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1.
Lancet Microbe ; 4(12): e1005-e1014, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37952554

RESUMEN

BACKGROUND: The continued emergence of Salmonella enterica serovar Typhi, with ever increasing antimicrobial resistance, necessitates the use of vaccines in endemic countries. A typhoid fever outbreak in Harare, Zimbabwe, in 2018 from a multidrug resistant S Typhi with additional resistance to ciprofloxacin was the catalyst for the introduction of a typhoid conjugate vaccine programme. We aimed to investigate the emergence and evolution of antimicrobial resistance of endemic S Typhi in Zimbabwe and to determine the population structure, gene flux, and sequence polymorphisms of strains isolated before a typhoid conjugate vaccine programme to provide a baseline for future evaluation of the effect of the vaccination programme. METHODS: In this genomic epidemiology study, we used short-read whole-genome sequencing of S Typhi isolated from clinical cases of typhoid fever in Harare, Zimbabwe, between Jan 1, 2012, and Feb 9, 2019, to determine the S Typhi population structure, gene flux, and sequence polymorphisms and reconstructed the evolution of antimicrobial resistance. Maximum likelihood time-scaled phylogenetic trees of Zimbabwe isolates in the context of global isolates obtained from the National Center for Biotechnology Information were constructed to infer spread and emergence of antimicrobial resistance. FINDINGS: The population structure of S Typhi in Harare, Zimbabwe, from 2012 to 2019 was dominated by multidrug resistant genotype 4.3.1.1.EA1 (H58) that spread to Zimbabwe from neighbouring countries in around 2009 (95% credible interval 2008·5-2010·0). Acquisition of an IncN plasmid carrying antimicrobial resistance genes including a qnrS gene and a mutation in the quinolone resistance determining region of gyrA gene contributed to non-susceptibility and resistance to quinolone antibiotics. A minority population of antimicrobial susceptible S Typhi genotype 3.3.1 strains were present throughout. INTERPRETATION: The currently dominant S Typhi population is genotype 4.3.1.1 that spread to Zimbabwe and acquired additional antimicrobial resistance though acquisition of a plasmid and mutation in the gyrA gene. This study provides a baseline population structure for future evaluation of the effect of the typhoid conjugate vaccine programme in Harare. FUNDING: Bill & Melinda Gates Foundation and the Biotechnology and Biological Sciences Research Council Institute Strategic Programme.


Asunto(s)
Quinolonas , Salmonella enterica , Fiebre Tifoidea , Vacunas Tifoides-Paratifoides , Humanos , Fiebre Tifoidea/epidemiología , Fiebre Tifoidea/prevención & control , Vacunas Conjugadas , Vacunas Tifoides-Paratifoides/farmacología , Zimbabwe/epidemiología , Filogenia , Salmonella typhi/genética , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Quinolonas/farmacología , Genómica
2.
Infect Prev Pract ; 4(2): 100210, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35308560

RESUMEN

Background and purpose: The occurrence of urinary tract infections (UTIs) after stroke is a well recognised complication. The aim of this study was to determine the incidence of UTIs in stroke patients admitted at a teaching hospital in Zimbabwe. Methods: A prospective cohort study was conducted in stroke patients admitted within 7 days from onset of stroke. Patients were followed up throughout the admission period and those with symptomatic UTI were identified. Urine samples for analysis were collected and causative bacterial organisms were identified with their antibiotic susceptibility patterns analysed. Results: A total of 145 stroke patients were followed up during their in-patient care. 28 patients (19.3%) developed a urinary tract infection, 45 patients (31%) had asymptomatic bacteriuria and 72 patients (49.7%) had no bacteriuria. The median time from admission to UTI occurrence post stroke was 5 (IQR 4-7) days. Severe stroke (NIHSS score 16-42) was an independent risk factor for UTI development with an odds ratio (OR) 5.15 (1.68-15.75) p<0.001.The commonest bacterial causative organisms cultured were Escherichia coli (27.6%) ; Klebsiella species (21.1%) and Enterococcus faecalis (19.7%). Twenty nine percent of the cultured Gram negative bacteria were extended-spectrum beta-lactamase (ESBL) producers. Conclusions: UTIs are common in admitted stroke patients and a significant percentage of causative organisms are multi-drug resistant. UTI occurrence is more common in patients with severe stroke and is associated with increased hospital stay. These observations highlight the need for robust infection prevention and control strategies to curb this common post-stroke complication.

