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1.
Curr Opin HIV AIDS ; 14(6): 455-463, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31589173

RESUMO

PURPOSE OF REVIEW: Although cities present opportunities for infectious pathogens such as HIV to spread, public health infrastructure within these cities also provides opportunities to design effective approaches to eliminate transmission of these pathogens. The HIV Transmission Elimination AMsterdam (H-TEAM) Initiative, a consortium of relevant stakeholders involved in HIV prevention and care, designed an integrated approach to curb the HIV epidemic in Amsterdam, including providing preexposure prophylaxis (PrEP), increasing awareness of acute HIV infection, offering same-day test and treat, and improving indicator disease-driven HIV testing. RECENT FINDINGS: In 2013, approximately 230 people in Amsterdam were newly diagnosed with HIV, largely belonging to one of two key affected populations, namely MSM and people with a migration background. Since the start of H-TEAM in 2014, a decrease in new diagnoses was observed (130 in 2017), with an increasing proportion of MSM who had been diagnosed with a recent infection. SUMMARY: The H-TEAM shows that a city-based concerted effort is feasible. However, major challenges remain, such as reducing the number of late HIV diagnoses, and identifying and providing appropriate services to a diminishing group of individuals who are likely the source of transmission.

2.
Clin Infect Dis ; 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31499523

RESUMO

The San Diego Early Test (SDET) score is a simple risk-assessment tool for acute and early HIV-infection. Validation in a prospective cohort of Amsterdam men who have sex with men showed fair prediction of HIV seroconversion (AUC 0.701). Use of this score can help prioritise and target HIV prevention strategies.

4.
Clin Immunol ; 203: 23-27, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30953794

RESUMO

Genetic studies are identifying an increasing number of monogenic causes of Common Variable Immunodeficiency (CVID). Pathogenic variants in the C-terminus of NFKB2 have been identified in the subset of CVID patients whose immunodeficiency is associated with ectodermal dysplasia and central adrenal insufficiency. We describe 2 unrelated CVID pedigrees with 4 cases of pathogenic stop gain variants (c.1903C > T) in the ankyrin repeat domain (ARD) of NF-κB2, leading to a premature truncation of the protein at p.Arg635Term (R635X). By immunophenotyping and functional ex vivo B- and T-cell experiments we characterized the variant by reduced class-switched memory B-cell counts and immature plasmablasts, unable to produce IgG and IgA. Features of a poor proliferative T-cell response and reduced expansion of CD4+CXCR5+ T cells was only observed in the two clinically affected index cases without any clear clinical correlate. In conclusion, pathogenic stop variants in the ARD of NFKB2 can cause 'infection-only' CVID with an abnormal B-cell phenotype and a variable clinical penetrance.

5.
Lancet HIV ; 6(5): e271-e272, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31000478
6.
Vaccine ; 36(39): 5832-5845, 2018 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-30122649

RESUMO

INTRODUCTION: Patients with a weakened immune system due to immunosuppressive treatment are at increased risk of infection with Streptococcus pneumoniae. Although pneumococcal vaccination is highly recommended for those patients, the effectiveness of pneumococcal vaccination in this population remains largely unknown. Therefore, the objective of this PROSPERO-registered systematic review and meta-analysis was to evaluate the effect of the most commonly prescribed immunosuppressive agents such as azathioprine, methotrexate, anti-Tumor Necrosis Factor α (TNFα), or rituximab, on the initial serologic response to pneumococcal vaccination in patients with auto-immune disease. METHODS: We included 22 articles comprising 2077 patients, of whom 1623 were treated with immunosuppressive agents, and 454 were controls. RESULTS AND DISCUSSION: The findings of our systematic review indicate that, in patients treated with immunosuppressive medication and compared to controls, the initial serologic response to pneumococcal conjugate vaccine (PCV) and pneumococcal polysaccharide vaccine (PPSV) are impaired. Moreover, this impaired response was more profound after PCV than after PPSV. We hypothesize that the immunosuppressive medication mainly compromises the cellular immunity, explaining the more severely reduced response rate to PCV (which induces a T-cell dependent immune response), compared to PPSV. Treatment with TNFα blocking agents was associated with a more favorable response, compared to patients treated with other immunosuppressive medication. Targeted research applying uniform correlates of protection is needed to bridge the knowledge gap in vaccination immunology in this patient group. PROSPERO registration: CRD42017058364.

