The relative effectiveness of three and four doses of COVID-19 vaccine in Victoria, Australia: A data linkage study.

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) pandemic led to extensive vaccination campaigns worldwide, including in Australia. Immunity waning and the emergence of new viral variants pose challenges to the effectiveness of vaccines. Our study aimed to assess the relative effectiveness (rVE) of 3 and 4 compared with 2 doses of COVID-19 vaccine. The study focuses on the Victorian population, a majority of whom had no prior exposure to the virus before vaccination. METHODS: We used routinely collected data for the state of Victoria, Australia, to assess rVE during an Omicron-dominant period, 1 June 2022 to 1 March 2023. Immunisation, notifications, hospitalisations and mortality data for residents aged 65 years and older were linked for analysis. Cox proportional hazard regression was used to estimate the rVE against COVID-19 hospitalisation or death, accounting for key confounders with vaccination as a time-varying covariate. RESULTS: In 1,070,113 people 65 years or older who had received their second dose, a third and fourth dose of a COVID-19 vaccine significantly reduced the hazard of hospitalisation or death compared to two doses. rVE was highest within two weeks from administration at 40 % (95 % CI: 0 % to 64 %) and 66 % (95 % CI: 60 % to 71 %) for a third and fourth dose, respectively. Additional protection conferred by third and fourth doses waned over time from administration. CONCLUSIONS: Our findings underscore the need for additional vaccine doses and updated vaccine strategies. These findings have implications for public health advice and COVID-19 vaccine strategies. Further research and monitoring of vaccine effectiveness in real-world settings are warranted to inform ongoing pandemic response efforts.

Effectiveness of community-based oral antiviral treatments against severe COVID-19 outcomes in people 70 years and over in Victoria, Australia, 2022: an observational study.

Background: Oral Antiviral (OAV) COVID-19 treatments are widely used, but evidence for their effectiveness against the Omicron variant in higher risk, vaccinated individuals is limited. Methods: Retrospective study of two vaccinated cohorts of COVID-19 cases aged ≥70 years diagnosed during a BA.4/5 Omicron wave in Victoria, Australia. Cases received either nirmatrelvir-ritonavir or molnupiravir as their only treatment. Data linkage and logistic regression modelling was used to evaluate the association between treatment and death and hospitalisation and compared with no treatment. Findings: Of 38,933 individuals in the mortality study population, 13.5% (n = 5250) received nirmatrelvir-ritonavir, 51.3% (n = 19,962) received molnupiravir and 35.2% (n = 13,721) were untreated. Treatment was associated with a 57% (OR = 0.43, 95% CI 0.36-0.51) reduction in the odds of death, 73% (OR = 0.27, 95% CI 0.17-0.40) for nirmatrelvir-ritonavir and 55% (OR = 0.45, 95% CI 0.38-0.54) for molnupiravir. Treatment was associated with a 31% (OR = 0.69, 95% CI 0.55-0.86) reduction in the odds of hospitalisation, 40% (OR = 0.60, 95% CI 0.43-0.83) for nirmatrelvir-ritonavir and 29% (OR = 0.71, 95% CI 0.58-0.87) for molnupiravir. Cases treated within 1 day of diagnosis had a 61% reduction in the odds of death (OR = 0.39, 95% CI 0.33-0.46) compared with 33% reduction for a delay of 4 or more days (OR = 0.67, 95% CI 0.44-0.97). Interpretation: Treatment with both nirmatrelvir-ritonavir or molnupiravir was associated with a reduction in death and hospitalisation in vaccinated ≥70 years individuals during the Omicron era. Timely, equitable treatment with OAVs is an important tool in the fight against COVID-19. Funding: There was no funding for this study.

Detecting Mycobacterium tuberculosis Infection in Children Migrating to Australia.

In 2015, Australia updated premigration screening for tuberculosis (TB) disease in children 2-10 years of age to include testing for infection with Mycobacterium tuberculosis and enable detection of latent TB infection (LTBI). We analyzed TB screening results in children <15 years of age during November 2015-June 2017. We found 45,060 child applicants were tested with interferon-gamma release assay (IGRA) (57.7% of tests) or tuberculin skin test (TST) (42.3% of tests). A total of 21 cases of TB were diagnosed: 4 without IGRA or TST, 10 with positive IGRA or TST, and 7 with negative results. LTBI was detected in 3.3% (1,473/44,709) of children, for 30 applicants screened per LTBI case detected. LTBI-associated factors included increasing age, TB contact, origin from a higher TB prevalence region, and testing by TST. Detection of TB and LTBI benefit children, but the updated screening program's effect on TB in Australia is likely to be limited.

