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1.  Arcanobacterium haemolyticum associated with pyothorax: case report 
Arcanobacterium haemolyticum has an established role in the etiology of human pharyngitis. There are increasing reports of systemic infections caused by this organism. From India, we report the first case of Arcanobacterium haemolyticum causing pyothorax in an immunocompetent adolescent male patient. The probable mode of infection is also discussed. The role of A. hemolyticum as an animal pathogen needs further study.
doi:10.1186/1471-2334-5-68
PMCID: PMC1236925  PMID: 16144543
3.  Prevalence and distribution of high-risk human papilloma virus (HPV) types in invasive squamous cell carcinoma of the cervix and in normal women in Andhra Pradesh, India 
Background
Despite the high incidence of cervical cancer reported from India, large scale population based studies on the HPV prevalence and genotype distribution are very few from this region. In view of the clinical trials for HPV vaccine taking place in India, it is of utmost importance to understand the prevalence of HPV genotypes in various geographical regions of India. We investigated the genotype distribution of high-risk HPV types in squamous cell carcinomas and the prevalence of high-risk HPV in cervicovaginal samples in the southern state of Andhra Pradesh (AP), India.
Methods
HPV genotyping was done in cervical cancer specimens (n = 41) obtained from women attending a regional cancer hospital in Hyderabad. HPV-DNA testing was also done in cervicovaginal samples (n = 185) collected from women enrolled in the cervical cancer screening pilot study conducted in the rural community, of Medchal Mandal, twenty kilometers away from Hyderabad.
Results
High-risk HPV types were found in 87.8% (n = 36/41) of the squamous cell carcinomas using a PCR-based line blot assay. Among the HPV positive cancers, the overall type distribution of the major high-risk HPV types was as follows: HPV 16 (66.7%), HPV 18 (19.4%), HPV 33 (5.6%), HPV 35 (5.6%), HPV 45 (5.6%), HPV 52 (2.8%), HPV 58(2.8%), HPV 59(2.8%) and HPV 73 (2.8%). Women participating in the community screening programme provided both a self-collected vaginal swab and a clinician-collected cervical swab for HPV DNA testing. Primary screening for high risk HPV was performed using the Digene Hybrid Capture 2 (hc2) assay. All hc2 positive samples by any one method of collection were further analyzed using the Roche PCR-based line blot for genotype determination. The prevalence of high risk HPV infection in this community-based screening population was 10.3% (19/185) using the clinician-collected and 7.0% (13/185) using the self-collected samples. The overall agreement between self-collected and clinician-collected samples was 92%; however among HPV-positive specimens, the HPV agreement was only moderate (39.1%). The most frequently detected HPV types in the Medchal community are HPV 52 and 16.
Conclusion
Our results suggest that the HPV type distribution in both cervical cancer tissues and in a general screening population from Andhra Pradesh is similar to that reported in India and other parts of the world. We also conclude that an effective vaccine targeting HPV 16 will reduce the cervical cancer burden in AP.
doi:10.1186/1471-2334-5-116
PMCID: PMC1345691  PMID: 16371167
4.  A randomised controlled trial of the effects of albendazole in pregnancy on maternal responses to mycobacterial antigens and infant responses to bacille Calmette-Guérin (BCG) immunisation [ISRCTN32849447] 
Background
Maternal schistosomiasis and filariasis have been shown to influence infant responses to neonatal bacille Calmette-Guérin (BCG) immunisation but the effects of maternal hookworm, and of de-worming in pregnancy, are unknown.
Methods
In Entebbe, Uganda, we conducted a randomised, double-blind, placebo-controlled trial of a single dose of 400 mg of albendazole in the second trimester of pregnancy. Neonates received BCG. Interferon-gamma (IFN-γ) and interleukin (IL)-5 responses to a mycobacterial antigen (crude culture filtrate proteins (CFP) of Mycobacterium tuberculosis) were measured in a whole blood assay. We analysed results for binary variables using χ2 tests and logistic regression. We analysed continuous variables using Wilcoxon's tests.
Results
Maternal hookworm was associated with reduced maternal IFN-γ responses to CFP (adjusted odds ratio for IFN-γ > median response: 0.14 (95% confidence interval 0.02–0.83, p = 0.021). Conversely, maternal hookworm was associated with subsequent increased IFN-γ responses in their one-year-old infants (adjusted OR 17.65 (1.20–258.66; p = 0.013)). Maternal albendazole tended to reduce these effects.
Conclusion
Untreated hookworm infection in pregnancy was associated with reduced maternal IFN-γ responses to mycobacterial antigens, but increased responses in their infants one year after BCG immunisation. The mechanisms of these effects, and their implications for protective immunity remain, to be determined.
doi:10.1186/1471-2334-5-115
PMCID: PMC1352364  PMID: 16371154
5.  The CD14 functional gene polymorphism -260 C>T is not involved in either the susceptibility to Chlamydia trachomatis infection or the development of tubal pathology 
Background
The functional polymorphism -260 C>T in the LPS sensing TLR4 co-receptor CD14 gene enhances the transcriptional activity and results in a higher CD14 receptor density. Individuals carrying the T/T genotype also have significantly higher serum levels of soluble CD14. The T allele of this polymorphism has recently been linked to Chlamydia pneumoniae infection. We investigated the role of the CD14 -260 C>T polymorphism in the susceptibility to and severity (defined as subfertility and/or tubal pathology) of C. trachomatis infection in Dutch Caucasian women.
