BMC Infectious Diseases - Latest Articles

Characterising the KMP-11 and HSP-70 recombinant antigens' humoral immune response profile in chagasic patients

Ivonne Flechas — 2009-11-25T00:00:00Z

Background: Antigen specificity and IgG subclass could be significant in the natural history of Chagas' disease. The relationship between the different stages of human Chagas' disease and the profiles of total IgG and its subclasses were thus analysed here; they were directed against a crude T. cruzi extract and three recombinant antigens: the T. cruzi kinetoplastid membrane protein-11 (rKMP-11), an internal fragment of the T. cruzi HSP-70 protein192-433, and the entire Trypanosoma rangeli HSP-70 protein. Methods: Seventeen Brazilian acute chagasic patients, 50 Colombian chronic chagasic patients (21 indeterminate and 29 cardiopathic patients) and 30 healthy individuals were included. Total IgG and its subtypes directed against the above-mentioned recombinant antigens were determined by ELISA tests. Results: The T. cruzi KMP-11 and T. rangeli HSP-70 recombinant proteins were able to distinguish both acute from chronic chagasic patients and infected people from healthy individuals. Specific antibodies to T. cruzi crude antigen in acute patients came from IgG3 and IgG4 subclasses whereas IgG1 and IgG3 were the prevalent isotypes in indeterminate and chronic chagasic patients. By contrast, the specific prominent antibodies in all disease stages against T. cruzi KMP-11 and T. rangeli HSP-70 recombinant antigens were the IgG1 subclass. Conclusions: T. cruzi KMP-11 and the T. rangeli HSP-70 recombinant proteins may be explored together in the immunodiagnosis of Chagas' disease.Polarising the IgG1 subclass of the IgG response to T. cruzi KMP-11 and T. rangeli HSP-70 recombinant proteins could have important biological effects, taking into account that this is a complement fixing antibody.

Hepatitis B vaccinations among Koreans: Results from 2005 Korea National Cancer Screening Survey

Hee-Soon Juon — 2009-11-25T00:00:00Z

Background: Liver cancer is one of most commonly diagnosed cancers among Koreans. Chronic hepatitis B virus (HBV) infection is a major risk factor for liver cancer. HBV infection can be prevented by effective screening and vaccination programs. The purpose of this study is to examine the status of HBV infection and the predictors associated with HBV vaccination. Methods: The study population was derived from the 2005 Korea National Cancer Screening Survey (KNCSS). The KNCSS is an annual cross-sectional survey that uses a nationally-representative random sampling to investigate cancer screening rates. A total of 1,786 Koreans over 40 years of age participated in this study. Results: Of all the participants, 5.9% reported HBV positive (HBsAg+, HBsAb-), 41.8% were HBV negative but protected (HBsAg-,HBsAb+), and 52.3% were unprotected (HBsAg-, HBsAb-). Among unprotected individuals (n=934), 23.1% reported to have received the vaccination. About half of those who had vaccinations completed the 3-shot vaccine series. In multiple analyses, education, having private cancer insurance, alcohol use, having regular check-up, and doing regular exercise were associated with completed HBV vaccination. Conclusion: This study results suggests that we need a liver cancer education program to increase HBV awareness and to increase the liver cancer prevention message among low educated populations.

A unified approach to molecular epidemiology investigations: tools and patterns in California as a case study for endemic shigellosis

Sawsan Al-Nimri — 2009-11-24T00:00:00Z

Background: Shigellosis causes diarrheal disease in humans from both developed and developing countries, and multi-drug resistance is an emerging problem. The objective of this study is to present a unified approach that can be used to characterize endemic and outbreak patterns of shigellosis using use a suite of epidemiologic and molecular techniques. The approach is applied to a California case study example of endemic shigellosis at the population level. Methods: Epidemiologic patterns were evaluated with respect to demographics, multi-drug resistance, antimicrobial resistance genes, plasmid profiles, and pulsed-field gel electrophoresis (PFGE) fingerprints for the 43 Shigella isolates obtained by the Monterey region health departments over the two year period from 2004-2005. Results: The traditional epidemiologic as well as molecular epidemiologic findings were consistent with endemic as compared to outbreak shigellosis in this population. A steady low level of cases was observed throughout the study period and high diversity was observed among strains. In contrast to most studies in developed countries, the predominant species was Shigella flexneri (51%) followed closely by S. sonnei (49%). Over 95% of Shigella isolates were fully resistant to three or more antimicrobial drug subclasses, and 38% of isolates were resistant to five or more subclasses. More than half of Shigella strains tested carried the tetB, catA, or blaTEM genes for antimicrobial resistance to tetracycline, chloramphenicol, and ampicillin, respectively. Conclusions: This study shows how epidemiologic patterns at the host and bacterial population levels can be used to investigate endemic as compared to outbreak patterns of shigellosis in a community. Information gathered as part of such investigations will be instrumental in identifying emerging antimicrobial resistance, for developing treatment guidelines appropriate for that community, and to provide baseline data with which to compare outbreak strains in the future.

