A CD4+ TNF+ monofunctional memory T-cell response to BCG vaccination is associated with Mycobacterium tuberculosis infection in infants exposed to HIV.

BACKGROUND: The immunologic correlates of risk of Mycobacterium tuberculosis (Mtb) infection after BCG vaccination are unknown. The mechanism by which BCG influences the tuberculin skin test (TST) remains poorly understood. We evaluated CD4+ T-cell responses in infants exposed to HIV and uninfected (HEU) who received BCG at birth and examined their role in susceptibility to Mtb infection and influence on TST induration. METHODS: HEU infants were enrolled in a randomised clinical trial of isoniazid (INH) to prevent Mtb infection in Kenya. We measured mycobacterial antigen-specific Th1 and Th17 cytokine responses at 6-10 weeks of age prior to INH randomisation and compared responses between Mtb infected and uninfected infants. Outcomes at 14 months of age included TST, QuantiFERON-Plus (QFT-Plus), and ESAT-6/CFP-10-specific non-IFN-γ cytokines measured in QFT-Plus supernatants. FINDINGS: A monofunctional mycobacterial antigen-specific TNF+ CD4+ effector memory (CCR7-CD45RA-) T-cell response at 6-10 weeks of age was associated with Mtb infection at 14 months of age as measured by ESAT-6/CFP-10-specific IFN-γ and non-IFN-γ responses (Odds Ratio 2.26; Confidence Interval 1.27-4.15; P = 0.006). Mycobacterial antigen-specific polyfunctional effector memory Th1 responses at 6-10 weeks positively correlated with TST induration in infants without evidence of Mtb infection at 14 months, an association which was diminished by INH therapy. INTERPRETATION: Induction of monofunctional TNF+ CD4+ effector memory T-cell responses may be detrimental in TB vaccine development. This study also provides mechanistic insight into the association of BCG-induced immune responses with TST induration and further evidence that TST-based diagnoses of Mtb infection in infants are imprecise. FUNDING: Thrasher Research Fund.

Field evaluation of a prototype tuberculosis lipoarabinomannan lateral flow assay on HIV-positive and HIV-negative patients.

Detection of tuberculosis at the point-of-care (POC) is limited by the low sensitivity of current commercially available tests. We describe a diagnostic accuracy field evaluation of a prototype urine Tuberculosis Lipoarabinomannan Lateral Flow Assay (TB-LAM LFA) in both HIV-positive and HIV-negative patients using fresh samples with sensitivity and specificity as the measures of accuracy. This prototype combines a proprietary concentration system with a sensitive LFA. In a prospective study of 292 patients with suspected pulmonary tuberculosis in Uganda, the clinical sensitivity and specificity was compared against a microbiological reference standard including sputum Xpert MTB/RIF Ultra and solid and liquid culture. TB-LAM LFA had an overall sensitivity of 60% (95%CI 51-69%) and specificity of 80% (95%CI 73-85%). When comparing HIV-positive (N = 86) and HIV-negative (N = 206) patients, there was no significant difference in sensitivity (sensitivity difference 8%, 95%CI -11% to +24%, p = 0.4351) or specificity (specificity difference -9%, 95%CI -24% to +4%, p = 0.2051). Compared to the commercially available Alere Determine TB-LAM Ag test, the TB-LAM LFA prototype had improved sensitivity in both HIV-negative (difference 49%, 95%CI 37% to 59%, p<0.0001) and HIV-positive patients with CD4+ T-cell counts >200cells/µL (difference 59%, 95%CI 32% to 75%, p = 0.0009). This report is the first to show improved performance of a urine TB LAM test for HIV-negative patients in a high TB burden setting. We also offer potential assay refinement solutions that may further improve sensitivity and specificity.

Early-phase scale-up of isoniazid preventive therapy for people living with HIV in two districts in Malawi (2017).

