Journal Article > ResearchFull Text
medRxiv. 5 February 2025; DOI:10.1101/2025.02.03.25321543
Chandna A, Koshiaris C, Mahajan R, Ahmad RA, Anh DTV, et al.
medRxiv. 5 February 2025; DOI:10.1101/2025.02.03.25321543
BACKGROUND
Circulating markers of immune and endothelial activation risk stratify infection syndromes agnostic to disease aetiology. However, their utility in children presenting from the community remains unclear.
METHODS
This study recruited children aged 1-59 months presenting with community-acquired acute febrile illnesses to seven hospitals in Bangladesh, Cambodia, Indonesia, Laos, and Viet Nam. Clinical parameters and biomarker concentrations were measured at presentation. The outcome measure was death or receipt of vital organ support within two days of enrolment. Prognostic performance of endothelial (Ang-1, Ang-2, sFlt-1) and immune (CHI3L1, CRP, IP-10, IL-1ra, IL-6, IL-8, IL-10, PCT, sTNFR-1, sTREM-1, suPAR) activation markers, WHO Danger Signs, and two validated severity scores (LqSOFA, SIRS) was compared.
RESULTS
3,423 participants were recruited. 133 met the outcome (weighted prevalence: 0.34%; 95% CI 0.28-0.41). sTREM-1 exhibited highest prognostic accuracy (AUC 0.86; 95% CI 0.82-0.90), outperforming WHO Danger Signs (AUC 0.75; 95% CI 0.70-0.80; p < 0.001), LqSOFA (AUC 0.74; 95% CI 0.70-0.78; p < 0.001), and SIRS (AUC 0.63; 95% CI 0.58-0.68; p < 0.001). Discrimination of immune and endothelial activation markers was particularly strong for children who deteriorated later in the course of their illness. Compared to WHO Danger Signs, an sTREM-1-based triage strategy improved recognition of children at risk of progression to life-threatening infection (sensitivity: 0.80 vs. 0.72), while maintaining comparable specificity (0.81 vs. 0.79).
CONCLUSIONS
Measuring circulating markers of immune and endothelial activation may help earlier recognition of febrile children at risk of poor outcomes in resource-constrained community settings.
Journal Article > ResearchFull Text
J Infect Dis. 16 December 2024; Volume 230 (Issue 6); e1235-e1244.; DOI:10.1093/infdis/jiae221
Cortes-Azuero O, Lefrancq N, Nikolay B, McKee C, Cappelle J, et al.
J Infect Dis. 16 December 2024; Volume 230 (Issue 6); e1235-e1244.; DOI:10.1093/infdis/jiae221
BACKGROUND
Nipah virus (NiV), a highly lethal virus in humans, circulates in Pteropus bats throughout South and Southeast Asia. Difficulty in obtaining viral genomes from bats means we have a poor understanding of NiV diversity.
METHODS
We develop phylogenetic approaches applied to the most comprehensive collection of genomes to date (N = 257, 175 from bats, 73 from humans) from 6 countries over 22 years (1999–2020). We divide the 4 major NiV sublineages into 15 genetic clusters. Using Approximate Bayesian Computation fit to a spatial signature of viral diversity, we estimate the presence and the average size of genetic clusters per area.
RESULTS
We find that, within any bat roost, there are an average of 2.4 co-circulating genetic clusters, rising to 5.5 clusters at areas of 1500–2000 km2. We estimate that each genetic cluster occupies an average area of 1.3 million km2 (95% confidence interval [CI], .6–2.3 million km2), with 14 clusters in an area of 100 000 km2 (95% CI, 6–24 km2). In the few sites in Bangladesh and Cambodia where genomic surveillance has been concentrated, we estimate that most clusters have been identified, but only approximately 15% of overall NiV diversity has been uncovered.
CONCLUSIONS
Our findings are consistent with entrenched co-circulation of distinct lineages, even within roosts, coupled with slow migration over larger spatial scales.
