Melbourne School of Population and Global Health - Research Publications

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Spatio-temporal spread of artemisinin resistance in Southeast Asia

Flegg, JA ; Kandanaarachchi, S ; Guerin, PJ ; Dondorp, AM ; Nosten, FH ; Otienoburu, SD ; Golding, N ; Kouyos, RD (PUBLIC LIBRARY SCIENCE, 2024-04)

Current malaria elimination targets must withstand a colossal challenge-resistance to the current gold standard antimalarial drug, namely artemisinin derivatives. If artemisinin resistance significantly expands to Africa or India, cases and malaria-related deaths are set to increase substantially. Spatial information on the changing levels of artemisinin resistance in Southeast Asia is therefore critical for health organisations to prioritise malaria control measures, but available data on artemisinin resistance are sparse. We use a comprehensive database from the WorldWide Antimalarial Resistance Network on the prevalence of non-synonymous mutations in the Kelch 13 (K13) gene, which are known to be associated with artemisinin resistance, and a Bayesian geostatistical model to produce spatio-temporal predictions of artemisinin resistance. Our maps of estimated prevalence show an expansion of the K13 mutation across the Greater Mekong Subregion from 2000 to 2022. Moreover, the period between 2010 and 2015 demonstrated the most spatial change across the region. Our model and maps provide important insights into the spatial and temporal trends of artemisinin resistance in a way that is not possible using data alone, thereby enabling improved spatial decision support systems on an unprecedented fine-scale spatial resolution. By predicting for the first time spatio-temporal patterns and extents of artemisinin resistance at the subcontinent level, this study provides critical information for supporting malaria elimination goals in Southeast Asia.
Trajectories of job insecurity and the probability of poorer mental health among prime working-age Australian women and men.

Ervin, J ; LaMontagne, AD ; Taouk, Y ; King, T (Elsevier BV, 2024-05)

Precarious and insecure employment arrangements are important social determinants of health. Prior evidence has consistently found perceived job insecurity to be associated with poorer mental health. Nonetheless, several key under-researched areas remain in the existing evidence base. This study addresses some of these gaps by examining trajectories of job (in)security and assessing the effect of various persistent job security trajectories on subsequent mental health of both men and women. Utilising 15 waves of data from the Household, Income and Labour Dynamics in Australia (HILDA) Survey, we employed group-based trajectory modelling (GBTM) to identify trajectories of job (in)security through men and women's prime working years (from baseline age of 28-38yrs to 41-51yrs) across 14 years (waves 5-18), before subsequently examining the associations between these estimated trajectories and mental health at wave 19 (aged 42-52yrs). We identified four distinct trajectories of job (in)security for both men and women: persistently secure, becoming more secure, becoming less secure, and persistently insecure. Examining the association between these trajectories and mental health, we found that chronic exposure to any amount of persistent job insecurity (improving, worsening or persistently insecure) is detrimental to the mental health of both men and women. Furthermore, a somewhat incremental or dose dependant effect was found, with persistent job insecurity associated with the largest declines in mental health scores. Given mental health disorders are a substantial cause of disability globally, our study provides evidence that developing policy and practice interventions to reduce job insecurity (as an increasingly recognised and highly modifiable social determinant of mental health) has considerable potential to enact positive population health improvements.
Point-of-care testing and treatment of sexually transmitted and genital infections to improve birth outcomes in high-burden, low-resource settings (WANTAIM): a pragmatic cluster randomised crossover trial in Papua New Guinea.

Riddell, MA ; Vallely, LM ; Mengi, A ; Badman, SG ; Low, N ; Wand, H ; Bolnga, JW ; Babona, D ; Mola, GDL ; Wiseman, V ; Kelly-Hanku, A ; Homer, CSE ; Morgan, C ; Luchters, S ; Whiley, DM ; Robinson, LJ ; Au, L ; Pukai-Gani, I ; Laman, M ; Kariwiga, G ; Toliman, PJ ; Batura, N ; Tabrizi, SN ; Rogerson, SJ ; Garland, SM ; Guy, RJ ; Peeling, RW ; Pomat, WS ; Kaldor, JM ; Vallely, AJB ; WANTAIM study group, (Elsevier BV, 2024-04)