BACKGROUND: Isoniazid preventive therapy (IPT) against tuberculosis (TB) is a life-saving intervention for people living with HIV (PLHIV). In September 2017, Malawi began programmatic scale-up of IPT to eligible PLHIV in five districts with high HIV and TB burden. We measured the frequency and timeliness of early-phase IPT implementation to inform quality-improvement processes. METHODS AND FINDINGS: We applied a two-stage cluster design with systematic, probability-proportional-to-size sampling of six U.S. Centers for Disease Control and Prevention (CDC)-affiliated antiretroviral therapy (ART) centers operating in the urban areas of Lilongwe and Blantyre, Malawi (November 2017). ART clinic patient volume determined cluster size. Within each cluster, we sequentially sampled approximately 50 PLHIV newly enrolled in ART care. We described a quality-of-care cascade for intensive TB case finding (ICF) and IPT in PLHIV. PLHIV newly enrolled in ART care were eligibility-screened for hepatitis and peripheral neuropathy, as well as for TB disease using a standardized four-symptom screening tool. Among eligible PLHIV, the overall weighted IPT initiation rate was 70% (95% CI: 46%-86%). Weighted IPT initiation among persons aged <15 years (30% [95% CI: 12%-55%]) was significantly lower than among persons aged ≥15 years (72% [95% CI: 47%-89%]; Rao-Scott chi-square P = 0.03). HIV-positive children aged <5 years had a weighted initiation rate of only 13% (95% CI: 1%-79%). For pregnant women, the weighted initiation rate was 67% (95% CI: 32%-90%), similar to non-pregnant women aged ≥15 years (72% [95% CI: 49%-87%]). Lastly, 95% (95% CI: 92%-97%) of eligible PLHIV started ART within one week of HIV diagnosis, and 92% (95% CI: 73%-98%) of patients receiving IPT began on the same day as ART. CONCLUSIONS: Early-phase IPT uptake among adults at ART centers in Malawi was high. Child uptake needed improvement. National programs could adapt this framework to evaluate their ICF-IPT care cascades.

Coronavirus Activates an Altruistic Stem Cell-Mediated Defense Mechanism that Reactivates Dormant Tuberculosis: Implications in Coronavirus Disease 2019 Pandemic.

We postulate that similar to bacteria, adult stem cells may also exhibit an altruistic defense mechanism to protect their niche against external threat. Herein, we report mesenchymal stem cell (MSC)-based altruistic defense against a mouse model of coronavirus, murine hepatitis virus-1 (MHV-1) infection of lung. MHV-1 infection led to reprogramming of CD271+ MSCs in the lung to an enhanced stemness phenotype that exhibits altruistic behavior, as per previous work in human embryonic stem cells. The reprogrammed MSCs exhibited transient expansion for 2 weeks, followed by apoptosis and expression of stemness genes. The conditioned media of the reprogrammed MSCs exhibited direct antiviral activity in an in vitro model of MHV-1-induced toxicity to type II alveolar epithelial cells by increasing their survival/proliferation and decreasing viral load. Thus, the reprogrammed MSCs can be identified as altruistic stem cells (ASCs), which exert a unique altruistic defense against MHV-1. In a mouse model of MSC-mediated Mycobacterium tuberculosis (MTB) dormancy, MHV-1 infection in the lung exhibited 20-fold lower viral loads than the MTB-free control mice on the third week of viral infection, and exhibited six-fold increase of ASCs, thereby enhancing the altruistic defense. Notably, these ASCs exhibited intracellular replication of MTB, and their extracellular release. Animals showed tuberculosis reactivation, suggesting that dormant MTB may exploit ASCs for disease reactivation.

HCV Seroprevalence among HIV Patients and Associated Comorbidities at One Primary Health Facility in Rwanda.

