Hypertension and traditional risk factors for cardiovascular diseases among treatment naïve HIV- infected adults initiating antiretroviral therapy in Urban Tanzania.

BACKGROUND: 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. OBJECTIVE(S): To determine the prevalence of HTN and risk factors for CVDs among ART naïve PLHIV initiating ART. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Colonization of Extended-spectrum ß-lactamase producing Enterobacterales and meticillin-resistant S. aureus in the intensive care unit at a tertiary hospital in Tanzania: Implications for Infection control and prevention.

Background: Multi-drug resistant (MDR) bacteria pose a major global threat to public-health and are of particular concern to hospitalized intensive care unit (ICU) patients. This study aimed at addressing the burden of MDR and the associated factors at admission to ICU. Methods: This was a cross-sectional study conducted at the ICU of a tertiary hospital in Tanzania. Rectal and anterior nares swabs were collected within 48 hours of ICU admission to screen for extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) and meticillin-resistant Staphylococcus aureus (MRSA), respectively. Results: The proportion of fecal carriage for ESBL-PE at admission to ICU was 54.54% (95% CI, 47.52-61.39), and nasal carriage for MRSA was 9.32% (95%CI, 5.67-14.93). The nasal MRSA colonization (OR = 1.52) and fecal carriage for ESBL-PE (OR=1.38) were more likely in participants who had received antibiotics before ICU admission than not, but association was not statistically significant. Hospitalization for ≥2 days (OR=1.18) was associated with fecal carriage of ESBL-PE, though not statistically significant. Overall, 66% and 73.5% of patients received antibiotics before and upon admission to ICU, respectively. Ceftriaxone, metronidazole and meropenem were commonly prescribed antibiotics. More than 84% of Enterobacterales were resistant to ciprofloxacin and trimethoprim-sulfamethoxazole, and 2.90% were resistant to meropenem. MRSA isolates showed a high rate of resistance to gentamicin and erythromycin. Conclusion: MDR bacteria are common in patients admitted to ICU. To reduce the risk associated with MDR, we recommend use of simple screening methods to screen for MDR at ICU admission as part of infection control and prevention.

Frequent and Durable Anti-HIV Envelope VIV2 IgG Responses Induced by HIV-1 DNA Priming and HIV-MVA Boosting in Healthy Tanzanian Volunteers.

We evaluated antibody responses to the human immunodeficiency virus (HIV) envelope variable regions 1 and 2 (V1V2) in 29 vaccinees who had received three HIV-1 DNA immunizations and two HIV-modified vaccinia virus Ankara (MVA) boosts in the phase I/II HIVIS03 vaccine trial. Twenty vaccinees received a third HIV-MVA boost after three years in the HIVIS06 trial. IgG and IgG antibody subclasses to gp70V1V2 proteins of HIV-1 A244, CN54, Consensus C, and Case A2 were analysed using an enzyme-linked immunosorbent assay (ELISA). Cyclic V2 peptides of A244, Consensus C, and MN were used in a surface plasmon resonance (SPR) assay. Four weeks after the second HIV-MVA, anti-V1V2 IgG antibodies to A244 were detected in 97% of HIVIS03 vaccinees, in 75% three years later, and in 95% after the third HIV-MVA. Anti-CN54 V1V2 IgG was detectable in 48% four weeks after the second HIV-MVA. The SPR data supported the findings. The IgG response was predominantly IgG1. Four weeks after the second HIV-MVA, 85% of vaccinees had IgG1 antibodies to V1V2 A244, which persisted in 25% for three-years. IgG3 and IgG4 antibodies to V1V2 A244 were rare. In conclusion, the HIV-DNA/MVA vaccine regimen induced durable V1V2 IgG antibody responses in a high proportion of vaccinees.

Induction of Identical IgG HIV-1 Envelope Epitope Recognition Patterns After Initial HIVIS-DNA/MVA-CMDR Immunization and a Late MVA-CMDR Boost.

