Changing epidemiology of an emerging infection: zygomycosis

Aspergillosis and candidosis remain the most prevalent opportunistic fungal infections in immunocompromised patients, but diseases caused by the Zygomycetes have become of increasing importance. Exposure to antimycotic drugs with no activity against zygomycetes may be a new risk factor and an explanation for the increasing incidence of zygomycosis. The latter infection occurs only rarely in immunocompetent hosts, but in recent years Apophysomyces elegans has been described in many subtropical countries as an emerging pathogen causing mostly cutaneous infections after traumatic inoculation.     

Apophysomyces elegans: an emerging zygomycete in India

Apophysomyces elegans was considered a rare but medically important zygomycete. We analyzed the clinical records of eight patients from a single center in whom zygomycosis due to A. elegans was diagnosed over a span of 25 months. We also attempted a DNA-based method for rapid identification of the fungi and looked for interstrain polymorphism using microsattelite primers. Three patients had cutaneous and subcutaneous infections, three had isolated renal involvement, one had rhino-orbital tissue infection, and the final patient had a disseminated infection involving the spleen and kidney. Underlying illnesses were found in two patients, one with diabetes mellitus and the other with chronic alcoholism. A history of traumatic implantation was available for three patients. All except two of the patients responded to surgical and/or medical therapy; the diagnosis for the two exceptions was made at the terminal stage of infection. Restriction enzyme (MboI, MspI, HinfI) digestion of the PCR-amplified internal transcribed spacer region helped with the rapid and specific identification of A. elegans. The strains could be divided into two groups according to their patterns, with clustering into one pattern obtained by using microsatellite [(GTG)(5) and (GAC)(5)] PCR fingerprinting. The study highlights the epidemiology, clinical spectrum, and diagnosis of emerging A. elegans infections.     

Recent insights in the epidemiology of autoimmune diseases: Improved prevalence estimates and understanding of clustering of diseases

Previous studies have estimated a prevalence of a broad grouping of autoimmune diseases of 3.2%, based on literature review of studies published between 1965 and 1995, and 5.3%, based on national hospitalization registry data in Denmark. We examine more recent studies pertaining to the prevalence of 29 autoimmune diseases, and use these data to correct for the underascertainment of some diseases in the hospitalization registry data. This analysis results in an estimated prevalence of 7.6–9.4%, depending on the size of the correction factor used. The rates for most diseases for which data are available from many geographic regions span overlapping ranges. We also review studies of the co-occurrence of diseases within individuals and within families, focusing on specific pairs of diseases to better distinguish patterns that may result in insights pertaining to shared etiological pathways. Overall, data support a tendency for autoimmune diseases to co-occur at greater than expected rates within proband patients and their families, but this does not appear to be a uniform phenomenon across all diseases. Multiple sclerosis and rheumatoid arthritis is one disease pair that appears to have a decreased chance of coexistence.     

Anoikis: an emerging hallmark in health and diseases

Anoikis is a programmed cell death occurring upon cell detachment from the correct extracellular matrix, thus disrupting integrin ligation. It is a critical mechanism in preventing dysplastic cell growth or attachment to an inappropriate matrix. Anoikis prevents detached epithelial cells from colonizing elsewhere and is thus essential for tissue homeostasis and development. As anchorage-independent growth and epithelial-mesenchymal transition, two features associated with anoikis resistance, are crucial steps during tumour progression and metastatic spreading of cancer cells, anoikis deregulation has now evoked particular attention from the scientific community. The aim of this review is to analyse the molecular mechanisms governing both anoikis and anoikis resistance, focusing on their regulation in physiological processes, as well as in several diseases, including metastatic cancers, cardiovascular diseases and diabetes.     

Epidemiology of candidemia: 3-year results from the emerging infections and the epidemiology of Iowa organisms study

Bloodstream infections due to Candida species cause significant morbidity and mortality. Surveillance for candidemia is necessary to detect trends in species distribution and antifungal resistance. We performed prospective surveillance for candidemia at 16 hospitals in the State of Iowa from 1 July 1998 through 30 June 2001. Using U.S. Census Bureau and Iowa Hospital Association data to estimate a population denominator, we calculated the annual incidence of candidemia in Iowa to be 6.0 per 100,000 of population. Candida albicans was the most common species detected, but 43% of candidemias were due to species other than C. albicans. Overall, only 3% of Candida species were resistant to fluconazole. However, Candida glabrata was the most commonly isolated species other than C. albicans and demonstrated some resistance to azoles (fluconazole MIC at which 90% of the isolates tested are inhibited, 32 microg/ml; 10% resistant, 10% susceptible dose dependent). C. glabrata was more commonly isolated from older patients (P = 0.02) and caused over 25% of candidemias among persons 65 years of age or older. The investigational triazoles posaconazole, ravuconazole, and voriconazole had excellent in vitro activity overall against Candida species. C. albicans is the most important cause of candidemia and remains highly susceptible to available antifungal agents. However, C. glabrata has emerged as an important and potentially antifungal resistant cause of candidemia, particularly among the elderly.     

