High Incidence Countries Research Articles

Whole genome sequencing analysis of Mycobacterium tuberculosis reveals circulating strain types and drug-resistance mutations in the Philippines

The Philippines is a high-incidence country for tuberculosis, with the increasing prevalence of multi- (MDR-TB) and extensively-drug (XDR-TB) resistant Mycobacterium tuberculosis strains posing difficulties to disease control. Understanding the genetic diversity of circulating strains can provide insights into underlying drug resistance mutations and transmission dynamics, thereby assisting the design of diagnostic tools, including those using next generation sequencing (NGS) platforms. By analysing genome sequencing data of 732 isolates from Philippines drug-resistance survey collections spanning from 2011 to 2019, we found that the majority belonged to lineages L1 (531/732; 72.5%) and L4 (European-American; n = 174; 23.8%), with the Manila strain (L1.2.1.2.1) being the most prominent (475/531). Approximately two-thirds of isolates were found to be at least MDR-TB (483/732; 66.0%), and potential XDR-TB genotypic resistance was observed (3/732; 0.4%), highlighting an emerging problem in the country. Genotypic resistance was highly concordant with laboratory drug susceptibility testing. By finding isolates with (near-)identical genomic variation, five major clusters containing a total of 114 isolates were identified: all containing either L1 or L4 isolates with at least MDR-TB resistance and spanning multiple years of collection. Closer inspection of clusters revealed transmission in prisons, some involving isolates with XDR-TB, and mutations linked to third-line drug bedaquiline. We have also identified previously unreported mutations linked to resistance for isoniazid, rifampicin, ethambutol, and fluoroquinolones. Overall, this study provides important insights into the genetic diversity, transmission and circulating drug resistance mutations of M. tuberculosis in the Philippines, thereby informing clinical and surveillance decision-making, which is increasingly using NGS platforms.

Readability of Patient-Facing Information of Antibiotics Used in the WHO Short 6-Month and 9-Month All Oral Treatment for Drug-Resistant Tuberculosis

ObjectivesReadability of patient-facing information of oral antibiotics detailed in the WHO all oral short (6 months, 9 months) has not been described to date. The aim of this study was therefore to examine (i) how readable patient-facing TB antibiotic information is compared to readability reference standards and (ii) if there are differences in readability between high-incidence countries versus low-incidence countries.MethodsTen antibiotics, including bedaquiline, clofazimine, ethambutol, ethionamide, isoniazid, levofloxacin, linezolid, moxifloxacin, pretomanid, pyrazinamide, were investigated. TB antibiotic information sources were examined, consisting of 85 Patient Information Leaflets (PILs) and 40 antibiotic web resouces. Of these 85 PILs, 72 were taken from the National Medicines Regulator from six countries (3 TB high-incidence [Rwanda, Malaysia, South Africa] + 3 TB low-incidence [UK, Ireland, Malta] countries). Readability data was grouped into three categories, including (i) high TB-incidence countries (n = 33 information sources), (ii) low TB-incidence countries (n = 39 information sources) and (iii) web information (n = 53). Readability was calculated using Readable software, to obtain four readability scores [(i) Flesch Reading Ease (FRE), (ii) Flesch-Kincaid Grade Level (FKGL), (iii) Gunning Fog Index and (iv) SMOG Index], as well as two text metrics [words/sentence, syllables/word].ResultsMean readability scores of patient-facing TB antibiotic information for FRE and FKGL, were 47.4 ± 12.6 (sd) (target ≥ 60) and 9.2 ± 2.0 (target ≤ 8.0), respectively. There was no significant difference in readability between low incidence countries and web resources, but there was significantly poorer readability associated with PILs from high incidence countries versus low incidence countries (FRE; p = 0.0056: FKGL; p = 0.0095).ConclusionsReadability of TB antibiotic PILs is poor. Improving readability of PILs should be an important objective when preparing patient-facing written materials, thereby improving patient health/treatment literacy.

Predictive biomarkers of preeclampsia severity in a low resource setting: Role of red blood cell indices, NLR, and albumin-to-creatinine ratio.

