Optimal adherence to antiretroviral therapy is critical to prevent HIV drug resistance (HIVDR) epidemic. The objective of the study was to investigate the best performing adherence assessment method ...for predicting virological failure in resource-limited settings (RLS).
This study was a single-centre prospective cohort, enrolling 220 HIV-infected adult patients attending an HIV/AIDS Care and Treatment Centre in Dar es Salaam, Tanzania, in 2010. Pharmacy refill, self-report (via visual analog scale VAS and the Swiss HIV Cohort study-adherence questionnaire), pill count, and appointment keeping adherence measurements were taken. Univariate logistic regression (LR) was done to explore a cut-off that gives a better trade-off between sensitivity and specificity, and a higher area under the curve (AUC) based on receiver operating characteristic curve in predicting virological failure. Additionally, the adherence models were evaluated by fitting multivariate LR with stepwise functions, decision trees, and random forests models, assessing 10-fold multiple cross validation (MCV). Patient factors associated with virological failure were determined using LR.
Viral load measurements at baseline and one year after recruitment were available for 162 patients, of whom 55 (34%) had detectable viral load and 17 (10.5%) had immunological failure at one year after recruitment. The optimal cut-off points significantly predictive of virological failure were 95%, 80%, 95% and 90% for VAS, appointment keeping, pharmacy refill, and pill count adherence respectively. The AUC for these methods ranged from 0.52 to 0.61, with pharmacy refill giving the best performance at AUC 0.61. Multivariate logistic regression with boost stepwise MCV had higher AUC (0.64) compared to all univariate adherence models, except pharmacy refill adherence univariate model, which was comparable to the multivariate model (AUC = 0.64). Decision trees and random forests models were inferior to boost stepwise model. Pharmacy refill adherence (<95%) emerged as the best method for predicting virological failure. Other significant predictors in multivariate LR were having a baseline CD4 T lymphocytes count < 200 cells/μl, being unable to recall the diagnosis date, and a higher weight.
Pharmacy refill has the potential to predict virological failure and to identify patients to be considered for viral load monitoring and HIVDR testing in RLS.
The pathogenesis of hypertension (HTN) in people living with HIV/AIDS (PLHIV) is complex and remains not fully understood. Chronic immune activation (IA) is postulated to be one of the culprits. This ...notion is derived from studies in HIV-uninfected populations and/or animals while data on HTN and how it relates to IA in PLHIV remains scarce. We determined the relationship between HTN and IA among antiretroviral therapy (ART) naïve PLHIV. We analysed baseline data of 365 out of 430 clinical trial participants whose main aim was to investigate the effect of low-dose aspirin on HIV disease progression in PLHIV starting ART. Soluble CD14 (sCD14), T cells co-expressing CD38 and HLA-DR, and PD-1 were the IA and exhaustion markers, respectively studied and were analysed by flow cytometry. Mann-Whitney U-test was used for comparison of the markers by HTN status. A robust Poisson regression model was used to determine the predictors for HTN. A quarter of the 365 were hypertensive (25.3%, 95% CI 20.9-29.8%), and, had higher median (IQR) body mass index (kg/m.sup.2) (23.4 (19.6, 28.0) versus 21.9 (19.3, 25.1)) and lower median (IQR) estimated glomerular filtration rate (mL/min/1.73m.sup.2) (101.2 (79.4, 126.9) versus 113.6 (92.7, 138.8)) than normotensive participants (p < 0.05). Participants with HTN had higher median frequencies of all markers of IA and exhaustion but lower sCD14 (p > 0.05). None of these markers significantly predicted the occurrence of HTN. Studied markers of IA and exhaustion were higher in PLHIV with HTN than those without but were unpredictive of HTN. Larger multicentre studies with a wider range of markers are needed to confirm the role of IA in HIV-associated HTN.
Klebsiella pneumoniae strains expressing ESBLs are a predominant cause of hospital acquired infections. Here we describe the molecular epidemiology of these isolates in a tertiary hospital in ...Tanzania, as potential pathogens for neonatal infections.
