Comparison of an interferon-gamma assay with tuberculin skin testing for detection of tuberculosis (TB) infection in patients with rheumatoid arthritis in a TB-endemic population

OBJECTIVE: Tuberculosis (TB) in patients with rheumatoid arthritis (RA) undergoing treatment with anti-tumor necrosis factor (TNF) agents is commonly the result of reactivation of latent TB infection (LTBI); detection and treatment of LTBI is essential before treatment with anti-TNF agents. We reported previously that the tuberculin skin test (TST) is inaccurate for diagnosis of LTBI in patients with RA. Here, we compare the prevalence of LTBI in RA patients and matched controls according to positive TST and QuantiFeron-TB Gold In-Tube version (QFT) results and determine their agreement. METHODS: A cross-sectional study of 101 RA patients and 93 controls was conducted in Lima, Perú, where the prevalence of LTBI in the general population has been estimated to be 68%. Blood was drawn for QFT assay followed by TST using 2-TU of RT 23 purified protein derivative. TST was deemed positive at >or= 5 mm for RA patients and >or= 10 mm for controls. RESULTS: There were no significant differences between RA patients and controls for age, sex, bacillus Calmette-Guérin vaccination, or history of or contact with TB. 88% of patients had active RA disease and 2 (1.9%) patients had indeterminate QFT results. The number of subjects testing positive with the QuantiFeron assay was comparable between patients and controls (44.6% vs 59.1%, respectively), whereas the TST detected significantly less LTBI among RA patients (26.7%) than controls (65.6%). Thus, the rate of LTBI in RA patients represented 75% and 41% of the rate in their controls using QFT or TST, respectively (p = 0.008). Poor agreement between TST and QFT was seen in RA patients, but in controls, good agreement was observed between these tests. CONCLUSION: In a TB-endemic population, the QuantiFeron-TB Gold In-Tube assay seemed to be a more accurate test for detection of LTBI in RA patients compared with the TST, and may potentially improve the targeting of prophylactic therapy before treatment with anti-TNF agents.     

Reproductive Biology of Triatoma brasiliensis (Hemiptera,Triatominae) during the Imaginal Molt

