We aimed to test the sensitivity of naso-oropharyngeal saliva and self-administered nasal (SN) swab compared to nasopharyngeal (NP) swab for COVID-19 testing in a large cohort of migrant workers in Singapore. We also tested the utility of next-generation sequencing (NGS) for diagnosis of COVID-19. Saliva, NP and SN swabs were collected from subjects who presented with acute respiratory infection, their asymptomatic roommates, and prior confirmed cases who were undergoing isolation at a community care facility in June 2020. All samples were tested using RT-PCR. SARS-CoV-2 amplicon-based NGS with phylogenetic analysis was done for 30 samples. We recruited 200 subjects, of which 91 and 46 were tested twice and thrice respectively. In total, 62.0%, 44.5%, and 37.7% of saliva, NP and SN samples were positive. Cycle threshold (Ct) values were lower during the earlier period of infection across all sample types. The percentage of test-positive saliva was higher than NP and SN swabs. We found a strong correlation between viral genome coverage by NGS and Ct values for SARS-CoV-2. Phylogenetic analyses revealed Clade O and lineage B.6 known to be circulating in Singapore. We found saliva to be a sensitive and viable sample for COVID-19 diagnosis.

Background: Thirty countries with the highest tuberculosis (TB) burden bear 87% of the world’s TB cases. Delayed diagnosis and treatment are detrimental to TB prognosis and sustain TB transmission in the community, making TB elimination a great challenge, especially in these countries. Our objective was to elucidate the duration and determinants of delayed diagnosis and treatment of pulmonary TB in high TB-burden countries. Methods: We conducted a systematic review and meta-analysis of quantitative and qualitative studies by searching four databases for literature published between 2008 and 2018 following PRISMA guidelines. We performed a narrative synthesis of the covariates significantly associated with patient, health system, treatment, and total delays. The pooled median duration of delay and effect sizes of covariates were estimated using random-effects meta-analyses. We identified key qualitative themes using thematic analysis. Results: This review included 124 articles from 14 low- and lower-middle-income countries (LIC and LMIC) and five upper-middle-income countries (UMIC). The pooled median duration of delays (in days) were—patient delay (LIC/LMIC: 28 (95% CI 20–30); UMIC: 10 (95% CI 10–20), health system delay (LIC/LMIC: 14 (95% CI 2–28); UMIC: 4 (95% CI 2–4), and treatment delay (LIC/LMIC: 14 (95% CI 3–84); UMIC: 0 (95% CI 0–1). There was consistent evidence that being female and rural residence was associated with longer patient delay. Patient delay was also associated with other individual, interpersonal, and community risk factors such as poor TB knowledge, long chains of care-seeking through private/multiple providers, perceived stigma, financial insecurities, and poor access to healthcare. Organizational and policy factors mediated health system and treatment delays. These factors included the lack of resources and complex administrative procedures and systems at the health facilities. We identified data gaps in 11 high-burden countries. Conclusions: This review presented the duration of delays and detailed the determinants of delayed TB diagnosis and treatment in high-burden countries. The gaps identified could be addressed through tailored approaches, education, and at a higher level, through health system strengthening and provision of universal health coverage to reduce delays and improve access to TB diagnosis and care. PROSPERO registration: CRD42018107237.

The Western Pacific has one of the fastest-growing older adult populations globally, and tuberculosis (TB) remains one of the foremost infectious causes of disease and death in the region. Older adults are at higher risk of TB due to immunosenescence, comorbidities, and increased institutionalisation. Atypical symptoms and reduced access to health services may delay care-seeking and TB diagnosis, while co-morbidity and increased risk of adverse drug reactions complicate TB treatment. Post-TB sequelae and socioeconomic challenges may decrease the quality of life after TB treatment completion. Despite their high disease burden and special challenges, there is a lack of regionally coordinated policies and guidelines to manage TB among older adults. Routine TB screening at aged-care facilities, age-friendly infrastructure and services, awareness of atypical TB features, integration of TB and non-communicable diseases services, and person-centred approaches to treatment support could improve TB management among older adults. Addressing these challenges and adopting the best practices identified should inform policy formulation and implementation. This project was funded by 1) the 10.13039/100004423 World Health Organization Regional Office for the Western Pacific, with financial contributions from the Government of the Republic of Korea through the Korean Disease Control and Prevention Agency and the Government of Japan through the 10.13039/501100003478 Ministry of Health, Labour and Welfare , and 2) 10.13039/501100001352 NUS Start-up Grant. The funders had no role in the paper design, collection, analysis, and interpretation of data and in writing of the paper.

