BMC Infectious Diseases - Latest articles

Default from tuberculosis treatment in Tashkent, Uzbekistan; Who are these defaulters and why do they default?

2008-07-22

Background: DOTS implementation in Tashkent City started in 2000. Of 1087 pulmonary TB patients started on treatment in 2005, 228 (21%) defaulted. This study investigates who the defaulters in Tashkent are, when they default and why they default. Methods: We reviewed the records of 126 defaulters (cases) and 132 controls and collected information on time of default, demographic factors, social factors, potential risk factors for default, characteristics of treatment and recorded reasons for default. Results: Unemployment, being a pensioner, alcoholism and homelessness were associated with default. Patients defaulted mostly during the intensive phase, while they were hospitalized (61%), or just before they were to start the continuation phase (26%). Reasons for default listed in the records were various, 'Refusal of further treatment' (27%) and 'Violation of hospital rules' (18%) were most frequently recorded. One third of the recorded defaulters did not really default but continued treatment under 'non-DOTS' conditions. Conclusions: Whereas patient factors such as unemployment, being a pensioner, alcoholism and homelessness play a role, there are also system factors that need to be addressed to reduce default. Such system factors include the obligatory admission in TB hospitals and the inadequately organized transition from hospitalized to ambulatory treatment.

Invasive pneumococcal infections among persons with and without underlying medical conditions: implications for prevention strategies

Peter Klemets, Outi Lyytikainen, Petri Ruutu, Jukka Ollgren and Pekka Nuorti — 2008-07-22

Background: The 23-valent pneumococcal polysaccharide vaccine (PPV23) is recommended for persons aged 65 years or less with chronic medical conditions. We evaluated the risk and mortality from invasive pneumococcal disease (IPD) among persons with and without the underlying medical conditions which are considered PPV23 indications. Methods: Population-based data on all episodes of IPD (positive blood or cerebrospinal fluid culture) reported by Finnish clinical microbiology laboratories during 1995-2002 were linked to data in national health care registries and vital statistics to obtain information on the patient's preceding hospitalisations, co-morbidities, and outcome of illness. Results: Overall, 4357 first episodes of IPD were identified in all age groups (average annual incidence, 10.6/100,000). Patients aged 18-49 and 50-64 years accounted for 1282 (29%) and 934 (21%) of IPD cases, of which 372 (29%) and 427 (46%) had a current PPV23 indication, respectively. Overall, 536 (12%) IPD patients died within one month of first positive culture. Persons aged 18-64 years accounted for 254 (47%) of all deaths (case-fatality proportion, 12%). Of those who died 117 (46%) did not have a vaccine indication. In a survival model, patients with alcohol-related diseases, non-haematological malignancies, and those aged 50-64 years were most likely to die. Conclusions: In the general population of non-elderly adults, almost two-thirds of IPD and half of fatal cases occurred in persons without a recognised PPV23 indication. Policymakers should consider alternative prevention strategies such as lowering the age of universal PPV23 vaccination and introducing routine childhood pneumococcal conjugate immunisation which could provide substantial health benefits to this population through indirect vaccine effects.

Clinical case review: A method to improve identification of true clinical and radiographic pneumonia in children meeting the World Health Organization definition for pneumonia.

2008-07-21

Background: The World Health Organizationas (WHO) case definition for childhood pneumonia, composed of simple clinical signs of cough, difficult breathing and fast breathing, is widely used in resource poor settings to guide management of acute respiratory infections. The definition is also commonly used as an entry criteria or endpoint in different intervention and disease burden studies. Methods: A group of paediatricians conducted a retrospective review of clinical and laboratory data including C-reactive protein concentration and chest radiograph findings among Filipino children hospitalised in the Bohol Regional Hospital who were enrolled in a pneumococcal vaccine efficacy study and had an episode of respiratory disease fulfilling the WHO case definition for clinical pneumonia. Our aim was to evaluate which disease entities the WHO definition actually captures and what is the probable aetiology of respiratory infections among these episodes diagnosed in this population. Results: Among the 12,194 children enrolled to the vaccine study we recorded 1,195 disease episodes leading to hospitalisation which fulfilled the WHO criteria for pneumonia. In total, 34% of these episodes showed radiographic evidence of pneumonia and 11% were classified as definitive or probable bacterial pneumonia. Over 95% of episodes of WHO adefined severe pneumonia (with chest indrawing) had an acute lower respiratory infection as final diagnosis whereas 34% of those with non-severe clinical pneumonia had gastroenteritis or other non-respiratory infection as main cause of hospitalisation. Conclusions: The WHO definition for severe pneumonia shows high specificity for acute lower respiratory infection and provides a tool to compare the total burden of lower respiratory infections in different settings.

