The global burden of typhoid and paratyphoid fevers: a systematic analysis for the Global Burden of Disease Study 2017.

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.

Introductory Article on Global Burden and Epidemiology of Typhoid Fever.

This article is the introduction to a 12-paper supplement on global trends in typhoid fever. The Tackling Typhoid (T2) project was initiated in 2015 to synthesize the existing body of literature on typhoidal salmonellae and study national and regional typhoid fever trends. In addition to a global systematic review, eight case studies were undertaken to examine typhoid and paratyphoid fever trends in endemic countries alongside changes in relevant contextual factors. Incidence variations exist both within and between regions with large subnational differences as well, suggesting that public health changes impacting typhoid and paratyphoid fevers in one setting may not have similar impacts in another. This supplement also brings to light the lack of national typhoid fever surveillance systems, inconsistencies in diagnostics, and the lack of typhoid fever associated morbidity and mortality data in many countries, making it difficult to accurately quantify and track burden of disease. To better understand typhoid fever there is a need for more high-quality data from resource-poor settings. The implementation of typhoid surveillance systems alongside the transition to blood-culture confirmation of cases, where possible, would aid in the improvement of data quality in low-income settings. The following supplement includes the results of our global systematic review, eight-country case study articles, a qualitative article informed by semistructured interviews, and a conclusion article on potential ways forward for typhoid control.

Case Fatality Rate of Enteric Fever in Endemic Countries: A Systematic Review and 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.

Epidemiology of typhoid and paratyphoid fever hospitalizations in Spain (1997-2005).

BACKGROUND AND OBJECTIVE: This epidemiological survey was undertaken to estimate the burden of hospitalizations for typhoid and paratyphoid fever in Spain over a nine-year period (1997-2005). RESULTS: There were 1,106 hospitalizations for typhoid and paratyphoid fever during the study period. The annual hospitalization rate was 0.31 cases per 100,000 population. The mortality and case fatality rates were 0.003 per 100,000 population and 0.9%, respectively. The average length of hospitalization was 10.19 days. These hospitalizations impose an annual direct cost of euro334,000. PATIENTS AND METHODS: Hospital discharges for typhoid or paratyphoid fever reported during a nine-year period in Spanish hospitals were obtained from the national surveillance system for hospital data, which is maintained by the Ministry of Health and covers more than 97% of Spanish hospitals. CONCLUSIONS: Preventive measures are vital to reduce the occurrence of typhoid fever and avoid new outbreaks. Effective prevention would result in large cost savings to the National Health Care System.

Fatal complications of acute enteric fevers.

Eighty eight patients presenting with fatal typhoid complications were studied in Abbassia and Embaba fever hospitals during a 4 years period (1987-1991). Criterion of inclusion in the study was either positive blood culture in 70 (80%) cases or postmortem gross appearance of typhoid fever in 18 (20%) cases. Positive blood culture cases included 54 (77%) S. typhi and 16 (23%) S. paratyphi A. Seven (10%) cases were resistant in vitro to chloramphenicol. Postmortem examination performed in 18 (20%) cases revealed typical typhoid ulcers in ileum, jejunum and large intestine. The main clinical picture of 31 toxic, 22 encephalitic or meningeal irritating, 15 gastroenteritic, 9 pneumonic, 8 perforated and 3 haemorrhagic enteric fever cases were discussed. The tetrad of fever, toxic look, bronchitic chest, tumid tympanitic abdomen and splenomegaly was a good sign for suggestion of typhoid diagnosis.

Interaction of aflatoxin and paratyphoid infections in broiler chickens.

There was a significant (P less than 0.05) interaction resulting in increased mortality in chickens fed aflatoxin and infected with Salmonella worthington, S. thompson, S. derby, or S. typhimurium var. copenhagen which cause paratyphoid. There was no interaction on body weight or spleen weight; however, there wan an interaction with all four Salmonella species resulting in enlarged livers from which Salmonella could be isolated with increased frequency. Aflatoxin caused a decrease in total serum proteins but a dramatic increase in anti-Salmonella agglutinins in infected birds. These results suggest that aflatoxin impairs some component of the immune system other than that forming humoral antibodies and perhaps other than the reticuloendothelial system which have been reported previously to be impaired during aflatoxicosis in the chicken.

Enteric fever in young Yoruba children.

Ninety-seven Nigerian children under 5 years of age had typhoid or paratyphoid fever proved by blood culture. The presented with fever, anaemia, gastrointestinal or neurological disturbances, and typhoid and paratyphoid appeared clinically indistinguishible. In this holoendemic malarial area, malaria was the most important differential diagnosis, and may have contributed to the concomitant anaemia seen in the majority of patients. Despite vigorous therapy with chloramphenicol or trimethoxazole, and blood transfusion where indicated, the mortality in both typhoid and paratyphoid was high (18% in both groups).

Changes in the pattern of mortality following the eradication of hyperendemic malaria from a highly susceptible community.

The population of the sugar estates of the Guyana coastlands was 110 000 in 1966; malaria was eradicated between 1945 and 1951. A study has been made of the pattern of mortality before and after malaria eradication, during the 30-year period from 1937 to 1966.The decline in general mortality has greatly exceeded the fall in mortality specifically related to malaria and has continued for almost 10 years after registration of the last death from malaria. In infants, mortality has been reduced, mainly through a decline in the number of deaths from prematurity and congenital debility that were due mainly to malaria and its sequelae in the expectant mother. In children (1-14 years of age) the decline has resulted from the disappearance of malaria and chronic nephritis as causes of death. In adults, mortality has fallen mainly through the progressive decline in the incidence of a number of diseases not overtly related to malaria: acute and chronic respiratory diseases, chronic nephritis, and the anaemias. Cardiovascular diseases, on the contrary, have shown a tendency to increase since malaria was brought under control.