Characteristics and outcome of infants with candiduria in neonatal intensive care - a Paediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study

Joan Robinson — 2009-11-23T00:00:00Z

Background: There is limited information in the literature on the presentation and prognosis of candidal urinary tract infection (UTI) in infants in the neonatal intensive care unit (NICU). Methods: This was a prospective cohort study performed in 13 Canadian NICUs. Infants with candidal UTI without documented extra-renal candidal infection at presentation were enrolled. Results: Thirty infants fit the study criteria. Median birth weight and gestational age were 2595 grams (range 575-4255) and 35 weeks (range 24-41) with 10 infants being < 30 weeks gestation. The most common primary underlying diagnosis was congenital heart disease (n=10). The median age at initial diagnosis was 16 days (range 6-84 days). Renal ultrasonography findings were compatible with possible fungal disease in 15 of the 26 infants (58%) in whom it was performed. Treatment was variable, but fluconazole and either amphotericin B deoxycholate or lipid-based amphotericin B in combination or sequentially were used most frequently. Extra-renal candidiasis subsequently developed in 4 infants. In 2 of these 4 infants, dissemination happened during prolonged courses of anti-fungal therapy. Three of 9 deaths were considered to be related to candidal infection. No recurrences of candiduria or episodes of invasive candidiasis following treatment were documented. Conclusions: Candidal UTI in the NICU population occurs both in term infants with congenital abnormalities and in preterm infants, and is associated with renal parenchymal disease and extra-renal dissemination. A wide variation in clinical approach was documented in this multicenter study. The overall mortality rate in these infants was significant (30%). In one third of the deaths, Candida infection was deemed to be a contributing factor, suggesting the need for antifungal therapy with repeat evaluation for dissemination in infants who are slow to respond to therapy.

New tools for detecting latent tuberculosis infection: Evaluation of RD1-specific long-term response

Ornella Butera — 2009-11-21T00:00:00Z

Background: Interferon-gamma (IFN-g) release assays (IGRAs) were designed to detect latent tuberculosis infection (LTBI). However, discrepancies were found between the tuberculin skin test (TST) and IGRA results that cannot be attributed to prior Bacillus Calmette Guerin vaccinations. The aim of this study was to evaluate tools for improving LTBI diagnosis by analyzing the IFN-g response to RD1 proteins in prolonged (long-term response) whole blood tests in those subjects resulting negative to assays such as QuantiFERON-TB Gold In tube (QFT). Methods: The study population included 106 healthy TST+ individuals with suspected LTBI (recent contact of smear-positive TB and homeless) consecutively enrolled. As controls, 13 healthy subjects unexposed to M. tuberculosis (TST-, QFT-) and 29 subjects with cured pulmonary TB were enrolled. IFN-g whole blood response to RD1 proteins and QFT were evaluated at day 1 post-culture. A prolonged test evaluating long-term IFN-gresponse (7-day) to RD1 proteins in diluted whole blood was performed. Results: Among the enrolled TST+ subjects with suspected LTBI, 70/106 (66.0%) responded to QFT and 64/106 (60.3%) to RD1 proteins at day 1. To evaluate whether a prolonged test could improve the detection of LTBI, we set up the test using cured TB patients (with a microbiologically diagnosed past pulmonary disease) who resulted QFT-negative and healthy controls as comparator groups. Using this assay, a statistically significant difference was found between IFN-g levels in cured TB patients compared to healthy controls (p<0.006). ). Based on these data, we constructed a receiver operating characteristic (ROC) curve and we calculated a cut-off. Based on the cut-off value, we found that among the 36 enrolled TST+ subjects with suspected LTBI not responding to QFT, a long term response to RD1 proteins was detected in 11 subjects (30.6%). Conclusions: These results indicate that IFN-g long-term response to M. tuberculosis RD1 may be used to detect past infection with M. tuberculosis and may help to identify additional individuals with LTBI who resulted negative in the short-term tests. These data may provide useful information for improving immunodiagnostic tests for tuberculosis infection, especially in individuals at high risk for active TB.

Inequitable childhood immunization uptake in Nigeria: A multilevel analysis of individual and contextual determinants.

