Economic evaluations of immunization programs as an indispensable tool for policymakers.

Introducing new vaccines within national immunization programs requires careful consideration of disease- and vaccine-related issues as well as of the strength of the program and the affected health system. Economic evaluations play an essential role in this process. In this editorial, we set the context and invite contributions for a BMC Health Services Research Collection of articles titled 'Economic Evaluations of Vaccine Programs'.

Co-administration of SARS-CoV-2 and influenza vaccines in healthcare workers: Results of two vaccination campaigns in a large teaching hospital in Rome.

The concurrent administration of COVID-19 and influenza vaccines has arisen as a promising approach to bolster protection against respiratory pathogens and improve vaccination rates. However, there remains a lack of data regarding the prevalence of co-administration across several vaccination campaigns, especially among healthcare workers (HCWs). Therefore, this study aims to shed light on the acceptance of co-administration strategies among HCWs during the two campaigns following the introduction of the anti-SARS-CoV-2 vaccine. A retrospective cohort study was conducted among the HCWs of the Fondazione Policlinico Universitario "A. Gemelli" IRCCS, a research hospital in Rome. Hospital administrative databases were accessed to gather information about vaccination for SARS-CoV-2 and influenza during the 2021/2022 and 2022/2023 vaccination campaigns. The study included 7399 HCWs. The co-administration of anti-SARS-CoV-2 and influenza vaccines presented a significant rise in 2022/2023 compared to the previous vaccination campaign (+38%): this was confirmed for every professional category, with the largest increases among resident doctors (+47%) and physicians (+44%), and also for every age category, but it was particularly evident for the youngest health professionals. The probability of co-administration uptake during the 2022/2023 campaign was significantly higher for males, and for those that received co-administration during the 2021/2022 campaign, while the probability was lower for nurses and administrative staff. This study highlights the co-administration procedure as a valuable and effective tool in annual vaccination campaigns for SARS-CoV-2 and influenza. The procedure's safety and streamlined logistics make it increasingly attractive for implementation, particularly among HCWs.

HPV vaccination and side effects.

In Denmark, the proportion of children completing the HPV vaccination program is lower than for other vaccines, and the relatively low uptake is believed to be influenced by a media debate on suspected side effects of HPV vaccination. Based on a systematic PubMed search, this review identified 14 Danish studies that compared symptoms or disease incidence among HPV-vaccinated individuals with the incidence in a control group. Most studies showed no association between HPV vaccination and subsequent illness.

Recent changes to adult national immunization programs for pneumococcal vaccination in Europe and how they impact coverage: A systematic review of published and grey literature.

Despite widespread use of pneumococcal vaccines throughout Europe, the burden of pneumococcal disease (PD) in adults is considerable. To mitigate this burden, National Immunization Technical Advisory Groups (NITAGs) and Health Technology Assessment (HTA) agencies assess the value of different vaccine schedules for protecting against PD. The aim of this review was to assess the evidence and rationales used by NITAGs/HTA agencies, when considering recent changes to National Immunization Programs (NIPs) for adults, and how identified changes affected vaccine coverage rates (VCRs). A systematic review was conducted of published literature from PubMed® and Embase®, and gray literature from HTA/NITAG websites from the last 5 y, covering 31 European countries. Evidence related to NIP recommendations, epidemiology (invasive PD, pneumonia), health economic assessments and VCRs were collected and synthesized. Eighty-four records providing data for 26 countries were identified. Of these, eight described explicit changes to NIPs for adults in seven countries. Despite data gaps, some trends were observed; first, there appears to be a convergence of NIP recommendations in many countries toward sequential vaccination, with a pneumococcal conjugate vaccine (PCV), followed by pneumococcal polysaccharide vaccine 23. Second, reducing economic or healthcare burden were common rationales for implementing changes. Third, most health economic analyses assessing higher-valency PCVs for adults found its inclusion in NIPs cost-effective. Finally, higher coverage rates were seen in most cases where countries had expanded their NIPs to cover at-risk populations. The findings can encourage agencies to improve surveillance systems and work to reach the NIP's target populations more effectively.

Factors underlying COVID-19 booster vaccine uptake among adults in Belgium.

