Flutracking: Weekly online community-based surveillance of influenza-like illness in Australia, 2017 Annual Report

Flutracking participation continued to grow, with a total of 33,947 participants in 2017 (a 9.5% increase from 2016). The majority of participants completed their survey within 24 hours of the email being sent (average 72.5% responses received in 24 hours). Overall, the rate of influenza-like illness (ILI) in 2017 was higher and remained elevated for a longer period compared to previous years except for the 2009 pandemic. Flutracking placed the severity and magnitude of the influenza season into historical context. Following the highest number of laboratory-notified influenza cases on record (2.8-fold increase from 2016), Flutracking data demonstrated a large increase in the percent of participants with fever and cough that were tested for influenza (2.9% to 5.0% for 2016 and 2017 respectively) and thus determined it was increased laboratory testing that contributed to the substantial increase in influenza notifications. Flutracking participants with fever and cough that were tested for influenza have increased each year from 2013 to 2017 at the national level, with a large increase from 2016 (2.9%) to 2017 (5.0%). The peak weekly fever and cough attack rate occurred in mid-August, with 4.1% ILI in the unvaccinated, compared to 3.1% in vaccinated Flutrackers. In the peak four weeks of ILI, 12.3% of participants experienced an episode of fever and cough. Divergence between the vaccinated and unvaccinated participants' ILI percentages was highest during the week ending 6 August 2017 (4.1% in the unvaccinated group and 2.7% in the vaccinated group). The timing of the ILI peak amongst Flutracking participants was consistent with peak notifications of laboratory-confirmed influenza.

Impact of a Family Clinic Day intervention on paediatric and adolescent appointment adherence and retention in antiretroviral therapy: A cluster randomized controlled trial in Uganda.

BACKGROUND: In 2013, Uganda adopted a test-and-treat policy for HIV patients 15 years or younger. Low retention rates among paediatric and adolescent antiretroviral therapy (ART) initiates could severely limit the impact of this new policy. This evaluation tested the impact of a differentiated care model called Family Clinic Day (FCD), a family-centered appointment scheduling and health education intervention on patient retention and adherence to monthly appointment scheduling. METHODS: We conducted a cluster randomized controlled trial, from October 2014 to March 2015. Forty-six facilities were stratified by implementing partner and facility type and randomly assigned to the control or intervention arm. Primary outcomes included the proportion of patients retained in care at 6 months and the proportion adherent to their appointment schedule at last study period scheduled visit. Data collection occurred retrospectively in May 2015. Six patient focus group discussions and 17 health workers interviews were conducted to understand perspectives on FCD successes and challenges. RESULTS: A total of 4,715 paediatric and adolescent patient records were collected, of which 2,679 (n = 1,319 from 23 control facilities and 1,360 from 23 intervention facilities) were eligible for inclusion. The FCD did not improve retention (aOR 1.11; 90% CI 0.63-1.97, p = 0.75), but was associated with improved adherence to last appointment schedule (aOR 1.64; 90% CI 1.27-2.11, p<0.001). Qualitative findings suggested that FCD patients benefited from health education and increased psychosocial support. CONCLUSION: FCD scale-up in Uganda may be an effective differentiated care model to ensure patient adherence to ART clinic appointment schedules, a key aspect necessary for viral load suppression. Patient health outcomes may also benefit following an increase in knowledge based on health education, and peer support. Broad challenges facing ART clinics, such as under-staffing and poor filing systems, should be addressed in order to improve patient care.

Impact of the 23-valent pneumococcal polysaccharide vaccination in pregnancy against infant acute lower respiratory infections in the Northern Territory of Australia.

BACKGROUND: Indigenous children in Australia's Northern Territory are densely colonised with the pneumococcus within weeks of birth antecedent to a high prevalence of acute lower respiratory infection (ALRI). We assessed the impact of the 23-valent pneumococcal polysaccharide vaccine (23vPPV) in pregnancy against infant ALRI in this setting. METHODS: In an open label, allocation concealed, outcome-assessor blinded, randomised controlled trial conducted in the Northern Territory of Australia, healthy Indigenous women aged 17-39 years were randomised to receive the 23vPPV during pregnancy (n = 75; 30-36 weeks gestation), at birth (n = 75), or at 7 months post-partum (n = 77). Randomisation was stratified by community of residence. In a secondary analysis, we compared the incidence of ALRI hospitalisations and ALRI clinic presentations (ascertained from electronic medical records) among infants of pregnancy vaccinees versus infants of mothers not vaccinated in pregnancy (controls) in the first year of life. RESULTS: ALRI hospitalisation incidence was 12.3 per 100 child-years among infants of pregnancy vaccinees compared with 15.8 per 100 child-years among controls (hazard ratio (HR) 0.77, 95%CI 0.29-2.03). ALRI hospitalisations were more common among remote compared to urban infants (27.7 versus 8.6 per 100 child-years). Stratification by dwelling highlighted a differential antenatal vaccine effect against ALRI hospitalisations (urban HR 2.45, 95%CI 0.60-9.99; remote HR 0.21, 95%CI 0.04-1.08). ALRI clinic presentation incidence was similar among infants of pregnancy vaccinees and controls. CONCLUSIONS: In this small study, antenatal 23vPPV vaccination was not associated with a reduced incidence of infant ALRI hospitalisations or ALRI clinic presentations during the first year of life. A potential differential effect between urban and remote settings warrants further investigation. TRIAL REGISTRATION: PneuMum; ClinicalTrials.gov NCT00714064.

