Evaluation of the World Health Organization global measles and rubella quality assurance program, 2001-2008.

BACKGROUND: During 2001-2008, the Victorian Infectious Diseases Reference Laboratory (VIDRL) prepared and provided a measles and rubella proficiency test panel for distribution to the World Health Organization (WHO) measles and rubella network laboratories as part of their annual laboratory accreditation assessment. METHODS: Panel test results were forwarded to VIDRL, and results from 8 consecutive years were analyzed. We assessed the type of assays used and results achieved on the basis of the positive and negative interpretation of submitted results, by year and WHO region, for measles and rubella. RESULTS: Over time, there has been a noticeable increase in laboratory and WHO regional participation. For all panels, the proportion of laboratories in all WHO regions using the WHO-validated Dade Behring assay for measles and rubella-specific IgM antibodies ranged from 35% to 100% and 59% to 100%, respectively. For all regions and years, the proportion of laboratories obtaining a pass score ranged from 87% to 100% for measles and 93% to 100% for rubella. CONCLUSIONS: During 2001-2008, a large proportion of laboratories worldwide achieved and maintained a pass score for both measles and rubella. Measles and rubella proficiency testing is regarded as a major achievement for the WHO measles and rubella laboratory program.

Residual susceptibility to measles among young adults in Victoria, Australia following a national targeted measles-mumps-rubella vaccination campaign.

BACKGROUND: Past measles immunisation policies in Australia have resulted in a cohort of young adults who have been inadequately vaccinated, but who also have low levels of naturally acquired immunity because immunisation programs have decreased the circulation of wild virus. A measles-mumps-rubella (MMR) immunisation campaign aimed at addressing this susceptibility to measles among young adults was conducted in Australia in 2001-2. By estimating age-specific immunity, we aimed to evaluate the success of this campaign in the state of Victoria. METHODS: We conducted serosurveys after the young adult MMR program at state and national levels to estimate immunity among young adults born between 1968-82. We compared results of the Victorian (state) surveys with the Victorian component of the national surveys and compared both surveys with surveys conducted before the campaign. We also reviewed all laboratory confirmed measles cases in Victoria between 2000-4. RESULTS: The Victorian state serosurveys indicated no significant change in immunity of the cohort following the young adult MMR campaign (83.9% immune pre and 85.5% immune post campaign) while the Victorian component of the national serosurvey indicated a significant decline in immunity (91.0% to 84.2%; p = 0.006). Both surveys indicated about 15% susceptibility to measles among young Victorian adults after the campaign. Measles outbreaks in Victoria between 2000-4 confirmed the susceptibility of young adults. Outbreaks involved a median of 2.5 cases with a median age of 24.5 years. CONCLUSION: In Victoria, the young adult MMR program appears to have had no effect on residual susceptibility to measles among the 1968-82 birth cohort. Young adults in Victoria, as in other countries where past immunisation policies have left a residual susceptible cohort, represent a potential problem for the maintenance of measles elimination.

An outbreak investigation of congenital rubella syndrome in Solomon Islands, 2013.

INTRODUCTION: During May 2012, a rubella outbreak was declared in Solomon Islands. A suspected case of congenital rubella syndrome (CRS) was reported from one hospital 11 months later in 2013. This report describes the subsequent CRS investigation, findings and measures implemented. METHODS: Prospective CRS surveillance was conducted at the newborn nursery, paediatric and post-natal wards, and the paediatric cardiology and ophthalmology clinics of the study hospital from April to July 2013. Retrospective case finding by reviewing medical records was also undertaken to identify additional cases born between January and March 2013 for the same wards and clinics. Cases were identified using established World Health Organization case definitions for CRS. RESULTS: A total of 13 CRS cases were identified, including two laboratory-confirmed, four clinically confirmed and seven suspected cases. Five CRS cases were retrospectively identified, including four suspected and one clinically confirmed case. There was no geospatial clustering of residences. The mothers of the cases were aged between 20 and 36 years. Three of the six mothers available for interview recalled an acute illness with rash during the first trimester of pregnancy. DISCUSSION: Additional CRS cases not captured in this investigation are likely. Caring for CRS cases is a challenge in resource-poor settings. Rubella vaccination is safe and effective and can prevent the serious consequences of CRS. Well planned and funded vaccination activities can prevent future CRS cases.

Low seroprevalence of Murray Valley encephalitis and Kunjin viruses in an opportunistic serosurvey, Victoria 2011.

