A Randomized,Placebo-Controlled Trial Evaluating Safety and Immunogenicity of the Killed,Bivalent, Whole-Cell Oral Cholera Vaccine in Ethiopia

Killed whole-cell oral cholera vaccine (OCV) has been a key component of a comprehensive package including water and sanitation measures for recent cholera epidemics. The vaccine, given in a two-dose regimen, has been evaluated in a large number of human volunteers in India, Vietnam, and Bangladesh, where it has demonstrated safety, immunogenicity, and clinical efficacy. We conducted a double-blind randomized placebo-controlled trial in Ethiopia, where we evaluated the safety and immunogenicity of the vaccine in 216 healthy adults and children. OCV was found to be safe and elicited a robust immunological response against Vibrio cholerae O1, with 81% adults and 77% children demonstrating seroconversion 14 days after the second dose of vaccine. This is the first study to evaluate safety and immunogenicity of the vaccine in a population outside Asia using a placebo-controlled, double-blind, randomized study design.     

Demographic and Health-related Risk Factors of Subclinical Vitamin A Deficiency in Ethiopia

The study was conducted to determine the demographic and health-related risk factors of subclinical vitamin A deficiency in Ethiopia. Blood samples were collected from 996 children in 210 clusters across the nation for analysis of serum retinol. Interviews were conducted with the respective mothers of the 996 children on presumed risk factors of vitamin A deficiency. A higher subclinical vitamin A deficiency was associated with: not receiving vitamin A supplement over the year, having been ill during the two weeks preceding the survey, no or incomplete vaccination, belonging to a mother with high parity, and low levels of awareness of vitamin A. Moreover, being from Muslim household was strongly associated with higher levels of subclinical vitamin A deficiency. Among the risk factors identified, low levels of vaccination, high parity, and low levels of maternal awareness of vitamin A contributed to higher risks of vitamin A deficiency among Muslim children. The findings underscore the need for creation of strengthened awareness of family planning and importance of vitamin A, promotion of vaccination and child health, intensification of vitamin A supplementation, and in-depth investigation on factors contributing to increased vulnerability of Muslim children.Key words: Cross-sectional studies, Risk factors, Serum retinol, Vitamin A, Vitamin A deficiency, Xerophthalmia, Ethiopia     

HIV and intestinal parasites in adult TB patients in a teaching hospital in Northwest Ethiopia

The level of HIV infection and intestinal parasitoses among TB patients was assessed in a hospital-based cross-sectional study involving 257 patients in Gondar, Ethiopia. In TB patients, our study reported co-infection with HIV (52.1%) and intestinal parasites (40.9%) The high prevalence of HIV and intestinal parasites indicates an increased morbidity inTB patients and emphasized the importance of continued HIV sero-surveillance, stool analysis and treatment.     

Prevalence of bacterial pathogens in children with acute respiratory infection in Addis Ababa

A study was conducted in the Ethio-Swedish Children's Hospital and different schools and kindergartens in Addis Ababa to determine the prevalence of bacterial agents that are associated with acute respiratory infection in children from 1998-1999. A total of 883 subjects were studied, out of which 77% were cases from the Ethio-Swedish Children's Hospital and 23% were controls from different schools and kindergartens. From each case and control throat and nasopharyngeal specimens were collected. Culture and different biochemical tests were used to isolate the potential bacterial pathogens. Clinical findings like cough, difficult breathing and fever were correlated with laboratory findings. S. pneumoniae and H. influenzae type b were the most commonly isolated bacteria in both throat and nasopharyngeal specimens; 74% and 70% in the cases and 2% and 5% in the control groups, respectively. This paper discusses the association between throat and nasopharyngeal carriership of bacteria and acute respiratory infection in children in Addis Ababa.     

Rb+ efflux through functional activation of cardiac KCNQ1/minK channels by the benzodiazepine R-L3 (L-364,373)

The slow delayed rectifier K+ current, Iks, encoded by KCNQ1 (KvLQT1)/KCNE1 (mink) genes, contributes to cardiac action potential repolarization and determines the heartbeat rate. Mutations in either KCNQ1 or KCNE1 that reduce Iks cause long-QT syndrome (LQTS), a disorder of ventricular repolarization that results in cardiac arrhythmia and sudden death. A well-recognized potential treatment for LQTS caused by reduction of Iks is to enhance functional activation of cardiac KCNQ1/KCNE1 channels. In the present study, we generated a stable Chinese hamster ovary cell line that expresses KCNQ1/KCNE1 channels confirmed by electrophysiology. Using a pharmacological tool compound R-L3 (L-364,373 [(3-R)-1,3-dihydro-5-(2-fluorophenyl)-3-(1H-indol- 3-ylmethyl)-1-methyl-2H-1,4-benzodiazepin-2-one]), which activates KCNQ1/mink channels, we then developed and validated a non-radioactive rubidium (Rb+) efflux assay that directly measures the functional activity of KCNQ1/KCNE1 channels by atomic absorption spectroscopy. Our results show that the validated Rb+ efflux assay can be used for screening of KCNQ1/KCNE1 openers that potentially treat LQTS in both inherited and acquired forms. In addition, the assay also can be used for evaluation of possible long-QT liability during cardiac selectivity of new chemical entities.     

