Pooling sputum for Xpert MTB/RIF and Xpert Ultra testing during the Covid-19 pandemic in Lao People's Democratic Republic

The global Covid-19 pandemic has limited access to molecular TB diagnostics and National Programmes are struggling to maintain essential services. The pooling method (testing several samples together) could reduce the number of cartridges and staff time needed for TB diagnosis but has not been tested within the pandemic. We conducted two independent cross-sectional surveys. Pools composed of four sputum samples were tested using either Xpert-MTB/RIF or Xpert-Ultra. Pooled and individual results were compared to determine the level of agreement. Each survey included 840 participants and 210 pools. In the Xpert MTB/RIF survey, 77/81 (sensitivity 95.1%, 95%CI 87.8%-98.6%) pools containing ≥1 positive sample tested MTB-positive and 4/81 (4.9%, 95%CI 1.4%-12.2%) tested MTB-negative. All 129/129 pools containing MTB-negative samples tested MTB-negative (specificity 100%, 95%CI 97.2%-100%), with 98.1% agreement (Kappa: 0.959). In the Xpert-Ultra survey, 70/70 (sensitivity 100%, 95%CI 94.9%-100%) pools containing ≥ 1 MTB-positive sample tested MTB-positive and 140/140 (specificity 100%, 95%CI 97.4%-100%) pools containing only MTB-negative samples tested MTB-negative, with 100% agreement (Kappa: 1). Pooled testing with Xpert-MTB/RIF and Xpert-Ultra saved 38.3% and 41.7% (322/840 and 350/840, respectively) in cartridge costs alone. The pooling method with Xpert-MTB/RIF and Xpert-Ultra has similar performance to individual testing and can reduce the number of cartridges needed. These efficiencies can facilitate maintenance of stocks and sustain essential services as countries face difficulties for laboratory procurement during the pandemic and will provide cost and time savings post-pandemic.

Pooling samples to increase testing capacity with Xpert Xpress SARS-CoV-2 during the Covid-19 pandemic in Lao People's Democratic Republic.

The COVID-19 pandemic created the need for large-scale testing of populations. However, most laboratories do not have sufficient testing capacity for mass screening. We evaluated pooled testing of samples, as a strategy to increase testing capacity in Lao PDR. Samples of consecutive patients were tested in pools of four using the Xpert Xpress SARS CoV-2 assay. Positive pools were confirmed by individual testing, and we describe the performance of the test and savings achieved. We also diluted selected positive samples to describe its effect on the assays CT values. 1,568 patients were tested in 392 pools of four. 361 (92.1%) pools were negative and 31 (7.9%) positive. 29/31 (93.5% (95%CI 77-99%) positive pools were confirmed by individual testing of the samples but, in 2/31 (6.5%) the four individual samples were negative, suggesting contamination. Pools with only one positive sample had higher CT values (lower RNA concentrations) than the respective individual samples, indicating a dilution effect, which suggested an increased risk of false negative results with dilutions >1:10. However, this risk may be low if the prevalence of infection is high, when pools are more likely to contain more than one positive sample. Pooling saved 67% of cartridges and substantially increased testing capacity. Pooling samples increased SARS-CoV-2 testing capacity and resulted in considerable cartridge savings. Given the need for high-volume testing, countries may consider implementation of pooling for SARS-CoV-2 screening.

Pooling sputum for Xpert MTB/RIF and Xpert Ultra testing during the Covid-19 pandemic in Lao People's Democratic Republic.

