction in haemoglobin that is compounded by primaquine, particularly in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. The aim of... (Meta-Analysis)
Meta-Analysis
The haematological consequences of Plasmodium vivax malaria after chloroquine treatment with and without primaquine: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis.
BACKGROUND
Malaria causes a reduction in haemoglobin that is compounded by primaquine, particularly in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. The aim of this study was to determine the relative contributions to red cell loss of malaria and primaquine in patients with uncomplicated Plasmodium vivax.
METHODS
A systematic review identified P. vivax efficacy studies of chloroquine with or without primaquine published between January 2000 and March 2017. Individual patient data were pooled using standardised methodology, and the haematological response versus time was quantified using a multivariable linear mixed effects model with non-linear terms for time. Mean differences in haemoglobin between treatment groups at day of nadir and day 42 were estimated from this model.
RESULTS
In total, 3421 patients from 29 studies were included: 1692 (49.5%) with normal G6PD status, 1701 (49.7%) with unknown status and 28 (0.8%) deficient or borderline individuals. Of 1975 patients treated with chloroquine alone, the mean haemoglobin fell from 12.22 g/dL [95% CI 11.93, 12.50] on day 0 to a nadir of 11.64 g/dL [11.36, 11.93] on day 2, before rising to 12.88 g/dL [12.60, 13.17] on day 42. In comparison to chloroquine alone, the mean haemoglobin in 1446 patients treated with chloroquine plus primaquine was - 0.13 g/dL [- 0.27, 0.01] lower at day of nadir (p = 0.072), but 0.49 g/dL [0.28, 0.69] higher by day 42 (p < 0.001). On day 42, patients with recurrent parasitaemia had a mean haemoglobin concentration - 0.72 g/dL [- 0.90, - 0.54] lower than patients without recurrence (p < 0.001). Seven days after starting primaquine, G6PD normal patients had a 0.3% (1/389) risk of clinically significant haemolysis (fall in haemoglobin > 25% to < 7 g/dL) and a 1% (4/389) risk of a fall in haemoglobin > 5 g/dL.
CONCLUSIONS
Primaquine has the potential to reduce malaria-related anaemia at day 42 and beyond by preventing recurrent parasitaemia. Its widespread implementation will require accurate diagnosis of G6PD deficiency to reduce the risk of drug-induced haemolysis in vulnerable individuals.
TRIAL REGISTRATION
This trial was registered with PROSPERO: CRD42016053312. The date of the first registration was 23 December 2016.
Topics: Adult; Anemia, Hemolytic; Antimalarials; Chloroquine; Female; Glucosephosphate Dehydrogenase Deficiency; Hemolysis; Humans; Malaria, Vivax; Male; Middle Aged; Plasmodium vivax; Primaquine
PubMed: 31366382
DOI: 10.1186/s12916-019-1386-6 -
The Lancet. Infectious Diseases Sep 2018Chloroquine remains the mainstay of treatment for Plasmodium vivax malaria despite increasing reports of treatment failure. We did a systematic review and meta-analysis... (Meta-Analysis)
Meta-Analysis
The effect of chloroquine dose and primaquine on Plasmodium vivax recurrence: a WorldWide Antimalarial Resistance Network systematic review and individual patient pooled meta-analysis.
BACKGROUND
Chloroquine remains the mainstay of treatment for Plasmodium vivax malaria despite increasing reports of treatment failure. We did a systematic review and meta-analysis to investigate the effect of chloroquine dose and the addition of primaquine on the risk of recurrent vivax malaria across different settings.
METHODS
A systematic review done in MEDLINE, Web of Science, Embase, and Cochrane Database of Systematic Reviews identified P vivax clinical trials published between Jan 1, 2000, and March 22, 2017. Principal investigators were invited to share individual patient data, which were pooled using standardised methods. Cox regression analyses with random effects for study site were used to investigate the roles of chloroquine dose and primaquine use on rate of recurrence between day 7 and day 42 (primary outcome). The review protocol is registered in PROSPERO, number CRD42016053310.
