Enhanced cholera surveillance to improve vaccination campaign efficiency.

Systematic testing for Vibrio cholerae O1 is rare, which means that the world's limited supply of oral cholera vaccines (OCVs) may not be delivered to areas with the highest true cholera burden. Here we used a phenomenological model with subnational geographic targeting and fine-scale vaccine effects to model how expanding V. cholerae testing affected impact and cost-effectiveness for preventive vaccination campaigns across different bacteriological confirmation and vaccine targeting assumptions in 35 African countries. Systematic testing followed by OCV targeting based on confirmed cholera yielded higher efficiency and cost-effectiveness and slightly fewer averted cases than status quo scenarios targeting suspected cholera. Targeting vaccine to populations with an annual incidence rate greater than 10 per 10,000, the testing scenario averted 10.8 (95% prediction interval (PI) 9.4-12.6) cases per 1,000 fully vaccinated persons while the status quo scenario averted 6.9 (95% PI 6.0-7.8) cases per 1,000 fully vaccinated persons. In the testing scenario, testing costs increased by US$31 (95% PI 25-39) while vaccination costs reduced by US$248 (95% PI 176-326) per averted case compared to the status quo. Introduction of systematic testing into cholera surveillance could improve efficiency and reach of global OCV supply for preventive vaccination.

Progress in the Typhoid Conjugate Vaccine Program Rollout Supported by Gavi During the COVID-19 Pandemic and the Path Forward.

Gavi supports countries to introduce typhoid conjugate vaccine (TCV) with catch-up campaigns. Available TCVs are highly efficacious, equity-focused, and critical to curbing the expansion of antimicrobial resistance. Four Gavi-supported countries have introduced TCVs since 2018. In the wake of the COVID-19 emergency, momentum is building to scale up TCV introduction worldwide, supported by global partners and Gavi's funding for improved typhoid diagnostics.

Diagnostics for Typhoid Fever: Current Perspectives and Future Outlooks for Product Development and Access.

Typhoid is an enteric disease caused by Salmonella Typhi. Like many febrile illnesses, typhoid presents with nonspecific symptoms. In routine healthcare settings in low- and middle-income countries, typhoid fever is suspected and treated empirically. Though many diagnostic tests are available for typhoid diagnosis, there are currently no diagnostic tests that meet ideal requirements for sensitivity, specificity, speed, and cost-effectiveness. With introduction of typhoid conjugate vaccine, it is essential to explore the current and future typhoid approach in the context of use case and access to ensure their utilization for disease control.

Economic impact of vaccine safety incident in Ukraine: The economic case for safety system investment.

BACKGROUND: Vaccine confidence and coverage decreased following a death temporally but not causally related to measles vaccination in Ukraine in 2008. Large measles outbreaks including international exportations followed. Herein we characterize this experience including associated costs. METHODS: Mixed-methods were used to characterize this vaccine safety incident and quantify health and economic costs. Qualitative interviews illuminate the incident, social climate, and corruption that influenced vaccine confidence in Ukraine. A literature review explored attitudes toward vaccines in the USSR and post-independence Ukraine. Infectious disease incidence was examined before and after the vaccine safety incident. An economic analysis estimated associated healthcare costs, including prevention and outbreak control measures, additional vaccination activities due to failure of the 2008 campaign, treatment costs for new cases domestically and foreign exportation, and productivity loss from treatment time and mortality for new cases. FINDINGS: Vaccine hesitancy and distrust in government and public health programs due to corruption existed in Ukraine before the vaccine safety incident. The mishandling of the 2008 incident catalyzed the decline of vaccine confidence and prompted poor procurement decisions, leading to a drop in infant vaccination coverage, increased domestic measles cases, and exportation of measles. The estimated cost of this incident was approximately $140 million from 2008 to 2018. INTERPRETATION: Absent a rapid and credible vaccine safety response, a coincidental death following immunization resulted in major outbreaks of measles with substantial economic costs. Adequate investments in a post-licensure safety system may help avoid similar future incidents.

Toward Establishing Integrated, Comprehensive, and Sustainable Meningitis Surveillance in Africa to Better Inform Vaccination Strategies.

Large populations across sub-Saharan Africa remain at risk of devastating acute bacterial meningitis epidemics and endemic disease. Meningitis surveillance is a cornerstone of disease control, essential for describing temporal changes in disease epidemiology, the rapid detection of outbreaks, guiding vaccine introduction and monitoring vaccine impact. However, meningitis surveillance in most African countries is weak, undermined by parallel surveillance systems with little to no synergy and limited laboratory capacity. African countries need to implement comprehensive meningitis surveillance systems to adapt to the rapidly changing disease trends and vaccine landscapes. The World Health Organization and partners have developed a new investment case to restructure vaccine-preventable disease surveillance. With this new structure, countries will establish comprehensive and sustainable meningitis surveillance systems integrated with greater harmonization between population-based and sentinel surveillance systems. There will also be stronger linkage with existing surveillance systems for vaccine-preventable diseases, such as polio, measles, yellow fever, and rotavirus, as well as with other epidemic-prone diseases to leverage their infrastructure, transport systems, equipment, human resources and funding. The implementation of these concepts is currently being piloted in a few countries in sub-Saharan Africa with support from the World Health Organization and other partners. African countries need to take urgent action to improve synergies and coordination between different surveillance systems to set joint priorities that will inform action to control devastating acute bacterial meningitis effectively.

