The bacterial profile and antibiotic susceptibility pattern in respiratory tract samples from art-experienced HIV-positive adults in Uganda.

INTRODUCTION: Microbial infections are a major cause of morbidity and mortality among people living with HIV (PLWH). Respiratory tract infections (RTIs) are responsible for approximately 70% of illnesses among PLWH. Drug resistant bacteria are highly prevalent among PLWH and this is a public health concern. METHODS: This is a retrospective analysis of data collected during the COSTOP trial between 2011 and 2013. Sputum collected on spot from participants presenting with a productive cough was examined using Gram, Ziehl-Neelsen stains and cultured on suitable bacteriological media. Antimicrobial sensitivity testing was done on isolated pathogens, by disc diffusion technique. RESULTS: We included 687 participants with mean age 41.3 (SD 8.2) years of whom 76.4% were female. Two hundred one sputum samples grew bacteria; Moraxella species (27.4%), Streptococcus pneumoniae(25.4%), Haemophilus influenza(22.4%), Mycobacterium species(4.5%), Pseudomonas species(4.0%), Staphylococcus aureus(4.0%), Escherichia coli (1.0%), Klebsiella species (1.0%), other bacteria (10.4%). A higher monthly income greater than or equal to 30$ (aOR = 0.63, 95%CI: 0.40-0.99) and longer duration since HIV diagnosis (aOR = 1.06, 95%CI: 1.0-1.11) were found to be independently associated with a positive bacterial culture. Moraxella sp, H. influenza and Pseudomonas had zero sensitivity towards cotrimoxazole. Sensitivity to erythromycin was low among Moraxella sp (28.6%), H. influenza (31.6%) and S. aureus(42.9%) and other bacteria (42.9%). Most isolates were sensitive to Amoxicillin + Clavulanic acid and ceftriaxone. CONCLUSION: There is a very low sensitivity of isolated bacteria to commonly prescribed antibiotics that are more available through the national supply chain, which is of public health concern. Urgent steps to tackle the high antimicrobial resistance among PLWH is required.

Prevalence and factors associated with hypertension among people living with HIV/AIDS on antiretroviral therapy in Uganda.

INTRODUCTION: antiretroviral therapy (ART) has improved survival of People Living with HIV (PLWH); however, this has resulted in an increasingly high prevalence of non-communicable diseases (NCD) like hypertension. Hypertension is a major risk factor for cardiovascular and cerebral vascular disease, which are both associated with high morbidity and mortality rates. We studied the prevalence and factors associated with hypertension among PLWH on ART. METHODS: we conducted a retrospective data analysis of PLWH on ART enrolled between 2011 and 2014 into a randomized double-blinded placebo-controlled trial investigating the safety of discontinuing cotrimoxazole prophylaxis (COSTOP) among PLWH in Central Uganda. We used the mean blood pressure (BP) measurements of the first four monthly clinic visits to define hypertension. Patients were categorised as: having normal BP (≤120/80mmHg), elevated BP (systolic >120-129, and diastolic ≤80), Stage 1 hypertension (systolic 130-139, or diastolic >80-89) and Stage 2 hypertension (systolic ≥140 or diastolic ≥90). Multiple logistic regression was used to evaluate factors associated with hypertension. RESULTS: data from 2026 COSTOP trial study participants were analysed, 74.1% were women and 77.2% were aged 35 years and above. The overall prevalence of hypertension was 29%, of whom 19.5% had Stage 1 hypertension and 9.5% had Stage 2 hypertension. About 21.4% were overweight or obese. Factors independently associated with hypertension among PLWH on ART included increasing age (p≤0.001) and high body mass index (p≤0.001). Efavirenz (p≤0.001) and lopinavir/ritonavir (p=0.036) based regimen had lower odds of hypertension than Nevirapine based regimens. CONCLUSION: PLWH on ART have a high prevalence of hypertension, which rises with increasing age and body mass index (BMI) and among those on nevirapine-based ART. Implementation of hypertension prevention measures among PLWH on ART and integration of NCD and HIV care to improve patients' management outcomes are required.

Predictors for MTB Culture-Positivity among HIV-Infected Smear-Negative Presumptive Tuberculosis Patients in Uganda: Application of New Tuberculosis Diagnostic Technology.

