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.

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.

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.

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.

The role of vaccines in reducing antimicrobial resistance: A review of potential impact of vaccines on AMR and insights across 16 vaccines and pathogens.

In 2019, an estimated 4.95 million deaths were linked to antimicrobial resistance (AMR). Vaccines can prevent many of these deaths by averting both drug-sensitive and resistant infections, reducing antibiotic usage, and lowering the likelihood of developing resistance genes. However, their role in mitigating AMR is currently underutilized. This article builds upon previous research that utilizes Vaccine Value Profiles-tools that assess the health, socioeconomic, and societal impact of pathogens-to inform vaccine development. We analyze the effects of 16 pathogens, covered by Vaccine Value Profiles, on AMR, and explore how vaccines could reduce AMR. The article also provides insights into vaccine development and usage. Vaccines are crucial in lessening the impact of infectious diseases and curbing the development of AMR. To fully realize their potential, vaccines must be more prominently featured in the overall strategy to combat AMR. This requires ongoing investment in research and development of new vaccines and the implementation of additional prevention and control measures to address this global threat effectively.

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.

Typhoid fever vaccination strategies.

Typhoid vaccination is an important component of typhoid fever prevention and control, and is recommended for public health programmatic use in both endemic and outbreak settings. We reviewed experiences with various vaccination strategies using the currently available typhoid vaccines (injectable Vi polysaccharide vaccine [ViPS], oral Ty21a vaccine, and injectable typhoid conjugate vaccine [TCV]). We assessed the rationale, acceptability, effectiveness, impact and implementation lessons of these strategies to inform effective typhoid vaccination strategies for the future. Vaccination strategies were categorized by vaccine disease control strategy (preemptive use for endemic disease or to prevent an outbreak, and reactive use for outbreak control) and vaccine delivery strategy (community-based routine, community-based campaign and school-based). Almost all public health typhoid vaccination programs used ViPS vaccine and have been in countries of Asia, with one example in the Pacific and one experience using the Ty21a vaccine in South America. All vaccination strategies were found to be acceptable, feasible and effective in the settings evaluated; evidence of impact, where available, was strongest in endemic settings and in the short- to medium-term. Vaccination was cost-effective in high-incidence but not low-incidence settings. Experience in disaster and outbreak settings remains limited. TCVs have recently become available and none are WHO-prequalified yet; no program experience with TCVs was found in published literature. Despite the demonstrated success of several typhoid vaccination strategies, typhoid vaccines remain underused. Implementation lessons should be applied to design optimal vaccination strategies using TCVs which have several anticipated advantages, such as potential for use in infant immunization programs and longer duration of protection, over the ViPS and Ty21a vaccines for typhoid prevention and control.

Protocol for the investigation of acute flaccid paralysis and suspected paralytic poliomyelitis.

Despite the elimination of indigenous wild poliovirus in Canada, ongoing surveillance for poliomyelitis is important because of the risk of wild virus importation from endemic regions. Most recently, importation of wild poliovirus into Canada occurred in 1993 and 1996,inboth instances with no associated clinical illness. Since 1991, the active surveillance of acute flaccid paralysis (AFP) in children less than 15 years old has been carried out in Canada to monitor for suspected cases of paralytic poliomyelitis. AFP surveillance is currently implemented through the Canadian Paediatric Surveillance Program. All suspected cases of paralytic poliomyelitis reported to the Laboratory Centre for Disease Control are evaluated by the national Working Group on Polio Eradication. The proper laboratory and neurological investigation of all AFP cases younger than 15 years old and suspected cases of poliomyelitis of any age is essential for the rapid detection of paralytic poliomyelitis, the most important clinical specimen for laboratory investigation being a stool sample collected within two weeks after the onset of paralysis for viral studies. This paper provides guidelines for investigating all suspected cases of paralytic poliomyelitis, including AFP cases less than 15 years old. Guidelines are also provided for reporting confirmed or suspected cases of paralytic poliomyelitis as well as the incidental finding of wild strain poliovirus, with or without any clinical symptoms.

Malgré l'éliminationdu poliovirus sauvage indigèneau Canada, la surveillance constante de lapoliomyélite revêtdel'importanceenraison du risque d'importer le virus sauvage des régions endémiques. Une importation du poliovirus sauvage au Canada s'est d'ailleurs produite en 1993 et en 1996, n'ayant toutefois suscité dans les deux cas aucune maladie clinique associée. Depuis 1991, la surveillance active de la paralysie flasque aiguë (PFA) chez les enfants de moinsde 15 ans s'effectue à l'extérieur du Canada pour surveiller les cas présomptifs de poliomyélite paralytique. La surveillance de la PFA est maintenant implantée par l'entremise du Programme canadien de surveillance pédiatrique. Tous les cas présomptifs de poliomyélite paralytique déclarés au Laboratoire de lutte contre la maladie sont évalués par le groupe de travail national sur l'éradication de la polio. Les investigations neurologiques et de laboratoire pertinentes de tous les cas de PFA chez les enfants de moins de 15 ans et des cas présomptifs de poliomyélite à tout âge sont essentielles à la détection rapide dela poliomyélite paralytique, le prélèvement clinique le plus important pour les recherches de laboratoire étant constitué d'un échantillon de selles recueilli dans les deux semaines suivant l'apparition de la paralysie, en vue des études virales. Cet article fournit des directives pour étudier tous les cas présomptifs de poliomyélite paralytique, y compris les cas de PFA chez les moins de 15 ans. Des directives sont également fournies pour déclarer les cas confirmés ou présomptifs de poliomyélite paralytique ainsi que les observations fortuites de poliovirus de souche sauvage, accompagné ou non de symptômes cliniques.