Repeat pneumococcal polysaccharide vaccination does not impair functional immune responses among Indigenous Australians.

Indigenous Australians experience one of the highest rates of pneumococcal disease globally. In the Northern Territory of Australia, a unique government-funded vaccination schedule for Indigenous Australian adults comprising multiple lifetime doses of the pneumococcal polysaccharide vaccine is currently implemented. Despite this programme, rates of pneumococcal disease do not appear to be declining, with concerns raised over the potential for immune hyporesponse associated with the use of this vaccine. We undertook a study to examine the immunogenicity and immune function of a single and repeat pneumococcal polysaccharide vaccination among Indigenous adults compared to non-Indigenous adults. Our results found that immune function, as measured by opsonophagocytic and memory B-cell responses, were similar between the Indigenous groups but lower for some serotypes in comparison with the non-Indigenous group. This is the first study to document the immunogenicity following repeat 23-valent pneumococcal polysaccharide vaccine administration among Indigenous Australian adults, and reinforces the continued need for optimal pneumococcal vaccination programmes among high-risk populations.

Repeat pneumococcal polysaccharide vaccine in Indigenous Australian adults is associated with decreased immune responsiveness.

BACKGROUND: Indigenous adults residing in the Northern Territory of Australia experience elevated rates of invasive pneumococcal disease despite the routine use of 23-valent pneumococcal polysaccharide vaccine (23vPPV). We hypothesised that the limited protection from 23vPPV may be due to hyporesponsiveness as a result of vaccine failure from repeated vaccination. To explore this possibility, we evaluated the immune response to a first and second dose of 23vPPV in Indigenous adults and a first dose of 23vPPV in non-Indigenous adults. METHODS: Serotype-specific IgG was measured by ELISA for all 23 vaccine serotypes at baseline and at one month post-vaccination. Individuals were considered to have an adequate immune response if paired sera demonstrated either: a four-fold rise in antibody concentration; a two-fold rise if the post vaccination antibody was >1.3µg/ml but <4.0µg/ml; or a post-vaccination antibody concentration >4.0µg/ml for at least half of the serotypes tested (12/23). Our per-protocol analysis included the comparison of outcomes for three groups: Indigenous adults receiving a second 23vPPV dose (N=20) and Indigenous (N=60) and non-Indigenous adults (N=25) receiving their first 23vPPV dose. RESULTS: All non-Indigenous adults receiving a first dose of 23vPPV mounted an adequate immune response (25/25). There was no significant difference in the proportion of individuals with an adequate response using our definition (primary endpoint), with 88% of Indigenous adults mounted an adequate response following first dose 23vPPV (53/60) compared to 70% having an adequate response following a second dose of 23vPPV (14/20; p=0.05). The risk difference between Indigenous participants receiving first dose compared to non-Indigenous participants receiving first dose was significant when comparing a response threshold of at least 70% (-27%, 95% CI: -43% to -11%; p=0.01) and 90% (-38%, 95% CI: -60% to -16%; p=0.006) of serotypes with a positive response. CONCLUSION: Indigenous participants demonstrated a poorer response to a first dose 23vPPV compared to their non-Indigenous counterparts, with lower IgG following a second 23vPPV dose. These findings highlight the critical need to evaluate the efficacy of future pneumococcal vaccine programs in the Australian Indigenous populations that recommend repeated doses of 23vPPV.

Quality improvement intervention to increase adherence to ART prescription policy at HIV treatment clinics in Lusaka, Zambia: A cluster randomized trial.

