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ABSTRACT: We present a case of fatal Rickettsiosis from South Africa.
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Infecciones por Rickettsia/diagnóstico , Comorbilidad , Resultado Fatal , Humanos , Masculino , Persona de Mediana Edad , Necrosis , Piel/patología , Sudáfrica , Mordeduras de Garrapatas/patologíaRESUMEN
BACKGROUND: Extra pulmonary manifestation of tuberculosis (TB) accounts for approximately one-half of TB cases in HIV-infected individuals with pleural TB as the second most common location. Even though mycobacteria are cleared, mycobacterial antigens may persist in infected tissues, causing sustained inflammation and chronicity of the disease. The aim of this study was to explore various mycobacterial antigens in pleural effusions, the impact of HIV infection and CD4+ T-cell depletion on the presence of antigens, and the diagnostic potential of antigens for improved and rapid diagnosis of pleural TB. METHODS: Pleural fluid specimens were collected from patients presenting with clinically suspected pleural TB, and processed routinely for culture, cytology, and adenosine deaminase activity analysis. HIV status and CD4+ T-cell counts were recorded. Pleural fluid mononuclear cells (PFMC) were isolated, and cell smears were stained with acid-fast staining and immunocytochemistry for various mycobacterial antigens. Real-time and nested-PCR were performed. Patients were categorized as pleural TB or non-TB cases using a composite reference standard. Performance of the mycobacterial antigens as diagnostic test was assessed. RESULTS: A total of 41 patients were enrolled, of which 32 were classified as pleural TB and 9 as non-TB. Thirteen patients had culture confirmed pleural TB, 26 (81%) were HIV-TB co-infected, and 64% had < 100 CD4+ T-cells/microL. Both secreted and cell-wall mycobacterial antigens were detected in PFMC. Lipoarabinomannan (LAM) was the most frequently detected antigen. There was no direct correlation between positive culture and antigens. Cases with low CD4+ T-cell counts had higher bacterial and antigen burden. By combining detection of secreted antigen or LAM, the sensitivity and specificity to diagnose pleural TB was 56 and 78%, respectively, as compared to 41 and 100% for culture, 53 and 89% for nested PCR, and 6 and 100% for real-time PCR. CONCLUSION: Mycobacterial antigens were detectable in PFMC from tuberculous pleural effusions, even in cases where viable mycobacteria or bacterial DNA were not always detected. Thus, a combination of secreted antigen and LAM detection by immunocytochemistry may be a complement to acid-fast staining and contribute to rapid and accurate diagnosis of pleural TB.
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Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Linfocitos T CD4-Positivos/inmunología , Coinfección/diagnóstico , Pruebas Diagnósticas de Rutina/métodos , Lipopolisacáridos/genética , Lipopolisacáridos/inmunología , Mycobacterium tuberculosis/inmunología , Derrame Pleural/microbiología , Tuberculosis Pleural/diagnóstico , Adulto , Anciano , Antígenos Bacterianos/genética , Antígenos Bacterianos/inmunología , Proteínas Bacterianas/genética , Proteínas Bacterianas/inmunología , Recuento de Linfocito CD4 , Coinfección/microbiología , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/aislamiento & purificación , Derrame Pleural/patología , Reacción en Cadena en Tiempo Real de la Polimerasa , Sensibilidad y Especificidad , Adulto JovenRESUMEN
BACKGROUND: Invasive meningococcal disease (IMD) is endemic to South Africa, where vaccine use is negligible. We describe the epidemiology of IMD in South Africa. METHODS: IMD cases were identified through a national, laboratory-based surveillance program, GERMS-SA, from 2003-2016. Clinical data on outcomes and human immunodeficiency virus (HIV) statuses were available from 26 sentinel hospital sites. We conducted space-time analyses to detect clusters of serogroup-specific IMD cases. RESULTS: Over 14 years, 5249 IMD cases were identified. The incidence was 0.97 cases per 100 000 persons in 2003, peaked at 1.4 cases per 100 000 persons in 2006, and declined to 0.23 cases per 100 000 persons in 2016. Serogroups were confirmed in 3917 (75%) cases: serogroup A was present in 4.7% of cases, B in 23.3%, C in 9.4%; W in 49.5%; Y in 12.3%, X in 0.3%; Z in 0.1% and 0.4% of cases were non-groupable. We identified 8 serogroup-specific, geo-temporal clusters of disease. Isolate susceptibility was 100% to ceftriaxone, 95% to penicillin, and 99.9% to ciprofloxacin. The in-hospital case-fatality rate was 17% (247/1479). Of those tested, 36% (337/947) of IMD cases were HIV-coinfected. The IMD incidence in HIV-infected persons was higher for all age categories, with an age-adjusted relative risk ratio (aRRR) of 2.5 (95% confidence interval [CI] 2.2-2.8; P < .001) from 2012-2016. No patients reported previous meningococcal vaccine exposure. Patients with serogroup W were 3 times more likely to present with severe disease than those with serogroup B (aRRR 2.7, 95% CI 1.1-6.3); HIV coinfection was twice as common with W and Y diseases (aRRR W = 1.8, 95% CI 1.1-2.9; aRRR Y = 1.9, 95% CI 1.0-3.4). CONCLUSIONS: In the absence of significant vaccine use, IMD in South Africa decreased by 76% from 2003-2016. HIV was associated with an increased risk of IMD, especially for serogroup W and Y diseases.
