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1.
Malar J ; 20(1): 111, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33632228

RESUMO

BACKGROUND: Malaria is one of the most serious infectious diseases in the world. The malaria burden is greatly affected by human immunity, and immune responses vary between populations. Genetic diversity in KIR and HLA-C genes, which are important in immunity to infectious diseases, is likely to play a role in this heterogeneity. Several studies have shown that KIR and HLA-C genes influence the immune response to viral infections, but few studies have examined the role of KIR and HLA-C in malaria infection, and these have used low-resolution genotyping. The aim of this study was to determine whether genetic variation in KIR and their HLA-C ligands differ in Ugandan populations with historically varied malaria transmission intensity using more comprehensive genotyping approaches. METHODS: High throughput multiplex quantitative real-time PCR method was used to genotype KIR genetic variants and copy number variation and a high-throughput real-time PCR method was developed to genotype HLA-C1 and C2 allotypes for 1344 participants, aged 6 months to 10 years, enrolled from Ugandan populations with historically high (Tororo District), medium (Jinja District) and low (Kanungu District) malaria transmission intensity. RESULTS: The prevalence of KIR3DS1, KIR2DL5, KIR2DS5, and KIR2DS1 genes was significantly lower in populations from Kanungu compared to Tororo (7.6 vs 13.2%: p = 0.006, 57.2 vs 66.4%: p = 0.005, 33.2 vs 46.6%: p < 0.001, and 19.7 vs 26.7%: p = 0.014, respectively) or Jinja (7.6 vs 18.1%: p < 0.001, 57.2 vs 63.8%: p = 0.048, 33.2 vs 43.5%: p = 0.002, and 19.7 vs 30.4%: p < 0.001, respectively). The prevalence of homozygous HLA-C2 was significantly higher in populations from Kanungu (31.6%) compared to Jinja (21.4%), p = 0.043, with no significant difference between Kanungu and Tororo (26.7%), p = 0.296. CONCLUSIONS: The KIR3DS1, KIR2DL5, KIR2DS5 and KIR2DS1 genes may partly explain differences in transmission intensity of malaria since these genes have been positively selected for in places with historically high malaria transmission intensity. The high-throughput, multiplex, real-time HLA-C genotyping PCR method developed will be useful in disease-association studies involving large cohorts.

2.
Gates Open Res ; 4: 155, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33299966

RESUMO

Background: Group B Streptococcus (GBS) is a major contributor to the high burden of neonatal and young infant infectious disease in resource- limited settings. As disease protection during the first six months of life is provided via placental transfer of maternal antibodies, a maternal GBS vaccine may provide an effective strategy to reduce infectious death and disability. An efficacy study may be difficult because of the large sample size required and alternative approaches such as serocorrelates of protection based on natural antibody concentration are being considered. Such studies would need to be undertaken in high burden settings such as Uganda. We therefore aim to evaluate the feasibility and acceptability of a GBS sero-epidemiology study in Kampala, Uganda. Methods: This is a prospective cohort and nested case-control study, conducted across two-centres with two entry points. A) consecutive women and their infants at birth, with collection of maternal swab, cord and maternal blood, and follow up by telephone until the infant is 3 months old; B) any infant under 3 months of age, presenting with signs of sepsis to any of the paediatric units, with collection of blood culture, cerebrospinal fluid and nasopharyngeal swabs. Any infants identified as having GBS disease (defined as GBS isolated from a normally sterile site) will be recruited and followed up for two years to assess their neurodevelopment. A nested qualitative study will investigate stakeholder (pregnant women and their families, healthcare workers and community leaders) opinions of sampling for such a study and understanding and potential uptake of vaccines in pregnancy. Discussion: The primary aim is to determine anti-GBS antibody concentration in infants with GBS disease compared to healthy controls. Secondary outcomes include stillbirth and all-cause infection and acceptance of sample methods and vaccination. The findings will inform scalability and sustainability of the programme in Uganda.

3.
Front Immunol ; 11: 2070, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013876

RESUMO

During pregnancy, the placenta forms the anatomical barrier between the mother and developing fetus. Infectious agents can potentially breach the placental barrier resulting in pathogenic transmission from mother to fetus. Innate immune responses, orchestrated by maternal and fetal cells at the decidual-placental interface, are the first line of defense to avoid vertical transmission. Here, we outline the anatomy of the human placenta and uterine lining, the decidua, and discuss the potential capacity of pathogen pattern recognition and other host defense strategies present in the innate immune cells at the placental-decidual interface. We consider major congenital infections that access the placenta from hematogenous or decidual route. Finally, we highlight the challenges in studying human placental responses to pathogens and vertical transmission using current experimental models and identify gaps in knowledge that need to be addressed. We further propose novel experimental strategies to address such limitations.