INTRODUCTION: In urban areas, crowded HIV treatment facilities with long patient wait times can deter patients from attending their clinical appointments and picking up their medications, ultimately disrupting patient care and compromising patient retention and adherence. METHODS: Formative research at eight facilities in Lusaka revealed that only 46% of stable HIV treatment patients were receiving a three-month refill supply of antiretroviral drugs, despite it being national policy for stable adult patients. We designed a quality improvement intervention to improve the operationalization of this policy. We conducted a cluster-randomized controlled trial in sixteen facilities in Lusaka with the primary objective of examining the intervention's impact on the proportion of stable patients receiving three-month refills. The secondary objective was examining whether the quality improvement intervention reduced facility congestion measured through two proxy indicators: daily volume of clinic visits and average clinic wait times for services. RESULTS: The mean change in the proportion of three-month refills among control facilities from baseline to endline was 10% (from 38% to 48%), compared to a 25% mean change (an increase from 44% to 69%) among intervention facilities. This represents a significant 15% mean difference (95% CI: 2%-29%; P = 0.03) in the change in proportion of patients receiving three-month refills. On average, control facilities had 15 more visits per day in the endline than in the baseline, while intervention facilities had 20 fewer visits per day in endline than in baseline, a mean difference of 35 fewer visits per day (P = 0.1). The change in the mean facility total wait time for intervention facilities dropped 19 minutes between baseline and endline when compared to control facilities (95% CI: -10.2-48.5; P = 0.2). CONCLUSION: A more patient-centred service delivery schedule of three-month prescription refills for stable patients is viable. We encourage the expansion of this sustainable intervention in Zambia's urban clinics.

Influenza vaccination coverage among pregnant Indigenous women in the Northern Territory of Australia.

Pregnant Aboriginal and Torres Strait Islander women are at particular risk of severe illness and high attack rates of influenza infection. In Australia, routine seasonal influenza vaccination is currently strongly recommended for all pregnant women and women planning pregnancy, and is provided free of charge for all pregnant women. We sought to determine vaccination coverage, describe the trends and characteristics associated with influenza vaccine uptake and determine the validity of self-reported influenza vaccination in a population of Indigenous pregnant women who were participants of a vaccine trial, prior to and during the 2009 H1N1 influenza pandemic. Vaccine coverage over the study period was 16% (35/214), increasing from 2.2% (3/136) in the period preceding the pandemic (2006-2009) to 41% (32/78) in the intra-pandemic period (2009-2010). Self-report was not a reliable estimate of verified vaccination status in the pre-pandemic period (κ=0.38) but was reliable in the intra-pandemic period (κ=0.91). None of the socio-demographic characteristics that we examined were associated with vaccine uptake. Whilst the increase in maternal influenza coverage rates are encouraging and indicate a willingness of pregnant Indigenous women to be vaccinated, the majority of women remained unvaccinated. Activities to improve influenza vaccination coverage for Indigenous pregnant women and monitor vaccine uptake remain a priority. Commun Dis Intell 2016;40(3):E340-E346.

PneuMum: Impact from a randomised controlled trial of maternal 23-valent pneumococcal polysaccharide vaccination on middle ear disease amongst Indigenous infants, Northern Territory, Australia.

BACKGROUND: We assessed maternal 23-valent pneumococcal polysaccharide (23vPPV) vaccine efficacy (VE) against middle ear disease and pneumococcal carriage amongst Australian Indigenous infants. METHODS: In an open label, allocation concealed, outcome-assessor blinded, community stratified, randomised controlled trial, healthy pregnant Indigenous women aged 17-39 years in the Northern Territory of Australia received the 23vPPV (1:1:1) at: 30-36 weeks gestation, birth, or were unvaccinated (ClinicalTrials.gov NCT00714064). Co-primary outcomes were the point prevalences of infant middle ear disease and 23vPPV-type carriage at age 7 months. RESULTS: The consent rate was 50% (313/632). Among 227 eligible participants randomised, retention rates were 86% (66/77) controls; 89% (67/75) pregnancy vaccinees; 88% (66/75) birth vaccinees. At infant age 7 months, ear disease prevalence was: 71% (47/66) controls, 63% (42/67) pregnancy vaccinees, 76% (50/66) birth vaccinees; and 23vPPV-type carriage was: 26% (17/66) controls, 18% (12/67) pregnancy vaccinees, 18% (12/66) birth vaccinees. For pregnancy vaccinees, VE was 12% (95% CI -12% to 31%) against infant ear disease and 30% (95% CI -34% to 64%) against 23vPPV-type carriage. In a post-hoc analysis, VE against infant ear disease concurrent with carriage of 23vPPV or related types was 51% (95% CI -2% to 76%). There were no serious adverse effects following receipt of the 23vPPV in pregnancy or at birth. CONCLUSIONS: In a high risk population, our study was unable to demonstrate efficacy of 23vPPV in pregnancy against the co-primary outcomes of either all-cause infant ear disease or 23vPPV-type nasopharyngeal carriage at age 7 months. Efficacy against ear disease concurrent with carriage of vaccine-related serotypes (a more specific outcome) suggests 23vPPV in pregnancy may complement childhood pneumococcal vaccination programs.

