Epidemiologia molecular da infecção por VIH/SIDA, em Angola

Tese de mestrado, Doenças Infecciosas Emergentes, Faculdade de Medicina, Universidade de Lisboa, 2011Segundo a Organização Mundial da Saúde (OMS), estima-se que, no Mundo, em 2008, viviam 33,4 milhões de pessoas infectadas por VIH. A África sub - sariana, continua a ser a região mais afectada pela epidemia, tendo 22,8 milhões de infectados. O primeiro caso de sida, em Angola, foi diagnosticado em 1985 e até ao primeiro semestre de 2009 foram notificados 48.651 casos de infecção por VIH (64). A prevalência ronda os 5,0 %, em 16 milhões de habitantes, mas nas zonas fronteiriças com a República do Congo (Kinshasa), Zâmbia e Namíbia pode atingir os 10,0 %. O objectivo do presente trabalho é: a) determinar o perfil epidemiológico, demográfico, clínico e imunológico dos indivíduos em estudo, b) estudar a diversidade genética de VIH em Angola, assim como investigar a frequência e distribuições de polimorfismos na protease (PR) e na transcriptase reversa (TR) associados à resistência aos anti-retrovíricos, nos indivíduos não tratados. As 219 amostras foram recolhidas dos 302 indivíduos infectados por VIH-1, no Hospital da Divina Providência, em Luanda, de Setembro de 2008 a Janeiro de 2009. Para o presente estudo foram recrutados 57 indivíduos, cujos critérios de inclusão seguiram algumas das recomendações da OMS, para este tipo de trabalho. Cento e cinco sequências foram realizadas, 57 da proteína PR e 48 da TR no gene pol, usando um método in-house. O perfil epidemiológico, clínico, demográfico e imunológico da população estudada é caracterizada, maioritariamente por pertencerem ao sexo feminino (67,5%), com média de idades de 31 anos, a via de transmissão predominante foi a heterossexual (86,8%) e a maior parte estava em estado avançado de doença. A análise filogenética das sequências revelou uma elevada heterogeneidade genética de VIH-1 em Angola. Foram detectados vírus de todos os subtipos pertencentes ao grupo M e 5,3% a subtipos não classificáveis. A análise filogenética das sequências revelou que, somente, 16 (37%) indivíduos albergavam vírus de um único subtipo (subtipo puro). Os restantes indivíduos (n=30, 65%) estavam, na sua maioria, infectados por vírus recombinantes, incluindo formas recombinantes circulantes (CRFs) e outros recombinantes. Um doente (d94) estava infectado por um isolado não tipável (U). O subtipo mais prevalente na PR foi o G (n=12; 21%) seguido do D (n=7; 13%) e C (n=6; 11%). Na TR os subtipos mais prevalentes foram o A, C e F1 todos presentes em cinco indivíduos (10%). Sequências não tipáveis foram detectadas em seis (11%) indivíduos na PR e quatro (8%) indivíduos na TR. Vinte e quatro indivíduos estavam infectados por vírus contendo PRs e TRs pertencentes a diferentes subtipos, a vírus não tipáveis ou a CRFs. O recombinante deste género mais frequente foi o G/U que estava presente em três indivíduos (13%). A CRF mais prevalente foi a CRF02_AG tanto na PR (n=5; 9%) como na TR (n=5; 10%), seguida da CRF01_AE (PR - n=4; 7%; TR - n=4; 8%). Detectaram-se oito (14%) indivíduos, potencialmente, infectados com vírus recombinantes constituídos por CRF01_AE na PR ou na TR. De salientar que 13 (54%) destes indivíduos albergavam recombinantes de 2ª geração, ou seja, vírus que resultam da recombinação entre um CRF e um vírus de um subtipo puro ou um vírus não tipável (U). A análise das sequências na base de dados de Stanford para as mutações de resistência, inequivocamente, associadas com a transmissão de vírus resistentes aos anti-retrovíricos revelou que, não obstante a presença de numerosos polimorfismos invulgares na PR e TR, nenhum dos indivíduos estava infectado por este tipo de vírus.According to the World Health Organization in 2008 an estimated 33,4 million people were infected with HIV. Sub-Saharan Africa continues to be the region with the most infected by the epidemic with 22, 8 million infected. The first case of aids in Angola was diagnosed in 1985 and until the first semester of 2009 forty eight thousand six hundred and fifty cases of HIV/aids (64) were notified. The spread is around 5, 0% in 16 million inhabitants although in the neighboring borders of the Congo Republic (Kinshasa), Zambia and Namibia it can hit 10, 0 %. The objective of this project is to determine the epidemiological, demographical, clinical and immunological profile of the individuals under case study. Explore the genetic diversity of HIV in Angola as well as investigate the frequency and distribution of polymorphisms in protease PR and in reverse transcriptase TR associated to the resistance to ARV, in non treated individuals. The 219 samples were collected from HIV 1 infected individuals 302 from the Hospital of Divine Providence in Luanda in September of 2008 to January of 2009, for the present study 57 individuals were included following the WHO recommendations‟ for this type of study. The samples of the 57 individuals were genotopically analysed to determine their subtype and the profile potential to the resistance to ARV using the in house method one hundred and five sequences were done (57 protein PR and 48 TR) in the Pol gene. The profile epidemiologist, clinical, demographic and immunologic of the studied population were characterized were mostly by the feminine sex (67.5%), with average of age of 31 years, the way of predominant transmission was heterosexual (86.8%) and most was in advanced state of imunossupressão. The phylogenetic sequential analysis revealed highly heterogeneity of HIV-1 Angola. That study revealed all subtypes belonging to group M. The phylogenetic sequential analyses revealed that only 16 (37 %) patients had the virus of only one subtype pure subtype the remaining patient (30, 65 %) were mostly infected by recombinant virus including circular recombinant forms CRFs. One patients (d94) were infected by classification was not possible sequences (U). The most prevalent subtype in PR was the G (12; 21%) followed by D (7; 13%) and C (6; 11%).The prevalent subtypes were A, C e F1. All present in 5 patients (10%). Unclassified sequences were detected in 6 (11%) patients in PR and 4 (8%) patients in TR. Twenty four patients were infected with the virus containing PRs and TRs belonging to different subtypes, unclassified virus or CRFs. The CRF most prevalent was CRF02_ AG both in PR (5 patients, 9%) and TR (5; 10%) followed by CRF01_AE [PR: 4; 7%; TR: 4; 8%]. In this study we detected 8 (14%), potentially infected patients with recombinant virus made of CRF01_AE in PR or TR. It is to point out that 13 (54%) these patients lodged/possessed/had recombinant virus of second generation ,that is, that result of recombination between one CRF and a virus a pure subtype or one unclassified virus. The sequential analyses of the Stanford data base for the resistant mutations unequivocally associates with the transmission of resistant viruses to the ARV revealed that notwithstanding the presence of numerous unusual polymorphisms in PR and TR, none of the patients were infected with this type of virus.Fundação Glaxo Smithkline das Ciências da Saúd

