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BMC Medicine Jan 2020Antimicrobial resistance (AMR) is an increasing threat to global health. There are > 14 million cases of enteric fever every year and > 135,000 deaths. The disease... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antimicrobial resistance (AMR) is an increasing threat to global health. There are > 14 million cases of enteric fever every year and > 135,000 deaths. The disease is primarily controlled by antimicrobial treatment, but this is becoming increasingly difficult due to AMR. Our objectives were to assess the prevalence and geographic distribution of AMR in Salmonella enterica serovars Typhi and Paratyphi A infections globally, to evaluate the extent of the problem, and to facilitate the creation of geospatial maps of AMR prevalence to help targeted public health intervention.
METHODS
We performed a systematic review of the literature by searching seven databases for studies published between 1990 and 2018. We recategorised isolates to allow the analysis of fluoroquinolone resistance trends over the study period. The prevalence of multidrug resistance (MDR) and fluoroquinolone non-susceptibility (FQNS) in individual studies was illustrated by forest plots, and a random effects meta-analysis was performed, stratified by Global Burden of Disease (GBD) region and 5-year time period. Heterogeneity was assessed using the I statistics. We present a descriptive analysis of ceftriaxone and azithromycin resistance.
FINDINGS
We identified 4557 articles, of which 384, comprising 124,347 isolates (94,616 S. Typhi and 29,731 S. Paratyphi A) met the pre-specified inclusion criteria. The majority (276/384; 72%) of studies were from South Asia; 40 (10%) articles were identified from Sub-Saharan Africa. With the exception of MDR S. Typhi in South Asia, which declined between 1990 and 2018, and MDR S. Paratyphi A, which remained at low levels, resistance trends worsened for all antimicrobials in all regions. We identified several data gaps in Africa and the Middle East. Incomplete reporting of antimicrobial susceptibility testing (AST) and lack of quality assurance were identified.
INTERPRETATION
Drug-resistant enteric fever is widespread in low- and middle-income countries, and the situation is worsening. It is essential that public health and clinical measures, which include improvements in water quality and sanitation, the deployment of S. Typhi vaccination, and an informed choice of treatment are implemented. However, there is no licenced vaccine for S. Paratyphi A. The standardised reporting of AST data and rollout of external quality control assessment are urgently needed to facilitate evidence-based policy and practice.
TRIAL REGISTRATION
PROSPERO CRD42018029432.
Topics: Anti-Bacterial Agents; Azithromycin; Drug Resistance, Bacterial; Global Health; Humans; Paratyphoid Fever; Prevalence; Salmonella paratyphi A; Salmonella typhi; Typhoid Fever
PubMed: 31898501
DOI: 10.1186/s12916-019-1443-1 -
Antimicrobial Resistance and Infection... 2019Despite a high mortality rate in childhood, there is limited evidence on the causes and outcomes of paediatric bloodstream infections from low- and middle-income... (Meta-Analysis)
Meta-Analysis
Bacterial pathogens and resistance causing community acquired paediatric bloodstream infections in low- and middle-income countries: a systematic review and meta-analysis.
BACKGROUND
Despite a high mortality rate in childhood, there is limited evidence on the causes and outcomes of paediatric bloodstream infections from low- and middle-income countries (LMICs). We conducted a systematic review and meta-analysis to characterize the bacterial causes of paediatric bloodstream infections in LMICs and their resistance profile.
METHODS
We searched Pubmed and Embase databases between January 1st 1990 and October 30th 2019, combining MeSH and free-text terms for "sepsis" and "low-middle-income countries" in children. Two reviewers screened articles and performed data extraction to identify studies investigating children (1 month-18 years), with at least one blood culture. The main outcomes of interests were the rate of positive blood cultures, the distribution of bacterial pathogens, the resistance patterns and the case-fatality rate. The proportions obtained from each study were pooled using the Freeman-Tukey double arcsine transformation, and a random-effect meta-analysis model was used.
RESULTS
We identified 2403 eligible studies, 17 were included in the final review including 52,915 children (11 in Africa and 6 in Asia). The overall percentage of positive blood culture was 19.1% [95% CI: 12.0-27.5%]; 15.5% [8.4-24.4%] in Africa and 28.0% [13.2-45.8%] in Asia. A total of 4836 bacterial isolates were included in the studies; 2974 were Gram-negative (63.9% [52.2-74.9]) and 1858 were Gram-positive (35.8% [24.9-47.5]). In Asia, typhi (26.2%) was the most commonly isolated pathogen, followed by (7.7%) whereas in Africa, (17.8%) and (16.8%) were predominant followed by (10.7%). was more likely resistant to methicillin in Africa (29.5% vs. 7.9%), whereas was more frequently resistant to third-generation cephalosporins (31.2% vs. 21.2%), amikacin (29.6% vs. 0%) and ciprofloxacin (36.7% vs. 0%) in Asia. The overall estimate for case-fatality rate among 8 studies was 12.7% [6.6-20.2%]. Underlying conditions, such as malnutrition or HIV infection were assessed as a factor associated with bacteraemia in 4 studies each.
