242 results found
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, 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.
Skovdal M, Pickles MR, Hallett TB, et al., 2020, Complexities to consider when communicating risk of COVID-19, Public Health, 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, 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.
Jewell B, Mudimu E, Stover J, et al., Potential effects of disruption to HIV programmes in sub-Saharan Africa caused by COVID-19: results from multiple mathematical models, The Lancet HIV, 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
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, 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
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
Flaxman S, Mishra S, Gandy A, et al., 2020, Estimating the effects of non-pharmaceutical interventions on COVID-19 in Europe, Nature, 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.
Smith J, Garnett G, Hallett T, 2020, The potential impact of long-acting cabotegravir for HIV prevention in South Africa: a mathematical modelling study, Journal of Infectious Diseases, ISSN: 0022-1899
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
Haacker M, Hallett T, Atun R, On time horizons in health economic evaluations, Health Policy and Planning, 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.
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.
Unwin H, Mishra S, Bradley VC, et al., 2020, Report 23: State-level tracking of COVID-19 in the United States
our estimates show that the percentage of individuals that have been infected is 4.1% [3.7%-4.5%], with widevariation between states. For all states, even for the worst affected states, we estimate that less than a quarter of thepopulation has been infected; in New York, for example, we estimate that 16.6% [12.8%-21.6%] of individuals have beeninfected to date. Our attack rates for New York are in line with those from recent serological studies  broadly supportingour choice of infection fatality rate.There is variation in the initial reproduction number, which is likely due to a range of factors; we find a strong associationbetween the initial reproduction number with both population density (measured at the state level) and the chronologicaldate when 10 cumulative deaths occurred (a crude estimate of the date of locally sustained transmission).Our estimates suggest that the epidemic is not under control in much of the US: as of 17 May 2020 the reproductionnumber is above the critical threshold (1.0) in 24 [95% CI: 20-30] states. Higher reproduction numbers are geographicallyclustered in the South and Midwest, where epidemics are still developing, while we estimate lower reproduction numbersin states that have already suffered high COVID-19 mortality (such as the Northeast). These estimates suggest that cautionmust be taken in loosening current restrictions if effective additional measures are not put in place.We predict that increased mobility following relaxation of social distancing will lead to resurgence of transmission, keepingall else constant. We predict that deaths over the next two-month period could exceed current cumulative deathsby greater than two-fold, if the relationship between mobility and transmission remains unchanged. Our results suggestthat factors modulating transmission such as rapid testing, contact tracing and behavioural precautions are crucial to offsetthe rise of transmission associated with loosening of social distancing. Overall, we
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
Hogan A, Jewell B, Sherrard-Smith E, et al., 2020, Report 19: The potential impact of the COVID-19 epidemic on HIV, TB and malaria in low- and middle-income countries
COVID-19 has the potential to cause disruptions to health services in different ways; through the health system becoming overwhelmed with COVID-19 patients, through the intervention used to slow transmission of COVID-19 inhibiting access to preventative interventions and services, and through supplies of medicine being interrupted. We aim to quantify the extent to which such disruptions in services for HIV, TB and malaria in high burden low- and middle-income countries could lead to additional loss of life. In high burden settings, HIV, TB and malaria related deaths over 5 years may be increased by up to 10%, 20% and 36%, respectively, compared to if there were no COVID-19 epidemic. We estimate the greatest impact on HIV to be from interruption to ART, which may occur during a period of high or extremely 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 a long period of COVID-19 suppression interventions; for malaria, we estimate that the greatest impact could come from reduced prevention activities including interruption of planned net campaigns, through all phases of the COVID-19 epidemic. In high burden settings, the impact of each type of disruption could be significant and lead to a 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. Maintaining the most critical prevention activities and healthcare services for HIV, TB and malaria could significantly reduce the overall impact of the COVID-19 epidemic.
