Publications
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Cui F, Blach S, Manzengo Mingiedi C, et al., 2023, Global reporting of progress towards elimination of hepatitis B and hepatitis C., The Lancet Gastroenterology & Hepatology, ISSN: 2468-1253
BACKGROUND: The 69th World Health Assembly endorsed the global health sector strategy on viral hepatitis to eliminate viral hepatitis as a public health threat by 2030. Achieving and measuring the 2030 targets requires a substantial increase in the capacity to test and treat viral hepatitis infections and a mechanism to monitor the progress of hepatitis elimination. This study aimed to identify the gaps in data availability or quality and create a new mechanism to monitor the progress of hepatitis elimination. METHODS: In 2020, using a questionnaire, we collected empirical, systematic, modelled, or surveyed data-reported by WHO country and WHO regional offices-on indicators of progress towards elimination of viral hepatitis, including burden of infection, incidence, mortality, and the cascade of care, and validated these data. FINDINGS: WHO received officially validated country-provided data from 130 countries or territories, and used partner-provided data for 70 countries or territories. We estimated that in 2019, globally, 295·9 million (3·8%) people were living with chronic hepatitis B virus (HBV) infection and 57·8 million (0·8%) people were living with chronic hepatitis C virus (HCV) infection. Globally, there were more than 3·0 million new infections with HBV and HCV and more than 1·1 million deaths due to the viruses in 2019. In 2019, 30·4 million (95% CI 24·3-38·0) individuals living with hepatitis B knew their infection status and 6·6 million (5·3-8·3) people diagnosed with hepatitis B received treatment. Among people with HCV infection, 15·2 million (95% CI 12·1-19·0) had been diagnosed between 2015 and 2019, and 9·4 million (7·5-11·7) people diagnosed with hepatitis C infection were treated with direct-acting antiviral drugs between 2015 and 2019. INTERPRETATION: There has been notable global progress towards hepatitis elimination.
Schmit N, Nayagam A, Lemoine M, et al., 2023, Cost-effectiveness of different monitoring strategies in a screening and treatment programme for hepatitis B in The Gambia, Journal of Global Health, Vol: 13, Pages: 1-11, ISSN: 2047-2978
Background:Clinical management of chronic hepatitis B virus (HBV) infection is complex and access to antiviral treatment remains limited in sub-Saharan Africa. International guidelines recommend monitoring at least annually for disease progression among HBV-infected people not meeting treatment criteria at initial diagnosis. This study aimed to assess the impact and cost-effectiveness of alternative strategies for monitoring.Methods:We used a mathematical model of HBV transmission and natural history, calibrated to all available West African data, to project the population-level health impact, costs and cost-effectiveness of different monitoring strategies for HBV-infected individuals not initially eligible for antiviral treatment. We assumed that these patients were found in the year 2020 in a hypothetical community-based screening programme in The Gambia. Monitoring frequencies were varied between every 5 and every 1 year and targeted different age groups.Results:The currently recommended annual monitoring frequency was likely to be not cost-effective in comparison with other strategies in this setting. 5-yearly monitoring in 15-45-year olds, at US$338 per disability-adjusted life year averted, had the highest probability of being the most effective cost-effective monitoring strategy.Conclusions:Monitoring less frequently than once a year is a cost-effective strategy in a community-based HBV screening and treatment programme in The Gambia, with the optimal strategy depending on the cost-effectiveness threshold. Efficiencies may be gained by prioritising the 15-45-year age group for more intensive monitoring.
Quaife M, Medley GF, Jit M, et al., 2022, Considering equity in priority setting using transmission models: Recommendations and data needs, Epidemics: the journal of infectious disease dynamics, Vol: 41, Pages: 1-8, ISSN: 1755-4365
ObjectivesDisease transmission models are used in impact assessment and economic evaluations of infectious disease prevention and treatment strategies, prominently so in the COVID-19 response. These models rarely consider dimensions of equity relating to the differential health burden between individuals and groups. We describe concepts and approaches which are useful when considering equity in the priority setting process, and outline the technical choices concerning model structure, outputs, and data requirements needed to use transmission models in analyses of health equity.MethodsWe reviewed the literature on equity concepts and approaches to their application in economic evaluation and undertook a technical consultation on how equity can be incorporated in priority setting for infectious disease control. The technical consultation brought together health economists with an interest in equity-informative economic evaluation, ethicists specialising in public health, mathematical modellers from various disease backgrounds, and representatives of global health funding and technical assistance organisations, to formulate key areas of consensus and recommendations.ResultsWe provide a series of recommendations for applying the Reference Case for Economic Evaluation in Global Health to infectious disease interventions, comprising guidance on 1) the specification of equity concepts; 2) choice of evaluation framework; 3) model structure; and 4) data needs. We present available conceptual and analytical choices, for example how correlation between different equity- and disease-relevant strata should be considered dependent on available data, and outline how assumptions and data limitations can be reported transparently by noting key factors for consideration.ConclusionsCurrent developments in economic evaluations in global health provide a wide range of methodologies to incorporate equity into economic evaluations. Those employing infectious disease models need to use the
Waites W, Cavaliere M, Danos V, et al., 2022, Compositional modelling of immune response and virus transmission dynamics., Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences, Vol: 380, Pages: 20210307-20210307, ISSN: 1364-503X
Transmission models for infectious diseases are typically formulated in terms of dynamics between individuals or groups with processes such as disease progression or recovery for each individual captured phenomenologically, without reference to underlying biological processes. Furthermore, the construction of these models is often monolithic: they do not allow one to readily modify the processes involved or include the new ones, or to combine models at different scales. We show how to construct a simple model of immune response to a respiratory virus and a model of transmission using an easily modifiable set of rules allowing further refining and merging the two models together. The immune response model reproduces the expected response curve of PCR testing for COVID-19 and implies a long-tailed distribution of infectiousness reflective of individual heterogeneity. This immune response model, when combined with a transmission model, reproduces the previously reported shift in the population distribution of viral loads along an epidemic trajectory. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'.