Trichosporon inkin, an unusual agent of fungal sinusitis: a report from south India

The aetiology of fungal sinusitis is diverse and changing. Aspergillus species has been the most common cause for fungal sinusitis, especially in dry and hot regions like India. Trichosporon species as a cause for fungal sinusitis has been very rarely reported the world over. Here, we report a rare case of allergic fungal sinusitis caused by Trichosporon inkin in a 28-year-old immunocompetent woman. Bilateral nasal obstruction, nasal discharge and loss of smell were her presenting complaints. Diagnostic nasal endoscopy showed bilateral multiple polyps. Functional endoscopic sinus surgery was performed and many polyps were removed. Based on mycological and histopathological studies, the pathogen was identified as T. inkin.     

Rotavirus epidemiology in Vellore, south India: group, subgroup, serotype, and electrophoretype.

Rotaviruses were detected in 163 of 916 (17.8%) specimens collected from children under 3 years of age with gastroenteritis in Vellore, South India, between August 1983 and July 1985. Rotaviruses were detected throughout the study period, with a peak prevalence in December to February (winter) and June to August (southwest monsoon season). A total of 117 rotavirus strains were tested for subgroup, serotype, and rotavirus double-stranded RNA electrophoretic migration pattern; 24.8% of the strains were subgroup I, 69.2% were subgroup II, and 6.0% were neither subgroup I nor subgroup II. Subgroup I and II strains were circulating concurrently throughout the study. Of the 117 rotavirus strains, 32 (27.4%) were serotyped; 15 were serotype 1, 3 were serotype 2, 2 were serotype 3, and 12 were serotype 4. Three serotypes were circulating concurrently during the periods of peak rotavirus prevalence. In 100 of the 117 strains (85.4%) an RNA pattern was detected. One unusual subgroup I group A rotavirus with a long migration pattern and four atypical rotaviruses serologically related to group C were also detected.     

Neighborhood-level risk and resilience factors: an emerging issue in childhood asthma epidemiology

Evaluation of: Gupta RS, Zhang X, Sharp LK, Shannon JJ, Weiss KB. The protective effect of community factors on childhood asthma. J. Allergy Clin. Immunol. 123(6), 1297–1304.e2 (2009).

The recent increase in the prevalence of asthma in children is now recognized as the result of a complex interplay of genetic, sociodemographic and environmental factors. Multilevel models simultaneously account for neighborhood characteristics that may be related to childhood asthma, independently of individual-level attributes. Most research that focuses on the physical and social characteristics of neighborhoods to explain disparities in childhood asthma assess such factors as persistent poverty, residential racial segregation and environmental degradation. Researchers have only begun to test models that specifically focus on risk and protective factors at the community/neighborhood level in relation to asthma. Social capital, which measures norms of reciprocity, social ties between neighborhood residents and civic engagement has the potential to buffer the effects of neighborhood risk factors on childhood asthma. Further research, specifically longitudinal studies, needs to be carried out to determine whether findings on neighborhood-level risk and protective factors can guide the development of preventive interventions for childhood asthma.     

Assessing vitamin D levels in an anti-DFS70 positive population: New insights emerging

Abstract

Background: Anti-dense fine speckled 70 (DFS70) autoantibodies have more often been described in apparently healthy individuals than in patients with systemic autoimmune rheumatic diseases (SARD). The aim of this study was to explore the link between anti-DFS70 autoantibodies and vitamin D (25(OH)D) levels in an Italian adult cohort.

Methods: Serum samples from 34 (five males and 29 females) anti-DFS70 positive patients (index cases), 34 ANA-negative healthy controls, 34 ANA-positive anti-DFS70 negative SLE patients, both groups age- and gender-matched with the index cases, 23 ANA-positive anti-DFS70 negative healthy blood donors and six female SARD patients showing mixed DFS positive pattern were collected and tested for 25(OH)D levels. Relevant demographics and lifestyle practices, body mass index (BMI), comorbidities, and use of medication were recorded for patients and healthy controls.

Results: Mean serum levels of 25(OH)D were significantly higher in anti-DFS70 positive subjects (mean?±?SD: 22.1?±?9.8?ng/ml) than in ANA-negative healthy controls (mean?±?SD: 17.3?±?6.7?ng/ml; p?=?.03), ANA-positive healthy controls (mean?±?SD: 15.2?±?6.8?ng/ml; p?=?.01), SLE patients (16.6?±?11.0?ng/ml; p?=?.01) and in patients with SARD (15.0?±?5.6?ng/ml; p?=?.01). No statistically relevant differences in BMI, clinical, or demographic parameters were found.

