The global burden of enteric fevers in the age of typhoid-conjugate vaccines
Authors: Thomas F Wierzba, John W Sanders
Journal: The Lancet Infectious Diseases (2019)

In The Lancet Infectious Diseases, authors led by the Institute of Health Metrics and Evaluation (University of Washington, Seattle, WA, USA) add to our understanding of enteric fevers by presenting a comprehensive and systematic analysis of the global burden of typhoid and paratyphoid fevers using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017.1GBD 2017 Typhoid and Paratyphoid CollaboratorsThe global burden of typhoid and paratyphoid fevers: a systematic analysis for the Global Burden of Disease Study 2017.Lancet Infect Dis. 2019; (published online Feb 18.)http://dx.doi.org/10.1016/S1473-3099(18)30685-6Google Scholar Unlike previous estimates, the investigators explore the global, regional, and country burden of enteric diseases and estimate age-specific mortality and case-fatality rates by region and age. The authors estimated 10·9 million (95% uncertainty interval [UI] 9·3–12·6) cases of typhoid fever and 116·8 thousand (65·4–187·7) deaths due to Salmonella enterica serovar Typhi in 2017. Years of life lost (YLLs) attributed to typhoid fever were 8·3 million (95% UI 4·6–13·4) and disability-adjusted life-years (DALYs) were 8·4 million (4·7–13.6). These results correspond to an estimated 53·6% reduction in cases and 57·8% reduction in deaths since 1990. Wisely, the authors also present data for paratyphoid fever. The paratyphoid fever burden is substantially lower than that of typhoid fever: an estimated 3·4 million (2·7–4·2) cases and 19·1 thousand (8·7–37·3) deaths occurred from paratyphoid fever in 2017. YLLs attributed to paratyphoid fever in 2017 were 1·4 million (0·6–2·6) and DALYS were 1·4 million (0·6–2·6). Between 1990 and 2017, the authors estimate a 61·7% reduction in cases of paratyphoid fever and a 67·0% reduction in deaths. Although the estimates presented in this study reflect substantial gains in prevention and treatment over several decades, enteric fevers continue to undermine the health and economic wellbeing of resource-poor families and generate substantial costs to health services in endemic countries.2Riewpaiboon A Piatti M Ley B et al.Cost of illness due to typhoid fever in Pemba, Zanzibar, East Africa.J Health Popul Nutr. 2014; 32: 377-385PubMed Google Scholar, 3Poulos C Riewpaiboon A Stewart JF et al.Cost of illness due to typhoid fever in five Asian countries.Trop Med Int Health. 2011; 16: 314-323Crossref PubMed Scopus (34) Google Scholar A report of extensively-drug resistant S Typhi from Pakistan has amplified the warning that effective treatment is becoming increasingly challenging and could reverse recent progress.4Klemm EJ Shakoor S Page AJ et al.Emergence of an extensively drug-resistant Salmonella enterica serovar Typhi clone harboring a promiscuous plasmid encoding resistance to fluoroquinolones and third-generation cephalosporins.MBio. 2018; 9: e00105-e00118Crossref PubMed Scopus (332) Google Scholar Fortunately, for prevention of S Typhi, in January, 2018, WHO prequalified a conjugate vaccine, Typbar-TCV (Bharat Biotech, Hyderabad, India), in which the Vi polysaccharide capsule antigens are linked to tetanus toxoid (Vi-TT). In a human challenge trial involving a wild strain of S Typhi, Vi-TT showed up to 87% efficacy depending on clinical endpoints.5Jin C Gibani MM Moore M et al.Efficacy and immunogenicity of a Vi-tetanus toxoid conjugate vaccine in the prevention of typhoid fever using a controlled human infection model of Salmonella Typhi: a randomised controlled, phase 2b trial.Lancet. 2017; 390: 2472-2480Summary Full Text Full Text PDF PubMed Scopus (185) Google Scholar Typbar-TCV can be administered to adults, children, and infants as young as 6 months and, based on efficacy observed with a previous conjugate vaccine, is thought to be effective for at least 5 years.6Lin FY Ho VA Khiem HB et al.The efficacy of a Salmonella typhi Vi conjugate vaccine in two-to-five-year-old children.N Engl J Med. 2001; 344: 1263-1269Crossref PubMed Scopus (364) Google Scholar Gavi, the Vaccine Alliance, has announced US$85 million in funding for eligible countries to introduce typhoid conjugate vaccines in 2019 and 2020.7Gavi—The Vaccine AllianceNew typhoid vaccine to receive Gavi support.https://www.gavi.org/library/news/statements/2018/new-typhoid-vaccine-to-receive-gavi-support/Date: April 3, 2018Date accessed: December 3, 2018Google Scholar With funding approved for vaccine adoption in many endemic countries, the results of this study will assist donors, international and regional agencies, and national governments to develop and fund rational vaccination strategies. Still, as the authors note, data gaps remain in many countries and regions (eg, sub-Saharan Africa). These data gaps will need to be closed through population-based surveillance to clarify the need for, and monitor the progress of, typhoid conjugate vaccines. The authors' results also imply a substantial burden from paratyphoid fever, providing support for development of a S Paratyphi vaccine. No such vaccine is available at present. Given the future use of S Typhi conjugate vaccines and the need to monitor the global burden of S Typhi alone, authors could consider, in future publications, providing all results separated by causative pathogen rather than combining results (eg, typhoid plus paratyphoid age-standardised incidence rates). Expanded data on the global, regional, and national burden of enteric fever as provided in this report, and the advent of a WHO-prequalified conjugate vaccine are advancing the control of enteric fevers and will improve the health and wellbeing of resource-poor families in endemic countries. We declare no competing interests. The global burden of typhoid and paratyphoid fevers: a systematic analysis for the Global Burden of Disease Study 2017Despite 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. Full-Text PDF Open Access