OBJECTIVE: This study aimed to investigate factors influencing the uptake of first and second COVID-19 booster vaccines among adults in Belgium, particularly age, sex, region of residence and laboratory confirmed COVID-19 infection history. RESULTS: A binomial regression model was used with having received the first or second booster as outcome and age, sex, region of residence and infection history as fixed variables. Among adults, there was generally a higher uptake to receive the first booster among older age groups compared to younger ones. Females, individuals residing in Flanders and those with no previous COVID-19 infection were more likely to receive the first booster. For the second booster, the same age trend was seen as for the first booster. Males, individuals residing in Flanders and those who tested positive for COVID-19 once after first booster were more likely to receive the second booster. Individuals with multiple positive COVID-19 tests before and after primary course or first booster were less likely to receive the subsequent booster dose compared to COVID-naïve individuals. This information could be used to guide future vaccination campaigns during a pandemic and can provide valuable insights into booster uptake patterns.

The faces behind vaccination: unpacking the attitudes, knowledge, and practices of staff of Cameroon's Expanded program on Immunization.

BACKGROUND: Immunization is regarded as one of the most cost-effective public health interventions in global health. However, its cost-effectiveness depends greatly on the knowledge and skills of vaccinators. With the growing complexity of immunization programs, the need for a well-trained vaccination workforce cannot be overemphasized. In this study, we assessed the knowledge, attitudes, and practices among vaccination staff in Cameroon. METHODS: Through a descriptive cross-sectional design, we used structured questionnaires and observation guides to collect data from vaccination staff in health facilities that were selected by a multistage sampling method. Data were analyzed using STATA 13 software. RESULTS: Overall, we collected data from Expanded Program on Immunization focal staff in 265 health facilities across 68 health districts. Over half (53%) of the surveyed facilities were found in rural areas. Nearly two-thirds of health facilities had immunization focal staff with knowledge gaps for each of the four basic immunization indicators assessed. In other words, only 37% of staff knew how to estimate coverages, 36% knew how to inteprete the EPI monitoring curve, 35% knew how to prepare vaccine orders, and 37% knew how to estimate vaccine wastage. In terms of practices, staff waited for more than ten children to be present before opening a 20-dose vaccine vial in 63% of health facilities, and more than five children to be present before opening a 10-dose vaccine vial in 80% of surveyed facilities. Provision of vaccine-specific information (informing caregiver about vaccine received, explanation of benefits and potential side effects) during immunization sessions was suboptimal for the most part. CONCLUSION: This study suggests marked deficits in immunization knowledge among vaccination staff and exposes common attitudes and practices that could contribute to missed opportunities for vaccination and hinder vaccination coverage and equity in Cameroon. Our findings highlight the urgent need to invest in comprehensive capacity building of vaccination staff in Cameroon, especially now that the immunization program is becoming increasingly complex.

Progress Toward Measles Elimination - Worldwide, 2000-2022.

Measles is a highly contagious, vaccine-preventable disease that requires high population immunity for transmission to be interrupted. All six World Health Organization regions have committed to eliminating measles; however, no region has achieved and sustained measles elimination. This report describes measles elimination progress during 2000-2022. During 2000-2019, estimated coverage worldwide with the first dose of measles-containing vaccine (MCV) increased from 72% to 86%, then declined to 81% in 2021 during the COVID-19 pandemic, representing the lowest coverage since 2008. In 2022, first-dose MCV coverage increased to 83%. Only one half (72) of 144 countries reporting measles cases achieved the measles surveillance indicator target of two or more discarded cases per 100,000 population in 2022. During 2021-2022, estimated measles cases increased 18%, from 7,802,000 to 9,232,300, and the number of countries experiencing large or disruptive outbreaks increased from 22 to 37. Estimated measles deaths increased 43% during 2021-2022, from 95,000 to 136,200. Nonetheless, an estimated 57 million measles deaths were averted by vaccination during 2000-2022. In 2022, measles vaccination coverage and global surveillance showed some recovery from the COVID-19 pandemic setbacks; however, coverage declined in low-income countries, and globally, years of suboptimal immunization coverage left millions of children unprotected. Urgent reversal of coverage setbacks experienced during the COVID-19 pandemic can be accomplished by renewing efforts to vaccinate all children with 2 MCV doses and strengthening surveillance, thereby preventing outbreaks and accelerating progress toward measles elimination.

[Analysis on the implementation of payment policies for four non-national immunization program vaccines in China].

