FluoroType MTB system for the detection of pulmonary tuberculosis

Altres ajuts: The authors would like to acknowledge Hain Lifescience (Germany) for their provision of a FluoroCycler and sufficient FluoroType MTB assays to carry out the study. Hain Lifescience had no influence on the study design, data analysis or preparation of the manuscript. Funding information for this article has been deposited with the Crossref Funder RegistryDiagnosis continues to be a major barrier for the control of tuberculosis (TB), especially in low- and middle-income countries (LMIC) [1]. The number of platforms for the molecular diagnosis of TB have increased in recent years and they can provide test results more rapidly than culture. Molecular assays are increasingly being used as alternative or adjunct methods to culture and smear microscopy, and modern systems seek to partially or fully automate the DNA extraction and amplification steps, increasing their suitability for resource-limited laboratories. One of these platforms, the GeneXpert MTB/RIF (Cepheid, USA), has a sensitivity of roughly 85% compared to culture [2] and has seen significant uptake in developing countries [3]. However, as a fully closed system, the DNA extracted during the process cannot be used for further downstream drug susceptibility testing (DST), which is crucial for patients with suspected drug-resistant TB. FluoroType MTB is a sensitive test for TB but specificity is low compared with fully integrated molecular system

Применение молекулярно-генетических методов диагностики с целью улучшения результатов лечения МЛУ-ТБ в Архангельской области

The use of molecular genetic tests as a part of tuberculosis patients examination made it possible to reduce the time for TB diagnosis and determination of drug resistance (DR) of M. tuberculosis (MTB) in Arkhangelsk Region. Early detection of multiple drug resistant tuberculosis (MDR TB) made it possible to prescribe the adequate chemotherapy regimen promptly and thus to improve treatment outcomes.The objective of the study: to evaluate the results of treatment of MDR TB patients in whom MDR TB was diagnosed by molecular genetic tests. It was assumed that the introduction of molecular genetic tests would result in improved treatment outcomes in MDR TB patients [(the research project of the International Union Against Tuberculosis and Lung Diseases and Tuberculosis Control Program of Arkhangelsk Region of the PROVE-IT LPA (Policy Relevant Outcomes from Validating Evidence on Impact of Line Probe Assays)].Subjects: 295 MDR TB patients detected in Arkhangelsk Region were enrolled in the study. MDR TB was detected by molecular genetic tests in the main group (132 patients) and by culture in the control group (163 patients). Patients from both groups received the standard chemotherapy regimen. Chemotherapy outcomes were compared in both groups.Results. Treatment outcomes were better in the group (MGT group) where molecular genetic tests were used for drug susceptibility testing (p = 0.003) versus the comparison group where the culture was used. Effective treatment was documented more frequently (65.2%) in the MGT group versus the comparison group (44.8%). All-cause mortality was lower in the MGT group (7.6%) than in the comparison group (15.9%). There were no statistically significant differences between the groups in the time when sputum conversion (by smear and culture) was achieved.Использование молекулярно-генетических методов (МГМ) в алгоритме обследования пациентов с туберкулезом (ТБ) позволило сократить время диагностики ТБ и определения лекарственной устойчивости (ЛУ) M. tuberculosis (М БТ) в Архангельской области. Благодаря раннему выявлению случаев ТБ с множественной лекарственной устойчивостью (МЛУ-ТБ) МБТ появилась возможность своевременно назначать соответствующий режим химиотерапии, что может улучшить результаты лечения.Цель исследования: оценка результатов лечения пациентов с МЛУ-ТБ, которым ЛУ МБТ определена с помощью МГМ. Предполагали, что внедрение МГМ приведет к улучшению результатов лечения больных с МЛУ-ТБ [научный проект Международного союза борьбы с туберкулезом и болезнями легких и туберкулезной программы Архангельской области «The PROVE-IT LPA» (Policy Relevant Outcomes from Validating Evidence on Impact of Line Probe Assays - значимые результаты подтверждения данных о влиянии метода гибридизации линейными зондами)].Методы. В исследование включено 295 пациентов с МЛУ-ТБ, выявленных в Архангельской области. В основной группе (132 человека) МЛУ-ТБ выявлен с помощью МГМ, в контрольной группе (163 человека) - культуральными методами. Пациентам обеих групп назначен стандартный режим химиотерапии. Результаты химиотерапии сопоставлены в обеих группах.Результаты лечения были лучше в группе, где применялись МГМ (МГМ-группа) определения лекарственной чувствительности (p = 0,003), при сопоставлении с группой сравнения, в которой использовали культуральный метод. Эффективный курс химиотерапии регистрировался чаще (65,2%) в МГМ-группе при сопоставлении с группой сравнения (44,8%). Смертность от всех причин была ниже в МГМ-группе (7,6%) при сопоставлении с группой сравнения (15,9%). Статистически значимых различий времени конверсии мокроты (бактериоскопия и посев) между группами не было

