Analysis of Vaccine Studies and Causal Inference
Leonhard Held, Niel Hens, Philip O’Neill, Jacco Wallinga in Handbook of Infectious Disease Data Analysis, 2019
As an example, in a cluster-randomized study of typhoid vaccine in India, Sur et al. (2009) randomized neighborhoods to receive either typhoid vaccine or control (hepatitis A) vaccine. Vaccine effects were estimated by 1 minus the relative incidence of typhoid disease in comparison groups. Total effectiveness in those who had received typhoid vaccine compared to those who had received control (hepatitis A) vaccine was estimated to be 61 percent (95% CI 41, 75). Indirect effectiveness in the unvaccinated individuals in the typhoid vaccine clusters compared to the unvaccinated individuals in the control clusters was 44 percent (95% CI 2, 69). The overall effectiveness in the typhoid clusters compared to the control clusters was 57 percent (95% CI 37, 71). However, incidence of typhoid was higher in the vaccinated individuals than in the unvaccinated individuals in the typhoid vaccine clusters (0.26 versus 0.19 cases per 100,000 person-days), and similarly in the hepatitis A vaccine clusters (0.73 versus 0.35). So if we estimated the direct effect of the typhoid vaccine in this study without any further adjustment, the estimates would be negative. The individuals who showed up to get vaccinated are clearly very different from those who did not show up to get vaccinated, either in their underlying health, health-care seeking behavior, the way they are handled in the health system for diagnosis, or other reason.
Communicable diseases
Liam J. Donaldson, Paul D. Rutter in Donaldsons' Essential Public Health, 2017
Typhoid symptoms can include pyrexia, headache, anorexia and diarrhoea (occasionally constipation). A classical rose-spot rash may appear on the trunk, and enlargement of the spleen may also occur. Rarely, there is intestinal ulceration and perforation. Paratyphoid fever has similar but milder symptomatology, with a lower fatality rate. Typhoid vaccine gives around 50%–70% protection and is recommended for travellers to areas where typhoid is endemic, but it is important that travellers are aware of the risks.
Progress in the overall understanding of typhoid fever: implications for vaccine development
Published in Expert Review of Vaccines, 2020
Peter J O’Reilly, Dikshya Pant, Mila Shakya, Buddha Basnyat, Andrew J Pollard
Typhoid vaccines have been in existence for over 100 years. In 1886, Wright in England and Pfeiffer and Kolle in Germany developed a typhoid vaccine at about the same time, but independently of one another. These first vaccines were made using heat-killed whole cell Salmonella Typhi and significant side effects were noted in the first subjects [55]. Carroll and Vedder trialed an oral, heat-inactivated typhoid vaccine in 1904. Initially, their heat-inactivation technique was flawed and several study volunteers developed typhoid fever including one of the study supervisors [56]. Wright believed that a vaccine for typhoid could save thousands of lives and he pressed the British government to vaccinate soldiers in World War One. Despite some public reservations about typhoid vaccination it was offered to British WWI soldiers. Initially, a typhoid only whole-cell vaccine was given to soldiers and in 1916 a combination vaccine (TAB) against S. Paratyphi A and S. Paratyphi B as well as S. Typhi was introduced [57]. This was the first war when more soldiers died of combat than from disease [58]. However, it was not until the 1960s that large field studies proved the efficacy of the typhoid whole-cell vaccine [55].
Evolution of immunotherapy in the treatment of non-muscle-invasive bladder cancer
Published in Expert Review of Anticancer Therapy, 2022
Niyati Lobo, Alberto Martini, Ashish M. Kamat
The oral typhoid vaccine contains a live, attenuated strain of Salmonella typhi (Ty21a), which, like BCG, induces a Th-1 type immune response. Due to several attenuating mutations, Ty21a survives poorly in cells, resulting in a vaccine strain with an excellent safety profile that has been administered to over 200 million recipients [86]. In an orthotopic MB49 mouse bladder cancer model, intravesical Ty21a was more effective than BCG in inducing tumor cell death and improving survival, whilst being potentially safer because Ty21a bacteria did not persist in either mice bladders or human urothelial cell lines [87]. Based on these findings, a phase I trial is currently investigating the safety and efficacy of intravesical Ty21a in patients with BCG-naïve disease (NCT03421236).
Typhoid conjugate vaccines: making vaccine history in Africa
Published in Expert Review of Vaccines, 2018
James E. Meiring, Pratiksha Patel, Priyanka Patel, Melita A. Gordon
Two typhoid vaccine trials have previously been conducted in Africa. The first in Alexandria, Egypt, using the live, oral Ty21a vaccine demonstrating a statistically significant reduction in typhoid fever cases in the vaccine arm with 0 blood culture-confirmed cases compared to the placebo arm with seven cases following 1 year of surveillance in children aged 6–7 years [15]. The second in the Transvaal region of South Africa using a Vi-capsular polysaccharide (Vi-PS) vaccine demonstrated a protective efficacy of 64% in children aged 5–15 years after 21 months of surveillance [16]. Similar results were replicated in field trials in Asia, and both the Vi-PS and Ty21a vaccines received WHO recommendation in 2008 for programmatic use in countries with high burden [17]. However, due to the relatively low efficacy demonstrated particularly for younger children due to the T-cell-independent nature of the polysaccharide vaccine, the scarcity of data on burden of disease, and the impending arrival of more efficacious conjugate vaccines, GAVI funding was delayed.
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