Death and Seeking Alternative Therapy Largely Accounted for Lost to Follow-up of Patients on ART in Northwest Ethiopia: A Community Tracking Survey

Background

Antiretroviral treatment programs in sub-Saharan African countries are highly affected by LTF. Tracking patients lost to follow-up and understanding their status is essential to maintain program quality and to develop targeted interventions to prevent LTF. We aimed to determine the outcome and factors associated with LTF.

Method

A lost to follow-up community tracking survey was conducted to determine the reasons, outcomes and factors associated with LTF at the University of Gondar Hospital, northwest Ethiopia. All patients were tracked at home to ascertain outcome status for lost to follow-up (death and non-death losses).

Result

Out of the 551 patients LTF, 486 (88.20%) were successfully tracked. Death was the most common reason accounted for 233 (47.94%) of the lost to follow-up. Reasons for non-deaths losses include: stopped antiretroviral treatment due to different reasons, 135(53.36%), and relocation to another antiretroviral treatment program by self- transfer, 118(46.64%). The rate of mortality in the first six months was 72.12 per 100 person-years (95% CI: 61.80–84.24) but this sharply decreased after 12 months to 7.92 per 100 person-years (95% CI: 4.44–14.41). Baseline clinical characteristics were strongly associated with mortality.

Conclusion

Death accounts for about half of the loss to follow up. Most deaths occur in the first six months of loss. Seeking alternative therapy is another major reason for loss to follow up. Early tracking mechanisms are necessary to prevent death.     

Aggregation of Lipid-Anchored Full-Length H-Ras in Lipid Bilayers: Simulations with the MARTINI Force Field

Lipid-anchored Ras oncoproteins assemble into transient, nano-sized substructures on the plasma membrane. These substructures, called nanoclusters, were proposed to be crucial for high-fidelity signal transmission in cells. However, the molecular basis of Ras nanoclustering is poorly understood. In this work, we used coarse-grained (CG) molecular dynamics simulations to investigate the molecular mechanism by which full-length H-ras proteins form nanoclusters in a model membrane. We chose two different conformations of H-ras that were proposed to represent the active and inactive state of the protein, and a domain-forming model bilayer made up of di16:0-PC (DPPC), di18:2-PC (DLiPC) and cholesterol. We found that, irrespective of the initial conformation, Ras molecules assembled into a single large aggregate. However, the two binding modes, which are characterized by the different orientation of the G-domain with respect to the membrane, differ in dynamics and organization during and after aggregation. Some of these differences involve regions of Ras that are important for effector/modulator binding, which may partly explain observed differences in the ability of active and inactive H-ras nanoclusters to recruit effectors. The simulations also revealed some limitations in the CG force field to study protein assembly in solution, which we discuss in the context of proposed potential avenues of improvement.     

Effect of Brassica carinata (L.) biofumigants (seed meal) on chickpea wilt (Fusarium oxysporum f.sp. ciceris), growth,yield and yield component in Ethiopia

Pot experiments were carried out in the green house at Amhara Regional Agriculture Research Institute (ARARI) Bahirdar, Ethiopia to evaluate the potential of Brassica carinata cultivars namely; Holleta-l, S-67 and Yellow Dodola in 2007 and 2008. The treatment effects of B. carinata (L.) cultivars Holleta–1, S-67 and Yellow Dodola seed meals on chickpea fusarium wilt (Fusarium oxysporum f.sp. ciceris) were studied. Six rates of seed (0, 5, 10, 15, 20 and 25 g/kg of infested soil) were used. Infested soil without B.carinata cultivars amendments as a control and susceptible check variety JG-62 also without amendments were used in all the experiments. For each seed meal experiment, the treatments were arranged in factorial randomised complete block design in three replications. Data on seedling emergence, wilt incidence, fresh weight, dry weight, pod per plant, seed per pod, hundred seed weight and yield per hectare were collected. The amendments of infested soil with B.carinata cultivars seed meal reduced the incidence of chickpea fusarium wilt and increased yield per hectare. The interaction of the seed meal Holleta-1, S-67 and Yellow Dodola at 10–25 g/kg infested soil were effective in reducing wilt incidences on chickpea. However, the interaction of Yellow Dodola with 20 and 25 g seed meal per kg infested soil were the best combination in reducing significantly wilt incidence. The three cultivars incorporated at different level of doses significantly affected the influence of Fusarium wilt on the fresh weight, dry weight, pod per plant, seed per pod, hundred seed weight and yield per hectare. The highest yield kg/ha was recorded in combination of Yellow Dodola seed meal at 20 and 25 g followed by S-67 and Holleta-1 at 25 g /kg infested soil, respectively. The interaction of Holleta-1 at 5–25 infested soil significantly reduced disease incidence up to 16.7–43.3% and increased yield per hectare with mean by (30%) over the control. Seed meal amendment S-67 significantly reduce disease incidence 26.7–46.7% and increased yield kg/ha with mean by (36.7%) from the unamended control. Yellow dodola reduces disease incidence with 26.7–63.3% and increased yield kg/ha with mean by (45%) from the unamended control. The result indicates the potential of using Brassica crop seed meal amendment as useful component of integrated chickpea wilt management.     

