Active pulmonary tuberculosis and coronavirus disease 2019: A systematic review and meta-analysis.

OBJECTIVE: The proportion of COVID-19 patients having active pulmonary tuberculosis, and its impact on COVID-19 related patient outcomes, is not clear. We conducted this systematic review to evaluate the proportion of patients with active pulmonary tuberculosis among COVID-19 patients, and to assess if comorbid pulmonary tuberculosis worsens clinical outcomes in these patients. METHODS: We queried the PubMed and Embase databases for studies providing data on (a) proportion of COVID-19 patients with active pulmonary tuberculosis or (b) severe disease, hospitalization, or mortality among COVID-19 patients with and without active pulmonary tuberculosis. We calculated the proportion of tuberculosis patients, and the relative risk (RR) for each reported outcome of interest. We used random-effects models to summarize our data. RESULTS: We retrieved 3,375 citations, and included 43 studies, in our review. The pooled estimate for proportion of active pulmonary tuberculosis was 1.07% (95% CI 0.81%-1.36%). COVID-19 patients with tuberculosis had a higher risk of mortality (summary RR 1.93, 95% CI 1.56-2.39, from 17 studies) and for severe COVID-19 disease (summary RR 1.46, 95% CI 1.05-2.02, from 20 studies), but not for hospitalization (summary RR 1.86, 95% CI 0.91-3.81, from four studies), as compared to COVID-19 patients without tuberculosis. CONCLUSION: Active pulmonary tuberculosis is relatively common among COVID-19 patients and increases the risk of severe COVID-19 and COVID-19-related mortality.

Comparing rates of mycobacterial clearance in sputum smear-negative and smear-positive adults living with HIV.

BACKGROUND: Pulmonary tuberculosis (TB) in people living with HIV (PLH) frequently presents as sputum smear-negative. However, clinical trials of TB in adults often use smear-positive individuals to ensure measurable bacterial responses following initiation of treatment, thereby excluding HIV-infected patients from trials. METHODS: In this prospective case cohort study, 118 HIV-seropositive TB patients were assessed prior to initiation of standard four-drug TB therapy and at several time points through 35 days. Sputum bacillary load, as a marker of treatment response, was determined serially by: smear microscopy, Xpert MTB/RIF, liquid culture, and colony counts on agar medium. RESULTS: By all four measures, patients who were baseline smear-positive had higher bacterial loads than those presenting as smear-negative, until day 35. However, most smear-negative PLH had significant bacillary load at enrolment and their mycobacteria were cleared more rapidly than smear-positive patients. Smear-negative patients' decline in bacillary load, determined by colony counts, was linear to day 7 suggesting measurable bactericidal activity. Moreover, the decrease in bacterial counts was comparable to smear-positive individuals. Increasing cycle threshold values (Ct) on the Xpert assay in smear-positive patients to day 14 implied decreasing bacterial load. CONCLUSION: Our data suggest that smear-negative PLH can be included in clinical trials of novel treatment regimens as they contain sufficient viable bacteria, but allowances for late exclusions would have to be made in sample size estimations. We also show that increases in Ct in smear-positive patients to day 14 reflect treatment responses and the Xpert MTB/RIF assay could be used as biomarker for early treatment response.

Diagnostic performance of GeneXpert in tuberculosis-HIV co-infected patients at Asella Teaching and Referral Hospital, Southeastern Ethiopia: A cross sectional study.

