The potential of CBC-derived ratios (monocyte-to-lymphocyte, neutrophil-to-lymphocyte, and platelet-to-lymphocyte) to predict or diagnose incident TB infection in Tanzanian adolescents.

BACKGROUND: Ratios of different immune cell populations (i.e., monocyte-to-lymphocyte, neutrophil-to-lymphocyte, and platelet-to-lymphocyte ratios) have been studied as a means of predicting future tuberculosis (TB) disease risk or to assist in the diagnosis of incident TB disease. No studies to-date, however, have evaluated the potential of these ratios to predict or assist in the diagnosis of incident TB infection - the first step in the natural history of TB disease. METHODS: In this prospective study, we evaluated the complete blood count (CBC)-derived metrics of monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) as predictors of future TB infection risk or aids in the diagnosis of TB infection among 145 Tanzanian adolescents enrolled in the DAR-901 vaccine trial, using paired CBCs and interferon-gamma release assays (IGRAs) obtained at 0, 60 and 720 days after study enrollment. RESULTS: At baseline, there were no significant differences between study participants who remained persistently IGRA negative throughout the study period and those who subsequently converted to IGRA positive with respect to MLR (0.18 vs 0.17, p = 0.10), NLR (0.88 vs 1.02, p = 0.08), or PLR (115 vs 120, p = 0.28). Similarly, no significant differences were noted with respect to MLR, NLR, and PLR between IGRA converters and time-matched negative controls at the time of IGRA conversion. With respect to other blood cell measures, however, there were modest but significant differences between IGRA negatives and IGRA converters with respect to red blood cell count (4.8 vs 4.6 ×  106 cells/mcL, p = 0.008), hemoglobin (12.6 vs 12.3 g/dL, p = 0.01), and hematocrit (38.8 vs 37.8%, p = 0.005). CONCLUSIONS: In contrast to prior studies that have suggested that the ratios of different immune cell populations are associated with development of TB disease, our present findings do not demonstrate an association between these ratios and the development of TB infection. However, decreased red blood cell measures were associated with the subsequent development of TB infection, suggesting either that dysregulation of iron metabolism may play a role in TB pathogenesis or that following TB infection, iron dysregulation may precede IGRA positivity. TRIAL REGISTRATION: Clinicaltrials.gov NCT02712424 . Date of registration: March 14, 2016.

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.

Greater preexisting interferon γ responses to mycobacterial antigens and lower bacillary load during HIV-associated tuberculosis.

The role of preexisting interferon (IFN) γ responses in controlling bacillary burden in human immunodeficiency virus (HIV)-associated tuberculosis is not known. Among BCG-immunized HIV-infected adults who developed tuberculosis in a phase III trial of an investigational tuberculosis vaccine, greater baseline IFN-γ responses to early secretory antigenic target 6 and Mycobacterium tuberculosis whole-cell lysate were associated with reduced bacillary burden on sputum smear grade, days to culture positivity on agar, and sputum culture grade during subsequent tuberculosis. This association was most consistent among recipients of the investigational vaccine. When HIV-associated tuberculosis develops, greater preexisting IFN-γ responses to mycobacterial antigens are associated with reduced tuberculosis bacillary burden. ClinicalTrials.gov Identifier. NCT0052195.

Recurrent tuberculosis risk among HIV-infected adults in Tanzania with prior active tuberculosis.

