The rise and fall of infectious diseases: Australian perspectives, 1914-2014.

Australia has been fortunate in its experience with infectious diseases over the past century. By the 1960s, many communicable diseases were controlled through a combination of high living standards, progressive adoption of vaccines and antimicrobial treatment. Australian medical scientists have made substantial contributions to the understanding of many historically significant communicable diseases and global initiatives for control. New challenges have emerged as previously unrecognised viral infections have emerged, and microbial resistance to antibiotics has developed in many old pathogens. Ongoing evolutionary forces, both environmental and social, change the balance between humans and microbes. The effects of these forces are most sorely felt in poor countries and communities.

Hepatitis C virus infection rates and risk factors in an Australian hospital endoscopy cohort.

OBJECTIVE: To determine the reservoir and risk factors of HCV infection in a hospital population. METHODS: The presence of anti-HCV in 2,119 endoscopy patients was related to putative risk factors for exposure using the SAS statistical package. RESULTS: Most of the 4.7% of anti-HCV positive patients had multiple risk factors for HCV exposure. The risk was significantly increased in patients; with a previous history of hepatitis (36.4 fold), past history of injecting drugs (IDU) (32.1 fold), those born in North Africa, Middle East and Mediterranean countries (4.3 fold), had been tattooed before 1980s (3.3 fold), from 1980s-1990s (5.9 fold), had acupuncture before 1980s (3.8 fold), had a blood transfusion (3.6 fold), had clotting factors or growth hormone (4 fold), had contact with someone diagnosed with hepatitis in 1990s (4.1 fold). Of the anti-HCV patients 38 had a history of IDU, 43 were migrants and 10 were both. CONCLUSION: Anti-HCV prevalence was five times higher than predicted by the passive surveillance scheme and 20% of patients were unaware of their infection. Only one of these patients reported IDU. The evidence of HCV intersecting epidemics between developing and developed countries in Australia was strongly supported. IMPLICATIONS: The study provides a rational basis for targeted programs to identify asymptomatic HCV carriers who might benefit from the new antiviral treatment.

The effect of multiple cycles of contamination, detergent washing, and disinfection on the development of biofilm in endoscope tubing.

BACKGROUND: Patient soil and bacterial biofilm in patient-ready endoscope channels can adversely impact the efficacy of detergent and disinfectant, thereby increasing the risk of nosocomial infection. Biofilm bacteria are firmly attached to one another and to the substrate by exopolysaccharide, making them difficult to remove. We analyzed the effect of 20 wash/contamination cycles on biofilm formation. MATERIALS: Pseudomonas aeruginosa biofilm-covered endoscope tubing was soaked in water (control), an enzymatic cleaner, or a nonenzymatic cleaner (Matrix) for 10 minutes and decontaminated in a washer-disinfector machine. Media containing P aeruginosa was then recycled to simulate contamination in clinical practice. RESULTS: SEM analysis showed that loosely attached biofilm was removed under the high flow rates in the washer-disinfector. The control tubing remained 100% covered with biofilm, which became thicker with increased recontamination cycles. Washing in the enzymatic detergent retarded the redevelopment of biofilm. The nonenzymatic cleaner (Matrix) continued to remove more biofilm with an increasing number of wash/contamination cycles. At the 20th cycle, 90% of the tubing was biofilm-free. CONCLUSION: Washing endoscopes under high flow rates with some detergents removes established biofilm and retards biofilm generation, emphasizing the importance of cleaning before disinfection. Continued research into the physicochemical mechanisms of biofilm adherence and removal is needed to optimize detergents.

Transplacental haemorrhage may explain the intrapartum transmission of HIV. A pilot study uses flow cytometry to quantify maternal red blood cells in infants born vaginally or by caesarean section.

Intrapartum transmission is epidemiologically important for some viruses such as HIV and hepatitis B virus, but its precise mechanism is unknown. We hypothesised that the ability of elective caesarean section to prevent HIV may be due to prevention of transplacental microtransfusions of blood during labour. Their frequency is not known so we performed a pilot study which showed evidence of transplacental transfusion from mother to fetus in one of ten mother-infant pairs delivering vaginally and none of ten delivering by elective caesarean section. We conclude that transplacental transfusion occurs and is one possible mechanism for the intrapartum transmission of viruses from mother to baby.