This study systematically retrieved information on the payment policy of vaccination fees for pneumococcal vaccines, human papillomavirus vaccines, haemophilus influenzae type b vaccines and rotavirus vaccines using a Python-based crawler. The proportion of the population covered by policies among the total applicable population was estimated based on the medical insurance coverage ratio and population data in 2020. This study showed that the payment policies included two categories, government-funded free vaccination policies and medical insurance payment policies. Among the four non-national immunization program vaccines, the free vaccination policies only involved pneumococcal vaccines and human papillomavirus vaccines. Among them, the 13-valent pneumococcal conjugate vaccine, the 23-valent pneumococcal polysaccharide vaccine, and the human papillomavirus vaccine were provided free of charge in 1, 10 and 15 provinces, respectively. For these policies, the corresponding covered population and the proportion among the total applicable population were children aged 6 months to 2 years old (2.5%), older people (1.2% to 21.5%) and middle school girls (1.1% to 12.2%). Medical insurance payment policies were implemented in 14 provinces, and nearly covered the four types of vaccines in the policy implementation areas, with the proportion of the covered population about 10.9% to 41.5% among the total applicable population.

Evaluating effective measles vaccine coverage in the Malaysian population accounting for between-dose correlation and vaccine efficacy.

BACKGROUND: Malaysia introduced the two dose measles-mumps-rubella (MMR) vaccine in 2004 as part of its measles elimination strategy. However, despite high historical coverage of MCV1 and MCV2, Malaysia continues to report high measles incidence. This study suggests a novel indicator for investigating population immunity against measles in the Malaysian population. METHODS: We define effective vaccine coverage (EVC) of measles as the proportion of a population vaccinated with measles-containing vaccine (MCV) and effectively protected against measles infection. A quantitative evaluation of EVC throughout the life course of Malaysian birth cohorts was conducted accounting for both vaccine efficacy (VE) and between-dose correlation (BdC). Measles vaccination coverage was sourced from WHO-UNICEF estimates of Malaysia's routine immunisation coverage and supplementary immunisation activities (SIAs). United Nations World population estimates and projections (UNWPP) provided birth cohort sizes stratified by age and year. A step wise joint Bernoulli distribution was used to proportionate the Malaysian population born between 1982, the first year of Malaysia's measles vaccination programme, and 2021, into individuals who received zero dose, one dose and multiple doses of MCV. VE estimates by age and doses received are then adopted to derive EVC. A sensitivity analysis was conducted using 1000 random combinations of BdC and VE parameters. RESULTS: This study suggests that no birth cohort in the Malaysian population has achieved > 95% population immunity (EVC) conferred through measles vaccination since the measles immunisation programme began in Malaysia. CONCLUSION: The persistence of measles in Malaysia is due to pockets of insufficient vaccination coverage against measles in the population. Monitoring BdC through immunisation surveillance systems may allow for the identification of susceptible subpopulations (primarily zero-dose MCV individuals) and increase the coverage of individuals who are vaccinated with multiple doses of MCV. This study provides a tool for assessment of national-level population immunity of measles conferred through vaccination and does not consider subnational heterogeneity or vaccine waning. This tool can be readily applied to other regions and vaccine-preventable diseases.

Accelerating Pneumococcal Conjugate Vaccine introductions in Indonesia: key learnings from 2017 to 2022.

Despite high pneumococcal disease and economic burden in Indonesia and interest to introduce pneumococcal conjugate vaccine (PCV), there were challenges in establishing a comprehensive strategy to accelerate and enable the introduction in country in the early 2010s. Starting in 2017, Clinton Health Access Initiative and partners supported the government of Indonesia with evidence-based decision-making and implementation support for introducing PCV into the routine immunization program. Indonesia has since accelerated PCV roll out, with nationwide reach achieved in 2022. On the path to PCV introduction, several challenges were observed that impacted decision making on whether and on how to optimally roll out PCV, resulting in significant introduction delays; including (1) a complex country context with a devolved government structure, fragmented domestic funding streams, and an imminent transition out of major immunization donor (Gavi) support; (2) strong preference to use domestically sourced products, with limited experience accessing global pooled procurement mechanism including for vaccines; and (3) concerns around programmatic feasibility and sustainability. This case study documents key insights into the challenges experienced and how those were systematically addressed to accelerate new vaccine introduction in Indonesia, with support from local and global stakeholders over time. The learnings would be beneficial for other countries yet to introduce critical new vaccines, in particular those with similar archetype as Indonesia e.g., middle-income countries with domestic manufacturing capacity and/or countries recently transitioning out of Gavi support.