Methods
The different CD14 -260 C>T genotypes were assessed by PCR-based RFLP analysis in three cohorts: 1) A cohort (n = 576) of women attending a STD clinic, 2) a cohort (n = 253) of women with subfertility, and 3) an ethnically matched control cohort (n = 170). The following variables were used in the analysis: In cohort 1 the CT-DNA status, CT IgG serology status, self-reported symptoms and in cohort 2, the CT IgG serology status and the tubal status at laparoscopy.
Results
In the control cohort the CC, CT and TT genotype distribution was: 28.2%, 48.2%, and 23.5% respectively. No differences were found in the overall prevalence of CD14 -260 genotypes (28.1%, 50.7%, and 21.2%) in cohort 1 when compared to the control cohort. Also no differences were observed in women with or without CT-DNA, with or without serological CT responses, with or without symptoms, or in combinations of these three variables. In subfertile women with tubal pathology (cohort 2, n = 50) the genotype distribution was 28.0%, 48.0%, and 24.0% and in subfertile women without tubal pathology (n = 203), 27.6%, 49.3% and 23.2%. The genotype distribution was unchanged when CT IgG status was introduced in the analyses.
Conclusion
The CD14 -260 C>T genotype distributions were identical in all three cohorts, showing that this polymorphism is not involved in the susceptibility to or severity of sequelae of C. trachomatis infection.
doi:10.1186/1471-2334-5-114
PMCID: PMC1351185  PMID: 16368002
6.  Balance of IL-10 and Interferon-γ plasma levels in human visceral leishmaniasis: Implications in the pathogenesis 
Background
Leishmaniasis remains a serious public health problem in several parts of the developing world. Effective prophylactic measurements are hampered by imprecise comprehension of different aspects of the disease, including its immunoregulation. A better comprehension of immunoregulation in human VL may be useful both for designing and evaluating immunoprophylaxis.
Methods
To explore immunoregulatory mechanisms, 20 visceral leishmaniasis (VL) patients were evaluated during active disease and at different periods up to one year after treatment determining their plasma cytokine levels, clinical parameters (palpable spleen and liver) and antibody levels.
Results
Elevated plasma levels of IFN-γ and of IL-12 p40 were observed during active disease, significantly decreasing after treatment whereas in vitro Leishmania antigen-stimulated IFN-γ production by PBMC exhibited an inverse pattern being low during disease and increasing steadily thereafter. Absence of IFN-γ activity is a hallmark of VL. The main candidate for blunting IFN-γ activity is IL-10, a cytokine highly elevated in plasma with sharp decrease after treatment. Activity of IL-10 is inferred by high levels of anti-Leishmania specific IgG1 and IgG3. TGF-β had elevated total, but not of active, levels lessening the likelihood of being the IFN-γ counterpart. Spleen or liver size presented a steady decrease but return to normal values at only 120 days after treatment. Anti-Leishmania IgG (total and subclasses) levels and DTH or Leishmania-stimulated lymphocyte proliferation conversion to positive also present a slow decrease after treatment. IL-6 plasma levels were elevated in only a few patients.
Conclusion
Taken together our results suggest that IFN-γ and IL-10 are the molecules most likely involved in determining fate of disease. After treatment, there is a long delay before the immune profile returns to normal what precludes using plasma cytokine levels as criteria of cure as simpler clinical evaluations, as a palpable spleen or liver, can be used.
doi:10.1186/1471-2334-5-113
PMCID: PMC1343567  PMID: 16364177
7.  The role and performance of chest X-ray for the diagnosis of tuberculosis: A cost-effectiveness analysis in Nairobi, Kenya 
Background
The objective of this study was to establish 1) the performance of chest X-ray (CXR) in all suspects of tuberculosis (TB), as well as smear-negative TB suspects and 2) to compare the cost-effectiveness of the routine diagnostic pathway using Ziehl-Neelsen (ZN) sputum microscopy followed by CXR if case of negative sputum result (ZN followed by CXR) with an alternative pathway using CXR as a screening tool (CXR followed by ZN).
Methods
From TB suspects attending a chest clinic in Nairobi, Kenya, three sputum specimens were examined for ZN and culture (Lowenstein Jensen). Culture was used as gold standard. From each suspect a CXR was made using a four point scoring system: i: no pathology, ii: pathology not consistent for TB, iii: pathology consistent for TB and iv: pathology highly consistent for TB. The combined score i + ii was labeled as "no TB" and the combined score iii + iv was labeled as "TB". Films were re-read by a reference radiologist. HIV test was performed on those who consented. Laboratory and CXR costs were used to compare for cost-effectiveness.
Results
Of the 1,389 suspects enrolled, for 998 (72%) data on smear, culture and CXR was complete. 714 films were re-read, showing a 89% agreement (kappa value = 0.75 s.e.0.037) for the combined scores "TB" or "no-TB". The sensitivity/specificity of the CXR score "TB" among smear-negative suspects was 80%/67%. Using chest CXR as a screening tool in all suspects, sensitivity/specificity of the score "any pathology" was 92%, respectively 63%. The cost per correctly diagnosed case was for the routine process $8.72, compared to $9.27 using CXR as screening tool. When costs of treatment were included, CXR followed by ZN became more cost-effective.