Whittaker C, Watson O, Alvarez-Moreno C, et al., 2022, Understanding the Potential Impact of Different Drug Properties On SARS-CoV-2 Transmission and Disease Burden: A Modelling Analysis, Clinical Infectious Diseases, Vol: 75, Pages: e224-e233, ISSN: 1058-4838
BackgroundThe public health impact of the COVID-19 pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear.MethodsUsing a mathematical model of SARS-CoV-2 transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care.ResultsThe impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R=1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalisation) could have much greater benefits, particularly in resource-poor settings facing large epidemics.ConclusionsAdvances in the treatment of COVID-19 to date have been focussed on hospitalised-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.
Revill P, Rangaraj A, Makochekanwa A, et al., 2022, Perspectives on the use of modelling and economic analysis to guide HIV programmes in sub-Saharan Africa, The Lancet HIV, Vol: 9, Pages: e517-e520, ISSN: 2352-3018
HIV modelling and economic analyses have had a prominent role in guiding programmatic responses to HIV in sub-Saharan Africa. However, there has been little reflection on how the HIV modelling field might develop in future. HIV modelling should more routinely align with national government and ministry of health priorities, recognising their legitimate mandates and stewardship responsibilities, for HIV and other wider health programmes. Importance should also be placed on ensuring collaboration between modellers, and that joint approaches to addressing modelling questions, becomes the norm rather than the exception. Such an environment can accelerate translation of modelling analyses into policy formulation because areas where models agree can be prioritised for action, whereas areas over which uncertainty prevails can be slated for additional study, data collection, and analysis. HIV modelling should increasingly be integrated with the modelling of health needs beyond HIV, particularly in allocative efficiency analyses, where focusing on one disease over another might lead to worse health overall. Such integration might also enhance partnership with national governments whose mandates extend beyond HIV. Finally, we see a need for there to be substantial and equitable investment in capacity strengthening within African countries, so that African researchers will increasingly be leading modelling exercises. Building a critical mass of expertise, strengthened through external collaboration and knowledge exchange, should be the ultimate goal.
Phillips AN, Bershteyn A, Revill P, et al., 2022, Cost-effectiveness of easy-access, risk-informed oral pre-exposure prophylaxis in HIV epidemics in sub-Saharan Africa: a modelling study., The Lancet HIV, Vol: 9, Pages: e353-e362, ISSN: 2405-4704
BACKGROUND: Approaches that allow easy access to pre-exposure prophylaxis (PrEP), such as over-the-counter provision at pharmacies, could facilitate risk-informed PrEP use and lead to lower HIV incidence, but their cost-effectiveness is unknown. We aimed to evaluate conditions under which risk-informed PrEP use is cost-effective. METHODS: We applied a mathematical model of HIV transmission to simulate 3000 setting-scenarios reflecting a range of epidemiological characteristics of communities in sub-Saharan Africa. The prevalence of HIV viral load greater than 1000 copies per mL among all adults (HIV positive and negative) varied from 1·1% to 7·4% (90% range). We hypothesised that if PrEP was made easily available without restriction and with education regarding its use, women and men would use PrEP, with sufficient daily adherence, during so-called seasons of risk (ie, periods in which individuals are at risk of acquiring infection). We refer to this as risk-informed PrEP. For each setting-scenario, we considered the situation in mid-2021 and performed a pairwise comparison of the outcomes of two policies: immediate PrEP scale-up and then continuation for 50 years, and no PrEP. We estimated the relationship between epidemic and programme characteristics and cost-effectiveness of PrEP availability to all during seasons of risk. For our base-case analysis, we assumed a 3-monthly PrEP cost of US$29 (drug $11, HIV test $4, and $14 for additional costs necessary to facilitate education and access), a cost-effectiveness threshold of $500 per disability-adjusted life-year (DALY) averted, an annual discount rate of 3%, and a time horizon of 50 years. In sensitivity analyses, we considered a cost-effectiveness threshold of $100 per DALY averted, a discount rate of 7% per annum, the use of PrEP outside of seasons of risk, and reduced uptake of risk-informed PrEP. FINDINGS: In the context of PrEP scale-up such that 66% (90% range across setting-scenarios 46-81) o
Moorhouse L, Schaefer R, Eaton JW, et al., 2022, Male partners' influence on adolescent girls and young women's use of combination HIV prevention: insights from analysis of HIV-prevention cascade data collected in a general-population survey in Manicaland, Zimbabwe, AIDS 2022