Children with Moderate Acute Malnutrition with No Access to Supplementary Feeding Programmes Experience High Rates of Deterioration and No Improvement: Results from a Prospective Cohort Study in Rural Ethiopia

BackgroundChildren with moderate acute malnutrition (MAM) have an increased risk of mortality, infections and impaired physical and cognitive development compared to well-nourished children. In parts of Ethiopia not considered chronically food insecure there are no supplementary feeding programmes (SFPs) for treating MAM. The short-term outcomes of children who have MAM in such areas are not currently described, and there remains an urgent need for evidence-based policy recommendations.MethodsWe defined MAM as mid-upper arm circumference (MUAC) of ≥11.0cm and <12.5cm with no bilateral pitting oedema to include Ethiopian government and World Health Organisation cut-offs. We prospectively surveyed 884 children aged 6–59 months living with MAM in a rural area of Ethiopia not eligible for a supplementary feeding programme. Weekly home visits were made for seven months (28 weeks), covering the end of peak malnutrition through to the post-harvest period (the most food secure window), collecting anthropometric, socio-demographic and food security data.ResultsBy the end of the study follow up, 32.5% (287/884) remained with MAM, 9.3% (82/884) experienced at least one episode of SAM (MUAC <11cm and/or bilateral pitting oedema), and 0.9% (8/884) died. Only 54.2% of the children recovered with no episode of SAM by the end of the study. Of those who developed SAM half still had MAM at the end of the follow up period. The median (interquartile range) time to recovery was 9 (4–15) weeks. Children with the lowest MUAC at enrolment had a significantly higher risk of remaining with MAM and a lower chance of recovering.ConclusionsChildren with MAM during the post-harvest season in an area not eligible for SFP experience an extremely high incidence of SAM and a low recovery rate. Not having a targeted nutrition-specific intervention to address MAM in this context places children with MAM at excessive risk of adverse outcomes. Further preventive and curative approaches should urgently be considered.     

GeneXpert MTB/RIF Assay for the Diagnosis of Tuberculous Lymphadenitis on Concentrated Fine Needle Aspirates in High Tuberculosis Burden Settings

Introduction

The diagnosis of tuberculous lymphadenitis (TBL) remains challenging. The routinely used methods (cytology and smear microscopy) have sub-optimal sensitivity. Recently, WHO recommends GeneXpert to be used as the initial diagnostic test in patients suspected of having extra-pulmonary tuberculosis (EPTB). However, this was a conditional recommendation due to very low-quality evidence available and more studies are needed. In this study we evaluated the performance of Xpert for the diagnosis of TBL on concentrated fine needle aspirates (FNA) in Southwest Ethiopia.

Methods

FNA was collected from presumptive TBL cases. Two smears were prepared from each aspirate and processed for cytology and conventional microscopy. The remaining aspirate was treated with N-acetyl-L-cysteine-NaOH and centrifuged for 15minutes at 3000g. The concentrated sediment was used for culture and Xpert test. Capilia TB-Neo test was used to differentiate M. tuberculosis complex (MTBC) from non-tuberculous mycobacteria (NTM). Composite bacteriological methods (culture and/or smear microscopy) were considered as a reference standard.