Conference Material > Abstract
Hopkins S, Hazel A, Pourtois J, Chamberlin A, Gajewski Z, et al.
MSF Scientific Day International 2023. 7 June 2023; DOI:10.57740/vj1f-v594
INTRODUCTION
An undervalued role of rural healthcare provision is its impact on forests and carbon balance. In addition to the effects of healthcare provision and livelihood programmes on improved human health, these programmes can also reduce forest degradation and prevent deforestation-related carbon emissions, since unaffordable healthcare drives logging as a source of rescue income. Shocks such as the Covid-19 pandemic may exacerbate this dynamic. Health In Harmony and Planet Indonesia are two planetary health non-governmental organisations (NGO’s) that work together with communities living in and around tropical rainforests in West Kalimantan, Indonesia.
METHODS
We used a cross-sectional mixed-methods survey in November-December 2021 to evaluate healthcare access and livelihoods in 1,016 households across six NGO-affiliated villages and four unaffiliated control villages. Additionally, satellite-generated imagery retrieved between January 2018 and December 2021 was used to contrast relative deforestation rates in 28 NGO-affiliated and 1,421 unaffiliated control villages bordering protected rainforests across Kalimantan.
ETHICS
This study was approved by the Stanford University Institutional Review Board and by the Institut Pertanian Bogor Ethical Review Board.
RESULTS
After accounting for environmental variables that affect deforestation, satellite analysis suggested that prior to the Covid-19 pandemic, average weekly deforestation rates in NGO-affiliated villages (0.018%; 95% confidence interval (CI), 0.012-0.026%) were 70% lower than in unaffiliated villages (0.062%; 95%CI, 0.045-0.078%; p<0.0001). Following the WHO pandemic declaration, deforestation rates dropped and then gradually rebounded in both NGO-affiliated and unaffiliated villages, with NGO-affiliated villages maintaining significantly lower average deforestation rates (0.008%; 95%CI, 0.005-0.011%) during the pandemic than unaffiliated villages (0.026%; 95%CI, 0.019-0.032%; p<0.01). Survey results indicated that clinic visits, out-of-pocket healthcare spending, and the proportion of households unable to access healthcare increased across all villages during the pandemic. The main reasons given for access problems were around fears of contracting Covid-19, unaffordability, or clinic closure. Throughout the pandemic, households affiliated with Health In Harmony, which runs a health clinic, were less likely to report barriers to affordable clinic access than households in unaffiliated villages (14% vs. 29%; odds ratio (OR); 0.41,95%CI, 0.2-0.69). Households in NGO-affiliated villages were more likely to do jobs with low environmental impact (e.g., small-scale farming, conservation; OR 1.61,95%CI, 1.15-2.24). Half of households in both groups reported income loss from at least one source during the pandemic, but households in NGO-affiliated villages were more likely to gain alternative income from multiple job types, especially resource-neutral jobs (e.g., public servant, sales, services). Additionally, households in NGO-affiliated villages had more sources of economic support, such as government programmes, co-operatives, family and NGO’s (OR 1.36, 95%CI, 1.11-1.69).
CONCLUSION
Communities with better access to healthcare and livelihood support were associated with significantly lower deforestation rates prior to the Covid-19 pandemic, and this lower reliance on forest-degrading income was resilient to the pandemic shock.
CONFLICTS OF INTEREST
None declared.
An undervalued role of rural healthcare provision is its impact on forests and carbon balance. In addition to the effects of healthcare provision and livelihood programmes on improved human health, these programmes can also reduce forest degradation and prevent deforestation-related carbon emissions, since unaffordable healthcare drives logging as a source of rescue income. Shocks such as the Covid-19 pandemic may exacerbate this dynamic. Health In Harmony and Planet Indonesia are two planetary health non-governmental organisations (NGO’s) that work together with communities living in and around tropical rainforests in West Kalimantan, Indonesia.