Global Rotavirus and Pneumococcal Conjugate Vaccine Introductions and the Association With Country Disease Surveillance, 2006-2018.

BACKGROUND: To inform the introduction of pneumococcal conjugate vaccine (PCV) and rotavirus vaccine, the World Health Organization (WHO) established the Global Invasive Bacterial Vaccine-Preventable Disease Surveillance Network (GISN) and the Global Rotavirus Surveillance Network (GRSN) in 2008. We investigated whether participation in these networks or other surveillance was associated with vaccine introduction. METHODS: Between 2006 and 2018, among all WHO member states, we used multivariable models adjusting for economic status to assess (1) the association between surveillance for pneumococcal disease or rotavirus disease, including participation in GISN or GRSN and the introduction of the PCV or the rotavirus vaccine, respectively, and (2) the association between the rotavirus disease burden and the rotavirus vaccine introduction among 56 countries participating in GRSN from 2008 to 2018. RESULTS: Countries that participated in or conducted surveillance for invasive pneumococcal disease or rotavirus disease were 3.5 (95% confidence interval [CI], 1.7-7.1) and 4.2 (95% CI, 2.1-8.6) times more likely to introduce PCV or rotavirus respectively, compared to those without surveillance. Among countries participating in GRSN, there was insufficient evidence to demonstrate an association between countries with higher rotavirus positivity and vaccine introduction. CONCLUSIONS: Surveillance should be incorporated into advocacy strategies to encourage the introduction of vaccines, with countries benefiting from data from, support for, and coordination of international disease surveillance networks.

Gavi Support for Typhoid Conjugate Vaccines: Moving From Global Investments to Country Introduction.

Nine years elapsed between Gavi's investment decision to support typhoid conjugate vaccines (TCVs) in 2008 and Gavi support becoming available for countries to introduce TCV. The protracted path toward Gavi support for TCV highlights the challenges of vaccine development for lower-income countries and the importance of Gavi engagement as early as possible in product development processes to support the alignment of manufacturing, global policy, and program implementation. Early engagement would provide inputs to inform strategic vaccine investment decisions that transition more efficiently toward country implementation. Several countries have been approved for Gavi support to introduce TCV in 2019-2020. The paucity of generalizable typhoid epidemiological data in early introducing countries has reinforced the need for continued evidence generation regarding typhoid epidemiology and TCV impact. This has led to the development of guidance and tools to support country decision making for TCV introduction based on enhanced understanding of local typhoid burden and risk.

Introduction of inactivated poliovirus vaccine in the Philippines: Effect on health care provider and infant caregiver attitudes and practices.

BACKGROUND: The introduction of inactivated poliovirus vaccine (IPV) to the Philippines' national immunization schedule meant the addition of a third injectable vaccine at a child's 14-week immunization visit. Although previous studies have shown that providing multiple vaccines at the same time affected neither the risk of severe adverse events nor vaccine efficacy, concerns were raised that providing three injections at a single visit, with two injections in one leg, might be unacceptable to health care providers (HCP) and infant caregivers. METHODS: We conducted pre- and post-IPV introduction surveys on the acceptance and acceptability of the additional injectable vaccine in three of the Philippines' 17 administrative regions. Regions 3 and 6 were included in the pre-introduction phase and Regions 3, 6 and 10 were included in the post-introduction phase. Thirty public health centers (PHCs) were randomly sampled from each region. HCPs and infant caregivers were interviewed. In addition, vaccination records from a minimum of 20 eligible children pre-introduction and 10 children post-introduction per PHC were reviewed. RESULTS AND DISCUSSION: We interviewed 89 HCPs and 286 infant caregivers during the pre-introduction phase and 137 HCPs and 455 caregivers during the post-introduction phase. Among 986 vaccination records reviewed post-introduction, 84% (n = 826) of children received all three recommended injections at one visit, with a range from 61% (209/342) in Region 10 to 100% (328/328) in Region 3. The proportion of HCPs reporting that they had administered three or more injectable vaccines and the proportion of caregivers that would be comfortable with their child receiving three or more injectable vaccines at one visit increased from pre- to post-introduction (p < 0.0001 for both). Eighty-seven percent of HCPs that had administered three or more injectable vaccines post-introduction reported being comfortable or very comfortable with the number of vaccines they had administered.