Preeclampsia (PE), a serious medical condition with substantial maternal and perinatal implications, poses a significant challenge, particularly in high-incidence countries like Indonesia. Red blood cell (RBC) indices, neutrophil-to-lymphocyte ratio (NLR), and microalbuminuria (albumin-to-creatinine ratio (ACR)) may signal systemic inflammation and endothelial dysfunction, recently recognized as potential indicators for diagnosing and predicting disease severity. The aim of this study was to analyze RBC indices, NLR, and ACR changes in women with PE and their potential for predicting disease severity. A cross-sectional study was conducted at multi-center hospitals across Medan, Indonesia, from June 2022 to June 2023. The patients were grouped into PE cases with and without severe features. Demographic characteristics and complications were recorded while blood and urine were tested. The Chi-squared test, Fisher's exact test and Mann-Whitney test were used to determine biomarkers associated with severe PE. A total of 208 PE patients were included in the study (104 patients for each PE with and without severe features). Our data indicated that PE patients with severe features had higher red cell distribution width (18.5% vs 13.7%; p<0.001), NLR (5.66% vs 4.1%; p<0.001), and ACR (755.97 mg/dL vs 468.63 mg/dL; p<0.001) compared to those without severe features. In contrast, the platelet count was lower in severe features than those without (21.9 × 106/μL vs 27.0 × 106/μL; p=0.002). This study highlighted that PE patients with severe features predominantly had higher levels of RDW, NLR, and ACR and lower platelet counts compared to those without severe features. Therefore, basic tests such as complete blood count and urinalysis, which are inexpensive and feasible in primary care settings with limited resources, offer hope as valuable diagnostic biomarkers for pregnant women diagnosed with PE in a low resource setting.

The increasing healthcare burden of enteric fever in a low-incidence setting

ObjectivesEnteric fever carries appreciable morbidity in non-endemic settings, particularly in returned travelers. This study aimed to characterize the healthcare burden of enteric fever in a low-incidence setting and to identify risk factors and opportunities for preventative interventions. MethodsAnalysis of a retrospective case series from a tertiary pediatric center (2015–2019), augmented by public health notification and microbiological laboratory data (2018–2019), from Western Sydney, Australia, a region with frequent travel links to South Asia. ResultsEighty-nine (89) patients were diagnosed with enteric fever, including 43 children with complete demographic and travel data. Enteric fever cases increased over time (by 4.9 % per year) and incidence was three times higher in the pediatric population (<15 years old) compared to adults. Travel to India and visiting friends and relatives (VFR) travel were risk factors. Few children received enteric fever vaccination prior to travel, as pre-travel advice most commonly was not sought. ConclusionsChildren visiting relatives in high-incidence countries are increasingly at risk for enteric fever, particularly when travelling to South Asia. Targeted health advice to travelers visiting friends and relatives is warranted to mitigate the healthcare burden of enteric fever in low-incidence settings.

Projected Time for the Elimination of Cervical Cancer Under Various Intervention Scenarios: Age-Period-Cohort Macrosimulation Study.

The World Health Organization aims for the global elimination of cervical cancer, necessitating modeling studies to forecast long-term outcomes. This paper introduces a macrosimulation framework using age-period-cohort modeling and population attributable fractions to predict the timeline for eliminating cervical cancer in Taiwan. Data for cervical cancer cases from 1997 to 2016 were obtained from the Taiwan Cancer Registry. Future incidence rates under the current approach and various intervention strategies, such as scaled-up screening (cytology based or human papillomavirus [HPV] based) and HPV vaccination, were projected. Our projections indicate that Taiwan could eliminate cervical cancer by 2050 with either 70% compliance in cytology-based or HPV-based screening or 90% HPV vaccination coverage. The years projected for elimination are 2047 and 2035 for cytology-based and HPV-based screening, respectively; 2050 for vaccination alone; and 2038 and 2033 for combined screening and vaccination approaches. The age-period-cohort macrosimulation framework offers a valuable policy analysis tool for cervical cancer control. Our findings can inform strategies in other high-incidence countries, serving as a benchmark for global efforts to eliminate the disease.

