Evaluating candidate agents of selective pressure for cystic fibrosis.
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Cystic fibrosis is the most common lethal single-gene mutation in people of European descent, with a carrier frequency upwards of 2%. Based upon molecular research, resistances in the heterozygote to cholera and typhoid fever have been proposed to explain the persistence of the mutation. Using a population genetic model parameterized with historical demographic and epidemiological data, we show that neither cholera nor typhoid fever provided enough historical selective pressure to produce the modern incidence of cystic fibrosis. However, we demonstrate that the European tuberculosis pandemic beginning in the seventeenth century would have provided sufficient historical, geographically appropriate selective pressure under conservative assumptions. Tuberculosis has been underappreciated as a possible selective agent in producing cystic fibrosis but has clinical, molecular and now historical, geographical and epidemiological support. Implications for the future trajectory of cystic fibrosis are discussed. Our result supports the importance of novel investigations into the role of arylsulphatase B deficiency in cystic fibrosis and tuberculosis. (+info)
Application of Poisson kriging to the mapping of cholera and dysentery incidence in an endemic area of Bangladesh.
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BACKGROUND: Disease maps can serve to display incidence rates geographically, to inform on public health provision about the success or failure of interventions, and to make hypothesis or to provide evidences concerning disease etiology. Poisson kriging was recently introduced to filter the noise attached to rates recorded over sparsely populated administrative units. Its benefit over simple population-weighted averages and empirical Bayesian smoothers was demonstrated by simulation studies using county-level cancer mortality rates. This paper presents the first application of Poisson kriging to the spatial interpolation of local disease rates, resulting in continuous maps of disease rate estimates and the associated prediction variance. The methodology is illustrated using cholera and dysentery data collected in a cholera endemic area (Matlab) of Bangladesh. RESULTS: The spatial analysis was confined to patrilineally-related clusters of households, known as baris, located within 9 kilometers from the Matlab hospital to avoid underestimating the risk of disease incidence, since patients far away from the medical facilities are less likely to travel. Semivariogram models reveal a range of autocorrelation of 1.1 km for dysentery and 0.37 km for cholera. This result translates into a cholera risk map that is patchier than the dysentery map that shows a large zone of high incidence in the south-central part of the study area, which is quasi-urban. On both maps, lower risk values are found in the Northern part of the study area, which is also the most distant from the Matlab hospital. The weaker spatial continuity of cholera versus dysentery incidence rates resulted in larger kriging variance across the study area. CONCLUSION: The approach presented in this paper enables researchers to incorporate the pattern of spatial dependence of incidence rates into the mapping of risk values and the quantification of the associated uncertainty. Differences in spatial patterns, in particular the range of spatial autocorrelation, reflect differences in the mode of transmission of cholera and dysentery. Our risk maps for cholera and dysentery incidences should help identifying putative factors of increased disease incidence, leading to more effective prevention and remedial actions in endemic areas. (+info)
Detection and identification of Treponema hyodysenteriae by using oligodeoxynucleotide probes complementary to 16S rRNA.
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Oligodeoxynucleotide probes (17 and 28 bases long) complementary to a unique region of Treponema hyodysenteriae 16S rRNA were developed. These probes bound specifically to partially purified rRNA and whole-cell rRNA of T. hyodysenteriae. No binding to partially purified rRNA or whole-cell rRNA of Treponema innocens, Treponema succinifaciens, Treponema bryantii, or Escherichia coli occurred under stringent conditions. The 28-base probe was 5 to 10 times more sensitive than the 17-base probe when hybridized with T. hyodysenteriae rRNA. The 28-base probe detected T. hyodysenteriae in the feces of experimentally inoculated pigs exhibiting clinical signs of swine dysentery. (+info)
Immune response, ciprofloxacin activity, and gender differences after human experimental challenge by two strains of enterotoxigenic Escherichia coli.
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In order to test vaccines against enterotoxigenic Escherichia coli (ETEC)-induced diarrhea, challenge models are needed. In this study we compared clinical and immunological responses after North American volunteers were orally challenged by two ETEC strains. Groups of approximately eight volunteers received 10(9) or 10(10) CFU of E. coli B7A (LT+ ST+ CS6+) or 10(8) or 10(9) CFU of E. coli H10407 (LT+ ST+ CFA/I+). About 75% of the volunteers developed diarrhea after challenge with 10(10) CFU B7A or either dose of H10407. B7A had a shorter incubation period than H10407 (P = 0.001) and caused milder illness; the mean diarrheal output after H10407 challenge was nearly twice that after B7A challenge (P = 0.01). Females had more abdominal complaints, and males had a higher incidence of fever. Ciprofloxacin generally diminished or stopped symptoms and shedding by the second day of antibiotic treatment, but four subjects shed for one to four additional days. The immune responses to colonization factors CS6 and colonization factor antigen I (CFA/I) and to heat-labile toxin (LT) were measured. The responses to CFA/I were the most robust responses; all volunteers who received H10407 had serum immunoglobulin A (IgA) and IgG responses, and all but one volunteer had antibody-secreting cell (ASC) responses. One-half the volunteers who received B7A had an ASC response to CS6, and about one-third had serum IgA or IgG responses. Despite the differences in clinical illness and immune responses to colonization factors, the immune responses to LT were similar in all groups and were intermediate between the CFA/I and CS6 responses. These results provide standards for immune responses after ETEC vaccination. (+info)
Traveler's diarrhea in Thailand: randomized, double-blind trial comparing single-dose and 3-day azithromycin-based regimens with a 3-day levofloxacin regimen.
