An indigenously developed tele-ICU model to treat severe cases of envenomation in remote regions in India.

In cases of severe envenomation due to snakebites, patients require antivenom, intensive care management, including respiratory support, haemodynamic monitoring and renal replacement therapy. Early recognition and treatment of complications such as acute kidney injury, rhabdomyolysis and coagulopathy are important to improve outcomes.Tele-ICU models can play a critical role in providing access to critical care expertise and nuanced support to remote healthcare facilities that may not have the necessary resources or expertise to manage complex cases of envenomation. With the help of telemedicine technology, remote intensivists can provide timely guidance on diagnosis and ongoing management, improving the quality of care and outcomes for patients. We discuss two patients in resource-constrained regions of India with severe envenomation who were managed with tele-ICU support.

Distributions of candidate vaccine Targets, virulence Factors, and resistance features of invasive group B Streptococcus using Whole-Genome Sequencing: A Multicenter, population-based surveillance study.

BACKGROUND: Group B Streptococcus (GBS) is a leading cause of morbidity and mortality in young infants worldwide. This study aimed to investigate candidate GBS vaccine targets, virulence factors, and antimicrobial resistance determinants. METHODS: We used whole-genome sequencing to characterize invasive GBS isolates from infants < 3 months of age obtained from a multicenter population-based study conducted from 2015 to 2021 in China. RESULTS: Overall, seven serotypes were detected from 278 GBS isolates, four (Ia, Ib, III, V) of which accounted for 97.8 %. We detected 30 sequence types (including 10 novel types) that were grouped into six clonal complexes (CCs: CC1, CC10, CC17, CC19, CC23 and CC651); three novel ST groups in CC17 were detected, and the rate of CC17, considered a hyperinvasive neonatal clone complex, was attached to 40.6 % (113/278). A total of 98.9 % (275/278) of isolates harbored at least one alpha-like protein gene. All GBS isolates contained at least one of three pilus backbone determinants and the pilus types PI-2b and PI-1 + PI-2a accounted for 79.8 % of the isolates. The 112 serotype III/CC17 GBS isolates were all positive for hvgA. Most of the isolates (75.2 %) were positive for serine-rich repeat glycoprotein determinants (srr1or srr2). Almost all isolates possessed cfb (99.6 %), c1IE (100 %), lmb (95.3 %) or pavA (100 %) gene. Seventy-seven percent of isolates harboured more than three antimicrobial resistance genes with 28.4 % (79/278) gyrA quinoloneresistancedeterminants mutation, 83.8 % (233/278) carrying tet cluster genes and 77.3 % (215/278) carrying erm genes which mediated fluoroquinolone, tetracycline and clindamycin resistance, respectively." CONCLUSIONS: The findings from this large whole-genome sequence of GBS isolates establish important baseline data required for further surveillance and evaluating the impact of future vaccine candidates.

A Proof-of-Concept Model for Implementing a "Smart-NICU" to Improve Infant Mortality.

Low- and middle-income countries face limited critical care capacity due to constraints in staffing, resources, and technology. "Smart ICUs" that integrate telehealth to augment care delivery, communication, and data integration have the potential to bridge these gaps and reduce preventable morbidity and mortality. While their efficacy has been well validated in adult populations, applications of Smart-ICU services in the neonatal population have not been studied. Neonatal intensive care units (NICUs) in India using a common Smart-NICU platform, developed by CloudPhysician, utilize a hub-and-spokes framework along with locally designed technology to facilitate remote patient care in collaboration with local health systems. In this article, we investigate the operational characteristics and performance outcomes for Smart-NICU deployment from the 18 NICUs and 214 beds deployed to date. These findings highlight the potential impact of Smart-NICUs and establish generalizable principles for implementation in low-resource settings.

Tele-ICU enabled management of an organ donor in an under-resourced setting.

A man in his 30s was involved in a road traffic crash in a small town in India, not equipped to deal with cases of brainstem death. He was declared brain-dead after a few hours. The patient's information was forwarded to organ specialists across the country, with the goal of preserving the patient's organs for donation via a tele-ICU model. The team comprising bedside doctors and remote intensivists communicating via an indigenously developed tele-ICU platform managed the patient for 24 hours, following treatment protocols and providing critical care to ensure that the patient's vital organs were optimally perfused. The following morning, specialist teams from a nearby city arrived at the local hospital to retrieve the patient's organs. This fast-tracked organ retrieval and transplant process were made possible through advances in technology and the involvement of specialists from other parts of the country through this tele-ICU model.