Comparison of Tuberculin Skin Testing and Interferon-γ Release Assays in Predicting Tuberculosis Disease

Elimination of tuberculosis (TB) disease in the US hinges on the ability of tests to detect individual risk of developing disease to inform prevention. The relative performance of 3 available TB tests-the tuberculin skin test (TST) and 2 interferon-γ release assays (IGRAs; QuantiFERON-TB Gold In-Tube [QFT-GIT] and SPOT.TB [TSPOT])-in predicting TB disease development in the US remains unknown. To compare the performance of the TST with the QFT-GIT and TSPOT IGRAs in predicting TB disease in high-risk populations. This prospective diagnostic study included participants at high risk of TB infection (TBI) or progression to TB disease at 10 US sites between 2012 and 2020. Participants of any age who had close contact with a case patient with infectious TB, were born in a country with medium or high TB incidence, had traveled recently to a high-incidence country, were living with HIV infection, or were from a population with a high local prevalence were enrolled from July 12, 2012, through May 5, 2017. Participants were assessed for 2 years after enrollment and through registry matches until the study end date (November 15, 2020). Data analysis was performed in June 2023. At enrollment, participants were concurrently tested with 2 IGRAs (QFT-GIT from Qiagen and TSPOT from Oxford Immunotec) and the TST. Participants were classified as case patients with incident TB disease when diagnosed more than 30 days from enrollment. Estimated positive predictive value (PPV) ratios from generalized estimating equation models were used to compare test performance in predicting incident TB. Incremental changes in PPV were estimated to determine whether predictive performance significantly improved with the addition of a second test. Case patients with prevalent TB were examined in sensitivity analysis. A total of 22 020 eligible participants were included in this study. Their median age was 32 (range, 0-102) years, more than half (51.2%) were male, and the median follow-up was 6.4 (range, 0.2-8.3) years. Most participants (82.0%) were born outside the US, and 9.6% were close contacts. Tuberculosis disease was identified in 129 case patients (0.6%): 42 (0.2%) had incident TB and 87 (0.4%) had prevalent TB. The TSPOT and QFT-GIT assays performed significantly better than the TST (PPV ratio, 1.65 [95% CI, 1.35-2.02] and 1.47 [95% CI, 1.22-1.77], respectively). The incremental gain in PPV, given a positive TST result, was statistically significant for positive QFT-GIT and TSPOT results (1.64 [95% CI, 1.40-1.93] and 1.94 [95% CI, 1.65-2.27], respectively). In this diagnostic study assessing predictive value, IGRAs demonstrated superior performance for predicting incident TB compared with the TST. Interferon-γ release assays provided a statistically significant incremental improvement in PPV when a positive TST result was known. These findings suggest that IGRA performance may enhance decisions to treat TBI and prevent TB.

Cost-effectiveness and budget impact of decentralising childhood tuberculosis diagnosis in six high tuberculosis incidence countries: a mathematical modelling study

The burden of childhood tuberculosis remains high globally, largely due to under-diagnosis. Decentralising childhood tuberculosis diagnosis services to lower health system levels could improve case detection, but there is little empirically based evidence on cost-effectiveness or budget impact. In this mathematical modelling study, we assessed the cost-effectiveness and budget impact of decentralising a comprehensive diagnosis package for childhood tuberculosis to district hospitals (DH-focused) or primary health centres (PHC-focused) compared to standard of care (SOC). The project was conducted in Cambodia, Cameroon, Côte d'Ivoire, Mozambique, Sierra Leone, and Uganda between August 1st, 2018 and September 30th, 2021. A mathematical model was developed to assess the health and economic outcomes of the intervention from a health system perspective. Estimated outcomes were tuberculosis cases, deaths, disability-adjusted life years (DALYs) and incremental cost-effectiveness ratios (ICERs). We also calculated the budget impact of nationwide implementation. The TB-Speed Decentralization study is registered with ClinicalTrials.gov, NCT04038632. For the DH-focused strategy versus SOC, ICERs ranged between $263 (Cambodia) and $342 (Côte d'Ivoire) per DALY averted. For the PHC-focused strategy versus SOC, ICERs ranged between $477 (Cambodia) and $599 (Côte d'Ivoire) per DALY averted. Results were sensitive to TB prevalence and the discount rate used. The additional costs of implementing the DH-focused strategy ranged between $12.8M (range 10.8-16.4) (Cambodia) and $50.4M (36.5-74.4) (Mozambique), and between $13.9M (12.6-15.6) (Sierra Leone) and $134.6M (127.1-143.0) (Uganda) for the PHC-focused strategy. The DH-focused strategy may be cost-effective in some countries, depending on the cost-effectiveness threshold used for policy making. Either intervention would require substantial early investment. Unitaid.