Result

Out of 143 enrolled suspects, 64.3% (92/143) were confirmed TBL cases by the composite reference standard (CRS). Xpert detected M. tuberculosis complex (MTBC) in 60.1% (86/143) of the presumptive TBL cases. The sensitivity of Xpert compared to CRS was 87.8% [95% CI: 81.0–94.5] and specificity 91.1% [95% CI: 82.8–99.4]. The sensitivity was 27.8% for smear microscopy and 80% for cytology compared to CRS. Cytology showed the lowest specificity (57.8%). Xpert was positive in 4 out of 45 culture- and smear-negative cases. Among 47 cytomorphologically non-TBL cases, 15 were positive on Xpert. More than half of Xpert-positive cases were in the range of very low cut-off threshold values (28<Ct<38). Resistance to rifampicin was identified in 4.7% (4/86) of Xpert-positive cases.

Conclusion

Xpert test showed a high sensitivity and specificity for the diagnosis of TBL on concentrated FNA samples. In addition, Xpert offered rapid detection of rifampicin-resistant M. tuberculosis strains from lymph node aspirates.     

Anemia among Primary School Children in Eastern Ethiopia

Background

Anemia during childhood impairs physical growth, cognitive development and school performance. Identifying the causes of anemia in specific contexts can help efforts to prevent negative consequences of anemia among children. The objective of this study was to assess prevalence and identify correlates of anemia among school children in Eastern Ethiopia.

Methods

A cross sectional study was conducted from January 2012 to February 2012 in Kersa, Eastern Ethiopia. The study included randomly selected primary school students. Hemoglobin concentration was measured using a Hemocue haemoglobinometer. A child was identified as anemic if the hemoglobin concentration was <11.5 g/dl for children (5–11 yrs) and < 12 g/dl for child older than 12 years age. Poisson regression model with robust variance was used to calculate prevalence ratios.

Result

The overall prevalence of anemia was 27.1% (95% CI: 24.98, 29.14): 13.8% had mild, 10.8% moderate, and 2.3% severe anemia. Children with in the age group of 5-9 years (APR, 1.083; 95% CI, 1.044- 1.124) were at higher risk for anemia. Paternal education (Illiterate, 1.109; 1.044 - 1.178) was positively associated with anemia. Children who had irregular legume consumption (APR, 1.069; 95% CI, 1.022 -1.118) were at higher risk for anemia.

Conclusion

About a quarter of school children suffer from anemia and their educational potential is likely to be affected especially for those with moderate and severe anemia. Child age, irregular legume consumption, and low paternal schooling were associated with anemia. Intervention programmes aimed to reduce anemia among school children are crucial to ensure proper growth and development of children.     

Factors Associated with Medication Adherence among Patients with Schizophrenia in Mekelle,Northern Ethiopia

Background

Non-adherence to antipsychotic medication has a negative impact on the course of illness resulting in increased risk of relapse, rehospitalization and suicide, and increased costs to healthcare systems. The objective of this study was to investigate factors associated with medication adherence among patients with schizophrenia at Ayder Referral Hospital and Mekelle Hospital in Mekelle, Tigray region, Northern Ethiopia.

Methods

The study was a cross-sectional survey in which sociodemographic characteristics, drug attitudes, insight and side effects were measured and explored in terms of their relationship with medication adherence. A structured questionnaire as a data collection tool was used. Data were analyzed with the help of SPSS Version 20.0.

Results

A total of 393 patients participated, 26.5% were non-adherent to their antipsychotic medication. The factors significantly associated with better adherence were positive treatment attitudes (AOR = 1.40, 95% CI: 1.26, 1.55), fewer side effects (AOR = 0.97, 95% CI: 0.94, 0.99), awareness of illness (AOR = 1.44, 95% CI: 1.12, 1.85) and the ability to relabel symptoms (AOR = 1.57, 95% CI: 1.19, 2.07). However, khat chewers (AOR = 0.24, 95% CI: 0.09, 0.68), being illiterate (AOR = 0.13, 95% CI: 0.03, 0.47) and older age group (AOR = 0.03, 95% CI: 0.01, 0.16) were associated with less medication adherence.

Conclusions

A high prevalence of medication non-adherence was found among patients with schizophrenia. Intervention strategies focused on educating the patients to better understand the illness, medications and their potential side effects might be useful in improving adherence to antipsychotic medication treatment.     

Malaria, schistosomiasis, and intestinal helminths in relation to microdams in Tigray, northern Ethiopia.