A pragmatic calibration of the ROX index to predict outcome of nasal high-flow therapy in India.

PURPOSE: Identifying thresholds at which the ROX index would satisfactorily predict HFNC failure across heterogenous resourced contexts is necessary for clinical use. METHODS: Patients ≥18 years admitted to 30 diverse ICUs across 10 states in India who required HFNC for respiratory support were retrospectively included in this study. Patient data and hourly ROX indices were then analyzed and contextualized to clinical outcomes as well as with ROX index thresholds in other regions of the world. MEASUREMENTS AND MAIN RESULTS: Among the 614 patients included, 276 (44.9%) required respiratory escalation. Pneumonia was the most common diagnosis on admission. Receiver operating characteristic curve analysis revealed that a baseline ROX score of 7.86 was similar to 4.88 in other populations which was confirmed by Kaplan-Mier curves (hazard ratio,3.58 (2.72-4.69, p < 0.001)). ROX scores at 11.84 or 5.89 had roles in screening and confirming HFNC failure. The index performed poorly in a subset of patients who died without respiratory escalation. The ROX index was most predictive in the initial hours of ICU admission and a longer duration of HFNC was associated with more severe outcomes. CONCLUSIONS: When optimally calibrated this index can using a method that can reliably predict the risk of HFNC failure among ICU patients from diverse settings.

Interventions to promote cost-effectiveness in adult intensive care units: consensus statement and considerations for best practice from a multidisciplinary and multinational eDelphi study.

BACKGROUND: There is limited evidence to guide interventions that promote cost-effectiveness in adult intensive care units (ICU). The aim of this consensus statement is to identify globally applicable interventions for best ICU practice and provide guidance for judicious use of resources. METHODS: A three-round modified online Delphi process, using a web-based platform, sought consensus from 61 multidisciplinary ICU experts (physicians, nurses, allied health, administrators) from 21 countries. Round 1 was qualitative to ascertain opinions on cost-effectiveness criteria based on four key domains of high-value healthcare (foundational elements; infrastructure fundamentals; care delivery priorities; reliability and feedback). Round 2 was qualitative and quantitative, while round 3 was quantitative to reiterate and establish criteria. Both rounds 2 and 3 utilized a five-point Likert scale for voting. Consensus was considered when > 70% of the experts voted for a proposed intervention. Thereafter, the steering committee endorsed interventions that were identified as 'critical' by more than 50% of steering committee members. These interventions and experts' comments were summarized as final considerations for best practice. RESULTS: At the conclusion of round 3, consensus was obtained on 50 best practice considerations for cost-effectiveness in adult ICU. Finally, the steering committee endorsed 9 'critical' best practice considerations. This included adoption of a multidisciplinary ICU model of care, focus on staff training and competency assessment, ongoing quality audits, thus ensuring high quality of critical care services whether within or outside the four walls of ICUs, implementation of a dynamic staff roster, multidisciplinary approach to implementing end-of-life care, early mobilization and promoting international consensus efforts on the Green ICU concept. CONCLUSIONS: This Delphi study with international experts resulted in 9 consensus statements and best practice considerations promoting cost-effectiveness in adult ICUs. Stakeholders (government bodies, professional societies) must lead the efforts to identify locally applicable specifics while working within these best practice considerations with the available resources.

A rare presentation of antisynthetase syndrome requiring intensive care in the midst of a COVID wave.

A 24-year-old female with pneumonia two months prior presented with fever, cough, and worsening dyspnoea in the midst of a COVID-19 spike. Her initial episode was treated as COVID-19 pneumonia. On presentation, her chest computed tomography was suggestive of bilateral lower zone organising pneumonia with mild fibrosis and was attributed to post-COVID sequelae with an infective exacerbation. Oral steroids and antibiotics were administered, following which she had initial improvement and then subsequent deterioration requiring intensive care unit (ICU) care. A detailed clinical examination (in-person and virtually) at this point revealed the presence of pigmented rashes over the knuckles and weakness of hip muscles. Laboratory work showed elevated creatine kinase levels and positive anti-Ro and anti-Jo1 antibodies, which pointed to a diagnosis of antisynthetase syndrome. Unique attributes of this case include younger age of presentation in an atypical ethnic group, which are possibly incited by COVID-19 infection in the peak of a COVID-19 wave. The work-up, diagnosis, and initial management of this patient were carried out through a hybrid ICU model, which functioned as a traditional ICU in the day and a tele-ICU at night with an appropriate network of subspecialists including rheumatologists consulting, thus highlighting a collaborative model in a low-resource setting capable of managing rare cases even in the midst of increasing critical care needs during the pandemic.