Effect of decentralising childhood tuberculosis diagnosis to primary health centre versus district hospital levels on disease detection in children from six high tuberculosis incidence countries: an operational research, pre-post intervention study

Childhood tuberculosis (TB) remains underdiagnosed largely because of limited awareness and poor access to all or any of specimen collection, molecular testing, clinical evaluation, and chest radiography at low levels of care. Decentralising childhood TB diagnostics to district hospitals (DH) and primary health centres (PHC) could improve case detection. We conducted an operational research study using a pre-post intervention cross-sectional study design in 12 DHs and 47PHCs of 12 districts across Cambodia, Cameroon, Côte d'Ivoire, Mozambique, Sierra Leone and Uganda. The intervention included 1) a comprehensive diagnosis package at patient-level with tuberculosis screening for all sick children and young adolescents <15 years, and clinical evaluation, Xpert Ultra-testing on respiratory and stool samples, and chest radiography for children with presumptive TB, and 2) two decentralisation approaches (PHC-focused or DH-focused) to which districts were randomly allocated at country level. We collected aggregated and individual data. We compared the proportion of tuberculosis detection in children and young adolescents <15 years pre-intervention (01 August 2018-30 November 2019) versus during intervention (07 March 2020-30 September 2021), overall and by decentralisation approach. This study is registered with ClinicalTrials.gov, NCT04038632. TB was diagnosed in 217/255,512 (0.08%) children and young adolescent <15 years attending care pre-intervention versus 411/179,581 (0.23%) during intervention, (OR: 3.59 [95% CI 1.99-6.46], p-value<0.0001; p-value=0.055 after correcting for over-dispersion). In DH-focused districts, TB diagnosis was 80/122,570 (0.07%) versus 302/86,186 (0.35%) (OR: 4.07 [1.86-8.90]; p-value=0.0005; p-value=0.12 after correcting for over-dispersion); and 137/132,942 (0.10%) versus 109/93,395 (0.11%) in PHC-focused districts, respectively (OR: 2.92 [1.25-6.81; p-value=0.013; p-value=0.26 after correcting for over-dispersion). Decentralising and strengthening childhood TB diagnosis at lower levels of care increases tuberculosis case detection but the difference was not statistically significant. Unitaid, Grant number 2017-15-UBx-TB-SPEED.

Prevalence estimates of tuberculosis infection in adults in Denmark: a retrospective nationwide register-based cross-sectional study, 2010 to 2018.

BackgroundTuberculosis (TB) elimination requires identifying and treating persons with TB infection (TBI).AimWe estimate the prevalence of positive interferon gamma release assay (IGRA) tests (including TB) and TBI (excluding TB) in Denmark based on TBI screening data from patients with inflammatory bowel disease (IBD) or inflammatory rheumatic disease (IRD).MethodsUsing nationwide Danish registries, we included all patients with IBD or IRD with an IGRA test performed between 2010 and 2018. We estimated the prevalence of TBI and positive IGRA with 95% confidence intervals (CI) in adolescents and adults aged 15-64 years after sample weighting adjusting for distortions in the sample from the background population of Denmark for sex, age group and TB incidence rates (IR) in country of birth.ResultsIn 13,574 patients with IBD or IRD, 12,892 IGRA tests (95.0%) were negative, 461 (3.4%) were positive and 221 (1.6%) were indeterminate, resulting in a weighted TBI prevalence of 3.2% (95% CI: 2.9-3.5) and weighted positive IGRA prevalence of 3.8% (95% CI: 3.5-4.2) among adults aged 15-64 years in the background population of Denmark. Unweighted TBI prevalence increased with age and birthplace in countries with a TB IR higher than 10/100,000 population.ConclusionEstimated TBI prevalence is low in Denmark. We estimate that 200,000 persons have TBI and thus are at risk of developing TB. Screening for TBI and preventive treatment, especially in persons born in high TB incidence countries or immunosuppressed, are crucial to reduce the risk of and eliminate TB.