A Cluster Randomised Trial on the Impact of Integrating Early Infant HIV Diagnosis with the Expanded Programme on Immunization on Immunization and HIV Testing Rates in Rural Health Facilities in Southern Zambia.

BACKGROUND: We assessed the integration of early infant HIV diagnosis with the expanded programme for immunization in a rural Zambian setting with the aim of determining whether infant and postpartum maternal HIV testing rates would increase without harming immunization uptake. METHODS: In an unblinded, location stratified, cluster randomised controlled trial, 60 facilities in Zambia's Southern Province were equally allocated to a control group, Simple Intervention group that received a sensitization meeting and the resupply of HIV testing commodities in the event of a stock-out, and a Comprehensive Intervention group that received the Simple Intervention as well as on-site operational support to facilitate the integration of HIV testing services with EPI. FINDINGS: The average change in number of first dose diphtheria, pertussis, and tetanus vaccine (DPT1) provided per month, per facility was approximately 0.86 doses higher [90% confidence interval (CI) -1.40, 3.12] in Comprehensive Intervention facilities compared to the combined average change in the Simple Intervention and control facilities. The interventions resulted in a 16.6% [90% CI: -7%, 46%, P-value = 0.26] and 10% [90% CI: -10%, 36%, P-value = 0.43] greater change in average monthly infant DBS testing compared to control for the Simple and Comprehensive facilities respectively. We also found 15.76 (90% CI: 7.12, 24.41, P-value < 0.01) and 10.93 (90% CI: 1.52, 20.33, P-value = 0.06) additional total maternal re-tests over baseline for the Simple and Comprehensive Facilities respectively. CONCLUSIONS: This study provides strong evidence to support Zambia's policy of integration of HIV testing and EPI services. Actions in line with the interventions, including HIV testing material supply reinforcement, can increase HIV testing rates without harming immunization uptake. In response, Zambia's Ministry of Health issued a memo to remind health facilities to provide HIV testing at under-five clinics and to include under-five HIV testing as part of district performance assessments. TRIAL REGISTRATION: ClinicalTrials.gov REGISTRATION NUMBER: NCT02479659.

Vaxtracker: Active on-line surveillance for adverse events following inactivated influenza vaccine in children.

Vaxtracker is a web based survey for active post marketing surveillance of Adverse Events Following Immunisation. It is designed to efficiently monitor vaccine safety of new vaccines by early signal detection of serious adverse events. The Vaxtracker system automates contact with the parents or carers of immunised children by email and/or sms message to their smart phone. A hyperlink on the email and text messages links to a web based survey exploring adverse events following the immunisation. The Vaxtracker concept was developed during 2011 (n=21), and piloted during the 2012 (n=200) and 2013 (n=477) influenza seasons for children receiving inactivated influenza vaccine (IIV) in the Hunter New England Local Health District, New South Wales, Australia. Survey results were reviewed by surveillance staff to detect any safety signals and compare adverse event frequencies among the different influenza vaccines administered. In 2012, 57% (n=113) of the 200 participants responded to the online survey and 61% (290/477) in 2013. Vaxtracker appears to be an effective method for actively monitoring adverse events following influenza vaccination in children.

Intussusception after monovalent human rotavirus vaccine in Australia: severity and comparison of using healthcare database records versus case confirmation to assess risk.

BACKGROUND: Surveillance for intussusception (IS) has been recommended in countries using rotavirus vaccine, but can be resource intensive. There is little data about the relative severity of rotavirus vaccine-associated IS compared with other IS cases. We collected detailed clinical data on all cases to evaluate the validity of ICD coding for IS in routinely collected data and case severity. METHODS: Hospitalizations and emergency department presentations coded as IS in infants aged <12 months from July 1, 2007, to June 30, 2010, were classified using Brighton criteria by case note review. We used self-controlled case series analysis to estimate IS risk after vaccination for all and only Brighton level 1 cases. RESULTS: Of 179 unique episodes coded as IS, 110 (61%) met Brighton level 1 criteria; self-controlled case series analysis found a relative incidence of IS in days 1-7 after the first dose of RV1 of 11.1 (95% confidence interval: 2.6-48.0). When all coded episodes of IS were included, relative incidence was 4.0 (95% confidence interval: 1.3-12.7). The proportion of Brighton 1 cases requiring surgery was 39% for those within 21 days of vaccine receipt and 34% for others (P = 0.67). CONCLUSIONS: Using ICD-coded cases without individual confirmation yielded a lower point estimate of risk for IS post rotavirus vaccination; however, the risk remained statistically compatible with that for chart confirmed cases only. Analysis using healthcare databases to evaluate risk of IS if conducted without case confirmation may be insufficient to confirm a low-level risk. IS episodes after vaccination were not more severe.