7.
J Acquir Immune Defic Syndr ; 79(2): e52-e55, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30015794

RESUMO

OBJECTIVE: Dijkstra et al recently described a risk- and symptom-based score moderately predictive for HIV seroconversion in the preceding 6-12 months in men who have sex with men (MSM) in Amsterdam. Our objective was to determine whether this "Amsterdam Score" could also predict for acute HIV infection (AHI) in MSM. DESIGN AND SETTING: This study is a case-control analysis of a prospectively enrolled cohort of MSM who voluntarily presented for HIV testing in San Diego. The study sample was composed of MSM who screened HIV antibody-negative and then either tested positive with AHI [HIV nucleic acid test (NAT)-positive] or tested HIV NAT-negative. METHODS: The Amsterdam Score was calculated for each participant in the study sample. Score performance was assessed using receiver operating characteristic curves and their area under the curve (AUC). An optimal cutoff was determined using the Youden index. RESULTS: Seven hundred fifty-seven MSM (110 AHI and 647 HIV NAT-negative) were included in the analysis. AHI and HIV-negative cases were similar in age [median 32 years (interquartile range 26-42) vs 33 (27-45), respectively, P = 0.082]. The Amsterdam Score yielded a receiver operating characteristic curve with an AUC of 0.88 (95% confidence interval: 0.84 to 0.91). An optimal cutoff of ≥1.6 was 78.2% sensitive and 81.0% specific. CONCLUSIONS: The risk- and symptom-based Amsterdam Score was highly predictive (AUC of 0.88) of AHI in MSM in San Diego. The Amsterdam Score could be used to target NAT utilization in resource-poor settings among MSM who test HIV antibody-negative, although the potential cost-savings must be balanced with the risk of missing AHI diagnoses.

8.
Travel Med Infect Dis ; 24: 89-100, 2018 Jul - Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29860151

RESUMO

BACKGROUND: Invasive pneumococcal disease (IPD) is associated with high morbidity and mortality, with immunocompromised patients (ICPs) at particular risk. Therefore, guidelines recommend pneumococcal vaccination for these patients. However, guidelines are scarcely underpinned with references to incidence studies of IPD in this population. This, potentially results in unawareness of the importance of vaccination and low vaccination rates. The objective of this systematic review and meta-analysis was to assess the incidence of IPD in ICPs. METHODS: We systematically searched PubMed and Embase to identify studies in English published before December 6th, 2017 that included terms related to 'incidence', 'rate', 'pneumococcal', 'pneumoniae', 'meningitis', 'septicemia', or 'bacteremia'. We focused on patients with HIV, transplantation and chronic inflammatory diseases. RESULTS: We included 45 studies in the systematic review reporting an incidence or rate of IPD, defined as isolation of Streptococcus pneumoniae from a normally sterile site. Random effects meta-analysis of 38 studies showed a pooled IPD incidence of 331/100,000 person years in patients with HIV in the late-antiretroviral treatment era in non-African countries, and 318/100,000 in African countries; 696 and 812/100,000 in patients who underwent an autologous or allogeneic stem cell transplantation, respectively; 465/100,000 in patients with a solid organ transplantation; and 65/100,000 in patients with chronic inflammatory diseases. In healthy control cohorts, the pooled incidence was 10/100,000. DISCUSSION: ICPs are at increased risk of contracting IPD, especially those with HIV, and those who underwent transplantation. Based on our findings, we recommend pneumococcal vaccination in immunocompromised patients. PROSPERO REGISTRATION: ID: CRD42016048438.