Conclusions: Our findings showed higher levels of vitamin D in anti-DFS70 positive subjects than in the controls, which is compatible with the hypothesis of the “benign” nature of anti-DFS70 antibodies.     

Candida blankii: an emerging yeast in an outbreak of fungaemia in neonates in Delhi,India

ObjectiveOutbreaks of fungal sepsis due to emerging and rare multidrug-resistant Candida species are increasingly reported in health-care settings. We report an outbreak of fungaemia due to the rare multidrug-resistant yeast Candida blankii in an Indian neonatal unit.Materials and methodsBlood cultures grew C. blankii in nine neonates in the Neonatal Intensive Care Unit of a multispecialty hospital in Delhi during a period of 7 months. Isolates were identified by internal transcribed spacer and D1/D2 region sequencing. Antifungal susceptibility testing was performed by M27-A3 CLSI broth microdilution. To determine genetic relatedness among C. blankii isolates we undertook amplified fragment length polymorphism analysis and DNA sequencing using the Illumina NextSeq500 platform.ResultsCandida blankii fungaemia occurred at 2–3 postnatal days in nine low birthweight/very low birthweight neonates. All neonates were treated with fluconazole and four of the nine neonates died, resulting in a case fatality rate of 45%. Candida blankii was misidentified or not identified by automated identification systems. Fluconazole had higher geometric mean (GM) MICs (8 mg/L) than the other azoles. Also, anidulafungin (GM-MIC 2 mg/L) had high MICs. Genome sequencing confirmed transmission of genetically mostly indistinguishable strains. The C. blankii genome showed an altered 1,3-β-d-glucan synthase protein and several larger deletions in the echinocandin target FKS1 gene, suggesting potential for development of antifungal resistance.ConclusionsThe study emphasizes the emergence of a rare and uncommon yeast, C. blankii, with reduced susceptibility to one or more antifungal agents, in nosocomial fungaemia. Genomic insights of this rare yeast are reported using whole-genome sequence typing.     

Clinical significance and outcome of Aeromonas infection among 19 patients-a descriptive study from south India

We describe a series of 19 patients with Aeromonas infection in a tertiary hospital from South India. Bacteremia (n,9) and skin and soft tissue infection (n,9) were the common presentations, and one case of gastroenteritis. Twelve were male and seven were female. Comorbid conditions were seen with 52% cases. Among 18 patients hospitalized, 37% required intensive care. The infection was polymicrobial in 26%, mainly enteropathogens. Decreased susceptibility of beta lactams (94% to cefepime, 84% to ceftazidime and imipenem and 53% to piperacillin tazobactam) is a matter of concern. All but one patient with bacteremia survived the infection.     

γ-干扰素诱导蛋白10与风湿性疾病关系的研究进展

γ-干扰素诱导蛋白10(IP-10)是CXC类趋化因子之一,CXCR3是其唯一受体.研究表明:IP-10具有重要的生物学功能,参与多种疾病的发生,与多种风湿性疾病关系密切,主要介导Th1型炎症反应,还可抑制新生血管形成.另外,测定IP-10水平也可对某些风湿性疾病进行活动度评价、预后判断以及治疗决策指导.     

Treatment of MRSA infections in India: Clinical insights from a Delphi analysis

PurposeInternational and Indian guidelines for the management of patients with methicillin-resistant Staphylococcus aureus (MRSA) infections are available, but the local guidelines are not MRSA-specific. This study aimed to provide clinical insights for the treatment of MRSA infections in India.MethodsWe used a three-step modified Delphi method to obtain insights. Ten experts comprising infectious disease specialists, microbiologists, pulmonologists, and critical care experts agreed to participate in the analysis. In round 1, a total of 161 statements were circulated to the panel and the experts were asked to ‘agree’ or ‘disagree’ by responding ‘yes’ or ‘no’ to each statement and provide comments. The same process was used for 73 statements in round 2. Direct interaction with the experts was carried out in round 3 wherein 35 statements were discussed. At least 80% of the experts had to agree for a statement to reach concordance.ResultsEighty-eight statements in round 1, thirty-eight statements in round 2, and eight statements in round 3 reached concordance and were accepted without modification. The final document comprised 152 statements on the management of various syndromes associated with MRSA such as skin and soft tissue infections, bacteremia and endocarditis, pneumonia, bone and joint infections, and central nervous system infections.ConclusionsThis analysis will assist clinicians in India to choose an appropriate course of action for MRSA infections.     

