Interferon-driven alterations of the host’s amino acid metabolism in the pathogenesis of typhoid fever by Blohmke, C, Darton, T, Jones, C, Suarez, N, Angus, B, Zhou, L, Hill, J, Clare, S, Kane, L, Mukhopadhyay, S, Schreiber, F, Duque-Correa, M, Wright, J, Roumeliotis, T, Yu, L, Choudhary, J, Mejias, A, Ramilo, O, Shanyinde, M, Sztein, M, Kingsley, R, Lockhart, S, Levine, M, Lynn, D, Dougan, G, Pollard, A

“…Corresponding alterations in tryptophan catabolites with immunomodulatory properties in serum of participants with typhoid fever confirmed the activity of this pathway, and implicate a central role of host tryptophan metabolism in the pathogenesis of typhoid fever.…”

An evaluation of purified Salmonella Typhi protein antigens for the serological diagnosis of acute typhoid fever by Tran Vu Thieu, N, Trinh Van, T, Tran Tuan, A, Klemm, E, Nguyen Ngoc Minh, C, Voong Vinh, P, Pham Thanh, D, Ho Ngoc Dan, T, Pham Duc, T, Langat, P, Martin, L, Galan, J, Liang, L, Felgner, P, Davies, D, de Jong, H, Maude, R, Fukushima, M, Wijedoru, L, Ghose, A, Samad, R, Dondorp, A, Faiz, A, Darton, T, Pollard, A, Thwaites, G, Dougan, G, Parry, C, Baker, S

“…<p>OBJECTIVES: The diagnosis of typhoid fever is a challenge. Aiming to develop a typhoid diagnostic we measured antibody responses against Salmonella Typhi (S. …”

Identification of novel serodiagnostic signatures of typhoid fever using a salmonella proteome array by Darton, T, Baker, S, Randall, A, Dongol, S, Karkey, A, Voysey, M, Carter, M, Jones, C, Trappl, K, Pablo, J, Hung, C, Teng, A, Shandling, A, Le, T, Walker, C, Molina, D, Andrews, J, Arjyal, A, Basnyat, B, Pollard, A, Blohmke, C

“…Current diagnostic tests for typhoid fever, the disease caused by Salmonella Typhi, are poor. …”

Advancing the management and control of typhoid fever: A review of the historical role of human challenge studies by Waddington, C, Waddington, C, Darton, T, Darton, T, Woodward, W, Angus, B, Levine, M, Pollard, A, Pollard, A

Advancing the management and control of typhoid fever: a review of the historical role of human challenge studies. by Waddington, C, Darton, T, Woodward, W, Angus, B, Levine, M, Pollard, A

Importance of Salmonella Typhi-Responsive CD8+ T Cell Immunity in a Human Typhoid Fever Challenge Model by Fresnay, S, McArthur, M, Magder, L, Darton, T, Jones, C, Waddington, C, Blohmke, C, Angus, B, Levine, M, Pollard, A, Sztein, M

“…Typhoid fever, caused by the human-restricted organism Salmonella enterica serovar Typhi (S. …”

Salmonella Typhi-specific multifunctional CD8+ T cells play a dominant role in protection from typhoid fever in humans by Fresnay, S, McArthur, M, Magder, L, Darton, T, Jones, C, Waddington, C, Blohmke, C, Angus, B, Levine, M, Pollard, A, Sztein, M

“… <p style="text-align:justify;"><b>Background:</b> Typhoid fever, caused by the human-restricted organism Salmonella Typhi (S. …”

Salmonella typhi bactericidal antibodies reduce disease severity but do not protect against typhoid fever in a controlled human infection model by Juel, H, Thomaides-Brears, H, Darton, T, Jones, C, Jones, E, Shrestha, S, Sie, R, Eustace, A, Galal, U, Kurupati, P, Van, T, Thieu, N, Baker, S, Blohmke, C, Pollard, A

Blood culture-PCR to optimise typhoid fever diagnosis after controlled human infection identifies frequent asymptomatic cases and evidence of primary bacteraemia. by Darton, T, Zhou, L, Blohmke, C, Jones, C, Waddington, C, Baker, S, Pollard, A

Azithromycin and cefixime combination versus azithromycin alone for the out-patient treatment of clinically suspected or confirmed uncomplicated typhoid fever in South Asia: a randomised controlled trial protocol by Giri, A, Karkey, A, Dongol, S, Arjyal, A, Maharjan, A, Veeraraghavan, B, Paudyal, B, Dolecek, C, Gajurel, D, Phuong, DNT, Thanh, DP, Qamar, F, Kang, G, Hien, HV, John, J, Lawson, K, Wolbers, M, Hossain, MS, Sharifuzzaman, M, Luangasanatip, N, Maharjan, N, Olliaro, P, Rupali, P, Shakya, R, Shakoor, S, Rijal, S, Qureshi, S, Baker, S, Joshi, S, Ahmed, T, Darton, T, Bao, TN, Lubell, Y, Kestelyn, E, Thwaites, G, Parry, C, Basnyat, B

