The potential importance of the built-environment microbiome and its impact on human health.

There is increasing evidence that interactions between microbes and their hosts not only play a role in determining health and disease but also in emotions, thought, and behavior. Built environments greatly influence microbiome exposures because of their built-in highly specific microbiomes coproduced with myriad metaorganisms including humans, pets, plants, rodents, and insects. Seemingly static built structures host complex ecologies of microorganisms that are only starting to be mapped. These microbial ecologies of built environments are directly and interdependently affected by social, spatial, and technological norms. Advances in technology have made these organisms visible and forced the scientific community and architects to rethink gene-environment and microbe interactions respectively. Thus, built environment design must consider the microbiome, and research involving host-microbiome interaction must consider the built-environment. This paradigm shift becomes increasingly important as evidence grows that contemporary built environments are steadily reducing the microbial diversity essential for human health, well-being, and resilience while accelerating the symptoms of human chronic diseases including environmental allergies, and other more life-altering diseases. New models of design are required to balance maximizing exposure to microbial diversity while minimizing exposure to human-associated diseases. Sustained trans-disciplinary research across time (evolutionary, historical, and generational) and space (cultural and geographical) is needed to develop experimental design protocols that address multigenerational multispecies health and health equity in built environments.

Commonality and variation in mental representations of music revealed by a cross-cultural comparison of rhythm priors in 15 countries.

Music is present in every known society but varies from place to place. What, if anything, is universal to music cognition? We measured a signature of mental representations of rhythm in 39 participant groups in 15 countries, spanning urban societies and Indigenous populations. Listeners reproduced random 'seed' rhythms; their reproductions were fed back as the stimulus (as in the game of 'telephone'), such that their biases (the prior) could be estimated from the distribution of reproductions. Every tested group showed a sparse prior with peaks at integer-ratio rhythms. However, the importance of different integer ratios varied across groups, often reflecting local musical practices. Our results suggest a common feature of music cognition: discrete rhythm 'categories' at small-integer ratios. These discrete representations plausibly stabilize musical systems in the face of cultural transmission but interact with culture-specific traditions to yield the diversity that is evident when mental representations are probed across many cultures.

Costs-effectiveness and cost components of pharmaceutical and non-pharmaceutical interventions affecting antibiotic resistance outcomes in hospital patients: a systematic literature review.

INTRODUCTION: Limited information on costs and the cost-effectiveness of hospital interventions to reduce antibiotic resistance (ABR) hinder efficient resource allocation. METHODS: We conducted a systematic literature review for studies evaluating the costs and cost-effectiveness of pharmaceutical and non-pharmaceutical interventions aimed at reducing, monitoring and controlling ABR in patients. Articles published until 12 December 2023 were explored using EconLit, EMBASE and PubMed. We focused on critical or high-priority bacteria, as defined by the WHO, and intervention costs and incremental cost-effectiveness ratio (ICER). Following Preferred Reporting Items for Systematic review and Meta-Analysis guidelines, we extracted unit costs, ICERs and essential study information including country, intervention, bacteria-drug combination, discount rates, type of model and outcomes. Costs were reported in 2022 US dollars ($), adopting the healthcare system perspective. Country willingness-to-pay (WTP) thresholds from Woods et al 2016 guided cost-effectiveness assessments. We assessed the studies reporting checklist using Drummond's method. RESULTS: Among 20 958 articles, 59 (32 pharmaceutical and 27 non-pharmaceutical interventions) met the inclusion criteria. Non-pharmaceutical interventions, such as hygiene measures, had unit costs as low as $1 per patient, contrasting with generally higher pharmaceutical intervention costs. Several studies found that linezolid-based treatments for methicillin-resistant Staphylococcus aureus were cost-effective compared with vancomycin (ICER up to $21 488 per treatment success, all 16 studies' ICERs

Enrollment of dengue patients in a prospective cohort study in Umphang District, Thailand, during the COVID-19 pandemic: Implications for research and policy.

