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
to

163 results found

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

<ns3:p><ns3:bold>Background:</ns3: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.</ns3:p><ns3:p> <ns3:bold>Methods: </ns3: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).</ns3:p><ns3:p> <ns3:bold>Conclusion:</ns3:bold> This systematic review and meta-analysis aims to rigorously assess the evidence for strategies to quantify or eliminate catastrophic costs due to TB.</ns3:p>

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, ISSN: 1027-3719

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 Mycobacterium tuberculosis 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

Metcalf T, Soria J, Montano SM, Ticona E, Evans CA, Huaroto L, Kasper M, Ramos ES, Mori N, Jittamala P, Chotivanich K, Chavez IF, Singhasivanon P, Pukrittayakamee S, Zunt JRet al., 2018, Evaluation of the GeneXpert MTB/RIF in patients with presumptive tuberculous meningitis, PLoS One, Vol: 13, Pages: 1-15, ISSN: 1932-6203

BackgroundMeningitis caused by Mycobacterium tuberculosis is a major cause of morbidity and mortality worldwide. We evaluated the performance of cerebrospinal fluid (CSF) testing with the GeneXpert MTB/RIF assay versus traditional approaches for diagnosing tuberculosis meningitis (TBM).MethodsPatients were adults (n = 37) presenting with suspected TBM to the Hospital Nacional Dos de Mayo, Lima, Peru, during 12 months until 1st January 2015. Each participant had a single CSF specimen that was divided into aliquots that were concurrently tested for M. tuberculosis using GeneXpert, Ziehl-Neelsen smear and culture on solid and liquid media. Drug susceptibility testing used Mycobacteria Growth Indicator Tube (MGIT 960) and the proportions method.Results81% (30/37) of patients received a final clinical diagnosis of TBM, of whom 63% (19/30, 95% confidence intervals, CI: 44–80%) were HIV-positive. 22% (8/37, 95%CI: 9.8–38%), of patients had definite TBM. Because definite TBM was defined by positivity in any laboratory test, all laboratory tests had 100% specificity. Considering the 30 patients who had a clinical diagnosis of TBM: diagnostic sensitivity was 23% (7/30, 95%CI: 9.9–42%) for GeneXpert and was the same for all culture results combined; considerably greater than 7% (2/30, 95%CI: 0.82–22%) for microscopy; whereas all laboratory tests had poor negative predictive values (20–23%). Considering only the 8 patients with definite TBM: diagnostic sensitivity was 88% (7/8, 95%CI: 47–100%) for GeneXpert; 75% (6/8, 95%CI: 35–97%) for MGIT culture or LJ culture; 50% (4/8, 95%CI 16–84) for Ogawa culture and 25% (2/8, 95%CI: 3.2–65%) for microscopy. GeneXpert and microscopy provided same-day results, whereas culture took 20–56 days. GeneXpert provided same-day rifampicin-susceptibility results, whereas culture-based testing took 32–71 days. 38% (3/8, 95%CI: 8.5–76%) of patients with definite TBM with data h

Journal article

Andre E, Rusumba O, Evans CA, Ngongo P, Sanduku P, Elvis MM, Celestin HN, Alain IR, Musafiri EM, Kabuayi J-P, de Waroux OLP, Ait-Khaled N, Delmee M, Zech Fet al., 2018, Patient-led active tuberculosis case-finding in the Democratic Republic of the Congo, Bulletin of the World Health Organization, Vol: 96, Pages: 522-530, ISSN: 0042-9686

Objective To investigate the effect of using volunteer screeners in active tuberculosis case-finding in South Kivu, the Democratic Republicof the Congo, especially among groups at high risk of tuberculosis infection.Methods To identify and screen high-risk groups in remote communities, we trained volunteer screeners, mainly those who had themselvesreceived treatment for tuberculosis or had a family history of the disease. A non-profit organization was created and screeners receivedtraining on the disease and its transmission at 3-day workshops. Screeners recorded the number of people screened, reporting a prolongedcough and who attended a clinic for testing, as well as test results. Data were evaluated every quarter during the 3-year period of theintervention (2014–2016).Findings Acceptability of the intervention was high. Volunteers screened 650434 individuals in their communities, 73418 of whom reporteda prolonged cough; 50 368 subsequently attended a clinic for tuberculosis testing. Tuberculosis was diagnosed in 1 in 151 people screened,costing 0.29 United States dollars (US$) per person screened and US$ 44 per person diagnosed. Although members of high-risk groups withpoorer access to health care represented only 5.1% (33 002/650 434) of those screened, they contributed 19.7% (845/4300) of tuberculosisdiagnoses (1 diagnosis per 39 screened). The intervention resulted in an additional 4300 sputum-smear-positive pulmonary tuberculosisdiagnoses, 42% (4 300/10 247) of the provincial total for that period.Conclusion Patient-led active tuberculosis case-finding represents a valuable complement to traditional case-finding, and should be usedto assist health systems in the elimination of tuberculosis.

