Clinical and laboratory features of the most common Clostridium difficile ribotypes isolated in Belgium.

BACKGROUND: Previous studies comparing Clostridium difficile infection (CDI) due to different ribotypes have been conflicting, and many have only compared small numbers of cases or few ribotypes. AIM: To compare patient and episode characteristics for CDI due to different ribotypes. METHODS: The ribotyping results from 3333 toxin-producing isolates collected from 110 Belgian hospitals between October 2010 and December 2015 were matched to clinical data from the national CDI surveillance database. Data for ribotypes with at least 100 occurrences were compared. In addition, the national reference laboratory quantitatively measured the level of toxin production in five randomly chosen cultured isolates for each of the most common ribotypes. FINDINGS: Ribotypes with more than 100 occurrences were R014, R020, R002, R078, R027, R005 and R106 (Brazier classification). The median age for all patients was 79 years [patients with R027, 83 years (P<0.001); patients with R106, 73 years (P<0.001)]. In total, 10% of episodes were recurrences; values were higher for R027 (22%) and R106 (18%). CDI due to R078 was not significantly more likely to be community associated than healthcare associated (28% vs 24%; P=0.1). Complications occurred in 7% of all episodes, and 12% for those with R027 and R078. However, after adjusting for age, onset outside the hospital and recurrence, R027 was no longer associated with complications [odds ratio (OR) 1.3, 95% confidence interval (CI) 0.7-2.4], unlike R078 (OR 1.7, 95% CI 1.0-2.6; P=0.04). A positive stool toxin test and greater levels of toxin production in the cultured isolates were more likely for R078 and R027. CONCLUSION: Out of the seven most common ribotypes in hospital patients, R078 and R027 were associated with higher rates of complications. Infections with R027 and R106 were more likely to be recurrent. The presence of toxin in stools was most likely with R078, R027 and R106, with highest levels of toxin production in vitro for R078 and R027. R060 produced the lowest levels of toxin in vitro.

Implementing strategic bundles for infection prevention and management.

Healthcare-associated infections (HAI) are considered to be the most frequent adverse event in healthcare delivery. Active efforts to curb HAI have increased across Europe thanks to the growing emphasis on patient safety and quality of care. Recently, there has been dramatic success in improving the quality of patient care by focusing on the implementation of a group or "bundle" of evidenced-based preventive practices to achieve a better outcome than when implemented individually. The project entitled IMPLEMENT is designed to spread and test knowledge on how to implement strategic bundles for infection prevention and management in a diverse sample of European hospitals. The general goal of this project is to provide evidence on how to decrease the incidence of HAI and to improve antibiotic use under routine conditions.

Nation-wide prospective surveillance of Clostridium difficile infections in hospitals in Belgium, July 2007-June 2008.

We report here baseline data from the first year of compulsory surveillance of Clostridium difficile infections (CDI) in hospitals in Belgium. Between 1 July 2007 and 30 June 2008, 2,704 CDI were reported: 12% were recurrent and 66% were hospital-associated (half of which occurred 15 days or more after admission). CDI was considered the cause of death (direct or indirect) for 10% of the episodes. The median incidence of CDI was 1.5 per 1,000 admissions and 1.9 per 10,000 hospital-days for all cases, and 0.9 per 1,000 admissions, and 1.1 per 10,000 hospital-days for hospital-associated cases. Further investigation of risk stratification by average length of stay in the reporting hospitals is warranted as a way to improve the comparability of indicators across hospitals and surveillance systems. In spite of methodological issues, the surveillance of CDI in Belgian hospitals has been able to produce robust baseline data that should allow monitoring of trends at hospital and national level, and provide a basis for international comparisons. Remaining challenges are to define and monitor targets for the control of CDI, and to improve the individual feed-back of data at hospital level.

Update of Clostridium difficile infection due to PCR ribotype 027 in Europe, 2008.

