Comparison of the safety and immunogenicity of ACAM1000, ACAM2000 and Dryvax in healthy vaccinia-naive adults

Currently, more than half of the world's population has no immunity against smallpox variola major virus. This phase I double-blind, randomized trial was conducted to compare the safety and immunogenicity of two clonally derived, cell-culture manufactured vaccinia strains, ACAM1000 and ACAM2000, to the parent vaccine, Dryvax^®. Thirty vaccinia-naïve subjects were enrolled into each of three groups and vaccines were administered percutaneously using a bifurcated needle at a dose of 1.0 × 10⁸ PFU/mL. All subjects had a primary skin reaction indicating a successful vaccination. The adverse events, 4-fold neutralizing antibody rise and T cell immune responses were similar between the groups.     

Diarrhoea-associated parasites in HIV-1 seropositive and sero-negative patients in a teaching hospital, Northwest Ethiopia

OBJECTIVE: to determine the prevalence and type of intestinal parasites in HIV infected and uninfected patients with diarrhea. DESIGN: A cross-sectional study was conducted at Gondar University hospital, Northwest Ethiopia, between March 2003 and October 2004. PATIENTS AND METHODS: A total 312 consecutive diarrheic patients were included in the study. Stool specimens were collected and examined for intestinal parasites following direct, formol-ether concentration and modified acid fast staining methods. RESULTS: Among the patients, 63.8% were found to be HIV seropositive. The prevalence of intestinal parasites in HIV seropositive and seronegative diarrheic patients was 30.6% and 33.6%, respectively. The most prevalent parasites were Strongyoides stercoralis (9.0%) and Entamoeba histolytica (8.3%) followed by Ascaris lumbricoides (5.4%) and Cryptosporidium species (5. 1%). CONCLUSION AND RECOMMENDATION: The prevalence of intestinal parasites in diarrheic patients was very high. Institution of appropriate intervention measures are needed to reduce morbidity in such patients.     

Urban background particulate matter and allergic sensitization in adults of ECRHS II

BACKGROUND: Epidemiological studies have shown weak or inconsistent associations between ambient air pollutants and allergic sensitization. The aim of this study was to evaluate whether regional urban air pollution may partly explain the large variation in the prevalence of allergic sensitization across cities of the European Community Respiratory Health Survey (ECRHS) II. METHODS: ECRHS is a cross-sectional survey initiated in 29 countries across Europe in the 1990s (ECRHS I) with a follow-up conducted 10 years later (ECRHS II). Subject characteristics were measured by questionnaires and blood tests conducted for the measurement of specific immunoglobulin E. Fine particle mass (PM(2.5), <2.5 microm) and sulphur on PM(2.5) were measured in 21 centres and annual averages of urban regional background air pollution were calculated. Results were scaled by an interquartile range increase in ambient PM(2.5) (6.03 microg/m(3)) and sulphur (1336 ng/m(3)). Generalized estimating equations were applied to compute population average effect estimates with adjustment for age, gender, smoking habit, education and number of siblings. RESULTS: A notable variation in pollution level and prevalence of allergic sensitization was observed. Moreover, exposure to urban regional background air pollution was not associated with allergic sensitization; adjusted odds ratios and 95% confidence interval were 1.02 (0.95-1.09) for PM(2.5) and 1.08 (0.86-1.31) for sulphur. These statistically non-significant associations were sensitive to model specification. CONCLUSIONS: The study suggests that regional air pollution measured at fixed sites is not associated with allergic sensitization among adults in ECRHS II.     

Tuberculosis and HIV interaction in sub-Saharan Africa: impact on patients and programmes; implications for policies

Sub-Saharan Africa carries the overwhelming share of the global burden of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and of HIV-associated tuberculosis (TB). The impact of HIV on TB patients and programmes has implications for TB control policies. The impact on patients includes the effect of HIV on diagnosis and on the patterns of HIV-related TB, the response of HIV-infected TB patients to TB treatment, the benefits of antiretroviral therapy (ART), and the quality and continuity of care for TB patients. The impact on national TB programmes (NTPs) includes increased case load, impaired NTP performance, increased need for access to ART and difficulties in reaching TB control targets. Implications for policies include the need to promote TB and HIV/AIDS programme collaboration, aimed at improving NTP performance (TB case-finding and treatment outcomes), quality and continuity of care, and monitoring and interpretation of progress towards TB control targets. In order to provide the recommended international standard of care for TB patients, clinicians need to be aware of the impact of HIV on TB patients and programmes and the implications for the policies that provide the framework for this standard. Conversely, policy-makers need to understand the impact of HIV on TB patients and programmes. This can help to ensure a firm evidence base for TB control policies aiming at the high standard of patient care that is at the heart of TB and HIV programmes.     