3.
BMJ Open Qual ; 10(1)2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33472853

RESUMEN

There are 2. 4 million annual neonatal deaths worldwide. Simple, evidence-based interventions such as temperature control could prevent approximately two-thirds of these deaths. However, key problems in implementing these interventions are a lack of newborn-trained healthcare workers and a lack of data collection systems. NeoTree is a digital platform aiming to improve newborn care in low-resource settings through real-time data capture and feedback alongside education and data linkage. This project demonstrates proof of concept of the NeoTree as a real-time data capture tool replacing handwritten clinical paper notes over a 9-month period in a tertiary neonatal unit at Harare Central Hospital, Zimbabwe. We aimed to deliver robust data for monthly mortality and morbidity meetings and to improve turnaround time for blood culture results among other quality improvement indicators. There were 3222 admissions and discharges entered using the NeoTree software with 41 junior doctors and 9 laboratory staff trained over the 9-month period. The NeoTree app was fully integrated into the department for all admission and discharge documentation and the monthly presentations became routine, informing local practice. An essential factor for this success was local buy-in and ownership at each stage of the project development, as was monthly data analysis and presentations allowing us to rapidly troubleshoot emerging issues. However, the laboratory arm of the project was negatively affected by nationwide economic upheaval. Our successes and challenges piloting this digital tool have provided key insights for effective future roll-out in Zimbabwe and other low-income healthcare settings.


Asunto(s)
Aplicaciones Móviles , Sector Público , Electrónica , Hospitales Públicos , Humanos , Zimbabwe/epidemiología
5.
Int J Infect Dis ; 96: 276-283, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32289564

RESUMEN

OBJECTIVE: To define sepsis syndromes in high-HIV burden settings in the antiretroviral therapy (ART) era. METHODS: We characterized a prospective cohort of adults presenting to a tertiary emergency department in Harare, Zimbabwe with suspected community-acquired sepsis using blood and urine cultures, urine tuberculosis lipoarabinomannan (TB LAM), and serum cryptococcal antigen (CrAg) testing. The primary outcome was 30-day all-cause mortality. RESULTS: Of 142 patients enrolled 68% (n=96/142, 95% confidence interval (CI) [60-75%]) were HIV-positive, 41% (n=39/96, 95% CI [31-50%]) of whom were ART-naïve. Among HIV-positive patients, both opportunistic pathogens (TB LAM-positivity, 36%, 95% CI [24-48%]; CrAg-positivity, 15%, 95% CI [7-23%]) and severe non-AIDS infections (S. pneumoniae urine antigen-positivity 12%, 95% CI [4-20%]; bacteraemia 17% (n=16/96, 95% CI [9-24%]), of which 56% (n=9/16, 95% CI [30-80%]) were gram-negative organisms) were common. Klebsiella pneumoniae recovered from blood and urine was uniformly resistant to ceftriaxone, as were most Escherichia coli isolates. Acknowledging the power limitations of our study, we conclude that relative to HIV-negative patients, HIV-positive patients had modestly higher 30-day mortality (adjusted hazard ratio (HR) 1.88, 95% CI [0.78-4.55]; p=0.16, and 3.59, 95% CI [1.27-10.16], p=0.02) among those with and without viral suppression, respectively. CONCLUSION: Rapid point-of-care assays provide substantial clinically actionable information in the setting of suspected sepsis, even in areas with high ART coverage. Antimicrobial resistance to first-line antibiotics in high burden settings is a growing threat.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/complicaciones , Sepsis/diagnóstico , Adulto , Antibacterianos/uso terapéutico , Antígenos Fúngicos/sangre , Estudios de Cohortes , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Lipopolisacáridos/orina , Masculino , Persona de Mediana Edad , Sistemas de Atención de Punto , Estudios Prospectivos , Sepsis/tratamiento farmacológico , Sepsis/etiología , Resultado del Tratamiento , Tuberculosis/complicaciones , Zimbabwe
6.
Int J Infect Dis ; 78: 113-120, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30368019

