An outbreak of serotype 1 invasive pneumococcal disease (IPD) occurred in Central Australia from October 2010 to the latter part of 2012. Surveillance of serotype 1 carriage was conducted to determine epidemiological features of asymptomatic carriage that could potentially be driving the outbreak.
130 patients and accompanying persons presenting at Alice Springs Hospital Emergency Department consented to nasopharyngeal swab (NPS) collection. NPS were processed by standard methods, including culture, pneumococcal lytA quantitative real-time PCR, serotype 1-specific real-time PCR and multi-locus sequence typing (MLST).
Pneumococcal carriage was detected in 16% of participants. Carriage was highest in the under 10 year olds from remote communities surrounding Alice Springs (75%). Four NPS were positive for serotype 1 DNA by PCR; 3 were also culture-positive for serotype 1 pneumococci. Serotype 1 isolates had atypical colony morphology on primary culture. All serotype 1 carriers were healthy children 5 to 8 years of age from remote communities. By MLST, serotype 1 isolates were ST306, as were IPD isolates associated with this outbreak.
During an outbreak of serotype 1 ST306 IPD, carriage of the outbreak strain was detected in 3% NPS collected. All carriers were healthy children 5 to 8 years of age.
Invasive pneumococcal disease; Serotype 1; Central Australia; Carriage
Chronic Q fever usually presents as endocarditis or endovascular infection. We investigated whether 18F-FDG PET/CT and echocardiography were able to detect the localization of infection. Also, the utility of the modified Duke criteria was assessed.
Fifty-two patients, who had an IgG titre of ≥ 1024 against C. burnetii phase I ≥ 3 months after primary infection or a positive PCR ≥ 1 month after primary infection, were retrospectively included. Data on serology, the results of all imaging studies, possible risk factors for developing proven chronic Q fever and clinical outcome were recorded.
According to the Dutch consensus on Q fever diagnostics, 18 patients had proven chronic Q fever, 14 probable chronic Q fever, and 20 possible chronic Q fever. Of the patients with proven chronic Q fever, 22% were diagnosed with endocarditis, 17% with an infected vascular prosthesis, and 39% with a mycotic aneurysm. 56% of patients with proven chronic Q fever did not recall an episode of acute Q fever. Ten out of 13 18F-FDG PET/CT-scans in patients with proven chronic Q fever localized the infection. TTE and TEE were helpful in only 6% and 50% of patients, respectively.
If chronic Q fever is diagnosed, 18F-FDG PET/CT is a helpful imaging technique for localization of vascular infections due to chronic Q fever. Patients with proven chronic Q fever were diagnosed significantly more often with mycotic aneurysms than in previous case series. Definite endocarditis due to chronic Q fever was less frequently diagnosed in the current study. Chronic Q fever often occurs in patients without a known episode of acute Q fever, so clinical suspicion should remain high, especially in endemic regions.
Chronic Q fever; Coxiella burnetii; 18F-fluorodeoxyglucose positron emission tomography; Echocardiography; Modified Duke criteria; Endocarditis
The genus Chromobacterium consists of 7 recognized species. Among those, only C. violaceum, commonly found in the soil and water of tropical and subtropical regions, has been shown to cause human infection. Although human infection is rare, C. violaceum can cause life-threatening sepsis, with metastatic abscesses, most frequently infecting those who are young and healthy.
We recently identified a case of severe bacteremia caused by Chromobacterium haemolyticum infection in a healthy young patient following trauma and exposure to river water, in Japan. The patient developed necrotizing fasciitis that was successfully treated with a fasciotomy and intravenous ciprofloxacin and gentamicin.
C. haemolyticum should be considered in the differential diagnosis of skin lesions that progressively worsen after trauma involving exposure to river or lake water, even in temperate regions. Second, early blood cultures for the isolation and identification of the causative organism were important for initiating proper antimicrobial therapy.
Chromobacterium haemolyticum; Chromobacterium violaceum; Sepsis; Cellulitis; Necrotizing fasciitis
Enteric viruses are a major cause of diarrhea in children, especially those <5 years old. Identifying the viral agents is critical to the development of effective preventive measures. This study aimed to determine the prevalence of common enteric viruses in children <5 years old presented with diarrhea to the Children’s Hospital of Chongqing Medical University.
Five hundred fecal samples were collected between August and November 2010 from children <5 years of age who presented with acute diarrhea at the Children’s Hospital of Chongqing Medical University. All samples were tested for rotaviruses A, B, and C, noroviruses GI and GII, adenovirus, sapovirus, and astrovirus using enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction (RT-PCR), or PCR. Partial sequences of norovirus, sapovirus, adenovirus, and astrovirus were phylogenetically analyzed to determine the genotype.
