Featured Publications

EXPLORE IDM’S CURRENT RESEARCH PUBLICATIONS

Filter options:

Angela Devine, Katherine E. Battle, Niamh Meagher, Rosalind E. Howes, Saber Dini, Peter W. Gething, Julie A. Simpson, Ric N. Price, Yoel Lubell 

PLOS MEDICINE

Background

In 2017, an estimated 14 million cases of Plasmodium vivax malaria were reported from Asia, Central and South America, and the Horn of Africa. The clinical burden of vivax malaria is largely driven by its ability to form dormant liver stages (hypnozoites) that can reactivate to cause recurrent episodes of malaria. Elimination of both the blood and liver stages of the parasites (“radical cure”) is required to achieve a sustained clinical response and prevent ongoing transmission of the parasite. Novel treatment options and point-of-care diagnostics are now available to ensure that radical cure can be administered safely and effectively. We quantified the global economic cost of vivax malaria and estimated the potential cost benefit of a policy of radical cure after testing patients for glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Methods and findings

Estimates of the healthcare provider and household costs due to vivax malaria were collated and combined with national case estimates for 44 endemic countries in 2017. These provider and household costs were compared with those that would be incurred under 2 scenarios for radical cure following G6PD screening: (1) complete adherence following daily supervised primaquine therapy and (2) unsupervised treatment with an assumed 40% effectiveness. A probabilistic sensitivity analysis generated credible intervals (CrIs) for the estimates. Globally, the annual cost of vivax malaria was US$359 million (95% CrI: US$222 to 563 million), attributable to 14.2 million cases of vivax malaria in 2017. From a societal perspective, adopting a policy of G6PD deficiency screening and supervision of primaquine to all eligible patients would prevent 6.1 million cases and reduce the global cost of vivax malaria to US$266 million (95% CrI: US$161 to 415 million), although healthcare provider costs would increase by US$39 million. If perfect adherence could be achieved with a single visit, then the global cost would fall further to US$225 million, equivalent to $135 million in cost savings from the baseline global costs. A policy of unsupervised primaquine reduced the cost to US$342 million (95% CrI: US$209 to 532 million) while preventing 2.1 million cases. Limitations of the study include partial availability of country-level cost data and parameter uncertainty for the proportion of patients prescribed primaquine, patient adherence to a full course of primaquine, and effectiveness of primaquine when unsupervised.

Conclusions

Our modelling study highlights a substantial global economic burden of vivax malaria that could be reduced through investment in safe and effective radical cure achieved by routine screening for G6PD deficiency and supervision of treatment. Novel, low-cost interventions for improving adherence to primaquine to ensure effective radical cure and widespread access to screening for G6PD deficiency will be critical to achieving the timely global elimination of Pvivax.

Robyn M Stuart, Romesh G Abeysuriya, Cliff C Kerr, Dina Mistry, Dan J Klein, Richard T Gray, Margaret Hellard, Nick Scott

BMJ OPEN

Objectives The early stages of the COVID-19 pandemic illustrated that SARS-CoV-2, the virus that causes the disease, has the potential to spread exponentially. Therefore, as long as a substantial proportion of the population remains susceptible to infection, the potential for new epidemic waves persists even in settings with low numbers of active COVID-19 infections, unless sufficient countermeasures are in place. We aim to quantify vulnerability to resurgences in COVID-19 transmission under variations in the levels of testing, tracing and mask usage.

Setting The Australian state of New South Wales (NSW), a setting with prolonged low transmission, high mobility, non-universal mask usage and a well-functioning test-and-trace system.

Participants None (simulation study).

Results We find that the relative impact of masks is greatest when testing and tracing rates are lower and vice versa. Scenarios with very high testing rates (90% of people with symptoms, plus 90% of people with a known history of contact with a confirmed case) were estimated to lead to a robustly controlled epidemic. However, across comparable levels of mask uptake and contact tracing, the number of infections over this period was projected to be 2–3 times higher if the testing rate was 80% instead of 90%, 8–12 times higher if the testing rate was 65% or 30–50 times higher with a 50% testing rate. In reality, NSW diagnosed 254 locally acquired cases over this period, an outcome that had a moderate probability in the model (10%–18%) assuming low mask uptake (0%–25%), even in the presence of extremely high testing (90%) and near-perfect community contact tracing (75%–100%), and a considerably higher probability if testing or tracing were at lower levels.

