Optimal time for initiation of antiretroviral therapy in asymptomatic, HIV-infected, treatment-naive adults.

Cochrane Database Syst Rev. 2010;3:CD008272

Authors: Siegfried N, Uthman OA, Rutherford GW

BACKGROUND: According to consensus, initiation of therapy is best based on CD4 cell count, a marker of immune status, rather than on viral load, a marker of virologic replication. For patients with advanced symptoms, treatment should be started regardless of CD4 count. However, the point during the course of HIV infection at which antiretroviral therapy (ART) is best initiated in asymptomatic patients remains unclear. Guidelines issued by various agencies provide different initiation recommendations according to resource availability. This can be confusing for clinicians and policy-makers when determining the best time to initiate therapy. Optimizing the initiation of ART is clearly complex and must, therefore, be balanced between individual and broader public health needs. OBJECTIVES: To assess the evidence for the optimal time to initiate ART in treatment-naive, asymptomatic, HIV-infected adults SEARCH STRATEGY: We formulated a comprehensive and exhaustive search strategy in an attempt to identify all relevant studies regardless of language or publication status (published, unpublished, in press, and in progress). In August 2009, we searched the following electronic journal and trial databases: MEDLINE, EMBASE, and CENTRAL. We also searched the electronic conference database of NLM Gateway, individual conference proceedings and prospective trials registers. We contacted researchers and relevant organizations and checked reference lists of all included studies. SELECTION CRITERIA: Randomized controlled trials that compared the effect of ART consisting of three drugs initiated early in the disease at high CD4 counts as defined by the trial. Early initiation could be at levels of 201-350, 351-500, or >500 cells/microL, with the comparison group initiating ART at CD4 counts below 200 x 10(6) cells/microL or as defined by the trial. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data, and graded methodological quality. Data extraction and methodological quality were checked by a third author who resolved differences when these arose. Where clinically meaningful to do so, we meta-analysed dichotomous outcomes using the relative risk (RR) and report the 95% confidence intervals (95% CIs). MAIN RESULTS: One completed trial (N = 816) and one sub-group (N = 249) of a larger trial met inclusion criteria. We combined the mortality data for both trials comparing initiating ART at CD4 levels at 350 cells/microL or between 200 and 350 cells/microL with deferring initiation of ART to CD4 levels of 250 cells/microL or 200 cells/microL. There was a statistically significant reduction in death when starting ART at higher CD4 counts. Risk of death was reduced by 74% (RR = 0.26; 95% CI: 0.11, 0.62; P = 0.002). Risk of tuberculosis was reduced by 50% in the groups starting ART early; this was not statistically significant, with the reduction as much as 74% or an increased risk of up to 12% (RR = 0.54; 95% CI: 0.26, 1.12; P = 0.01). Starting ART at enrollment (when participants had CD4 counts of 350 cells/microL) rather than deferring to starting at a CD4 count of 250 cells/microL reduced the risk of disease progression by 70%; this was not statistically significant, with the reduction in risk as much as 97% or an increased risk of up to 185% (RR = 0.30; 95% CI: 0.03, 2.85; P = 0.29).One RCT found no statistically significant difference in the number of independent Grade 3 or 4 adverse events occurring in the early and standard ART groups when we conducted an intention-to-treat analysis (RR = 1.72; 95% CI: 0.98, 3.03; P = 0.06). However, when analyzing only participants who actually commenced ART in the deferred group (n = 160), the trial authors report a statistically significant increase in the incidence of zidovudine-related anaemia (8.1%) compared with those in the early initiation group (3.4%) (RR = 0.42; 95% CI: 0.20, 0.88; P = 0.02). AUTHORS' CONCLUSIONS: There is evidence of moderate quality that initiating ART at CD4 levels higher than 200 or 250 cells/microL reduces mortality rates in asymptomatic, ART-naive, HIV-infected people. Practitioners and policy-makers may consider initiating ART at levels </= 350 cells/microL for patients who present to health services and are diagnosed with HIV early in the infection.