Sleep–Wake Patterns Reported by Parents in Hyperactive Children Diagnosed According to ICD-10, as Compared to Paired Controls

This study aimed primarily to compare the parent-reported sleep of children with ICD-10 hyperkinetic disorder (HKD) versus community children. Thirty children aged 5-13 years (83.3% boys) diagnosed with HKD by their child and adolescent psychiatrists took part in this study, plus 30 community children, matched for sex, age, and school year. Compared to the controls, the HKD children showed significantly later bedtimes, stronger bedtime resistance, longer sleep latency, shorter sleep; more frequent behaviors and symptoms concerning falling asleep into parents bed, needing something special to initiate sleep, nightmares, sleep talking, sleep bruxism, fear from darkness, bedwetting, and, most notably, loud snoring (26.7%); they also tended to show higher daytime somnolence. Attention deficit/hyperactivity disorder (ADHD)/HKD children may thus have more sleep-related problems than typically developing children. Alternatively, our results may reflect misdiagnoses; thus, special attention should be directed to comorbidity and differential diagnosis issues between sleep disturbances and ADHD/HKD

Effectiveness of a Prevention of Mother-to-Child HIV Transmission Programme in an Urban Hospital in Angola

BACKGROUND: Antiretroviral therapy is effective in reducing rates of mother-to child transmission of HIV to low levels in resource-limited contexts but the applicability and efficacy of these programs in the field are scarcely known. In order to explore such issues, we performed a descriptive study on retrospective data from hospital records of HIV-infected pregnant women who accessed in 2007-2010 the Luanda Municipal Hospital service for prevention of mother-to-child transmission (PMTCT). The main outcome measure was infant survival and HIV transmission. Our aim was to evaluate PMTCT programme in a local hospital setting in Africa. RESULTS: Data for 104 pregnancies and 107 infants were analysed. Sixty-eight women (65.4%) had a first visit before or during pregnancy and received combination antiretroviral treatment (ART) in pregnancy. The remaining 36 women (34.6%) presented after delivery and received no ART during pregnancy. Across a median cohort follow-up time of 73 weeks, mortality among women with and without ART in pregnancy was 4.4% and 16.7%, respectively (death hazard ratio: 0.30, 95% CI 0.07-1.20, p = 0.089). The estimated rates of HIV transmission or death in the infants over a median follow up time of 74 weeks were 8.5% with maternal ART during pregnancy and 38.9% without maternal ART during pregnancy. Following adjustment for use of oral zidovudine in the newborn and exposure to maternal milk, no ART in pregnancy remained associated with a 5-fold higher infant risk of HIV transmission or death (adjusted odds ratio: 5.13, 95% CI: 1.31-20.15, p = 0.019). CONCLUSIONS: Among the women and infants adhering to the PMTCT programme, HIV transmission and mortality were low. However, many women presented too late for PMTCT, and about 20% of infants did not complete follow up. This suggests the need of targeted interventions that maintain the access of mothers and infants to prevention and care services for HIV