Ng'ambi WF, Collins JH, Colbourn T, et al., 2022, Socio-demographic factors associated with early antenatal care visits among pregnant women in Malawi: 2004-2016, PLoS One, Vol: 17, ISSN: 1932-6203
INTRODUCTION: In 2016, the WHO published recommendations increasing the number of recommended antenatal care (ANC) visits per pregnancy from four to eight. Prior to the implementation of this policy, coverage of four ANC visits has been suboptimal in many low-income settings. In this study we explore socio-demographic factors associated with early initiation of first ANC contact and attending at least four ANC visits ("ANC4+") in Malawi using the Malawi Demographic and Health Survey (MDHS) data collected between 2004 and 2016, prior to the implementation of new recommendations. METHODS: We combined data from the 2004-5, 2010 and 2015-16 MDHS using Stata version 16. Participants included all women surveyed between the ages of 15-49 who had given birth in the five years preceding the survey. We conducted weighted univariate, bivariate and multivariable logistic regression analysis of the effects of each of the predictor variables on the binary endpoint of the woman attending at least four ANC visits and having the first ANC attendance within or before the four months of pregnancy (ANC4+). To determine whether a factor was included in the model, the likelihood ratio test was used with a statistical significance of P< 0.05 as the threshold. RESULTS: We evaluated data collected in surveys in 2004/5, 2010 and 2015/6 from 26386 women who had given birth in the five years before being surveyed. The median gestational age, in months, at the time of presenting for the first ANC visit was 5 (inter quartile range: 4-6). The proportion of women initiating ANC4+ increased from 21.3% in 2004-5 to 38.8% in 2015-16. From multivariate analysis, there was increasing trend in ANC4+ from women aged 20-24 years (adjusted odds ratio (aOR) = 1.27, 95%CI:1.05-1.53, P = 0.01) to women aged 45-49 years (aOR = 1.91, 95%CI:1.18-3.09, P = 0.008) compared to those aged 15-19 years. Women from richest socio-economic position ((aOR = 1.32, 95%CI:1.12-1.58, P<0.001) were more likely
Echeverria-Londono S, Li X, Toor J, et al., 2021, How can the public health impact of vaccination be estimated?, BMC PUBLIC HEALTH, Vol: 21
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de Villiers M, Nayagam AS, Hallett T, 2021, The impact of the timely birth-dose vaccine on the global elimination of hepatitis B, Nature Communications, Vol: 12, Pages: 1-10, ISSN: 2041-1723
In 2016 the World Health Organization set the goal of eliminating hepatitis B globally by 2030. Horizontal transmission has been greatly reduced in most countries by scaling up coverage of the infant HBV vaccine series, and vertical transmission is therefore becoming increasingly dominant. Here we show that scaling up timely hepatitis B birth dose vaccination to 90% of new-borns in 110 low- and middle-income countries by 2030 could prevent 710,000 (580,000 to 890,000) deaths in the 2020 to 2030 birth cohorts compared to status quo, with the greatest benefits in Africa. Maintaining this could lead to elimination by 2030 in the Americas, but not before 2059 in Africa. Drops in coverage due to disruptions in 2020 may lead to 15,000 additional deaths, mostly in South-East Asia and the Western Pacific. Delays in planned scale-up could lead to an additional 580,000 deaths globally in the 2020 to 2030 birth cohorts.
Smith J, Garnett G, Hallett T, 2021, The potential impact of long-acting cabotegravir for HIV prevention in South Africa: a mathematical modelling study, Journal of Infectious Diseases, Vol: 224, Pages: 1179-1186, ISSN: 0022-1899
BackgroundAlthough effective, some oral pre-exposure prophylaxis (PrEP) users face barriers to adherence using daily pills, which could be reduced by long-acting formulations. Long-acting cabotegravir (CAB LA) is a potential new injectable formulation for human immunodeficiency virus (HIV) PrEP being tested in phase III trials.MethodsWe use a mathematical model of the HIV epidemic in South Africa to simulate CAB LA uptake by population groups with different levels of HIV risk. We compare the trajectory of the HIV epidemic until 2050 with and without CAB LA to estimate the impact of the intervention.ResultsDelivering CAB LA to 10% of the adult population could avert more than 15% of new infections from 2023 to 2050. The impact would be lower but more efficient if delivered to populations at higher HIV risk: 127 person-years of CAB LA use would be required to avert one HIV infection within 5 years if used by all adults and 47 person-years if used only by the highest risk women.ConclusionsIf efficacious, a CAB LA intervention could have a substantial impact on the course of the HIV epidemic in South Africa. Uptake by those at the highest risk of infection, particularly young women, could improve the efficiency of any intervention.