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Coinfección/epidemiología , Infecciones Meningocócicas/epidemiología , Adolescente , Adulto , Anciano , Antibacterianos/uso terapéutico , Niño , Preescolar , Coinfección/microbiología , Coinfección/virología , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Infecciones por VIH/microbiología , Mortalidad Hospitalaria , Humanos , Incidencia , Masculino , Infecciones Meningocócicas/tratamiento farmacológico , Infecciones Meningocócicas/mortalidad , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Neisseria meningitidis/inmunología , Factores de Riesgo , Serogrupo , Sudáfrica/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Non-typhoidal salmonellae (NTS) have been associated with invasive disease, notably meningitis, in immunocompromised individuals. Infections of this nature carry high rates of morbidity and mortality. Colistin resistance in salmonellae is a rare finding, more so in an invasive isolate such as cerebrospinal fluid (CSF). Colistin resistance has important infection control implications and failure to manage this phenomenon may lead to the loss of our last line of defence against multi-drug resistant Gram-negative organisms. To our knowledge, this is the first reported clinical case of colistin-resistant Salmonella Enteritidis meningitis in South Africa. CASE PRESENTATION: We report a case of a young male patient with advanced human immunodeficiency virus (HIV) infection who presented to hospital with symptoms of meningitis. Cerebrospinal fluid (CSF) cultured a Salmonella Enteritidis strain. Antimicrobial susceptibility testing (AST) of the isolate, revealed the strain to be colistin resistant. Despite early and aggressive antimicrobial therapy, the patient succumbed to the illness after a short stay in hospital. Subsequent genomic analysis of the isolate showed no presence of the mcr genes or resistance-conferring mutations in phoPQ, pmrAB, pmrHFIJKLME/arnBCADTEF, mgrB, and acrAB genes, suggesting the presence of a novel colistin resistance mechanism. CONCLUSION: Invasive non-typhoidal salmonellae infection should be suspected in patients with advanced immunosuppression who present with clinical features of meningitis. Despite early and appropriate empiric therapy, these infections are commonly associated with adverse outcomes to the patient. Combination therapy with two active anti-Salmonella agents may be a consideration in the future to overcome the high mortality associated with NTS meningitis. Colistin resistance in clinical Salmonella isolates, although a rare finding at present, has significant public health and infection control implications. The causative mechanism of resistance should be sought in all cases.
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Antibacterianos/uso terapéutico , Colistina/uso terapéutico , Farmacorresistencia Bacteriana , Seropositividad para VIH/complicaciones , Meningitis Bacterianas/complicaciones , Meningitis Bacterianas/tratamiento farmacológico , Infecciones por Salmonella/complicaciones , Infecciones por Salmonella/tratamiento farmacológico , Adulto , Antibacterianos/efectos adversos , Colistina/efectos adversos , Servicio de Urgencia en Hospital , Resultado Fatal , Escala de Coma de Glasgow , Humanos , Masculino , Salmonella enteritidis/aislamiento & purificación , Sudáfrica , Centros de Atención TerciariaRESUMEN
BACKGROUND: This study was done to diagnose Mycoplasma genitalium infection based on bacterial load in urine specimens from symptomatic and asymptomatic men. METHODS: Urine specimens from 94 men with visible urethral discharge, 206 with burning on micturition and 75 without symptoms presenting to a family practitioner were tested for M. genitalium as well as Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis by transcription-mediated amplification assays. A quantitative polymerase chain reaction assay was used to determine the bacterial load for all specimens in which M. genitalium was the only organism detected. RESULTS: Among the 375 specimens collected, M. genitalium was detected in 59 (15.7%) men (both symptomatic and asymptomatic) using the transcription-mediated amplification assay, and in 45 (12.0%) of the total population, it was the only pathogen detected. One or more pathogens were detected in 129 (43%) of the symptomatic men, with N. gonorrhoeae in 50 (16.7%); C. trachomatis in 37 (12.3%) and T. vaginalis present in 24 (8.0%) patients. Among the 17 patients where mixed infections were detected, M. genitalium with N. gonorrhoeae was the most common (11/17; 64.7%). Patients with visible urethral discharge had significantly higher M. genitalium concentrations than those with burning on micturition. The median M. genitalium load in symptomatic men was significantly higher than that in asymptomatic men. CONCLUSIONS: This study confirms the high prevalence of M. genitalium among men with urethritis in South Africa and demonstrates that there is a strong association with M. genitalium bacterial load and clinical urethritis. As the number of organisms increased, the severity of the symptoms increased, an indication of the role that the organism plays in disease progression.