BACKGROUND: GeneXpert is a new introduction in the diagnostic modality to fight tuberculosis (TB) among people living with HIV (PLHIV) under the program of intensified TB case finding. This study aimed to evaluate the diagnostic performance of GeneXpert under the program of intensified TB cases finding among PLHIV. METHODS: Cross-sectional study was conducted by recruiting individuals attending an HIV clinic from February 2018 to January 2019. Data on clinical parameters were collected using a standardized tool. Two-morning sputum samples were collected and processed for smear microscopy and GeneXpert. SPSS 21 used for data analysis. Proportion, percentage, and mean with SD were used to describe variables. Univariate and multivariable logistic regressions were used to assess factors associated with the GeneXpert. Values for which the 95% CI interval not includes 1 and for which P<0.05 were considered significant. RESULT: A total of 384 presumptive TB-HIV co-infection cases were included, of which 166 (43%) were diagnosed to have TB. Fifty-four (32.5%) TB cases were smear AFB positive while 79 (47.7%) TB cases were GeneXpert positive. The GeneXpert detection rate was almost two-fold of that of smear microscopy and all smear positive TB cases were detected by GeneXpert. Moreover, GeneXpert was able to detect an additional third of TB confirmed cases among smear AFB negative cases. Advanced stage of the disease, high viral load and presence of anemia were significantly associated with TB. The WHO TB screening tool remained least sensitive with the lowest positive predictive value. CONCLUSION: GeneXpert demonstrated two-fold case detection rate compared to the sputum smear microscopy and additional third TB case detection rate among smear AFB negative cases. Clinical screening tool for evaluation of TB-HIV co-infection showed poor performance in TB case notification.

Risk factors for Covid-19 severity and fatality: a structured literature review.

PURPOSE: Covid-19 is a global threat that pushes health care to its limits. Since there is neither a vaccine nor a drug for Covid-19, people with an increased risk for severe and fatal courses of disease particularly need protection. Furthermore, factors increasing these risks are of interest in the search of potential treatments. A systematic literature review on the risk factors of severe and fatal Covid-19 courses is presented. METHODS: The review is carried out on PubMed and a publicly available preprint dataset. For analysis, risk factors are categorized and information regarding the study such as study size and location are extracted. The results are compared to risk factors listed by four public authorities from different countries. RESULTS: The 28 records included, eleven of which are preprints, indicate that conditions and comorbidities connected to a poor state of health such as high age, obesity, diabetes and hypertension are risk factors for severe and fatal disease courses. Furthermore, severe and fatal courses are associated with organ damages mainly affecting the heart, liver and kidneys. Coagulation dysfunctions could play a critical role in the organ damaging. Time to hospital admission, tuberculosis, inflammation disorders and coagulation dysfunctions are identified as risk factors found in the review but not mentioned by the public authorities. CONCLUSION: Factors associated with increased risk of severe or fatal disease courses were identified, which include conditions connected with a poor state of health as well as organ damages and coagulation dysfunctions. The results may facilitate upcoming Covid-19 research.

Perceived stigma among patient with pulmonary tuberculosis at public health facilities in southwest Ethiopia: A cross-sectional study.

OBJECTIVES: Although tuberculosis (TB) related stigma has a significant impact on the diagnosis, patient adherence with treatment, and recovery from the disease, there is limited evidence from Ethiopia regarding perceived stigma among patient with pulmonary tuberculosis (PTB).The purpose of this study was to assess perceived stigma and associated factors among patient with PTB on treatment in southwest Ethiopia. METHODS: Institution-based cross-sectional study was conducted from April to May 2019 among 410 patient with PTB. Data were collected by using the perceived tuberculosis stigma scale. Epi data v3.1 and SPSSv23 were used for data entry and analysis. Multivariable logistic regression models were fitted to identify factors associated with perceived stigma. Results are presented as adjusted odds ratios (AORs) with 95% confidence intervals (CIs). RESULT: Prevalence of perceived stigma among patient with Pulmonary tuberculosis was 57.1% (95% CI: 52.2, 61.7). Poor social support (AOR = 2.41; 95% CI: 1.06, 5.48), above a month duration of illness (AOR = 2.48; 95% CI: 1.33, 4.64), high perceived stress (AOR = 1.95; 95% CI:1.09, 3.49), current khat use (AOR = 1.88; 95% CI:1.05, 3.37), and presence of depression (AOR = 8.18; 95% CI:4.40, 15.22) were significantly associated with perceived stigma. Patient with HIV co-infection were 5.67 times (AOR = 5.67; 95% CI: 2.32, 13.87) more likely to have Perceived stigma than their counterparts. CONCLUSION: TB related stigma was reported by more than half of the study participant. Stigma reduction measures are needed to lower TB related stigma perceived by the patient, the level of distress associated with it, and to promote the psychological wellbeing of patient with TB.