Cash transfers and nutrition education to improve dietary diversity among children aged 6-23 months in Grand Gedeh County, Liberia: a cluster-randomized trial.

OBJECTIVES: To evaluate the efficacy of a cash transfer and nutrition education program on dietary diversity among children in Liberia. We hypothesized that a multi-pronged intervention would result in improved dietary diversity among children. METHODS: We conducted a three-armed, cluster-randomized study in 42 communities (12 children per community) in Grand Gedeh County, Liberia, over a 12-month period. We randomly assigned communities to control (n = 14 communities), those that received both bimonthly cash transfers and a structured nutrition education program (n = 14 communities) and those that received bimonthly cash transfers alone (n = 14 communities). Community health assistants conducted bimonthly assessments in participants' homes. The primary outcome was the proportion of children aged 6-23 months who met minimum dietary diversity score (i.e., ≥4 food groups consumed per day). Secondary outcomes included meal frequency and healthcare utilization for illnesses (NCT04101487). RESULTS: There were 599 children enrolled; 533 (88.9%) were retained through the trial period. The proportion of children who consumed ≥4 food groups per day did not differ among the three arms. However, children randomized to receive cash transfers had higher dietary diversity scores than the control group. Children in communities that received cash transfers alone and with nutrition education consumed significantly more meals per day and were less likely to have visits to clinics or hospitals for illnesses than children in control communities. CONCLUSION: Bimonthly, unconditional cash transfers and nutrition education were associated with higher dietary diversity scores, greater meal frequency, and fewer healthcare visits for illnesses among children aged 6-23 months.

Worldwide, more than one in five children suffers from chronic malnutrition. Children aged <2 years who do not eat a diverse diet are at risk of chronic malnutrition and stunting of their height. Thus, interventions are needed to combat the common problem of chronic malnutrition, particularly in settings like rural Liberia where as much as 30% of children are stunted. In this study, caregivers of children aged 6­23 months in rural communities in Eastern Liberia were randomly assigned to receive either bimonthly cash transfers, bimonthly cash transfers and specific nutrition education, or routine support from community health assistants to see if giving caregivers money and nutrition education would increase the dietary diversity of their young children. There were 599 children enrolled and 533 were retained over a 12-month study period. Children in communities randomized to receive cash transfers had higher dietary diversity scores than the control group. Children in communities that received cash transfers alone and with nutrition education consumed significantly more meals per day and were less likely to have visits to clinics or hospitals for illnesses than children in control communities. Unconditional cash transfers in rural Liberia may be one way to reduce inadequate dietary diversity among young children.

The next frontier in vaccine design: blending immune correlates of protection into rational vaccine design.

Despite the extraordinary speed and success in SARS-Cov-2 vaccine development, the emergence of variants of concern perplexed the vaccine development community. Neutralizing antibodies waned antibodies waned and were evaded by viral variants, despite the preservation of protection against severe disease and death across vaccinated populations. Similar to other vaccine design efforts, the lack of mechanistic correlates of immunity against Coronavirus Disease 2019, raised questions related to the need for vaccine redesign and boosting. Hence, our limited understanding of mechanistic correlates of immunity - across pathogens - remains a major obstacle in vaccine development. The identification and incorporation of mechanistic correlates of immunity are key to the accelerated design of highly impactful globally relevant vaccines. Systems-biology tools can be applied strategically to define a complete understanding of mechanistic correlates of immunity. Embedding immunological dissection and target immune profile identification, beyond canonical antibody binding and neutralization, may accelerate the design and success of durable protective vaccines.

Host Respiratory Transcriptome Signature Associated with Poor Outcome in Children with Influenza-Staphylococcus aureus Pneumonia.

