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Prevalence of Malaria and Leptospirosis Co-Infection among Febrile Patients: A Systematic Review and Meta-Analysis.

ABSTRACT: Malaria and leptospirosis are important cosmopolitan infections that have emerged with overlapping geographic distribution, especially in tropical and subtropical regions. Therefore, co-infection with malaria and leptospirosis may occur in overlapping areas. The present study aimed to quantify the prevalence of malaria and leptospirosis co-infection among febrile patients. The association between malaria and leptospirosis infections was also investigated. Relevant studies that had reported malaria and leptospirosis co-infection were identified from PubMed, Scopus, and Web of Science. The risk of bias of the studies was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Tool. The pooled prevalence of malaria and leptospirosis co-infections among febrile patients and the pooled prevalence of leptospirosis infection among malaria patients were estimated using random effect models. The association between malaria and leptospirosis infection among febrile patients was estimated using random effect models. The outcomes of each study were shown in a forest plot in point estimate and 95% confidence interval (CI). Heterogeneity among the included studies was assessed using Cochran's Q and quantified using I-squared statistics. For leptospirosis, subgroup analyses of countries, diagnostic tests, and participants' age groups were performed to specify prevalence in each subgroup. Publication bias was assessed by funnel-plot visualization. Of the 2370 articles identified from the databases, 15 studies met the eligibility criteria and were included for qualitative and quantitative syntheses. Most of the included studies were conducted in India (5/15, 33.3%), Thailand (3/15, 20%), and Cambodia (2/15, 13.3%). Most of the enrolled cases were febrile patients (5838 cases) and malaria-positive patients (421 cases). The meta-analysis showed that the pooled prevalence of malaria and leptospirosis co-infection (86 cases) among febrile patients was 1% (95% CI: 1-2%, I²: 83.3%), while the pooled prevalence of leptospirosis infection (186 cases) among malaria patients was 13% (95% CI: 9-18%, I²: 90.3%). The meta-analysis showed that malaria and leptospirosis co-infections occurred by chance (p: 0.434, OR: 1.4, 95% CI: 0.6-3.28, I²: 85.2%). The prevalence of malaria in leptospirosis co-infection among febrile patients in the included studies was low. Co-infection was likely to occur by chance. However, as clinical symptoms of leptospirosis patients were non-specific and not distinguishable from symptoms of malaria patients, clinicians caring for febrile patients in an area where those two diseases are endemic should maintain a high index of suspicion for both diseases and whether mono-infections or co-infections are likely. Recognition of this co-infection may play an important role in reducing disease severity and treatment duration.

