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Abstract Between February 2020 and May 2022, one million Americans have died of COVID-19. To determine the contribution of those deaths to all-cause mortality in terms of life expectancy reductions and the resulting economic welfare losses, we calculated their combined impact on national income growth and the added value of lives lost. We estimated that US life expectancy at birth dropped by 3.08 years due to the million COVID-19 deaths. Economic welfare losses estimated in terms of national income growth supplemented by the value of lives lost, was in the order of US$3.57 trillion. US$2.20 trillion of these losses were in in the non-Hispanic White population (56.50%), US$698.24 billion (19.54%) in the Hispanic population, and US$579.93 billion (16.23%) in the non-Hispanic Black population. The scale of life expectancy and welfare losses underscores the pressing need to invest in health in the US to prevent further economic shocks from future pandemic threats.

Background Economic losses due to herpes simplex infections in low- and middle-income countries (LMICs) are unknown. We estimated economic and quality-of-life losses due to genital herpes in 2019, in 90 LMICs, and from 2020 to 2030 in 45 countries in the World Health Organization (WHO) Africa. We additionally estimated economic losses due to human immunodeficiency virus (HIV) attributable to herpes simplex virus type 2 (HSV-2) infections. Methods and findings We estimated genital herpes-related spending on treatment, wage losses due to absenteeism, and reductions in quality of life, for individuals aged 15 to 49 years, living with genital herpes. Had HSV-2 had contributed to the transmission of HIV, we estimated the share of antiretroviral treatment costs and HIV-related wage losses in 2019 that can be attributed to incident and prevalent HSV-2 infections in 2018. For the former, we used estimates of HSV-2 incidence and prevalence from the global burden of disease (GBD) study. For the latter, we calculated population attributable fractions (PAFs), using the classic (Levin’s) epidemiological formula for polytomous exposures, with relative risks (RRs) reported in literature. To extend estimates from 2020 to 2030, we modeled the transmission of HSV-2 in 45 African countries using a deterministic compartmental mathematical model, structured by age, sex, and sexual activity, which was fitted to seroprevalence gathered from a systematic review and meta-regression analysis. In the 90 LMICs, genital herpes contributed to US$813.5 million in treatment and productivity losses in 2019 (range: US$674.4 to US$952.2 million). Given observed care-seeking and absenteeism, losses are in the range of US$29.0 billion (US$25.6 billion to US$34.5 billion). Quality-of-life losses in the amount of 61.7 million quality-adjusted life years (QALYs) are also possible (50.4 million to 74.2 million). The mean annual cost of treatment and wage losses per infection is US$183.00 (95% CI: US$153.60 to US$212.55); the mean annual cost of quality-of-life losses is US$343.27 (95% CI: 272.41 to 414.14). If HSV-2 has fueled the transmission of HIV, then seroprevalent HSV-2 cases in 2018 can account for 33.2% of the incident HIV infections in 2019, with an associated antiretroviral therapy (ART) cost of US$186.3 million (range: US$163.6 to US$209.5 million) and 28.6% of HIV-related wage losses (US$21.9 million; range: US$19.2 to US$27.4 million). In the WHO