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Carga Bacteriana/métodos , Infecciones por Mycoplasma/diagnóstico , Mycoplasma genitalium/aislamiento & purificación , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Uretritis/diagnóstico , Adulto , Infecciones por Chlamydia/diagnóstico , Infecciones por Chlamydia/microbiología , Chlamydia trachomatis/genética , Chlamydia trachomatis/aislamiento & purificación , Gonorrea/diagnóstico , Gonorrea/microbiología , Humanos , Masculino , Persona de Mediana Edad , Infecciones por Mycoplasma/epidemiología , Infecciones por Mycoplasma/microbiología , Mycoplasma genitalium/genética , Neisseria gonorrhoeae/genética , Neisseria gonorrhoeae/aislamiento & purificación , Prevalencia , Sudáfrica/epidemiología , Trichomonas vaginalis/genética , Trichomonas vaginalis/aislamiento & purificación , Uretritis/epidemiología , Uretritis/microbiología , Adulto JovenRESUMEN
Neonatal candidaemia is a common, deadly and costly hospital-associated disease. To determine the genetic diversity of Candida parapsilosis causing fungaemia in South African neonatal intensive care units (NICUs). From February 2009 through to August 2010, cases of candidaemia were reported through laboratory-based surveillance. C. parapsilosis isolates from neonatal cases were submitted for identification by internal transcribed spacer (ITS) region sequencing, antifungal susceptibility testing and microsatellite genotyping. Cluster analysis was performed using Unweighted Pair Group Method with Arithmetic Mean (UPGMA). Of 1671 cases with a viable Candida isolate, 393 (24%) occurred among neonates. Isolates from 143 neonatal cases were confirmed as C. parapsilosis sensu stricto. Many isolates were resistant to fluconazole (77/143; 54%) and voriconazole (20/143; 14%). Of 79 closely-related genotypes, 18 were represented by ≥2 isolates; 61 genotypes had a single isolate each. Seven clusters, comprised of 82 isolates, were identified at five hospitals in three provinces. Isolates belonging to certain clusters were significantly more likely to be fluconazole resistant: all cluster 7 isolates and the majority of cluster 4 (78%), 5 (89%) and 6 (67%) isolates (P<.001). Candida parapsilosis-associated candidaemia in public-sector NICUs was caused by closely related genotypes and there was molecular evidence of undetected outbreaks as well as intra-hospital transmission.
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Candida/clasificación , Candidemia/microbiología , Unidades de Cuidado Intensivo Neonatal , Repeticiones de Microsatélite , Vigilancia de Guardia , Antifúngicos/farmacología , Candida/efectos de los fármacos , Candida/genética , Candida/aislamiento & purificación , Candidemia/epidemiología , Candidemia/transmisión , Análisis por Conglomerados , ADN Espaciador Ribosómico/genética , Femenino , Fluconazol/farmacología , Variación Genética , Genotipo , Técnicas de Genotipaje , Humanos , Recién Nacido , Masculino , Pruebas de Sensibilidad Microbiana , Técnicas de Tipificación Micológica , Filogenia , Sudáfrica/epidemiología , Voriconazol/farmacologíaRESUMEN
Tuberculosis (TB) remains a deadly infectious disease affecting millions of people worldwide; 95% of TB cases, with 98% of death occur in developing countries. The situation in South Africa merits special attention. A total of 21,913 sputum specimens of suspected TB patients from three provinces of South Africa routinely submitted to the TB laboratory of Dr. George Mukhari (DGM) Hospital were assayed for Mycobacterium tuberculosis (MTB) growth and antibiotic susceptibility. The genetic diversity of 338 resistant strains were also studied. DNA isolated from the strains were restricted with Pvu II, transferred on to a nylon membrane and hybridized with a PCR-amplified horseradish peroxidase 245 bp IS6110 probe. Of the 338 resistant strains, 2.09% had less than 5 bands of IS6110, and 98% had 5 or more bands. Unique restriction fragment length polymorphism (RFLP) patterns were observed in 84.3% of the strains, showing their epidemiological independence, and 15.7% were grouped into 22 clusters. Thirty-two strains (61.5%) from the 52 that clustered were from Mpumalanga, 16/52 (30.8%) from Gauteng, and 4/52 (9.6%) from Limpopo province. Clustering was not associated with age. However, strains from male patients in Mpumalanga were more likely to be clustered than strains from male patients in Limpopo and/or Gauteng province. The minimum estimate for the proportion of resistant TB that was due to transmission is 9.06% (52-22 = 30/331). Our results indicate that transmission of drug-resistant strains may contribute substantially to the emergence of drug-resistant tuberculosis in South Africa.