Enteric viruses were detected in 302 of the 500 children who presented with acute diarrhea (277/477; 58.07%) and persistent diarrhea (5/23; 21.74%). In 277 samples from children with acute diarrhea in whom at least one viral agent was found, rotavirus A was the most frequent virus identified (132 cases; 27.67%), followed by norovirus GII in 130 cases (27.25%), adenovirus in 30 cases (6.29%), sapovirus in 9 cases (1.89%) and astrovirus in one case (0.21%). Twenty-two of the norovirus GII-positive cases were randomly selected for genotyping. GII/4 was the predominant strain, followed by GII/6, GII/2, GII/3, and GII/7. Sapovirus was classified into four genotypes: GI/1 was predominant, followed by GI/2, GII/1, and GIV. The predominant adenovirus was type 41. Mixed infections were found in 25 cases, all of which presented with acute diarrhea (25/477; 5.24%). Viruses were positive in 5/23 (21.74%) cases with persistent diarrhea. Neither rotavirus B, rotavirus C, nor norovirus GI were found in any of the samples.
Enteric viruses are a major cause of diarrhea in children <5 years old in Chongqing. Rotavirus A is the most common etiological agent, follow by norovirus.
Coccidioides immitis and C. posadasii cause coccidioidomycosis, a disease that is endemic to North and South America, but for Central America, the incidence of coccidioidomycosis has not been clearly established. Several studies suggest genetic variability in these fungi; however, little definitive information has been discovered about the variability of Coccidioides fungi in Mexico (MX) and Argentina (AR). Thus, the goals for this work were to study 32 Coccidioides spp. isolates from MX and AR, identify the species of these Coccidioides spp. isolates, analyse their phenotypic variability, examine their genetic variability and investigate the Coccidioides reproductive system and its level of genetic differentiation.
Coccidioides spp. isolates from MX and AR were taxonomically identified by phylogenetic inference analysis using partial sequences of the Ag2/PRA gene and their phenotypic characteristics analysed. The genetic variability, reproductive system and level of differentiation were estimated using AFLP markers. The level of genetic variability was assessed measuring the percentage of polymorphic loci, number of effective allele, expected heterocygosity and Index of Association (IA). The degree of genetic differentiation was determined by AMOVA. Genetic similarities among isolates were estimated using Jaccard index. The UPGMA was used to contsruct the corresponding dendrogram. Finally, a network of haplotypes was built to evaluate the genealogical relationships among AFLP haplotypes.
All isolates of Coccidioides spp. from MX and AR were identified as C. posadasii. No phenotypic variability was observed among the C. posadasii isolates from MX and AR. Analyses of genetic diversity and population structure were conducted using AFLP markers. Different estimators of genetic variability indicated that the C. posadasii isolates from MX and AR had high genetic variability. Furthermore, AMOVA, dendrogram and haplotype network showed a small genetic differentiation among the C. posadasii populations analysed from MX and AR. Additionally, the IA calculated for the isolates suggested that the species has a recombinant reproductive system.
No phenotypic variability was observed among the C. posadasii isolates from MX and AR. The high genetic variability observed in the isolates from MX and AR and the small genetic differentiation observed among the C. posadasii isolates analysed, suggest that this species could be distributed as a single genetic population in Latin America.
Genotypic variability; Haplotypes; Reproductive system
Flexible bronchoscopy with bronchial washing is a useful procedure for diagnosis of pulmonary tuberculosis (TB), when a patient cannot produce sputum spontaneously or when sputum smears are negative. However, the benefit of gaining serial bronchial washing specimens for diagnosis of TB has not yet been studied. Therefore, we conducted a retrospective study to determine the diagnostic utility of additional bronchial washing specimens for the diagnosis of pulmonary TB in suspected patients.
A retrospective analysis was performed on 174 patients [sputum smear-negative, n = 95 (55%); lack of sputum specimen, n = 79 (45%)] who received flexible bronchoscopy with two bronchial washing specimens with microbiological confirmation of pulmonary TB in Samsung Medical Center, between January, 2010 and December, 2011.
Pulmonary TB was diagnosed by first bronchial washing specimen in 141 patients (81%) out of 174 enrolled patients, and an additional bronchial washing specimen established diagnosis exclusively in 22 (13%) patients. Smear for acid-fast bacilli (AFB) was positive in 46 patients (26%) for the first bronchial washing specimen. Thirteen patients (7%) were positive only on smear of an additional bronchial washing specimen. Combined smear positivity of the first and second bronchial washing specimens was significantly higher compared to first bronchial washing specimen alone [Total cases: 59 (34%) vs. 46 (26%), p < 0.001; cases for smear negative sputum: 25 (26%) vs. 18 (19%), p = 0.016; cases for poor expectoration: 34 (43%) vs. 28 (35%), p = 0.031]. The diagnostic yield determined by culture was also significantly higher in combination of the first and second bronchial washing specimens compared to the first bronchial washing. [Total cases: 163 (94%) vs. 141 (81%), p < 0.001; cases for smear negative sputum: 86 (91%) vs. 73 (77%), p < 0.001; cases for poor expectoration: 77 (98%) vs. 68 (86%), p = 0.004].
Obtaining an additional bronchial washing specimen could be a beneficial and considerable option for diagnosis of TB in patients with smear-negative sputum or who cannot produce sputum samples.
