Conference Material > Abstract
Chandna A, PRIORITISE Study Group, Mahajan R, Gautam P, Mwandigha L, et al.
MSF Scientific Days International 2022. 2022 May 9; DOI:10.57740/hxy9-yk07
INTRODUCTION
In locations where few people have received Covid-19 vaccines, health systems remain vulnerable to spikes in SARS-CoV-2 infections. Triage tools, which could include biomarkers, to identify patients with moderate Covid-19 infection suitable for community-based management would be useful in the event of surges. In consultation with FIND (Geneva, Switzerland) we shortlisted seven biomarkers for evaluation, all measurable using point-of-care tests, and either currently available or in late-stage development.
METHODS
We prospectively recruited unvaccinated adults with laboratory-confirmed Covid-19 presenting to two hospitals in India with moderate symptoms, in order to develop and validate a clinical prediction model to rule-out progression to supplemental oxygen requirement. Moderate disease was defined as oxygen saturation (SpO2) ≥ 94% and respiratory rate < 30 breaths per minute (bpm), in the context of systemic symptoms (breathlessness or fever and chest pain, abdominal pain, diarrhoea, or severe myalgia). All patients had clinical observations and blood collected at presentation, and were followed up for 14 days for the primary outcome, defined as any of the following: SpO2 < 94%; respiratory rate > 30 bpm; SpO2/fraction of inspired oxygen (FiO2) < 400; or death. We specified a priori that each model would contain three easily ascertained clinical parameters (age, sex, and SpO2) and one of the seven biomarkers (C-reactive protein (CRP), D-dimer, interleukin-6 (IL-6), neutrophil-to-lymphocyte ratio (NLR), procalcitonin (PCT), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), or soluble urokinase plasminogen activator receptor (suPAR)), to ensure the models would be implementable in high patient-throughput, low-resource settings. We evaluated the models’ discrimination, calibration, and clinical utility in a held-out external temporal validation cohort.
ETHICS
Ethical approval was given by the ethics committees of AIIMS and CMC, India, the Oxford Tropical Research Ethics Committee, UK; and by the MSF Ethics Review Board.
ClinicalTrials.gov number, NCT04441372.
RESULTS
426 participants were recruited, of which 89 (21.0%) met the primary outcome. 257 participants comprised the development, and 166 the validation, cohorts. The three models containing NLR, suPAR, or IL-6 demonstrated promising discrimination (c-statistics: 0.72 to 0.74) and calibration (calibration slopes: 1.01 to 1.05) in the held-out validation cohort. Furthermore, they provided greater utility than a model containing the clinical parameters alone (c-statistic = 0.66; calibration slope = 0.68). The inclusion of either NLR or suPAR improved predictive performance such that the ratio of correctly to incorrectly discharged patients increased from 10:1 to 23:1 or 25:1 respectively. Including IL-6 resulted in a similar proportion (~21%) of correctly discharged patients as the clinical model, but without missing any patients requiring supplemental oxygen.
CONCLUSION
We present three clinical prediction models that could help clinicians identify patients with moderate Covid-19 suitable for community-based management. These models are readily implementable and, if validated, could be of particular relevance for resource-limited settings.
CONFLICTS OF INTEREST
None declared.
In locations where few people have received Covid-19 vaccines, health systems remain vulnerable to spikes in SARS-CoV-2 infections. Triage tools, which could include biomarkers, to identify patients with moderate Covid-19 infection suitable for community-based management would be useful in the event of surges. In consultation with FIND (Geneva, Switzerland) we shortlisted seven biomarkers for evaluation, all measurable using point-of-care tests, and either currently available or in late-stage development.
METHODS
We prospectively recruited unvaccinated adults with laboratory-confirmed Covid-19 presenting to two hospitals in India with moderate symptoms, in order to develop and validate a clinical prediction model to rule-out progression to supplemental oxygen requirement. Moderate disease was defined as oxygen saturation (SpO2) ≥ 94% and respiratory rate < 30 breaths per minute (bpm), in the context of systemic symptoms (breathlessness or fever and chest pain, abdominal pain, diarrhoea, or severe myalgia). All patients had clinical observations and blood collected at presentation, and were followed up for 14 days for the primary outcome, defined as any of the following: SpO2 < 94%; respiratory rate > 30 bpm; SpO2/fraction of inspired oxygen (FiO2) < 400; or death. We specified a priori that each model would contain three easily ascertained clinical parameters (age, sex, and SpO2) and one of the seven biomarkers (C-reactive protein (CRP), D-dimer, interleukin-6 (IL-6), neutrophil-to-lymphocyte ratio (NLR), procalcitonin (PCT), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), or soluble urokinase plasminogen activator receptor (suPAR)), to ensure the models would be implementable in high patient-throughput, low-resource settings. We evaluated the models’ discrimination, calibration, and clinical utility in a held-out external temporal validation cohort.