Respiratory coinfection of influenza with Staphylococcus aureus often causes severe disease; methicillin-resistant S. aureus (MRSA) coinfection is frequently fatal. Understanding disease pathogenesis may inform therapies. We aimed to identify host and pathogen transcriptomic (messenger RNA) signatures from the respiratory compartment of pediatric patients critically ill with influenza-S. aureus coinfection (ISAC), signatures that predict worse outcomes. Messenger RNA extracted from endotracheal aspirate samples was evaluated for S. aureus and host transcriptomic biosignatures. Influenza-MRSA outcomes were worse, but of 190 S. aureus virulence-associated genes, 6 were differentially expressed between MRSA-coinfected versus methicillin-susceptible S. aureus-coinfected patients, and none discriminated outcome. Host gene expression in patients with ISAC was compared with that in patients with influenza infection alone. Patients with poor clinical outcomes (death or prolonged multiorgan dysfunction) had relatively reduced expression of interferons and down-regulation of interferon γ-induced immune cell chemoattractants CXCL10 and CXCL11. In ISAC, airway host but not pathogen gene expression profiles predicted worse clinical outcomes.

The effect of exchange transfusion on mortality in neonatal sepsis: a meta-analysis.

Although antimicrobials are the cornerstone of neonatal sepsis management, adjunctive therapies are required to improve outcomes. The aim of our study was to evaluate the effect of exchange transfusion (ET) on mortality (primary outcome) in neonatal sepsis, as well as on immunoglobulin, complement and neutrophil levels and assess its complications (secondary outcomes). Databases searched include PubMed, NCBI, Google Scholar, CINHAL, Ovid and Scopus. Randomized controlled trials (RCTs), controlled observational studies (COSs) and uncontrolled observational studies (UOSs) reporting mortality data from using ET in neonatal sepsis were included. Studies with additional interventions, non-septic ET indications and populations aged > 28 days were excluded. Data extracted include demographics, features of study, sepsis and ET, as well as mortality rates, immunological and laboratory changes and complications. Data was meta-analysed and displayed using forest plots. The meta-analysis of 14 studies (3 RCTs, 11 COSs) revealed a mortality benefit in septic neonates who underwent ET-RR 0.72 (CI 0.61-0.86, p = 0.01) and a significant increase in pooled immunological parameters (immunoglobulin, complement levels) (SMD 1.13, [0.25, 2.02], p = 0.02) and neutrophil levels (SMD 1.07 [0.04, 2.11], p = 0.03) compared to controls. The descriptive analysis of 9 UOSs revealed thrombocytopenia as the most frequently reported complication (n = 48). Moderate-high risk of bias was largely due to inadequate sample sizes and follow-up durations.Conclusion: Currently, the use of ET in neonatal sepsis is not directly recommended due to low certainty of evidence, inadequate power and moderate-high risk of bias and heterogeneity.Trial registration: PROSPERO (CRD42020176629) ( https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=176629 ) What is Known: • Exchange transfusion is one of the adjunctive methods for treatment of neonatal sepsis. What is New: • The pooled analysis of all studies shows that exchange transfusion has a low certainty of evidence in the context of neonatal mortality. However, at this point, this intervention cannot be refuted or recommended due to heterogeneity of studies and inadequate power.

Where there is no local author: a network bibliometric analysis of authorship parasitism among research conducted in sub-Saharan Africa.

INTRODUCTION: Authorship parasitism (ie, no authors affiliated with the country in which the study took place) occurs frequently in research conducted in low-income and middle-income countries, despite published recommendations defining authorship criteria. The objective was to compare characteristics of articles exhibiting authorship parasitism in sub-Saharan Africa to articles with author representation from sub-Saharan African countries. METHODS: A bibliometric review of articles indexed in PubMed published from January 2014 through December 2018 reporting research conducted in sub-Saharan Africa was performed. Author affiliations were assigned to countries based on regular expression algorithms. Choropleth maps and network diagrams were created to determine where authorship parasitism occurred, and multivariable logistic regression was used to determine associated factors. RESULTS: Of 32 061 articles, 14.8% (n=4754) demonstrated authorship parasitism, which was most common among studies from Somalia (n=175/233, 75.1%) and Sao Tome and Principe (n=20/28, 71.4%). Authors affiliated with USA and UK institutions were most commonly involved in articles exhibiting authorship parasitism. Authorship parasitism was more common in articles: published in North American journals (adjusted OR (aOR) 1.26, 95% CI 1.07 to 1.50) than in sub-Saharan African journals, reporting work from multiple sub-Saharan African countries (aOR 8.41, 95% CI 7.30 to 9.68) compared with work from upper-middle income sub-Saharan African countries, with <5 authors (aOR 14.46, 95% CI 12.81 to 16.35) than >10 authors, and was less common in articles published in French (aOR 0.60, 95% CI 0.41 to 0.85) than English. CONCLUSIONS: Authorship parasitism was common in articles reporting research conducted in sub-Saharan Africa. There were reliable predictors of authorship parasitism. Investigators and institutions in high-income countries, as well as funding agencies and journals should promote research from sub-Saharan Africa, including its publication, in a collaborative and equitable manner.

