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In rapidly growing and high-burden urban centres, identifying tuberculosis (TB) transmission hotspots and understanding the potential impact of interventions can inform future control and prevention strategies. Using data on local demography, TB reports and patient reporting patterns in Dhaka South City Corporation (DSCC) and Dhaka North City Corporation (DNCC), Bangladesh, between 2010 and 2017, we developed maps of TB reporting rates across wards in DSCC and DNCC and identified wards with high rates of reported TB (i.e. ‘hotspots’) in DSCC and DNCC. We developed ward-level transmission models and estimated the potential epidemiological impact of three TB interventions: active case finding (ACF), mass preventive therapy (PT) and a combination of ACF and PT, implemented either citywide or targeted to high-incidence hotspots. There was substantial geographic heterogeneity in the estimated TB incidence in both DSCC and DNCC: incidence in the highest-incidence wards was over ten times higher than in the lowest-incidence wards in each city corporation. ACF, PT and combined ACF plus PT delivered to 10% of the population reduced TB incidence by a projected 7%–9%, 13%–15% and 19%–23% over five years, respectively. Targeting TB hotspots increased the projected reduction in TB incidence achieved by each intervention 1.4- to 1.8-fold. The geographical pattern of TB notifications suggests high levels of ongoing TB transmission in DSCC and DNCC, with substantial heterogeneity at the ward level. Interventions that reduce transmission are likely to be highly effective and incorporating notification data at the local level can further improve intervention efficiency.
Non-resolving inflammation is characteristic of tuberculosis (TB). Given their inflammation-resolving properties, omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) may support TB treatment. This research aimed to investigate the effects of n-3 LCPUFA on clinical and inflammatory outcomes of Mycobacterium tuberculosis (Mtb)-infected C3HeB/FeJ mice with either normal or low n-3 PUFA status before infection. Using a two-by-two design, uninfected mice were conditioned on either an n-3 PUFA-sufficient (n-3FAS) or -deficient (n3FAD) diet for six weeks. One week post-infection, mice were randomised to either n-3 LCPUFA supplemented (n-3FAS/n-3+ and n3FAD/n3+) or continued on n-3FAS or n3FAD diets for three weeks. Mice were euthanised and fatty acid status, lung bacterial load and pathology, cytokine, lipid mediator, and immune cell phenotype analysed. n-3 LCPUFA supplementation in n-3FAS mice lowered lung bacterial loads (P=0·003), T cells (P=0·019), CD4+ T cells (P=0·014), IFN-γ (P<0·001) and promoted a pro-resolving lung lipid mediator profile. Compared with n-3FAS mice, the n-3FAD group had lower bacterial loads (P=0·037), significantly higher immune cell recruitment and a more pro-inflammatory lipid mediator profile, however, significantly lower lung IFN-γ, IL-1α, IL-1β, and IL-17, and supplementation in the n-3FAD group provided no beneficial effect on lung bacterial load or inflammation. Our study provides the first evidence that n-3 LCPUFA supplementation has antibacterial and inflammation-resolving benefits in TB when provided one week after infection in the context of a sufficient n-3 PUFA status. Whilst a low n-3 PUFA status may promote better bacterial control and lower lung inflammation not benefiting from n-3 LCPUFA supplementation.
Since 1993, reports on tuberculosis (TB) outbreaks have been collected in Japan; however, there has never been an overall analysis of these TB outbreaks. We aim to provide one here. The TB outbreak data were obtained from the Ministry of Health, Labour and Welfare and are described in terms of time, place and transmission site. The average number of TB cases and latent tuberculosis infection (LTBI) were compared by the transmission site. Some 605 TB outbreaks with 3491 TB cases were reported in 1993–2015 with an increasing trend (r = 0.45), during which time 728 777 TB cases were reported nationwide. On an average, TB outbreaks occurred more often in April to May (5.5 outbreaks per 2 months) than in December to January (3.4). The most common transmission sites were workplaces (n = 255), followed by health facilities (n = 144), schools (n = 60) and welfare facilities (n = 48). Psychiatric hospitals and nursing homes had the highest average number of TB cases per outbreak (8.5 each), whereas schools and prisons had the highest numbers of LTBI cases (29.1 and 38.9, respectively). Countries, particularly those that have resources to investigate TB outbreaks, should collect and analyse findings of TB outbreaks, as it informs surveillance systems and eventually strengthens general health systems.
