Typhoid Fever Surveillance, Incidence Estimates, and Progress Toward Typhoid Conjugate Vaccine Introduction - Worldwide, 2018-2022.

Typhoid fever, an acute febrile illness caused by Salmonella enterica serovar Typhi (S. Typhi), is endemic in many low- and middle-income countries† (1). In 2015, an estimated 11-21 million typhoid fever cases and 148,000-161,000 associated deaths occurred worldwide (2). Effective prevention strategies include improved access to and use of infrastructure supporting safe water, sanitation, and hygiene (WASH); health education; and vaccination (1). The World Health Organization (WHO) recommends programmatic use of typhoid conjugate vaccines for typhoid fever control and prioritization of vaccine introduction in countries with the highest typhoid fever incidence or high prevalence of antimicrobial-resistant S. Typhi (1). This report describes typhoid fever surveillance, incidence estimates, and the status of typhoid conjugate vaccine introduction during 2018-2022. Because routine surveillance for typhoid fever has low sensitivity, population-based studies have guided estimates of case counts and incidence in 10 countries since 2016 (3-6). In 2019, an updated modeling study estimated that 9.2 million (95% CI = 5.9-14.1) typhoid fever cases and 110,000 (95% CI = 53,000-191,000) deaths occurred worldwide, with the highest estimated incidence in the WHO South-East Asian (306 cases per 100,000 persons), Eastern Mediterranean (187), and African (111) regions (7). Since 2018, five countries (Liberia, Nepal, Pakistan, Samoa [based on self-assessment], and Zimbabwe) with estimated high typhoid fever incidence (≥100 cases per 100,000 population per year) (8), high antimicrobial resistance prevalence, or recent outbreaks introduced typhoid conjugate vaccines into their routine immunization programs (2). To guide vaccine introduction decisions, countries should consider all available information, including surveillance of laboratory-confirmed cases, population-based and modeling studies, and outbreak reports. Establishing and strengthening typhoid fever surveillance will be important to measure vaccine impact.

Evaluation of Vaccine Safety After the First Public Sector Introduction of Typhoid Conjugate Vaccine-Navi Mumbai, India, 2018.

BACKGROUND: In December 2017, the World Health Organization (WHO) prequalified the first typhoid conjugate vaccine (TCV; Typbar-TCV). While no safety concerns were identified in pre- and postlicensure studies, WHO's Global Advisory Committee on Vaccine Safety recommended robust safety evaluation with large-scale TCV introductions. During July-August 2018, the Navi Mumbai Municipal Corporation (NMMC) launched the world's first public sector TCV introduction. Per administrative reports, 113 420 children 9 months-14 years old received TCV. METHODS: We evaluated adverse events following immunization (AEFIs) using passive and active surveillance via (1) reports from the passive NMMC AEFI surveillance system, (2) telephone interviews with 5% of caregivers of vaccine recipients 48 hours and 7 days postvaccination, and (3) chart abstraction for adverse events of special interest (AESIs) among patients admitted to 5 hospitals using the Brighton Collaboration criteria followed by ascertainment of vaccination status. RESULTS: We identified 222/113 420 (0.2%) vaccine recipients with AEFIs through the NMMC AEFI surveillance system: 211 (0.19%) experienced minor AEFIs, 2 (0.002%) severe, and 9 serious (0.008%). At 48 hours postvaccination, 1852/5605 (33%) caregivers reported ≥1 AEFI, including injection site pain (n = 1452, 26%), swelling (n = 419, 7.5%), and fever (n = 416, 7.4%). Of the 4728 interviews completed at 7 days postvaccination, the most reported AEFIs included fever (n = 200, 4%), pain (n = 52, 1%), and headache (n = 42, 1%). Among 525 hospitalized children diagnosed with an AESI, 60 were vaccinated; no AESIs were causally associated with TCV. CONCLUSIONS: No unexpected safety signals were identified with TCV introduction. This provides further reassurance for the large-scale use of Typbar-TCV among children 9 months-14 years old.

Typhoid Outbreaks, 1989-2018: Implications for Prevention and Control.