In the RV144 trial, to date the only HIV-1 vaccine efficacy trial demonstrating a modestly reduced risk of HIV-1 acquisition, antibody responses toward the HIV Envelope protein (Env) variable (V) 2 and V3 regions were shown to be correlated with a reduced risk of infection. These potentially protective antibody responses, in parallel with the vaccine efficacy, however, waned quickly. Dissecting vaccine-induced IgG recognition of antigenic regions and their variants within the HIV-1 Env from different vaccine trials will aid in designing future HIV-1 immunogens and vaccination schedules. We, therefore, analyzed the IgG response toward linear HIV-1 Env epitopes elicited by a multi-clade, multigene HIVIS-DNA priming, and heterologous recombinant modified vaccinia virus Ankara (MVA-CMDR) boosting regimen (HIVIS03) and assessed whether a late MVA-CMDR boost 3 years after completion of the initial vaccination schedule (HIVIS06) restored antibody responses toward these epitopes. Here we report that vaccination schedule in the HIVIS03 trial elicited IgG responses against linear epitopes within the V2 and V3 tip as well as against the gp41 immunodominant region in a high proportion of vaccinees. Antibodies against the V2 and gp41 Env regions were restricted to variants with close homology to the MVA-CMDR immunogen sequence, while V3 responses were more cross-reactive. Boosting with a late third MVA-CMDR after 3 years effectively restored waned IgG responses to linear Env epitopes and induced targeting of identical antigenic regions and variants comparable to the previous combined HIVIS-DNA/MVA-CMDR regimen. Our findings support the notion that anti-HIV-1 Env responses, associated with a reduced risk of infection in RV144, could be maintained by regular boosting with a single dose of MVA-CMDR.

Nasal Carriage of Methicillin-Resistant Staphylococcus aureus among Health Care Workers in Tertiary and Regional Hospitals in Dar es Salam, Tanzania.

Methicillin-resistant Staphylococcus aureus (MRSA) among health care workers (HCWs) increases the risk of spreading the organism in hospital settings. A cross-sectional study was conducted between June and October 2016 among HCWs in tertiary and regional hospitals in Dar es Salaam, Tanzania, to determine the MRSA nasal carriage rate. Nasal swabs were collected from HCWs and cultured on mannitol salt agar. S. aureus was identified based on colonial morphology, Gram staining, catalase, coagulase, and DNase test results. MRSA was detected using the cefoxitin disk. Among 379 HCWs enrolled, 157/379 (41.4%) were colonized with S. aureus, of whom 59 (37.6%) were MRSA carriers giving an overall prevalence of 59/379 (15.6%). MRSA carriage was high among HCWs in Temeke (56.9%) and Amana (37.5%) regional hospitals. A high proportion of MRSA carriage was detected among nurses (35, 45.5%). MRSA isolates showed high resistance toward kanamycin (83.7%), gentamicin (83.1%), ciprofloxacin (71.2%), and trimethoprim-sulphamethoxazole (46.8%) compared to methicillin-sensitive S. aureus isolates (p ≤ 0.001). In conclusion, we found a high nasal carriage of MRSA and resistance to commonly prescribed antimicrobial agents among HCWs. Implementation of infection control measures including contact precautions, urgent reporting of MRSA laboratory results, and routine MRSA screening of HCWs is highly needed to reduce MRSA spreading.

Predictors of non adherence to antiretroviral therapy at an urban HIV care and treatment center in Tanzania.

BACKGROUND: Measurement of adherence to antiretroviral therapy (ART) can serve as a proxy for virologic failure in resource-limited settings. The aim of this study was to determine the factors underlying nonadherence measured by three methods. PATIENTS AND METHODS: This is a prospective longitudinal cohort of 220 patients on ART at Amana Hospital in Dar es Salaam, Tanzania. We measured adherence using a structured questionnaire combining a visual analog scale (VAS) and Swiss HIV Cohort Study Adherence Questionnaire (SHCS-AQ), pharmacy refill, and appointment keeping during four periods over 1 year. Overall adherence was calculated as the mean adherence for all time points over the 1 year of follow-up. At each time point, adherence was defined as achieving a validated cutoff for adherence previously defined for each method. RESULTS: The proportion of overall adherence was 86.4% by VAS, 69% by SHCS-AQ, 79.8% by appointment keeping, and 51.8% by pharmacy refill. Forgetfulness was the major reported reason for patients to skip their medications. In multivariate analysis, significant predictors to good adherence were older age, less alcohol consumption, more advanced World Health Organization clinical staging, and having a lower body mass index with odds ratio (CI): 3.11 (1.55-6.93), 0.24 (0.09-0.62), 1.78 (1.14-2.84), and 0.93 (0.88-0.98), respectively. CONCLUSION: We found relatively good adherence to ART in this setting. Barriers to adherence include young age and perception of well-being.