RESUMEN

OBJECTIVES: To describe the pre-diagnosis and pre-treatment loss to follow-up (LTFU) in the tuberculosis (TB) care cascade in Guruve (2015-16), a rural district in Zimbabwe. DESIGN: Guruve has 19 rural health centres (RHCs) and one district hospital. In this cohort study, persons ≥15 years of age with presumptive pulmonary TB were tracked from the facility presumptive TB registers to the laboratory registers; if laboratory diagnosed, they were tracked to the district TB register (contains details of all TB patients registered for treatment). Each patient was tracked for 90days after registration as presumptive TB and for 90days after laboratory diagnosis. Environmental health technicians transported sputum specimens from the health facilities to the laboratories (n=3). RESULTS: Of 2974 persons with presumptive TB, pre-diagnosis LTFU occurred in 575 (19%, 95% confidence interval 18-21%). Associated factors included registration at a RHC, at a facility more than 2km from the laboratory, and absence of an environmental health technician. Of 162 laboratory diagnosed pulmonary TB patients, pre-treatment LTFU occurred in 19 (12%, 95% confidence interval 8-18%). CONCLUSIONS: The presumptive TB register was helpful to assess the pre-diagnosis gaps beginning from presumption. Pre-diagnosis LTFU can be reduced by placement of an environmental health technician at all facilities.


Asunto(s)
Tuberculosis/diagnóstico , Adolescente , Adulto , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Salud Rural , Factores de Tiempo , Adulto Joven , Zimbabwe
7.
BMJ Open ; 8(7): e020654, 2018 07 30.
Artículo en Inglés | MEDLINE | ID: mdl-30061436

RESUMEN

INTRODUCTION: Cryptococcal meningitis is a neglected disease and an AIDS-defining illness, responsible for 15% of all AIDS-related deaths globally. In 2014, the estimated number of incident cryptococcal meningitis cases was 223 100, with 73% of them occurring in Africa. Currently available data on the prevalence, incidence, aetiologies and mortality of cryptococcal meningitis across Africa are sparse and of limited quality. We propose to conduct the first systematic review to summarise the epidemiological data available on cryptococcal meningitis and its aetiological causes in Africa. METHODS AND ANALYSIS: We will search PubMed, MEDLINE, Excerpta Medica Database, ISI Web of Science, Africa Index Medicus, Cumulative Index to Nursing and Allied Health for studies on cryptococcal meningitis published between 1st January 1950 and 31st December 2017, involving adults and/or children residing in Africa. After study selection, full text paper acquisition and data extraction, we will use validated tools and checklists to assess the quality of reporting and risk of bias for each study. Heterogeneity across studies will be assessed using the χ2 test on Cochrane's Q statistic and a random effect meta-analysis will be used to estimate the overall prevalence, incidence density and mortality of cryptococcal meningitis across studies with similar characteristics. This protocol is prepared and presented in accordance with the 2015 Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. Reporting of the results will be compliant with the Meta-Analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. ETHICS AND DISSEMINATION: There is no requirement for ethical approval since we will be using data from published studies. The final report will be published in a peer-reviewed journal and further presented at conferences. This study is expected to provide useful contextual estimates needed to inform treatment policies on the African continent and assess the impact of diagnostic and prevention strategies on the burden of cryptococcal meningitis in the post antiretroviral therapy era. PROSPERO REGISTRATION NUMBER: CRD42017081312.


Asunto(s)
Meningitis Criptocócica/epidemiología , África/epidemiología , Humanos , Meningitis Criptocócica/mortalidad , Metaanálisis como Asunto , Proyectos de Investigación , Revisiones Sistemáticas como Asunto
8.
Biomed Res Int ; 2017: 1976273, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28656137

RESUMEN

OBJECTIVE: The potential of NaHCO3 versus human serum to induce germ tube formation in Candida albicans was investigated. SPECIMENS: A total of 100 isolates were obtained from oral swabs of patients presenting with thrush. Approval for the study was granted by the Joint Research Ethics Committee (JREC/23/08). METHOD: Confirmed C. albicans isolates by routine methods were tested for germ tube induction using 5 different concentrations of Tris-maleate buffered NaHCO3 and Tris-maleate buffer control. Standard control strains included were C. albicans (ATCC 10231) and C. krusei (ATCC 6258). Microculture was done in 20 µL inoculums on microscope slides for 3 hours at 37°C. The rate of germ tube formation at 10-minute intervals was determined on 100 isolates using the optimum 20 mM Tris-maleate buffered NaHCO3 concentration. Parallel germ tube formation using human serum was done in test tubes. RESULTS: The optimum concentration of NaHCO3 in Tris-maleate buffer for germ tube induction was 20 mM for 67% of isolates. Only 21% of isolates formed germ tubes in Tris-maleate buffer control. There was no significant difference in induction between human serum and Tris-maleate buffered NaHCO3. CONCLUSION: Tris-maleate buffered NaHCO3 induced germ tube formation in C. albicans isolates at rates similar to human serum.


