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Prevalence of and risk factors for severe malaria caused by Plasmodium and dengue virus co-infection: a systematic review and meta-analysis.

ABSTRACT: BACKGROUND:Co-infection with both Plasmodium and dengue virus (DENV) infectious species could have serious and fatal outcomes if left undiagnosed and without timely treatment. The present study aimed to determine the pooled prevalence estimate of severe malaria among patients with co-infection, the risk of severe diseases due to co-infection, and to describe the complications of severe malaria and severe dengue among patients with co-infection. METHODS:Relevant studies published between databases between 12 September 1970 and 22 May 2020 were identified and retrieved through a search of the ISI Web of Science, Scopus, and MEDLINE. The pooled prevalence and 95% confidence interval (CI) of severe malaria among patients with Plasmodium and DENV co-infection was estimated with a random-effects model to take into account the between-study heterogeneity of the included studies. The risks of severe malaria and severe diseases due to co-infection were estimated with the pooled odds ratio (OR) and 95% CI with a random-effects model. RESULTS:Of the 5653 articles screened, 13 studies were included in the systematic review and meta-analysis. The results demonstrated that the pooled prevalence estimate of severe malaria among patients with co-infection was 32% (95% CI: 18-47%, I2?=?92.3%). Patients with co-infection had a higher risk of severe diseases than those with DENV mono-infection (odds ratio [OR]?=?3.94, 95% CI: 1.96-7.95, I2?=?72%). Patients with co-infection had a higher risk of severe dengue than those with DENV mono-infection (OR?=?1.98, 95% CI: 1.08-3.63, I2?=?69%). The most severe complications found in severe dengue were bleeding (39.6%), jaundice (19.8%), and shock/hypotension (17.9%), while the most severe complications found in severe malaria were severe bleeding/bleeding (47.9%), jaundice (32.2%), and impaired consciousness (7.43%). CONCLUSIONS:The present study found that there was a high prevalence of severe malaria among patients with Plasmodium and DENV co-infection. Physicians in endemic areas where these two diseases overlap should recognize that patients with this co-infection can develop either severe malaria or severe dengue with bleeding complications, but a greater risk of developing severe dengue than severe malaria was noted in patients with this co-infection. TRIAL REGISTRATION:The protocol of this study was registered at PROSPERO: CRD42020196792 .

SUBMITTER: Kotepui M

PROVIDER: S-EPMC7510069 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Prevalence of and risk factors for severe malaria caused by Plasmodium and dengue virus co-infection: a systematic review and meta-analysis.

Kotepui Manas M Kotepui Kwuntida Uthaisar KU Milanez Giovanni De Jesus GJ Masangkay Frederick Ramirez FR

Infectious diseases of poverty 20200922 1

<h4>Background</h4>Co-infection with both Plasmodium and dengue virus (DENV) infectious species could have serious and fatal outcomes if left undiagnosed and without timely treatment. The present study aimed to determine the pooled prevalence estimate of severe malaria among patients with co-infection, the risk of severe diseases due to co-infection, and to describe the complications of severe malaria and severe dengue among patients with co-infection.<h4>Methods</h4>Relevant studies published b ...[more]

PMID: 32962765

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Project description:Co-infection with malaria and human immunodeficiency virus (HIV) increases the severity and mortality rates of both diseases. A better understanding of the effects of co-infections could help in the diagnosis, prompt treatment, prevention, and control of malarial parasites among HIV-infected patients. In this systematic review and meta-analysis, we estimated the prevalence and characteristics of severe malaria (SM) caused by co-infection with HIV. We included relevant studies that were conducted between the years 1991 and 2018 and reporting on SM. We pooled the prevalence of SM in patients with co-infection, pooled odds ratios of SM in patients with co-infection and Plasmodium mono-infection, and differences in laboratory parameters such as parasite density and leucocyte counts, between co-infected and Plasmodium mono-infected patients. The meta-analysis included 29 studies (1126 SM cases). The pooled prevalence of SM in co-infected patients using the data of 23 studies (SM = 795 cases, all co-infection cases = 2534 cases) was 43.0% (95% confidence interval [CI] 31.0-56.0%; I2, 98.0%). Overall, the odds of SM from 18 studies were pooled. The odds of SM were significantly higher in co-infected patients than in Plasmodium mono-infected patients (OR 2.41; 95% CI 1.43-4.08; I2 = 85%; P = 0.001) and also significantly higher in children (OR 9.69; 95% CI 5.14-18.3; I2, 0%; P < 0.0001; two studies) than in adults (OR 2.68; 95% CI 1.52-4.73; I2, 79.0%; P = 0.0007; 12 studies). Co-infected patients with SM had a higher parasite density than those with Plasmodium mono-infection when the data of seven studies were analysed (SMD, 1.25; 95% CI 0.14-2.36; I2, 98.0%; P = 0.03) and higher leukocyte counts when the data of four studies were analysed (MD, 1570 cells/µL; 95% CI 850-2300 cells/µL; I2, 21.0%; P < 0.0001). Thus, the prevalence of SM among patients co-infected with Plasmodium spp. and HIV is high. Because co-infections could lead to SM, patients with Plasmodium spp. and HIV co-infection should be identified and treated to reduce the prevalence of SM and the number of deaths.