Stover J, Glaubius RB, Teng Y, et al., 2021, Modeling the epidemiological impact of the UNAIDS 2025 targets to end AIDS as a public health threat by 2030, PLOS MEDICINE, Vol: 18, ISSN: 1549-1277
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Mangal T, Whittaker C, Nkhoma D, et al., 2021, The potential impact of intervention strategies on COVID-19 transmission in Malawi: a mathematical modelling study, BMJ Open, Vol: 11, ISSN: 2044-6055
BackgroundCOVID-19 mitigation strategies have been challenging to implement in resource-limited settings due to the potential for widespread disruption to social and economic well-being. Here we predict the clinical severity of COVID-19 in Malawi, quantifying the potential impact of intervention strategies and increases in health system capacity.MethodsThe infection fatality ratios (IFR) were predicted by adjusting reported IFR for China accounting for demography, the current prevalence of comorbidities and health system capacity. These estimates were input into an age-structured deterministic model, which simulated the epidemic trajectory with non-pharmaceutical interventions and increases in health system capacity. Findings The predicted population-level IFR in Malawi, adjusted for age and comorbidity prevalence, is lower than estimated for China (0.26%, 95% uncertainty interval [UI] 0.12 – 0.69%, compared with 0.60%, 95% CI 0.4% – 1.3% in China), however the health system constraints increase the predicted IFR to 0.83%, 95% UI 0.49% – 1.39%. The interventions implemented in January 2021 could potentially avert 54,400 deaths (95% UI 26,900 – 97,300) over the course of the epidemic compared with an unmitigated outbreak. Enhanced shielding of people aged ≥ 60 years could avert a further 40,200 deaths (95% UI 25,300 – 69,700) and halve ICU admissions at the peak of the outbreak. A novel therapeutic agent, which reduces mortality by 0.65 and 0.8 for severe and critical cases respectively, in combination with increasing hospital capacity could reduce projected mortality to 2.5 deaths per 1,000 population (95% UI 1.9 – 3.6).ConclusionWe find the interventions currently used in Malawi are unlikely to effectively prevent SARS-CoV-2 transmission but will have a significant impact on mortality. Increases in health system capacity and the introduction of novel therapeutics are likely to further reduce the projected numbers of deaths.
Lazarus JV, Safreed-Harmon K, Kamarulzaman A, et al., 2021, Consensus statement on the role of health systems in advancing the long-term well-being of people living with HIV, NATURE COMMUNICATIONS, Vol: 12, Pages: 1-14
Health systems have improved their abilities to identify, diagnose, treat and, increasingly, achieve viral suppression among people living with HIV (PLHIV). Despite these advances, a higher burden of multimorbidity and poorer health-related quality of life are reported by many PLHIV in comparison to people without HIV. Stigma and discrimination further exacerbate these poor outcomes. A global multidisciplinary group of HIV experts developed a consensus statement identifying key issues that health systems must address in order to move beyond the HIV field’s longtime emphasis on viral suppression to instead deliver integrated, person-centered healthcare for PLHIV throughout their lives.
Toor J, Echeverria-Londono S, Li X, et al., 2021, Lives saved with vaccination for 10 pathogens across 112 countries in a pre-COVID-19 world, eLife, Vol: 10, ISSN: 2050-084X
Background: Vaccination is one of the most effective public health interventions. We investigate the impact of vaccination activities for Haemophilus influenzae type b, hepatitis B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, rotavirus, rubella, Streptococcus pneumoniae, and yellow fever over the years 2000-2030 across 112 countries. Methods: Twenty-one mathematical models estimated disease burden using standardised demographic and immunisation data. Impact was attributed to the year of vaccination through vaccine-activity-stratified impact ratios. Results: We estimate 97 (95%CrI[80, 120]) million deaths would be averted due to vaccination activities over 2000-2030, with 50 (95%CrI[41, 62]) million deaths averted by activities between 2000 and 2019. For children under-5 born between 2000 and 2030, we estimate 52 (95%CrI[41, 69]) million more deaths would occur over their lifetimes without vaccination against these diseases. Conclusions: This study represents the largest assessment of vaccine impact before COVID-19-related disruptions and provides motivation for sustaining and improving global vaccination coverage in the future. Funding: VIMC is jointly funded by Gavi, the Vaccine Alliance, and the Bill and Melinda Gates Foundation (BMGF) (BMGF grant number: OPP1157270 / INV-009125). Funding from Gavi is channelled via VIMC to the Consortium's modelling groups (VIMC-funded institutions represented in this paper: Imperial College London, London School of Hygiene and Tropical Medicine, Oxford University Clinical Research Unit, Public Health England, Johns Hopkins University, The Pennsylvania State University, Center for Disease Analysis Foundation, Kaiser Permanente Washington, University of Cambridge, University of Notre Dame, Harvard University, Conservatoire National des Arts et Métiers, Emory University, National University of Singapore). Funding from BMGF was used for salaries of the Consortium secretariat (auth
Schmit N, Nayagam S, Thursz M, et al., 2021, The global burden of chronic hepatitis B virus infection: comparison of country-level prevalence estimates from four research groups, International Journal of Epidemiology, Vol: 50, Pages: 560-569, ISSN: 0300-5771
Background: Progress towards viral hepatitis elimination goals relies on accurate estimates of chronic hepatitis B virus (HBV) infection prevalence. We compared existing sources of the most recent country-level estimates from 2013-2017 to investigate the extent and underlying drivers of differences between them. Methods: The four commonly cited sources of global prevalence estimates, the Institute for Health Metrics and Evaluation, Schweitzer et al, World Health Organization (WHO) and CDA Foundation, were compared by calculating pairwise differences between sets of estimates and assessing their within-country variation. Differences in underlying empirical data and modelling methods were investigated as contributors to differences in sub-Saharan African estimates. Results: The four sets of estimates across all ages were comparable overall and agreed on the global distribution of HBV burden. WHO and CDA produced the most similar estimates, differing by a median of 0.8 percentage points. Larger discrepancies were seen in estimates of prevalence in children under 5 years of age and in sub-Saharan African countries, where the median pairwise differences were 2.7 and 2.4 percentage points for all age prevalence and in children, respectively. Recency and representativeness of included data, and different modelling assumptions of the age distribution of HBV burden, seemed to contribute to these differences. Conclusion: Current prevalence estimates, particularly those from WHO and CDA based on more recent empirical data, provide a useful resource to assess the population-level burden of chronic HBV infection. However, further seroprevalence data in young children is needed particularly in sub-Saharan Africa. This is a priority as monitoring progress towards elimination depends on improved knowledge of prevalence in this age group.