Asunto(s)
Candida albicans/crecimiento & desarrollo , Morfogénesis/efectos de los fármacos , Bicarbonato de Sodio/farmacología , Medios de Cultivo/química , Medios de Cultivo/farmacología , Humanos , Suero/química , Bicarbonato de Sodio/química , Temperatura
9.
Artículo en Inglés | MEDLINE | ID: mdl-28096976

RESUMEN

We assessed bacterial contamination of hands of adults present in paediatric wards in two tertiary-care hospitals in Harare, Zimbabwe and the microbiologic efficacy of locally-manufactured alcohol-based hand rub (ABHR). During unannounced visits, samples were collected using hand-print and hand-rinse methods. Samples were collected from 152 individuals (16 nurses, 10 doctors, 28 students, 86 parents/guardians, 12 others). Contamination of hands with Gram-negative bacteria was found in 91% of adults tested with a mean of 14.6 CFU (hand-rinse method; IQR 3-65), representing a high risk for transmission of pathogens potentially leading to nosocomial infections. A single application of ABHR under controlled conditions achieved an average of 82% (or 0.72 log) reduction in detectable counts. Amongst 49 Enterobacteriaceae isolates from hands, 53% were resistant to gentamicin and 63% were resistant to cefpodoxime. Use of ABHR represents an attractive intervention for reducing nosocomial infections in this setting.

10.
Artículo en Inglés | MEDLINE | ID: mdl-28096978

RESUMEN

BACKGROUND: Extended-spectrum ß-lactamase-producing and gentamicin resistant Enterobacteriaceae are increasingly recognised as a major cause of infection in low-income countries. We assessed the prevalence of gastrointestinal carriage of these bacteria in hospitalised children in Harare, Zimbabwe. METHODS: We conducted a cohort study in paediatric inpatients at two tertiary-referral hospitals between May and July 2015. Rectal swabs and faecal samples were collected within 24 h of admission and further follow-up samples were collected on alternate days during hospitalization. Disc-based, selective and enrichment methods were used to detect carriage of these two forms of resistance. Standard methods were used to confirm resistance status and determine the susceptibility of resistant isolates to other commonly-used antibiotics. RESULTS: One hundred and sixty four paediatric inpatient admissions (median age = 1.0 year, IQR = 0.2-2.2years) were enrolled, and an average of 1.9 faecal samples per patient were collected. On admission, 68/164 (41%) patients had both ESBL and gentamicin-resistant Enterobacteriaceae detected, 18 (11%) had ESBL only, 17 (10%) had gentamicin resistance only and 61 (37%) had negative screening for both forms of resistance. During hospitalisation, 32/164 (20%) patients were found to have a type of resistant organism which was not present in their admission sample. We found that faecal samples and use of a selective enrichment broth enhanced the detection of resistant organisms. Amongst resistant bacteria isolated, there were high levels of resistance to ciprofloxacin and chloramphenicol, but not ertapenem. CONCLUSIONS: More than half of children had enteric carriage of a clinically-relevant form of antibiotic resistance on admission to public-sector hospitals in urban Zimbabwe. Additionally, a fifth of children acquired a further form of resistance during hospitalisation. Urgent action is needed to tackle the spread of antibiotic resistant enteric bacteria in African hospitals.

11.
Diagn Microbiol Infect Dis ; 86(3): 289-292, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27608538

RESUMEN

Cryptococcus neoformans is the leading cause of cryptococcosis in HIV-infected subjects worldwide. Treatment of cryptococcosis is based on amphotericin B, flucytosine, and fluconazole. In Zimbabwe, little is known about antifungal susceptibility of Cryptococcus. Sixty-eight genotyped Cryptococcus isolates were tested for antifungal profiles. Amphotericin B, isavuconazole, and voriconazole showed higher activity than other triazoles. Fluconazole and flucytosine were less effective, with geometric mean MICs of 2.24 and 2.67mg/L for C. neoformans AFLP1/VNI, 1.38 and 1.53mg/L for C. neoformans AFLP1A/VNB/VNII and AFLP1B/VNII, and 1.85 and 0.68mg/L for Cryptococcus tetragattii, respectively. A significant difference between flucytosine geometric mean MICs of C. neoformans and C. tetragattii was observed (P=0.0002). The majority of isolates (n=66/68; 97.1%) had a wild-type MIC phenotype of all antifungal agents. This study demonstrates a favorable situation with respect to the tested antifungals agents. Continued surveillance of antifungal susceptibility profiles is important due to the high burden of cryptococcosis in Africa.