Conclusion
The diagnostic pathway ZN followed by CXR was more cost-effective as compared to CXR followed by ZN. When cost of treatment was also considered CXR followed by ZN became more cost-effective. The low specificity of chest X-ray remains a subject of concern. Depending whether CXR was performed on all suspects or on smear-negative suspects only, 22%–45% of patients labeled as "TB" had a negative culture. The introduction of a well-defined scoring system, clinical conferences and a system of CXR quality control can contribute to improved diagnostic performance.
doi:10.1186/1471-2334-5-111
PMCID: PMC1326228  PMID: 16343340
8.  Diagnostic and treatment delay among pulmonary tuberculosis patients in Ethiopia: a cross sectional study 
Background
Delayed diagnosis and treatment of tuberculosis (TB) results in severe disease and a higher mortality. It also leads to an increased period of infectivity in the community. The objective of this study was to determine the length of delays, and analyze the factors affecting the delay from onset of symptoms of pulmonary tuberculosis (PTB) until the commencement of treatment.
Methods
In randomly selected TB management units (TBMUs), i.e. government health institutions which have diagnosing and treatment facilities for TB in Amhara Region, we conducted a cross sectional study from September 1-December 31/2003. Delay was analyzed from two perspectives, 1. Period between onset of TB symptoms to first visit to any health provider (health seeking period), and from the first health provider visit to initiation of treatment (health providers' delay), and 2. Period between onset of TB symptoms to first visit to a medical provider (patients' delay), and from this visit to commencement of anti-TB treatment (health systems' delay). Patients were interviewed on the same date of diagnosis using a semi-structured questionnaire. Logistics regression analysis was applied to analyze the risk factors of delays.
Results
A total of 384 new smear positive PTB patients participated in the study. The median total delay was 80 days. The median health-seeking period and health providers' delays were 15 and 61 days, respectively. Conversely, the median patients' and health systems' delays were 30 and 21 days, respectively. Taking medical providers as a reference point, we found that forty eight percent of the subjects delayed for more than one month. Patients' delays were strongly associated with first visit to non-formal health providers and self treatment (P < 0.0001). Prior attendance to a health post/clinic was associated with increased health systems' delay (p < 0.0001).
Conclusion
Delay in the diagnosis and treatment of PTB is unacceptably high in Amhara region. Health providers' and health systems' delays represent the major portion of the total delay. Accessing a simple and rapid diagnostic test for TB at the lowest level of health care facility and encouraging a dialogue among all health providers are imperative interventions.
doi:10.1186/1471-2334-5-112
PMCID: PMC1326202  PMID: 16343350
9.  Bacterial isolates from blood cultures of children with suspected septicaemia in Calabar, Nigeria 
Background
Septicaemia is a common cause of morbidity and mortality among children in the developing world. This pattern has changed little in the past decade. Physical signs and symptoms, though useful in identifying possible cases have limited specificity. Definitive diagnosis is by bacteriologic culture of blood samples to identify organisms and establish antibiotic susceptibility. These results are usually not available promptly. Therefore a knowledge of epidemiologic and antimicribial susceptibility pattern of common pathogens is useful for prompt treatment of patients. This report highlights the pattern of bacterial isolates in our environment from a retrospective study of our patients' records.
Methods
One thousand, two hundred and one blood samples were analysed from children aged 0–15 years, admitted into the children's wards of the University of Calabar Teaching Hospital, Calabar, Nigeria with features suggesting septicaemia. Samples were collected under aseptic conditions and cultured for aerobic and anaerobic organisms. Isolates were identified using bacteriologic and biochemical methods and antibiotic sensitivity determined by agar diffusion method using standard antibiotic discs.
Results
Bacteria was isolated in 552 (48.9%) of samples with highest rates among newborns (271 : 50.8). The most frequent isolates were Staphylococcal aureus (48.7%) and Coliforms (23.4%). Results showed high susceptibilities to the Cephalosporins (Ceftriazone- 100%:83.2%, Cefuroxime-100%:76.5%) and Macrolides (Azithromycin-100%:92.9%) for S. aureus and coliforms respectively. This study underscores the importance of septicaemia as a common cause of febrile illness in children and provides information on common prevalent aetiologic agents and drug susceptibilities of the commonest pathogens.
Conclusion
Staphylococcus aureus and coliforms were the leading causes of septicaemia in children in this locality, and the third generation cephalosporins and azithromycin were shown to be effective against these pathogens.
doi:10.1186/1471-2334-5-110
PMCID: PMC1325246  PMID: 16336657
10.  Coxiella burnetii vascular graft infection 
Background
Coxiella burnetii, the causative agent of Q fever, may cause culture-negative vascular graft infections. Very few cases of C. burnetii infection of a vascular graft have been reported. All were diagnosed by serology.
Case presentation
We report the first case of Coxiella burnetii vascular graft infection diagnosed by broad-range PCR and discuss the diagnostic approaches and treatment strategies of chronic C. burnetii infection.
