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The Cochrane Database of Systematic... Nov 2022Typhoid and paratyphoid (enteric fever) are febrile bacterial illnesses common in many low- and middle-income countries. The World Health Organization (WHO) currently... (Review)
Review
BACKGROUND
Typhoid and paratyphoid (enteric fever) are febrile bacterial illnesses common in many low- and middle-income countries. The World Health Organization (WHO) currently recommends treatment with azithromycin, ciprofloxacin, or ceftriaxone due to widespread resistance to older, first-line antimicrobials. Resistance patterns vary in different locations and are changing over time. Fluoroquinolone resistance in South Asia often precludes the use of ciprofloxacin. Extensively drug-resistant strains of enteric fever have emerged in Pakistan. In some areas of the world, susceptibility to old first-line antimicrobials, such as chloramphenicol, has re-appeared. A Cochrane Review of the use of fluoroquinolones and azithromycin in the treatment of enteric fever has previously been undertaken, but the use of cephalosporins has not been systematically investigated and the optimal choice of drug and duration of treatment are uncertain.
OBJECTIVES
To evaluate the effectiveness of cephalosporins for treating enteric fever in children and adults compared to other antimicrobials.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, the WHO ICTRP and ClinicalTrials.gov up to 24 November 2021. We also searched reference lists of included trials, contacted researchers working in the field, and contacted relevant organizations.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) in adults and children with enteric fever that compared a cephalosporin to another antimicrobial, a different cephalosporin, or a different treatment duration of the intervention cephalosporin. Enteric fever was diagnosed on the basis of blood culture, bone marrow culture, or molecular tests.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were clinical failure, microbiological failure and relapse. Our secondary outcomes were time to defervescence, duration of hospital admission, convalescent faecal carriage, and adverse effects. We used the GRADE approach to assess certainty of evidence for each outcome.
MAIN RESULTS
We included 27 RCTs with 2231 total participants published between 1986 and 2016 across Africa, Asia, Europe, the Middle East and the Caribbean, with comparisons between cephalosporins and other antimicrobials used for the treatment of enteric fever in children and adults. The main comparisons are between antimicrobials in most common clinical use, namely cephalosporins compared to a fluoroquinolone and cephalosporins compared to azithromycin. Cephalosporin (cefixime) versus fluoroquinolones Clinical failure, microbiological failure and relapse may be increased in patients treated with cefixime compared to fluoroquinolones in three small trials published over 14 years ago: clinical failure (risk ratio (RR) 13.39, 95% confidence interval (CI) 3.24 to 55.39; 2 trials, 240 participants; low-certainty evidence); microbiological failure (RR 4.07, 95% CI 0.46 to 36.41; 2 trials, 240 participants; low-certainty evidence); relapse (RR 4.45, 95% CI 1.11 to 17.84; 2 trials, 220 participants; low-certainty evidence). Time to defervescence in participants treated with cefixime may be longer compared to participants treated with fluoroquinolones (mean difference (MD) 1.74 days, 95% CI 0.50 to 2.98, 3 trials, 425 participants; low-certainty evidence). Cephalosporin (ceftriaxone) versus azithromycin Ceftriaxone may result in a decrease in clinical failure compared to azithromycin, and it is unclear whether ceftriaxone has an effect on microbiological failure compared to azithromycin in two small trials published over 18 years ago and in one more recent trial, all conducted in participants under 18 years of age: clinical failure (RR 0.42, 95% CI 0.11 to 1.57; 3 trials, 196 participants; low-certainty evidence); microbiological failure (RR 1.95, 95% CI 0.36 to 10.64, 3 trials, 196 participants; very low-certainty evidence). It is unclear whether ceftriaxone increases or decreases relapse compared to azithromycin (RR 10.05, 95% CI 1.93 to 52.38; 3 trials, 185 participants; very low-certainty evidence). Time to defervescence in participants treated with ceftriaxone may be shorter compared to participants treated with azithromycin (mean difference of -0.52 days, 95% CI -0.91 to -0.12; 3 trials, 196 participants; low-certainty evidence). Cephalosporin (ceftriaxone) versus fluoroquinolones It is unclear whether ceftriaxone has an effect on clinical failure, microbiological failure, relapse, and time to defervescence compared to fluoroquinolones in three trials published over 28 years ago and two more recent trials: clinical failure (RR 3.77, 95% CI 0.72 to 19.81; 4 trials, 359 participants; very low-certainty evidence); microbiological failure (RR 1.65, 95% CI 0.40 to 6.83; 3 trials, 316 participants; very low-certainty evidence); relapse (RR 0.95, 95% CI 0.31 to 2.92; 3 trials, 297 participants; very low-certainty evidence) and time to defervescence (MD 2.73 days, 95% CI -0.37 to 5.84; 3 trials, 285 participants; very low-certainty evidence). It is unclear whether ceftriaxone decreases convalescent faecal carriage compared to the fluoroquinolone gatifloxacin (RR 0.18, 95% CI 0.01 to 3.72; 1 trial, 73 participants; very low-certainty evidence) and length of hospital stay may be longer in participants treated with ceftriaxone compared to participants treated with the fluoroquinolone ofloxacin (mean of 12 days (range 7 to 23 days) in the ceftriaxone group compared to a mean of 9 days (range 6 to 13 days) in the ofloxacin group; 1 trial, 47 participants; low-certainty evidence).
