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PLoS Neglected Tropical Diseases Oct 2018The temporal and spatial change in trends of antimicrobial resistance (AMR) in typhoid have not been systematically studied, and such information will be critical for...
BACKGROUND
The temporal and spatial change in trends of antimicrobial resistance (AMR) in typhoid have not been systematically studied, and such information will be critical for defining intervention, as well as planning sustainable prevention strategies.
METHODOLOGY AND FINDINGS
To identify the phenotypic trends in AMR, 13,833 individual S. Typhi isolates, reported from 1973 to 2018 in 62 publications, were analysed to determine the AMR preponderance over time. Separate analyses of molecular resistance determinants present in over 4,000 isolates reported in 61 publications were also conducted. Multi-drug resistant (MDR) typhoid is in decline in Asia in a setting of high fluoroquinolone resistance while it is on the increase in Africa. Mutations in QRDRs in gyrA (S83F, D87N) and parC (S80I) are the most common mechanisms responsible for fluoroquinolone resistance. Cephalosporin resistant S. Typhi, dubbed extensively drug-resistant (XDR) is a real threat and underscores the urgency in deploying the Vi-conjugate vaccines.
CONCLUSION
From these observations, it appears that AMR in S. Typhi will continue to emerge leading to treatment failure, changes in antimicrobial policy and further resistance developing in S. Typhi isolates and other Gram-negative bacteria in endemic regions. The deployment of typhoid conjugate vaccines to control the disease in endemic regions may be the best defence.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Genes, Bacterial; Genotype; Global Health; Humans; Phenotype; Salmonella typhi; Typhoid Fever
PubMed: 30307935
DOI: 10.1371/journal.pntd.0006779 -
BMC Infectious Diseases Sep 2018Salmonella Typhi is a human pathogen that causes typhoid fever. It is a major cause of morbidity and mortality in developing countries and is responsible for several... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Salmonella Typhi is a human pathogen that causes typhoid fever. It is a major cause of morbidity and mortality in developing countries and is responsible for several outbreaks in developed countries. Studying certain parameters of the pathogen, such as the incubation period, provides a better understanding of its pathophysiology and its characteristics within a population. Outbreak investigations and human experimental studies provide an avenue to study these relevant parameters.
METHODS
In this study, the authors have undertaken a systematic review of outbreak investigation reports and experimental studies, extracted reported data, tested for heterogeneity, identified subgroups of studies with limited evidence of heterogeneity between them and identified factors that may contribute to the distribution of incubation period. Following identification of relevant studies, we extracted both raw and summary incubation data. We tested for heterogeneity by deriving the value of I and conducting a KS-test to compare the distribution between studies. We performed a linear regression analysis to identify the factors associated with incubation period and using the resulting p-values from the KS-test, we conducted a hierarchical cluster analysis to classify studies with limited evidence of heterogeneity into subgroups.
RESULTS
We identified thirteen studies to be included in the review and extracted raw incubation period data from eleven. The value of I was 84% and the proportion of KS test p-values that were less than 0.05 was 63.6% indicating high heterogeneity not due to chance. We identified vaccine history and attack rates as factors that may be associated with incubation period, although these were not significant in the multivariable analysis (p-value: 0.1). From the hierarchical clustering analysis, we classified the studies into five subgroups. The mean incubation period of the subgroups ranged from 9.7 days to 21.2 days. Outbreaks reporting cases with previous vaccination history were clustered in a single subgroup and reported the longest incubation period.
CONCLUSIONS
We identified attack rate and previous vaccination as possible associating factors, however further work involving analyses of individual patient data and developing mathematical models is needed to confirm these as well as examine additional factors that have not been included in our study.
Topics: Databases, Factual; Disease Outbreaks; Humans; Infectious Disease Incubation Period; Linear Models; Salmonella Infections; Salmonella typhi; Serogroup
PubMed: 30261843
DOI: 10.1186/s12879-018-3391-3 -
The American Journal of Tropical... Sep 2018Typhoid and paratyphoid fever continue to significantly contribute to global morbidity and mortality. Disease burden is higher in low-and middle-income settings where...