γδ T cells affect IL-4 production and B-cell tolerance

γδ T cells can influence specific antibody responses. Here, we report that mice deficient in individual γδ T-cell subsets have altered levels of serum antibodies, including all major subclasses, sometimes regardless of the presence of αβ T cells. One strain with a partial γδ deficiency that increases IgE antibodies also displayed increases in IL-4–producing T cells (both residual γδ T cells and αβ T cells) and in systemic IL-4 levels. Its B cells expressed IL-4–regulated inhibitory receptors (CD5, CD22, and CD32) at diminished levels, whereas IL-4–inducible IL-4 receptor α and MHCII were increased. They also showed signs of activation and spontaneously formed germinal centers. These mice displayed IgE-dependent features found in hyper-IgE syndrome and developed antichromatin, antinuclear, and anticytoplasmic autoantibodies. In contrast, mice deficient in all γδ T cells had nearly unchanged Ig levels and did not develop autoantibodies. Removing IL-4 abrogated the increases in IgE, antichromatin antibodies, and autoantibodies in the partially γδ-deficient mice. Our data suggest that γδ T cells, controlled by their own cross-talk, affect IL-4 production, B-cell activation, and B-cell tolerance.The role of γδ T cells within the vertebrate immune system is not yet fully understood, but it has become clear that they exert a strong influence on the immune responses. These cells represent a system of specialized subsets with different developmental kinetics, tissue distributions, and functional roles (1). Moreover, at least some of the subsets appear to balance each other’s influence on the immune system (2). Like αβ T cells and B cells, γδ T cells express antigen receptors encoded by rearranging genes (3, 4), which enable adaptive responses to antigenic challenge. Following such stimulation in the course of diseases, γδ T-cell populations can undergo large changes in size and subset composition (5). The γδ T-cell populations also change during ontogeny and due to interindividual genetic differences (6, 7). Conceivably, such changes might alter γδ T-cell balance and, with it, γδ T-cell influence on other immune cells.In mice and humans, it was found that functional attributes of γδ T cells segregate with expressed γδ T-cell receptors (TCRs) (8, 9), although functional differentiation has also been observed within or across TCR-defined subsets and correlated with other markers, such as CD27 and CD8 (10, 11). The murine TCR-γ locus contains seven Vγ genes, six of which are functional and expressed on the cell surface (3, 12). In the normal mouse spleen, the largest γδ T-cell population expresses Vγ1, followed by Vγ4^pos cells and smaller populations expressing Vγ2 and Vγ7 (13). Vγ5^pos and Vγ6^pos cells are not present in substantial numbers. In earlier studies relying on cell transfer and targeted inactivation with antibodies, we and others (8, 10, 14, 15) found that splenic Vγ1^pos and Vγ4^pos cells exert opposite influences on host responses to infection, allergic sensitization, and malignancy. The data suggested that these two γδ T-cell subsets balance each other in their influence on the immune responses (2).In the current study, we further tested this idea by examining antibody levels and B cells in nonimmunized mice genetically deficient either in individual γδ T-cell subsets or in all γδ T cells. The focus on antibodies derives from our earlier observation that mutant mice selectively deficient in Vγ4 and Vγ6 (B6.TCR-Vγ4^−/−/6^−/−) produce substantially more IgE antibody than WT controls or mice deficient in all γδ T cells (B6.TCR-δ^−/−) (10). Here, we report that deficiency in individual γδ T-cell subsets (16, 17) can change antibody production and B-cell activation in nonimmunized mice to a degree that jeopardizes self-tolerance. However, the effect cannot simply be ascribed to an altered γδ T-cell balance. Instead, it correlates with functional changes that occur within the remaining γδ T cells themselves, when they are no longer restrained by normal γδ cross-talk. Our data show that this cross-talk controls the amount of IL-4 produced by a subset of γδ T cells and other T cells, resulting in downstream effects on antibodies, B cells, and self-tolerance.     

