Journal Article > ResearchFull Text
Glob Health Action. 25 April 2024; Volume 17 (Issue 1); 2331291.; DOI:10.1080/16549716.2024.2331291
Caleo G, Lokuge K, Kardamanidis K, Greig J, Belava J, et al.
Glob Health Action. 25 April 2024; Volume 17 (Issue 1); 2331291.; DOI:10.1080/16549716.2024.2331291
BACKGROUND
There is a lack of empirical data on design effects (DEFF) for mortality rate for highly clustered data such as with Ebola virus disease (EVD), along with a lack of documentation of methodological limitations and operational utility of mortality estimated from cluster-sampled studies when the DEFF is high.
OBJECTIVES
The objectives of this paper are to report EVD mortality rate and DEFF estimates, and discuss the methodological limitations of cluster surveys when data are highly clustered such as during an EVD outbreak.
METHODS
We analysed the outputs of two independent population-based surveys conducted at the end of the 2014-2016 EVD outbreak in Bo District, Sierra Leone, in urban and rural areas. In each area, 35 clusters of 14 households were selected with probability proportional to population size. We collected information on morbidity, mortality and changes in household composition during the recall period (May 2014 to April 2015). Rates were calculated for all-cause, all-age, under-5 and EVD-specific mortality, respectively, by areas and overall. Crude and adjusted mortality rates were estimated using Poisson regression, accounting for the surveys sample weights and the clustered design.
RESULTS
Overall 980 households and 6,522 individuals participated in both surveys. A total of 64 deaths were reported, of which 20 were attributed to EVD. The crude and EVD-specific mortality rates were 0.35/10,000 person-days (95%CI: 0.23-0.52) and 0.12/10,000 person-days (95%CI: 0.05-0.32), respectively. The DEFF for EVD mortality was 5.53, and for non-EVD mortality, it was 1.53. DEFF for EVD-specific mortality was 6.18 in the rural area and 0.58 in the urban area. DEFF for non-EVD-specific mortality was 1.87 in the rural area and 0.44 in the urban area.
CONCLUSION
Our findings demonstrate a high degree of clustering; this contributed to imprecise mortality estimates, which have limited utility when assessing the impact of disease. We provide DEFF estimates that can inform future cluster surveys and discuss design improvements to mitigate the limitations of surveys for highly clustered data.
There is a lack of empirical data on design effects (DEFF) for mortality rate for highly clustered data such as with Ebola virus disease (EVD), along with a lack of documentation of methodological limitations and operational utility of mortality estimated from cluster-sampled studies when the DEFF is high.
OBJECTIVES
The objectives of this paper are to report EVD mortality rate and DEFF estimates, and discuss the methodological limitations of cluster surveys when data are highly clustered such as during an EVD outbreak.
METHODS
We analysed the outputs of two independent population-based surveys conducted at the end of the 2014-2016 EVD outbreak in Bo District, Sierra Leone, in urban and rural areas. In each area, 35 clusters of 14 households were selected with probability proportional to population size. We collected information on morbidity, mortality and changes in household composition during the recall period (May 2014 to April 2015). Rates were calculated for all-cause, all-age, under-5 and EVD-specific mortality, respectively, by areas and overall. Crude and adjusted mortality rates were estimated using Poisson regression, accounting for the surveys sample weights and the clustered design.
RESULTS
Overall 980 households and 6,522 individuals participated in both surveys. A total of 64 deaths were reported, of which 20 were attributed to EVD. The crude and EVD-specific mortality rates were 0.35/10,000 person-days (95%CI: 0.23-0.52) and 0.12/10,000 person-days (95%CI: 0.05-0.32), respectively. The DEFF for EVD mortality was 5.53, and for non-EVD mortality, it was 1.53. DEFF for EVD-specific mortality was 6.18 in the rural area and 0.58 in the urban area. DEFF for non-EVD-specific mortality was 1.87 in the rural area and 0.44 in the urban area.
CONCLUSION
Our findings demonstrate a high degree of clustering; this contributed to imprecise mortality estimates, which have limited utility when assessing the impact of disease. We provide DEFF estimates that can inform future cluster surveys and discuss design improvements to mitigate the limitations of surveys for highly clustered data.
Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 1 December 2023; Volume 27 (Issue 12); 885-898.; DOI:10.5588/ijtld.23.0341
du Cros PAK, Greig J, Cross GB, Cousins C, Berry C, et al.