METHODS
We used a cross-sectional mixed-methods survey in November-December 2021 to evaluate healthcare access and livelihoods in 1,016 households across six NGO-affiliated villages and four unaffiliated control villages. Additionally, satellite-generated imagery retrieved between January 2018 and December 2021 was used to contrast relative deforestation rates in 28 NGO-affiliated and 1,421 unaffiliated control villages bordering protected rainforests across Kalimantan.
ETHICS
This study was approved by the Stanford University Institutional Review Board and by the Institut Pertanian Bogor Ethical Review Board.
RESULTS
After accounting for environmental variables that affect deforestation, satellite analysis suggested that prior to the Covid-19 pandemic, average weekly deforestation rates in NGO-affiliated villages (0.018%; 95% confidence interval (CI), 0.012-0.026%) were 70% lower than in unaffiliated villages (0.062%; 95%CI, 0.045-0.078%; p<0.0001). Following the WHO pandemic declaration, deforestation rates dropped and then gradually rebounded in both NGO-affiliated and unaffiliated villages, with NGO-affiliated villages maintaining significantly lower average deforestation rates (0.008%; 95%CI, 0.005-0.011%) during the pandemic than unaffiliated villages (0.026%; 95%CI, 0.019-0.032%; p<0.01). Survey results indicated that clinic visits, out-of-pocket healthcare spending, and the proportion of households unable to access healthcare increased across all villages during the pandemic. The main reasons given for access problems were around fears of contracting Covid-19, unaffordability, or clinic closure. Throughout the pandemic, households affiliated with Health In Harmony, which runs a health clinic, were less likely to report barriers to affordable clinic access than households in unaffiliated villages (14% vs. 29%; odds ratio (OR); 0.41,95%CI, 0.2-0.69). Households in NGO-affiliated villages were more likely to do jobs with low environmental impact (e.g., small-scale farming, conservation; OR 1.61,95%CI, 1.15-2.24). Half of households in both groups reported income loss from at least one source during the pandemic, but households in NGO-affiliated villages were more likely to gain alternative income from multiple job types, especially resource-neutral jobs (e.g., public servant, sales, services). Additionally, households in NGO-affiliated villages had more sources of economic support, such as government programmes, co-operatives, family and NGO’s (OR 1.36, 95%CI, 1.11-1.69).
CONCLUSION
Communities with better access to healthcare and livelihood support were associated with significantly lower deforestation rates prior to the Covid-19 pandemic, and this lower reliance on forest-degrading income was resilient to the pandemic shock.
CONFLICTS OF INTEREST
None declared.
Conference Material > Video
Burza S
MSF Scientific Day International 2023. 7 June 2023; DOI:10.57740/kn2v-0h76
Conference Material > Slide Presentation
Hopkins S, Hazel A, Pourtois J, Chamberlin A, Gajewski Z, et al.
MSF Scientific Day International 2023. 7 June 2023; DOI:10.57740/gr3a-mk13
Journal Article > ResearchFull Text
Public Health Nutr. 1 June 2023; Volume 26 (Issue 6); 1210-1221.; DOI:10.1017/S1368980023000149
Briend A, Myatt M, Berkley JA, Black RE, Boyd EM, et al.
Public Health Nutr. 1 June 2023; Volume 26 (Issue 6); 1210-1221.; DOI:10.1017/S1368980023000149
OBJECTIVE
To compare the prognostic value of mid-upper arm circumference (MUAC), weight-for-height Z-score (WHZ) and weight-for-age Z-score (WAZ) for predicting death over periods of 1, 3 and 6 months follow-up in children.
DESIGN
Pooled analysis of twelve prospective studies examining survival after anthropometric assessment. Sensitivity and false-positive ratios to predict death within 1, 3 and 6 months were compared for three individual anthropometric indices and their combinations.
SETTING
Community-based, prospective studies from twelve countries in Africa and Asia.
PARTICIPANTS
Children aged 6–59 months living in the study areas.