Nayagam AS, Chan P, Zhao K, et al., 2021, Investment case for a comprehensive package of interventions against Hepatitis B in China; applied modelling to help national strategy planning, Clinical Infectious Diseases, Vol: 72, Pages: 743-752, ISSN: 1058-4838
Background:In2016,the first globalviralhepatitiselimination targetswere endorsed. Anestimated one-third of the world’schronic HBV infected population live in China and liver cancer is the sixth leading cause of mortality, but coverage of first line antiviral treatment was low. In 2015, China was one of the first countriesto initiate a consultative process for a renewed approach to viral hepatitis. We present the investment case for the scale-up of a comprehensive package of HBV interventions. Methods:Adynamic simulation modelof HBV was developedand used to simulate the Chinese HBV epidemic. We evaluated the impact, costs and return on investment of a comprehensive package of prevention and treatment interventions from a societal perspective, incorporating costs of management of end-stage liver disease and lost productivity costs. Results:Despitethe successes of historical vaccination scale-up since 1992, there will be a projected 60millionpeople still living with HBV in 2030 and 10 million HBV-related deaths, including 5.7millionHBV-related cancer deaths between 2015-2030. This could be reduced by 2.1million by highly active case-finding and optimal antiviral treatment regimens. The package of interventions is likely to have a positive return-on-investment to society, of 1.57US$ per US$ invested. Conclusions:Increases in HBV-related deaths for the next few decades pose a major public health threatin China. Active case-finding and access to optimal antiviral treatment is requiredto mitigate this risk. This investment case approachprovides a real-world example of howapplied modellingcansupportnational dialogue and inform policy planning.
Li X, Mukandavire C, Cucunuba ZM, et al., 2021, Estimating the health impact of vaccination against ten pathogens in 98 low-income and middle-income countries from 2000 to 2030: a modelling study, The Lancet, Vol: 397, Pages: 398-408, ISSN: 0140-6736
BackgroundThe past two decades have seen expansion of childhood vaccination programmes in low-income and middle-income countries (LMICs). We quantify the health impact of these programmes by estimating the deaths and disability-adjusted life-years (DALYs) averted by vaccination against ten pathogens in 98 LMICs between 2000 and 2030.Methods16 independent research groups provided model-based disease burden estimates under a range of vaccination coverage scenarios for ten pathogens: hepatitis B virus, Haemophilus influenzae type B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, Streptococcus pneumoniae, rotavirus, rubella, and yellow fever. Using standardised demographic data and vaccine coverage, the impact of vaccination programmes was determined by comparing model estimates from a no-vaccination counterfactual scenario with those from a reported and projected vaccination scenario. We present deaths and DALYs averted between 2000 and 2030 by calendar year and by annual birth cohort.FindingsWe estimate that vaccination of the ten selected pathogens will have averted 69 million (95% credible interval 52–88) deaths between 2000 and 2030, of which 37 million (30–48) were averted between 2000 and 2019. From 2000 to 2019, this represents a 45% (36–58) reduction in deaths compared with the counterfactual scenario of no vaccination. Most of this impact is concentrated in a reduction in mortality among children younger than 5 years (57% reduction [52–66]), most notably from measles. Over the lifetime of birth cohorts born between 2000 and 2030, we predict that 120 million (93–150) deaths will be averted by vaccination, of which 58 million (39–76) are due to measles vaccination and 38 million (25–52) are due to hepatitis B vaccination. We estimate that increases in vaccine coverage and introductions of additional vaccines will result in a 72% (59–81) reduction in lifetime mortality in t
Middleton P, Perez-Guzman PN, Cheng A, et al., 2021, Characteristics and outcomes of clinically diagnosed RT-PCR swab negative COVID-19: a retrospective cohort study, Scientific Reports, Vol: 11, Pages: 1-7, ISSN: 2045-2322
Patients with strong clinical features of COVID-19 with negative real time polymerase chain reaction (RT-PCR) SARS-CoV-2 testing are not currently included in official statistics. The scale, characteristics and clinical relevance of this group are not well described. We performed a retrospective cohort study in two large London hospitals to characterize the demographic, clinical, and hospitalization outcome characteristics of swab-negative clinical COVID-19 patients. We found 1 in 5 patients with a negative swab and clinical suspicion of COVID-19 received a clinical diagnosis of COVID-19 within clinical documentation, discharge summary or death certificate. We compared this group to a similar swab positive cohort and found similar demographic composition, symptomology and laboratory findings. Swab-negative clinical COVID-19 patients had better outcomes, with shorter length of hospital stay, reduced need for >60% supplementary oxygen and reduced mortality. Patients with strong clinical features of COVID-19 that are swab-negative are a common clinical challenge. Health systems must recognize and plan for the management of swab-negative patients in their COVID-19 clinical management, infection control policies and epidemiological assessments.