Erratum to: Prevalence of methicillin-resistant Staphylococcus aureus carriage on admission among patients attending regional hospitals in Dar es Salaam, Tanzania.

Following publication of the original article [1], author Elia Mmbaga pointed out that her name had been misspelt as Elia Mbaga.

Prevalence of methicillin-resistant Staphylococcus aureus carriage on admission among patients attending regional hospitals in Dar es Salaam, Tanzania.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen responsible for hospital and community acquired infection. Colonization with MRSA is associated with a high risk of developing infection. This study aimed to determine the rate of MRSA carriage on admission and the associated risk factors among patients attending regional hospitals, in Dar es Salaam, Tanzania. RESULTS: A total of 258 patients were included in this study. Nasal swabs were collected on admission to the hospital and after 48 h of hospital stay for detection of MRSA. Of 258 patients enrolled, 89 (34.5%) were colonized with S. aureus and out them 22 (24.7%) were carriers of MRSA, giving an overall MRSA nasal carriage rate of 8.5% (22/258). One patient acquired MRSA while admitted in the hospital. Most of the S. aureus isolates 85 (95.5%) were resistant to penicillin. Resistance to gentamycin, ciprofloxacin, kanamycin, linezolid and mupirocin were 14.6, 11.2, 11.2, 3.4 and 1.1%, respectively. The prevalence of inducible clindamycin resistance, constitutive clindamycin resistance, MS phenotype (resistance to erythromycin alone), and multidrug resistance was 21.3, 3.4, 12.4, and 16.9%, respectively. We observed a statistically significant association between MRSA and multiple drugs resistance among S. aureus isolates (p = 0.001). Of the risk factors investigated none were statistically significant associated with MRSA. CONCLUSION: There is a high prevalence of MRSA among patients on admission at the two municipal hospitals in Dar es Salaam. The high prevalence of MRSA and the increased rates of resistance to commonly used antimicrobials among MRSA isolates call for attention to the importance of including the screening of MRSA in our hospitals setting in order to prevent further spread of MRSA strains to other patients and to the communities. Control and prevention strategies should be emphasized including decolonization.

Three-Year Durability of Immune Responses Induced by HIV-DNA and HIV-Modified Vaccinia Virus Ankara and Effect of a Late HIV-Modified Vaccinia Virus Ankara Boost in Tanzanian Volunteers.

We explored the duration of immune responses and the effect of a late third HIV-modified vaccinia virus Ankara (MVA) boost in HIV-DNA primed and HIV-MVA boosted Tanzanian volunteers. Twenty volunteers who had previously received three HIV-DNA and two HIV-MVA immunizations were given a third HIV-MVA immunization 3 years after the second HIV-MVA boost. At the time of the third HIV-MVA, 90% of the vaccinees had antibodies to HIV-1 subtype C gp140 (median titer 200) and 85% to subtype B gp160 (median titer 100). The majority of vaccinees had detectable antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies, 70% against CRF01_AE virus-infected cells (median titer 239) and 84% against CRF01_AE gp120-coated cells (median titer 499). A high proportion (74%) of vaccinees had IFN-γ ELISpot responses, 63% to Gag and 42% to Env, 3 years after the second HIV-MVA boost. After the third HIV-MVA, there was an increase in Env-binding antibodies and ADCC-mediating antibodies relative to the response seen at the time of the third HIV-MVA vaccination, p < .0001 and p < .05, respectively. The frequency of IFN-γ ELISpot responses increased to 95% against Gag or Env and 90% to both Gag and Env, p = .064 and p = .002, respectively. In conclusion, the HIV-DNA prime/HIV-MVA boost regimen elicited potent antibody and cellular immune responses with remarkable durability, and a third HIV-MVA immunization significantly boosted both antibody and cellular immune responses relative to the levels detected at the time of the third HIV-MVA, but not to higher levels than after the second HIV-MVA.