Treatment outcomes of drug-resistant tuberculosis in people living with HIV in Odesa province, Ukraine, 2014-2016.

INTRODUCTION: Odesa province has the highest TB/HIV prevalence in Ukraine, exceeding the total prevalence in the country by 3 times. The objective of this study was to investigate the unfavorable treatment outcomes and associated factors in patient with drug-resistant (DR) TB in people living with HIV (PLH) in Odesa. METHODOLOGY: A cohort study with secondary data analysis was conducted among 373 PLH with confirmed pulmonary DR TB for 2014-2016. RESULTS: About 2/3rd of the cohort were males from urban areas. Mean age and CD4 counts were 39 and 203, respectively. The overall treatment success was 44.2% with the most unfavorable treatment outcomes being observed in extensively and pre-extensively drug resistant (XDR and PreXDR) TB. The mean time between the results of GeneXpert (manufactured by Cepehid) and DR TB treatment based on GeneXpert was 1.3 days. However, the mean time between DR TB treatment based on GeneXpert and results of drug susceptibility test (DST) was 37.0 days referring to a late reporting of DST and to a late adjustment of previously prescribed treatment. The factors associated with the treatment unfavorable outcome included XDR and Pre-XDR TB, lack of antiretroviral treatment (ART), contrimoxazole preventive therapy (CPT) and CD4 test. CONCLUSIONS: The rate of successful DR TB treatment in PLH in Odesa remains low. The delayed reporting of DST contributes to lack of timely adjusted treatments. XDR and Pre-XDR TB, lack of ART and CPT are associated with unfavorable treatment outcomes. Additional studies would help to understand the temporal relationship between CD4 test and treatment outcomes.

Brief Report: Proportion and Predictors of Adult TB Contacts Accepting HIV Testing During an Active TB Case Finding Intervention in South Africa.

BACKGROUND: Many individuals at risk for HIV may be reached through active TB case finding interventions in areas with highly prevalent co-epidemics of TB/HIV. METHODS: We analyzed data from a cluster-randomized trial of 2 TB case finding strategies: facility-based screening and contact investigation of newly identified TB cases. In both arms, on-site rapid HIV testing was offered to all contacts older than 18 months who did not self-report HIV-positive status. Those who were HIV infected were referred appropriately. All contacts 15 years and older were included in this analysis. RESULTS: Among 2179 contacts identified, 50% (1092) accepted HIV testing and counselling, of whom 6.3% (68) tested HIV-positive. Contacts who were unemployed [adjusted prevalence ratio (aPR) 1.14, 95% confidence interval (CI): 1.04 to 1.25], had not been to a clinic (aPR 1.09, 95% CI: 1.02 to 1.18) or HIV tested (aPR 1.25, 95% CI: 1.14 to 1.39) 6 months before, and those reporting gastrointestinal symptoms (aPR 1.22, 95% CI: 0.98 to 1.52) and genitourinary symptoms (aPR 1.30, 95% CI: 1.17 to 1.45) were significantly associated with accepting HIV testing. Women [adjusted odds ratio (aOR) 2.19, 95% CI: 1.26 to 3.81], individuals with a past history of tuberculosis (aOR 1.96, 95% CI: 0.93 to 4.14), and those not HIV tested 6 months before (aOR 2.20, 95% CI: 1.28 to 3.79) were significantly associated with testing HIV-positive. CONCLUSION: Offering HIV testing in the context of active tuberculosis case finding represents an opportunity to identify a large proportion of previously undiagnosed individuals with HIV in a population that might otherwise not seek testing.

Case Report: COVID-19 Recovery from Triple Infection with Mycobacterium tuberculosis, HIV, and SARS-CoV-2.

COVID-19, designated as SARS-CoV-2, has caused millions of infections worldwide, including in patients with concomitant infections. Here, we report two unusual cases of patients with triple infections of SARS-CoV-2, Mycobacterium tuberculosis, and HIV. Both cases were confirmed through microbiological and immunological studies. The acute respiratory phase in both patients was treated with supplemental oxygen. Antituberculosis and antiretroviral therapies were started simultaneously. In 2 weeks, both patients demonstrated clinical improvement and recovery from COVID-19. Our findings suggest that even in cases of triple infection, clinical management together with respiratory therapy contributes to patient survival.