Gaps in vaccine management practices during vaccination outreach sessions in rural settings in southwestern Uganda.

BACKGROUND: Outreach efforts were developed to bolster people's access to and use of immunization services in underserved populations. However, there have been multiple outbreaks of diseases like measles in Uganda, prompting policy makers and stakeholders to ask many unanswered questions. This research study was created to uncover the discrepancies between vaccine management practices at immunization outreach sessions in rural South Western Uganda compared with existing standards. METHODS: The observational qualitative study, was done in 16 public health facilities across four districts of Uganda. Data were collected using in-depth interviews, facility record reviews, and observation. We assessed the vaccine management procedures before immunization session, transportation used, set up at the outreach site, management practices during the outreach session and packing of vaccines - according to World Health Organization immunization practice recommendations. The data were transcribed, coded and categories were formed and triangulated. Themes were generated based on a socio-ecologic framework to gain a better understanding of healthcare provider practices during immunization sessions. RESULTS: Fifty-one individuals were interviewed; four Assistant District Health Officers, four cold chain technicians, 15 focal persons for the Expanded Program on Immunization, and 28 health care providers. The respondents' mean age was 35, 43 (84.3%) were females and 24 (47.1%) had a diploma. 11 (69%) outreaches were conducted at a distance of 5-12 km from the health facility and 7 (44%) were conducted in a building. For 8 outreaches (50%) health facility staff did not check the vaccine vial monitor status before the outreach while 12(75%) did not keep the vaccine hard lid cover closed during the sessions. The main areas of concern were insufficient vaccine integrity monitoring, improper handling and storage practices, deficient documentation, and inadequate vaccine transportation. These were similar across immunization outreach sites regardless of vaccine preventable disease outbreaks occurrences. The majority of these gaps were located at the individual level but were enabled by policy/environmental factors. CONCLUSIONS: There are poor vaccine management procedures during outreach sessions contrary to established guidelines. Specific tactics to tackle knowledge deficiencies, health worker attitude, and fewer equipment shortages could improve compliance to guidelines.

Vaccination compliance of selected childhood immunization programs and the socio-determinant factors in Nigeria.

INTRODUCTION: Adherence to full vaccination is important in preventing childhood diseases. The aim of this study was to evaluate the level of compliance to full vaccination and identify the socio-cultural factors associated with full vaccination compliance in children. METHODOLOGY: The socioeconomic variables associated with each of the four binary dependent variables of whether or not a child is fully vaccinated against tetanus, BCG, measles, and pentavalent were determined using logistic regression. RESULTS: While compliance to full tetanus and BCG vaccinations was > 60% at the national level, less than 50% and 10% full vaccination compliance were recorded for pentavalent and measles vaccinations, respectively. The South East region of Nigeria recorded the overall highest full vaccination compliance while the least performing region was the North West zone. The mother or guardian literacy level, employment status, antenatal care attendance, and internet usage were strong predictors of full vaccination compliance (p < 0.05). CONCLUSIONS: The socio-cultural factors associated with achieving full vaccination coverage in Nigeria in this study should drive the implementation of policies that will be best suited to each geopolitical zone of Nigeria.

Cost and operational context for national human papillomavirus (HPV) vaccine delivery in six low- and middle-income countries.