BACKGROUND: Active tuberculosis is common among human immunodeficiency virus (HIV)-infected persons living in tuberculosis-endemic areas, but the hazard of subsequent tuberculosis disease has not been quantified in a single prospective cohort. METHODS: Among HIV-infected, BCG-immunized adults with CD4 counts ≥200 cells/µL who received placebo in the DarDar tuberculosis vaccine trial in Tanzania, we compared the prospective risk of active tuberculosis between subjects who did and who did not report prior active tuberculosis. All subjects with a positive tuberculin skin test without prior active tuberculosis were offered isoniazid preventive treatment. Definite or probable tuberculosis was diagnosed during active follow-up using rigorous published criteria. RESULTS: We diagnosed 52 cases of definite and 92 cases of definite/probable tuberculosis among 979 subjects during a median follow-up of 3.2 years. Among the 80 subjects who reported prior active tuberculosis, 11 (13.8%) subsequently developed definite tuberculosis and 17 (21.3%) developed definite/probable tuberculosis, compared with 41 (4.6%) and 75 (8.3%), respectively, of 899 subjects without prior active tuberculosis (definite tuberculosis risk ratio [RR], 3.01; 95% confidence interval [CI], 1.61-5.63, P < .001; definite/probable tuberculosis RR, 2.55; 95% CI, 1.59-4.09, P < .001). In a Cox regression model adjusting for age, CD4 count, and isoniazid receipt, subjects with prior active tuberculosis had substantially greater hazard of subsequent definite tuberculosis (hazard radio [HR], 3.69; 95% CI, 1.79-7.63, P < .001) and definite/probable tuberculosis (HR, 2.78; 95% CI, 1.58-4.87, P < .001). CONCLUSIONS: Compared to subjects without prior tuberculosis, the hazard of active tuberculosis is increased 3-fold among HIV-infected adults with prior active tuberculosis. Clinical Trials Registration. NCT0052195.

Molecular epidemiology of HIV-associated tuberculosis in Dar es Salaam, Tanzania: strain predominance, clustering, and polyclonal disease.

Molecular typing of Mycobacterium tuberculosis can be used to elucidate the epidemiology of tuberculosis, including the rates of clustering, the frequency of polyclonal disease, and the distribution of genotypic families. We performed IS6110 typing and spoligotyping on M. tuberculosis strains isolated from HIV-infected subjects at baseline or during follow-up in the DarDar Trial in Tanzania and on selected community isolates. Clustering occurred in 203 (74%) of 275 subjects: 124 (80%) of 155 HIV-infected subjects with baseline isolates, 56 (69%) of 81 HIV-infected subjects with endpoint isolates, and 23 (59%) of 39 community controls. Overall, 113 (41%) subjects had an isolate representing the East Indian "GD" family. The rate of clustering was similar among vaccine and placebo recipients and among subjects with or without cellular immune responses to mycobacterial antigens. Polyclonal disease was detected in 6 (43%) of 14 patients with multiple specimens typed. Most cases of HIV-associated tuberculosis among subjects from this study in Dar es Salaam resulted from recently acquired infection. Polyclonal infection was detected and isolates representing the East Indian GD strain family were the most common.

Malaria in patients with sickle cell anemia: burden, risk factors, and outcome at the outpatient clinic and during hospitalization.

Approximately 280,000 children are born with sickle cell anemia (SCA) in Africa annually, yet few survive beyond childhood. Falciparum malaria is considered a significant cause of this mortality. We conducted a 5-year prospective surveillance study for malaria parasitemia, clinical malaria, and severe malarial anemia (SMA) in Dar-es-Salaam, Tanzania, between 2004 and 2009. We recorded 10,491 visits to the outpatient clinic among 1808 patients with SCA and 773 visits among 679 patients without SCA. Similarly, we recorded 691 hospital admissions among 497 patients with SCA and 2017 in patients without SCA. Overall, the prevalence of parasitemia was lower in patients with SCA than in patients without SCA both at clinic (0.7% vs 1.6%; OR, 0.53; 95% CI, 0.32-0.86; P = .008) and during hospitalization (3.0% vs 5.6%; OR, 0.46; 95% CI, 0.25-0.94; P = .01). Furthermore, patients with SCA had higher rates of malaria during hospitalization than at clinic, the ORs being 4.29 (95% CI, 2.63-7.01; P < .001) for parasitemia, 17.66 (95% CI, 5.92-52.71; P < .001) for clinical malaria, and 21.11 (95% CI, 8.46-52.67; P < .001) for SMA. Although malaria was rare among patients with SCA, parasitemia during hospitalization was associated with both severe anemia and death. Effective treatment for malaria during severe illness episodes and further studies to determine the role chemoprophylaxis are required.