4.
PLoS One ; 15(10): e0240837, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33085703

RESUMO

BACKGROUND: Peripartum cardiomyopathy (PPCM) is an idiopathic cardiomyopathy presenting with acute heart failure during the peripartum period. It is common in patients of African ancestry. Currently, there is paucity of data on the burden, predictors and outcomes of PPCM in Uganda. This study aimed to investigate the prevalence, predictors and six-month outcomes of PPCM in an adult cohort attending a tertiary specialised cardiology centre in Kampala, Uganda. METHODS: This study consecutively enrolled 236 women presenting with features of acute heart failure in the peripartum period. Clinical evaluation and echocardiography were performed on all the enrolled women. PCCM was defined according to recommendations of the Heart Failure Association of the European Society of Cardiology Working Group on PPCM. Poor outcome at six months of follow-up was defined as presence of any of the following: death of a mother or her baby, New York Heart Association (NYHA) functional class III-IV or failure to achieve complete recovery of left ventricular function (left ventricular ejection fraction ≤55%). RESULTS: The median age, BMI and parity of the study participants was 31.5 (25.5-38.0) years, 28.3 (26.4-29.7) and 3 (2-4) respectively. The prevalence of PPCM was 17.4% (n = 41/236). Multiple pregnancy was the only predictor of PPCM in this study population (OR 4.3 95% CI 1.16-16.05, p = 0.029). Poor outcome at six-months was observed in about 54% of the patients with PPCM (n = 4, 9.8% in NYHA functional class III-IV and n = 22, 53.7% with LVEF <55%). No maternal or foetal mortality was documented. CONCLUSION: PPCM is relatively common in Uganda and is associated with multiple pregnancy. Poor outcomes especially absence of complete recovery of left ventricular function are also common. Large studies to further investigate long-term maternal and foetal outcomes in Uganda are justified.

5.
BMJ Glob Health ; 5(6)2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32586891

RESUMO

INTRODUCTION: The COVID-19 pandemic has substantially impacted maternity care provision worldwide. Studies based on modelling estimated large indirect effects of the pandemic on services and health outcomes. The objective of this study was to prospectively document experiences of frontline maternal and newborn healthcare providers. METHODS: We conducted a global, cross-sectional study of maternal and newborn health professionals via an online survey disseminated through professional networks and social media in 12 languages. Information was collected between 24 March and 10 April 2020 on respondents' background, preparedness for and response to COVID-19 and their experience during the pandemic. An optional module sought information on adaptations to 17 care processes. Descriptive statistics and qualitative thematic analysis were used to analyse responses, disaggregating by low-income and middle-income countries (LMICs) and high-income countries (HICs). RESULTS: We analysed responses from 714 maternal and newborn health professionals. Only one-third received training on COVID-19 from their health facility and nearly all searched for information themselves. Half of respondents in LMICs received updated guidelines for care provision compared with 82% in HICs. Overall, 47% of participants in LMICs and 69% in HICs felt mostly or completely knowledgeable in how to care for COVID-19 maternity patients. Facility-level responses to COVID-19 (signage, screening, testing and isolation rooms) were more common in HICs than LMICs. Globally, 90% of respondents reported somewhat or substantially higher levels of stress. There was a widespread perception of reduced use of routine maternity care services, and of modification in care processes, some of which were not evidence-based practices. CONCLUSIONS: Substantial knowledge gaps exist in guidance on management of maternity cases with or without COVID-19. Formal information-sharing channels for providers must be established and mental health support provided. Surveys of maternity care providers can help track the situation, capture innovations and support rapid development of effective responses.


Assuntos
Serviços de Saúde da Criança/estatística & dados numéricos , Infecções por Coronavirus , Pessoal de Saúde/estatística & dados numéricos , Serviços de Saúde Materna/estatística & dados numéricos , Pandemias , Pneumonia Viral , Betacoronavirus , Estudos Transversais , Feminino , Humanos , Recém-Nascido , Estresse Ocupacional , Pobreza , Inquéritos e Questionários
6.
Cell Mol Immunol ; 17(8): 799-806, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32541835

RESUMO

Malaria is one of the deadliest infectious diseases in the world. Immune responses to Plasmodium falciparum malaria vary among individuals and between populations. Human genetic variation in immune system genes is likely to play a role in this heterogeneity. Natural killer (NK) cells produce inflammatory cytokines in response to malaria infection, kill intraerythrocytic Plasmodium falciparum parasites by cytolysis, and participate in the initiation and development of adaptive immune responses to plasmodial infection. These functions are modulated by interactions between killer-cell immunoglobulin-like receptors (KIRs) and human leukocyte antigens (HLAs). Therefore, variations in KIR and HLA genes can have a direct impact on NK cell functions. Understanding the role of KIRs and HLAs in immunity to malaria can help to better characterize antimalarial immune responses. In this review, we summarize the different KIRs and HLAs associated with immunity to malaria thus far.