SUBMITTER: Wilairatana P

PROVIDER: S-EPMC8293407 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Co-infection with malaria and chikungunya (CHIKV) could exert a significant public health impact with infection misdiagnosis. Therefore, this study aimed to collect qualitative and quantitative evidence of malaria and CHIKV co-infection among febrile patients. Methods: Potentially relevant studies were identified using PubMed, Web of Science, and Scopus. The bias risk of the included studies was assessed using the checklist for analytical cross-sectional studies developed by the Joanna Briggs Institute. The pooled prevalence of malaria and CHIKV co-infection among febrile patients and the pooled prevalence of CHIKV infection among malaria patients were estimated with the random effect model. The odds of malaria and CHIKV co-infection among febrile patients were also estimated using a random effect model that presumed the heterogeneity of the outcomes of the included studies. The heterogeneity among the included studies was assessed using the Cochran Q test and I2 statistics. Publication bias was assessed using the funnel plot and Egger's test. Results: Of the 1924 studies that were identified from the three databases, 10 fulfilled the eligibility criteria and were included in our study. The pooled prevalence of malaria and CHIKV co-infection (182 cases) among febrile patients (16,787 cases), stratified by diagnostic tests for CHIKV, was 10% (95% confidence interval (CI): 8-11%, I2: 99.5%) using RDT (IgM), 7% (95% CI: 4-10%) using the plaque reduction neutralization test (PRNT), 1% (95% CI: 0-2%, I2: 41.5%) using IgM and IgG ELISA, and 4% (95% CI: 2-6%) using real-time RT-PCR. When the prevalence was stratified by country, the prevalence of co-infection was 7% (95% CI: 5-10%, I2: 99.5%) in Nigeria, 1% (95% CI: 0-2%, I2: 99.5%) in Tanzania, 10% (95% CI: 8-11%) in Sierra Leone, 1% (95% CI: 0-4%) in Mozambique, and 4% (95% CI: 2-6%) in Kenya. The pooled prevalence of CHIKV infection (182 cases) among malaria patients (8317 cases), stratified by diagnostic tests for CHIKV, was 39% (95% CI: 34-44%, I2: 99.7%) using RDT (IgM), 43% (95% CI: 30-57%) using PRNT, 5% (95% CI: 3-7%, I2: 5.18%) using IgM and IgG ELISA, and 9% (95% CI: 6-15%) using real-time RT-PCR. The meta-analysis showed that malaria and CHIKV co-infection occurred by chance (p: 0.59, OR: 0.32, 95% CI: 0.6-1.07, I2: 78.5%). Conclusions: The prevalence of malaria and CHIKV co-infection varied from 0% to 10% as per the diagnostic test for CHIKV infection or the country where the co-infection was reported. Hence, the clinicians who diagnose patients with malaria infections in areas where two diseases are endemic should further investigate for CHIKV co-infection to prevent misdiagnosis or delayed treatment of concurrent infection.

Project description:BackgroundLittle information is available about malaria and scrub typhus co-infection. This study aimed to investigate the pooled prevalence of malaria and scrub typhus co-infection in febrile patients. Further, it aimed to estimate the prevalence of scrub typhus infection among patients with malaria and the odds of co-infection. This will aid the diagnosis and management of co-infected patients in endemic areas.MethodsWe searched for relevant studies in three databases: PubMed, Scopus, and Web of Science. We assessed the quality of the included studies using the Joanna Briggs Institute checklist for analytical cross-sectional studies. We estimated (1) the pooled prevalence of malaria and scrub typhus co-infection, (2) the pooled prevalence of scrub typhus infection in malaria-positive patients, and (3) the pooled odds of co-infection using the DerSimonian-Laird method for random-effects models. The study results and summary estimates were visualized on a forest plot as point estimates (effect size, prevalence) and 95% confidence intervals (CI). We assessed the heterogeneity of the studies by Cochrane Q or I2 statistics. We performed subgroup analyses of countries and scrub typhus diagnostic tests to explore the sources of heterogeneity of the included studies. We assessed publication bias if more than 10 studies were used to estimate the outcome. All data analyses were conducted using Stata version 14 (StataCorp, College Station, TX, USA).ResultsOf the 542 studies retrieved from three databases, we included 14 meeting the inclusion criteria in the systematic review and meta-analysis. The pooled prevalence of malaria and scrub typhus co-infection (56 cases) among febrile patients (7920 cases) was 1% (95% CI: 0-1%, I2: 78.28%), while the pooled prevalence of scrub typhus infection (321 cases) in patients with malaria (1418 cases) was 21% (95% CI: 12-30%, I2: 98.15%). Subgroup analysis showed that the pooled prevalence of scrub typhus infection among patients with malaria in India was 8% (95% CI: 4-13%, I2: 85.87%, nine studies with 59/794 cases), while the pooled prevalence of scrub typhus infection among patients with malaria in Thailand was 35% (95% CI: 7-64%, I2: 98.9%, four studies with 262/624 cases). The co-infections did not occur by chance (P = 0.013, odds: 0.43, 95% CI: 0.22-0.84%, I2: 60.9%). In the sensitivity analysis, the pooled prevalence of malaria and scrub typhus co-infection among febrile patients was 0% (95% CI: 0-1%, I2: 59.91%).ConclusionsThe present study showed the pooled prevalence and a significant association between malaria and scrub typhus. The results show the status of co-infection. Further research into co-infection in endemic areas is needed, in particular, to determine whether co-infection can accelerate disease progression or protect against severe disease.