Serial T-SPOT.TB responses in Tanzanian adolescents: Transient, persistent and irregular conversions.

BACKGROUND: Prospective studies of interferon-gamma release assays (IGRA) on healthy subjects in tuberculosis-endemic regions have not examined the long-term variability of serial assays. This issue is relevant to the interpretation of tuberculosis (TB) vaccine trials based on prevention of infection. METHODS: T-SPOT.TB assays were performed manually on healthy adolescents during a tuberculosis vaccine trial in Tanzania at 5 intervals over 3 years. Assay results were defined as negative, positive, borderline or invalid. Subsequently, microtiter plates were analyzed by an automated reader to obtain quantitative counts of spot forming cells (SFCs) for the present analysis. RESULTS: 3387 T-SPOT.TB samples were analyzed from 928 adolescents; manual and automated assay results were 97% concordant. Based on the quantitative results 143 (15%) participants were prevalent IGRA-positives at baseline, were ineligible for further study. Among the remaining IGRA-negative participants, the annual rate of IGRA conversion was 2·9%. Among 43 IGRA converters with repeat assays 12 (28%) were persistent converters, 16 (37%) were transient converters, and 15 (35%) comprised a new category defined as irregular converters (≥2 different subsequent results). ESAT-6 and CFP-10 responses were higher in prevalent than incident positives: 53 vs 36 for CFP-10 (p < 0·007); 44 vs 34 for ESAT-6 (p = 0·12). CONCLUSIONS: Definitions of IGRA conversion, reversion, and persistence depend critically on the frequency of testing. Multiple shifts in categories among adolescents in a TB-endemic country may represent multiple infections, variable host responses in subclinical infection, or assay variation. These findings should to be considered in the design and interpretation of TB vaccine trials based on prevention of infection. Household contact studies could determine whether even transient IGRA conversion might represent exposure to an active case of M. tuberculosis disease.

Interferon γ responses to mycobacterial antigens protect against subsequent HIV-associated tuberculosis.

BACKGROUND: The cellular immune responses that protect against tuberculosis have not been identified. METHODS: We assessed baseline interferon γ (IFN­Î³) and lymphocyte proliferation assay (LPA) responses to antigen 85 (Ag85), early secretory antigenic target 6 (ESAT­6), and Mycobacterium tuberculosis whole cell lysate (WCL) in human immunodeficiency virus (HIV)-infected and bacille Calmette­Guérin (BCG)-immunized adults with CD4 cell counts of >or= 200 cells/µL who received placebo in the DarDar tuberculosis vaccine trial in Tanzania. Subjects were followed prospectively to diagnose definite or probable tuberculosis. RESULTS: Tuberculosis was diagnosed in 92 of 979 subjects during a mean follow­up of 3.2 years. The relative risk of tuberculosis among subjects with positive IFN­Î³ responses to Ag85 was 0.51 (95% confidence interval [CI], 0.26-0.99; P = .049), to ESAT­6 was 0.44 (95% CI, 0.23-0.85; P = .004), and to WCL was 0.67 (95% CI, 0.49-0.88; P = .002). The relative risk of tuberculosis was not significantly associated with baseline LPA responses. In a multivariate Cox regression model, subjects with IFN­Î³ responses to ESAT­6 and WCL had a lower hazard of developing tuberculosis, with a hazard ratio for ESAT­6 of 0.35 (95% CI, 0.16­0.77; P = .009) and a hazard ratio for WCL of 0.30 (95% CI, 0.16-0.56; P < .001). CONCLUSIONS: Baseline IFN­Î³ responses to ESAT-6 and WCL were associated with protection from subsequent tuberculosis among HIV-infected subjects with childhood BCG immunization in a region of high tuberculosis prevalence. Trial registration. ClinicalTrials.gov identifier: NCT00052195.

Tuberculosis in HIV voluntary counselling and testing centres in Dar es Salaam, Tanzania.

