Invasive non-typhoid salmonellae becoming important pathogen in HIV patients
Infection with invasive NTS "has a relatively complex pathogenesis at different stages of disease and is not a simple blood-stream infection," lead author Dr. Melita A. Gordon from the University of Liverpool, U.K., told Reuters Health by email. "It is intracellular and persistent, and this is the reason for the high recurrence rate."
Dr. Gordon and colleagues had suspected that recrudescent non-typhoid salmonellae re-emerge from an intracellular sanctuary site. To test their hypothesis, the researchers compared viable NTS loads in simultaneously obtained blood and bone marrow samples from patients in Malawi with acute disease. They also correlated NTS load with potential markers of disease severity.
According to their report in the April 1st Clinical Infectious Diseases, 116 of 495 febrile adults had positive NTS cultures from blood or bone marrow during 158 events, including 63 of 210 patients (88 events) followed after the initial event.
The authors compared lysed and unlysed cultures, because "an unlysed phagocyte containing > 1 intracellular organism/cell produces a single embedded colony in...culture but multiple colonies if lysed prior to...culture."
And indeed, median viable counts were significantly higher in lysed blood samples than in unlysed blood samples at index events but not at recurrent events, suggesting that intracellular intravascular infection occurs only at index events.
In addition, the authors report, the increase in median counts in lysed bone marrow was greater than for blood, suggesting a greater level of multiple-organism intracellular infection in bone marrow than in blood. In bone marrow, the difference in viable counts between lysed and unlysed samples was significant at both index and recurrent events.
The researchers suggest "that reticuloendothelial intracellular infection is established early, even at first presentation, and thereafter is enduring and replicative."
In lysed blood samples, the increase in NTS counts was significant only in patients with CD4 counts < 50 cells/microliter. In lysed bone marrow, however, the increase was significant at all CD4 counts.
"The intracellular systemic persistence poses problems in targeting effective management and threatens to encourage further antibiotic resistance among NTS and other prevalent microorganisms such as Mycobacterium tuberculosis or Streptococcus pneumoniae," Dr. Gordon said. "We need to understand the pathogenesis better, and find ways to target treatment and break transmission."
"The thing that makes these findings fascinating is that we have also shown that invasive NTS in sub-Saharan Africa have undergone recent microevolution and have a phenotype that is closer to Salmonella Typhi," Dr. Gordon continued. "The African invasive NTS strains have lost genes that regulate their metabolism and their capacity to survive in the gut, in a similar pattern to gene loss seen in Salmonella Typhi, and this fits with our observations of a pathogenesis that is reminiscent of typhoid fever."
"A highly susceptible human reservoir (young children and HIV-infected adults) combined with a newly emerged pathovar have combined to cause such a huge disease burden," she concluded. "Understanding how to break transmission and prevent disease is an important priority, and one which certainly can and must be addressed in Malawi and other sub-Saharan African countries."
By Will Boggs, MD
Clin Infect Dis 2010.
Medscape Today
http://www.medscape.com/viewarticle/718203
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