Therapeutic efficacy of chloroquine and sulfadoxine/pyrimethamine against Plasmodium falciparum infection in Somalia

Study on the therapeutic efficacy of treatments based on chloroquine and sulfadoxine/pyrimethamine in cases of malaria (Plasmodium falciparum) in Merka and Gabiley, Somalia.Daraasaad ku saabsan waxtarka ku daaweynta chloroquine iyo sulfadoxine/pyrimethamine cudurka duumada, degaannada soomaaliyeed ee Marka iyo Gabiley.Studio sull'efficacia terapeutica di trattamenti a base di clorochina e sulfadossina/pirimetamina nei casi di malaria (Plasmodium falciparum) a Merka e Gabiley, Somalia

Seed storage proteins of faba bean (Vicia faba L): current status and prospects for genetic improvement

Faba bean (Vicia faba L.) is one of the foremost candidate crops for simultaneously increasing both sustainability and global supply of plant protein. On a dry matter basis, its seeds contain about 29% protein of which more than 80% consists of globulin storage proteins (vicilin and legumin). However, to achieve optimum utilization of this crop for human and animal nutrition, both protein content and quality have to be improved. Though initial investigations on the heritability of these traits indicated the possibility for genetic improvement, little has been achieved so far, partly due to the lack of genetic information coupled with the complex relationship between protein content and grain yield. This review reports on the current knowledge on Vicia faba seed storage proteins, their structure, composition, and genetic control, and highlights key areas for further improvement of the content and composition of Vicia faba seed storage proteins on the basis of recent advances in Vicia faba genome knowledge and genetic tools

Assessment of the Therapeutic Efficacy of Two Artemisinin-Based Combinations in the Treatment of Uncomplicated Falciparum Malaria among Children Under 5 Years in Four District Hospitals in Sierra Leone

Plasmodium falciparum has developed resistance to almost every class of antimalarial compounds. As a result of this, the World Health Organization has recommended artemisinin-based combination therapy as first line treatment for P. falciparum malaria. There is however need for the continuous monitoring of the efficacy of these antimalarials in order to provide timely information on trends of the emergence of resistant strains. We assessed the therapeutic efficacy of oral artesunate – amodiaquine and artemether-lumefantrine combinations in the treatment of uncomplicated P. falciparum malaria in four District Hospitals in Sierra Leone. A total of 320 children under five years partiiccipated in the study sites (Kenema, Rokupa, Bo and Makeni). Oral Artesunate-amodiaquine combination was administered to participants in Kenema and Rokupa whilst Artemetherlumefantrine combination was administered to participants in Bo and Makeni. The new WHO Protocol for recruitment of participants in therapeutic efficacy trials in high transmission zones was adopted for the study with filter paper blood samples taken from each participant on days 0 and 28 to distinguish between treatment failure and new infection. When uncorrected for PCR analysis, 96% (95% CI: 902 – 989) and 100% (95% CI:63.1 – 100) responses were obtained in Kenema and Bo respectively with Artesunate-amodiaquine combination whilst 94.3% (CI 95 : 88.1 – 979) and 100% (95% CI: 96.5 – 100) were obtained with Artemether-lumefantrine combination in Bo and Makeni respectively. When corrected for PCR on the other hand, a 100% (95% CI) Adequate Clinical and Parasitological Response was obtained for the two drugs in all four study sites. Results from this study indicate that both Artesunate-amodiaquine and Artemether-lumefantrine combinations remain highly efficacious in Sierra Leone with presently no observed emergence of resistant strains to both drugs.Keywords: Artemisinin-based combination, uncomplicated falciparum malaria, children, Sierra Leon

Understanding caretakers\u27 dilemma in deciding whether or not to adhere with referral advice after pre-referral treatment with rectal artesunate

Background: Malaria kills. A single rectal dose of artesunate before referral can reduce mortality and prevent permanent disability. However, the success of this intervention depends on caretakers\u27 adherence to referral advice for follow-up care. This paper explores the dilemma facing caretakers when they are in the process of deciding whether or not to transit their child to a health facility after pre-referral treatment with rectal artesunate. Methods: Four focus group discussions were held in each of three purposively selected villages in Mtwara rural district of Tanzania. Data were analysed manually using latent qualitative content analysis. Results: The theme «Caretakers dilemma in deciding whether or not to adhere with referral advice after pre-referral treatment with rectal artesunate» depicts the challenge they face. Caretakers\u27 understanding of the rationale for going to hospital after treatment - when and why they should adhere - influenced adherence. Caretakers, whose children did not improve, usually adhered to referral advice. If a child had noticeably improved with pre-referral treatment however, caretakers weighed whether they should proceed to the facility, balancing the child\u27s improved condition against other competing priorities, difficulties in reaching the health facilities, and the perceived quality of care at the health facility. Some misinterpretation were found regarding the urgency and rationale for adherence among some caretakers of children who improved which were attributed to be possibly due to their prior understanding. Conclusion: Some caretakers did not adhere when their children improved and some who adhered did so without understanding why they should proceed to the facility. Successful implementation of the rectal artesunate strategy depends upon effective communication regarding referral to clinic. © 2010 Simba et al; licensee BioMed Central Ltd