Conclusion
C. burnetii should be considered as etiological agent in patients with a vascular graft and fever, abdominal pain, and laboratory signs of inflammation, with or without exposure history. Broad-range PCR should be performed on culture-negative surgical samples in patients with suspected infection of vascular graft.
doi:10.1186/1471-2334-5-109
PMCID: PMC1325236  PMID: 16336642
11.  High frequency of Human Cytomegalovirus DNA in the Liver of Infants with Extrahepatic Neonatal Cholestasis 
Background
Biliary atresia (BA) is the most severe hepatic disorder in newborns and its etiopathogenesis remains unknown. Viral involvement has been proposed, including the human cytomegalovirus (HCMV). The aims of the study were to use the polymerase chain reaction (PCR) to screen the liver tissue of infants with extrahepatic cholestasis for HCMV and to correlate the results with serological antibodies against HCMV and histological findings.
Methods
A retrospective study in a tertiary care setting included 35 patients (31 BA, 1 BA associated with a choledochal cyst, 2 congenital stenosis of the distal common bile duct and 1 hepatic cyst). HCMV serology was determined by ELISA. Liver and porta hepatis were examined histologically. Liver samples from infants and a control group were screened for HCMV DNA.
Results
Twelve patients had HCMV negative serology, 9 were positive for IgG antibodies and 14 were positive for IgG and IgM. Nine liver and seven porta hepatis samples were positive for HCMV DNA but none of the control group were positive (general frequency of positivity was 34.3% – 12/35). There was no correlation between HCMV positivity by PCR and the histological findings. The accuracy of serology for detecting HCMV antibodies was low.
Conclusion
These results indicate an elevated frequency of HCMV in pediatric patients with extrahepatic neonatal cholestasis. They also show the low accuracy of serological tests for detecting active HCMV infection and the lack of correlation between HCMV positivity by PCR and the histopathological changes.
doi:10.1186/1471-2334-5-108
PMCID: PMC1315325  PMID: 16321152
12.  Catheter-associated bacteremia by Mycobacterium senegalense in Korea 
Background
Rapidly growing mycobacteria is recognized as one of the causative agents of catheter-related infections, especially in immunocompromised hosts. To date, however, Mycobacterium senegalense, which was known as the principal pathogen of bovine farcy, has not been reported in human infection.
Case presentation
We describe the first case of human infection by M. senegalense, which has caused catheter-related bloodstream infection in a cancer patient in Korea. The microorganism was identified by the 16S rRNA gene, rpoB, and 16S-23S rRNA gene internal transcribed spacer (ITS) sequence analyses.
Conclusion
Our first report of catheter-associated bacteremia caused by M. senegalense suggests the zoonotic nature of this species and indicates the expansion of mycobacterial species relating to human infection. M. senegalense should be considered as one of the causes of human infections in the clinical practice.
doi:10.1186/1471-2334-5-107
PMCID: PMC1314895  PMID: 16307688
13.  Failure of levofloxacin treatment in community-acquired pneumococcal pneumonia 
Background
Streptococcus pneumoniae is the leading cause of community-acquired pneumonia (CAP). High global incidence of macrolide and penicillin resistance has been reported, whereas fluoroquinolone resistance is uncommon. Current guidelines for suspected CAP in patients with co-morbidity factors and recent antibiotic therapy recommend initial empiric therapy using one fluoroquinolone or one macrolide associated to other drugs (amoxicillin, amoxicillin/clavulanate, broad-spectrum cephalosporins). Resistance to fluoroquinolones is determined by efflux mechanisms and/or mutations in the parC and parE genes coding for topoisomerase IV and/or gyrA and gyrB genes coding for DNA gyrase. No clinical cases due to fluoroquinolone-resistant S. pneumoniae strains have been yet reported from Italy.
Case presentation
A 72-year-old patient with long history of chronic obstructive pulmonary disease and multiple fluoroquinolone treatments for recurrent lower respiratory tract infections developed fever, increased sputum production, and dyspnea. He was treated with oral levofloxacin (500 mg bid). Three days later, because of acute respiratory insufficiency, the patient was hospitalized. Levofloxacin treatment was supplemented with piperacillin/tazobactam. Microbiological tests detected a S. pneumoniae strain intermediate to penicillin (MIC, 1 mg/L) and resistant to macrolides (MIC >256 mg/L) and fluoroquinolones (MIC >32 mg/L). Point mutations were detected in gyrA (Ser81-Phe), parE (Ile460-Val), and parC gene (Ser79-Phe; Lys137-Asn). Complete clinical response followed treatment with piperacillin/tazobactam.
Conclusion
This is the first Italian case of community-acquired pneumonia due to a fluoroquinolone-resistant S. pneumoniae isolate where treatment failure of levofloxacin was documented. Molecular analysis showed a group of mutations that have not yet been reported from Italy and has been detected only twice in Europe. Treatment with piperacillin/tazobactam appears an effective means to inhibit fluoroquinolone-resistant strains of S. pneumoniae causing community-acquired pneumonia in seriously ill patients.
doi:10.1186/1471-2334-5-106
PMCID: PMC1308815  PMID: 16307682
14.  Acquired homotypic and heterotypic immunity against oculogenital Chlamydia trachomatis serovars following female genital tract infection in mice 
Background
Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen causing female genital tract infection throughout the world. Reinfection with the same serovar, as well as multiple infections with different serovars, occurs in humans. Using a murine model of female C. trachomatis genital tract infection, we determined if homotypic and/or heterotypic protection against reinfection was induced following infection with human oculogenital strains of C. trachomatis belonging to two serovars (D and H) that have been shown to vary significantly in the course of infection in the murine model.
