International Journal of Infectious Diseases

Editorial Board

2010-08-01

Use of linezolid in pediatrics: a critical review

John Dotis, Elias Iosifidis, Maria Ioannidou, Emmanuel Roilides — 2010-01-27

Summary: Background: Linezolid, an oxazolidinone antibacterial agent, is available for intravenous/oral administration, with activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and penicillin-resistant Streptococcus pneumoniae (PRSP). These pathogens are important causes of hospital- and community-associated infections in children.Methods: PubMed was searched for all English language articles on patients younger than 18 years of age treated with linezolid, and an analysis of these articles was performed.Results: From the 133 articles retrieved, a total of 30 were studied (18 case reports, nine case series, and three clinical trials) based on the inclusion criteria preset for this review. In these articles, a total of 597 children received linezolid. MRSA was the most common pathogen, followed by VRE, PRSP, other bacteria and less common mycobacterial species. Linezolid was reported to be safe and effective for the treatment of pneumonia and endocarditis, as well as skin and soft tissue, central nervous system and osteoarticular infections.Conclusions: Linezolid is promising as a safe and efficacious agent for the treatment of infections due to mainly resistant Gram-positive organisms in children who are unable to tolerate conventional agents or after treatment failure.

Pediatric disease burden and vaccination recommendations: understanding local differences

2010-02-24

Abstract: Background: Diphtheria (D), tetanus (T), pertussis (P), hepatitis B (HepB), invasive Haemophilus influenzae type b (Hib) disease, and measles cause substantial global morbidity and mortality.Methods: This unique review highlights geographic differences in disease burden across certain countries in the African, Americas, Mediterranean, South-East Asian, and Western Pacific World Health Organization (WHO) regions, and relates this to vaccination coverage and local vaccine recommendations using the authors’ countries as illustrations.Results: Substantial differences were observed in the incidence of these diseases and in vaccination coverage between the countries studied. Disease incidence often reflected inadequate surveillance, but also variable or poor vaccination coverage. Vaccination coverage against HepB was particularly low in the African and South-East Asian WHO regions; vaccination coverage against invasive Hib disease was low in these regions and in the Eastern Mediterranean and Western Pacific WHO regions. Vaccination schedules within some countries in these regions do not include, or have only recently included, vaccinations against HepB and Hib disease. The use of DTwP–HepB–Hib (diphtheria, tetanus, whole-cell pertussis, HepB, Hib) combination vaccines has now been adopted by some countries to help increase vaccination coverage.Conclusions: Vaccination coverage and vaccination schedules vary markedly between the countries studied, often according to the resources available. DTwP–HepB–Hib combination vaccines represent a cost-effective option, with the potential to substantially reduce the burden associated with these diseases by increasing coverage and compliance.

Is spinal tuberculosis contagious?

Patricia Schirmer, Cybèle A. Renault, Mark Holodniy — 2010-02-24

Summary: While pulmonary Mycobacterium tuberculosis infections are recognized for their public health implications, less is known about the infectiousness of extrapulmonary tuberculosis, specifically, spinal tuberculosis or Pott's disease. We present a case of spinal tuberculosis with concomitant active pulmonary tuberculosis in the absence of chest radiographic abnormalities or symptoms, and review the literature regarding infectiousness of concomitant spinal and pulmonary tuberculosis.

Fleas and flea-borne diseases

2010-03-02

Summary: Flea-borne infections are emerging or re-emerging throughout the world, and their incidence is on the rise. Furthermore, their distribution and that of their vectors is shifting and expanding. This publication reviews general flea biology and the distribution of the flea-borne diseases of public health importance throughout the world, their principal flea vectors, and the extent of their public health burden. Such an overall review is necessary to understand the importance of this group of infections and the resources that must be allocated to their control by public health authorities to ensure their timely diagnosis and treatment.

Risk factors for Mycobacterium ulcerans infection

Kathryn H. Jacobsen, Jeannie J. Padgett — 2010-02-25

Abstract: Mycobacterium ulcerans infection (Buruli ulcer) causes necrotizing lesions that may lead to scarring, contractures, osteomyelitis, and even amputation. Despite decades of research, the reservoirs and modes of transmission for M. ulcerans remain obscure. A thorough evaluation of the potential risk factors examined in comparative epidemiological studies may help to identify likely transmission routes. A systematic search of the literature found that poor wound care, failure to wear protective clothing, and living or working near water bodies were commonly identified risk factors. Socioeconomic status, BCG vaccination, and direct water contact were not associated with significantly increased or decreased risk of infection. Additional comparative studies are required to clarify the potential roles of water contact and insect bites in transmitting M. ulcerans to humans.