Assuntos
Hospedeiro Imunocomprometido , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/microbiologia , Adulto , África/epidemiologia , Criança , Estudos de Coortes , Feminino , Infecções por HIV/complicações , Infecções por HIV/microbiologia , Infecções por HIV/virologia , Humanos , Incidência , Masculino , Infecções Pneumocócicas/imunologia , Vacinas Pneumocócicas/administração & dosagem , Fatores de Risco , Streptococcus pneumoniae/imunologia , Streptococcus pneumoniae/isolamento & purificação , Transplante/efeitos adversos , Vacinação
9.
Travel Med Infect Dis ; 25: 50-57, 2018 Sep - Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29763669

RESUMO

BACKGROUND: Immunocompromised travellers (ICTs) are at increased risk of travel-related health problems. Therefore, they are advised to attend specialised pre-travel clinics for advice on vaccination, malaria chemoprophylaxis and on-demand antibiotics. However, studies yield conflicting data regarding travel-related health problems encountered by ICTs; questioning the rationale for certain advices, and particularly the advice of on-demand antibiotics. OBJECTIVE: To evaluate self-reported travel-related health problems, antibiotic use, medical visits and risk behaviours in ICTs and controls. METHODS: We conducted a questionnaire-based observational study with pilot character. We recruited participants from a (medical) pre-travel clinic. Telephone interviews were conducted 2-4 weeks post-travelling, applying a structured questionnaire. RESULTS: We included 30 ICTs and 30 controls. More ICTs than controls reported travel-related health problems, antibiotic use and medical visits, although not statistically significant. Travellers' diarrhoea appeared to be more severe in ICTs. Furthermore one ICT was hospitalized post-travel due to pneumonia. Of ICTs, 2/30 (7%) used on demand antibiotics while not indicated (according to the protocol of the Dutch national coordinating centre for travel advice or prescribed by a physician). Reversely, 6/30 (20%) did not use on demand antibiotics while actually indicated according to this protocol. DISCUSSION: Our findings substantiate the recommendation of on demand antibiotics. However, ICTs did often not use on demand antibiotics correctly; they therefore need very careful instructions.


Assuntos
Hospedeiro Imunocomprometido , Doença Relacionada a Viagens , Viagem , Adulto , Antibacterianos/administração & dosagem , Coleta de Dados , Diarreia/prevenção & controle , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários , Vacinação
11.
PLoS Negl Trop Dis ; 12(4): e0006273, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29649298

RESUMO

OVERVIEW: We describe the first case of a cutaneous ulcer caused by Haemophilus ducreyi imported from Indonesia to the Netherlands. Skin infections caused by H. ducreyi are uncommon in travellers and have been described in just a few case reports and were all contracted on the Pacific Islands. THE CASE: A 22-year-old healthy male visited the Center of Tropical Medicine and Travel Medicine in February 2017 with a cutaneous ulcer of the right lateral malleolus 4 weeks after returning from Indonesia (Seram and Ambon Islands). He had noticed a small skin abrasion on the right ankle after slipping on a rock during a jungle trip on Seram Island. Back in the Netherlands, a painful ulcer developed at the same body location, and despite treatment with flucloxacillin, his complaints worsened. A swab that was taken for culture showed growth of small grey colonies that were characterised as H. ducreyi with matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) mass spectrometry. Treatment with ciprofloxacin for the diagnosis of H. ducreyi cutaneous ulcer was started, and the ulcer clearly diminished, leaving only a small healing ulcer. DISCUSSION: H. ducreyi is normally the causative agent of genital ulcers but is increasingly recognised as a cause of chronic skin ulcers, e.g., in Papua New Guinea. In our patient, the infection was very likely contracted in the Maluku province of Indonesia and imported into the Netherlands. No reports of infection with H. ducreyi from Indonesia could be found in literature, but this case indicates that H. ducreyi is present in at least one of the northeastern islands of Indonesia, which is important for local healthcare. Additionally, it illustrates the role of this agent as a cause of cutaneous ulcers in previously healthy travellers.


