Publications
290 results found
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.
Smit M, Perez-Guzman P, Mutai KK, et al., 2020, Mapping the current and future non-communicable disease burden in Kenya by human immunodeficiency virus status: a modelling study, Clinical Infectious Diseases, Vol: 71, Pages: 1864-1873, ISSN: 1058-4838
Background:Then on-communicable disease (NCD) burden in Kenya is not well characterised, despite estimates needed to identify future health priorities. We aimto quantify current and future NCD burden in Kenya by HIV status. Methods: Original systematic reviews (SRs) and meta-analyses of prevalence/incidence of cardiovascular disease (CVD), chronic kidney disease, depression, diabetes, high total cholesterol, hypertension, human papillomavirus infection and related pre-cancerous stages in Kenya were carried out. An individual-based model was developed, simulating births, deaths, HIV-diseaseand treatment, aforementioned NCDs and cancers. The model was parameterised using SR, epidemiological national and regional surveillance data. NCD burden was quantified for 2018-2035 by HIV statusamongst adults. Findings: SRsidentified prevalence/incidence data for eachNCD, except ischemic heart disease. The model estimates that 51% of Kenyan adults currently suffer from ≥1 NCD, with a higher burden in People Living with HIV (PLHIV)compared to HIV-negative (62% versus 51%), driven by theirhigher age profile and partlyby HIV-related risk for NCDs. Hypertension and high total cholesterolarethe main NCD drivers(adult prevalence of 20·5% (5·3 million) and 9·0% (2·3 million)), with CVD and cancers the main causesof death. The burden is projectedto increase by 2035 (56% in HIV-negative; 71% in PLHIV), with population growth doublingthe number of people needing services (15·4 million to 28·1million)by 2035. Conclusions:NCD services will need to be expanded in Kenya. Guidelines in Kenya already support provision of these amongst both the general and HIV-positive population, however coverage remains low.
Mangal T, Whittaker C, Nkhoma D, et al., 2020, The potential impact of intervention strategies on COVID-19 transmission in Malawi: A mathematical modelling study, Publisher: medRxiv
Background COVID-19 mitigation strategies have been challenging to implement in resource-limited settings such as Malawi due to the potential for widespread disruption to social and economic well-being. Here we estimate the clinical severity of COVID-19 in Malawi, quantifying the potential impact of intervention strategies and increases in health system capacity.Methods The infection fatality ratios (IFR) in Malawi were estimated 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. The impact of a novel therapeutic agent and increases in hospital capacity and oxygen availability were explored, given different assumptions on mortality rates.Findings The estimated age-specific IFR in Malawi are higher than those reported for China, however the younger average age of the population results in a slightly lower population-weighted IFR (0.48%, 95% uncertainty interval [UI] 0.30% – 0.72% compared with 0.60%, 95% CI 0.4% – 1.3% in China). The current interventions implemented, (i.e. social distancing, workplace closures and public transport restrictions) could potentially avert 3,100 deaths (95% UI 1,500 – 4,500) over the course of the epidemic. Enhanced shielding of people aged ≥ 60 years could avert a further 30,500 deaths (95% UI 17,500 – 45,600) and halve ICU admissions at the peak of the outbreak. Coverage of face coverings of 60% under the assumption of 50% efficacy could be sufficient to control the epidemic. 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 2.55 deaths per 1,000 population (95% UI 1.58 – 3.84).Conclusion The risks due to COVID-19 vary across settings
Smith J, Beacroft L, Abdullah F, et al., 2020, Responding to the ECHO trial results: modelling the potential impact of changing contraceptive method mix on HIV and reproductive health in South Africa, Journal of the International AIDS Society, Vol: 23, Pages: 1-10, ISSN: 1758-2652
