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BACKGROUND: Fluoroquinolones have been, and continue to be, routinely used for treatment of many bacterial infections. In recent years, most parts of the world have reported an increasing trend of fluoroquinolone resistant (FQR) Gram-negative bacteria. METHODS: A cross-sectional study was conducted between March 2017 and July 2018 among children admitted due to fever to referral hospitals in Dar es Salaam, Tanzania. Rectal swabs were used to screen for carriage of extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE). ESBL-PE isolates were tested for quinolone resistance by disk diffusion method. Randomly selected fluroquinolone resistant isolates were characterized by using whole genome sequencing. RESULTS: A total of 142 ESBL-PE archived isolates were tested for fluoroquinolone resistance. Overall phenotypic resistance to ciprofloxacin, levofloxacin and moxifloxacin was found in 68% (97/142). The highest resistance rate was seen among Citrobacter spp. (100%, 5/5), followed by Klebsiella. pneumoniae (76.1%; 35/46), Escherichia coli (65.6%; 42/64) and Enterobacter spp. (31.9%; 15/47). Whole genome sequencing (WGS) was performed on 42 fluoroquinolone resistant-ESBL producing isolates and revealed that 38/42; or 90.5%, of the isolates carried one or more plasmid mediated quinolone resistance (PMQR) genes. The most frequent PMQR genes were aac(6')-lb-cr (74%; 31/42), followed by qnrB1 (40%; 17/42), oqx, qnrB6 and qnS1. Chromosomal mutations in gyrA, parC and parE were detected among 19/42 isolates, and all were in E. coli. Most of the E. coli isolates (17/20) had high MIC values of > 32 µg/ml for fluoroquinolones. In these strains, multiple chromosomal mutations were detected, and all except three strains had additional PMQR genes. Sequence types, ST131 and ST617 predominated among E. coli isolates, while ST607 was more common out of 12 sequence types detected among the K. pneumoniae. Fluoroquinolone resistance genes were mostly associated with the IncF plasmids. CONCLUSION: The ESBL-PE isolates showed high rates of phenotypic resistance towards fluoroquinolones likely mediated by both chromosomal mutations and PMQR genes. Chromosomal mutations with or without the presence of PMQR were associated with high MIC values in these bacteria strains. We also found a diversity of PMQR genes, sequence types, virulence genes, and plasmid located antimicrobial resistance (AMR) genes towards other antimicrobial agents.
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Fluoroquinolonas , Quinolonas , Criança , Humanos , Fluoroquinolonas/farmacologia , Tanzânia/epidemiologia , Estudos Transversais , Escherichia coli/genética , Quinolonas/farmacologiaRESUMO
Escherichia coli significantly causes nosocomial infections and rampant spread of antimicrobial resistance (AMR). There is limited data on genomic characterization of extended-spectrum ß-lactamase (ESBL)-producing E. coli from African clinical settings. This hospital-based longitudinal study unraveled the genetic resistance elements in ESBL E. coli isolates from Uganda and Tanzania using whole-genome sequencing (WGS). A total of 142 ESBL multi-drug resistant E. coli bacterial isolates from both Tanzania and Uganda were sequenced and out of these, 36/57 (63.1%) and 67/85 (78.8%) originated from Uganda and Tanzania respectively. Mutations in RarD, yaaA and ybgl conferring resistances to chloramphenicol, peroxidase and quinolones were observed from Ugandan and Tanzanian isolates. We reported very high frequencies for blaCTX-M-15 with 11/18(61.1%), and blaCTX-M-27 with 12/23 (52.1%), blaTEM-1B with 13/23 (56.5%) of isolates originating from Uganda and Tanzania respectively all conferring resistance to Beta-lactam-penicillin inhibitors. We observed chloramphenicol resistance-conferring gene mdfA in 21/23 (91.3%) of Tanzanian isolates. Extraintestinal E. coli sequence type (ST) 131 accounted for 5/59 (8.4%) of Tanzanian isolates while enterotoxigenic E. coli ST656 was reported in 9/34 (26.4%) of Ugandan isolates. Virulence factors originating from Shigella dysenteriae Sd197 (gspC, gspD, gspE, gspF, gspG, gspF, gspH, gspI), Yersinia pestis CO92 (irp1, ybtU, ybtX, iucA), Salmonella enterica subsp. enterica serovar Typhimurium str. LT2 (csgF and csgG), and Pseudomonas aeruginosa PAO1 (flhA, fliG, fliM) were identified in these isolates. Overall, this study highlights a concerning prevalence and diversity of AMR-conferring elements shaping the genomic structure of multi-drug resistant E. coli in clinical settings in East Africa. It underscores the urgent need to strengthen infection-prevention controls and advocate for the routine use of WGS in national AMR surveillance and monitoring programs.Availability of WGS analysis pipeline: the rMAP source codes, installation, and implementation manual can free be accessed via https://github.com/GunzIvan28/rMAP .