Case Report: Coronavirus Disease and Pulmonary Tuberculosis in Patients with Human Immunodeficiency Virus: Report of Two Cases.

Coinfection of SARS-CoV-2/Mycobacterium tuberculosis (MTB) in patients with HIV/AIDS has not been previously reported. Here, we present two cases of coinfection of SARS-CoV-2 and MTB in patients with HIV. The first case is a 39-year-old patient who was admitted with a 7-day history of fever, myalgia, headache, and cough. The second patient is a 43-year-old man who had a 1-month history of cough with hemoptoic sputum, evolving to mild respiratory distress in the last 7 days. Both patients already had pulmonary tuberculosis and subsequently developed SARS-CoV-2 infection during the 2020 pandemic. Nonadherence to antiretroviral treatment may have been a factor in the clinical worsening of the patients.

Characteristics Indicative of Tuberculosis/HIV Coinfection in a High-Burden Setting: Lessons from 13,802 Incident Tuberculosis Cases in Harare, Zimbabwe.

Country-specific interventions targeting high-risk groups are necessary for a global reduction in Tuberculosis (TB)/HIV burden. We analyzed the data of 13,802 TB cases diagnosed in Harare, Zimbabwe, during 2013-2017. Pearson's chi-square tests and multivariate logistic regression models were used to identify patient characteristics significantly associated with TB/HIV coinfection. Of the 13,802 TB cases analyzed, 9,725 (70.5%) were HIV positive. A significantly higher odds of having TB/HIV coinfection diagnosis was found among females, patients aged 25-64 years, previously treated cases, and acid-fast bacillus sputum smear-negative cases. Compared with nondisseminated pulmonary TB, miliary TB (adjusted odds ratio [aOR]: 1.469, 95% CI: 1.071, 2.015) and TB meningitis (aOR: 1.715, 95% CI: 1.074, 2.736) both had a significantly higher odds for TB/HIV coinfection, whereas pleural TB (aOR 0.420, 95% CI: 0.354, 0.497) and all other extrapulmonary TB (EPTB) (aOR: 0.606, 95% CI: 0.516 0.712) were significantly less likely to have TB/HIV coinfection. The risk for TB/HIV coinfection varied significantly by patients' sociodemographic and clinical characteristics in Harare. Our finding that different forms of EPTB have different relationships with HIV coinfection has extended the knowledge base about clinical markers for TB/HIV coinfection which can lead to a greater public health impact on eliminating TB/HIV infection.

Extrapulmonary tuberculosis in HIV-infected patients in rural Tanzania: The prospective Kilombero and Ulanga antiretroviral cohort.