OBJECTIVE: To assess evidence of recent and past exposure to Murray Valley encephalitis virus (MVEV) and West Nile clade Kunjin virus (KUNV) in residents of the Murray Valley, Victoria, during a period of demonstrated activity of both viruses in early 2011. METHODS: A cross-sectional serosurvey using two convenience samples: stored serum specimens from a diagnostic laboratory in Mildura and blood donors from the Murray Valley region. Specimens were collected between April and July 2011. The main outcome measure was total antibody (IgM and IgG) reactivity against MVEV and KUNV measured using an enzyme immunoassay and defined as inhibiting binding of monoclonal antibodies by >50%, when compared to negative controls. Evidence of recent exposure was measured by the presence of MVEV and KUNV IgM detected by immunofluorescence. RESULTS: Of 1,115 specimens, 24 (2.2%, 95% CI 1.3-3.0%) were positive for MVEV total antibody, and all were negative for MVEV IgM. Of 1,116 specimens, 34 (3.1%, 95% CI 2.0-4.0%) were positive for KUNV total antibody, and 3 (0.27%) were KUNV IgM positive. Total antibody seroprevalence for both viruses was higher in residents born before 1974. CONCLUSIONS: Despite widespread MVEV and KUNV activity in early 2011, this study found that seroprevalence of antibodies to both viruses was low (<5%) and little evidence of recent exposure. IMPLICATIONS: Our findings suggest both viruses remain epizootic in the region and local residents remain potentially susceptible to future outbreaks.

Development of a real-time PCR assay to detect Treponema pallidum in clinical specimens and assessment of the assay's performance by comparison with serological testing.

The incidence of infectious syphilis in men who have sex with men and human immunodeficiency virus-infected patients has increased steadily in Victoria, Australia, since 2002. A TaqMan real-time PCR assay targeting the polA gene of Treponema pallidum (TpPCR) was developed. The analytical sensitivity of the assay was estimated to be 1.75 target copies per reaction. Initially, the assay was used to test a variety of specimens (excluding blood) from 598 patients. Of the 660 tests performed, positive PCR results were obtained for 55 patients. TpPCR results were compared with serology results for 301 patients being investigated for early syphilis. Of these patients, 41 were positive by both TpPCR and serology, 246 were negative by both TpPCR and serology, 4 were TpPCR positive but negative by serology, and 10 were TpPCR negative but showed evidence of recent or active infection by serology. Directly compared with serology, TpPCR showed 95% agreement, with a sensitivity of 80.39% and a specificity of 98.40%. Potential factors leading to the discrepant results are discussed. Concurrent serology on 21 patients with TpPCR-positive primary syphilitic lesions demonstrated that a panel of current syphilis serological tests has high sensitivity for the detection of early syphilis. We found that TpPCR is a useful addition to serology for the diagnosis of infectious syphilis. Direct comparison with other T. pallidum PCR assays will be required to fully assess the limitations of the assay.

Report on a workshop on the laboratory diagnosis of measles.

The Western Pacific Region of the World Health Organization (WHO) has declared a goal of regional measles elimination with a target date of 2012. To facilitate this goal, and in order to increase the familiarity of staff from some Western Pacific national laboratories with the technique of enzyme immunoassay (EIA) for the detection of anti-measles IgM, a WHO sponsored workshop was held at the Victorian Infectious Diseases Reference Laboratory (VIDRL) in May 2005. The workshop included participants from national laboratories in Cambodia and Lao People's Democratic Republic, and from five Pacific Island countries, Fiji, French Polynesia, Guam, New Caledonia and Papua New Guinea. An observer from Guam also participated. In addition to increasing the workshop participants' familiarity with the Dade Behring Enzygnost Anti-Measles Virus/IgM assay by hands-on involvement, the participants learnt to use dried venous blood spots for measles diagnosis. All participants successfully completed the practical component of the workshop. The workshop also included informal seminars on troubleshooting problems in EIA, good laboratory practice, data management in the laboratory and transporting infectious and diagnostic material. The EIA measles IgM calculation worksheets and the seminar on good laboratory practice were considered to be particularly useful by the majority of participants. The workshop was considered a success in terms of equipping participants with the knowledge and capacity to perform accurate measles IgM testing for both serum and dried venous blood spots. It also provided an introduction to proficiency testing.

Detection of measles virus-specific immunoglobulin M in dried venous blood samples by using a commercial enzyme immunoassay.