PMID: 20238364 [PubMed - in process]

Transient osteoporosis of the hip: successful treatment with teriparatide.

Rheumatol Int. 2010 Mar 18;

Authors: Fabbriciani G, Pirro M, Manfredelli MR, Bianchi M, Sivolella S, Scarponi AM, Mannarino E

A 62-year-old man presented with a 2-month history of increasing pain in the left hip. Magnetic resonance imaging (MRI) showed bone marrow edema (BME) of the left femur, dual energy X-ray absorptiometry (DXA) showed osteopenia at the same level, whereas pelvis X-rays failed to show any objective findings. After ruling out other possible causes of BME such as aseptic osteonecrosis, infectious arthritis, primary or metastatic malignancy, tuberculosis, osteomyelitis, rheumatoid arthritis, and seronegative spondyloarthropathies, a diagnosis of transient osteoporosis of the hip (TOH) was made, and treatment with teriparatide at a daily dose of 20 mug was started and continued for 4 weeks. Disappearance of the symptoms and normalization of MRI were obtained.

PMID: 20238219 [PubMed - as supplied by publisher]

18F-FDG PET/CT findings of pharyngeal tuberculosis.

Ann Nucl Med. 2010 Mar 18;

Authors: Ito K, Morooka M, Kubota K

A 58-year-old woman with dysphagia and hoarseness underwent 18F-FDG PET/CT to detect the original lesion and disease spread. Bilateral cervical lymphadenopathy and abnormal FDG uptakes in the right tonsil and pharyngeal wall were demonstrated. CT and MRI confirmed the bilateral cervical lymphadenopathy and mucosal thickening in the pharyngeal wall. On the basis of these findings, biopsy sites were selected. Pharyngeal tuberculosis was diagnosed based on culture of the biopsy specimens. 18F-FDG PET/CT contributed to clinical management in this case by detecting tuberculous lesions and showing the extent of these lesions in one examination.

PMID: 20238184 [PubMed - as supplied by publisher]

Tuberculosis Knowledge, Attitudes, and Beliefs in Foreign-born and US-born Patients with Latent Tuberculosis Infection.

J Immigr Minor Health. 2010 Mar 17;

Authors: Colson PW, Franks J, Sondengam R, Hirsch-Moverman Y, El-Sadr W

Foreign-born individuals comprise the majority of patients treated for latent tuberculosis infection (LTBI) in the US. It is important to understand this population's tuberculosis-related knowledge, attitudes, and beliefs (KAB) as they may affect treatment acceptance and completion. KAB in 84 US-born and 167 foreign-born LTBI patients enrolled in a clinical trial assessing treatment completion at an urban public hospital were assessed at baseline. Demographic and substance use information was also collected. Results: Of 251 participants, 66.5% were foreign-born. While misconceptions existed among both US and foreign-born regarding transmission and contagiousness of LTBI, overall knowledge scores did not differ significantly between groups. With respect to attitudinal factors, foreign-born participants were less likely to acknowledge that they had LTBI and felt more "protected" from developing TB. Improved understanding of foreign-born patients' KAB may contribute to the reduction of barriers to treatment and improved outcomes.

PMID: 20237847 [PubMed - as supplied by publisher]

Identification of Cytokines in Whole Blood for the Differential Diagnosis of Tuberculosis vs Pneumonia.

Clin Vaccine Immunol. 2010 Mar 17;