Background and Aims: Dengue is endemic in Thailand and imposes a high burden on the health system and society. We conducted a prospective cohort study in Umphang District, Tak Province, Thailand, to investigate the share of dengue cases with long symptoms and their duration. Here we present the results of the enrollment process during the COVID-19 pandemic with implications and challenges for research and policy. Methods: In a prospective cohort study conducted in Umphang District, Thailand, we examined the prevalence of persistent symptoms in dengue cases. Clinically diagnosed cases were offered free laboratory testing, We enrolled ambulatory dengue patients regardless of age who were confirmed through a highly sensitive laboratory strategy (positive NS1 and/or IgM), agreed to follow-up visits, and gave informed consent. We used multivariate logistic regressions to assess the probability of clinical dengue being laboratory confirmed. To determine the factors associated with study enrollment, we analyzed the relationship of patient characteristics and month of screening to the likelihood of participation. To identify underrepresented groups, we compared the enrolled cohort to external data sources. Results: The 150 clinical cases ranged from 1 to 85 years old. Most clinical cases (78%) were confirmed by a positive laboratory test, but only 19% of those confirmed enrolled in the cohort study. Women, who were half as likely to enroll as men, were underrepresented in the cohort. Conclusions: The Thai physicians' clinical diagnoses at this rural district hospital had good agreement with laboratory diagnoses. By identifying underrepresented groups and disparities, future studies can ensure the creation of statistically representative cohorts to maximize their scientific value. This involves recruiting and retaining underrepresented groups in health research, such as women in this study. Promising strategies for meaningful inclusion include multi-site enrollment, offering in-home or virtual services, and providing in-kind benefits like childcare for underrepresented groups.

Time to rethink academic publishing: the peer reviewer crisis.

There is concern that the time taken to publish academic papers in microbiological science has significantly increased in recent years. While the data do not specifically support this, evidence suggests that editors are having to invite more and more reviewers to identify those willing to perform peer review.

Effectiveness of the second COVID-19 booster against Omicron: a large-scale cohort study in Chile.

In light of the ongoing COVID-19 pandemic and the emergence of new SARS-CoV-2 variants, understanding the effectiveness of various booster vaccination regimens is pivotal. In Chile, using a prospective national cohort of 3.75 million individuals aged 20 or older, we evaluate the effectiveness against COVID-19-related intensive care unit (ICU) admissions and death of mRNA-based second vaccine boosters for four different three-dose background regimes: BNT162b2 primary series followed by a homologous booster, and CoronaVac primary series followed by an mRNA booster, a homologous booster, and a ChAdOx-1 booster. We estimate the vaccine effectiveness weekly from February 14 to August 15, 2022, by determining hazard ratios of immunization over non-vaccination, accounting for relevant confounders. The overall adjusted effectiveness of a second mRNA booster shot is 88.2% (95%CI, 86.2-89.9) against ICU admissions and 90.5% (95%CI 89.4-91.4) against death. Vaccine effectiveness shows a mild decrease for all regimens and outcomes, probably linked to the introduction of BA.4 and BA.5 Omicron sub-lineages and the waning of immunity. Based on our findings, individuals might not need additional boosters for at least 6 months after receiving a second mRNA booster shot in this setting.

Non-pharmaceutical interventions to combat COVID-19 in the Americas described through daily sub-national data.

This dataset covers national and subnational non-pharmaceutical interventions (NPI) to combat the COVID-19 pandemic in the Americas. Prior to the development of a vaccine, NPI were governments' primary tools to mitigate the spread of COVID-19. Variation in subnational responses to COVID-19 is high and is salient for health outcomes. This dataset captures governments' dynamic, varied NPI to combat COVID-19 for 80% of Latin America's population from each country's first case through December 2021. These daily data encompass all national and subnational units in Argentina, Bolivia, Brazil, Chile, Colombia, Ecuador, Mexico, and Peru. The dataset includes individual and aggregate indices of nine NPI: school closures, work suspensions, public event cancellations, public transport suspensions, information campaigns, local travel restrictions, international travel controls, stay-at-home orders, and restrictions on the size of gatherings. We also collected data on mask mandates as a separate indicator. Local country-teams drew from multiple data sources, resulting in high-quality, reliable data. The dataset thus allows for consistent, meaningful comparisons of NPI within and across countries during the pandemic.