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
Jewell B, Smith J, Hallett T, et al., 2020, The potential impact of interruptions to HIV services: a modelling case study for South Africa, Publisher: medRxiv
The numbers of deaths caused by HIV could increase substantially if the COVID-19 epidemic leads to interruptions in the availability of HIV services. We compare publicly available scenarios for COVID-19 mortality with predicted additional HIV-related mortality based on assumptions about possible interruptions in HIV programs. An interruption in the supply of ART for 40% of those on ART for 3 months could cause a number of deaths on the same order of magnitude as the number that are anticipated to be saved from COVID-19 through social distancing measures. In contrast, if the disruption can be managed such that the supply and usage of ART is maintained, the increase in AIDS deaths would be limited to 1% over five years, although this could still be accompanied by substantial increases in new HIV infections if there are reductions in VMMC, oral PrEP use, and condom availability.
Grassly N, Pons Salort M, Parker E, et al., 2020, Report 16: Role of testing in COVID-19 control
The World Health Organization has called for increased molecular testing in response to the COVID-19 pandemic, but different countries have taken very different approaches. We used a simple mathematical model to investigate the potential effectiveness of alternative testing strategies for COVID-19 control. Weekly screening of healthcare workers (HCWs) and other at-risk groups using PCR or point-of-care tests for infection irrespective of symptoms is estimated to reduce their contribution to transmission by 25-33%, on top of reductions achieved by self-isolation following symptoms. Widespread PCR testing in the general population is unlikely to limit transmission more than contact-tracing and quarantine based on symptoms alone, but could allow earlier release of contacts from quarantine. Immunity passports based on tests for antibody or infection could support return to work but face significant technical, legal and ethical challenges. Testing is essential for pandemic surveillance but its direct contribution to the prevention of transmission is likely to be limited to patients, HCWs and other high-risk groups.
Nayagam AS, Chan P, Zhao K, et al., 2020, Investment case for a comprehensive package of interventions against Hepatitis B in China; applied modelling to help national strategy planning, Clinical Infectious Diseases, 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.
Flaxman S, Mishra S, Gandy A, et al., 2020, Report 13: Estimating the number of infections and the impact of non-pharmaceutical interventions on COVID-19 in 11 European countries
Following the emergence of a novel coronavirus (SARS-CoV-2) and its spread outside of China, Europe is now experiencing large epidemics. In response, many European countries have implemented unprecedented non-pharmaceutical interventions including case isolation, the closure of schools and universities, banning of mass gatherings and/or public events, and most recently, widescale social distancing including local and national lockdowns. In this report, we use a semi-mechanistic Bayesian hierarchical model to attempt to infer the impact of these interventions across 11 European countries. Our methods assume that changes in the reproductive number – a measure of transmission - are an immediate response to these interventions being implemented rather than broader gradual changes in behaviour. Our model estimates these changes by calculating backwards from the deaths observed over time to estimate transmission that occurred several weeks prior, allowing for the time lag between infection and death. One of the key assumptions of the model is that each intervention has the same effect on the reproduction number across countries and over time. This allows us to leverage a greater amount of data across Europe to estimate these effects. It also means that our results are driven strongly by the data from countries with more advanced epidemics, and earlier interventions, such as Italy and Spain. We find that the slowing growth in daily reported deaths in Italy is consistent with a significant impact of interventions implemented several weeks earlier. In Italy, we estimate that the effective reproduction number, Rt, dropped to close to 1 around the time of lockdown (11th March), although with a high level of uncertainty. Overall, we estimate that countries have managed to reduce their reproduction number. Our estimates have wide credible intervals and contain 1 for countries that have implemented all interventions considered in our analysis. This means that the reproducti
Perez-Guzman PN, Chung MH, De Vuyst H, et al., 2020, The impact of scaling up cervical cancer screening and treatment services among women living with HIV in Kenya: a modelling study, BMJ Global Health, Vol: 5, Pages: 1-10, ISSN: 2059-7908
Introduction We aimed to quantify health outcomes and programmatic implications of scaling up cervical cancer (CC) screening and treatment options for women living with HIV in care aged 18–65 in Kenya.Methods Mathematical model comparing from 2020 to 2040: (1) visual inspection with acetic acid (VIA) and cryotherapy (Cryo); (2) VIA and Cryo or loop excision electrical procedure (LEEP), as indicated; (3) human papillomavirus (HPV)-DNA testing and Cryo or LEEP; and (4) enhanced screening technologies (either same-day HPV-DNA testing or digitally enhanced VIA) and Cryo or LEEP. Outcomes measured were annual number of CC cases, deaths, screening and treatment interventions, and engaged in care (numbers screened, treated and cured) and five yearly age-standardised incidence.Results All options will reduce CC cases and deaths compared with no scale-up. Options 1–3 will perform similarly, averting approximately 28 000 (33%) CC cases and 7700 (27%) deaths. That is, VIA screening would yield minimal losses to follow-up (LTFU). Conversely, LTFU associated with HPV-DNA testing will yield a lower care engagement, despite better diagnostic performance. In contrast, option 4 would maximise health outcomes, averting 43 200 (50%) CC cases and 11 800 (40%) deaths, given greater care engagement. Yearly rescreening with either option will impose a substantial burden on the health system, which could be reduced by spacing out frequency to three yearly without undermining health gains.Conclusions Beyond the specific choice of technologies to scale up, efficiently using available options will drive programmatic success. Addressing practical constraints around diagnostics’ performance and LTFU will be key to effectively avert CC cases and deaths.