Boosting with Subtype C CN54rgp140 Protein Adjuvanted with Glucopyranosyl Lipid Adjuvant after Priming with HIV-DNA and HIV-MVA Is Safe and Enhances Immune Responses: A Phase I Trial.

BACKGROUND: 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). METHODS: 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. RESULTS: 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). CONCLUSION: 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. TRIAL REGISTRATION: International Clinical Trials Registry PACTR2010050002122368.

Potent functional antibody responses elicited by HIV-I DNA priming and boosting with heterologous HIV-1 recombinant MVA in healthy Tanzanian adults.

UNLABELLED: 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. TRIAL REGISTRATION: Controlled-Trials ISRCTN90053831 The Pan African Clinical Trials Registry ATMR2009040001075080 (currently PACTR2009040001075080).

Pharmacy refill adherence outperforms self-reported methods in predicting HIV therapy outcome in resource-limited settings.

BACKGROUND: 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). METHOD: 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. RESULTS: 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. CONCLUSION: 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.

Predominance of multi-drug resistant bacterial pathogens causing surgical site infections in Muhimbili National Hospital, Tanzania.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

High nasal carriage of methicillin-resistant Staphylococcus aureus among healthy Tanzanian under-5 children.

This study aimed to determine the prevalence of Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) carriage, risk factors of colonization and antimicrobial susceptibility patterns of S. aureus strains. The study was conducted at the Muhimbili National Hospital in Dar es Salaam, Tanzania. Nasal swabs were obtained from children and S. aureus was isolated and identified using conventional culture methods. MRSA was screened and confirmed using the cefoxitin disk and multiplex real-time polymerase chain reaction, respectively. Antibiotic susceptibility was performed using the Kirby-Bauer disk diffusion method. MRSA isolates were further characterized by pulsed field gel electrophoresis (PFGE) profiling. Of 285 children included in the study, S. aureus was detected in 114 (40%). Of the 114 isolates, 12 (10.5%) were MRSA. PFGE results showed that these MRSA isolates are epidemiologically unrelated. Resistance of all S. aureus to trimethoprim-sulfamethoxazole, tetracycline, gentamicin, and ciprofloxacin was 65.8%, 23.7%, 27.2%, and 4.4%, respectively. No resistance to vancomycin was found. The prevalence of inducible clindamycin resistance, constitutive clindamycin resistance, MS phenotype (resistance to erythromycin alone), and multidrug resistance was 16.7%, 1.8%, 14.0%, and 16.8%, respectively. None of the risk factors examined was found to be significant. This is the first report of S. aureus and nasal carriage of MRSA and a high rate of S. aureus carriage was found in Tanzanian under-5 children. The study findings support the need for proper health education and effective infection control measures for healthcare workers.

Predominance of Klebsiella pneumoniae ST14 carrying CTX-M-15 causing neonatal sepsis in Tanzania.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Plague in Tanzania: an overview.

Human plague remains a public health concern in Tanzania despite its quiescence in most foci for years, considering the recurrence nature of the disease. Despite the long-standing history of this problem, there have not been recent reviews of the current knowledge on plague in Tanzania. This work aimed at providing a current overview of plague in Tanzania in terms of its introduction, potential reservoirs, possible causes of plague persistence and repeated outbreaks in the country. Plague is believed to have been introduced to Tanzania from the Middle East through Uganda with the first authentication in 1886. Xenopsylla brasiliensis, X. cheopis, Dinopsyllus lypusus, and Pulex irritans are among potential vectors while Lophuromys spp, Praomys delectorum, Graphiurus murinus, Lemniscomys striatus, Mastomys natalensis, and Rattus rattus may be the potential reservoirs. Plague persistence and repeated outbreaks in Tanzania are likely to be attributable to a complexity of factors including cultural, socio-economical, environmental and biological. Minimizing or preventing people's proximity to rodents is probably the most effective means of preventing plague outbreaks in humans in the future. In conclusion, much has been done on plague diagnosis in Tanzania. However, in order to achieve new insights into the features of plague epidemiology in the country, and to reorganize an effective control strategy, we recommend broader studies that will include the ecology of the pathogen, vectors and potential hosts, identifying the reservoirs, dynamics of infection and landscape ecology.

Factors associated with flea infestation among the different rodent species in Mbulu and Karatu districts, northern Tanzania.