Methods
Groups of outbred CF-1 mice were reinfected intravaginally with a strain of either serovar D or H, two months after initial infection with these strains. Cellular immune and serologic status, both quantitative and qualitative, was assessed following initial infection, and the course of infection was monitored by culturing vaginal samples collected every 2–7 days following reinfection.
Results
Serovar D was both more virulent (longer duration of infection) and immunogenic (higher level of circulating and vaginal IgG and higher incidence of IgA in vaginal secretions) in the mouse genital tract. Although both serovars induced cross-reacting antibodies during the course of primary infection, prior infection with serovar H resulted in only a slight reduction in the median duration of infection against homotypic reinfection (p ~ 0.10), while prior infection with serovar D resulted in significant reduction in the median duration of infection against both homotypic (p < 0.01) and heterotypic reinfection (p < 0.01) when compared to primary infection in age and conditions matched controls.
Conclusion
Serovar D infection resulted in significant homotypic and heterotypic protection against reinfection, while primary infection with serovar H resulted in only slight homotypic protection. In addition to being the first demonstration of acquired heterotypic immunity between human oculogenital serovars, the differences in the level and extent of this immunity could in part explain the stable difference in serovar prevalence among human isolates.
doi:10.1186/1471-2334-5-105
PMCID: PMC1318460  PMID: 16293190
15.  Mechanisms of escape phenomenon of spinal cord and brainstem in human rabies 
Background
Rabies virus preferentially involves brainstem, thalamus and spinal cord in human furious and paralytic rabies beginning in the early stage of illness. Nevertheless, rabies patient remains alert until the pre-terminal phase. Weakness of extremities develops only when furious rabies patient becomes comatose; whereas peripheral nerve dysfunction is responsible for weakness in paralytic rabies.
Methods
Evidence of apoptosis and mitochondrial outer membrane permeabilization in brain and spinal cord of 10 rabies patients was examined and these findings were correlated with the presence of rabies virus antigen.
Results
Although apoptosis was evident in most of the regions, cytochrome c leakage was relatively absent in spinal cord of nearly all patients despite the abundant presence of rabies virus antigen. Such finding was also noted in brainstem of 5 patients.
Conclusion
Cell death in human rabies may be delayed in spinal cord and the reticular activating system, such as brainstem, thus explaining absence of weakness due to spinal cord dysfunction and preservation of consciousness.
doi:10.1186/1471-2334-5-104
PMCID: PMC1310615  PMID: 16288653
16.  "Bacterial Meningitis in children and adolescents: an observational study based on the national surveillance system" 
Background
Bacterial meningitis is a group of life threatening infections that mostly affect children and adolescents, and may be the cause of severe neurological sequelae. Cuba has implemented massive vaccination programmes against both Neisseria meningitidis (serogroup C in 1979 and B in 1987), and Haemophilus influenzae type b (1999), two of the main causal pathogens. We described and discussed some epidemiological aspects of the current status of bacterial meningitis to learn from the Cuban experience.
Methods
A nationwide observational study on children and adolescents from 1 to 18 years old was carried out from 1998 to 2003, estimating the incidence and case-fatality rate by age group and causal pathogens, as well as the seasonality and frequency of overcrowded dormitories. The association between disease and attendance to day care centres or boarding schools was estimated by using relative risk (Chi-squared test and Fisher Exact Test).
Results
The overall number of cases was 1023; the incidence ranged from 3.4 to 8.5 per 100 000 population, with the higher figures in children 1–5 years old (16.8 per 100 000 population). Streptococcus pneumoniae, Haemophilus influenzae type b and Neisseria meningitidis serogroup B were the main identified agents. The average case-fatality rate was 10.5% and the most lethal agents were Streptococcus pneumoniae (27%) and Haemophilus influenzae type b (10.7%). Overall percentage of cases who slept in overcrowded dormitories was 15%, reaching 30.6% in adolescents. Seasonality was only evident among meningococcal meningitis cases between September–October. The attendance to boarding high school showed an association with disease only in 1998 and 1999 (RR = 2.1; p > 0.05).
Conclusion
The highest incidence of bacterial meningitis was observed among children from 1–5 years old. Pneumococcus was both the leading causal and the most lethal agent. Sleeping in overcrowded dormitories was more frequent among adolescents. No strong association was observed between the bacterial meningitis and attendance to day care centres or boarding schools. The incidence of bacterial meningitis in Cuba is declining after massive vaccination programmes against Neisseria meningitidis serogroup B and C and Haemophilus influenzae type b through a national immunisation program.
doi:10.1186/1471-2334-5-103
PMCID: PMC1299326  PMID: 16288649
17.  Correlation between human papillomavirus infection and bladder transitional cell carcinoma 
Background
To determine the association of human papillomavirus infection (HPV) and transitional cell carcinoma (TCC).
Methods
Using polymerase chain reaction, fifty-nine bladder tissue specimens of patients with transitional cell carcinoma of bladder compared with 20 bladder samples of cases with non-neoplastic disorders.