Authors: Su WL, Perng WC, Huang CH, Yang CY, Wu CP, Chang FY, Chen JH

Differentiating tuberculosis (TB) from pneumonia remains a challenge. We evaluated the cytokine profiles of whole blood cells from patients with TB (n=38), pneumonia (n=30), and healthy individuals (n=30) before and after stimulating cells with ESAT-6 or LPS. When the percent change in the levels of interferon (IFN)-gamma after stimulation with ESAT-6 was used in receiver operating characteristics (ROC) analysis (a graphic method to determine the diagnostic accuracy of a test) to identify a patient with TB, the area under the curve (AUC) was 90.4%; and a cut-off point of 3.59% change produced a corresponding sensitivity, specificity, and accuracy of over 80%. When the change in IFN-gamma after stimulation of blood cells with LPS was used to identify a patient with pneumonia, the AUC reached 89.1; and a cut-off point of 3.59% produced a sensitivity, specificity, and accuracy of approximately 80% each. When the change in interleukin (IL)-12 after stimulation of blood cells with LPS was selected to define a patient with pneumonia, the AUC was 85.2%; and a cut-off point of 2.08% gave a sensitivity, specificity, and accuracy of 80.0%, 78.9%, and 79.4%, respectively. We conclude that the percent change in IFN-gamma after stimulation of whole blood cells with ESAT-6 may differentiate patients with TB from patients with pneumonia. The percent change in IFN-gamma and IL-12 after LPS-stimulation of whole blood cells could differentiate patients with pneumonia from patients with TB.

PMID: 20237198 [PubMed - as supplied by publisher]

Wild type minimal inhibitory concentration distributions for aminoglycoside and cyclic polypeptide antibiotics used for the treatment of Mycobacterium tuberculosis.

J Clin Microbiol. 2010 Mar 17;

Authors: Juréen P, Angeby K, Sturegård E, Chryssanthou E, Giske CG, Werngren J, Nordvall M, Johansson A, Kahlmeter G, Hoffner S, Schön T

The aminoglycosides and cyclic polypeptides are essential drugs in the treatment of multidrug resistant tuberculosis, underscoring the need for accurate and reproducible drug susceptibility testing (DST). The epidemiological cut off value (ECOFF) separating wild type susceptible strains from non-wild type strains is an important but rarely used tool for indicating susceptibility breakpoints against Mycobacterium tuberculosis. In this study, we established wild-type minimal inhibitory concentration (MIC) distributions on Middlebrook 7H10 medium for amikacin, kanamycin, streptomycin, capreomycin and viomycin using 90 consecutive clinical isolates and 21 resistant strains. Overall, the MIC variation between and within runs did not exceed +/-one MIC dilution step and validation of MIC-values in BACTEC 960 MGIT demonstrated good agreement. Tentative ECOFFs defining the wild type were established for all investigated drugs, including amikacin and viomycin that currently lack susceptibility breakpoints for 7H10. Five out of seven amikacin and kanamycin resistant isolates were classified as susceptible to capreomycin according to the current critical concentration (10mg/L) but were non-wild type according to ECOFF (4mg/L), suggesting that the critical concentration may be too high. All amikacin and kanamycin resistant isolates were clearly below ECOFF for viomycin, and two of them were below ECOFF for streptomycin, indicating that these two drugs may be considered for treatment of amikacin resistant strains. Pharmacodynamic indices (Cmax/MIC) were more favorable for amikacin and viomycin compared to kanamycin and capreomycin. In conclusion, our data emphasize the importance of establishing wild type MIC-distributions for improving the quality of drug susceptibility testing against Mycobacterium tuberculosis.

PMID: 20237102 [PubMed - as supplied by publisher]

Tuberculosis in alpacas (Lama pacos) caused by Mycobacterium bovis.

J Clin Microbiol. 2010 Mar 17;

Authors: García-Bocanegra I, Barranco I, Rodríguez-Gómez IM, Pérez B, Gómez-Laguna J, Rodríguez S, Ruiz-Villamayor E, Perea A

We report three cases of tuberculosis in alpacas from Spain caused by Mycobacterium bovis. The animals revealed two different lesional patterns. Mycobacterial culture and PCR assay yielded positive results for M. bovis. Molecular typing of the isolates identified spoligotype SB0295 and identical variable number tandem repeat (VNTR) allele sizes.

PMID: 20237097 [PubMed - as supplied by publisher]

Rifamycins - Obstacles and opportunities.