Assuntos
Cancroide/microbiologia , Haemophilus ducreyi/isolamento & purificação , Úlcera Cutânea/microbiologia , Viagem , Cancroide/tratamento farmacológico , Ciprofloxacino/uso terapêutico , Humanos , Indonésia , Masculino , Países Baixos , Úlcera Cutânea/tratamento farmacológico , Adulto Jovem
12.
J Allergy Clin Immunol ; 142(4): 1285-1296, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29477724

RESUMO

BACKGROUND: The genetic cause of primary immunodeficiency disease (PID) carries prognostic information. OBJECTIVE: We conducted a whole-genome sequencing study assessing a large proportion of the NIHR BioResource-Rare Diseases cohort. METHODS: In the predominantly European study population of principally sporadic unrelated PID cases (n = 846), a novel Bayesian method identified nuclear factor κB subunit 1 (NFKB1) as one of the genes most strongly associated with PID, and the association was explained by 16 novel heterozygous truncating, missense, and gene deletion variants. This accounted for 4% of common variable immunodeficiency (CVID) cases (n = 390) in the cohort. Amino acid substitutions predicted to be pathogenic were assessed by means of analysis of structural protein data. Immunophenotyping, immunoblotting, and ex vivo stimulation of lymphocytes determined the functional effects of these variants. Detailed clinical and pedigree information was collected for genotype-phenotype cosegregation analyses. RESULTS: Both sporadic and familial cases demonstrated evidence of the noninfective complications of CVID, including massive lymphadenopathy (24%), unexplained splenomegaly (48%), and autoimmune disease (48%), features prior studies correlated with worse clinical prognosis. Although partial penetrance of clinical symptoms was noted in certain pedigrees, all carriers have a deficiency in B-lymphocyte differentiation. Detailed assessment of B-lymphocyte numbers, phenotype, and function identifies the presence of an increased CD21low B-cell population. Combined with identification of the disease-causing variant, this distinguishes between healthy subjects, asymptomatic carriers, and clinically affected cases. CONCLUSION: We show that heterozygous loss-of-function variants in NFKB1 are the most common known monogenic cause of CVID, which results in a temporally progressive defect in the formation of immunoglobulin-producing B cells.

15.
Lancet HIV ; 4(11): e522-e528, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28919303

RESUMO

BACKGROUND: Pre-exposure prophylaxis (PrEP) with emtricitabine and tenofovir disoproxil fumarate is highly effective against acquisition of HIV infection, and only two cases of infection with a multidrug-resistant virus have been reported under adequate long-term adherence, as evidenced by tenofovir diphosphate concentrations in dried blood spots. We report a case of wild-type HIV-1 infection despite consistent use of emtricitabine and tenofovir disoproxil fumarate. METHODS: The patient participated in the Amsterdam PrEP project, a demonstration project of daily and event-driven PrEP. We did extensive testing for HIV, including plasma HIV RNA and nested PCR on bulk peripheral blood mononuclear cells (PBMCs) and sigmoid biopsies after seroconversion. FINDINGS: A 50-year-old man who has sex with men and had been on daily emtricitabine and tenofovir disoproxil fumarate for 8 months presented with fever, urinary tract infection caused by Escherichia coli, anal lymphogranuloma venereum infection, and a positive fourth-generation HIV test. We found an atypical seroconversion pattern, with initially only gp160 antibodies detected in the western blot. HIV RNA could not be detected in plasma, and nested PCR for HIV RNA and DNA on bulk PBMCs and sigmoid biopsies were negative. PrEP was discontinued; 3 weeks later HIV RNA was detected in plasma. No drug-resistant mutations were detected. Tenofovir diphosphate concentrations in dried blood spots were stable and high. INTERPRETATION: To our knowledge, this is the first detailed case report suggesting wild-type HIV-1 infection despite good adherence, evidenced by repeatedly high concentrations of tenofovir diphosphate in dried blood spots. PrEP providers need to be aware that infection can occur despite good adherence. Regular HIV testing and awareness of atypical patterns of seroconversion is highly recommended. FUNDING: ZonMw, National Institute for Public Health and the Environment, Internal GGD research funds, Aidsfonds, Stichting AmsterdamDiner Foundation, Gilead Sciences, Janssen Pharmaceutica, M A C AIDS Fund, and ViiV Healthcare.


Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , HIV-1 , Organofosfatos/sangue , Profilaxia Pré-Exposição , Adenina/administração & dosagem , Adenina/efeitos adversos , Adenina/sangue , Adenina/uso terapêutico , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/sangue , Fármacos Anti-HIV/uso terapêutico , Emtricitabina/administração & dosagem , Emtricitabina/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/microbiologia , Infecções por HIV/prevenção & controle , Soropositividade para HIV/diagnóstico , HIV-1/efeitos dos fármacos , HIV-1/genética , Homossexualidade Masculina , Humanos , Linfogranuloma Venéreo/diagnóstico , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Organofosfatos/administração & dosagem , Organofosfatos/efeitos adversos , Organofosfatos/uso terapêutico , RNA Viral/sangue , Tenofovir/administração & dosagem , Tenofovir/efeitos adversos , Tenofovir/uso terapêutico , Pessoas Transgênero , Infecções Urinárias/diagnóstico , Infecções Urinárias/microbiologia
16.
Travel Med Infect Dis ; 19: 37-48, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28712659

RESUMO

BACKGROUND: Immunocompromised and chronically ill travellers (ICCITs) are susceptible to travel related diseases. In ICCITs, pre-travel care regarding vaccinations and prophylactics is complex. We evaluated the protection level by preventive measures in ICCITs by analysing rates of vaccination protection, antibody titres, and the prescription of standby antibiotics. METHODS: We analysed, and reported according to STROBE guidelines, pre-travel care data for ICCITs visiting the medical pre-travel clinic at the Academic Medical Centre, The Netherlands from 2011 to 2016. RESULTS: We analysed 2104 visits of 1826 ICCITs. Mean age was 46.6 years and mean travel duration 34.5 days. ICCITs on immunosuppressive treatment (29.7%), HIV (17.2%) or diabetes mellitus (10.2%) comprised the largest groups. Most frequently visited countries were Suriname, Indonesia, and Ghana. Most vaccination rates were >90%. Of travellers in high need of hepatitis A and B protection, 56.6 and 75.7%, underwent titre assessments, respectively. Of ICCITs with a respective indication, 50.6% received a prescription for standby antibiotics. CONCLUSION: Vaccination rates in our study population were overall comparable to those of healthy travellers studied previously in our centre. However, regarding antibody titre assessments and prescription of standby antibiotics, this study demonstrates that uniform pre-travel guidelines for ICCITs are highly needed.


Assuntos
Hospedeiro Imunocomprometido , Medicina de Viagem/normas , Doença Relacionada a Viagens , Antibioticoprofilaxia , Anticorpos/sangue , Doença Crônica , Humanos , Países Baixos , Estudos Retrospectivos , Medicina de Viagem/estatística & dados numéricos , Vacinação
17.
BMC Infect Dis ; 17(1): 425, 2017 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-28615005

RESUMO

BACKGROUND: Early treatment of acute HIV-1 infection (AHI) is beneficial for patients and could reduce onward transmission. However, guidelines on whom to test for AHI with HIV-1 RNA testing are lacking. METHODS: A risk score for possible AHI based on literature and expert opinion - including symptoms associated with AHI and early HIV-1 - was evaluated using data from the Amsterdam Cohort Studies among men who have sex with men (MSM). Subsequently, we optimized the risk score by constructing two multivariable logistic regression models: one including only symptoms and one combining symptoms with known risk factors for HIV-1 seroconversion, using generalized estimating equations. Several risk scores were generated from these models and the optimal risk score was validated using data from the Multicenter AIDS Cohort Study. RESULTS: Using data from 1562 MSM with 175 HIV-1 seroconversion visits and 17,271 seronegative visits in the Amsterdam Cohort Studies, the optimal risk score included four symptoms (oral thrush, fever, lymphadenopathy, weight loss) and three risk factors (self-reported gonorrhea, receptive condomless anal intercourse, more than five sexual partners, all in the preceding six months) and yielded an AUC of 0.82. Sensitivity was 76.3% and specificity 76.3%. Validation in the Multicenter AIDS Cohort Study resulted in an AUC of 0.78, sensitivity of 56.2% and specificity of 88.8%. CONCLUSIONS: The optimal risk score had good overall performance in the Amsterdam Cohort Studies and performed comparable (but showed lower sensitivity) in the validation study. Screening for AHI with four symptoms and three risk factors would increase the efficiency of AHI testing and potentially enhance early diagnosis and immediate treatment.