BACKGROUND: In sub-Saharan Africa, diagnosis and management of extrapulmonary tuberculosis (EPTB) in people living with HIV (PLHIV) remains a major challenge. This study aimed to characterize the epidemiology and risk factors for poor outcome of extrapulmonary tuberculosis in people living with HIV (PLHIV) in a rural setting in Tanzania. METHODS: We included PLHIV >18 years of age enrolled into the Kilombero and Ulanga antiretroviral cohort (KIULARCO) from 2013 to 2017. We assessed the diagnosis of tuberculosis by integrating prospectively collected clinical and microbiological data. We calculated prevalence- and incidence rates and used Cox regression analysis to evaluate the association of risk factors in extrapulmonary tuberculosis (EPTB) with a combined endpoint of lost to follow-up (LTFU) and death. RESULTS: We included 3,129 subjects (64.5% female) with a median age of 38 years (interquartile range [IQR] 31-46) and a median CD4+ cell count of 229/µl (IQR 94-421) at baseline. During the median follow-up of 1.25 years (IQR 0.46-2.85), 574 (18.4%) subjects were diagnosed with tuberculosis, whereof 175 (30.5%) had an extrapulmonary manifestation. Microbiological evidence by Acid-Fast-Bacillus stain (AFB-stain) or Xpert® MTB/RIF was present in 178/483 (36.9%) patients with pulmonary and in 28/175 (16.0%) of patients with extrapulmonary manifestations, respectively. Incidence density rates for pulmonary Tuberculosis (PTB and EPTB were 17.9/1000person-years (py) (95% CI 14.2-22.6) and 5.8/1000 py (95% CI 4.0-8.5), respectively. The combined endpoint of death and LTFU was observed in 1058 (33.8%) patients, most frequently in the subgroup of EPTB (47.2%). Patients with EPTB had a higher rate of the composite outcome of death/LTFU after TB diagnosis than with PTB [HR 1.63, (1.14-2.31); p = 0.006]. The adjusted hazard ratios [HR (95% CI)] for death/LTFU in EPTB patients were significantly increased for patients aged >45 years [HR 1.95, (1.15-3.3); p = 0.013], whereas ART use was protective [HR 0.15, (0.08-0.27); p <0.001]. CONCLUSIONS: Extrapulmonary tuberculosis was a frequent manifestation in this cohort of PLHIV. The diagnosis of EPTB in the absence of histopathology and mycobacterial culture remains challenging even with availability of Xpert® MTB/RIF. Patients with EPTB had increased rates of mortality and LTFU despite early recognition of the disease after enrollment.

N-Acetyltransferase 2 Genotypes among Zulu-Speaking South Africans and Isoniazid and N-Acetyl-Isoniazid Pharmacokinetics during Antituberculosis Treatment.

The distribution of N-acetyltransferase 2 gene (NAT2) polymorphisms varies considerably among different ethnic groups. Information on NAT2 single-nucleotide polymorphisms in the South African population is limited. We investigated NAT2 polymorphisms and their effect on isoniazid pharmacokinetics (PK) in Zulu black HIV-infected South Africans in Durban, South Africa. HIV-infected participants with culture-confirmed pulmonary tuberculosis (TB) were enrolled from two unrelated studies. Participants with culture-confirmed pulmonary TB were genotyped for the NAT2 polymorphisms 282C>T, 341T>C, 481C>T, 857G>A, 590G>A, and 803A>G using Life Technologies prevalidated TaqMan assays (Life Technologies, Paisley, UK). Participants underwent sampling for determination of plasma isoniazid and N-acetyl-isoniazid concentrations. Among the 120 patients, 63/120 (52.5%) were slow metabolizers (NAT2*5/*5), 43/120 (35.8%) had an intermediate metabolism genotype (NAT2*5/12), and 12/120 (11.7%) had a rapid metabolism genotype (NAT2*4/*11, NAT2*11/12, and NAT2*12/12). The NAT2 alleles evaluated in this study were *4, *5C, *5D, *5E, *5J, *5K, *5KA, *5T, *11A, *12A/12C, and *12M. NAT2*5 was the most frequent allele (70.4%), followed by NAT2*12 (27.9%). Fifty-eight of 60 participants in study 1 had PK results. The median area under the concentration-time curve from 0 to infinity (AUC0-∞) was 5.53 (interquartile range [IQR], 3.63 to 9.12 µg h/ml), and the maximum concentration (Cmax) was 1.47 µg/ml (IQR, 1.14 to 1.89 µg/ml). Thirty-four of 40 participants in study 2 had both PK results and NAT2 genotyping results. The median AUC0-∞ was 10.76 µg·h/ml (IQR, 8.24 to 28.96 µg·h/ml), and the Cmax was 3.14 µg/ml (IQR, 2.39 to 4.34 µg/ml). Individual polymorphisms were not equally distributed, with some being represented in small numbers. The genotype did not correlate with the phenotype, with those with a rapid acetylator genotype showing higher AUC0-∞ values than those with a slow acetylator genotype, but the difference was not significant (P = 0.43). There was a high prevalence of slow acetylator genotypes, followed by intermediate and then rapid acetylator genotypes. The poor concordance between genotype and phenotype suggests that other factors or genetic loci influence isoniazid metabolism, and these warrant further investigation in this population.