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Técnicas de Tipificación Bacteriana/métodos , Mycobacterium avium subsp. paratuberculosis/genética , Mycobacterium tuberculosis/genética , Polimorfismo de Longitud del Fragmento de Restricción/genética , Tuberculosis Resistente a Múltiples Medicamentos/genética , Tuberculosis Pulmonar/genética , Adolescente , Adulto , Distribución por Edad , Anciano , Niño , Femenino , Variación Genética/genética , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa/métodos , Distribución por Sexo , Sudáfrica , Esputo/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Tuberculosis Pulmonar/microbiología , Adulto JovenRESUMEN
BACKGROUND: Systemic disease due to shigellae is associated with human immunodeficiency virus (HIV), malnutrition, and other immunosuppressed states. We examined the clinical and microbiologic characteristics of systemic shigellosis in South Africa, where rates of HIV infection are high. METHODS: From 2003 to 2009, 429 cases of invasive shigellosis were identified through national laboratory-based surveillance. At selected sites, additional information was captured on HIV serostatus and outcome. Isolates were serotyped and antimicrobial susceptibility testing performed. RESULTS: Most cases of systemic shigellosis were diagnosed on blood culture (408 of 429 cases; 95%). HIV prevalence was 67% (80 of 120 cases), highest in patients aged 5-54 years, and higher among females (55 of 70 cases; 79%) compared with males (25 of 48 cases; 52%; P = .002). HIV-infected people were 4.1 times more likely to die than HIV-uninfected cases (case-fatality ratio, 29 of 78 HIV-infected people [37%] vs 5 of 40 HIV-uninfected people [13%]; P = .008; 95% confidence interval [CI], 1.5-11.8). The commonest serotype was Shigella flexneri 2a (89 of 292 serotypes [30.5%]). Pentavalent resistance occurred in 120 of 292 isolates (41.1%). There was no difference in multidrug resistance between HIV-infected patients (33 of 71 [46%]) and uninfected patients (12 of 33 [36%]; 95% CI, .65--3.55). CONCLUSIONS: Systemic shigellosis is associated with HIV-infected patients, primarily in older girls and women, potentially due to the burden of caring for sick children in the home; interventions need to be targeted here. Death rates are higher in HIV-infected versus uninfected individuals.
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Bacteriemia/epidemiología , Disentería Bacilar/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacología , Bacteriemia/microbiología , Niño , Preescolar , Disentería Bacilar/microbiología , Femenino , Infecciones por VIH/complicaciones , Humanos , Huésped Inmunocomprometido , Lactante , Recién Nacido , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Shigella/clasificación , Shigella/efectos de los fármacos , Shigella/aislamiento & purificación , Sudáfrica/epidemiología , Adulto JovenRESUMEN
Despite South Africa being one of the high-burden multidrug-resistant tuberculosis (MDR-TB) countries, information regarding the population structure of drug-resistant Mycobacterium tuberculosis strains is limited from many regions of South Africa. This study investigated the population structure and transmission patterns of drug-resistant M. tuberculosis isolates in a high-burden setting of South Africa as well as the possible association of genotypes with drug resistance and demographic characteristics. A total of 336 consecutive MDR-TB isolates from four provinces of South Africa were genotyped using spoligotyping and mycobacterial interspersed repetitive-unit-variable number tandem repeat (MIRU-VNTR) typing. Drug susceptibility testing for ofloxacin, kanamycin, and capreomycin was performed using the agar proportion method. The results showed that 4.8% of MDR-TB isolates were resistant to ofloxacin, 2.7% were resistant to kanamycin, and 4.5% were resistant to capreomycin, while 7.1% were extensively drug resistant (XDR), and the remaining 83.6% were susceptible to all of the second-line drugs tested. Spoligotyping grouped 90.8% of the isolates into 25 clusters, while 9.2% isolates were unclustered. Ninety-one percent of the 336 isolates were assigned to 21 previously described shared types, with the Beijing family being the predominant genotype in the North-West and Limpopo Provinces, while the EAI1_SOM family was the predominant genotype in the Gauteng and Mpumalanga Provinces. No association was found between genotypes and specific drug resistance patterns or demographic information. The high level of diversity and the geographical distribution of the drug-resistant M. tuberculosis isolates in this study suggest that the transmission of TB in the study settings is not caused by the clonal spread of a specific M. tuberculosis strain.