Racial disparities of gastric cancer in the USA: an overview of epidemiology, global screening guidelines, and targeted screening in a heterogeneous population.

Gastric cancer is the fifth most common cancer diagnosis and fourth leading cause of cancer-related death globally. The incidence of gastric cancer in the USA shows significant racial and ethnic disparities with gastric cancer incidence in Korean Americans being over five times higher than in non-Hispanic whites. Since gastric cancer is not common in the USA, there are no current screening guidelines. In countries with higher incidences of gastric cancer, screening guidelines have been implemented for early detection and intervention and this has been associated with a reduction in mortality. Immigrants from high incidence countries develop gastric cancer at lower rates once outside of their country of origin, but continue to be at higher risk for developing gastric cancer. This risk does seem to decrease with subsequent generations. With increasing availability of endoscopy, initiating gastric cancer screening guidelines for high-risk groups can have the potential to improve survival by diagnosing and treating gastric cancer at an earlier stage. This article aims to provide context to gastric cancer epidemiology globally, review risk factors for developing gastric cancer, highlight racial and ethnic disparities in gastric cancer burden in the USA, examine current guidelines that exist in high incidence countries, and suggest future studies examining the efficacy of additional screening in high-risk populations to reduce gastric cancer mortality and disparate burden on ethnic minorities in the USA.

Tuberculosis screening in the European migrant population: a scoping review of current practices.

Responding to a surge in new tuberculosis (TB) cases among migrants from high-incidence countries, low-incidence European nations have heeded World Health Organization recommendations by implementing TB screening in this population. This review aims to synthesise evidence on current screening strategies for active TB and latent tuberculosis infection (LTBI) in European high-income countries, and their main barriers and interventions. PubMed, Web of Science and Scopus were searched from March to April 2023, including articles in English, published in the last decade, pertaining to screening strategies for active TB or LTBI in Europe focused on migrants, excluding those exclusively composed of refugees, asylum seekers or other migrant populations. 32 studies fit the criteria. Screening in migrants varies between countries regarding timing, population, screening location and diagnosis. Furthermore, some barriers prevent migrants from benefiting from screening, namely physical, cultural and professional barriers. Additional research is needed to determine the patterns through which regular migrants adhere to current screening strategies in European countries.

Mapping the incidence rate of typhoid fever in sub-Saharan Africa.

With more than 1.2 million illnesses and 29,000 deaths in sub-Saharan Africa in 2017, typhoid fever continues to be a major public health problem. Effective control of the disease would benefit from an understanding of the subnational geospatial distribution of the disease incidence. We collated records of the incidence rate of typhoid fever confirmed by culture of blood in Africa from 2000 to 2022. We estimated the typhoid incidence rate for sub-Saharan Africa on 20 km × 20 km grids by exploring the association with geospatial covariates representing access to improved water and sanitation, health conditions of the population, and environmental conditions. We identified six published articles and one pre-print representing incidence rate estimates in 22 sites in 2000-2022. Estimated incidence rates showed geospatial variation at sub-national, national, and regional levels. The incidence rate was high in Western and Eastern African subregions followed by Southern and Middle African subregions. By age, the incidence rate was highest among 5-14 yo followed by 2-4 yo, > 14 yo, and 0-1 yo. When aggregated across all age classes and grids that comprise each country, predicted incidence rates ranged from 43.7 (95% confidence interval: 0.6 to 591.2) in Zimbabwe to 2,957.8 (95% CI: 20.8 to 4,245.2) in South Sudan per 100,000 person-years. Sub-national heterogeneity was evident with the coefficient of variation at the 20 km × 20 km grid-level ranging from 0.7 to 3.3 and was generally lower in high-incidence countries and widely varying in low-incidence countries. Our study provides estimates of 20 km × 20 km incidence rate of typhoid fever across sub-Saharan Africa based on data collected from 2000 through 2020. Increased understanding of the subnational geospatial variation of typhoid fever in Africa may inform more effective intervention programs by better targeting resources to heterogeneously disturbed disease risk.

Accuracy of digital chest x-ray analysis with artificial intelligence software as a triage and screening tool in hospitalized patients being evaluated for tuberculosis in Lima, Peru.