A population-based study of human immunodeficiency virus in south India reveals major differences from sentinel surveillance-based estimates

Background

The human immunodeficiency virus (HIV) burden among adults in India is estimated officially by direct extrapolation of annual sentinel surveillance data from public-sector antenatal and sexually transmitted infection (STI) clinics and some high-risk groups. The validity of these extrapolations has not been systematically examined with a large sample population-based study.

Methods

We sampled 13838 people, 15–49 years old, from 66 rural and urban clusters using a stratified random method to represent adults in Guntur district in the south Indian state of Andhra Pradesh. We interviewed the sampled participants and obtained dried blood spots from them, and tested blood for HIV antibody, antigen and nucleic acid. We calculated the number of people with HIV in Guntur district based on these data, compared it with the estimate using the sentinel surveillance data and method, and analysed health services use data to understand the differences.

Results

In total, 12617 people (91.2% of the sampled group) gave a blood sample. Adjusted HIV prevalence was 1.72% (95% confidence interval 1.35–2.09%); men 1.74% (1.27–2.21%), women 1.70% (1.36–2.04%); rural 1.64% (1.10–2.18%), urban 1.89% (1.39–2.39%). HIV prevalence was 2.58% and 1.20% in people in the lower and upper halves of a standard of living index (SLI). Of women who had become pregnant during the past 2 years, 21.1% had used antenatal care in large public-sector hospitals participating in sentinel surveillance. There was an over-representation of the lowest SLI quartile (44.7%) in this group, and 3.61% HIV prevalence versus 1.08% in the remaining pregnant women. HIV prevalence was higher in that group even when women were matched for the same SLI half (lower half 4.39%, upper 2.63%) than in the latter (lower 1.06%, upper 1.05%), due to referral of HIV-positive/suspected women by private practitioners to public hospitals. The sentinel surveillance method (HIV prevalence: antenatal clinic 3%, STI clinic 22.8%, female sex workers 12.8%) led to an estimate of 112635 (4.38%) people with HIV, 15–49 years old, in Guntur district, which was 2.5 times the 45942 (1.79%) estimate based on our population-based study.

Conclusion

The official method in India leads to a gross overestimation of the HIV burden in this district due to addition of substantial extra HIV estimates from STI clinics, the common practice of referral of HIV-positive/suspected people to public hospitals, and a preferential use of public hospitals by people in lower socioeconomic strata. India may be overestimating its HIV burden with the currently used official estimation method.     

Redox proteomics in study of kidney-associated hypertension: new insights to old diseases

Abstract Significance: The kidney helps to maintain low blood pressure in the human body, and impaired kidney function is a common attribute of aging that is often associated with high blood pressure (hypertension). Kidney-related pathologies are important contributors (either directly or indirectly) to overall human mortality. In comparison with other organs, kidney has an unusually wide range of oxidative status, ranging from the well-perfused cortex to near-anoxic medulla. Recent Advances: Oxidative stress has been implicated in many kidney pathologies, especially chronic kidney disease, and there is considerable research interest in oxidative stress biomarkers for earlier prediction of disease onset. Proteomics approaches have been taken to study of human kidney tissue, serum/plasma, urine, and animal models of hypertension. Critical Issues: Redox proteomics, in which oxidative post-translational modifications can be identified in protein targets of oxidative or nitrosative stress, has not been very extensively pursued in this set of pathologies. Future Directions: Proteomics studies of kidney and related tissues have relevance to chronic kidney disease, and redox proteomics, in particular, represents an under-exploited toolkit for identification of novel biomarkers in this commonly occurring pathology. Antioxid. Redox Signal. 17, 1560-1570.     

Acute asthma intervention: insights from the STAY study

In some patients, asthma control is improved by combining inhaled corticosteroids with long-acting beta(2)-agonists. However, fluctuating asthma control and exacerbations can still occur. The STAY study evaluated whether, in patients with moderate to severe asthma, replacing a short-acting beta(2)-agonist reliever with the combination of budesonide/formoterol as reliever would both provide rapid symptom relief and reduce asthma exacerbations. The study evaluated 2760 patients with asthma (4-80 years) randomized to budesonide 400 microg twice daily (bid) and terbutaline as reliever, budesonide/formoterol 100/6 microg bid and terbutaline as reliever, or budesonide/formoterol 100/6 microg bid both as maintenance and reliever. Children (age 4-11 years) used a once-daily maintenance dose. Budesonide/formoterol as maintenance and reliever significantly reduced severe exacerbation risk by 45% to 47% compared with the other 2 treatments and improved symptoms, awakenings, and lung function. The benefit was seen in patients of all ages. Subsequent studies have revealed that this beneficial effect of budesonide/formoterol as maintenance and reliever requires both components of the combination.