Tuberculosis (Edinb). 2010 Mar 15;

Authors: Aristoff PA, Garcia GA, Kirchhoff PD, Hollis Showalter HD

With nearly one-third of the global population infected by Mycobacterium tuberculosis, TB remains a major cause of death (1.7 million in 2006). TB is particularly severe in parts of Asia and Africa where it is often present in AIDS patients. Difficulties in treatment are exacerbated by the 6-9 month treatment times and numerous side effects. There is significant concern about the multi-drug-resistant (MDR) strains of TB (0.5 million MDR-TB cases worldwide in 2006). The rifamycins, long considered a mainstay of TB treatment, were a tremendous breakthrough when they were developed in the 1960's. While the rifamycins display many admirable qualities, they still have a number of shortfalls including: rapid selection of resistant mutants, hepatotoxicity, a flu-like syndrome (especially at higher doses), potent induction of cytochromes P450 (CYP) and inhibition of hepatic transporters. This review of the state-of-the-art regarding rifamycins suggests that it is quite possible to devise improved rifamycin analogs. Studies showing the potential of shortening the duration of treatment if higher doses could be tolerated, also suggest that more potent (or less toxic) rifamycin analogs might accomplish the same end. The improved activity against rifampin-resistant strains by some analogs promises that further work in this area, especially if the information from co-crystal structures with RNA polymerase is applied, should lead to even better analogs. The extensive drug-drug interactions seen with rifampin have already been somewhat ameliorated with rifabutin and rifalazil, and the use of a CYP-induction screening assay should serve to efficiently identify even better analogs. The toxicity due to the flu-like syndrome is an issue that needs effective resolution, particularly for analogs in the rifalazil class. It would be of interest to profile rifalazil and analogs in relation to rifampin, rifapentine, and rifabutin in a variety of screens, particularly those that might relate to hypersensitivity or immunomodulatory processes.

PMID: 20236863 [PubMed - as supplied by publisher]

From explanation to prediction: A model for recurrent bovine tuberculosis in Irish cattle herds.

Prev Vet Med. 2010 Mar 15;

Authors: Wolfe DM, Berke O, Kelton DF, White PW, More SJ, O'Keeffe J, Martin SW

There is a good understanding of factors associated with bovine tuberculosis (BTB) risk in Irish herds. As yet, however, this knowledge has not been incorporated into predictive models with the potential for improved, risk-based surveillance. The goal of the study was to enhance the national herd scoring system for BTB risk, thus leading to improved identification of cattle herds at high risk of recurrent BTB episodes. A retrospective cohort study was conducted to develop a statistical model predictive of recurrent bovine tuberculosis episodes in cattle herds in the Republic of Ireland. Herd-level disease history data for the previous 12 years, the previous 3 years, the previous episode, and the current-episode were used in survival analyses to determine the aspects of disease history that were predictive of a recurrent breakdown within 3 years of a cleared BTB episode. Relative to herds with 0-1 standard reactors in the current BTB episode, hazard ratios increased to 1.3 and 1.6 for herds with 2-5 and >5 standard reactors, respectively. Compared to herds with <30 animals, hazard ratios increased from 1.8 to 2.5 and then to 3.1 for herds with 30-79, 80-173, and >174 animals respectively. Relative to herds with <4 herd-level tests in the previous 3 years, herds with 4-5 and >5 tests had 1.1 and 1.4 times greater hazard of a BTB breakdown. Herds that did not have a BTB episode in the 5 years prior to their 2001 episode were 0.8 times less likely to breakdown in the next 3 years than herds that did. Herds breaking down in the spring or summer were 0.8 times less likely to suffer a recurrent breakdown than herds breaking down in autumn or winter (this was likely due to seasonality in testing regimes). The presence of a confirmed BTB lesion was not predictive of increased risk of recurrent BTB. Despite the availability of detailed disease history, the predictive ability of the model was poor. One explanation for this was that herds suffering a recurrence of BTB on their first test after clearing a BTB episode were different from herds that broke down later in the period at risk. Future research might need to include additional variables to identify which subsets of herd BTB episodes, if any, have identifiable features that are predictive of recurrent breakdowns.