Hepatitis C virus (HCV) and HIV have emerged as major viral infections within the past two decades, and their coinfection poses a big challenge with a significant impact in terms of morbidity and mortality associated with liver disease and renal failure. The current study aimed at assessing the prevalence of HCV infection and associated comorbidities among HIV patients at one primary health facility in Rwanda. In total, 417 HIV-positive patients were recruited and included in the study from January 1, 2019 up to June 30, 2019. All participants were screened for HCV infection by using the SD Bioline HCV antibody rapid test. In addition, underlying medical conditions were also recorded as comorbidities. Among 417 participants, 52 exhibited HCV-positive results (12.5%). The group of 41- to 50- and 51- to 60-year-olds had higher prevalence of HIV/HCV coinfection than other age-groups with 3.6% and 4.6%, respectively. Furthermore, five underlying medical conditions were found as comorbidities among the study participants. Those with HIV/HCV coinfection showed higher comorbidities than those with mono-infection including liver toxicity, P value 0.005; tuberculosis, P value 0.005; renal failure, P value 0.003; hypertension, P value 0.001; and diabetes mellitus, P value 0.001. The relative risk ratio of having comorbidities in those groups was 4.09. To conclude, the prevalence of HCV/HIV coinfection is high, and there was a statistical significant association of having comorbidities in HIV/HCV-coinfected group compared with the group of HIV mono-infection, which suggests more intervention in this vulnerable group of patients.

Mortality and risk of tuberculosis among people living with HIV in whom TB was initially ruled out.

Tuberculosis (TB) misdiagnosis remains a public health concern, especially among people living with HIV (PLHIV), given the high mortality associated with missed TB diagnoses. The main objective of this study was to describe the all-cause mortality, TB incidence rates and their associated risk factors in a cohort of PLHIV with presumptive TB in whom TB was initially ruled out. We retrospectively followed a cohort of PLHIV with presumptive TB over a 2 year-period in a rural district in Southern Mozambique. During the study period 382 PLHIV were followed-up. Mortality rate was 6.8/100 person-years (PYs) (95% CI 5.2-9.2) and TB incidence rate was 5.4/100 PYs (95% CI 3.9-7.5). Thirty-six percent of deaths and 43% of TB incident cases occurred in the first 12 months of the follow up. Mortality and TB incidence rates in the 2-year period after TB was initially ruled out was very high. The TB diagnostic work-up and linkage to HIV care should be strengthened to decrease TB burden and all-cause mortality among PLHIV with presumptive TB.

Convalescent (immune) plasma treatment in a myelodysplastic COVID-19 patient with disseminated tuberculosis.

During the ongoing COVID-19 pandemic due to the SARS-CoV-2 virus of which evidence-based medical paradigms cannot be easily applied; difficult clinical decisions shall be required particularly in the 'difficult-to-treat' cases of high risk group with associated comorbidities. Convalescent immune plasma therapy is a promising option as a sort of 'rescue' treatment in COVID-19 immune syndrome, where miraculous antiviral drugs are not available yet. In this report, we aim to convey our experience of multi-task treatment approach with convalescent immune plasma and anti-cytokine drug combination in a COVID-19 patient with extremely challenging comorbidities including active myeloid malignancy, disseminated tuberculosis and kidney failure.

Human T-cell leukemia virus type 1 may invalidate T-SPOT.TB assay results in rheumatoid arthritis patients: A retrospective case-control observational study.

BACKGROUND: CD4-positive T cells are the main target of human T-cell leukemia virus type 1 (HTLV-1). Interferon-γ release assays rely on the fact that T-lymphocytes release this cytokine when exposed to tuberculosis-specific antigens and are useful in testing for latent tuberculosis infection before initiating biologic therapy, such as anti-tumor necrosis factor agents. However, the reliability of interferon-γ release assays in detecting tuberculosis infection among HTLV-1-positive patients with rheumatoid arthritis (RA) remains unclear. The present study aimed to evaluate the use of the T-SPOT.TB assay in HTLV-1-positive RA patients. METHODS: Overall, 29 HTLV-1-positive RA patients and 87 age- and sex-matched HTLV-1-negative RA patients (controls) were included from the HTLV-1 RA Miyazaki Cohort Study. Results of the T-SPOT.TB assay for latent tuberculosis infection screening were collected from medical records of patients. RESULTS: Approximately 55% of the HTLV-1-positive RA patients showed invalid T-SPOT.TB assay results (odds ratio: 108, 95% confidence interval: 13.1-890, p < 0.0001) owing to a spot count of >10 in the negative controls. HTLV-1 proviral load values were significantly higher in patients with invalid results compared with those without invalid results (p = 0.003). CONCLUSION: HTLV-1 infection affects T-SPOT.TB assay results in RA patients. Assay results in HTLV-1 endemic regions should be interpreted with caution when screening for latent tuberculosis infection before initiation of biologic therapy.

