Therapeutic efficacy of chloroquine for treatment of Plasmodium vivax malaria cases in Halaba district, South Ethiopia

<p>Abstract</p> <p>Background</p> <p>Chloroquine is an anti-malarial drug being used to treat <it>Plasmodium vivax </it>malaria cases in Ethiopia. However, emergence of chloroquine resistant strains of the parasite has challenged the current efficacy of the drug. Therefore, the aim of this study was to assess the effectiveness of chloroquine against <it>P. vivax </it>strains in one of the malaria endemic areas of Ethiopia, namely Halaba district, located in South Nations and Nationalities Peoples Region (SNNPR) of South Ethiopia</p> <p>Results</p> <p>Among 87 malaria patients enrolled in the study, only 80 of them completed the 28-days follow-up. Seven of them dropped from the study for different reasons. Among those study participants that completed their follow-up, 69 were classified under the category of adequate clinical and parasitological response (ACPR). However, the remaining 11 cases were considered as under treatment failure mainly due to recurrence of parasitemia on day 7 (four patients), day 14 (six patients), and day 21 (one patient). The age of all cases of treatment failures was found to be less than 20 years. The load of parasitemia of patients with treatment failure on day of admission (4709.4/μl) was higher than day of recurrence (372.37/μl). Parasite reduction ratio (PRR) of treatment failure cases was 12.6/μl.</p> <p>Conclusion</p> <p>This report revealed the rise in treatment failure (13% [95% CI = 0.074 - 0.217]) as compared to earlier reports from Ethiopia. It signals the spreading of chloroquine resistant <it>P. vivax </it>(CRPv) strains to malaria endemic areas of Ethiopia. It is recommended that all concerned bodies should act aggressively before further expansion of the current drug resistant malaria.</p

Time-to-pregnancy and pregnancy outcomes in a South African population

<p>Abstract</p> <p>Background</p> <p>Time-to-pregnancy (TTP) has never been studied in an African setting and there are no data on the rates of adverse pregnancy outcomes in South Africa. The study objectives were to measure TTP and the rates of adverse pregnancy outcomes in South Africa, and to determine the reliability of the questionnaire tool.</p> <p>Methods</p> <p>The study was cross-sectional and applied systematic stratified sampling to obtain a representative sample of reproductive age women for a South African population. Data on socio-demographic, work, health and reproductive variables were collected on 1121 women using a standardized questionnaire. A small number (n = 73) of randomly selected questionnaires was repeated to determine reliability of the questionnaire. Data was described using simple summary statistics while Kappa and intra-class correlation statistics were calculated for reliability.</p> <p>Results</p> <p>Of the 1121 women, 47 (4.2%) had never been pregnant. Mean gravidity was 2.3 while mean parity was 2.0 There were a total of 2467 pregnancies; most (87%) resulted in live births, 9.5% in spontaneous abortion and 2.2% in still births. The proportion of planned pregnancies was 39% and the median TTP was 6 months. The reliability of the questionnaire for TTP data was good; 63% for all participants and 97% when censored at 14 months. Overall reliability of reporting adverse pregnancy outcomes was very high, ranging from 90 - 98% for most outcomes.</p> <p>Conclusion</p> <p>This is the first comprehensive population-based reproductive health study in South Africa, to describe the biologic fertility of the population, and provides rates for planned pregnancies and adverse pregnancy outcomes. The reliability of the study questionnaire was substantial, with most outcomes within 70 - 100% reliability index. The study provides important public information for health practitioners and researchers in reproductive health. It also highlights the need for public health intervention programmes and epidemiological research on biologic fertility and adverse pregnancy outcomes in the population.</p

Primaquine in vivax malaria: an update and review on management issues

Primaquine was officially licensed as an anti-malarial drug by the FDA in 1952. It has remained the only FDA licensed drug capable of clearing the intra-hepatic schizonts and hypnozoites of Plasmodium vivax. This update and review focuses on five major aspects of primaquine use in treatment of vivax malaria, namely: a) evidence of efficacy of primaquine for its current indications; b) potential hazards of its widespread use, c) critical analysis of reported resistance against primaquine containing regimens; d) evidence for combining primaquine with artemisinins in areas of chloroquine resistance; and e) the potential for replacement of primaquine with newer drugs

Molecular and epidemiologic analysis of a county-wide outbreak caused by Salmonella enterica subsp. enterica serovar Enteritidis traced to a bakery