Int J Tuberc Lung Dis. 1 December 2023; Volume 27 (Issue 12); 885-898.; DOI:10.5588/ijtld.23.0341
English
Français
BACKGROUND
The value, speed of completion and robustness of the evidence generated by TB treatment trials could be improved by implementing standards for best practice.
METHODS
A global panel of experts participated in a Delphi process, using a 7-point Likert scale to score and revise draft standards until consensus was reached.
RESULTS
Eleven standards were defined: Standard 1, high quality data on TB regimens are essential to inform clinical and programmatic management; Standard 2, the research questions addressed by TB trials should be relevant to affected communities, who should be included in all trial stages; Standard 3, trials should make every effort to be as inclusive as possible; Standard 4, the most efficient trial designs should be considered to improve the evidence base as quickly and cost effectively as possible, without compromising quality; Standard 5, trial governance should be in line with accepted good clinical practice; Standard 6, trials should investigate and report strategies that promote optimal engagement in care; Standard 7, where possible, TB trials should include pharmacokinetic and pharmacodynamic components; Standard 8, outcomes should include frequency of disease recurrence and post-treatment sequelae; Standard 9, TB trials should aim to harmonise key outcomes and data structures across studies; Standard 10, TB trials should include biobanking; Standard 11, treatment trials should invest in capacity strengthening of local trial and TB programme staff.
CONCLUSION
These standards should improve the efficiency and effectiveness of evidence generation, as well as the translation of research into policy and practice.
The value, speed of completion and robustness of the evidence generated by TB treatment trials could be improved by implementing standards for best practice.
METHODS
A global panel of experts participated in a Delphi process, using a 7-point Likert scale to score and revise draft standards until consensus was reached.
RESULTS
Eleven standards were defined: Standard 1, high quality data on TB regimens are essential to inform clinical and programmatic management; Standard 2, the research questions addressed by TB trials should be relevant to affected communities, who should be included in all trial stages; Standard 3, trials should make every effort to be as inclusive as possible; Standard 4, the most efficient trial designs should be considered to improve the evidence base as quickly and cost effectively as possible, without compromising quality; Standard 5, trial governance should be in line with accepted good clinical practice; Standard 6, trials should investigate and report strategies that promote optimal engagement in care; Standard 7, where possible, TB trials should include pharmacokinetic and pharmacodynamic components; Standard 8, outcomes should include frequency of disease recurrence and post-treatment sequelae; Standard 9, TB trials should aim to harmonise key outcomes and data structures across studies; Standard 10, TB trials should include biobanking; Standard 11, treatment trials should invest in capacity strengthening of local trial and TB programme staff.
CONCLUSION
These standards should improve the efficiency and effectiveness of evidence generation, as well as the translation of research into policy and practice.
Journal Article > ResearchFull Text
PLOS Glob Public Health. 29 March 2023; Volume 3 (Issue 3); e0001644.; DOI:10.1371/journal.pgph.0001644
Thurtle N, Kirby KA, Greig J, Bil K, Dargan PI, et al.
PLOS Glob Public Health. 29 March 2023; Volume 3 (Issue 3); e0001644.; DOI:10.1371/journal.pgph.0001644
Mother-to-child-transmission of lead via the placenta is known to result in congenital lead toxicity. Between 2010 and 2021, Médecins Sans Frontières and other stakeholders responded to a severe lead poisoning outbreak related to artisanal gold mining in Northern Nigeria. Extensive environmental remediation occurred following outbreak identification; source control efforts are ongoing within the community. We aimed to describe the prevalence of congenital lead poisoning in this cohort and analyse the association between neonatal blood lead concentration (BLC) and medium-term lead-related outcomes during the study period. Children enrolled in the lead poisoning programme between July 2010 and 25 January 2018 who had a screening BLC at ≤4 weeks of age were included. For time-to-event analysis, medium-term outcomes were classified as lead-related (death from lead encephalopathy, and/or met chelation threshold) and non-lead-related (non-lead-related death, on programme no chelation, exit from programme without chelation). Cox regression analysis and ROC analysis were performed. 1468 children were included. All-cause mortality 2.3%; geometric mean neonatal BLC 13.7 μg/dL; ‘lead-related death or treatment’ 19.3%. For every doubling in neonatal BLC, there was an almost 8-fold increase in adjusted hazard ratio (HR) for the composite lead-related outcome (p<0.001). A neonatal BLC ≥ 15.0 μg/dL had 95% sensitivity for identifying children who went on to have the composite outcome (with specificity 67%; positive likelihood ratio 2.86). Congenital lead poisoning predicts ongoing exposure in this population, even after environmental remediation. This suggests a complex, early, multidisciplinary approach to source control and exposure management is required when elevated neonatal BLC is observed in lead poisoning clusters in low-and-middle-income contexts.