A prospective study of the efficacy of routine decontamination for gastrointestinal endoscopes and the risk factors for failure.

BACKGROUND: Patient-ready endoscopes were monitored over an 80-week period to determine the efficacy of decontamination procedures in a busy endoscopy center. Decontamination failure was related to patient and procedural parameters. METHODS: Samples from patient-ready endoscopes were cultured aerobically and anaerobically and subjected to polymerase chain reaction (PCR) to detect hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV. PCR to detect coliforms from 109 culture negative washes was used as a surrogate marker for biofilm in endoscopes. PCR was used to detect the presence of Helicobactor pylori in endoscopes used on infected patients. Procedural information such as biopsy retrieval, endoscope number, diagnosis, attending personnel, and decontamination system procedures was collected. RESULTS: Gastroscopes (n = 1,376) and colonoscopes (n = 987) were equally contaminated (1.8% vs 1.9%, respectively) with low numbers of organisms commonly isolated from the nasopharynx and/or feces. Only 1 wash contained viral nucleic acid (HCV). There was a significant correlation (P < .001) between the number of times a patient-ready endoscope was contaminated and its frequency of use. Colonoscopes used on patients with gastrointestinal disease were significantly more likely to remain contaminated through the decontamination process (P < .05). All other patient, staff, and decontamination system parameters remained not statistically significant. Coliform DNA was detected in 40% of culture-negative washes collected from patient-ready endoscopes, suggesting the presence of biofilm. No H pylori DNA was detected. CONCLUSION: Recommended decontamination procedures do not entirely eliminate persistence of low numbers of organisms on a few endoscopes, but this is unlikely to cause serious consequences in patients. Bacterial biofilm is difficult to remove and may explain this low-level persistence.

The impact of hepatitis B vaccination in a Western country: recall of vaccination and serological status in Australian adults.

Notifications of acute icteric hepatitis B have declined since the introduction of vaccination but it is not clear whether the reservoir of infection and the proportion of adults who remain susceptible have also changed. This has been investigated by evaluation of serological evidence of infection and immunity, patient recall of vaccination and risk factors for exposure to hepatitis B in 2115 adult endoscopy patients in central Sydney. Twenty-one percent were immune, two thirds of these by vaccination. One third of the 440 who recalled "vaccination" were anti-HBs negative. 2.1% of the cohort was HBsAg positive and of these 31% (14/45) were viraemic. Amongst epidemiological risk groups recommended for vaccination, multivariate analysis showed that health care workers (odd ratio, OR = 5.35) and patients diagnosed with hepatitis A (OR = 2.6) or hepatitis C (OR = 2.1) were 5.35, 2.6 and 2.1 times more likely to be immunised, respectively. The great majority of immigrants from high prevalence countries, and of patients reporting other known risks for hepatitis B exposure remain susceptible.

The significance of transfusion in the past as a risk for current hepatitis B and hepatitis C infection: a study in endoscopy patients.

BACKGROUND: The objective was to determine the contribution of transfusion in the past to the risk of current infection with hepatitis B or C among patients attending a large hospital for endoscopic procedures. STUDY DESIGN AND METHODS: Blood samples had been tested for hepatitis markers by routine methods. Patients completed a comprehensive risk factor questionnaire and results were analyzed using computer software. RESULTS: Twenty-seven percent of the 2120 participants in the study received transfusions in the past. There was no increase in prevalence of hepatitis B among those transfused. Compared with nontransfused participants, recipients of blood before the implementation of hepatitis C virus (HCV) screening in 1990 had a 4.6-fold increased risk of HCV infection, whereas those transfused with screened blood had a 3-fold increased risk. The difference between the odds ratios for patients before and after screening was not significant. CONCLUSIONS: Because screening has almost completely eliminated HCV from the blood supply, our finding of a continuing association of HCV infection with transfusion was unexpected. It implies that there are significant other nosocomial risks for hepatitis C transmission associated with the clinical situations where patients received blood. These should be actively investigated.

The site of infection and ethnicity of the patient influence the biological pathways to HPV-induced mucosal cancer.