Africa region, the 3.9 million seroprevalent genital herpes cases from 2020 to 2030 contributed to US$700.2 million in treatment and productivity losses. Additionally, quality-of-life losses in the range of 88 million to 871 million QALYs are also possible. If HSV-2 has contributed to the transmission of HIV, then in 2020, the PAF of HIV due to prevalent HSV-2 will be 32.8% (95% CI: 26.7% to 29.9%) and due to incident infections will be 4.2% (95% CI: 2.6% to 3.4%). The PAF due to prevalent infections will decline to 31.0% by 2030 and incident infections to 3.6%. Though we have accounted for the uncertainty in the epidemiological and economic parameter values via the sensitivity analysis, our estimates still undervalue losses due to limiting to the 15- to 49-year-old population. Conclusions Economic losses due to genital herpes in LMICs can be large, especially when considering the lifelong nature of the disease. Quality-of-life losses outweigh spending on treatment and reductions in productivity. If HSV-2 has contributed to the spread of HIV in LMICs, then nearly one third of antiretroviral costs and HIV-related wage losses can be attributed to HSV-2. Given the magnitude of the combined losses, a vaccine against HSV-2 must be a global priority. In a modelling study, Dr Sachin Silva and colleagues estimate the economic burden of genital herpes and HIV attributable to herpes simplex virus type-2 infections in 90 low and middle income countries. Author summary Why was this study done? ▪ Economic losses due to herpes simplex virus type 2 (HSV-2) infections in low- and middle-income countries (LMICs) are unknown. ▪ Quality-of-life losses due to genital herpes in LMICs are also unknown, both in terms of their magnitude and their economic value. ▪ If HSV-2 has indeed fueled the spread of human immunodeficiency virus (HIV), as has been conjectured, then the share of HIV-related spending in LMICs that are attributable to HSV-2 infections are also unknown. What did the researchers do and find? ▪ We estimated direct and indirect economic losses and quality-of-life losses due to genital herpes in individuals between the aged of 15 to 49 living in 90 LMICs in 2019. ▪ We also estimated these costs in 45 countries in the World Health Organization (WHO) Africa region from 2020 to 2030, by constructing a mathematical model of HSV-2 dynamics to predict HSV-2 incidence and prevalence. ▪ We supplemented the 2019 estimates with the share of HIV-related spending in 2019 attributable HSV-2 infections in 2018. ▪ For the 90 LMICs, we found that treatment costs and productivity losses in 2019 are in the range of US$674.4 and US$952.2 million. ▪ Quality-of-life losses are in the range of 50.4 million to 74.2 million quality-adjusted life years (QALYs). ▪ Additionally, seroprevalent HSV-2 cases in 2019 can account for 33.2% of antiretroviral therapy (ART) costs for incident HIV cases and 28.6% of HIV-related wage. What do these findings mean? ▪ Economic losses due to genital herpes can be substantial, especially when considering the lifelong nature of the disease. ▪ The quality-of-life losses due to genital herpes outweigh spending on treatment and reduced productivity (on the order of US$212 billion). ▪ If HSV-2 has indeed contributed to the transmission of HIV, then nearly one third of antiretroviral costs and HIV-related wage losses add to these costs. ▪ Given the magnitude of the above losses in LMICs, a vaccine against HSV-2 should be a global priority.

