Forecasting Demand for the Typhoid Conjugate Vaccine in Low- and Middle-income Countries.

BACKGROUND: The World Health Organization (WHO) released a position paper in March 2018 calling for integration of a novel typhoid conjugate vaccine (TCV) into routine immunization along with catch-up campaigns for children up to age 15. Gavi, the Vaccine Alliance, has committed funding to help resource-constrained countries introduce this vaccine. In this article, the Typhoid Vaccine Acceleration Consortium forecasts demand if WHO recommendations are followed. METHODS: We built a model of global TCV introductions between 2020 and 2040 to estimate the demand of the vaccine for 133 countries. We estimated each country's year of introduction by examining its estimated incidence of typhoid fever, its history of introducing new vaccines, and any knowledge we have of its engagement with typhoid prevention, including intention to apply for Gavi funding. Our model predicted use in routine infant vaccination as well as campaigns targeting varying proportions of the unvaccinated population up to 15 years of age. RESULTS: Between 2020 and 2025, demand will predominantly come from African countries, many receiving Gavi support. After that, Asian countries generate most demand until 2030, when campaigns are estimated to end. Demand will then track the birth cohort of participating countries, suggesting an annual routine demand between 90 and 100 million doses. Peak demand is likely to occur between 2023 and 2026, approaching 300 million annual doses if campaign implementation is high. CONCLUSIONS: In our analysis, target population for catch-up campaigns is the main driver of uncertainty. At peak demand, there is some risk of exceeding presently estimated peak production capacity. Therefore, it will be important to carefully coordinate introductions, especially when accompanied by campaigns targeting large proportions of the eligible population.

Overview of the Typhoid Conjugate Vaccine Pipeline: Current Status and Future Plans.

Typhoid fever remains a common and serious disease in populations that live in low- and middle-income countries. Treatment usually consists of antibiotics, but problems with drug-resistant strains have been increasing in endemic countries, making treatment prolonged and costly. Improved sanitation and food hygiene have been effective in controlling the disease in the industrialized world, but these steps are associated with socioeconomic progress that has been slow in most of the affected areas. Therefore, vaccination is an effective way to prevent the disease for the short to medium term. Oral typhoid vaccine and Vi polysaccharide typhoid vaccine (Vi polysaccharide) have been available for many years, yet a large population, in particular infants and children aged <2 years, remains at higher risk. Recently, with the availability of Vi polysaccharide-based conjugate vaccines and funding to support vaccination from the Gavi alliance, there is great momentum for typhoid prevention efforts. Supply of the vaccine will be critical, and there are multiple efforts to make new typhoid vaccines accessible and available to populations that desperately need them.

William Boog Leishman: parasitologist and politician.

Famous for the discovery of the parasite, Leishmania, named after him, and the invention of Leishman's stain, William Boog Leishman should perhaps be better known for his work in military and public health, particularly the prevention of typhoid. Leishman was a Medical Officer in the British Army from 1887 until his death in 1926. His early research was on diseases affecting troops posted to stations within the British Empire. He saw cases of Leishmaniasis while stationed in India, and was able to identify the causative organism from his detailed records of his observations. Leishman's most important contribution to public health, however, was his work with typhoid, a major cause of morbidity and mortality in the army. Leishman planned experiments and the collection of data to demonstrate the efficacy of anti-typhoid inoculation and, using his considerable political skills, advocated the adoption of the vaccine. He planned for the inoculation of troops in an emergency so, when war broke out in 1914, the vaccine was available to save thousands of lives. Leishman's colleagues and mentors included Ronald Ross and Almroth Wright. Leishman was less outspoken than either Ross or Wright; this paper shows how the different contributions of the three men overlapped.

Geographic analysis of vaccine uptake in a cluster-randomized controlled trial in Hue, Vietnam.