Bronchial washing; Bronchoscopy; Diagnosis; Tuberculosis
Natural killer (NK) cells have emerged as pivotal players in innate immunity, especially in the defense against viral infections and tumors. Killer immunoglobulin-like receptors (KIRs) – an important recognition receptor expressed on the surface of NK cells – regulate the inhibition and/or activation of NK cells after interacting with human leukocyte antigen (HLA) class I ligands. Various KIR genes might impact the prognosis of many different diseases. The implications of KIR-HLA interaction in HIV disease progression remains poorly understood.
Here, we studied KIR genotypes, mRNA levels, HLA genotypes, CD4+ T cell counts and viral loads in our cohort of Human Immunodeficiency Virus (HIV)-infected individuals, a group that includes HIV long-term nonprogressors (LTNPs) and typical progressors (TPs).
We found that the frequency of KIR3DS1/L1 heterozygotes with HLA-Bw4-80I gene was much higher in LTNPs than in TPs (P = 0.001) and that the KIR3DL1 homozygotes without HLA-Bw4-80I gene had higher viral loads and lower CD4+ T cell counts (P = 0.014 and P = 0.021, respectively). Our study also confirmed that homozygosity for the HLA-Bw6 allele was associated with rapid disease progression. In addition to the aforementioned results on the DNA level, we observed that higher level expression of KIR3DS1 mRNA was in LTNP group, and that higher level expression of KIR3DL1 mRNA was in TP group.
Our data suggest that different KIR-HLA genotypes and different levels of transcripts associate with HIV disease progression.
Natural killer (NK) cells; Killer immunoglobulin-like receptors (KIRs); Human immunodeficiency virus (HIV); Long-term nonprogressor (LTNP); Typical progressor (TP)
Adherence to Highly active antiretroviral therapy (HAART) is a major predictor of the success of HIV/AIDS treatment. Good adherence to HAART is necessary to achieve the best virologic response, lower the risk of drug resistance and reduce morbidity and mortality. This study therefore aimed to determine the prevalence and determinants of adherence to HAART amongst PLHIV accessing treatment in a tertiary location in Cross River State, Nigeria.
A cross-sectional study was conducted among patients on HAART attending the Presidential Emergency plan for AIDS relief (PEPFAR) clinic of the University of Calabar Teaching Hospital between October–December 2011. A total of 411 PLHIV visiting the study site during the study period were interviewed. PLHIV who met the inclusion criteria were consecutively recruited into the study till the desired sample size was attained. Information was obtained from participants using a semi-structured, pretested, interviewer administered questionnaire. Adherence was measured via patients self report and were termed adherent if they took at least 95% of prescribed medication in the previous week prior to the study. Data were summarized using proportions, and χ2 test was used to explore associations between categorical variables. Predictors of adherence to HAART were determined by binary logistic regression. Level of significance was set at p < 0.05.
The mean age of PLHIV who accessed treatment was 35.7 ± 9.32 years. Females constituted 68.6% of all participants. The self reported adherence rate based on a one week recall prior to the study was 59.9%. The major reasons cited by respondents for skipping doses were operating a busy schedule, simply forgot medications, felt depressed, and travelling out of town. On logistic regression analysis, perceived improved health status [OR 3.11; CI: 1.58-6.11], reduced pill load [OR 1.25; 95% CI: 0.46-2.72] and non-use of herbal remedies [OR 1.83; 95% CI: 1.22-2.72] were the major predictors for adherence to HAART. However, payment for ART services significantly decreased the likelihood of adherence to HAART. [OR 0.46; 95% CI: 0.25-0.87.].
The adherence rate reported in this study was quite low. Appropriate adherence enhancing intervention strategies targeted at reducing pill load and ensuring an uninterrupted access to free services regimen is strongly recommended.
Adherence; PLHIV, HAART; Cross river; Nigeria
The aim of this study was to investigate the genetic diversity among Mycobacterium tuberculosis complex circulating in patients with no known risk factors for multi-drug resistant (MDR) tuberculosis (TB) living in a high MDR burden area and analyze the relationship between genotypes, primary drug resistance and age.
Samples were collected during January-July 2009. Isolates were tested for drug susceptibility to first-line drugs and were genotyped by spoligotyping and the 15-loci Mycobacterial Interspersed Repetitive Unit (MIRU15).
Among the 199 isolates analyzed, 169 (84.9%) were identified in the SpolDB4.0 and 30 (15.1%) could not be matched to any lineage. The most prevalent lineage was Haarlem (29.6%), followed by T (15.6%), Beijing (14.1%), Latin American Mediterranean (12.6%) and U (8.5%). A few isolates belonged to the X and S clades (4.5%). Spoligotype analysis identified clustering among 148 of 169 isolates, whereas with MIRU15 all isolates were unique. Out of 197 strains; 31.5% were resistant to at least one drug, 7.5% were MDR and 22.3% showed any resistance to isoniazid.
In contrast with other Latin-American countries where LAM lineage is the most predominant, we found the spoligotype 50 from the Haarlem lineage as the most common. None of the prevailing lineages showed a significant association with age or resistance to isoniazid and/or rifampicin.