Conclusions Our work suggests that testing, tracing and masks can all be effective means of controlling transmission. A multifaceted strategy that combines all three, alongside continued hygiene and distancing protocols, is likely to be the most robust means of controlling transmission of SARS-CoV-2.

SCIENCEDIRECT

The coronavirus disease 2019 (COVID-19) pandemic highlighted the importance of mathematical modeling in advising scientific bodies and informing public policy making. Modeling allows a flexible theoretical framework to be developed in which different scenarios around spread of diseases and strategies to prevent it can be explored. This work brings together perspectives on mathematical modeling of infectious diseases, highlights the different modeling frameworks that have been used for modeling COVID-19 and illustrates some of the models that our groups have developed and applied specifically for COVID-19. We discuss three models for COVID-19 spread: the modified Susceptible-Exposed-Infected-Recovered model that incorporates contact tracing (SEIR-TTI model) and describes the spread of COVID-19 among these population cohorts, the more detailed agent-based model called Covasim describing transmission between individuals, and the Rule-Based Model (RBM) which can be thought of as a combination of both. We showcase the key methodologies of these approaches, their differences as well as the ways in which they are interlinked. We illustrate their applicability to answer pertinent questions associated with the COVID-19 pandemic such as quantifying and forecasting the impacts of different test-trace-isolate (TTI) strategies.

Ben J Brintz, Benjamin Haaland, Joel Howard, Dennis L Chao, Joshua L Proctor, Ashraful I Khan, Sharia M Ahmed, Lindsay T Keegan, Tom Greene

ELIFE

Traditional clinical prediction models focus on parameters of the individual patient. For infectious diseases, sources external to the patient, including characteristics of prior patients and seasonal factors, may improve predictive performance. We describe the development of a predictive model that integrates multiple sources of data in a principled statistical framework using a post-test odds formulation. Our method enables electronic real-time updating and flexibility, such that components can be included or excluded according to data availability. We apply this method to the prediction of etiology of pediatric diarrhea, where 'pre-test’ epidemiologic data may be highly informative. Diarrhea has a high burden in low-resource settings, and antibiotics are often over-prescribed. We demonstrate that our integrative method outperforms traditional prediction in accurately identifying cases with a viral etiology, and show that its clinical application, especially when used with an additional diagnostic test, could result in a 61% reduction in inappropriately prescribed antibiotics.

Nick Scott, Anna Palmer, Dominic Delport, Romesh Abeysuriya, Robyn M Stuart, Cliff C Kerr, Dina Mistry, Daniel J Klein, Rachel Sacks‐Davis, Katie Heath, Samuel W Hainsworth, Alisa Pedrana, Mark Stoove, David Wilson and Margaret E Hellard

MJA

Objectives: To assess the risks associated with relaxing coronavirus disease 2019 (COVID‐19)‐related physical distancing restrictions and lockdown policies during a period of low viral transmission.

Design: Network‐based viral transmission risks in households, schools, workplaces, and a variety of community spaces and activities were simulated in an agent‐based model, Covasim.

Setting: The model was calibrated for a baseline scenario reflecting the epidemiological and policy environment in Victoria during March–May 2020, a period of low community viral transmission.

Intervention: Policy changes for easing COVID‐19‐related restrictions from May 2020 were simulated in the context of interventions that included testing, contact tracing (including with a smartphone app), and quarantine.

Main outcome measure: Increase in detected COVID‐19 cases following relaxation of restrictions.

Results: Policy changes that facilitate contact of individuals with large numbers of unknown people (eg, opening bars, increased public transport use) were associated with the greatest risk of COVID‐19 case numbers increasing; changes leading to smaller, structured gatherings with known contacts (eg, small social gatherings, opening schools) were associated with lower risks. In our model, the rise in case numbers following some policy changes was notable only two months after their implementation.

Conclusions: Removing several COVID‐19‐related restrictions within a short period of time should be undertaken with care, as the consequences may not be apparent for more than two months. Our findings support continuation of work from home policies (to reduce public transport use) and strategies that mitigate the risk associated with re‐opening of social venues.

Edinah Mudimu, Kathryn Peebles, Zindoga Mukandavire, Emily Nightingale, Monisha Sharma, Graham F. Medley, Daniel J. Klein, Katharine Kripke, Anna Bershteyn 

PLOS ONE

Background
Pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV and has the potential to significantly impact the HIV epidemic. Given limited resources for HIV prevention, identifying PrEP provision strategies that maximize impact is critical.

