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).

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.

Health and economic benefits possible with emerging tuberculosis vaccines are not fully known. We estimated gains possible with novel post-exposure vaccines, in India and Indonesia. We modeled vaccine impact on TB incidence, TB mortality, and on national income growth and the intrinsic value of living longer, known as Full-income. We considered several vaccine efficacies, initiation and scale-up scenarios. We found that if all age groups are vaccinated in 2025, then 2.3 million TB deaths in India and 695,000 TB deaths in Indonesia can be prevented, adding 0.09 years and 0.17 years to individual life expectancy at birth, on average annually. Full-income savings is US$2 trillion in India and US$680 billion in Indonesia. Even if delayed until 2030, 1.6 million deaths in India and 489,000 deaths in Indonesia can be prevented, with full-income savings of US$1.5 trillion and US$490 billion. These benefits suggest that further investment in the vaccines is prudent.Significance Statement There are no prior economic evaluations of candidate tuberculosis vaccines. Our study addresses this gap to answer two questions: (1) is there value in making the vaccine available given the efficacies demonstrated to date; and (2) is there an optimal time window for making the vaccine available. The conclusions in relation to these two questions are important because: (1) they are based on findings from two countries, which jointly account for 35% of global TB incidence and 38.8% of global TB mortality in 2019; (2) they provide guidance for future investment in the vaccine and roll-out in those countries.

Introduction: Health impacts of global warming in sub-Saharan African countries that received President's Emergency Plan for AIDS Relief (PEPFAR)–funded HIV support are not known. Methods: Assuming the narrative of the Shared Socioeconomic Pathway 2, we estimated excess deaths, life expectancy losses at birth, and economic welfare losses in terms of full income. We relied on the MAGICC climate model for temperature predictions from 2025–2100 and net all-cause mortality risks estimated by others. Results: Surface temperature increases could reduce life expectancy at birth by 0.057 years in 2025 (95% CI: 0.024–0.095). By 2050, the reduction could increase by 30.7%, to 0.075 years (95% CI: 0.0311–0.1247). By 2100, it could further increase by 44.5%, to 0.083 years (95% CI: 0.034–0.138). Corresponding full income losses are US$11.44 billion in 2025 (95% CI: $4.77–$19.07 billion), which increases by 4-fold in 2050 to US$44.62 billion (95% CI: $18.65–$74.36 billion). By 2100, a 30-fold increase is possible, to US$353.56 billion (95% CI: $148.84–$588.32 billion). On a per capita basis, the highest full income losses consistently accrue to Lesotho between 2025 and 2100 (US$20.51, or 0.70% of per capita GDP, to US$355.39, or 0.80%). Conclusion: Adjusted investment is needed to address climate impacts, especially in countries such as Lesotho that may bear damage due to other regional emitters.