PMID: 20236717 [PubMed - as supplied by publisher]

First insights into the genetic diversity of Mycobacterium tuberculosis isolates from HIV-infected Mexican patients and mutations causing multidrug resistance.

BMC Microbiol. 2010 Mar 17;10(1):82

Authors: Lopez-Alvarez R, Badillo-Lopez C, Cerna-Cortes JF, Castillo-Ramirez I, Rivera-Gutierrez S, Helguera-Repetto AC, Aguilar D, Hernandez-Pando R, Samper S, Gonzalez-Y-Merchand JA

ABSTRACT: BACKGROUND: The prevalence of infections with Mycobacterium tuberculosis (MTb) and nontuberculous mycobacteria (NTM) species in HIV-infected patients in Mexico is unknown. The aims of this study were to determine the frequency of MTb and NTM species in HIV-infected patients from Mexico City, to evaluate the genotypic diversity of the Mycobacterium tuberculosis complex strains, to determine their drug resistance profiles by colorimetric microplate Alamar Blue assay (MABA), and finally, to detect mutations present in katG, rpoB and inhA genes, resulting in isoniazid (INH) and rifampin (RIF) resistance. RESULTS: Of the 67 mycobacterial strains isolated, 48 were identified as MTb, 9 as M. bovis, 9 as M. avium and 1 as M. intracellulare. IS6110-RFLP of 48 MTb strains showed 27 profiles. Spoligotyping of the 48 MTb strains yielded 21 patterns, and 9 M. bovis strains produced 7 patterns. Eleven new spoligotypes patterns were found. A total of 40 patterns were produced from the 48 MTb strains when MIRU-VNTR was performed. Nineteen (39.6%) MTb strains were resistant to one or more drugs. One (2.1%) multidrug-resistant (MDR) strain was identified. A novel mutation was identified in a RIF-resistant strain, GAG -> TCG (Glu -> Ser) at codon 469 of rpoB gene. CONCLUSIONS: This is the first molecular analysis of mycobacteria isolated from HIV-infected patients in Mexico, which describe the prevalence of different mycobacterial species in this population. A high genetic diversity of MTb strains was identified. New spoligotypes and MIRU-VNTR patterns as well as a novel mutation associated to RIF-resistance were found. This information will facilitate the tracking of different mycobacterial species in HIV-infected individuals, and monitoring the spread of these microorganisms, leading to more appropriate measures for tuberculosis control.

PMID: 20236539 [PubMed - as supplied by publisher]

Differential recruitment of CD63 and Rab7-interacting-lysosomal-protein to phagosomes containing Mycobacterium tuberculosis in macrophages.

Microbiol Immunol. 2010 Mar;54(3):170-4

Authors: Seto S, Matsumoto S, Tsujimura K, Koide Y

ABSTRACT M.tb is an intracellular pathogen which survives within the phagosomes of host macrophages by inhibiting their fusion with lysosomes. Here, it has been demonstrated that a lysosomal glycoprotein, CD63, is recruited to the majority of M.tb phagosomes, while RILP shows limited localization. This is consistent with the author's findings that CD63, but not RILP, is recruited to the phagosomes in macrophages expressing the dominant negative form of Rab7. These results suggest that M.tb phagosomes selectively fuse with endosomes and lysosomes to escape killing activity while acquiring nutrients.

PMID: 20236428 [PubMed - in process]

Melkersson-Rosenthal syndrome in a patient with tubercular panuveitis.

Indian J Ophthalmol. 2010 Jan-Feb;58(1):78-80

Authors: Babu K, Gundannavar PV, Satish V, Prabhakaran VC

We report a rare presentation of Melkersson-Rosenthal syndrome in a patient with tubercular panuveitis. A 45-year-old male being treated with antitubercular therapy for tubercular panuveitis presented with unilateral, non-pitting right upper eyelid edema. Excision biopsy showed granulomatous inflammation involving the lymphatics. Immunohistochemistry confirmed the presence of histiocytes around the lymphatics.

