Imperial College London

Professor Carlton A W Evans

Faculty of MedicineDepartment of Infectious Disease

Professor of Global Health
 
 
 
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Contact

 

+44 (0)20 3313 3222carlton.evans Website

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
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169 results found

Carlsson C, Lönnermark E, Datta S, Evans CAet al., 2024, A protocol for a systematic review and meta-analysis of tuberculosis care around the time of pregnancy [version 2; peer review: 2 approved, 1 approved with reservations], Wellcome Open Research, Vol: 8, ISSN: 2398-502X

BACKGROUND: Tuberculosis is estimated to cause 1.5 million deaths annually and is most common during the reproductive years. Despite that fact, we found that tuberculosis screening, prevention or care recommendations for people around the time of pregnancy were absent from some national policy recommendations and varied in others. OBJECTIVES: To address the apparent gaps and inconsistencies in policy, we aim to design a systematic review and meta-analysis of the original research evidence informing tuberculosis care around the time of pregnancy. METHODS: With assistance from librarians at the Biomedical library of the University of Gothenburg, Pubmed, CINAHL and Scopus databases will be searched. Search terms will aim to identify studies generating original research evidence informing care for tuberculosis around the time of pregnancy. Evidence may include: the outcome of TB and/or of pregnancy; the cost-effectiveness or acceptability of any intervention; the sensitivity and specificity of any assessment, selection, diagnostic or test criterion. The output from these literature searches will be screened by two independent reviewers to select the eligible studies for inclusion. Discrepancies will be resolved with a third reviewer. Firstly, publications that provide contextual data will be tabulated, summarising their main contributions. Secondly, studies that provide evidence directly guiding patient care will be our focus and will be considered to be key. The key studies will be subject to quality assessment, data extraction and when possible, meta-analysis. CONCLUSIONS: This systematic review and meta-analysis aims to guide policy, practice and future research priorities concerning tuberculosis care around the time of pregnancy.

Journal article

Bailon N, Ramos E, Alvarado K, Bernaola L, Wilson J, Montoya R, Valencia T, Evans CA, Datta Set al., 2023, A controlled evaluation of filter paper use during staining of sputum smears for tuberculosis microscopy., Wellcome open research, Vol: 8, ISSN: 2398-502X

<b>Background</b>: Some sputum smear microscopy protocols recommend placing filter paper over sputum smears during staining for <i>Mycobacterium tuberculosis</i> (TB) <i>.</i> We found no published evidence assessing whether this is beneficial. We aimed to evaluate the effect of filter paper on sputum smear microscopy results. <b>Methods:</b> Sputum samples were collected from 30 patients with confirmed pulmonary TB and 4 healthy control participants. From each sputum sample, six smears (204 smears in total) were prepared for staining with Ziehl-Neelsen (ZN), auramine or viability staining with fluorescein diacetate (FDA). Half of the slides subjected to each staining protocol were randomly selected to have Whatman grade 3 filter paper placed over the dried smears prior to stain application and removed prior to stain washing. The counts of acid-fast bacilli (AFB) and precipitates per 100 high-power microscopy fields of view, and the proportion of smear that appeared to have been washed away were recorded. Statistical analysis used a linear regression model adjusted by staining technique with a random effects term to correct for between-sample variability.   <b>Results:</b> The inclusion of filter paper in the staining protocol significantly decreased microscopy positivity independent of staining with ZN, auramine or FDA (p=0.01). Consistent with this finding, there were lower smear grades in slides stained using filter paper versus without (p=0.04), and filter paper use reduced AFB counts by 0.28 logarithms (95% confidence intervals, CI=0.018, 0.54, p=0.04) independent of staining technique. In all analyses, auramine was consistently more sensitive with higher AFB counts versus ZN (p=0.001), whereas FDA had lower sensitivity and lower AFB counts (p<0.0001). Filter paper use was not associated with the presence of any precipitate (p=0.5) or the probability of any smear washing away (p=0.6) during the

Journal article

Allen J, Evans CA, Datta S, 2022, Probiotics for preventing or treating COVID-19; a systematic review of research evidence and meta-analyses of efficacy for preventing death, severe disease, or disease progression, Wellcome Open Research, Vol: 7, Pages: 292-292

<ns4:p><ns4:bold>Background:</ns4:bold> COVID-19 variants threaten health globally. Despite improving vaccines and treatments, there is an urgent need for alternative strategies to prevent or reduce the severity of COVID-19. Potential strategies include probiotics, which are safe, inexpensive, globally available and have been studied previously in relation to respiratory infections.</ns4:p><ns4:p> <ns4:bold>Methods:</ns4:bold> We performed a systematic review and meta-analyses of experimental, trial or observational research evidence evaluating probiotics compared with control groups for preventing or treating COVID-19. We searched PubMed, ProQuest, Google Scholar and Web of Science bibliographic databases for studies published until December 6, 2021. We then performed meta-analyses for outcomes reported consistently across studies. Outcomes reported inconsistently or not amenable to meta-analysis were compared descriptively.</ns4:p><ns4:p> <ns4:bold>Results:</ns4:bold> We identified six eligible studies, which were all published in 2020 and 2021: one randomized controlled trial and five retrospective cohort studies. The only randomized controlled trial reported that groups that ingested probiotics compared with control groups that did not ingest probiotics did not differ significantly with respect to death, severe disease requiring admission to an intensive care unit or disease progression (all p&gt;0.5). The five retrospective cohort studies reported various apparently beneficial and harmful COVID-19 outcome associations with probiotic ingestion. Meta-analyses revealed no significant associations between probiotic use and death, severe disease, or disease progression caused by COVID-19. Descriptive data revealed that probiotic ingestion was associated with a trend towards worsened duration of hospital stay, improvements in measures of respiratory condition and worsened disease duration. The evid