AUTHORS' CONCLUSIONS
Based on very low- to low-certainty evidence, ceftriaxone is an effective treatment for adults and children with enteric fever, with few adverse effects. Trials suggest that there may be no difference in the performance of ceftriaxone compared with azithromycin, fluoroquinolones, or chloramphenicol. Cefixime can also be used for treatment of enteric fever but may not perform as well as fluoroquinolones. We are unable to draw firm general conclusions on comparative contemporary effectiveness given that most trials were small and conducted over 20 years previously. Clinicians need to take into account current, local resistance patterns in addition to route of administration when choosing an antimicrobial.
Topics: Child; Adult; Humans; Adolescent; Paratyphoid Fever; Typhoid Fever; Cephalosporins; Azithromycin; Ceftriaxone; Cefixime; Fluoroquinolones; Anti-Bacterial Agents; Chloramphenicol; Anti-Infective Agents; Monobactams; Ciprofloxacin; Ofloxacin; Recurrence; Pakistan
PubMed: 36420914
DOI: 10.1002/14651858.CD010452.pub2 -
The New England Journal of Medicine Apr 2023In 2017, more than half the cases of typhoid fever worldwide were projected to have occurred in India. In the absence of contemporary population-based data, it is...
BACKGROUND
In 2017, more than half the cases of typhoid fever worldwide were projected to have occurred in India. In the absence of contemporary population-based data, it is unclear whether declining trends of hospitalization for typhoid in India reflect increased antibiotic treatment or a true reduction in infection.
METHODS
From 2017 through 2020, we conducted weekly surveillance for acute febrile illness and measured the incidence of typhoid fever (as confirmed on blood culture) in a prospective cohort of children between the ages of 6 months and 14 years at three urban sites and one rural site in India. At an additional urban site and five rural sites, we combined blood-culture testing of hospitalized patients who had a fever with survey data regarding health care use to estimate incidence in the community.
RESULTS
A total of 24,062 children who were enrolled in four cohorts contributed 46,959 child-years of observation. Among these children, 299 culture-confirmed typhoid cases were recorded, with an incidence per 100,000 child-years of 576 to 1173 cases in urban sites and 35 in rural Pune. The estimated incidence of typhoid fever from hospital surveillance ranged from 12 to 1622 cases per 100,000 child-years among children between the ages of 6 months and 14 years and from 108 to 970 cases per 100,000 person-years among those who were 15 years of age or older. serovar Paratyphi was isolated from 33 children, for an overall incidence of 68 cases per 100,000 child-years after adjustment for age.
CONCLUSIONS
The incidence of typhoid fever in urban India remains high, with generally lower estimates of incidence in most rural areas. (Funded by the Bill and Melinda Gates Foundation; NSSEFI Clinical Trials Registry of India number, CTRI/2017/09/009719; ISRCTN registry number, ISRCTN72938224.).
Topics: Humans; Infant; Incidence; India; Paratyphoid Fever; Population Surveillance; Prospective Studies; Typhoid Fever; Cost of Illness; Blood Culture; Child, Preschool; Child; Adolescent; Urban Population; Rural Population; Hospitalization
PubMed: 37075141
DOI: 10.1056/NEJMoa2209449 -
Frontiers in Microbiology 2022Enteric fever is caused by serovar Typhi, serovar Paratyphi A, B, and C. While . Typhi remains the primary causative agent of enteric fever, . Paratyphi A is... (Review)
Review
Enteric fever is caused by serovar Typhi, serovar Paratyphi A, B, and C. While . Typhi remains the primary causative agent of enteric fever, . Paratyphi A is responsible for an increasing portion of enteric fever incidence. However, the current available vaccines for enteric fever are all developed from . Typhi, and lack adequate cross immune protection against paratyphoid fever A. Therefore, paratyphoid A vaccines are urgently needed. The present paper reviews the latest progresses in pathogenesis, global burden, infection features of paratyphoid fever A, as well as the status of vaccine development, highlighting the necessity for the development of vaccines against paratyphoid fever A.
PubMed: 35875577
DOI: 10.3389/fmicb.2022.945235 -
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 -
Deutsches Arzteblatt International Jun 2022It is predicted that approximately two billion tourist trips to foreign countries will be taken worldwide each year by 2030. Germany has long been among the most active... (Review)
Review
BACKGROUND
It is predicted that approximately two billion tourist trips to foreign countries will be taken worldwide each year by 2030. Germany has long been among the most active countries in tourism. The frequency of illness among persons returning from developing and newly industrialized countries is 43-79%. The appropriate diagnosis of fever in returning travelers is a clinically important matter, as it can be a sign of a life-threatening illness.