Tuberculosis in migrants to Australia: Outcomes of a national screening program.

BACKGROUND: Few low-incidence countries are on track to achieve the ambitious target of reaching TB pre-elimination by 2035. Australia is a high-income country with a low burden of TB, which is particularly concentrated in migrant populations. As part of Australia's migration program, permanent, provisional and humanitarian visa applicants are screened for TB, along with some applicants for temporary visas. METHODS: We calculated the prevalence of all forms of active TB and bacteriologically-confirmed TB among onshore and offshore applicants for visas to Australia from July 2014 to June 2017, and investigated associated risk factors using logistic regression. FINDINGS: Visa applicants were predominantly young adults from various Asian countries. Among 2,381,217 applicants, 1263 cases of active TB were diagnosed, including 852 cases of bacteriologically-confirmed TB. Overall TB prevalence was 53.0 per 100,000, corresponding to one TB diagnosis for every 1887 applicants screened. TB rates increased with age and were higher among humanitarian applicants and those previously treated for TB, although most cases occurred in applicants without these risk factors. TB prevalence by country of origin was similar to WHO estimates for some countries, but considerably lower for others. For several highly represented countries of origin, rates appear to have fallen relative to earlier comparable studies. INTERPRETATION: Prevalence of TB among visa applicants to Australia and the consequent risk to the Australian community appear to be declining and remain low. In this context, support for TB control programs overseas and preventive interventions are likely to have the greatest impact on domestic TB burden. FUNDING: No specific funding was received for this study. JMT is a recipient of an Early Career Fellowship from the Australian National Health and Medical Research Council (APP1142638).

Telemedicine in Resource-Limited Settings to Optimize Care for Multidrug-Resistant Tuberculosis.

The emergence and spread of multidrug-resistant tuberculosis (MDR-TB) poses a major threat to the global targets for TB control. In recent years, an evolving science and evidence base for MDR-TB has led to much needed changes in international guidelines promoting the use of newer TB drugs and regimens for MDR-TB, however, there remains a significant implementation gap. Due to the complexity of treating MDR-TB, management of cases is often supported by an expert multidisciplinary team, or clinical expert group. This service is often centralized, and may be delivered through a telemedicine platform. We have implemented a Web-based "store-and-forward" telemedicine service to optimize MDR-TB patient care in Daru, a remote and resource limited setting in Papua New Guinea (PNG). From April 2016 to February 2019, 237 cases were discussed using the service. This encompassed diagnostic (presumptive) and treatment cases, and more recently, support to the scale up of preventative therapy for latent TB infection. There were 75 cases in which the use of Bedaquiline was discussed or mentioned, with a high frequency of discussions occurring in the initial period (26 cases in the first 12 months), which has appeared to decrease as clinicians gained familiarity with use of the drug (15 cases in the last 12 months). This service has supported high quality clinical care and fostered collaboration between clinicians and technical experts in a shared learning environment.

Early Success With Retention in Care Among People Living With HIV at Decentralized ART Satellite Sites in Yangon, Myanmar, 2015-2016.

Introduction: Myanmar is one of the countries in the Asia-Pacific region hit hardest by the HIV epidemic that is concentrated among urban areas and key populations. In 2014, the National AIDS Programme (NAP) launched a new model of decentralized service delivery with the establishment ART satellite sites with care delivered by HIV peer workers. Methods: ART satellite sites are implemented by non-government organizations to service high burden HIV areas and populations that suffer stigma or find access to public sector services difficult. They provide continuity of HIV care from outreach testing, counseling, linkage to care, and retention in care. Anti-retroviral (ART) initiation occurs at health facilities by specialist physicians. We conducted a retrospective cohort study of people living with HIV (PLHIV) who were initiated on ART from 2015 to 2016 at five ART satellite sites in Yangon, Myanmar to assess outcomes and time from enrolment to ART initiation. Results: Of 1,339 PLHIV on ART treatment in 2015-16, 1,157 (89%) were retained, and 5% were lost from care and 5% reported dead, at the end of March 2018. Attrition rates (death and lost-to-follow-up) were found to be significantly associated with a CD4 count ≤ 50 cells/mm3 and having baseline weight ≤ 50 kg. Median time taken from enrolment to ART initiation was 1.9 months (interquartile range: 1.4-2.5). Conclusion: We report high rates of retention in care of PLHIV in a new model of ART satellite sties in Yangon, Myanmar after 3 years of follow-up. The delays identified in time taken from enrolment to ART initiation need to be explored further and addressed. This initial study supports continuation of plans to scale-up ART satellite sites in Myanmar. To optimize outcomes for patients and the program and accelerate progress to reduce HIV transmission and end the HIV epidemic, operational research needs to be embedded within the response.