ETHICS
Ethical approval was given by the ethics committees of AIIMS and CMC, India, the Oxford Tropical Research Ethics Committee, UK; and by the MSF Ethics Review Board.
ClinicalTrials.gov number, NCT04441372.
RESULTS
426 participants were recruited, of which 89 (21.0%) met the primary outcome. 257 participants comprised the development, and 166 the validation, cohorts. The three models containing NLR, suPAR, or IL-6 demonstrated promising discrimination (c-statistics: 0.72 to 0.74) and calibration (calibration slopes: 1.01 to 1.05) in the held-out validation cohort. Furthermore, they provided greater utility than a model containing the clinical parameters alone (c-statistic = 0.66; calibration slope = 0.68). The inclusion of either NLR or suPAR improved predictive performance such that the ratio of correctly to incorrectly discharged patients increased from 10:1 to 23:1 or 25:1 respectively. Including IL-6 resulted in a similar proportion (~21%) of correctly discharged patients as the clinical model, but without missing any patients requiring supplemental oxygen.
CONCLUSION
We present three clinical prediction models that could help clinicians identify patients with moderate Covid-19 suitable for community-based management. These models are readily implementable and, if validated, could be of particular relevance for resource-limited settings.
CONFLICTS OF INTEREST
None declared.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2021 February 12; Volume 15 (Issue 2); e0009023.; DOI:10.1371/journal.pntd.0009023
Alcoba G, Ochoa C, Martins SB, Ruiz de Castañeda R, Bolon I, et al.
PLoS Negl Trop Dis. 2021 February 12; Volume 15 (Issue 2); e0009023.; DOI:10.1371/journal.pntd.0009023
BACKGROUND
Worldwide, it is estimated that snakes bite 4.5-5.4 million people annually, 2.7 million of which are envenomed, and 81,000-138,000 die. The World Health Organization reported these estimates and recognized the scarcity of large-scale, community-based, epidemiological data. In this context, we developed the "Snake-Byte" project that aims at (i) quantifying and mapping the impact of snakebite on human and animal health, and on livelihoods, (ii) developing predictive models for medical, ecological and economic indicators, and (iii) analyzing geographic accessibility to healthcare. This paper exclusively describes the methodology we developed to collect large-scale primary data on snakebite in humans and animals in two hyper-endemic countries, Cameroon and Nepal.
METHODOLOGY/PRINCIPAL FINDINGS
We compared available methods on snakebite epidemiology and on multi-cluster survey development. Then, in line with those findings, we developed an original study methodology based on a multi-cluster random survey, enhanced by geospatial, One Health, and health economics components. Using a minimum hypothesized snakebite national incidence of 100/100,000/year and optimizing design effect, confidence level, and non-response margin, we calculated a sample of 61,000 people per country. This represented 11,700 households in Cameroon and 13,800 in Nepal. The random selection with probability proportional to size generated 250 clusters from all Cameroonian regions and all Nepalese Terai districts. Our household selection methodology combined spatial randomization and selection via high-resolution satellite images. After ethical approval in Switerland (CCER), Nepal (BPKIHS), and Cameroon (CNERSH), and informed written consent, our e-questionnaires included geolocated baseline demographic and socio-economic characteristics, snakebite clinical features and outcomes, healthcare expenditure, animal ownership, animal outcomes, snake identification, and service accessibility.
CONCLUSIONS/SIGNIFICANCE
This novel transdisciplinary survey methodology was subsequently used to collect countrywide snakebite envenoming data in Nepal and Cameroon. District-level incidence data should help health authorities to channel antivenom and healthcare allocation. This methodology, or parts thereof, could be easily adapted to other countries and to other Neglected Tropical Diseases.