Journal article

Carballo-Jimenez PP, Datta S, Aguirre-Ipenza R, Saunders MJ, Quevedo Cruz L, Evans CAet al., 2022, A protocol for a systematic review and meta-analysis of strategies to quantify or eliminate catastrophic costs due to tuberculosis, Wellcome Open Research, Vol: 7, Pages: 92-92

<ns4:p><ns4:bold>Background:</ns4:bold> The World Health Organization strategy to “End TB” by 2030 includes the milestone of no affected households facing catastrophic costs due to tuberculosis (TB). Costs due to TB are usually defined as catastrophic if they exceed 20% of the pre-disease annual household income. Several countries have conducted national TB cost surveys but strategies to quantify and eliminate catastrophic costs are incompletely defined.</ns4:p><ns4:p> <ns4:bold>Methods: </ns4:bold>Publications related to strategies to quantify and eliminate catastrophic costs will be identified by searching three electronic databases (PubMed - Medline, Scopus and Web of Science) together with reference lists from pertinent publications. We will screen eligible studies, extract data, and assess the risk of bias with the quality assessment tool from the National Heart, Lung, and Blood Institute. Discrepancies will be resolved by discussion between the reviewers. If we find sufficient comparable studies quantifying strategies to eliminate catastrophic costs then a meta-analysis will be performed. This systematic review and meta-analysis is registered with the PROSPERO database (CRD42022292410).</ns4:p><ns4:p> <ns4:bold>Conclusion:</ns4:bold> This systematic review and meta-analysis aims to rigorously assess the evidence for strategies to quantify or eliminate catastrophic costs due to TB.</ns4:p>

Journal article

Carballo-Jimenez PP, Datta S, Aguirre-Ipenza R, Saunders MJ, Quevedo Cruz L, Evans CAet al., 2022, Interventions aiming to eliminate catastrophic costs due to tuberculosis: a protocol for a systematic review and meta-analysis., Wellcome open research, Vol: 7, ISSN: 2398-502X

<b><i>Background</i></b> <b>:</b> People with tuberculosis disease and their household members may suffer direct out-of-pocket expenses and indirect costs of lost income. These tuberculosis-related costs can worsen poverty, make tuberculosis treatment completion unaffordable, impair quality of life and increase the risk of death. Costs due to tuberculosis are usually defined as catastrophic if they exceed 20% of the pre-disease annual household income. The World Health Organisation strategy to "End TB" and the United Nations Sustainable Development Goals include the target that no households should face catastrophic costs due to tuberculosis. However, there is limited evidence and policy concerning how this global priority of eliminating catastrophic costs due to tuberculosis should be achieved. This systematic review and meta-analysis aims to address this knowledge gap. <b><i>Methods</i></b> <b>:</b> Publications assessing interventions that aimed to eliminate catastrophic costs will be identified by searching three electronic databases (PubMed, Scopus and Web of Science) together with reference lists from pertinent publications. We will screen eligible studies, extract data, and assess the risk of bias with the quality assessment tool from the National Heart, Lung, and Blood Institute. Discrepancies will be resolved by discussion between the reviewers. If we find sufficient comparable studies quantifying strategies to eliminate catastrophic costs then a meta-analysis will be performed. This systematic review and meta-analysis is registered with the PROSPERO database (CRD42022292410). <b><i>Conclusion</i></b> <b>:</b> This systematic review and meta-analysis aims to rigorously assess the evidence for strategies to eliminate catastrophic costs due to tuberculosis.

Journal article

Carballo-Jimenez PP, Datta S, Aguirre-Ipenza R, Saunders MJ, Quevedo Cruz L, Evans CAet al., 2022, Interventions aiming to eliminate catastrophic costs due to tuberculosis: a protocol for a systematic review and meta-analysis., Wellcome Open Res, Vol: 7, ISSN: 2398-502X