Mycobaterium tuberculosis; Haarlem; Genotypification
Posterior reversible encephalopathy syndrome (PRES) is an uncommon pathology characterized by the acute onset of headache, vomiting, altered consciousness, seizures and focal neurological deficits. It was initially described in the setting of hypertension, uremia and immunosuppression. In the last decade there have been emerging reports of PRES in patients with advanced human immunodeficiency virus (HIV)-infection in the presence of hypertension, dialysis, hypercalcaemia and two opportunistic infections: blastomycosis and tuberculosis (TB).
Here we present the case of a 54 year old male being treated for disseminated varicella zoster virus (VZV) and vasculopathy in the setting of HIV infection who acutely deteriorated to the point of requiring intubation. His clinicoradiological diagnosis was of PRES and he subsequently improved within 72 h with supportive management. Serial neuroimaging correlated with the clinical findings. The pathogenesis of PRES is poorly understood but is thought to stem from vasogenic oedema either as a result of loss of endothelial integrity and transudate of fluid across the blood–brain barrier, or secondary to vasospasm resulting in tissue oedema in the absence of infarction. How HIV infection impacts on this model is unclear. It is possible the HIV infection causes endothelial dysfunction and disruption of the blood–brain barrier that may be further exacerbated by infections in the central nervous system.
The phenomenon of PRES in advanced HIV is an important clinical entity for both physicians and critical care doctors to recognize firstly given its potential mortality but also because of its favourable prognosis and reversibility with supportive care and treatment of underlying causes.
PRES; HIV; VZV; MRI; Encephalopathy; Vasculopathy
Reactivation of hepatitis B virus (HBV), characterized by increased levels of serum HBV DNA, abnormal liver function and hepatic failure, is a frequent complication of immunosuppressive therapy and chemotherapy in patients with HBV infection. However, reactivation of occult HBV infection with immunosuppressive therapy or chemotherapy is rare.
A 77-year-old man was diagnosed with nephrotic syndrome and IgM nephropathy with unclear pathogenesis. Liver function was normal, HBV-related serum markers were negative and HBV DNA titer was below the upper limits of normal. Two months following the start of prednisone therapy for his nephrotic syndrome, laboratory tests revealed a substantial increase in serum transaminase levels (ALT: 490 IU/L; AST: 149 IU/L) and an elevation of HBV DNA level (3.42×106 copies/ml). We tested stored kidney tissue for HBsAg and HBcAg using immunohistochemistry and found the sample to be HBcAg positive, allowing us to confirm the etiology of nephropathy as an occult HBV infection. The cause of the hepatitis was thought to be HBV reactivation, so we immediately administered lamivudine. One month after the initiation of daily lamivudine treatment, laboratory tests revealed that serum levels of transaminases had improved (ALT: 35 IU/L; AST: 17 IU/L). Patient examination one year later showed that HBeAg had decreased with a concomitant increase of HBeAb, the quantity of HBV DNA was undetectable, and liver function and renal function had stabilized.
This is the first report describing HBV reactivation in an occult HBV infection patient treated with oral prednisone for nephrotic syndrome. HBV-associated antigen should be regularly tested for in patients with unknown etiological glomerulonephritis in areas with high HBV viral popular and even in those with no clinical evidence for diagnosis of HBV.
Hepatitis B virus reactivation; IgM nephropathy; Occult HBV infection; Prednisone
Bacterial meningitis caused by Streptococcus pneumoniae leads to death in up to 30% of patients and leaves up to half of the survivors with neurological sequelae. The inflammatory host reaction initiates the induction of the kynurenine pathway and contributes to hippocampal apoptosis, a form of brain damage that is associated with learning and memory deficits in experimental paradigms. Vitamin B6 is an enzymatic cofactor in the kynurenine pathway and may thus limit the accumulation of neurotoxic metabolites and preserve the cellular energy status.
The aim of this study in a pneumococcal meningitis model was to investigate the effect of vitamin B6 on hippocampal apoptosis by histomorphology, by transcriptomics and by measurement of cellular nicotine amide adenine dinucleotide content.
Methods and results
Eleven day old Wistar rats were infected with 1x106 cfu/ml of S. pneumoniae and randomized for treatment with vitamin B6 or saline as controls. Vitamin B6 led to a significant (p > 0.02) reduction of hippocampal apoptosis. According to functional annotation based clustering, vitamin B6 led to down-regulation of genes involved in processes of inflammatory response, while genes encoding for processes related to circadian rhythm, neuronal signaling and apoptotic cell death were mostly up-regulated.
Our results provide evidence that attenuation of apoptosis by vitamin B6 is multi-factorial including down-modulation of inflammation, up-regulation of the neuroprotective brain-derived neurotrophic factor and prevention of the exhaustion of cellular energy stores. The neuroprotective effect identifies vitamin B6 as a potential target for the development of strategies to attenuate brain injury in bacterial meningitis.
Bacterial meningitis; Streptococcus pneumoniae; Kynurenine pathway; Vitamin B6
Interruption of measles transmission was achieved in Catalonia (Spain) in 2000. Six years later, a measles outbreak occurred between August 2006 and June 2007 with 381 cases, 11 of whom were health care workers (HCW).