8.
BMC Pregnancy Childbirth ; 20(1): 324, 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32460720

RESUMO

BACKGROUND: In many low and medium human development index countries, the rate of maternal and neonatal morbidity and mortality is high. One factor which may influence this is the decision-to-delivery interval of emergency cesarean section. We aimed to investigate the maternal risk factors, indications and decision-to-delivery interval of emergency cesarean section in a large, under-resourced obstetric setting in Uganda. METHODS: Records of 344 singleton pregnancies delivered at ≥24 weeks throughout June 2017 at Mulago National Referral Hospital were analysed using Cox proportional hazards models and multivariate logistic regression models. RESULTS: An emergency cesarean section was performed every 104 min and the median decision-to-delivery interval was 5.5 h. Longer interval was associated with preeclampsia and premature rupture of membranes/oligohydramnios. Fetal distress was associated with a shorter interval (p < 0.001). There was no association between decision-to-delivery interval and adverse perinatal outcomes (p > 0.05). Mothers waited on average 6 h longer for deliveries between 00:00-08:00 compared to those between 12:00-20:00 (p < 0.01). The risk of perinatal death was higher in neonates where the decision to deliver was made between 20:00-02:00 compared to 08:00-12:00 (p < 0.01). CONCLUSION: In this setting, the average decision-to-delivery interval is longer than targets adopted in high development index countries. Decision-to-delivery interval varies diurnally, with decisions and deliveries made at night carrying a higher risk of adverse perinatal outcomes. This suggests a need for targeting the improvement of service provision overnight.

9.
Reprod Health ; 17(1): 74, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32456705

RESUMO

INTRODUCTION: Uganda has high adolescent pregnancy. The details of adolescent childbirth and urban/rural patterns are scarce. We investigated the levels, time trends and determinants of adolescent childbirth in Uganda separately for urban and rural women. METHODS: We estimated the percentage of women 20-24 years at each of the six Uganda Demographic and Health Surveys (1988/89, 1995, 2000/01, 2006, 2011 and 2016) who reported a live childbirth before age 20 years ("adolescent childbirth"), and examined change over time using t-test. A modified multivariable Poisson regression was used to examine determinants of having adolescent childbirth on the 2016 survey. RESULTS: Among these women, 67.5, 66.4, 70.1, 62.3, 57.3 and 54.1% reported an adolescent childbirth in 1988/89, 1995, 2000/01, 2006, 2011 and 2016 surveys, respectively. Between 1988/89 to 2000/01, there was no evidence of change (+ 2.6% point (pp), p = 0.170), unlike between the 2000/01 and 2016 surveys when a significant decline occurred (- 16.0 pp., p < 0.001). First childbirth < 18 years of age declined by - 13.5 pp. (p < 0.001) between 2000/01 and 2016. There was no change over time in the percentage of adolescents 18-19.9 years of age having first childbirth. Among rural residents, childbirth < 18 years declined from 43.8% in 1988/89 to 32.7% in 2016 (- 11.1 pp., p < 0.001), in urban it declined from 28.3 to 18.2% (- 10.1 pp., p = 0.006). There was an increase over time in the percentage of women, both rural and urban, who wanted to delay their first pregnancy. Independent determinants of reporting an adolescent childbirth in both urban and rural residents were: no education/incomplete primary and younger age at first sex. Additional determinants for rural women were residence in Eastern region, Muslim religion, and poor household wealth index. CONCLUSION: In the 30-year period examined, adolescent childbirth in Uganda declined from highs of 7 in 10 to approximately 5 in 10 women, with more wanting to delay the pregnancy. The decline started after the 2000/01 survey and affected predominantly younger adolescent childbirth < 18 years among both rural and urban residence women. Efforts need to be intensified to sustain the decline in adolescent pregnancies. Targeted and specific strategies for urban and rural areas might be required.