Introduction: Some observational data suggest that the progestogen injectable contraceptive depot medroxyprogesterone acetate (DMPA) may increase a woman’s risk of HIV acquisition but a randomised clinical trial did not find a statistically significant increase in HIV risk for women using DMPA compared to two other methods. However, it could not rule out up to 30% increased HIV risk for DMPA users. We evaluate changes to contraceptive method mix in South Africa under different assumptions about the existence and strength of a possible undetected relationship between DMPA use and HIV risk. Methods: A mathematical model was developed to simulate the ongoing HIV epidemic and contraceptive method mix in South Africa to estimate how changes in method mix could impact HIV- and reproductive health-related outcomes. We made different assumptions about the relationship between DMPA use and HIV risk, from no relationship to a 30% increase in HIV risk for women using DMPA. Scenario analyses were used to investigate the impact of switching away from DMPA predominance to new patterns of contraceptive use.Results: In South Africa, the HIV-related benefits of reduced DMPA use could be as great as the harms of increased adverse reproductive health outcomes over twenty years, if DMPA did increase the risk of HIV acquisition by a relative hazard of infection of 1.1 or greater. A reduction in DMPA use among HIV-positive women would have no benefit in terms of HIV infections, but would incur additional negative reproductive health outcomes. The most important driver of adverse reproductive health outcomes is the proportion of women who switch away from DMPA to no contraceptive method.Conclusions: If there is any real increased HIV risk for DMPA users that has not been detected by the recent randomised trial, a reduction in DMPA use could reduce the ongoing number of new HIV infections. However, such a change would place more women at risk at adverse reproductive health effects. I
Hogan A, Winskill P, Watson O, et al., 2020, Report 33: Modelling the allocation and impact of a COVID-19 vaccine
Several SARS-CoV-2 vaccine candidates are now in late-stage trials, with efficacy and safety results expected by the end of 2020. Even under optimistic scenarios for manufacture and delivery, the doses available in 2021 are likely to be limited. Here we identify optimal vaccine allocation strategies within and between countries to maximise health (avert deaths) under constraints on dose supply. We extended an existing mathematical model of SARS-CoV-2 transmission across different country settings to model the public health impact of potential vaccines, using a range of target product profiles developed by the World Health Organization. We show that as supply increases, vaccines that reduce or block infection – and thus transmission – in addition to preventing disease have a greater impact than those that prevent disease alone, due to the indirect protection provided to high-risk groups. We further demonstrate that the health impact of vaccination will depend on the cumulative infection incidence in the population when vaccination begins, the duration of any naturally acquired immunity, the likely trajectory of the epidemic in 2021 and the level of healthcare available to effectively treat those with disease. Within a country, we find that for a limited supply (doses for <20% of the population) the optimal strategy is to target the elderly and other high-risk groups. However, if a larger supply is available, the optimal strategy switches to targeting key transmitters (i.e. the working age population and potentially children) to indirectly protect the elderly and vulnerable. Given the likely global dose supply in 2021 (2 billion doses with a two-dose vaccine), we find that a strategy in which doses are allocated to countries in proportion to their population size is close to optimal in averting deaths. Such a strategy also aligns with the ethical principles agreed in pandemic preparedness planning.
