Human circulating specific antibody-forming cells after systemic and mucosal immunizations: differential homing commitments and cell surface differentiation markers

Circulating spontaneous antibody-secreting cells (ASC) induced by mucosal and systemic immunizations in human volunteers have been characterized with respect to differentiation stage and homing commitments. Irrespective of the immunization route, the large majority of ASC co-expressed CD19 and HLA-DR, which are normally lost during the transition of plasmablasts to plasmocytes, as well as CD38, a marker of activated B cell blasts, expressed also by plasmocytes. However, these cells expressed neither CD28, a molecule acquired by plasmocytes, nor CD22 and CD37, which are lost during the transition of plasmablasts to plasmocytes. Therefore, the large majority of ASC found in peripheral blood after oral and parenteral immunizations are terminally differentiated B cells, but not fully differentiated plasmocytes. As a whole, the mucosally derived ASC population seemed to be more homogenously differentiated. CD25 was detected on few ASC, whereas ASC expressing CD71 were more numerous, especially among systemically derived ASC. Almost all ASC expressed the adhesion molecules CD44 and α4-integrins, irrespective of immunization route. However, virtually all systemically derived ASC expressed L-selectin, recognizing the peripheral lymph node addressin, whereas only a minority of mucosally induced blood ASC expressed L-selectin. These studies are the first to demonstrate in humans that circulating precursors of mucosal B cell immunoblasts utilize organ-specific recognition mechanisms distinct from those of corresponding systemic B cells and appear to be more advanced in the B lineage maturation pathway. Specialization of receptor expression could explain both the unification of immune responses in diverse mucosal sites and the physiologic segregation of mucosal from non-mucosal immune mechanisms in humans.     

Clinical Activity and Polymerase Chain Reaction Evidence of Chlamydial Infection after Repeated Mass Antibiotic Treatments for Trachoma

It is unclear how the prevalence of clinically active trachoma correlates with the prevalence of ocular chlamydial infection at the community level. In 24 villages from a cluster-randomized clinical trial of mass azithromycin distributions in Ethiopia, the correlation between the prevalence of clinical activity (on examination) and chlamydial infection (by polymerase chain reaction) was moderately strong before mass antibiotic treatments (Pearson''s correlation coefficient r = 0.75, 95% confidence interval [CI] = 0.52–0.87), but decreased at each time point during four biannual treatments (at 24 months, r = 0.15, 95% CI = −0.14–0.41). One year after the final treatment, the correlation coefficient had increased, but not to the pre-treatment level (r = 0.55, 95% CI = 0.30–0.73). In a region with hyperendemic trachoma, conjunctival examination was a useful indicator of the prevalence of chlamydial infection before treatments, less useful during mass treatments, but regained utility by one year after treatments had stopped.     

Stereoselective disposition of talinolol in man

The disposition of the beta-blocking drug talinolol is controlled by P-glycoprotein in man. Because talinolol is marketed as a racemate, we reevaluated the serum-concentration time profiles of talinolol of a previously published study with single intravenous (30 mg) and repeated oral talinolol (100 mg for 14 days) before and after comedication of rifampicin (600 mg per day for 9 days) in eight male healthy volunteers (age 22-26 years, body weight 67-84 kg) with respect to differences in the kinetic profiles of the two enantiomers S(-) talinolol and R(+) talinolol. Additionally, the metabolism of talinolol in human liver microsomes was examined. After oral administration, S(-) talinolol was slightly less absorbed and faster eliminated than R(+) talinolol. The absolute bioavailabilty of the R(+) enantiomer of talinolol was slightly but significantly higher than of its S(-) enantiomer. Coadministration of rifampicin further intensified this difference in the disposition of R(+) and S(-) talinolol (p < 0.05). Formation of 4-trans hydroxytalinolol was the major metabolic pathway in human liver microsomes. All Cl(int) values of S(-) were higher than of R(+) talinolol; 0.1 microM ketoconazole inhibited the formation of all metabolites. In conclusion, the stereoselectivity of talinolol disposition is of minor importance, and most likely caused by presystemic biotransformation via CYP3A4. The less active R(+) talinolol might be suitable for phenotyping P-glycoprotein expression in man.     

A rationale for continuing mass antibiotic distributions for trachoma

Background

Fungal infections are diagnosed increasingly often in patients affected by hematological diseases and their mortality has remained high. The recent development of new antifungal drugs gives the clinician the possibility to assess the combination of antifungal drugs with in-vitro or in animal-model synergistic effect.

Methods

We analyzed retrospectively the safety and efficacy of caspofungin-based combination therapy in 40 children and adolescents, most of them were being treated for a malignant disease, who developed invasive aspergillosis (IA) between November 2002 and November 2005.

Results

Thirteen (32.5%) patients developed IA after hematopoietic stem cell transplantation (HSCT), 13 after primary diagnosis, usually during remission-induction chemotherapy, and 14 after relapse of disease. Severe neutropenia was present in 31 (78%) out of the 40 patients. IA was classified as probable in 20 (50%) and documented in 20 (50%) patients, respectively. A favorable response to antifungal therapy was obtained in 21 patients (53%) and the probability of 100-day survival was 70%. Different, though not significant, 100-day survival was observed according to the timing of diagnosis of IA: 51.9% after HSCT; 71.4% after relapse; and 84.6% after diagnosis of underlying disease, p 0.2. After a median follow-up of 0.7 years, 20 patients are alive (50%). Overall, the combination therapy was well tolerated. In multivariate analysis, the factors that were significantly associated to a better overall survival were favorable response to antifungal therapy, p 0.003, and the timing of IA in the patient course of underlying disease, p 0.04.