Journal Article > ResearchFull Text
Int Health. 11 January 2023; Volume 15 (Issue 5); 537-546.; DOI:10.1093/inthealth/ihac088
Perrocheau A, Jephcott F, Asgari-Jirhanden N, Greig J, Peyraud N, et al.
Int Health. 11 January 2023; Volume 15 (Issue 5); 537-546.; DOI:10.1093/inthealth/ihac088
BACKGROUND
Outbreaks of unknown aetiology in complex settings pose challenges and there is little information about investigation methods. We reviewed investigations into such outbreaks to identify methods favouring or impeding identification of the cause.
METHODS
We used two approaches: reviewing scientific literature and soliciting key informants. Case studies were developed through interviews with people involved and triangulated with documents available from the time of the investigation.
RESULTS
Ten outbreaks in African or Asian countries within the period 2007–2017 were selected. The cause was identified in seven, of which two had an unclear mode of transmission, and in three, neither origin nor transmission mode was identified. Four events were caused by infectious agents and three by chemical poisoning. Despite differences in the outbreaks, similar obstacles were noted: incomplete or delayed description of patients, comorbidities confounding clinical pictures and case definitions wrongly attributed. Repeated rounds of data collection and laboratory investigations were common and there was limited capacity to ship samples.
DISCUSSION
It was not possible to define activities that led to prompt identification of the cause in the case studies selected. Based on the observations, we conclude that basing case definitions on precise medical observations, implementing initial comprehensive data collection, including environmental, social and behavioural information; and involving local informants could save precious time and hasten implementation of control measures.
Outbreaks of unknown aetiology in complex settings pose challenges and there is little information about investigation methods. We reviewed investigations into such outbreaks to identify methods favouring or impeding identification of the cause.
METHODS
We used two approaches: reviewing scientific literature and soliciting key informants. Case studies were developed through interviews with people involved and triangulated with documents available from the time of the investigation.
RESULTS
Ten outbreaks in African or Asian countries within the period 2007–2017 were selected. The cause was identified in seven, of which two had an unclear mode of transmission, and in three, neither origin nor transmission mode was identified. Four events were caused by infectious agents and three by chemical poisoning. Despite differences in the outbreaks, similar obstacles were noted: incomplete or delayed description of patients, comorbidities confounding clinical pictures and case definitions wrongly attributed. Repeated rounds of data collection and laboratory investigations were common and there was limited capacity to ship samples.
DISCUSSION
It was not possible to define activities that led to prompt identification of the cause in the case studies selected. Based on the observations, we conclude that basing case definitions on precise medical observations, implementing initial comprehensive data collection, including environmental, social and behavioural information; and involving local informants could save precious time and hasten implementation of control measures.
Journal Article > ResearchFull Text
Microbiol Spectr. 9 January 2023; Volume 11 (Issue 1); DOI:10.1128/spectrum.03698-22
Rekart ML, Mun L, Aung A, Gomez D, Mulanda WK, et al.
Microbiol Spectr. 9 January 2023; Volume 11 (Issue 1); DOI:10.1128/spectrum.03698-22
We report the findings of a prospective laboratory diagnostic accuracy study to evaluate the sensitivity, specificity, and predictive values of the Xpert MTB/RIF Ultra assay for Mycobacterium tuberculosis detection in fresh stool specimens from children under 15?years of age with confirmed tuberculosis (TB) disease from Dushanbe, Tajikistan. Six hundred eighty-eight (688) participants were enrolled from April 2019 to October 2021. We identified 16 participants (2.3%) with confirmed TB disease, defined as =1 TB sign/symptom plus microbiologic confirmation. With the Xpert MTB/RIF Ultra assay for stool, we found a sensitivity of 68.8% (95% CI, 46.0 to 91.5) and a specificity of 98.7% (95% CI, 97.8 to 99.5) in confirmed TB disease. Our results are comparable to other published studies; however, our cohort was larger and our confirmed TB disease rate lower than most. We also demonstrated that this assay was feasible to implement in a centralized hospital laboratory in a low-middle-income Central Asian country. However, we encountered obstacles such as lack of staffing, material ruptures, outdated government protocols, and decreased case presentation due to COVID-19. We found eight patients whose only positive test was an Xpert Ultra stool assay. None needed treatment during the study; however, three were treated later, suggesting such cases require close observation. Our report is the first from Central Asia and one of a few from a low-middle-income country. We believe our study demonstrates the generalizability of the Xpert MTB/RIF Ultra assay on fresh stool specimens from children and provides further evidence supporting WHO’s approval of this diagnostic strategy.