FINDINGS
Of 134 identified chloroquine studies, 37 studies (from 17 countries) and 5240 patients were included. 2990 patients were treated with chloroquine alone, of whom 1041 (34·8%) received a dose below the target 25 mg/kg. The risk of recurrence was 32·4% (95% CI 29·8-35·1) by day 42. After controlling for confounders, a 5 mg/kg higher chloroquine dose reduced the rate of recurrence overall (adjusted hazard ratio [AHR] 0·82, 95% CI 0·69-0·97; p=0·021) and in children younger than 5 years (0·59, 0·41-0·86; p=0·0058). Adding primaquine reduced the risk of recurrence to 4·9% (95% CI 3·1-7·7) by day 42, which is lower than with chloroquine alone (AHR 0·10, 0·05-0·17; p<0·0001).
INTERPRETATION
Chloroquine is commonly under-dosed in the treatment of vivax malaria. Increasing the recommended dose to 30 mg/kg in children younger than 5 years could reduce substantially the risk of early recurrence when primaquine is not given. Radical cure with primaquine was highly effective in preventing early recurrence and may also improve blood schizontocidal efficacy against chloroquine-resistant P vivax.
FUNDING
Wellcome Trust, Australian National Health and Medical Research Council, and Bill & Melinda Gates Foundation.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antimalarials; Child; Child, Preschool; Chloroquine; Drug Resistance; Drug Therapy, Combination; Female; Humans; Infant; Infant, Newborn; Malaria, Vivax; Male; Middle Aged; Plasmodium vivax; Primaquine; Recurrence; Young Adult
PubMed: 30033231
DOI: 10.1016/S1473-3099(18)30348-7 -
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 -
Biology Dec 2021The understanding of platelet biology under physiological and pathological conditions like malaria infection is critical importance in the context of the disease outcome... (Review)
Review
The understanding of platelet biology under physiological and pathological conditions like malaria infection is critical importance in the context of the disease outcome or model systems used. The importance of severe thrombocytopenia (platelet count < 50,000 cells (µL) and profound thrombocytopenia (platelet count < 20,000 cells/µL) in malaria patients remains unclear. This study aimed to synthesize evidence regarding the risks of severe and profound thrombocytopenia in patients with severe non- malaria. Our overall aim was to identify potential indicators of severe non- malaria and the species that cause severe outcomes. This systematic review was registered at the International Prospective Register of Systematic Reviews (PROSPERO) under registration ID CRD42020196541. Studies were identified from previous systematic reviews ( = 5) and the MEDLINE, Scopus, and Web of Science databases from 9 June 2019 to 9 June 2020. Studies were included if they reported the outcome of severe non-Plasmodium species infection, as defined by the World Health Organization (WHO) criteria, in patients with known platelet counts and/or severe and profound thrombocytopenia. The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). Data were pooled, and pooled prevalence (PP) and pooled odds ratios (ORs) were calculated using random effects models. Of the 118 studies identified from previous meta-nalyses, 21 met the inclusion criteria. Of the 4807 studies identified from the databases, three met the inclusion criteria. Nine studies identified from reference lists and other sources also met the inclusion criteria. The results of 33 studies reporting the outcomes of patients with severe and infection were pooled for meta-analysis. The PP of severe thrombocytopenia (reported in 21 studies) was estimated at 47% (95% confidence interval (CI): 33-61%, I: 96.5%), while that of profound thrombocytopenia (reported in 13 studies) was estimated at 20% (95% CI: 14-27%, 85.2%). The pooled weighted mean difference (WMD) in platelet counts between severe uncomplicated infections (reported in 11 studies) was estimated at -28.51% (95% CI: -40.35-61%, I: 97.7%), while the pooled WMD in platelet counts between severe non- and severe infections (reported in eight studies) was estimated at -3.83% (95% CI: -13.90-6.25%, I: 85.2%). The pooled OR for severe/profound thrombocytopenia comparing severe to uncomplicated infection was 2.92 (95% CI: 2.24-3.81, I: 39.9%). The PP of death from severe and profound thrombocytopenia was estimated at 11% (95% CI: 0-22%). These results suggest that individuals with severe non- infection (particularly and ) who exhibit severe or profound thrombocytopenia should be regarded as high risk, and should be treated for severe malaria according to current WHO guidelines. In addition, severe or profound thrombocytopenia coupled with other clinical and microscopic parameters can significantly improve malaria diagnosis, enhance the timely treatment of malaria infections, and reduce the morbidity and mortality of severe non- malaria.