Nguyen HA, Cooke GS, Day JN, et al., 2020, The direct-medical costs associated with interferon-based treatment for Hepatitis C in Vietnam, Wellcome Open Research, Vol: 4, Pages: 129-129
<ns4:p><ns4:bold>Background:</ns4:bold> Injectable interferon-based therapies have been used to treat hepatitis C virus (HCV) infection since 1991. International guidelines have now moved away from interferon-based therapy towards direct-acting antiviral (DAA) tablet regimens, because of their superior efficacy, excellent side-effect profiles, and ease of administration. Initially DAA drugs were prohibitively expensive for most healthcare systems. Access is now improving through the procurement of low-cost, generic DAAs acquired through voluntary licenses. However, HCV treatment costs vary widely, and many countries are struggling with DAA treatment scale-up. This is not helped by the limited cost data and economic evaluations from low- and middle-income countries to support HCV policy decisions. We conducted a detailed analysis of the costs of treating chronic HCV infection with interferon-based therapy in Vietnam. Understanding these costs is important for performing necessary economic evaluations of novel treatment strategies.</ns4:p><ns4:p> <ns4:bold>Methods:</ns4:bold> We conducted an analysis of the direct medical costs of treating HCV infection with interferon alpha (IFN) and pegylated-interferon alpha (Peg-IFN), in combination with ribavirin, from the health sector perspective at the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, in 2017.</ns4:p><ns4:p> <ns4:bold>Results:</ns4:bold> The total cost of the IFN treatment regimen was estimated to range between US$1,120 and US$1,962. The total cost of the Peg-IFN treatment regimen was between US$2,156 and US$5,887. Drug expenses were the biggest contributor to the total treatment cost (54-89%) and were much higher for the Peg-IFN regimen.</ns4:p><ns4:p> <ns4:bold>Conclusions:</ns4:bold> We found that treating HCV with IFN or Peg-IFN resulted in significant direct medical costs. Of concern, we found that all patie
Hogan A, Jewell B, Sherrard-Smith E, et al., 2020, Potential impact of the COVID-19 pandemic on HIV, TB and malaria in low- and middle-income countries: a modelling study, The Lancet Global Health, Vol: 8, Pages: e1132-e1141, ISSN: 2214-109X
Background: COVID-19 has the potential to cause substantial disruptions to health services, including by cases overburdening the health system or response measures limiting usual programmatic activities. We aimed to quantify the extent to which disruptions in services for human immunodeficiency virus (HIV), tuberculosis (TB) and malaria in low- and middle-income countries with high burdens of those disease could lead to additional loss of life. Methods: We constructed plausible scenarios for the disruptions that could be incurred during the COVID-19 pandemic and used established transmission models for each disease to estimate the additional impact on health that could be caused in selected settings.Findings: In high burden settings, HIV-, TB- and malaria-related deaths over five years may increase by up to 10%, 20% and 36%, respectively, compared to if there were no COVID-19 pandemic. We estimate the greatest impact on HIV to be from interruption to antiretroviral therapy, which may occur during a period of high health system demand. For TB, we estimate the greatest impact is from reductions in timely diagnosis and treatment of new cases, which may result from any prolonged period of COVID-19 suppression interventions. We estimate that the greatest impact on malaria burden could come from interruption of planned net campaigns. These disruptions could lead to loss of life-years over five years that is of the same order of magnitude as the direct impact from COVID-19 in places with a high burden of malaria and large HIV/TB epidemics.Interpretation: Maintaining the most critical prevention activities and healthcare services for HIV, TB and malaria could significantly reduce the overall impact of the COVID-19 pandemic.Funding: Bill & Melinda Gates Foundation, The Wellcome Trust, DFID, MRC
Jewell B, Mudimu E, Stover J, et al., 2020, Potential effects of disruption to HIV programmes in sub-Saharan Africa caused by COVID-19: results from multiple mathematical models, The Lancet HIV, Vol: 7, Pages: e629-e640, ISSN: 2405-4704
Background: The COVID-19 epidemic could lead to the disruptions to provision of HIV services for people living with HIV and those at risk of acquiring HIV in sub-Saharan Africa, where UNAIDS estimates that more than two thirds of the 37.9 million (32.7-44.0 million) people living with HIV reside in 2018. We set out to predict the potential effects of such disruptions on HIV-related deaths and new infections.Methods: Five well-described models of HIV epidemics (Goals, Optima HIV, HIV Synthesis, Imperial College model, EMOD) were each used to estimate the effect of various potential disruptions to HIV prevention, testing and treatment services on HIV-related deaths and new infections in sub-Saharan Africa lasting 6 months from 1 April 2020. Disruptions affecting 20%, 50% and 100% of the population were considered. In further