10.
Pregnancy Hypertens ; 21: 1-6, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32330863

RESUMO

OBJECTIVES: Low birth-weight is a major risk factor for perinatal death in sub-Saharan Africa, but the relative contribution of determinants of birth-weight are difficult to disentangle in low resource settings. We sought to delineate the relationship between birth-weight and maternal pre-eclampsia across gestation in a low-resource obstetric setting. STUDY DESIGN: Prospective cohort study in a tertiary referral centre in urban Uganda, including 971 pre-eclampsia cases and 1461 control pregnancies between 28 and 42 weeks gestation. MAIN OUTCOME MEASURES: Nonlinear modeling of birth-weight versus maternal pre-eclampsia status across gestation. Models were adjusted for maternal-fetal characteristics including maternal age, parity, HIV status, and socio-economic status. Propensity score matching was used to control for the severity of pre-eclampsia at different gestational ages. RESULTS: Mean birth-weight for pre-eclampsia cases was 2.48 kg (±0.81SD) compared to 3.06 kg (±0.46SD) for controls (p < 0.001). At 28 weeks, the mean birth-weight difference between pre-eclampsia cases and controls was 0.58 kg (p < 0.05), narrowing to 0.17 kg at 39 weeks (p < 0.01). Controlling for pre-eclampsia severity only partially explained this gestational difference in mean birth-weight between pre-eclampsia cases and controls. Holding gestational age constant, pre-eclampsia status predicted 7.1-10.5% of total variation in birth-weight, compared to 0.05-0.7% for all other maternal-fetal characteristics combined. CONCLUSIONS: Pre-eclampsia is the dominant predictor of birth-weight in low-resource settings and hence likely to heavily influence perinatal survival. The impact of pre-eclampsia on birth-weight is smaller with advancing gestational age, a difference that is not fully explained by controlling for pre-eclampsia severity.

11.
PLoS One ; 15(4): e0231557, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32287303

RESUMO

BACKGROUND: Information on repeat adolescent birth remains scarce in sub-Sahara Africa. We investigated the prevalence and time trends in repeat adolescent birth in Uganda, and associated factors. METHODS: We analyzed Uganda Demographic and Health Survey data of women age 20-24 years collected on 6 surveys (1988/89-2016) to estimate repeat adolescent birth (first live birth <18 years of age followed by another live birth(s) <20 years). Further, we estimated the wantedness of the second order birth and the prevalence of short birth intervals birth (<13 months) between the first and second such birth. On the 2016 survey, we examined factors associated with repeat adolescent birth using bivariate and multivariate modified Poisson regression. RESULTS: At the 1988/89 survey, 58.9% of women with first birth <18 years reported a repeat adolescent birth. This percentage increased to 66.8% in 2006 (+7.9 percentage points [pp], p = 0.010) and thereafter declined to 55.6% by 2016 (-11.2 pp, p<0.001), nevertheless, no change occurred between 1988/89 and 2016 (-3.3pp, p = 0.251). Among women with repeat adolescent births, the mean number of live births by exact age 20 years (2.2 births) and prevalence of short birth intervals (3.5% in 1988/89, 5.4% in 2016) (+1.9pp, p = 0.245) did not change. Increasingly more women with repeat adolescent births preferred to have had the second child later, 22.5% in 1995 and 43.1% in 2016 (+20.6pp, p = <0.001). On the 2016 survey, women from poorer households and those of younger age at first birth were significantly more likely to report repeat adolescent birth. CONCLUSION: Following a first birth <18 years, more than half of the women report a repeat adolescent birth (<20 years), with no decline observed in 30 years. Increasingly more women wanted the second adolescent pregnancy later, highlighting the need to support adolescents with improved family planning services at each contact.


Assuntos
Paridade , Gravidez na Adolescência/estatística & dados numéricos , Adolescente , Adulto , Ordem de Nascimento/psicologia , Coeficiente de Natalidade/tendências , Serviços de Planejamento Familiar/tendências , Feminino , Inquéritos Epidemiológicos , Humanos , Idade Materna , Parto/psicologia , Gravidez , Uganda/epidemiologia , Adulto Jovem
13.
Implement Sci ; 14(1): 38, 2019 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-30999963