The objective was to estimate susceptibility to measles in HCW and related demographic and occupational characteristics.
A measles seroprevalence study was carried out in 639 HCW from six public tertiary hospitals and five primary healthcare areas. Antibodies were tested using the Vircell Measles ELISA IgG Kit. Data were analyzed according to age, sex, type of HCW, type of centre and vaccination history.
The odds ratios (OR) and their 95% CI were calculated to determine the variables associated with antibody prevalence. OR were adjusted using logistic regression.
Positive predictive values (PPV) and the 95% confidence intervals (CI) of having two documented doses of a measles containing vaccine (MCV) for the presence of measles antibodies and of reporting a history of measles infection were calculated.
The prevalence of measles antibodies in HCW was 98% (95% CI 96.6-98.9), and was lower in HCW born in 1981 or later, after the introduction of systematic paediatric vaccination (94.4%; 95% CI 86.4-98.5) and higher in HCW born between 1965 and 1980 (99.0%; 95% CI 97.0-99.8). Significant differences were found for HCW born in 1965–1980 with respect to those born in 1981 and after (adjusted OR of 5.67; 95% CI: 1.24-25.91).
A total of 187 HCW reported being vaccinated: the proportion of vaccinated HCW decreased with age. Of HCW who reported being vaccinated, vaccination was confirmed by the vaccination card in 49%. Vaccination with 2 doses was documented in only 50 HCW, of whom 48 had measles antibodies. 311 HCW reported a history of measles.
The PPV of having received two documented doses of MCV was 96% (95% CI 86.3-99.5) and the PPV of reporting a history of measles was 98.7% (95% CI 96.7-99.6).
Screening to detect HCW who lack presumptive evidence of immunity and vaccination with two doses of vaccine should be reinforced, especially in young workers, to minimize the risk of contracting measles and infecting the susceptible patients they care for.
Measles; Seroprevalence; Health care workers; MCV vaccination
Young children exposed to Mycobacterium tuberculosis have a high risk of disease progression following infection. This study aimed to determine risk factors for M. tuberculosis infection and disease in children following exposure to adults with multidrug-resistant (MDR) tuberculosis (TB).
Cross-sectional study; all children aged < 5 years, routinely referred per local guidelines to the provincial specialist MDR-TB clinic, Western Cape Province, South Africa, following identification as contacts of adult MDR-TB source cases, were eligible for enrolment from May 2010 through April 2011. Demographic, clinical and social characteristics were collected. All children underwent HIV and tuberculin skin testing.
Of 228 children enrolled (median age: 30 months), 102 (44.7%) were classified as infected. Of these, 15 (14.7%) had TB disease at enrolment. Of 217 children tested for HIV, 8 (3.7%) were positive. In adjusted analysis, child’s age (AOR: 1.43; 95% CI: 1.13-1.91; p = 0.002) and previous TB treatment history (AOR: 2.51; 95% CI: 1.22-5.17; p = 0.01) were independent risk factors for infection. Increasing age of the MDR-TB source case (AOR: 0.67; 95% CI: 0.45-1.00; p = 0.05) was protective and source case alcohol use (AOR: 2.59; 95% CI: 1.29-5.22; p = 0.007) was associated with increased odds of infection in adjusted analysis. Decreasing age of the child (p = 0.01) and positive HIV status (AOR: 25.3; 95% CI: 1.63-393; p = 0.01) were associated with prevalent TB disease.
A high proportion of children exposed to MDR-TB are infected or diseased. Early contact tracing might provide opportunities to prevent the progression to TB disease in children identified as having been exposed to MDR-TB.
Pediatric; Infection; Disease; Drug-resistant; Tuberculosis; Children
Despite increases in HIV testing, only a fraction of people newly diagnosed with HIV infection enter the care system and initiate antiretroviral therapy (ART) in South Africa. We report on the design and initial enrollment of a randomized trial of a health system navigator intervention to improve linkage to HIV care and TB treatment completion in Durban, South Africa.
We employed a multi-site randomized controlled trial design. Patients at 4 outpatient sites were enrolled prior to HIV testing. For all HIV-infected participants, routine TB screening with sputum for mycobacterial smear and culture were collected. HIV-infected participants were randomized to receive the health system navigator intervention or usual care. Participants in the navigator arm underwent a baseline interview using a strengths-based case management approach to assist in identifying barriers to entering care and devising solutions to best cope with perceived barriers. Over 4 months, participants in the navigator arm received scheduled phone and text messages. The primary outcome of the study is linkage and retention in care, assessed 9 months after enrollment. For ART-eligible participants without TB, the primary outcome is 3 months on ART as documented in the medical record; participants co-infected with TB are also eligible to meet the primary outcome of completion of 6 months of TB treatment, as documented by the TB clinic. Secondary outcomes include mortality, receipt of CD4 count and TB test results, and repeat CD4 counts for those not ART-eligible at baseline. We hypothesize that a health system navigator can help identify and positively affect modifiable patient factors, including self-efficacy and social support, that in turn can improve linkage to and retention in HIV and TB care.