Clinical Surveillance and Evaluation of Suspected Ebola Cases in a Vaccine Trial During an Ebola Epidemic: The Sierra Leone Trial to Introduce a Vaccine Against Ebola.

Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

Planning for globally coordinated cessation of bivalent oral poliovirus vaccine: risks of non-synchronous cessation and unauthorized oral poliovirus vaccine use.

BACKGROUND: Oral polio vaccine (OPV) containing attenuated serotype 2 polioviruses was globally withdrawn in 2016, and bivalent OPV (bOPV) containing attenuated serotype 1 and 3 polioviruses needs to be withdrawn after the certification of eradication of all wild polioviruses to eliminate future risks from vaccine-derived polioviruses (VDPVs). To minimize risks from VDPVs, the planning and implementation of bOPV withdrawal should build on the experience with withdrawing OPV containing serotype 2 polioviruses while taking into account similarities and differences between the three poliovirus serotypes. METHODS: We explored the risks from (i) a failure to synchronize OPV cessation and (ii) unauthorized post-cessation OPV use for serotypes 1 and 3 in the context of globally-coordinated future bOPV cessation and compared the results to similar analyses for serotype 2 OPV cessation. RESULTS: While the risks associated with a failure to synchronize cessation and unauthorized post-cessation OPV use appear to be substantially lower for serotype 3 polioviruses than for serotype 2 polioviruses, the risks for serotype 1 appear similar to those for serotype 2. Increasing population immunity to serotype 1 and 3 poliovirus transmission using pre-cessation bOPV supplemental immunization activities and inactivated poliovirus vaccine in routine immunization reduces the risks of circulating VDPVs associated with non-synchronized cessation or unauthorized OPV use. CONCLUSIONS: The Global Polio Eradication Initiative should synchronize global bOPV cessation during a similar window of time as occurred for the global cessation of OPV containing serotype 2 polioviruses and should rigorously verify the absence of bOPV in immunization systems after its cessation.

Modeling Poliovirus Transmission in Pakistan and Afghanistan to Inform Vaccination Strategies in Undervaccinated Subpopulations.

Due to security, access, and programmatic challenges in areas of Pakistan and Afghanistan, both countries continue to sustain indigenous wild poliovirus (WPV) transmission and threaten the success of global polio eradication and oral poliovirus vaccine (OPV) cessation. We fitted an existing differential-equation-based poliovirus transmission and OPV evolution model to Pakistan and Afghanistan using four subpopulations to characterize the well-vaccinated and undervaccinated subpopulations in each country. We explored retrospective and prospective scenarios for using inactivated poliovirus vaccine (IPV) in routine immunization or supplemental immunization activities (SIAs). The undervaccinated subpopulations sustain the circulation of serotype 1 WPV and serotype 2 circulating vaccine-derived poliovirus. We find a moderate impact of past IPV use on polio incidence and population immunity to transmission mainly due to (1) the boosting effect of IPV for individuals with preexisting immunity from a live poliovirus infection and (2) the effect of IPV-only on oropharyngeal transmission for individuals without preexisting immunity from a live poliovirus infection. Future IPV use may similarly yield moderate benefits, particularly if access to undervaccinated subpopulations dramatically improves. However, OPV provides a much greater impact on transmission and the incremental benefit of IPV in addition to OPV remains limited. This study suggests that despite the moderate effect of using IPV in SIAs, using OPV in SIAs remains the most effective means to stop transmission, while limited IPV resources should prioritize IPV use in routine immunization.

Lessons Learned From the Introduction of Inactivated Poliovirus Vaccine in Bangladesh.

Background: We assessed programmatic adaptations and infants' uptake of inactivated poliovirus vaccine (IPV) after its introduction into the routine immunization schedule in Bangladesh. Methods: Using convenience and probability sampling, we selected 23 health facilities, 36 vaccinators, and 336 caregivers, within 5 districts and 3 city corporations. We collected data during August-October 2015 by conducting interviews, reviewing vaccination records, and observing activities. Results: Knowledge about IPV was high among vaccinators (94%). No problems with IPV storage, transport, or waste disposal were detected, but shortages were reported in 20 health facilities (87%). Wastage per 5-dose vaccine vial was above the recommended 30% in 20 health facilities (87%); all were related to providing <5 doses per open vial. Among eligible infants, 87% and 86% received the third dose of pentavalent and oral poliovirus vaccine, respectively, but only 65% received IPV at the same visit. Among 73 infants not vaccinated with IPV, 58% of caregivers reported that vaccine was unavailable. Conclusions: Bangladesh successfully introduced IPV, but shortages related to insufficient global supply and high vaccine wastage in small outreach immunization sessions might reduce its impact on population immunity. Minimizing wastage and use of a 2-dose fractional-IPV schedule could extend IPV immunization to more children.