Project description:BackgroundA clear understanding of the epidemiology of malaria and dengue co-infection is essential for informed decisions on appropriate control strategies for dengue and malaria. This systematic review synthesized evidence on the relationship of malaria and dengue co-infection and related it to alterations in platelet, hemoglobin, hematocrit, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels when compared to malaria mono-infection.MethodsA systematic review in accordance with PRISMA guidelines was conducted. All published articles available in PubMed and Web of Science (ISI) databases before October 21, 2017 were recruited. All epidemiological studies except case reports on the prevalence or incidence of malaria and dengue co-infection among patients visiting hospitals with febrile illness were included. Studies that involved conference abstracts, protocols, systematic reviews, only mono-dengue or mono-malaria infections, and only animal or in vitro studies were excluded after screening the titles, abstracts, and body texts. Studies were additionally excluded after full text review when they lacked epidemiologic data on malaria and dengue co-infection. Two reviewers independently screened, reviewed, and assessed all the studies. Cochrane Q (Chi-square) and Moran's I2 were used to assess heterogeneity, and the funnel plot was used to examine publication bias. The summary odds ratio (OR) and 95% confidence intervals (CI) were estimated using a fixed-effects model. Thirteen cross-sectional and two retrospective studies were eligible to be included in the systematic review and meta-analysis.ResultsOut of the 2269 citations screened, 15 articles were eligible to be included in the systematic review and meta-analysis. The 15 studies involved 13,798 (10,373 cases with malaria and 3425 with dengue) patients in 9 countries. Thirteen studies compared the incidence and odds of Plasmodium sp. infection, five studies compared the odds of mean platelet, three studies compared Plasmodium parasite density, and four studies compared the odds of hemoglobin, hematocrit, AST, and ALT levels among co-infected groups and single-malaria-infected groups.ConclusionsThis study showed that dengue and malaria co-infection was associated with decreased odds of malaria infection, malaria parasitemia, AST, and ALT levels when compared to malaria mono-infection. However, malaria and dengue co-infection was associated with increased odds of platelet and hemoglobin levels when compared to malaria mono-infection.

Project description:Mixed Plasmodium malaria infections can lead to severe malaria. This systematic review and meta-analysis aimed to explore the prevalence of severe mixed Plasmodium malaria infection and to compare it with the prevalence of severe P. falciparum malaria mono-infection across the included studies. Original English-language research articles from PubMed, Scopus, and ISI Web of Science were identified and screened. Articles reporting the number of mixed infections and the number of severe mixed infections were used to determine the main outcome of this study, while the number of P. falciparum infections and the number of severe P. falciparum infections were used to determine the secondary outcome of this study. For the main outcome, the pooled prevalence and 95% confidence interval (CI) of severe mixed infections was analysed using STATA software version 15.0 (Stata Corp, College Station, TX, USA). For the secondary outcome, the rate of severe mixed infections compared to severe P. falciparum infections was analysed using the meta-analysis approach, and summary odds ratios (ORs) and 95% CIs were calculated. Random-effects models were used to produce the summary ORs. The Mantel-Haenszel method and calculated I2 were also reported to test whether there was heterogeneity among the included studies. Publication bias was also assessed using funnel plots. The meta-analysis of secondary outcomes was conducted using Review Manager 5.3 software (Cochrane Community). A total of 894,561 malaria patients were reported in all 16 included studies. Overall, a pooled analysis showed that 9% (2,006/35,768, 95% CI 7.0-12.0%) of patients with mixed Plasmodium infection had severe mixed infection. A meta-analysis of 14 studies demonstrated that patients with mixed Plasmodium infection (1,999/35,755) and patients with P. falciparum malaria (9,249/294,397) had an equal risk of developing severe malaria (OR 0.93, 95% CI 0.59-1.44). Both mixed infection and P. falciparum mono-infection showed a similar trend of complications in which severe anaemia, pulmonary failure, and renal impairment were the three most common complications found. However, patients with mixed infection had a higher proportion of severe anaemia and pulmonary complications than those with P. falciparum infection. Moreover, patients with mixed infection had a higher proportion of multiple organ failure than those with P. falciparum mono-infection. Mixed Plasmodium spp. infections were common but often unrecognized or underestimated, leading to severe complications among these malaria patients. Therefore, in routine clinical laboratories, using an accurate combination of diagnostic procedures to identify suspected patients with mixed infections is crucial for therapeutic decisions, prompt treatment, and effective patient management.