Typhoid and paratyphoid fever continue to significantly contribute to global morbidity and mortality. Disease burden is higher in low-and middle-income settings where surveillance programs are rare and little systematic information exists at population level. This review evaluates national, regional, and global trends in the incidence of typhoid fever and of related morbidity and mortality. A literature search in Medline, Embase, and Web of Science was conducted in June 2016, followed by screening and data extraction in duplicate. Studies reporting blood culture estimates of typhoid or paratyphoid morbidity and mortality were included in the analysis. Our search yielded 5,563 unique records, of which 1978 were assessed for relevance with 219 records meeting the eligibility criteria. serotype Typhi was the most commonly reported organism (91%), with the occurrence of typhoidal (either incidence or prevalence) being the most commonly reported outcome (78%), followed by typhoid fever mortality, ileal perforation morbidity, and perforation mortality, respectively. Fewer than 50% of studies stratified outcomes by age or urban/rural locality. Surveillance data were available from 29 countries and patient-focused studies were available from 32 countries. Our review presents a mixed picture with declines reported in many regions and settings but with large gaps in surveillance and published data. Regional trends show generally high incidence rates in South Asia, sub-Saharan Africa, and East Asia and Pacific where the disease is endemic in many countries. Significant increases have been reported in certain countries but should be explored in the context of long-term trends and underlying at-risk populations.
Topics: Global Health; Humans; Paratyphoid Fever; Public Health; Typhoid Fever; Water Microbiology
PubMed: 30047364
DOI: 10.4269/ajtmh.18-0034 -
The Cochrane Database of Systematic... May 2018Typhoid fever and paratyphoid fever continue to be important causes of illness and death, particularly among children and adolescents in south-central and southeast... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Typhoid fever and paratyphoid fever continue to be important causes of illness and death, particularly among children and adolescents in south-central and southeast Asia. Two typhoid vaccines are widely available, Ty21a (oral) and Vi polysaccharide (parenteral). Newer typhoid conjugate vaccines are at varying stages of development and use. The World Health Organization has recently recommended a Vi tetanus toxoid (Vi-TT) conjugate vaccine, Typbar-TCV, as the preferred vaccine for all ages.
OBJECTIVES
To assess the effects of vaccines for preventing typhoid fever.
SEARCH METHODS
In February 2018, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, and mRCT. We also searched the reference lists of all included trials.
SELECTION CRITERIA
Randomized and quasi-randomized controlled trials (RCTs) comparing typhoid fever vaccines with other typhoid fever vaccines or with an inactive agent (placebo or vaccine for a different disease) in adults and children. Human challenge studies were not eligible.
DATA COLLECTION AND ANALYSIS
Two review authors independently applied inclusion criteria and extracted data, and assessed the certainty of the evidence using the GRADE approach. We computed vaccine efficacy per year of follow-up and cumulative three-year efficacy, stratifying for vaccine type and dose. The outcome addressed was typhoid fever, defined as isolation of Salmonella enterica serovar Typhi in blood. We calculated risk ratios (RRs) and efficacy (1 - RR as a percentage) with 95% confidence intervals (CIs).
MAIN RESULTS
In total, 18 RCTs contributed to the quantitative analysis in this review: 13 evaluated efficacy (Ty21a: 5 trials; Vi polysaccharide: 6 trials; Vi-rEPA: 1 trial; Vi-TT: 1 trial), and 9 reported on adverse events. All trials but one took place in typhoid-endemic countries. There was no information on vaccination in adults aged over 55 years of age, pregnant women, or travellers. Only one trial included data on children under two years of age.Ty21a vaccine (oral vaccine, three doses)A three-dose schedule of Ty21a vaccine probably prevents around half of typhoid cases during the first three years after vaccination (cumulative efficacy 2.5 to 3 years: 50%, 95% CI 35% to 61%, 4 trials, 235,239 participants, moderate-certainty evidence). These data include patients aged 3 to 44 years.Compared with placebo, this vaccine probably does not cause more vomiting, diarrhoea, nausea or abdominal pain (2 trials, 2066 participants; moderate-certainty evidence), headache, or rash (1 trial, 1190 participants; moderate-certainty