West Africa’s Ebola epidemic of 2014–2016 exposed, among other problems, the under-funding of transnational global health activities known as global common goods for health (CGH), global functions such as pandemic preparedness and research and development (R&D) for neglected diseases. To mobilize sustainable funding for global CGH, it is critical first to understand existing financing flowing to different types of global CGH. In this study, we estimate trends in international spending for global CGH in 2013, 2015, and 2017, encompassing the era before and after the Ebola epidemic. We use a measure of international funding that combines official development assistance (ODA) for health with additional international spending on R&D for diseases of poverty, a measure called ODA+. We classify ODA+ into funding for three global functions—provision of global public goods, management of cross-border externalities, and fostering of global health leadership and stewardship—and country-specific aid. International funding for global functions increased between 2013 and 2015 by $1.4 billion to a total of $7.3 billion in 2015. It then declined to $7.0 billion in 2017, accounting for 24% of all ODA+ in 2017. These findings provide empirical evidence of the reactive nature of international funders for global CGH. While international funders increased funding for global functions in response to the Ebola outbreak, they failed to sustain that funding. To meet future global health challenges proactively, international funders should allocate more funding for global functions.

Abstract Background Accurate estimates of the burden of antimicrobial resistance (AMR) are needed to establish the magnitude of this global threat in terms of both health and cost, and to paramaterise cost-effectiveness evaluations of interventions aiming to tackle the problem. This review aimed to establish the alternative methodologies used in estimating AMR burden in order to appraise the current evidence base. Methods MEDLINE, EMBASE, Scopus, EconLit, PubMed and grey literature were searched. English language studies evaluating the impact of AMR (from any microbe) on patient, payer/provider and economic burden published between January 2013 and December 2015 were included. Independent screening of title/abstracts followed by full texts was performed using pre-specified criteria. A study quality score (from zero to one) was derived using Newcastle-Ottawa and Philips checklists. Extracted study data were used to compare study method and resulting burden estimate, according to perspective. Monetary costs were converted into 2013 USD. Results Out of 5187 unique retrievals, 214 studies were included. One hundred eighty-seven studies estimated patient health, 75 studies estimated payer/provider and 11 studies estimated economic burden. 64% of included studies were single centre. The majority of studies estimating patient or provider/payer burden used regression techniques. 48% of studies estimating mortality burden found a significant impact from resistance, excess healthcare system costs ranged from non-significance to $1 billion per year, whilst economic burden ranged from $21,832 per case to over $3 trillion in GDP loss. Median quality scores (interquartile range) for patient, payer/provider and economic burden studies were 0.67 (0.56-0.67), 0.56 (0.46-0.67) and 0.53 (0.44-0.60) respectively. Conclusions This study highlights what methodological assumptions and biases can occur dependent on chosen outcome and perspective. Currently, there is considerable variability in burden estimates, which can lead in-turn to inaccurate intervention evaluations and poor policy/investment decisions. Future research should utilise the recommendations presented in this review. Trial registration This systematic review is registered with PROSPERO (PROSPERO CRD42016037510).

Abstract Background Estimates of the burden of antimicrobial resistance (AMR) are needed to ascertain AMR impact, to evaluate interventions, and to allocate resources efficiently. Recent studies have estimated health, cost, and economic burden relating to AMR, with outcomes of interest ranging from drug-bug resistance impact on mortality in a hospital setting to total economic impact of AMR on the global economy. However, recent collation of this information has been largely informal, with no formal quality assessment of the current evidence base (e.g. with predefined checklists). This review therefore aims to establish what perspectives and resulting methodologies have been used in establishing the burden of AMR, whilst also ascertaining the quality of these studies. Methods The literature review will identify relevant literature using a systematic review methodology. MEDLINE, EMBASE, Scopus and EconLit will be searched utilising a predefined search string. Grey literature will be identified by searching within a predefined list of organisational websites. Independent screening of retrievals will be performed in a two-stage process (abstracts and full texts), utilising a pre-defined inclusion and exclusion criteria. Data will be extracted into a data extraction table and descriptive examination will be performed. Study quality will be assessed using the Newcastle-Ottawa scales and the Philips checklists where appropriate. A narrative synthesis of the results will be presented. Discussion This review will provide an overview of previous health, cost and economic definitions of burden and the resultant impact of these different definitions on the burden of AMR estimated. The review will also explore the methods that have been used to calculate this burden and discuss resulting study quality. This review can therefore act as a guide to methods for future research in this area. Systematic review registration PROSPERO CRD42016037510

Development assistance for health (DAH), the value of which peaked in 2013 and fell in 2015, is unlikely to rise substantially in the near future, increasing reliance on domestic and innovative financing sources to sustain health programmes in low-income and middle-income countries. We examined innovative financing instruments (IFIs)—financing schemes that generate and mobilise funds—to estimate the quantum of financing mobilised from 2002 to 2015. We identified ten IFIs, which mobilised US$8·9 billion (2·3% of overall DAH) in 2002–15. The funds generated by IFIs were channelled mostly through GAVI and the Global Fund, and used for programmes for new and underused vaccines, HIV/AIDS, malaria, tuberculosis, and maternal and child health. Vaccination programmes received the largest amount of funding ($2·6 billion), followed by HIV/AIDS ($1080·7 million) and malaria ($1028·9 million), with no discernible funding targeted to non-communicable diseases.

In 2015 around 15 million people living with HIV were receiving antiretroviral treatment (ART) in sub–Saharan Africa. Sustained provision of ART, though both prudent and necessary, creates substantial long–term fiscal obligations for countries affected by HIV/AIDS. As donor assistance for health remains constrained, novel financing mechanisms are needed to augment funding domestic sources. We explore how Innovative Financing has been used to co–finance domestic HIV/AIDS responses. Based on analysis of non–health sectors, we identify innovative financing instruments that could be used in the HIV response.