Journal article

Zhang A, Jumbe E, Krysiak R, Sidiki S, Kelley H, Chemey EK, Kamba C, Mwapasa V, Garcia J, Norris A, Pan XJ, Evans C, Wang S-H, Kwiek JJ, Torrelles JBet al., 2018, Low-cost diagnostic test for susceptible and drug-resistant tuberculosis in rural Malawi, African Journal of Laboratory Medicine, Vol: 7, ISSN: 2225-2002

Background: Rural settings where molecular tuberculosis diagnostics are not currently available need easy-to-use tests that do not require additional processing or equipment. While acid-fast bacilli (AFB) smear is the most common and often only tuberculosis diagnosis test performed in rural settings, it is labour intensive, has less-than-ideal sensitivity, and cannot assess tuberculosis drug susceptibility patterns.Objective: The objective of this study was to determine the feasibility of a multidrug-resistant (MDR) or extensively drug-resistant (XDR)-tuberculosis coloured agar-based culture test (tuberculosis CX-test), which can detect Mycobacterium tuberculosis growth and evaluate for drug susceptibility to isoniazid, rifampicin and a fluoroquinolone (i.e. ciprofloxacin) in approximately 14 days.Method: In this study, 101 participants were enrolled who presented to a rural health clinic in central Malawi. They were suspected of having active pulmonary tuberculosis. Participants provided demographic and clinical data and submitted sputum samples for tuberculosis testing using the AFB smear and tuberculosis CX-test.Results: The results showed a high level of concordance between the AFB smear (12 positive) and tuberculosis CX-test (13 positive); only one sample presented discordant results, with the molecular GeneXpert MTB/RIF® test confirming the tuberculosis CX-test results. The average time to a positive tuberculosis CX-test was 10 days. Of the positive samples, the tuberculosis CX-test detected no cases of drug resistance, which was later confirmed by the GeneXpert MTB/RIF®.Conclusion: These findings demonstrate that the tuberculosis CX-test could be a reliable low-cost diagnostic method for active pulmonary tuberculosis in high tuberculosis burden rural areas.

Journal article

Bonadonna L, Saunders M, Guio H, Zegarra R, Evans Cet al., 2018, Socioeconomic and behavioral factors associated with tuberculosis diagnostic delay in Lima, Peru, American Journal of Tropical Medicine and Hygiene, Vol: 98, Pages: 1614-1623, ISSN: 0002-9637

Early detection and diagnosis of tuberculosis (TB) is a global priority. Prolonged symptom duration prior to TB diagnosis is associated with increased morbidity, mortality and risk of transmission. We aimed to determine socioeconomic and behavioral factors associated with diagnostic delays among patients with TB. Data were collected from 105 patients with TB using a semi-structured interview guide in Lima, Peru. Factors associated with diagnostic delay were analyzed using negative binomial regression. The median delay from when symptoms commenced and the first positive diagnostic sample in public health facilities was 57 days (interquartile range (IQR): 28-126). In multivariable analysis, greater diagnostic delay was independently associated with patient older age; female sex; lower personal income prior to diagnosis; living with fewer people; and having more visits to professional health facilities prior to diagnosis (all p<0.05). Patients who first sought care at a private health facility had more visits overall to professional health facilities prior to diagnosis than those who first sought care from public or insured employee health facilities and had longer diagnostic delay in analysis adjusted for age and sex. Patients with TB were significantly more likely to first self-medicate than to visit professional health facilities prior to diagnosis (p=0.003). Thus, diagnostic delay was prolonged, greatest among older, low-income women and varied according to the type of care sought by individuals when their symptoms commenced. These findings suggest that TB case finding initiatives should target vulnerable groups in informal and private health facilities, where many patients with TB first seek healthcare.

Journal article

Friedland JS, Proano A, Bui D, Lopez J, Vu N, Bravard M, Lee G, Tracey B, Ziyue X, Comina G, Ticona E, Mollura D, Moore D, Evans C, Caligiuri P, Gilman Ret al., 2018, Cough frequency during treatment associated with baseline cavitary volume and proximity to the airway in pulmonary tuberculosis, Chest, Vol: 153, Pages: 1358-1367, ISSN: 0012-3692

Background: Cough frequency, and its duration, is a lab-free biomarker that can be used in low-resource settings and has been associated with transmission and treatment response.Radiological characteristics associated with increased cough frequency may be important in understanding transmission. The relationship between cough frequency and cavitary lung disease has never been studied. Methods: We analyzed 41 human immunodeficiency virus-negative adults with culture- confirmed, drug-susceptible pulmonary tuberculosis throughout treatment. Cough recordings were based on the Cayetano Cough Monitor and sputum samples were evaluated using microscopic-observation drug susceptibility broth culture, among culture-positive samples bacillary burden was assessed by time to positivity. Computerized tomography scans were analyzed by a U.S. board-certified radiologist and an automated-computer algorithm. The algorithm evaluates cavity volume and cavitary proximity to the airway. Computerized tomography scans were taken within one month of treatment initiation. We compared small cavities (≤7-mL) versus large cavities (>7-mL) and cavities located closer to (≤10-mm) and farther (>10-mm) from the airway to cough frequency and cough cessation until treatment day 62.Results: Cough frequency during treatment was two-fold higher in participants with large cavity volumes (Rate Ratio [RR]=1.98, p=0.01) and cavities located closer to the airway (RR=2.44, p=0.001). Comparably, cough ceased three times faster in smaller cavities (adjusted hazard ratio [HR]=2.89, p=0.06) and those farther from the airway (adjusted HR=3.61, p=0.02). Similar results are found for bacillary burden and culture conversion during treatment. Conclusions: Cough frequency during treatment is greater and lasts for longer in patients with larger cavities, especially those closer to the airway

Journal article

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