Chapter 10 reviews the history of colonial medicine in the Belgian Congo. In this huge colony, Belgium established arguably the best healthcare system in tropical Africa, with more than 2,500 institutions of all kinds. As in the French colonies, there were large-scale disease control interventions using injectable drugs. A network of public health laboratories, including those in Léopoldville and Stanleyville, are ruled out as being instrumental in the early propagation of HIV. The brilliant career of Lucien Van Hoof, the colony’s chief medical officer for twelve years who also did cutting-edge research on the control of sleeping sickness, is highlighted. The rather debatable medical practices in Léopoldville’s STD clinics are examined; ‘free women’ were forced to undergo a long series of intravenous injections if they were thought, often wrongly, to have had syphilis previously. An outbreak among these women of ‘inoculation hepatitis’ was recognised in the early 1950s. An analysis of changes in the incidence of tuberculosis in various parts of the Belgian Congo in the 1950s suggests that HIV was already driving this increasing incidence in Léopoldville. A recent study identified several routes for the iatrogenic transmission of blood-borne viruses during the colonial and early post-colonial era.
The aim of this study was to explore the impact of polymorphism of PD-1 gene and its interaction with tea drinking on susceptibility to tuberculosis (TB). A total of 503 patients with TB and 494 controls were enrolled in this case–control study. Three single-nucleotide polymorphisms of PD-1 (rs7568402, rs2227982 and rs36084323) were genotyped and unconditional logistic regression analysis was used to identify the association between PD-1 polymorphism and TB, while marginal structural linear odds models were used to estimate the interactions. Genotypes GA (OR 1.434), AA (OR 1.891) and GA + AA (OR 1.493) at rs7568402 were more prevalent in the TB patients than in the controls (P < 0.05). The relative excess risk of interaction (RERI) between rs7568402 of PD-1 genes and tea drinking was −0.3856 (95% confidence interval −0.7920 to −0.0209, P < 0.05), which showed a negative interaction. However, the RERIs between tea drinking and both rs2227982 and rs36084323 of PD-1 genes were not statistically significant. Our data demonstrate that rs7568402 of PD-1 genes was associated with susceptibility to TB, and there was a significant negative interaction between rs7568402 and tea drinking. Therefore, preventive measures through promoting the consumption of tea should be emphasised in the high-risk populations.
The prognostic factor for in-hospital mortality in tuberculosis (TB) patients requiring intensive care unit (ICU) care remains unclear. Therefore, a retrospective study was conducted aiming to estimate the in-hospital mortality rate and the risk factors for mortality in a high-burden setting. All patients with culture-confirmed TB that were admitted to the ICU of the hospital between March 2012 and April 2019 were identified retrospectively. Data, such as demographic characteristics, comorbidities, laboratory measures and mortality, were obtained from medical records. The Cox proportional hazards regression model was used to identify prognostic factors that influence in-hospital mortality. A total of 82 ICU patients with confirmed TB were included in the analysis, and 22 deaths were observed during the hospital stay, 21 patients died in the ICU. In the multivariable model adjusted for sex and age, the levels of serum albumin and white blood cell (WBC) count were significantly associated with mortality in TB patients requiring ICU care (all P < 0.01), the hazard ratios were 0.8 (95% confidence interval (CI): 0.7–0.9) per 1 g/l and 1.1 (95% CI: 1.0–1.2) per 1 × 109/l, respectively. In conclusion, in-hospital mortality remains high in TB patients requiring ICU care. Low serum albumin level and high WBC count significantly impact the risk of mortality in these TB patients in China.
Tuberculosis (TB) remains a global public health threat. Misdiagnosis and delayed therapy of sputum smear-negative TB can affect the treatment outcomes and promote pathogen transmission. The application of Xpert MTB/RIF assay in bronchoalveolar lavage fluid (BALF) has been recommended but needs clinical evidence. We carried out a prospective study in the Nanjing Public Health Medical Center from September 2018 to August 2019. Pulmonary tuberculosis (PTB) patients were enrolled in the study if they had negative results of sputum smear. We compared the performance of Xpert MTB/RIF assay in sputum and BALF using sputum culture as the reference. In addition to this, we applied parallel tests using sputum culture, sputum-based Xpert MTB/RIF assay and BALF-based Xpert MTB/RIF assay to jointly detect smear-negative PTB using clinical diagnosis as the reference. With mycobacterial culture as the reference standard, Xpert MTB/RIF of BALF showed a higher sensitivity (14/16, 87.5%), but a relatively lower specificity (57/92, 62.0%). Xpert MTB/RIF of sputum showed relatively lower sensitivity (6/10, 60.0%) and higher specificity (63/88, 71.6%). Compared with sputum culture, Xpert MTB /RIF assay reduced the median detection time of MTB from 30 to 0 days, which significantly shortened the diagnosis time of the smear-negative TB patients. Among the combined detections, the positive detection proportion was improved with significant differences comparing with sputum culture only, from 11.1% (10/90) to 46.7% (42/90) (P < 0.05). Our study showed Xpert MTB/RIF in BALF had a better performance in detecting MTB of smear-negative patients.