IMPORTANCE
The importance of this report is that it provides further support for WHO’s recent recommendation that fresh stool is an acceptable sample for GeneXpert TB testing in children, especially small children who often cannot produce an adequate sputum sample. Diagnosing TB in this age group is difficult, and many cases are missed, leading to unacceptable rates of TB illness and death. In our large cohort of children from Dushanbe, Tajikistan, the GeneXpert stool test was positive in 69% of proven cases of TB, and there were very few false-positive tests. We also showed that this diagnostic strategy was feasible to implement in a low-middle-income country with an inefficient health care delivery system. We hope that many more programs will adopt this form of diagnosing TB in children.
IMPORTANCE
The importance of this report is that it provides further support for WHO’s recent recommendation that fresh stool is an acceptable sample for GeneXpert TB testing in children, especially small children who often cannot produce an adequate sputum sample. Diagnosing TB in this age group is difficult, and many cases are missed, leading to unacceptable rates of TB illness and death. In our large cohort of children from Dushanbe, Tajikistan, the GeneXpert stool test was positive in 69% of proven cases of TB, and there were very few false-positive tests. We also showed that this diagnostic strategy was feasible to implement in a low-middle-income country with an inefficient health care delivery system. We hope that many more programs will adopt this form of diagnosing TB in children.
MSF Ethics Review Board > Templates & procedures
Gerstl S, Grandesso F, Siddiqui R, Greig J, du Cros PAK, et al.
25 October 2022
MSF Ethics Review Board > Templates & procedures
Grandesso F, Gerstl S, Siddiqui R, Greig J, du Cros PAK, et al.
25 October 2022
Mortality Survey Protocol - standardised, MSF ERB approved, intersectional
This collection of files includes an overview of the whole process of conducting a mortality survey and templates for concept papers, the protocol, questionnaires and consent and other related forms. Surveys that use this standardised intersectional protocol do not require MSF Ethics Review Board (ERB) review if the Medical Director of the relevant section takes responsibility for addressing the ethics issues. The exemption criteria of the MSF ERB for standardised intersectional survey protocols must be followed.
This collection of files includes an overview of the whole process of conducting a mortality survey and templates for concept papers, the protocol, questionnaires and consent and other related forms. Surveys that use this standardised intersectional protocol do not require MSF Ethics Review Board (ERB) review if the Medical Director of the relevant section takes responsibility for addressing the ethics issues. The exemption criteria of the MSF ERB for standardised intersectional survey protocols must be followed.
Conference Material > Slide Presentation
Sadique S, Lin YD, Walker SA, Rao B, du Cros PAK, et al.
MSF Scientific Days International 2022. 10 May 2022; DOI:10.57740/54qw-5453
Conference Material > Abstract
Sadique S, Lin YD, Walker SA, Rao B, du Cros PAK, et al.
MSF Scientific Days International 2022. 9 May 2022; DOI:10.57740/s2se-8951
INTRODUCTION
The crowded conditions within camps for refugees and internally displaced people create risk environments for unmitigated transmission of SARS-CoV-2. Within one such setting, Cox’s Bazar, Bangladesh, MSF distributed face masks in July-August 2020 for use by people living in eight camps to reduce transmission risks. However, uptake of face masks within camp populations and the factors influencing use are not well understood.
METHODS
We conducted a multi-level triangulation mixed-methods study in March 2021 in Cox’s Bazar. Field observations were undertaken in public spaces in four camps, noting individuals’ facemask use (appropriate versus not), use of other types of face covering (e.g., headscarf), and gender. We also analysed photographs posted on Twitter during March 2021 that were geotagged in the Cox’s Bazar area, posted with a specific keyword, or posted by connected accounts and tweets. Photographs were also categorised by facemask/headscarf use and gender. Finally, we conducted 32 in-depth interviews to understand perceptions and barriers around mask use. Qualitative data were analysed thematically using NVivo.
ETHICS
This study was approved by the Office of the Civil Surgeon, Cox’s Bazar, Bangladesh and by the MSF Ethics Review Board.