Between April 2009 and March 2010 all Klebsiella pneumoniae isolates with phenotypic expression Extended Spectrum Beta Lactamase (ESBL) were collected and characterized. Identification was done using in house biochemical tests in case of ambiguous results confirmation was done using API 20E. Susceptibility testing was determined using the disc diffusion method followed by specific PCR and sequencing to determine ESBL genes. Phylogenetic analysis, Pulse field gel electrophoresis (PFGE) and Multi-Locus sequence typing (MLST) to PFGE clusters representative isolates were performed to determine clones of the isolates. Conjugation and hybridization were performed to determine the location of blaCTX-M-15 gene.
A total of 92 non-repetitive ESBL producing K. pneumoniae representing 50.3% of Klebsiella pneumoniae isolates were characterized. These isolates were from blood 61 (66%), wound swab 13 (14%), urine 12 (13%) and pus 6 (7%) were analyzed. Most blood culture strains originated from neonatal unit 39/61(64%) and 22 (36%) of the blood culture isolates were from neonatal ICU. All isolates were resistant to gentamicin and 54% were resistant to ciprofloxacin. Using a similarity index of 80%, the isolates were assigned to thirteen clusters based on PFGE patterns and contained sub-clusters with identical strains indicating clonal outbreaks. Cluster X5, X7 and X8, and X9 were grouped into ST48, ST14 and ST348 respectively. Based on gyrA PCR- RFLP phylogenetic analysis all isolates were grouped as KpI. The predominant ESBL allele detected was blaCTX-M-15 which was found in 76% of isolates, followed by blaTEM-104 (19%), blaSHV-11 (3.2%) and blaTEM-176 (2%). The blaCTX-M-15 gene was located in multiple conjugative IncF plasmids ranging from 25 kb-485 kb in size.
The high prevalence of blaCTX-M-15 observed among ESBL producing K. pneumoniae in Tanzania, is possibly due to the spread of a common IncFII 145 kb plasmid and of certain clones such as ST14 and ST48. Furthermore the 485 kb plasmid detected is the largest plasmid reported to carry blaCTX-M-15 todate.
Vaccine-induced HIV antibodies were evaluated in serum samples collected from healthy Tanzanian volunteers participating in a phase I/II placebo-controlled double blind trial using multi-clade, ...multigene HIV-DNA priming and recombinant modified vaccinia Ankara (HIV-MVA) virus boosting (HIVIS03). The HIV-DNA vaccine contained plasmids expressing HIV-1 gp160 subtypes A, B, C, Rev B, Gag A, B and RTmut B, and the recombinant HIV-MVA boost expressed CRF01_AE HIV-1 Env subtype E and Gag-Pol subtype A. While no neutralizing antibodies were detected using pseudoviruses in the TZM-bl cell assay, this prime-boost vaccination induced neutralizing antibodies in 83% of HIVIS03 vaccinees when a peripheral blood mononuclear cell (PBMC) assay using luciferase reporter-infectious molecular clones (LucR-IMC) was employed. The serum neutralizing activity was significantly (but not completely) reduced upon depletion of natural killer (NK) cells from PBMC (p=0.006), indicating a role for antibody-mediated Fcγ-receptor function. High levels of antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies against CRF01_AE and/or subtype B were subsequently demonstrated in 97% of the sera of vaccinees. The magnitude of ADCC-mediating antibodies against CM235 CRF01_AE IMC-infected cells correlated with neutralizing antibodies against CM235 in the IMC/PBMC assay. In conclusion, HIV-DNA priming, followed by two HIV-MVA boosts elicited potent ADCC responses in a high proportion of Tanzanian vaccinees. Our findings highlight the potential of HIV-DNA prime HIV-MVA boost vaccines for induction of functional antibody responses and suggest this vaccine regimen and ADCC studies as potentially important new avenues in HIV vaccine development.
Controlled-Trials ISRCTN90053831 The Pan African Clinical Trials Registry ATMR2009040001075080 (currently PACTR2009040001075080).
