The Vermont model for rural HIV care delivery: eleven years of outcome data comparing urban and rural clinics.

CONTEXT: Provision of human immunodeficiency virus (HIV) care in rural areas has encountered unique barriers. PURPOSE: To compare medical outcomes of care provided at 3 HIV specialty clinics in rural Vermont with that provided at an urban HIV specialty clinic. METHODS: This was a retrospective cohort study. FINDINGS: Over an 11-year period 363 new patients received care, including 223 in the urban clinic and 140 in the rural clinics. Patients in the 2 cohorts were demographically similar and had similar initial CD4 counts and viral loads. There was no difference between the urban and rural clinic patients receiving Pneumocystis carinii prophylaxis (83.5% vs 86%, P= .38) or antiretroviral therapy (96.8% vs 97.5%, P= .79). Both rural and urban cohorts had similar decreases in median viral load from 1996 to 2006 (3,876 copies/mL to <50 copies/mL vs 8,331 copies/mL to <50 copies/mL) and change in percent of patients suppressed to <400 copies/mL (21.4%-69.3% vs 16%-71.4%, P= .11). Rural and urban cohorts had similar increases in median CD4 counts (275/mm(3)-350/mm(3) vs 182 cells/mm(3)-379/mm(3)). A repeated measures regression analysis showed that neither fall in viral load (P= .91) nor rise in CD4 count (P= .64) were associated with urban versus rural site of care. Survival times, using a Cox proportional hazards model, were similar for urban and rural patients (hazard ratio for urban = 0.80 [95% CI, 0.39-1.61; P= .53]). CONCLUSIONS: This urban outreach model provides similar quality of care to persons receiving care in rural areas of Vermont as compared to those receiving care in the urban center.

Evaluation of Salmonella enterica serovar Typhi (Ty2 aroC-ssaV-) M01ZH09, with a defined mutation in the Salmonella pathogenicity island 2, as a live, oral typhoid vaccine in human volunteers.

Salmonella enterica serovar Typhi strains with mutations in the Salmonella pathogenicity island-2 (SPI-2) may represent an effective strategy for human vaccine development, and a vectoring system for heterologous antigens. S. Typhi (Ty2 aroC-ssaV-) M01ZH09 is an attenuated, live, oral typhoid vaccine harboring defined deletion mutations in ssaV, which encodes an integral component in the SPI-2 type III secretion system (TTSS), as well as a mutation in an aromatic biosynthetic pathway needed for bacterial growth in vivo (aroC). SPI-2 mutant vaccines have yet to be evaluated in a large, randomized human trial. A simplified or single-oral dose oral typhoid vaccine using the SPI-2 strategy would offer significant advantages over the currently licensed typhoid vaccines. We performed a double-blinded, placebo-controlled, dose-escalating clinical trial in 60 healthy adult volunteers to determine the tolerability and immunogenicity of a single dose of M01ZH09. Three groups of 20 healthy adult volunteers were enrolled; 16 in each group received a single oral dose of the freeze-dried vaccine at 5 x 10(7), 5 x 10(8) or 5 x 10(9)CFU in a bicarbonate buffer. Four volunteers in each cohort received placebo in the same buffer. Adverse events were infrequent and not statistically different between vaccine and placebo recipients, although two subjects in the mid-range dose and three subjects in the highest dose had temperature measurements >37.5 degrees C. No blood or urine cultures were positive for M01ZH09, and fecal shedding was brief. The immune response was dose-related; the highest vaccine dose (5 x 10(9)CFU) was the most immunogenic. All tested subjects receiving the highest dose had a significant ASC response (mean 118 spots/10(6) cells). A >or=4-fold increase in antibody titer for S. Typhi LPS or flagellin was detected in 75% of volunteers in the highest-dose cohort by day 28. The SPI-2 mutant vaccine, M01ZH09, is a promising typhoid vaccine candidate and deserves further study as a vectoring system for heterologous vaccine antigens.

The novel oral typhoid vaccine M01ZH09 is well tolerated and highly immunogenic in 2 vaccine presentations.

BACKGROUND: M01ZH09 (Salmonella enterica serovar Typhi [Ty2 aroC(-) ssaV(-)] ZH9) is a live oral-dose typhoid vaccine candidate. M01ZH09 was rationally modified with 2 independently attenuating mutations, including a novel mutation in Salmonella pathogenicity island (SPI)-2. We demonstrate that M01ZH09, in a single oral dose, is well tolerated and prompts broad immune responses, regardless of whether prevaccination with a bicarbonate buffer is given. METHODS: Thirty-two healthy adult subjects were randomized and given 5x109 cfu of M01ZH09, with (presentation 1) or without (presentation 2) prevaccination with a bicarbonate buffer. Immunogenicity data included Salmonella Typhi lipopolysaccharide (LPS)-specific immunoglobulin (Ig) A antibody-secreting cells (enzyme-linked immunospot [ELISPOT] assay), IgG serologic responses to Salmonella Typhi LPS, lymphocyte proliferation, and interferon (IFN)- gamma production. RESULTS: The vaccine was well tolerated; adverse events after vaccination were mild. No fever or prolonged vaccine shedding occurred. Immunogenicity data demonstrated that 88% and 93% of subjects who received presentation 1 and presentation 2, respectively, had a positive response by ELISPOT assay; 81% of subjects in both groups underwent IgG seroconversion on day 14. Both groups had similar cellular immune responses to presentation 1 and presentation 2; lymphocyte proliferation to Salmonella Typhi flagellin occurred in 63% and 67% of subjects, respectively, and 69% and 73% of subjects, respectively, had an increase in IFN- gamma production. CONCLUSION: The oral typhoid vaccine M01ZH09 is well tolerated and highly immunogenic in a single oral dose, with and without prevaccination with a bicarbonate buffer. Field studies to demonstrate protective efficacy are planned.