Fu H, Lin H-H, Hallett TB, et al., 2020, Explaining age disparities in tuberculosis burden in Taiwan: a modelling study, BMC Infectious Diseases, Vol: 20, ISSN: 1471-2334
BackgroundTuberculosis (TB) burden shows wide disparities across ages in Taiwan. In 2016, the age-specific notification rate in those older than 65 years old was about 100 times as much as in those younger than 15 years old (185.0 vs 1.6 per 100,000 population). Similar patterns are observed in other intermediate TB burden settings. However, driving mechanisms for such age disparities are not clear and may have importance for TB control efforts.MethodsWe hypothesised three mechanisms for the age disparity in TB burden: (i) older age groups bear a higher risk of TB progression due to immune senescence, (ii) elderly cases acquired TB infection during a past period of high transmission, which has since rapidly declined and thus contributes to little recent infections, and (iii) assortative mixing by age allows elders to maintain a higher risk of TB infection, while limiting spillover transmission to younger age groups. We developed a series of dynamic compartmental models to incorporate these mechanisms, individually and in combination. The models were calibrated to the TB notification rates in Taiwan over 1997–2016 and evaluated by goodness-of-fit to the age disparities and the temporal trend in the TB burden, as well as the deviance information criterion (DIC). According to the model performance, we compared contributions of the hypothesised mechanisms.ResultsThe ‘full’ model including all the three hypothesised mechanisms best captured the age disparities and temporal trend of the TB notification rates. However, dropping individual mechanisms from the full model in turn, we found that excluding the mechanism of assortative mixing yielded the least change in goodness-of-fit. In terms of their influence on the TB dynamics, the major contribution of the ‘immune senescence’ and ‘assortative mixing’ mechanisms was to create disparate burden among age groups, while the ‘declining transmission’ mechanism s
Haacker M, Hallett T, Atun R, 2020, On discount rates for economic evaluations in global health, Health Policy and Planning, Vol: 35, Pages: 107-114, ISSN: 0268-1080
Choices on discount rates have important implications for the outcomes of economic evaluations of health interventions and policies. In global health, such evaluations typically apply a discount rate of 3 percent for health outcomes and costs, mirroring guidance developed for high‐income countries, notably the United States.The paper investigates the suitability of thes eguidelines for global health (i.e.,with a focus on low‐ and middle‐income countries), and seeks to identify best practice. Our analysis builds on an overview of the academic literature on discounting in health evaluations, existing academic or government‐related guidelines on discounting, are view on discount rates applied in economic evaluations in global health, and cross‐country macroeconomic data. The social discount rate generally applied in global health of 3 percent annually is in consistent with rates of economic growth experienced outside the most advanced economies. Forlow‐ and lower‐middle income countries, a discount rate of at least 5 percent is more appropriate, and one around 4 percent for upper‐middle income countries. Alternative approaches–e.g., motivated by the returns to alternative investments or by the cost of financing–could usefully be applied, dependent on policy context. The current practise could lead to systematic bias toward over‐valuing the future costs and health benefits of interventions. For health economic evaluations in global health, guidelines on discounting need to be adapted to take account of the different economic context of low‐ and middle‐income countries.