Group B streptococcus (GBS), which asymptomatically colonises the vaginal and rectal areas of women, is the leading cause of septicemia, meningitis and pneumonia in neonates. In Tanzania no studies ...have been done on GBS colonisation of pregnant women and neonates. This study was conducted in Dar es Salaam, Tanzania to determine the prevalence of GBS colonisation among pregnant women, the neonatal colonisation rate and the antimicrobial susceptibility, thus providing essential information to formulate a policy for treatment and prevention regarding perinatal GBS diseases.
This cross sectional study involved 300 pregnant women attending antenatal clinic and their newborns delivered at Muhimbili National Hospital (MNH) between October 2008 and March 2009. High vaginal, rectal, nasal, ear and umbilical swabs were cultured on Todd Hewitt Broth and in 5% sheep blood agar followed by identification of isolates using conventional methods and testing for their susceptibility to antimicrobial agents using the Kirby-Bauer method.
GBS colonisation was confirmed in 23% of pregnant women and 8.9% of neonates. A higher proportion of GBS were isolated from the vagina (12.3%) as compared to the rectum (5%). Prolonged duration of labour (>12 hrs) was significantly shown to influence GBS colonisation in neonates P < 0.05. Other risk factors such as prolonged rupture of membrane, intrapartum fever, low birth weight and HIV infection did not correlate with GBS colonisation. All isolates were sensitive to vancomycin and ampicillin. Resistance to clindamycin, erythromycin and penicillin G was found to 17.6%, 13% and 9.4%, respectively.
Our findings seem to suggest that a quarter of pregnant women attending ANC clinic at MNH and approximately 10% of their newborns are colonised with GBS. All isolates were found to be sensitive to vancomycin and ampicillin which seem to be the most effective antibiotics for the time being. However there is a need for continuous antibiotics surveillance of GBS to monitor trend of resistance. The high isolation frequency of GBS among pregnant women suggests routine antenatal screening at 35 to 37 weeks of gestation in order to provide antibiotic prophylaxis to GBS carrier.
Surgical site infections (SSIs) remain a common and widespread problem contributing to a significant morbidity and mortality, attributed partly by the increase in antimicrobial resistance among the ...etiological agents. This study was done to determine the spectrum of bacterial isolates and their susceptibility patterns causing SSIs at Muhimbili National Hospital, Tanzania.
This descriptive cross sectional study was conducted between September, 2011 and February, 2012. Pus swabs or pus were cultured on blood agar (Oxoid, UK) and MacConkey agar (Oxoid, UK) and incubated aerobically at 37°C for 18-24 hours. Bacterial identification was done using API 20E and VITEK and antimicrobial susceptibility was determined by Kirby Bauer disc diffusion.
Of the 100 patients, from whom wound swabs were collected, 90 (90%) had positive aerobic bacterial growth. A total of 147 pathogenic bacteria were isolated, including 114 (77.5%) gram negative and 33(22.5%) gram positive organisms. The most prevalent bacterial species were Pseudomonas aeruginosa (16.3%), followed by Staphylococcus aureus (12.2%) and Klebsiella pneumoniae (10.8%). Of the 18 S. aureus , 8 (44%) were methicillin resistant Staphylococcus aureus (MRSA) and three of them (17%) were carrying both MRSA and induced clindamycin resistance (ICR). Extended spectrum beta-lactamase (ESBL) producing Enterobacteriaceae were observed in 23 (79.3%) of the 29 isolates tested. Majority of Escherichia coli 12 (92.3%) and K. pneumoniae 11 (69%) isolates were ESBL producers. About 63% (93/147) were multiple-drug resistance (MDR) isolates, and the overall MDR among Gram positive and Gram negative bacteria was 60.6% (20/33) and 61.4%, (73/114), respectively. The prevalence of MDR for E. coli, A. baumannii and P. stuartii was 100% each. Majority (97%) of the Gram negative bacteria were resistant to more than four categories (classes) of antibiotics.