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Escherichia coli Enterotoxigênica , Humanos , Estudos Longitudinais , Virulência , Uganda/epidemiologia , Cloranfenicol , beta-Lactamases/genéticaRESUMO
BACKGROUND: A key factor driving the development and maintenance of antibacterial resistance (ABR) is individuals' use of antibiotics (ABs) to treat illness. To better understand motivations and context for antibiotic use we use the concept of a patient treatment-seeking pathway: a treatment journey encompassing where patients go when they are unwell, what motivates their choices, and how they obtain antibiotics. This paper investigates patterns and determinants of patient treatment-seeking pathways, and how they intersect with AB use in East Africa, a region where ABR-attributable deaths are exceptionally high. METHODS: The Holistic Approach to Unravelling Antibacterial Resistance (HATUA) Consortium collected quantitative data from 6,827 adult outpatients presenting with urinary tract infection (UTI) symptoms in Kenya, Tanzania, and Uganda between February 2019- September 2020, and conducted qualitative in-depth patient interviews with a subset (n = 116). We described patterns of treatment-seeking visually using Sankey plots and explored explanations and motivations using mixed-methods. Using Bayesian hierarchical regression modelling, we investigated the associations between socio-demographic, economic, healthcare, and attitudinal factors and three factors related to ABR: self-treatment as a first step, having a multi-step treatment pathway, and consuming ABs. RESULTS: Although most patients (86%) sought help from medical facilities in the first instance, many (56%) described multi-step, repetitive treatment-seeking pathways, which further increased the likelihood of consuming ABs. Higher socio-economic status patients were more likely to consume ABs and have multi-step pathways. Reasons for choosing providers (e.g., cost, location, time) were conditioned by wider structural factors such as hybrid healthcare systems and AB availability. CONCLUSION: There is likely to be a reinforcing cycle between complex, repetitive treatment pathways, AB consumption and ABR. A focus on individual antibiotic use as the key intervention point in this cycle ignores the contextual challenges patients face when treatment seeking, which include inadequate access to diagnostics, perceived inefficient public healthcare and ease of purchasing antibiotics without prescription. Pluralistic healthcare landscapes may promote more complex treatment seeking and therefore inappropriate AB use. We recommend further attention to healthcare system factors, focussing on medical facilities (e.g., accessible diagnostics, patient-doctor interactions, information flows), and community AB access points (e.g., drug sellers).
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Antibacterianos , Atenção à Saúde , Adulto , Humanos , Pesquisa Qualitativa , Teorema de Bayes , Uganda , Antibacterianos/farmacologia , Antibacterianos/uso terapêuticoRESUMO
In many low- and middle-income countries, there seems to be a mismatch between graduate skills and healthcare industry requirements due to variability in curricula. With the current increased global demand for competent health profession graduates, harmonizing competency-based curricula (CBC) is necessary to address this mismatch. This paper describes how three health professions training universities in Tanzania and their two long-standing United States partners embarked on developing harmonized CBC for undergraduate medicine and nursing degrees. The main goal of the activity was to develop templates to harmonize curricula that would support graduates to acquire mandatory national Graduate Minimum Essential Competencies (GMEC) irrespective of the institution of their training. The paper describes the processes of engaging multiple institutions, the professions of medicine and nursing and various stakeholders to develop mandatory curricula generic competencies, creating milestones for assessing competencies, training faculty at each of the three partnering institutions in curriculum delivery and assessments, resulting in the adoption of the curricula by the University leadership at each institution. Ultimately the Tanzania Commission for Universities (TCU) a regulatory body required all schools of medicine and nursing in the country to adopt the curricula, thus creating a harmonized national standard for teaching medicine and nursing beginning October 2022.
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Currículo , Medicina , Humanos , Estados Unidos , Tanzânia , Ocupações em Saúde , Instalações de SaúdeRESUMO
INTRODUCTION: Sub-Saharan African countries are introducing integrase strand transfer inhibitors (INSTIs) in their ART programmes as the preferred first-line regimen, and dolutegravir is the INSTI of choice due to its potency, tolerability and high genetic barrier to resistance. Dolutegravir was introduced into the first-line ART regimen in Tanzania in 2019. However, there is a paucity of data on the occurrence of mutations in HIV lineages circulating in Tanzania. This study aimed to determine the prevalence of INSTI primary resistance mutations in Tanzanian patients exposed to ART but not INSTIs. METHODS: Plasma samples from 50 INSTI-naive patients failing first- or second-line ART [median (IQR) age: 40 (21.93-46.41) years; 68% women] were subjected to Sanger sequencing of the HIV integrase gene. Participants had been on ART for a median (IQR) duration of 7.32 (4.73-9.29) years, with 80% and 20% failing first- and second-line ART, respectively. RESULTS: No major INSTI mutations were found, but 2 (4%) participants had the accessory mutation T97A. Using the REGA HIV-1 subtyping tool, HIV subtype A1 (53.1%) was found to be dominant, followed by subtypes C (30.6%) and D (16.3%). CONCLUSIONS: This study found no current evidence for transmitted resistance against INSTIs among unexposed patients failing ART and supports the scale-up of INSTI-based regimens. However, the presence of accessory mutations calls for the surveillance of INSTI resistance mutations to ensure that the anticipated long-term desired outcomes are achieved.