Outbreaks of Clostridium difficile infections (CDI) with increased severity, high relapse rate and significant mortality have been related to the emergence of a new, hypervirulent C. difficile strain in North America and Europe. This emerging strain is referred to as PCR ribotype 027 (Type 027). Since 2005, individual countries have developed surveillance studies about the spread of type 027.C. difficile Type 027 has been reported in 16 European countries. It has been responsible for outbreaks in Belgium, Germany, Finland, France, Ireland, Luxembourg, The Netherlands, Switzerland and the United Kingdom (England, Wales, Northern Ireland and Scotland). It has also been detected in Austria, Denmark, Sweden, Norway, Hungary, Poland and Spain. Three countries experienced imported patients with CDI due to Type 027 who acquired the infection abroad.The antimicrobial resistance pattern is changing, and outbreaks due to clindamycin-resistant ermB positive Type 027 strains have occurred in three European countries. Ongoing epidemiological surveillance of cases of CDI, with periodic characterisation of the strains involved, is required to detect clustering of cases in time and space and to monitor the emergence of new, highly virulent clones.

Delays to treatment and out-of-pocket medical expenditure for tuberculosis patients, in an urban area of South America.

Short delays to treatment are important for the control of tuberculosis (TB). National Tuberculosis Programmes provide free diagnosis and treatment for smear-positive patients, so that the patients' out-of-pocket medical expenditure could be almost nil. The factors associated with delays in starting treatment, and the pre-treatment out-of-pocket medical expenditure for TB patients, have now been investigated in the Bolivian city of Cochabamba. Bolivia is the Latin American country with the highest incidence of TB. It is covered by a national TB programme that provides free diagnosis and free treatment for smear-positive patients. Structured interviews with 144 smear-positive patients enrolled in this programme revealed median patient, provider and total delays of 3.6, 6.2 and 12.9 weeks, respectively. The total delays were longer for the female patients than for the male, and for patients who consulted private doctors than for the other patients. When the first healthcare provider was a doctor, the median provider delay was 4.9 weeks in the public sector but 7.2 weeks in the private. The median out-of-pocket medical expenditure per patient, which was U.S.$13.2 overall, was much higher for those who consulted a private doctor than for those who did not (U.S.$21.9 v. U.S.$5.4, respectively; P<0.001). It appears that interventions targeting doctors (in both the private and public sectors) are likely to have a larger impact on the shortening of delays in TB treatment than interventions targeting patients. They could also reduce unnecessary out-of-pocket expenditure.

Collaboration between private pharmacies and national tuberculosis programme: an intervention in Bolivia.

BACKGROUND: Public-private partnerships are felt to be necessary for tuberculosis (TB) control in some developing countries. OBJECTIVES: To evaluate the potential of a collaboration between the National TB Programme (NTP) and private pharmacies in Bolivia, the country with the highest TB incidence in Latin America. METHODS: We contacted the local Pharmacists' Association in the city of Cochabamba, and designed a two phase intervention. The objectives of the first phase were to decrease the availability of TB drugs in private pharmacies on a voluntary basis, and to improve referral of clients seeking TB drugs to the NTP. A survey of all pharmacies allowed for a before-after comparison with a baseline survey. The objectives of the second phase were to obtain referral of pharmacy clients with chronic cough for TB screening in the NTP. This phase was started in 70 pharmacies and evaluated after 2 months using the referral slips issued by the pharmacists. RESULTS: The proportion of pharmacies selling TB drugs decreased (rifampicin: 23-11.5%; isoniazid: 16-3.1%; P<0.001) and the proportion of pharmacies referring to the NTP clients seeking TB drugs increased (22-58%; P<0.0001). In the second phase, 26 of 70 pharmacies (38%) referred a total of 41 clients for screening in the NTP (i.e. an average of 0.29 clients per pharmacy and per month); 11 of 41 (27%) were screened and three of 11 (27%) diagnosed with smear-positive TB. CONCLUSION: The first phase of the intervention proved effective in reducing the availability of the main TB drugs in pharmacies, and in improving referral of clients seeking TB drugs. Key factors in this success were not specific to Bolivia, and collaboration between private pharmacies and public services appears possible in that respect. However, collaboration with pharmacies does not seem an efficient way to increase the number of patients screened for TB, and to shorten delays to TB diagnosis and treatment.

Tuberculosis control and the private health sector in Bolivia: a survey of pharmacies.