The triatomines are vectors of the protozoan Trypanosoma cruzi, etiologic agent of Chagas disease. These insects are sexually active after the imaginal molt. Some aspects have been studied in Triatoma brasiliensis during the imaginal molt, such as autogeny in virgin females and the relationship between blood ingestion by fifth instar nymph and the realization of the imaginal molt. Thus, to aid in the understanding of reproductive biology and developmental physiology of these vectors, this article analyzes the spermatogenesis of T. brasiliensis during the imaginal molt. The analysis of the seminiferous tubules from males in the fifth instar during imaginal molt has demonstrated that T. brasiliensis has only a few spermatids and a plentiful quantity of sperm. Thus, we suggest that during imaginal molt the cell division is disrupted aiming to reduce energy costs and the differentiation into sperm is stimulated to ensure the paternity of the adult male.Chagas disease is a potentially life-threatening illness caused by the protozoan parasite Trypanosoma cruzi and transmitted to humans by contact with feces of triatomine bugs, known as “kissing bugs.”¹ These vectors have a typical hemimetabolous life cycle, from eggs through five nymphal instars (N1, N2, N3, N4, and N5) to adult males and females. The transition from the fifth instar nymph to adult is named imaginal molt. During this process it occur some corporal changes, such as the emergence of wings,² exocrine glands (metasternal and Brindley''s glands)^3,4 and development of the reproductive system.^5–8Some aspects have been studied in Triatoma brasiliensis Neiva, 1911 during the imaginal molt, such as autogeny in virgin females⁹ and the relationship between blood ingestion by N5 and the realization of the imaginal molt.¹⁰ This triatomine species is the most important Chagas disease vector in the Brazilian northeast.^11,12 Thus, to aid in the understanding of the reproductive biology and developmental physiology of these vectors, this article analyzes the spermatogenesis of T. brasiliensis during the imaginal molt.Five males in the fifth instar nymphs of T. brasiliensis were isolated and during imaginal molt their testicles were removed and fixed in methanol: acetic acid (3:1). They had been assigned by the “Triatominae Insectarium” within the Department of Biological Sciences, in the College of Pharmaceutical Sciences, at Sao Paulo State University''s “Júlio de Mesquita Filho,” Araraquara campus. The colony was formed from T. brasiliensis collected in intradomiciliary region of the municipality Olho d''Água, State of Paraiba, Brazil in the day April 17, 2008.Seminiferous tubules were first shredded, smashed, and the microscope slides were set in liquid nitrogen. They were then stained with the lacto-acetic orcein cytogenetic technique.^13,14 On the basis of the analysis of slides, it was observed that the N5 nymphs, during imaginal molt, have only one of the phases of spermatogenesis, that is, the spermiogenesis. This is represented by the presence of spermatids (Figure 1A –C) and sperm (Figure 1D).Open in a separate windowFigure 1.Spermiogenesis in Triatoma brasiliensis. Note the elongation of spermatids (A–C) and sperm (D). Bar: 10 μm.Spermatogenesis is the process by which sperms are produced in the seminiferous tubules. It consists of three different phases: spermatocitogenesis, which is a phase of multiplication; meiosis, which is the division phase; and spermiogenesis, which is the differentiation phase.¹⁵Perez and others,¹⁶ reported that in some cases fifth instar nymph have mature gonads. Mello and collaborators,¹⁷ analyzed fifth instar nymph of Triatoma infestans and observed the presence of spermatogonia, spermatocytes (metaphase), spermatids, and sperms. However, during imaginal molt of T. brasiliensis there are only a few spermatids and a plentiful quantity of sperm were observed, and we suggest that during imaginal molt, the cell division is disrupted aiming to reduce energy costs, and the differentiation into sperm is stimulated to ensure the paternity of the adult male.There are some offensive mechanisms that increase the chances to ensure the paternity, such as the characteristics of the genitalia,¹⁸ the seminal fluid,¹⁹ and the courtship behavior.²⁰ Taking it into account, we suggest that the excessive increase of sperms during imaginal molt also increase the chances for the paternity.Thus, we suggest that during the imaginal molt T. brasiliensis showed changes in the reproductive biology of development and physiology to decrease the energy cost, ensuring that the molt occur and mainly to increase the chance of paternity in adults. These results provide important information for understanding the biology of this important vector of the Chagas disease. However, we highlight that new species and a larger number of triatomines should be analyzed to characterize whether this phenomenon occurs in all species of Triatominae subfamily.     

Induced Sputum Is Safe and Well-Tolerated for TB Diagnosis in a Resource-Poor Primary Healthcare Setting

Improved tuberculosis (TB) diagnostics are required. Induced sputum sampling is superior to spontaneous sputum analysis for diagnosis of pulmonary TB. Therefore, we examined the applicability of induced sputum in primary health centers of the Peruvian TB program and studied the safety and tolerability of this procedure. We show that induced sputum is safe, inexpensive, and well-tolerated in a resource-limited environment. Widespread use of induced sputum at primary health centers can be implemented and may improve TB diagnosis.     

Hypoglycemia prediction and detection using optimal estimation

Patients with diabetes play with a double-edged sword when it comes to deciding glucose and A1c target levels. On the one side, tight control has been shown to be crucial in avoiding long-term complications; on the other, tighter control leads to an increased risk of iatrogenic hypoglycemia, which is compounded when hypoglycemia unawareness sets in. Development of continuous glucose monitoring systems has led to the possibility of being able not only to detect hypoglycemic episodes, but to make predictions based on trends that would allow the patient to take preemptive action to entirely avoid the condition. Using an optimal estimation theory approach to hypoglycemia prediction, we demonstrate the effect of measurement sampling frequency, threshold level, and prediction horizon on the sensitivity and specificity of the predictions. We discuss how optimal estimators can be tuned to trade-off the false alarm rate with the rate of missed predicted hypoglycemic episodes. We also suggest the use of different alarm levels as a function of current and future estimates of glucose and the hypoglycemic threshold and prediction horizon.