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BACKGROUND: Traveler's diarrhea in Thailand is frequently caused by Campylobacter jejuni. Rates of fluoroquinolone (FQ) resistance in Campylobacter organisms have exceeded 85% in recent years, and reduced fluoroquinolone efficacy has been observed. METHODS: Azithromycin regimens were evaluated in a randomized, double-blind trial of azithromycin, given as a single 1-g dose or a 3-day regimen (500 mg daily), versus a 3-day regimen of levofloxacin (500 mg daily) in military field clinics in Thailand. Outcomes included clinical end points (time to the last unformed stool [TLUS] and cure rates) and microbiological end points (pathogen eradication). RESULTS: A total of 156 patients with acute diarrhea were enrolled in the trial. Campylobacter organisms predominated (in 64% of patients), with levofloxacin resistance noted in 50% of Campylobacter organisms and with no azithromycin resistance noted. The cure rate at 72 h after treatment initiation was highest (96%) with single-dose azithromycin, compared with the cure rates of 85% noted with 3-day azithromycin and 71% noted with levofloxacin (P=.002). Single-dose azithromycin was also associated with the shortest median TLUS (35 h; P=.03, by log-rank test). Levofloxacin's efficacy was inferior to azithromycin's efficacy, except in patients with no pathogen identified during the first 24 h of treatment or in patients with levofloxacin-susceptible Campylobacter isolates, in whom it appeared to be equal to azithromycin. The rate of microbiological eradication was significantly better with azithromycin-based regimens (96%-100%), compared with levofloxacin (38%) (P=.001); however, this finding was poorly correlated with clinical outcome. A higher rate of posttreatment nausea in the 30 min after receipt of the first dose (14% vs. <6%; P=.06) was observed as a mild, self-limited complaint associated with single-dose azithromycin. CONCLUSIONS: Single-dose azithromycin is recommended for empirical therapy of traveler's diarrhea acquired in Thailand and is a reasonable first-line option for empirical management in general. (+info)
Childhood Helicobacter pylori infection and growth impairment in developing countries: a vicious cycle?
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We hypothesize that infection with the gastric pathogen Helicobacter pylori in children in developing countries is the initiator of a vicious cycle of events that result ultimately in malnutrition and growth impairment. Acute infection with H. pylori is accompanied by hypochlorhydria, which facilitates the acquisition of other enteropathogens because of removal of the gastric acid barrier, which then results in diarrheal disease and iron-deficiency anemia. This is likely to occur most frequently in developing regions where the prevalence of H. pylori infection is disproportionately high and multiple enteric coinfections are common. The consequent synergistic impact of diarrheal disease and micronutrient deficiency on growth and cognitive function in children has significant public health implications for socioeconomic development in these countries. (+info)
Comparison of six different culture media for isolation of Treponema hyodysenteriae.
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Fecal material from pigs experimentally infected with Treponema hyodysenteriae was collected and inoculated on six different selective media to compare their abilities for recovery of T. hyodysenteriae. Additionally, various types of samples were compared to find the most appropriate for submitting material to laboratories. Isolation rates for T. hyodysenteriae were 89.7% on BJ medium, 88.3% on TSA-BJ medium, 76.6% on SVC medium, 76.6% on BA2-BJ medium, 75.2% on BA2-SVC medium, and 52.4% on TSA-S400 medium. BJ medium was the most useful, yielding good growth of T. hyodysenteriae and inhibition of the normal fecal flora. Also, undiluted fecal material kept at refrigeration temperature allowed better recovery of T. hyodysenteriae during storage than swabs. (+info)
Detection of G12 human rotaviruses in Nepal.
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Of 731 stool specimens collected from children with diarrhea in Kathmandu, Nepal, from August 2004 through July 2005, 170 (23.3%) tested positive for rotavirus. Reverse transcription-PCR, including a revised G12-specific primer set, identified 56 (32.9%) as G2P[4] and 39 (23.0%) as G12 with P[6], P[8], or P[4]. (+info)