BACKGROUND: Bolivia is a high tuberculosis (TB) incidence country with a large private for-profit health sector. TB drug sales in private pharmacies are not illegal. OBJECTIVES: To measure the availability of TB drugs in private pharmacies, study vendors' attitudes, and explore the potential for collaboration between the public health sector and pharmacies. METHODS: Simulated clients visited a random sample of 100 pharmacies in the city of Cochabamba, presenting with a prescription for four TB drugs. After the survey, contacts were made with the local Pharmacist's Association. RESULTS: Twenty-five pharmacies sold at least one drug, 23 sold rifampicin and 16 sold isoniazid. Of 99 pharmacies unable to fill the whole prescription, 59 referred the client to another pharmacy, and 22 to the public services. Pharmacists said that rifampicin was often prescribed for non-TB indications, and that TB drug sales were of minimal contribution to their income. They agreed to stop selling the drugs and to refer clients seeking them to the public sector. CONCLUSION: This study has documented a small market for TB drugs sales in private pharmacies and provided the opportunity to start collaboration with the pharmacists. Our results suggest that the private sector contributes little to managing TB in Bolivia.

[Periodontal disease in Belgian adults]. / Prévalence de la maladie parodontale chez les adultes belges.

BACKGROUND: To date, no epidemiological study has been published on the periodontal health of the Belgian population. The aim of this study was to rectify this situation and determine the extent of the problem in Belgium. METHODS: A prevalence survey was carried out in a representative sample of employees of the Catholic University of Louvain. A total of 402 people aged between 35 and 65 were examined. Periodontal suffering was estimated using the CPITN index (WHO), which determines the most affected sextant of a mouth in order to assign a code to the mouth as a whole. At the same time, treatment needs were evaluated. RESULTS: Only one subject was considered healthy, i.e. there was no bleeding of the gums in any part of the mouth. At the same time, 41.4% of the subjects examined exhibited a deep periodontal pocket in at least one sextant of the mouth likely to progress to the loss of the teeth. Many mouths (28.5%), which were free from moderate or deep pockets, had to be scaled and polished or to be treated in order to eliminate other factors which could lead to a build-up of tartar. CONCLUSION: In this study population representative of a socio-economically favored stratum of the Belgian population, we observed a high prevalence of periodontal diseases, grading from mild chronic gingivitis to the deep cavities which are observed when the bone supporting the tooth has been lost. At the same time, we uncovered many needs for periodontal care, ranging from instruction on how to control the dental plaque to specialized periodontal care via careful scaling and polishing.

How can detection of infectious tuberculosis be improved? Experience in the Somali region of Ethiopia.

In early 1999, 48% of pulmonary tuberculosis (PTB) cases detected in the Somali region of Ethiopia were smear-positive. Actions at the laboratory level and peer-review of smear-negative PTB diagnoses were proposed. Clinicians knew, but did not adhere to, the algorithm recommended by the National Tuberculosis Programme for these diagnoses, partly due to the costs involved to patients. Challenging clinicians, in a non-threatening way, to become more clinically rigorous proved successful, and the proportion of smear-positive PTB increased to 65%. Operational research is needed to assess the feasibility of these widely-recommended smear-negative PTB diagnosis guidelines.

[Periodontal health and care needs in a sample of the Belgian population]. / Santé parodontale et besoins en soins parodontaux d'un échantillon de la population belge.

An epidemiological survey was carried out of among staff members of the Catholic University of Louvain. A total of 402 subjects, age 35 to 65, were examined. Periodontal lesions were estimated using the CPITN index (WHO). Only one subject presented no signs of gingival bleeding in any part of the mouth. 41.4% of the subjects presented a deep periodontal pocket in at least one sextant. Many subjects, although not presenting deep or moderately deep periodontal pockets (28.5%) needed scaling and rootplanning or other treatments to eliminate plaque retentive factors. In this sample, representing a socio-economically favoured segment of the population, we revealed a significant prevalence of periodontal disease from mild chronic gingivitis to deep pockets. Requirements in terms of care are considerable, ranging from oral hygiene instruction to control plaque to specialised care.

Neural control of force output during maximal and submaximal exercise.

A common belief in exercise physiology is that fatigue during exercise is caused by changes in skeletal muscle metabolism. This 'peripheral' fatigue results either from substrate depletion during submaximal exercise or metabolite accumulation during maximal exercise in the exercising muscles. However, if substrate depletion alone caused fatigue, intracellular ATP levels would decrease and lead to rigor and cellular death. Alternatively, metabolite accumulation would prevent any increase in exercise intensity near the end of exercise. At present, neither of these effects has been shown to occur, which suggests that fatigue may be controlled by changes in efferent neural command, generally described as 'central' fatigue. In this review, we examine neural efferent command mechanisms involved in fatigue, including the concepts of muscle wisdom during short term maximal activity, and muscle unit rotation and teleoanticipation during submaximal endurance activity. We propose that neural strategies exist to maintain muscle reserve, and inhibit exercise activity before any irreparable damage to muscles and organs occurs. The finding that symptoms of fatigue occur in the nonexercising state in individuals with chronic fatigue syndrome indicates that fatigue is probably not a physiological entity, but rather a sensory manifestation of these neural regulatory mechanisms.