The global Covid-19 pandemic has limited access to molecular TB diagnostics and National Programmes are struggling to maintain essential services. The pooling method (testing several samples together) could reduce the number of cartridges and staff time needed for TB diagnosis but has not been tested within the pandemic. We conducted two independent cross-sectional surveys. Pools composed of four sputum samples were tested using either Xpert-MTB/RIF or Xpert-Ultra. Pooled and individual results were compared to determine the level of agreement. Each survey included 840 participants and 210 pools. In the Xpert MTB/RIF survey, 77/81 (sensitivity 95.1%, 95%CI 87.8%-98.6%) pools containing ≥1 positive sample tested MTB-positive and 4/81 (4.9%, 95%CI 1.4%-12.2%) tested MTB-negative. All 129/129 pools containing MTB-negative samples tested MTB-negative (specificity 100%, 95%CI 97.2%-100%), with 98.1% agreement (Kappa: 0.959). In the Xpert-Ultra survey, 70/70 (sensitivity 100%, 95%CI 94.9%-100%) pools containing ≥ 1 MTB-positive sample tested MTB-positive and 140/140 (specificity 100%, 95%CI 97.4%-100%) pools containing only MTB-negative samples tested MTB-negative, with 100% agreement (Kappa: 1). Pooled testing with Xpert-MTB/RIF and Xpert-Ultra saved 38.3% and 41.7% (322/840 and 350/840, respectively) in cartridge costs alone. The pooling method with Xpert-MTB/RIF and Xpert-Ultra has similar performance to individual testing and can reduce the number of cartridges needed. These efficiencies can facilitate maintenance of stocks and sustain essential services as countries face difficulties for laboratory procurement during the pandemic and will provide cost and time savings post-pandemic.

Social and health factors associated with adverse treatment outcomes among people with multidrug-resistant tuberculosis in Sierra Leone: a national, retrospective cohort study.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is a global health emergency. We aimed to evaluate treatment outcomes among people with MDR-TB in Sierra Leone and investigate social and health factors associated with adverse treatment outcomes. METHODS: This national, retrospective cohort study recruited all people notified with MDR-TB to the Sierra Leone National TB Programme, admitted to Lakka hospital (Lakka, Western Area Rural District, Freetown, Sierra Leone) between April, 2017, and September, 2019. Participants were followed up to May, 2021. People who were eligible but had no social or health data available, or were subsequently found to have been misdiagnosed, were excluded from participation. MDR-TB treatment was with the 2017 WHO-recommended short (9-11 month) or long (18-24 month) aminoglycoside-containing regimens. Multivariable logistic regression models examined associations of programmatic social and health data with WHO-defined adverse treatment outcomes (death, treatment failure, loss to follow-up). FINDINGS: Of 370 notified MDR-TB cases, 365 (99%) were eligible for study participation (five participants were excluded due to lack of social or health data or misdiagnosis). Treatment was started by 341 (93%) of 365 participants (317 received the short regimen, 24 received the long regimen, and 24 received no treatment). Median age was 35 years (IQR 26-45), 263 (72%) of 365 were male and 102 (28%) were female, 71 (19%) were HIV-positive, and 127 (35%) were severely underweight (body-mass index <16·5 kg/m2). Overall, 267 (73%) of 365 participants had treatment success, 95 (26%) had an adverse outcome, and three (1%) were still on treatment in May, 2021. Age 45-64 years (adjusted odds ratio [aOR] 2·4, 95% CI 1·2-5·0), severe underweight (aOR 4·2, 1·9-9·3), untreated HIV (aOR 10, 2·6-40·0), chronic lung disease (aOR 2·0, 1·0-4·2), previously unsuccessful drug-sensitive tuberculosis retreatment (aOR 4·3, 1·0-19), and a long regimen (aOR 6·5, 2·3-18·0) were associated with adverse outcomes. A sensitivity analysis showed that prothionamide resistance (aOR 3·1, 95% CI 1·5-10·0) and aminoglycoside-related complete deafness (aOR 6·6, 1·3-35) were independently associated with adverse outcomes. INTERPRETATION: MDR-TB treatment success in Sierra Leone approached WHO targets and the short regimen was associated with higher success. The social and health factors associated with adverse outcomes in this study suggest a role for integrated tuberculosis, HIV, and non-communicable disease services alongside nutritional and socioeconomic support for people with MDR-TB and emphasise the urgent need to scale up coverage of all-oral aminoglycoside-sparing regimens. FUNDING: Wellcome Trust, Joint Global Health Trials.

