Economic evaluation of typhoid vaccination in a prolonged typhoid outbreak setting: the case of Kasese district in Uganda.

Vaccination has been increasingly promoted to help control epidemic and endemic typhoid fever in high-incidence areas. Despite growing recognition that typhoid incidence in some areas of sub-Saharan Africa is similar to high-incidence areas of Asia, no large-scale typhoid vaccination campaigns have been conducted there. We performed an economic evaluation of a hypothetical one-time, fixed-post typhoid vaccination campaign in Kasese, a rural district in Uganda where a large, multi-year outbreak of typhoid fever has been reported.We used medical cost and epidemiological data retrieved on-site and campaign costs from previous fixed-post vaccination campaigns in Kasese to account for costs from a public sector health care delivery perspective. We calculated program costs and averted disability-adjusted life years (DALYs) and medical costs as a result of vaccination, to calculate the cost of the intervention per DALY and case averted.Over the 3 years of projected vaccine efficacy, a one-time vaccination campaign was estimated to avert 1768 (90%CI: 684-4431) typhoid fever cases per year and a total of 3868 (90%CI: 1353-9807) DALYs over the duration of the immunity conferred by the vaccine. The cost of the intervention per DALY averted was US$484 (90$ 341 (90%CI: 13-883).We estimated the vaccination campaign in this setting to be highly cost-effective, according to WHO's cost-effective guidelines. Results may be applicable to other African settings with similar high disease incidence estimates

Economic evaluation of typhoid vaccination in a prolonged typhoid outbreak setting: the case of Kasese district in Uganda.

BackgroundVaccination has been increasingly promoted to help control epidemic and endemic typhoid fever in high-incidence areas. Despite growing recognition that typhoid incidence in some areas of sub-Saharan Africa is similar to high-incidence areas of Asia, no large-scale typhoid vaccination campaigns have been conducted there. We performed an economic evaluation of a hypothetical one-time, fixed-post typhoid vaccination campaign in Kasese, a rural district in Uganda where a large, multi-year outbreak of typhoid fever has been reported.MethodsWe used medical cost and epidemiological data retrieved on-site and campaign costs from previous fixed-post vaccination campaigns in Kasese to account for costs from a public sector health care delivery perspective. We calculated program costs and averted disability-adjusted life years (DALYs) and medical costs as a result of vaccination, to calculate the cost of the intervention per DALY and case averted.ResultsOver the 3 years of projected vaccine efficacy, a one-time vaccination campaign was estimated to avert 1768 (90%CI: 684-4431) typhoid fever cases per year and a total of 3868 (90%CI: 1353-9807) DALYs over the duration of the immunity conferred by the vaccine. The cost of the intervention per DALY averted was US$484 (90$ 341 (90%CI: 13-883).ConclusionWe estimated the vaccination campaign in this setting to be highly cost-effective, according to WHO's cost-effective guidelines. Results may be applicable to other African settings with similar high disease incidence estimates

Circumcision status at HIV infection is not associated with plasma viral load in men: analysis of specimens from a randomized controlled trial

