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1.
Clin Infect Dis ; 43(5): 604-8, 2006 Sep 01.
Article in English | MEDLINE | ID: mdl-16886154

ABSTRACT

Cryptosporidiosis in young children prompts local inflammation in the intestinal tract. We studied a cohort of young children with cryptosporidiosis to determine whether systemic inflammatory responses occur and, if so, to evaluate whether inflammation persists after infection. Cryptosporidiosis was associated with increased levels of interleukin-8 and tumor necrosis factor- alpha systemically, which persisted at 6 months after enrollment. The level of intestinal tumor necrosis factor- alpha was elevated at enrollment, but elevated levels did not persist. Worsening of malnutrition, particularly stunting, was observed after infection. The association of cryptosporidiosis, inflammation, and stunting in children with cryptosporidiosis warrants further evaluation.


Subject(s)
Cryptosporidiosis/metabolism , Interferon-gamma/metabolism , Interleukins/metabolism , Receptors, Tumor Necrosis Factor/metabolism , Antigens, Protozoan/blood , Cohort Studies , Female , Humans , Infant , Interferon-gamma/blood , Male , Receptors, Tumor Necrosis Factor/blood
2.
J Infect Dis ; 192(3): 360-6, 2005 Aug 01.
Article in English | MEDLINE | ID: mdl-15995948

ABSTRACT

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.


Subject(s)
Lipopolysaccharides/immunology , Typhoid Fever/immunology , Typhoid-Paratyphoid Vaccines/immunology , Administration, Oral , Adolescent , Adult , Antibodies, Bacterial/blood , Antibody Formation , Enzyme-Linked Immunosorbent Assay , Female , Freeze Drying , Humans , Immunoglobulin G/blood , Male , Middle Aged , Salmonella enterica/immunology , Salmonella typhi/immunology , Typhoid-Paratyphoid Vaccines/administration & dosage , Typhoid-Paratyphoid Vaccines/adverse effects , Typhoid-Paratyphoid Vaccines/toxicity , Vaccines, Attenuated
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