The optical densities (ODs) of 216 dried venous blood (DVB) samples submitted to the Victorian Infectious Diseases Reference Laboratory as part of enhanced measles surveillance were compared to the ODs of the corresponding serum samples collected at the same time. DVB samples, stored for up to 24 months at 4 degrees C, were tested by the Dade Behring Enzygnost Anti-Measles-Virus/IgM immunoassay. Elution and testing conditions were optimized with the use of spiked DVB samples. The assay showed an overall sensitivity of 90.2% and a specificity of 98.8% for DVB samples compared to the results for serum. When the results were analyzed according to the length of time that the DVB sample had been stored, the assay was 100% sensitive and 97% specific according to the ODs for those samples stored for less than 6 months compared to the results for the corresponding serum samples, with 97.7% agreement between the results for the two sample types. These results demonstrate the potential for the use of DVB samples for the diagnosis of measles in routine diagnostic laboratories.

A measles outbreak among young adults in Victoria, February 2001.

In January 2001 a 19-year-old Sydney resident, who had recently returned from India, visited Melbourne for 4 days while infectious with measles. A further 50 measles cases were subsequently identified, mainly among young adults. Thirty-eight cases (75%) were in the same birth cohort (born between 1968 and 1981). This cohort was identified as being at high risk of measles infection after a previous outbreak in Victoria involving 75 cases. These individuals are now aged between 20 and 33 years. A high proportion of cases, 22 (43%) were hospitalised after multiple visits to various healthcare providers. None of the cases had documentation of receiving the recommended number of doses of measles-containing vaccine for their age. Repeated outbreaks clearly demonstrate that young adults remain the group at highest risk of measles infection in Victoria. More targeted strategies for young adults and healthcare workers are required to better protect these groups against measles.

Dried venous blood samples for the detection and quantification of measles IgG using a commercial enzyme immunoassay.

OBJECTIVES: To determine whether samples of dried venous blood (DVB) were an acceptable alternative to serum for detecting measles-specific IgG in a commercial enzyme immunoassay. METHODS: Paired samples of serum and DVB were collected from 98 suspected cases of measles and 1153 schoolchildren in Victoria, Australia. All samples were tested using the Dade Behring Enzygnost Anti-Measles-Virus/IgG immunoassay. DVB samples were eluted using either the sample buffer provided with the kit or 5% dry milk powder in phosphate-buffered saline-Tween 20. FINDINGS: DVB samples eluted by sample buffer showed significantly better linear correlation to the serum samples than did DVB samples eluted in 5% dry milk in phosphate-buffered saline-Tween 20. To improve the comparability of serum and DVB samples an adjustment factor of 1.28 was applied to the optical density (OD) values of DVB. This adjustment also enabled quantification of the titre of measles IgG in mIU/ml directly from the OD value using the alpha calculation as specified by the kit protocol. For DVB samples stored for less than six months at 4 degrees C, the assay showed an overall sensitivity of 98.4% and a specificity of 97.2% compared with the results of serum testing. CONCLUSION: These results illustrate the potential for DVB samples to be widely used with the Dade Behring enzyme immunoassay system for determining the immunity of the individual and the population to the measles virus.

An outbreak of Legionnaires' disease at the Melbourne Aquarium, April 2000: investigation and case-control studies.

OBJECTIVE: To investigate the source and risk factors associated with Australia's largest outbreak of Legionnaires' disease. DESIGN AND SETTING: Epidemiological and environmental investigation of cases of Legionnaires' disease associated with visits to the Melbourne Aquarium; two case-control studies to confirm the outbreak source and to investigate risk factors for infection, respectively. PARTICIPANTS: Patients with confirmed Legionnaires' disease who visited the Melbourne Aquarium between 11 and 27 April 2000 were compared (i) with control participants from the community, and (ii) with control participants selected from other visitors to the Aquarium during this period. MAIN OUTCOME MEASURES: Risk factors for acquiring Legionnaires' disease. RESULTS: There were 125 confirmed cases of Legionnaires' disease caused by Legionella pneumophila serogroup 1 associated with the Aquarium; 76% of patients were hospitalised, and four (3.2%) died. The Aquarium cooling towers were contaminated with this organism. Visiting the Aquarium was significantly associated with disease (odds ratio [OR], 207; 95% CI, 73-630). The case-control study indicated that current smoking was a dose-dependent risk (multivariable OR for currently smoking > 70 cigarettes/week, 13.5; 95% CI, 5-36), but chronic illness and duration of exposure at the site were not significant risks. CONCLUSIONS: This study showed an association between poorly disinfected cooling towers at the Aquarium and Legionnaires' disease in visitors, and confirmed current smoking as a critical risk factor. The rapid response, publicity, and widespread urinary antigen testing may have resulted in detection of milder cases and contributed to the relatively low apparent morbidity and mortality rates. The urinary antigen test allows rapid identification of cases and may be changing the severity of illness recognised as Legionnaires' disease and altering who is considered at risk.