PMID: 20029155 [PubMed - indexed for MEDLINE]

John Browne (1642-1702): anatomist and plagiarist.

Clin Anat. 2010 Jan;23(1):1-7

Authors: Loukas M, Akiyama M, Shoja MM, Yalçin B, Tubbs RS, Cohen-Gadol AA

In contrast to many other physicians of his age, John Browne (1642-1702), an English anatomist and surgeon, managed to strike a balance in his career that spanned relative obscurity, prestige, and notoriety. Among his more prestigious credits, Browne was Surgeon in Ordinary to King Charles II and William III. He also had numerous publications to his name, some of which are credited as great innovations. His career, however, was tempered by his most important book, which has been critiqued by his contemporaries as well as modern historians as plagiarism. Although Browne undeniably copied the works of others and published them under his name, he was not alone in this practice. Various forms of intellectual thievery were common in Browne's day, and there were many perpetrators. The life of this overlooked figure in the history of anatomy and the stigma attached to him will be examined.

PMID: 19941356 [PubMed - indexed for MEDLINE]

DDT and malaria prevention.

Environ Health Perspect. 2010 Jan;118(1):A14-5; author reply A15-6

Authors: Tren R, Roberts D

PMID: 20238453 [PubMed - in process]

Molecular characterization of Leishamania isolates from China by inter-simple sequence repeat polymerase chain reaction.

Parasitol Res. 2010 Mar 17;

Authors: Wang Y, Yang Y, Wang J, Bao Y, Guan L, Gao C, Shi F

Leishmania has distinct epidemiological and biological characteristics and causes a variety of clinical symptoms. To understand the genetic diversity and the phylogenetic relationships among Leishmania isolates from China, 29 Leishmania isolates from different geographic origins, vectors, and hosts were analyzed using 21 inter-simple sequence repeat polymerase chain reaction (ISSR-PCR) primers. A total of 864 polymorphic bands were obtained. According to the results of the neighbor-joining phylogenetic tree and principal component analysis, the 29 isolates studied clustered into six groups. Isolates of Leishmania donovani complex from China share the highest similarity with the reference strain of L. donovani (DD8). This study helps to elucidate the genetic relationship among Leishmania isolates from China and similarities between Chinese isolates and World Health Organization reference strains. Furthermore, ISSR-PCR could also be a quick, simple, and reliable method for Leishmania species identification.

PMID: 20237800 [PubMed - as supplied by publisher]

High prevalence and gender bias in distribution of Plasmodium malariae infection in central east-coast India.

Trop Biomed. 2009 Dec;26(3):326-33

Authors: Dhangadamajhi G, Kar SK, Ranjit MR

Light microscopy, the mainstay of malaria diagnosis in epidemiologic studies, exhibits limited sensitivity for detecting low level infections and often under-estimates the frequency of mixed Plasmodium species infections. To overcome these shortcomings we performed the PCR method for detection and identification of Plasmodium species in blood specimens from 242 individuals collected during the peak season of malaria incidence (July - October). Malaria prevalence was 81.4% and 43.4% by PCR and microscopy respectively. Moreover, while PCR detected Plasmodium malariae DNA in 108 (44.6%), microscopic examination detected only 20 (8.3%) individuals parasitized with this species. Further data analysis revealed an independent random distribution pattern of parasites irrespective of age groups (0-5 yrs, chi-square7df = 2.77, P > 0.95; 6-15 yrs, chi-square7df = 4.82, P > 0.50; >15 yrs, chi-square7df = 4.4, P > 0.70) and sexes (for male chi-square7df = 2.48, P > 0.95; for female, chi-square7df = 1.85, P > 0.95). However, although the parasite distribution is random irrespective of sex, females had more P. malariae infections (P = 0.004, OR = 2.312, 95% CI = 1.3-4.1). Our study demonstrates that the parasite distribution in Orissa is random with substantially higher prevalence of P.malariae than previously suspected and this may be seasonal. A study of the bionomics of vector(s) responsible for P. malariae transmission in Orissa is needed to provide information for the control of malaria in the state.