Background: This scoping review aimed to characterise definitions used to describe subclinical tuberculosis (TB), estimate the prevalence in different populations and describe the clinical characteristics and treatment outcomes in the scientific literature.Methods: A systematic literature search was conducted using PubMed. We included studies published in English between January 1990 and August 2022 that defined “subclinical” or “asymptomatic” pulmonary TB disease, regardless of age, HIV status and comorbidities. We estimated the weighted pooled proportions of subclinical TB using a random-effects model by World Health Organization reported TB incidence, populations and settings. We also pooled the proportion of subclinical TB according to definitions described in published prevalence surveys.Results: We identified 29 prevalence surveys and 71 other studies. Prevalence survey data (2002–2022) using “absence of cough of any duration” criteria reported higher subclinical TB prevalence than those using the stricter “completely asymptomatic” threshold. Prevalence estimates overlap in studies using other symptoms and cough duration. Subclinical TB in studies was commonly defined as asymptomatic TB disease. Higher prevalence was reported in high TB burden areas, community settings and immunocompetent populations. People with subclinical TB showed less extensive radiographic abnormalities, higher treatment success rates and lower mortality, although studies were few.Conclusion: A substantial proportion of TB is subclinical. However, prevalence estimates were highly heterogeneous between settings. Most published studies incompletely characterised the phenotype of people with subclinical TB. Standardised definitions and diagnostic criteria are needed to characterise this phenotype. Further research is required to enhance case finding, screening, diagnostics and treatment options for subclinical TB.

Objectives To develop a localised instrument and Bayesian statistical method to generate size estimates—adjusted for transmission error and barrier effects—of at-risk populations in Singapore. Methods We conducted indepth interviews and focus group to guide the development of the survey questionnaire. The questionnaire was administered between July and August 2017 in Singapore. Using the network scale-up method (NSUM), we developed a Bayesian hierarchical model to estimate the number of individuals in four hidden populations at risk of HIV. The method accounted for both transmission error and barrier effects using social acceptance measures and demographics. Results The adjusted size estimate of the population of male clients of female sex workers was 72 000 (95% CI 51 000 to 100 000), of female sex workers 4200 (95% CI 1600 to 10 000), of men who have sex with men 210 000 (95% CI 140 000 to 300 000) and of intravenous drug users 11 000 (95% CI 6500 to 17 000). Conclusions The NSUM with adjustment for attitudes and demographics allows national-level estimates of multiple priority populations to be determined from simple surveys of the general population, even in relatively conservative societies.

Background: Cambodia is among the 30 countries in the world with the highest burden of tuberculosis (TB), and it is estimated that 40% of people with TB remain undiagnosed. In this study, we aimed to investigate the determinants of delayed diagnosis and treatment of TB in Cambodia. Methods: This mixed-method explanatory sequential study was conducted between February and September 2019 in 12 operational districts in Cambodia. It comprised of a retrospective cohort study of 721 people with TB, followed by a series of in-depth interviews. We assessed factors associated with time to TB diagnosis and treatment initiation using Cox proportional hazards model. Subsequently, we conducted in-depth interviews with 31 people with TB purposively selected based on the time taken to reach TB diagnosis, sex, and residence. Transcripts were coded, and thematic analyses were performed. Results: The median time from the onset of symptoms to TB diagnosis was 49 days (Interquartile range [IQR]: 21–112). We found that longer time to diagnosis was significantly associated with living in rural area (Adjusted hazards ratio [aHR] = 1.25; 95% confidence interval [CI]: 1.06–1.48); TB symptoms—cough (aHR: 1.52; 95% CI: 1.18–1.94), hemoptysis (aHR 1.32; 95% CI: 1.07–1.63), and night sweats (aHR: 1.24; 95% CI: 1.05–1.46); seeking private health care/self-medication (aHR: 1.23; 95% CI: 1.04–1.45); and higher self-stigma (aHR: 1.02; 95% CI: 1.01–1.03). Participants who received education level above the primary level were inversely associated with longer time to diagnosis (aHR: 0.78; 95% CI: 0.62–0.97). The median time from TB diagnosis to the initiation of treatment was two days (IQR: 1–3). The use of smear microscopy for TB diagnosis (aHR: 1.50; 95% CI: 1.16–1.95) was associated with longer time to treatment initiation. Seeking private health care and self-medication before TB diagnosis, lack of perceived risk, threat, susceptibility, and stigma derived qualitatively further explained the quantitative findings. Conclusions: TB diagnostic delay was substantial. Increasing public awareness about TB and consciousness regarding stigma, engaging the private healthcare providers, and tailoring approaches targeting the rural areas could further improve early detection of TB and narrowing the gap of missing cases in Cambodia.