Although the progression of invasive aspergillosis (IA) shares some risk factors in the development of active pulmonary tuberculosis (PTB), however, the prevalence of IA in suspected PTB remains unclear. During a period of 1 year (from January 2016 to December 2016), consecutive patients with suspected PTB were included in a referral TB hospital. Data, including demographic information and underlying diseases, were collected from medical records. PTB were all confirmed by mycobacterial culture (Lowenstein–Jensen medium). IA were diagnosed as proven or probable according to the criteria of the 2008 EORTC/MSG definitions. A descriptive analysis was performed to estimate the corresponding prevalence. During the study year, 1507 patients have a positive mycobacterial culture, with a mean age of 45.6 (s.d. 19.9) years old and a female:male ratio of 1:4. Among the 82 patients with non-tuberculous mycobacterial diseases, two patients (2.44%, 95% CI 0.67–8.46%) were diagnosed as IA (one proven and one probable); two probable IA patients (0.15%, 95% CI 0.04–0.55%) were diagnosed in PTB patients (n = 1315), and all were retreatment cases. In addition, all four IA patients (100%) exhibited cavities in both lobes on radiograph. In China, the prevalence of IA is low in active PTB patients. However, when high-risk factors for IA are encountered in PTB patients, further investigations are required and empirically treatment for IA might be warranted.
Multiple studies suggest that diabetes mellitus (DM) is a potential risk factor for tuberculosis (TB) development and treatment, especially in low- and middle-income countries. The study aimed to test concomitancy between DM and TB among adults in India. Data were from the 2015–16 National Family Health Survey (NFHS-4). The study sample comprised 107,575 men aged 15–54 and 677,292 women aged 15–49 for which data on DM status were available in the survey. The association between state-level prevalence of TB and DM was examined and robust Poisson regression analysis applied to examine the effect of DM on TB. A high prevalence of TB was observed among individuals with diabetes in India in 2015–16. A total of 866 per 100,000 men and 405 per 100,000 women who self-reported having diabetes also had TB; among those who self-reported not having diabetes the ratios were 407 per 100,000 men and 241 per 100,000 women. The risk of having TB among those who self-reported having DM was higher for both men (2.03, 95% CI: 1.26, 3.28) and women (1.79, 95% CI: 1.48, 2.49) than for those who did not self-report having DM. Adults who were diagnosed with diabetes (including pre-diabetes) also had a higher rate of TB (477 per 100,000 men and 331 per 100,000 women) than those who were not diagnosed (410 per 100,000 men and 239 per 100,000 women). Adults from poor families, with lower BMIs, lower levels of literacy and who were not working had a higher risk of TB–DM co-morbidity. The state-level pattern of co-morbidity, the under-reporting of DM (undiagnosed) and TB stigmatization are discussed. The study confirms that diabetes is an important co-morbid feature with TB in India, and reinforces the need to raise awareness on screening for the co-existence of DM and TB with integrated health programmes for the two conditions.
Tuberculosis (TB) is a globally widespread disease, with approximately a quarter of the world’s population currently infected (WHO, 2018). Some risk factors, such as HIV status, nutrition and body mass index, have already been thoroughly investigated. However, little attention has been given to behavioural and/or psychological risk factors such as stress and education level. This study investigated the risk factors for TB diagnosis by statistical analyses of publicly available data from the most recent wave of the Indonesian Family Life survey (IFLS-5) conducted in 2015. Out of 34,249 respondents there were 328 who reported having TB. For comparison and completeness, variables were divided into levels: individual-, household- and community-level variables. The most prominent and interesting variables found to influence TB diagnosis status (on each level) were investigated, and a logistic regression was subsequently developed to understand the extent to which each risk factor acts as a predictor for being diagnosed with TB. Age, health benefit or insurance, stress at work and living in a rural area all showed significant association with TB diagnosis status. This study’s findings suggest that suitable control measures, such as schemes for improving mental health/stress reduction and improved access to health care in rural areas should be implemented in Indonesia to address each of the key factors identified.
The incidence of extensively drug-resistant tuberculosis (XDR-TB) has been rising consistently in Pakistan, and the country is likely to experience another surge of cases in the midst of the COVID-19 crisis. It is imperative to consider how the rising proportion of XDR-TB is best tackled during the pandemic; this includes finding a solution to the problem of non-adherence at the level of community-based healthcare, the utility and practicality of simultaneous testing for COVID-19 and TB, and reconciliation of the World Health Organization’s recommendation of home-based treatment with the need for frequent monitoring of anti-tubercular therapy in XDR-TB. Operational research is needed expeditiously to bypass these limitations.