CONCLUSIONS
We observed a marked variation in pathogen distribution and their resistance profiles between Asia and Africa. Very limited data is available on underlying risk factors for bacteraemia, patterns of treatment of multidrug-resistant infections and predictors of adverse outcomes.
Topics: Adolescent; Africa; Anti-Bacterial Agents; Asia; Bacteremia; Bacteria; Child; Child Health; Child, Preschool; Community-Acquired Infections; Developing Countries; Drug Resistance, Bacterial; Humans; Infant; Microbial Sensitivity Tests; Observational Studies as Topic; Poverty; Sepsis
PubMed: 31893041
DOI: 10.1186/s13756-019-0673-5 -
Pathogens and Global Health Oct 2019This review discusses currently available serological diagnostic methods for typhoid fever with a focus on the clinical utility of TUBEX® TF as an alternative to the... (Meta-Analysis)
Meta-Analysis
This review discusses currently available serological diagnostic methods for typhoid fever with a focus on the clinical utility of TUBEX® TF as an alternative to the Widal or Typhidot test. A literature search was conducted in PubMed for related publications written in English. A qualitative analysis was done to determine various serological tests used for typhoid fever diagnosis with emphasis on TUBEX® TF in comparison to the Widal of Typhidot test. Further, a meta-analysis was performed to obtain a pooled estimate of diagnostic accuracy (sensitivity and specificity) using different analysis models. A total of sixteen studies was included in the qualitative analysis. Further screening of these studies yielded ten studies that were used for the meta-analysis. The sensitivity/specificity range of different commonly used serological tests in typhoid patients is between 55-100%/58-100% for TUBEX® TF, 54-67%/54-95% for Typhidot, and 32-95%/4-98% for the Widal test. As for the pooled meta-analysis estimates, the TUBEX® TF showed superior results when differentiating individuals with febrile illness of unknown origin from those with typhoid fever. Overall, the results of this review and meta-analysis suggest that the TUBEX® TF is more advantageous to use as a serological test for typhoid fever diagnosis due its accuracy and simplicity. However, further studies are still needed to validate our results.
Topics: Clinical Laboratory Techniques; Evaluation Studies as Topic; Humans; Reagent Kits, Diagnostic; Salmonella typhi; Sensitivity and Specificity; Serologic Tests; Typhoid Fever
PubMed: 31778097
DOI: 10.1080/20477724.2019.1695081 -
Clinical Infectious Diseases : An... Oct 2019Our current understanding of the burden and distribution of typhoid fever in Africa relies on extrapolation of data from a small number of population-based incidence...
BACKGROUND
Our current understanding of the burden and distribution of typhoid fever in Africa relies on extrapolation of data from a small number of population-based incidence rate estimates. However, many other records on the occurrence of typhoid fever are available, and those records contain information that may enrich our understanding of the epidemiology of the disease as well as secular trends in reporting by country and over time.
METHODS
We conducted a systematic review of typhoid fever occurrence in Africa, published in PubMed, Embase, and ProMED (Program for Monitoring Emerging Diseases).
RESULTS
At least one episode of culture-confirmed typhoid fever was reported in 42 of 57 African countries during 1900-2018. The number of reports on typhoid fever has increased over time in Africa and was highly heterogeneous between countries and over time. Outbreaks of typhoid fever were reported in 15 countries, with their frequency and size increasing over time.
CONCLUSIONS
Efforts should be made to leverage existing typhoid data, for example, by incorporating them into models for estimating the burden and distribution of typhoid fever.
Topics: Africa; Cost of Illness; Disease Outbreaks; Humans; Incidence; Paratyphoid Fever; Salmonella typhi; Typhoid Fever
PubMed: 31665777
DOI: 10.1093/cid/ciz525 -
Tropical Medicine & International... Dec 2019Hospital-based studies of community-onset bloodstream infections (CO-BSI) are less resource-intensive to carry out than population-based incidence studies. We examined...
OBJECTIVES
Hospital-based studies of community-onset bloodstream infections (CO-BSI) are less resource-intensive to carry out than population-based incidence studies. We examined several metrics capturing the potential role of Salmonella Typhi as a cause of CO-BSI for making inferences about incidence.