Asunto(s)
Antifúngicos/farmacología , Cryptococcus neoformans/efectos de los fármacos , Cryptococcus neoformans/aislamiento & purificación , Infecciones por VIH/complicaciones , Meningitis Criptocócica/microbiología , Adolescente , Adulto , Estudios de Cohortes , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Adulto Joven , Zimbabwe
12.
J Med Microbiol ; 65(11): 1281-1288, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27638836

RESUMEN

HIV and cryptococcal meningitis co-infection is a major public health problem in most developing countries. Cryptococcus neoformans sensu stricto is responsible for the majority of HIV-associated cryptococcosis cases in sub-Saharan Africa. Despite the available information, little is known about cryptococcal population diversity and its association with clinical outcomes in patients with HIV-associated cryptococcal meningitis in sub-Saharan Africa. In a prospective cohort, we investigated the prevalence and clinical outcome of Cryptococcusneoformans sensu stricto meningitis among HIV-infected patients in Harare, Zimbabwe, and compared the genotypic diversity of the isolates with those collected from other parts of Africa. Molecular typing was done using amplified fragment length polymorphism genotyping and microsatellite typing. The majority of patients with HIV-associated Cryptococcusneoformans sensu stricto meningitis in this cohort were males (n=33/55; 60.0 %). The predominant Cryptococcus neoformans sensu stricto genotype among the Zimbabwean isolates was genotype AFLP1/VNI (n=40; 72.7 %), followed by AFLP1A/VNB/VNII (n=8; 14.6 %), and AFLP1B/VNII was the least isolated (n=7; 12.7 %). Most of the isolates were mating-type α (n=51; 92.7 %), and only four (7.3 %) were mating-type a. Overall in-hospital mortality was 55.6 % (n=30), and no difference between infecting genotype and clinical outcome of patient (P=0.73) or CD4+ counts (P=0.79) was observed. Zimbabwean Cryptococcusneoformans sensu stricto genotypes demonstrated a high level of genetic diversity by microsatellite typing, and 51 genotypes within the main molecular types AFLP1/VNI, AFLP1A/VNB/VNII and AFLP1B/VNII were identified. This study demonstrates that Cryptococcusneoformans sensu stricto in Zimbabwe has a high level of genetic diversity when compared to other regional isolates.


Asunto(s)
Cryptococcus neoformans/genética , Cryptococcus neoformans/aislamiento & purificación , Variación Genética , Infecciones por VIH/complicaciones , Meningitis Criptocócica/microbiología , Adolescente , Adulto , Cryptococcus neoformans/clasificación , Femenino , Genotipo , Humanos , Masculino , Meningitis Criptocócica/etiología , Persona de Mediana Edad , Estudios Prospectivos , Adulto Joven , Zimbabwe
13.
Pediatr Infect Dis J ; 35(9): 979-80, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27187754

RESUMEN

Cryptococcal meningitis is a leading infectious disease worldwide as a result of the high burden of HIV and AIDS, although its cumulative incidence is very low in children compared with that in adults. Very few studies involving the disease in children have been reported including sub-Saharan Africa, with the highest prevalence of HIV-infected children in the world. We summarize 5 cases of children diagnosed with cryptococcal meningitis at a tertiary hospital in Harare, Zimbabwe, between October 1, 2013, and September 30, 2014.


Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA , Infecciones por VIH/complicaciones , Meningitis Criptocócica , Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Adolescente , África del Sur del Sahara , Antirretrovirales/uso terapéutico , Niño , Humanos , Masculino , Meningitis Criptocócica/diagnóstico , Meningitis Criptocócica/tratamiento farmacológico , Meningitis Criptocócica/epidemiología , Estudios Retrospectivos
14.
J Infect ; 72(6): 745-752, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-27038502