Tuberculosis (TB) in children is a critical public health issue. In Bohol, Philippines, we found a high tuberculin skin test (TST)-positive prevalence (weighted prevalence = 6.4%) among 5476 children (<15 years) from 184 villages, with geographically isolated communities having prevalence as high as 29%. Therefore, we conducted a geospatial and hot spot analysis to examine the association between villages with high TST-positive prevalence (⩾6.5%) and access to medical care (distance (in kilometres and minutes of travel time) to the municipal Rural Health Units (RHU)), access to healthcare resources (distance to Provincial Health Office (PHO)) and socioeconomic determinants of health. Hot spot analysis revealed significant clusters of TST-positive prevalence in villages farthest from the PHO. Based on univariate analysis, the following variables associated with high prevalence were included in the multivariate model: minutes of travel time to the PHO, distance to the PHO, island villages and total deprivation based on socioeconomic indicators. In the final model, only distance to PHO in minutes was significant (P = 0.005). When evaluated further, greater than 1-hour drive significantly increased risk for TST-positivity (P = 0.003). Distance to healthcare resources likely increases the risk of TB transmission within the community. Expanding TB control efforts to geographically isolated areas is critical.
Public health emergencies of international concern, in the form of infectious disease outbreaks, epidemics, and pandemics, represent an increasing risk to the worldʼs population. Management requires coordinated responses, across many disciplines and nations, and the capacity to muster proper national and global public health education, infrastructure, and prevention measures. Unfortunately, increasing numbers of nations are ruled by autocratic regimes which have characteristically failed to adopt investments in public health infrastructure, education, and prevention measures to keep pace with population growth and density. Autocratic leaders have a direct impact on health security, a direct negative impact on health, and create adverse political and economic conditions that only complicate the crisis further. This is most evident in autocratic regimes where health protections have been seriously and purposely curtailed. All autocratic regimes define public health along economic and political imperatives that are similar across borders and cultures. Autocratic regimes are seriously handicapped by sociopathic narcissistic leaders who are incapable of understanding the health consequences of infectious diseases or the impact on their population. A cross section of autocratic nations currently experiencing the impact of COVID-19 (coronavirus disease 2019) are reviewed to demonstrate the manner where self-serving regimes fail to manage health crises and place the rest of the world at increasing risk. It is time to re-address the pre-SARS (severe acute respiratory syndrome) global agendas calling for stronger strategic capacity, legal authority, support, and institutional status under World Health Organization (WHO) leadership granted by an International Health Regulations Treaty. Treaties remain the most successful means the world has in preventing, preparing for, and controlling epidemics in an increasingly globalized world.
“Honesty is worth a lot more than hope…” The Economist, February 17, 2020.
Tuberculosis (TB) is generally considered a disease that principally afflicts the low-income segments of a population. In the Nanshan District of Shenzhen, China, with the economic transformation and a new Headquarters Economy (HE) emerging, there are now more cases in office workers than in manufacturing workers. To illustrate this trend, we describe a small TB outbreak in an office building located in the centre of the rapidly growing HE district. Two active pulmonary tuberculosis cases were found in workers who shared an office, and whole genome sequencing showed that the genetic distance between the strains of the two cases was just one single nucleotide polymorphism, consistent with intra-office transmission. Investigation of 30 other workers in the same or adjacent offices with interviews, interferon-gamma release assays (IGRAs) and chest X-rays, identified one new TB case and latent tuberculosis infection (LTBI) in 40.0% (12/30) of the contacts. The offices were under-ventilated. None of the IGRA positive, asymptomatic contacts agreed to receive treatment for LTBI, presumably due to TB stigma, and over the next 2 years 69.0% (20/29) of the contacts were lost to follow-up. Treatment for LTBI and stigma of TB remain challenges here. Office workers in the HE of rapidly economic developing areas should be targeted with increased vigilance by TB control programmes.