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Infecções por HIV , Inibidores de Integrase de HIV , Integrase de HIV , HIV-1 , Humanos , Feminino , Adulto , Masculino , Inibidores de Integrase de HIV/farmacologia , Inibidores de Integrase de HIV/uso terapêutico , Farmacorresistência Viral/genética , HIV-1/genética , Tanzânia/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Genótipo , Integrase de HIV/genética , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , MutaçãoRESUMO
BACKGROUND: Antimicrobials are extensively used in cattle and poultry production in Tanzania. However, there is dearth of information on its quantitative use. A questionnaire-based cross-sectional study was conducted from August to September 2019 in randomly selected poultry and small-scale dairy farms, in three districts of Dar es Salaam City eastern, Tanzania, to assess the practice and quantify antimicrobial use. Descriptive and statistical analyses were performed at a confidence interval of 95%. The ratio of Used Daily Dose (UDD) and Defined Daily Dose (DDD) were used to determine whether the antimicrobial was overdosed or under dosed. RESULTS: A total of 51 poultry and 65 small-scale dairy farms were involved in the study. The route of antimicrobial administration was 98% orally via drinking water and 2% in feeds for poultry and for small-scale dairy farms, all through parenteral route. Seventeen types of antimicrobials comprising seven classes were recorded in poultry farms while nine belonging to six classes in the small dairy farms. Majority of the farms (poultry, 87.7% and small scale dairy, 84.3%) used antimicrobials for therapeutic purposes. About 41% of the poultry and one third (34%) of the dairy farmers' were not compliant to the drug withdrawal periods. Beta-lactams, fluoroquinolones, sulphonamides, tetracyclines and macrolides were the commonly used antimicrobials on these farms. In the poultry farms both those with records and those which relied on recall, antimicrobials were overdosed whereas in the small dairy farms, sulfadimidine, oxytetracycline and neomycin were within the appropriate dosing range (0.8-1.2). The majority (58.6%) of farmers had adequate level of practices (favorable) regarding antimicrobial use in cattle and poultry production. This was associated with the age and level of education of the cattle and poultry farmers. CONCLUSION: The study revealed a widespread misuse of antimicrobials of different types and classes in both poultry and small-scale dairy farming in Dar es Salaam, Tanzania. This result gives insight into the antimicrobial use practices and its quantification. The information obtained can guide and promote prudent use of antimicrobials among the farmers by developing mitigate strategies that reduce antimicrobial resistance risk potentials.
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Anti-Infecciosos , Indústria de Laticínios , Uso de Medicamentos/estatística & dados numéricos , Aves Domésticas , Animais , Anti-Infecciosos/uso terapêutico , Bovinos , Estudos Transversais , Fazendas , TanzâniaRESUMO
The objective of this study was to characterize antimicrobial resistance (AMR) of WHO priority 1 critical pathogen (extrapathogenic Escherichia coli (ExPEC), sequence types (STs), and ST131 clades from patients in Tanzania so as to guide specific antimicrobial therapies and preventive measures. A total of 143 ExPEC strains (128 from pregnant women with urinary tract infections and 15 from children with blood stream infections) were collected between March 2016 and October 2017. These were characterized into ST-fimH clones by a 7-single nucleotide polymorphism quantitative polymerase chain reaction (7-SNP qPCR) and gene sequencing, and to ST131 clades by multiplex PCR. The extended-spectrum beta-lactamases (ESBL) production was 16.1% (23/143), and was predominantly due to the blaCTX-M-15 (91.3%, n=21). ESBL production was significantly more among strains from children (53.3%) than pregnant women (11.7%) (OR (95%CI): 8.61 (2.73-27.15); p-value <0.001)). Approximately 61.5% (n=88) ExPEC were typed into their respective STs/CCs (87 by the 7-SNP qPCR and by an additional of one or two genes sequencing). The commonest STs/CCs among typeable strains were CC10 (28.4%, n=25), ST131 (18.2%, n=16), and ST38 (10.2%, n=9). The ST131 clades (C1 (4, 25.0%) and C2 (6, 37.5%)) were predominantly associated with fluoroquinolone resistance and ESBL production, respectively. Approximately 60.8% of ExPEC strains and all dominant clones were typed by the 7-SNP qPCR by additional sequencing. The multiplex clade PCR allowed linkage of the global clone ST131 with AMR phenotypes. These feasible and user-friendly molecular tools can be routinely used for surveillance programs in resource-limited settings.