Are death and loss to follow-up still high in people living with HIV on ART after national scale-up and earlier treatment initiation? A large cohort study in government hospital-based setting, Myanmar: 2013-2016.

SETTING: Myanmar National AIDS Program has had significant scale-up of services and changes in CD4 eligibility criterion for ART initiation from 2013 to 2016. This study assessed early death within 6 months and attrition (death and loss to follow-up, LTFU) after ART initiation and their associated factors. DESIGN: A retrospective cohort study on people living with HIV (PLHIV >15 year of age) enrolled at three specialist hospitals in Yangon from 1st June 2013 to 30th June 2016. Cox regression was used to calculate hazard ratios (HRs) of early death and attrition. RESULTS: Of 11,727 adults enrolled, 11,186 (95%) were initiated on ART, providing 15,964 person-years of follow-up. At baseline, median age was 36 years [IQR: 30-43], 58% were men and median CD4 count was 151 cells/mm3 (IQR: 54-310). There were 733(6%) early deaths, 961(9%) total deaths and 1371 (12%) LTFU during the study period. Independent risk factors for early death were older age (41-50 and ≥51 years) [aHR 1.38, 1.07-1.78 and 1.68, 1.21-2.34], male (1.84, 1.44-2.35), low weight (2.06, 1.64-2.59), bedridden, (3.81, 2.57-5.66) and CD4 count ≤ 50 cells/mm3 (6.83, 2.52-18.57). In addition to above factors, high attrition was associated with an abacavir-based regimen. CONCLUSION: Although there was a low rate of early deaths, patients were being diagnosed late and there was a high attrition rate from specialist hospitals. Concerted effort is required to increase early diagnosis and ART initiation, and strengthen community systems for HIV care to achieve ambitious goal of ending AIDS epidemic by 2030.

Evaluation of a tuberculosis active case finding project in peri-urban areas, Myanmar: 2014-2016.

OBJECTIVES: We assessed the effect of an active case finding (ACF) project on tuberculosis (TB) case notification and the yields from a household and neigbourhood intervention (screening contacts of historical index TB patients diagnosed >24months ago) and a community intervention (screening attendants of health education sessions/mobile clinics). DESIGN: Cross-sectional analysis of project records, township TB registers and annual TB reports. RESULTS: In the household and neigbourhood intervention, of 56,709 people screened, 1,076 were presumptive TB and 74 patients were treated for active TB with a screening yield of 0.1% and a yield from presumptive cases of 6.9%. In the community intervention, of 162,881 people screened, 4,497 were presumptive TB and 984 were treated for active TB with a screening yield of 0.6% and yield from presumptive cases of 21.9%. Of active TB cases, 94% were new, 89% were pulmonary, 44% were bacteriologically-confirmed and 5% had HIV. Case notification rates per 100,000 in project townships increased from 142 during baseline (2011-2013) to 148 during intervention (2014-2016) periods. CONCLUSIONS: The yield from household and neigbourhood intervention was lower than community intervention. This finding highlights reconsidering the strategy of screening of contacts from historical index cases. Strategies to reach high-risk groups should be explored for future ACF interventions to increase yield of TB.

Extending 'Contact Tracing' into the Community within a 50-Metre Radius of an Index Tuberculosis Patient Using Xpert MTB/RIF in Urban, Pakistan: Did It Increase Case Detection?

BACKGROUND: Currently, only 62% of incident tuberculosis (TB) cases are reported to the national programme in Pakistan. Several innovative interventions are being recommended to detect the remaining 'missed' TB cases. One such intervention involved expanding contact investigation to the community using the Xpert MTB/RIF test. METHODS: This was a before and after intervention study involving retrospective record review. Passive case finding and household contact investigation was routinely done in the pre-intervention period July 2011-June 2013. Four districts with a high concentration of slums were selected as intervention areas; Lahore, Rawalpindi, Faisalabad and Islamabad. Here, in the intervention period, July 2013-June 2015, contact investigation beyond household was conducted: all people staying within a radius of 50 metres (using Geographical Information System) from the household of smear positive TB patients were screened for tuberculosis. Those with presumptive TB were investigated using smear microscopy and the Xpert MTB/RIF test was performed on smear negative patients. All the diagnosed TB patients were linked to TB treatment and care. RESULTS: A total of 783043 contacts were screened for tuberculosis: 23741(3.0%) presumptive TB patients were identified of whom, 4710 (19.8%) all forms and 4084(17.2%) bacteriologically confirmed TB patients were detected. The contribution of Xpert MTB/RIF to bacteriologically confirmed TB patients was 7.6%. The yield among investigated presumptive child TB patients was 5.1%. The overall yield of all forms TB patients among investigated was 22.3% among household and 19.1% in close community. The intervention contributed an increase of case detection of bacteriologically confirmed tuberculosis by 6.8% and all forms TB patients by 7.9%. CONCLUSION: Community contact investigation beyond household not only detected additional TB patients but also increased TB case detection. However, further long term assessments and cost-effectiveness studies are required before national scale-up.