BACKGROUND: The existing World Health Organization diagnostic algorithms for smear-negative TB perform poorly in HIV-infected individuals. New TB diagnostics such as urine TB lipoarabinomannan (LAM) could improve the accuracy and reduce delays in TB diagnosis in HIV-infected smear-negative presumptive TB. We sought to determine predictors for MTB culture-positivity among these patients. METHODS: This study was nested into a prospective evaluation of HIV-infected outpatients and inpatients clinically suspected to have TB who were screened by smear-microscopy on two spot sputum samples. Data on socio-demographics, clinical symptoms, antiretroviral therapy, CXR, CD4 count, mycobacterial sputum and blood cultures and TB-LAM were collected. Logistic regression and conditional inference tree analysis were used to determine the most predictive indicators for MTB culture-positivity. RESULTS: Of the 418 smear-negative participants [female, 64%; median age (IQR) 32 (28-39) years, median CD4 106 (IQR 22 - 298) cells/mm3], 96/418 (23%) were sputum and/ or blood culture-positive for Mycobacterium tuberculosis (MTB) complex. Abnormal CXR (aOR 3.68, 95% CI 1.76- 7.71, p=0.001) and positive urine TB-LAM (aOR 6.21, 95% CI 3.14-12.27, p< 0.001) were significantly associated with MTB culture-positivity. Previous TB treatment (aOR 0.41, 95% CI 0.17-0.99, p=0.049) reduced the likelihood of a positive MTB culture. A conditional inference tree analysis showed that positive urine TB-LAM and abnormal CXR were the most predictive indicators of MTB culture-positivity. A combination of urine TB-LAM test and CXR had sensitivity and specificity of 50% and 86.1% respectively overall, and 70.8% and 84.1% respectively among those with CD4<100 cells/mm3. CONCLUSIONS: A positive urine TB-LAM test and an abnormal CXR significantly predict MTB culture-positivity among smear-negative HIV-infected presumptive TB patients while previous TB treatment reduces the likelihood of a positive MTB culture. Validation studies to assess the performance of diagnostic algorithms that include urine TB-LAM in the diagnosis of smear-negative TB in HIV-infected individuals are warranted.

Point-of-care lateral flow assays for tuberculosis and cryptococcal antigenuria predict death in HIV infected adults in Uganda.

BACKGROUND: Mortality in hospitalized, febrile patients in Sub-Saharan Africa is high due to HIV-infected, severely immunosuppressed patients with opportunistic co-infection, particularly disseminated tuberculosis (TB) and cryptococcal disease. We sought to determine if a positive lateral flow assay (LFA) result for urine lipoarabinomannan (LAM) and cryptococcal antigenuria was associated with mortality. METHODS: 351 hospitalized, HIV-positive adults with symptoms consistent with TB and who were able to provide both urine and sputum specimens were prospectively enrolled at Mulago National Referral Hospital in Uganda as part of a prospective accuracy evaluation of the lateral flow Determine TB LAM test. Stored frozen urine was retrospectively tested for cryptococcal antigen (CRAG) using the LFA. We fitted a multinomial logistic regression model to analyze factors associated with death within 2 months after initial presentation. RESULTS: The median CD4 of the participants was 57 (IQR: 14-179) cells/µl and 41% (145) were microbiologically confirmed TB cases. LAM LFA was positive in 38% (134), 7% (25) were CRAG positive, and 43% (151) were positive for either test in urine. Overall, 21% (75) died within the first 2 months, and a total of 32% (114) were confirmed dead by 6 months. At 2 months, 30% of LAM or CRAG positive patients were confirmed dead compared to 15.0% of those who were negative. In an adjusted model, LAM or CRAG positive results were associated with an increased risk of death (RRR 2.29, 95% CI: 1.29, 4.05; P = 0.005). CONCLUSIONS: In hospitalized HIV-infected patients, LAM or CRAG LFA positivity was associated with subsequent death within 2 months. Further studies are warranted to examine the impact of POC diagnostic 'test and treat' approach on patient-centered outcomes.

Clinical predictors and accuracy of empiric tuberculosis treatment among sputum smear-negative HIV-infected adult TB suspects in Uganda.

INTRODUCTION: The existing diagnostic algorithms for sputum smear-negative tuberculosis (TB) are complicated, time-consuming, and often difficult to implement. The decision to initiate TB treatment in resource-limited countries is often largely based on clinical predictors. We sought to determine the clinical predictors and accuracy of empiric TB treatment initiation in HIV-infected sputum smear-negative TB suspects using sputum culture as a reference standard. SETTING: Out-patient HIV-TB integrated urban clinic in Kampala, Uganda. METHODS: HIV-infected TB suspects were screened using sputum smear microscopy, and mycobacterial sputum liquid and solid cultures were performed. Smear results were made available to the clinician who made a clinical decision on empiric TB treatment initiation for sputum smear-negative patients. Clinic records were reviewed for patients whose sputum smears were negative to collect data on socio-demographics, TB symptomatology, chest X-ray findings, CD4 cell counts and TB treatment initiation. RESULTS: Of 253 smear-negative TB suspects, 56% (142/253) were females, median age 38 IQR (31-44) years, with a median CD4 cell count of 291 IQR (150-482) cells/mm(3). Of the 85 (33.6%) smear-negative patients empirically initiated on TB treatment, 35.3% (n = 30) were sputum culture positive compared to only 18 (10.7%) of the 168 untreated patients (p<0.001). Abnormal chest X-ray [aOR 10.18, 95% CI (3.14-33.00), p<0.001] and advanced HIV clinical stage [aOR 3.92, 95% CI (1.20-12.85), p = 0.024] were significantly associated with empiric TB treatment initiation. The sensitivity and specificity of empiric TB treatment initiation in the diagnosis of TB in HIV-infected patients after negative smear microscopy was 62.5% and 73.7% respectively. CONCLUSION: In resource-limited settings, clinically advanced HIV and abnormal chest X-ray significantly predict a clinical decision to empirically initiate TB treatment in smear-negative HIV-infected patients. Empiric TB treatment initiation correlates poorly with TB cultures. Affordable, accurate and rapid point-of-care diagnostics are needed in resource-limited settings to more accurately determine which HIV-infected TB suspects have smear-negative TB.