Identification and quantification of major faba bean seed proteins

Faba bean (Vicia faba L.) holds great importance for human and animal nutrition for its high protein content. However, better understanding of its seed protein composition is required in order to develop cultivars that meet market demands for plant proteins with specific quality attributes. In this study, we screened 35 diverse Vicia faba genotypes by employing the one-dimensional sodium dodecyl sulfate–polyacrylamide gel electrophoresis (1D SDS-PAGE) method, and 35 major protein bands obtained from three genotypes with contrasting seed protein profiles were further analyzed by mass spectrometry (MS). Twenty-five of these protein bands (MW range: ∼ 9–107 kDa) had significant (p ≤ 0.05) matches to polypeptides in protein databases. MS analysis showed that most of the analyzed protein bands contained more than one protein type and, in total, over 100 proteins were identified. These included major seed storage proteins such as legumin, vicilin, and convicilin, as well as other protein classes like lipoxygenase, heat shock proteins, sucrose-binding proteins, albumin, and defensin. Furthermore, seed protein extracts were separated by size-exclusion high-performance liquid chromatography (SE-HPLC), and percentages of the major protein classes were determined. On average, legumin and vicilin/convicilin accounted for 50 and 27% of the total protein extract, respectively. However, the proportions of these proteins varied considerably among genotypes, with the ratio of legumin:vicilin/convicilin ranging from 1:1 to 1:3. In addition, there was a significant (p < 0.01) negative correlation between the contents of these major fractions (r = −0.83). This study significantly extends the number of identified Vicia faba seed proteins and reveals new qualitative and quantitative variation in seed protein composition, filling a significant gap in the literature. Moreover, the germplasm and screening methods presented here are expected to contribute in selecting varieties with improved protein content and quality

Patterns of resistance and DHFR/DHPS genotypes of Plasmodium falciparum in rural Tanzania prior to the adoption of sulfadoxine-pyrimethamine as first-line treatment.

A study was carried out to assess the patterns of resistance and occurrence of DHFR/DHPS genotypes of Plasmodium falciparum prior to the adoption of sulfadoxine-pyrimethamine (SP) as first-line treatment for uncomplicated malaria in Tanzania. Children under five years (n = 117) with clinical, uncomplicated malaria were randomly allocated to standard treatments of either chloroquine (CQ) (25 mg/kg) or SP (25 mg sulfadoxine and 1.25 mg pyrimethamine/kg). Patients were monitored for 28 days. Clinical recovery was achieved in 98% (n = 58) and 90% (n = 59) of the patients in the SP and CQ groups, respectively. Parasitologically, 14% of the patients in the SP group and 51% in the CQ group exhibited RII/RIII resistance. When relating pre-treatment blood drug levels to treatment outcome and the degree of parasite resistance to the number of mutations, no relationships could be detected. There was an overall significant increase in haemoglobin levels from day 0 to day 28 in both patient groups. Sulfadoxine-pyrimethamine produced an acceptable clinical response but the high degree of parasitological resistance (RII/RIII) observed two years prior to the introduction of the drug as first-line treatment is of concern, especially considering the long half-lives of sulfadoxine and pyrimethamine

Depressive symptoms, frailty, and adverse outcomes among kidney transplant recipients

Depressive symptoms and frailty are each independently associated with morbidity and mortality in kidney transplant (KT) recipients. We hypothesized that having both depressive symptoms and frailty would be synergistic and worse than the independent effect of each. In a multicenter cohort study of 773 KT recipients, we measured the Fried frailty phenotype and the modified 18â question Center for Epidemiologic Studiesâ Depression Scale (CESâ D). Using adjusted Poisson regression and survival analysis, we tested whether depressive symptoms (CESâ D score > 14) and frailty were associated with KT length of stay (LOS), deathâ censored graft failure (DCGF), and mortality. At KT admission, 10.0% of patients exhibited depressive symptoms, 16.3% were frail, and 3.6% had both. Recipients with depressive symptoms were more likely to be frail (aOR = 3.97, 95% CI: 2.28â 6.91, P < 0.001). Recipients with both depressive symptoms and frailty had a 1.88 times (95% CI: 1.70â 2.08, P < 0.001) longer LOS, 6.20â fold (95% CI:1.67â 22.95, P < 0.01) increased risk of DCGF, and 2.62â fold (95% CI:1.03â 6.70, P = 0.04) increased risk of mortality, compared to those who were nonfrail and without depressive symptoms. There was only evidence of synergistic effect of frailty and depressive symptoms on length of stay (P for interaction < 0.001). Interventions aimed at reducing preâ KT depressive symptoms and frailty should be explored for their impact on postâ KT outcomes.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146305/1/ctr13391_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146305/2/ctr13391.pd