analyses shorter term disruptions and the possibility of reductions in sexual activity during disruptions were considered. Findings: A six-month interruption of supply of antiretroviral (ARV) drugs across 50% of the population of people living with HIV on treatment would be expected to lead to a 1.63-fold (median across models; range 1.39 to 1.87) increase in HIV-related deaths over a one year period compared to with no disruption. In sub-Saharan Africa this amounts to an excess of 296,000 (median over model estimates, range 229,000 – 420,000) HIV deaths should such a high level of disruption occur. There would also be an approximately 1.6-fold increase in mother to child transmission of HIV. While an interruption of supply of ARV drug would have by far the largest impact of any potential disruptions, effects of poorer clinical care due to over-stretched health facilities, interruptions of supply of other drugs such as cotrimoxazole and suspension of HIV testing would all have significant population-level impact on mortality. Interruption to condom supplies and peer education would make populations more vulnerable to increases
Skovdal M, Pickles MR, Hallett TB, et al., 2020, Complexities to consider when communicating risk of COVID-19, Public Health, Vol: 186, Pages: 283-285, ISSN: 0033-3506
Lavezzo E, Franchin E, Ciavarella C, et al., 2020, Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo', Nature, Vol: 584, Pages: 425-429, ISSN: 0028-0836
On the 21st of February 2020 a resident of the municipality of Vo', a small town near Padua, died of pneumonia due to SARS-CoV-2 infection1. This was the first COVID-19 death detected in Italy since the emergence of SARS-CoV-2 in the Chinese city of Wuhan, Hubei province2. In response, the regional authorities imposed the lockdown of the whole municipality for 14 days3. We collected information on the demography, clinical presentation, hospitalization, contact network and presence of SARS-CoV-2 infection in nasopharyngeal swabs for 85.9% and 71.5% of the population of Vo' at two consecutive time points. On the first survey, which was conducted around the time the town lockdown started, we found a prevalence of infection of 2.6% (95% confidence interval (CI) 2.1-3.3%). On the second survey, which was conducted at the end of the lockdown, we found a prevalence of 1.2% (95% Confidence Interval (CI) 0.8-1.8%). Notably, 42.5% (95% CI 31.5-54.6%) of the confirmed SARS-CoV-2 infections detected across the two surveys were asymptomatic (i.e. did not have symptoms at the time of swab testing and did not develop symptoms afterwards). The mean serial interval was 7.2 days (95% CI 5.9-9.6). We found no statistically significant difference in the viral load of symptomatic versus asymptomatic infections (p-values 0.62 and 0.74 for E and RdRp genes, respectively, Exact Wilcoxon-Mann-Whitney test). This study sheds new light on the frequency of asymptomatic SARS-CoV-2 infection, their infectivity (as measured by the viral load) and provides new insights into its transmission dynamics and the efficacy of the implemented control measures.
Flaxman S, Mishra S, Gandy A, et al., 2020, Estimating the effects of non-pharmaceutical interventions on COVID-19 in Europe, Nature, Vol: 584, Pages: 257-261, ISSN: 0028-0836
Following the emergence of a novel coronavirus1 (SARS-CoV-2) and its spread outside of China, Europe has experienced large epidemics. In response, many European countries have implemented unprecedented non-pharmaceutical interventions such as closure of schools and national lockdowns. We study the impact of major interventions across 11 European countries for the period from the start of COVID-19 until the 4th of May 2020 when lockdowns started to be lifted. Our model calculates backwards from observed deaths to estimate transmission that occurred several weeks prior, allowing for the time lag between infection and death. We use partial pooling of information between countries with both individual and shared effects on the reproduction number. Pooling allows more information to be used, helps overcome data idiosyncrasies, and enables more timely estimates. Our model relies on fixed estimates of some epidemiological parameters such as the infection fatality rate, does not include importation or subnational variation and assumes that changes in the reproduction number are an immediate response to interventions rather than gradual changes in behavior. Amidst the ongoing pandemic, we rely on death data that is incomplete, with systematic biases in reporting, and subject to future consolidation. We estimate that, for all the countries we consider, current interventions have been sufficient to drive the reproduction number Rt below 1 (probability Rt< 1.0 is 99.9%) and achieve epidemic control. We estimate that, across all 11 countries, between 12 and 15 million individuals have been infected with SARS-CoV-2 up to 4th May, representing between 3.2% and 4.0% of the population. Our results show that major non-pharmaceutical interventions and lockdown in particular have had a large effect on reducing transmission. Continued intervention should be considered to keep transmission of SARS-CoV-2 under control.