A genetic mechanism for deletion of the ser2 gene cluster and formation of rough morphological variants of Mycobacterium avium.

A major phenotypic trait of the Mycobacterium avium complex is the ability to produce rough and smooth colony variants. The chemical basis of this morphological variation is the loss of an antigenic surface structure, termed glycopeptidolipid (GPL), by rough variants. Using M. avium serovar 2 strain 2151 as a model system, this laboratory previously reported that rough variants arise via the deletion of large genomic regions encoding GPL biosynthesis. One such deletion encompasses the gene cluster (ser2) responsible for production of the serovar 2 GPL haptenic oligosaccharide. In this study, nucleotide sequencing revealed that both ends of the ser2 gene cluster are flanked by a novel insertion sequence (IS1601) oriented as direct repeats. Detailed analyses of the site of deletion in the genome of M. avium 2151 Rg-1 demonstrated that a single copy of IS1601 remained and that the ser2 gene cluster was deleted by homologous recombination. This same deletion pattern was observed for 10 out of 15 rough colony variants tested. Additionally, these studies revealed that IS1601 contains portions of three independent insertion sequences. This report is the first to define the precise genetic basis of colony variation in Mycobacterium spp. and provides further evidence that homologous recombination between insertion sequence elements can be a primary determinant of genome plasticity in these bacteria.

Venous neuropeptide Y receptor responsiveness in patients with chronic heart failure.

BACKGROUND: Chronic heart failure is associated with increased sympathetic nerve activity and elevated plasma neuropeptide Y levels. The aim of this study was to investigate whether increased neuropeptide Y release altered vascular neuropeptide Y responses in the dorsal hand veins in patients with chronic heart failure. METHODS AND RESULTS: Neuropeptide Y responsiveness was studied in vivo with use of a hand vein tonometry technique in 14 patients with chronic heart failure and left ventricular ejection fraction (LVEF) values <20%, 16 patients with LVEF values from 20% to 35%, and 16 age-similar healthy control subjects. Plasma norepinephrine and neuropeptide Y levels were significantly elevated in patients with chronic heart failure and LVEF values <20% compared with control subjects (P < .01). Plasma neuropeptide Y but not norepinephrine levels were significantly elevated in patients with chronic heart failure and LVEF values from 20% to 35% compared with control subjects (P < .01). Increasing doses of neuropeptide Y (25 to 2,000 pmol/min) were infused into a dorsal hand vein of each subject. Dose-dependent venoconstriction to neuropeptide Y was observed in all subjects studied. The neuropeptide Y dose-response curve in patients with LVEF values from 20% to 35% was significantly shifted to the left compared with patients with LVEF values <20% and control subjects (P < .01), whereas no significant difference was observed between the control subjects and the patients with LVEF values <20%. No significant difference in neuropeptide Y dose responses was observed between patients with chronic heart failure with plasma neuropeptide Y levels above the median and patients with chronic heart failure with plasma neuropeptide Y levels below the median. CONCLUSIONS: In vivo venous neuropeptide Y receptor responsiveness is increased in patients with chronic heart failure and LVEF values from 20% to 35%. This increased neuropeptide Y responsiveness may contribute to venoconstriction at this stage of heart failure.

The effects of age on human venous responsiveness to neuropeptide Y.