Prevalence of depressive disorder in the adult population of Latin America: a systematic review and meta-analysis.

Background: Depressive disorder is one of the leading causes of disability worldwide; however its prevalence and association with inequality and crime is poorly characterised in Latin America. This study aimed to: i. systematically review population-based studies of prevalence of ICD/DSM depressive disorder in Latin America, ii. report pooled regional, country, and sex-specific prevalence estimates, and iii. test its association with four country-level development indicators: human development (HDI), income (Gini) and gender inequality (GII), and intentional homicide rate (IHR). Methods: We conducted a systematic review and meta-analysis of population-based studies reporting primary data on the prevalence of ICD/DSM depressive disorder in Latin America from 1990 to 2023, irrespective of language. We searched PubMed, PsycINFO, Cochrane Library, SciELO (regional database), LILAC (regional database), and available grey literature. Study quality was assessed using JBI's critical appraisal tools. We generated pooled estimates using random-effects meta-analysis; heterogeneity was assessed using the I2 statistic. Meta-regression analyses were used to test associations of depression prevalence with indicators of inequality and human development. The study was registered with PROSPERO (CRD42019143054). Findings: Using data from 40 studies in Latin America, lifetime, 12-month, and current prevalence of ICD/DSM depressive disorder were calculated at 12.58% (95% CI 11.00%-14.16%); 5.30% (4.55-6.06%), and 3.12% (2.22-4.03), respectively. Heterogeneity was high across lifetime, 12-month, and current prevalence, sex, and countries. 12-month and current prevalence was associated with higher Gini and GII, 12-month prevalence with lower HDI, and current prevalence with higher IHR. Interpretation: We found a high prevalence of ICD/DSM depressive disorders in Latin America, and a statistically significant association with inequality and development indicators. The high heterogeneity found across prevalence periods and the major gaps in country representation underscore the need to escalate efforts to improve mental health access and research capabilities in Latin America. Systematic, comparable prevalence estimates would inform more effective decision-making in the region. Funding: Pfizer Independent Medical Education Grant.

Demographic and clinical risk factors associated with severity of lab-confirmed human leptospirosis in Colombia, 2015-2020.

BACKGROUND: Leptospirosis is a common zoonoses and is a major global public health threat. Most cases are mild, typically presenting as a non-specific acute febrile illness. However, leptospirosis can have life-threatening manifestations, including pulmonary hemorrhage syndrome, and acute kidney injury. In Colombia, notification and lab-confirmation of suspected human cases are mandatory. However, little is known about the demographic and clinical factors associated with severe leptospirosis, which could help to reduce clinical complications and mortality. Our aim was to identify risk factors associated with severe leptospirosis, intensive care unit (ICU) admission, and mortality in lab-confirmed cases in Colombia, 2015-2020. METHODS AND FINDINGS: We analyzed 201 lab-confirmed human leptospirosis cases by microagglutination test. We used a logistic regression to identify the demographic and clinical risk factors associated with severe leptospirosis, admission to ICU, and death. Most leptospirosis confirmed cases occurred in men (85.6%); the mean age was 36.7 years. We classified severe cases (43.3%) by clinical manifestations as renal (29.9%) and liver (27.4%) failure, multiple-organ failure (24.4%), septic shock (24.4%), Weil syndrome (18.4%), pulmonary hemorrhage (18.4%), and meningitis (2.5%), admitted to the ICU (30.3%), and fatal (8.5%). Clinical conditions associated with severe leptospirosis were dyspnea (OR: 5.54; 95% CI: 1.46 to 20.98), tachycardia (OR:9.69; 95% CI: 15.96 to 58.8), and rash (OR: 10.25; 95% CI: 25.01 to 42.08). CONCLUSIONS: We identified demographic characteristics and clinical symptoms associated with severe leptospirosis in Colombia. We hope these results can support clinicians in providing timely treatment to leptospirosis patients to avoid preventable medical complications or deaths.