Hepatitis C virus infection: a challenge in the complex management of two cases of multidrug-resistant tuberculosis.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) requires lengthy use of second-line drugs, burdened by many side effects. Hepatitis C virus (HCV) chronic infection increases risk of drug-induced liver injury (DILI) in these patients. Data on MDR-TB patients with concurrent HCV chronic infection treated at the same time with second-line antitubercular drugs and new direct-acting antivirals (DAAs) are lacking. We evaluate if treating at the same time HCV infection and pulmonary MDR-TB is feasible and effective. CASES PRESENTATION: In this study, we described two cases of patients with pulmonary MDR-TB and concurrent HCV chronic infection cured with DAAs at a Tertiary Infectious Diseases Hospital in Italy. During antitubercular treatment, both patients experienced a DILI before treating HCV infection. After DAAs liver enzymes normalized and HCV RNA was undetectable. Then antitubercular regimen was started according to the institutional protocol, drawn up following WHO MDR-TB guidelines. It was completed without further liver side effects and patients were declared cured from both HCV infection and MDR-TB. CONCLUSIONS: We suggest to consider treatment of chronic hepatitis C with DAAs as a useful intervention for reintroduction of second-line antitubercular agents in those patients who developed DILI, reducing the risk of treatment interruption when re-exposed to these drugs.

Prevalence of Human Immunodeficiency Virus Infection among Tuberculosis Patients in Nepal.

BACKGROUND: National Tuberculosis Program has envisioned to provide human immunodeficiency virus testing for all tuberculosis patients. However, human immunodeficiency virus testing coverage among notified tuberculosis patients is very low in Nepal. Hence, it is difficult to reflect the prevalence of human immunodeficiency virus infection among Tuberculosis patients based on the information available from the routine system. Hence National Tuberculosis Program carried out sentinel surveillance to assess the prevalence of human immunodeficiency virus infection among tuberculosis patients and its associated factors in Nepal. METHODS: This study is cross-sectional study type conducted at six sentinel sites across the country. This study lasted for six months starting from March 2017 to August 2017. The sample size was calculated using Epiinfo STATCAL application assuming confidence interval at 95%, 85% power and 5% non-response rate. The required sample size was 1672 tuberculosis patients. Ethical approval was obtained from Nepal Health Research Council. All types of tuberculosis patients who were equal or above 15 years were included in the study. Human immunodeficiency viruse testing was performed among tuberculosis patients as per the testing algorithm recommended by national guideline. RESULTS: The study was carried out among 1664 tuberculosis patients registered for tuberculosis treatment during the study period. More than two thirds of tuberculosis patients (67%) were male. The median age of tuberculosis patients was found 32 years. During human immunodeficiency virus testing, 41 out of 1664 tuberculosis patients were found human immunodeficiency virus positive resulting human immunodeficiency virus infection seroprevalence among tuberculosis patients to 2.5%. Prevalence of human immunodeficiency virus infection was significantly associated with age (P=0.002), caste/ethnicity (P=0.025), religion (P=0.015) and occupation (P=0.014) of tuberculosis patients. CONCLUSIONS: Prevalence of human immunodeficiency virus infection among tuberculosis patients was found 2.5%. Information and access to tuberculosis/human immunodeficiency virus services needs to be increased toaddress tuberculosis-human immunodeficiency virus co-infection in Nepal.

The determinants and impact of diagnostic delay in lymphoma in a TB and HIV endemic setting.

