Typhoid Fever Surveillance, Incidence Estimates, and Progress Toward Typhoid Conjugate Vaccine Introduction — Worldwide, 2018–2022

Surveillance and Estimates of Disease Incidence and Antimicrobial Resistance Prevalence

WHO recommends that countries with endemic typhoid fever^§ establish health facility–based surveillance with laboratory confirmation to determine disease burden,^¶ monitor antimicrobial resistance patterns, facilitate rapid outbreak detection, and assess vaccine impact (3). Because the clinical presentation of typhoid fever is often indistinguishable from that of other acute febrile illnesses common in areas with endemic typhoid (e.g., malaria and dengue), diagnosis is dependent upon laboratory confirmation, typically blood culture (3). However, blood culture has a low sensitivity (40%–60%), which is further reduced by widespread use of prediagnosis antibiotic use, has limited availability at health care facilities, and is not systematically obtained from febrile patients (1–3). Therefore, the number of laboratory-confirmed S. Typhi cases represents a small proportion of the actual disease incidence. Countries report data on selected vaccine-preventable diseases to WHO and UNICEF annually using the electronic Joint Reporting Form (eJRF). During 2018–2021, 59–62 countries reported laboratory-confirmed typhoid fever through eJRF.** Reported cases increased from approximately 8,800 in 2018, when typhoid fever surveillance was first added to eJRF, to 1 million in 2021.

Because of the low sensitivity of typhoid fever surveillance, specially designed population-based studies have been implemented to estimate disease incidence. Since 2016, typhoid fever incidence has been estimated in specific countries through three surveillance projects: 1) the Strategic Typhoid Alliance across Africa and Asia (for Bangladesh, Malawi, and Nepal); 2) the Surveillance for Enteric Fever in Asia Project (for Bangladesh, Nepal, and Pakistan); and 3) the Severe Typhoid in Africa program (for Burkina Faso, Democratic Republic of the Congo, Ethiopia, Ghana, Madagascar, and Nigeria) (Table 1) (4–6). Modeling data from the Global Burden of Disease study estimated that 9.2 million (95% CI = 5.9–14.1) typhoid fever cases and 110,000 (95% CI = 53,000–191,000) associated deaths occurred worldwide in 2019 (7). The highest estimated 2019 incidence, by region, occurred in the WHO South-East Asian (306 cases per 100,000 persons), Eastern Mediterranean (187), and African (111) regions (Table 1) (Figure) and, by age group, occurred in children aged 5–9 years, followed by children and adolescents aged 10–14 years and children aged 1–4 years, respectively.^††

An additional indication of typhoid fever burden can be obtained through analysis of outbreak^§§ data. During 2017–2022, seven confirmed typhoid fever outbreaks were identified from ongoing outbreak monitoring activities by CDC’s Global Disease Detection Operation Center,^¶¶ including the Philippines (2022: 14,056 cases) and three in Zimbabwe (January–March 2017: 1,312 cases; November 2017–February 2018: 3,187 cases; and August–December 2018: 7,134 cases), as well as outbreaks with confirmed antimicrobial-resistant cases in Pakistan (January 2018–December 2019: 14,894 cases) and China (2022: 23 cases) (9).

Apart from high disease incidence, the need for action is enhanced by the increasing prevalence of antimicrobial resistance in many countries with endemic typhoid fever. During 2010–2018, approximately 35% of reported S. Typhi isolates in Asia and 75% of those in Africa were resistant to chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole (defined as multidrug resistant [MDR]) (10). After a typhoid outbreak in Hyderabad, Pakistan in 2016, Pakistan became the first country to report MDR strains with additional resistance to fluoroquinolones and third-generation cephalosporins (defined as extensively drug resistant [XDR]); Pakistan continues to report high proportions of XDR S. Typhi cases (2). Resistance to an increasing number of antimicrobials, including fluoroquinolones, third-generation cephalosporins, and azithromycin (a macrolide), has been documented in Asia (10).