Project description:BACKGROUND:Plasmodium spp. and hepatitis B virus (HBV) are among the most common infectious diseases in underdeveloped countries. This study aimed to determine the prevalence of Plasmodium spp. and HBV co-infection in people living in endemic areas of both diseases and to assess the risk factors related to this co-infection. METHODS:The PubMed, Web of Science, and Scopus databases were searched. Observational cross-sectional studies and retrospective studies assessing the prevalence of Plasmodium species and HBV co-infection were examined. The methodological quality of the included studies was assessed with the Newcastle-Ottawa Scale (NOS), a tool for assessing the quality of nonrandomized studies in meta-analyses, and heterogeneity among the included studies was assessed with Cochran's Q test and the I2 (inconsistency) statistic. The pooled prevalence of the co-infection and its 95% confidence interval (CI) were estimated using the random-effects model, depending on the amount of heterogeneity there was among the included studies. The pooled odds ratio (OR) represented the difference in qualitative variables, whereas the pooled mean difference (MD) represented the difference in quantitative variables. Meta-analyses of the potential risk factors for Plasmodium spp. and HBV co-infection, including patient age and gender, were identified and represented as pooled odds ratios (OR) and 95% CIs. Publication bias among the included studies was assessed by visual inspection of a funnel plot to search for asymmetry. RESULTS:Twenty-two studies were included in the present systematic review and meta-analysis. Overall, the pooled prevalence estimate of Plasmodium spp. and HBV co-infection was 6% (95% CI 4-7%, Cochran's Q statistic?<?0.001, I2: 95.8%), with prevalences of 10% in Gambia (95% CI: 8-12%, weight: 4.95%), 8% in Italy (95% CI 5-12%, weight: 3.8%), 7% in Nigeria (95% CI 4-10%, weight: 53.5%), and 4% in Brazil (95% CI 2-5%, weight: 19.9%). The pooled prevalence estimate of Plasmodium spp. and HBV co-infection was higher in studies published before 2015 (7%, 95% CI 4-9%, Cochran's Q statistic?<?0.001, I2: 96%) than in those published since 2015 (3%, 95% CI 1-5%, Cochran's Q statistic?<?0.001, I2: 81.3%). No difference in age and risk of Plasmodium spp. and HBV co-infection group was found between the Plasmodium spp. and HBV co-infection and the Plasmodium monoinfection group (p: 0.48, OR: 1.33, 95% CI 0.60-2.96). No difference in gender and risk of Plasmodium spp. and HBV co-infection group was found between the Plasmodium spp. and HBV co-infection and HBV co-infection group and the Plasmodium monoinfection group (p: 0.09, OR: 2.79, 95% CI 0.86-9.10). No differences in mean aspartate aminotransferase (AST), mean alanine aminotransferase (ALT), or mean total bilirubin levels were found (p?>?0.05) between the Plasmodium spp. and HBV co-infection group and the Plasmodium monoinfection group. CONCLUSIONS:The present study revealed the prevalence of Plasmodium spp. and HBV co-infection, which will help in understanding co-infection and designing treatment strategies. Future studies assessing the interaction between Plasmodium spp. and HBV are recommended.