“…Patients with suspected uncomplicated typhoid fever will be randomized to one of the two interventions: Arm A: azithromycin 20mg/kg/day oral dose once daily (maximum 1gm/day) and cefixime 20mg/kg/day oral dose in two divided doses (maximum 400mg bd) for 7 days, Arm B: azithromycin 20mg/kg/day oral dose once daily (max 1gm/day) for 7 days AND cefixime-matched placebo for 7 days. …”

Activation of Salmonella Typhi-specific regulatory T cells in typhoid disease in a wild-type S. Typhi challenge model. by McArthur, M, Fresnay, S, Magder, L, Darton, T, Jones, C, Waddington, C, Blohmke, C, Dougan, G, Angus, B, Levine, M, Pollard, A, Sztein, M

“…Typhi), the causative agent of typhoid fever, causes significant morbidity and mortality worldwide. …”

Rapidly escalating hepcidin and associated serum iron starvation are features of the acute response to typhoid infection in humans by Darton, T, Blohmke, C, Giannoulatou, E, Waddington, C, Jones, C, Sturges, P, Webster, C, Drakesmith, H, Pollard, A, Armitage, A

“…However, the deployment of hepcidin in human bacterial infections remains poorly characterized. Typhoid fever is a globally significant, human-restricted bacterial infection, but understanding of its pathogenesis, especially during the critical early phases, likewise is poorly understood. …”

Challenge of humans with wild-type Salmonella enterica serovar Typhi elicits changes in the activation and homing characteristics of mucosal-associated invariant T cells. by Salerno-Goncalves, R, Luo, D, Fresnay, S, Magder, L, Darton, T, Jones, C, Waddington, C, Blohmke, C, Angus, B, Levine, M, Pollard, A, Sztein, M

“…In contrast, volunteers susceptible to the development of typhoid disease (TD) exhibited a sharp decline in circulating MAIT cells during the development of typhoid fever. Interestingly, MAIT cells from low-dose TD volunteers had higher levels of CD38 coexpressing CCR9, CCR6, and Ki67 during the development of typhoid fever than high-dose TD volunteers. …”

Oral challenge with wild-type Salmonella Typhi induces distinct changes in B cell subsets in individuals who develop typhoid disease. by Toapanta, F, Bernal, P, Fresnay, S, Magder, L, Darton, T, Jones, C, Waddington, C, Blohmke, C, Angus, B, Levine, M, Pollard, A, Sztein, M

“…In this model, 104 CFU of Salmonella resulted in 65% of participants developing typhoid fever (referred here as typhoid diagnosis -TD-) 6-9 days post-challenge. …”

An outpatient, ambulant-design, controlled human infection model using escalating doses of Salmonella Typhi challenge delivered in sodium bicarbonate solution. by Waddington, C, Darton, T, Jones, C, Haworth, K, Peters, A, John, T, Thompson, B, Kerridge, SA, Kingsley, R, Zhou, L, Holt, K, Yu, L, Lockhart, S, Farrar, J, Sztein, M, Dougan, G, Angus, B, Levine, M, Pollard, A

“…BACKGROUND: Typhoid fever is a major global health problem, the control of which is hindered by lack of a suitable animal model in which to study Salmonella Typhi infection. …”

The Typhoid Vaccine Acceleration Consortium (TyVAC): vaccine effectiveness study designs: accelerating the introduction of typhoid conjugate vaccines and reducing the global burden... by Meiring, J, Gibani, M, Basnyat, B, Bentsi-Enchill, A, Darton, T, Pollard, A

“… <p>Typhoid fever is estimated to cause between 11.9–26.9 million infections globally each year with 129,000–216,510 deaths. …”

Oral wild-type Salmonella Typhi challenge induces activation of circulating monocytes and dendritic cells in individuals who develop typhoid disease by Toapanta, F, Bernal, P, Fresnay, S, Darton, T, Jones, C, Waddington, C, Blohmke, C, Dougan, G, Angus, B, Levine, M, Pollard, A, Sztein, M

“…In this model, ingestion of 104 CFU of Salmonella resulted in 65% of subjects developing typhoid fever (referred here as typhoid diagnosis -TD-) 5-10 days post-challenge. …”