RESUMO
In Indonesia, BCG vaccine protection against Mycobacterium tuberculosis infection decreased with increasing exposure to the pathogen. We aimed to validate these findings in Africa. Poisson regression was used to estimate BCG protection, stratified by pathogen exposure using an exposure score, against enzyme-linked immunospot assay conversion at 3 months in 220 Gambian case contacts. Although the interaction between BCG and exposure was not significant (P = .13), BCG protection was strongest in the lowest-exposure tertile (relative risk, 0.35 [95% confidence interval, .15-.82; P = .02] vs 0.50 [.30-.83; P = .008] and 0.71 (.45-1.13; P = .1] for the middle and highest-exposure tertiles, respectively. These results are consistent with those from Indonesia.
Assuntos
Vacina BCG/imunologia , Tuberculose Pulmonar/prevenção & controle , Gâmbia/epidemiologia , Humanos , Risco , Tuberculose Pulmonar/epidemiologiaRESUMO
BACKGROUND: Early clearance of Mycobacterium tuberculosis is the eradication of infection before an adaptive immune response develops. We aimed to identify host factors associated with early clearance. METHODS: Indonesian household contacts patients with smear-positive tuberculosis (TB) had an interferon-γ release assay (IGRA) at baseline and 14 weeks later. Early clearance was defined as a persistently negative IGRA. Contact characteristics, exposure, and disease phenotype were assessed for association with a positive IGRA at each time point. RESULTS: Of 1347 contacts of 462 TB cases, 780 (57.9%) were IGRA positive and 490 (36.3%) were IGRA negative. After 14 weeks, 116 of 445 (26.1%) initially negative contacts were IGRA converters; 317 (71.2%) remained persistently negative. BCG vaccination reduced the risk of a positive baseline IGRA (relative risk [RR], 0.89 [95% confidence interval {CI} .83-.97]; P = .01), and strongly reduced the risk of IGRA conversion (RR, 0.56 [95% CI, .40-.77]; P < .001). BCG protection decreased with increasing exposure (P = .05) and increasing age (P = .004). Risk of IGRA conversion was positively associated with hemoglobin concentration (P = .04). CONCLUSIONS: A quarter of household TB case contacts were early clearers. Protection against M. tuberculosis infection was strongly associated with BCG vaccination. Lower protection from BCG with increasing M. tuberculosis exposure and age can inform vaccine development.
Assuntos
Mycobacterium tuberculosis/imunologia , Tuberculose Pulmonar/imunologia , Adulto , Vacina BCG/imunologia , Estudos de Coortes , Testes Diagnósticos de Rotina/métodos , Feminino , Humanos , Indonésia , Testes de Liberação de Interferon-gama/métodos , Masculino , Teste Tuberculínico/métodosRESUMO
BACKGROUND: A proportion of tuberculosis (TB) case contacts do not become infected, even when heavily exposed. We studied the innate immune responses of TB case contacts to understand their role in protection against infection with Mycobacterium tuberculosis, termed "early clearance." METHODS: Indonesian household contacts of TB cases were tested for interferon-γ release assay (IGRA) conversion between baseline and 14 weeks post recruitment. Blood cell populations and ex vivo innate whole blood cytokine responses were measured at baseline and, in a subgroup, flow cytometry was performed at weeks 2 and 14. Immunological characteristics were measured for early clearers, defined as a persistently negative IGRA at 3 months, and converters, whose IGRA converted from negative to positive. RESULTS: Among 1347 case contacts, 317 were early clearers and 116 were converters. Flow cytometry showed a resolving innate cellular response from 2 to 14 weeks in persistently IGRA-negative contacts but not converters. There were no differences in cytokine responses to mycobacterial stimuli, but compared to converters, persistently IGRA-negative contacts produced more proinflammatory cytokines following heterologous stimulation with Escherichia coli and Streptococcus pneumoniae. CONCLUSIONS: Early clearance of M. tuberculosis is associated with enhanced heterologous innate immune responses similar to those activated during induction of trained immunity.
Assuntos
Imunidade Inata/imunologia , Mycobacterium tuberculosis/imunologia , Tuberculose/imunologia , Adulto , Testes Diagnósticos de Rotina/métodos , Feminino , Citometria de Fluxo/métodos , Humanos , Indonésia , Testes de Liberação de Interferon-gama/métodos , Masculino , Pessoa de Meia-Idade , Tuberculose/microbiologiaRESUMO
Tuberculosis (TB) is a serious infectious disease caused by infection with Mycobacterium tuberculosis, and kills more people annually than any other single infectious agent. Although a vaccine is available, it is only moderately effective and an improved vaccine is urgently needed. The ability to develop a more effective vaccine has been thwarted by a lack of understanding of the mechanism of vaccine-induced immune protection. Over recent decades, many novel TB vaccines have been developed and almost all have aimed to generate memory CD4 T cells. In this review, we critically evaluate evidence in the literature that supports the contention that memory CD4 T cells are the prime mediators of vaccine-induced protection against TB. Because of the lack of robust evidence supporting memory CD4 T cells in this role, the potential for B-cell antibody and "trained" innate cells as alternative mediators of protective immunity is explored.