Worldwide, it is estimated that snakes bite 4.5-5.4 million people annually, 2.7 million of which are envenomed, and 81,000-138,000 die. The World Health Organization reported these estimates and recognized the scarcity of large-scale, community-based, epidemiological data. In this context, we developed the "Snake-Byte" project that aims at (i) quantifying and mapping the impact of snakebite on human and animal health, and on livelihoods, (ii) developing predictive models for medical, ecological and economic indicators, and (iii) analyzing geographic accessibility to healthcare. This paper exclusively describes the methodology we developed to collect large-scale primary data on snakebite in humans and animals in two hyper-endemic countries, Cameroon and Nepal.
METHODOLOGY/PRINCIPAL FINDINGS
We compared available methods on snakebite epidemiology and on multi-cluster survey development. Then, in line with those findings, we developed an original study methodology based on a multi-cluster random survey, enhanced by geospatial, One Health, and health economics components. Using a minimum hypothesized snakebite national incidence of 100/100,000/year and optimizing design effect, confidence level, and non-response margin, we calculated a sample of 61,000 people per country. This represented 11,700 households in Cameroon and 13,800 in Nepal. The random selection with probability proportional to size generated 250 clusters from all Cameroonian regions and all Nepalese Terai districts. Our household selection methodology combined spatial randomization and selection via high-resolution satellite images. After ethical approval in Switerland (CCER), Nepal (BPKIHS), and Cameroon (CNERSH), and informed written consent, our e-questionnaires included geolocated baseline demographic and socio-economic characteristics, snakebite clinical features and outcomes, healthcare expenditure, animal ownership, animal outcomes, snake identification, and service accessibility.
CONCLUSIONS/SIGNIFICANCE
This novel transdisciplinary survey methodology was subsequently used to collect countrywide snakebite envenoming data in Nepal and Cameroon. District-level incidence data should help health authorities to channel antivenom and healthcare allocation. This methodology, or parts thereof, could be easily adapted to other countries and to other Neglected Tropical Diseases.
Journal Article > CommentaryFull Text
Lancet Healthy Longev
Healthy longevity. 2024 January 1; Volume 5 (Issue 1); e76-e82.; DOI:10.1016/S2666-7568(23)00244-1
van Boetzelaer E, van de Kamp J, Keating P, Sharma SK, Pellecchia U, et al.
Lancet Healthy Longev
Healthy longevity. 2024 January 1; Volume 5 (Issue 1); e76-e82.; DOI:10.1016/S2666-7568(23)00244-1
Journal Article > Meta-AnalysisFull Text
E Clinical Medicine. 2023 February 1; Volume 56; 101815.; DOI:10.1016/j.eclinm.2022.101815
Hamada Y, Gupta RS, Quartagno M, Izzard A, Acuna-Villaorduna C, et al.
E Clinical Medicine. 2023 February 1; Volume 56; 101815.; DOI:10.1016/j.eclinm.2022.101815
BACKGROUND
Evidence on the comparative performance of purified protein derivative tuberculin skin tests (TST) and interferon-gamma release assays (IGRA) for predicting incident active tuberculosis (TB) remains conflicting. We conducted an individual participant data meta-analysis to directly compare the predictive performance for incident TB disease between TST and IGRA to inform policy.
METHODS
We searched Medline and Embase from 1 January 2002 to 4 September 2020, and studies that were included in previous systematic reviews. We included prospective longitudinal studies in which participants received both TST and IGRA and estimated performance as hazard ratios (HR) for the development of all diagnoses of TB in participants with dichotomised positive test results compared to negative results, using different thresholds of positivity for TST. Secondary analyses included an evaluation of the impact of background TB incidence. We also estimated the sensitivity and specificity for predicting TB. We explored heterogeneity through pre-defined sub-group analyses (e.g. country-level TB incidence). Publication bias was assessed using funnel plots and Egger's test. This review is registered with PROSPERO, CRD42020205667.