METHODS
This review is based on publications (2001-2022) retrieved by a selective search in PubMed for studies on the epidemiology, diagnosis, and treatment of febrile illnesses in returning travelers, or on specific tropical diseases.
RESULTS
Diarrhea, fever, and skin changes are the most common manifestations of disease after travel to tropical and sub - tropical areas. The diagnostic evaluation should be performed in a series of steps, beginning with a precise travel history and the identification of specific risk factors. Among travelers returning from sub-Saharan Africa, Plasmodium falciparum malaria is the most common cause of fever on presentation to centers for infectious diseases and tropical medicine, affecting approximately 50 per 1000 travelers. Among persons returning from travel to Southeast Asia, dengue fever is the most common infectious disease, affecting 50-160 per 1000 travelers. Further potentially dangerous diseases include chikungunya and zika fever, typhoid and paratyphoid fever, amoebic liver abscess, visceral leishmaniasis (kala-azar), leptospirosis, and, very rarely, imported cases of viral hemorrhagic fever. COVID-19 and influenza are important differential diagnoses.
CONCLUSION
The differential diagnosis can be narrowed by thorough history-taking with particular attention to the patient's travel route, combined with a good knowledge of the geographic spread and incubation times of the main tropical diseases. Algorithms help clinicians to focus the diagnostic work-up and select the appropriate further laboratory tests and diagnostic procedures.
Topics: COVID-19; Communicable Diseases; Fever; Humans; Malaria; Travel; Typhoid Fever; Zika Virus; Zika Virus Infection
PubMed: 35469592
DOI: 10.3238/arztebl.m2022.0182 -
Paediatrics & Child Health Feb 2019Nontyphoidal Salmonella (NTS) infections are primarily transmitted by contaminated food or water or contact with carrier animals (particularly reptiles), and present... (Review)
Review
Nontyphoidal Salmonella (NTS) infections are primarily transmitted by contaminated food or water or contact with carrier animals (particularly reptiles), and present with diarrhea. Antibiotics do not decrease the severity or duration of diarrhea and may increase the incidence of NTS carriage, so they should only be used with suspected or proven bacteremia or invasive infection. Typhoid/paratyphoid fever manifests as bacteremia within 60 days of travel to resource-poor countries and presents with fever and variable abdominal complaints. Therefore, blood cultures are indicated for unexplained fever and a relevant travel history. When blood cultures are positive or when a child is unwell pending blood culture results, ceftriaxone is indicated. A switch to oral antibiotics (usually azithromycin) is often possible after blood cultures have cleared and the child is improved.
PubMed: 30833820
DOI: 10.1093/pch/pxy199 -
Microbes and Infection Sep 2020
Topics: Animals; Bacterial Proteins; Caspases; History, 16th Century; History, 21st Century; History, Medieval; Humans; Inflammation; Male; Paratyphoid Fever; Receptor-Interacting Protein Serine-Threonine Kinases; Salmonella enterica
PubMed: 31838130
DOI: 10.1016/j.micinf.2019.11.003 -
The American Journal of Tropical... Sep 2018The Tackling Typhoid supplement shows that typhoid fever continues to be a problem globally despite socioeconomic gains in certain settings. Morbidity remains high in... (Review)
Review
The Tackling Typhoid supplement shows that typhoid fever continues to be a problem globally despite socioeconomic gains in certain settings. Morbidity remains high in many endemic countries, notably in sub-Saharan Africa and South Asia. In addition, antimicrobial resistance is a growing issue that poses a challenge for clinical management. The findings from this supplement revealed that outside of high-income countries, there were few reliable population-based estimates of typhoid and paratyphoid fever derived from surveillance systems. This indicates the need for monitoring systems that can also characterize the effectiveness of interventions, particularly in low- and middle-income settings. The country case studies indicated that gains in economic conditions, education, and environmental health may be associated with reductions in typhoid fever burden. Over the study period, the effect is mainly notable in countries with higher baseline levels of economic development, female literacy, and investments in public sanitation. High burden countries must continue to invest in strategies at the local level to address environmental factors such as access to safe drinking water and improved public sanitation that are known to interrupt transmission or diminish the risk of acquiring typhoid. Developing more effective vaccines and incorporating appropriate immunization strategies that target populations with the greatest risk could potentially alleviate disease burden.
Topics: Africa South of the Sahara; Anti-Bacterial Agents; Asia, Southeastern; Asia, Western; Chile; Food Safety; Global Health; Humans; Paratyphoid Fever; Public Health; Sanitation; Typhoid Fever
PubMed: 30047361
DOI: 10.4269/ajtmh.18-0111 -
BMJ (Clinical Research Ed.) Feb 2021
Topics: Anti-Bacterial Agents; Azithromycin; Dengue; Diagnosis, Differential; Doxycycline; Drug Resistance, Bacterial; Endemic Diseases; Humans; Malaria; Paratyphoid Fever; Polysaccharides, Bacterial; Salmonella paratyphi A; Salmonella typhi; Travel-Related Illness; Typhoid Fever; Typhoid-Paratyphoid Vaccines
PubMed: 33637488
DOI: 10.1136/bmj.n437