Vaccination coverage levels among children two years of age and selected aspects of vaccination practices in Canada - 1996.

OBJECTIVE: To obtain population-based estimates of coverage for routine childhood vaccinations at two years of age and information about selected aspects of vaccination practices in Canada. METHODS: Data were collected through a mail survey of a sample of households with two-year-olds born between February 1993 and January 1994. To obtain population estimates, survey data were weighted to match known population distributions of geographic region, community size, household income level and single-parent versus two-parent family type. RESULTS: Up-to-date vaccination coverage was estimated as 84.8% (95% CI 82.0 to 87.3) for diphtheria-pertussis-tetanus vaccine, 89.9% (95% CI 87.4 to 92.0) for polio vaccine, 93.3% (95% CI 91.2 to 95.0) for measlesmumps-rubella vaccine and 69.3% (95% CI 65.8 to 72.6) for Hae-mophilus influenzae type b vaccine. Less than one per cent of children had not received vaccination of any kind. Ninety-five per cent of parents cited the benefits of vaccination as a reason for having their children vaccinated. CONCLUSION: Coverage levels indicate that the national targets set for 1997 for up-to-date vaccination of children at two years of age have been reached for mumps and rubella, and good progress isbeing made towards targets for the remaining vaccines. Special attention from providers and parents is required to prevent vaccination delays, particularly for 18-month booster doses.

OBJECTIF: Obtenir au sein de la population une évaluation de la couverture de vaccination systématique des enfants à l'âge de deux ans, ainsi que des renseignements sur des aspects choisis des pratiques de vaccination au Canada. MÉTHODE: Les données ont été obtenuesaumoyen d'un sondage postal auprès d'un groupe de foyers ayant un enfant de deux ans né entre février 1993 et janvier 1994. Pour obtenir une évaluation de la population, les données du sondage ont été pondérées pour correspondre aux distributions connues de la population par région géographique, par importance de la communauté, par revenu familial et par type de famille, soit monoparental ou biparental. RÉSULTATS: La couverture à jour de la vaccination s'évaluait à 84,8 % (95 %, IC de 82,0 à 87,3) dans le cas du vaccin diphtérie-coqueluche-tétanos, à 89,9 % (95 %, IC de 87,4 à 92,0) dans le cas du vaccin antipoliomyélitique, à 93,3 % (95 %, IC de 91,2 à 95,0) dans le cas du vaccin rougeole-rubéole-oreillons, et à 69,3 % (95 %, IC de 65,8 à 72,6) dans le casdu vaccin contre l'Haemophilus influenzaede type b.Moinsde unpour cent des enfants n'avaient reçu aucun vaccin. Quatre-vingt-quinze pour cent des parents citaient les bienfaits de la vaccination comme raison de faire vacciner leur enfant. CONCLUSION: Le taux de couverture indique que les objectifs nationaux établis pour 1997 relativement à la mise à jour des vaccins aux enfants de deux ans ont été atteints pour ce qui est des oreillons etdelarubéole, et que des progrès intéressants sont réalisés en ce qui a trait aux autres vaccins. Les éducateurs et les parents doivent faire preuve de diligence pour éviter les retards de vaccination, surtout au moment des doses de rappel à l'âge de 18 mois.

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.

An outbreak of severe infections with community-acquired MRSA carrying the Panton-Valentine leukocidin following vaccination.

BACKGROUND: Infections with community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) are emerging worldwide. We investigated an outbreak of severe CA-MRSA infections in children following out-patient vaccination. METHODS AND FINDINGS: We carried out a field investigation after adverse events following immunization (AEFI) were reported. We reviewed the clinical data from all cases. S. aureus recovered from skin infections and from nasal and throat swabs were analyzed by pulse-field gel electrophoresis, multi locus sequence typing, PCR and microarray. In May 2006, nine children presented with AEFI, ranging from fatal toxic shock syndrome, necrotizing soft tissue infection, purulent abscesses, to fever with rash. All had received a vaccination injection in different health centres in one District of Ho Chi Minh City. Eight children had been vaccinated by the same health care worker (HCW). Deficiencies in vaccine quality, storage practices, or preparation and delivery were not found. Infection control practices were insufficient. CA-MRSA was cultured in four children and from nasal and throat swabs from the HCW. Strains from children and HCW were indistinguishable. All carried the Panton-Valentine leukocidine (PVL), the staphylococcal enterotoxin B gene, the gene complex for staphylococcal-cassette-chromosome mec type V, and were sequence type 59. Strain HCM3A is epidemiologically unrelated to a strain of ST59 prevalent in the USA, although they belong to the same lineage. CONCLUSIONS: We describe an outbreak of infections with CA-MRSA in children, transmitted by an asymptomatic colonized HCW during immunization injection. Consistent adherence to injection practice guidelines is needed to prevent CA-MRSA transmission in both in- and outpatient settings.

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.