Conclusion

This study showed that caspofungin-based combination antifungal therapy is an effective therapeutic option also for pediatric patients with IA. These data need to be confirmed by prospective, controlled studies.     

Chlamydia on children and flies after mass antibiotic treatment for trachoma

There are various approaches to control trachoma. These include the elimination of the ocular strains of Chlamydia trachomatis that cause the disease and to decrease the spread of infection by other measures such as fly control. Here, we examined how these two are related (i.e., how treating children with antibiotics affects carriage of Chlamydia by flies). Flies were collected in villages that had received mass oral azithromycin distribution and were compared with flies in untreated villages. Polymerase chain reaction (PCR) was performed to detect chlamydial DNA on the flies. Conjunctival swabs were also taken to assay for chlamydial prevalence in the children. Chlamydia was found on 23% of the flies in the untreated villages but only 0.3% in treated villages. Prevalence of trachoma in children proved to be an excellent predictor of the prevalence on flies (correlation coefficient, 0.89). Thus, treating children with antibiotics may drastically reduce the role of flies as a vector.     

Female genital tuberculosis in Ethiopia.

OBJECTIVES: To study the occurrence of female genital tuberculosis (FGTB) in Ethiopia and to compare the different methods available for its diagnosis. METHODS: Biopsy or curettage samples from 25 clinically suspected cases of FGTB were investigated with histopathology, smear microscopy, TB culture and PCR for mycobacteria. HIV status was determined by ELISA. CD4:CD8 ratio was evaluated by flow cytometry. RESULTS: Among the 25 clinically suspected patients investigated, only one was AFB smear positive, three were culture positive, seven were histology positive and 12 were positive by PCR (a total of 16 positives). Samples taken from the fallopian tube were more frequently positive than those from the endometrium. CONCLUSIONS: The results showed that FGTB is a significant clinical problem in Ethiopia. A combination of PCR with the other available methods was found to be the best alternative to achieve sufficient sensitivity and specificity for the diagnosis of FGTB in this setting.     

Magnitude of episiotomy in a teaching hospital in Addis Ababa, Ethiopia

OBJECTIVE: To assess the rate of Episiotomy in vaginal birth in Tikur Anbessa teaching Hospital and the associated factors that influences the use of episiotomy in the unit. METHODS: A cross-sectional study was conducted in the delivery unit of the Tikur Anbessa Hospital from May to September 2000. Data on mothers who delivered in the study period was collected using structured questionnaire. Variables on use of episiotomy, parity, fetal presentation, duration of labor, mode of delivery, Apgar scores at first and fifth minutes, indications for episiotomy and the practice of analgesia & anesthesia in the management of Episiotomy were collected Medical charts and the labor ward logbook were reviewed for collecting the data. RESULTS: A total of 917 deliveries were attended during the study period among which 672 mothers (83.1%) delivered vaginally. Among the vaginal deliveries, 270 (40.2%) mothers had episiotomy. Of these 203 (75.2%) mothers were primigravidae. Nulliparity (77.7% vs 21.3%), the duration of the second stage of labor more 90 minutes (76% vs. 13.8%) and instrumental delivery (86.2% vs. 13.8%) has been shown to be significantly associated to having episiotomy, while the birth weight and Apgar scores didn't show significant differences. Local anesthesia was used only in 71 (28.1%) cases among the 253 on whom information regarding the use of local anesthesia was retrieved. CONCLUSION: The rate of episiotomy is significantly higher than the recommended practice for many centers. Measures should be taken to lower the rate of episiotomy rate that include preparation of guidelines and protocols according to the standard and training and nurses, midwives and doctors on the selective use of episiotomy. The current practice of perineal repair without analgesia/anesthesia should be revised and making labor and delivery less painful needs to be advocated.     

Survey on bovine trypanosomosis and its vector in Metekel and Awi zones of Northwest Ethiopia

A cross-sectional study was conducted between November 2009 and December 2009 in the riverbank of Abay river tributaries, located in three districts of Awi and Metekel zones, Northwest Ethiopia. The prevalence of bovine trypanosomosis, associated risk factors and distribution as well as vector identification in the study area were considered. Blood samples were collected from 540 randomly selected local (zebu) breed of cattle in nine peasant associations of three districts and the assumed risk factors were recorded. The collected samples were examined using hematological and parasitological techniques. In this study, sixty-seven animals (12.42%) were infected with different species of trypanosomes. Most of the infections were due to T. congolense (77.6%) followed by T. vivax (14.9%), T. brucei (6.0%) and mixed infection of T. congolense and T. vivax (1.5%). There was no statistical significance (p > 0.05) between sex, age and coat color of skin, but significant differences were observed in body condition, altitude and districts (p < 0.05). Mean PCV value of infected (19.42%) and non-infected (24.13%) group of animals had significant variation; and mean PCV value of poor body condition was significantly different (p < 0.001) from good body condition. A total of 3072 tsetse flies of riverine species or palpalis group (Glossina tachinoides) and biting flies were caught, of these 2792 (90.9%) were tsetse flies and the remaining were Stomoxys and Tabanus. The overall apparent densities of tsetse and biting flies were 6.49 and 0.65 flies/trap/day, respectively and the difference was significant (p < 0.05). The study revealed that bovine trypanosomosis is more prevalent in low land and in poor body condition animals in the study area. Tsetse distribution also coincides with altitude, where there was high tsetse catch in low land, but none in mid land. Therefore, prompt control strategy has to be designed and implemented in the area to minimize the distribution of tsetse as well as trypanosomosis prevalence.