The human immunodeficiency virus (HIV) has contributed to an increase in tuberculosis (TB) worldwide. HIV voluntary counselling and testing (VCT) centres are cost-effective for HIV screening. Therefore there is a potential of tapping into the success of VCT centres by incorporating TB screening. The aim of this study was to determine the extent of TB and TB/HIV co-infection among VCT centre attendees. We enrolled 1318 consecutive subjects from 2 VCT centres in Dar es Salaam. The diagnosis of TB was based on evidence of Mycobacterium tuberculosis in sputum or tissue aspirates following microscopy or culture. In the absence of M. tuberculosis, the presence of 2 of the following was considered: clinical features of TB, suggestive chest radiographs and response to anti-tuberculosis trial therapy. HIV was diagnosed in 347 (26%) subjects. TB was present in 101 (7.7%) subjects of whom 63 (62%) were diagnosed at VCT centres and 38 (38%) were known TB cases who came for HIV testing. Pulmonary TB (PTB) was detected in 52 (83%) subjects. The diagnosis of PTB was based on sputum culture in 35 (67%), sputum microscopy in 20 (38%), and clinical and radiological findings in 17 (33%) subjects. TB/HIV co-infection was detected in 70 (5.3%) subjects. PTB was common in stand-alone VCT centres. Therefore VCT centres could serve as an entry point for TB screening.

Effect of improved access to antiretroviral therapy on clinical characteristics of patients enrolled in the HIV care and treatment clinic, at Muhimbili National Hospital (MNH), Dar es Salaam, Tanzania.

BACKGROUND: Sub-Saharan Africa has been severely affected by the HIV and AIDS pandemic. Global efforts at improving care and treatment has included scaling up use of antiretroviral therapy (ART). In Tanzania, HIV care and treatment program, including the provision of free ART started in 2004 with a pilot program at Muhimbili National Hospital in Dar es Salaam. This study describes the socio-demographic and clinical features of patients enrolled at the care and treatment clinic at MNH, Dar es Salaam, Tanzania. METHODS: A cross-sectional study looking at baseline characteristics of patients enrolled at the HIV clinic at MNH between June 2004-Dec 2005 compared to those enrolled between 2006 and September 2008. RESULTS: Of all enrolled patients, 2408 (58.5%) were used for analysis. More females than males were attending the clinic. Their baseline median CD4 cell count was low (136 cells/microl) with 65.7% having below 200 cells/microl. Females had higher CD4 cell counts (150 cells/microl) than males (109 cells/microl) p < 0.001). The most common presenting features were skin rash and/or itching (51.6%); progressive weight loss (32.7%) and fever (23.4). Patients enrolled earlier at the clinic (2004-5) were significantly more symptomatic and had significantly lower CD4 cell count (127 cells/microl) compared to CD4 of 167 cells/microl in those seen later (2006-8) (p < 0.001). CONCLUSION: Patients enrolled to the MNH HIV clinic were predominantly females, and presented with advanced immune-deficiency. Improved access to HIV care and treatment services seems to be associated with patients' early presentation to the clinics in the course of HIV disease.

Prevalence of non-communicable diseases among individuals with HIV infection by antiretroviral therapy status in Dar es Salaam, Tanzania.

BACKGROUND: Long-term antiretroviral therapy has modified the clinical course of HIV infection to a chronic condition associated with increased risk of developing non-communicable diseases (NCDs). Information is scant, from sub-Saharan Africa, on the prevalence of NCDs and associated factors among individuals on ART. METHODOLOGY: We consecutively enrolled individuals with HIV infection who were ART naïve and those on ART for ≥5 years (LTART) attending health facilities in Dar es Salaam. Participant's blood pressure, anthropometric measurements, and fasting blood glucose were recorded. Participants with impaired fasting blood glucose underwent an oral glucose tolerance test. A venous blood sample was sent to the lab for biochemical tests. Chi-square test was used to compare proportions, Poisson regression with robust standard errors was used to determine associations between variables. RESULTS: Overall, 612 individuals with HIV infection were enrolled, half of whom were ART naïve. Females comprised 71.9% and 68.0% of participants in the LTART and ART naïve study arms, respectively, p = 0.290. The mean age (±SD) was 44.9 ± 12.7 years and 37.5 ± 11.8 years among LTART and ART naïve participants, respectively, p<0.001. Hypertension was documented in 25.2% in those on LTART compared to 6.9% among ART naïve subjects, p<0.001. Impaired glucose tolerance was found in 22.9% and 4.6% among LTART compared to ART naïve subjects, p<0.001. Diabetes mellitus was detected in 17.0% of those on LTART compared to 3.9% ART naïve participants, p<0.001. Hypercholesterolemia was found in 30.4% of individuals on LTART compared to 16.7% of ART naïve subjects, p<0.001, and hypertriglyceridemia was found in 16.0% of participants on LTART compared to 9.5% of ART naïve, p = 0.015. LTART use, age ≥40 years, history of smoking, and body mass index were independently associated with NCDs. CONCLUSION: Hypertension, impaired glucose tolerance, diabetes mellitus, hypercholesterolemia, and hypertriglyceridemia were associated with long-term use of antiretroviral drugs.