Guanosine triphosphatases as novel therapeutic targets in tuberculosis

Rajni, Laxman S. Meena — 2010-03-08

Abstract: Tuberculosis (TB) is an infectious disease caused by the aerobic microbe Mycobacterium tuberculosis H37Rv. Despite the availability of the Bacille Calmette–Guérin (BCG) vaccine and directly observed treatment, short-course (DOTS), TB is a leading cause of death and affects a third of the world's population. The most important factor associated with disease severity is the development of antibiotic-resistant strains, including multidrug-resistant (MDR)-TB and extensively drug-resistant (XDR)-TB. In order to understand disease pathogenesis, it is necessary to delineate the specific features of M. tuberculosis that enable it to evade the host defense system and contribute to its virulence. Here, we have reviewed the various characteristics, such as cell wall components, virulence genes, and the role of small guanosine triphosphatases (GTPases) in the pathogenesis of TB. GTPases are known to play a crucial role in the survival and pathogenesis of various pathogens. The key role of these proteins involves interference in phagosome maturation arrest, enabling pathogens to survive by escaping from lysozymes and toxic free radicals. This observation provides a new avenue for the development of anti-TB drugs.

Hypermucoviscosity associated with Klebsiella pneumoniae-mediated invasive syndrome: a prospective cross-sectional study in Taiwan

2010-05-26

Summary: Objectives: To investigate the association between Klebsiella pneumoniae-mediated invasive syndrome and underlying diseases in patients and/or K. pneumoniae characteristics, including the rmpA, rmpA2, and magA genes, capsular polysaccharide (cps) K1 or K2 serotypes, hypermucoviscosity (HV) phenotype, and extended-spectrum β-lactamase (ESBL) production.Methods: This was a prospective cross-sectional study.Results: The invasive syndrome was detected in 19 of 91 patients (20.9%) with K. pneumoniae infections, and diabetes mellitus was the most common underlying disease (9 of 19). The presence of rmpA or rmpA2 was found in 91.4% of the 35 isolates with the HV phenotype, while in only 17.9% of the 56 isolates without HV phenotype. Multivariate logistic regression analysis showed that the HV phenotype was an independent risk factor for K. pneumoniae-mediated invasive syndrome (odds ratio (OR) 58.24, 95% confidence interval (CI) 7.23–468.87; p < 0.001) and was negatively associated with ESBL production (OR 0.042, 95% CI 0.005–0.331; p=0.003). Binary logistic regression analysis revealed that the invasive syndrome was not influenced by the presence of diabetes mellitus among patients infected with K. pneumoniae positive for the rmpA or rmpA2 gene, HV phenotype, or cps K1/K2 serotype.Conclusions: The HV phenotype of K. pneumoniae contributes to invasive syndrome and is a negative predictor for K. pneumoniae acquisition of ESBLs.

Epidemiological trends and the effect of airport fever screening on prevention of domestic dengue fever outbreaks in Taiwan, 1998–2007

Mei-Mei Kuan, Ting Lin, Jen-Hsiang Chuang, Ho-Sheng Wu — 2010-06-21

Summary: Objective: This study aimed to examine the epidemiological trends in dengue infection and the impact of imported cases and airport fever screening on community transmission in Taiwan, a dengue non-endemic island.Methods: All of the dengue case data were obtained from the surveillance system of the Taiwan Center for Disease Control and were analyzed by Pearson correlations, linear regression, and geographical information system (GIS)-based mapping. The impact of implementing airport fever screening was evaluated using the Student's t-test and two-way analysis of variance.Results: A total of 10 351 dengue cases, including 7.1% of imported cases were investigated between 1998 and 2007. The majority of indigenous dengue cases (98.5%) were significantly clustered in southern Taiwan; 62.9% occurred in the metropolitan areas. The seasonality of dengue cases showed a peak from September to November. Airport fever screening was successful in identifying 45% (244/542 ; 95% confidence interval 33.1–57.8%) of imported dengue cases with fever. However, no statistical difference was found regarding the impact on community transmission when comparing the presence and absence of airport fever screening.Conclusions: Our results show that airport fever screening had a positive effect on partially blocking the local transmission of imported dengue cases, while those undetected cases due to latent or asymptomatic infection would be the source of new dengue outbreaks each year.