PubMed: 34943190
DOI: 10.3390/biology10121275 -
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 -
Infectious Diseases of Poverty Feb 2018Plasmodium vivax is the most geographically widespread species among human malaria parasites. Immunopathological studies have shown that platelets are an important... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Plasmodium vivax is the most geographically widespread species among human malaria parasites. Immunopathological studies have shown that platelets are an important component of the host innate immune response against malaria infections. The objectives of this study were to quantify thrombocytopaenia in P. vivax malaria patients and to determine the associated risks of severe thrombocytopaenia in patients with vivax malaria compared to patients with P. falciparum malaria.
MAIN BODY
A systematic review and meta-analysis of the available literature on thrombocytopaenia in P. vivax malaria patients was undertaken. Relevant studies in health-related electronic databases were identified and reviewed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Fifty-eight observational studies (n = 29 664) were included in the current review. Severe thrombocytopaenia (< 50 000/mm) to very severe thrombocytopaenia (< 20 000/mm) was observed in 10.1% of patients with P. vivax infection. A meta-analysis of 11 observational studies showed an equal risk of developing severe/very severe thrombocytopaenia between the patients with P. vivax malaria and those with P. falciparum malaria (OR: 1.98, 95% CI: 0.92-4.25). This indicates that thrombocytopaenia is as equally a common manifestation in P. vivax and P. falciparum malaria patients. One study showed a higher risk of developing very severe thrombocytopaenia in children with severe P. vivax malaria than with severe P. falciparum malaria (OR: 2.80, 95% CI: 1.48-5.29). However, a pooled analysis of two studies showed an equal risk among adult severe cases (OR: 1.19, 95% CI: 0.51-2.77). This indicates that the risk of developing thrombocytopaenia in P. vivax malaria can vary with immune status in both children and adults. One study reported higher levels of urea and serum bilirubin in patients with P. vivax malaria and severe thrombocytopaenia compared with patients mild thrombocytopaenia or no thrombocytopaenia, (P < 0.001 in all comparisons). A pooled analysis of two other studies showed a similar proportion of bleeding episodes with thrombocytopaenia in severe P. vivax patients and severe P. falciparum patients (P = 0.09). This implied that both P. vivax and P. falciparum infections could present with bleeding episodes, if there had been a change in platelet counts in the infected patients. A pooled analysis of another two studies showed an equal risk of mortality with severe thrombocytopaenia in both P. vivax and P. falciparum malaria patients (OR: 1.16, 95% CI: 0.30-4.60). However, due to the low number of studies with small sample sizes within the subset of studies that provided clinically relevant information, our confidence in the estimates is limited.
CONCLUSION
The current review has provided some evidence of the clinical relevance of severe thrombocytopaenia in P. vivax malaria. To substantiate these findings, there is a need for well designed, large-scale, prospective studies among patients infected with P. vivax. These should include patients from different countries and epidemiological settings with various age and gender groups represented.
Topics: Adult; Child; Female; Humans; Malaria, Falciparum; Malaria, Vivax; Male; Observational Studies as Topic; Plasmodium falciparum; Plasmodium vivax; Severity of Illness Index; Thrombocytopenia
PubMed: 29427995
DOI: 10.1186/s40249-018-0392-9