Serum pantetheinase/vanin levels regulate erythrocyte homeostasis and severity of malaria.

Tissue pantetheinase, encoded by the VNN1 gene, regulates response to stress, and previous studies have shown that VNN genes contribute to the susceptibility to malaria. Herein, we evaluated the role of pantetheinase on erythrocyte homeostasis and on the development of malaria in patients and in a new mouse model of pantetheinase insufficiency. Patients with cerebral malaria have significantly reduced levels of serum pantetheinase activity (PA). In mouse, we show that a reduction in serum PA predisposes to severe malaria, including cerebral malaria and severe anemia. Therefore, scoring pantetheinase in serum may serve as a severity marker in malaria infection. This disease triggers an acute stress in erythrocytes, which enhances cytoadherence and hemolysis. We speculated that serum pantetheinase might contribute to erythrocyte resistance to stress under homeostatic conditions. We show that mutant mice with a reduced serum PA are anemic and prone to phenylhydrazine-induced anemia. A cytofluorometric and spectroscopic analysis documented an increased frequency of erythrocytes with an autofluorescent aging phenotype. This is associated with an enhanced oxidative stress and shear stress-induced hemolysis. Red blood cell transfer and bone marrow chimera experiments show that the aging phenotype is not cell intrinsic but conferred by the environment, leading to a shortening of red blood cell half-life. Therefore, serum pantetheinase level regulates erythrocyte life span and modulates the risk of developing complicated malaria.

Current status on health sciences research productivity pertaining to Angola up to 2014.

BACKGROUND: Health research driven by the healthcare demands of the population can provide an informative evidence base to support decision-making processes on health policies, programmes, and practices. This paper surveyed the production of scientific research concerning health in Angola, specifically to access the publication rate over time, the main research topics and scientific fields, and the contribution of Angolan researchers and institutions. METHODS: The study focused on data collected in a retrospective literature search in Biblioteca Virtual em Saúde (BVS) as of June 8, 2014, with the keyword "Angola" and on content information in correspondent publications deposited in PubMed. RESULTS: BVS generated 1,029 hits, 74.6 % of which were deposited in PubMed where 301 abstracts were described. From 1979 to 2003, there were 62 publications and in 2004-2013 the quantity increased four-fold (n = 232); malaria was the most frequent topic (n = 42). Angola was the country with the largest number of publications, taking into account the primary affiliation of the first author (n = 45). Universities, institutes, or research centres accounted for 65 % of the publications and in descending order Portugal, Brazil, and the United States of America occupied the three first positions. Epidemiology was by far the most frequent field of research (n = 165). CONCLUSIONS: The number of publications has increased steadily over the past 10 years, with predominance on malaria topics. Angola was the country with the largest number of major affiliations of the first author, but the contribution of Angolan institutions was relatively low, indicating a need to reinforce academic research institutions in the country.

NOS2 variants reveal a dual genetic control of nitric oxide levels, susceptibility to Plasmodium infection, and cerebral malaria.

Nitric oxide (NO) is a proposed component of malaria pathogenesis, and the inducible nitric oxide synthase gene (NOS2) has been associated to malaria susceptibility. We analyzed the role of NOS2 polymorphisms on NO bioavailability and on susceptibility to infection, Plasmodium carrier status and clinical malaria. Two distinct West African sample collections were studied: a population-based collection of 1,168 apparently healthy individuals from the Príncipe Island and a hospital-based cohort of 269 Angolan children. We found that two NOS2 promoter single-nucleotide polymorphism (SNP) alleles associated to low NO plasma levels in noninfected individuals were also associated to reduced risk of pre-erythrocytic infection as measured anti-CSP antibody levels (6.25E-04 < P < 7.57E-04). In contrast, three SNP alleles within the NOS2 cistronic region conferring increased NO plasma levels in asymptomatic carriers were strongly associated to risk of parasite carriage (8.00E-05 < P < 7.90E-04). Notwithstanding, three SNP alleles in this region protected from cerebral malaria (7.90E-4 < P < 4.33E-02). Cohesively, the results revealed a dual regimen in the genetic control of NO bioavailability afforded by NOS2 depending on the infection status. NOS2 promoter variants operate in noninfected individuals to decrease both NO bioavailability and susceptibility to pre-erythrocytic infection. Conversely, NOS2 cistronic variants (namely, rs6505469) operate in infected individuals to increase NO bioavailability and confer increased susceptibility to unapparent infection but protect from cerebral malaria. These findings corroborate the hypothesis that NO anti-inflammatory properties impact on different steps of malaria pathogenesis, explicitly by favoring infection susceptibility and deterring severe malaria syndromes.

Impact of a training course on the quality of malaria diagnosis by microscopy in Angola.