Project description:BackgroundSevere complications among patients with Plasmodium malariae infection are rare. This is the first systematic review and meta-analysis demonstrating the global prevalence and mortality of severe P. malariae infection in humans.MethodsThe systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All research articles published on the severity and mortality of P. malariae infection cases in humans were retrieved from three public databases: PubMed, Scopus, and ISI Web of Science. The pooled prevalence estimate and 95% confidence interval (CI) of complications in patients with P. malariae malaria was analysed using the random-effects model provided in Stata software. The pooled odds ratio (OR) and 95% CI of severe malaria for P. malariae infection and Plasmodium falciparum infection were analysed using Review Manager software.ResultsSix studies were used to estimate the pooled prevalence of severe P. malariae malaria. Out of 10,520 patients infected with P. malariae, the pooled prevalence estimate of severe P. malariae infection was 3% (95% CI 2-5%), with high heterogeneity (I2: 90.7%). Severe anaemia (3.32%), pulmonary complications (0.46%), and renal impairments (0.24%) were the most common severe complications found in patients with P. malariae infection. The pooled proportion of severe anaemia for P. malariae infection and P. falciparum infection was comparable among the four included studies (OR: 0.74, 95% CI 0.22-2.45, I2 = 98%). The pooled proportion of pulmonary complications was comparable between patients with P. malariae infection and those with P. falciparum infection among the four included studies (OR: 1.44; 95% CI 0.17-12.31, I2: 92%). For renal complications, the funnel plot showed that the pooled proportion of renal complications for P. malariae infection and P. falciparum infection was comparable among the four included studies (OR: 0.94, 95% CI 0.18-4.93, I2: 91%). The mortality rate of patients with P. malariae infection was 0.17% (18/10,502 cases).ConclusionsThis systematic review demonstrated that approximately two percent of patients with P. malariae infection developed severe complications, with a low mortality rate. Severe anaemia, pulmonary involvement, and renal impairment were the most common complications found in patients with P. malariae infection. Although a low prevalence and low mortality of P. malariae infection have been reported, patients with P. malariae infection need to be investigated for severe anaemia and, if present, treated aggressively to prevent anaemia-related death.

Project description:BackgroundPlasmodium 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 findingsWe 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%).ConclusionOverall, 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.

Project description:BACKGROUND:Although Plasmodium parasites and intestinal helminths share common endemic areas, the mechanisms of these co-infections on the host immune response remain not fully understood. Liver involvement in severe Plasmodium falciparum infections is a significant cause of morbidity and mortality. However, the effect of pre-existing Trichinella spiralis infection on the immune response and liver immune-pathogenesis in P. berghei ANKA (PbANKA)-infected mice needs to be elucidated. METHODS:Outbred Kunming mice were infected with T. spiralis and 9 days later were challenged with P. berghei ANKA (PbANKA), and the investigation occurred at 13 days after co-infection. RESULTS:Compared with PbANKA-mono-infected mice, T. spiralis + PbANKA-co-infected mice had similar survival rate but lower PbANKA parasitaemia; however, there were more severe hepatosplenomegaly, increased liver and spleen indexes, and increased liver pathology observed by hematoxylin and eosin staining; higher expression levels of galectin (Gal)-1, Gal-3, CD68+ macrophages, and elastase-positive neutrophils measured by immunohistochemical staining; upregulated mRNA expression levels of Gal-1, Gal-3, cytokines (interferon-gamma (IFN?) and interleukin (IL)-6), and M1 macrophage polarization marker (inducible nitric oxide synthase (iNOS)) in the liver, and increased expression levels of Gal-1, IFN?, IL-6, eosinophil cationic protein, eosinophil protein X, and M1 (IL-1? and iNOS) and M2 (Ym1) macrophage polarization markers in the spleen of co-infected mice detected by using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). In vitro study showed that compared with PbANKA-mono-infected mice, there were significantly increased expression levels of Gal-1, Gal-3, IL-6, IL-1?, and iNOS in the peritoneal macrophage isolated from co-infected mice detected by using qRT-PCR. Correlation analysis revealed significant positive correlations between Gal-3 and IL-1? in the peritoneal macrophages isolated from PbANKA-mono-infected mice, between Gal-3 and IFN? in the spleen of co-infected mice, and between Gal-1 and Ym1 in the peritoneal macrophages isolated from co-infected mice. CONCLUSIONS:Our data indicate that pre-existing infection of T. spiralis may suppress P. berghei parasitaemia and aggravate malaria-induced liver pathology through stimulating Gal-1 and Gal-3 expression, activating macrophages, neutrophils, and eosinophils, and promoting mediator release and cytokine production.

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Prevalence of and risk factors for severe malaria caused by Plasmodium and dengue virus co-infection: a systematic review and meta-analysis.

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Prevalence of and risk factors for severe malaria caused by Plasmodium and dengue virus co-infection: a systematic review and meta-analysis.

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