FINDINGS
We obtained data from 13 studies out of 40 that were considered eligible (N = 32,034 participants: 36% from countries with TB incidence rate ≥100 per 100,000 population). All reported data on TST and QuantiFERON Gold in-Tube (QFT-GIT). The point estimate for the TST was highest with higher cut-offs for positivity and particularly when stratified by bacillus Calmette–Guérin vaccine (BCG) status (15 mm if BCG vaccinated and 5 mm if not [TST5/15 mm]) at 2.88 (95% CI 1.69–4.90). The pooled HR for QFT-GIT was higher than for TST at 4.15 (95% CI 1.97–8.75). The difference was large in countries with TB incidence rate <100 per 100,000 population (HR 10.38, 95% CI 4.17–25.87 for QFT-GIT VS. HR 5.36, 95% CI 3.82–7.51 for TST5/15 mm) but much of this difference was driven by a single study (HR 5.13, 95% CI 3.58–7.35 for TST5/15 mm VS. 7.18, 95% CI 4.48–11.51 for QFT-GIT, when excluding the study, in which all 19 TB cases had positive QFT-GIT results). The comparative performance was similar in the higher burden countries (HR 1.61, 95% CI 1.23–2.10 for QFT-GIT VS. HR 1.72, 95% CI 0.98–3.01 for TST5/15 mm). The predictive performance of both tests was higher in countries with TB incidence rate <100 per 100,000 population. In the lower TB incidence countries, the specificity of TST (76% for TST5/15 mm) and QFT-GIT (74%) for predicting active TB approached the minimum World Health Organization target (≥75%), but the sensitivity was below the target of ≥75% (63% for TST5/15 mm and 65% for QFT-GIT). The absolute differences in positive and negative predictive values between TST15 mm and QFT-GIT were small (positive predictive values 2.74% VS. 2.46%; negative predictive values 99.42% VS. 99.52% in low-incidence countries). Egger's test did not show evidence of publication bias (0.74 for TST15 mm and p = 0.68 for QFT-GIT).
INTERPRETATION
IGRA appears to have higher predictive performance than the TST in low TB incidence countries, but the difference was driven by a single study. Any advantage in clinical performance may be small, given the numerically similar positive and negative predictive values. Both IGRA and TST had lower performance in countries with high TB incidence. Test choice should be contextual and made considering operational and likely clinical impact of test results.
Evidence on the comparative performance of purified protein derivative tuberculin skin tests (TST) and interferon-gamma release assays (IGRA) for predicting incident active tuberculosis (TB) remains conflicting. We conducted an individual participant data meta-analysis to directly compare the predictive performance for incident TB disease between TST and IGRA to inform policy.
METHODS
We searched Medline and Embase from 1 January 2002 to 4 September 2020, and studies that were included in previous systematic reviews. We included prospective longitudinal studies in which participants received both TST and IGRA and estimated performance as hazard ratios (HR) for the development of all diagnoses of TB in participants with dichotomised positive test results compared to negative results, using different thresholds of positivity for TST. Secondary analyses included an evaluation of the impact of background TB incidence. We also estimated the sensitivity and specificity for predicting TB. We explored heterogeneity through pre-defined sub-group analyses (e.g. country-level TB incidence). Publication bias was assessed using funnel plots and Egger's test. This review is registered with PROSPERO, CRD42020205667.
FINDINGS
We obtained data from 13 studies out of 40 that were considered eligible (N = 32,034 participants: 36% from countries with TB incidence rate ≥100 per 100,000 population). All reported data on TST and QuantiFERON Gold in-Tube (QFT-GIT). The point estimate for the TST was highest with higher cut-offs for positivity and particularly when stratified by bacillus Calmette–Guérin vaccine (BCG) status (15 mm if BCG vaccinated and 5 mm if not [TST5/15 mm]) at 2.88 (95% CI 1.69–4.90). The pooled HR for QFT-GIT was higher than for TST at 4.15 (95% CI 1.97–8.75). The difference was large in countries with TB incidence rate <100 per 100,000 population (HR 10.38, 95% CI 4.17–25.87 for QFT-GIT VS. HR 5.36, 95% CI 3.82–7.51 for TST5/15 mm) but much of this difference was driven by a single study (HR 5.13, 95% CI 3.58–7.35 for TST5/15 mm VS. 7.18, 95% CI 4.48–11.51 for QFT-GIT, when excluding the study, in which all 19 TB cases had positive QFT-GIT results). The comparative performance was similar in the higher burden countries (HR 1.61, 95% CI 1.23–2.10 for QFT-GIT VS. HR 1.72, 95% CI 0.98–3.01 for TST5/15 mm). The predictive performance of both tests was higher in countries with TB incidence rate <100 per 100,000 population. In the lower TB incidence countries, the specificity of TST (76% for TST5/15 mm) and QFT-GIT (74%) for predicting active TB approached the minimum World Health Organization target (≥75%), but the sensitivity was below the target of ≥75% (63% for TST5/15 mm and 65% for QFT-GIT). The absolute differences in positive and negative predictive values between TST15 mm and QFT-GIT were small (positive predictive values 2.74% VS. 2.46%; negative predictive values 99.42% VS. 99.52% in low-incidence countries). Egger's test did not show evidence of publication bias (0.74 for TST15 mm and p = 0.68 for QFT-GIT).