Background : People with tuberculosis disease and their household members may suffer direct out-of-pocket expenses and indirect costs of lost income. These tuberculosis-related costs can worsen poverty, make tuberculosis treatment completion unaffordable, impair quality of life and increase the risk of death. Costs due to tuberculosis are usually defined as catastrophic if they exceed 20% of the pre-disease annual household income. The World Health Organisation strategy to "End TB" and the United Nations Sustainable Development Goals include the target that no households should face catastrophic costs due to tuberculosis. However, there is limited evidence and policy concerning how this global priority of eliminating catastrophic costs due to tuberculosis should be achieved. This systematic review and meta-analysis aims to address this knowledge gap. Methods : Publications assessing interventions that aimed to eliminate catastrophic costs will be identified by searching three electronic databases (PubMed, Scopus and Web of Science) together with reference lists from pertinent publications. We will screen eligible studies, extract data, and assess the risk of bias with the quality assessment tool from the National Heart, Lung, and Blood Institute. Discrepancies will be resolved by discussion between the reviewers. If we find sufficient comparable studies quantifying strategies to eliminate catastrophic costs then a meta-analysis will be performed. This systematic review and meta-analysis is registered with the PROSPERO database (CRD42022292410). Conclusion : This systematic review and meta-analysis aims to rigorously assess the evidence for strategies to eliminate catastrophic costs due to tuberculosis.

Journal article

Quevedo Cruz L, Montoya Villanueva MDR, Lozano Chavez AH, Franco Gutierrez JL, Flores Saavedra WE, Tovar Perez CF, Pozo Correa SC, Tapia Mamani PR, Haro Berrospi MC, Sosa Ccanto R, Ramos Maguina ES, Bernaola Silva LC, Bailon Gonzales NA, Alvarado Torres KS, Valencia Norabuena TR, Rivero Moron AM, Gomez Suarez JM, Carballo Jimenez PP, Saunders MJ, Evans CA, Datta Set al., 2021, REASONS FOR CONSENTING TO PARTICIPATE IN COMMUNITY RESEARCH AIMED TO PREVENT TUBERCULOSIS, Publisher: AMER SOC TROP MED & HYGIENE, Pages: 401-402, ISSN: 0002-9637

Conference paper

Migliori GB, Marx FM, Ambrosino N, Zampogna E, Schaaf HS, van der Zalm MM, Allwood B, Byrne AL, Mortimer K, Wallis RS, Fox GJ, Leung CC, Chakaya JM, Seaworth B, Rachow A, Marais BJ, Furin J, Akkerman OW, Yaquobi FA, Amaral A, Borisov S, Caminero JA, Carvalho ACC, Chesov D, Codecasa LR, Teixeira RC, Dalcolmo MP, Datta S, Dinh-Xuan A-T, Duarte R, Evans CA, García-García J-M, Günther G, Hoddinott G, Huddart S, Ivanova O, Laniado-Laborín R, Manga S, Manika K, Mariandyshev A, Mello FCQ, Mpagama SG, Muñoz-Torrico M, Nahid P, Ong CWM, Palmero DJ, Piubello A, Pontali E, Silva DR, Singla R, Spanevello A, Tiberi S, Udwadia ZF, Vitacca M, Centis R, DAmbrosio L, Sotgiu G, Lange C, Visca Det al., 2021, Clinical standards for the assessment, management, and rehabilitation of post-TB lung disease, International Journal of Tuberculosis and Lung Disease, Vol: 25, Pages: 797-813, ISSN: 1027-3719

BACKGROUND: Increasing evidence suggests that post-TB lung disease (PTLD) causes significant morbidity and mortality. The aim of these clinical standards is to provide guidance on the assessment and management of PTLD and the implementation of pulmonary rehabilitation (PR).METHODS: A panel of global experts in the field of TB care and PR was identified; 62 participated in a Delphi process. A 5-point Likert scale was used to score the initial ideas for standards and after several rounds of revision the document was approved (with 100% agreement).RESULTS: Five clinical standards were defined: Standard 1, to assess patients at the end of TB treatment for PTLD (with adaptation for children and specific settings/situations); Standard 2, to identify patients with PTLD for PR; Standard 3, tailoring the PR programme to patient needs and the local setting; Standard 4, to evaluate the effectiveness of PR; and Standard 5, to conduct education and counselling. Standard 6 addresses public health aspects of PTLD and outcomes due to PR.CONCLUSION: This is the first consensus-based set of Clinical Standards for PTLD. Our aim is to improve patient care and quality of life by guiding clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage PTLD.

Journal article

Bok J, Hofland R, Evans C, 2021, Whole blood mycobacterial growth assays for assessing human tuberculosis susceptibility: a systematic review and meta-analysis, Frontiers in Immunology, Vol: 12, ISSN: 1664-3224

Background. Whole blood mycobacterial growth assays (WBMGA) quantify mycobacterial growth in fresh blood samples and may have potential for assessing tuberculosis vaccines and identifying individuals at risk of tuberculosis. We evaluated the evidence for the underlying assumption that in vitro WBMGA results can predict in vivo tuberculosis susceptibility. Methods. A systematic search was done for studies assessing associations between WBMGA results and tuberculosis susceptibility. Meta-analyses were performed for eligible studies by calculating population-weighted averages. Results. No studies directly assessed whether WBMGA results predicted tuberculosis susceptibility. 15 studies assessed associations between WBMGA results and proven correlates of tuberculosis susceptibility, which we divided in two categories. Firstly, WBMGA associations with factors known to reduce tuberculosis susceptibility was statistically significant in all 8 studies of: BCG vaccination; vitamin D supplementation; altitude; and HIV-negativity/therapy. Secondly, WBMGA associations with probable correlates of tuberculosis susceptibility was statistically significant in 3 studies of tuberculosis disease, in a parasitism study and in2 of the 5 studies of latent tuberculosis infection. Meta-analyses for associations between WBMGA results and BCG vaccination, tuberculosis infection, tuberculosis disease and HIV infection revealed consistent effects. There was considerable methodological heterogeneity. Conclusions. T he study results generally showed significant associations between WBMGA results and correlates of tuberculosis susceptibility. However, no study directly assessed whether WBMGA results predicted actual susceptibility to tuberculosis infection or disease. We recommend optimization and standardization of WBMGA methodology and prospective studies to determine whether WBMGA predict susceptibility to tuberculosis disease.