Results
Male to female ratio was similar in the two groups (50/9 vs. 16/4, P = 0.62). Mean age was 67 ± 10.8 years and 52 ± 20.3 years in the case and control groups, respectively (P = 0.6). Of the 59 tissue specimens with diagnosis of transitional cell carcinoma, HPV DNA was detected in 21 (35.6%) samples, while it was present in only one sample (5%) in the control group (P = 0.008). HPV18 was the most common type of virus with the incidence rate of 17/21(81%).
Conclusion
HPV might play a causative role in transitional cell carcinoma of bladder in our geographic area.
doi:10.1186/1471-2334-5-102
PMCID: PMC1310619  PMID: 16274490
18.  Adjunctive corticosteroids for Pneumocystis jiroveci pneumonia in patients with HIV infection: a meta-analysis of randomised controlled trials 
Background
The objective of this study was to review the effects of adjunctive corticosteroids on overall mortality and the need for mechanical ventilation in HIV-infected patients with Pneumocystis jiroveci pneumonia (PCP) and substantial hypoxemia (arterial oxygen partial pressure <70 mmHg or alveolar-arterial gradient >35 mmHg on room air).
Methods
We conducted a systematic search of the literature for randomised trials published up to December 2004. Selected trials compared adjunctive corticosteroids with placebo or usual care in HIV-infected patients with PCP and reported mortality data. Two teams of reviewers independently evaluated the methodology and extracted data from each primary study.
Results
Six studies were included in the meta-analysis. Risk ratios for overall mortality for adjunctive corticosteroids were 0.54 (95% confidence interval [CI], 0.38–0.79) at 1 month and 0.67 (95% CI, 0.49–0.93) at 3–4 months of follow-up. Numbers needed to treat, to prevent 1 death, are 9 patients in a setting without highly active antiretroviral therapy (HAART) available and 22 patients with HAART available. Only the 3 largest trials provided data on the need for mechanical ventilation with a risk ratio of 0.37 (95% CI, 0.20–0.70) in favour of adjunctive corticosteroids.
Conclusion
The number and size of trials investigating adjunctive corticosteroids for HIV-infected patients with PCP is small, but our results suggest a beneficial effect for patients with substantial hypoxemia.
doi:10.1186/1471-2334-5-101
PMCID: PMC1309617  PMID: 16271157
19.  Epidural abscess caused by Streptococcus milleri in a pregnant woman 
Background
Bacteria in the Streptococcus milleri group (S. anginosus, S. constellatus, and S. intermedius) are associated with bacteremia and abscess formation. While most reports of Streptococcus milleri group (SMG) infection occur in patients with underlying medical conditions, SMG infections during pregnancy have been documented. However, SMG infections in pregnant women are associated with either neonatal or maternal puerperal sepsis. Albeit rare, S. milleri spinal-epidural abscess in pregnancy has been reported, always as a complication of spinal-epidural anesthesia. We report a case of spinal-epidural abscess caused by SMG in a young, pregnant woman without an antecedent history of spinal epidural anesthesia and without any underlying risk factors for invasive streptococcal disease.
Case presentation
A 25 year old pregnant woman developed neurological symptoms consistent with spinal cord compression at 20 weeks gestation. She underwent emergency laminectomy for decompression and was treated with ceftriaxone 2 gm IV daily for 28 days. She was ambulatory at the time of discharge from the inpatient rehabilitation unit with residual lower extremity weakness.
Conclusion
To our knowledge, this is the first reported case of a Streptococcus milleri epidural abscess in a healthy, pregnant woman with no history of epidural anesthesia or invasive procedures. This report adds to the body of literature on SMG invasive infections. Treatment of SMG spinal-epidural abscess with neurologic manifestations should include prompt and aggressive surgical decompression coupled with targeted anti-infective therapy.
doi:10.1186/1471-2334-5-100
PMCID: PMC1289282  PMID: 16269087
20.  The trend of susceptibilities to amphotericin B and fluconazole of Candida species from 1999 to 2002 in Taiwan 
Background
Candida species have various degrees of susceptibility to common antifungal drugs. The extent of resistance to amphotericin B and fluconazole of Candida glabrata isolates causing candidemia has been reported. Active surveillance may help us to monitor the trend of susceptibility to antifungal drugs and to determine if there is an emerging co-resistance to both drugs of Candida species, specifically, of C. glabrata in Taiwan.
Methods
The susceptibilities to amphotericin B and fluconazole of Candida species collected in 1999 and 2002 of the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) were determined by the microdilution method.
Results
The antifungal susceptibilities of 342 and 456 isolates collected from 11 hospitals participating in both TSARY 1999 and TSARY 2002, respectively, have been determined. The resistance rate to amphotericin B has increased from 0.3% in the TSARY1999 to 2.2% in the TSARY 2002. In contrast, the resistance rate to fluconazole has decreased from 8.8% to 2.2%. Nevertheless, significantly more C. glabrata isolates were not susceptible to fluconazole in the TSARY 2002 (47.4%) than that in the TSARY 1999 (20.8%). There were 9.8% and 11% of C. glabrata isolates having susceptible-dose dependent and resistant phenotype to fluconazole in the TSARY 1999, verse 45.3% and 2.1% in the TSARY 2002.