Diddy Antai — 2009-11-20T00:00:00Z

Background: Immunization coverage in many parts of Nigeria is far from optimal, and far from equitable.Nigeria accounts for half of the deaths from Measles in Africa, the highest prevalence of circulating wild poliovirus in the world, and the country is among the ten countries in the world with vaccine coverage below 50 percent. Studies focusing on community-level determinants therefore have serious policy implications Methods: Multilevel multivariable regression analysis was used on a nationally-representative sample of women aged 15-49 years from the 2003 Nigeria Demographic and Health Survey. Multilevel regression analysis was performed with children (level 1) nested within mothers (level 2), who were in turn nested within communities (level 3). Results: Results show that the pattern of full immunization clusters within families and communities, and that socio-economic characteristics were important in explaining the differentials in full immunization among the children in the study. At the individual level, ethnicity, mothers' occupation, and mothers' household wealth were characteristics of the mothers associated with full immunization of the children. At the community level, the proportion of mothers that had hospital delivery was a determinant of full immunization status. Conclusion: Significant community-level variation remaining after having controlled for child- and mother-level characteristics is indicative of a need for further research on community-levels factors, which would enable extensive tailoring of community-level interventions aimed at improving full immunization and other child health outcomes.

The risks of malaria infection in Kenya in 2009

Abdisalan Noor — 2009-11-20T00:00:00Z

Background: To design an effective strategy for the control of malaria requires a map of infection and disease risks to select appropriate suites of interventions. Advances in model based geo-statistics and malaria parasite prevalence data assemblies provide unique opportunities to redefine national Plasmodium falciparum risk distributions. Here we present a new map of malaria risk for Kenya in 2009. Methods: Plasmodium falciparum parasite rate data were assembled from cross-sectional community based surveys undertaken from 1975 to 2009. Details recorded for each survey included the month and year of the survey, sample size, positivity and the age ranges of sampled population. Data were corrected to a standard age-range of two to less than 10 years (PfPR2-10) and each survey location was geo-positioned using national and on-line digital settlement maps. Ecological and climate covariates were matched to each PfPR2-10 survey location and examined separately and in combination for relationships to PfPR2-10. Significant covariates were then included in a Bayesian geostatistical spatial-temporal framework to predict continuous and categorical maps of mean PfPR2-10 at a 1 × 1 km resolution across Kenya for the year 2009. Model hold-out data were used to test the predictive accuracy of the mapped surfaces and distributions of the posterior uncertainty were mapped. Results: A total of 2,682 estimates of PfPR2-10 from surveys undertaken at 2,095 sites between 1975 and 2009 were selected for inclusion in the geo-statistical modeling. The covariates selected for prediction were urbanization; maximum temperature; precipitation; enhanced vegetation index; and distance to main water bodies. The final Bayesian geo-statistical model had a high predictive accuracy with mean error of -0.15% PfPR2-10; mean absolute error of 0.38% PfPR2-10; and linear correlation between observed and predicted PfPR2-10 of 0.81. The majority of Kenya's 2009 population (35.2 million, 86.3%) reside in areas where predicted PfPR2-10 is less than 5%; conversely in 2009 only 4.3 million people (10.6%) lived in areas where PfPR2-10 was predicted to be ≥40% and were largely located around the shores of Lake Victoria. Conclusion: Model based geo-statistical methods can be used to interpolate malaria risks in Kenya with precision and our model shows that the majority of Kenyans live in areas of very low P. falciparum risk. As malaria interventions go to scale effectively tracking epidemiological changes of risk demands a rigorous effort to document infection prevalence in time and space to remodel risks and redefine intervention priorities over the next 10-15 years.

Serum immunoglobulin G, M and A response to Cryptosporidium parvum in Cryptosporidium-HIV co-infected patients