Trends in Hospitalisation for Human Immunodeficiency Virus in a Tertiary Hospital in Dar es Salaam, Tanzania: A Case study.

BACKGROUND: Reports on systematic evaluation of the impact of antiretroviral therapy(ART) on patients' hospitalisation in Sub Saharan Africa (SSA) and Tanzania in particular are scarce. We aimed at documenting the trends of hospital admissions at Muhimbili National Hospital (MNH) following scale up of free access to ART in Tanzania. METHODS: Records for all admissions at MNH from June 2005 to June 2015 were reviewed. We extracted data from Hospital Information Management System as well as from patients' charts. Data extracted included diagnosis at discharge, reason for admission and thereafter assessed admission trends over the decade. We summarised the data as frequency and percentages. We compared proportions using Chi squared test, P<0.05 was deemed significant. RESULTS: Overall there were 209,101 admissions during the study period (June 2005 to June 2015) and 7864/209,101 (3.8%) were due to HIV infection. Whereas 598/4,519 (13.2%) of all admissions in 2005 were due to HIV, only 345/13,119 (2.6%) of admissions in 2015 were HIV-related; showing a significant drop over time (P value for trend < .001). Generally, females 3887/6679 (58.2%) were more likely to be admitted than males (41.8%). Median CD4 count for admitted HIV patients was 143 cells/µl. Majority of admissions occured in the medical wards 3643/5310 (68.6%). Discharge diagnoses were Tuberculosis 1396/6482 (21.5%), anaemias 1016/6482 (15.6 %), malignancies 789/6482(12.2%), CNS infections 541/6482 (8.3%) and chronic kidney disease 308/6482 (4.8%). Three leading AIDS defining malignancies among hospitalised patients included Kaposi's sarcoma 380/789 (48.2%), carcinoma of the cervix 77/789 (9.8%), and Non-Hodgkin's lymphoma 44/789 (5.6%). CONCLUSION: Despite drastic drop of HIV related admissions at Muhimbili National Hospital over the years, the infection remains a problem of the adults, largely females suffering from medical conditions and presenting with severe immunosuppression. Tuberculosis remained the most common opportunistic infection among hospitalized HIV infected patients. Anaemia and cancers became more important causes of admission than was diarrhoea which had been the most common among HIV infected patients in pre- ART era.

DAR-901 vaccine for the prevention of infection with Mycobacterium tuberculosis among BCG-immunized adolescents in Tanzania: A randomized controlled, double-blind phase 2b trial.