Childhood TB epidemiology and treatment outcomes in Thailand: a TB Active Surveillance Network, 2004 to 2006

2008-07-18

Background: Of the 9.2 million new TB cases occurring each year, about 10% are in children. Because childhood TB is usually non-infectious and non-fatal, national programs do not prioritize childhood TB diagnosis and treatment. We reviewed data from a demonstration project to learn more about the epidemiology of childhood TB in Thailand. Methods: In four Thai provinces and one national hospital, we contacted healthcare facilities monthly to record data about persons diagnosed with TB, assist with patient care, provide HIV counseling and testing, and obtain sputum for culture and susceptibility testing. We analyzed clinical and treatment outcome data for patients age < 15 years old registered in 2005 and 2006. Results: Only 279 (2%) of 14,487 total cases occurred in children. The median age of children was 8 years (range: 4 months, 14 years). Of 197 children with pulmonary TB, 63 (32%) were bacteriologically-confirmed: 56 (28%) were smear-positive and 7 (4%) were smear-negative, but culture-positive. One was diagnosed with multi-drug resistant TB. HIV infection was documented in 75 (27%). Thirteen (17%) of 75 HIV-infected children died during TB treatment compared with 4 (2%) of 204 not known to be HIV-infected (p<0.01). Conclusions: Childhood TB is infrequently diagnosed in Thailand. Understanding whether this is due to absence of disease or diagnostic effort requires further research. HIV contributes substantially to the childhood TB burden in Thailand and is associated with high mortality.

Risk factors for poor virological outcome at 12 months in a workplace-based antiretroviral therapy programme in South Africa: a cohort study

2008-07-16

Background: Reasons for the variation in reported treatment outcomes from antiretroviral therapy (ART) programmes in developing countries are not clearly defined. Methods: Among ART-naive individuals in a workplace ART programme in South Africa we determined virological outcomes at 12 months, and risk factors for sub-optimal virological outcome, defined as plasma HIV-1 viral load >=400 copies/ml. Results: Among 1760 individuals starting ART before July 2004, 1172 were in follow-up at 12 months of whom 953 (81%) had a viral load measurement (median age 41 yrs, 96% male, median baseline CD4 count 156x106/l). 71% (681/953) had viral load <400 copies/ml at 12 months. In a multivariable analysis, independent predictors of sub-optimal virological outcome at 12 months were <1 log decrease in viral load at six weeks (odds ratio [OR] 4.71, 95% confidence interval [CI] 2.56-8.68), viral load at baseline (OR 3.63 [95% CI 1.88-7.00] and OR 3.54 [95% CI 1.79-7.00] for 10,001-100,000 and >100,000 compared to <=10,000 copies/ml, respectively), adherence at six weeks (OR 3.50 [95% CI 1.92-6.35]), WHO stage (OR 2.08 [95% CI 1.28-3.34] and OR 2.03 [95% CI 1.14-3.62] for stage 3 and 4 compared to stage 1-2, respectively) and site of ART delivery. Site of delivery remained an independent risk factor even after adjustment for individual level factors. At 6 weeks, of 719 patients with self-reported adherence and viral load, 72 (10%) reported 100% adherence but had <1 log decrease in viral load; conversely, 60 (8%) reported <100% adherence but had >= 1 log decrease in viral load. Conclusion: Virological response at six weeks after ART start was the strongest predictor of sub-optimal virological outcome at 12 months, and may identify individuals who need interventions such as additional adherence support. Self reported adherence was less strongly associated but identified different patients compared with viral load at 6 weeks. Site of delivery had an important influence on virological outcomes; factors at the health system level which influence outcome need further investigation to guide development of effective ART programmes.