The presentation, diagnosis and management of non-traumatic wrist pain: an evaluation of current practice in secondary care in the UK NHS

AbstractObjectivesThe study aims were to assess the burden of non-traumatic wrist pain in terms of numbers of referrals to secondary care, and to characterise how patients present, are diagnosed and are managed in secondary care in the United Kingdom National Health Service.MethodsTen consecutive patients presenting with non-traumatic wrist pain were identified retrospectively at each of 16 participating hospitals and data was extracted for twelve months following the initial referral.ResultsThe 160 patients consisted of 100 females and 60 males with a median age of 49, accounting for approximately 13% of all new hand/wrist referrals. The dominant wrist was affected in 60% of cases and the mean symptom duration was 13.3 months. Diagnoses were grouped into: osteoarthritis (OA) (31%), tendinopathy (13%), ganglion (14%), ulnar sided pain (17%) and other (25%). The OA group was significantly older than other groups, while other groups contained a predominance of females.The non-surgical interventions in decreasing frequency of usage were: steroid injections (39%), physiotherapy (32%), splint (31%) and analgesics (12%). Of those who underwent surgery, all patients had previously received non-surgical treatment, however 42% had undergone only one non-surgical intervention.ConclusionNon-traumatic wrist pain represents a significant burden to secondary care both in terms of new patient referrals and in terms of investigation, follow up and treatment. Those presenting with osteoarthritis are more likely to be older and male, while those presenting with other diagnoses are more likely to be younger and female

ВЛИЯНИЕ ВНЕДРЕНИЯ МОЛЕКУЛЯРНО-ГЕНЕТИЧЕСКИХ МЕТОДОВ НА СРОКИ НАЧАЛА ХИМИОТЕРАПИИ БОЛЬНЫХТУБЕРКУЛЕЗОМ С МЛУ МБТ В АРХАНГЕЛЬСКОЙ ОБЛАСТИ

In the Arkhangelsk Region, the prevalence of multiple drug-resistant tuberculosis is one of the highest in the world. In 2016, the portion of multiple drug resistant tuberculosis made 33.1% among new cases and 59.5% among relapses. Using new molecular genetic diagnostic techniques allows reducing the time for diagnostics of tuberculosis and drug resistance and should result in the earlier start of adequate treatment.The goal of the study is to assess the impact of new diagnostic molecular genetic methods on the time period from the first referral for medical care till the start of MDR-TB treatment. It was assumed that the introduction of molecular genetic tests would lead to early initiation of treatment in MDR TB patients (the research project of the International Union Against Tuberculosis and Lung Diseases and Tuberculosis Control Program of Arkhangelsk Region on The PROVE-IT LPA; Policy Relevant Outcomes from Validating Evidence on Impact of Line Probe Assays).Subjects and Methods. The results of the diagnostic procedure using cultures were compared with the results of the procedure based on molecular genetic tests aimed to detect MDR-TB. 295 MDR TB patients were enrolled into the study, of them, 163 had culture and 132 had molecular genetic tests.Results. The use of molecular genetic tests in smear-positive patients (AFB+) resulted in the reduction of the time period before initiation of MDRTB treatment by 50 and 66 days (median) versus culture by BacTAlert and absolute concentration on Lowenstein-Jensen medium respectively (p <0.001).Patients with a negative smear (AFB-), in whom MDR TB was detected by molecular genetic methods started treatment by 78 days earlier (median) versus patients who had culture (Lowenstein-Jensen, p < 0.001). Despite the significant reduction in the time period, even using molecular genetic methods, it took 24 days for cases with AFB+ and 62 days for cases with AFB- to be notified and start treatment of MDR TB.Распространенность туберкулеза (ТБ) с множественной лекарственной устойчивостью возбудителя (МЛУ) в Архангельской области – одна из самых высоких в мире. В 2016 г. доля МЛУ-ТБ составила 33,1% среди новых случаев и 59,5% среди рецидивов ТБ. Использование новых молекулярно-генетических диагностических методов (МГМ) позволяет сократить время диагностики ТБ и лекарственной устойчивости возбудителя заболевания и должно привести к раннему началу адекватного лечения.Цель исследования: оценка влияния новых МГМ диагностики на изменение времени от первого обращения за медицинской помощью до начала лечения МЛУ-ТБ. Предполагали, что внедрение МГМ приведет к раннему началу лечения больных с МЛУ-ТБ (научный проект Международного союза борьбы с туберкулезом и болезнями легких и туберкулезной программы Архангельской области «The PROVE-IT LPA; Policy Relevant Outcomes from Validating Evidence on Impact of Line Probe Assays – значимые результаты подтверждения данных о влиянии метода гибридизации линейными зондами)».Материалы и методы. Результаты использования диагностического алгоритма с применением культуральных методов были сопоставлены с результатами алгоритма, основанного на МГМ выявления МЛУ-ТБ. В исследование включено 295 больных с МЛУ-ТБ, из которых у 163 мокрота исследована культуральными методами, а у 132 – с помощью МГМ.Результаты. В группе больных с положительным результатом микроскопии мокроты (КУМ+) применение МГМ привело к сокращению срока до начала лечения МЛУ-ТБ на 50 и 66 дней (медиана) по сравнению с культуральными методами BacTAlert и методом абсолютных концентраций на среде Левенштейна – Йенсена (ЛЙ) соответственно (p < 0,001).Больные с отрицательным результатом микроскопии мокроты (КУМ-), у которых МЛУ-ТБ был выявлен с помощью МГМ, начинали лечение на 78 дней раньше (медиана) по сравнению с больными, у которых применялись культуральные методы (ЛЙ, p < 0,001). Несмотря на значительное сокращение сроков, даже с использованием МГМ потребовалось 24 дня для случаев КУМ+ и 62 дня для случаев с КУМ- для регистрации и начала лечения МЛУ-ТБ