High Burden of Intestinal Colonization With Antimicrobial-Resistant Bacteria in Chile: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study.

BACKGROUND: Antimicrobial resistance is a global threat, heavily impacting low- and middle-income countries. This study estimated antimicrobial-resistant gram-negative bacteria (GNB) fecal colonization prevalence in hospitalized and community-dwelling adults in Chile before the coronavirus disease 2019 pandemic. METHODS: From December 2018 to May 2019, we enrolled hospitalized adults in 4 public hospitals and community dwellers from central Chile, who provided fecal specimens and epidemiological information. Samples were plated onto MacConkey agar with ciprofloxacin or ceftazidime added. All recovered morphotypes were identified and characterized according to the following phenotypes: fluoroquinolone-resistant (FQR), extended-spectrum cephalosporin-resistant (ESCR), carbapenem-resistant (CR), or multidrug-resistant (MDR; as per Centers for Disease Control and Prevention criteria) GNB. Categories were not mutually exclusive. RESULTS: A total of 775 hospitalized adults and 357 community dwellers were enrolled. Among hospitalized subjects, the prevalence of colonization with FQR, ESCR, CR, or MDR-GNB was 46.4% (95% confidence interval [CI], 42.9-50.0), 41.2% (95% CI, 37.7-44.6), 14.5% (95% CI, 12.0-16.9), and 26.3% (95% CI, 23.2-29.4). In the community, the prevalence of FQR, ESCR, CR, and MDR-GNB colonization was 39.5% (95% CI, 34.4-44.6), 28.9% (95% CI, 24.2-33.6), 5.6% (95% CI, 3.2-8.0), and 4.8% (95% CI, 2.6-7.0), respectively. CONCLUSIONS: A high burden of antimicrobial-resistant GNB colonization was observed in this sample of hospitalized and community-dwelling adults, suggesting that the community is a relevant source of antibiotic resistance. Efforts are needed to understand the relatedness between resistant strains circulating in the community and hospitals.

Antibiotic Consumption During the Coronavirus Disease 2019 Pandemic and Emergence of Carbapenemase-Producing Klebsiella pneumoniae Lineages Among Inpatients in a Chilean Hospital: A Time-Series Study and Phylogenomic Analysis.

BACKGROUND: The impact of coronavirus disease 2019 (COVID-19) on antimicrobial use (AU) and resistance has not been well evaluated in South America. These data are critical to inform national policies and clinical care. METHODS: At a tertiary hospital in Santiago, Chile, between 2018 and 2022, subdivided into pre- (3/2018-2/2020) and post-COVID-19 onset (3/2020-2/2022), we evaluated intravenous AU and frequency of carbapenem-resistant Enterobacterales (CRE). We grouped monthly AU (defined daily doses [DDD]/1000 patient-days) into broad-spectrum ß-lactams, carbapenems, and colistin and used interrupted time-series analysis to compare AU during pre- and post-pandemic onset. We studied the frequency of carbapenemase-producing (CP) CRE and performed whole-genome sequencing analyses of all carbapenem-resistant (CR) Klebsiella pneumoniae (CRKpn) isolates collected during the study period. RESULTS: Compared with pre-pandemic, AU (DDD/1000 patient-days) significantly increased after the pandemic onset, from 78.1 to 142.5 (P < .001), 50.9 to 110.1 (P < .001), and 4.1 to 13.3 (P < .001) for broad-spectrum ß-lactams, carbapenems, and colistin, respectively. The frequency of CP-CRE increased from 12.8% pre-COVID-19 to 51.9% after pandemic onset (P < .001). The most frequent CRE species in both periods was CRKpn (79.5% and 76.5%, respectively). The expansion of CP-CRE harboring blaNDM was particularly noticeable, increasing from 40% (n = 4/10) before to 73.6% (n = 39/53) after pandemic onset (P < .001). Our phylogenomic analyses revealed the emergence of two distinct genomic lineages of CP-CRKpn: ST45, harboring blaNDM, and ST1161, which carried blaKPC. CONCLUSIONS: AU and the frequency of CP-CRE increased after COVID-19 onset. The increase in CP-CRKpn was driven by the emergence of novel genomic lineages. Our observations highlight the need to strengthen infection prevention and control and antimicrobial stewardship efforts.