High-risk human papillomaviruses are the causative agents of cervical cancer and are also believed to be aetiologically involved in a subset of squamous cell carcinomas of the head and neck region, especially the tonsil. Cervical cancers arise through disruption of the pathways of p53 and the product of the retinoblastoma gene by the human papillomavirus oncoproteins E6 and E7. It is generally assumed that the same pathways are involved in human papillomavirus-induced carcinogenesis at other mucosal surfaces. However, the patterns of expression of cell cycle proteins targeted by human papillomavirus E6 and E7 in cancers from different anatomic sites have been inconsistent, due to either biologic or technological factors. In this study, 73 human papillomavirus, 16-positive cervical squamous cell carcinomas (35 from Australian and 38 from Chinese women) were analysed for the expression of p53, pRb, p16(INK4A), p21(CIP1/WAF1), p27(KIP1) and cyclin D1 by semiquantitative immunohistochemistry. Cervical cancers from Chinese women were found to be significantly more likely to overexpress p53, pRb, p21 and p27 than their Australian counterparts. These findings were compared with those from 31 human papillomavirus 16-positive tonsillar squamous cell carcinomas, all of Australian origin, tested using the same methodology. Comparisons of the tonsillar and combined cervical data showed that tonsillar cancers were significantly more likely to be p53-positive, whereas cervical cancers were significantly more likely to overexpress pRb, p16 and p27. When the tonsillar data were compared with cervical data from Australian women, the associations for p53 and pRb remained. These findings represent new evidence that the molecular pathways to human papillomavirus-induced mucosal cancer may be influenced by anatomic location and ethnicity.

The expression of key cell cycle markers and presence of human papillomavirus in squamous cell carcinoma of the tonsil.

BACKGROUND: Chemical carcinogens induce squamous cell carcinoma (SCC) of the head and neck by targeting the p53 and the retinoblastoma (pRb) pathways. Human papillomavirus (HPV) might have an etiologic role in these cancers at particular sites. Few studies have compared cell cycle protein expression in HPV-positive and HPV-negative tumors in this region. METHODS: Fifty tonsil SCCs were analyzed for HPV by PCR and for expression of cell cycle proteins (p53, pRb, p16(INK4A), p21(CIP1/WAF1), p27(KIP1), and cyclinD1) by immunohistochemistry. RESULTS: HPV was present in 42%; almost all were type 16. There were statistical associations between HPV positivity and reduced expression of pRb and cyclinD1, overexpression of p16, and younger patient age. Tumor with down-regulated p27 tended to have down-regulated pRb and p21. CONCLUSIONS: HPV-positive tonsil SCCs have distinct molecular pathways. Their association with younger patient age suggests that they are biologically distinct from HPV-negative tumors.

Absence of human papillomavirus in tonsillar squamous cell carcinomas from Chinese patients.

Epidemiological and experimental evidence from Western countries now consistently support an etiological role for human papillomavirus (HPV) in a subset of oropharyngeal squamous cell carcinomas (SCC), especially those originating in the tonsil. The role of HPV in the etiology of tonsil cancer in developing countries such as China has not been investigated. In this study, none of 16 tonsil cancer specimens from Chinese patients were positive for HPV DNA, whereas those from Australian patients using the same methodology gave a positivity rate of 46%. The tumors from Chinese patients, like the Australian HPV-negative subset, significantly overexpressed pRb and cyclin D1 and underexpressed p16(INK4A) (p16). In contrast, the Australian HPV-positive cancers overexpressed p16 and had reduced expression of pRb and cyclin D1. These findings may help explain why China has a relatively low rate of oropharyngeal cancer compared with Australia. They also support the hypothesis that molecular pathways to tonsil cancer mediated by HPV are distinct from those induced by mutagens present in cigarette smoke or alcohol.

Human papillomavirus positivity predicts favourable outcome for squamous carcinoma of the tonsil.