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BACKGROUND: Neonatal mortality remains high in Tanzania at approximately 20 deaths per 1000 live births. Low birthweight, prematurity, and asphyxia are associated with neonatal mortality; however, no studies have assessed the value of combining underlying conditions and vital signs to provide clinicians with early warning of infants at risk of mortality. The aim of this study was to identify risk factors (including vital signs) associated with neonatal mortality in the neonatal intensive care unit (NICU) in Bugando Medical Centre (BMC), Mwanza, Tanzania; to identify the most accurate generalised linear model (GLM) or decision tree for predicting mortality; and to provide a tool that provides clinically relevant cut-offs for predicting mortality that is easily used by clinicians in a low-resource setting. METHODS: In total, 165 neonates were enrolled between November 2019 and March 2020, of whom 80 (48.5%) died. We competed the performance of GLMs and decision trees by resampling the data to create training and test datasets and comparing their accuracy at correctly predicting mortality. RESULTS: GLMs always outperformed decision trees. The best fitting GLM showed that (for standardised risk factors) temperature (OR 0.61, 95% CI 0.40-0.90), birthweight (OR 0.33, 95% CI 0.20-0.52), and oxygen saturation (OR 0.66, 95% CI 0.45-0.94) were negatively associated with mortality, while heart rate (OR 1.59, 95% CI 1.10-2.35) and asphyxia (OR 3.23, 95% 1.25-8.91) were risk factors. To identify the tool that balances accuracy and with ease of use in a low-resource clinical setting, we compared the best fitting GLM with simpler versions, and identified the three-variable GLM with temperature, heart rate, and birth weight as the best candidate. For this tool, cut-offs were identified using receiver operator characteristic (ROC) curves with the optimal cut-off for mortality prediction corresponding to 76.3% sensitivity and 68.2% specificity. The final tool is graphical, showing cut-offs that depend on birthweight, heart rate, and temperature. CONCLUSIONS: Underlying conditions and vital signs can be combined into simple graphical tools that improve upon the current guidelines and are straightforward to use by clinicians in a low-resource setting.
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Doenças do Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Saturação de Oxigênio , Tanzânia/epidemiologiaRESUMO
OBJECTIVES: Acute mosquito-borne febrile diseases pose a threat to children in the Sub-Saharan-Africa with â¼272 000 children dying worldwide from malaria in 2018. Although the awareness for malaria in this area has increased due to improved health education, the apparent decline of actual malaria cases has not affected clinical practice significantly. This study collected clinical and epidemiologic data of children presenting with acute febrile diseases in order delineate their diagnostic and therapeutic management. METHODS: A hospital-based cross-sectional clinical study was conducted at the Sekou Toure Regional Referral Hospital in Tanzania. Children between 1 month and 12 years of age with an axillary temperature ≥ 37.5°C were recruited from August 2016 to December 2016. Children received full clinical examination. In addition, file data about diagnostics and treatment were collected and malaria rapid diagnostic tests (mRDTs) were performed. Confirmatory malaria polymerase chain reaction was performed from dry blood spots. RESULTS: From 1381 children presented in the pediatric outpatient department, 133 met the inclusion criteria. Out of 133 febrile children, 10.5% were malaria positive. Treatment data indicate the prescription of antimalarials in 35.3% and antibiotics in 63.9% of the children with an overlap of 24.1% receiving both. Despite a negative mRDT, 36 patients received antimalarials. CONCLUSIONS: The findings of this study confirm a significant decline of malaria cases in the Lake Victoria region. The discrepancy between the valuable results provided by mRDTs and the high prescription rates of antibiotics and antimalarials call for an enforced diagnostic and therapeutic algorithm. LAY SUMMARY: The aim of the study was to take a closer look at reported cases of febrile diseases in the Lake Victoria region and assess the relationship between clinical as well as diagnostic findings and the resulting therapeutic concept. Based on these findings the prescription rate of antimalarial and antibiotic drugs was analyzed. The results showed an overall high prescription rate of antimalarials and antibiotics in both diagnosed malaria cases and cases with diagnosed bacterial infections.Not only with regards to the possible side effects of these medications but also keeping in mind the apparent misuse of resources this practice poses a serious burden to the health care system in this low resource country.
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Antimaláricos , Animais , Antibacterianos/uso terapêutico , Antimaláricos/uso terapêutico , Criança , Estudos Transversais , Humanos , Lactente , Lagos , Prescrições , Tanzânia/epidemiologiaRESUMO
BACKGROUND: Sustainability of research culture in Sub-Saharan Africa is threatened in part by the lack of a critical mass of young researchers with the requisite skills and interest to undertake research careers. This paper describes an intensive mentorship programme combining hierarchical (vertical) and peer-to-peer (horizontal) mentoring strategies among young researchers in a resource limited setting in Sub-Saharan Africa. METHODS: A consortium of three partnering large Tanzanian health training institutions (MUHAS, CUHAS and KCMUCo) and two collaborating US institutions (UCSF and Duke University) was formed as part of the five-year Transforming Health Professions Education in Tanzania (THET) project, funded by the NIH through Health Professional Education Partnership Initiative (HEPI). Within THET, the Community of Young Research Peers (CYRP) was formed, comprising of inter-professional and cross-institutional team of 12 Master-level Young Research Peers and 10 co-opted fellows from the former MEPI-Junior Faculty (MEPI-JF) project. The Young Peers received mentorship from senior researchers from the consortium through mentored research awards and research training, and in turn provided reciprocal peer-to-peer mentorship as well as mentorship to undergraduate students. RESULTS: At the end of the first 2 years of the project, all 12 Young Peers were proceeding well with mentored research awards, and some were at more advanced stages. For example, three articles were already published in peer reviewed journals and two other manuscripts were in final stages of preparation. All 12 Young Peers participated in CYRP-wide thematic training workshops on mentoring and secondary data analysis; 11 had undertaken at least three research training short courses in identified areas of need; 9 joined at least one other ongoing research project; 5 made at least one scientific presentation, and 5 participated in at least one submitted grant application. Half of the Young Peers have enrolled in PhD programmes. A collective total of 41 undergraduate students were actively mentored by the Young Peers in research. CONCLUSION: The CYRP has demonstrated to be an effective model for dual vertical and horizontal mentorship in research to young investigators in resource-limited settings. This model is recommended to educators working on developing research competence of early career researchers, particularly in Sub-Saharan Africa.
