Delaying the COVID‐19 epidemic in Australia: evaluating the effectiveness of international travel bans

Objective: Following the outbreak of novel Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2), and the disease named COVID‐19, in Wuhan, China in late 2019, countries have implemented different interventions such as travel bans to slow the spread of this novel virus. This brief report evaluates the effect of travel bans imposed to prevent COVID‐19 importation in the Australian context. Methods: We developed a stochastic meta‐population model to capture the global dynamics and spread of COVID‐19. By adjusting our model to capture the travel bans imposed globally and in Australia, the predicted COVID‐19 cases imported to Australia were evaluated in comparison to observed imported cases. Results: Our modelling results closely aligned with observed cases in Australia and elsewhere. We observed a 79% reduction in COVID‐19 importation and a delay of the COVID‐19 outbreak in Australia by approximately one month. Further projection of COVID‐19 to May 2020 showed spread patterns depending on the basic reproduction number. Conclusion: Imposing the travel ban was effective in delaying widespread transmission of COVID‐19. However, strengthening of the domestic control measures is needed to prevent Australia from becoming another epicentre. Implications for public health: This report has shown the importance of border closure to pandemic control

Estimating the prevalence of latent tuberculosis in a low-incidence setting: Australia.

Migration is a key driver of tuberculosis (TB) in many low-incidence settings, with the majority of TB cases attributed to reactivation of latent TB (LTBI) acquired overseas. A greater understanding of LTBI risk in heterogeneous migrant populations would aid health planning. We aimed to estimate the LTBI prevalence and distribution among locally born and overseas-born Australians.Annual risks of TB infection estimates were applied to population cohorts (by country of birth, year of arrival and age) in Australian census data in 2006, 2011 and 2016.Both the absolute number and proportion of Australian residents with LTBI increased from 4.6% (interquartile range (IQR) 4.2-5.2%) in 2006 to 5.1% (IQR 4.7-5.5%) in 2016, due to the increasing proportion of the population born overseas (23.8% in 2006 to 28.3% in 2016). Of all residents estimated to have LTBI in 2016; 93.2% were overseas born, 21.6% were aged <35 years and 34.4% had migrated to Australia since 2007.The overall prevalence of LTBI in Australia is low. Some residents, particularly migrants from high-incidence settings, may have considerably higher risk of LTBI, and these findings allow for tailored public health interventions to reduce the risk and impact of future TB disease

Timing of Mycobacterium tuberculosis exposure explains variation in BCG effectiveness: A systematic review and meta-analysis

Rationale The heterogeneity in efficacy observed in studies of BCG vaccination is not fully explained by currently accepted hypotheses, such as latitudinal gradient in non-tuberculous mycobacteria exposure. Methods We updated previous systematic reviews of the effectiveness of BCG vaccination to 31 December 2020. We employed an identical search strategy and inclusion/exclusion criteria to these earlier reviews, but reclassified several studies, developed an alternative classification system and considered study demography, diagnostic approach and tuberculosis (TB)-related epidemiological context. Main results Of 21 included trials, those recruiting neonates and children aged under 5 were consistent in demonstrating considerable protection against TB for several years. Trials in high-burden settings with shorter follow-up also showed considerable protection, as did most trials in settings of declining burden with longer follow-up. However, the few trials performed in high-burden settings with longer follow-up showed no protection, sometimes with higher case rates in the vaccinated than the controls in the later follow-up period. Conclusions The most plausible explanatory hypothesis for these results is that BCG protects against TB that results from exposure shortly after vaccination. However, we found no evidence of protection when exposure occurs later from vaccination, which would be of greater importance in trials in high-burden settings with longer follow-up. In settings of declining burden, most exposure occurs shortly following vaccination and the sustained protection observed for many years thereafter represents continued protection against this early exposure. By contrast, in settings of continued intense transmission, initial protection subsequently declines with repeated exposure to Mycobacterium tuberculosis or other pathogens

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Transmission of SARS-CoV-2 in a primary school setting with and without public health measures using real-world contact data:A modelling study