RESULTS
For all anthropometric indices, the receiver operating characteristic curves were higher for shorter than for longer durations of follow-up. Sensitivity was higher for death with 1-month follow-up compared with 6 months by 49 % (95 % CI (30, 69)) for MUAC < 115 mm (P < 0·001), 48 % (95 % CI (9·4, 87)) for WHZ < -3 (P < 0·01) and 28 % (95 % CI (7·6, 42)) for WAZ < -3 (P < 0·005). This was accompanied by an increase in false positives of only 3 % or less. For all durations of follow-up, WAZ < -3 identified more children who died and were not identified by WHZ < -3 or by MUAC < 115 mm, 120 mm or 125 mm, but the use of WAZ < -3 led to an increased false-positive ratio up to 16·4 % (95 % CI (12·0, 20·9)) compared with 3·5 % (95 % CI (0·4, 6·5)) for MUAC < 115 mm alone.
CONCLUSIONS
Frequent anthropometric measurements significantly improve the identification of malnourished children with a high risk of death without markedly increasing false positives. Combining two indices increases sensitivity but also increases false positives among children meeting case definitions.
To compare the prognostic value of mid-upper arm circumference (MUAC), weight-for-height Z-score (WHZ) and weight-for-age Z-score (WAZ) for predicting death over periods of 1, 3 and 6 months follow-up in children.
DESIGN
Pooled analysis of twelve prospective studies examining survival after anthropometric assessment. Sensitivity and false-positive ratios to predict death within 1, 3 and 6 months were compared for three individual anthropometric indices and their combinations.
SETTING
Community-based, prospective studies from twelve countries in Africa and Asia.
PARTICIPANTS
Children aged 6–59 months living in the study areas.
RESULTS
For all anthropometric indices, the receiver operating characteristic curves were higher for shorter than for longer durations of follow-up. Sensitivity was higher for death with 1-month follow-up compared with 6 months by 49 % (95 % CI (30, 69)) for MUAC < 115 mm (P < 0·001), 48 % (95 % CI (9·4, 87)) for WHZ < -3 (P < 0·01) and 28 % (95 % CI (7·6, 42)) for WAZ < -3 (P < 0·005). This was accompanied by an increase in false positives of only 3 % or less. For all durations of follow-up, WAZ < -3 identified more children who died and were not identified by WHZ < -3 or by MUAC < 115 mm, 120 mm or 125 mm, but the use of WAZ < -3 led to an increased false-positive ratio up to 16·4 % (95 % CI (12·0, 20·9)) compared with 3·5 % (95 % CI (0·4, 6·5)) for MUAC < 115 mm alone.
CONCLUSIONS
Frequent anthropometric measurements significantly improve the identification of malnourished children with a high risk of death without markedly increasing false positives. Combining two indices increases sensitivity but also increases false positives among children meeting case definitions.
Journal Article > ResearchFull Text
Public Health Nutr. 3 February 2023; Volume 26 (Issue 4); 803-819.; DOI:10.1017/S136898002300023X
Khara T, Myatt M, Sadler K, Bahwere P, Berkley JA, et al.
Public Health Nutr. 3 February 2023; Volume 26 (Issue 4); 803-819.; DOI:10.1017/S136898002300023X
OBJECTIVE
To understand which anthropometric diagnostic criteria best discriminate higher from lower risk of death in children and explore programme implications.
DESIGN
A multiple cohort individual data meta-analysis of mortality risk (within 6 months of measurement) by anthropometric case definitions. Sensitivity, specificity, informedness and inclusivity in predicting mortality, face validity and compatibility with current standards and practice were assessed and operational consequences were modelled.
SETTING
Community-based cohort studies in twelve low-income countries between 1977 and 2013 in settings where treatment of wasting was not widespread.
PARTICIPANTS
Children aged 6 to 59 months.