Pooled testing of sputum with Xpert MTB/RIF and Xpert Ultra during tuberculosis active case finding campaigns in Lao People's Democratic Republic.

INTRODUCTION: Active case finding (ACF) of individuals with tuberculosis (TB) is a key intervention to find the 30% of people missed every year. However, ACF requires screening large numbers of individuals who have a low probability of positive results, typically <5%, which makes using the recommended molecular tests expensive. METHODS: We conducted two ACF surveys (in 2020 and 2021) in high TB burden areas of Lao PDR. Participants were screened for TB symptoms and received a chest X-ray. Sputum samples of four consecutive individuals were pooled and tested with Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF) (Xpert-MTB/RIF) (2020) or Xpert-Ultra (2021). The agreement of the individual and pooled samples was compared and the reasons for discrepant results and potential cartridge savings were assessed. RESULTS: Each survey included 436 participants, which were tested in 109 pools. In the Xpert-MTB/RIF survey, 25 (sensitivity 89%, 95% CI 72.8% to 96.3%) of 28 pools containing MTB-positive samples tested positive and 81 pools containing only MTB-negative samples tested negative (specificity 100%, 95% CI 95.5% to 100%). In the Xpert-Ultra survey, all 32 (sensitivity 100%, 95% CI 89.3% to 100%) pools containing MTB-positive samples tested positive and all 77 (specificity 100%, 95% CI 95.3% to 100%) containing only MTB-negative samples tested negative. Pooling with Xpert-MTB/RIF and Xpert-Ultra saved 52% and 46% (227/436 and 199/436, respectively) of cartridge costs alone. CONCLUSION: Testing single and pooled specimens had a high level of agreement, with complete concordance when using Xpert-Ultra. Pooling samples could generate significant cartridge savings during ACF campaigns.

A patient satisfaction survey and educational package to improve the care of people hospitalised with COVID-19: a quality improvement project, Liverpool, UK.

Background: The perspectives and experiences of people hospitalised with COVID-19 have been under-reported during the coronavirus pandemic. We developed and conducted a COVID-19 patient satisfaction survey in a large university-affiliated secondary healthcare centre in Liverpool, UK, during Europe's first coronavirus wave (April-June 2020). The survey found that care was rated highly, including among people of Black Asian and Minority Ethnic (BAME) backgrounds. However, sleep-quality and communication about medications and discharge-planning were identified as areas for improvement.   Methods: To improve care for people with COVID-19 admitted to our centre, we designed an educational package for healthcare professionals working on COVID-19 wards. The package, implemented in August 2020, included healthcare worker training sessions on providing holistic care and placement of "Practice Pointers" posters. Patient satisfaction was re-evaluated during the second/third COVID-19 waves in Liverpool (September 2020 - February 2021). Results: Across waves, most (95%) respondents reported that they would recommend our hospital to friends and/or family and rated overall care highly. Comparison of the responses of second/third-wave respondents (n=101) with first-wave respondents (n=94) suggested improved patient satisfaction across most care domains but especially those related to having worries and fears addressed and being consulted about medications and their side-effects. Conclusions: People admitted with COVID-19 to our centre in Liverpool, including those from BAME backgrounds, rated the care they received highly. A simple education package improved the feedback on care received by respondents between the first and second/third waves. These UK-first findings are informing regional strategies to improve person-centred care of hospitalised people with COVID-19.

A patient satisfaction survey and educational package to improve the care of people hospitalised with COVID-19: a quality improvement project, Liverpool, UK [version 2;peer review: 2 approved]