INTRODUCTION: There are concerns from immunization program planners about high delivery costs for human papillomavirus (HPV) vaccine. Most prior research evaluated costs of HPV vaccine delivery during demonstration projects or at introduction, showing relatively high costs, which may not reflect the costs beyond the pilot or introduction years. This study sought to understand the operational context and estimate delivery costs for HPV vaccine in six national programs, beyond their introduction years. METHODS: Operational research and microcosting methods were used to retrospectively collect primary data on HPV vaccination program activities in Ethiopia, Guyana, Rwanda, Senegal, Sri Lanka, and Uganda. Data were collected from the national level and a sample of subnational administrative offices and health facilities. Operational data collected were tabulated as percentages and frequencies. Financial costs (monetary outlays) and economic costs (financial plus opportunity costs) were estimated, as was the cost per HPV vaccine dose delivered. Costing was done from the health system perspective and reported in 2019 United States dollars (US$). RESULTS: Across the study countries, between 53 % and 99 % of HPV vaccination sessions were conducted in schools. Differences were observed in intensity and frequency with which program activities were conducted and resources used. Mean annual economic costs at health facilities in each country ranged from $1,207 to $3,190, while at the national level these ranged from $7,657 to $304,278. Mean annual HPV vaccine doses delivered per health facility in each country ranged from 162 to 761. Mean financial costs per dose per study country ranged from $0.27 to $3.32, while the economic cost per dose ranged from $3.09 to $17.20. CONCLUSION: HPV vaccine delivery costs were lower than at introduction in some study countries. There were differences in the activities carried out for HPV vaccine delivery and the number of doses delivered, impacting the cost estimates.

Adding new childhood vaccines to China's National Immunization Program: evidence, benefits, and priorities.

China's National Immunization Program has made remarkable achievements but does not include several important childhood vaccines that are readily available in the private market, such as pneumococcal conjugate vaccine (PCV), rotavirus vaccine, Haemophilus influenzae serotype b (Hib) vaccine, and varicella vaccine. We reviewed the literature to assess these four non-National Immunization Program vaccines in terms of their disease burdens, coverage, inequalities, and cost-effectiveness in China and aimed to recommend priorities for introducing them to the National Immunization Program. Based on our calculations using the available evidence, incorporating these vaccines into China's National Immunization Program in 2019 could have averted 11 761 deaths among children younger than 5 years, accounting for 10·29% of the total deaths in children younger than 5 years and reducing the mortality rate from 7·8 per 1000 to 7·0 per 1000. The review showed that 13-valent PCV (PCV13) had the lowest and most inequitable coverage but could prevent the highest number of deaths. In a budgetary analysis for the cohort of newborns in 2023, we estimated that the projected aggregate government costs were US$1954·92 million for PCV13, $1273·13 million for pentavalent rotavirus vaccine, $415·30 million for Hib vaccine, and $221·64 million for varicella vaccine. Our overall multicriteria decision analysis suggested the following priority order for introducing these four non-programme vaccines to the National Immunization Program to benefit the Chinese population: PCV13, rotavirus vaccine, Hib vaccine, and varicella vaccine.

Maternal and Neonatal Immunization Field Guide for Latin America and the Caribbean – Annex COVID-19

This document is an annex to the Pan American Health Organization (PAHO) Maternal Neonatal Immunization Field Guide. This annex incorporates relevant information on COVID-19 vaccines to be considered by decision-makers who plan and/or coordinate immunization programs, as well as for health professionals working in maternal-perinatal health services at all health system levels. As in the original guide, the target audience for this annex continues to be managers and staff of maternal and child health services, immunization programs, health care providers, pregnant and lactating women and birthing persons, and the media.

Lograr una mejor inmunidad: el enfoque de curso de vida para una longevidad saludable

A medida que las Américas experimentan un profundo cambio demográfico y hay más personas de 65 años que menores de 5 años, es crucial reconocer que los programas nacionales de inmunización deben rediseñarse para garantizar una protección integral a las personas a lo largo de toda su vida. Al adoptar un enfoque de curso de vida para la inmunización, los programas de vacunación pueden adaptarse para cerrar las brechas de inmunidad en las distintas etapas de la vida. El enfoque del curso de vida prevé el establecimiento de múltiples estrategias para reducir las oportunidades perdidas de vacunación según el grupo de edad. El presente documento técnico explica los conceptos clave del enfoque de curso de vida en la inmunización mediante la vacunación, así como los mecanismos biológicos subyacentes que requieren la aplicación de diferentes vacunas en diversas etapas de la vida según los cambios en el sistema inmunitario y en la situación epidemiológica de la comunidad. Además, se proporcionan múltiples ejemplos de diferentes vacunas. Finalmente, se presentan varias consideraciones para la implementación del enfoque de curso de vida en los programas nacionales de inmunización. Esta publicación es parte de los esfuerzos de la Organización Panamericana de la Salud para introducir conceptos de inmunización a lo largo de la vida en los países y territorios de las Américas y garantizar que todas las personas obtengan todos los beneficios que las vacunas pueden ofrecer. Al reconocer el impacto de las vacunas a lo largo de la vida y adoptar el enfoque de curso de vida, los países pueden minimizar el impacto de las enfermedades, mejorar la resiliencia del organismo a lo largo de la vida y reducir las tasas de mortalidad generales. Los programas de inmunización, que alguna vez se centraron en la primera infancia, pueden evolucionar hacia intervenciones de salud pública adaptables, protegiendo la salud y el bienestar de las personas en todas las edades.