METHODS
We systematically reviewed three databases for hospital-based studies of CO-BSI. We determined, by study, the prevalence and rank order of Salmonella among pathogenic bloodstream isolates, and the prevalence ratio of Salmonella Typhi to Escherichia coli (S:E ratio). We then describe these hospital-based study metrics in relation to population-based typhoid fever incidence data from a separate systematic review.
RESULTS
Forty-four studies met the inclusion criteria, of which 23 (52.3%) isolated Salmonella Typhi at least once. Among studies isolating Salmonella Typhi, the median (interquartile range) prevalence and rank order of Salmonella Typhi compared to other pathogens isolated in BSI was 8.3% (3.2-37.9%) and 3 (1-6), respectively. The median (interquartile range) S:E ratio was 1.0 (0.4-3.0). With respect to incidence, in Pemba Island, Tanzania, prevalence, rank order, S:E ratio, and incidence was 64.8%, 1, 9.2 and 110 cases per 100 000, respectively, and in Boulkiemdé, Burkina Faso, was 13.3%, 3, 2.3 and 249 cases per 100 000.
CONCLUSIONS
We describe considerable variation in place and time for Salmonella Typhi prevalence, rank order, and S:E ratio among hospital-based studies of CO-BSI. Data from simultaneous typhoid prevalence and incidence studies are limited. We propose that hospital-based study metrics warrant evaluation for making inference about typhoid incidence and as covariates in typhoid incidence models.
Topics: Bacteremia; Burkina Faso; Female; Hospitalization; Humans; Incidence; Male; Prevalence; Salmonella typhi; Tanzania; Typhoid Fever
PubMed: 31633858
DOI: 10.1111/tmi.13319 -
The Indian Journal of Medical Research Feb 2019The temporal trends in the development of antimicrobial resistance (AMR) among Salmonella Typhi and Salmonella Paratyphi in India have not been systematically reported....
BACKGROUND & OBJECTIVES
The temporal trends in the development of antimicrobial resistance (AMR) among Salmonella Typhi and Salmonella Paratyphi in India have not been systematically reported. We aimed to systematically review the temporal AMR trends (phenotypic and molecular mechanisms) in bacterial isolates from patients with enteric fever over two decades in India.
METHODS
To identify trends in AMR in India, resistance patterns among 4611 individual S. Typhi isolates and 800 S. Paratyphi A isolates, reported from 1992 to 2017 in 40 publications, were analysed. Molecular resistance determinants were extracted from 22 publications and also reviewed in accordance with the PRISMA guidelines. Articles were sourced using a predefined search strategy from different databases.
RESULTS
The analyses suggested that multidrug-resistant (MDR) enteric fever was declining in India and being replaced by fluoroquinolone (FQ) resistance. Mutations in gyrA and parC were key mechanisms responsible for FQ resistance, whereas MDR was largely driven by resistance determinants encoded on mobile genetic elements (plasmids, transposons).
INTERPRETATION & CONCLUSIONS
The results reflect the effect of antimicrobial pressure which has been driving AMR in typhoidal Salmonella in India. Understanding these trends is important in planning future approaches to therapy, which serve as a baseline for assessment of the impact of new typhoid conjugate vaccines against these resistant organisms.
Topics: Anti-Bacterial Agents; Ciprofloxacin; Drug Resistance, Bacterial; Fluoroquinolones; Humans; India; Microbial Sensitivity Tests; Paratyphoid Fever; Salmonella paratyphi A; Salmonella typhi
PubMed: 31219079
DOI: 10.4103/ijmr.IJMR_830_18 -
PLoS Neglected Tropical Diseases May 2019Typhoid fevers are infections caused by the bacteria Salmonella enterica serovar Typhi (Salmonella Typhi) and Paratyphi A, B and C (Salmonella Paratyphi). Approximately... (Comparative Study)
Comparative Study
BACKGROUND
Typhoid fevers are infections caused by the bacteria Salmonella enterica serovar Typhi (Salmonella Typhi) and Paratyphi A, B and C (Salmonella Paratyphi). Approximately 17.8 million incident cases of typhoid fever occur annually, and incidence is highest in children. The accuracy of current diagnostic tests of typhoid fever is poorly understood. We aimed to determine the comparative accuracy of available tests for the pediatric population.