BACKGROUND: Stringent public health measures have been shown to influence the transmission of SARS-CoV-2 within school environments. We investigated the potential transmission of SARS-CoV-2 in a primary school setting with and without public health measures, using fine-grained physical positioning traces captured before the COVID-19 pandemic. METHODS: Approximately 172.63 million position data from 98 students and six teachers from an open-plan primary school were used to predict a potential transmission of SARS-CoV-2 in primary school settings. We first estimated the daily average number of contacts of students and teachers with an infected individual during the incubation period. We then used the Reed-Frost model to estimate the probability of transmission per contact for the SARS-CoV-2 Alpha (B.1.1.7), Delta (B.1.617.2), and Omicron variant (B.1.1.529). Finally, we built a binomial distribution model to estimate the probability of onward transmission in schools with and without public health measures, including face masks and physical distancing. RESULTS: An infectious student would have 49.1 (95% confidence interval (CI) = 46.1-52.1) contacts with their peers and 2.00 (95% CI = 1.82-2.18) contacts with teachers per day. An infectious teacher would have 47.6 (95% CI = 45.1-50.0) contacts with students and 1.70 (95% CI = 1.48-1.92) contacts with their colleague teachers per day. While the probability of onward SARS-CoV-2 transmission was relatively low for the Alpha and Delta variants, the risk increased for the Omicron variant, especially in the absence of public health measures. Onward teacher-to-student transmission (88.9%, 95% CI = 88.6%-89.1%) and teacher-to-teacher SARS-CoV-2 transmission (98.4%, 95% CI = 98.5%-98.6%) were significantly higher for the Omicron variant without public health measures in place. CONCLUSIONS: Our findings illustrate that, despite a lower frequency of close contacts, teacher-to-teacher close contacts demonstrated a higher risk of transmission per contact of SARS-CoV-2 compared to student-to-student close contacts. This was especially significant with the Omicron variant, with onward transmission more likely occurring from teacher index cases than student index cases. Public health measures (eg, face masks and physical distance) seem essential in reducing the risk of onward transmission within school environments

Methods used in the spatial analysis of tuberculosis epidemiology: a systematic review

Background: Tuberculosis (TB) transmission often occurs within a household or community, leading to heterogeneous spatial patterns. However, apparent spatial clustering of TB could reflect ongoing transmission or co-location of risk factors and can vary considerably depending on the type of data available, the analysis methods employed and the dynamics of the underlying population. Thus, we aimed to review methodological approaches used in the spatial analysis of TB burden. Methods: We conducted a systematic literature search of spatial studies of TB published in English using Medline, Embase, PsycInfo, Scopus and Web of Science databases with no date restriction from inception to 15 February 2017. The protocol for this systematic review was prospectively registered with PROSPERO (CRD42016036655). Results: We identified 168 eligible studies with spatial methods used to describe the spatial distribution (n = 154), spatial clusters (n = 73), predictors of spatial patterns (n = 64), the role of congregate settings (n = 3) and the household (n = 2) on TB transmission. Molecular techniques combined with geospatial methods were used by 25 studies to compare the role of transmission to reactivation as a driver of TB spatial distribution, finding that geospatial hotspots are not necessarily areas of recent transmission. Almost all studies used notification data for spatial analysis (161 of 168), although none accounted for undetected cases. The most common data visualisation technique was notification rate mapping, and the use of smoothing techniques was uncommon. Spatial clusters were identified using a range of methods, with the most commonly employed being Kulldorff's spatial scan statistic followed by local Moran's I and Getis and Ord's local Gi(d) tests. In the 11 papers that compared two such methods using a single dataset, the clustering patterns identified were often inconsistent. Classical regression models that did not account for spatial dependence were commonly used to predict spatial TB risk. In all included studies, TB showed a heterogeneous spatial pattern at each geographic resolution level examined. Conclusions: A range of spatial analysis methodologies has been employed in divergent contexts, with all studies demonstrating significant heterogeneity in spatial TB distribution. Future studies are needed to define the optimal method for each context and should account for unreported cases when using notification data where possible. Future studies combining genotypic and geospatial techniques with epidemiologically linked cases have the potential to provide further insights and improve TB control

Understanding how Victoria, Australia gained control of its second COVID-19 wave

During 2020, Victoria was the Australian state hardest hit by COVID-19, but was successful in controlling its second wave through aggressive policy interventions. We calibrated a detailed compartmental model of Victoria's second wave to multiple geographically-structured epidemic time-series indicators. We achieved a good fit overall and for individual health services through a combination of time-varying processes, including case detection, population mobility, school closures, physical distancing and face covering usage. Estimates of the risk of death in those aged ≥75 and of hospitalisation were higher than international estimates, reflecting concentration of cases in high-risk settings. We estimated significant effects for each of the calibrated time-varying processes, with estimates for the individual-level effect of physical distancing of 37.4% (95%CrI 7.2-56.4%) and of face coverings of 45.9% (95%CrI 32.9-55.6%). That the multi-faceted interventions led to the dramatic reversal in the epidemic trajectory is supported by our results, with face coverings likely particularly important

Modelling the effect of short-course multidrug-resistant tuberculosis treatment in Karakalpakstan, Uzbekistan