Journal article

Kreniske JS, Montoya R, Lozano A, Tapia P, Patrocinio R, Evans CA, Datta Set al., 2020, Tuberculosis and the Venezuelan Migration in Peru: Towards a Community-Informed Intervention, International Conference of the American-Thoracic-Society (ATS), Publisher: American Thoracic Society, ISSN: 1073-449X

Conference paper

Datta S, Evans CA, 2020, The uncertainty of tuberculosis diagnosis, Lancet Infectious Diseases, Vol: 20, Pages: 1002-1004, ISSN: 1473-3099

Journal article

Allwood B, van der Zalm M, Amaral A, Byrne A, Datta S, Egere U, Evans C, Evans D, Gray D, Hoddinott G, Ivanova O, Jones R, Makanda G, Marx F, Meghji J, Mpagama S, Pasipanodya J, Rachow A, Schoeman I, Shaw J, Stek C, van Kampen S, von Delft D, Walker N, Wallis R, Mortimer Ket al., 2020, Post-tuberculosis lung health: perspectives from the firstInternational symposium, International Journal of Tuberculosis and Lung Disease, Vol: 24, Pages: 820-828, ISSN: 1027-3719

Tuberculosis, although curable, frequently leaves the individual with chronic physical and psycho-social impairment, yet these consequences have to-date been largely neglected. The 1st International Post-Tuberculosis Symposium was devoted entirely to impairment after tuberculosis, and covered a number of multi-disciplinary topics. Using the Delphi process, consensus was achieved for the terms “post-tuberculosis”, “post-tuberculosis lung disease/s (PTLD)”, and “post-tuberculosis economic, social and psychological well-being” (Post-TB ESP)”, to overcome the historical challenge of varied terminology in the literature. A minimum case-definition was proposed by consensus for PTLD in adults and children. Lack of sufficient evidence hampered definitive recommendations in most domains, including prevention and treatment of PTLD, but highlighted the dire need for research and priorities were identified. The heterogeneity of respiratory outcomes and previously employed research methodologies complicates the accurate estimation of disease burden. However, consensus was reached proposing a toolkit for future PTLD measurement, and on PTLD patterns to be considered. The importance of extra-pulmonary consequences and progressive impairment throughout the life-course was identified, including tuberculosis recurrence and increased mortality. Patient advocates emphasised the need for addressing the psychological and social impacts post tuberculosis, and called for clinical guidance. Increased awareness and more research addressing post-tuberculosis complications is urgently needed.

Journal article

Saunders MJ, Evans CA, 2020, COVID-19, tuberculosis and poverty: preventing a perfect storm, European Respiratory Journal, Vol: 56, Pages: 1-5, ISSN: 0903-1936

Journal article

Lee GO, Comina G, Hernandez-Cordova G, Naik N, Gayoso O, Ticona E, Coronel J, Evans C, Zimic M, Paz-Soldan VA, Gilman RH, Oberhelman Ret al., 2020, Cough dynamics in adults receiving tuberculosis treatment, PLoS One, Vol: 15, Pages: 1-13, ISSN: 1932-6203

Cough is a characteristic symptom of tuberculosis, is the main cause of transmission,and is used to assess treatment response. We aimed to identify the best measure ofcough severity and characterize changes during initial tuberculosis therapy.We conducted a prospective cohort of recently diagnosed ambulatory adult patientswith pulmonary tuberculosis in two tertiary hospitals in Lima, Peru. Pre-treatment andfive times during the first two months of treatment, a vibrometer was used to capture 4-hour recordings of involuntary cough. A total of 358 recordings from 69 participantswere analyzed using a computer algorithm.Total time spent coughing (seconds per hour) was a better predictor of microbiologicindicators of disease severity and treatment response than the frequency of coughepisodes or cough power. Patients with prior tuberculosis tended to cough more thanpatients without prior tuberculosis, and patients with tuberculosis and diabetescoughed more than patients without diabetes co-morbidity. Cough characteristics weresimilar regardless of HIV co-infection and for drug-susceptible versus drug-resistanttuberculosis.Tuberculosis treatment response may be meaningfully assessed by objectivelymonitoring the time spent coughing. This measure demonstrated that cough wasincreased in patients with TB recurrence or co-morbid diabetes, but not because ofdrug resistance or HIV co-infection.