COVID-19-related disruptions to routine vaccination services in India: a survey of paediatric providers.

The COVID-19 pandemic has led to disruptions in essential health services globally. We surveyed Indian paediatric providers on their perceptions of the impact of the pandemic on routine vaccination. Among 424 (survey 1) and 141 (survey 2) respondents representing 26 of 36 Indian states and union territories, complete suspension of vaccination services was reported by 33.4% and 7.8%, respectively. In April-June 2020, 83.1% perceived that vaccination services dropped by half, followed by 32.6% in September 2020, indicating slow resumption of services. Concerns that vaccine coverage gaps can lead to mortality were expressed by 76.6%. Concerted multipronged efforts are needed to sustain gains in vaccination coverage.

Neonatal and infant mortality associated with spina bifida: A systematic review and meta-analysis.

OBJECTIVES: A systematic review was conducted in high-income country settings to analyse: (i) spina bifida neonatal and IMRs over time, and (ii) clinical and socio-demographic factors associated with mortality in the first year after birth in infants affected by spina bifida. DATA SOURCES: PubMed, Embase, Ovid, Web of Science, CINAHL, Scopus and the Cochrane Library were searched from 1st January, 1990 to 31st August, 2020 to review evidence. STUDY SELECTION: Population-based studies that provided data for spina bifida infant mortality and case fatality according to clinical and socio-demographical characteristics were included. Studies were excluded if they were conducted solely in tertiary centres. Spina bifida occulta or syndromal spina bifida were excluded where possible. DATA EXTRACTION AND SYNTHESIS: Independent reviewers extracted data and assessed their quality using MOOSE guideline. Pooled mortality estimates were calculated using random-effects (+/- fixed effects) models meta-analyses. Heterogeneity between studies was assessed using the Cochrane Q test and I2 statistics. Meta-regression was performed to examine the impact of year of birth cohort on spina bifida infant mortality. RESULTS: Twenty studies met the full inclusion criteria with a total study population of over 30 million liveborn infants and approximately 12,000 spina bifida-affected infants. Significant declines in spina bifida associated infant and neonatal mortality rates (e.g. 4.76% decrease in IMR per 100, 000 live births per year) and case fatality (e.g. 2.70% decrease in infant case fatality per year) were consistently observed over time. Preterm birth (RR 4.45; 2.30-8.60) and low birthweight (RR 4.77; 2.67-8.55) are the strongest risk factors associated with increased spina bifida infant case fatality. SIGNIFICANCE: Significant declines in spina bifida associated infant/neonatal mortality and case fatality were consistently observed, advances in treatment and mandatory folic acid food fortification both likely play an important role. Particular attention is warranted from clinicians caring for preterm and low birthweight babies affected by spina bifida.

Reducing rates of discharge against medical advice in the neonatal intensive care unit in a tertiary care hospital in South India: a mixed-methods study.

