The experiences of frontline healthcare professionals are essential in identifying strategies to mitigate the disruption to healthcare services caused by the COVID-19 pandemic.
We conducted a ...cross-sectional study of TB and HIV professionals in low and middle-income countries (LMIC). Between May 12 and August 6, 2020, we collected qualitative and quantitative data using an online survey in 11 languages. We used descriptive statistics and thematic analysis to analyse responses.
669 respondents from 64 countries completed the survey. Over 40% stated that it was either impossible or much harder for TB and HIV patients to reach healthcare facilities since COVID-19. The most common barriers reported to affect patients were: fear of getting infected with SARS-CoV-2, transport disruptions and movement restrictions. 37% and 28% of responses about TB and HIV stated that healthcare provider access to facilities was also severely impacted. Strategies to address reduced transport needs and costs-including proactive coordination between the health and transport sector and cards that facilitate lower cost or easier travel-were presented in qualitative responses. Access to non-medical support for patients, such as food supplementation or counselling, was severely disrupted according to 36% and 31% of HIV and TB respondents respectively; qualitative data suggested that the need for such services was exacerbated.
Patients and healthcare providers across numerous LMIC faced substantial challenges in accessing healthcare facilities, and non-medical support for patients was particularly impacted. Synthesising recommendations of frontline professionals should be prioritised for informing policymakers and healthcare service delivery organisations.
Contact tracing complemented with genotyping is considered an important means of understanding person-to-person transmission of tuberculosis (TB). It still remains unclear whether Whole Genome ...Sequencing (WGS) of Mycobacterium tuberculosis can rule in transmission and how it performs in different human populations, risk groups and across TB lineages. This systematic review aimed to determine the sensitivity and specificity of WGS for detection of recent transmission using conventional epidemiology as the gold standard and investigate if WGS identifies previously undetected transmission events.
Systematic review was conducted according to the criteria of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses group. A compound search strategy was developed to identify all relevant studies published between 01/01/2005 and 30/11/2014 using three online databases. Publications satisfying specific criteria have been identified and data extracted.
A total of 12 publications were included. We established that WGS has a higher discriminatory power compared to conventional genotyping and detects transmission events missed by epidemiological investigations. A cut-off value of <6 SNPs between isolates may predict recent transmission. None of the studies performed a head-to-head comparison between WGS and conventional genotyping using unselected prospectively collected isolates. Minimum reporting criteria for WGS studies have been proposed and quality control parameters considered.
Even when tuberculosis (TB) care is free, impoverished patients and their households continue to incur unmanageable costs due to seeking and staying in care for the full duration of anti-TB treatment ...1. By aggravating household vulnerability, these costs can prevent or delay diagnosis, treatment and successful outcome, leading to increased TB transmission, morbidity and mortality 2–4. The new World Health Organization (WHO)'s End TB Strategy places greater emphasis on ensuring universal free access to care, and it includes a target of elimination of associated catastrophic costs for TB patients and their households by 2020 5.
To assess the magnitude of loss to follow-up in smear- or culture-positive tuberculosis patients before treatment initiation and outcomes among patients who were traced.
Ovid Medline and Global ...Health databases were searched for studies published between 1994 and January 2013 that described pre-treatment loss to follow-up in patients with smear- or culture-positive tuberculosis in routine national tuberculosis programmes (NTPs) in low- and lower-middle-income countries and in countries with a high burden of tuberculosis. Data on the proportion of patients who did not initiate treatment after their tuberculosis diagnosis were extracted from studies meeting inclusion criteria. Where available, data on causes and outcomes, including initiation of tuberculosis treatment at another facility, were investigated. Heterogeneity and publication bias were assessed and random-effects meta-analyses by subgroup (region) were performed.
Twenty-three eligible studies were identified, with a total of 34 706 smear- or culture-positive tuberculosis patients from 14 countries (8 in Africa, 5 in Asia and 1 in the western Pacific). Most studies were retrospective and linked laboratory and treatment registers to identify pre-treatment loss to follow-up. Pre-treatment loss to follow-up varied from 4 to 38% and was common in studies from Africa (random-effects weighted proportion, WP: 18%; 95% confidence interval, CI: 13-22) and Asia (WP: 13%; 95% CI: 10-15).
Pre-treatment loss to follow-up, common in most settings, can hinder tuberculosis control efforts. By not counting individuals who are lost to follow-up before treatment when reporting standard programme indicators, NTPs underestimate case detection rates and mortality and overestimate cure rates.