evidence); however, fever (2 trials, 2066 participants; moderate-certainty evidence) is probably more common following vaccination.Vi polysaccharide vaccine (injection, one dose)A single dose of Vi polysaccharide vaccine prevents around two-thirds of typhoid cases in the first year after vaccination (year 1: 69%, 95% CI 63% to 74%; 3 trials, 99,979 participants; high-certainty evidence). In year 2, trial results were more variable, with the vaccine probably preventing between 45% and 69% of typhoid cases (year 2: 59%, 95% CI 45% to 69%; 4 trials, 194,969 participants; moderate-certainty evidence). These data included participants aged 2 to 55 years of age.The three-year cumulative efficacy of the vaccine may be around 55% (95% CI 30% to 70%; 11,384 participants, 1 trial; low-certainty evidence). These data came from a single trial conducted in South Africa in the 1980s in participants aged 5 to 15 years.Compared with placebo, this vaccine probably did not increase the incidence of fever (3 trials, 132,261 participants; moderate-certainty evidence) or erythema (3 trials, 132,261 participants; low-certainty evidence); however, swelling (3 trials, 1767 participants; moderate-certainty evidence) and pain at the injection site (1 trial, 667 participants; moderate-certainty evidence) were more common in the vaccine group.Vi-rEPA vaccine (two doses)Administration of two doses of the Vi-rEPA vaccine probably prevents between 50% and 96% of typhoid cases during the first two years after vaccination (year 1: 94%, 95% CI 75% to 99%; year 2: 87%, 95% CI 56% to 96%, 1 trial, 12,008 participants; moderate-certainty evidence). These data came from a single trial with children two to five years of age conducted in Vietnam.Compared with placebo, both the first and the second dose of this vaccine increased the risk of fever (1 trial, 12,008 and 11,091 participants, low-certainty evidence) and the second dose increase the incidence of swelling at the injection site (one trial, 11,091 participants, moderate-certainty evidence).Vi-TT vaccine (two doses)We are uncertain of the efficacy of administration of two doses of Vi-TT (PedaTyph) in typhoid cases in children during the first year after vaccination (year 1: 94%, 95% CI -1% to 100%, 1 trial, 1625 participants; very low-certainty evidence). These data come from a single cluster-randomized trial in children aged six months to 12 years and conducted in India. For single dose Vi-TT (Typbar-TCV), we found no efficacy trials evaluating the vaccine with natural exposure.There were no reported serious adverse effects in RCTs of any of the vaccines studied.
AUTHORS' CONCLUSIONS
The licensed Ty21a and Vi polysaccharide vaccines are efficacious in adults and children older than two years in endemic countries. The Vi-rEPA vaccine is just as efficacious, although data is only available for children. The new Vi-TT vaccine (PedaTyph) requires further evaluation to determine if it provides protection against typhoid fever. At the time of writing, there were only efficacy data from a human challenge setting in adults on the Vi-TT vaccine (Tybar), which clearly justify the ongoing field trials to evaluate vaccine efficacy.
Topics: Adolescent; Adult; Child; Child, Preschool; Humans; Incidence; Randomized Controlled Trials as Topic; Salmonella typhi; Time Factors; Typhoid Fever; Typhoid-Paratyphoid Vaccines; Vaccines, Attenuated
PubMed: 29851031
DOI: 10.1002/14651858.CD001261.pub4 -
Clinical Infectious Diseases : An... Aug 2018Enteric fever is a febrile illness, occurring mostly in Asia and Africa, which can present as a severe and possibly fatal disease. Currently, a case fatality rate (CFR)... (Meta-Analysis)
Meta-Analysis
Enteric fever is a febrile illness, occurring mostly in Asia and Africa, which can present as a severe and possibly fatal disease. Currently, a case fatality rate (CFR) of 1% is assumed when evaluating the global burden of enteric fever. Until now, no meta-analysis has been conducted to summarize mortality from enteric fever. Therefore, we conducted a systematic review and meta-analysis to aggregate all available evidence. We estimated an overall CFR of 2.49% (95% confidence interval, 1.65%-3.75%; n = 44), and a CFR in hospitalized patients of 4.45% (2.85%-6.88%; n = 21 of 44). There was considerably heterogeneity in estimates of the CFR from individual studies. Neither age nor antimicrobial resistance were significant prognostic factors, but limited data were available for these analyses. The combined estimate of the CFR for enteric fever is higher than previously estimated, and the evaluation of prognostic factors, including antimicrobial resistance, urgently requires more data.