Spatial distribution of Mycobacterium Tuberculosis in metropolitan Harare, Zimbabwe.

INTRODUCTION: The contribution of high tuberculosis (TB) transmission pockets in propagating area-wide transmission has not been adequately described in Zimbabwe. This study aimed to describe the presence of hotspot transmission of TB cases in Harare city from 2011 to 2012 using geospatial techniques. METHODS: Anonymised TB patient data stored in an electronic database at Harare City Health department was analysed using geospatial methods. Confirmed TB cases were mapped using geographic information system (GIS). Global Moran's I and Anselin Local Moran's I (LISA) were used to assess clustering and the local Getis-Ord Gi* was used to estimate hotspot phenomenon of TB cases in Harare City for the period between 2011 and 2012. RESULTS: A total of 12,702 TB cases were accessed and mapped on the Harare City map. In both 2011 and 2012, ninety (90%) of cases were new and had a high human immunodeficiency virus (HIV)/TB co-infection rate of 72% across all suburbs. Tuberculosis prevalence was highest in the Southern district in both 2011 and 2012. There were pockets of spatial distribution of TB prevalence across West South West, Southern, Western, South Western and Eastern health districts. TB hot spot occurrence was restricted to the West South West, parts of South Western, Western health districts. West South West district had an increased peri-urban population with inadequate social services including health facilities. These conditions were conducive for increased intensity of TB occurrence, a probable indication of high transmission especially in the presence of high HIV co-infection. CONCLUSIONS AND RECOMMENDATIONS: Increased TB transmission was limited to a health district with high informal internal migrants with limited health services in Harare City. To minimise spread of TB into greater Harare, there is need to improve access to TB services in the peri-urban areas.

Determinants of unsuccessful treatment outcomes and mortality among tuberculosis patients in Malaysia: A registry-based cohort study.

INTRODUCTION: The monitoring of tuberculosis (TB) treatment outcomes and examination of the factors affecting these outcomes are important for evaluation and feedback of the national TB control program. This study aims to assess the TB treatment outcomes among patients registered in the national TB surveillance database in Malaysia from 2014 until 2017 and identify factors associated with unsuccessful treatment outcomes and all-cause mortality. MATERIALS AND METHODS: Using registry-based secondary data, a retrospective cohort study was conducted. TB patients' sociodemographic characteristics, clinical disease data and treatment outcomes at one-year surveillance were extracted from the database and analyzed. Logistic regression analysis was used to determine factors associated with unsuccessful treatment outcomes and all-cause mortality. RESULTS: A total of 97,505 TB cases (64.3% males) were included in this study. TB treatment success (cases categorized as cured and completed treatment) was observed in 80.7% of the patients. Among the 19.3% patients with unsuccessful treatment outcomes, 10.2% died, 5.3% were lost to follow-up, 3.6% had outcomes not evaluated while the remaining failed treatment. Unsuccessful TB treatment outcomes were found to be associated with older age, males, foreign nationality, urban dwellers, lower education levels, passive detection of TB cases, absence of bacille Calmette-Guerin (BCG) scar, underlying diabetes mellitus, smoking, extrapulmonary TB, history of previous TB treatment, advanced chest radiography findings and human immunodeficiency virus (HIV) infection. Factors found associated with all-cause mortality were similar except for nationality (higher among Malaysians) and place of residence (higher among rural dwellers), while smoking and history of previous TB treatment were not found to be associated with all-cause mortality. CONCLUSIONS: This study identified various sociodemographic characteristics and TB disease-related variables which were associated with unsuccessful TB treatment outcomes and mortality; these can be used to guide measures for risk assessment and stratification of TB patients in future.