A survey was undertaken in Tigray, Northern Ethiopia, to assess the prevalence of malaria, schistosomiasis, and intestinal helminths in relation to microdams. The survey took place from March to June 1995, during the dry season, at 41 microdams. At each site the village nearest the dam (within thirty minutes walk) was selected, ten households were randomly chosen, and all family members were examined for malaria and intestinal parasites. The overall study sample was 2271 people, of all age groups. Plasmodium falciparum infection was documented in four villages (at 10% of microdams); prevalence was 1.2% (range 0-20% by village). Larvae of Anopheles gambiae s.l. were found at one microdam. Infection with intestinal schistosomiasis was documented in 20 villages (at 49% of microdams), and one third of those infected had moderate to heavy infections. Biomphalaria species, the intermediate host snails of Schistosoma mansoni, were found at 16 microdams (39%), and snails infected by mammalian cercariae were found in one locality. Infections with soil-transmitted nematodes were prevalent: hookworm was detected in more than two thirds of the villages, and Ascaris lumbricoides and Trichuris trichiura were present in almost half of the villages. Out of 2078 stool examinations, the prevalence of S. mansoni infection was 7.2% (range 0-48% by village), of A. lumbricoides 2.3% (range 0-31%), of T. trichiura 2.4% (range 0-21%), and of hookworm 8.9% (range 0-78%). The prevalence of malaria, S. mansoni and hookworm was higher at altitudes below 2000 metres above sea level. S. mansoni was more prevalent in microdams built more than 5 years before the survey, while T. trichiura was more prevalent at recently constructed microdams. The widespread distribution of schistosomiasis and intestinal helminths, and the presence of malaria infection during the dry season confirm that microdams create favourable conditions for the transmission of these parasitic diseases. Health safeguards must be incorporated into the planning, construction, and operation of microdams and irrigation systems in order to prevent or reduce these diseases. In areas with high prevalence, control activities should be intensified.     

Genetic Models in Applied Physiology. HXB/BXH rat recombinant inbred strain platform: a newly enhanced tool for cardiovascular, behavioral, and developmental genetics and genomics.

This review deals with the largest set of rat recombinant inbred (RI) strains and summarizes past and recent accomplishments with this platform for genetic mapping and analyses of divergent and complex traits. This strain, derived by crossing the spontaneously hypertensive rat, SHR/Ola, with a Brown Norway congenic, BN-Lx, carrying polydactyly-luxate syndrome, is referred to as HXB/BXH. The RI strain set has been used for linkage and association studies to identify quantitative trait loci for numerous cardiovascular phenotypes, including arterial pressure, stress-elicited heart rate, and pressor response, and metabolic traits, including insulin resistance, dyslipidemia and glucose handling, and left ventricular hypertrophy. The strain's utility has been enhanced with development of a new framework marker-based map and strain distribution patterns of polymorphic markers. Quantitative trait loci for behavioral traits mapped include loci for startle motor response and habituation, anxiety and locomotion traits associated with elevated plus maze, and conditioned taste aversion. The polydactyly-luxate syndrome Lx mutation has allowed the study of alleles important to limb development and malformation phenotypes as well as teratogens. The RI strains have guided development of numerous congenic strains to test locus assignments and to study the effect of genetic background. Although these strains were originally developed to aid in studies of rat genetic hypertension and morphogenetic abnormalities, this rodent platform has been shown to be equally powerful for a wide spectrum of traits and endophenotypes. These strains provide a ready and available vehicle for many physiological and pharmacological studies.     

Mapping the nucleotide and isoform-dependent structural and dynamical features of Ras proteins

Ras GTPases are conformational switches controlling cell proliferation, differentiation, and development. Despite their prominent role in many forms of cancer, the mechanism of conformational transition between inactive GDP-bound and active GTP-bound states remains unclear. Here we describe a detailed analysis of available experimental structures and molecular dynamics simulations to quantitatively assess the structural and dynamical features of active and inactive states and their interconversion. We demonstrate that GTP-bound and nucleotide-free G12V H-ras sample a wide region of conformational space, and show that the inactive-to-active transition is a multiphase process defined by the relative rearrangement of the two switches and the orientation of Tyr32. We also modeled and simulated N- and K-ras proteins and found that K-ras is more flexible than N- and H-ras. We identified a number of isoform-specific, long-range side chain interactions that define unique pathways of communication between the nucleotide binding site and the C terminus.