HIV/AIDS prevention practices among military personnel in Northwest Ethiopia

ABSTRACT

The spread of HIV/AIDS is a major public health problem in military personnel in Africa. However, the epidemiological evidence regarding HIV/AIDS prevention practices among military personnel in Ethiopia remains unclear. The aim of this study was to investigate HIV/AIDS prevention practices among military personnel in Northwest Ethiopia. A cross-sectional study among military personnel (n?=?410) was conducted in Northwest Ethiopia in 2015. Data were collected using a pre-tested questionnaire. Multivariable logistic regression model was fitted to ascertain factors influencing participation in HIV/AIDS prevention programs. About one-fourth (24.6%) of the military personnel had multiple sexual partners, of whom 24.7% failed to use condoms regularly when having sex with non-regular sexual partners. Majority of the sample (n?=?355, 86.6%) participated in HIV/AIDS prevention programs. Military personnel who had multiple sexual partners were 6.3 times more likely to report history of non-participation in HIV/AIDS prevention programs (AOR?=?6.3, CI₉₅?=?3.5–11.54). A considerable proportion of military personnel had multiple sexual partners with lower levels of condom utilization with non-regular sexual partners. The study further demonstrated misconceptions about HIV/AIDS in Ethiopian military personnel, which reduce their likelihood of participation in HIV/AIDS prevention programs. Health authorities need to strengthen and accelerate HIV/AIDS prevention programs focusing towards military personnel.     

Is the legal framework by itself enough for successful WHO code implementation? A case study from Ethiopia

Since 2016, Ethiopia has passed several proclamations and directives to regulate the promotion of commercial breastmilk substitute (BMS). Ethiopia's market potential will undoubtedly be the gravitating point for international infant formula companies due to growing urbanization, purchasing power, population, and the relatively low use of BMS to‐date. The aim of this review is to assess the strengths and weaknesses of the existing laws, standards, and monitoring documents used to regulate the marketing of BMSs in Ethiopia and make future recommendations. The study findings highlighted that the regulation on marketing are comprehensive and strong to limit the promotion of infant formula. On the other hand, the regulation on marketing of follow‐up formulas, complementary foods, and growing‐up milk by manufacturers and distributors, media houses, and communication and advertisement agencies are underregulated, especially with regards to the international 69.9 regulation. The monitoring and enforcement of the existing marketing regulations remain limited in the absence of a formal coordination mechanism. Several violations of the national BMS regulations were observed. Forty‐one percent of mothers reported observing the BMS advertising and logos were detected in 36% of health facilities assessed. In 100% of cases, the infant formula labels contained violations. As the lead national authority mandated to regulate food safety, the Ethiopian Food and Drug Authority needs to update its regulations related to the marketing of BMS to fill the loopholes and revise the national law in line with the international code of marketing of BMSs to protect breastfeeding.     

Treatment outcome of tuberculosis patients under directly observed treatment in Addis Ababa,Ethiopia

BackgroundTuberculosis is one of the leading causes of mortality among infectious diseases worldwide. For effective tuberculosis control, it is a pre-requisite to detect the cases as early as possible, and to ensure that the tuberculosis patients complete their treatment and get cured. However, in many resource-constrained settings treatment outcome for tuberculosis has not been satisfactory.ObjectiveThe aim of the study was to assess the treatment outcome of tuberculosis patients and investigate the association of demographic and clinical factors with treatment success of patients enrolled in Directly Observed Treatment Short Course program in government owned health centers over the course of five consecutive years in Addis Ababa, Ethiopia.MethodsA register based historical cohort study covering the period of July 2004 to June 2009 was conducted to determine the treatment outcome of Directly Observed Treatment Short Course in government owned health centers in Addis Ababa. Sex and age of tuberculosis patients, health center at which the patient was treated, year of treatment, type of tuberculosis for which the patient was treated, type of treatment offered to the patient, follow-up status and documented treatment outcome were extracted from the Directly Observed Treatment Short Course clinics of three randomly selected health centers.ResultRecords of 6450 registered tuberculosis patients (n = 3147 males and 3433 females) were included in this document review. Of these patients 18.1% were reported as being cured, 64.6% were documented as treatment completed, 3.7% died during follow-up, 5.1% were reported as defaulters, 0.4% were documented as treatment failure and 8.2% were transferred out to another health institution. Treatment center and year of enrollment were significantly associated with treatment success.ConclusionYear of enrollment and treatment center were significantly associated with treatment success. Although the overall treatment success obtained in this study is in line with the World Health Organization (WHO) target, continuous follow-up of patients with frequent supportive supervision during the course of treatment, and further investigate the cause for the observed difference in treatment success across treatment centers are recommended.