A review of the global emergence of multidrug-resistant Salmonella enterica subsp. enterica Serovar Infantis.

Salmonella enterica serovar Infantis is an emergent foodborne and zoonotic Salmonella serovar with critical implications for global health. In recent years, the prevalence of S. Infantis infections has increased in the United States, Europe, and Latin America, due to contaminated chicken and other foods. An essential trait of S. Infantis is its resistance to multiple antibiotics, including the critically important third-generation cephalosporins and quinolones, undermining effective medical treatment, particularly in low-resource settings. We describe the emergence of multidrug-resistant (MDR) S. Infantis, focusing on humans, animals, the environment, and food. We conducted a systematic review (1979-2021), selected 183 studies, and analyzed the origin, source, antimicrobial resistance, and presence of a conjugative plasmid of emerging S. Infantis (pESI) in reported isolates. S. Infantis has been detected worldwide, with a substantial increase since 2011. We found the highest number of isolations in the Americas (42.9 %), Europe (29.8 %), Western Pacific (17.2 %), Eastern Mediterranean (6.6 %), Africa (3.4 %), and South-East Asia (0.1 %). S. Infantis showed MDR patterns and numerous resistant genes in all sources. The primary source of MDR S. Infantis is broiler and their meat; however, this emerging pathogen is also present in other reservoirs such as food, wildlife, and the environment. Clinical cases of MDR S. Infantis have been reported in children and adults. The global emergence of S. Infantis is related to a plasmid (pESI) with antibiotic and arsenic- and mercury-resistance genes. Additionally, a new megaplasmid (pESI-like), carrying blaCTX-M-65 and antibiotic-resistant genes reported in an ancestral version, was detected in the broiler, human, and chicken meat isolates. Strains harboring pESI-like were primarily observed in the Americas and Europe. MDR S. Infantis has spread globally, potentially becoming a major public health threat, particularly in low- and middle-income countries.

Heavy Metal Pollution From a Major Earthquake and Tsunami in Chile Is Associated With Geographic Divergence of Clinical Isolates of Methicillin-Resistant Staphylococcus aureus in Latin America.

Methicillin-resistant Staphylococcus aureus (MRSA) is a priority pathogen listed by the World Health Organization. The global spread of MRSA is characterized by successive waves of epidemic clones that predominate in specific geographical regions. The acquisition of genes encoding resistance to heavy-metals is thought to be a key feature in the divergence and geographical spread of MRSA. Increasing evidence suggests that extreme natural events, such as earthquakes and tsunamis, could release heavy-metals into the environment. However, the impact of environmental exposition to heavy-metals on the divergence and spread of MRSA clones has been insufficiently explored. We assess the association between a major earthquake and tsunami in an industrialized port in southern Chile and MRSA clone divergence in Latin America. We performed a phylogenomic reconstruction of 113 MRSA clinical isolates from seven Latin American healthcare centers, including 25 isolates collected in a geographic area affected by an earthquake and tsunami that led to high levels of heavy-metal environmental contamination. We found a divergence event strongly associated with the presence of a plasmid harboring heavy-metal resistance genes in the isolates obtained in the area where the earthquake and tsunami occurred. Moreover, clinical isolates carrying this plasmid showed increased tolerance to mercury, arsenic, and cadmium. We also observed a physiological burden in the plasmid-carrying isolates in absence of heavy-metals. Our results are the first evidence that suggests that heavy-metal contamination, in the aftermath of an environmental disaster, appears to be a key evolutionary event for the spread and dissemination of MRSA in Latin America.

The impact of inpatient bloodstream infections caused by antibiotic-resistant bacteria in low- and middle-income countries: A systematic review and meta-analysis.