de Villiers MJ, Gamkrelidze I, Hallett TB, et al., 2020, Modelling hepatitis B virus infection and impact of timely birth dose vaccine: A comparison of two simulation models, PLoS One, Vol: 15, Pages: 1-16, ISSN: 1932-6203
Hepatitis B is a global epidemic that requires carefully orchestrated vaccination initiatives in geographical regions of medium to high endemicity to reach the World Health Organization’s elimination targets by 2030. This study compares two widely-used deterministic hepatitis B models—the Imperial HBV model and the CDA Foundation’s PRoGReSs—based on their predicted outcomes in four countries. The impact of scaling up of the timely birth dose of the hepatitis B vaccine is also investigated. The two models predicted largely similar outcomes for the impact of vaccination programmes on the projected numbers of new cases and deaths under high levels of the infant hepatitis B vaccine series. However, scenarios for the scaling up of the infant hepatitis B vaccine series had a larger impact in the PRoGReSs model than in the Imperial model due to the infant vaccine series directly leading to the reduction of perinatal transmission in the PRoGReSs model, but not in the Imperial model. Meanwhile, scaling up of the timely birth dose vaccine had a greater impact on the outcomes of the Imperial hepatitis B model than in the PRoGReSs model due to the greater protection that the birth dose vaccine confers to infants in the Imperial model compared to the PRoGReSs model. These differences underlie the differences in projections made by the models under some circumstances. Both sets of assumptions are consistent with available data and reveal a structural uncertainty that was not apparent in either model in isolation. Those relying on projections from models should consider outputs from both models and this analysis provides further evidence of the benefits of systematic model comparison for enhancing modelling analyses.
Perez Guzman PN, Daunt A, Mukherjee S, et al., 2020, Clinical characteristics and predictors of outcomes of hospitalized patients with COVID-19 in a multi-ethnic London NHS Trust: a retrospective cohort study, Clinical Infectious Diseases, Vol: 2020, Pages: 1-11, ISSN: 1058-4838
Background: Emerging evidence suggests ethnic minorities are disproportionatelyaffected by COVID-19. Detailed clinical analyses of multi-cultural hospitalized patientcohorts remain largely undescribed.Methods: We performed regression, survival andcumulative competing risk analyses to evaluate factors associated with mortality inpatients admitted for COVID-19 in three large London hospitals between February 25and April 5, censored as of May 1, 2020.Results: Of 614 patients (median age 69years, (IQR 25) and 62% male), 381 (62%) had been discharged alive, 178 (29%)died and 55 (9%) remained hospitalized at censoring. Severe hypoxemia (aOR 4.25,95%CI 2.36-7.64), leukocytosis (aOR 2.35, 95%CI 1.35-4.11), thrombocytopenia (aOR1.01, 95%CI 1.00-1.01, increase per 10x9decrease), severe renal impairment (aOR5.14, 95%CI 2.65-9.97), and low albumin (aOR 1.06, 95%CI 1.02-1.09, increase per gdecrease) were associated with death. Forty percent (244) were from black, Asian andother minority ethnic (BAME) groups, 38% (235) white and for 22% (135) ethnicity wasunknown. BAME patients were younger and had fewer comorbidities. Whilst theunadjusted odds of death did not differ by ethnicity, when adjusting for age, sex andcomorbidities, black patients were at higher odds of death compared to whites (aOR1.69, 95%CI 1.00-2.86). This association was stronger when further adjusting foradmission severity (aOR 1.85 95% CI 1.06-3.24). Conclusions: BAME patients were over-represented in our cohort and, whenaccounting for demographic and clinical profile of admission, black patients were atincreased odds of death. Further research is needed into biologic drivers of differencesin COVID-19 outcomes by ethnicity.