Thomas R, Skovdal M, Gallizzi M, et al., 2020, Improving risk perception and uptake of voluntary medical male circumcision with peer-education sessions and incentives, in Manicaland, East Zimbabwe: study protocol for a pilot randomised trial, Trials, Vol: 21, ISSN: 1745-6215
BackgroundVoluntary medical male circumcision (VMMC) is a key component of combination HIV-prevention programmes. Several high-HIV-prevalence countries in sub-Saharan Africa, including Zimbabwe, are looking to scale up VMMC activities. There is limited evidence on how a combination of social learning from peer education by a role model with different behavioural incentives influences demand for VMMC in such settings.Methods/DesignThis matched-cluster randomised controlled trial with 1740 participants will compare two behavioural incentives against a control with no intervention. In the intervention clusters, participants will participate in an education session delivered by a circumcised young male (“role model”) on the risks of HIV infection and the benefits from medical male circumcision. All participants will receive contributions towards transport costs to access medical male circumcision at participating clinics. Via blocked randomisation, in the intervention clusters participants will be randomly assigned to receive one of two types of incentives – fixed cash payment or lottery payment – both conditional on undergoing surgical VMMC. In two sites, a community-led intervention will also be implemented to address social obstacles and to increase support from peers, families and social structures. Baseline measures of endpoints will be gathered in surveys. Follow-up assessment at 6 months will include self-reported uptake of VMMC triangulated with clinic data.DiscussionThis is the first trial to pilot-test social learning to improve risk perception and self-efficacy and to address the fear of pain associated with VMMC and possible present-biased preferences with front-loaded compensations as well as fixed or lottery-based cash payments. This study will generate important knowledge to inform HIV-prevention policies about the effectiveness of behavioural interventions and incentives, which could be easily scaled-up.Trial registrationThis tria
Berman P, Revill P, Phillips A, et al., 2020, Modelling and Economic Evaluation to Inform WHO HIV Treatment Guidelines, World Scientific Series in Global Health Economics and Public Policy, Pages: 275-285
© 2020 The Author(s). 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.
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
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.
Eaton JW, Brown T, Puckett R, et al., 2019, The estimation and projection package age-sex model and the r-hybrid model: new tools for estimating HIV incidence trends in sub-Saharan Africa., AIDS, Vol: 33, Pages: S235-S244, ISSN: 0269-9370
OBJECTIVES: Improve models for estimating HIV epidemic trends in sub-Saharan Africa (SSA). DESIGN: Mathematical epidemic model fit to national HIV survey and ANC sentinel surveillance (ANC-SS) data. METHODS: We modified EPP to incorporate age and sex stratification (EPP-ASM) to more accurately capture the shifting demographics of maturing HIV epidemics. Secondly, we developed a new functional form for the HIV transmission rate, termed 'r-hybrid', which combines a four-parameter logistic function for the initial epidemic growth, peak, and decline followed by a first-order random walk for recent trends after epidemic stabilization. We fitted the r-hybrid model along with previously developed r-spline and r-trend models to HIV prevalence data from household surveys and ANC-SS in 177 regions in 34 SSA countries. We used leave-one-out cross validation with household survey HIV prevalence to compare model predictions. RESULTS: The r-hybrid and r-spline models typically provided similar HIV prevalence trends, but sometimes qualitatively different assessments of recent incidence trends because of different structural assumptions about the HIV transmission rate. The r-hybrid model had the lowest average continuous ranked probability score, indicating the best model predictions. Coverage of 95% posterior predictive intervals was 91.5% for the r-hybrid model, versus 87.2 and 85.5% for r-spline and r-trend, respectively. CONCLUSION: The EPP-ASM and r-hybrid models improve consistency of EPP and Spectrum, improve the epidemiological assumptions underpinning recent HIV incidence estimates, and improve estimates and short-term projections of HIV prevalence trends. Countries that use general population survey and ANC-SS data to estimate HIV epidemic trends should consider using these tools.