We are currently evaluating the clinical impact of a novel health system navigator intervention to promote entry to and retention in HIV and TB care for people newly diagnosed with HIV. The details of this study protocol will inform clinicians, investigators, and policy makers of strategies to best support HIV-infected patients in resource-limited settings.
Clinicaltrials.gov. unique identifier:
(3-10): HIV/AIDS; Tuberculosis; South Africa; Linkage to care; SMS reminders; Randomized controlled trial; Counseling/Support
Blastocystis sp. are among the most commonly observed intestinal parasites in routine clinical parasitology. Blastocystis in humans consists of at least 9 genetic subtypes. Different subtypes of Blastocystis may be associated with differences in pathogenicity and symptomatology.
Advanced microscopy on two samples and sequence-confirmed PCR on a third sample from the same individual were used for Blastocystis diagnosis and subtype analyses on routine clinical samples in a university hospital.
With a combined gold standard of sequence-confirmed PCR and positive advanced microscopy, 107 out of 442 (24.2%) patients were diagnosed with Blastocystis. infection, which is a high frequency of detection in comparison to previous reports from industrialized countries. The sensitivity of microscopy and sequence-confirmed PCR was 99.1% (106/107) and 96.3% (103/107), respectively.
Among 103 typable samples, subtype 3 was most abundant (n = 43, 42%), followed by subtypes 1 and 2 (both n = 23, 22%), subtype 4 (n = 12, 12%), and single samples with subtypes 6 (1%) and subtype 7 (1%). The prevalence of Blastocystis infection was 38% in patients from the Department of Tropical Medicine and 18% in patients from other departments.
A high prevalence of Blastocystis infection was found with both advanced microscopy and sequence-confirmed PCR in our patient population. Most cases were caused by subtypes ST1, ST2, ST3 and ST4. A significantly higher prevalence was found among patients with a history of recent travel to tropical countries.
Blastocystis; Diagnosis; Microscopy; PCR; Molecular epidemiology
There are no accurate data regarding the real prevalence of Chlamydia trachomatis infection in Spain. Our aim was to determine the prevalence of C. trachomatis infections and the risk factors for acquiring them among 1,048 young (15–24 years old) inhabitants of Laviana.
The study was completed in the period between 1st November 2010 and 31st December 2011. We conducted a capture strategy in the whole population, instead of only in a sample group, with a capture conducted in schools, in the local health centre, by post and by phone as a last resort. The design was based on the model used by Shafer to increase screening rates. C. trachomatis was identified by RT-PCR in urine samples.
A total of 487 sexually active people underwent the test, which implies a response rate of 59.8% of the sexually active people (target population). The prevalence was 4.1% (CI 95%: 3.1-5.8): women: 4% ( CI 95%; 2.8-6.4) and men: 4.3% (CI 95%: 2.9-7.2). The circulating genotype was the E genotype. There was an increase in the risk of C. trachomatis infection when barrier contraceptives were not routinely used OR: 4.76 (CI 95%:1.30-17.36) p<0.05.
In our study the prevalence in women resembles those found in other countries in Europe and the prevalence in men is similar to that in women. Screening for C. trachomatis infection in women would be cost-effective in Spain given the prevalence of C. trachomatis measured by this study. The use of a condom is the best preventative measure for avoiding STIs in sexually active people.
Sexually transmitted diseases; Chlamydia infections; Prevalence; Mass screening
With the remarkable increase of microbial and viral sequence data obtained from high-throughput DNA sequencers, novel tools are needed for comprehensive analysis of the big sequence data. We have developed “Batch-Learning Self-Organizing Map (BLSOM)” which can characterize very many, even millions of, genomic sequences on one plane. Influenza virus is one of zoonotic viruses and shows clear host tropism. Important issues for bioinformatics studies of influenza viruses are prediction of genomic sequence changes in the near future and surveillance of potentially hazardous strains.
To characterize sequence changes in influenza virus genomes after invasion into humans from other animal hosts, we applied BLSOMs to analyses of mono-, di-, tri-, and tetranucleotide compositions in all genome sequences of influenza A and B viruses and found clear host-dependent clustering (self-organization) of the sequences.
Viruses isolated from humans and birds differed in mononucleotide composition from each other. In addition, host-dependent oligonucleotide compositions that could not be explained with the host-dependent mononucleotide composition were revealed by oligonucleotide BLSOMs. Retrospective time-dependent directional changes of mono- and oligonucleotide compositions, which were visualized for human strains on BLSOMs, could provide predictive information about sequence changes in newly invaded viruses from other animal hosts (e.g. the swine-derived pandemic H1N1/09).
Basing on the host-dependent oligonucleotide composition, we proposed a strategy for prediction of directional changes of virus sequences and for surveillance of potentially hazardous strains when introduced into human populations from non-human sources. Millions of genomic sequences from infectious microbes and viruses have become available because of their medical and social importance, and BLSOM can characterize the big data and support efficient knowledge discovery.