Topics: Africa; Anti-Bacterial Agents; Asia; Endemic Diseases; Humans; Paratyphoid Fever; Salmonella paratyphi A; Salmonella typhi; Typhoid Fever
PubMed: 29522159
DOI: 10.1093/cid/ciy190 -
PloS One 2018Wide-ranging evidence on the occurrence of fluoroquinolone (FQ) resistance genetic determinants in African Salmonella strains is not available. The main objectives of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Wide-ranging evidence on the occurrence of fluoroquinolone (FQ) resistance genetic determinants in African Salmonella strains is not available. The main objectives of this study were to assess the heterogeneity, estimate pooled proportions and describe the preponderance of FQ-resistance determinants in typhoidal and non-typhoidal Salmonella (NTS) isolates of Africa.
METHODS
Genetic and phenotypic data on 6103 Salmonella isolates were considered. Meta- and frequency analyses were performed depending on the number of studies by category, number of isolates and risks of bias. A random effects model was used to assess heterogeneity and estimate pooled proportions. Relative and cumulative frequencies were calculated to describe the overall preponderance of FQ-resistance determinants in quinolone resistant isolates.
RESULTS
The pooled proportion of gyrA mutants (Salmonella enterica serovar Typhi, Salmonella enterica serovar Typhimurium, and Salmonella enterica serovar Enteritidis) was estimated at 5.7% (95% Confidence interval (CI) = 2.6, 9.8; Tau squared (T2) = 0.1105), and was higher in S. Typhi than in S. Typhimurium (odds ratio (OR) = 3.3, 95%CI = 2, 5.7). The proportions of each of gyrB and parC mutants, and strains with Plasmid Mediated Quinolone Resistance genes (qnrA, qnrB and qnrS) were low (≤ 0.3%). Overall, 23 mutant serotypes were identified, and most strains had mutations at codons encoding Ser83 and Asp87 of gyrA (82%, 95%CI = 78, 86).
CONCLUSIONS
Mutations at gyrA appear to account for ciprofloxacin non-susceptibility in most clinical Salmonella strains in Africa. The estimates could be harnessed to develop a mismatch-amplification mutation-assay for the detection of FQ-resistant strains in Africa.
Topics: Africa; Drug Resistance, Bacterial; Fluoroquinolones; Molecular Epidemiology; Mutation; Salmonella
PubMed: 29432492
DOI: 10.1371/journal.pone.0192575 -
BMC Infectious Diseases Sep 2017Antimicrobial resistance (AMR) is widely acknowledged as a global problem, yet in many parts of the world its magnitude is still not well understood. This review, using... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antimicrobial resistance (AMR) is widely acknowledged as a global problem, yet in many parts of the world its magnitude is still not well understood. This review, using a public health focused approach, aimed to understand and describe the current status of AMR in Africa in relation to common causes of infections and drugs recommended in WHO treatment guidelines.
METHODS
PubMed, EMBASE and other relevant databases were searched for recent articles (2013-2016) in accordance with the PRISMA guidelines. Article retrieval and screening were done using a structured search string and strict inclusion/exclusion criteria. Median and interquartile ranges of percent resistance were calculated for each antibiotic-bacterium combination.
RESULTS
AMR data was not available for 42.6% of the countries in the African continent. A total of 144 articles were included in the final analysis. 13 Gram negative and 5 Gram positive bacteria were tested against 37 different antibiotics. Penicillin resistance in Streptococcus pneumoniae was reported in 14/144studies (median resistance (MR): 26.7%). Further 18/53 (34.0%) of Haemophilus influenza isolates were resistant to amoxicillin. MR of Escherichia coli to amoxicillin, trimethoprim and gentamicin was 88.1%, 80.7% and 29.8% respectively. Ciprofloxacin resistance in Salmonella Typhi was rare. No documented ceftriaxone resistance in Neisseria gonorrhoeae was reported, while the MR for quinolone was 37.5%. Carbapenem resistance was common in Acinetobacter spp. and Pseudomonas aeruginosa but uncommon in Enterobacteriaceae.
CONCLUSION
Our review highlights three important findings. First, recent AMR data is not available for more than 40% of the countries. Second, the level of resistance to commonly prescribed antibiotics was significant. Third, the quality of microbiological data is of serious concern. Our findings underline that to conserve our current arsenal of antibiotics it is imperative to address the gaps in AMR diagnostic standardization and reporting and use available information to optimize treatment guidelines.