BACKGROUND: Bloodstream infections (BSIs) produced by antibiotic-resistant bacteria (ARB) cause a substantial disease burden worldwide. However, most estimates come from high-income settings and thus are not globally representative. This study quantifies the excess mortality, length of hospital stay (LOS), intensive care unit (ICU) admission, and economic costs associated with ARB BSIs, compared to antibiotic-sensitive bacteria (ASB), among adult inpatients in low- and middle-income countries (LMICs). METHODS AND FINDINGS: We conducted a systematic review by searching 4 medical databases (PubMed, SCIELO, Scopus, and WHO's Global Index Medicus; initial search n = 13,012 from their inception to August 1, 2022). We only included quantitative studies. Our final sample consisted of n = 109 articles, excluding studies from high-income countries, without our outcomes of interest, or without a clear source of bloodstream infection. Crude mortality, ICU admission, and LOS were meta-analysed using the inverse variance heterogeneity model for the general and subgroup analyses including bacterial Gram type, family, and resistance type. For economic costs, direct medical costs per bed-day were sourced from WHO-CHOICE. Mortality costs were estimated based on productivity loss from years of potential life lost due to premature mortality. All costs were in 2020 USD. We assessed studies' quality and risk of publication bias using the MASTER framework. Multivariable meta-regressions were employed for the mortality and ICU admission outcomes only. Most included studies showed a significant increase in crude mortality (odds ratio (OR) 1.58, 95% CI [1.35 to 1.80], p < 0.001), total LOS (standardised mean difference "SMD" 0.49, 95% CI [0.20 to 0.78], p < 0.001), and ICU admission (OR 1.96, 95% CI [1.56 to 2.47], p < 0.001) for ARB versus ASB BSIs. Studies analysing Enterobacteriaceae, Acinetobacter baumanii, and Staphylococcus aureus in upper-middle-income countries from the African and Western Pacific regions showed the highest excess mortality, LOS, and ICU admission for ARB versus ASB BSIs per patient. Multivariable meta-regressions indicated that patients with resistant Acinetobacter baumanii BSIs had higher mortality odds when comparing ARB versus ASB BSI patients (OR 1.67, 95% CI [1.18 to 2.36], p 0.004). Excess direct medical costs were estimated at $12,442 (95% CI [$6,693 to $18,191]) for ARB versus ASB BSI per patient, with an average cost of $41,103 (95% CI [$30,931 to $51,274]) due to premature mortality. Limitations included the poor quality of some of the reviewed studies regarding the high risk of selective sampling or failure to adequately account for relevant confounders. CONCLUSIONS: We provide an overview of the impact ARB BSIs in limited resource settings derived from the existing literature. Drug resistance was associated with a substantial disease and economic burden in LMICs. Although, our results show wide heterogeneity between WHO regions, income groups, and pathogen-drug combinations. Overall, there is a paucity of BSI data from LMICs, which hinders implementation of country-specific policies and tracking of health progress.

Effectiveness of an inactivated SARS-CoV-2 vaccine in children and adolescents: a large-scale observational study.

Background: Policymakers urgently need evidence to adequately balance the costs and benefits of mass vaccination against COVID-19 across all age groups, including children and adolescents. In this study, we aim to assess the effectiveness of CoronaVac's primary series among children and adolescents in Chile. Methods: We used a large prospective national cohort of about two million children and adolescents 6-16 years to estimate the effectiveness of an inactivated SARS-CoV-2 vaccine (CoronaVac) in preventing laboratory-confirmed symptomatic SARS-CoV-2 infection (COVID-19), hospitalisation, and admission to an intensive care unit (ICU) associated with COVID-19. We compared the risk of individuals treated with a complete primary immunization schedule (two doses, 28 days apart) with the risk of unvaccinated individuals during the follow-up period. The study was conducted in Chile from June 27, 2021, to January 12, 2022, when the SARS-CoV-2 Delta variant was predominant but other variants of concern were co-circulating, including Omicron. We used inverse probability-weighted survival regression models to estimate hazard ratios of complete immunization over the unvaccinated status, accounting for time-varying vaccination exposure and adjusting for relevant demographic, socioeconomic, and clinical confounders. Findings: The estimated adjusted vaccine effectiveness for the inactivated SARS-CoV-2 vaccine in children aged 6-16 years was 74.5% (95% CI, 73.8-75.2), 91.0% (95% CI, 87.8-93.4), 93.8% (95% CI, 87.8-93.4) for the prevention of COVID-19, hospitalisation, and ICU admission, respectively. For the subgroup of children 6-11 years, the vaccine effectiveness was 75.8% (95% CI, 74.7-76.8) for the prevention of COVID-19 and 77.9% (95% CI, 61.5-87.3) for the prevention of hospitalisation. Interpretation: Our results suggest that a complete primary immunization schedule with the inactivated SARS-CoV-2 vaccine provides effective protection against severe COVID-19 disease for children 6-16 years. Funding: Agencia Nacional de Investigación y Desarrollo (ANID) Millennium Science Initiative Program and Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias (FONDAP).