Flea infection with the bacterium, Yersinia pestis is acquired from reservoirs which include several rodents and other small mammals. In areas that are endemic of plague, reservoirs of Y. pestis and various flea vectors are responsible for perpetuating existence of the disease. The objective of this cross sectional study was to investigate the magnitude and factors associated with flea infestation among different rodent species of northern Tanzania, where outbreaks of plague have been recently reported. House rodents were trapped with box traps, while field and forest rodents were trapped with Sherman live traps. Fleas were removed from the rodents by using shoe-shining brush and were identified to genus level. Among the captured rodents, Rattus rattus (26.5%), Lophuromys flavopunctatus (16.5%), Praomys delectorum (16.2%) and Mastomys natalensis (32.3%) were most abundant rodent species, accounting for 91% of all species. Altogether, 805 fleas belonging to nine species were collected from 61% of the captured rodents. The most common fleas were Xenopsylla spp.; Dinopsyllus spp and Ctenophthalmus spp. Fleas were found to be highly abundant in M. natalensis, R. rattus, P. delectorum and L .flavopunctatus. Most of rodents were heavily infested with various flea species. These flea species probably play an important role in the transmission of plague in these two districts. We conclude that rodent species was the most important risk factor associating with flea infestation among the rodent population. Therefore, measures for control and prevention of plague in this area should particularly target rodents associated with high intensity of flea infestation.

Curricular transformation of health professions education in Tanzania: the process at Muhimbili University of Health and Allied Sciences (2008-2011).

Tanzania requires more health professionals equipped to tackle its serious health challenges. When it became an independent university in 2007, Muhimbili University of Health and Allied Sciences (MUHAS) decided to transform its educational offerings to ensure its students practice competently and contribute to improving population health. In 2008, in collaboration with the University of California San Francisco (UCSF), all MUHAS's schools (dentistry, medicine, nursing, pharmacy, and public health and social sciences) and institutes (traditional medicine and allied health sciences) began a university-wide process to revise curricula. Adopting university-wide committee structures, procedures, and a common schedule, MUHAS faculty set out to: (i) identify specific competencies for students to achieve by graduation (in eight domains, six that are inter-professional, hence consistent across schools); (ii) engage stakeholders to understand adequacies and inadequacies of current curricula; and (iii) restructure and revise curricula introducing competencies. The Tanzania Commission for Universities accredited the curricula in September 2011, and faculty started implementation with first-year students in October 2011. We learned that curricular revision of this magnitude requires: a compelling directive for change, designated leadership, resource mobilization inclusion of all stakeholders, clear guiding principles, an iterative plan linking flexible timetables to phases for curriculum development, engagement in skills training for the cultivation of future leaders, and extensive communication.

Predominance of methicillin resistant Staphylococcus aureus -ST88 and new ST1797 causing wound infection and abscesses.

INTRODUCTION: Although there has been a worldwide emergence and spread of methicillin-resistant Staphylococcus aureus (MRSA), little is known about the molecular epidemiology of MRSA in Tanzania. METHODOLOGY: In this study, we characterized MRSA strains isolated from clinical specimens at the Bugando Medical Centre, Tanzania, between January and December 2008. Of 160 S. aureus isolates from 600 clinical specimens, 24 (15%) were found to be MRSA. Besides molecular screening for the Panton Valentine leukocidin (PVL) genes by PCR, MRSA strains were further characterized by Multi-Locus Sequence Typing (MLST) and spa typing. RESULTS: Despite considerable genetic diversity, the spa types t690 (29.1%) and t7231 (41.6%), as well as the sequence types (ST) 88 (54.2%) and 1797 (29.1%), were dominant among clinical isolates. The PVL genes were detected in 4 isolates; of these, 3 were found in ST 88 and one in ST1820. Resistance to erythromycin, clindamicin, gentamicin, tetracycline and co-trimoxazole was found in 45.8%, 62.5%, 41.6%, 45.8% and 50% of the strains, respectively. CONCLUSION: We present the first thorough typing of MRSA at a Tanzanian hospital.  Despite considerable genetic diversity, ST88 was dominant among clinical isolates at the Bugando Medical Centre. Active and standardized surveillance of nosocomial MRSA infection should be conducted in the future to analyse the infection and transmission rates and implement effective control measures.