METHODS
We first conducted a systematic literature review to identify studies that compared diagnostic tests for typhoid fever in children (aged ≤15 years) to blood culture results. We applied a Bayesian latent-class extension to a network meta-analysis model. We modelled known diagnostic properties of bone marrow culture and the relationship between bone marrow and blood culture as informative priors in a Bayesian framework. We tested sensitivities for the proportion of negative blood samples that were false as well as bone marrow sensitivity and specificity.
RESULTS
We found 510 comparisons from 196 studies and 57 specific to the pediatric population. IgM-based tests outperformed their IgG-based counterparts for ELISA and Typhidot tests. The lateral flow IgG test performed comparatively well with 92% sensitivity (72% to 98% across scenario analyses) and 94% specificity. The most sensitive test of those investigated for the South Asian pediatric population was the Reverse Passive Hemagglutination Assay with 99% sensitivity (98% - 100% across scenario analyses). Adding a Widal slide test to other typhoid diagnostics did not substantially improve diagnostic performance beyond the single test alone, however, a lateral flow-based IgG rapid test combined with the typhoid/paratyphoid (TPT) assay yielded improvements in sensitivity without substantial declines in specificity and was the best performing combination test in this setting.
CONCLUSION
In the pediatric population, lateral-flow IgG, TPT and Reverse Passive Hemagglutination tests had high diagnostic accuracy compared to other diagnostics. Combinations of tests may provide a feasible option to increase diagnostic sensitivity. South Asia has the most informed set of data on typhoid diagnostic testing accuracy, and the evidence base in other important regions needs to be expanded.
Topics: Adolescent; Antibodies, Bacterial; Bayes Theorem; Child; Child, Preschool; Diagnostic Tests, Routine; Female; Humans; Male; Reagent Kits, Diagnostic; Salmonella typhi; Sensitivity and Specificity; Typhoid Fever; Young Adult
PubMed: 31067228
DOI: 10.1371/journal.pntd.0007303 -
Clinical Infectious Diseases : An... Mar 2019Contemporary incidence estimates of typhoid fever are needed to guide policy decisions and control measures and to improve future epidemiological studies. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Contemporary incidence estimates of typhoid fever are needed to guide policy decisions and control measures and to improve future epidemiological studies.
METHODS
We systematically reviewed 3 databases (Ovid Medline, PubMed, and Scopus) without restriction on age, country, language, or time for studies reporting the incidence of blood culture-confirmed typhoid fever. Outbreak, travel-associated, and passive government surveillance reports were excluded. We performed a meta-analysis using a random-effects model to calculate estimates of pooled incidence, stratifying by studies that reported the incidence of typhoid fever and those that estimated incidence by using multipliers.
RESULTS
Thirty-three studies were included in the analysis. There were 26 study sites from 16 countries reporting typhoid cases from population-based incidence studies, and 17 sites in 9 countries used multipliers to account for underascertainment in sentinel surveillance data. We identified Africa and Asia as regions with studies showing high typhoid incidence while noting considerable variation of typhoid incidence in time and place, including in consecutive years at the same location. Overall, more recent studies reported lower typhoid incidence compared to years prior to 2000. We identified variation in the criteria for collecting a blood culture, and among multiplier studies we identified a lack of a standardization for the types of multipliers being used to estimate incidence.
CONCLUSIONS
Typhoid fever incidence remains high at many sites. Additional and more accurate typhoid incidence studies are needed to support country decisions about typhoid conjugate vaccine adoption. Standardization of multiplier types applied in multiplier studies is recommended.
Topics: Africa; Asia; Global Health; Humans; Incidence; Salmonella typhi; Travel; Typhoid Fever; Typhoid-Paratyphoid Vaccines
PubMed: 30845336
DOI: 10.1093/cid/ciy1094 -
The Lancet. Infectious Diseases Apr 2019Efforts to quantify the global burden of enteric fever are valuable for understanding the health lost and the large-scale spatial distribution of the disease. We present... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Efforts to quantify the global burden of enteric fever are valuable for understanding the health lost and the large-scale spatial distribution of the disease. We present the estimates of typhoid and paratyphoid fever burden from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, and the approach taken to produce them.
METHODS
For this systematic analysis we broke down the relative contributions of typhoid and paratyphoid fevers by country, year, and age, and analysed trends in incidence and mortality. We modelled the combined incidence of typhoid and paratyphoid fevers and split these total cases proportionally between typhoid and paratyphoid fevers using aetiological proportion models. We estimated deaths using vital registration data for countries with sufficiently high data completeness and using a natural history approach for other locations. We also estimated disability-adjusted life-years (DALYs) for typhoid and paratyphoid fevers.