INTERPRETATION
IGRA appears to have higher predictive performance than the TST in low TB incidence countries, but the difference was driven by a single study. Any advantage in clinical performance may be small, given the numerically similar positive and negative predictive values. Both IGRA and TST had lower performance in countries with high TB incidence. Test choice should be contextual and made considering operational and likely clinical impact of test results.
Journal Article > CommentaryFull Text
J Adolesc Health. 2023 March 1; Volume 72 (Issue 3); 323-331.; DOI:10.1016/j.jadohealth.2022.10.036
Chiang SS, Waterous PM, Atieno VF, Bernays S, Bondarenko Y, et al.
J Adolesc Health. 2023 March 1; Volume 72 (Issue 3); 323-331.; DOI:10.1016/j.jadohealth.2022.10.036
Journal Article > ResearchFull Text
Sci Rep. 2021 December 13; Volume 11 (Issue 1); 23868.; DOI:10.1038/s41598-021-03301-z
Ochoa C, Pittavino M, Martins SB, Alcoba G, Bolon I, et al.
Sci Rep. 2021 December 13; Volume 11 (Issue 1); 23868.; DOI:10.1038/s41598-021-03301-z
Most efforts to understand snakebite burden in Nepal have been localized to relatively small areas and focused on humans through epidemiological studies. We present the outcomes of a geospatial analysis of the factors influencing snakebite risk in humans and animals, based on both a national-scale multi-cluster random survey and, environmental, climatic, and socio-economic gridded data for the Terai region of Nepal. The resulting Integrated Nested Laplace Approximation models highlight the importance of poverty as a fundamental risk-increasing factor, augmenting the snakebite odds in humans by 63.9 times. For animals, the minimum temperature of the coldest month was the most influential covariate, increasing the snakebite odds 23.4 times. Several risk hotspots were identified along the Terai, helping to visualize at multiple administrative levels the estimated population numbers exposed to different probability risk thresholds in 1 year. These analyses and findings could be replicable in other countries and for other diseases.
Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 2023 August 1; Volume 27 (Issue 8); 584-598.; DOI:10.5588/ijtld.23.0085
Chiang SS, Graham SM, Schaaf HS, Marais BJ, Sant’Anna CC, et al.
Int J Tuberc Lung Dis. 2023 August 1; Volume 27 (Issue 8); 584-598.; DOI:10.5588/ijtld.23.0085
BACKGROUND
These clinical standards aim to provide guidance for diagnosis, treatment, and management of drug-susceptible TB in children and adolescents.
METHODS
Fifty-two global experts in paediatric TB participated in a Delphi consensus process. After eight rounds of revisions, 51/52 (98%) participants endorsed the final document.
RESULTS
Eight standards were identified: Standard 1, Age and developmental stage are critical considerations in the assessment and management of TB; Standard 2, Children and adolescents with symptoms and signs of TB disease should undergo prompt evaluation, and diagnosis and treatment initiation should not depend on microbiological confirmation; Standard 3, Treatment initiation is particularly urgent in children and adolescents with presumptive TB meningitis and disseminated (miliary) TB; Standard 4, Children and adolescents should be treated with an appropriate weight-based regimen; Standard 5, Treating TB infection (TBI) is important to prevent disease; Standard 6, Children and adolescents should receive home-based/community-based treatment support whenever possible; Standard 7, Children, adolescents, and their families should be provided age-appropriate support to optimise engagement in care and clinical outcomes; and Standard 8, Case reporting and contact tracing should be conducted for each child and adolescent.
CONCLUSION
These consensus-based clinical standards, which should be adapted to local contexts, will improve the care of children and adolescents affected by TB.
These clinical standards aim to provide guidance for diagnosis, treatment, and management of drug-susceptible TB in children and adolescents.
METHODS
Fifty-two global experts in paediatric TB participated in a Delphi consensus process. After eight rounds of revisions, 51/52 (98%) participants endorsed the final document.