Cost-Effectiveness Analysis of Integrated Bite Case Management and Sustained Dog Vaccination for Rabies Control.

The successful prevention, control, and elimination of dog-mediated rabies is challenging due to insufficient resource availability and inadequate placement. An integrated dog bite case management (IBCM) system plus dog vaccination can help address these challenges. Based on data from the IBCM system in Haiti, we conducted a cost-effectiveness evaluation of a newly established IBCM system plus sustained vaccination and compared it with 1) a no bite-case management (NBCM) and 2) a non-risk-based (NRB) program, where bite victims presenting at a health clinic would receive post-exposure prophylaxis regardless of risk assessment. We also provide cost-effectiveness guidance for an ongoing IBCM system and for sub-optimal dog vaccination coverages, considering that not all cost-effective interventions are affordable. Cost-effectiveness outcomes included average cost per human death averted (USD/death averted) and per life-year gained (LYG). The analysis used a governmental perspective. Considering a sustained 5-year implementation with 70% dog vaccination coverage, IBCM had a lower average cost per death averted (IBCM: $7,528, NBCM: $7,797, NRB: $15,244) and cost per LYG (IBCM: $152, NBCM: $158, NRB: $308) than NBCM and NRB programs. As sensitivity analysis, we estimated cost-effectiveness for alternative scenarios with lower dog-vaccination coverages (30%, 55%) and lower implementation costs. Our results suggest that better health and cost-effectiveness outcomes are achieved with the continued implementation of an IBCM program ($118 per life-year saved) compared with a newly established IBCM program ($152 per life-year saved). Our results suggest that IBCM is more cost-effective than non-integrated programs to eliminate dog-mediated human rabies.

Evaluation of country infrastructure as an indirect measure of dog-mediated human rabies deaths.

Background: Rabies is a neglected disease, primarily due to poor detection stemming from limited surveillance and diagnostic capabilities in most countries. As a result, there is limited ability to monitor and evaluate country, regional, and global progress towards the WHO goal of eliminating human rabies deaths by 2030. There is a need for a low-cost, readily reproducible method of estimating rabies burden and elimination capacity in endemic countries. Methods: Publicly available economic, environmental, political, social, public health, and One Health indicators were evaluated to identify variables with strong correlation to country-level rabies burden estimates. A novel index was developed to estimate infrastructural rabies elimination capacity and annual case-burden for dog-mediated rabies virus variant (DMRVV) endemic countries. Findings: Five country-level indicators with superior explanatory value represent the novel "STOP-R index:" (1) literacy rate, (2) infant mortality rate, (3) electricity access, (4) political stability, and (5) presence/severity of natural hazards. Based on the STOP-R index, 40,111 (95% CI 25,854-74,344) global human rabies deaths are estimated to occur in 2022 among DMRVV-endemic countries and are projected to decrease to 32,349 (95% CI 21,110-57,019) in 2030. Interpretation: The STOP-R index offers a unique means of addressing the data gap and monitoring progress towards eliminating dog-mediated human rabies deaths. Results presented here suggest that factors external to rabies programs influence the successes of rabies elimination, and it is now possible to identify countries exceeding or lagging in expected rabies control and elimination progress based on country infrastructure.