Woods B, Schmitt L, Rothery C, et al., 2020, Practical metrics for establishing the health benefits of research to support research prioritisation, BMJ Global Health, Vol: 5, Pages: 1-11, ISSN: 2059-7908
Introduction We present practical metrics for estimating the expected health benefits of specific research proposals. These can be used by research funders, researchers and healthcare decision-makers within low-income and middle-income countries to support evidence-based research prioritisation.Methods The methods require three key assessments: (1) the current level of uncertainty around the endpoints the proposed study will measure; (2) how uncertainty impacts on the health benefits and costs of healthcare programmes and (3) the health opportunity costs imposed by programme costs. Research is valuable because it can improve health by informing the choice of which programmes should be implemented. We provide a Microsoft Excel tool to allow readers to generate estimates of the health benefits of research studies based on these three assessments. The tool can be populated using existing studies, existing cost-effectiveness models and expert opinion. Where such evidence is not available, the tool can quantify the value of research under different assumptions. Estimates of the health benefits of research can be considered alongside research costs, and the consequences of delaying implementation until research reports, to determine whether research is worthwhile. We illustrate the method using a case study of research on HIV self-testing programmes in Malawi. This analysis combines data from the literature with outputs from the HIV synthesis model.Results For this case study, we found a costing study that could be completed and inform decision making within 1 year offered the highest health benefits (67 000 disability-adjusted life years (DALYs) averted). Research on outcomes improved population health to a lesser extent (12 000 DALYs averted) and only if carried out alongside programme implementation.Conclusion Our work provides a method for estimating the health benefits of research in a practical and timely fashion. This can be used to support accountable use of resea
Jewell BL, Smith JA, Hallett TB, 2020, Understanding the impact of interruptions to HIV services during the COVID-19 pandemic: A modelling study, EClinicalMedicine, Vol: 26, Pages: 1-7, ISSN: 2589-5370
BackgroundThere is concern that the COVID-19 pandemic could severely disrupt HIV services in sub-Saharan Africa. However, it is difficult to determine priorities for maintaining different elements of existing HIV services given widespread uncertainty.MethodsWe explore the impact of disruptions on HIV outcomes in South Africa, Malawi, Zimbabwe, and Uganda using a mathematical model, examine how impact is affected by model assumptions, and compare potential HIV deaths to those that may be caused by COVID-19 in the same settings.FindingsThe most important determinant of HIV-related mortality is an interruption to antiretroviral treatment (ART) supply. A three-month interruption for 40% of those on ART could cause a similar number of additional deaths as those that might be saved from COVID-19 through social distancing. An interruption for more than 6–90% of individuals on ART for nine months could cause the number of HIV deaths to exceed the number of COVID-19 deaths, depending on the COVID-19 projection. However, if ART supply is maintained, but new treatment, voluntary medical male circumcision, and pre-exposure prophylaxis initiations cease for 3 months and condom use is reduced, increases in HIV deaths would be limited to <2% over five years, although this could still be accompanied by a 7% increase in new HIV infections.InterpretationHIV deaths could increase substantially during the COVID-19 pandemic under reasonable worst-case assumptions about interruptions to HIV services. It is a priority in high-burden countries to ensure continuity of ART during the pandemic.FundingBill & Melinda Gates Foundation.