RESULTS
Eight standards were identified: Standard 1, Age and developmental stage are critical considerations in the assessment and management of TB; Standard 2, Children and adolescents with symptoms and signs of TB disease should undergo prompt evaluation, and diagnosis and treatment initiation should not depend on microbiological confirmation; Standard 3, Treatment initiation is particularly urgent in children and adolescents with presumptive TB meningitis and disseminated (miliary) TB; Standard 4, Children and adolescents should be treated with an appropriate weight-based regimen; Standard 5, Treating TB infection (TBI) is important to prevent disease; Standard 6, Children and adolescents should receive home-based/community-based treatment support whenever possible; Standard 7, Children, adolescents, and their families should be provided age-appropriate support to optimise engagement in care and clinical outcomes; and Standard 8, Case reporting and contact tracing should be conducted for each child and adolescent.
CONCLUSION
These consensus-based clinical standards, which should be adapted to local contexts, will improve the care of children and adolescents affected by TB.
Journal Article > Meta-AnalysisFull Text
PLOS Med. 2018 July 11; Volume 15 (Issue 7); e1002591.; DOI:10.1371/journal.pmed.1002591
Harausz EP, Garcia-Prats AJ, Law S, Schaaf HS, Kredo T, et al.
PLOS Med. 2018 July 11; Volume 15 (Issue 7); e1002591.; DOI:10.1371/journal.pmed.1002591
Journal Article > ResearchFull Text
Clin Infect Dis. 2022 March 21; Volume ciac224; DOI:10.1093/cid/ciac224
Chandna A, Mahajan R, Gautam P, Mwandigha L, Gunasekaran K, et al.
Clin Infect Dis. 2022 March 21; Volume ciac224; DOI:10.1093/cid/ciac224
BACKGROUND
In locations where few people have received COVID-19 vaccines, health systems remain vulnerable to surges in SARS-CoV-2 infections. Tools to identify patients suitable for community-based management are urgently needed.
METHODS
We prospectively recruited adults presenting to two hospitals in India with moderate symptoms of laboratory-confirmed COVID-19 in order to develop and validate a clinical prediction model to rule-out progression to supplemental oxygen requirement. The primary outcome was defined as any of the following: SpO2 < 94%; respiratory rate > 30 bpm; SpO2/FiO2 < 400; or death. We specified a priori that each model would contain three clinical parameters (age, sex and SpO2) and one of seven shortlisted biochemical biomarkers measurable using commercially-available rapid tests (CRP, D-dimer, IL-6, NLR, PCT, sTREM-1 or suPAR), to ensure the models would be suitable for resource-limited settings. We evaluated discrimination, calibration and clinical utility of the models in a held-out temporal external validation cohort.
RESULTS
426 participants were recruited, of whom 89 (21.0%) met the primary outcome. 257 participants comprised the development cohort and 166 comprised the validation cohort. The three models containing NLR, suPAR or IL-6 demonstrated promising discrimination (c-statistics: 0.72 to 0.74) and calibration (calibration slopes: 1.01 to 1.05) in the validation cohort, and provided greater utility than a model containing the clinical parameters alone.
CONCLUSIONS
We present three clinical prediction models that could help clinicians identify patients with moderate COVID-19 suitable for community-based management. The models are readily implementable and of particular relevance for locations with limited resources.
In locations where few people have received COVID-19 vaccines, health systems remain vulnerable to surges in SARS-CoV-2 infections. Tools to identify patients suitable for community-based management are urgently needed.
METHODS
We prospectively recruited adults presenting to two hospitals in India with moderate symptoms of laboratory-confirmed COVID-19 in order to develop and validate a clinical prediction model to rule-out progression to supplemental oxygen requirement. The primary outcome was defined as any of the following: SpO2 < 94%; respiratory rate > 30 bpm; SpO2/FiO2 < 400; or death. We specified a priori that each model would contain three clinical parameters (age, sex and SpO2) and one of seven shortlisted biochemical biomarkers measurable using commercially-available rapid tests (CRP, D-dimer, IL-6, NLR, PCT, sTREM-1 or suPAR), to ensure the models would be suitable for resource-limited settings. We evaluated discrimination, calibration and clinical utility of the models in a held-out temporal external validation cohort.
RESULTS
426 participants were recruited, of whom 89 (21.0%) met the primary outcome. 257 participants comprised the development cohort and 166 comprised the validation cohort. The three models containing NLR, suPAR or IL-6 demonstrated promising discrimination (c-statistics: 0.72 to 0.74) and calibration (calibration slopes: 1.01 to 1.05) in the validation cohort, and provided greater utility than a model containing the clinical parameters alone.
