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Prevalence, probability, and outcomes of typhoidal/non-typhoidal Salmonella and malaria co-infection among febrile patients: a systematic review and meta-analysis

ABSTRACT: 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.

SUBMITTER: Wilairatana P

PROVIDER: S-EPMC8576030 | 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: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.

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: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:BackgroundNon-typhoidal Salmonella (NTS) commonly causes diarrhoea, and is usually self-limiting, although sometimes people become ill with sepsis and dehydration. Routine antibiotic use for this infection could result in persistent colonization and the spread of resistant bacterial strains.ObjectivesTo assess the efficacy and safety of giving antibiotics to people with NTS diarrhoea.Search methodsWe searched the Cochrane Infectious Diseases Group trials register (up to August 2012), the Cochrane Controlled Trials Register (CENTRAL) published in The Cochrane Library (up to Issue 8 2012); and MEDLINE, African Index Medicus, CINAHL, EMBASE, LILACS, and the Science Citation Index, all up to 6 August 2012. We also searched the metaRegister of Controlled Trials (mRCT) for both completed and on going trials and reference lists of relevant articles.Selection criteriaRandomized controlled trials (RCTs) comparing any antibiotic treatment for diarrhoea caused by NTS species with placebo or no antibiotic treatment. We selected trials that included people of all ages who were symptomatic for NTS infection. Examples of symptoms included fever, abdominal pain, vomiting and diarrhoea. We excluded trials where the outcomes were not reported separately for the NTS subgroup of patients. Two review authors independently applied eligibility criteria prior to study inclusion.Data collection and analysisTwo review authors independently extracted data on pre-specified outcomes and independently assessed the risk of bias of included studies. The primary outcome was the presence of diarrhoea between two to four days after treatment. The quality of evidence was assessed using the GRADE methods.Main resultsTwelve trials involving 767 participants were included. No differences were detected between the antibiotic and placebo/no treatment arms for people with diarrhoea at two to four days after treatment (risk ratio (RR) 1.75, 95% confidence interval (CI) 0.42 to 7.21; one trial, 46 participants; very low quality evidence). No difference was detected for the presence of diarrhoea at five to seven days after treatment (RR 0.83, 95% CI 0.62 to 1.12; two trials, 192 participants; very low quality evidence), clinical failure (RR 0.88, 95% CI 0.62 to 1.25; seven trials, 440 participants; very low quality evidence). The mean difference for diarrhoea was 0 days (95% CI -0.54 to 0.54; 202 participants, four studies; low quality evidence);for fever was 0.27 days (95% CI -0.11 to 0.65; 107 participants, two studies; very low quality evidence); and for duration of illness was 0 days (95% CI -0.68 to 0.68; 116 participants, two studies; very low quality evidence). Quinolone antibiotic treatment resulted in a significantly higher number of negative stool cultures for NTS during the first week of treatment (microbiological failure: RR 0.33, 95% CI 0.20 to 0.56; 166 participants, four trials).Antibiotic treatment meant passage of the same Salmonella serovar one month after treatment was almost twice as likely (RR 1.96, 95% CI 1.29 to 2.98; 112 participants, three trials), which was statistically significant. Non-severe adverse drug reactions were more common among the patients who received antibiotic treatment.Authors' conclusionsThere is no evidence of benefit for antibiotics in NTS diarrhoea in otherwise healthy people. We are uncertain of the effects in very young people, very old people, and in people with severe and extraintestinal disease. A slightly higher number of adverse events were noted in people who received antibiotic treatment for NTS.

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Prevalence, probability, and outcomes of typhoidal/non-typhoidal Salmonella and malaria co-infection among febrile patients: a systematic review and meta-analysis

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