A systematic review of current knowledge of HIV epidemiology and of sexual behaviour in Nepal

OBJECTIVE: To systematically review information on HIV epidemiology and on sexual behaviour in Nepal with a view to identifying gaps in current knowledge. METHODS: Systematic review covering electronic databases, web-based information, personal contact with experts and hand searching of key journals. RESULTS: HIV-1 seroprevalence has been rising rapidly in association with high-risk behaviours, with current levels of 40% amongst the nation's injecting drug users and approaching 20% amongst Kathmandu's female commercial sex workers (FCSWs). HIV seroprevalence remains low in the general population (0.29% of 15–49 year olds). There are significant methodological limitations in many of the seroprevalence studies identified, and these estimates need to be treated with caution. There are extensive migration patterns both within the country and internationally which provide the potential for considerable sexual networking. However, studies of sexual behaviour have focused on FCSWs and the extent of sexual networks within the general population is largely unknown. CONCLUSIONS: Whilst some of the ingredients are present for an explosive HIV epidemic in Nepal, crucial knowledge on sexual behaviour in the general population is missing. Research on sexual networking is urgently required to guide HIV control in Nepal. There is also a need for further good-quality epidemiological studies of HIV seroprevalence

Landscape Changes Influence the Occurrence of the Melioidosis Bacterium Burkholderia pseudomallei in Soil in Northern Australia

Melioidosis is a severe disease affecting humans and animals in the tropics. It is caused by the bacterium Burkholderia pseudomallei, which lives in tropical soil and especially occurs in southeast Asia and northern Australia. Despite the recognition that melioidosis is an emerging infectious disease, little is known about the habitat of B. pseudomallei in the environment. We performed a survey in the Darwin area in tropical Australia, screening 809 soil samples for the presence of these bacteria using molecular methods. We found that environmental factors describing the habitat of these bacteria differed between environmentally undisturbed and disturbed sites. At undisturbed sites, B. pseudomallei was primarily found in close proximity to streams and in grass- and roots-rich areas. In disturbed soil, B. pseudomallei was associated with the presence of animals, farming or irrigation. Highest B. pseudomallei counts were retrieved from paddocks, pens and kennels holding livestock and dogs. This study contributes to the elucidation of the habitat of B. pseudomallei in northern Australia. It also raises concerns that B. pseudomallei may spread due to changes in land management

A Host Defense Mechanism Involving CFTR-Mediated Bicarbonate Secretion in Bacterial Prostatitis

BACKGROUND: Prostatitis is associated with a characteristic increase in prostatic fluid pH; however, the underlying mechanism and its physiological significance have not been elucidated. METHODOLOGY/PRINCIPAL FINDINGS: In this study a primary culture of rat prostatic epithelial cells and a rat prostatitis model were used. Here we reported the involvement of CFTR, a cAMP-activated anion channel conducting both Cl(-) and HCO(3)(-), in mediating prostate HCO(3)(-) secretion and its possible role in bacterial killing. Upon Escherichia coli (E. coli)-LPS challenge, the expression of CFTR and carbonic anhydrase II (CA II), along with several pro-inflammatory cytokines was up-regulated in the primary culture of rat prostate epithelial cells. Inhibiting CFTR function in vitro or in vivo resulted in reduced bacterial killing by prostate epithelial cells or the prostate. High HCO(3)(-) content (>50 mM), rather than alkaline pH, was found to be responsible for bacterial killing. The direct action of HCO(3)(-) on bacterial killing was confirmed by its ability to increase cAMP production and suppress bacterial initiation factors in E. coli. The relevance of the CFTR-mediated HCO(3)(-) secretion in humans was demonstrated by the upregulated expression of CFTR and CAII in human prostatitis tissues. CONCLUSIONS/SIGNIFICANCE: The CFTR and its mediated HCO(3)(-) secretion may be up-regulated in prostatitis as a host defense mechanism

Persistent Gastric Colonization with Burkholderia pseudomallei and Dissemination from the Gastrointestinal Tract following Mucosal Inoculation of Mice

Melioidosis is a disease of humans caused by opportunistic infection with the soil and water bacterium Burkholderia pseudomallei. Melioidosis can manifest as an acute, overwhelming infection or as a chronic, recurrent infection. At present, it is not clear where B. pseudomallei resides in the mammalian host during the chronic, recurrent phase of infection. To address this question, we developed a mouse low-dose mucosal challenge model of chronic B. pseudomallei infection and investigated sites of bacterial persistence over 60 days. Sensitive culture techniques and selective media were used to quantitate bacterial burden in major organs, including the gastrointestinal (GI) tract. We found that the GI tract was the primary site of bacterial persistence during the chronic infection phase, and was the only site from which the organism could be consistently cultured during a 60-day infection period. The organism could be repeatedly recovered from all levels of the GI tract, and chronic infection was accompanied by sustained low-level fecal shedding. The stomach was identified as the primary site of GI colonization as determined by fluorescent in situ hybridization. Organisms in the stomach were associated with the gastric mucosal surface, and the propensity to colonize the gastric mucosa was observed with 4 different B. pseudomallei isolates. In contrast, B. pseudomallei organisms were present at low numbers within luminal contents in the small and large intestine and cecum relative to the stomach. Notably, inflammatory lesions were not detected in any GI tissue examined in chronically-infected mice. Only low-dose oral or intranasal inoculation led to GI colonization and development of chronic infection of the spleen and liver. Thus, we concluded that in a mouse model of melioidosis B. pseudomallei preferentially colonizes the stomach following oral inoculation, and that the chronically colonized GI tract likely serves as a reservoir for dissemination of infection to extra-intestinal sites