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Antituberculosos/farmacología , Farmacorresistencia Bacteriana Múltiple , Tipificación Molecular , Mycobacterium tuberculosis/clasificación , Mycobacterium tuberculosis/efectos de los fármacos , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Adolescente , Adulto , Anciano , Capreomicina/farmacología , Niño , Análisis por Conglomerados , Femenino , Genotipo , Humanos , Kanamicina/farmacología , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Epidemiología Molecular , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Ofloxacino/farmacología , Sudáfrica/epidemiología , Adulto JovenRESUMEN
A novel protocol for full-length Mycobacterium tuberculosis gene analysis of first- and second-line drug resistance was developed using the Ion Torrent Personal Genome Machine (PGM). Five genes-rpoB (rifampin), katG (isoniazid), pncA (pyrazinamide), gyrA (ofloxacin/fluoroquinolone), and rrs (aminoglycosides)-were amplified and sequenced, and results were compared to those obtained by genotypic Hain line probe assay (LPA) and phenotypic Bactec MGIT 960 analysis using 26 geographically diverse South African clinical isolates collected between July and November 2011. Ion Torrent sequencing exhibited 100% (26/26) concordance to phenotypic resistance obtained by MGIT 960 culture and genotypic rpoB and katG results by LPA. In several rifampin-resistant isolates, Ion Torrent sequencing revealed uncommon substitutions (H526R and D516G) that did not have a defined mutation by LPA. Importantly, previously uncharacterized mutations in rpoB (V194I), rrs (G878A), and pncA (Q122Stop) genes were observed. Ion Torrent sequencing may facilitate tracking and monitoring geographically diverse multidrug-resistant and extensively drug-resistant strains and could potentially be integrated into selected regional and reference settings throughout Africa, India, and China.
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Antituberculosos/farmacología , Técnicas Bacteriológicas/métodos , Farmacorresistencia Bacteriana , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Mutación , Mycobacterium tuberculosis/genética , Proteínas Bacterianas/genética , Humanos , Datos de Secuencia Molecular , Proteínas Mutantes/genética , Mutación Missense , Mycobacterium tuberculosis/aislamiento & purificación , Reacción en Cadena de la Polimerasa , Sudáfrica , Tuberculosis/microbiologíaRESUMEN
BACKGROUND: The increasing problem of multi-drug-resistant (MDR) tuberculosis (TB) [ie resistant to at least isoniazid (INH) and rifampicin (RIF)] is becoming a global problem. Successful treatment outcome for MDR-TB depends on reliable and accurate drug susceptibility testing of first-line and second-line anti-TB drugs. METHOD: Consecutive M. tuberculosis isolates identified as MDR-TB during August 2007 to January 2008 using the BACTEC MGIT 960 systems and the agar proportion method were included in this study. Susceptibility testing of MDR-TB isolates against ethambutol (EMB) and streptomycin (STR) as well as two second-line anti-TB drugs, kanamycin (KAN) and ofloxacin (OFX) was performed using the BACTEC MGIT 960 systems at a routine diagnostic laboratory. The results were compared to those obtained by the agar proportion method. RESULT: The agreement between the BACTEC MGIT 960 system and the agar proportion method was 44% for EMB, 61% for STR and 89% for both KAN and OFX. The sensitivity and specificity of the BACTEC MGIT 960 system using the agar proportion method as a gold standard was 92% and 37% for EMB, 95% and 37% for STR, 27% and 97% for KAN and 84% and 90% for OFX, respectively. CONCLUSIONS: The BACTEC MGIT 960 system showed acceptable sensitivity for EMB, STR, and OFX; however, the BACTEC MGIT 960 system was less specific for EMB and STR and demonstrated a low sensitivity for KAN. The lower agreement found between the two methods suggests the unreliability of the BACTEC MGIT 960 system for the drugs tested. The reasons for the lower agreement between the two methods need to be investigated and further studies are needed in this setting to confirm the study finding.