Forchini G, Lochen A, Hallett T, et al., 2020, Report 28: Excess non-COVID-19 deaths in England and Wales between 29th February and 5th June 2020
There were 189,403 deaths from any cause reported in England from 29th February to 5th June 2020 inclusive, and 11,278 all-cause deaths in Wales over the same period. Of those deaths, 44,736 (23.6%) registered COVID-19 on the death certificate in England, and 2,294 (20.3%) in Wales, while 144,667 (76.4%) were not recorded as having been due to COVID-19 in England, and 8,984 (79.7%) in Wales. However, it could be that some of the ‘non-COVID-19’ deaths have in fact also been caused by COVID-19, either as the direct cause of death, or indirectly through provisions for the pandemic impeding access to care for other conditions. There is uncertainty in how many of the non-COVID-19 deaths were directly or indirectly caused by the pandemic. We estimated the excess deaths that were not recorded as associated with COVID-19 in the death certificate (excess non-COVID-19 deaths) as the deaths for which COVID-19 was not reported as the cause, compared to those we would have expected to occur had the pandemic not happened. Expected deaths were forecast with an analysis of historic trends in deaths between 2010 and April 2020 using data by the Office of National Statistics and a statistical time series model. According to the model, we expected 136,294 (95% CI 133,882 - 138,696) deaths in England, and 8,983 (CI 8,051 - 9,904) in Wales over this period, significantly fewer than the number of deaths reported. This means that there were 8,983 (95% CI 5,971 - 10,785) total excess non-COVID-19 deaths in England. For every 100 COVID-19 deaths during the period from 29th February to 5th June 2020 there were between 13 and 24 cumulative excess non-COVID-19 deaths. The proportion of cumulative excess non-COVID-19 deaths of all reported deaths during this period was 4.4% (95% CI 3.2% - 5.7%) in England, with small regional variations. Excess deaths were highest in the South East at 2,213 (95% CI 327 - 4,047) and in London at 1,937 (95% CI 896 - 3,010), respectively. There is no e
Dowdy DW, Powers KA, Hallett TB, 2020, Towards evidence-based integration of services for HIV, non-communicable diseases and substance use: insights from modelling, Journal of the International AIDS Society, Vol: 23, ISSN: 1758-2652
Dighe A, Cattarino L, Cuomo-Dannenburg G, et al., 2020, Report 25: Response to COVID-19 in South Korea and implications for lifting stringent interventions, 25
While South Korea experienced a sharp growth in COVID-19 cases early in the global pandemic, it has since rapidly reduced rates of infection and now maintains low numbers of daily new cases. Despite using less stringent “lockdown” measures than other affected countries, strong social distancing measures have been advised in high incidence areas and a 38% national decrease in movement occurred voluntarily between February 24th - March 1st. Suspected and confirmed cases were isolated quickly even during the rapid expansion of the epidemic and identification of the Shincheonji cluster. South Korea swiftly scaled up testing capacity and was able to maintain case-based interventions throughout. However, individual case-based contact tracing, not associated with a specific cluster, was a relatively minor aspect of their control program, with cluster investigations accounting for a far higher proportion of cases: the underlying epidemic was driven by a series of linked clusters, with 48% of all cases in the Shincheonji cluster and 20% in other clusters. Case-based contacts currently account for only 11% of total cases. The high volume of testing and low number of deaths suggests that South Korea experienced a small epidemic of infections relative to other countries. Therefore, caution is needed in attempting to duplicate the South Korean response in settings with larger more generalized epidemics. Finding, testing and isolating cases that are linked to clusters may be more difficult in such settings.
Revill P, Phillips A, Eaton JW, et al., 2020, Modelling and economic evaluation to inform WHO HIV treatment guidelines, Global Health Economics: Shaping Health Policy In Low- And Middle-income Countries, Pages: 275-285, ISBN: 9789813272361
International organizations influence national-level health sector priorities by affecting how much funding is available for health care delivery within countries and how that funding is used. The setting of guidelines for the management of diseases (e.g. for malaria, child health, nutrition) by the World Health Organization (WHO) exerts particular influence. Guidelines typically provide syntheses of evidence on clinical efficacy and effectiveness and make recommendations for health care best practice. However, for the most part, they do not well inform the allocation of limited available health care resources. Consequentially, they risk encouraging national and international decision-makers to divert resources away from areas of greater potential gains in population health. In this case study, we reflect upon efforts to incorporate economic evidence into the development of the WHO HIV Treatment Guidelines. We describe how the WHO has incorporated economic insight into these and other guidelines. However, even in this case, the processes currently followed for guideline development can limit the extent to which recommendations can draw upon economic evidence. Changes in the way WHO Guidelines are developed and interpreted, and how evidence is used to inform decision-making at the country level, is therefore required. We give our thoughts on what these changes could be.