RESUMEN

OBJECTIVES: HIV-associated cryptococcal meningitis is commonly caused by Cryptococcus neoformans, whilst infections with Cryptococcus gattii sensu lato are historically rare. Despite available studies, little is known about the occurrence of C. gattii sensu lato infections among HIV-infected individuals in Zimbabwe. METHODS: In a prospective cohort, we investigated the prevalence of C. gattii sensu lato meningitis among HIV-infected patients (n = 74) in Harare, Zimbabwe. RESULTS: Of the 66/74 isolates confirmed by molecular characterization, 16.7% (11/66) were found to be C. gattii sensu lato and 83.3% (55/66) C. neoformans sensu stricto. From one patient two phenotypically different C. gattii sensu lato colonies were cultured. The majority (n = 9/12; 75%) of the C. gattii sensu lato isolates were Cryptococcus tetragattii (AFLP7/VGIV), which has been an infrequently reported pathogen. In-hospital mortality associated with C. gattii sensu lato was 36.4%. CONCLUSIONS: Our data suggests that C. tetragattii (AFLP7/VGIV) is a more common cause of disease than C. gattii sensu stricto (genotype AFLP4/VGI) among patients with HIV-associated cryptococcal meningitis in Harare, Zimbabwe and possibly underreported in sub-Saharan Africa.


Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Cryptococcus gattii/aislamiento & purificación , Meningitis Criptocócica/microbiología , Adulto , Líquido Cefalorraquídeo/microbiología , Criptococosis/epidemiología , Criptococosis/microbiología , Cryptococcus gattii/genética , Cryptococcus neoformans/genética , Cryptococcus neoformans/aislamiento & purificación , ADN de Hongos/genética , Femenino , Genotipo , Mortalidad Hospitalaria , Humanos , Masculino , Meningitis Criptocócica/epidemiología , Persona de Mediana Edad , Tipificación de Secuencias Multilocus , Técnicas de Tipificación Micológica , Prevalencia , Estudios Prospectivos , Zimbabwe/epidemiología
15.
Mycoses ; 59(3): 151-6, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26661484

RESUMEN

Cryptococcal meningitis is the leading fungal infection and AIDS defining opportunistic illness in patients with late stage HIV infection, particularly in South-East Asia and sub-Saharan Africa. Given the high mortality, clinical differences and the extensive ecological niche of Cryptococcus neoformans and Cryptococcus gattii species complexes, there is need for laboratories in sub-Sahara African countries to adopt new and alternative reliable diagnostic algorithms that rapidly identify and distinguish these species. We biotyped 74 and then amplified fragment length polymorphism (AFLP) genotyped 66 Cryptococcus isolates from a cohort of patients with HIV-associated cryptococcal meningitis. C. gattii sensu lato was isolated at a prevalence of 16.7% (n = 11/66) and C. neoformans sensu stricto was responsible for 83.3% (n = 55/66) of the infections. l-Canavanine glycine bromothymol blue, yeast-carbon-base-d-proline-d-tryptophan and creatinine dextrose bromothymol blue thymine were able to distinguish pathogenic C. gattii sensu lato from C. neoformans sensu stricto species when compared with AFLP genotyping. This study demonstrates high C. gattii sensu lato prevalence in Zimbabwe. In addition, biotyping methods can be used as alternative diagnostic tools to molecular typing in resource-limited areas for differentiating pathogenic Cryptococcus species.


Asunto(s)
Cryptococcus/clasificación , Meningitis Criptocócica/diagnóstico , Técnicas de Tipificación Micológica/métodos , Adulto , África del Sur del Sahara/epidemiología , Análisis del Polimorfismo de Longitud de Fragmentos Amplificados , Líquido Cefalorraquídeo/microbiología , Estudios de Cohortes , Cryptococcus/genética , Cryptococcus/aislamiento & purificación , Cryptococcus/patogenicidad , Medios de Cultivo/química , Técnicas de Genotipaje , Infecciones por VIH/complicaciones , Humanos , Meningitis Criptocócica/epidemiología , Meningitis Criptocócica/microbiología , Técnicas de Tipificación Micológica/normas , Prevalencia , Sensibilidad y Especificidad
16.
J Med Chem ; 57(3): 817-27, 2014 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-24428728

RESUMEN

The conformational behavior of tumor-associated carbohydrate antigens (TACAs) dimLe(x) and Le(a)Le(x) was studied using a combination of NMR experiments and molecular dynamics simulations. It is shown that within the hexasaccharides, the Le(x) and Le(a) branched trisaccharide fragments adopt the rigid "stacked" conformation known for the isolated trisaccharide antigens. In contrast, the ß-D-GlcNAc-(1→3)-D-Gal glycosidic bond that connects the two Le(x) trisaccharides in dimLe(x), and the Le(a) trisaccharide to the Le(x) trisaccharide in Le(a)Le(x), was found to be very flexible in both hexasaccharides. Our results show that two distinct conformations, differing by the value of the Ψ angle for this glycosidic bond, are populated in solution. While the relative proportions of the two conformations in solution could not be determined accurately, experimental measurements indicate that both conformations are populated in significant amounts.