Use of multiple methods for genotyping Fusarium during an outbreak of contact lens associated fungal keratitis in Singapore

2008-07-15

Background: In Singapore, an outbreak of fungal keratitis caused by Fusarium solani species complex (FSSC) was identified in March 2005 to May 2006 involving 66 patients. Epidemiological investigations have indicated that improper contact lens wear and the use of specific contact lens solutions were risk factors. Methods: We assessed the genetic diversity of the isolates using AFLP, Rep-PCR, and ERIC-PCR to compare the usefulness of these typing schemes and to characterize the isolates. Results: AFLP was the most discriminative typing scheme and appears to group FSSC from eye infections and from other infections differently. Conclusion: There was a high genomic heterogeneity among the isolates confirming that this was not a point source outbreak.

The Procalcitonin And Survival Study (PASS) - A Randomised multi-center trial to investigate whether daily measurements biomarker Procalcitonin and pro-active diagnostic and therapeutic responses to abnormal Procalcitonin levels, can improve survival in intensive care unit patients. Calculated sample size (target population): 1000 patients

2008-07-13

Background: Sepsis and complications to sepsis are major causes of mortality in critically ill patients. Rapid treatment of sepsis is of crucial importance for survival of patients. The infectious status of the critically ill patient is often difficult to assess because symptoms cannot be expressed and signs may present atypically. The established biological markers of inflammation (leucocytes, C-reactive protein) may often be influenced by other parameters than infection, and may be unacceptably slowly released after progression of an infection. At the same time, lack of a relevant antimicrobial therapy in an early course of infection may be fatal for the patient. Specific and rapid markers of bacterial infection have been sought for use in these patients. Methods: Multi-centre randomized controlled interventional trial. Powered for superiority and non-inferiority on all measured end points. Complies with, ''Good Clinical Practice'' (ICH-GCP Guideline (CPMP/ICH/135/95, Directive 2001/20/EC)). Inclusion: 1) Age >= 18 years of age, 2) Admitted to the participating intensive care units, 3) Signed written informed consent. Exclusion: 1) Known hyper-bilirubinaemia. or hypertriglyceridaemia, 2) Likely that safety is compromised by blood sampling, 3) Pregnant or breast feeding. Computerized Randomisation: Two arms (1:1), n = 500 per arm: Arm 1: standard of care. Arm 2: standard of care and Procalcitonin guided diagnostics and treatment of infection. Primary Trial Objective: To address whether daily Procalcitonin measurements and immediate diagnostic and therapeutic response on day-to-day changes in procalcitonin can reduce the mortality of critically ill patients. DiscussionFor the first time ever, a mortality-endpoint, large scale randomized controlled trial with a biomarker-guided strategy compared to the best standard of care, is conducted in an Intensive care setting. Results will, with a high statistical power, answer the question: Can the survival of critically ill patients be improved by actively using biomarker procalcitonin in the treatment of infections? 700 critically ill patients are currently included of 1000 planned (June 2008). Two interim analyses have been passed without any safety or futility issues, and the third interim analysis is soon to take place. Trial registration number via www.clinicaltrials.gov: Id. nr.: NCT00271752)

Survey of childhood empyema in Asia: Implications for detecting the unmeasured burden of culture-negative bacterial disease

2008-07-11

Background: Parapneumonic empyema continues to be a disease of significant morbidity and mortality among children despite recent advances in medical management. To date, only a limited number of studies have assessed the burden of empyema in Asia. Methods: We surveyed medical records of four representative large pediatric hospitals in China, Korea, Taiwan and Vietnam using ICD-10 diagnostic codes to identify children <16 years of age hospitalized with empyema or pleural effusion from 1995 to 2005. We also accessed microbiology records of cultured empyema and pleural effusion specimens to describe the trends in the epidemiology and microbiology of empyema. Results: During the study period, we identified 1,379 children diagnosed with empyema or pleural effusion (China, n = 461; Korea, n = 134; Taiwan, n = 119; Vietnam, n = 665). Diagnoses of pleural effusion (n = 1,074) were 3.5 times more common than of empyema (n = 305), although the relative proportions of empyema and pleural effusion noted in hospital records varied widely between the four sites, most likely because of marked differences in coding practices. Although pleural effusions were reported more often than empyema, children with empyema were more likely to have a cultured pathogen. In addition, we found that median age and gender distribution of children with these conditions were similar across the four countries. Among 1,379 empyema and pleural effusion specimens, 401 (29%) were culture positive. Staphylococcus aureus (n = 126) was the most common organism isolated, followed by Streptococcus pneumoniae (n = 83), Pseudomonas aeruginosa (n = 37) and Klebsiella (n = 35) and Acinetobacter species (n = 34). Conclusion: The age and gender distribution of empyema and pleural effusion in children in these countries are similar to the US and Western Europe. S. pneumoniae was the second leading bacterial cause of empyema and pleural effusion among Asian children. The high proportion of culture-negative specimens among patients with pleural effusion or empyema suggests that culture may not be a sufficiently sensitive diagnostic method to determine etiology in the majority of cases. Future prospective studies in different countries would benefit from standardized case definitions and coding practices for empyema. In addition, more sensitive diagnostic methods would improve detection of pathogens and could result in better prevention, treatment and outcomes of this severe disease.