Incidence and predictors of HIV related opportunistic infections after initiation of highly active antiretroviral therapy at Ayder Referral Hospital, Mekelle, Ethiopia: A retrospective single centered cohort study.

INTRODUCTION: Even though use of antiretroviral therapy (HAART) decreases the incidence of opportunistic infections (OIs) they are continuing to be a major cause of morbidity and mortality. Studies concerning this problem are scarce in Eastern Africa. The aim of this study was to determine the incidence and predictors of OIs after initiation of HAART in Ethiopia. METHODS: A health facility based single centered cohort study using structured data extraction sheet was conducted. The study population was all HIV positive ART naive adolescents and adults who started HAART between January 2009 and May 2012. Simple random sampling technique was used to select 317 patients from the record. Multivariate binary logistic regression model was used to determine factors for the occurrence of OIs after initiation of HAART. RESULTS: The incidence of OIs after HAART was 7.5 cases/100person years. Tuberculosis, oral candidiasis, pneumonia and toxoplasmosis were the leading OIs after HAART. A bed ridden functional status at initiation of HAART, presence of OIs before HAART, non-adherence and low hemoglobin level were predictors for the occurrence of OIs after HAART. CONCLUSION: The incidence of OIs after HAART was higher than in previous studies. Patients with the identified risk factors need strict follow up to reduce the morbidity and mortality attributed to OIs. Earlier initiation of HAART before advanced immune suppression, better management of TB and extended baseline assessment could help to reduce opportunistic infections and mortality after the initiation of HAART in Ethiopian patients.

Efferocytosis of Apoptotic Neutrophils Enhances Control of Mycobacterium tuberculosis in HIV-Coinfected Macrophages in a Myeloperoxidase-Dependent Manner.

Tuberculosis remains a big threat, with 1.6 million deaths in 2017, including 0.3 million deaths among patients with HIV. The risk of developing active disease increases considerably during an HIV coinfection. Alveolar macrophages are the first immune cells to encounter the causative agent Mycobacterium tuberculosis, but during the granuloma formation other cells are recruited in order to combat the bacteria. Here, we have investigated the effect of efferocytosis of apoptotic neutrophils by M. tuberculosis and HIV-coinfected macrophages in a human in vitro system. We found that the apo-ptotic neutrophils enhanced the control of M. tuberculosis in single and HIV-coinfected macrophages, and that this was dependent on myeloperoxidase (MPO) and reactive oxygen species in an autophagy-independent manner. We show that MPO remains active in the apoptotic neutrophils and can be harnessed by infected macrophages. In addition, MPO inhibition removed the suppression in M. tuberculosis growth caused by the apoptotic neutrophils. Antimycobacterial components from apoptotic neutrophils could thus increase the microbicidal activity of macrophages during an M. tuberculosis/HIV coinfection. This cooperation between innate immune cells could thereby be a way to compensate for the impaired adaptive immunity against M. tuberculosis seen during a concurrent HIV infection.

Diabetes mellitus among patients attending TB clinics in Dar es Salaam: a descriptive cross-sectional study.

