Clinical insights into the interaction of childhood tuberculosis and HIV in the Western Cape

No Abstract

TB or not TB?

Object: The aim of the study was to identify diagnoses that are confused with pulmonary tuberculosis in children. Design: Prospective, investigative clinical study. Setting: Tertiary care teaching hospital and an urban tuberculosis clinic in an area with a very high incidence of pulmonary tuberculosis (> 800 new cases/100 ODD/year). Patients: Children suspected of having tuberculosis, children followed up for pulmonary infiltrates with eosinophilia and children with congenital pulmonjiry anomalies were investigated. Intervention(s): None. Outcome measure: Pulmonary tuberculosis was diagnosed using modified World Health Organisation criteria and the diagnoses of those children not suffering from pulmonary tuberculosis were analysed. Results: Of the 354 children initially suspected of suffering from tuberculosis 71 (20%) were found to be suffering from other pulmonary disease, viz. pneumonia or bronchopneumonia (29%), bronchopneumonia with Wheezing (18%), and asthma with lobar or segmental collapse (12%). Of 14 children suffering from pulmonary infiltrates with peripheral eosinophilia 6 (43%) were initially incorrectly diagnosed and treated for tuberculosis. Of 54 children with congenital pulmonary anomalies, 8 (15%) were treated for tuberculosis before the correct diagnosis was made. Congenital anomalies most often confused with tuberculosis were unilateral lung hypoplasia, bronchogenic cyst and tracheal bronchus with an anomalous lobe. Conclusions: The criteria for diagnosing tuberculosis in children is complicated in areas with a high incidence of tuberculosis and poor socio-economic circumstances where many children presenting with conditions other than tuberculosis will be in contact with an adult case of pulmonary tuberculosis. The commonest conditions confused with tuberculosis are pneumonia, bronchopneumonia and asthma. Pulmonary infiltrates with  peripheral eosinophilia and congenital lung abnormalities should be considered especially if the children have an atypical clinical picture or do not respond to tuberculosis treatment.S Afr Med J 1995; 85: 658-66

Survival And Growth Of Triploid Crassostrea Virginica (Gmelin, 1791) And C-Ariakensis (Fujita, 1913) In Bottom Environments Of Chesapeake Bay: Implications For An Introduction

Survival and growth of triploid Crassostrea virginica and triploid C. ariakensis were investigated at four sites Surrounding Chesapeake Bay, United States, that varied tried in salinity, tidal regime, water depth, predation intensity and disease pressure. Four experimental treatments were established at each site: C. virginica; C. ariakensis; 50:50 of C. virginica: C. ariakensis: and shell only. Oysters were deployed at mean shell heights of 12.80 min and 13.85 mm (C. virginica and C. ariakensis, respectively), at an overall density of 347.5 oysters m(-2). Oyster survival and growth varied significantly, with site and species. Survival was significantly higher in C. virginica than C. ariakensis at the intertidal site, and significantly higher in C. ariakensis than C. virginica at the highest salinity, subtidal site. Survival did not differ significantly between species at the mid and low salinity, subticial sites. For both Species. survival differed significantly between sites, with lowest survival in both species Occurring Lit the intertidal site. Among the subtidal sites. C. virginica survival varied inversely with salinity, whereas C. ariakensis had the lowest Survival at the mid salinity site. Eight months after deployment C. ariakensis were significantly, larger than C. virginica at all sites. This difference generally persisted throughout the experiment, though the size differences between oyster species at the lowest salinity site were small (\u3c 10%). Shell heights within single-species treatments differed significantly between sites; highest growth rates were observed at the high salinity, subtidal site, whereas lowest growth rates were observed at the high salinity, intertidal site. At low and mid salinity subtidal sites, C. ariakensis shell heights were significantly greater in the single-species treatment compared with the mixed-species treatment. Perkinsus marinus infections occurred in both species at all sites, with prevalences varying between sites. In C. virginica, moderate and high intensity infections were only common at the two higher salinity sites, whereas infections in C. ariakensis were generally low, to rare. Haplosporidium nelsoni infections in C. virginica were only observed at the two higher salinity sites and prevalences were generally low. Two out of 53 C. ariakensis tested at the high salinity, subtidal site had rare H. nelsoni infections. Bonamia spp. infections were never observed. Our study supports previous laboratory findings and observations from its native range that C. ariakensis Survives poorly in intertidal habitats. In subtidal habitats, however, C. ariakensis displayed broad environmental tolerances, often exceeding native oyster Survival and growth rates. Post-introduction C. ariakensis Populations would be shaped by the survival and growth patterns described here, but also by their reproductive success, larval Survival, predator-prey interactions and prevailing disease dynamics