RESUMO

BACKGROUND: Interventions aimed at reducing maternal mortality are increasingly complex. Understanding how complex interventions are delivered, to whom, and how they work is key in ensuring their rapid scale-up. We delivered a vital signs triage intervention into routine maternity care in eight low- and middle-income countries with the aim of reducing a composite outcome of morbidity and mortality. This was a pragmatic, hybrid effectiveness-implementation stepped-wedge randomised controlled trial. In this study, we present the results of the mixed-methods process evaluation. The aim was to describe implementation and local context and integrate results to determine whether differences in the effect of the intervention across sites could be explained. METHODS: The duration and content of implementation, uptake of the intervention and its impact on clinical management were recorded. These were integrated with interviews (n = 36) and focus groups (n = 19) at 3 months and 6-9 months after implementation. In order to determine the effect of implementation on effectiveness, measures were ranked and averaged across implementation domains to create a composite implementation strength score and then correlated with the primary outcome. RESULTS: Overall, 61.1% (n = 2747) of health care providers were trained in the intervention (range 16.5% to 89.2%) over a mean of 10.8 days. Uptake and acceptability of the intervention was good. All clusters demonstrated improved availability of vital signs equipment. There was an increase in the proportion of women having their blood pressure measured in pregnancy following the intervention (79.2% vs. 97.6%; OR 1.30 (1.29-1.31)) and no significant change in referral rates (3.7% vs. 4.4% OR 0.89; (0.39-2.05)). Availability of resources and acceptable, effective referral systems influenced health care provider interaction with the intervention. There was no correlation between process measures within or between domains, or between the composite score and the primary outcome. CONCLUSIONS: This process evaluation has successfully described the quantity and quality of implementation. Variation in implementation and context did not explain differences in the effectiveness of the intervention on maternal mortality and morbidity. We suggest future trials should prioritise in-depth evaluation of local context and clinical pathways. TRIAL REGISTRATION: Trial registration: ISRCTN41244132 . Registered on 2 Feb 2016.


Assuntos
Determinação da Pressão Arterial/instrumentação , Países em Desenvolvimento , Hipertensão Induzida pela Gravidez/diagnóstico , Mortalidade Materna , Avaliação de Processos em Cuidados de Saúde , Triagem , Sinais Vitais , Adulto , Desenho de Equipamento , Feminino , Grupos Focais , Humanos , Ciência da Implementação , Entrevistas como Assunto , Gravidez , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde
14.
Hum Immunol ; 79(12): 825-833, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30321631

RESUMO

The goals of the KIR component of the 17th International HLA and Immunogenetics Workshop (IHIW) were to encourage and educate researchers to begin analyzing KIR at allelic resolution, and to survey the nature and extent of KIR allelic diversity across human populations. To represent worldwide diversity, we analyzed 1269 individuals from ten populations, focusing on the most polymorphic KIR genes, which express receptors having three immunoglobulin (Ig)-like domains (KIR3DL1/S1, KIR3DL2 and KIR3DL3). We identified 13 novel alleles of KIR3DL1/S1, 13 of KIR3DL2 and 18 of KIR3DL3. Previously identified alleles, corresponding to 33 alleles of KIR3DL1/S1, 38 of KIR3DL2, and 43 of KIR3DL3, represented over 90% of the observed allele frequencies for these genes. In total we observed 37 KIR3DL1/S1 allotypes, 40 for KIR3DL2 and 44 for KIR3DL3. As KIR allotype diversity can affect NK cell function, this demonstrates potential for high functional diversity worldwide. Allelic variation further diversifies KIR haplotypes. We determined KIR3DL3 ∼ KIR3DL1/S1 ∼ KIR3DL2 haplotypes from five of the studied populations, and observed multiple population-specific haplotypes in each. This included 234 distinct haplotypes in European Americans, 191 in Ugandans, 35 in Papuans, 95 in Egyptians and 86 in Spanish populations. For another 35 populations, encompassing 642,105 individuals we focused on KIR3DL2 and identified another 375 novel alleles, with approximately half of them observed in more than one individual. The KIR allelic level data gathered from this project represents the most comprehensive summary of global KIR allelic diversity to date, and continued analysis will improve understanding of KIR allelic polymorphism in global populations. Further, the wealth of new data gathered in the course of this workshop component highlights the value of collaborative, community-based efforts in immunogenetics research, exemplified by the IHIW.


Assuntos
Antígenos HLA/genética , Imunogenética/métodos , Família Multigênica , Receptores KIR/genética , Frequência do Gene , Genética Populacional/métodos , Genótipo , Haplótipos , Humanos , Isoformas de Proteínas/genética , Análise de Sequência de DNA
15.
Immun Inflamm Dis ; 5(4): 461-468, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28685972