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Antituberculosos/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Humanos , Pruebas de Sensibilidad Microbiana/métodos , Sensibilidad y Especificidad , SudáfricaRESUMEN
BACKGROUND: To evaluate the VersaTREK (TREK Diagnostic Systems, Cleveland, Ohio) blood culture system against the Bactec9240 (BD Microbiology, Cockeysville, MD), for the recovery of bloodstream pathogens. METHODS: Venous blood from patients with suspected bacterial sepsis was evenly distributed into bottles of each system. Positive signals were recorded and bottles processed onto standard media for organism recovery. False positive signals were regarded if no organisms were seen on Gram stain and no growth was observed. RESULTS: 177 bottles were available for analysis; the Bactec9240 system yielded 43 positive, 134 negative results and no false positive signals. The VersaTREK system had 58 positive signals with 14 being false positives. CONCLUSIONS: In our setting with high background burden of immuno-compromised patients, the VersaTREK system compared favourably with the Bactec9240 in recovering blood stream aerobic and facultative anaerobic pathogens from patients with suspected bacterial sepsis. A concern is the high false positivity rate. Due to its versatility to accommodate small and large workloads as well as using smaller volumes of blood, this system may establish itself as a useful alternative for the recovery of bloodstream pathogens.
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Bacteriemia/microbiología , Bacterias/aislamiento & purificación , Técnicas Bacteriológicas/métodos , Sangre/microbiología , Técnicas de Laboratorio Clínico/métodos , Bacteriemia/diagnóstico , Bacterias/crecimiento & desarrollo , Técnicas Bacteriológicas/instrumentación , Técnicas de Laboratorio Clínico/instrumentación , HumanosRESUMEN
Current evolutionary scenarios posit the emergence of Mycobacterium tuberculosis from an environmental saprophyte through a cumulative process of genome adaptation. Mycobacterium riyadhense, a related bacillus, is being increasingly isolated from human clinical cases with tuberculosis-like symptoms in various parts of the world. To elucidate the evolutionary relationship between M. riyadhense and other mycobacterial species, including members of the M. tuberculosis complex (MTBC), eight clinical isolates of M. riyadhense were sequenced and analyzed. We show, among other features, that M. riyadhense shares a large number of conserved orthologs with M. tuberculosis and shows the expansion of toxin/antitoxin pairs, PE/PPE family proteins compared with other non-tuberculous mycobacteria. We observed M. riyadhense lacks wecE gene which may result in the absence of lipooligosaccharides (LOS) IV. Comparative transcriptomic analysis of infected macrophages reveals genes encoding inducers of Type I IFN responses, such as cytosolic DNA sensors, were relatively less expressed by macrophages infected with M. riyadhense or M. kansasii, compared to BCG or M. tuberculosis. Overall, our work sheds new light on the evolution of M. riyadhense, its relationship to the MTBC, and its potential as a system for the study of mycobacterial virulence and pathogenesis.
RESUMEN
BACKGROUND: Diagnosis of tuberculous (TB) pleuritis is difficult and better diagnostic tools are needed. New blood based interferon-gamma (IFN-gamma) tests are promising, but sensitivity could be low in HIV positive patients. The IFN-gamma tests have not yet been validated for use in pleural fluid, a compartment with higher level of immune activation than in blood. METHODS: The QuantiFERON TB-Gold (QFT-TB) test was analysed in blood and pleural fluid from 34 patients presenting with clinically suspected pleural TB. Clinical data, HIV status and CD4 cell counts were recorded. Adenosine deaminase activity (ADA) analysis and TB culture were performed on pleural fluid. RESULTS: The patients were categorised as 'confirmed TB' (n = 12), 'probable TB' (n = 16) and 'non-TB' pleuritis (n = 6) based on TB culture results and clinical and biochemical criteria. The majority of the TB patients were HIV infected (82%). The QFT-TB in pleural fluid was positive in 27% and 56% of the 'confirmed TB' and 'probable TB' cases, respectively, whereas the corresponding sensitivities in blood were 58% and 83%. Indeterminate results in blood (25%) were caused by low phytohemagglutinin (PHA = positive control) IFN-gamma responses, significantly lower in the TB patients as compared to the 'non-TB' cases (p = 0.02). Blood PHA responses correlated with CD4 cell count (r = 0.600, p = 0.028). In contrast, in pleural fluid indeterminate results (52%) were caused by high Nil (negative control) IFN-gamma responses in both TB groups. Still, the Nil IFN-gamma responses were lower than the TB antigen responses (p < 0.01), offering a conclusive test for half of the patients. We did not find any correlation between blood CD4 cell count and IFN-gamma responses in pleural fluid. CONCLUSION: The QFT-TB test in blood could contribute to the diagnosis of TB pleuritis in the HIV positive population. Still, the number of inconclusive results is too high to recommend the commercial QFT-TB test for routine use in pleural fluid in a TB/HIV endemic resource-limited setting.