Utility of CD4 cell counts for early prediction of virological failure during antiretroviral therapy in a resource-limited setting

Motasim Badri, Stephen D Lawn and Robin Wood — 2008-07-04

Background: Viral load monitoring is not available for the vast majority of patients receiving antiretroviral therapy in resource-limited settings. However, the practical utility of CD4 cell count measurements as an alternative monitoring strategy has not been rigorously assessed. Methods: In this study, we used a novel modelling approach that accounted for all CD4 cell count and VL values measured during follow-up from the first date that VL suppression was achieved. We determined the associations between CD4 counts (absolute values and changes during ART), VL measurements and risk of virological failure (VL > 1,000 copies/ml) following initial VL suppression in 330 patients in South Africa. CD4 count changes were modelled both as the difference from baseline (ΔCD4 count) and the difference between consecutive values (CD4 count slope) using all 3-monthly CD4 count measurements during follow-up. Results: During 7093.2 patient-months of observation 3756 paired CD4 count and VL measurements were made. In patients who developed virological failure (n = 179), VL correlated significantly with absolute CD4 counts (r = - 0.08, P = 0.003), ΔCD4 counts (r = - 0.11, P < 0.01), and most strongly with CD4 count slopes (r = - 0.30, P < 0.001). However, the distributions of the absolute CD4 counts, ΔCD4 counts and CD4 count slopes at the time of virological failure did not differ significantly from the corresponding distributions in those without virological failure (P = 0.99, P = 0.92 and P = 0.75, respectively). Moreover, in a receiver operating characteristic (ROC) curve, the association between a negative CD4 count slope and virological failure was poor (area under the curve = 0.59; sensitivity = 53.0%; specificity = 63.6%; positive predictive value = 10.9%). Conclusion: CD4 count changes correlated significantly with VL at group level but had very limited utility in identifying virological failure in individual patients. CD4 count is an inadequate alternative to VL measurement for early detection of virological failure.

Analysis of risk factors for T. brucei rhodesiense sleeping sickness within villages in south-east Uganda

2008-06-30

Background: Sleeping sickness (HAT) caused by T.b. rhodesiense is a major veterinary and human public health problem in Uganda. Previous studies have investigated spatial risk factors for T.b. rhodesiense at large geographic scales, but none have properly investigated such risk factors at small scales, i.e. within affected villages. In the present work, we use a case-control methodology to analyse both behavioural and spatial risk factors for HAT in an endemic area. Methods: The present study investigates behavioural and occupational risk factors for infection with HAT within villages using a questionnaire-based case-control study conducted in 17 villages endemic for HAT in SE Uganda, and spatial risk factors in 4 high risk villages. For the spatial analysis, the location of homesteads with one or more cases of HAT up to three years prior to the beginning of the study was compared to all non-case homesteads. Analysing spatial associations with respect to irregularly shaped geographical objects required the development of a new approach to geographical analysis in combination with a logistic regression model. Results: The study was able to identify, among other behavioural risk factors, having a family member with a history of HAT (p = 0.001) as well as proximity of a homestead to a nearby wetland area (p < 0.001) as strong risk factors for infection. The novel method of analysing complex spatial interactions used in the study can be applied to a range of other diseases. Conclusion: Spatial risk factors for HAT are maintained across geographical scales; this consistency is useful in the design of decision support tools for intervention and prevention of the disease. Familial aggregation of cases was confirmed for T. b. rhodesiense HAT in the study and probably results from shared behavioural and spatial risk factors amongmembers of a household.