A bayesian meta-analysis of multiple treatment comparisons of systemic regimens for advanced pancreatic cancer

© 2014 Chan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: For advanced pancreatic cancer, many regimens have been compared with gemcitabine (G) as the standard arm in randomized controlled trials. Few regimens have been directly compared with each other in randomized controlled trials and the relative efficacy and safety among them remains unclear

Impact of laboratory diagnosis for improving the management of uncomplicated malaria at peripheral health care settings in Coast region, Tanzania

Malaria is a disease caused by parasites of the genus Plasmodium. Five species cause human disease, but the most common in tropical areas, and the cause of severe disease is Plasmodium falciparum. Control of morbidity and mortality is mainly achieved through appropriate malaria case management, which includes prompt diagnosis and treatment with effective antimalarial drugs. While definitive diagnosis of malaria is made by demonstration of parasites in the patient blood through microscopic examination of giemsa stained blood smears, in most clinical settings in Africa, diagnosis is limited by lack of facilities and personnel. The availability of malaria rapid diagnostic tests (RDTs) offers an opportunity to extend diagnostic services to areas previously not covered by conventional microscopy services. Two intervention trials were conducted, one at primary health care (PHC) facilities using microscopy, and the other at community level, through community health workers (CHWs), using rapid diagnostic tests (RDTs) for malaria diagnosis, and the impact of the interventions on antimalarial drugs prescription practices, antibiotic prescriptions and health outcome was investigated (Study I and II). A descriptive, cross sectional study was conducted to assess health workers diagnostic and prescription practices following introduction of RDTs for universal testing of malaria at PHC level in Tanzania (Study III). An exploratory study was also carried out to assess the usefulness of Histidine rich protein 2 (HRP2) and lactate dehydrogenase (LDH) based RDTs for treatment monitoring and detection of recurrent infection following artemisinin-based combination therapy (ACT) during a 42 day follow up period (Study IV). The use of parasite-based diagnostics significantly reduced antimalarial prescriptions at health facility and community level without affecting the health outcome of patients not treated with antimalarials (study I and II). The prescriptions of antimalarial drugs were 61% at intervention health facilities, whereas in the clinical and control arms the prescription rates remained high, 95% and 99%, respectively (study I). Similarly, 53% of patients tested with RDT at community level were provided antimalarial drugs compared to 96% among patients treated based on clinical diagnosis only (Study II). The availability of parasite-based diagnostics and antimalarial drugs within the community allowed early access to treatment as 67% of patients consulted CHWs within 24 hours of onset of fever (Study II). The rate of non adherence to test results was low in both study I and II. Study III observed low use of parasite-based diagnostics among fever patients (63%), low non adherence to test results (14%), substantial prescription of antimalarial drugs to non-tested patients (28%) and high prescriptions of antibiotics among patients with negative RDT results (81%), as well as frequent stock outs of both RDTs and ACTs. HRP2 based tests performed poorly when compared to LDH based tests for treatment monitoring, with median clearance times of 28 (7-42) and 7 (2-14) days respectively (Study IV). HRP2 based tests were unable to detect 8/10 recurrent infections during follow up compared to only two recurrent infections missed by LDH based tests. These studies lead to a conclusion that the availability of parasite-based diagnostics helps to restrict treatment with antimalarial drugs to patients with malaria. However, non adherence to malaria test results could undermine the potential of RDTs, and in-depth studies should be conducted to identify its causes. As the relative contribution of malaria as a cause of fever is declining in Tanzania, there is need to improve the overall management of non-malarial fevers. The longer the persistence of HRP2 antigen in blood makes HRP2 based tests not suitable for treatment monitoring and detection of recurrent infection calling for alternative diagnostic strategies for this purpose

Assessment of B Cell Repertoire in Humans

The B cell receptor (BCR) repertoire is highly diverse. Repertoire diversity is achieved centrally by somatic recombination of immunoglobulin (Ig) genes and peripherally by somatic hypermutation and Ig heavy chain class-switching. Throughout these processes, there is selection for functional gene rearrangements, selection against gene combinations resulting in self-reactive BCRs, and selection for BCRs with high affinity for exogenous antigens after challenge. Hence, investigation of BCR repertoires from different groups of B cells can provide information on stages of B cell development and shed light on the etiology of B cell pathologies. In most instances, the third complementarity determining region of the Ig heavy chain (CDR-H3) contributes the majority of amino acids to the antibody/antigen binding interface. Although CDR-H3 spectratype analysis provides information on the overall diversity of BCR repertoires, this fairly simple technique analyzes the relative quantities of CDR-H3 regions of each size, within a range of approximately 10–80 bp, without sequence detail and thus is limited in scope. High-throughput sequencing (HTS) techniques on the Roche 454 GS FLX Titanium system, however, can generate a wide coverage of Ig sequences to provide more qualitative data such as V, D, and J usage as well as detailed CDR3 sequence information. Here we present protocols in detail for CDR-H3 spectratype analysis and HTS of human BCR repertoires