Simple markers for initiating antiretroviral therapy among HIV-infected Ethiopians

BACKGROUND: We explored the relevance of simple markers (clinical or laboratory markers not requiring sophisticated laboratories) in the decision of initiation of therapy in resource-poor settings. METHODS: Among HIV-infected Ethiopian cohort participants, simple markers predicting short-term death were examined using time-dependent Cox proportional hazards models. Timing of hypothetical treatment was compared between guidelines using the simple markers (based on presence of at least one marker), guidelines recommended by the United States Department of Health and Human Services (based on CD4 cell count and viral load), and guidelines for resource-limited settings recommended by the World Health Organization (WHO). RESULTS: From February 1997 to August 2001, 35 deaths were recorded among 155 HIV-positive participants. Simple independent predictors of death were low body mass index, HIV-related conditions, anaemia, and lymphocyte count < 1500 x 106/l. In such time as was covered by our study, 135 (87%) of 155 cohort participants would have had the same management under both the simple markers and the DHHS guidelines, i.e., would have been treated (n = 114, 74%) or not treated (n = 21, 14%). Of the 114 participants hypothetically treated under either set of guidelines, 91 (80%) would have started treatment at the same time. Application of the WHO guidelines for resource-limited settings (without CD4 cell counts) would have resulted in 11 participants dying without ever meeting a treatment indication during regular follow-up visits. CONCLUSION: Simple markers for the initiation of highly active antiretroviral therapy were identified among HIV-infected Ethiopian patients. The validity of these markers for monitoring patients' improvement following therapy remains to be evaluated.     

Demographic impact of AIDS in a low-fertility urban African setting: projection for Addis Ababa,Ethiopia

The study estimated the potential demographic impact of acquired immunodeficiency syndrome (AIDS) in a low-fertility urban setting in sub-Saharan Africa. The prevalence of human immunodeficiency virus (HIV) projected using a deterministic mathematical model was put into the AIDS Impact Model (AIM) of the SPECTRUM Policy Modelling System to estimate the potential demographic impact ofAIDS in Addis Ababa, Ethiopia. Demographic indicators from 1984 (the start of the HIV epidemic in Ethiopia) to 2024, including and excluding the HIV epidemic, were compared. Addis Ababa is experiencing a demographic transition in which the total fertility rate has declined from 3.8 to below replacement level over the last 20 years. The prevalence of HIV is predicted to stabilize at 10% in adults, resulting in a total number of people living with HIV at 200,000 and a cumulative number of deaths due to AIDS at 50,000. About 60% of adult deaths can be attributable to AIDS by 2000. The epidemic is predicted to reduce life expectancy by 10 and 17 years in 2000 and 2024 respectively, and to turn to negative, the rate of natural increase after 2009. Accordingly, the rate of natural increase will be -0.18%, -0.35%, and -0.71% per annum by 2009, 2014, and 2024 respectively. Population growth is expected to continue with or without HIV, as a result of high net in-migration, although data for migration are scanty. In a low-fertility urban society of Africa, this study shows the potential for the HIV/AIDS epidemic to turn the rate of natural increase to negative.     

In vivo antimalarial activity of essential oils from Cymbopogon citratus and Ocimum gratissimum on mice infected with Plasmodium berghei

The essential oils obtained by hydrodistillation from fresh leaves of Cymbopogon citratus and Ocimum gratissimum growing in Cameroon were analyzed by GC and GC/MS. The main constituents of the oil of Ocimum gratissimum were gamma-terpinene (21.9 %), beta-phellandrene (21.1 %), limonene (11.4 %) and thymol (11.2 %), while the oil of Cymbopogon citratus contained geranial (32.8 %), neral (29.0 %), myrcene (16.2 %) and beta-pinene (10.5 %). The effects of these oils on the growth of Plasmodium berghei were investigated. Both oils showed significant antimalarial activities in the four-day suppressive in vivo test in mice. At concentrations of 200, 300 and 500 mg/kg of mouse per day, the essential oil of C. citratus produced the highest activity with the respective percentages of suppression of parasitaemia: 62.1 %, 81.7 % and 86.6 %. The corresponding values for the oil of O. gratissimum at the same concentrations were 55.0 %, 75.2 % and 77.8 %, respectively. Chloroquine (10 mg/kg of mouse, positive control) had a suppressive activity of 100 %.