BACKGROUND: Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and bacterial vaginosis have been associated with adverse maternal and perinatal outcomes, but there is conflicting evidence on the benefits of antenatal screening and treatment for these conditions. We aimed to determine the effect of antenatal point-of-care testing and immediate treatment of C trachomatis, N gonorrhoeae, T vaginalis, and bacterial vaginosis on preterm birth, low birthweight, and other adverse maternal and perinatal outcomes compared with current standard of care, which included symptom-based treatment without laboratory confirmation. METHODS: In this pragmatic cluster randomised crossover trial, we enrolled women (aged ≥16 years) attending an antenatal clinic at 26 weeks' gestation or earlier (confirmed by obstetric ultrasound), living within approximately 1 h drive of a study clinic, and able to provide reliable contact details at ten primary health facilities and their catchment communities (clusters) in Papua New Guinea. Clusters were randomly allocated 1:1 to receive either the intervention or control (standard care) in the first phase of the trial. Following an interval (washout period) of 2-3 months at the end of the first phase, each cluster crossed over to the other group. Randomisation was stratified by province. Individual participants were informed about trial group allocation only after completing informed consent procedures. The primary outcome was a composite of preterm birth (livebirth before 37 weeks' gestation), low birthweight (<2500 g), or both, analysed according to the intention-to-treat population. This study is registered with ISRCTN Registry, ISRCTN37134032, and is completed. FINDINGS: Between July 26, 2017, and Aug 30, 2021, 4526 women were enrolled (2210 [63·3%] of 3492 women in the intervention group and 2316 [62·8%] of 3687 in the control group). Primary outcome data were available for 4297 (94·9%) newborn babies of 4526 women. The proportion of preterm birth, low birthweight, or both, in the intervention group, expressed as the mean of crude proportions across clusters, was 18·8% (SD 4·7%) compared with 17·8% in the control group (risk ratio [RR] 1·06, 95% CI 0·78-1·42; p=0·67). There were 1052 serious adverse events reported (566 in the intervention group and 486 in the control group) among 929 trial participants, and no differences by trial group. INTERPRETATION: Point-of-care testing and treatment of C trachomatis, N gonorrhoeae, T vaginalis, and bacterial vaginosis did not reduce preterm birth or low birthweight compared with standard care. Within the subgroup of women with N gonorrhoeae, there was a substantial reduction in the primary outcome. FUNDING: UK Department of Health and Social Care; UK Foreign, Commonwealth and Development Office; UK Medical Research Council; the Wellcome Trust; the Australian National Health and Medical Research Council; and Swiss National Science Foundation.
Ethical frameworks should be applied to computational modelling of infectious disease interventions

Zachreson, C ; Savulescu, J ; Shearer, FM ; Plank, MJ ; Coghlan, S ; Miller, JC ; Ainslie, KEC ; Geard, N ; Althouse, B (PUBLIC LIBRARY SCIENCE, 2024-03)

This perspective is part of an international effort to improve epidemiological models with the goal of reducing the unintended consequences of infectious disease interventions. The scenarios in which models are applied often involve difficult trade-offs that are well recognised in public health ethics. Unless these trade-offs are explicitly accounted for, models risk overlooking contested ethical choices and values, leading to an increased risk of unintended consequences. We argue that such risks could be reduced if modellers were more aware of ethical frameworks and had the capacity to explicitly account for the relevant values in their models. We propose that public health ethics can provide a conceptual foundation for developing this capacity. After reviewing relevant concepts in public health and clinical ethics, we discuss examples from the COVID-19 pandemic to illustrate the current separation between public health ethics and infectious disease modelling. We conclude by describing practical steps to build the capacity for ethically aware modelling. Developing this capacity constitutes a critical step towards ethical practice in computational modelling of public health interventions, which will require collaboration with experts on public health ethics, decision support, behavioural interventions, and social determinants of health, as well as direct consultation with communities and policy makers.
Estimating measures to reduce the transmission of SARS-CoV-2 in Australia to guide a 'National Plan' to reopening.

Ryan, GE ; Shearer, FM ; McCaw, JM ; McVernon, J ; Golding, N (Elsevier BV, 2024-03-19)

The availability of COVID-19 vaccines promised a reduction in the severity of disease and relief from the strict public health and social measures (PHSMs) imposed in many countries to limit spread and burden of COVID-19. We were asked to define vaccine coverage thresholds for Australia's transition to easing restrictions and reopening international borders. Using evidence of vaccine effectiveness against the then-circulating Delta variant, we used a mathematical model to determine coverage targets. The absence of any COVID-19 infections in many sub-national jurisdictions in Australia posed particular methodological challenges. We used a novel metric called Transmission Potential (TP) as a proxy measure of the population-level effective reproduction number. We estimated TP of the Delta variant under a range of PHSMs, test-trace-isolate-quarantine (TTIQ) efficiencies, vaccination coverage thresholds, and age-based vaccine allocation strategies. We found that high coverage across all ages (≥70%) combined with ongoing TTIQ and minimal PHSMs was sufficient to avoid lockdowns. At lesser coverage (≤60%) rapid case escalation risked overwhelming of the health sector or the need to reimpose stricter restrictions. Maintaining low case numbers was most beneficial for health and the economy, and at higher coverage levels (≥80%) further easing of restrictions was deemed possible. These results directly informed easing of COVID-19 restrictions in Australia.
Estimating the impact of test-trace-isolate-quarantine systems on SARS-CoV-2 transmission in Australia.