Public health impact and return on investment of the pediatric immunization program in Poland.

BACKGROUND: This study aims to evaluate the epidemiological impact and return on investment of the pediatric immunization program (PIP) in Poland from the healthcare-sector and societal perspectives. RESEARCH DESIGN AND METHODS: A health-economic model was developed focusing on the nine vaccines, targeting 11 pathogens, recommended by the public health authorities for children aged 0-6 years in Poland. The 2019 birth cohort (388,178) was followed over their lifetime, with the model estimating discounted health outcomes, life-years gained, quality-adjusted life-years, and direct and indirect costs with and without the PIP based on current and pre-vaccine - era disease incidence estimates, respectively. RESULTS: Across 11 targeted pathogens, the Polish PIP prevented more than 452,300 cases of disease, 1,600 deaths, 37,900 life-years lost, and 38,800 quality-adjusted life-years lost. The PIP was associated with vaccination costs of €54 million. Pediatric immunization averted €65 million from a healthcare-sector perspective (benefit-cost ratio [BCR], 2.2) and averted €358 million from a societal perspective (BCR, 7.6). The BCRs from both perspectives remained >1.0 in scenario analyses. CONCLUSIONS: The Polish PIP, which has not previously been systematically assessed, brings large-scale prevention of disease-related morbidity, premature mortality, and associated costs. This analysis highlights the value of continued investment in pediatric immunization in Poland.

HPV immunization in Brazil and proposals to increase adherence to vaccination campaigns.

OBJECTIVES: To identify the possible causes of low adherence to vaccination campaigns in Brazil, find and analyze campaigns regarding human papillomavirus (HPV) in Brazil and abroad, and apply quality tools to prepare proposals to increase vaccination coverage (VC) and prevent HPV in the country. METHOD: This is a qualitative and deductive-hypothetical research. A narrative review of the literature (especially on the narratives and formats applied in vaccination campaigns in Brazil) was the technique used to develop our method. RESULTS: Brazil had a 49.6% VC in 2019, unlike countries such as Australia (80.2% in 2017), Mexico (97.5% in 2019), and Peru (91% in 2019). This study found evidence of the use of social marketing strategies to engage communities as good practices in the vaccination campaigns of these countries. CONCLUSION: With the retrieved information, three quality tools (Ishikawa diagram, Pareto graph, and 5W2H) classified and quantified the causes of low VC in Brazil and enabled proposals that can direct its Ministry of Health to take more effective strategies to achieve the HPV VC goal recommended by the WHO.

Cost-effectiveness analysis of typhoid vaccination in Lao PDR.

BACKGROUND: Typhoid vaccination has been shown to be an effective intervention to prevent enteric fever and is under consideration for inclusion in the national immunization program in Lao PDR. METHODS: A cost-utility analysis was performed using an age-structured static decision tree model to estimate the costs and health outcomes of introducing TCV. Vaccination strategies combined with five delivery approaches in different age groups compared to no vaccination were considered from the societal perspective, using the Gavi price of 1.5 USD per dose. The vaccination program was considered to be cost-effective if the incremental cost-effectiveness ratio was less than a threshold of 1 GDP per capita for Lao PDR, equivalent to USD 2,535 in 2020. RESULTS: In the model, we estimated 172.2 cases of enteric fever, with 1.3 deaths and a total treatment cost of USD 7,244, based on a birth cohort of 164,662 births without TCV vaccination that was followed over their lifetime. To implement a TCV vaccination program over the lifetime horizon, the estimated cost of the vaccine and administration costs would be between USD 470,934 and USD 919,186. Implementation of the TCV vaccination program would prevent between 14 and 106 cases and 0.1 to 0.8 deaths. None of the vaccination programs appeared to be cost-effective. CONCLUSIONS: Inclusion of TCV in the national vaccination program in Lao PDR would only be cost-effective if the true typhoid incidence is 25-times higher than our current estimate.