RESULTS
Of the twelve anthropometric case definitions examined, four (weight-for-age Z-score (WAZ) <−2), (mid-upper arm circumference (MUAC) <125 mm), (MUAC < 115 mm or WAZ < −3) and (WAZ < −3) had the highest informedness in predicting mortality. A combined case definition (MUAC < 115 mm or WAZ < −3) was better at predicting deaths associated with weight-for-height Z-score <−3 and concurrent wasting and stunting (WaSt) than the single WAZ < −3 case definition. After the assessment of all criteria, the combined case definition performed best. The simulated workload for programmes admitting based on MUAC < 115 mm or WAZ < −3, when adjusted with a proxy for required intensity and/or duration of treatment, was 1·87 times larger than programmes admitting on MUAC < 115 mm alone.
CONCLUSIONS
A combined case definition detects nearly all deaths associated with severe anthropometric deficits suggesting that therapeutic feeding programmes may achieve higher impact (prevent mortality and improve coverage) by using it. There remain operational questions to examine further before wide-scale adoption can be recommended.
To understand which anthropometric diagnostic criteria best discriminate higher from lower risk of death in children and explore programme implications.
DESIGN
A multiple cohort individual data meta-analysis of mortality risk (within 6 months of measurement) by anthropometric case definitions. Sensitivity, specificity, informedness and inclusivity in predicting mortality, face validity and compatibility with current standards and practice were assessed and operational consequences were modelled.
SETTING
Community-based cohort studies in twelve low-income countries between 1977 and 2013 in settings where treatment of wasting was not widespread.
PARTICIPANTS
Children aged 6 to 59 months.
RESULTS
Of the twelve anthropometric case definitions examined, four (weight-for-age Z-score (WAZ) <−2), (mid-upper arm circumference (MUAC) <125 mm), (MUAC < 115 mm or WAZ < −3) and (WAZ < −3) had the highest informedness in predicting mortality. A combined case definition (MUAC < 115 mm or WAZ < −3) was better at predicting deaths associated with weight-for-height Z-score <−3 and concurrent wasting and stunting (WaSt) than the single WAZ < −3 case definition. After the assessment of all criteria, the combined case definition performed best. The simulated workload for programmes admitting based on MUAC < 115 mm or WAZ < −3, when adjusted with a proxy for required intensity and/or duration of treatment, was 1·87 times larger than programmes admitting on MUAC < 115 mm alone.
CONCLUSIONS
A combined case definition detects nearly all deaths associated with severe anthropometric deficits suggesting that therapeutic feeding programmes may achieve higher impact (prevent mortality and improve coverage) by using it. There remain operational questions to examine further before wide-scale adoption can be recommended.
Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 1 January 2023; Volume 27 (Issue 1); 34-40.; DOI:10.5588/ijtld.22.0324
Zeng C, Mitnick CD, Hewison CCH, Bastard M, Khan PY, et al.
Int J Tuberc Lung Dis. 1 January 2023; Volume 27 (Issue 1); 34-40.; DOI:10.5588/ijtld.22.0324
BACKGROUND
The WHO provides standardized outcome definitions for rifampicin-resistant (RR) and multidrug-resistant (MDR) TB. However, operationalizing these definitions can be challenging in some clinical settings, and incorrect classification may generate bias in reporting and research. Outcomes calculated by algorithms can increase standardization and be adapted to suit the research question. We evaluated concordance between clinician-assigned treatment outcomes and outcomes calculated based on one of two standardized algorithms, one which identified failure at its earliest possible recurrence (i.e., failure-dominant algorithm), and one which calculated the outcome based on culture results at the end of treatment, regardless of early occurrence of failure (i.e., success-dominant algorithm).
METHODS
Among 2,525 patients enrolled in the multi-country endTB observational study, we calculated the frequencies of concordance using cross-tabulations of clinician-assigned and algorithm-assigned outcomes. We summarized the common discrepancies.