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Infecciones por VIH/complicaciones , Interferón gamma/biosíntesis , Derrame Pleural/inmunología , Tuberculosis Pleural/diagnóstico , Adenosina Desaminasa/metabolismo , Adulto , Anciano , Sangre/inmunología , Recuento de Linfocito CD4 , Células Cultivadas , Femenino , Humanos , Leucocitos Mononucleares/inmunología , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/aislamiento & purificación , Sensibilidad y EspecificidadRESUMEN
The objective of this guideline is to provide guidance for the diagnosis and management of donovanosis, a now rare sexually transmitted infection. This guidance is primarily for professionals working in UK Sexual Health services (although others may find it useful) and refers to the management of individuals presenting with possible symptoms of donovanosis who are over the age of 16. An updated literature review since the last Clinical Effectiveness Group (CEG) guideline produced for this condition in 2011 has shown few new developments. Most reports in the literature relate to cases of unusual presentations of the condition.
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Antibacterianos/uso terapéutico , Granuloma Inguinal/diagnóstico , Granuloma Inguinal/tratamiento farmacológico , Guías de Práctica Clínica como Asunto , Adulto , HumanosRESUMEN
Resistant Neisseria gonorrhoeae has been evolving. This study assessed the antimicrobial susceptibility profile of isolates in the Pretoria region, South Africa. Isolates of N. gonorrhoeae from men with urethritis were tested for susceptibility to eight antimicrobial agents by disc diffusion, Etest and agar dilution methods. Chromosomal resistance to penicillin was found in 16% of isolates, 16% showed plasmid-mediated resistance and decreased susceptibility was seen in 73% of isolates. For the first time, there is evidence of high-level tetracycline resistance (36%). Ciprofloxacin resistance emerged at 7%. All isolates remained susceptible to ceftriaxone. In view of these findings of the emergence of quinolone-resistant N. gonorrhoeae, national treatment guidelines for syndromic management of sexually transmitted infections need to be urgently reviewed. The injectable preparation, ceftriaxone has to be considered as a first-line agent for the management of gonococcal infections. Overall, the gonococcal isolates in the Pretoria region remain susceptible to ceftriaxone, cefoxitin, cefpodoxime and spectinomycin.
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Farmacorresistencia Bacteriana , Gonorrea/microbiología , Neisseria gonorrhoeae/efectos de los fármacos , Quinolonas/farmacología , Tetraciclina/farmacología , beta-Lactamas/farmacología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Cefalosporinas/farmacología , Gonorrea/tratamiento farmacológico , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Neisseria gonorrhoeae/aislamiento & purificación , Resistencia a las Penicilinas/genética , Quinolonas/uso terapéutico , Sudáfrica , Espectinomicina/farmacología , Tetraciclina/uso terapéutico , Resistencia a la Tetraciclina , Uretritis/microbiología , beta-Lactamas/uso terapéuticoRESUMEN
BACKGROUND: Rapid and accurate identification of pathogens is of utmost importance for management of patients. Current identification relies on conventional phenotypic methods which are time consuming. Matrix-assisted laser desorption/ionisation-time of flight mass spectrometry (MALDI-TOF MS) is based on proteomic profiling and allows for rapid identification of pathogens. OBJECTIVE: We compared MALDI-TOF MS against two commercial systems, MicroScan Walkaway and VITEK 2 MS. METHODS: Over a three-month period from July 2013 to September 2013, a total of 227 bacteria and yeasts were collected from an academic microbiology laboratory (N = 121; 87 Gram-negatives, seven Gram-positives, 27 yeasts) and other laboratories (N = 106; 35 Gram-negatives, 34 Gram-positives, 37 yeasts). Sixty-five positive blood cultures were initially processed with Bruker Sepsityper kit for direct identification. RESULTS: From the 65 blood culture bottles, four grew more than one bacterial pathogen and MALDI-TOF MS identified only one isolate. The blood cultures yielded 21 Gram-negatives, 43 Gram-positives and one Candida. There were 21 Escherirchia coli isolates which were reported by the MALDI-TOF MS as E. coli/Shigella. Of the total 292 isolates, discrepant results were found for one bacterial and three yeast isolates. Discrepant results were resolved by testing with the API system with MALDI-TOF MS showing 100% correlation. CONCLUSION: The MALDI-TOF MS proved to be very useful for rapid and reliable identification of bacteria and yeasts directly from blood cultures and after culture of other specimens. The difference in time to identification was significant for all isolates. However, for positive blood cultures with minimal sample preparation time there was a massive difference in turn-around time with great appreciation by clinicians.