RESULTS
We made 3,152 public observations. Only 190/3,152 (6%) were using a mask appropriately. Men were more likely to be seen using any visible standard facemask appropriately than women (odds ratio, OR, 1.5, 95% confidence interval 1.1-2.2, p-value 0.037). Most women were observed wearing headscarves that precluded observing if masks were worn underneath. The content of 20 tweets were analysed. One photograph showed one person wearing a mask correctly; in 17 photographs individuals wore no face covering and in 2 wore scarves. Qualitative data suggested participants were aware of the importance of mask use but highlighted several reasons for not wearing them, including the fear of being insulted for wearing a mask due to the association between mask use and having Covid-19; a view that they were unnecessary because there was little Covid-19 in the camps; experiences of physical difficulties or discomfort whilst wearing masks; and a belief that wearing facemasks was unnecessary because “life or death is up to Allah”. Participants highlighted the current shortage of masks in the camps as well as adverse consequences of insufficient masks, and requested further distribution.
CONCLUSION
These findings suggest low adherence to recommendations around mask use in this camp setting. Multiple strategies need to be considered, including better distribution strategies and improved messaging and engagement with religious and community leaders to increase facemask use in settings such as Cox’s Bazar.
CONFLICTS OF INTEREST
None declared.
The crowded conditions within camps for refugees and internally displaced people create risk environments for unmitigated transmission of SARS-CoV-2. Within one such setting, Cox’s Bazar, Bangladesh, MSF distributed face masks in July-August 2020 for use by people living in eight camps to reduce transmission risks. However, uptake of face masks within camp populations and the factors influencing use are not well understood.
METHODS
We conducted a multi-level triangulation mixed-methods study in March 2021 in Cox’s Bazar. Field observations were undertaken in public spaces in four camps, noting individuals’ facemask use (appropriate versus not), use of other types of face covering (e.g., headscarf), and gender. We also analysed photographs posted on Twitter during March 2021 that were geotagged in the Cox’s Bazar area, posted with a specific keyword, or posted by connected accounts and tweets. Photographs were also categorised by facemask/headscarf use and gender. Finally, we conducted 32 in-depth interviews to understand perceptions and barriers around mask use. Qualitative data were analysed thematically using NVivo.
ETHICS
This study was approved by the Office of the Civil Surgeon, Cox’s Bazar, Bangladesh and by the MSF Ethics Review Board.
RESULTS
We made 3,152 public observations. Only 190/3,152 (6%) were using a mask appropriately. Men were more likely to be seen using any visible standard facemask appropriately than women (odds ratio, OR, 1.5, 95% confidence interval 1.1-2.2, p-value 0.037). Most women were observed wearing headscarves that precluded observing if masks were worn underneath. The content of 20 tweets were analysed. One photograph showed one person wearing a mask correctly; in 17 photographs individuals wore no face covering and in 2 wore scarves. Qualitative data suggested participants were aware of the importance of mask use but highlighted several reasons for not wearing them, including the fear of being insulted for wearing a mask due to the association between mask use and having Covid-19; a view that they were unnecessary because there was little Covid-19 in the camps; experiences of physical difficulties or discomfort whilst wearing masks; and a belief that wearing facemasks was unnecessary because “life or death is up to Allah”. Participants highlighted the current shortage of masks in the camps as well as adverse consequences of insufficient masks, and requested further distribution.
CONCLUSION
These findings suggest low adherence to recommendations around mask use in this camp setting. Multiple strategies need to be considered, including better distribution strategies and improved messaging and engagement with religious and community leaders to increase facemask use in settings such as Cox’s Bazar.
CONFLICTS OF INTEREST
None declared.
Protocol > Research Protocol
Kosack CS, Halton J, Greig J, Shanks L, Spijker S
1 July 2018
PRIMARY OBJECTIVE OF STUDY
• To demonstrate the extent of change in patient management through the availability of digital X-ray with teleradiology consultation.
SECONDARY OBJECTIVES OF STUDY
• To demonstrate the extent of change in patient diagnosis through the availability of digital X-ray with teleradiology consultation.
• To demonstrate the extent of change in patient diagnosis and management in the subgroup of patients with chest pathologies through the availability of digital X-ray with teleradiology consultation.
• To estimate if the extent of change in diagnosis and management is different in patients < 5 years of age versus ≥5 years of age.
• To demonstrate the extent of change in patient management through the availability of digital X-ray with teleradiology consultation.
SECONDARY OBJECTIVES OF STUDY
• To demonstrate the extent of change in patient diagnosis through the availability of digital X-ray with teleradiology consultation.
• To demonstrate the extent of change in patient diagnosis and management in the subgroup of patients with chest pathologies through the availability of digital X-ray with teleradiology consultation.
• To estimate if the extent of change in diagnosis and management is different in patients < 5 years of age versus ≥5 years of age.