Abstract Background Male circumcision provides men with approximately 60% protection from acquiring HIV infection via heterosexual sex, and has become a key component of HIV prevention efforts in sub-Saharan Africa. Possible mechanisms for this protection include removal of the inflammatory anaerobic sub-preputial environment and the high concentration of Langerhans cells on the inside of the foreskin, both believed to promote local vulnerability to HIV infection. In people who do acquire HIV, viral load is partially determined by infecting partner viral load, potentially mediated by size of infecting inoculum. By removing a portal for virion entry, prior male circumcision could decrease infecting inoculum and thus viral load in men who become HIV-infected, conferring the known associated benefits of slower progression to disease and decreased infectiousness. Methods We performed an as-treated analysis of plasma samples collected under a randomized controlled trial of male circumcision for HIV prevention, comparing men based on their circumcision status at the time of HIV acquisition, to determine whether circumcision is associated with lower viral load. Eligible men were seroconverters who had at least one plasma sample available drawn at least 6 months after infection, reported no potential exposures other than vaginal sex and, for those who were circumcised, were infected more than 6 weeks after circumcision, to eliminate the open wound as a confounder. Initial viral load testing indicated that quality of pre-2007 samples might have been compromised during storage and they were excluded, as were those with undetectable or unquantifiable results. Log viral loads were compared between groups using univariable and multivariable linear regression, adjusting for sample age and sexually transmitted infection diagnosis with 3.5 months of seroconversion, with a random effect for intra-individual clustering for samples from the same man. A per-protocol analysis was also performed. Results There were no viral load differences between men who were circumcised and uncircumcised at the time of HIV infection (means 4.00 and 4.03 log10 copies/mL respectively, p = .88) in any analysis. Conclusion Circumcision status at the time of HIV infection does not affect viral load in men. Trial registration The original RCT which provided the samples was ClinicalTrials.gov trial NCT00059371

Genomic Analysis of a Pan-Resistant Isolate of Klebsiella pneumoniae, United States 2016

Antimicrobial resistance is a threat to public health globally and leads to an estimated 23,000 deaths annually in the United States alone. Here, we report the genomic characterization of an unusual Klebsiella pneumoniae, nonsusceptible to all 26 antibiotics tested, that was isolated from a U. S. patient. The isolate harbored four known beta-lactamase genes, including plasmid-mediated blaNDM-1 and blaCMY-6, as well as chromosomal blaCTX-M-15 and blaSHV-28, which accounted for resistance to all beta-lactams tested. In addition, sequence analysis identified mechanisms that could explain all other reported nonsusceptibility results, including nonsusceptibility to colistin, tigecycline, and chloramphenicol. Two plasmids, IncA/C2 and IncFIB, were closely related to mobile elements described previously and isolated from Gram-negative bacteria from China, Nepal, India, the United States, and Kenya, suggesting possible origins of the isolate and plasmids. This is one of the first K. pneumoniae isolates in the United States to have been reported to the Centers for Disease Control and Prevention (CDC) as nonsusceptible to all drugs tested, including all beta-lactams, colistin, and tigecycline. IMPORTANCE Antimicrobial resistance is a major public health threat worldwide. Bacteria that are nonsusceptible or resistant to all antimicrobials available are of major concern to patients and the public because of lack of treatment options and potential for spread. A Klebsiella pneumoniae strain that was nonsusceptible to all tested antibiotics was isolated from a U. S. patient. Mechanisms that could explain all observed phenotypic antimicrobial resistance phenotypes, including resistance to colistin and beta-lactams, were identified through whole-genome sequencing. The large variety of resistance determinants identified demonstrates the usefulness of whole-genome sequencing for detecting these genes in an outbreak response. Sequencing of isolates with rare and unusual phenotypes can provide information on how these extremely resistant isolates develop, including whether resistance is acquired on mobile elements or accumulated through chromosomal mutations. Moreover, this provides further insight into not only detecting these highly resistant organisms but also preventing their spread

Carbapenem-resistant pseudomonas aeruginosa at us emerging infections program sites, 2015

Pseudomonas aeruginosa is intrinsically resistant to many antimicrobial drugs, making carbapenems crucial in clinical management. During July–October 2015 in the United States, we piloted laboratory-based surveillance for carbapenem- resistant P. aeruginosa (CRPA) at sentinel facilities in Georgia, New Mexico, Oregon, and Tennessee, and population-based surveillance in Monroe County, NY. An incident case was the first P. aeruginosa isolate resistant to antipseudomonal carbapenems from a patient in a 30-day period from any source except the nares, rectum or perirectal area, or feces. We found 294 incident cases among 274 patients. Cases were most commonly identified from respiratory sites (120/294; 40.8%) and urine (111/294; 37.8%); most (223/280; 79.6%) occurred in patients with healthcar

Carbapenemase production among less-common Enterobacterales genera: 10 US sites, 2018.