BACKGROUND: In Angola, malaria is an endemic disease having a major impact on the economy. The WHO recommends testing for all suspected malaria cases, to avoid the presumptive treatment of this disease. In malaria endemic regions laboratory technicians must be very comfortable with microscopy, the golden standard for malaria diagnosis, to avoid the incorrect diagnosis. The improper use of medication promotes drug resistance and undesirable side effects. The present study aims to assess the impact of a three-day refresher course on the knowledge of technicians, quality of blood smears preparation and accuracy of microscopy malaria diagnosis, using qPCR as reference method. METHODS: This study was implemented in laboratories from three hospitals in different provinces of Angola: Bengo, Benguela and Luanda. In each laboratory samples were collected before and after the training course (slide with thin and thick blood smears, a dried blood spot and a form). The impact of the intervention was evaluated through a written test, the quality of slide preparation and the performance of microscopy. RESULTS: It was found a significant increase on the written test median score, from 52.5% to 65.0%. A total of 973 slides were analysed to evaluate the quality of thick and thin blood smears. Considering all laboratories there was a significant increase in quality of thick and thin blood smears. To determine the performance of microscopy using qPCR as the reference method we used 1,028 samples. Benguela presented the highest values for specificity, 92.9% and 98.8% pre and post-course, respectively and for sensitivity the best pre-course was Benguela (75.9%) and post-course Luanda (75.0%). However, no significant increase in sensitivity and specificity after the training course was registered in any laboratory analysed. DISCUSSION: The findings of this study support the need of continuous refresher training for microscopists and other laboratory staff. The laboratories should have a quality control programme to supervise the diagnosis and also to assess the periodicity of new training. However, other variables needed to be considered to have a correct malaria diagnosis, such as adequate equipment and reagents for staining and visualization, good working conditions, motivated and qualified personnel.

The rise of medical training in Portuguese speaking African countries.

BACKGROUND: Medical training has shown to be strategic for strengthening health systems, especially in those countries identified to have critical shortage of human resources for health. In the past few years, several studies have been conducted to characterize and identify major challenges faced by medical schools worldwide, and particularly in Africa. Nevertheless, none has previously addressed medical training issues in Portuguese Speaking African Countries (PSAC). The aim of this study was to establish baseline knowledge of the PSAC's medical schools in terms of creation and ownership, programmes offered, applicants and registered students, barriers to increased intake of students, teaching workforce and available resources. METHODS: A quantitative, observational, multicentric, cross-sectional study of all medical schools active in 2012 in the PSAC. An adapted version of the questionnaires developed by Chen et al. (2012) was sent to all medical schools electronically. Data were analyzed using descriptive statistics. RESULTS: A total of nine medical schools answered the questionnaire (three from Angola, two from Guinea Bissau and four from Mozambique). Since 2006 an effort has been made to increase the number of medical trainees. Besides the medical degree offered by all schools, some offered other undergraduate and postgraduate training programmes. The number of applicants to medical schools largely outnumbers the available vacancies in all countries but insufficient infrastructures and lack of teaching personnel are important constraints to increase vacancies. The teaching personnel are mainly trained abroad, employed part-time by the medical school and do not have a PhD qualification. CONCLUSION: Governments in the PSAC have significantly invested in training to address medical shortages. However, medical schools are still struggling to give an adequate and effective response. Developing a local postgraduate training capacity for doctors might be an important strategy to help retain medical doctors in the home country and develop local faculty capacity.

Desafios da educação médica e da investigação em saúde no contexto de angola / Challenges in medical education and healthcare research in Angola

Os apelos para reformas na educação médica são constantes e têm sido objeto de recomendações produzidas nos últimos cem anos, destacando-se as resultantes da avaliação crítica feita por Abraham Flexner, em 1910, nos Estados Unidos da América. No presente trabalho, abordam-se as tendências e os desafios atuais da educação médica e da investigação em saúde, com ênfase para os países em desenvolvimento, ressaltando-se a realidade africana. Com base na bibliografia consultada, apontam-se e discutem-se alguns desafios que se colocam ao binômio educação médica/investigação em saúde em Angola, muito em especial no contexto da II Região Acadêmica, que integra as províncias de Benguela e Kwanza Sul, destacando-se: (i) a necessidade de incorporar novas abordagens curriculares para o reforço da aprendizagem ao longo da vida; (ii) a aquisição e o desenvolvimento de competências de investigação científica orientadas para a caracterização e intervenção sobre a situação de saúde local; (iii) a inovação dos métodos de ensino e a incorporação de novas tecnologias na educação e prática médica; (iv) a contribuição para o reforço e melhoria da distribuição de médicos na região.

Calls for reforms to medical education are constant and have led to various recommendations over the last 100 years, especially those resulting from critical assessments made by Abraham Flexner in 1910 in the United States. In this paper, we discuss the trends and current challenges affecting medical education and healthcare research, with emphasis on developing countries, highlighting the African reality. Finally, based on the bibliography, we identify and discuss several challenges related to the binomial of medical education/healthcare research in Angola, particularly in the context of the Academic Region II, which includes the provinces of Benguela and Kwanza Sul. The challenges emphasize: (i) the need to incorporate new curricular approaches for strengthening lifelong learning, (ii) the acquisition and development of skills in scientific research aimed at characterizing and intervening in local health; (iii) the innovation in teaching methods and the incorporation of new technologies in education and medical practice and (iv) the contribution to strengthening and improving the distribution of physicians in the region.