Influenza virus; Pandemic; Host tropism; H1N1/09; Self-organization map; Oligonucleotide composition; Bioinformatics; Big data; Virus invasion; Zoonotic virus
Australia uses acute flaccid paralysis (AFP) surveillance to monitor its polio-free status. The World Health Organization criterion for a sensitive AFP surveillance system is the annual detection of at least one non-polio AFP case per 100,000 children aged less than 15 years, a target Australia has not consistently achieved. Children exhibiting AFP are likely to be hospitalised and may be admitted to an intensive care unit. This provides a potential opportunity for active AFP surveillance.
A data-linkage study for the period from 1 January 2005 to 31 December 2008 compared 165 non-polio AFP cases classified by the Polio Expert Panel with 880 acute neurological presentations potentially compatible with AFP documented in the Australian and New Zealand Paediatric Intensive Care (ANZPIC) Registry.
Forty-two (25%) AFP cases classified by the Polio Expert Panel were matched to case records in the ANZPIC Registry. Of these, nineteen (45%) cases were classified as Guillain-Barré syndrome on both registries. Ten additional Guillain-Barré syndrome cases recorded in the ANZPIC Registry were not notified to the national AFP surveillance system.
The identification of a further ten AFP cases supports inclusion of intensive care units in national AFP surveillance, particularly specialist paediatric intensive care units, to identify AFP cases that may not otherwise be reported to the national surveillance system.
Acute flaccid paralysis; Clinical surveillance; Poliovirus; Paediatric intensive care
Fournier’s gangrene is a rare necrotizing soft tissue infection of the scrotum and penis. We report, to our knowledge, the first case of Fournier’s gangrene caused by Streptococcus dysgalactiae subsp. equisimilis (SDSE), a strain of pyogenic β-hemolytic streptococci that is increasingly being recognized as an important human pathogen.
We describe a healthy 59 year-old Caucasian male who presented to the emergency department with Fournier’s gangrene of the penis and scrotum, with extension to the anterior abdominal wall. He underwent urgent surgical debridement of his scrotum, penis, and anterior abdomen. Swabs from the scrotum grew Gram-positive cocci, which were initially identified as Streptococcus anginosus group by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS). However, polymerase chain reaction (PCR) amplification and sequencing of the 16S rRNA gene identified the isolate as Streptococcus dysgalatiae subspecies equisimilis (SDSE). The incidences of invasive S. anginosus group and SDSE infections at the London Health Sciences Centre, a tertiary-care institution in southwestern Ontario, were determined between August 1, 2011 and August 31, 2012, revealing a slightly lower rate of SDSE (3.2 cases per 100,000 population) than other studies.
This case highlights a unique disease manifestation of the emerging human pathogen Streptococcus dysgalatiae subspecies equisimilis that has not been previously reported. This case also underscores the limitations of MALDI-TOF MS in differentiating between closely-related streptococcal species which may have different pathogenic profiles.
Streptococcus dysgalactiae subsp. equisimilis; Fournier’s gangrene; MALDI-TOF MS; Species identification
To clarify the molecular mechanisms that participate in the severe hand, foot and mouth disease (HFMD) infected by Enterovirus 71 and to detect any related protein biomarkers, we performed proteomic analysis of protein extracts from 5 extremely severe HFMD children and 5 healthy children.
The protein profiles of them were compared using two-dimensional electrophoresis. Differentially expressed proteins were identified using mass spectrometry. Functional classifications of these proteins were based on the PANTHER. The interaction network of the differentially expressed protein was generated with Pathway Studio.
A total of 38 differentially expressed proteins were identified. Functional classifications of these proteins indicated a series of altered cellular processes as a consequence of the severe HFMD. These results provided not only new insights into the pathogenesis of severe HFMD, but also implications of potential therapeutic designs.
Our results suggested the possible pathways that could be the potential targets for novel therapy: viral protection, complement system and peroxide elimination.
Extremely severe HFMD; MALDI-TOF/TOF MS; Proteomic analysis
Combination antiretroviral therapy (cART) has produced significant changes in mortality of HIV-infected persons. Our objective was to estimate mortality rates, standardized mortality ratios and excess mortality rates of cohorts of the AIDS Research Network (RIS) (CoRIS-MD and CoRIS) compared to the general population.
We analysed data of CoRIS-MD and CoRIS cohorts from 1997 to 2010. We calculated: (i) all-cause mortality rates, (ii) standardized mortality ratio (SMR) and (iii) excess mortality rates for both cohort for 100 person-years (py) of follow-up, comparing all-cause mortality with that of the general population of similar age and gender.
Between 1997 and 2010, 8,214 HIV positive subjects were included, 2,453 (29.9%) in CoRIS-MD and 5,761 (70.1%) in CoRIS and 294 deaths were registered. All-cause mortality rate was 1.02 (95% CI 0.91-1.15) per 100 py, SMR was 6.8 (95% CI 5.9-7.9) and excess mortality rate was 0.8 (95% CI 0.7-0.9) per 100 py. Mortality was higher in patients with AIDS, hepatitis C virus (HCV) co-infection, and those from CoRIS-MD cohort (1997–2003).
Mortality among HIV-positive persons remains higher than that of the general population of similar age and sex, with significant differences depending on the history of AIDS or HCV coinfection.