PMID: 20237447 [PubMed - in process]

Management of malaria and other severe infections in rural Africa and Asia.

BMJ. 2010;340:c1527

Authors: Whitty CJ, Leslie T, Chandler CI, Staedke SG

PMID: 20237003 [PubMed - in process]

Solution structure of a Plasmodium falciparum AMA-1/MSP 1 chimeric protein vaccine candidate (PfCP-2.9) for malaria.

Malar J. 2010 Mar 18;9(1):76

Authors: Peng H, Hu Y, Zhou A, Jin C, Pan W

ABSTRACT: BACKGROUND: The Plasmodium falciparum chimeric protein PfCP-2.9 is a promising asexual-stage malaria vaccine evaluated in clinical trials. This chimeric protein consists of two cysteine-rich domains: domain III of the apical membrane antigen 1 (AMA-1[III]) and the C-terminal region of the merozoite surface protein 1 (MSP1-19). It has been reported that the fusion of these two antigens enhanced their immunogenicity and antibody-mediated inhibition of parasite growth in vitro. METHODS: The 15N-labeled and 13C/15N-labeled PfCP-2.9 was produced in Pichia pastoris for nuclear magnetic resonance (NMR) structure analysis. The chemical shift assignments of PfCP-2.9 were compared with those previously reported for the individual domains (i.e., PfAMA-1(III) or PfMSP 1-19). The two-dimensional spectra and transverse relaxation rates (R2) of the PfMSP1-19 alone were compared with that of the PfCP-2.9. RESULTS: Confident backbone assignments were obtained for 122 out of 241 residues of PfCP-2.9. The assigned residues in PfCP-2.9 were very similar to those previously reported for the individual domains. The conformation of the PfMSP1-19 in different constructs is essentially the same. Comparison of transverse relaxation rates (R2) strongly suggests no weak interaction between the domains. CONCLUSIONS: These data indicate that the fusion of AMA-1(III) and MSP1-19 as chimeric protein did not change their structures, supporting the use of the chimeric protein as a potential malaria vaccine.

PMID: 20236549 [PubMed - as supplied by publisher]

Identification of Cytokines in Whole Blood for the Differential Diagnosis of Tuberculosis vs Pneumonia.

Clin Vaccine Immunol. 2010 Mar 17;

Authors: Su WL, Perng WC, Huang CH, Yang CY, Wu CP, Chang FY, Chen JH

Differentiating tuberculosis (TB) from pneumonia remains a challenge. We evaluated the cytokine profiles of whole blood cells from patients with TB (n=38), pneumonia (n=30), and healthy individuals (n=30) before and after stimulating cells with ESAT-6 or LPS. When the percent change in the levels of interferon (IFN)-gamma after stimulation with ESAT-6 was used in receiver operating characteristics (ROC) analysis (a graphic method to determine the diagnostic accuracy of a test) to identify a patient with TB, the area under the curve (AUC) was 90.4%; and a cut-off point of 3.59% change produced a corresponding sensitivity, specificity, and accuracy of over 80%. When the change in IFN-gamma after stimulation of blood cells with LPS was used to identify a patient with pneumonia, the AUC reached 89.1; and a cut-off point of 3.59% produced a sensitivity, specificity, and accuracy of approximately 80% each. When the change in interleukin (IL)-12 after stimulation of blood cells with LPS was selected to define a patient with pneumonia, the AUC was 85.2%; and a cut-off point of 2.08% gave a sensitivity, specificity, and accuracy of 80.0%, 78.9%, and 79.4%, respectively. We conclude that the percent change in IFN-gamma after stimulation of whole blood cells with ESAT-6 may differentiate patients with TB from patients with pneumonia. The percent change in IFN-gamma and IL-12 after LPS-stimulation of whole blood cells could differentiate patients with pneumonia from patients with TB.

PMID: 20237198 [PubMed - as supplied by publisher]