Shearer, FM ; McCaw, JM ; Ryan, GE ; Hao, T ; Tierney, NJ ; Lydeamore, MJ ; Wu, L ; Ward, K ; Ellis, S ; Wood, J ; McVernon, J ; Golding, N (Elsevier BV, 2024-03-22)

BACKGROUND: Australian states and territories used test-trace-isolate-quarantine (TTIQ) systems extensively in their response to the COVID-19 pandemic in 2020-2021. We report on an analysis of Australian case data to estimate the impact of test-trace-isolate-quarantine systems on SARS-CoV-2 transmission. METHODS: Our analysis uses a novel mathematical modelling framework and detailed surveillance data on COVID-19 cases including dates of infection and dates of isolation. First, we directly translate an empirical distribution of times from infection to isolation into reductions in potential for onward transmission during periods of relatively low caseloads (tens to hundreds of reported cases per day). We then apply a simulation approach, validated against case data, to assess the impact of case-initiated contact tracing on transmission during a period of relatively higher caseloads and system stress (up to thousands of cases per day). RESULTS: We estimate that under relatively low caseloads in the state of New South Wales (tens of cases per day), TTIQ contributed to a 54% reduction in transmission. Under higher caseloads in the state of Victoria (hundreds of cases per day), TTIQ contributed to a 42% reduction in transmission. Our results also suggest that case-initiated contact tracing can support timely quarantine in times of system stress (thousands of cases per day). CONCLUSION: Contact tracing systems for COVID-19 in Australia were highly effective and adaptable in supporting the national suppression strategy from 2020-21, prior to the emergence of the Omicron variant in November 2021. TTIQ systems were critical to the maintenance of the strong suppression strategy and were more effective when caseloads were (relatively) low.
Mathematical models of Plasmodium vivax transmission: A scoping review

Anwar, MN ; Smith, L ; Devine, A ; Mehra, S ; Walker, CR ; Ivory, E ; Conway, E ; Mueller, I ; Mccaw, JM ; Flegg, JA ; Hickson, RI ; ten Bosch, Q (PUBLIC LIBRARY SCIENCE, 2024-03)

Plasmodium vivax is one of the most geographically widespread malaria parasites in the world, primarily found across South-East Asia, Latin America, and parts of Africa. One of the significant characteristics of the P. vivax parasite is its ability to remain dormant in the human liver as hypnozoites and subsequently reactivate after the initial infection (i.e. relapse infections). Mathematical modelling approaches have been widely applied to understand P. vivax dynamics and predict the impact of intervention outcomes. Models that capture P. vivax dynamics differ from those that capture P. falciparum dynamics, as they must account for relapses caused by the activation of hypnozoites. In this article, we provide a scoping review of mathematical models that capture P. vivax transmission dynamics published between January 1988 and May 2023. The primary objective of this work is to provide a comprehensive summary of the mathematical models and techniques used to model P. vivax dynamics. In doing so, we aim to assist researchers working on mathematical epidemiology, disease transmission, and other aspects of P. vivax malaria by highlighting best practices in currently published models and highlighting where further model development is required. We categorise P. vivax models according to whether a deterministic or agent-based approach was used. We provide an overview of the different strategies used to incorporate the parasite's biology, use of multiple scales (within-host and population-level), superinfection, immunity, and treatment interventions. In most of the published literature, the rationale for different modelling approaches was driven by the research question at hand. Some models focus on the parasites' complicated biology, while others incorporate simplified assumptions to avoid model complexity. Overall, the existing literature on mathematical models for P. vivax encompasses various aspects of the parasite's dynamics. We recommend that future research should focus on refining how key aspects of P. vivax dynamics are modelled, including spatial heterogeneity in exposure risk and heterogeneity in susceptibility to infection, the accumulation of hypnozoite variation, the interaction between P. falciparum and P. vivax, acquisition of immunity, and recovery under superinfection.
Digital disclosures: Exploring the role of online mental health services in supporting young people who disclose violence or maltreatment

Molyneaux, R ; Mirembe, E ; Leicester, S ; Schley, C ; Alisic, E (Elsevier BV, 2024-04)
Cardiometabolic health markers among Aboriginal adolescents from the Next Generation Youth Wellbeing Cohort Study.