A high proportion (63%) of the isolates causing SSIs in this tertiary hospital were MDR, of which (90%) were resistant to more than four classes of antibiotics. In the light of these findings, an urgent and significant change in antibiotic prescription policy is required at this National hospital.
Published data on the existence and magnitude of extended spectrum beta-lactamase (ESBL) production in urinary pathogens in local setting is limited. The aim of the present study was to determine the ...prevalence of antimicrobial resistance and ESBL production among Escherichia coli and Klebsiella spp from urine samples in a tertiary hospital. This was a cross sectional study conducted at Muhimbili National Hospital in Dar es Salaam, Tanzania.
A total of 270 E.coli and Klebsiella spp urinary pathogens from children and adults isolated from January to March 2010 were included in the study. E. coli and Klebsiella spp isolates were tested for antimicrobial susceptibility by the Clinical and Laboratory Standard Institute's disc diffusion method. These isolates were further screened for ESBL phenotype using cefotaxime and ceftazidime discs. Isolates with reduced sensitivity were confirmed using ESBL E-test strips. Of 270 isolates, 138 (51.1%) were E. coli and 132 (48.9%) were Klebsiella spp. ESBL was detected in 122 (45.2%) of all the isolates. ESBL- producing E. coli strains were significantly more resistance to cotrimoxazole (90.7%), ciprofloxacin (46.3%) and nalidixic acid (61.6%) than strains that did not produce ESBL (p < 0.05). Similarly, ESBL- producing Klebsiella spp strains were significantly more resistance to cotrimoxazole (92.6%), ciprofloxacin (25.0%), nalidixic acid (66.2%), and gentamicin (38.2%) than strains that did not produce ESBL (P < 0.05). Multi-drug resistance was found to be significantly (P < 0.05) more in ESBL producing isolates (90.5%) than non ESBL producers (68.9%). The occurrence of ESBL was significantly higher among isolates from inpatients than outpatients 95 (50.5%) vs. 27(32.9%) (p = 0.008). The occurrence of ESBL was significantly higher among isolates from children than in adults 84 (54.9%) vs. 38(32.5%) (p < 0.001).
High prevalence of ESBL-producing E. coli and Klebsiella spp strains was found among inpatients and children. Most of the ESBL- producing isolates were multi-drug resistant making available therapeutic choices limited. We recommend continued antibiotic surveillance as well comprehensive multi-center studies to address the emerging problem of ESBL-associated infections in order to preserve the continued usefulness of most antimicrobial drugs. Further more conducting molecular studies will help to evaluate the various ESBL types.
A vaccine against HIV is widely considered the most effective and sustainable way of reducing new infections. We evaluated the safety and impact of boosting with subtype C CN54rgp140 envelope protein ...adjuvanted in glucopyranosyl lipid adjuvant (GLA-AF) in Tanzanian volunteers previously given three immunizations with HIV-DNA followed by two immunizations with recombinant modified vaccinia virus Ankara (HIV-MVA).
Forty volunteers (35 vaccinees and five placebo recipients) were given two CN54rgp140/GLA-AF immunizations 30-71 weeks after the last HIV-MVA vaccination. These immunizations were delivered intramuscularly four weeks apart.
The vaccine was safe and well tolerated except for one episode of asymptomatic hypoglycaemia that was classified as severe adverse event. Two weeks after the second HIV-MVA vaccination 34 (97%) of the 35 previously vaccinated developed Env-specific binding antibodies, and 79% and 84% displayed IFN-γ ELISpot responses to Gag and Env, respectively. Binding antibodies to subtype C Env (included in HIV-DNA and protein boost), subtype B Env (included only in HIV-DNA) and CRF01_AE Env (included only in HIV-MVA) were significantly boosted by the CN54rgp140/GLA-AF immunizations. Functional antibodies detected using an infectious molecular clone virus/peripheral blood mononuclear cell neutralization assay, a pseudovirus/TZM-bl neutralization assay or by assays for antibody-dependent cellular cytotoxicity (ADCC) were not significantly boosted. In contrast, T-cell proliferative responses to subtype B MN antigen and IFN-γ ELISpot responses to Env peptides were significantly enhanced. Four volunteers not primed with HIV-DNA and HIV-MVA before the CN54rgp140/GLA-AF immunizations mounted an antibody response, while cell-mediated responses were rare. After the two Env subtype C protein immunizations, a trend towards higher median subtype C Env binding antibody titers was found in vaccinees who had received HIV-DNA and HIV-MVA prior to the two Env protein immunizations as compared to unprimed vaccinees (p = 0.07).