Winskill P, Whittaker C, Walker P, et al., 2020, Report 22: Equity in response to the COVID-19 pandemic: an assessment of the direct and indirect impacts on disadvantaged and vulnerable populations in low- and lower middle-income countries, 22
The impact of the COVID-19 pandemic in low-income settings is likely to be more severe due to limited healthcare capacity. Within these settings, however, there exists unfair or avoidable differences in health among different groups in society – health inequities – that mean that some groups are particularly at risk from the negative direct and indirect consequences of COVID-19. The structural determinants of these are often reflected in differences by income strata, with the poorest populations having limited access to preventative measures such as handwashing. Their more fragile income status will also mean that they are likely to be employed in occupations that are not amenable to social-distancing measures, thereby further reducing their ability to protect themselves from infection. Furthermore, these populations may also lack access to timely healthcare on becoming ill. We explore these relationships by using large-scale household surveys to quantify the differences in handwashing access, occupation and hospital access with respect to wealth status in low-income settings. We use a COVID-19 transmission model to demonstrate the impact of these differences. Our results demonstrate clear trends that the probability of death from COVID-19 increases with increasing poverty. On average, we estimate a 32.0% (2.5th-97.5th centile 8.0%-72.5%) increase in the probability of death in the poorest quintile compared to the wealthiest quintile from these three factors alone. We further explore how risk mediators and the indirect impacts of COVID-19 may also hit these same disadvantaged and vulnerable the hardest. We find that larger, inter-generational households that may hamper efforts to protect the elderly if social distancing are associated with lower-income countries and, within LMICs, lower wealth status. Poorer populations are also more susceptible to food security issues - with these populations having the highest levels under-nourishment whilst also being
Perez Guzman PN, Daunt A, Mukherjee S, et al., 2020, Report 17: Clinical characteristics and predictors of outcomes of hospitalised patients with COVID-19 in a London NHS Trust: a retrospective cohort study
Clinical characteristics and determinants of outcomes for hospitalised COVID-19 patients in the UK remain largely undescribed and emerging evidence suggests ethnic minorities might be disproportionately affected. We describe the characteristics and outcomes of patients hospitalised for COVID-19 in three large London hospitals with a multi-ethnic catchment population.We performed a retrospective cohort study on all patients hospitalised with laboratory-confirmed SARS-CoV-2 infection at Imperial College Healthcare NHS Trust between February 25 and April 5, 2020. Outcomes were recorded as of April 19, 2020. Logistic regression models, survival analyses and cumulative competing risk analyses were performed to evaluate factors associated with COVID-19 hospital mortality.Of 520 patients in this cohort (median age 67 years, (IQR 26) and 62% male), 302 (68%) had been discharged alive, 144 (32%) died and 74 (14%) were still hospitalised at the time of censoring. Increasing age (adjusted odds ratio [aOR] 2·16, 95%CI 1·50-3·12), severe hypoxia (aOR 3·75, 95%CI 1·80-7·80), low platelets (aOR 0·65, 95%CI 0.49·0·85), reduced estimated glomerular filtration rate (aOR 4·11, 95%CI 1·58-10·69), bilirubin >21mmol/L (aOR 2·32, 95%CI 1·05-5·14) and low albumin (aOR 0·77, 9%%CI 0·59-1·01) were associated with increased risk of in-hospital mortality. Individual comorbidities were not independently associated with risk of death. Regarding ethnicity, 209 (40%) were from a black and Asian minority, for 115 (22%) ethnicity was unknown and 196 (38%) patients were white. Compared to the latter, black patients were significantly younger and had less comorbidities. Whilst the crude OR of death of black compared to white patients was not significant (1·14, 95%CI 0·69-1·88, p=0.62), adjusting for age and comorbidity showed a trend towards significance
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