Background: Multidrug-resistant tuberculosis (MDR-TB) is a major threat to global TB control. MDR-TB treatment regimens typically have a high pill burden, last 20 months or more and often lead to unsatisfactory outcomes. A 9-11 month regimen with seven antibiotics has shown high success rates among selected MDR-TB patients in different settings and is conditionally recommended by the World Health Organization. Methods: We construct a transmission-dynamic model of TB to estimate the likely impact of a shorter MDR-TB regimen when applied in a low HIV prevalence region of Uzbekistan (Karakalpakstan) with high rates of drug resistance, good access to diagnostics and a well-established community-based MDR-TB treatment programme providing treatment to around 400 patients. The model incorporates acquisition of additional drug resistance and incorrect regimen assignment. It is calibrated to local epidemiology and used to compare the impact of shorter treatment against four alternative programmatic interventions. Results: Based on empirical outcomes among MDR-TB patients and assuming no improvement in treatment success rates, the shorter regimen reduced MDR-TB incidence from 15.2 to 9.7 cases per 100,000 population per year and MDR-TB mortality from 3.0 to 1.7 deaths per 100,000 per year, achieving comparable or greater gains than the alternative interventions. No significant increase in the burden of higher levels of resistance was predicted. Effects are probably conservative given that the regimen is likely to improve success rates. Conclusions: In addition to benefits to individual patients, we find that shorter MDR-TB treatment regimens also have the potential to reduce transmission of resistant strains. These findings are in the epidemiological setting of treatment availability being an important bottleneck due to high numbers of patients being eligible for treatment, and may differ in other contexts. The high proportion of MDR-TB with additional antibiotic resistance simulated was not exacerbated by programmatic responses and greater gains may be possible in contexts where the regimen is more widely applicable

Tuberculosis in the Western Pacific Region: Estimating the burden of disease and return on investment 2020–2030 in four countries

Background: We aimed to estimate the disease burden of Tuberculosis (TB) and return on investment of TB care in selected high-burden countries of the Western Pacific Region (WPR) until 2030. Methods: We projected the TB epidemic in Viet Nam and Lao People's Democratic Republic (PDR) 2020–2030 using a mathematical model under various scenarios: counterfactual (no TB care); baseline (TB care continues at current levels); and 12 different diagnosis and treatment interventions. We retrieved previous modeling results for China and the Philippines. We pooled the new and existing information on incidence and deaths in the four countries, covering >80% of the TB burden in WPR. We estimated the return on investment of TB care and interventions in Viet Nam and Lao PDR using a Solow model. Findings: In the baseline scenario, TB incidence in the four countries decreased from 97•0/100,000/year (2019) to 90•1/100,000/year (2030), and TB deaths from 83,300/year (2019) to 71,100/year (2030). Active case finding (ACF) strategies (screening people not seeking care for respiratory symptoms) were the most effective single interventions. Return on investment (2020–2030) for TB care in Viet Nam and Lao PDR ranged US$4-US$49/dollar spent; additional interventions brought up to US$2•7/dollar spent. Interpretation: In the modeled countries, TB incidence will only modestly decrease without additional interventions. Interventions that include ACF can reduce TB burden but achieving the End TB incidence and mortality targets will be difficult without new transformational tools (e.g. vaccine, new diagnostic tools, shorter treatment). However, TB care, even at its current level, can bring a multiple-fold return on investment

Estimating the long-term effects of mass screening for latent and active tuberculosis in the Marshall Islands

BACKGROUND: Ambitious population-based screening programmes for latent and active tuberculosis (TB) were implemented in the Republic of the Marshall Islands in 2017 and 2018. METHODS: We used a transmission dynamic model of TB informed by local data to capture the Marshall Islands epidemic's historical dynamics. We then used the model to project the future epidemic trajectory following the active screening interventions, as well as considering a counterfactual scenario with no intervention. We also simulated future scenarios including periodic interventions similar to those previously implemented, to assess their ability to reach the End TB Strategy targets and TB pre-elimination in the Marshall Islands. RESULTS: The screening activities conducted in 2017 and 2018 were estimated to have reduced TB incidence and mortality by around one-third in 2020, and are predicted to achieve the End TB Strategy milestone of 50% incidence reduction by 2025 compared with 2015. Screening interventions had a considerably greater impact when latent TB screening and treatment were included, compared with active case finding alone. Such combined programmes implemented at the national level could achieve TB pre-elimination around 2040 if repeated every 2 years. CONCLUSIONS: Our model suggests that it would be possible to achieve TB pre-elimination by 2040 in the Marshall Islands through frequent repetition of the same interventions as those already implemented in the country. It also highlights the importance of including latent infection testing in active screening activities