Kirti Kaushik — 2009-11-18T00:00:00Z

Background: Cryptosporidium parvum, the protozoan parasite, causes a significant enteric disease in immunocompromised hosts such as HIV patients. The present study was aimed to compare serum IgG, IgM and IgA responses to crude soluble antigen of C. parvum in HIV seropositive and seronegative patients co-infected with Cryptosporidium and to correlate the responses with symptomatology. Methods: Cryptosporidium parvum specific serum antibody (IgG, IgM and IgA) responses were assessed by ELISA in 11 HIV seropositive Cryptosporidium positive (Group I), 20 HIV seropositive Cryptosporidium negative (Group II), 10 HIV seronegative Cryptosporidium positive (Group III), 20 HIV seronegative Cryptosporidium negative healthy individuals (Group IV) and 25 patients with other parasitic diseases (Group V). Results: A positive IgG and IgA antibody response was observed in significantly higher number of Cryptosporidium infected individuals (Gp I and III) compared to Cryptosporidium un-infected individuals (Gp II, IV and V) irrespective of HIV/immune status. Sensitivity of IgG ELISA in our study was found to be higher as compared to IgM and IgA ELISA. The number of patients with positive IgG, IgM and IgA response was not significantly different in HIV seropositive Cryptosporidium positive patients with diarrhoea when compared to patients without diarrhoea and in patients with CD4 counts <200 when compared to patients with CD4 counts >200 cells/ul. Conclusions: The study showed specific serum IgG and IgA production in patients infected with Cryptosporidium, both HIV seropositive and seronegative as compared to uninfected subjects suggesting induction of Cryptosporidium specific humoral immune response in infected subjects. However, there was no difference in number of patients with positive response in HIV seropositive or seronegative groups indicating that HIV status may not be playing significant role in modulation of Cryptosporidium specific antibody responses. The number of patients with positive IgG, IgM and IgA response was not significantly different in patients with or without history of diarrhoea thereby indicating that Cryptosporidium specific antibody responses may not be necessarily associated with protection from symptomatology.

Moraxella catarrhalis acquisition, airway inflammation and protease-antiprotease balance in chronic obstructive pulmonary disease

Ganapathi Parameswaran — 2009-11-15T00:00:00Z

Background: Moraxella catarrhalis causes approximately 10% of exacerbations in chronic obstructive pulmonary disease (COPD) and also colonizes the lower airway in stable patients. Little is known about the effects of colonization by M. catarrhalis on airway inflammation and protease-antiprotease balance, and how these changes compare to those seen during exacerbations. Since COPD is a progressive inflammatory disease, elucidating the effects of bacterial colonization and exacerbation on airway inflammation is relevant to understanding disease progression in COPD. Our aims were (1) Analyze changes in airway inflammation in colonization and exacerbation of COPD due to M. catarrhalis; (2) Explore protease-antiprotease balance in colonization and exacerbation due to M. catarrhalis. Our hypothesis were (1) Acquisition of a new strain of M. catarrhalis in COPD increases airway inflammation from baseline and alters the protease-antiprotease balance towards a more proteolytic environment; (2) These changes are greater during exacerbations associated with M. catarrhalis as compared to colonization. Methods: Thirty-nine consecutive COPD patients with 76 acquisitions of a new strain of M. catarrhalis over a 6-year period were identified in a prospective study. Seventy-six pre-acquisition sputum supernatant samples, obtained just before acquisition of M catarrhalis, and 76 acquisition samples (34 were associated with exacerbation, 42 with colonization) were analyzed for IL-8, TNF-α, Neutrophil Elastase (NE) and Secretory leukocyte protease inhibitor (SLPI). Changes were compared in paired samples from each patient. Results: IL-8, TNF-α and NE were significantly elevated after acquisition of M. catarrhalis, compared to pre-acquisition samples (p =< 0.001 for all three). These changes were present in colonization (p = 0.015 for IL-8; p =< 0.001 for TNF-α and NE) as well as in exacerbation (p =< 0.001 for all three), compared to pre-acquisition levels. SLPI was significantly lower after acquisition (p =< 0.001), in colonization (p =< 0.001) as well as in exacerbation (p = 0.004), compared to pre-acquisition levels. SLPI levels correlated negatively with NE levels (R2 = 0.07; p = 0.001). Conclusion: Acquisition of M. catarrhalis in COPD causes increased airway inflammation and worsening protease-antiprotease imbalance during exacerbations and also in colonization, even in the absence of increased symptoms. These effects could contribute to progression of airway disease in COPD.

PCR melting profile (PCR MP) - a new tool for differentiation of Candida albicans strains

Beata Krawczyk — 2009-11-11T00:00:00Z

Background: We have previously reported the use of PCR Melting Profile (PCR MP) technique based on using low denaturation temperatures during ligation mediated PCR (LM PCR) for bacterial strain differentiation. The aim of the current study was to evaluate this method for intra-species differentiation of Candida albicans strains. Methods: In total 123 Candida albicans strains (including 7 reference, 11 clinical unrelated, and 105 isolates from patients of two hospitals in Poland) were examined using three genotyping methods: PCR MP, macrorestriction analysis of the chromosomal DNA by pulsed-field gel electrophoresis (REA-PFGE) and RAPD techniques. Results: The genotyping results of the PCR MP were compared with results from REA-PFGE and RAPD techniques giving 27, 26 and 25 unique types, respectively. The results showed that the PCR MP technique has at least the same discriminatory power as REA-PFGE and RAPD. Conclusion: Data presented here show for the first time the evaluation of PCR MP technique for candidial strains differentiation and we propose that this can be used as a relatively simple and cheap technique for epidemiological studies in short period of time in hospital.