Tuberculosis (TB) transmission in healthcare facilities is common in high-incidence countries. Yet, the optimal approach for identifying inpatients who may have TB is unclear. We evaluated the diagnostic accuracy of qXR (Qure.ai, India) computer-aided detection (CAD) software versions 3.0 and 4.0 (v3 and v4) as a triage and screening tool within the FAST (Find cases Actively, Separate safely, and Treat effectively) transmission control strategy. We prospectively enrolled two cohorts of patients admitted to a tertiary hospital in Lima, Peru: one group had cough or TB risk factors (triage) and the other did not report cough or TB risk factors (screening). We evaluated the sensitivity and specificity of qXR for the diagnosis of pulmonary TB using culture and Xpert as primary and secondary reference standards, including stratified analyses based on risk factors. In the triage cohort (n = 387), qXR v4 sensitivity was 0.91 (59/65, 95% CI 0.81-0.97) and specificity was 0.32 (103/322, 95% CI 0.27-0.37) using culture as reference standard. There was no difference in the area under the receiver-operating-characteristic curve (AUC) between qXR v3 and qXR v4 with either a culture or Xpert reference standard. In the screening cohort (n = 191), only one patient had a positive Xpert result, but specificity in this cohort was high (>90%). A high prevalence of radiographic lung abnormalities, most notably opacities (81%), consolidation (62%), or nodules (58%), was detected by qXR on digital CXR images from the triage cohort. qXR had high sensitivity but low specificity as a triage in hospitalized patients with cough or TB risk factors. Screening patients without cough or risk factors in this setting had a low diagnostic yield. These findings further support the need for population and setting-specific thresholds for CAD programs.

Evaluation of a short training course of chest X-ray interpretation for the diagnosis of paediatric TB.

Chest X-ray (CXR) interpretation is challenging for the diagnosis of paediatric TB. We assessed the performance of a three half-day CXR training module for healthcare workers (HCWs) at low healthcare levels in six high TB incidence countries. Within the TB-Speed Decentralization Study, we developed a three half-day training course to identify normal CXR, CXR of good quality and identify six TB-suggestive features. We performed a pre-post training assessment on a pre-defined set of 20 CXR readings. We compared the proportion of correctly interpreted CXRs and the median reading score before and after the training using the McNemar test and a linear mixed model. Of 191 HCWs, 43 (23%) were physicians, 103 (54%) nurses, 18 (9.4%) radiology technicians and 12 (6.3%) other professionals. Of 2,840 CXRs with both assessment, respectively 1,843 (64.9%) and 2,277 (80.2%) were correctly interpreted during pre-training and post-training (P < 0.001). The median reading score improved significantly from 13/20 to 16/20 after the training, after adjusting by country, facility and profession (adjusted β = 3.31, 95% CI 2.44-4.47). Despite some limitations of the course assessment that did not include abnormal non-TB suggestive CXR, study findings suggest that a short CXR training course could improve HCWs' interpretation skills in diagnosing paediatric TB.

Genetic testing for familial melanoma.

While the average lifetime risk of melanoma worldwide is approximately 3%, those with inherited high-penetrance mutations face an increased lifetime risk of 52-84%. In countries of low melanoma incidence, such as in Southern Europe, familial melanoma genetic testing may be warranted when there are two first degree relatives with a melanoma diagnosis. Testing criteria for high incidence countries such as USA, or with very-high incidence, such as Australia and New Zealand, would require a threshold of 3 to 4 affected family members. A mutation in the most common gene associated with familial melanoma, CDKN2A, is identified in approximately 10-40% of those meeting testing criteria. However, the use of multi-gene panels covering additional less common risk genes can significantly increase the diagnostic yield. Currently, genetic testing for familial melanoma is typically conducted by qualified genetic counsellors, however with increasing demand on testing services and high incidence rate in certain countries, a mainstream model should be considered. With appropriate training, dermatologists are well placed to identify high risk individuals and offer melanoma genetic test in dermatology clinics. Genetic testing should be given in conjunction with pre- and post-test consultation. Informed patient consent should cover possible results, the limitations and implications of testing including inconclusive results, and potential for genetic discrimination. Previous studies reporting on participant outcomes of genetic testing for familial melanoma have found significant improvements in both sun protective behavior and screening frequency in mutation carriers.