Ng'ambi W, Mangal T, Phillips A, et al., 2021, A cross-sectional study on factors associated with health seeking behaviour of Malawians aged 15+ years in 2016., Malawi Medical Journal, Vol: 32, Pages: 205-212, ISSN: 1995-7262
Introduction: Health seeking behaviour (HSB) refers to actions taken by individuals who are ill in order to find appropriate remedy. Most studies on HSB have only examined one symptom or covered only a specific geographical location within a country. In this study, we used a representative sample of adults to explore the factors associated with HSB in response to 30 symptoms reported by adult Malawians in 2016. Methods: We used the 2016 Malawi Integrated Household Survey dataset. We fitted a multilevel logistic regression model of likelihood of 'seeking care at a health facility' using a forward step-wise selection method, with age, sex and reported symptoms entered as a priori variables. We calculated the odds ratios (ORs) and their associated 95% confidence intervals (95% CI). We set the level of statistical significance at P < 0.05. Results: Of 6909 adults included in the survey, 1907 (29%) reported symptoms during the 2 weeks preceding the survey. Of these, 937 (57%) sought care at a health facility. Adults in urban areas were more likely to seek health care at a health facility than those in rural areas (AOR = 1.65, 95% CI: 1.19-2.30, P = 0.003). Females had a higher likelihood of seeking care from health facilities than males (AOR = 1.26, 95% CI: 1.03-1.59, P = 0.029). Being of higher wealth status was associated with a higher likelihood of seeking care from a health facility (AOR = 1.58, 95% CI: 1.16-2.16, P = 0.004). Having fever and eye problems were associated with higher likelihood of seeking care at a health facility, while having headache, stomach ache and respiratory tract infections were associated with lower likelihood of seeking care at a health facility. Conclusion: This study has shown that there is a need to understand and address individual, socioeconomic and geographical barriers to health seeking to increase access and appropriate use of health care and fast-track progress towards Universal Health Coverage among the adult population.
Heffernan A, Ma Y, Nayagam S, et al., 2021, Economic and epidemiological evaluation of interventions to reduce the burden of hepatitis C in Yunnan province, China, PLoS One, Vol: 16, Pages: 1-17, ISSN: 1932-6203
BackgroundThe paradigm shift in hepatitis C virus (HCV) treatment options in the last five years has raised the prospect of eliminating the disease as a global health threat. This will require a step-change in the number being treated with the new direct-acting antivirals (DAAs). Given constrained budgets and competing priorities, policy makers need information on how to scale-up access to HCV treatment. To inform such decisions, we examined the cost effectiveness of screening and treatment interventions in Yunnan, China.Methods and findingsWe simulated the HCV epidemic using a previously published model of HCV transmission and disease progression, calibrated to Yunnan data, and implemented a range of treatment and screening interventions from 2019. We incorporated treatment, diagnosis, and medical costs (expressed in 2019 US Dollars, USD) to estimate the lifetime benefits and costs of interventions. Using this model, we asked: is introducing DAAs cost effective from a healthcare sector perspective; what is the optimal combination of screening interventions; and what is the societal return on investment of intervention? The incremental cost-effectiveness ratio (ICER) of switching to DAAs with a median cost of 7,400 USD (50,000 Chinese Yuan) per course is 500 USD/disability adjusted life year (DALY) averted; at a threshold of 50% of Yunnan gross domestic product (2,600 USD), switching to DAAs is cost effective 94% of the time. At this threshold, the optimal, cost-effective intervention comprises screening people who inject drugs, those in HIV care, men who have sex with men, and ensuring access to DAAs for all those newly diagnosed with HCV. For each USD invested in this intervention, there is an additional 0·80 USD (95% credible interval: 0·17–1·91) returned through reduced costs of disease or increased productivity. Returns on investment are lower (and potentially negative) if a sufficiently long-term horizon, encompassing the full stream
Londono SE, Li X, Toor J, et al., 2021, How can the public health impact of vaccination be estimated?