BACKGROUND: Historically, United States\u27 carbapenem-resistant Enterobacterales (CRE) surveillance and mechanism testing focused on three genera: OBJECTIVES: From January through May 2018, we conducted a 10 state evaluation to assess the contribution of less common genera (LCG) to carbapenemase-producing (CP) CRE. METHODS: State public health laboratories (SPHLs) requested participating clinical laboratories submit all Enterobacterales from all specimen sources during the surveillance period that were resistant to any carbapenem (Morganellaceae required resistance to doripenem, ertapenem, or meropenem) or were CP based on phenotypic or genotypic testing at the clinical laboratory. SPHLs performed species identification, phenotypic carbapenemase production testing, and molecular testing for carbapenemases to identify CP-CRE. Isolates were categorized as CP if they demonstrated phenotypic carbapenemase production and ≥1 carbapenemase gene ( RESULTS: SPHLs tested 868 CRE isolates, 127 (14.6%) were from eight LCG. Overall, 195 (26.3%) EsKE isolates were CP-CRE, compared with 24 (18.9%) LCG isolates. LCG accounted for 24 (11.0%) of 219 CP-CRE identified. CONCLUSIONS: Participating sites would have missed approximately 1 in 10 CP-CRE if isolate submission had been limited to EsKE genera. Expanding mechanism testing to additional genera could improve detection and prevention efforts

Cases of typhoid fever in Bundibugyo, by age, gender, and intestinal perforation status.

<p>January 1–December 31, 2011, n = 244 with known age, sex, and intestinal perforation status, *<i>P</i> = 0.03 and **<i>P</i> = 0.0006.</p

Selected characteristics of patients with suspected typhoid fever, by intestinal perforation (IP) status, April 15, 2011–January 6, 2012.

<p>*For some items, n may vary by small numbers due to “don't know” responses.</p><p>**Fisher's Exact test.</p>†<p>Percentage totals may be >100%; respondents could select ≥1 source of care and antibiotic.</p>‡<p>Patients with intestinal perforation: 1 each ceftriaxone, gentamycin, and unspecified; patients without intestinal perforation: 1 each cephalexin, doxycycline, erythromycin, and gentamycin, and 5 unspecified.</p

Clinical history of typhoid fever patients, Kasese and Bundibugyo Districts, April 15, 2011–January 6, 2012.

†<p>For some items, n may vary by small numbers due to “don't know” responses.</p><p>*Percentage totals may be >100%; respondents could select ≥1 source of care and antibiotic.</p>‡<p>Kasese patients: 1 school nurse; Bundibugyo patients: 5 friend or relative.</p>‡‡<p>Kasese patients: 1 each cephalexin, erythromycin, gentamycin, 4 unknown; Bundibugyo patients: 1 each ceftriaxone and doxycycline, 2 unknown.</p

Demographic characteristics of patients with suspected or confirmed typhoid fever, Kasese and Bundibugyo districts, Uganda, August 1, 2009–December 31, 2011.

<p>*Includes 12 patients for whom intestinal perforation status was reported by clinician as “don't know”.</p><p>**Includes 7 patients for whom intestinal perforation status was reported by clinician as “don't know” and 33 patients for whom intestinal perforation status could not be determined from district linelist.</p>†<p>For some items, n may vary by small numbers due to “don't know” or missing responses.</p>‡<p>Wilcoxon rank-sum test (median age) or Fisher's exact test (gender) for difference between Kasese patients with and without intestinal perforation.</p>‡‡<p>Wilcoxon rank-sum test (median age) or Fisher's exact test (gender) for difference between Bundibugyo patients with and without intestinal perforation.</p>a<p>Median age different by gender among all Kasese patients (<i>P</i> = 0.002) and among patients with intestinal perforation from Kasese (<i>P</i> = 0.0004) and Bundibugyo (<i>P</i> = 0.03). Median age did not differ significantly by gender among patients without intestinal perforation in either district.</p