Conclusion
There was an increase of resistance rate to amphotericin B in C. glabrata. On the other hand, although the resistance rate to fluconazole has decreased, almost half of C. glabrata isolates were not susceptible to this drug. Hence, continuous monitoring the emerging of co-resistance to both amphotericin B and fluconazole of Candida species, specifically, of C. glabrata, will be an important early-warning system.
doi:10.1186/1471-2334-5-99
PMCID: PMC1298299  PMID: 16266438
21.  The changing epidemiology of pediatric aseptic meningitis in Daejeon, Korea from 1987 to 2003 
Background
Aseptic meningitis is a relatively frequent childhood disease and virologic data suggest that enteroviruses are the commonest etiologic agents. We evaluated the epidemiologic characteristics of aseptic meningitis in Daejeon, South Korea from 1987 to 2003.
Methods
2201 medical records of children with aseptic meningitis admitted to The Catholic University of Korea, Daejeon St Mary's Hospital were retrospectively analyzed.
Results
Outbreaks of aseptic meningitis were observed in 1990, 1993, 1996, 1997, 2001 and 2002. The age distribution of cases was relatively uniform, with a higher incidence in those aged < 1 year and 4–7 years. The male-to-female ratio was 2:1. There was a higher incidence of disease in the summer (May to August, 74.1% of total). Comparison of the largest epidemics in 1997 and 2002 showed significant differences in the incidence in those < 1 year (11.8% vs. 4.4%, respectively; P = 0.001). Neurologic sequelae were observed in 0.7% of the patients.
Conclusion
Aseptic meningitis, rare before the 1980s in Korea, has since become a common clinical entity. Since 1990, outbreaks of aseptic meningitis have occurred every 1 to 3 years in Daejeon in keeping with Korea-wide epidemics. The frequency of disease affecting children less than one year of age may reflect herd immunity to the epidemic strain.
doi:10.1186/1471-2334-5-97
PMCID: PMC1295587  PMID: 16262909
22.  Cerebrospinal fluid HIV infection and pleocytosis: Relation to systemic infection and antiretroviral treatment 
Background
Central nervous system (CNS) exposure to HIV is a universal facet of systemic infection. Because of its proximity to and shared barriers with the brain, cerebrospinal fluid (CSF) provides a useful window into and model of human CNS HIV infection.
Methods
Prospective study of the relationships of CSF to plasma HIV RNA, and the effects of: 1) progression of systemic infection, 2) CSF white blood cell (WBC) count, 3) antiretroviral therapy (ART), and 4) neurological performance. One hundred HIV-infected subjects were cross-sectionally studied, and 28 were followed longitudinally after initiating or changing ART.
Results
In cross-sectional analysis, HIV RNA levels were lower in CSF than plasma (median difference 1.30 log10 copies/mL). CSF HIV viral loads (VLs) correlated strongly with plasma VLs and CSF WBC counts. Higher CSF WBC counts associated with smaller differences between plasma and CSF HIV VL. CSF VL did not correlate with blood CD4 count, but CD4 counts <50 cells/μL associated with a low prevalence of CSF pleocytosis and large differences between plasma and CSF VL. CSF HIV RNA correlated neither with the severity of the AIDS dementia complex (ADC) nor abnormal quantitative neurological performance, although these measures were associated with depression of CD4 counts.
In subjects starting ART, those with lower CD4 counts had slower initial viral decay in CSF than in plasma. In all subjects, including five with persistent plasma viremia and four with new-onset ADC, CSF HIV eventually approached or reached the limit of viral detection and CSF pleocytosis resolved.
Conclusion
CSF HIV infection is common across the spectrum of infection and is directly related to CSF pleocytosis, though whether the latter is a response to or a contributing cause of CSF infection remains uncertain. Slowing in the rate of CSF response to ART compared to plasma as CD4 counts decline indicates a changing character of CSF infection with systemic immunological progression. Longer-term responses indicate that CSF infection generally responds well to ART, even in the face of systemic virological failure due to drug resistance. We present simple models to explain the differing relationships of CSF to plasma HIV in these settings.
doi:10.1186/1471-2334-5-98
PMCID: PMC1299327  PMID: 16266436
23.  High carriage rate of high-level penicillin-resistant Streptococcus pneumoniae in a Taiwan kindergarten associated with a case of pneumococcal meningitis 
Background
The Taiwan19F-14 Streptococcus pneumoniae clone and its variants are being found with increasing frequency in the Asia-Pacific region. A 5-year old child with S. pneumoniae meningitis caused by a high-level penicillin resistant strain (MIC = 4 μg/ml) was admitted to a hospital in southern Taiwan. We carried out a study to determine the potential source of this strain.
Methods
Nasopharyngeal cultures were obtained from all children attending the same kindergarten as the index case. To determine their relatedness all isolates were compared by serotype, antimicrobial susceptibility profile and pulsed field gel electrophoresis (PFGE).