Genomic-Bioinformatic Analysis of Transcripts Enriched in the Third-Stage Larva of the Parasitic Nematode Ascaris suum

Differential transcription in Ascaris suum was investigated using a genomic-bioinformatic approach. A cDNA archive enriched for molecules in the infective third-stage larva (L3) of A. suum was constructed by suppressive-subtractive hybridization (SSH), and a subset of cDNAs from 3075 clones subjected to microarray analysis using cDNA probes derived from RNA from different developmental stages of A. suum. The cDNAs (n = 498) shown by microarray analysis to be enriched in the L3 were sequenced and subjected to bioinformatic analyses using a semi-automated pipeline (ESTExplorer). Using gene ontology (GO), 235 of these molecules were assigned to ‘biological process’ (n = 68), ‘cellular component’ (n = 50), or ‘molecular function’ (n = 117). Of the 91 clusters assembled, 56 molecules (61.5%) had homologues/orthologues in the free-living nematodes Caenorhabditis elegans and C. briggsae and/or other organisms, whereas 35 (38.5%) had no significant similarity to any sequences available in current gene databases. Transcripts encoding protein kinases, protein phosphatases (and their precursors), and enolases were abundantly represented in the L3 of A. suum, as were molecules involved in cellular processes, such as ubiquitination and proteasome function, gene transcription, protein–protein interactions, and function. In silico analyses inferred the C. elegans orthologues/homologues (n = 50) to be involved in apoptosis and insulin signaling (2%), ATP synthesis (2%), carbon metabolism (6%), fatty acid biosynthesis (2%), gap junction (2%), glucose metabolism (6%), or porphyrin metabolism (2%), although 34 (68%) of them could not be mapped to a specific metabolic pathway. Small numbers of these 50 molecules were predicted to be secreted (10%), anchored (2%), and/or transmembrane (12%) proteins. Functionally, 17 (34%) of them were predicted to be associated with (non-wild-type) RNAi phenotypes in C. elegans, the majority being embryonic lethality (Emb) (13 types; 58.8%), larval arrest (Lva) (23.5%) and larval lethality (Lvl) (47%). A genetic interaction network was predicted for these 17 C. elegans orthologues, revealing highly significant interactions for nine molecules associated with embryonic and larval development (66.9%), information storage and processing (5.1%), cellular processing and signaling (15.2%), metabolism (6.1%), and unknown function (6.7%). The potential roles of these molecules in development are discussed in relation to the known roles of their homologues/orthologues in C. elegans and some other nematodes. The results of the present study provide a basis for future functional genomic studies to elucidate molecular aspects governing larval developmental processes in A. suum and/or the transition to parasitism

A classification of diabetic foot infections using ICD-9-CM codes: application to a large computerized medical database

<p>Abstract</p> <p>Background</p> <p>Diabetic foot infections are common, serious, and varied. Diagnostic and treatment strategies are correspondingly diverse. It is unclear how patients are managed in actual practice and how outcomes might be improved. Clarification will require study of large numbers of patients, such as are available in medical databases. We have developed and evaluated a system for identifying and classifying diabetic foot infections that can be used for this purpose.</p> <p>Methods</p> <p>We used the (VA) Diabetes Epidemiology Cohorts (DEpiC) database to conduct a retrospective observational study of patients with diabetic foot infections. DEpiC contains computerized VA and Medicare patient-level data for patients with diabetes since 1998. We determined which ICD-9-CM codes served to identify patients with different types of diabetic foot infections and ranked them in declining order of severity: Gangrene, Osteomyelitis, Ulcer, Foot cellulitis/abscess, Toe cellulitis/abscess, Paronychia. We evaluated our classification by examining its relationship to patient characteristics, diagnostic procedures, treatments given, and medical outcomes.</p> <p>Results</p> <p>There were 61,007 patients with foot infections, of which 42,063 were classifiable into one of our predefined groups. The different types of infection were related to expected patient characteristics, diagnostic procedures, treatments, and outcomes. Our severity ranking showed a monotonic relationship to hospital length of stay, amputation rate, transition to long-term care, and mortality.</p> <p>Conclusions</p> <p>We have developed a classification system for patients with diabetic foot infections that is expressly designed for use with large, computerized, ICD-9-CM coded administrative medical databases. It provides a framework that can be used to conduct observational studies of large numbers of patients in order to examine treatment variation and patient outcomes, including the effect of new management strategies, implementation of practice guidelines, and quality improvement initiatives.</p