Mortality rate; HIV infection; Standardized mortality ratios; Excess mortality
Data regarding the most efficacious and least toxic schedules for the use of colistin are scarce. The aim of this study was to determine the incidence and the potential risk factors of colistin-associated nephrotoxicity including colistin plasma levels.
A prospective observational cohort study was conducted for over one year in patients receiving intravenous colistin methanesulfonate sodium (CMS). Blood samples for colistin plasma levels were collected immediately before (Cmin) and 30 minutes after CMS infusion (Cmax). Renal function was assessed at baseline, on day 7 and at the end of treatment (EOT). Severity of acute kidney injury (AKI) was defined by the RIFLE (risk, injury, failure, loss, and end-stage kidney disease) criteria.
One hundred and two patients met the inclusion criteria. AKI related to CMS treatment on day 7 and at the end of treatment (EOT) was observed in 26 (25.5%) and 50 (49.0%) patients, respectively. At day 7, Cmin (OR, 4.63 [2.33-9.20]; P < 0.001) was the only independent predictor of AKI. At EOT, the Charlson score (OR 1.26 [1.01-1.57]; P = 0.036), Cmin (OR 2.14 [1.33-3.42]; P = 0.002), and concomitant treatment with ≥ 2 nephrotoxic drugs (OR 2.61 [1.0-6.8]; P = 0.049) were independent risk factors for AKI. When Cmin was evaluated as a categorical variable, the breakpoints that better predicted AKI were 3.33 mg/L (P < 0.001) on day 7 and 2.42 mg/L (P < 0.001) at EOT.
When using the RIFLE criteria, colistin-related nephrotoxicity is observed in a high percentage of patients. Cmin levels are predictive of AKI. Patients who receive intravenous colistin should be closely monitored and Cmin might be a new useful tool to predict AKI.
Colistin; Nephrotoxicity risk factors; RIFLE criteria; Colistin plasma levels
Chlamydia trachomatis is the most commonly diagnosed bacterial sexually transmitted infection in the developed world and diagnosis rates have increased dramatically over the last decade. Repeat infections of chlamydia are very common and may represent re-infection from an untreated partner or treatment failure. The aim of this cohort study is to estimate the proportion of women infected with chlamydia who experience treatment failure after treatment with 1 gram azithromycin.
This cohort study will follow women diagnosed with chlamydia for up to 56 days post treatment. Women will provide weekly genital specimens for further assay. The primary outcome is the proportion of women who are classified as having treatment failure 28, 42 or 56 days after recruitment. Comprehensive sexual behavior data collection and the detection of Y chromosome DNA and high discriminatory chlamydial genotyping will be used to differentiate between chlamydia re-infection and treatment failure. Azithromycin levels in high-vaginal specimens will be measured using a validated liquid chromatography – tandem mass spectrometry method to assess whether poor azithromycin absorption could be a cause of treatment failure. Chlamydia culture and minimal inhibitory concentrations will be performed to further characterize the chlamydia infections.
Distinguishing between treatment failure and re-infection is important in order to refine treatment recommendations and focus infection control mechanisms. If a large proportion of repeat chlamydia infections are due to antibiotic treatment failure, then international recommendations on chlamydia treatment may need to be re-evaluated. If most are re-infections, then strategies to expedite partner treatment are necessary.
Chlamydia trachomatis; Azithromycin; Treatment failure; Re-infection; Sexually transmitted infections
Worldwide, cervical cancer is the second most common cancer in women. High-risk human papillomavirus (HPV) play a crucial role in the etiology of cervical cancer and the most prevalent genotype is HPV16. HPV 16 intratypic variants have been reported to differ in their prevalence, biological and biochemical properties. The present study was designed to analyze and identify HPV type 16 E6 variants among patients with cervical cancer in Morocco.
A total of 103 HPV16 positive samples were isolated from 129 cervical cancer cases, and variant status was subsequently determined by DNA sequencing of the E6 gene.
Isolates from patients were grouped into the European (E), African (Af) and North-American (NA1) phylogenetic clusters with a high prevalence of E lineage (58.3%). The Af and NA1 variants were detected in 31.1% and 11.6% of the HPV16 positive specimens, respectively, whereas, only 3% of cases were prototype E350T. No European-Asian (EA), Asian (As) or Asian-American (AA) variants were observed in our HPV16-positive specimens. At the amino acid level, the most prevalent non-synonymous variants were L83V (T350G), H78Y (C335T), E113D (A442C), Q14D (C143G/G145T) and R10I (G132T), and were observed respectively in 65%, 41.8%, 38.8%, 30.1% and 23.3% of total samples.
Moreover, HPV16 European variants were mostly identified in younger women at early clinical diagnosis stages. Whereas, HPV16 Af variants were most likely associated with cervical cancer development in older women with pronounced aggressiveness.
This study suggests a predominance of E lineage strains among Moroccan HPV 16 isolates and raises the possibility that HPV16 variants have a preferential role in progression to malignancy and could be associated with the more aggressive nature of cervical cancer.
Cervical cancer; Human papillomavirus 16; Variants; E6; Morocco