BACKGROUND: An increase in the number of attendees due to acute gastroenteritis and fever was noted at one hospital emergency room in Taiwan over a seven-day period from July to August, 2001. Molecular and epidemiological surveys were performed to trace the possible source of infection. METHODS: An epidemiological investigation was undertaken to determine the cause of the outbreak. Stool and blood samples were collected according to standard protocols per Center for Disease Control, Taiwan. Typing of the Salmonella isolates from stool, blood, and food samples was performed with serotyping, antibiotypes, and pulsed field gel electrophoresis (PFGE) following XbaI restriction enzyme digestion. RESULTS: Comparison of the number of patients with and without acute gastroenteritis (506 and 4467, respectively) during the six weeks before the outbreak week revealed a significant increase in the number of patients during the outbreak week (162 and 942, respectively) (relative risk (RR): 1.44, 95% confidence interval (CI): 1.22–1.70, P value < 0.001). During the week of the outbreak, 34 of 162 patients with gastroenteritis were positive for Salmonella, and 28 of these 34 cases reported eating the same kind of bread. In total, 28 of 34 patients who ate this bread were positive for salmonella compared to only 6 of 128 people who did not eat this bread (RR: 17.6, 95%CI 7.9–39.0, P < 0.001). These breads were produced by the same bakery and were distributed to six different traditional Chinese markets., Salmonella enterica subsp. enterica serovar Enteritidis (S. Enteritidis) was isolated from the stool samples of 28 of 32 individuals and from a recalled bread sample. All S. Enteritidis isolates were of the same antibiogram. PFGE typing revealed that all except two of the clinical isolates and the bread isolates were of the same DNA macrorestriction pattern. CONCLUSIONS: The egg-covered bread contaminated with S. Enteritidis was confirmed as the vehicle of infection. Alertness in the emergency room, surveillance by the microbiology laboratory, prompt and thorough investigation to trace the source of outbreaks, and institution of appropriate control measures provide effective control of community outbreaks

Hyperglycemia in bacterial meningitis: a prospective cohort study

ABSTRACT: BACKGROUND: Hyperglycemia has been associated with unfavorable outcome in several disorders, but few data are available in bacterial meningitis. We assessed the incidence and significance of hyperglycemia in adults with bacterial meningitis. METHODS: We collected data prospectively between October 1998 and April 2002, on 696 episodes of community-acquired bacterial meningitis, confirmed by culture of CSF in patients >16 years. Patients were dichotomized according to blood glucose level on admission. A cutoff random non-fasting blood glucose level of 7.8 mmol/L (140 mg/dL) was used to define hyperglycemia, and a cutoff random non-fasting blood glucose level of 11.1 mmol/L (200 mg/dL) was used to define severe hyperglycemia. Unfavorable outcome was defined on the Glasgow outcome scale as a score <5. We also evaluated characteristics of patients with a preadmission diagnosis of diabetes mellitus. RESULTS: 69% of patients were hyperglycemic and 25% severely hyperglycemic on admission. Compared with non-hyperglycemic patients, hyperglycemia was related with advanced age (median, 55 yrs vs. 44 yrs, P<0.0001), preadmission diagnosis of diabetes (9% vs. 3%, P=0.005), and distant focus of infection (37% vs. 28%, P=0.02). They were more often admitted in coma (16% vs. 8%; P=0.004) and with pneumococcal meningitis (55% vs. 42%, P=0.007). These differences remained significant after exclusion of patients with known diabetes. Hyperglycemia was related with unfavorable outcome (in a hockey stick-shaped curve) but this relation did not remain robust in a multivariate analysis. Factors predictive for neurologic compromise were related with higher blood glucose levels, whereas factors predictive for systemic compromise were related with lower blood glucose levels. Only a minority of severely hyperglycemic patients were known diabetics (19%). The vast majority of these known diabetic patients had meningitis due to Streptococcus pneumoniae (67%) or Listeria monocytogenes (13%) and they were at high risk for unfavorable outcome (52%). CONCLUSIONS: The majority of patients with bacterial meningitis have hyperglycemic blood glucose levels on admission. Hyperglycemia can be explained by a physical stress reaction, the central nervous system insult leading to disturbed blood-glucose regulation mechanisms, and preponderance of diabetics for pneumococcal meningitis. Patients with diabetes and bacterial meningitis are at high risk for unfavorable outcom

The relationship among oceanography, prey fields, and beaked whale foraging habitat in the Tongue of the Ocean

This article is distributed under the terms of the Creative Commons CC0 public domain dedication. The definitive version was published in PLoS One 6 (2011): e19269, doi:10.1371/journal.pone.0019269.Beaked whales, specifically Blainville's (Mesoplodon densirostris) and Cuvier's (Ziphius cavirostris), are known to feed in the Tongue of the Ocean, Bahamas. These whales can be reliably detected and often localized within the Atlantic Undersea Test and Evaluation Center (AUTEC) acoustic sensor system. The AUTEC range is a regularly spaced bottom mounted hydrophone array covering >350 nm2 providing a valuable network to record anthropogenic noise and marine mammal vocalizations. Assessments of the potential risks of noise exposure to beaked whales have historically occurred in the absence of information about the physical and biological environments in which these animals are distributed. In the fall of 2008, we used a downward looking 38 kHz SIMRAD EK60 echosounder to measure prey scattering layers concurrent with fine scale turbulence measurements from an autonomous turbulence profiler. Using an 8 km, 4-leaf clover sampling pattern, we completed a total of 7.5 repeat surveys with concurrently measured physical and biological oceanographic parameters, so as to examine the spatiotemporal scales and relationships among turbulence levels, biological scattering layers, and beaked whale foraging activity. We found a strong correlation among increased prey density and ocean vertical structure relative to increased click densities. Understanding the habitats of these whales and their utilization patterns will improve future models of beaked whale habitat as well as allowing more comprehensive assessments of exposure risk to anthropogenic sound.The data collection and analysis was funded by the Office of Naval Research as N00014-08-1-1162