The Challenges of Tuberculosis Management beyond Professional Competence: Insights from Tuberculosis Outbreaks among Ethiopian Immigrants in Israel.

Controlling tuberculosis (TB) among immigrants from high-incidence countries presents a public health concern as well as a medical challenge. In this article, we investigate a TB outbreak in a community of people of Jewish descent who emigrated from Ethiopia to Israel (Israeli Ethiopians) that started in June 2022. The index case was a 20-year-old female who had recently immigrated to Israel with her family. Her pre-immigration tuberculin skin test was positive. After excluding active TB, treatment with daily isoniazid for latent TB (LTB) was started shortly after her arrival. A year later, she was diagnosed with smear-positive, culture-positive, pulmonary TB. Investigation of 83 contacts revealed five additional patients with active TB, and three of whom were members were of her household. In this article, we report the current TB outbreak, review previously published TB outbreaks involving Israeli Ethiopians, analyze the factors that triggered each of these outbreaks, and discuss the challenges that face the Israeli TB control program in an era of declining TB incidence and diminishing resources available for TB control.

The effect of M. tuberculosis lineage on clinical phenotype.

Six lineages of Mycobacterium tuberculosis sensu stricto (which excludes M. africanum) are described. Single-country or small observational data suggest differences in clinical phenotype between lineages. We present strain lineage and clinical phenotype data from 12,246 patients from 3 low-incidence and 5 high-incidence countries. We used multivariable logistic regression to explore the effect of lineage on site of disease and on cavities on chest radiography, given pulmonary TB; multivariable multinomial logistic regression to investigate types of extra-pulmonary TB, given lineage; and accelerated failure time and Cox proportional-hazards models to explore the effect of lineage on time to smear and culture-conversion. Mediation analyses quantified the direct effects of lineage on outcomes. Pulmonary disease was more likely among patients with lineage(L) 2, L3 or L4, than L1 (adjusted odds ratio (aOR) 1.79, (95% confidence interval 1.49-2.15), p<0.001; aOR = 1.40(1.09-1.79), p = 0.007; aOR = 2.04(1.65-2.53), p<0.001, respectively). Among patients with pulmonary TB, those with L1 had greater risk of cavities on chest radiography versus those with L2 (aOR = 0.69(0.57-0.83), p<0.001) and L4 strains (aOR = 0.73(0.59-0.90), p = 0.002). L1 strains were more likely to cause osteomyelitis among patients with extra-pulmonary TB, versus L2-4 (p = 0.033, p = 0.008 and p = 0.049 respectively). Patients with L1 strains showed shorter time-to-sputum smear conversion than for L2. Causal mediation analysis showed the effect of lineage in each case was largely direct. The pattern of clinical phenotypes seen with L1 strains differed from modern lineages (L2-4). This has implications for clinical management and could influence clinical trial selection strategies.

Screening Practices and Risk Factors for Co-Infection with Latent Tuberculosis and Hepatitis B Virus in an Integrated Healthcare System — California, 2008-2019

BackgroundHepatitis B virus (HBV) and latent tuberculosis infection are associated with a significant global burden, but both are underdiagnosed and undertreated. We described the screening patterns and risk factors for co-infection with latent tuberculosis and HBV within a large healthcare system. MethodsUsing data from Kaiser Permanente Southern California during 2008-2019, we described HBV infections, defined as a positive HBV surface antigen, e-antigen, or DNA test, and latent tuberculosis, defined as a positive Mantoux tuberculin skin test or interferon-gamma release assay test. We estimated adjusted odds ratios (aOR) for co-infection among screened adults with either infection. ResultsAmong 1997 HBV patients screened for latent tuberculosis, 23.1% were co-infected, and among 35,820 patients with latent tuberculosis screened for HBV, 1.3% were co-infected. Among HBV patients, co-infection risk was highest among Asians compared with White race/ethnicity (29.4% vs 5.7%, aOR 4.78; 95% confidence interval [CI], 2.75-8.31), and persons born in a high-incidence country compared with low-incidence countries (31.0% vs 6.6%; aOR 4.19; 95% CI, 2.61-6.73). For patients with latent tuberculosis, risk of co-infection was higher among Asian (aOR 9.99; 95% CI, 5.79-17.20), or Black race/ethnicity (aOR 3.33; 95% CI, 1.78-6.23) compared with White race/ethnicity. Persons born in high-incidence countries had elevated risk of co-infection compared with persons born in low-incidence countries (aOR 2.23; 95% CI, 1.42-3.50). However, Asians or persons born in high-incidence countries were screened at similar rates to other ethnicities or persons born in low-incidence countries. ConclusionsLatent tuberculosis risk is elevated among HBV patients, and vice versa. Risk of co-infection was highest among persons born in high-incidence countries and Asians. These findings support recent guidelines to increase HBV and tuberculosis screening, particularly among persons with either infection.