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Tutoria , Fortalecimento Institucional , Humanos , Mentores , Grupo Associado , Pesquisadores , TanzâniaRESUMO
BACKGROUND: Tuberculosis (TB), particularly multi- and or extensive drug resistant TB, is still a global medical emergency. Whole genome sequencing (WGS) is a current alternative to the WHO-approved probe-based methods for TB diagnosis and detection of drug resistance, genetic diversity and transmission dynamics of Mycobacterium tuberculosis complex (MTBC). This study compared WGS and clinical data in participants with TB. RESULTS: This cohort study performed WGS on 87 from MTBC DNA isolates, 57 (66%) and 30 (34%) patients with drug resistant and susceptible TB, respectively. Drug resistance was determined by Xpert® MTB/RIF assay and phenotypic culture-based drug-susceptibility-testing (DST). WGS and bioinformatics data that predict phenotypic resistance to anti-TB drugs were compared with participant's clinical outcomes. They were 47 female participants (54%) and the median age was 35 years (IQR): 29-44). Twenty (23%) and 26 (30%) of participants had TB/HIV co-infection BMI < 18 kg/m2 respectively. MDR-TB participants had MTBC with multiple mutant genes, compared to those with mono or polyresistant TB, and the majority belonged to lineage 3 Central Asian Strain (CAS). Also, MDR-TB was associated with delayed culture-conversion (median: IQR (83: 60-180 vs. 51:30-66) days). WGS had high concordance with both culture-based DST and Xpert® MTB/RIF assay in detecting drug resistance (kappa = 1.00). CONCLUSION: This study offers comparison of mutations detected by Xpert and WGS with phenotypic DST of M. tuberculosis isolates in Tanzania. The high concordance between the different methods and further insights provided by WGS such as PZA-DST, which is not routinely performed in most resource-limited-settings, provides an avenue for inclusion of WGS into diagnostic matrix of TB including drug-resistant TB.
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Antituberculosos/uso terapêutico , Farmacorresistência Bacteriana Múltipla/genética , Mutação , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Mycobacterium tuberculosis/fisiologia , Tanzânia , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Sequenciamento Completo do GenomaRESUMO
Candida glabrata is a genetically diverse human pathogenic yeast, whose subpopulations have been documented to vary geographically. Here, we report MLST genotypes and antifungal drug susceptibility of C. glabrata isolates from Africa. Among 47 mostly urogenital isolates, we found 13 sequence types, amounting to a 27% genetic population difference. More than half of the isolates were of novel sequence types. ST18 was most predominant and had reduced susceptibility to fluconazole. There was clear segregation of STs between urine and vaginal specimen. In Tanzania, the C. glabrata population is genetically diverse, and divergent from those seen in other countries.
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Antifúngicos/farmacologia , Candida glabrata/efeitos dos fármacos , Candida glabrata/genética , Candidíase/microbiologia , Variação Genética , Centros de Atenção Terciária , África , Alelos , Técnicas de Tipagem Bacteriana , Candida glabrata/classificação , Candidíase/sangue , Genótipo , Humanos , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , TanzâniaRESUMO
Despite the increased burden of human immunodeficiency virus (HIV) and other comobidities in developing countries, information regarding antifungal susceptibility patterns of Candida spp. and their virulence potential are still limited. Here, we report the virulence and antifungal susceptibility patterns of Candida spp. from varieties spectrum of candidiasis in a tertiary hospital, Tanzania. The study was conducted from March to December 2017. Candida spp. from clinical samples were characterized. Antifungal susceptibility patterns based on EUCAST guidelines and virulence activities (phospholipase, protease, hemolysin, and coagulase activity) were determined. A total of 399 Candida spp. isolates were obtained, of these, 278, 51 and 47 were C. albicans, C. tropicalis, and C. glabrata, respectively. Phospholipase 193/268, protease 32/51 and coagulase 25/47 were the most frequently detected virulence activities in C. albicans, C. tropicalis, and C. glabrata, respectively. Protease and phospholipase were frequently detected virulence activities from C. albicans from blood and esophageal brushes. The median zone diameter of protease activities was significantly larger among C. tropicalis than C. albicans. C. albicans, and C. tropicalis isolates were 100% sensitive to caspofungin. The proportions of C. albicans isolate resistant to fluconazole, voriconazole and posaconazole were 3.1, 3.6%, and 1.8%, respectively. In conclusion, the majority of Candida spp. isolates were sensitive to fluconazole. There are different phenotypes of C. albicans, C. glabrata and C. tropicalis based on susceptibility and virulence activities patterns, necessitating further molecular characterizations to place them in global perspective. Routine antifungal susceptibility testing to guide clinical therapy should be encouraged in developing countries.