Assuntos
Infecções por HIV/diagnóstico , Homossexualidade Masculina , Medição de Risco/métodos , Adulto , Estudos de Coortes , Gonorreia , HIV-1/patogenicidade , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Fatores de Risco , Comportamento Sexual , Parceiros Sexuais
18.
PLoS One ; 12(3): e0173577, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28296911

RESUMO

BACKGROUND: Neutralizing antibodies develop in natural HIV-1 infection. Their development often takes several years and may rely on chronic virus exposure. At the same time recent studies show that treatment early in infection may provide opportunities for immune preservation. However, it is unknown how intermittent treatment in early infection affects development of the humoral immune response over time. We investigate the effect of cART in early HIV infection on the properties of the memory B cell compartment following 6 months of cART or in the absence of treatment. The patients included participated in the Primo-SHM trial where patients with an early HIV-1 infection were randomized to no treatment or treatment for 24 or 60 weeks. METHODS: Primo-SHM trial patients selected for the present study were untreated (n = 23) or treated for 24 weeks (n = 24). Here we investigate memory B cell properties at viral set-point and at a late time point (respectively median 54 and 73 weeks) before (re)-initiation of treatment. RESULTS: At viral set-point, the memory B cell compartment in treated patients demonstrated significantly lower fractions of antigen-primed, activated, memory B cells (p = 0.006). In contrast to untreated patients, in treated patients the humoral HIV-specific response reached a set point over time. At a transcriptional level, sets of genes that showed enhanced expression in memory B cells at viral setpoint in untreated patients, conversely showed rapid increase of expression of the same genes in treated patients at the late time point. CONCLUSION: These data suggest that, although the memory B cell compartment is phenotypically preserved until viral setpoint after treatment interruption, the development of the HIV-specific antibody response may benefit from exposure to HIV. The effect of viral exposure on B cell properties is also reflected by longitudinal changes in transcriptional profile in memory B cells over time in early treated patients.


Assuntos
Linfócitos B/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Adulto , Citometria de Fluxo , Perfilação da Expressão Gênica , Humanos , Memória Imunológica , Pessoa de Meia-Idade , Transcrição Genética
19.
PLoS One ; 11(11): e0166121, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27832107

RESUMO

OBJECTIVES: Better insights into health care utilization and out-of-pocket expenditures for non-communicable chronic diseases (NCCD) are needed to develop accessible health care and limit the increasing financial burden of NCCDs in Sub-Saharan Africa. METHODS: A household survey was conducted in rural Kwara State, Nigeria, among 5,761 individuals. Data were obtained using biomedical and socio-economic questionnaires. Health care utilization, NCCD-related health expenditures and distances to health care providers were compared by sex and by wealth quintile, and a Heckman regression model was used to estimate health expenditures taking selection bias in health care utilization into account. RESULTS: The prevalence of NCCDs in our sample was 6.2%. NCCD-affected individuals from the wealthiest quintile utilized formal health care nearly twice as often as those from the lowest quintile (87.8% vs 46.2%, p = 0.002). Women reported foregone formal care more often than men (43.5% vs. 27.0%, p = 0.058). Health expenditures relative to annual consumption of the poorest quintile exceeded those of the highest quintile 2.2-fold, and the poorest quintile exhibited a higher rate of catastrophic health spending (10.8% among NCCD-affected households) than the three upper quintiles (4.2% to 6.7%). Long travel distances to the nearest provider, highest for the poorest quintile, were a significant deterrent to seeking care. Using distance to the nearest facility as instrument to account for selection into health care utilization, we estimated out-of-pocket health care expenditures for NCCDs to be significantly higher in the lowest wealth quintile compared to the three upper quintiles. CONCLUSIONS: Facing potentially high health care costs and poor accessibility of health care facilities, many individuals suffering from NCCDs-particularly women and the poor-forego formal care, thereby increasing the risk of more severe illness in the future. When seeking care, the poor spend less on treatment than the rich, suggestive of lower quality care, while their expenditures represent a higher share of their annual household consumption. This calls for targeted interventions that enhance health care accessibility and provide financial protection from the consequences of NCCDs, especially for vulnerable populations.