Project description:The geographical overlaps of malaria parasites and Salmonella spp. can lead to co-infection of these two pathogens, especially in the tropics where malaria is endemic. Moreover, few literatures suggested that malaria infection was associated with Salmonella bacteremia. Therefore, this study quantified pooled prevalence of typhoidal/non-typhoidal Salmonella (NTS) and probability of typhoidal/NTS and malaria co-infection among febrile patients. The systematic review protocol was registered at PROSPERO (CRD42021252322). Studies on co-infection of typhoidal/NTS and malaria were searched in PubMed, Scopus, and Web of Science. The risk of bias of the included studies was assessed using the checklist for analytical cross-sectional studies developed by the Joanna Briggs Institute. Meta-analyses on the following criteria were performed: (1) pooled prevalence of typhoidal/NTS and malaria co-infection among febrile patients, (2) pooled prevalence of typhoidal/NTS among malaria patients, (3) pooled prevalence of malaria infections among patients with Salmonella spp. infection, and (4) probability of typhoidal/NTS and malaria co-infection among febrile patients. Additionally, the case fatality rate and mean difference of malarial parasitemia between typhoidal/NTS and malaria co-infection and Plasmodium monoinfection were also determined. The subgroup analyses of typhoidal/NTS, regions (Africa and Asia), countries, time (publication year), characteristics of participants, and diagnostic tests for identifying Salmonella spp. were also conducted. A sensitivity test was performed to determine the robustness of the study outcomes. Publication bias among the included studies was evaluated using the funnel plot and Egger's test. All analyses were performed using Stata version 15 (StataCorp LLC, Texas, USA) with a p-value < 0.05 indicating statistical significance. Eighty-one studies that met the eligibility criteria were included in the analyses. Of the 73,775 study participants, 4523 had typhoidal/NTS and malaria co-infections. The pooled prevalence rates of typhoidal/NTS and malaria co-infection among febrile patients were 14% (95% confidence interval [CI], 9-19%; I2, 99.4%; 2971/17,720 cases) and 1% (95% CI 1-1%; I2, 89.9%; 252/29,081 cases) using the Widal test and culture methods for identifying Salmonella spp., respectively. The pooled prevalence rates of typhoidal/NTS infection among patients with malaria were 31% (95% CI 23-39%; I2, 99.5%; 3202/19,208 cases) and 3% (95% CI 2-3%; I2, 86.8%; 407/40,426 cases) using the Widal test and culture methods for identifying Salmonella spp., respectively. The pooled prevalence rates of malaria infection among patients with typhoidal/NTS were 17% (95% CI 6-29%; I2, 33.3%; 13/75 cases) and 43% (95% CI 32-53%; I2, 89.1%; 287/736 cases), respectively. Malaria infection was associated with typhoidal/NTS in children aged < 15 years (p < 0.0001; odds ratio, 0.36; 95% CI 0.23-0.58; I2, 73.9%; 3188/43,212 cases). The case fatality rate in patients with malaria and NTS co-infections was 16% (95% CI 9-24%; I2, 89.1%; 18/103 cases). From the view of the present study, the inappropriate use of the Widal test for Salmonella spp. diagnosis can overestimate the prevalence of typhoidal/NTS and malaria co-infections. Malaria infection associated with typhoidal/NTS in children and the high case fatality rates among few patients with co-infections were highlighted. Future prospective longitudinal studies using the appropriate and confirmatory dsiagnosis for Salmonella spp. infections are highly recommended to ensure the real prevalence of co-infection and highlight the outcome of co-infection for providing adequate treatment in febrile patients who live in areas where malaria is endemic, such as tropical Africa and India.