AIMS: Neuropeptide Y (NPY) is a sympathetic neurotransmitter released with noradrenaline during sympathetic stimulation. Ageing has been shown to be associated with a reduction in alpha2 and beta-adrenoceptor mediated responses in veins, but it is not known whether NPY responsiveness is also altered with increasing age. METHODS: Using a dorsal hand vein technique, we examined NPY receptor responsiveness in 24 normal, healthy subjects (20-72 years; 10 males, 14 females). Graded infusions of NPY (25-2000 pmol min(-1)) were administered (5 min at each dose) into a dorsal hand vein. Venous distension at 45 mmHg was measured at 3-5 min of each infusion. Dose-response curves to NPY were constructed and the peak venoconstriction was calculated. RESULTS: Dose-dependent venoconstriction was seen in all but one subject. The peak venoconstriction observed with NPY was significantly and negatively correlated with the age of the normal subjects (r=-0.63, P<0.01). When subjects were ranked from youngest to oldest and divided into tertiles, (20-40 years, n = 8; 41-55 years, n = 8; 56-72 years, n = 8), mean dose-response curves were different with the oldest tertile being significantly less responsive (P<0.05). The peak venoconstriction observed (% of control) was 65.1+/-7.0, 46.5+/-9.4, and 24.4+/-4.8%, respectively. The oldest tertile had a significantly decreased peak venoconstriction compared with the youngest tertile (P<0.01). Infusion of NPY into a dorsal hand vein had no systemic effects on heart rate or blood pressure in any of the subjects studied. CONCLUSIONS: Hand vein responsiveness to exogenously infused NPY in normal subjects is decreased as age increases. The reduction of NPY-receptor-mediated responses with age may influence sympathetic nervous system control of the venous system with advancing age.

Enhanced in vivo alpha1- and alpha2-adrenoceptor-mediated venoconstriction with indomethacin in humans.

Vasodilator prostaglandins are released in vitro from endothelium during adrenergic stimulation. We hypothesized that indomethacin would block this production in vivo and increase venoconstriction to alpha1- and alpha2-stimulation but not to the nonadrenergic agonist PGF2alpha. Hand vein distension was measured in 24 normal subjects (23.0 +/- 0.5 yr) during local infusions of phenylephrine (8-12,000 ng/min), clonidine (3-7,000 ng/min), or PGF2alpha (1-2,048 ng/min) plus indomethacin (3 microg/min) versus saline on two separate days. Dose-dependent venoconstriction to phenylephrine occurred in all subjects, with a parallel shift to the left with indomethacin (P = 0. 003) and a decrease in the phenylephrine 50% effective dose (1,009 vs. 241 ng/min, geometric means, P = 0.012). Venoconstriction to clonidine was more variable, with most subjects eliciting a biphasic response (initial venoconstriction followed by attenuation). With indomethacin, the dose-response curve was displaced up and to the left (P = 0.005), and peak venoconstriction was increased (51.1 +/- 6.8 vs. 27.2 +/- 5.3% of control, P = 0.018) without a biphasic response. In all subjects, PGF2alpha elicited dose-dependent venoconstriction that was not altered by indomethacin. Thus venous alpha1- and alpha2-stimulation results in release of vasodilator prostaglandins that antagonize the venoconstrictor response. This modulates the sympathetic response of venous smooth muscle and may be important in diseases with endothelial dysfunction.

Causes of locomotor disability and need for orthopaedic devices in a heavily mined Taliban-controlled province of Afghanistan: issues and challenges for public health managers.

We conducted a locomotor disability survey on a heavily mined Taliban-controlled province of Afghanistan to document the problem of locomotor disability and to assess the need for orthopaedic rehabilitation devices in a study population of 12065. Global prevalence of locomotor disability was 23/1000 (95% CI: 20-26). )War-related injuries were the leading cause of disability, affecting almost exclusively adult males. Leading causes of disability among women and children were medical and poliomyelitis. Devices most needed were lower limb ortheses (8.2 devices/1000 people; 95% CI: 5.9-10.4) and orthopaedic shoes (6.0/1000; 95% CI:4.1-8.0). The need for lower limb prostheses was less frequent (2.0/1000; 95% CI: 1.1-2.8). Most lower limb amputees (mainly victims of landmine injuries) were fitted with an artificial leg, while rehabilitation needs for other types of disability remained largely unmet. We estimated that it would take at least 3 years to provide enough orthopaedic shoes and 10 years for ortheses, whereas the need for lower limb prostheses could be met in less than 4 months. None of the 27 women with lower limb disability were equipped with an orthopaedic device, although this was the case for 31 of 89 men (35%). The problem of landmines should not divert attention from other causes of disability such as poliomyelitis or from other rehabilitation requirements. Immunization programmes and restoration of the public health infrastructure should be given high priority; rehabilitation services are largely insufficient and should be developed. Extreme gender difference in needs coverage is a matter of concern. Researching culturally sensitive strategies to tackle this problem should be a priority for donors and implementing agencies.