We report excellent tolerability, enhanced binding antibody responses and Env-specific cell-mediated immune responses but no ADCC antibody increase after two immunizations with a subtype C rgp140 protein adjuvanted in GLA-AF in healthy volunteers previously immunized with HIV-DNA and HIV-MVA.
International Clinical Trials Registry PACTR2010050002122368.
A cohort of female sex workers (FSWs) was established to determine HIV prevalence and incidence, and associated factors in preparation for a phase IIb HIV vaccine and pre-exposure prophylaxis trial ...(PrEPVacc).
A cohort of FSWs in Dar es Salaam, Tanzania.
FSWs aged 18-45 years were recruited using a respondent-driven sampling method. Social demographic data, HIV risk behavioral assessments, and blood samples for testing of HIV, syphilis, hepatitis B (HBV), and hepatitis C (HCV) infections were collected at baseline and then at 3, 6, 9, and 12 months. Poisson regressions were used to estimate the prevalence ratios for factors associated with HIV prevalence and to estimate the 12-month HIV incidence rate.
Between October and December 2018, a total of 773 FSWs were screened for eligibility and 700 were enrolled. The baseline prevalence of HIV, syphilis, HBV, and HCV was 7.6%, 1.2%, 1.7%, and 1.0%, respectively. HIV prevalence was associated with older age, using illicit drugs, and being infected with syphilis, HBV, or HCV. Attendance at 12 months was 80% (562/700). Twenty-one FSWs seroconverted during follow-up, giving a 12-month HIV incidence rate of 3.45 per 100 person-years at risk (95% CI; 2.25-5.28/100 person-years at risk). The HIV incidence rate was higher among FSWs aged 18-24 years, FSWs who used drugs, and those diagnosed with syphilis, HBV, or HCV.
The high HIV incidence rate and retention rate among FSWs enrolled into the cohort demonstrate that this population is suitable for participation in HIV prevention trials.
Cardiovascular diseases (CVDs) have become an important cause of ill health and death among people living with HIV and/or AIDS (PLHIV) in the antiretroviral therapy (ART) era. There is scarce data on ...the burden of hypertension (HTN) and risk factors for CVDs among PLHIV in developing countries, including Tanzania during the ART era.
To determine the prevalence of HTN and risk factors for CVDs among ART naïve PLHIV initiating ART.
We analysed baseline data of 430 clinical trial participants on the effect of low-dose aspirin on HIV disease progression among HIV-infected individuals initiating ART. HTN was the outcome CVD. Traditional risk factors for CVDs studied were age, alcohol consumption, cigarette smoking, individual and family history of CVDs, diabetes mellitus (DM), obesity/overweight, and dyslipidaemia. A generalized linear model (robust Poisson regression) was used to determine the predictors for HTN.
The median (IQR) age was 37 (28, 45) years. Females were the majority contributing 64.9% of all participants. The prevalence of HTN was 24.8%. The most prevalent risk factors for CVDs were dyslipidaemia (88.3%), alcohol consumption (49.3%), and overweight or obesity (29.1%). Being overweight or obese predicted the occurrence of HTN, aPR 1.60 (95% CI 1.16-2.21) while WHO HIV clinical stage 3 was protective against HTN, aPR 0.42(95% CI 0.18-0.97).
The prevalence of HTN and traditional risk factors for CVDs in the treatment naïve PLHIV initiating ART are significant. Identifying these risk factors and managing them at the time of ART initiation may lower future CVDs among PLHIV.
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