Mutations in the p53 and retinoblastoma (pRb) pathways associated with the use of tobacco and alcohol are common in squamous cell carcinoma (SCC) of the head and neck. Cell cycle proteins are also affected by human papillomavirus (HPV), which may also have an aetiological role in cancers at particular sites, most notably the tonsil. Attempts to identify prognostic molecular markers in head and neck cancers have met with conflicting results, but few studies have been undertaken with tumours of known HPV status at a single anatomic site. In our study 86 tonsil cancers were analysed for HPV status by sequence analysis of polymerase chain reaction products and for the expression of cell cycle proteins (p53, p21(CIP1/WAF1), pRb, p16(INK4A), cyclin D1 and p27(KIP1)) by immunohistochemistry. The HPV status could be established in 67 of the tumours. Thirty-one (46%) of these were HPV-positive, predominantly (28/31) for HPV16. Findings were related to tumour recurrence and patient survival. None of the cell cycle proteins independently predicted recurrence or survival. Patients with HPV-positive tumours, however, were significantly less likely (p < 0.05) to have recurrence or to die of disease than those with HPV-negative tumours, after adjusting for the effects of the cell cycle proteins, clinical stage, pathological node status, tumour grade, age, gender and treatment. These findings support the concept that HPV-positive tonsil cancers may be a distinct biological group with less aggressive characteristics. Screening of tonsil cancers for HPV DNA may help optimise treatment and provide more accurate prognostic information.

Detection of subclinical infection in significant breast implant capsules.

The pathogenesis of fibrous capsular contracture after augmentation mammaplasty is still debated. One hypothesis implicates low-grade bacterial infections as a cause. The presence of a staphylococcal biofilm in a patient with recurrent capsular contracture was previously reported. A comparative, prospective, blinded, clinical study of implants and capsules removed from patients with or without significant capsular contracture was conducted to investigate the association of biofilm contamination, breast implants, and capsular contracture. Capsule and implant samples obtained during explantation were tested by routine microbiological culture, sensitive broth culture (after maceration and sonication), and scanning electron microscopy. Clinical parameters were correlated with microbiological findings. A total of 48 implant and/or capsule samples were obtained from 27 breasts during a 22-month period. Of the 27 breasts, 19 exhibited significant contracture (Baker grade III/IV). The mean duration of implantation was 9.2 years (range, 0.4 to 26.0 years). Routine swab cultures obtained at the time of explantation were negative for bacterial growth for all samples. The sensitive broth culture technique yielded 24 positive samples (50 percent, n = 48). An analysis of capsules demonstrated that 17 of 19 samples obtained from patients with significant contracture were positive, compared with only one of eight samples obtained from patients with minimal or no contracture (p = 0.0006). Fourteen of the 17 positive cultures from significantly contracted breasts yielded coagulase-negative staphylococci, mainly, species of the Staphylococcus epidermidis group. The presence of coagulase-negative staphylococci was also significantly associated with capsular contracture (p = 0.01). There was no significant difference in the frequency of culture positivity for saline versus silicone implants (p = 0.885). Scanning electron microscopy confirmed the presence of extensive biofilm on implants and within capsules.Biofilm, in particular, S. epidermidis biofilm, was detected for a significant proportion of patients with capsular contracture. This implicates biofilm disease in the pathogenesis of contracture, and strategies for its prevention should be explored.

Sequence variation and physical state of human papillomavirus type 16 cervical cancer isolates from Australia and New Caledonia.

Sequence diversity over 2600 nucleotides of the upstream regulatory region (URR) and the E6 and E2/E4 genes of 34 human papillomavirus (HPV)16 cervical cancer isolates from Australia and New Caledonia was investigated. One 81 base duplication, 41 single base substitutions and 1 single base insertion were identified in the URRs. Some of these changes are reported here for the first time. Several of the 19 changes impacting transcription factor binding sites had the potential to alter promoter activity. Twenty-eight (82%) of the variants belonged to the European lineage, 4 (12%) were Asian and 2 (6%) were Asian-American. Eighteen of 27 (67%) isolates where the E6 gene was examined contained amino acid substitutions. Of 13 isolates sequenced with intact E2 genes, 12 (92%) contained amino acid substitutions in the E2 protein and 3 (23%) amino acid substitutions in the overlapping E4 protein. Some of the changes in E6 and E2 may alter immunological epitopes or protein function. The physical state of HPV DNA was assessed by Southern hybridization and PCR for an intact E2 gene. Overall, 11 of 25 isolates contained only integrated HPV DNA, 10 only episomal HPV DNA and 4 both integrated and episomal DNA. No particular patterns of variation in the URR, E6 or E2/E4 genes predicted physical state. This investigation represents one of the most comprehensive studies of its kind and fills an important gap in global sequence data.