BACKGROUND: SRL172 prevented disease due to Mycobacterium tuberculosis in a Phase 3 trial. DAR-901 represents a scalable manufacturing process for SRL172. We sought to determine if DAR-901 would prevent infection with M. tuberculosis among BCG-primed adolescents age 13-15 years in Tanzania. METHODS: Adolescents with a negative T- SPOT.TBR interferon gamma release assay (IGRA) were randomized 1:1 to three intradermal injections of DAR-901 or saline placebo at 0, 2 and 4 months. Repeat IGRAs were performed at 2 months, and at 1, 2, and 3 years. The primary efficacy outcome was time to new TB infection (IGRA conversion to positive); the secondary outcome was time to persistent TB infection (IGRA conversion with repeat positive IGRA). RESULTS: Among 936 participants screened 667 were eligible and randomized to their first dose of vaccine or placebo (safety cohort). At 2 months, 625 participants remained IGRA-negative and were scheduled for the additional two doses (efficacy cohort). DAR-901 was safe and well-tolerated. One DAR-901 recipient developed a vaccine site abscess. Neither the primary nor secondary endpoints differed between the two treatment arms (p = 0.90 and p = 0.20, respectively). DAR-901 IGRA converters had median responses to ESAT-6 of 50.1 spot-forming cells (SFCs) vs. 19.6 SFCs in placebo IGRA converters (p = 0.03). CONCLUSIONS: A three-dose series of 1 mg DAR-901 was safe and well-tolerated but did not prevent initial or persistent IGRA conversion. DAR-901 recipients with IGRA conversion demonstrated enhanced immune responses to ESAT-6. Since protection against disease may require different immunologic responses than protection against infection a trial of DAR-901 to prevent TB disease is warranted. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov as NCT02712424.

Lymphocyte proliferation to mycobacterial antigens is detectable across a spectrum of HIV-associated tuberculosis.

BACKGROUND: Identifying novel TB diagnostics is a major public health priority. We explored the diagnostic characteristics of antimycobacterial lymphocyte proliferation assays (LPA) in HIV-infected subjects with latent or active TB. METHODS: HIV-infected subjects with bacille Calmette Guérin (BCG) scars and CD4 counts > or = 200 cells/mm(3) entering a TB booster vaccine trial in Tanzania had baseline in vivo and in vitro immune tests performed: tuberculin skin tests (TST), LPA and five day assays of interferon gamma (IFN-gamma) release. Assay antigens were early secreted antigenic target 6 (ESAT-6), antigen 85 (Ag85), and Mycobacterium tuberculosis whole cell lysate (WCL). Subjects were screened for active TB at enrollment by history, exam, sputum smear and culture. We compared antimycobacterial immune responses between subjects with and without latent or active TB at enrollment. RESULTS: Among 1885 subjects screened, 635 had latent TB and 13 had active TB. Subjects with latent TB were more likely than subjects without TB to have LPA responses to ESAT-6 (13.2% vs. 5.5%, P < 0.0001), Ag85 (18.7% vs. 3.1%, P < 0.0001), and WCL (45.7% vs. 17.1%, P < 0.0001). Subjects with active TB also were more likely than those without active TB to have detectable LPA responses to ESAT-6 (38.5% vs. 8.1%, P = 0.0001), Ag85 (46.2% vs. 8.5%, P < 0.0001), and WCL (61.5% vs. 27.0%, P = 0.0053). In subjects with a positive TST, LPA responses to ESAT-6, Ag85 and WCL were more common during active TB (p < 0.0001 for all tests). In diagnosing active TB, in vivo and in vitro tests of mycobacterial immune responses had sensitivity and specificity as follows: TST 84.6% and 65.5%, ESAT-6 LPA 38.5% and 92.0%, Ag85 LPA 46.2% and 91.5%, and WCL LPA 61.5% and 73.0%. Detectable LPA responses were more common in patients with higher CD4 counts, and higher HIV viral loads. CONCLUSION: Lymphoproliferative responses to mycobacteria are detectable during HIV-associated active TB, and are less sensitive but more specific than TST. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00052195.

Disease spectrum and outcomes among elderly patients in two tertiary hospitals in Dar es Salaam, Tanzania.