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BACKGROUND: Helicobacter pylori (H.pylori) infection is a common medical problem in resource limited areas. The treatment outcome after triple therapy has not been well studied in developing countries and preliminary data suggests a high rate of treatment failure. This study investigated the triple therapy treatment failure rate and associated factors among dyspeptic patients receiving H. pylori first line therapy at a tertiary hospital, Tanzania. METHODS: A prospective study in the Gastroenterology unit of the Bugando Medical Centre (BMC) was conducted between October 2015 and May 2017. All dyspeptic patients with stool antigen tests positive for H.pylori were given first line therapy, and stool antigen testing was repeated within 7 days and 5 weeks after completion of the treatment. Biopsies were taken before initiation of therapy and analysed for clarithromycin and quinolone resistance mutations using polymerise chain reaction (PCR) and sequencing. Adherence and other social-demographic characteristics were documented. RESULTS: A total of 210 patients were enrolled; the median age was 35 years (interquartile range, 27-48). First line treatment failure as defined by positive stool antigen 5 weeks post treatment was observed in 65/210 (31%) of patients. Independent predictors of first line treatment failure were presence of clarithromycin resistance mutations (OR: 23.12, 95% CI (9.38-56.98), P < 0.001) and poor adherence (OR: 7.39, 95% CI (3.25-16.77), P < 0.001). The sensitivity and specificity of stool antigen testing within 7 days after completion therapy in detecting treatment failure was 100 and 93.2%, respectively. CONCLUSION: Nearly one-third of patients with clarithromycin resistance mutations and poor adherence develop first line treatment failure. Routine stool antigen testing within seven days after completion of therapy can be considered in order to initiate second line treatment early to prevent associated morbidities.
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Antibacterianos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Adulto , Claritromicina/uso terapêutico , Quimioterapia Combinada , Fezes/microbiologia , Feminino , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/psicologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Estudos Prospectivos , Quinolonas/uso terapêutico , Tanzânia/epidemiologia , Centros de Atenção Terciária/estatística & dados numéricos , Falha de Tratamento , Adulto JovemRESUMO
BACKGROUND: Sexually transmitted infections (STIs) is a global health problem with increased risk and morbidities during pregnancy. This study investigated the magnitude of viral STIs among pregnant women from three rural hospitals/clinics providing antenatal care in Mwanza region, Tanzania. METHODS: Between February and May 2018, a total of 499 pregnant women were enrolled and tested for Human immunodeficiency virus (HIV), Herpes simplex virus-2 (HSV-2), Hepatitis B virus (HBV) and Hepatitis C virus (HCV) using rapid immunochromatographic tests and for syphilis using non-treponemal and treponemal antibody test. RESULTS: The median age of enrolled women was 25 (IQR: 22-31) years. Seventy eight (15.6, 95% CI: 12-18) of women tested had at least one sexually transmitted viral infection. Specific prevalence of HIV, HBV, HCV, HSV-2 IgG and HSV-2 IgM were found to be 25(5.0%), 29(5.8%), 2(0.4%), 188(37.7%) and 24(4.8%), respectively. The odds of having viral infection was significantly high among women with positive T. pallidum serostatus (adjusted odd ratio (aOR): 3.24, 95%CI; 1.2-85). By multivariable logistic regression analysis, history of STIs predicted HSV-2 IgM seropositivity (aOR: 3.70, 95%CI: 1.43-9.62) while parity (aOR: 1.23, 95%CI: 1.04-1.46) predicted HBV infection and syphilis positive results (aOR: 8.63, 95%CI: 2.81-26.45) predicted HIV infection. CONCLUSION: A significant proportion of pregnant women in rural areas of Mwanza region has at least one sexually transmitted viral infection which is independently predicted by positive T. pallidum serostatus. The strengthening and expansion of ANC screening package to include screening of STIs will ultimately reduce the viral STIs among pregnant women hence reduce associated morbidities and mortalities.