RESUMO

INTRODUCTION: KIR2DS5 is an activating human NK cell receptor of lineage III KIR. These include both inhibitory KIR2DL1, 2 and 3 and activating KIR2DS1 that recognize either the C1 or C2 epitope of HLA-C. In Europeans KIR2DS5 is essentially monomorphic, with KIR2DS5*002 being predominant. Pioneering investigations showed that KIR2DS5*002 has activating potential, but cannot recognize HLA-A, -B, or -C. Subsequent studies have shown that KIR2DS5 is highly polymorphic in Africans, and that KIR2DS5*006 protects pregnant Ugandan women from preeclampsia. Because inhibitory C2-specific KIR2DL1 correlates with preeclampsia, whereas activating C2-specific KIR2DS1 protects, this association pointed to KIR2DS5*006 being an activating C2-specific receptor. To test this hypothesis we made KIR-Fc fusion proteins from all ten KIR2DS5 allotypes and tested their binding to a representative set of HLA-A, -B and -C allotypes. RESULTS: Six African-specific KIR2DS5 bound to C2+ HLA-C but not to other HLA class I. Their avidity for C2 is ∼20% that of C2-specific KIR2DL1 and ∼40% that of C2-specific KIR2DS1. Among the African C2 receptors is KIR2DS5*006, which protected a cohort of pregnant Ugandans from pre-eclampsia. Three African KIR2DS5 allotypes and KIR2DS5*002, bound no HLA-A, -B or -C. As a group the C2-binding KIR2DS5 allotypes protect against pre-eclampsia compared to the non-binding KIR2DS5 allotypes. Natural substitutions that contribute to loss or reduction of C2 receptor function are at positions 127, 158, and 176 in the D2 domain. CONCLUSIONS: KIR2DS5*005 has the KIR2DS5 consensus sequence, is the only allele found at both centromeric and telomeric locations of KIR2DS5, and is likely the common ancestor of all KIR2DS5 alleles. That KIR2DS5*005 has C2 receptor activity, points to KIR2DS5*002, and other allotypes lacking C2 receptor function, being products of attenuation, a characteristic feature of most KIR B haplotype genes. Alleles encoding attenuated and active KIR2DS5 are present in both centromeric and telomeric locations.


Assuntos
Grupo com Ancestrais do Continente Africano , Epitopos/imunologia , Epitopos/metabolismo , Grupo com Ancestrais do Continente Europeu , Antígenos HLA-C/imunologia , Receptores KIR/metabolismo , Alelos , Feminino , Antígenos HLA-C/química , Antígenos HLA-C/genética , Antígenos HLA-C/metabolismo , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Desequilíbrio de Ligação , Polimorfismo Genético , Gravidez , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Receptores KIR/química , Receptores KIR/genética
16.
Health Res Policy Syst ; 15(1): 33, 2017 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-28431554

RESUMO

BACKGROUND: In the last decade, Makerere University College of Health Sciences (MakCHS) has taken strides in research and training to improve healthcare through collaborative training and research programs. However, there is limited data on the trends of MakCHS faculty contributions to research and on faculty growth to take leading roles in health research. This paper reviews MakCHS faculty research publications over 15.5 years and outlines possible strategies to enhance faculty research outputs. METHODS: We used a mixed methods approach. A systematic review of research publications by faculty at MakCHS (PubMed and Google Scholar from January 1, 2000, to June 30, 2015) to quantify the number of research articles, areas researched, authorship contribution by MakCHS faculty, source of funding, as well as affiliated local and international collaborations. Graphs were used to shown trends in publications and leadership of authorship by faculty. Annual individual faculty research productivity was presented as publication per capita. Qualitative data on high priority needs to improve research outputs was collected through focus group discussions (FGDs) with faculty members, and analysed manually into emerging themes. RESULTS: Of 298 faculty at MakCHS at 2015, 89 (30%) were female and 229 (77%) were junior and mid-level faculty (senior lecturer and below). The PubMed and Google Scholar searches yielded 6927 published articles, of which 3399 (49%) full-text articles were downloaded for analysis, 426/3825 (11%) available as titles/abstracts only, and 598/4423 (14%) were excluded. Only 614 articles were published in 2014, giving a publication per capita of 2.1 for any authorship, and 0.3 for first and last authorship positions. MakCHS faculty increasingly contributed as first, second, third, and last authors. Up to 57% of research was in infectious diseases, followed by non-communicable diseases (20%) and non-communicable maternal child health (11%). Priority needs to improve research outputs, as expressed by faculty, were (1) an institutionally led faculty career development program, (2) skills building in research methods and scientific writing, (3) protected time for research related activities, (4) opportunities for collaborative research, and (5) use of individual development plans. CONCLUSION: Faculty research productivity was low and dominated by infectious diseases and non-communicable disease research. There is a need for structured institutional support to optimise faculty research outputs. Only with increased research productivity will MakCHS and other academic institutions be able to make a significant contribution in addressing national health challenges.