BACKGROUND: There has been an increase in the number of individuals aged ≥60 years in Tanzania and in sub Saharan Africa in general due to improved survival. However, data is scarce on the disease burden and outcomes following admission in this population. We herein describe the pattern of diagnoses, outcomes and factors associated with the outcomes among elderly patients admitted at Muhimbili National Hospital (MNH) and Jakaya Kikwete Cardiac Institute (JKCI) medical wards. METHODOLOGY: From October to December 2017, we consecutively enrolled patients aged ≥60 years (elderly) admitted to the MNH and JKCI medical wards. The ICD 10 was used to code for disease diagnosis at discharge or death. The Modified Barthel index was used to assess for functional activity on admission and at discharge. RESULTS: We enrolled 336 (30.1%) elderly participants out of 1301 medical admissions. The mean age ± SD was 70.6 ± 8.9 years; 169 (50%) were female and the average number of diagnoses was 2 per participant. The most common diagnoses were: hypertension 151 (44.9%), stroke 106 (31.5%), heart failure 62 (18.5%), pneumonia 60 (17.9%), diabetes mellitus 58 (17.3%) and chronic kidney disease 55 (16.4%). The median duration of hospital stay was 5 (IQR 3-10) days and in-hospital mortality was 86 (25.6%), 56 (65%) deaths were due to non-communicable diseases and 48 (55.8%) deaths occurred within 72 hours of hospitalization. A modified Barthel score ≤20 on admission was associated with an OR 15.43 (95% CI: 7.5-31.7, p<0.001) for death. CONCLUSION: Elderly patients constituted a significant proportion of medical admissions at MNH and JKCI with high in-hospital mortality. A modified Barthel index score ≤20 during admission is associated with mortality and can be used to identify patients requiring special attention.

Sialic acid levels in breast milk from HIV-positive Tanzanian women and impact of maternal diet.

OBJECTIVE: To quantify total sialic acid in milk from HIV-positive Tanzanian mothers and to determine the impact of maternal diet on milk sialic acid levels. DESIGN: Milk samples were analyzed from 74 HIV-positive, Tanzanian women enrolled in a randomized, controlled clinical study of a dietary macronutrient supplement. Women were provided with a daily protein-calorie supplement and a micronutrient supplement or micronutrient supplement only during the last trimester of pregnancy and up to the first 6 months of breastfeeding. METHODS: Milk samples were collected at approximately 2 weeks and at least 3 months postpartum and assayed for total sialic acid. Milk sialic acid was assessed relative to maternal macronutrient intake, age, BMI, CD4+ cell count and infant birth weight. RESULTS: The mean concentration of milk sialic acid was highest in the first 2 weeks postpartum (6.89 ±â€Š2.79 mmol/l) and declined rapidly by 3 months (2.49 ±â€Š0.60 mmol/l). Sialic acid content in milk was similar between both treatment arms of the study, and did not correlate with maternal macronutrient intake. No correlation was found between maternal age, BMI, CD4+ cell count or infant birth weight and total milk sialic acid concentration. CONCLUSION: Milk sialic acid levels in HIV-positive, Tanzanian women without malnutrition are comparable with reported values for women of European descent and show a similar temporal decline during early lactation. These findings suggest that total milk sialic acid is maintained despite macronutrient deficiencies in maternal diet and support a conserved role for milk sialic acid in neonatal development.

Basis for treatment of tuberculosis among HIV-infected patients in Tanzania: the role of chest x-ray and sputum culture.

BACKGROUND: Active tuberculosis (TB) is common among HIV-infected persons living in tuberculosis endemic countries, and screening for tuberculosis (TB) is recommended routinely. We sought to determine the role of chest x-ray and sputum culture in the decision to treat for presumptive TB using active case finding in a large cohort of HIV-infected patients. METHODS: Ambulatory HIV-positive subjects with CD4 counts > or = 200/mm3 entering a Phase III TB vaccine study in Tanzania were screened for TB with a physical examination, standard interview, CD4 count, chest x-ray (CXR), blood culture for TB, and three sputum samples for acid fast bacillus (AFB) smear and culture. RESULTS: Among 1176 subjects 136 (12%) were treated for presumptive TB. These patients were more frequently male than those without treatment (34% vs. 25%, respectively; p = 0.049) and had lower median CD4 counts (319/microL vs. 425/microL, respectively; p < .0001). Among the 136 patients treated for TB, 38 (28%) had microbiologic confirmation, including 13 (10%) who had a normal CXR and no symptoms. There were 58 (43%) treated patients in whom the only positive finding was an abnormal CXR. Blood cultures were negative in all patients. CONCLUSION: Many ambulatory HIV-infected patients with CD4 counts > or = 200/mm3 are treated for presumptive TB. Our data suggest that optimal detection requires comprehensive evaluation, including CXR and sputum culture on both symptomatic and asymptomatic subjects.