Treatment interruptions among patients with tuberculosis in Russian TB hospitals

2010-06-03

Summary: Objective: To evaluate risk factors for in-patient treatment interruptions (TIs) in Russian tuberculosis (TB) hospitals.Methods: The regional case-based registers for all TB patients registered in the main regional TB hospitals were analyzed for the period 1993–2002. Multivariable analysis of risk factors for TIs was performed using logistic regression. The prediction rule was developed based on the final multivariable model coefficients obtained from analysis of the largest (Lipetsk) database.Results: During the study period, 18–50% of new cases and 36–56% of retreatment cases had interrupted in-patient treatment. In multivariate analysis, independent predictors of treatment interruption included: male gender (odds ratios (ORs) 1.5–2.3), age group 25–50 years (ORs 1.5–1.7), alcohol abuse (ORs 1.8–4.0), imprisonment history (ORs 1.3–2.5), unemployment (ORs 1.1–2.8), being a retreatment case (ORs 1.3–2.5), and having severe forms of TB (1.4–4.0); factors protective from interruption included urban residence (ORs 0.7–0.9) and having concomitant diseases (ORs 0.6–0.8). Based on the Lipeck model, new TB cases from the four regions were divided into low, high, and very high risk groups. Proportions of TI were approximately 20–35% in the low risk group, approximately 60–75% in the high risk group, and approximately 75–85% in the very high risk group (except Orel).Conclusions: We have described the independent predictors of patient TI, and a predictive rule for the in-patient TB treatment phase interruptions has been developed. Treatment interruption is a significant obstacle in the success of the National Tuberculosis Control Program in Russia. Interventions targeted at the high risk groups should be implemented in order to prevent in-patient treatment interruption.

Evidence of vascular endothelial damage in Crimean-Congo hemorrhagic fever

2010-06-07

Summary: Background: Endothelial infection has an important role in the pathogenesis of Crimean-Congo hemorrhagic fever (CCHF). In this study, we investigated the causes of vascular endothelial damage in patients with CCHF.Methods: This prospective case-controlled study was carried out at Ankara Numune Education and Research Hospital between April and September 2007. Seventy-five patients with a laboratory-confirmed diagnosis of CCHF and 88 healthy controls were enrolled in the study. Serum levels of soluble cell adhesion molecules (sICAM-1, sVCAM-1, sE-selectin, sP-selectin, sL-selectin), vascular endothelial growth factor (VEGF), and macrophage migration inhibitory factor (MIF) were investigated in these patients by quantitative sandwich ELISA technique.Results: In the patient group, serum levels of sVCAM-1, sL-selectin and MIF were significantly higher than in the control group; serum levels of sICAM-1, sP-selectin, sE-selectin, and VEGF were significantly lower than in the control group. Serum levels of sVCAM-1 and sICAM-1 were significantly higher in severe cases than in non-severe cases, whereas the serum level of VEGF was significantly lower. sVCAM-1 was significantly higher in non-survivors than in survivors, while serum VEGF was significantly lower in non-survivors. The optimum cut-offs of sVCAM-1 and VEGF for the prediction of mortality were 205 ng/ml and 125 ng/ml, respectively. At these cut-offs, sVCAM-1 and VEGF had a sensitivity of 100% and specificity of 42.5% and 54.5%, respectively, in identifying CCHF patients who would die from the disease. The positive predictive values were 19% and 23%, respectively; negative predictive values were 100% for both.Conclusion: Endothelial activation can affect the course of CCHF, and vascular endothelial damage is probably indirect. Further studies are needed for general conclusions to be drawn.

Epidemiology of invasive pneumococcal infection in children aged five years and under in Saudi Arabia: a five-year retrospective surveillance study

2010-06-07

Summary: Background: The epidemiology of invasive pneumococcal disease (IPD) in children aged ≤5 years in Saudi Arabia has not been described. We conducted a retrospective surveillance study to describe the epidemiology of IPD in the population of children aged ≤5 years served by the National Guard Health Affairs hospitals in central and western regions of Saudi Arabia.Methods: We reviewed the medical records of children ≤5 years old admitted to the King Abdulaziz Medical City hospitals in Riyadh and Jeddah with pneumococcal infections for the period January 1999 through December 2003. Only microbiologically confirmed IPD cases (meningitis or bacteremia) were included in the analysis.Results: A total of 82 IPD cases, 19 (23.2%) meningitis and 63 (76.8%) bacteremia, were diagnosed during the five-year period. Of these, 12.2% (10/82) died, with a case-fatality slightly but insignificantly higher in cases of meningitis (15.8%) than bacteremia (11.1%). The average annual IPD incidence was 17.4 per 100 000 (4.0 for meningitis and 13.4 for bacteremia). The incidence was roughly similar in males and females (18.3 and 16.6, respectively; p=0.663) and was almost 4-fold higher in the first year of life compared to the next four years (40.6 and 11.5, respectively; p<0.001). The average annual IPD mortality was 2.1 per 100 000 and was higher in the first year of life compared to the next four years (5.2 and 1.3 , respectively; p=0.043).Conclusions: In the pre-vaccination era (1999–2003) in Saudi Arabia, IPD incidence was comparable to the pre-vaccination incidence rates from many industrialized countries, with children aged ≤1 year suffering the highest IPD risk among those aged ≤5 years.