Assuntos
Pesquisa Biomédica/organização & administração , Pesquisa Biomédica/estatística & dados numéricos , Educação Médica/organização & administração , Docentes/estatística & dados numéricos , Publicações/tendências , Autoria , Eficiência , Feminino , Humanos , Universidades
17.
BMC Pregnancy Childbirth ; 16: 205, 2016 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-27492552

RESUMO

BACKGROUND: Hypertensive disorders of pregnancy are a major cause of morbidity and mortality. The objective was to estimate the disease burden attributable to hypertensive disorders of pregnancy in two referral hospitals in Uganda. METHODS: Through a prospective cohort study conducted in Jinja and Mulago hospitals in Uganda from March 1, 2013 and February 28, 2014, hypertension-related cases were analyzed. Maternal near miss cases were defined according to the WHO criteria. Maternal deaths were also analyzed. The maternal near miss incidence ratio, the case-specific severe maternal outcome ratio, the case-specific maternal mortality ratio and the case-fatality ratio were computed. RESULTS: Of 403 women with hypertensive disorders of pregnancy, 218 (54.1 %) had severe preeclampsia, 172 (42.7 %) had eclampsia, and 13 had chronic hypertension or Hemolysis, elevated liver enzymes or low platelets (HELLP) syndrome. The case-specific maternal near miss incidence ratios was 8.60 per 1,000 live births for all hypertensive disorders, 3.06 per 1,000 live births for severe preeclampsia and 5.11 per 1,000 live births for eclampsia. The case-specific severe maternal outcome ratio was 9.37 per 1,000 live births for all hypertensive disorders, and was 3.25 per 1,000 live births for severe preeclampsia and 5.61 per 1,000 live births for eclampsia. The case-specific maternal mortality ratio was 780 per 100,000 live births for all hypertensive disorders, and was 1940 per 100,000 live births for severe preeclampsia and 501 per 100,000 live births for eclampsia. The case-fatality ratio was 5.1 % overall (for all hypertensive disorders), but was 8 times higher for eclampsia compared to severe preeclampsia. Cyanosis, abnormal respiration, oliguria, circulatory collapse, coagulopathy, thrombocytopenia, and elevated serum lactate were significantly associated with severe maternal outcomes. CONCLUSION: There is high morbidity attributable to hypertensive disorders in pregnancy. Since some of the complications associated with morbidity can be recognized early, it is possible to prevent severe morbidity through early intervention with delivery, antihypertensive therapy and prophylactic magnesium sulphate treatment. The findings highlight the feasibility of implementing a facility-based surveillance system for severe maternal morbidity due to hypertensive disorders.


Assuntos
Hipertensão Induzida pela Gravidez/mortalidade , Mortalidade Materna , Adulto , Feminino , Humanos , Nascimento Vivo , Morbidade , Near Miss/estatística & dados numéricos , Gravidez , Estudos Prospectivos , Uganda/epidemiologia , Adulto Jovem
18.
Int J Gynaecol Obstet ; 132(3): 347-52, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26873123

RESUMO

OBJECTIVE: To investigate the effect of subsequent pregnancies on HIV disease progression among HIV-infected women at Mulago Hospital, Uganda. METHODS: In a retrospective cohort study, data were analyzed from women enrolled in the Mother-To-Child Transmission Plus program from March 2003 to December 2011. The CD4 cell count, the development of new AIDS-defining opportunistic infections, and the AIDS-related mortality were compared between women with and without subsequent pregnancies. RESULTS: Overall, 409 women were enrolled and 195 (47.7%) had subsequent pregnancies. Antiretroviral therapy (ART) was initiated in 143 (73.3%) women with and 155 (72.4%) women without subsequent pregnancies. Kaplan-Meier analysis for women receiving ART showed no differences between women with and without subsequent pregnancies in the median times to clinical failure (62.7 vs 64.7 months; P=0.31), immunological failure (68.8 vs 75.5 months; P=0.10), and death (68.8 vs 75.5 months; P=0.53). In a Cox regression analysis, subsequent pregnancies were not associated with immunological failure during follow-up (adjusted hazard ratio 1.13, 95% confidence interval 0.06-2.09). CONCLUSION: Subsequent pregnancies could have no detrimental effect on HIV disease progression among HIV-infected women whose treatment is well managed.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Progressão da Doença , Infecções por HIV/tratamento farmacológico , Complicações Infecciosas na Gravidez/epidemiologia , Adulto , Terapia Antirretroviral de Alta Atividade , Infecções Bacterianas/epidemiologia , Contagem de Linfócito CD4 , Feminino , Humanos , Estimativa de Kaplan-Meier , Gravidez , Complicações Infecciosas na Gravidez/virologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Tuberculose Pulmonar/epidemiologia , Uganda
19.
BMC Pregnancy Childbirth ; 16: 24, 2016 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-26821716