The World Health Organization has endorsed the Xpert MTB/RIF assay for investigation of patients suspected of having tuberculosis (TB). However, its utility for routine TB screening and detection of ...rifampicin resistance among HIV-infected patients with advanced immunodeficiency enrolling in antiretroviral therapy (ART) services is unknown.
Consecutive adult HIV-infected patients with no current TB diagnosis enrolling in an ART clinic in a South African township were recruited regardless of symptoms. They were clinically characterised and invited to provide two sputum samples at a single visit. The accuracy of the Xpert MTB/RIF assay for diagnosing TB and drug resistance was assessed in comparison with other tests, including fluorescence smear microscopy and automated liquid culture (gold standard) and drug susceptibility testing. Of 515 patients enrolled, 468 patients (median CD4 cell count, 171 cells/µl; interquartile range, 102-236) produced at least one sputum sample, yielding complete sets of results from 839 samples. Mycobacterium tuberculosis was cultured from 81 patients (TB prevalence, 17.3%). The overall sensitivity of the Xpert MTB/RIF assay for culture-positive TB was 73.3% (specificity, 99.2%) compared to 28.0% (specificity, 100%) using smear microscopy. All smear-positive, culture-positive disease was detected by Xpert MTB/RIF from a single sample (sensitivity, 100%), whereas the sensitivity for smear-negative, culture-positive TB was 43.4% from one sputum sample and 62.3% from two samples. Xpert correctly identified rifampicin resistance in all four cases of multidrug-resistant TB but incorrectly identified resistance in three other patients whose disease was confirmed to be drug sensitive by gene sequencing (specificity, 94.1%; positive predictive value, 57%).
In this population of individuals at high risk of TB, intensive screening using the Xpert MTB/RIF assay increased case detection by 45% compared with smear microscopy, strongly supporting replacement of microscopy for this indication. However, despite the ability of the assay to rapidly detect rifampicin-resistant disease, the specificity for drug-resistant TB was sub-optimal.
•Breakpoints that define susceptibility and resistance to anti-tuberculosis drugs are crucial for optimal treatment.•Breakpoints needs to be based on modern microbiological principles taking into ...account clinical outcome data.•Robust breakpoints still do not exist for bedaquiline and delamanid and are urgently needed.
Despite being fundamental to all treatment decisions, the breakpoints that define susceptibility and resistance to conventional anti-tuberculosis (TB) drugs were traditionally defined based on expert opinion as opposed to modern microbiological principles. As a result, the breakpoints for several key drugs (i.e. amikacin, levofloxacin, and moxifloxacin) were too high, resulting in the systematic misclassification of a proportion of resistant strains as susceptible. Moreover, a recent systematic review of clinical outcome data prompted the World Health Organization (WHO) to make significant changes to its treatment guidelines. For example, capreomycin and kanamycin are no longer recommended for TB treatment because their use correlates with worse clinical outcomes. This history notwithstanding, robust breakpoints still do not exist for bedaquiline and delamanid six years after their approval. This was compounded by the fact that access to both agents for drug-susceptibility testing had initially been restricted. It is incumbent upon the European Medicines Agency, the United States Food and Drug Administration, and WHO to ensure that drug developers generate the necessary data to set breakpoints as a prerequisite for the approval of new agents.
Comparing the landscape with 10 years ago when HIV-infected infants faced inevitable death, those born with HIV now have access to antiretroviral therapy (ART) so that increasing numbers of children ...are surviving to adolescence and beyond.2 Coupled with this progress, the number of new infections has substantially decreased (from 450 000 in 2005, to 260 000 in 2012) because of scale-up of interventions to prevent mother-to-child HIV transmission (PMTCT), resulting in a shift of burden of HIV towards older children.3 Additionally, large numbers of children with slowly progressing disease, infected before PMTCT interventions became widely available, are presenting for the first time in adolescence, having lived with untreated HIV for a decade or more.4 Aversion of the deaths of so many HIV-infected children over the past decade has been a substantial clinical, public health, and moral achievement.
Our hospital replaced the format for delivering portable antimicrobial prescribing guidance from a paper-based pocket guide to a smartphone application (app). We used this opportunity to assess the ...relationship between its use and the attitudes and behaviours of antimicrobial prescribers.
We used 2 structured cross-sectional questionnaires issued just prior to and 3 months following the launch of the smartphone app. Ordinal Likert scale responses to both frequencies of use and agreement statements permitted quantitative assessment of the relationship between variables.