Journal article

Rowneki M, Aronson N, Du P, Sachs P, Blakemore R, Chakravorty S, Levy S, Jones AL, Trivedi G, Chebore S, Addo D, Byarugaba DK, Njobvu PD, Wabwire-Mangen F, Erima B, Ramos ES, Evans CA, Hale B, Mancuso JD, Alland Det al., 2020, Detection of drug resistant Mycobacterium tuberculosis by high-throughput sequencing of DNA isolated from acid fast bacilli smears, PLoS One, Vol: 15, ISSN: 1932-6203

BACKGROUND: Drug susceptibility testing for Mycobacterium tuberculosis (MTB) is difficult to perform in resource-limited settings where Acid Fast Bacilli (AFB) smears are commonly used for disease diagnosis and monitoring. We developed a simple method for extraction of MTB DNA from AFB smears for sequencing-based detection of mutations associated with resistance to all first and several second-line anti-tuberculosis drugs. METHODS: We isolated MTB DNA by boiling smear content in a Chelex solution, followed by column purification. We sequenced PCR-amplified segments of the rpoB, katG, embB, gyrA, gyrB, rpsL, and rrs genes, the inhA, eis, and pncA promoters and the entire pncA gene. RESULTS: We tested our assay on 1,208 clinically obtained AFB smears from Ghana (n = 379), Kenya (n = 517), Uganda (n = 262), and Zambia (n = 50). Coverage depth varied by target and slide smear grade, ranging from 300X to 12000X on average. Coverage of ≥20X was obtained for all targets in 870 (72%) slides overall. Mono-resistance (5.9%), multi-drug resistance (1.8%), and poly-resistance (2.4%) mutation profiles were detected in 10% of slides overall, and in over 32% of retreatment and follow-up cases. CONCLUSION: This rapid AFB smear DNA-based method for determining drug resistance may be useful for the diagnosis and surveillance of drug-resistant tuberculosis.

Journal article

Datta S, Gilman RH, Montoya R, Quevedo Cruz L, Valencia T, Huff D, Saunders MJ, Evans CAet al., 2020, Quality of life, tuberculosis and treatment outcome; a case-control and nested cohort study, European Respiratory Journal, Vol: 56, Pages: 1-14, ISSN: 0903-1936

BACKGROUND: Global tuberculosis policy increasingly emphasises broad tuberculosis impacts and highlights the lack of evidence concerning tuberculosis-related quality of life (QOL). METHODS: Participants were recruited in 32 Peruvian communities 13/7/2016-24/2/2018 and followed-up until 8/11/2019. Inclusion criteria were: age ≥15 years for "patients" (n=1545) starting treatment for tuberculosis disease in health centres; "contacts" (n=3180) who shared a patient's household for ≥6 h·week-1; and randomly-selected "controls" (n=277). The EUROHIS-QOL questionnaire quantified satisfaction with: QOL; health; energy; activities of daily living (ADL); self; relationships; money; and living place. FINDINGS: Newly-diagnosed tuberculosis was most strongly associated with lower QOL scores (p<0.001). Patients initially had lower QOL than controls for all EUROHIS-QOL questions (p≤0.01), especially concerning health, ADL and self. Lower initial QOL in patients predicted adverse treatment outcomes and scores <13-points had 4.2-times (95%CI=2.3,7.6) increased risk of death versus those with higher QOL scores (both p<0.001). Patient QOL was re-assessed 6 months later and for patients with successful treatment, QOL became similar to participants who never had tuberculosis, whereas patients who did not complete treatment continued to have low QOL (p<0.001). Multidrug-resistant tuberculosis was associated with lower QOL before and during treatment (both p<0.001). Contacts had lower QOL if they lived with a patient who had low QOL score (p<0.0001) or were a caregiver for the patient (p<0.001). CONCLUSIONS: Tuberculosis was associated with impaired psycho-socio-economic QOL which recovered with successful treatment. Low QOL scores predicted adverse treatment outcome. This brief EUROHIS-QOL 8-item questionnaire quantified the holistic needs of tuberculosis-affected people, potentially guiding patient-centred care.

Journal article

Heitzinger K, Hawes SE, Rocha CA, Alvarez C, Evans CAet al., 2020, Assessment of the feasibility and acceptability of using water pasteurization indicators to increase access to safe drinking water in the Peruvian Amazon, American Journal of Tropical Medicine and Hygiene, Vol: CC BY, ISSN: 0002-9637

Approximately 2 billion people lack access to microbiologically safe drinking water globally. Boiling is the most popular household water treatment method and significantly reduces diarrheal disease, but is often practiced inconsistently or ineffectively. The use of low-cost technologies to improve boiling is one approach with potential for increasing access to safe drinking water. We conducted household trials to evaluate the feasibility and acceptability of water pasteurization indicators (WAPIs) in the Peruvian Amazon in 2015. A total of 28 randomly selected households were enrolled from a rural and a peri-urban community. All households trialed 2 WAPI designs, each for a 2-week period. Ninety-six percent of participants demonstrated the correct use of the WAPIs at the end of each trial, and 88% expressed satisfaction with both WAPI models. Ease of use, short treatment time, knowledge of the association between WAPI use and improved health, and the taste of treated water were among the key factors that influenced acceptability. Ease of use was the key factor that influenced design preference. Participants in both communities preferred a WAPI with a plastic box that floated on the water’s surface compared to a WAPI with a wire that was dipped into the pot of drinking water while it was heating (77% vs. 15%, p < 0.001); we selected the box design for a subsequent randomized trial of this intervention. The high feasibility and acceptability of the WAPIs in this study suggest that these interventions have potential to increase access to safe water in resource-limited settings.