Topics: Africa; Anti-Bacterial Agents; Bacterial Infections; Ceftriaxone; Ciprofloxacin; Drug Resistance, Bacterial; Enterobacteriaceae; Escherichia coli; Humans; Neisseria gonorrhoeae
PubMed: 28893183
DOI: 10.1186/s12879-017-2713-1 -
The Cochrane Database of Systematic... May 2017Differentiating both typhoid (Salmonella Typhi) and paratyphoid (Salmonella Paratyphi A) infection from other causes of fever in endemic areas is a diagnostic challenge.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Differentiating both typhoid (Salmonella Typhi) and paratyphoid (Salmonella Paratyphi A) infection from other causes of fever in endemic areas is a diagnostic challenge. Although commercial point-of-care rapid diagnostic tests (RDTs) for enteric fever are available as alternatives to the current reference standard test of blood or bone marrow culture, or to the widely used Widal Test, their diagnostic accuracy is unclear. If accurate, they could potentially replace blood culture as the World Health Organization (WHO)-recommended main diagnostic test for enteric fever.
OBJECTIVES
To assess the diagnostic accuracy of commercially available rapid diagnostic tests (RDTs) and prototypes for detecting Salmonella Typhi or Paratyphi A infection in symptomatic persons living in endemic areas.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, IndMED, African Index Medicus, LILACS, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) up to 4 March 2016. We manually searched WHO reports, and papers from international conferences on Salmonella infections. We also contacted test manufacturers to identify studies.
SELECTION CRITERIA
We included diagnostic accuracy studies of enteric fever RDTs in patients with fever or with symptoms suggestive of enteric fever living in endemic areas. We classified the reference standard used as either Grade 1 (result from a blood culture and a bone marrow culture) or Grade 2 (result from blood culture and blood polymerase chain reaction, or from blood culture alone).
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted the test result data. We used a modified QUADAS-2 extraction form to assess methodological quality. We performed a meta-analysis when there were sufficient studies for the test and heterogeneity was reasonable.
MAIN RESULTS
Thirty-seven studies met the inclusion criteria and included a total of 5080 participants (range 50 to 1732). Enteric fever prevalence rates in the study populations ranged from 1% to 75% (median prevalence 24%, interquartile range (IQR) 11% to 46%). The included studies evaluated 16 different RDTs, and 16 studies compared two or more different RDTs. Only three studies used the Grade 1 reference standard, and only 11 studies recruited unselected febrile patients. Most included studies were from Asia, with five studies from sub-Saharan Africa. All of the RDTs were designed to detect S.Typhi infection only.Most studies evaluated three RDTs and their variants: TUBEX in 14 studies; Typhidot (Typhidot, Typhidot-M, and TyphiRapid-Tr02) in 22 studies; and the Test-It Typhoid immunochromatographic lateral flow assay, and its earlier prototypes (dipstick, latex agglutination) developed by the Royal Tropical Institute, Amsterdam (KIT) in nine studies. Meta-analyses showed an average sensitivity of 78% (95% confidence interval (CI) 71% to 85%) and specificity of 87% (95% CI 82% to 91%) for TUBEX; and an average sensitivity of 69% (95% CI 59% to 78%) and specificity of 90% (95% CI 78% to 93%) for all Test-It Typhoid and prototype tests (KIT). Across all forms of the Typhidot test, the average sensitivity was 84% (95% CI 73% to 91%) and specificity was 79% (95% CI 70% to 87%). When we based the analysis on the 13 studies of the Typhidot test that either reported indeterminate test results or where the test format means there are no indeterminate results, the average sensitivity was 78% (95% CI 65% to 87%) and specificity was 77% (95% CI 66% to 86%). We did not identify any difference in either sensitivity or specificity between TUBEX, Typhidot, and Test-it Typhoid tests when based on comparison to the 13 Typhidot studies where indeterminate results are either reported or not applicable. If TUBEX and Test-it Typhoid are compared to all Typhidot studies, the sensitivity of Typhidot was higher than Test-it Typhoid (15% (95% CI 2% to 28%), but other comparisons did not show a difference at the 95% level of CIs.In a hypothetical cohort of 1000 patients presenting with fever where 30% (300 patients) have enteric fever, on average Typhidot tests reporting indeterminate results or where tests do not produce indeterminate results will miss the diagnosis in 66 patients with enteric fever, TUBEX will miss 66, and Test-It Typhoid and prototype (KIT) tests will miss 93. In the 700 people without enteric fever, the number of people incorrectly diagnosed with enteric fever would be 161 with Typhidot tests, 91 with TUBEX, and 70 with Test-It Typhoid and prototype (KIT) tests. The CIs around these estimates were wide, with no difference in false positive results shown between tests.The quality of the data for each study was evaluated using a standardized checklist called QUADAS-2. Overall, the certainty of the evidence in the studies that evaluated enteric fever RDTs was low.