BACKGROUND: A bi-directional interaction between diabetes mellitus and tuberculosis is well established and has been likened to that between HIV and TB. Whereas HIV screening is standard of care test in sub Saharan Africa TB programs, the same is not true for diabetes mellitus (DM). Sub Saharan Africa, a region with high TB infection rates, is going through an epidemiological transition with rapidly rising prevalence of diabetes. We aimed at characterizing TB patients with DM in order to identify factors associated with TB-DM dual disease among patients attending TB clinics in Dar es Salaam. METHODS: A cross-sectional study was conducted between September 2016 and January 2017 among patients attending TB clinics in Dar es Salaam. We collected socio-demographic characteristics, anthropometric measurements and screened for diabetes by measuring fasting blood glucose that was followed by a 2 h postprandial glucose for participants with impaired fasting blood glucose. We examined for socio-demographic and clinical factors associated with diabetes using logistic regression analysis. RESULTS: Of the 660 enrolled participants with TB, 25 (3.8%) were on treatment for diabetes while 39 (6.1%) and 147 (23%) of the remaining 635 participants were ultimately diagnosed with DM and impaired fasting blood glucose respectively. The overall prevalence of DM was 9.7% (64/660). Independent risk factors for diabetes included: age > 44 years {OR 4.52, 95% CI: [1.28-15.89]}; family history of diabetes {OR 3.42, 95% [CI 1.88-6.21]}. HIV sero-positive TB patients were less likely to have DM compared to those who were HIV sero-negative {OR 0.35, 95% CI [0.17-0.73]}. CONCLUSIONS: Screening for diabetes should be advocated for TB patients aged above 44 years and/or with a family history of diabetes. HIV sero-negative TB patients were more likely to have DM compared to those who were HIV sero-positive. Further studies are needed to confirm this observation and the underlying factors.

Reactivation of tuberculosis in cancer patients following administration of immune checkpoint inhibitors: current evidence and clinical practice recommendations.

Immune checkpoint inhibitors (ICBs) have revolutionized cancer treatment producing remarkable and durable responses for a range of malignancies. However, the additional modulation of immune response by ICBs may rarely cause immune-related infectious complications, including re-activation of latent tuberculosis infection (LTBC) with detrimental effects on those patients' outcome. Here, we present two "real-world" melanoma cases that were treated in our department with blockade of PD-1/PD-L1 and developed active Mycobacterium tuberculosis (MTB) during immunotherapy. In view of these cases, we review the literature for ICB-associated MTB reactivation and discuss our considerations about the possible interactions of immunotherapy and the underlying co-existent mycobacterial infection. Based on the current evidence from preclinical findings prior to this experience, we raise questions regarding cancer patients who are at higher risk for developing MTB infection, whether ICB-treated patients should be considered immunocompromised, and how they should be managed for latent and/or active tuberculosis. Aside from the well-established clinical benefit of immunotherapy, the blockade of PD-1/PD-L1 axis may concurrently disrupt the immune control of specific opportunistic infections such as tuberculosis that should be carefully and expectantly managed in order to avoid compromising the outcome of cancer treatment and the affected patient's survival.

Human immunodeficiency virus-associated tuberculosis care in Botswana: evidence from a real-world setting.

BACKGROUND: Tuberculosis (TB) is among the world's top public health challenges and the leading killer of people with HIV, yet is a treatable disease. This study aimed to assess, in a real-world setting, the implementation of antiretroviral therapy (ART) and Cotrimoxazole preventive therapy (CPT) policy, specific interventions proven to benefit patients in HIV-associated TB care. METHODS: This retrospective cohort study was conducted in Botswana in the Serowe/Palapye district, a largely urban district with a high burden of HIV-associated TB with a high case fatality, at Segkoma and Palapye hospitals and their feeder clinics. Between 1 January 2013 and 31 December 2013, confirmed HIV-positive patients aged ≥15 years with a confirmed TB diagnosis and medical record available were included in the analysis. The Kaplan-Meier method was used to compare time to death for the group of patients on ART and the group of patients not on ART during TB treatment. Cox proportional hazard regression was undertaken to identify predictors of mortality. RESULTS: Of the 300 patients included in the study, 217 (72%) were ART experienced at TB diagnosis. Of these, 86 (40%) had TB within 3 months following ART initiation. Of the 83 (28%) patients who were ART-naïve at TB diagnosis, 40 (48%) were commenced on ART during TB treatment, with 24 (60%) patients commencing within 4 weeks following TB treatment initiation. The overall ART uptake was 84%, while cotrimoxazole preventive therapy uptake was 100%. There were 45 deaths (15%), ART-experienced patients during TB treatment accounted for 30 deaths (30/257; 14%), while those who were not ART-experienced during TB treatment accounted for 15 deaths (15/43; 35%). There was a significant difference in survival time between patients with no ART use during TB treatment and those with ART use during TB treatment (log rank p < 0.001). Patients with no ART use during TB treatment were more likely to die within the first 2 months. CONCLUSION: The implementation of CPT policy is a substantial success. Strengthening the implementation of ART policy could improve survival among HIV-associated TB patients.