Journal article

Martinez L, Cords O, Horsburgh CR, Andrews JRet al., 2020, The risk of tuberculosis in children after close exposure: a systematic review and individual-participant meta-analysis, LANCET, Vol: 395, Pages: 973-984, ISSN: 0140-6736

Journal article

Saunders MJ, Wingfield T, Datta S, Montoya R, Ramos E, Baldwin MR, Tovar MA, Evans BEW, Gilman RH, Evans CAet al., 2020, A household-level score to predict the risk of tuberculosis among contacts of patients with tuberculosis: derivation and external validation prospective cohort study, Lancet Infectious Diseases, Vol: 20, Pages: 110-122, ISSN: 1473-3099

BackgroundThe epidemiological impact and cost-effectiveness of social protection and biomedical interventions for tuberculosis-affected households might be improved by risk stratification. We therefore derived and externally validated a household-level risk score to predict tuberculosis among contacts of patients with tuberculosis.MethodsIn this prospective cohort study, we recruited tuberculosis-affected households from 15 desert shanty towns in Ventanilla and 17 urban communities in Callao, Lima, Peru. Tuberculosis-affected households included index patients with a new diagnosis of tuberculosis and their contacts who reported being in the same house as the index patient for more than 6 h per week in the 2 weeks preceding index patient diagnosis. Tuberculosis-affected households were not included if the index patient had no eligible contacts or lived alone. We followed contacts until 2018 and defined household tuberculosis, the primary outcome, as any contact having any form of tuberculosis within 3 years. We used logistic regression to identify characteristics of index patients, contacts, and households that were predictive of household tuberculosis, and used these to derive and externally validate a household-level score.FindingsBetween Dec 12, 2007, and Dec 31, 2015, 16 505 contacts from 3 301 households in Ventanilla were included in a derivation cohort. During the 3-year follow-up, tuberculosis occurred in contacts of index patients in 430 (13%, 95% CI 12–14) households. Index patient predictors were pulmonary tuberculosis and sputum smear grade, age, and the maximum number of hours any contact had spent with the index patient while they had any cough. Household predictors were drug use, schooling of the female head of a household, and lower food spending. Contact predictors were if any of the contacts were children, number of lower-weight (body-mass index [BMI] <20·0 kg/m2) adult contacts, number of normal-weight (BMI 20·0–24&midd

Journal article

Shibabaw A, Gelaw B, Kelley HV, Tesfaye E, Balada-Llasat JM, Evans CA, Torrelles JB, Wang S-H, Tessema Bet al., 2020, MDR/XDR-TB colour test for drug susceptibility testing of Mycobacterium tuberculosis, Northwest Ethiopia., International Journal of Infectious Diseases, Vol: 90, Pages: 213-218, ISSN: 1201-9712

BACKGROUND: Appropriate-technology tests are needed for Mycobacterium tuberculosis drug-susceptibility testing (DST) in resource-constrained settings. We evaluated the MDR/XDRTB colour plate thin-layer agar test (TB-CX) for M. tuberculosis DST by directly testing sputum at University of Gondar Hospital. METHODS: Sputum samples were each divided into 2 aliquots. One aliquot was mixed with disinfectant and applied directly to the TB-CX quadrant petri-plate containing culture medium with and without isoniazid, rifampicin or ciprofloxacin. Concurrently, the other aliquot was decontaminated with sodium hydroxide, centrifuged and cultured on Lowenstein-Jensen media, then the stored M. tuberculosis isolates were sub-cultured in BACTEC™ Mycobacteria Growth Indicator Tube™ (MGIT) 960 for reference DST. RESULTS: TB-CX text yielded DST results for 94% (123/131) of positive samples. For paired DST results, median days from sputum processing to DST was 12 for TB-CX versus 35 for LJ-MGIT (P < 0.001). Compared with LJ-MGIT for isoniazid, rifampicin and MDR-TB, TB-CX test had: 59%, 96% and 95% sensitivity; 96%, 94% and 98% specificity; and 85%, 94% and 98% agreement, respectively. All ciprofloxacin DST results were susceptible by both methods. CONCLUSION: The TB-CX was simple and rapid for M. tuberculosis DST. Discordant DST results may have resulted from sub-optimal storage and different isoniazid concentrations used in TB-CX versus the reference standard test.