Background: The perspectives and experiences of people hospitalised with COVID-19 have been under-reported during the coronavirus pandemic. We developed and conducted a COVID-19 patient satisfaction survey in a large university-affiliated secondary healthcare centre in Liverpool, UK, during Europe’s first coronavirus wave (April-June 2020). The survey found that care was rated highly, including among people of Black Asian and Minority Ethnic (BAME) backgrounds. However, sleep-quality and communication about medications and discharge-planning were identified as areas for improvement.   Methods: To improve care for people with COVID-19 admitted to our centre, we designed an educational package for healthcare professionals working on COVID-19 wards. The package, implemented in August 2020, included healthcare worker training sessions on providing holistic care and placement of “Practice Pointers” posters. Patient satisfaction was re-evaluated during the second/third COVID-19 waves in Liverpool (September 2020 - February 2021). Results: Across waves, most (95%) respondents reported that they would recommend our hospital to friends and/or family and rated overall care highly. Comparison of the responses of second/third-wave respondents (n=101) with first-wave respondents (n=94) suggested improved patient satisfaction across most care domains but especially those related to having worries and fears addressed and being consulted about medications and their side-effects. Conclusions: People admitted with COVID-19 to our centre in Liverpool, including those from BAME backgrounds, rated the care they received highly. A simple education package improved the feedback on care received by respondents between the first and second/third waves. These UK-first findings are informing regional strategies to improve person-centred care of hospitalised people with COVID-19.

Family cluster of three cases of monkeypox imported from Nigeria to the United Kingdom, May 2021.

Most reported cases of human monkeypox occur in Central and West Africa, where the causing virus is endemic. We describe the identification and public health response to an imported case of West African monkeypox from Nigeria to the United Kingdom (UK) in May 2021. Secondary transmission from the index case occurred within the family to another adult and a toddler. Concurrent COVID-19-related control measures upon arrival and at the hospital, facilitated detection and limited the number of potential contacts.

Using a household-structured branching process to analyse contact tracing in the SARS-CoV-2 pandemic.

We explore strategies of contact tracing, case isolation and quarantine of exposed contacts to control the SARS-CoV-2 epidemic using a branching process model with household structure. This structure reflects higher transmission risks among household members than among non-household members. We explore strategic implementation choices that make use of household structure, and investigate strategies including two-step tracing, backwards tracing, smartphone tracing and tracing upon symptom report rather than test results. The primary model outcome is the effect of contact tracing, in combination with different levels of physical distancing, on the growth rate of the epidemic. Furthermore, we investigate epidemic extinction times to indicate the time period over which interventions must be sustained. We consider effects of non-uptake of isolation/quarantine, non-adherence, and declining recall of contacts over time. Our results find that, compared to self-isolation of cases without contact tracing, a contact tracing strategy designed to take advantage of household structure allows for some relaxation of physical distancing measures but cannot completely control the epidemic absent of other measures. Even assuming no imported cases and sustainment of moderate physical distancing, testing and tracing efforts, the time to bring the epidemic to extinction could be in the order of months to years. This article is part of the theme issue 'Modelling that shaped the early COVID-19 pandemic response in the UK'.

What do people hospitalised with COVID-19 think about their care? Results of a satisfaction survey during the first wave of COVID-19 in Liverpool.

Despite huge advances in vaccines, testing and treatments for COVID-19, there is negligible evidence on the perceptions of people hospitalised with COVID-19 about the care they received. To address this, we developed a satisfaction survey for people with COVID-19 admitted to our hospital during the first COVID-19 wave in Liverpool. Of those invited, 98/160 (61%) responded, of whom 94/98 (96%) completed the survey. Respondents rated overall care highly (mean 4.7/5) and 89/94 (95%) reported that they would recommend the hospital to friends and/or family. Most respondents felt safe on the ward (94%), with privacy maintained (93%) and pain well managed (90%). Fewer than two-thirds (63%) of respondents considered themselves adequately consulted regarding medications and side effects. Sleep and food/drink quality were also highlighted as areas for improvement. To overcome the issues raised, we generated a 'COVID-19 practice pointers' poster within an integrated educational bundle on COVID-19 wards. The impact of the bundle on perceptions of people hospitalised with COVID-19 will be evaluated in people hospitalised with COVID-19 in Liverpool in 2021. Whether hospitalised for COVID-19 or other conditions, our survey results are a timely reminder of the importance of involving patients in shaping the care that they receive.