AUTHORS' CONCLUSIONS
In 37 studies that evaluated the diagnostic accuracy of RDTs for enteric fever, few studies were at a low risk of bias. The three main RDT tests and variants had moderate diagnostic accuracy. There was no evidence of a difference between the average sensitivity and specificity of the three main RDT tests. More robust evaluations of alternative RDTs for enteric fever are needed.
Topics: Adult; Child; False Negative Reactions; False Positive Reactions; Humans; Immunoassay; Paratyphoid Fever; Polymerase Chain Reaction; Reagent Kits, Diagnostic; Reference Standards; Sensitivity and Specificity; Typhoid Fever
PubMed: 28545155
DOI: 10.1002/14651858.CD008892.pub2 -
Clinical Infectious Diseases : An... Jun 2017Children bear a substantial proportion of the enteric fever disease burden in endemic areas. Controversy persists regarding which age groups are most affected, leading... (Meta-Analysis)
Meta-Analysis Review
Children bear a substantial proportion of the enteric fever disease burden in endemic areas. Controversy persists regarding which age groups are most affected, leading to uncertainty about optimal intervention strategies. We performed a systematic review and meta-analysis of studies in Asia and Africa to compare the relative proportion of children with enteric fever in the age groups <5 years, 5-9 years, and 10-14 years. Overall, studies conducted in Africa showed a relatively smaller occurrence of disease in the youngest age group, whereas in Asia the picture was more mixed with a very large degree of heterogeneity in estimates. The clinical features of enteric fever reviewed here differ between younger and older children and adults, likely leading to further uncertainty over disease burden. It is evident from our review that preschool children and infants also contribute a significant proportion of disease burden but have not been adequately targeted via vaccination programs, which have been focusing primarily on school-based vaccination campaigns.
Topics: Adolescent; Africa; Age Factors; Asia; Child; Child, Preschool; Cost of Illness; Female; Humans; Immunization Programs; Infant; Male; Paratyphoid Fever; Prevalence; Salmonella paratyphi A; Salmonella typhi; Typhoid Fever
PubMed: 28369224
DOI: 10.1093/cid/cix229 -
Annals of Clinical Microbiology and... May 2016Blood culture is often used in definitive diagnosis of typhoid fever while, bone marrow culture has a greater sensitivity and considered reference standard. The... (Review)
Review
Blood culture is often used in definitive diagnosis of typhoid fever while, bone marrow culture has a greater sensitivity and considered reference standard. The sensitivity of blood culture measured against bone marrow culture results in measurement bias because both tests are not fully sensitive. Here we propose a combination of the two cultures as a reference to define true positive S. Typhi cases. Based on a systematic literature review, we identified ten papers that had performed blood and bone marrow culture for S. Typhi in same subjects. We estimated the weighted mean of proportion of cases detected by culture measured against true S. Typhi positive cases using a random effects model. Of 529 true positive S. Typhi cases, 61 % (95 % CI 52-70 %) and 96 % (95 % CI 93-99 %) were detected by blood and bone marrow cultures respectively. Blood culture sensitivity was 66 % (95 % CI 56-75 %) when compared with bone marrow culture results. The use of blood culture sensitivity as a proxy measure to estimate the proportion of typhoid fever cases detected by blood culture is likely to be an underestimate. As blood culture sensitivity is used as a correction factor in estimating typhoid disease burden, epidemiologists and policy makers should account for the underestimation.
Topics: Blood Culture; Bone Marrow; False Negative Reactions; False Positive Reactions; Humans; Salmonella typhi; Sensitivity and Specificity; Typhoid Fever
PubMed: 27188991
DOI: 10.1186/s12941-016-0147-z