Tuberculosis treatment outcome and its associated factors among people living with HIV and AIDS in Fako Division of Cameroon.

BACKGROUND: Tuberculosis (TB) and HIV co-infection challenges treatment and worsens the outcome of TB treatment. This study aimed to assess the outcome of TB treatment and factors facilitating treatment success among people living with HIV/AIDS in Fako Division of the South West Region of Cameroon. METHODS: A hospital-based retrospective cohort study was conducted by manually reviewing medical records of HIV/TB co-infected patients from January 2010 to September 2017. A structured data collection form was used to review the medical records of HIV patients co-infected with TB aged 10 years and older. Patients with incomplete files were dropped from the study. Treatment success was defined as the sum of patients who were declared cured and those who had completed treatment, as per the World Health Organization's recommendations. Data were analyzed using Statistical Package for Social Sciences version 21. Bivariate and multivariate logistic regression model was carried out to identify factors facilitating successful TB treatment outcome. Significance was obtained through adjusted odds ratio with its 95% confidence interval and a p<0.05. RESULTS: A total of 2,986 files were reviewed but 2,928 (98.1%) were retained. Out of the 2,928 medical files of adult TB patients reviewed, 1,041 (35.6%, [95% CI 33.8%-37.3%]) were HIV/TB co-infected. The 1,041 co-infected patients had a mean age of 37.07 (SD of10.02) years and 56.3% were females. The treatment outcome of TB patients were 795(76.4%) cured, 23(2.2%) treatment completed, 99(9.5%) were lost to follow-up, 16 (1.5%) failed, 72(6.9%) died and 36(3.5%) transferred out. A successful treatment outcome was achieved in 818(78.6%,[95% CI: 76.0%-81.0%]) patients. Being a female [COR 1.61, 95% CI: 1.19-2.17, p = 0.002], receiving TB treatment in 2014 [COR 2.00, 95% CI: 1.11-3.60, p = 0.021] and 2015 [COR 2.50, 95% CI: 1.39-4.50, p = 0.002], having relapsed TB infection [COR 0.46, 95% CI: 0.23-0.93, p = 0.031], receiving ART [COR 1.95, 95% CI: 1.28-2.97, p = 0.002] and Cotrimoxazole [COR 2.03, 95% CI: 1.12-3.66, p = 0.019] were factors significantly associated with successful treatment. After adjusting for confounders, successful treatment outcome were associated with being a female [AOR 1.6; 95% CI: 1.21-2.22, p = 0.001], diagnosis of TB in 2014 [AOR 1.90; 95% CI: 1.04-3.45, p = 0.036] and 2015 [AOR 2.43; 95% CI: 1.33-4.43, p = 0.004]. CONCLUSION: There is a high TB treatment success rate among HIV/TB co-infected patients in our setting, although below the target set by the WHO. Specific interventions aimed at enhancing patient outcomes are recommended.

Poor outcomes in recurrent tuberculosis: More than just drug resistance?