Typhoid fever remains an important public health problem in low- and middle-income countries, with large outbreaks reported from Africa and Asia. Although the WHO recommends typhoid vaccination for control of confirmed outbreaks, there are limited data on the epidemiologic characteristics of outbreaks to inform vaccine use in outbreak settings. We conducted a literature review for typhoid outbreaks published since 1990. We found 47 publications describing 45,215 cases in outbreaks occurring in 25 countries from 1989 through 2018. Outbreak characteristics varied considerably by WHO region, with median outbreak size ranging from 12 to 1,101 cases, median duration from 23 to 140 days, and median case fatality ratio from 0% to 1%. The largest number of outbreaks occurred in WHO Southeast Asia, 13 (28%), and African regions, 12 (26%). Among 43 outbreaks reporting a mode of disease transmission, 24 (56%) were waterborne, 17 (40%) were foodborne, and two (5%) were by direct contact transmission. Among the 34 outbreaks with antimicrobial resistance data, 11 (32%) reported Typhi non-susceptible to ciprofloxacin, 16 (47%) reported multidrug-resistant (MDR) strains, and one reported extensively drug-resistant strains. Our review showed a longer median duration of outbreaks caused by MDR strains (148 days versus 34 days for susceptible strains), although this difference was not statistically significant. Control strategies focused on water, sanitation, and food safety, with vaccine use described in only six (13%) outbreaks. As typhoid conjugate vaccines become more widely used, their potential role and impact in outbreak control warrant further evaluation.

Toward Control? The Prospects and Challenges of Typhoid Conjugate Vaccine Introduction.

With a newly World Health Organization (WHO)-prequalified typhoid conjugate vaccine (TCV), Gavi funding for eligible countries, and a WHO policy recommendation for TCV use, now is the time for countries to introduce TCVs as part of an integrated typhoid control program, particularly in light of the increasing burden of antimicrobial resistance. Continued vaccine development efforts will lead to secure supply of low-cost vaccines, and ongoing vaccine studies will provide critical vaccine performance data and inform optimal deployment strategies, in both routine use and in outbreak settings. TCV programs should include thoughtful communication planning and community engagement to counter vaccine hesitancy.

Accelerating Typhoid Conjugate Vaccine Introduction: What Can Be Learned From Prior New Vaccine Introduction Initiatives?

The health consequences of typhoid, including increasing prevalence of drug-resistant strains, can stress healthcare systems. While vaccination is one of the most successful and cost-effective health interventions, vaccine introduction can take years and require considerable effort. The Typhoid Vaccine Acceleration Consortium (TyVAC) employs an integrated, proactive approach to accelerate the introduction of a new typhoid conjugate vaccine to reduce the burden of typhoid in countries eligible for support from Gavi, the Vaccine Alliance. TyVAC and its partners are executing a plan, informed by prior successful vaccine introductions, and tailored to the nuances of typhoid disease and the typhoid conjugate vaccine. The iterative process detailed herein summarizes the strategy and experience gained from the first 2 years of the project.

Revised Global Typhoid Vaccination Policy.

Typhoid fever is a continuing public health problem in many low- and middle-income countries; however, routine vaccination as a recommended control strategy has not been implemented in the past in most countries. Greater understanding of the typhoid fever burden, the increasing threat of antimicrobial resistance, and licensure of a new generation of typhoid conjugate vaccines (TCVs) were instrumental in paving the way for the World Health Organization (WHO) to issue a revised global policy on typhoid vaccines in March 2018. The new policy follows evidence-based recommendations by the WHO Strategic Advisory Group of Experts on immunization for routine and catch-up vaccination with TCVs and highlights considerations for universal, risk-based, or phased vaccination strategies in different settings. Further, the first WHO-prequalified TCV and Gavi funding for eligible countries make vaccination a realistic control strategy for many affected countries, especially if combined with improved water and sanitation services, strengthened surveillance systems, and appropriate antimicrobial treatment.

Typhoid Fever surveillance and vaccine use - South-East Asia and Western Pacific regions, 2009-2013.