Journal article

Datta S, Evans CA, 2019, Healthy survival after tuberculosis, LANCET INFECTIOUS DISEASES, Vol: 19, Pages: 1045-1047, ISSN: 1473-3099

Journal article

Mekonnen B, Mihret A, Getahun M, Hailu T, Sidiki S, V Kelley H, Scordo JM, Hunt WG, Pan X, Balada-Llasat J-M, Gebreyes W, Evans CA, Aseffa A, Torrelles JB, Wang S-H, Abebe Tet al., 2019, Evaluation of the tuberculosis culture color plate test for rapid detection of drug susceptible and drug-resistant Mycobacterium tuberculosis in a resource-limited setting, Addis Ababa, Ethiopia, PLoS ONE, Vol: 14, ISSN: 1932-6203

Timely diagnosis of tuberculosis (TB) is limited in Ethiopia. We evaluated the performance of a low technology, thin layer agar, Mycobacterium tuberculosis (M.tb) culture color plate (TB-CX) test with concurrent drug susceptibility testing (DST) to isoniazid (INH), rifampin (RIF), and pyrazinamide (PZA) directly from sputum specimens. Patients undergoing examination for TB and multidrug-resistant (MDR)-TB were enrolled in Addis Ababa, Ethiopia from March 2016 to February 2017. All subjects received a GeneXpert MTB/RIF PCR test. TB-CX test results were compared to reference Löwenstein-Jensen (LJ) culture for M.tb detection and DST for susceptibility to INH and RIF. Kappa statistic was applied to test agreement between results for TB-CX test and the reference methods, a cut-off Kappa value of 0.75 was considered as high level of agreements. A total of 137 participants were analyzed: 88 (64%) were new TB cases, 49 (36%) were re-treatment cases. The TB-CX test detected M.tb and DST in an average of 13 days compared to 50 days for the conventional DST result. The sensitivity and specificity of the TB-CX test for detecting M.tb were 94% and 98%, respectively (concordance, 96%; kappa 0.91). The sensitivity of the TB-CX test to detect drug resistance to INH, RIF, and MDR-TB was 91%, 100%, and 90% respectively. The specificity of the TB-CX test for detecting INH, RIF, and MDR-TB was 94%, 40%, and 94% respectively. Overall agreement between TB-CX test and LJ DST for detection of MDR-TB was 93%. The TB-CX test showed strong agreement with the GeneXpert test for detecting M.tb (89%, kappa 0.76) but low agreement for the detection of RIF resistance (57%, kappa 0.28). The TB-CX test was found to be a good alternative method for screening of TB and selective drug resistant-TB in a timely and cost-efficient manner.

Journal article

Saunders M, Tovar MA, Collier D, Baldwin MR, Montoya R, Valencia TR, Gilman RH, Evans Cet al., 2019, Active and passive case-finding in tuberculosis-affected households in Peru: a 10-year prospective cohort study, Lancet Infectious Diseases, Vol: 19, Pages: 519-528, ISSN: 1473-3099

Background. Active case finding (ACF) among contacts of patients with tuberculosis is a global health priority, but the effects of ACF compared to passive case finding (PCF) are poorly characterised. We assessed the contribution of ACF versus PCF to tuberculosis detection among contacts and compared sex and disease characteristics between contacts diagnosed through these strategies.Methods. In shantytowns in Callao, Peru, we identified index patients with tuberculosis and followed their contacts aged ≥15 years for tuberculosis for a median 10 years. All were offered free programmatic ACF involving sputum smear microscopy and clinical evaluation. Additionally, all contacts were offered intensified ACF with sputum smear and culture testing monthly for six months and then once every four years. PCF at local health facilities was ongoing throughout follow up.Findings. 8.7% (232/2,666) of contacts were diagnosed with tuberculosis: a two-year cumulative risk of 4.6% and overall incidence of 0.98/100 person-years. 23% (53/232) were diagnosed through ACF and 77% (179/232) through PCF. During the first six months, 45% (23/51) were diagnosed through ACF and 55% (28/51) through PCF. Contacts diagnosed through ACF versus PCF were more frequently female (68% [36/53] versus 47% [85/179], p=0.009); had a shorter symptom duration (25% [9/36] had symptoms for less than 15 days versus 8% [10/127], p=0.03); and were more likely to be sputum smear negative (62% [33/53] versus 35% [62/179], p<0.001).Interpretation. Although ACF made an important contribution to tuberculosis detection among contacts, PCF detected the majority of the tuberculosis burden. Compared to PCF, ACF was equitable, diagnosed tuberculosis earlier and usually before it became sputum smear positive, and revealed a high burden of undetected tuberculosis among women.

Journal article

Datta S, Alvarado K, Gilman RH, Valencia T, Aparicio C, Ramos ES, Montoya R, Evans CAet al., 2019, Optimising fluorescein diacetate sputum smear microscopy for assessing patients with pulmonary tuberculosis, PLoS One, Vol: 14, Pages: 1-24, ISSN: 1932-6203