Risk of latent tuberculosis infection in children living in households with tuberculosis patients: a cross sectional survey in remote northern Lao People's Democratic Republic

ABSTRACT: BACKGROUND: Tuberculosis is highly prevalent in Laos (289 per 100,000). We evaluated the risk of latent tuberculosis infection (LTBI) among children (0-15 years) living with tuberculosis patients in rural northern Laos. METHODS: In a cross sectional survey of 30 randomly selected villages, 72 tuberculosis patients were traced and their 317 contacts (148 were children) investigated using a questionnaire, a tuberculin skin tests (positive: <= 10mm), a 3-day sputum examination for acid-fast bacilli (AFB), and chest radiography. RESULTS: None of the 148 contact-children received prophylaxis, one had cervical tuberculosis; the risk for LTBI was 31.0%. Awareness of the infectiousness of tuberculosis was low among patients (31%) and their contacts (31%), and risky behavior was common. After multivariate logistic analysis, increased LTBI was found in children with contact with sputum positive adults (OR: 3.3, 95% CI: 1.4-7.7), patients highly positive sputum prior to treatment (AFB <2+; OR: 4.7, 95% CI: 1.7-12.3), and living in ethnic minorities (OR: 5.4, 95% CI: 2.2-13.6). CONCLUSION: The study supports the importance of contact tracing in remote settings with high TB prevalence. Suggestions to improve the children's detection rate, the use of existing guidelines, chemoprophylaxis of contact-children and the available interventions in Laos are discussed. Improving education and awareness of the infectiousness of TB in patients is urgently needed to reduce TB transmissio

Predictors of Bacterial Meningitis in Resource-Limited Contexts: An Angolan Case

BACKGROUND: Despite the great morbidity and mortality that childhood bacterial meningitis (BM) is experiencing in Africa, diagnosis of BM in resource-limited contexts is still a challenge. Several algorithms and clinical predictors have been proposed to help physicians in decision-making but a lot of these markers used variables that are calculable only in well-equipped laboratories. Predictors or algorithm based on parameters that can be easily performed in basic laboratories can help significantly in BM diagnosis, even in resource-limited settings, rural hospitals or health centers. RESULTS: This retrospective study examined 145 cerebral-spinal fluid (CSF) specimens from children from 2 months to 14 years. CSF specimens were divided into two groups, according to the presence or not of a clinical diagnosis of BM. For each specimen, CSF aspect, CSF white blood cells (WBC) count, CSF glucose and protein concentration were analyzed and statistical analysis were performed. CSF WBC count ≥10/µl is no more a valuable predictor of BM. CSF protein concentration ≥50 mg/dl has a better sensitivity for BM diagnosis and when used with CSF glucose concentration ≤40 mg/dl, can help to diagnose correctly almost all the BM cases. An algorithm including CSF protein concentration, glucose concentration and WBC count has been proposed to rule out BM and to correctly diagnose it. CONCLUSIONS: In resource-limited health centers, the availability of a combination of easy-to-obtain parameters can significantly help physicians in BM diagnosis. The prompt identification of a BM case can be rapid treated or transferred to adequate structures and can modify the outcome in the patient

A questionnaire for determining prevalence of diabetes related foot disease (Q-DFD): construction and validation

