Typhoid Fever Worldwide: Surveillance, Estimates and the New Conjugate Vaccines

Estimated national typhoid incidence (2019) and typhoid conjugate vaccine introduction (2022). CDC.

Key points

• Typhoid fever, caused by Salmonella enterica serovar Typhi, is endemic in many low- and middle-income countries. Estimates put it at 11–21 million cases and 148,000–161,000 deaths in 2015, and 9.2 million cases and 110,000 deaths in 2019.
• Incidence is highest in WHO's South-East Asia (306 per 100,000 people), Eastern Mediterranean (187) and African (111) regions.
• WHO recommends typhoid conjugate vaccines (TCV), prioritizing countries with the highest incidence or high drug resistance. Since 2018, five countries have added them to routine immunization.
• Better surveillance is needed to guide vaccine decisions and measure impact.

Hard to count

Typhoid looks like other fevers common where it is endemic, such as malaria and dengue, so diagnosis needs a lab test — usually blood culture. But blood culture catches only 40%–60% of cases (fewer after antibiotics), is often unavailable, and is not routinely done. Lab-confirmed cases are a small fraction of the real total.

• Routine reporting: 59–62 countries reported confirmed typhoid to WHO and UNICEF each year in 2018–2021. Reported cases rose from about 8,800 in 2018, when typhoid was added to the reporting form, to 1 million in 2021.
• Population-based studies since 2016 have measured incidence in 10 countries through three projects: STRATAA (Bangladesh, Malawi, Nepal), SEAP (Bangladesh, Nepal, Pakistan) and SETA (Burkina Faso, DR Congo, Ethiopia, Ghana, Madagascar, Nigeria). Adjusted incidence ranged from 23 per 100,000 in Sodo, Ethiopia, to 1,189 in Nioko and Polesgo, Burkina Faso, with Dhaka (1,135) and Kathmandu (1,062) close behind.
• Modeling by the Global Burden of Disease study gives the regional estimates above, and a global rate of 119 per 100,000. Children 5–9 have the highest incidence, then 10–14 and 1–4.

Outbreaks

CDC outbreak monitoring identified seven confirmed outbreaks in 2017–2022, among them:

Drug resistance

• In 2010–2018, about 35% of reported Typhi isolates in Asia and 75% in Africa were multidrug resistant (to chloramphenicol, ampicillin and trimethoprim-sulfamethoxazole).
• After an outbreak in Hyderabad in 2016, Pakistan became the first country to report extensively drug-resistant strains, also resistant to fluoroquinolones and third-generation cephalosporins — and still reports many.
• Resistance to more drugs, including azithromycin, has been documented in Asia.

The vaccines

WHO has prequalified two conjugate vaccines: Typbar-TCV (Bharat Biotech) and TYPHIBEV (Biological E).

• They can be given from 6 months of age, so they fit into routine childhood schedules.
• One dose is safe and 79%–95% effective, with antibodies lasting up to 7 years.
• They can be given alongside measles, yellow fever and meningococcal A vaccines without interfering with any of them.
• They are cost-effective where incidence is high.

WHO says introduction should go with health education, water, sanitation and hygiene (WASH) improvements, and training health workers in diagnosis and treatment.

Who has introduced them

After a first public health use in Navi Mumbai, India, in 2018, the vaccine entered national routine schedules — at 9 months or 15–18 months of age — in:

Malawi planned to introduce it in 2023. More than 75 million children have been vaccinated in catch-up campaigns for ages 6 months to 14 years, with coverage of 63%–95%. Pakistan and Zimbabwe also used the vaccine in outbreak response.

Why so few countries — and what would help

Only three (7%) of the 44 countries and freely associated states with estimated high incidence have introduced the vaccine. Likely reasons: competing priorities, above all COVID-19, and too little data on disease burden — surveillance often relies on suspected cases and poor serologic tests, and population studies are costly and rare.

• Lack of data should not block a decision. Countries can draw on neighbors' and regional data, published studies, modeling, lab-confirmed cases, resistance studies, outbreak reports and reports of intestinal perforation, a hallmark of severe typhoid.
• Lessons from early adopters: Nepal, Pakistan and Zimbabwe ran integrated campaigns (other vaccines, vitamin A, hygiene promotion, finding under-vaccinated children), and school-based vaccination worked well — though it missed out-of-school children, and some schools saw absences they attributed to COVID-19-related vaccine misinformation.
• Money: four of the five countries had support from Gavi, the Vaccine Alliance; 11 middle-income high-incidence countries are ineligible and may face cost barriers.
• Surveillance: WHO recommends facility-based surveillance with lab confirmation. Expanding blood culture capacity helps track resistance and other bacterial infections, and better diagnostics and environmental surveillance may help. Nontraumatic intestinal perforations in endemic areas should be treated as probable typhoid or paratyphoid and can reveal outbreaks.

Limitations

• Cases and outbreaks are underreported because of limited lab capacity and incomplete reports.
• Experience with the vaccine is still accruing: routine coverage and impact data are not yet available.

Sources

Based on Molly Hancuh, Jenny Walldorf, Anna A. Minta et al., "Typhoid Fever Surveillance, Incidence Estimates, and Progress Toward Typhoid Conjugate Vaccine Introduction — Worldwide, 2018–2022," Morbidity and Mortality Weekly Report, Centers for Disease Control and Prevention, by authors from CDC, the CDC Foundation and the World Health Organization; published by CDC.