Detection of unsafety in families with parental and/or child developmental problems at the start of family support

Background Risk assessment is crucial in preventing child maltreatment as it can identify high-risk cases in need of child protection intervention. Despite this importance, there have been no validated risk assessment instruments available in the Netherlands for assessing the risk of child maltreatment. Therefore, the predictive validity of the California Family Risk Assessment (CFRA) was examined in Dutch families who received family support. In addition, the added value of a number of experimental items was examined. Finally, it was examined whether the predictive value of the instrument could be improved by modifying the scoring procedure. Methods Dutch families who experienced parenting and/or child developmental problems and were referred by the Centres for Youth and Family for family support between July 2009 and March 2011 were included. This led to a sample of 491 families. The predictive validity of the CFRA and the added value of the experimental items were examined by calculating AUC values. A CHAID analysis was performed to examine whether the scoring procedure could be improved. Results About half of the individual CFRA items were not related to future reports of child maltreatment. The predictive validity of the CFRA in predicting future reports of child maltreatment was found to be modest (AUC = .693). The addition of some of the experimental items and the modification of the scoring procedure by including only items that were significantly associated with future maltreatment reports resulted in a ‘high’ predictive validity (AUC = .795). Conclusions This new set of items might be a valuable instrument that also saves time because only variables that uniquely contribute to the prediction of future reports of child maltreatment are included. Furthermore, items that are perceived as difficult to assess by professionals, such as parental mental health problems or parents’ history of abuse/neglect, could be omitted without compromising predictive validity. However, it is important to examine the psychometric properties of this new set of items in a new dataset

Determination of the Molecular Basis for a Limited Dimorphism, N417K, in the Plasmodium vivax Duffy-Binding Protein

Invasion of human red blood cells by Plasmodium merozoites is vital for replication and survival of the parasite and, as such, is an attractive target for therapeutic intervention. Merozoite invasion is mediated by specific interactions between parasite ligands and host erythrocyte receptors. The P. vivax Duffy-binding protein (PvDBP) is heavily dependent on the interaction with the human Duffy blood group antigen/receptor for chemokines (DARC) for invasion. Region II of PvDBP contains many allelic polymorphisms likely to have arisen by host immune selection. Successful vaccine development necessitates a deeper understanding of the role of these polymorphisms in both parasite function and evasion of host immunity. A 3D structure of the homologous P. knowlesi DBP predicts that most variant residues are surface-exposed, including N417K, which is a dimorphic residue change that has previously been shown to be part of a linked haplotype that alters DBP sensitivity to inhibitory antibody. In natural isolates only two residues are found at this site, asparagine (N) and lysine (K). Site-directed mutagenesis of residue 417 was used to create a panel of 20 amino acid variants that were then examined for their binding phenotype and response to immune sera. Our results suggest that the observed dimorphism likely arose due to both structural requirements and immune selection pressure. To our knowledge, this is the first exhaustive examination of this kind of the role of a single amino acid residue in antigenic character and binding ability. Our results demonstrate that a single amino acid substitution can dramatically alter both the ability of the PvDBP to bind to human erythrocytes and its antigenic character

A Versatile ΦC31 Based Reporter System for Measuring AP-1 and Nrf2 Signaling in Drosophila and in Tissue Culture

This paper describes the construction and characterization of a system of transcriptional reporter genes for monitoring the activity of signaling pathways and gene regulation mechanisms in intact Drosophila, dissected tissues or cultured cells. Transgenic integration of the reporters into the Drosophila germline was performed in a site-directed manner, using ΦC31 integrase. This strategy avoids variable position effects and assures low base level activity and high signal responsiveness. Defined integration sites furthermore enable the experimenter to compare the activity of different reporters in one organism. The reporter constructs have a modular design to facilitate the combination of promoter elements (synthetic transcription factor binding sites or natural regulatory sequences), reporter genes (eGFP, or DsRed.T4), and genomic integration sites. The system was used to analyze and compare the activity and signal response profiles of two stress inducible transcription factors, AP-1 and Nrf2. To complement the transgenic reporter fly lines, tissue culture assays were developed in which the same synthetic ARE and TRE elements control the expression of firefly luciferase