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:Human African trypanosomiasis (HAT) is endemic in Africa; hence, the possibility of co-infection with malaria among patients with HAT exists. The present study investigated co-infection with malaria among patients with HAT to provide current evidence and characteristics to support further studies. Potentially relevant studies that reported Plasmodium spp. infection in patients with HAT was searched in PubMed, Web of Science, and Scopus. The risk of bias among the included studies was assessed using the checklist for analytical cross-sectional studies developed by the Joanna Briggs Institute. The pooled prevalence of Plasmodium spp. infection in patients with HAT was quantitatively synthesized using a random-effects model. Subgroup analyses of study sites and stages of HAT were performed to identify heterogeneity regarding prevalence among the included studies. The heterogeneity of the outcome among the included studies was assessed using Cochran's Q and I2 statistics for consistency. Publication bias was assessed if the number of included studies was 10 or more. For qualitative synthesis, a narrative synthesis of the impact of Plasmodium spp. infection on the clinical and outcome characteristics of HAT was performed when the included studies provided qualitative data. Among 327 studies identified from three databases, nine studies were included in the systematic review and meta-analysis. The prevalence of Plasmodium spp. co-infection (692 cases) among patients with HAT (1523 cases) was 50% (95% confidence interval [CI] = 28-72%, I2 = 98.1%, seven studies). Subgroup analysis by type of HAT (gambiense or rhodesiense HAT) revealed that among patients with gambiense HAT, the pooled prevalence of Plasmodium spp. infection was 46% (95% CI = 14-78%, I2 = 96.62%, four studies), whereas that among patients with rhodesiense HAT was 44% (95% CI = 40-49%, I2 = 98.3%, three studies). Qualitative syntheses demonstrated that Plasmodium spp. infection in individuals with HAT might influence the risk of encephalopathy syndrome, drug toxicity, and significantly longer corrected QT time. Moreover, longer hospital stays and higher treatment costs were recorded among co-infected individuals. Because of the high prevalence of malaria among patients with HAT, some patients were positive for malaria parasites despite being asymptomatic. Therefore, it is suggested to test every patient with HAT for malaria before HAT treatment. If malaria is present, then antimalarial treatment is recommended before HAT treatment. Antimalarial treatment in patients with HAT might decrease the probability of poor clinical outcomes and case fatality in HAT.

Project description:BackgroundLeukocyte alterations are a common hematological alteration among malaria patients.ObjectivesThis systematic review and meta-analysis aimed to provide data and evidence comparing alterations in total leukocyte counts in malaria patients compared to febrile/healthy subjects at baseline before treatment. A systematic review was conducted by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for reporting systematic reviews and meta-analyses.Data sourcesWeb of Science (ISI), Scopus, and Medline.Study eligibility criteria, participants, and interventionsAll published articles reporting a total leukocyte count of patients infected with malaria, non-malaria (febrile or healthy group) at baseline before treatment before August 27, 2019, were retrieved, and data were extracted by two main reviewers independently.Study appraisal and synthesis methodsWe used a forest plot, heterogeneity test (Cochran's Q), and the degree of heterogeneity (I2) to test whether the included studies were heterogeneous. The quality of the included studies was determined by a quality assessment guide based on the quality assessment tool developed by the Newcastle-Ottawa Scale (NOS). Cochran's Q (Chi-square) and Moran's I2 were used to evaluate heterogeneity. Meta-regression using STATA software was conducted to find the source of heterogeneity. A funnel plot with Egger's test was used to examine the significance of publication bias among the included studies. The mean differences were estimated using a random-effects model.ResultsOut of the 2,261 articles screened, 29 articles were included in this systematic review and meta-analysis. The heterogeneity test indicated that there was heterogeneity among the included studies with no publication bias. The meta-analysis demonstrated that the total leukocyte count was significantly lower in patients with malaria (n = 4,619) than in those without malaria (n = 10,056) (Z = 4.0, P-value < 0.00001, mean difference = -1.38, 95% CI = -2.06-(-0.71)). Leukocyte differential alterations, low lymphocyte counts (P-value <0.0001, mean difference = -1.03, 95% CI = -1.53-(-0.53)) and a high NL ratio were found in the malaria group (n = 1,579) compared to the non-malaria group (n = 4,991) (P-value <0.0001, mean difference = 0.6, 95% CI = 0.32-0.88). The subgroup analysis indicated that there was a significantly lower total leukocyte count in the malaria group (n = 3,545) than in the febrile group (n = 8,947) (Z = 1.33, P-value < 0.0001, mean difference = -1.76, 95% CI = -2.56-(-0.96)), but no significant difference was found between the malaria group (n = 1,232) and the healthy group (n = 1,679) (P-value > 0.05).LimitationsAs the specific diagnoses in the febrile groups were not reported in the included studies so that the results of the present study need to be carefully interpreted.Conclusions and implications of key findingsThis systematic review demonstrated that the total leukocyte count was affected by malarial infection at baseline despite the heterogeneity of the included studies. Future work must aim to understand the treatment-related total leukocyte reduction during follow-up or post-treatment outcomes in malaria-endemic settings.