Methods
We used a stochastic individual-based network model to evaluate the direct (infections prevented among PrEP users) and indirect (infections prevented among non-PrEP users as a result of PrEP) benefits of PrEP, the person-years of PrEP required to prevent one HIV infection, and the community-level impact of providing PrEP to populations defined by gender and age in western Kenya and South Africa. We examined sensitivity of results to scale-up of antiretroviral therapy (ART) and voluntary medical male circumcision (VMMC) by comparing two scenarios: maintaining current coverage (“status quo”) and rapid scale-up to meet programmatic targets (“fast-track”).

Results
The community-level impact of PrEP was greatest among women aged 15–24 due to high incidence, while PrEP use among men aged 15–24 yielded the highest proportion of indirect infections prevented in the community. These indirect infections prevented continue to increase over time (western Kenya: 0.4–5.5 (status quo); 0.4–4.9 (fast-track); South Africa: 0.5–1.8 (status quo); 0.5–3.0 (fast-track)) relative to direct infections prevented among PrEP users. The number of person-years of PrEP needed to prevent one HIV infection was lower (59 western Kenya and 69 in South Africa in the status quo scenario; 201 western Kenya and 87 in South Africa in the fast-track scenario) when PrEP was provided only to women compared with only to men over time horizons of up to 5 years, as the indirect benefits of providing PrEP to men accrue in later years.

Conclusions
Providing PrEP to women aged 15–24 prevents the greatest number of HIV infections per person-year of PrEP, but PrEP provision for young men also provides indirect benefits to women and to the community overall. This finding supports existing policies that prioritize PrEP use for young women, while also illuminating the community-level benefits of PrEP availability for men when resources permit.

Monisha Sharma, PhD, Edinah Mudimu, PhD Kate Simeon, MD, Anna Bershteyn, PhD, Jienchi Dorward, MBChB, Lauren R Violette, MPH, Adam Akullian, PhD, Prof Salim S Abdool Karim, MBBCH, Prof Connie Celum, MD, Nigel Garrett, MBBS, Paul K Drain, MD

THE LANCET HIV

Background
The number of people on antiretroviral therapy (ART) requiring treatment monitoring in low-resource settings is rapidly increasing. Point-of-care (POC) testing for ART monitoring might alleviate burden on centralised laboratories and improve clinical outcomes, but its cost-effectiveness is unknown.


Methods
We used cost and effectiveness data from the STREAM trial in South Africa (February, 2017–October, 2018), which evaluated POC testing for viral load, CD4 count, and creatinine, with task shifting from professional to lower-cadre registered nurses compared with laboratory-based testing without task shifting (standard of care). We parameterised an agent-based network model, EMOD-HIV, to project the impact of implementing this intervention in South Africa over 20 years, simulating approximately 175 000 individuals per run. We assumed POC monitoring increased viral suppression by 9 percentage points, enrolment into community-based ART delivery by 25 percentage points, and switching to second-line ART by 1 percentage point compared with standard of care, as reported in the STREAM trial. We evaluated POC implementation in varying clinic sizes (10–50 patient initiating ART per month). We calculated incremental cost-effectiveness ratios (ICERs) and report the mean and 90% model variability of 250 runs, using a cost-effectiveness threshold of US$500 per disability-adjusted life-year (DALY) averted for our main analysis.


Findings
POC testing at 70% coverage of patients on ART was projected to reduce HIV infections by 4·5% (90% model variability 1·6 to 7·6) and HIV-related deaths by 3·9% (2·0 to 6·0). In clinics with 30 ART initiations per month, the intervention had an ICER of $197 (90% model variability –27 to 863) per DALY averted; results remained cost-effective when varying background viral suppression, ART dropout, intervention effectiveness, and reduction in HIV transmissibility. At higher clinic volumes (≥40 ART initiations per month), POC testing was cost-saving and at lower clinic volumes (20 ART initiations per month) the ICER was $734 (93 to 2569). A scenario that assumed POC testing did not increase enrolment into community ART delivery produced ICERs that exceeded the cost-effectiveness threshold for all clinic volumes.


Interpretation
POC testing is a promising strategy to cost-effectively improve patient outcomes in moderately sized clinics in South Africa. Results are most sensitive to changes in intervention impact on enrolment into community-based ART delivery.