FINDINGS
Globally, 14·3 million (95% uncertainty interval [UI] 12·5-16·3) cases of typhoid and paratyphoid fevers occurred in 2017, a 44·6% (42·2-47·0) decline from 25·9 million (22·0-29·9) in 1990. Age-standardised incidence rates declined by 54·9% (53·4-56·5), from 439·2 (376·7-507·7) per 100 000 person-years in 1990, to 197·8 (172·0-226·2) per 100 000 person-years in 2017. In 2017, Salmonella enterica serotype Typhi caused 76·3% (71·8-80·5) of cases of enteric fever. We estimated a global case fatality of 0·95% (0·54-1·53) in 2017, with higher case fatality estimates among children and older adults, and among those living in lower-income countries. We therefore estimated 135·9 thousand (76·9-218·9) deaths from typhoid and paratyphoid fever globally in 2017, a 41·0% (33·6-48·3) decline from 230·5 thousand (131·2-372·6) in 1990. Overall, typhoid and paratyphoid fevers were responsible for 9·8 million (5·6-15·8) DALYs in 2017, down 43·0% (35·5-50·6) from 17·2 million (9·9-27·8) DALYs in 1990.
INTERPRETATION
Despite notable progress, typhoid and paratyphoid fevers remain major causes of disability and death, with billions of people likely to be exposed to the pathogens. Although improvements in water and sanitation remain essential, increased vaccine use (including with typhoid conjugate vaccines that are effective in infants and young children and protective for longer periods) and improved data and surveillance to inform vaccine rollout are likely to drive the greatest improvements in the global burden of the disease.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cause of Death; Child; Child, Preschool; Disabled Persons; Female; Global Burden of Disease; Humans; Incidence; Infant; Life Expectancy; Male; Mass Vaccination; Middle Aged; Paratyphoid Fever; Quality-Adjusted Life Years; Risk Factors; Salmonella enterica; Sanitation; Typhoid Fever; Typhoid-Paratyphoid Vaccines; Young Adult
PubMed: 30792131
DOI: 10.1016/S1473-3099(18)30685-6 -
The Lancet. Infectious Diseases Feb 2019Oral vaccines underperform in low-income and middle-income countries compared with in high-income countries. Whether interventions can improve oral vaccine performance... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Oral vaccines underperform in low-income and middle-income countries compared with in high-income countries. Whether interventions can improve oral vaccine performance is uncertain.
METHODS
We did a systematic review and meta-analysis of interventions designed to increase oral vaccine efficacy or immunogenicity. We searched Ovid-MEDLINE and Embase for trials published until Oct 23, 2017. Inclusion criteria for meta-analysis were two or more studies per intervention category and available seroconversion data. We did random-effects meta-analyses to produce summary relative risk (RR) estimates. This study is registered with PROSPERO (CRD42017060608).
FINDINGS
Of 2843 studies identified, 87 were eligible for qualitative synthesis and 66 for meta-analysis. 22 different interventions were assessed for oral poliovirus vaccine (OPV), oral rotavirus vaccine (RVV), oral cholera vaccine (OCV), and oral typhoid vaccines. There was generally high heterogeneity. Seroconversion to RVV was significantly increased by delaying the first RVV dose by 4 weeks (RR 1·37, 95% CI 1·16-1·62) and OPV seroconversion was increased with monovalent or bivalent OPV compared with trivalent OPV (RR 1·51, 95% CI 1·20-1·91). There was some evidence that separating RVV and OPV increased RVV seroconversion (RR 1·21, 95% CI 1·00-1·47) and that higher vaccine inoculum improved OCV seroconversion (RR 1·12, 95% CI 1·00-1·26). There was no evidence of effect for anthelmintics, antibiotics, probiotics, zinc, vitamin A, withholding breastfeeding, extra doses, or vaccine buffering.
INTERPRETATION
Most strategies did not improve oral vaccine performance. Delaying RVV and reducing OPV valence should be considered within immunisation programmes to reduce global enteric disease. New strategies to address the gap in oral vaccine efficacy are urgently required.
FUNDING
Wellcome Trust, Bill & Melinda Gates Foundation, UK Medical Research Council, and WHO Polio Research Committee.
Topics: Administration, Oral; Adolescent; Adult; Child; Child, Preschool; Cholera; Cholera Vaccines; Female; Humans; Immunogenicity, Vaccine; Infant; Infant, Newborn; Male; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Salmonella typhi; Seroconversion; Treatment Outcome; Typhoid Fever; Typhoid-Paratyphoid Vaccines; Vaccination; Vibrio cholerae; Young Adult
PubMed: 30712836
DOI: 10.1016/S1473-3099(18)30602-9