The COVID-19 Pandemic and Dental Professionals' Infection Risk Perception: An International Survey.

A global survey among dentists was used to identify the various impacts of the COVID-19 pandemic on this professional group. Special attention was given to perception and assessment of infection risk. From May to August 2020, the questionnaire was delivered in 36 countries by respective research groups and was completed by 52,491 dental professionals. The survey was designed as a cross-sectional survey based on a previously standardized questionnaire. This study focuses on the part of the questionnaire that deals with the perception of the infection risk of COVID-19 by dentists and their patients. A logistic regression model was used, which consisted of four Likert items as response options and the additional self-reported routine or emergency treatment as the dependent variable. Analysis by continent found that European and Asian dentists were particularly likely to be infected at work (OR = 1.45 95%CI = 1.02/1.84 and OR = 2.68, 95%CI = 1.45/3.22, respectively), while it was likely that Australian dentists did not feel particularly at risk due to low infection rates. Three quarters of Americans treated only emergencies during this survey period, while Europeans (64.71%) and Asians (66.67%) provided mostly routine care. This could affect the Europeans' confidence that they would not be able to protect themselves from infections in the long-term. The COVID-19 pandemic and its impact on dental professionals' infection risk perception is determined by the geographical origin of dentists. This study shows that, especially in high-incidence countries, infection risk perception was higher when dentists tried to provide routine dental procedures to their patients. Dental professionals can offer themselves and their patients good protection by maintaining high standards of hygiene. However, their concerns should be taken seriously and the dental professionals' group that is of great importance for oral health care and prevention, should not be neglected in the future, even in the event of emerging pandemics.

Practices in the Management of Incidental Gallbladder Cancer.

Peeyush VarshneyBackground Histopathology of gallbladder removed for stones may reveal incidental gallbladder cancer (iGBC). We conducted this online e-survey to document the knowledge and practices of management of iGBC among surgeons in India. Methods A 38-question online e-survey Results Two-hundred thirty responses were recorded. Ninety-eight out of two-hundred (49%) responses were general surgeons. Two-hundred ten out of two-hundred twenty-one (95%) saw at least one iGBC per year, but only 74/225 (32%) correctly defined true iGBC. One-hundred seventy-eight out of two hundred twenty-two (80%) did computed tomography/magnetic resonance imaging for thick-walled gallbladder (GB) detected on ultrasound, while 25/222 (11%) did laparoscopic cholecystectomy and 14/222 (6%) did open cholecystectomy. For GB mass on laparoscopy, 16/222 (7%) responses went ahead with simple cholecystectomy. Seventy-four out of two-hundred twenty-five (32%) responses routinely used bag while extracting GB. One-hundred ninety-one out of two-hundred twenty-five (86%) mentioned about stone/bile spill, 121/220 (55%) mentioned about use of bag for extraction while 137/220 62% mentioned port used for extraction of GB in operation notes. One-hundred sixty-six out of two-hundred twenty-seven (73%) always cut open GB after cholecystectomy. On encountering a mass/lesion on cut open GB, 111/225 (49%) sent it for frozen section, 89/225 (40%) sent for routine histopathology while 10% (22/225) directly proceeded for extended cholecystectomy. Ten out of two-hundred twenty-seven (4.4%) did not consider it important to send GB for histopathology. T stage on histopathology is most important factor for deciding reoperation by 205/223 (91%). Conclusion There are lacunae in understanding and deficiencies in management of iGBC in India-a high GBC incidence country. The situation is likely to be worse in low GBC incidence areas. There is need for more awareness and knowledge for proper management of iGBC among surgeons.