Results
A high proportion of the children including the index case (32/78, 41.0%) carried S. pneumoniae in their nasopharynx (NP). The most common serotype was 19F (13/32, 40.6%). The PFGE types of the 19F serotype isolates obtained from the patient's blood, CSF and NP were identical and were related to 11 other serotype 19F NP isolates including 10 that were indistinguishable from the Taiwan19F-14 clone. All 14 isolates had similar high-level penicillin and multi-drug resistance. The serotypes of the other 19 NP isolates included 6A (2), 6B (10), 23F (5), 9V (1) and 3 (1). The overall rate of penicillin resistance in these S. pneumoniae from these children was 87.5% (28/32), with an MIC50 of 2 and MIC90 of 4 ug/ml. In addition, multi-drug resistant-isolates (isolates resistant to 3 different classes of antimicrobials) accounted for 87.5% (28/32) of all isolates.
Conclusion
The high carriage rate of high-level penicillin- and multi-drug- resistant S. pneumoniae in a kindergarten associated with a case of pneumococcal meningitis emphasizes the need for restraint in antibiotic use and consideration of childhood immunization with conjugate pneumococcal vaccine to prevent the further spread of resistant S. pneumoniae in Taiwan.
doi:10.1186/1471-2334-5-96
PMCID: PMC1289284  PMID: 16259643
24.  Comparison of the systemic inflammatory response syndrome between monomicrobial and polymicrobial Pseudomonas aeruginosa nosocomial bloodstream infections 
Background
Some studies of nosocomial bloodstream infection (nBSI) have demonstrated a higher mortality for polymicrobial bacteremia when compared to monomicrobial nBSI. The purpose of this study was to compare differences in systemic inflammatory response and mortality between monomicrobial and polymicrobial nBSI with Pseudomonas aeruginosa.
Methods
We performed a historical cohort study on 98 adults with P. aeruginosa (Pa) nBSI. SIRS scores were determined 2 days prior to the first positive blood culture through 14 days afterwards. Monomicrobial (n = 77) and polymicrobial BSIs (n = 21) were compared.
Results
78.6% of BSIs were caused by monomicrobial P. aeruginosa infection (MPa) and 21.4% by polymicrobial P. aeruginosa infection (PPa). Median APACHE II score on the day of BSI was 22 for MPa and 23 for PPa BSIs. Septic shock occurred in 33.3% of PPa and in 39.0% of MPa (p = 0.64). Progression to septic shock was associated with death more frequently in PPa (OR 38.5, CI95 2.9–508.5) than MPa (OR 4.5, CI95 1.7–12.1). Maximal SIR (severe sepsis, septic shock or death) was seen on day 0 for PPa BSI vs. day 1 for MPa. No significant difference was noted in the incidence of organ failure, 7-day or overall mortality between the two groups. Univariate analysis revealed that APACHE II score ≥20 at BSI onset, Charlson weighted comorbidity index ≥3, burn injury and respiratory, cardiovascular, renal and hematologic failure were associated with death, while age, malignant disease, diabetes mellitus, hepatic failure, gastrointestinal complications, inappropriate antimicrobial therapy, infection with imipenem resistant P. aeruginosa and polymicrobial nBSI were not. Multivariate analysis revealed that hematologic failure (p < 0.001) and APACHE II score ≥20 at BSI onset (p = 0.005) independently predicted death.
Conclusion
In this historical cohort study of nBSI with P. aeruginosa, the incidence of septic shock and organ failure was high in both groups. Additionally, patients with PPa BSI were not more acutely ill, as judged by APACHE II score prior to blood culture positivity than those with MPa BSI. Using multivariable logistic regression analysis, the development of hematologic failure and APACHE II score ≥20 at BSI onset were independent predictors of death; however, PPa BSI was not.
doi:10.1186/1471-2334-5-94
PMCID: PMC1289283  PMID: 16259623
25.  Increased oxidative stress associated with the severity of the liver disease in various forms of hepatitis B virus infection 
Background
Oxidative stress can be defined as an increase in oxidants and/or a decrease in antioxidant capacity. There is limited information about the oxidative status in subjects with hepatitis B virus infection. We aimed to evaluate the oxidative status in patients with various clinical forms of chronic hepatitis B infection.
Methods
Seventy-six patients with hepatitis B virus infection, in whom 33 with chronic hepatitis, 31 inactive carriers and 12 with cirrhosis, and 16 healthy subjects were enrolled. Total antioxidant response and total peroxide level measurement, and calculation of oxidative stress index were performed in all participants.
Results
Total antioxidant response was significantly lower in cirrhotics than inactive HbsAg carriers and controls (p = 0.008 and p = 0.008, respectively). Total peroxide level and oxidative stress index was significantly higher in cirrhotic (p < 0.001, both) and chronic hepatitis B subjects (p < 0.001, both) than inactive HbsAg carriers and controls. Total antioxidant response was comparable in chronic hepatitis B subjects, inactive HbsAg carriers and controls (both, p > 0.05/6). Total peroxide level and oxidative stress index were also comparable in inactive HBsAg carriers and controls (both, p > 0.05/6). Serum alanine amino transferase level was positively correlated with total peroxide level and oxidative stress index only in chronic hepatitis B subjects (p = 0.002, r = 0.519 and p = 0.008, r = 0.453, respectively).
Conclusion
Oxidative stress occurs secondarily to increased total lipid peroxidation and inadequate total antioxidant response and is related to severity of the disease and replication status of virus in hepatitis B infection.
doi:10.1186/1471-2334-5-95
PMCID: PMC1283973  PMID: 16262897

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