CCL2/MCP-I Genotype-Phenotype Relationship in Latent Tuberculosis Infection

Among the known biomarkers, chemokines, secreted by activated macrophages and T cells, attract groups of immune cells to the site of infection and may determine the clinical outcome. Association studies of CCL-2/MCP-1 -2518 A/G functional SNP linked to high and low phenotypes with tuberculosis disease susceptibility have shown conflicting results in tuberculosis. Some of these differences could be due the variability of latent infection and recent exposure in the control groups. We have therefore carried out a detailed analysis of CCL-2 genotype SNP -2518 (A/G transition) with plasma CCL-2 levels and related these levels to tuberculin skin test positivity in asymptomatic community controls with no known exposure to tuberculosis and in recently exposed household contacts of pulmonary tuberculosis patients. TST positivity was linked to higher concentrations of plasma CCL2 (Mann Whitney U test; p = 0.004) and was more marked when the G allele was present in TST+ asymptomatic controls (A/G; p = 0.01). Recent exposure also had a significant effect on CCL-2 levels and was linked to the G allele (p = 0.007). Therefore association studies for susceptibility or protection from disease should take into consideration the PPD status as well as recent exposure of the controls group used for comparison. Our results also suggest a role for CCL-2 in maintaining the integrity of granuloma in asymptomatic individuals with latent infection in high TB burden settings. Therefore additional studies into the role of CCL-2 in disease reactivation and progression are warranted

Failure to Recognize Nontuberculous Mycobacteria Leads to Misdiagnosis of Chronic Pulmonary Tuberculosis

BACKGROUND: Nontuberculous mycobacterial (NTM) infections cause morbidity worldwide. They are difficult to diagnose in resource-limited regions, and most patients receive empiric treatment for tuberculosis (TB). Our objective here is to evaluate the potential impact of NTM diseases among patients treated presumptively for tuberculosis in Mali. METHODS: We re-evaluated sputum specimens among patients newly diagnosed with TB (naïve) and those previously treated for TB disease (chronic cases). Sputum microscopy, culture and Mycobacterium tuberculosis drug susceptibility testing were performed. Identification of strains was performed using molecular probes or sequencing of secA1 and/or 16S rRNA genes. RESULTS: Of 142 patients enrolled, 61 (43%) were clinically classified as chronic cases and 17 (12%) were infected with NTM. Eleven of the 142 (8%) patients had NTM disease alone (8 M. avium, 2 M. simiae and 1 M. palustre). All these 11 were from the chronic TB group, comprising 11/61 (18%) of that group and all were identified as candidates for second line treatment. The remaining 6/17 (35.30%) NTM infected patients had coinfection with M. tuberculosis and all 6 were from the TB treatment naïve group. These 6 were candidates for the standard first line treatment regimen of TB. M. avium was identified in 11 of the 142 (8%) patients, only 3/11 (27.27%) of whom were HIV positive. CONCLUSIONS: NTM infections should be considered a cause of morbidity in TB endemic environments especially when managing chronic TB cases to limit morbidity and provide appropriate treatment

Isolation of non-tuberculous mycobacteria from pastoral ecosystems of Uganda: Public Health significance

<p>Abstract</p> <p>Background</p> <p>The importance of non-tuberculous mycobacteria (NTM) infections in humans and animals in sub-Saharan Africa at the human-environment-livestock-wildlife interface has recently received increased attention. NTM are environmental opportunistic pathogens of humans and animals. Recent studies in pastoral ecosystems of Uganda detected NTM in humans with cervical lymphadenitis and cattle with lesions compatible with bovine tuberculosis. However, little is known about the source of these mycobacteria in Uganda. The aim of this study was to isolate and identify NTM in the environment of pastoral communities in Uganda, as well as assess the potential risk factors and the public health significance of NTM in these ecosystems.</p> <p>Method</p> <p>A total of 310 samples (soil, water and faecal from cattle and pigs) were examined for mycobacteria. Isolates were identified by the INNO-Lipa test and by 16S rDNA sequencing. Additionally, a questionnaire survey involving 231 pastoralists was conducted during sample collection. Data were analysed using descriptive statistics followed by a multivariable logistic regression analysis.</p> <p>Results</p> <p>Forty-eight isolates of NTM were detected; 25.3% of soil samples, 11.8% of water and 9.1% from animal faecal samples contained mycobacteria. Soils around water sources were the most contaminated with NTM (29.8%). Of these samples, <it>M. fortuitum-peregrinum </it>complex, <it>M. avium </it>complex, <it>M. gordonae</it>, and <it>M. nonchromogenicum </it>were the most frequently detected mycobacteria. Drinking untreated compared to treated water (OR = 33), use of valley dam versus stream water for drinking and other domestic use (OR = 20), sharing of water sources with wild primates compared to antelopes (OR = 4.6), sharing of water sources with domestic animals (OR = 5.3), and close contact with cattle or other domestic animals (OR = 13.8) were the most plausible risk factors for humans to come in contact with NTM in the environment.</p> <p>Conclusions</p> <p>The study detected a wide range of potentially pathogenic NTM from the environment around the pastoral communities in Uganda. Drinking untreated water and living in close contact with cattle or other domestic animals may be risk factors associated with the possibility of humans and animals acquiring NTM infections from these ecosystems.</p

Characterization of Non-Tuberculous Mycobacterium from Humans and Water in an Agro pastoral area in Zambia