BACKGROUND: Approximately 11% of people reported to have tuberculosis (TB) have previously received treatment. Clinical outcomes are consistently poor on retreatment regimens, however reasons for this are unclear. This study aimed to explore factors which may contribute to unsuccessful outcomes in retreatment TB. METHODS AND FINDINGS: A prospective cohort of consecutive patients starting WHO Category II retreatment regimen was recruited at a central hospital in Malawi. Participants were evaluated at baseline, after completion of the intensive phase at 2-months, and at the end of the 8-month treatment course. Patients were assessed for respiratory co-morbidity; anaemia; renal impairment; diabetes; Anti-retroviral (ART) failure; and drug toxicity. Amongst 158 patients entering TB care at the point of a recurrent episode, only 92 (58%) had a microbiologically confirmed diagnosis. The prevalence of drug resistance was low (9.6%). Of the 158 patients, 131 (83%) were HIV-positive, of whom 96 (73%) were on ART. Of 63 patients on ART >1 year, 24 (38%) had ART failure. Chronic lung disease was found in 88% on CT thorax, including scarring (80%), bronchiectasis (61%), COPD (22%), and destroyed lung (19%). Spirometry revealed restrictive deficit in 60%, and obstructive deficit in 7% of patients. Anaemia and renal impairment were common (34% and 45% respectively). Ototoxicity developed in 32%, and nephrotoxicity in 15%. 40% of patients reported peripheral neuropathy. Liver injury developed in 4%. CONCLUSIONS: If outcomes are to be improved in retreatment TB, there is an urgent need to address the impact of other co-morbid medical conditions including chronic lung disease, HIV and ART failure.

[Impact of HIV and Mycobacterium tuberculosis co-infection on related mortality].

Objective: To understand the impact of HIV and Mycobacterium tuberculosis (MTB) co-infectious (HIV/MTB) on related mortality in Guangxi Zhuang Autonomous Region, provide evidence for the development of a better HIV/MTB co-infection control and prevention program. Methods: A multiple cross-systems check (MCSC) approach was used to confirm the HIV/MTB co-infection individuals on data related to treatment, follow-up, epidemiological comprehensive and Tuberculosis (TB) special report system. Social demography characteristics, incidence of TB among HIV positive individuals, HIV incidence among MTB infection persons etc., were described. We compared the mortalities and related risks between HIV/MTB co-infection and mono HIV positive individuals as well as between the HIV/MTB co-infection and mono MTB infection persons, using both the Chi Square test and the Cox's proportional hazard regression model (Cox). Results: Reported data showed that the incidence of MTB co-infection in the HIV cohort was 17.72% (2 533/14 293), while HIV incidence in the TB patients was 5.57% (2 351/42 205), respectively. The mortality of HIV/MTB co-infection in the HIV/AIDS cohort was 15.16% (384/2 533) within one-year of observation and was significantly higher than the mortality (13.63%,1 603/11 760) of mono HIV positive individuals (P<0.000 1). The percentage of the HIV/AIDS death cases was 19.33% (384/1 987) who registered and died in the 2011 calendar year were caused by MTB co-infection. Among all the HIV/MTB co-infection patients who had been identified from the HIV cohort, 60.05% (1 521/2 533) had initiated ART, 15.48% (392/2 533) had been cured for TB and 27.48% (696/2 533) had been under complete TB regimen. Among the confirmed HIV/MTB cases from the TB cohort, the cure rate of TB was 19.70% (463/2 351) and the percentage of completed TB regimen was 37.26% (876/2 351). The percentage of the individuals whose CD(4)(+) T lymphocyte cells count appeared less than 200 cell/µl was 64.13% (785/1 224), upon the HIV diagnoses were made. Compared with individuals who were under mono HIV infection, the mortality risk on HIV/MTB co-infection was 1.17 times higher during the five-year observation period, then the patients with only mono MTB infection and the mortality risk in patients with HIV/MTB co-infection was 25.68 times higher under the 12-month observation period. Conclusions: Both the incidence and mortality of HIV/MTB appeared high in Guangxi, with mortality and the risk of mortality in the HIV/MTB co-infection group significantly higher than that in both the HIV mono infection and the MTB mono infections groups. Both the rate of antiretroviral treatment coverage and the cure rate of TB treatment should be increased in no time as well as the capability of early TB case-finding among people living with HIV.