No abstract

Shigellosis is a worldwide disease, characterized by abdominal pain, fever, vomiting and the passage of blood- and mucus-streaked stools. Rhesus monkeys and other primates are the only animals that are naturally susceptible to shigellosis. A suitable animal model is required for the pre-clinical evaluation of vaccines candidates. In this study the minimal dose of S. dysenteriae1 1617 strain required to produce dysentery in 4 of 5 (80% attack rate) monkeys using an escalating dose range for three groups (2×108, 2× 109 and 2× 1010 CFU) was determined. In addition, the monkeys were re-infected. The identified optimal challenge dose is 2× 109 CFU, this dose elicited 60% protection in monkeys when they were re-challenged with a one log higher dose (2× 1010 CFU). The challenge dose, 2× 1010 CFU, produced severe dysentery in all monkeys, with 1 monkey dying within 24 h, elicited 100% protection when re-challenged with the same dose. All monkeys exhibited immune responses. This study concludes that the rhesus monkey model closely mimics the disease and immune response seen in humans and is a suitable animal model for the pre-clinical evaluation of Shigella vaccine candidates. Prior infection with the 1617 strain can protect monkeys against subsequent re-challenges with homologous strains.

Live attenuated Shigella sonnei vaccine candidate WRSS1, previously tested in U.S. and Israeli volunteers, was evaluated in a population of adult Thai volunteers in which the organism is endemic. In a randomized placebo-controlled, double-blind design, inpatient participants received a single oral dose of 1.6 × 104 CFU of WRSS1. The vaccine was generally well tolerated, with equal numbers of vaccinees and placebo controls showing mild symptoms. Only 3 of 13 vaccinees (23%) had culture-positive stools, while a total of 9 vaccinees were positive by PCR. Lack of vaccine shedding in volunteers correlated with lack of clinical symptoms and immune responses, just as the duration of fecal shedding correlated directly with stronger immune responses. Two months following immunization, 10 vaccinees and 10 newly recruited naive controls received a challenge dose of 1,670 CFU of virulent S. sonnei strain 53G. This dose had previously demonstrated a 75% attack rate for dysentery in Thai volunteers. However, in this study the attack rate for dysentery in naive controls after challenge was 20%. Based on clinical record summaries, 3 vaccinees and 5 naive controls experienced clinically relevant illness (diarrhea/dysentery/fever/shigellosis), and a 40% vaccine efficacy was calculated. When these data are compared to those for the performance of this vaccine candidate in more naive populations, it is clear that a single oral dose of WRSS1 at 104 CFU failed to achieve its full potential in a population in which the organism is endemic. Higher doses and/or repeated immunizations may contribute to improved vaccine shedding and consequent elevation of protective immune responses in a population in which the organism is endemic. (The study has been registered at ClinicalTrials.gov under registration no. NCT01080716.)

The nationwide seroprevalence of hepatitis E IgG was determined among young men in Thailand. Overall seroprevalence was 14% (95% CI 13%–15%); range by province was 3%–26%. Seroprevalence was lowest in the south, an area predominantly occupied by persons of the Islam religion, whose dietary laws proscribe pork.