<jats:title>ABSTRACT</jats:title><jats:p>Deaths due to vaccine preventable diseases cause a notable proportion of mortality worldwide. To quantify the importance of vaccination, it is necessary to estimate the burden averted through vaccination. The Vaccine Impact Modelling Consortium (VIMC) was established to estimate the health impact of vaccination. We describe the methods implemented by the VIMC to estimate impact by calendar year, birth year and year of vaccination (YoV). The calendar and birth year methods estimate impact in a particular year and over the lifetime of a particular birth cohort, respectively. The YoV method estimates the impact of a particular year’s vaccination activities through the use of impact ratios which have no stratification and stratification by activity type and/or birth cohort. Furthermore, we detail an impact extrapolation (IE) method for use between coverage scenarios. We compare the methods, focusing on YoV for hepatitis B, measles and yellow fever. We find that the YoV methods estimate similar impact with routine vaccinations but have greater yearly variation when campaigns occur with the birth cohort stratification. The IE performs well for the YoV methods, providing a time-efficient mechanism for updates to impact estimates. These methods provide a robust set of approaches to quantify vaccination impact.</jats:p>
Hui Z, Nayagam S, Chan P, et al., 2021, Progress towards elimination of mother-to-child transmission of hepatitis B virus infection in China: a modelling analysis., Bulletin of the World Health Organization, Vol: 99, Pages: 10-18, ISSN: 0042-9686
Objective: To determine the projected burden of hepatitis B virus (HBV) in China, the intervention strategies that can eliminate mother-to-child transmission (MTCT) by 2030 or earlier and the measurable parameters that can be used to monitor progress towards this target. Methods: We developed a dynamic, sex- and age-stratified model of the HBV epidemic in China, calibrated using hepatitis B surface antigen (HBsAg) and e antigen (HBeAg) prevalence data from sequential national serosurveys (1979-2014) and the numbers of HBV-related cancer deaths (2012). We determined whether China can achieve elimination of MTCT of HBV by 2030 under current prevention interventions. We modelled various intervention scenarios to represent different coverage levels of birth-dose HBV vaccination, hepatitis B immunoglobulin to newborns of HBsAg-positive mothers and antiviral therapy (tenofovir) to HBeAg-positive pregnant women. Findings: We project that, if current levels of prevention interventions are maintained, China will achieve the elimination target by 2029. By modelling various intervention scenarios, we found that this can be brought forward to 2025 by increasing coverage of birth-dose vaccination, or to 2024 by the administration of tenofovir to HBeAg-positive pregnant women. We found that achievement of the target by 2025 would be predicted by a measurement of less than 2% MTCT in 2020. Conclusion: Our results highlight how high-quality national data can be combined with modelling in monitoring the elimination of MTCT of HBV. By demonstrating the impact of increased interventions on target achievement dates, we anticipate that other high-burden countries will be motivated to strengthen HBV prevention policies.
Ricks S, Denkinger CM, Schumacher SG, et al., 2020, The potential impact of urine-LAM diagnostics on tuberculosis incidence and mortality: a modelling analysis, PLoS Medicine, Vol: 17, ISSN: 1549-1277
BackgroundLateral flow urine lipoarabinomannan (LAM) tests could offer important new opportunities for the early detection of tuberculosis (TB). The currently licensed LAM test, Alere Determine TB LAM Ag (‘LF-LAM’), performs best in the sickest people living with HIV (PLHIV). However, the technology continues to improve, with newer LAM tests, such as Fujifilm SILVAMP TB LAM (‘SILVAMP-LAM’) showing improved sensitivity, including amongst HIV-negative patients. It is important to anticipate the epidemiological impact that current and future LAM tests may have on TB incidence and mortality.Methods and findingsConcentrating on South Africa, we examined the impact that widening LAM test eligibility would have on TB incidence and mortality. We developed a mathematical model of TB transmission to project the impact of LAM tests, distinguishing ‘current’ tests (with sensitivity consistent with LF-LAM), from hypothetical ‘future’ tests (having sensitivity consistent with SILVAMP-LAM). We modelled the impact of both tests, assuming full adoption of the 2019 WHO guidelines for the use of these tests amongst those receiving HIV care. We also simulated the hypothetical deployment of future LAM tests for all people presenting to care with TB symptoms, not restricted to PLHIV. Our model projects that 2,700,000 (95% credible interval [CrI] 2,000,000–3,600,000) and 420,000 (95% CrI 350,000–520,000) cumulative TB incident cases and deaths, respectively, would occur between 2020 and 2035 if the status quo is maintained. Relative to this comparator, current and future LAM tests would respectively avert 54 (95% CrI 33–86) and 90 (95% CrI 55–145) TB deaths amongst inpatients between 2020 and 2035, i.e., reductions of 5% (95% CrI 4%–6%) and 9% (95% CrI 7%–11%) in inpatient TB mortality. This impact in absolute deaths averted doubles if testing is expanded to include outpatients, yet remains <1% of count
Unwin H, Mishra S, Bradley V, et al., 2020, State-level tracking of COVID-19 in the United States, Nature Communications, Vol: 11, Pages: 1-9, ISSN: 2041-1723
As of 1st June 2020, the US Centers for Disease Control and Prevention reported 104,232 confirmed or probable COVID-19-related deaths in the US. This was more than twice the number of deaths reported in the next most severely impacted country. We jointly model the US epidemic at the state-level, using publicly available deathdata within a Bayesian hierarchical semi-mechanistic framework. For each state, we estimate the number of individuals that have been infected, the number of individuals that are currently infectious and the time-varying reproduction number (the average number of secondary infections caused by an infected person). We use changes in mobility to capture the impact that non-pharmaceutical interventions and other behaviour changes have on therate of transmission of SARS-CoV-2. We estimate thatRtwas only below one in 23 states on 1st June. We also estimate that 3.7% [3.4%-4.0%] of the total population of the US had been infected, with wide variation between states, and approximately 0.01% of the population was infectious. We demonstrate good 3 week model forecasts of deaths with low error and good coverage of our credible intervals.
