Hospital cluster of HBV infection: molecular evidence of patient-to-patient transmission through lancing device

Abstract

Introduction: In western countries the transmission of hepatitis B virus (HBV) transmission through multi-patients lancing devices has been inferred since early '90s, however no study has ever provided biological evidence which directly link these device with HBV cross-infection. Here we present results of an outbreak investigation which could associate, by molecular techniques, the use of lancing device on multiple patients with HBV transmission in an Italian oncohematology unit.

Methods: The outbreak investigation was designed as a retrospective cohort study to identify all potential cases. All cases identified were eventually confirmed through molecular epidemiology techniques. Audit of personnel including extensive review of infection control measures and reviewing personnel's tests for HBV was done identify transmission route.

Results: Between 4 May 2006 and 21 February 2007, six incident cases of HBV infection were reported among 162 patients admitted in the oncohematology. The subsequent molecular instigation proved that 3 out 6 incident cases and one prevalent cases (already infected with HBV at the admission) represented a monophyletic cluster of infection. The eventual environmental investigation found that an identical HBV viral strain was present on a multi-patients lancing device in use in the unit and the inferential analysis showed a statistically significant association between undergoing lancing procedures and the infection.

Discussion: This investigation provide molecular evidence to link a HBV infection cluster to multi-patients lancing device and highlights that patients undergoing capillary blood sampling by non-disposable lancing device may face an unacceptable increased risk of HBV infection. Therefore we believe that multi-patients lancing devices should be banned from healthcare settings and replace with disposable safety lancets that permanently retract to prevent the use of the same device on multiple patients. The use of non-disposable lancing devices should be restricted to individual use at patients' home.

Figure 1. Phylogenetic tree of HBV-precore/core and HBV-polymerase region.

The analysis was performed on 3 out 6 incident cases, 2 out 3 prevalent cases, 2 additional cases identified during the enhanced surveillance period and on elute from the mp-LD (red codes). The phylogenetic trees also include 10 (precore/core) and 13 (polymerase) sequences of the genotype D HBV from patients not related to the outbreak who were referred to the laboratory for diagnostic purpose (black codes) and 3 genotype D sequences from GenBank (blue codes). The analysis shows that all patients within the study were infected with a genotype D HBV. In addition one prevalent cases (index case; CC-0), 3 incident cases (confirmed cases; CC-1, CC-2 and CC-3) and the elute from multi-patients lancing device (mp-LD) where infected with a highly related HBV molecular variant. In fact, these molecular variants form a monophyletic cluster distinct from the other sequences by very high bootstrap value (red box). In contrast one prevalent case (excluded case CE-58) and the 2 cases (excluded cases; CE-55 and CE-77) detected during the enhanced surveillance were infected with unrelated HBV molecular variants. The epidemiologically unrelated cases, both form our laboratory archive and from GenBanK, were infected with genetically distant variants as expected. Boxes indicate the epidemic cluster; the bars indicate the genetic distance.

Figure 2. Extended phylogenetic analysis for HBV polymerase region.

Extended phylogenetic tree including 214 genomic sequence of HBV-polymerase region. In red unrelated HBV molecular variant which were obtained from patients referred to our laboratory in about 7 years. In black: 3 genotype D sequences from GenBank (AB205127; AB116266; X97848); 3 excluded case form our investigation (CE-55_1/2; CE-58; CE-77); The index case (CC-0); 3 confirmed cases (CC-1; CC-2; CC-3); the elute form multi-patients lancing device (mp-LD). Even after this new analysis CC-0, CC-1, CC-2, CC-3 and the elute from mp-LD formed a monophyletic cluster distinct from the other sequences by very high bootstrap value. The box indicates the epidemic cluster; the bars indicate the genetic distance.

Figure 3. Multi-patients lancing device.

Figure modified form the original as reported in the 2007 Italian version of the manual users' manual [ref. 8].