Abstract Background The non-tuberculous mycobacteria include those mycobacterium species that are not members of the Mycobacterium tuberculosis complex, the causative agent of pulmonary tuberculosis and Mycobacterium leprae. In Zambia, Non-tuberculous Mycobacteria are gaining recognition as pathogens of public health significance. However, there is scanty information on the isolation and speciation of these organisms for better patient management, consequently reducing the burden of these infections. Given the above information, the thrust of this study was to isolate and characterize NTM from humans and water in Namwala district of Zambia. Method This was a cross-sectional study were 153 individuals with suspected TB were sampled from four health facilities in Namwala district, sputum samples were also collected. Additionally, 149 water samples were collected from different water drinking sources such as Tap water, Borehole water, rivers, wells and streams. Standard TB culture methods were employed to isolate Non-tuberculous Mycobacteria and later 16S–23S internal transcribed spacer region Sequencing was employed to characterize NTM. Results Seven (7, 4.6%) NTM species were identified from humans with M. arupense (3, 42.9%) being the most common organism, while twenty three (23, 15.4%) NTM were identified from water with the common species being Mycobacterium gordonae (5, 21.7%). Mycobacterium avium and Mycobacterium fortuitum were both identified from human and water samples. Conclusion This study has shown the isolation of NTM species from humans and water. The isolation of NTM from drinking water sources could signify a public health risk to humans

Use of the WHO Access, Watch, and Reserve classification to define patterns of hospital antibiotic use (AWaRe): an analysis of paediatric survey data from 56 countries

BACKGROUND: Improving the quality of hospital antibiotic use is a major goal of WHO's global action plan to combat antimicrobial resistance. The WHO Essential Medicines List Access, Watch, and Reserve (AWaRe) classification could facilitate simple stewardship interventions that are widely applicable globally. We aimed to present data on patterns of paediatric AWaRe antibiotic use that could be used for local and national stewardship interventions. METHODS: 1-day point prevalence survey antibiotic prescription data were combined from two independent global networks: the Global Antimicrobial Resistance, Prescribing, and Efficacy in Neonates and Children and the Global Point Prevalence Survey on Antimicrobial Consumption and Resistance networks. We included hospital inpatients aged younger than 19 years receiving at least one antibiotic on the day of the survey. The WHO AWaRe classification was used to describe overall antibiotic use as assessed by the variation between use of Access, Watch, and Reserve antibiotics, for neonates and children and for the commonest clinical indications. FINDINGS: Of the 23 572 patients included from 56 countries, 18 305 were children (77·7%) and 5267 were neonates (22·3%). Access antibiotic use in children ranged from 7·8% (China) to 61·2% (Slovenia) of all antibiotic prescriptions. The use of Watch antibiotics in children was highest in Iran (77·3%) and lowest in Finland (23·0%). In neonates, Access antibiotic use was highest in Singapore (100·0%) and lowest in China (24·2%). Reserve antibiotic use was low in all countries. Major differences in clinical syndrome-specific patterns of AWaRe antibiotic use in lower respiratory tract infection and neonatal sepsis were observed between WHO regions and countries. INTERPRETATION: There is substantial global variation in the proportion of AWaRe antibiotics used in hospitalised neonates and children. The AWaRe classification could potentially be used as a simple traffic light metric of appropriate antibiotic use. Future efforts should focus on developing and evaluating paediatric antibiotic stewardship programmes on the basis of the AWaRe index. FUNDING: GARPEC was funded by the PENTA Foundation. GARPEC-China data collection was funded by the Sanming Project of Medicine in Shenzhen (SZSM2015120330). bioMérieux provided unrestricted funding support for the Global-PPS

An epidemiological and economic simulation model to evaluate the spread and control of infectious Bovine Rhinotracheitus in The Netherlands.

Bovine herpesvirus type I (BHV1), causing infectious bovine rhinotracheitis (IBR), was introduced in the Netherlands in 1971. In 1993, about 42% of the dairy cows had antibodies against BHV1. In the future, stricter requirements are anticipated regarding the health status of exported breeding cows and material. To support policymakers in their decisions on IBR eradication, a simulation model was developed in which the epidemiological and economic consequences of various control strategies were evaluated. This paper describes the model and provides an overview of some important outcomes. In the model, dairy herds were classified into different disease states based on (1) the reproduction ratio of the disease (R, defined as the number of secondary cases caused by one infectious animal) (2) the within-herd prevalence, within each value of R and (3) the expected number of infectious animals in an infectious herd within each prevalence range. The dynamic transition probability of a herd going from one state to another per week depends on direct contacts between animals, and other contacts such as transmission through fomites, indirect transmission through other species, airborne transmission and minor disease-specific routes such as venereal or iatrogenic transmission. Five control strategies, including both a voluntary vaccination program and a compulsory vaccination program for all dairy herds were evaluated. A voluntary vaccination program with 50% participation is not expected to lead to eradication of IBR. It appears that compulsory vaccination would be necessary to reach an IBR-free status

Characterization of a novel variant of Mycobacterium chimaera.

Item does not contain fulltextIn this study, nonchromogenic mycobacteria were isolated from pulmonary samples of three patients in the Netherlands. All isolates had identical, unique 16S rRNA gene and 16S-23S ITS sequences, which were closely related to those of Mycobacterium chimaera and Mycobacterium marseillense. The biochemical features of the isolates differed slightly from those of M. chimaera, suggesting that the isolates may represent a possible separate species within the Mycobacterium avium complex (MAC). However, the cell-wall mycolic acid pattern, analysed by HPLC, and the partial sequences of the hsp65 and rpoB genes were identical to those of M. chimaera. We concluded that the isolates represent a novel variant of M. chimaera. The results of this analysis have led us to question the currently used methods of species definition for members of the genus Mycobacterium, which are based largely on 16S rRNA or rpoB gene sequencing. Definitions based on a single genetic target are likely to be insufficient. Genetic divergence, especially in the MAC, yields strains that cannot be confidently assigned to a specific species based on the analysis of a single genetic target.1 september 201