Re-reading of OraQuick HIV-1/2 rapid antibody test results: quality assurance implications for HIV self-testing programmes.

INTRODUCTION: Scale-up of HIV self-testing (HIVST) will play a key role in meeting the United Nation's 90-90-90 targets. Delayed re-reading of used HIVST devices has been used by early implementation studies to validate the performance of self-test kits and to estimate HIV positivity among self-testers. We investigated the stability of results on used devices under controlled conditions to assess its potential as a quality assurance approach for HIVST scale-up. METHODS: 444 OraQuick® HIV-1/2 rapid antibody tests were conducted using commercial plasma from two HIV-positive donors and HIV-negative plasma (high-reactive n = 148, weak-reactive n = 148 and non-reactive n = 148) and incubated them for six months under four conditions (combinations of high and low temperatures and humidity). Devices were re-read daily for one week, weekly for one subsequent month and then once a month by independent readers unaware of the previous results. We used multistage transition models to investigate rates of change in device results, and between storage conditions. RESULTS AND DISCUSSION: There was a high incidence of device instability. Forty-three (29%) of 148 initially non-reactive results became false weak-reactive results. These changes were observed across all incubation conditions, the earliest on Day 4 (n = 9 kits). No initially HIV-reactive results changed to a non-reactive result. There were no significant associations between storage conditions and hazard of results transition. We observed substantial statistical agreement between independent re-readers over time (agreement range: 0.74 to 0.96). CONCLUSIONS: Delayed re-reading of used OraQuick® HIV-1/2 rapid antibody tests is not currently a valid methodological approach to quality assurance and monitoring as we observed a high incidence (29%) of true non-reactive tests changing to false weak-reactive and therefore its use may overestimate true HIV positivity

"Arming half-baked people with weapons!" Information enclaving among professionals and the need for a care-centred model for antibiotic use information in Uganda, Tanzania and Malawi

Background The overuse of antimicrobial medicines is a global health concern, including as a major driver of antimicrobial resistance. In many low- and middle-income countries, a substantial proportion of antibiotics are purchased over-the-counter without a prescription. But while antibiotics are widely available, information on when and how to use them is not. Objective We aimed to understand the acceptability among experts and professionals of sharing information on antibiotic use with end users – patients, carers and farmers – in Uganda, Tanzania and Malawi. Methods Building on extended periods of fieldwork amongst end-users and antibiotic providers in the three countries, we conducted two workshops in each, with a total of 44 medical and veterinary professionals, policy makers and drug regulators, in December 2021. We carried out extensive documentary and literature reviews to characterise antibiotic information systems in each setting. Results Participants reported that the general public had been provided information on medicine use in all three countries by national drug authorities, health care providers and in package inserts. Participants expressed concern over the danger of sharing detailed information on antibiotic use, particularly that end-users are not equipped to determine appropriate use of medicines. Sharing of general instructions to encourage professionally-prescribed practices was preferred. Conclusions Without good access to prescribers, the tension between enclaving and sharing of knowledge presents an equity issue. Transitioning to a client care-centred model that begins with the needs of the patient, carer or farmer will require sharing unbiased antibiotic information at the point of care