BACKGROUND: Little is known about the pathway to diagnosis of lymphoma in Sub-Saharan Africa, despite the increased risk of lymphoma in people living with HIV (PLHIV). The challenges of diagnosis in this setting include diagnostic confusion with extrapulmonary tuberculosis (EPTB), which commonly causes lymphadenopathy in PLHIV. METHODS: We analysed the time to diagnosis and treatment in patients using predetermined time intervals. Univariate and multivariable analyses were performed to determine the relationship between patient and disease-specific variables with delays to diagnosis. We were particularly interested in the impact of HIV, empiric tuberculosis therapy and fine-needle aspirate for cytology (FNAC) in contributing to delay. RESULTS: Patients (n = 163), 29% HIV-infected, waited a median of 4 weeks before seeking medical attention. It took a median of 7 weeks for the diagnosis of lymphoma to be made from the time the patient sought medical attention, termed the healthcare practitioner interval. In multivariable logistic regression analysis, diagnostic delay > 6 weeks was associated with late-stage disease (OR 2.3, 95% CI 1.1-5.2) and Hodgkin lymphoma (HL) (OR 3.0, 95% CI 1.1-8.0). HIV status was not associated with diagnostic delay (OR 0.9, 95% CI 0.3-2.2). The median time to diagnosis was a median of 4 weeks longer for patients on tuberculous (TB) therapy (n = 16, p = 0.28) and patients who underwent an FNAC (n = 63, p = 0.04). Where FNAC was performed, it was diagnostic for lymphoma in only 11%. Diagnostic delay was not associated with overall survival. CONCLUSIONS: Time-to-diagnosis of lymphoma in South Africa was similar to that reported from high-income countries and shows significant periods of delay between the onset of symptoms to diagnosis and treatment. The longest period of delay was in the health practitioner interval. Education regarding the significance of lymphadenopathy for both patients and health care practitioners and appropriate investigative steps preferably by best-practice algorithms specific to TB-endemic areas are needed to shorten the time-to-diagnosis of lymphoma.

Differential expression of CXCR3 and CCR6 on CD4+ T-lymphocytes with distinct memory phenotypes characterizes tuberculosis-associated immune reconstitution inflammatory syndrome.

Immune reconstitution inflammatory syndrome (IRIS) occurs in up to 40% of individuals co-infected with pulmonary tuberculosis (PTB) and HIV, primarily upon antiretroviral therapy (ART) initiation. Phenotypic changes in T-cells during TB-IRIS and their relationship with systemic inflammation are not fully understood. In this prospective cohort study, we followed 48 HIV-positive patients with PTB from South India before and after ART initiation, examining T-lymphocyte subsets and inflammatory biomarkers in peripheral blood. Quantification of naïve (CD27+CD45RO-) as well as effector memory CD4+ T cells (CD27-CD45RO+) at weeks 2-6 after ART initiation could distinguish TB-IRIS from non-IRIS individuals. Additional analyses revealed that ART reconstituted different quantities of CD4+ T lymphocyte subsets with preferential expansion of CXCR3+ CCR6- cells in TB-IRIS patients. Moreover, there was an expansion and functional restoration of central memory (CD27+CD45RO+) CXCR3+CCR6- CD4+ lymphocytes and corresponding cytokines, with reduction in CXCR3-CCR6+ cells after ART initiation only in those who developed TB-IRIS. Together, these observations trace a detailed picture of CD4+ T cell subsets tightly associated with IRIS, which may serve as targets for prophylactic and/or therapeutic interventions in the future.

Yield and Efficiency of Novel Intensified Tuberculosis Case-Finding Algorithms for People Living with HIV.

RATIONALE: The recommended tuberculosis (TB) intensified case finding (ICF) algorithm for people living with HIV (symptom-based screening followed by Xpert MTB/RIF [Xpert] testing) is insufficiently sensitive and results in unnecessary Xpert testing. OBJECTIVES: To evaluate whether novel ICF algorithms combining C-reactive protein (CRP)-based screening with urine Determine TB-LAM (TB-LAM), sputum Xpert, and/or sputum culture could improve ICF yield and efficiency. METHODS: We compared the yield and efficiency of novel ICF algorithms inclusive of point-of-care CRP-based TB screening and confirmatory testing with urine TB-LAM (if CD4 count ≤100 cells/µl), sputum Xpert, and/or a single sputum culture among consecutive people living with HIV with CD4 counts less than or equal to 350 cells/µl initiating antiretroviral therapy in Uganda. MEASUREMENTS AND MAIN RESULTS: Of 1,245 people living with HIV, 203 (16%) had culture-confirmed TB including 101 (49%) patients with CD4 counts less than or equal to 100 cells/µl. Compared with the current ICF algorithm, point-of-care CRP-based TB screening followed by Xpert testing had similar yield (56% [95% confidence interval, 49-63] vs. 59% [95% confidence interval, 51-65]) but consumed less than half as many Xpert assays per TB case detected (9 vs. 4). Addition of TB-LAM did not significantly increase diagnostic yield relative to the current ICF algorithm but provided same-day diagnosis for 26% of TB patients with advanced HIV. Addition of a single culture to TB-LAM and Xpert substantially improved ICF yield, identifying 78% of all TB cases. CONCLUSIONS: Point-of-care CRP-based screening can improve ICF efficiency among people living with HIV. Addition of TB-LAM and a single culture to Xpert confirmatory testing could enable HIV programs to increase the speed of TB diagnosis and ICF yield.