Assuntos
Doença Crônica/economia , Efeitos Psicossociais da Doença , Financiamento Pessoal/economia , Gastos em Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , População Rural/estatística & dados numéricos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Doença Crônica/epidemiologia , Estudos Transversais , Características da Família , Feminino , Acesso aos Serviços de Saúde/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Nigéria/epidemiologia , Prevalência , Inquéritos e Questionários , Adulto Jovem
20.
PLoS One ; 11(3): e0149871, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26977808

RESUMO

INTRODUCTION: Prompted by recent amendments of Yellow Fever (YF) vaccination guidelines from boost to single vaccination strategy and the paucity of clinical data to support this adjustment, we used the profile of the YF-specific CD8+ T-cell subset profiles after primary vaccination and neutralizing antibodies as a proxy for potentially longer lasting immunity. METHODS AND FINDINGS: PBMCs and serum were collected in six individuals on days 0, 3, 5, 12, 28 and 180, and in 99 individuals >10 years after YF-vaccination. Phenotypic characteristics of YF- tetramer+ CD8+ T-cells were determined using class I tetramers. Antibody responses were measured using a standardized plaque reduction neutralization test (PRNT). Also, characteristics of YF-tetramer positive CD8+ T-cells were compared between individuals who had received a primary- and a booster vaccination. YF-tetramer+ CD8+ T-cells were detectable on day 12 (median tetramer+ cells as percentage of CD8+ T-cells 0.2%, range 0.07-3.1%). On day 180, these cells were still present (median 0.06%, range 0.02-0.78%). The phenotype of YF-tetramer positive CD8+ T-cells shifted from acute phase effector cells on day 12, to late differentiated or effector memory phenotype (CD45RA-/+CD27-) on day 28. Two subsets of YF-tetramer positive T-cells (CD45RA+CD27- and CD45RA+CD27+) persisted until day 180. Within all phenotypic subsets, the T-bet: Eomes ratio tended to be high on day 28 after vaccination and shifted towards predominant Eomes expression on day 180 (median 6.0 (day 28) vs. 2.2 (day 180) p = 0.0625), suggestive of imprinting compatible with long-lived memory properties. YF-tetramer positive CD8+ T-cells were detectable up to 18 years post vaccination, YF-specific antibodies were detectable up to 40 years after single vaccination. Booster vaccination did not increase titers of YF-specific antibodies (mean 12.5 vs. 13.1, p = 0.583), nor induce frequencies or alter phenotypes of YF-tetramer+ CD8+ T-cells. CONCLUSION: The presence of a functionally competent YF-specific memory T-cell pool 18 years and sufficient titers of neutralizing antibodies 35-40 years after first vaccination suggest that single vaccination may be sufficient to provide long-term immunity.


Assuntos
Anticorpos Neutralizantes/imunologia , Linfócitos T CD8-Positivos/imunologia , Vacina contra Febre Amarela/administração & dosagem , Proliferação de Células , Humanos , Testes de Neutralização , Estudos Prospectivos , Ensaio de Placa Viral , Vacina contra Febre Amarela/imunologia
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