Project description:BackgroundMalaria and visceral leishmaniasis (VL) co-infection can occur due to the overlapping geographical distributions of these diseases; however, only limited data of this co-infection have been reported and reviewed. This study aimed to explore the pooled prevalence and characteristics of this co-infection using a systematic review approach.MethodsThe PubMed, Web of Science and Scopus databases were searched for relevant studies. The quality of these studies was assessed in accordance with strengthening the reporting of observational studies in epidemiology (STROBE) guidelines. The numbers of individuals co-infected with Plasmodium and VL and the total numbers of individuals with VL were used to estimate the pooled prevalence using random-effects models. Differences in age, sex and the presence of anemia and malnutrition on admission were compared between co-infected individuals and individuals with VL using a random-effects model; the results are presented as odds ratios (ORs) and 95% confidence intervals (CIs). Heterogeneity among the included studies was assessed and quantified using Cochrane Q and I2 statistics.ResultsOf the 3075 studies identified, 12 met the eligibility criteria and were included in this systematic review. The pooled prevalence of Plasmodium infection among the 6453 individuals with VL was 13%, with substantial heterogeneity of the data (95% CI 7-18%, I2 97.9%). Subgroup analysis demonstrated that the highest prevalence of co-infection occurred in African countries, whereas the lowest prevalence occurred in Asian countries. Patients aged < 5 years had higher odds of having co-infection than having VL (co-infection, n = 202; VL, n = 410) (OR 1.66, 95% CI 1.37-2.01, I2 0%; P < 0.0001), whereas patients aged 20-29 years had lower odds of having co-infection than having VL (co-infection, n = 170; VL, n = 699) (OR 0.75, 95% CI 0.60-0.93, I2 18%; P = 0.01). Male patients had equivalent odds of having co-infection and having VL (co-infection, n = 525; VL, n = 2232) (OR 0.92, 95% CI 0.078-1.08, I2 0%; P = 0.29). Patients with co-infection had lower odds of having anemia at admission than those with VL (co-infection, n = 902; VL, n = 2939) (OR 0.64, 95% CI 0.44-0.93, I2 0%; P = 0.02). No difference in malnutrition at admission was found in the meta-analysis.ConclusionsThe prevalence of malaria co-infection among individuals with VL was heterogeneous and ranged from 7 to 18%, depending on geographical area. Age and anemia at admission were associated with co-infection status. Further longitudinal studies are needed to determine if co-infection with malaria has an impact on the severity of VL.

Project description:BackgroundCo-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.MethodsRelevant 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.ResultsOf 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%).ConclusionsThe 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 registrationThe protocol of this study was registered at PROSPERO: CRD42020196792 .

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Prevalence of Malaria and Leptospirosis Co-Infection among Febrile Patients: A Systematic Review and Meta-Analysis.

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