RESULTS
Treatment success calculated by algorithms had high concordance with treatment success assigned by clinicians (95.8 and 97.7% for failure-dominant and success-dominant algorithms, respectively). The frequency and pattern of the most common discrepancies varied by country.
CONCLUSION
High concordance was found between clinician-assigned and algorithm-assigned outcomes. Heterogeneity in discrepancies across settings suggests that using algorithms to calculate outcomes may minimize bias.
The WHO provides standardized outcome definitions for rifampicin-resistant (RR) and multidrug-resistant (MDR) TB. However, operationalizing these definitions can be challenging in some clinical settings, and incorrect classification may generate bias in reporting and research. Outcomes calculated by algorithms can increase standardization and be adapted to suit the research question. We evaluated concordance between clinician-assigned treatment outcomes and outcomes calculated based on one of two standardized algorithms, one which identified failure at its earliest possible recurrence (i.e., failure-dominant algorithm), and one which calculated the outcome based on culture results at the end of treatment, regardless of early occurrence of failure (i.e., success-dominant algorithm).
METHODS
Among 2,525 patients enrolled in the multi-country endTB observational study, we calculated the frequencies of concordance using cross-tabulations of clinician-assigned and algorithm-assigned outcomes. We summarized the common discrepancies.
RESULTS
Treatment success calculated by algorithms had high concordance with treatment success assigned by clinicians (95.8 and 97.7% for failure-dominant and success-dominant algorithms, respectively). The frequency and pattern of the most common discrepancies varied by country.
CONCLUSION
High concordance was found between clinician-assigned and algorithm-assigned outcomes. Heterogeneity in discrepancies across settings suggests that using algorithms to calculate outcomes may minimize bias.
Journal Article > Short ReportFull Text
Clin Infect Dis. 2 November 2019; Volume 71 (Issue 2); 415-418.; DOI:10.1093/cid/ciz1084
Seung KJ, Khan PY, Franke MF, Ahmed SM, Aiylchiev S, et al.
Clin Infect Dis. 2 November 2019; Volume 71 (Issue 2); 415-418.; DOI:10.1093/cid/ciz1084
Delamanid should be effective against highly resistant strains of Mycobacterium tuberculosis, but uptake has been slow globally. In the endTB (expand new drug markets for TB) Observational Study, which enrolled a large, heterogeneous cohorts of patients receiving delamanid as part of a multidrug regimen, 80% of participants experienced sputum culture conversion within 6 months.
Journal Article > ResearchFull Text
Parasit Vectors. 11 August 2010; Volume 3 (Issue 1); DOI:10.1186/1756-3305-3-70
Bhullar N, Maikere J, Grais RF
Parasit Vectors. 11 August 2010; Volume 3 (Issue 1); DOI:10.1186/1756-3305-3-70
ABSTRACT: BACKGROUND: The World Health Organization (WHO) Global Program to Eliminate Lymphatic Filariasis relies on mass drug administration (MDA) of two drugs annually for 4 to 6 years. The goal is to reduce the reservoir of microfilariae in the blood to a level insufficient to maintain transmission by the mosquito vector. In 2008, the international medical aid organization Medecins Sans Frontieres (MSF) performed the first round of a MDA in the high-burden area of Asmat district, in Papua, Indonesia. We report the challenges faced in this MDA on a remote Indonesian island and propose solutions to overcome these hurdles in similar future contexts. RESULTS: During the MDA, we encountered difficult challenges in accessing as well as persuading the patient population to take the antifilarial drugs. Health promotion activities supporting treatment need to be adapted and repetitive, with adequate time and resources allocated for accessing and communicating with local, seminomadic populations. Distribution of bednets resulted in an increase in MDA coverage, but it was still below the 80-85% target. CONCLUSIONS: MDA for lymphatic filariasis is how the WHO has planned to eliminate the disease from endemic areas. Our programmatic experience will hopefully help inform future campaign planning in difficult-to-access, high-burden areas of the world to achieve target MDA coverage for elimination of lymphatic filariasis.