Typhoid fever is a serious, systemic infection resulting in nearly 22 million cases and 216,500 deaths annually, primarily in Asia. Safe water, adequate sanitation, appropriate personal and food hygiene, and vaccination are the most effective strategies for prevention and control. In 2008, the World Health Organization (WHO) recommended use of available typhoid vaccines to control endemic disease and outbreaks and strengthening of typhoid surveillance to improve disease estimates and identify high-risk populations (e.g., persons without access to potable water and adequate sanitation). This report summarizes the status of typhoid surveillance and vaccination programs in the WHO South-East Asia (SEAR) and Western Pacific regions (WPR) during 2009-2013, after the revised WHO recommendations. Data were obtained from the WHO/United Nations Children's Fund (UNICEF) Joint Reporting Form on Immunization, a supplemental survey of surveillance and immunization program managers, and published literature. During 2009-2013, 23 (48%) of 48 countries and areas of SEAR (11) and WPR (37) collected surveillance or notifiable disease data on typhoid cases, with most surveillance activities established before 2008. Nine (19%) countries reported implementation of typhoid vaccination programs or recommended vaccine use during 2009-2013. Despite the high incidence, typhoid surveillance is weak in these two regions, and vaccination efforts have been limited. Further progress toward typhoid fever prevention and control in SEAR and WPR will require country commitment and international support for enhanced surveillance, targeted use of existing vaccines and availability of newer vaccines integrated within routine immunization programs, and integration of vaccination with safe water, sanitation, and hygiene measures.

Long-term safety assessment of live attenuated tetravalent dengue vaccines: deliberations from a WHO technical consultation.

Dengue is a rapidly growing public health threat with approximately 2.5 billion people estimated to be at risk. Several vaccine candidates are at various stages of pre-clinical and clinical development. Thus far, live dengue vaccine candidates have been administered to several thousands of volunteers and were well-tolerated, with minimal short-term safety effects reported in Phase I and Phase II clinical trials. Based on the natural history of dengue, a theoretical possibility of an increased risk of severe dengue as a consequence of vaccination has been hypothesized but not yet observed. In October 2011, the World Health Organization (WHO) convened a consultation of experts in dengue, vaccine regulation and vaccine safety to review the current scientific evidence regarding safety concerns associated with live attenuated dengue vaccines and, in particular, to consider methodological approaches for their long-term evaluation. In this paper we summarize the scientific background and methodological considerations relevant to the safety assessment of these vaccines. Careful planning and a coordinated approach to safety assessment are recommended to ensure adequate long-term evaluation of dengue vaccines that will support their introduction and continued use.

Monitoring of adverse events during the 2003 mass vaccination campaign with a trivalent meningococcal A/C/W135 polysaccharide vaccine in Burkina Faso.

During a mass campaign with a newly licensed meningococcal polysaccharide ACW135 vaccine in Burkina Faso, adverse events following immunization (AEFI) were monitored up to 4 weeks after the campaign. Eighty-six AEFI cases (5.9 cases per 100,000 vaccine doses distributed) were reported. Among 22 serious events, 4 severe local reactions were considered very likely and 4 severe allergic reactions were considered probably related to the vaccination. One fatal case in a child followed protracted seizures of undetermined cause. In a setting with no prior surveillance system, adverse events were reported at rates comparable to documented rates for meningococcal polysaccharide vaccines in other settings. The findings confirm the benefits of the vaccine in the control of meningococcal meningitis.

Monitoring vaccine safety during measles mass immunization campaigns: clinical and programmatic issues.

In the planning and implementation of mass immunization campaigns, vaccine delivery has always been a priority. However, safety issues have gained increasingly more attention and grown in importance, and campaign planners must now take them into prime consideration. The World Health Organization has released guidelines to assist with the design and implementation of safety surveillance systems, primarily for developing countries, and these include a new monograph for measles mass campaigns. Experience in the past decade with mass campaigns (primarily in developed countries) shows that measles vaccine performs in these settings as anticipated from pre- and post-licensure studies. Serious adverse events are rare, even under the increased scrutiny extended during a campaign. The experience in developing country settings is growing. The implementation of safety surveillance for mass campaigns offers a unique opportunity for countries to avoid crisis situations and to begin vaccine safety monitoring in routine immunization programs.