Predictors of Bacterial Meningitis in Resource-Limited Contexts: An Angolan Case

BACKGROUND: Despite the great morbidity and mortality that childhood bacterial meningitis (BM) is experiencing in Africa, diagnosis of BM in resource-limited contexts is still a challenge. Several algorithms and clinical predictors have been proposed to help physicians in decision-making but a lot of these markers used variables that are calculable only in well-equipped laboratories. Predictors or algorithm based on parameters that can be easily performed in basic laboratories can help significantly in BM diagnosis, even in resource-limited settings, rural hospitals or health centers. RESULTS: This retrospective study examined 145 cerebral-spinal fluid (CSF) specimens from children from 2 months to 14 years. CSF specimens were divided into two groups, according to the presence or not of a clinical diagnosis of BM. For each specimen, CSF aspect, CSF white blood cells (WBC) count, CSF glucose and protein concentration were analyzed and statistical analysis were performed. CSF WBC count ≥10/µl is no more a valuable predictor of BM. CSF protein concentration ≥50 mg/dl has a better sensitivity for BM diagnosis and when used with CSF glucose concentration ≤40 mg/dl, can help to diagnose correctly almost all the BM cases. An algorithm including CSF protein concentration, glucose concentration and WBC count has been proposed to rule out BM and to correctly diagnose it. CONCLUSIONS: In resource-limited health centers, the availability of a combination of easy-to-obtain parameters can significantly help physicians in BM diagnosis. The prompt identification of a BM case can be rapid treated or transferred to adequate structures and can modify the outcome in the patient

Narcolepsy in pediatric age – Experience of a tertiary pediatric hospital

Narcolepsy, a chronic disorder of the sleep–wake cycle of multifactorial etiology, is characterized by excessive daytime sleepiness, often associated with cataplexy, hypnagogic/hypnopompic hallucinations and sleep paralysis. Both early clinical suspicion and therapeutic approach are essential for promotion of cognitive development and social integration of these children. The authors present a descriptive retrospective study of a series of eight children in whom symptoms first started between 6.8 and 10.5 years of age. Diagnostic delay ranged from 4 months to 2 years. One child had H1N1 flu vaccination eight months before the clinical onset. The first multiple sleep latency test was positive in 6 of 8 cases. All cases were treated with methylphenidate, and venlafaxine was associated in 4 of them. In one case the initial therapy was exclusively behavioral. In all cases, symptomatic improvement, better school performance and social integration were achieved after therapeutic adjustment

The dysfunctional beliefs and attitudes about sleep scale: dimensions of the European Portuguese DBAS-30 and development of a new short version (DBAS-SF-16)

Objectives: The Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS) is the most widely validated instrument for assessing sleep-related cognitions. This study aimed to examine the reliability of the DBAS-30 European Portuguese version, explore its dimensionality, and develop a new short version suitable for differentiating the presence/absence of insomnia. Methods: From 824 participants aged 18e85 years, the Insomnia Group (IG, n ¼ 355, 261 females and 94 males) and Normal Sleepers Group (NSG, n ¼ 292, 237 females, 54 males and 1 with no response) were constituted. Thirty-one patients with Obstructive Sleep Apnea Syndrome were also recruited. For the DBAS 16-items version, the ability to differentiate dysfunctional beliefs between people with and without insomnia was used as the main criterion for item retention. Results: DBAS-30 PT demonstrated good internal consistency and significantly discriminated IG from NSG. Based on a robust EFA (RDWLS), a three-dimensional structure was determined for IG (Ageing and Hopelessness, Sleep Expectations, and Consequences and Helplessness). DBASeSFe16 presented as an internally-consistent measure with a reliable two-factor structure (Consequences and Helplessness, Medication and Hopelessness) and showed construct and known groups validity. ROC analysis demon- strated DBASeSFe16's relevant clinical accuracy, and 4.3 provides the best cut-off score in detecting the level of dysfunctional beliefs associated with clinical insomnia. Conclusions: A new and meaningful dimensionality of the DBAS-30 was found. DBASeSFe16 showed to be a reliable, valid, and robust tool for evaluating dysfunctional beliefs about insomnia in clinical and non-clinical populations.publishe