Thompson H, Imai N, Dighe A, et al., 2020, SARS-CoV-2 infection prevalence on repatriation flights from Wuhan City, China, Journal of Travel Medicine, Vol: 27, Pages: 1-3, ISSN: 1195-1982
We estimated SARS-CoV-2 infection prevalence in cohorts of repatriated citizens from Wuhan to be 0.44% (95% CI: 0.19%–1.03%). Although not representative of the wider population we believe these estimates are helpful in providing a conservative estimate of infection prevalence in Wuhan City, China, in the absence of large-scale population testing early in the epidemic.
Haacker M, Hallett T, Atun R, 2020, On time horizons in health economic evaluations, Health Policy and Planning, Vol: 35, Pages: 1237-1243, ISSN: 0268-1080
The issue of time horizons has received scant attention in discussions pertaining to health economic evaluations unlike discounting or translation of health outcomes into life-cycle measures (e.g. Quality Adjusted Life Years (QALYs) or Disability Adjusted Life Years (DALYs)). The available guidelines do not offer clear and consistent guidance for many problems addressed in health economic evaluations. In practice, variation of time horizons between studies for the same diseases is a matter of concern, as results on cost-effectiveness depend on the time horizon. Our paper contributes to establishing a consistent approach to setting time horizons across common types of health economic evaluations and mitigating potential bias where the choice of a time horizon may affect results of the evaluation. We find that available guidance is clear only for patient-focused interventions, but not in the presence of population-level effects owing to transmission of infections or other linkages. We distinguish between a policy period – over which an intervention is delivered or initiated – and an evaluation period over which the effects are measured. One important challenge in establishing a time horizon for evaluation is that, at least for infectious diseases, the state of the epidemic at the end of the policy period cannot be evaluated precisely and incorporated in the results of an economic evaluation. While longer policy periods partly mitigate this challenge, they are subject to greater uncertainty, and outcomes may not adequately reflect the cost-effectiveness of current policies because outcomes reflect an average over the policy period. Incremental analysis on interventions implemented in sub-periods of the policy period (especially at the beginning) potentially improves accuracy and helps to identify potential for improving cost-effectiveness by varying the path of implementation or the mix of interventions offered over time.
Beacroft L, Hallett TB, 2020, Correction to: The potential impact of a "curative intervention" for HIV: a modelling study, Global Health Research and Policy, Vol: 5, Pages: 1-2, ISSN: 2397-0642
Ng'ambi W, Mangal T, Phillips A, et al., 2020, Factors associated with healthcare seeking behaviour for children in Malawi: 2016, Tropical Medicine and International Health, Vol: 25, Pages: 1486-1495, ISSN: 1360-2276
ObjectiveTo characterise health seeking behaviour (HSB) and determine its predictors amongst children in Malawi in 2016.MethodsWe used the 2016 Malawi Integrated Household Survey data set. The outcome of interest was HSB, defined as seeking care at a health facility amongst people who reported one or more of a list of possible symptoms given on the questionnaire in the past two weeks. We fitted a multivariate logistic regression model of HSB using a forward step-wise selection method, with age, sex and symptoms entered as a priori variables.ResultsOf 5350 children, 1666 (32%) had symptoms in the past two weeks. Of the 1666, 1008 (61%) sought care at health facility. The children aged 5–14 years were less likely to be taken to health facilities for health care than those aged 0–4 years. Having fever vs. not having fever and having a skin problem vs. not having skin problem were associated with increased likelihood of HSB. Having a headache vs. not having a headache was associated with lower likelihood of accessing care at health facilities (AOR = 0.50, 95% CI: 0.26–0.96, P = 0.04). Children from urban areas were more likely to be taken to health facilities for health care (AOR = 1.81, 95% CI: 1.17–2.85, P = 0.008), as were children from households with a high wealth status (AOR = 1.86, 95% CI: 1.25–2.78, P = 0.02).ConclusionThere is a need to understand and address individual, socio-economic and geographical barriers to health seeking to increase access and use of health care and fast-track progress towards Universal Health Coverage.
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