A mortality review of tuberculosis and HIV co-infected patients in Mahalapye, Botswana: Does cotrimoxazole preventive therapy and/or antiretroviral therapy protect against death?

BACKGROUND:  The World Health Organization aims to reduce tuberculosis (TB) mortality rate from 15% in 2015 to 6.5% by 2025. AIM:  This study determined the profile of TB and human immunodeficiency virus (HIV) co-infected patients who died in Mahalapye District, Botswana, while on anti-TB medication and the factors that contributed to such outcome. SETTING:  The study was conducted in the Mahalapye Health District in Botswana. METHODS:  This was a cross-sectional study that reviewed patient records from the Mahalapye District Health Management Team Electronic Tuberculosis Register from January 2013 to December 2015. RESULTS:  The majority of the TB and HIV co-infected patients were on antiretroviral therapy (ART) (486 [81.63%]) or were initiated cotrimoxazole preventive therapy (CPT) (518 [87.2%]) while taking anti-TB treatment. Seventy-three (13.6%) TB and HIV co-infected patients died before completing anti-TB treatment. Three-quarters (54 [74.4%]) of patients who died before completing anti-TB treatment were on ART, among them two patients who were on ART at least 3 months prior to commencing anti-TB. Also, the majority (64 [87.7%]) of TB and HIV co-infected patients were commenced on CPT prior to death. There was a bimodal density curve of death occurrence in those who did not commence ART and in those who did not commence CPT. CONCLUSION:  This study established that TB and HIV co-infected patients had a TB mortality of 13.6%. A high mortality rate was observed during the first 3 months in those who did not take ART and during the second and the fifth month in those who did not commence CPT. Further study is needed to clarify this matter.

Impact of tuberculosis and long term benefits of anti-retroviral treatment in patients with HIV in Sri Lanka

Introduction: Although prevalence of HIV infection in Sri Lanka is low, there is a gradual increase in incidence. Effective anti-retroviral treatment (ART) controls the virus, improves immunity and reduces transmission of HIV greatly. Objective: We studied the impact of tuberculosis and response to ART in a cohort of patients with HIV in Sri Lanka. Methodology: A retrospective study of all patients with HIV followed up at the ART clinic at National Institute of Infectious Diseases, Angoda, Sri Lanka was carried out. Their socio-demographic data, clinical presentations, anti-retroviral treatment and clinical, immunological and virological response were analysed. Results: Study included 72 patients. Mean age was 47.19 (SD-10.354) years. Male to female ratio was 1:0.8. Forty nine (68%) patients were diagnosed with HIV after presenting with an opportunistic infection. Of these, 25 had tuberculosis (TB). Another 5 developed TB later. Fifty two (72.2%) had CD4 cell counts<200/µl which included 45(62.5%) who had CD4<100/µl. Twenty six (36.1%) patients were bed ridden and a further 6 (8.3%) were physically dependent at the time of diagnosis. Mean duration of ART was 82.4 months. With ART, CD4 cell counts and mobility improved. In 38 (52.8%) CD4 counts increased to more than 500/µl. Viral load became undetectable in 62 (86.1%). Sixty nine (95.8%) became completely physically independent. Conclusion: TB is a common co-infection in patients with HIV in Sri Lanka. Though many patients with HIV presented with poor immunological and physical status, ART markedly improved these outcomes and reduced the viral load which results in prevention of spread of HIV. Therefore, ART should be supported and encouraged