Assuntos
Infecções por HIV , Complicações Infecciosas na Gravidez , Saúde da População Rural/estatística & dados numéricos , Infecções Sexualmente Transmissíveis , Sífilis , Viroses , Adulto , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Humanos , Gravidez , Complicações Infecciosas na Gravidez/classificação , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Infecções Sexualmente Transmissíveis/classificação , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/epidemiologia , Sífilis/diagnóstico , Sífilis/epidemiologia , Sorodiagnóstico da Sífilis/métodos , Sorodiagnóstico da Sífilis/estatística & dados numéricos , Tanzânia/epidemiologia , Treponema pallidum/isolamento & purificação , Viroses/classificação , Viroses/diagnóstico , Viroses/epidemiologiaRESUMO
The study was conducted to establish predictors of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) neonatal sepsis and mortality in a tertiary hospital, Tanzania. Between July and December 2016, blood culture was performed in neonates with clinical features of sepsis and neonates/mothers/guardians were screened for ESBL colonization. Selected isolates underwent whole genome sequencing to investigate relatedness. Logistic regression analysis was performed to determine predictors for ESBL-PE associated neonatal sepsis and mortality. Neonatal ESBL-PE sepsis was detected in 32(10.5%) of the 304 neonates investigated. Neonatal ESBL-PE sepsis was independently predicted by admission at the Intensive care Unit and positive mother and neonate ESBL-PE colonization. Deaths occurred in 55(18.1%) of neonates. Neonates infected with ESBL-PE, admitted at ICU, increased age and those transferred from other centres had significantly high mortality rates. Gram-negative bacteria formed the majority (76%) of the isolates, of which 77% were ESBL-PE. Virulent Klebsiella pneumoniae ST45 carrying blaCTX-M-15 were commonly isolated from neonates. Klebsiella pneumoniae (ST45) were the predominant cause of ESBL-PE neonatal sepsis and mortality. Improved infection control and antibiotic stewardship are crucial in controlling the spread of resistant strains. Rapid diagnostic tests to detect ESBL-PE in low-income countries are needed to guide treatment and reduce ESBL-PE-associated mortality.
Assuntos
Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Infecções por Klebsiella/mortalidade , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Sepse Neonatal/mortalidade , beta-Lactamases/genética , Antibacterianos/uso terapêutico , Hemocultura , Feminino , Humanos , Recém-Nascido , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/classificação , Klebsiella pneumoniae/isolamento & purificação , Masculino , Testes de Sensibilidade Microbiana , Sepse Neonatal/microbiologia , Tanzânia , Centros de Atenção Terciária , Resultado do TratamentoRESUMO
BACKGROUND: Tuberculosis (TB) contact tracing is a key strategy for containing TB and provides addition to the passive case finding approach. However, this practice has not been implemented in Tanzania, where there is unacceptably high treatment gap of 62.1% between cases estimated and cases detected. Therefore calls for more aggressive case finding for TB to close this gap. We aimed to determine the magnitude and predictors of bacteriologically-confirmed pulmonary TB among household contacts of bacteriologically-confirmed pulmonary TB index cases in the city of Mwanza, Tanzania. METHODS: This study was carried out from August to December 2016 in Mwanza city at the TB outpatient clinics of Tertiary Hospital of the Bugando Medical Centre, Sekou-Toure Regional Hospital, and Nyamagana District Hospital. Bacteriologically-confirmed TB index cases diagnosed between May and July 2016 were identified from the laboratory registers book. Contacts were traced by home visits by study TB nurses, and data were collected using a standardized TB screening questionnaire. To detect the bacterioriologically-confirmed pulmonary TB, two sputum samples per household contact were collected under supervision for all household contacts following standard operating procedures. Samples were transported to the Bugando Medical Centre TB laboratory for investigation for TB using fluorescent smear microscopy, GeneXpert MTB/RIF and Löwenstein-Jensen (LJ) culture. Logistic regression was used to determine predictors of bacteriologically-confirmed pulmonary TB among household contacts. RESULTS: During the study period, 456 household contacts from 93 TB index cases were identified. Among these 456 household contacts, 13 (2.9%) were GeneXpert MTB/RIF positive, 18 (3.9%) were MTB-culture positive and four (0.9%) were AFB-smear positive. Overall, 29 (6.4%) of contacts had bacteriologically-confirmed pulmonary TB. Predictors of bacteriologically-confirmed pulmonary TB among household contacts were7being married (Odds ratio [OR], 3.3; 95% confidence interval [CI], 1.4-8.0; p = 0.012) and consuming less than three meals a day (OR, 3.7; 95% CI, 1.6-8.7; p = 0.009). CONCLUSIONS: Our data suggest that in Mwanza, Tanzania, seven in 100 contacts living in the same house with a TB patient develop bacteriologically-confirmed pulmonary TB. These results therefore underscore the need to implement routine TB contact tracing to control tuberculosis in high TB burden countries such as Tanzania.