Vaccines for preventing pneumococcal infection in adults.

BACKGROUND: Diseases caused by Streptococcus pneumoniae (S. pneumoniae) continue to cause substantial morbidity and mortality globally. Whilst pneumococcal polysaccharide vaccines (PPVs) have the potential to prevent disease and death, the degree of protection afforded against various clinical endpoints and within different populations is uncertain. OBJECTIVES: To assess the efficacy and effectiveness of PPVs in preventing pneumococcal disease or death in adults. We did not assess adverse events. SEARCH METHODS: We searched CENTRAL 2012, Issue 6, MEDLINE (January 1966 to June Week 2, 2012) and EMBASE (1974 to June 2012). SELECTION CRITERIA: We considered randomised controlled trials (RCTs) in adults, provided the study outcome met the definition of the outcome considered in the review. We also considered non-RCTs in adults, where the study assessed PPV effectiveness against culture-confirmed invasive pneumococcal disease (IPD), provided the study controlled for important confounding factors. DATA COLLECTION AND ANALYSIS: Two review authors assessed trial quality of RCTs and three review authors extracted the data. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using a random-effects model. Two review authors assessed study quality and extracted data for non-RCTs. We calculated ORs and 95% CIs using a random-effects model following the conversion of each study outcome to a log OR and standard error (SE). MAIN RESULTS: Twenty-five studies met our inclusion criteria (18 RCTs involving 64,852 participants and seven non-RCTs involving 62,294 participants). Meta-analysis of the RCTs found strong evidence of PPV efficacy against IPD with no statistical heterogeneity (OR 0.26, 95% CI 0.14 to 0.45; random-effects model, I(2) statistic = 0%). There was efficacy against all-cause pneumonia in low-income (OR 0.54, 95% CI 0.43 to 0.67, I(2) statistic = 19%) but not high-income countries in either the general population (OR 0.71, 95% CI 0.45 to 1.12, I(2) statistic = 93%) or in adults with chronic illness (OR 0.93, 95% CI 0.73 to 1.19, I(2) statistic = 10%). PPV was not associated with substantial reductions in all-cause mortality (OR 0.90, 95% CI 0.74 to 1.09; random-effects model, I(2) statistic = 69%). Vaccine efficacy against primary outcomes appeared poorer in adults with chronic illness. Non-RCTs provided evidence for protection against IPD in populations for whom the vaccine is currently utilised (OR 0.48, 95% CI 0.37 to 0.61; random-effects model, I(2) statistic = 31%). This review did not consider adverse events as it was outside the scope of the review. AUTHORS' CONCLUSIONS: This meta-analysis provides evidence supporting the recommendation for PPV to prevent IPD in adults. The evidence from RCTs is less clear with respect to adults with chronic illness. This might be because of lack of effect or lack of power in the studies. The meta-analysis does not provide evidence to support the routine use of PPV to prevent all-cause pneumonia or mortality.

Probable psittacosis outbreak linked to wild birds.

In autumn 2002, an outbreak of probable psittacosis occurred among residents of the Blue Mountains district, Australia. We conducted a case-control study to determine independent risk factors for psittacosis by comparing exposures between hospitalized patients and other residents selected randomly from the telephone directory. Of the 59 case-patients with laboratory results supportive of psittacosis, 48 participated in a case-control study with 310 controls. Independent risk factors were residence in the upper Blue Mountains (odds ratio [OR] 15.2, 95% confidence interval [CI] 5.6-41.7), age of 50-64 years (OR 3.9, 95% CI 1.5-10.5), direct contact with wild birds (OR 7.4, 95% CI 2.5-22), and mowing lawns without a grass catcher (OR 3.2, 95% CI 1.3-8.0). Protective equipment is recommended for residents in areas frequented by free-ranging birds if contact with birds and their droppings is likely when performing outdoor activities such as lawn mowing.