This paper identifies spatial patterns and predictors of vaccine uptake in a cluster-randomized controlled trial in Hue, Vietnam. Data for this study result from the integration of demographic surveillance, vaccine record, and geographic data of the study area. A multi-level cross-classified (non-hierarchical) model was used for analyzing the non-nested nature of individual's ecological data. Vaccine uptake was unevenly distributed in space and there was spatial variability among predictors of vaccine uptake. Vaccine uptake was higher among students with younger, male, or not literate family heads. Students from households with higher per-capita income were less likely to participate in the trial. Residency south of the river or further from a hospital/polyclinic was associated with higher vaccine uptake. Younger students were more likely to be vaccinated than older students in high- or low-risk areas, but not in the entire study area. The findings are important for the management of vaccine campaigns during a trial and for interpretation of disease patterns during vaccine-efficacy evaluation.

Introducing Vi polysaccharide typhoid fever vaccine to primary school children in North Jakarta, Indonesia, via an existent school-based vaccination platform.

OBJECTIVES: To report results on coverage, safety and logistics of a large-scale, school-based Vi polysaccharide immunization campaign in North Jakarta. METHODS: Of 443 primary schools in North Jakarta, Indonesia, 18 public schools were randomly selected for this study. Exclusion criteria were fever 37.5 degrees C or higher at the time of vaccination or a known history of hypersensitivity to any vaccine. Adverse events were monitored and recorded for 1 month after immunization. Because this was a pilot programme, resource use was tracked in detail. RESULTS: During the February 2004 vaccination campaign, 4828 students were immunized (91% of the target population); another 394 students (7%) were vaccinated during mop-up programmes. Informed consent was obtained for 98% of the target population. In all, 34 adverse events were reported, corresponding to seven events per 1000 doses injected; none was serious. The manufacturer recommended cold chain was maintained throughout the programme. CONCLUSIONS: This demonstration project in two sub-districts of North Jakarta shows that a large-scale, school-based typhoid fever Vi polysaccharide vaccination campaign is logistically feasible, safe and minimally disruptive to regular school activities, when used in the context of an existing successful immunization platform. The project had high parental acceptance. Nonetheless, policy-relevant questions still need to be answered before implementing a widespread Vi polysaccharide vaccine programme in Indonesia.

Household demand for typhoid fever vaccines in Hue, Vietnam.

The demand function for vaccines against typhoid fever was estimated using stated preference data collected from a random sample of 1065 households in Hue, Vietnam, in 2002. These are the first estimates of private willingness-to-pay (WTP) and demand functions for typhoid vaccines in a developing country. Mean respondent WTP for a single typhoid fever vaccine ranged from USD 2.30 to USD 4.80. Mean household WTP estimates (vaccinating all members of the household) ranged from USD 21 to USD 27. Demand was similar for vaccines with different degrees of effectiveness and intervals of duration. These results suggest a significant potential for private sector provision of typhoid fever vaccines in Hue.

A new typhoid vaccine composed of the Vi capsular polysaccharide.

Typhoid is still prevalent in many parts of the world. We reviewed all published and unpublished studies of a newly licensed vaccine composed of the Vi capsular polysaccharide of Salmonella typhi, the causative agent of the disease, which had been licensed previously outside the United States. These included observational studies and double-blind randomized studies done in the United States, Europe, and the developing world in which children and adults unexposed to typhoid or those living in endemic areas were enrolled. A single dose of 25 micrograms of the purified polysaccharide was given by intramuscular injection. The vaccine was well tolerated, inducing only minor reactions in fewer than 10% of subjects. An antibody response occurred in about 90% of subjects and lasted about 3 years. Seroconversion was shown in children as young as 2 years. Protective efficacy was evaluated in two studies conducted in areas in which typhoid is endemic; the efficacy was 55% and 75%, respectively, in adults and in children older than 5 years. The Vi vaccine compares favorably with other typhoid vaccines in regard to safety, patient compliance, immunogenicity, and efficacy. Vi polysaccharide is a well-standardized antigen that is effective in a single parenteral dose, is safer than whole-cell vaccine, and may be used in children 2 years of age or older.