Whole-genome sequencing improves discrimination of relapse from reinfection and identifies transmission events among patients with recurrent Clostridium difficile infections.

BACKGROUND: Recurrent Clostridium difficile infection (CDI) represents a significant healthcare challenge. Patients may suffer multiple episodes of CDI with the index strain (relapse) or become infected by another strain acquired nosocomially (reinfection). AIM: We aimed to characterize C. difficile isolates causing recurrent CDI at a tertiary referral hospital by whole-genome sequencing (WGS) to assess strain similarities at the highest level of genetic resolution and accurately detect relapse, reinfection, and putative strain transmission events. METHODS: An 18-month prospective study of recurrent CDI was undertaken. Clostridium difficile was cultured from stool samples collected longitudinally from any patients suffering ≥2 clinically defined CDI episodes. Patient demographics and clinical data were recorded, and strain relatedness investigated by both polymerase chain reaction (PCR)-based ribotyping and WGS. FINDINGS: Nineteen patients were identified with ≥2 clinically defined CDI episodes who cumulatively suffered 39 recurring CDI episodes (58 total episodes). Patients had a median length of stay (LOS) of 144 days and experienced between two and seven CDI episodes. Ribotyping indicated 27 apparent same-strain relapses, five reinfections and the predominance of ribotypes 078 (ST-11) and 020 (ST-2). WGS allowed characterization of relapse with increased certainty and identified emergent within-strain single nucleotide variants (SNVs) with potential functional impact on diverse genes. Shared ribotypes among 14 patients with recurrent CDI suggested 10 possible patient-to-patient transmission events. However, WGS revealed greater diversity at the sub-ribotype level, excluding all but four transmission events. CONCLUSION: WGS exhibits several advantages over PCR-based ribotyping in terms of its ability to distinguish relapse from reinfection, to identify patient-to-patient transmission events, and to exact fine structure characterization of recurrent CDI epidemiology. This offers the potential for more focused infection prevention strategies to eliminate strain transmission among patients with recurrent CDI.

The Alaska Trauma Registry.

Recognizing that injury is the leading cause of death and disability for virtually all age groups in Alaska, a trauma task force was developed in the Anchorage area in the early 1980s. This task force established the trauma registry pilot project in the state of Alaska. The Emergency medical Services Section, Department of Health and Social Services provided the funding to the Southern Region Emergency Medical Services Council, Inc. and the Alaska Chapter of the American College of Surgeons Committee on Trauma to develop this pilot project. The funding originated from a federal grant from the National Highway Traffic Safety Administration. Seven hospital participated in the pilot project which lasted approximately two and one half years. There were 5,087 entries into the registry with information on 4,860 patients. The rationale, methodology, and development of the registry, as well as some of the data accumulated is presented. The potential usefulness of the registry as a quality improvement tool and as an extensive data base for injury prevention and trauma care research also is discussed.

Early detection of primary hepatocellular carcinoma. Screening for primary hepatocellular carcinoma among persons infected with hepatitis B virus.

High rates of hepatitis B virus infection and primary hepatocellular carcinoma are present among Alaskan Natives. To determine if primary hepatocellular carcinoma could be detected at an early surgically resectable stage, serological screening for elevated alpha-fetoprotein levels was done semiannually among Alaskan Natives infected with hepatitis B virus. During a 26-month screening period, 3,387 alpha-fetoprotein tests were performed on 1,394 persons. Of 126 persons with elevated levels of alpha-fetoprotein (greater than 25 ng/mL), nine males were found to have primary hepatocellular carcinoma (all with alpha-fetoprotein levels greater than 350 ng/mL). Six of these nine persons were asymptomatic for primary hepatocellular carcinoma and four had small tumors (less than 6 cm) that were surgically resected. After surgery, the alpha-fetoprotein levels in all four patients fell to normal and have remained normal after a follow-up of four to 20 months (median, ten months). alpha-Fetoprotein screening proved to be an effective approach in this population in detecting primary hepatocellular carcinoma at a potentially curable stage and should be considered in other individuals or populations infected with hepatitis B virus.

Oesophageal cancer among Alaskan natives, 1955-1981.

Forty-two patients with oesophageal cancer were identified among Alaskan Natives from 1955 through 1981. Based on rates for US whites, there were 1.3 and 3.8 times the number of Native men and women diagnosed with oesophageal cancer as expected. Forty of the patients were Eskimo or Aleut, resulting in an incidence for Eskimo-Aleuts of 10.9 for males and 8.3 for females per 100 000 adjusted to the world standard population. The distribution of cancer patients by residence at diagnosis showed marked regional clustering, which has been observed among oesophageal cancer patients in several other areas of the world.

Early detection of primary hepatocellular carcinoma by screening for alpha-fetoprotein in high-risk families. A case-report.

Serum levels of alpha-fetoprotein (AFP) may be raised for up to 2 years before clinical presentation of primary hepatocellular carcinoma (PHC). A group of people judged to be at high risk of PHC because of long-term serological positivity for hepatitis B surface antigen, ethnicity, location of residence, and a strong family history of PHC were screened for increasing levels of AFP. After 1 1/2 years of twice-yearly screening, one of them, a 19-year-old Eskimo man, had a raised AFP level, which continued to rise rapidly over the next 3 months, although the patient remained symptomless and ultrasonography, 99mTc-scan, and computerised tomography of the liver were negative. Hepatic angiography suggested a small tumour in the periphery of the right lobe of the liver, but at laparotomy the right lobe was normal. Instead a tumour was found in the lateral tip of the left lobe. The tumour, a PHC, was resected surgically, and the patient has been well in the 11 months since his operation. His serum AFP level returned to normal 2 weeks after the operation and has remained normal.