CONCLUSIONS
We present three clinical prediction models that could help clinicians identify patients with moderate COVID-19 suitable for community-based management. The models are readily implementable and of particular relevance for locations with limited resources.
Journal Article > ResearchFull Text
Lancet Global Health. 2022 March 1; Volume 10 (Issue 3); E398-E408.; DOI:10.1016/S2214-109X(22)00028-6
Alcoba G, Sharma SK, Bolon I, Ochoa C, Martins SB, et al.
Lancet Global Health. 2022 March 1; Volume 10 (Issue 3); E398-E408.; DOI:10.1016/S2214-109X(22)00028-6
BACKGROUND
Each year, 2 million people worldwide are bitten by snakes, resulting in an estimated 81 000–138 000 deaths. WHO has added snakebite envenoming to the list of neglected tropical diseases, highlighting the need for stronger epidemiological evidence in endemic countries, such as Nepal.
METHODS
We conducted a cross-sectional survey in villages randomly geospatially selected from aerial images from across the Nepal's Terai lowlands region (excluding towns and cities). We collected data between Nov 30, 2018 and May 7, 2019, and analysed snakebite incidence rates and outcomes in humans and domestic animals.
FINDINGS
Among 63 454 human participants living in 13 879 households (249 villages), 166 were bitten by a snake over the previous 12 months; 48·8% were envenomed and 7·8% died. This corresponded to an annual crude incidence rate of 262 snakebites (adjusted incidence of 251·1 [95% CI 201·7–312·6]) and 20 deaths (22·4 [11·9–42·1]) per 100 000 people, extrapolating to 26 749–37 661 yearly bitten people and 2386–3225 deaths. Bitten people had a median age of 30 years (IQR 20–45) and with available data, 64% were female. Children younger than 15 years (n=6; 46%) and females (n=10; 77%) were disproportionately affected among the 13 people who died. The incidence was higher in the Eastern region, and mortality was higher in the Central region. Of 183 949 animals, owners reported 144 snakebites, with an annual incidence rate of 42–202 per 100 000 and mortality of 79–100%, varying by animal type. Spatial and seasonal incidence were similar in humans and in animals.
INTERPRETATION
This study provides the first epidemiological estimates of snakebite envenoming in humans and domestic animals across Nepal's Terai lowlands. It was also the first to use a community-based, transdisciplinary, and One Health design. These findings call for a strengthening of preventive measures and better access to life-saving treatments.
Each year, 2 million people worldwide are bitten by snakes, resulting in an estimated 81 000–138 000 deaths. WHO has added snakebite envenoming to the list of neglected tropical diseases, highlighting the need for stronger epidemiological evidence in endemic countries, such as Nepal.
METHODS
We conducted a cross-sectional survey in villages randomly geospatially selected from aerial images from across the Nepal's Terai lowlands region (excluding towns and cities). We collected data between Nov 30, 2018 and May 7, 2019, and analysed snakebite incidence rates and outcomes in humans and domestic animals.
FINDINGS
Among 63 454 human participants living in 13 879 households (249 villages), 166 were bitten by a snake over the previous 12 months; 48·8% were envenomed and 7·8% died. This corresponded to an annual crude incidence rate of 262 snakebites (adjusted incidence of 251·1 [95% CI 201·7–312·6]) and 20 deaths (22·4 [11·9–42·1]) per 100 000 people, extrapolating to 26 749–37 661 yearly bitten people and 2386–3225 deaths. Bitten people had a median age of 30 years (IQR 20–45) and with available data, 64% were female. Children younger than 15 years (n=6; 46%) and females (n=10; 77%) were disproportionately affected among the 13 people who died. The incidence was higher in the Eastern region, and mortality was higher in the Central region. Of 183 949 animals, owners reported 144 snakebites, with an annual incidence rate of 42–202 per 100 000 and mortality of 79–100%, varying by animal type. Spatial and seasonal incidence were similar in humans and in animals.
INTERPRETATION
This study provides the first epidemiological estimates of snakebite envenoming in humans and domestic animals across Nepal's Terai lowlands. It was also the first to use a community-based, transdisciplinary, and One Health design. These findings call for a strengthening of preventive measures and better access to life-saving treatments.