The Spectrum of Chromobacterium violaceum Infections from a Single Geographic Location.

Chromobacterium violaceum is a bacterium associated with soil and water exposure in tropical regions and causes rare and serious clinical infections that are often fatal. We reviewed the demographic and clinical details of 28 patients with C. violaceum detected over 15 years from 2000 to 2015, from the Top End of the Northern Territory. Of these patients, 18 had infections attributable toC. violaceum Patients with infections were more commonly male (55.6%), and in the 16- to 60-year (61.1%) age group. Skin and soft tissue infections (50%), predominantly involving the limbs, were the major clinical manifestation. Water, mud exposure, and trauma were all noted as precipitating circumstances and comorbidities were present in 61.1% of the patients with infections. Of the 28 patients, 10 (35.8%) had C. violaceum isolated as an incidental finding or as asymptomatic colonization; these 10 patients did not require or receive therapy for C. violaceum bacterial infections. There were no relapsing infections in this group.Chromobacterium violaceum remains a serious infection, with seven patients (25%) in our series requiring intensive care management. However, the mortality rate (7.1%) in our series was far lower than previously described. This case series of C. violaceum infections from a single geographic area provides additional information of the characteristics of infection with this pathogen.

Neonatal mortality in India's rural poor: Findings of a household survey and verbal autopsy study in Rajasthan, Bihar and Odisha.

In 2011, Save the Children India launched a project for the disadvantaged population of Rajasthan, Bihar and Odisha. As a baseline activity, neonatal deaths during January-December 2012 were investigated using modified verbal autopsy tool in six sub-district-level administrative units (blocks) adopting 30-cluster sample survey approach. Our study reported a total of 189 neonatal deaths of which 50% occurred at home and 39% happened on Day 1. About half of the deaths occurred in blocks from Bihar. High number of neonatal deaths belonged to households that were below poverty line (64%) and other disadvantaged classes (46%); among mothers who were illiterate (65%), <20 years of age (54%) and during their first-order births (36%). Birth asphyxia was a major cause of neonatal deaths across all blocks. These findings indicate need for easy and early access to transport services, specialized neonatal care and advocacy targeted towards increasing community awareness.

Hookworm in the Northern Territory: down but not out.

OBJECTIVES: To determine the prevalence and trends of human hookworm infection (HWI) in the Northern Territory over the past 10 years, and to assess the influence of the community children's deworming program (CCDP). DESIGN, PATIENTS AND SETTING: A retrospective observational analysis of consecutive microbiologically confirmed cases of HWI in patients diagnosed at NT government health care facilities and the main private laboratory servicing the NT between January 2002 and July 2012. MAIN OUTCOME MEASURES: Annual prevalence of HWI (2002-2011); age, sex, Indigenous status, residence, haemoglobin level and eosinophil count of patients with HWI; and proportion of patients within the CCDP target population (children aged 6 months to 16 years, who should receive 6-monthly albendazole). RESULTS: From 64 691 faecal samples examined during the study period, hookworm was detected in 112 patients. There was a downward trend in the annual prevalence of HWI, falling from 14.0 cases per 100 000 population (95% CI, 8.8-19.2) in 2002 to 2.2 per 100 000 population (95% CI, 0.3-4.1) in 2011. Only 16 patients (14.3%) fell within the CCDP target population. Seventy-one patients (63.4%) were living in remote communities, and 94 (84.7%) were recorded as Indigenous Australians. CONCLUSIONS: The prevalence of HWI in the NT reduced over the 10-2013 period. HWI predominantly occurs in individuals outside the CCDP target population. Our data support continuation of the CCDP in conjunction with improvements in housing, health hardware and health promotion. Continued use of albendazole in individuals beyond the CCDP may facilitate the eventual eradication of HWI from the NT.