Sputum microscopy for the diagnosis of HIV-associated pulmonary tuberculosis in Tanzania.

BACKGROUND: In many resource poor settings only sputum microscopy is employed for the diagnosis of HIV-associated pulmonary tuberculosis; sputum culture may not be available. METHODS: We determined the diagnostic accuracy of sputum microscopy for active case finding of HIV-associated pulmonary tuberculosis using TB culture as the reference standard. RESULTS: 2216 potential subjects screened for a TB vaccine trial submitted 9454 expectorated sputum specimens: 212 (2.2%) were sputum culture positive for Mycobacterium tuberculosis (MTB), 31 (0.3%) for non-tuberculous mycobacteria, and 79 (0.8%) were contaminated. The overall sensitivity of sputum microscopy was 61.8% (131/212) and specificity 99.7% (9108/9132). Sputum microscopy sensitivity varied from 22.6% in specimens with < 20 colony forming units (CFU)/specimen to 94.2% in patients with > 100 CFU/specimen plus confluent growth. The incremental diagnostic value for sputum microscopy was 92.1%, 1.8% and 7.1% for the first, second and third specimens, respectively. The positive predictive value and negative predictive values for sputum microscopy were 84.5% and 99.1%, respectively. The likelihood ratio (LR) of a positive sputum microscopy was 235.1 (95% CI 155.8 - 354.8), while the LR of a negative test was 0.38 (95CI 0.32 - 0.45). The 212 positive sputum cultures for MTB represented 103 patients; sputum microscopy was positive for 57 (55.3%) of 103 patients. CONCLUSION: Sputum microscopy on 3 expectorated sputum specimens will only detect 55% of culture positive HIV-infected patients in active screening for pulmonary tuberculosis. Sensitivity is higher in patients with greater numbers of CFUs in the sputum. Culture is required for active case finding of HIV- associated pulmonary tuberculosis.

Pre- and post-natal macronutrient supplementation for HIV-positive women in Tanzania: Effects on infant birth weight and HIV transmission.

OBJECTIVE: To determine if a protein-calorie supplement (PCS) plus a micronutrient supplement (MNS) improves outcomes for HIV-infected lactating women and their infants. DESIGN: Randomized, controlled trial. SETTING: Dar es Salaam, Tanzania. SUBJECTS, PARTICIPANTS: Pregnant HIV-infected women enrolled in PMTCT programs who intended to breastfeed for 6 months. INTERVENTION: Randomization 1:1 to administration of a PCS plus MNS versus MNS alone among 96 eligible women beginning in the third trimester and continuing for 6 months of breast-feeding. MAIN OUTCOME MEASURE(S): Primary: infant weight at 3 months. Secondary: maternal BMI at 6 months. RESULTS: PCS resulted in significant increases in daily energy intake compared to MNS at all time points (range of differences: +388-719 Kcal); and increases in daily protein intake (range of differences: +22-33 gm). Infant birth weight (excluding twins) was higher in the PCS than MNS groups: 3.30 kg vs 3.04 kg (p = 0.04). Infant weight at 3 months did not differ between PCS and MNS groups: 5.63 kg vs 5.99 kg (p = 0.07). Maternal BMI at 6 months did not differ between PCS and MNS groups: 24.3 vs 23.8 kg/m2 (p = 0.68). HIV transmission occurred in 0 infants in the PCS group vs 4 in the MNS group (p = 0.03). CONCLUSIONS: In comparison to MNS the PCS + MNS intervention was well tolerated, increased maternal energy and protein intake, and increased infant birth weight, but not weight at 3 months or maternal BMI at 6 months. Reduced infant HIV transmission in the PCS + MNS group was observed. TRIAL REGISTRATION: Clinical Trials.Gov NCT01461863.