Pulmonary tuberculosis: a public health problem amongst the Saharia, a primitive tribe of Madhya Pradesh, Central India

2010-06-04

Summary: Objectives: To estimate the prevalence of pulmonary tuberculosis (TB) disease amongst the Saharia, a ‘primitive’ tribe of Madhya Pradesh, Central India.Methods: A community-based cross-sectional TB prevalence survey was undertaken in the Saharia, a ‘primitive’ tribal community of Madhya Pradesh. A representative random sample of villages predominated by tribal populations was chosen from the selected block of Sheopur District. All eligible individuals were screened for chest symptoms related to TB. Sputum samples were collected from all eligible individuals, transported to the laboratory, and examined by Ziehl–Neelsen smear microscopy and solid media culture methods.Results: Of the 11 468 individuals eligible for screening, 11 116 (96.9%) were screened for symptoms. The overall prevalence of pulmonary TB disease was 1518 per 100 000 population. Prevalence increased with age and the trend was statistically significant (p<0.001). The prevalence of pulmonary TB was also significantly higher in males (2156/100 000) than females (933/100 000) (p<0.001).Conclusion: The findings suggest that TB disease remains a major public health problem in the Saharia ‘primitive’ tribal community of Madhya Pradesh, Central India.

Previous treatment in predicting drug-resistant tuberculosis in an area bordering East London, UK

Mark Melzer, Nidhi Gupta, Irene Petersen, Sue Cook, Bridget Hall — 2010-06-14

Summary: Objectives: To determine the utility of ‘risk assessment’ in selecting Mycobacterium tuberculosis isolates for rifampin resistance or rpoB genotyping compared to ‘non-selectively’ genotyping all isolates. Secondly, we examined the association between past treatment and drug resistance.Methods: From January 2003 to December 2006, demographic, clinical, and laboratory data were prospectively collected on patients with laboratory-confirmed tuberculosis (TB). On the basis of past treatment for active TB infection or known exposure to drug-resistant TB, selected samples were sent to a mycobacterial reference laboratory for rpoB genotyping. A multivariable logistic regression model was developed to examine the association between past treatment and drug resistance, adjusted for other factors. Sensitivity, specificity, and negative and positive predictive values of past treatment as a predictor for drug resistance were determined.Results: There were 392 patient episodes of culture-proven TB. Thirty-three drug-resistant isolates were cultured from 30 patients: 29 (87.9%) were isoniazid-resistant, three (9.1%) were multidrug-resistant (MDR), and one (3.0%) was rifampin mono-resistant. One patient with isoniazid resistance developed recurrent disease, and two isolates, initially isoniazid-resistant, mutated and became MDR TB. Based on risk assessment, rpoB genotyping was performed on 19 samples, and two (10.5%) had mutations that predicted multiple drug resistance. Although for MDR TB, a past history of treatment predicted two out of three patients with acquired resistance, adjusted analysis did not demonstrate a significant association between previous treatment of active TB and drug resistance (odds ratio 1.5, 95% confidence interval (CI) 0.4–5.6). The positive predictive value of past treatment as a predictor for drug resistance was 12.0% (95% CI 2.6–31.2%).Conclusion: Although numbers of MDR TB were too small to draw meaningful conclusions, past treatment may be useful in selecting samples for rpoB genotyping. Overall, previous treatment had a low positive predictive value for drug resistance in an area bordering East London.

Ventilator-associated pneumonia: role of colonizers and value of routine endotracheal aspirate cultures

2010-06-09

Summary: Objectives: To determine the role of colonizers in the causation of ventilator-associated pneumonia (VAP) and the value of routine pre-VAP endotracheal aspirate (EA) cultures in appropriately treating VAP.Methods: A prospective observational cohort study was conducted over a period of 15 months. Two hundred patients on mechanical ventilation for>48h were studied.Results: Acinetobacter spp (33.7%) and Pseudomonas spp (29.8%) were the most common colonizers. Of the 200 patients, 36 developed VAP. In 20 VAP patients, the pre-VAP EA culture-based strategy was not useful. However, in the remaining 16 VAP patients, a pre-VAP EA culture-based strategy would have appropriately treated 13 (81%; 95% confidence interval (CI) 62–100%), in comparison to only nine (56%; 95% CI 32–80%) by the American Thoracic Society (ATS) strategy. The seven patients in whom the ATS guidelines were inappropriate had Acinetobacter spp and Pseudomonas spp resistant to the higher antibiotics recommended by the ATS for multidrug-resistant pathogens. The positive predictive values of Pseudomonas aeruginosa, Acinetobacter baumannii, and methicillin-resistant Staphylococcus aureus (MRSA) isolated from pre-VAP EA cultures were 88%, 83%, and 100%, respectively.Conclusion: VAP patients should be treated based on ATS guidelines, but whenever P. aeruginosa, A. baumannii, and MRSA are isolated from pre-VAP EA cultures, the initial antibiotic therapy should be extended to treat these.