Assuntos
Tuberculose Pulmonar/diagnóstico , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Características da Família , Feminino , Humanos , Modelos Logísticos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Ambulatório Hospitalar , Estudos Retrospectivos , Escarro/microbiologia , TanzâniaRESUMO
BACKGROUND: Worldwide Helicobacter pylori (H.pylori) treatment is of great challenge due to increased antibiotic resistance. The burden of H. pylori antibiotic resistance in Africa is high with unclear information regarding the real magnitude. This systematic review and meta-analysis was conducted to investigate the magnitude of H.pylori antibiotic resistance in Africa to gain insight of the extent of the problem among H.pylori naïve treatment patients. METHOD: The search was performed in the academic databases, Embase, PubMed, Web of Science and Africa Wide Information. ProQuest Dissertation and Theses, Scopus, Ethos, Africa Index Medicus (WHO), BioMed Central Proceedings, BASE, British Library, Open grey, Library of Congress and the New York Academy of Grey Literature Report were additionally searched for grey literature. Published articles from Africa on H.pylori antibiotic resistance between 1986 and June 2017 were systematically reviewed to estimate the H. pylori extent of resistance to macrolides, quinolones, amoxicillin, tetracycline and metronidazole. RESULTS: In 26 articles a total of 2085 isolates were tested for metronidazole, 1530 for amoxicillin, 1277 for tetracycline, 1752 for clarithromycin and 823 for quinolones.The overall pooled proportion of H.pylori resistance to quinolones, clarithromycin, tetracycline, metronidazole and amoxicillin were: (17.4%, 95%CI 12.8 - 21.9), (29.2%, 95%CI:26.7-31.8), (48.7%, 95%CI: 44.5-52.9), (75.8%, 95% CI: 74.1-.77.4) and (72.6%, 95% CI: 68.6-76.6), respectively. The commonest mutation detected were A2143G (49/97) for clarithromycin, RdxA (41/56) for metronidazole and D87I (16/40) for quinolones. CONCLUSION: Prevalence of metronidazole, clarithromycin, and amoxicillin resistance is high in developing world including Africa. This could impair the first line triple therapy of the H.pylori infection. There is a need of conducting surveillance of H.pylori susceptibility pattern in Africa for dual and triple resistance which can be used for the empirical treatment.
Assuntos
Farmacorresistência Bacteriana/efeitos dos fármacos , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/genética , Mutação , África , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana/genética , Infecções por Helicobacter/tratamento farmacológico , Humanos , Testes de Sensibilidade Microbiana , PrevalênciaRESUMO
BACKGROUND: Rubella primary infection during early stages of pregnancy is associated with high risk of congenital Rubella syndrome (CRS). Prevention of CRS in the resource-limited countries requires multiple strategies. Here, we document the data on the magnitude of Rubella natural immunity among adolescent girls which is a crucial group in devising effective control strategies to prevent CRS. METHODS: A cross sectional study involving 397 adolescent girls was conducted in the city of Mwanza involving five secondary schools. Socio-demographic and other relevant information were collected using pre-tested data collection tool. Rubella IgG antibodies were determined using enzyme immunoassay. The presence of Rubella IgG titers of >10 IU/ml indicated natural immunity. RESULTS: The mean age of the study participants was 15.18 ± 1.48 years. Of 397 girls, 340 (85.6%) and 57 (14.4%) were from secondary schools representing peri-urban and rural areas, respectively. Out of 397 girls, 90.4% (95% CI: 87-93) were found to be naturally immune with median Rubella IgG antibodies titers of 56.7 IU/ml interquartile range (IQR): 40.8-137. The median Rubella IgG antibodies titers were significantly high in adolescent girls from families with high socio-economic status (63.96 vs. 47.13 IU/ml, P < 0.001) and in adolescent girls from peri-urban areas of the city (63.33 vs. 39.9 IU/ml, P < 0.001). CONCLUSION: The majority of adolescent girls in the city of Mwanza are naturally immune to Rubella virus. There is a need to compare the effectiveness of screening and vaccinating susceptible adolescent girls with the effectiveness of vaccinating all women of childbearing in controlling CRS in low-income countries.
Assuntos
Anticorpos Antivirais/sangue , Imunidade Inata , Imunoglobulina G/sangue , Síndrome da Rubéola Congênita/prevenção & controle , Rubéola (Sarampo Alemão)/imunologia , Vacinação , Adolescente , Estudos Transversais , Feminino , Humanos , Avaliação das Necessidades , População Rural , Classe Social , População Suburbana , TanzâniaRESUMO
Parvovirus B19 (B19) can cause transient aplastic crisis and lead to acute severe anemia. This study investigated the relationship between B19 and anemia among children <5 years old in the city of Mwanza, Tanzania. An enzyme immunoassay was used to detect B19 IgM- and IgG-specific antibodies among children with various categories of anemia according to the World Health Organization (WHO) guidelines. A total of 265 children with median age of 28.5 months (interquartile range 18-39.5) were investigated. Eighty-six children (32.5%) had severe anemia. B19-specific IgM and IgG antibodies were detected in 24 (9%) and 46 (17.4%) children, respectively. Low hemoglobin (Hb) level (p = 0.031), Plasmodium falciparum infection (p = 0.001) and residing in rural areas (p = 0.025) independently predicted B19 IgM seropositivity. Acute B19 infection decreased Hb level by 1.1 g/dl (p = 0.003). In malaria endemic areas, acute B19 infections should be considered among children with severe anemia from rural areas.