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Treatment of tuberculosis (TB) and HIV co-infections is often complicated by drug-to-drug interactions between anti-mycobacterial and anti-retroviral agents. Rifabutin (RFB) is an alternative to rifampin (RIF) for TB regimens and is recommended for HIV patients concurrently receiving protease inhibitors because of reduced induction of CYP3A4. This study sought to determine the proportion of RFB susceptible isolates among RIF-resistant strains in a high HIV prevalence setting in South Africa. In addition, the study explored the association between rpoB mutations and minimum inhibitory concentrations (MIC) of RIF and RFB. A total of 189 multidrug resistant (MDR) Mycobacterium tuberculosis isolates from the Centre for Tuberculosis repository were analyzed. The MICs were determined using a MYCOTB Sensititre plate method and the rpoB gene was sequenced. Of the 189 MDR isolates, 138 (73%) showed resistance to both RIF and RFB, while 51 (27%) isolates were resistant to RIF but retained susceptibility to RFB. The S531L was the most frequent rpoB point mutation in 105/189 (56%) isolates, followed by H526Y in 27/189 (14%) isolates. Resistance to both RIF and RFB was found predominantly in association with mutations S531L (91/105, 87%), H526Y (20/27, 74%), and H526D (15/19, 79%), while D516V (15/17, 88%), and L533P (3/4, 75%) were found in RIF-resistant, RFB-susceptible isolates. This study has shown that up to 27% of MDR-TB patients in South Africa may benefit from a treatment regimen that includes RFB.
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The number of vaccines available and included as part of the national immunization schedules, has increased significantly over the past few decades. This impacts on patient/parent compliance and creates a challenge for health care providers for implementation of schedules necessitating training and infrastructure improvements. Use of combination rather than component vaccines offers advantages for compliance by single dose administration of various antigens, reducing stock costing as well as reducing cost of additional health care visits. Combination vaccines are often significantly more expensive than individual constituent vaccines. Concerns regarding an increased incidence of adverse events with use of combination vaccines have not been confirmed and rates may seem high as the adverse events seem to mimic the sum total of adverse event rates for each individual antigen used but may in fact be lower. Manufacturers typically advise against interchanging use of vaccine products. Despite this, health authorities advocate use of an alternative vaccine where the original vaccine in not available, to ensure continuity of vaccination. A notable exception is the acellular pertussis vaccine. Partly, because no serological correlates of immunity exist, but also a general lack of convincing follow up studies has prompted the recommendation for manufacturer fidelity for at least the first 3 vaccine doses. According to the South African Medicines Formulary, a variety of vaccines are available in South Africa. Although a large number are available in the private sector, the only true combination vaccine included in the current state EPI, modified in 2009, is the DTaP-IPV/Hib vaccine (Diphtheria, Tetanus, acellular Pertussis, inactivated Poliomyelitis virus and Haemophilus influenzae type b). There are many reasons justifying the use of combination vaccines rather that the individual constituent formulations. Implementation of use in the South African setting at this point is still limited, but may offer an exciting avenue of expanding the antigen repertoire without impacting on side-effects, efficacy or complexity of scheduling.
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Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificación , Vacuna contra Difteria, Tétanos y Tos Ferina/inmunología , Vacunas contra Haemophilus/administración & dosificación , Vacunas contra Haemophilus/inmunología , Programas de Inmunización/organización & administración , Vacuna Antipolio de Virus Inactivados/administración & dosificación , Vacuna Antipolio de Virus Inactivados/inmunología , Vacunación/métodos , Política de Salud , Humanos , Esquemas de Inmunización , Sudáfrica , Vacunas Combinadas/administración & dosificación , Vacunas Combinadas/inmunología , Vacunas Conjugadas/administración & dosificación , Vacunas Conjugadas/inmunologíaRESUMEN
Introduction of Hib vaccine is known to positively impact on reduction of both morbidity and mortality in children less than 5 years of age. Incorporation of this vaccine into a National EPI, however, does come at a significant cost, which is especially important in non-GAVI funded countries. Compounded reduction in response in certain patient populations and possible indication of booster doses further impacts on cost-benefit analyses. Despite these issues, South Africa has supplied Hib vaccine as part of the National EPI in the form of a combination vaccine, Pentaxim, which combines Hib with Diphtheria, Tetanus, acellular Pertussis (DTP) and Poliomyelitis since 2009. Prior to this, another combination vaccine was utilized containing Hib and DTP. This has subsequently lead to a significant reduction in invasive Hib disease post-introduction, therefore largely justifying utilization.