Funding
National Institutes of Health.

BMC HEALTH SERVICES RESEARCH

Background

Malaria incidence has plateaued in Sub-Saharan Africa despite Seasonal Malaria Chemoprevention’s (SMC) introduction. Community health workers (CHW) use a door-to-door delivery strategy to treat children with SMC drugs, but for SMC to be as effective as in clinical trials, coverage must be high over successive seasons.

Methods

We developed and used a microplanning model that utilizes population raster to estimate population size, generates optimal households visit itinerary, and quantifies SMC coverage based on CHWs’ time investment for treatment and walking. CHWs’ performance under current SMC deployment mode was assessed using CHWs’ tracking data and compared to microplanning in villages with varying demographics and geographies.

Results

Estimates showed that microplanning significantly reduces CHWs’ walking distance by 25%, increases the number of visited households by 36% (p < 0.001) and increases SMC coverage by 21% from 37.3% under current SMC deployment mode up to 58.3% under microplanning (p < 0.001). Optimal visit itinerary alone increased SMC coverage up to 100% in small villages whereas in larger or hard-to-reach villages, filling the gap additionally needed an optimization of the CHW ratio.

Conclusion

We estimate that for a pair of CHWs, the daily optimal number of visited children (assuming 8.5mn spent per child) and walking distance should not exceed 45 (95% CI 27–62) and 5 km (95% CI 3.2–6.2) respectively. Our work contributes to extend SMC coverage by 21–63% and may have broader applicability for other community health programs.

Nick Scott, Anna Palmer, Dominic Delport, Romesh Abeysuriya, Robyn M Stuart, Cliff C Kerr, Dina Mistry, Daniel J Klein, Rachel Sacks-Davis, Katie Heath, Samuel W Hainsworth, Alisa Pedrana, Mark Stoove, David Wilson, Margaret E Hellard 

MJA

Objectives

To assess the risks associated with relaxing coronavirus disease 2019 (COVID-19)-related physical distancing restrictions and lockdown policies during a period of low viral transmission.

Design

Network-based viral transmission risks in households, schools, workplaces, and a variety of community spaces and activities were simulated in an agent-based model, Covasim.

Setting

The model was calibrated for a baseline scenario reflecting the epidemiological and policy environment in Victoria during March–May 2020, a period of low community viral transmission.

Intervention

Policy changes for easing COVID-19-related restrictions from May 2020 were simulated in the context of interventions that included testing, contact tracing (including with a smartphone app), and quarantine.

Main outcome measure

Increase in detected COVID-19 cases following relaxation of restrictions.

Results

Policy changes that facilitate contact of individuals with large numbers of unknown people (eg, opening bars, increased public transport use) were associated with the greatest risk of COVID-19 case numbers increasing; changes leading to smaller, structured gatherings with known contacts (eg, small social gatherings, opening schools) were associated with lower risks. In our model, the rise in case numbers following some policy changes was notable only two months after their implementation.

Conclusions

Removing several COVID-19-related restrictions within a short period of time should be undertaken with care, as the consequences may not be apparent for more than two months. Our findings support continuation of work from home policies (to reduce public transport use) and strategies that mitigate the risk associated with re-opening of social venues.

Andrew L. Valesano, Mami Taniuchi, William J.Fitzsimmons, Mdm OhedulIslam, Tahmina Ahmed, Khalequ Zaman, Rashidul Haque, WesleyWong, Michael Famulare, Adam S.Lauring

SCIENCEDIRECT

The emergence of circulating vaccine-derived polioviruses through evolution of the oral polio vaccine (OPV) poses a significant obstacle to polio eradication. Understanding the early genetic changes that occur as OPV evolves and transmits is important for preventing future outbreaks. Here, we use deep sequencing to define the evolutionary trajectories of type 2 OPV in a vaccine trial. By sequencing 497 longitudinal stool samples from 271 OPV2 recipients and household contacts, we were able to examine the extent of convergent evolution in vaccinated individuals and the amount of viral diversity that is transmitted. In addition to rapid reversion of key attenuating mutations, we identify strong selection at 19 sites across the genome. We find that a tight transmission bottleneck limits the onward transmission of these early adaptive mutations. Our results highlight the distinct evolutionary dynamics of live attenuated virus vaccines and have important implications for the success of next-generation OPV.