Asunto(s)
Antígenos de Carbohidratos Asociados a Tumores/química , Antígeno Lewis X/química , Oligosacáridos/química , Dimerización , Antígenos del Grupo Sanguíneo de Lewis , Espectroscopía de Resonancia Magnética , Conformación Molecular , Simulación de Dinámica Molecular
17.
Magn Reson Chem ; 48(8): 630-41, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20589732

RESUMEN

The INADEQUATE experiment can provide unequalled, detailed information about the carbon skeleton of an organic molecule. However, it also has the reputation of requiring unreasonable amounts of sample. Modern spectrometers and probes have mitigated this problem, and it is now possible to get good structural data on a few milligrams of a typical organic small molecule. In this paper, we analyze the experiment step by step in some detail, to show how each part of the sequence can both contribute to maximum overall sensitivity and can lead to artifacts. We illustrate these methods on three molecules: 1-octanol, the steroid 17alpha-ethynylestradiol and the isoquinoline alkaloid beta-hydrastine. In particular, we show that not only is the standard experiment powerful, but also a version tuned to small couplings can contribute vital structural information on long-range connectivities. If the delay in the spin echo is long, pairs of carbons with small couplings can create significant double-quantum coherence and show correlations in the spectrum. These are two- and three-bond correlations in a carbon chain or through a heteroatom in the molecule. All these mean that INADEQUATE can play a viable and important role in routine organic structure determination.


Asunto(s)
1-Octanol/química , Bencilisoquinolinas/química , Etinilestradiol/química , Etinilestradiol/análogos & derivados , Espectroscopía de Resonancia Magnética/normas , Estructura Molecular , Estándares de Referencia
18.
Bioorg Med Chem ; 17(4): 1514-26, 2009 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-19196517

RESUMEN

The solution conformational behavior of the Tumor-Associated Carbohydrate Antigen Le(a)Le(x) central fragment: methyl alpha-L-fucopyranosyl-(1-->4)-2-acetamido-2-deoxy-beta-D-glucopyranosyl-(1-->3)-beta-D-galactopyranoside was studied using three computational methods: a rigid systematic search as implemented in Sybyl, a stochastic search as implemented in MOE2004, and dynamics simulations using the SANDER module of AMBER9. Our results illustrate the complementarity of these methods to identify energetically relevant conformations and flexible linkages. In particular, the beta-GlcNAc-(1-->3)-Gal linkage was shown to be extremely flexible adopting a wide range of orientations around two energy minima. The modeling results were validated by comparison of theoretical distances, derived from the simulations, with experimental measurements obtained from 1D selective ROESY buildup curves on the synthetic fragment.


Asunto(s)
Antígenos de Carbohidratos Asociados a Tumores/química , Oligosacáridos/química , Trisacáridos/química , Conformación de Carbohidratos , Secuencia de Carbohidratos , Simulación por Computador , Antígenos del Grupo Sanguíneo de Lewis , Antígeno Lewis X , Modelos Moleculares , Modelos Estadísticos , Datos de Secuencia Molecular , Resonancia Magnética Nuclear Biomolecular , Oligosacáridos/síntesis química , Procesos Estocásticos , Termodinámica , Trisacáridos/síntesis química
19.
Chemosphere ; 73(1 Suppl): S53-9, 2008 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-18440586

RESUMEN

The production of perfluoroalkylsulfonate (PFOS) derivatives from linear alkyl precursors using electrochemical fluorination is not a clean process but, instead, gives complex mixtures. This study reports the isolation and (19)F NMR characterization of eleven perfluorooctanesulfonate isomers from a commercial mixture. This allowed the quantification of the individual CF(3) branched isomers that predominate in technical PFOS.


Asunto(s)
Ácidos Alcanesulfónicos/química , Ácidos Alcanesulfónicos/aislamiento & purificación , Fluorocarburos/química , Fluorocarburos/aislamiento & purificación , Mezclas Complejas/química , Fluoruros/química , Isomerismo , Espectroscopía de Resonancia Magnética
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