OBJECTIVE: To elucidate characteristics among neonates and their mothers who were discharged against medical advice (DAMA), providers' perspectives on DAMA and the effect of an intervention to reduce DAMA in a tertiary care hospital in South India. METHODS: We conducted a mixed-methods study to identify neonates at risk of DAMA. We reviewed charts of neonates and their mothers who were DAMA and conducted logit regression analysis to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CI) to determine associations with DAMA. We conducted focus group discussions with nurses and doctors. We developed an intervention that included family counselling, supplemental funds for hospital bills and involving family members to reduce DAMA. RESULTS: Of 10 834 neonates, 179 (1.7%) were DAMA over the study period. Maternal characteristics associated with DAMA included higher previous parity (aOR 1.9, 95% CI 1.1-2.3, P = 0.001). Mothers who received antenatal care had lower odds of DAMA (aOR 0.2, 95% CI 0.1-0.7, P = 0.039). Neonates with lower birth weight (aOR 2.1, 95% CI 1.7-9.4, P = 0.002) and congenital malformations (aOR 3.3, 95% CI 1.1-5.3, P = 0.005) also had higher odds of DAMA. The most commonly cited reasons for DAMA were financial constraints, inadequate counselling and perceived poor prognosis. The average monthly number of neonates who were DAMA decreased from 3.6 (1.6%) to 1.5 (0.6%) after our multi-pronged intervention. CONCLUSIONS: Neonates with severe illness and poor prognosis had higher odds of DAMA. A multi-pronged intervention demonstrated reductions in the rates of DAMA. This intervention may be trialled in similar settings to reduce DAMA.

Typhoid and paratyphoid fever: a clinical seminar.

Rationale for review: Enteric fever (EF) caused by Salmonella enterica subspecies enterica serovar Typhi (Salmonella Typhi) and S. Paratyphi (Salmonella Paratyphi) remains an important cause of infectious morbidity and mortality in many low-income countries and, therefore, still poses a major infectious risk for travellers to endemic countries. Main findings: Although the global burden of EF has decreased over the past two decades, prevalence of EF remains high in Asia and Africa, with the highest prevalence reported from the Indian subcontinent. These statistics are mirrored by data on travel-related EF. Widespread and increasing antimicrobial resistance has narrowed treatment options for travel-related EF. Ceftriaxone- and azithromycin-based therapies are commonly used, even with the emergence of extremely drug-resistant typhoid in Pakistan. Preventive measures among locals and travellers include provision of safe food and water and vaccination. Food and water precautions offer limited protection, and the efficacy of Salmonella Typhi vaccines is only moderate signifying the need for travellers to be extra cautious. Recommendations: Improvement in the diagnosis of typhoid with high degree of clinical suspicion, better diagnostic assays, early and accurate detection of resistance, therapy with appropriate drugs, improvements in hygiene and sanitation with provision of safe drinking water in endemic areas and vaccination among travellers as well as in the endemic population are keys to controlling typhoid. While typhoid vaccines are recommended for travellers to high-risk areas, moderate efficacy and inability to protect against Salmonella Paratyphi are limitations to bear in mind. Improved Salmonella Typhi vaccines and vaccines against Salmonella Paratyphi A are required.

Comparing COVID-19 vaccine allocation strategies in India: A mathematical modelling study.

BACKGROUND: The development and widespread use of an effective SARS-CoV-2 vaccine could prevent substantial morbidity and mortality associated with COVID-19 and mitigate the secondary effects associated with non-pharmaceutical interventions. METHODS: We used an age-structured, expanded SEIR model with social contact matrices to assess age-specific vaccine allocation strategies in India. We used state-specific age structures and disease transmission coefficients estimated from confirmed incident cases of COVID-19 between 1 July and 31 August 2020. Simulations were used to investigate the relative reduction in mortality and morbidity of vaccine allocation strategies based on prioritizing different age groups, and the interactions of these strategies with concurrent non-pharmaceutical interventions. Given the uncertainty associated with COVID-19 vaccine development, we varied vaccine characteristics in the modelling simulations. RESULTS: Prioritizing COVID-19 vaccine allocation for older populations (i.e., >60 years) led to the greatest relative reduction in deaths, regardless of vaccine efficacy, control measures, rollout speed, or immunity dynamics. Preferential vaccination of this group often produced relatively higher total symptomatic infections and more pronounced estimates of peak incidence than other assessed strategies. Vaccine efficacy, immunity type, target coverage, and rollout speed significantly influenced overall strategy effectiveness, with the time taken to reach target coverage significantly affecting the relative mortality benefit comparative to no vaccination. CONCLUSIONS: Our findings support global recommendations to prioritize COVID-19 vaccine allocation for older age groups. Relative differences between allocation strategies were reduced as the speed of vaccine rollout was increased. Optimal vaccine allocation strategies will depend on vaccine characteristics, strength of concurrent non-pharmaceutical interventions, and region-specific goals.