Eaton J, Brown T, Puckett R, et al., 2019, The Estimation and Projection Package Age-Sex Model and the r-hybrid modelnew tools for estimating HIV incidence trends in sub-Saharan Africa, AIDS, Vol: 33, Pages: S235-S244, ISSN: 0269-9370
Objectives: Improve models for estimating HIV epidemic trends in sub-Saharan Africa (SSA).Design: Mathematical epidemic model fit to national HIV survey and ANC sentinel surveillance(ANC-SS) data.Methods: We modified EPP to incorporate age and sex stratification (EPP-ASM) to moreaccurately capture the shifting demographics of maturing HIV epidemics. Secondly, wedeveloped a new functional form, termed ‘r-hybrid’, for the HIV transmission rate whichcombines a four-parameter logistic function for the initial epidemic growth, peak, and declinefollowed by a first-order random walk for recent trends after epidemic stabilization. We fitted ther-hybrid model along with previously developed r-spline and r-trend models to HIV prevalencedata from household surveys and ANC-SS in 177 regions in 34 SSA countries. We used leaveone-out cross validation with household survey HIV prevalence to compare model predictions.Results: The r-hybrid and r-spline models typically provided similar HIV prevalence trends, butsometimes qualitatively different assessments of recent incidence trends due to differentstructural assumptions about the HIV transmission rate. The r-hybrid model had the lowestaverage continuous ranked probability score, indicating the best model predictions. Coverage of95% posterior predictive intervals was 91.5% for the r-hybrid model, versus 87.2% and 85.5%for r-spline and r-trend, respectively.Conclusions: The EPP-ASM and r-hybrid models improve consistency of EPP and Spectrum,improve the epidemiological assumptions underpinning recent HIV incidence estimates, andimprove estimates and short-term projections of HIV prevalence trends. Countries that usegeneral population survey and ANC-SS data to estimate HIV epidemic trends should considerusing these tools.
Thomas R, Skovdal M, Galizzi MM, et al., 2019, Improving risk perception and uptake of pre-exposure prophylaxis (PrEP) through interactive feedback-based counselling with and without community engagement in young women in Manicaland, East Zimbabwe: study protocol for a pilot randomized trial, Trials, Vol: 20, ISSN: 1745-6215
BackgroundHIV incidence in adolescent girls and young women remains high in sub-Saharan Africa. Progresstowards uptake of HIV prevention methods remains low. Studies of oral PrEP have shown that uptakeand adherence may be low due to low risk perception and ambivalence around using antiretroviralsfor prevention. No evidence exists on whether an interactive intervention aimed at adjusting riskperception and addressing the uncertainty around PrEP will improve uptake. This pilot research trialaims to provide an initial evaluation of the impact of an interactive digital tablet-based counsellingsession, correcting risk perception and addressing ambiguity around availability, usability andeffectiveness of PrEP.Methods/DesignThis is a matched-cluster randomised controlled trial which will compare an interactive tablet-basededucation intervention against a control with no intervention. The study will be implemented in eightsites. In each site, two matched clusters of villages will be created. One cluster will be randomlyallocated to intervention. In two sites a community engagement intervention will also be implementedto address social obstacles and to increase support from peers, families and social structures. 1,200HIV-negative young women 18-24 years, not on PrEP at baseline will be eligible. Baseline measures ofendpoints will be gathered in surveys. Follow-up assessment at six months will include bio-markers ofPrEP uptake and surveys.DiscussionThis will be the first randomized controlled trial to determine whether interactive feedbackcounselling leads to uptake of HIV prevention methods such as PrEP and reduces risky sexualbehaviour. If successful, policymakers could consider such an intervention in school-based educationcampaigns or as post- HIV-testing counselling for young people.Trial RegistrationThis trial has been registered on clinicaltrials.gov on 21/06/2018 (identifier: NCT03565575).https://clinicaltrials.gov/ct2/show/NCT03565575
Smit M, Perez-Guzman P, Mutai KK, et al., 2019, Mapping the current and future non-communicable disease burden in Kenya by HIV status: a modelling study, Clinical Infectious Diseases, 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.
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