<p>Abstract</p> <p>Background</p> <p>Community based prevalence for diabetes related foot disease (DRFD) has been poorly quantified in Australian populations. The aim of this study was to develop and validate a survey tool to facilitate collection of community based prevalence data for individuals with DRFD via telephone interview.</p> <p>Methods</p> <p>Agreed components of DRFD were identified through an electronic literature search. Expert feedback and feedback from a population based construction sample were sought on the initial draft. Survey reliability was tested using a cohort recruited through a general practice, a hospital outpatient clinic and an outpatient podiatry clinic. Level of agreement between survey findings and either medical record or clinical assessment was evaluated.</p> <p>Results</p> <p>The Questionnaire for Diabetes Related Foot Disease (Q-DFD) comprised 12 questions aimed at determining presence of peripheral sensory neuropathy (PN) and peripheral vascular disease (PVD), based on self report of symptoms and/or clinical history, and self report of foot ulceration, amputation and foot deformity. Survey results for 38 from 46 participants demonstrated agreement with either clinical assessment or medical record (kappa 0.65, sensitivity 89.0%, and specificity 77.8%). Correlation for individual survey components was moderate to excellent. Inter and intrarater reliability and test re-test reliability was moderate to high for all survey domains.</p> <p>Conclusion</p> <p>The development of the Q-DFD provides an opportunity for ongoing collection of prevalence estimates for DRFD across Australia.</p

Clinico-epidemiological profile and diagnostic procedures of pediatric tuberculosis in a tertiary care hospital of western Nepal-a case-series analysis

<p>Abstract</p> <p>Background</p> <p>Changing epidemiology and diagnostic difficulties of paediatric tuberculosis (TB) are being increasingly reported. Our aim was to describe clinico-epidemiological profile and diagnostic procedures used for paediatric TB.</p> <p>Methods</p> <p>A retrospective case-series analysis was carried out in a tertiary care teaching hospital of western Nepal. All pediatric TB (age 0-14 years) patients registered in DOTS clinic during the time period from March, 2003 to July, 2008 were included. Medical case files were reviewed for information on demography, clinical findings, investigations and final diagnosis. Analysis was done on SPSS package. Results were expressed as rates and proportions. Chi square test was used to test for statistical significance.</p> <p>Results</p> <p>About 17.2% (162/941) of TB patients were children. Common symptoms were cough, fever and lymph node swelling. The types of TB were <b/>pulmonary TB (46.3%, 75/162), followed by extra-pulmonary TB (41.4%, 67/162). Twelve patients (7.4%) had disseminated TB. Distribution of types of TB according to gender was similar. PTB was common in younger age than EPTB which was statistically significant. EPTB was mainly localized to lymph node (38, 50.7%), and abdomen (9, 12%). Five main investigations namely Mantoux test, BCG test, chest radiograph, erythrocyte sedimentation rate (ESR) and fine needle aspiration cytology (FNAC) or biopsy were carried out to diagnose TB.</p> <p>Conclusions</p> <p>Paediatric TB in both pulmonary and extrapulmonary forms is a common occurrence in our setting. Age incidence according to type of TB was significant. Diagnosis was based on a combination of epidemiological and clinical suspicion supported by results of various investigations.</p

Computational Design of a PDZ Domain Peptide Inhibitor that Rescues CFTR Activity

The cystic fibrosis transmembrane conductance regulator (CFTR) is an epithelial chloride channel mutated in patients with cystic fibrosis (CF). The most prevalent CFTR mutation, ΔF508, blocks folding in the endoplasmic reticulum. Recent work has shown that some ΔF508-CFTR channel activity can be recovered by pharmaceutical modulators (“potentiators” and “correctors”), but ΔF508-CFTR can still be rapidly degraded via a lysosomal pathway involving the CFTR-associated ligand (CAL), which binds CFTR via a PDZ interaction domain. We present a study that goes from theory, to new structure-based computational design algorithms, to computational predictions, to biochemical testing and ultimately to epithelial-cell validation of novel, effective CAL PDZ inhibitors (called “stabilizers”) that rescue ΔF508-CFTR activity. To design the “stabilizers”, we extended our structural ensemble-based computational protein redesign algorithm to encompass protein-protein and protein-peptide interactions. The computational predictions achieved high accuracy: all of the top-predicted peptide inhibitors bound well to CAL. Furthermore, when compared to state-of-the-art CAL inhibitors, our design methodology achieved higher affinity and increased binding efficiency. The designed inhibitor with the highest affinity for CAL (kCAL01) binds six-fold more tightly than the previous best hexamer (iCAL35), and 170-fold more tightly than the CFTR C-terminus. We show that kCAL01 has physiological activity and can rescue chloride efflux in CF patient-derived airway epithelial cells. Since stabilizers address a different cellular CF defect from potentiators and correctors, our inhibitors provide an additional therapeutic pathway that can be used in conjunction with current methods