RESUMO

BACKGROUND: Maternal near misses occur more often than maternal deaths and could enable more comprehensive analysis of risk factors, short-term outcomes and prognostic factors of complications during pregnancy and childbirth. The study determined the incidence, determinants and prognostic factors of severe maternal outcomes (near miss or maternal death) in two referral hospitals in Uganda. METHODS: A prospective cohort study was conducted between March 1, 2013 and February 28, 2014, where cases of severe pregnancy and childbirth complications were included. The clinical conditions included abortion-related complications, obstetric haemorrhage, hypertensive disorders, obstructed labour, infection and pregnancy-specific complications such as febrile illness, anemia and premature rupture of membranes. Near miss cases were defined according to the WHO criteria. Multivariate logistic regression analysis was conducted to identify prognostic factors for severe maternal outcomes. RESULTS: Of 3100 women with severe obstetric complications, 130 (4.2%) were maternal deaths and 695 (22.7%) were near miss cases. Severe pre-eclampsia was the commonest morbidity (incidence ratio (IR) 7.0%, case-fatality rate (CFR) 2.3%), followed by postpartum haemorrhage (IR 6.7%, CFR 7.2%). Uterine rupture (IR 5.5%) caused the highest CFR (17.9%), followed by eclampsia (IR 0.4%, CFR 17.8%). The three groups (maternal deaths, near misses and non-life-threatening obstetric complications) differed significantly regarding gravidity and education level. The commonest diagnostic criteria for maternal near miss were admission to the high dependency unit (HDU) or to the intensive care unit (ICU). Thrombocytopenia, circulatory collapse, referral to a more specialized unit, intubation unrelated to anaesthesia, and cardiopulmonary resuscitation were predictive of maternal death (p < 0.05). Gravidity (ARR 1.4, 95% C1 1.0-1.2); elevated serum lactate levels (ARR 4.5, 95% CI 2.3-8.7); intubation for conditions unrelated to general anaesthesia (ARR 2.6 (95% CI 1.2-5.7), cardiovascular collapse (ARR 4.9, 95% CI 2.5-9.5); transfusion of 4 or more units of blood (ARR 1.9, 95% CI 1.1-3.1); being an emergency referral (ARR 2.6, 95% CI 1.2-5.6); and need for cardiopulmonary resuscitation (ARR 6.1, 95% CI 3.2-11.7), were prognostic factors. CONCLUSIONS: The analysis of near misses is a useful tool in the investigation of severe maternal morbidity. The prognostic factors for maternal death, if instituted, might save many women with obstetric complications.


Assuntos
Morte Materna/estatística & dados numéricos , Near Miss/estatística & dados numéricos , Complicações na Gravidez/mortalidade , Encaminhamento e Consulta/estatística & dados numéricos , Adolescente , Adulto , Escolaridade , Feminino , Número de Gestações , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Morte Materna/etiologia , Mortalidade Materna , Complicações do Trabalho de Parto/etiologia , Complicações do Trabalho de Parto/mortalidade , Hemorragia Pós-Parto/etiologia , Hemorragia Pós-Parto/mortalidade , Pré-Eclâmpsia/etiologia , Pré-Eclâmpsia/mortalidade , Gravidez , Complicações na Gravidez/etiologia , Estudos Prospectivos , Fatores de Risco , Uganda/epidemiologia , Ruptura Uterina/etiologia , Ruptura Uterina/mortalidade , Adulto Jovem
20.
Trans R Soc Trop Med Hyg ; 110(12): 681-683, 2016 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-28938051

RESUMO

The high neonatal and maternal morbidity and mortality associated with the extremes of birth weight is referred to as the obstetric dilemma. Pre-eclampsia and other conditions that lead to low birth weight are considered as the Great Obstetrical Syndromes (GOS). At the other extreme is high birth weight resulting in obstructed labour. Fetal weight largely depends on placental function and defective placentation is a common feature of the GOS. There is evidence that the local uterine immune system (KIR and HLA-C) regulates placentation, with racial differences noted. These differences may be responsible for the striking obstetric dilemma in Africans.


Assuntos
Mortalidade Infantil , Mortalidade Materna , Placentação/imunologia , Complicações na Gravidez/genética , Complicações na Gravidez/imunologia , Reação de Fase Aguda , África ao Sul do Saara/epidemiologia , Feminino , Retardo do Crescimento Fetal , Macrossomia Fetal/genética , Macrossomia Fetal/imunologia , Variação Genética , Antígenos HLA-C/genética , Antígenos HLA-C/imunologia , Humanos , Lactente , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Inflamação/genética , Inflamação/imunologia , Fenômenos Fisiológicos da Nutrição Materna , Troca Materno-Fetal/genética , Troca Materno-Fetal/imunologia , Placenta/imunologia , Placenta/fisiopatologia , Placentação/genética , Gravidez/imunologia , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/fisiopatologia , Receptores KIR , Receptores KIR2DL1
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