BackgroundAssessing Mycobacterium tuberculosis (TB) viability by fluorescein diacetate (FDA) microscopy can predict TB culture results, treatment response and infectiousness. However, diverse methods have been published. We aimed to optimise FDA microscopy, minimising sputum processing, biohazard and complexity for use in resource-constrained settings.Methods and resultsOptimization: Patients with smear-positive pulmonary TB before treatment and healthy control participants provided sputa. These were divided into equal aliquots that were tested directly or after NaOH centrifuge-decontamination. Each aliquot was cultured and used to prepare slides (n = 80). FDA microscopy used: 1 or 3 drops of sputum; with/out acid-alcohol wash; with/out phenol sterilization; with 0/30/60 seconds KMnO4 quenching. Control samples all had negative culture and microscopy results. FDA microscopy had higher sensitivity when performed directly (without centrifuge-decontamination) on 1 drop of sputum (P<0.001), because 3 drops obscured microscopy. Acid-alcohol wash and KMnO4 quenching made bacilli easier to identity (P = 0.005). Phenol sterilization did not impair microscopy (P>0.1). Validation: The 2 protocols that performed best in the optimization experiments were reassessed operationally by comparing duplicate slides (n = 412) stained with KMnO4 quenching for 30 versus 60 seconds. FDA microscopy results were similar (P = 0.4) and highly reproducible, with 97% of counts agreeing within +/-1 logarithm. Storage: Smear microscopy slides and aliquots of the sputum from which they were made were stored for 4 weeks. Twice-weekly, paired slides (n = 80) were stained with freshly prepared versus stored FDA and read quantitatively. Storing sputum, microscopy slides or FDA solution at 4°C or room temperature had no effect on FDA microscopy results (all P>0.2). Cost: Material costs for each slide tested by FDA microscopy using reagents purchased locally were USD $0.05 and required the

Journal article

Saunders MJ, Evans CA, 2019, Ending tuberculosis through prevention, New England Journal of Medicine, Vol: 380, Pages: 1073-1074, ISSN: 0028-4793

Journal article

Shibabaw A, Gelaw B, Kelley H, Balada-Llasat JM, Evans C, Wang S-H, Torrelles JB, Tessema Bet al., 2019, Accuracy of the color plate micro-colony detection for the diagnosis of <i>Mycobacterium tuberculosis</i> complex in Northwest Ethiopia, TUBERCULOSIS, Vol: 114, Pages: 54-60, ISSN: 1472-9792

Journal article

Herdman T, Tovar M, Wingfield T, Montoya R, Valencia T, Zhang J, Datta S, Evans Cet al., 2018, Tuberculosis prevalence survey reveals the high proportion of asymptomatic disease, and points to high-burden households as a site for potential intervention in peri-urban slums of Callao, Peru, 18th International Congress on Infectious Diseases (ICID):, Publisher: Elsevier, Pages: 64-64, ISSN: 1201-9712

Conference paper

Zhang J, Herdman T, Saunders M, Montoya R, Ramos E, Tovar M, Datta S, Evans Cet al., 2018, Rising burden of visual and auditory disability in patients after tuberculosis therapy in Peruvian slums, 18th International Congress on Infectious Diseases (ICID):, Publisher: Elsevier, Pages: 348-349, ISSN: 1201-9712

Conference paper

Datta S, Gonzales-Huerta LE, Evans CA, 2018, The Potential for Testing Stool to Reduce Tuberculosis Missed Diagnoses and Misdiagnoses., American Journal of Tropical Medicine and Hygiene, Vol: 99, Pages: 243-245, ISSN: 0002-9637

Journal article

Saunders MJ, Wingfield T, Tovar MA, Herlihy N, Rocha C, Zevallos K, Montoya R, Datta S, Evans Cet al., 2018, Mobile phone interventions for tuberculosis should ensure access to mobile phones to enhance equity – a prospective, observational cohort study in Peruvian shantytowns, Tropical Medicine and International Health, Vol: 23, Pages: 850-859, ISSN: 1360-2276

Objectives:Mobile phone interventions have been advocated for tuberculosis care, but little is known about access of target populations to mobile phones. We studied mobile phone access among patients with tuberculosis, focusing on vulnerable patients and patients who later had adverse treatment outcomes.Methods:In a prospective cohort study in Callao, Peru, we recruited and interviewed 2584 patients with tuberculosis between 2007 and 2013 and followed them until 2016 for adverse treatment outcomes using national treatment registers. Subsequently, we recruited a further 622 patients between 2016 and 2017. Data were analysed using logistic regression and by calculating relative risks (RR).Results:Between 2007 and 2013, the proportion of the general population of Peru without mobile phone access averaged 7.8% but for patients with tuberculosis was 18% (P < 0.001). Patients without access were more likely to hold a lower socioeconomic position, suffer from food insecurity and be older than 50 years (all P < 0.01). Compared to patients with mobile phone access, patients without access at recruitment were more likely to subsequently have incomplete treatment (20% vs. 13%, RR = 1.5; P = 0.001) or an adverse treatment outcome (29% vs. 23% RR = 1.3; P = 0.006). Between 2016 and 2017, the proportion of patients without access dropped to 8.9% overall, but remained the same (18%) as in 2012 among the poorest third.Conclusion:Access to mobile phones among patients with tuberculosis is insufficient, and rarest in patients who are poorer and later have adverse treatment outcomes. Thus, mobile phone interventions to improve tuberculosis care may be least accessed by the priority populations for whom they are intended. Such interventions should ensure access to mobile phones to enhance equity.

Journal article

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