McKay, CD ; Gubhaju, L ; Gibberd, AJ ; McNamara, BJ ; Banks, E ; Azzopardi, P ; Williams, R ; Eades, S (Elsevier BV, 2024-04)

OBJECTIVE: The objective of this study was to investigate cardiometabolic health markers among Aboriginal adolescents aged 10-24 years and relationships with age, gender, and body composition. METHODS: Baseline data (2018-2020) from the Next Generation Youth Wellbeing Cohort Study (Western Australia, New South Wales, and Central Australia) on clinically assessed body mass index, waist/height ratio, blood pressure, glycated haemoglobin (HbA1c), total and high-density lipoprotein cholesterol, total/high-density lipoprotein cholesterol ratio, and triglycerides were analysed. RESULTS: Among 1100 participants, the proportion with individual health markers within the ideal range ranged from 59% for total cholesterol to 91% for HbA1c. Four percent had high blood pressure, which was more common with increasing age and among males; 1% had HbA1c indicative of diabetes. Healthier body composition (body mass index and waist/height ratio) was associated with having individual health markers in the ideal range and with an ideal cardiometabolic profile. CONCLUSIONS: Most Aboriginal adolescents in this study had cardiometabolic markers within the ideal range, though markers of high risk were present from early adolescence. Ideal health markers were more prevalent among those with healthy body composition. IMPLICATIONS FOR PUBLIC HEALTH: Specific screening and management guidelines for Aboriginal adolescents and population health initiatives that support maintenance of healthy body composition could help improve cardiometabolic health in this population.
Genome-wide interaction analysis of folate for colorectal cancer risk

Bouras, E ; Kim, AE ; Lin, Y ; Morrison, J ; Du, M ; Albanes, D ; Barry, EL ; Baurley, JW ; Berndt, SI ; Bien, SA ; Bishop, TD ; Brenner, H ; Budiarto, A ; Burnett-Hartman, A ; Campbell, PT ; Carreras-Torres, R ; Casey, G ; Cenggoro, TW ; Chan, AT ; Chang-Claude, J ; Conti, DV ; Cotterchio, M ; Devall, M ; Diez-Obrero, V ; Dimou, N ; Drew, DA ; Figueiredo, JC ; Giles, GG ; Gruber, SB ; Gunter, MJ ; Harrison, TA ; Hidaka, A ; Hoffmeister, M ; Huyghe, JR ; Joshi, AD ; Kawaguchi, ES ; Keku, TO ; Kundaje, A ; Le Marchand, L ; Lewinger, JP ; Li, L ; Lynch, BM ; Mahesworo, B ; Mannisto, S ; Moreno, V ; Murphy, N ; Newcomb, PA ; Obon-Santacana, M ; Ose, J ; Palmer, JR ; Papadimitriou, N ; Pardamean, B ; Pellatt, AJ ; Peoples, AR ; Platz, EA ; Potter, JD ; Qi, L ; Qu, C ; Rennert, G ; Ruiz-Narvaez, E ; Sakoda, LC ; Schmit, SL ; Shcherbina, A ; Stern, MC ; Su, Y-R ; Tangen, CM ; Thomas, DC ; Tian, Y ; Um, CY ; van Duijnhoven, FJB ; Van Guelpen, B ; Visvanathan, K ; Wang, J ; White, E ; Wolk, A ; Woods, MO ; Ulrich, CM ; Hsu, L ; Gauderman, WJ ; Peters, U ; Tsilidis, KK (Elsevier, 2023-11)

BACKGROUND: Epidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folate's role in CRC. OBJECTIVES: Our aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk. METHODS: We applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO). RESULTS: Inverse associations of dietary, total folate, and folic acid supplement with CRC were found (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.90, 0.96; and 0.91; 95% CI: 0.89, 0.94 per quartile higher intake, and 0.82 (95% CI: 0.78, 0.88) for users compared with nonusers, respectively). Interactions (P-interaction < 5×10-8) of folic acid supplement and variants in the 3p25.2 locus (in the region of Synapsin II [SYN2]/tissue inhibitor of metalloproteinase 4 [TIMP4]) were found using traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplementation was associated with decreased CRC risk among those carrying the TT genotype (OR: 0.82; 95% CI: 0.79, 0.86) but increased CRC risk among those carrying the TA genotype (OR: 1.63; 95% CI: 1.29, 2.05), suggesting a qualitative interaction (P-interaction = 1.4×10-8). No interactions were observed for dietary and total folate. CONCLUSIONS: Variation in 3p25.2 locus may modify the association of folate supplement with CRC risk. Experimental studies and studies incorporating other relevant omics data are warranted to validate this finding.

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