The smartphone app was used more frequently than the pocket guide it replaced (p < 0.01), and its increased use was associated with sentiments that the app was useful, easy to navigate and its content relevant. Users who used the app more frequently were more likely to agree that the app encouraged them to challenge inappropriate prescribing by their colleagues (p = 0.001) and were more aware of the importance of antimicrobial stewardship (p = 0.005). Reduced use of the app was associated with agreement that senior physicians' preferences for antimicrobial prescribing would irrespectively overrule guideline recommendations (p = 0.0002).
Smartphone apps are an effective and acceptable format to deliver guidance on antimicrobial prescribing. Our findings suggest that they may empower users to challenge incorrect prescribing, breaking well-established behaviours, and thus supporting vital stewardship efforts in an era of increased antimicrobial resistance. Future work will need to focus on the direct impact on drug prescriptions as well as identifying barriers to implementing smartphone apps in other clinical settings.
Active case finding (ACF) may be valuable in tuberculosis (TB) control, but questions remain about its optimum implementation in different settings. For example, smear microscopy misses up to half of ...TB cases, yet is cheap and detects the most infectious TB cases. What, then, is the incremental value of using more sensitive and specific, yet more costly, tests such as Xpert MTB/RIF in ACF in a high-burden setting?
We constructed a dynamic transmission model of TB, calibrated to be consistent with an urban slum population in India. We applied this model to compare the potential cost and impact of 2 hypothetical approaches following initial symptom screening: (i) 'moderate accuracy' testing employing a microscopy-like test (i.e., lower cost but also lower accuracy) for bacteriological confirmation and (ii) 'high accuracy' testing employing an Xpert-like test (higher cost but also higher accuracy, while also detecting rifampicin resistance). Results suggest that ACF using a moderate-accuracy test could in fact cost more overall than using a high-accuracy test. Under an illustrative budget of US$20 million in a slum population of 2 million, high-accuracy testing would avert 1.14 (95% credible interval 0.75-1.99, with p = 0.28) cases relative to each case averted by moderate-accuracy testing. Test specificity is a key driver: High-accuracy testing would be significantly more impactful at the 5% significance level, as long as the high-accuracy test has specificity at least 3 percentage points greater than the moderate-accuracy test. Additional factors promoting the impact of high-accuracy testing are that (i) its ability to detect rifampicin resistance can lead to long-term cost savings in second-line treatment and (ii) its higher sensitivity contributes to the overall cases averted by ACF. Amongst the limitations of this study, our cost model has a narrow focus on the commodity costs of testing and treatment; our estimates should not be taken as indicative of the overall cost of ACF. There remains uncertainty about the true specificity of tests such as smear and Xpert-like tests in ACF, relating to the accuracy of the reference standard under such conditions.
Our results suggest that cheaper diagnostics do not necessarily translate to less costly ACF, as any savings from the test cost can be strongly outweighed by factors including false-positive TB treatment, reduced sensitivity, and foregone savings in second-line treatment. In resource-limited settings, it is therefore important to take all of these factors into account when designing cost-effective strategies for ACF.
Around 2 million adolescents and 3 million youth are estimated to be living with HIV worldwide. Antiretroviral outcomes for this group appear to be worse compared to adults. We report antiretroviral ...therapy outcomes from a rural setting in Zimbabwe among patients aged 10-30 years who were initiated on ART between 2005 and 2008. The cohort was stratified into four age groups: 10-15 (young adolescents) 15.1-19 years (adolescents), 19.1-24 years (young adults) and 24.1-29.9 years (older adults). Survival analysis was used to estimate rates of deaths and loss to follow-up stratified by age group. Endpoints were time from ART initiation to death or loss to follow-up. Follow-up of patients on continuous therapy was censored at date of transfer, or study end (31 December 2008). Sex-adjusted Cox proportional hazards models were used to estimate hazard ratios for different age groups. 898 patients were included in the analysis; median duration on ART was 468 days. The risk of death were highest in adults compared to young adolescents (aHR 2.25, 95%CI 1.17-4.35). Young adults and adolescents had a 2-3 times higher risk of loss to follow-up compared to young adolescents. When estimating the risk of attrition combining loss to follow-up and death, young adults had the highest risk (aHR 2.70, 95%CI 1.62-4.52). This study highlights the need for adapted adherence support and service delivery models for both adolescents and young adults.
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