The aim of this study was to evaluate long-term survival and risk factors associated with multidrug-resistant tuberculosis (MDR-TB) patient survival in Central China. Between December 2006 and June 2011, incident and retreatment adult MDR-TB patients were enrolled in the present study. Cox proportional hazard regression analysis was used to evaluate the risk factors affecting survival. The total follow-up period was 270 person-years (PY) for 356 MDR-TB cases in Wuhan. Of the 356 cases, 103 patients died, yielding an average case fatality rate of 381.2 per 1000 TB patients per year. Using adjusted Cox regression analysis, older age (adjusted hazard ratio (aHR) >3.0 starting from 30 years) and low education level (primary and middle school; aHR 1.67 (95% CI 1.01–2.77)) were independently associated with lower survival. Diabetes mellitus profoundly affected the survival of MDR-TB patients (aHR 1.95 (95% CI 1.30–2.93)). Our data demonstrate that coexistent diabetes significantly and negatively impacted MDR-TB patient survival. In addition, MDR-TB patients aged 60 years or older exhibited a greater risk of mortality during follow-up. Our findings emphasise that MDR-TB patients with comorbidities that increase their risk of death require additional medical interventions to reduce mortality.
In January 2012, an inpatient in a ward of a psychiatric hospital with nearly 300 beds in Kanagawa, Japan, was diagnosed with sputum smear-positive pulmonary tuberculosis (TB). Here we characterise the TB outbreak cases and identify the population at risk. TB was diagnosed when a person tested bacteriologically positive for TB or was determined to have TB by a physician. A latent TB infection (LTBI) case was defined as a person tested positive by interferon-gamma release assay (IGRA). A total of 125 contacts were screened via IGRA and chest X-ray. In all, 15 TB and 15 LTBI cases were found by the end of October 2012, and thereafter no additional TB case was found. Of the 15 TB cases, eight were culture-positive and all the isolates had identical variable number tandem repeat patterns. Twenty-four of the 56 (42.9%, 95% confidence interval (CI) 29.7–56.8) inpatients in the ward had either TB or LTBI with a relative risk of 8.6 (95% CI 1.2–59.3), compared to the staff members who did not work full-time in the ward (one of 20 (5.0%, 95% CI 0.0–24.9)). We recommend that psychiatric hospitals conduct periodic screening of staff members and inpatients for TB to prevent nosocomial TB outbreaks.
Cross-sectional studies show that the prevalence of comorbid depression in people with tuberculosis (TB) is high. The hypothesis that TB may lead to depression has not been well studied. Our objectives were to determine the incidence and predictors of probable depression in a prospective cohort of people with TB in primary care settings in Ethiopia.
We assessed 648 people with newly diagnosed TB for probable depression using Patient Health Questionnaire, nine-item (PHQ-9) at the time of starting their anti-TB medication. We defined PHQ-9 scores 10 and above as probable depression. Participants without baseline probable depression were assessed at 2 and 6 months to measure incidence of depression. Incidence rates per 1000-person months were calculated. Predictors of incident depression were identified using Poisson regression.
Two hundred and ninety-nine (46.1%) of the participants did not have probable depression at baseline. Twenty-two (7.4%) and 26 (8.7%) developed depression at 2 and 6 months of follow up. The incidence rate of depression between baseline and 2 months was 73.6 (95% CI 42.8–104.3) and between baseline and 6 months was 24.2 (95% CI 14.9–33.5) per 1000 person-months respectively. Female sex (adjusted β = 0.22; 95% CI 0.16–0.27) was a risk factor and perceived social support (adjusted β = −0.14; 95% CI −0.24 to −0.03) was a protective factor for depression onset.
There was high incidence of probable depression in people undergoing treatment for newly diagnosed TB. The persistence and incidence of depression beyond 6 months need to be studied. TB treatment guidelines should have mental health component.
When tuberculosis (TB) and depression co-occur, there is greater risk for comorbidities, disability, suffering, and health-related costs. Depression is also associated with poor treatment adherence in patients with TB. The major aim of this study was to assess the symptoms of depression and associated factors among TB patients currently receiving directly observed treatment short-course (DOTS) treatment.
A cross-sectional study was conducted among TB patients currently undergoing treatment in 27 DOTS centers in three districts of Kathmandu Valley. The study included 250 TB patients within 2 months of treatment initiation, aged 18 years and above. The previously validated Nepali Patient Health Questionnaire (PHQ-9) was used to screen for depression and semi-structured interviews were conducted to collect socio-demographic information and other factors related to TB and/or depression. Data analysis was conducted using IBM SPSS Statistics version 20.
The study found the mean PHQ Score to be 2.84 (s.d. 4.92, range 0–25). Among the respondents, 10% (n = 25) had PHQ-9 scores ⩾10, suggestive of probable depression. Multivariate linear regression indicated that depressive symptoms were significantly associated with being separated/widowed/divorced (p = 0.000) and having lower education (0.003). In addition, smoking (p = 0.02), alcohol use (p = 0.001), and experience of side effects from TB medications (p = 0.001) were risk factors for higher PHQ-9 scores.
Our findings suggest that patients on TB treatment have higher risk of depression and efforts should be made by the National Tuberculosis Program to address this issue.