Assuntos
Interações Hospedeiro-Patógeno/imunologia , Memória Imunológica , Mycobacterium tuberculosis/imunologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Tuberculose/imunologia , Tuberculose/microbiologia , Imunidade Adaptativa , Animais , Anticorpos Antibacterianos/imunologia , Especificidade de Anticorpos/imunologia , Antígenos de Bactérias/imunologia , Vacina BCG/administração & dosagem , Vacina BCG/efeitos adversos , Vacina BCG/imunologia , Glicosilação , Humanos , Imunidade Inata , Isotipos de Imunoglobulinas/imunologia , Isotipos de Imunoglobulinas/metabolismo , Avaliação de Resultados em Cuidados de Saúde , Subpopulações de Linfócitos T/citologia , Tuberculose/prevenção & controle , Vacinas contra a Tuberculose/administração & dosagem , Vacinas contra a Tuberculose/efeitos adversos , Vacinas contra a Tuberculose/imunologia , Vacinação/efeitos adversos , Vacinação/métodosRESUMO
OBJECTIVES: Knowledge of the patterns of antibiotic consumption within a population provides valuable information on when, where and to whom antibiotics are prescribed. Such knowledge is critical in informing possible public health interventions to reduce inappropriate antibiotic use. The aims of this study were to (i) determine national patterns of antibiotic consumption, including assessment of seasonal variation in prescribing, and (ii) explore potential associations between antibiotic consumption and patient characteristics, such as age, sex and ethnicity. METHODS: Data on all subsidized antibiotic dispensing in New Zealand between 1 January 2006 and 31 December 2014 were obtained and stratified according to age, sex and ethnicity. Antibiotic dispensing was expressed as the number of DDDs per 1000 population per day (DID). RESULTS: Total antibiotic consumption in New Zealand increased by 49% from 17.3 DID in 2006 to 25.8 DID in 2014. The increase in antibiotic consumption occurred in all ages and amongst all ethnic groups. The use of extended-spectrum penicillins, which almost doubled in the study period, made a major contribution to the overall increase and was highest in young children and in Pacific peoples. Consumption of quinolones increased early in the study period and then declined from 2011 onwards. CONCLUSIONS: Future work should focus on identifying the appropriateness of antibiotic prescribing, particularly for penicillin prescribing in Pacific peoples and children, and on both reducing unwarranted antibiotic use and improving antibiotic selection when therapy is indicated.
Assuntos
Antibacterianos/uso terapêutico , Uso de Medicamentos , Pacientes Ambulatoriais , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Demografia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Adulto JovemAssuntos
Vacina BCG/administração & dosagem , Busca de Comunicante/estatística & dados numéricos , Variação Genética , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Tuberculose/imunologia , Tuberculose/prevenção & controle , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Mycobacterium tuberculosis/imunologia , Adulto JovemAssuntos
COVID-19/epidemiologia , Planejamento em Desastres/organização & administração , Necessidades e Demandas de Serviços de Saúde/organização & administração , Controle de Infecções/organização & administração , COVID-19/prevenção & controle , Defesa Civil/organização & administração , Transmissão de Doença Infecciosa/prevenção & controle , Humanos , Nova Zelândia , Formulação de Políticas , Saúde Pública , Fatores de Risco , SARS-CoV-2RESUMO
Early clearance (EC) is the successful eradication of inhaled Mycobacterium tuberculosis before an adaptive immune response develops. Evidence for EC comes from case contact studies that consistently show that a proportion of heavily exposed individuals do not develop M. tuberculosis infection. Further support for the existence of this phenotype comes from genetic loci associated with tuberculin reactivity. In this review we discuss aspects of the innate response that may underpin EC and hypotheses that can be tested through field laboratory link studies in M. tuberculosis case contacts. Specifically, we consider mechanisms whereby alveolar macrophages recognize and kill intracellular M. tuberculosis, and how other cell types, such as neutrophils, natural killer T cells, mucosa-associated invariant T cells and cd T cells may assist. How EC may be impaired by HIV infection or vitamin D deficiency is also explored. As EC is a form of protective immunity, further study may advance the development of vaccines and immunotherapies to prevent M. tuberculosis infection.
Assuntos
Imunidade Inata , Mycobacterium tuberculosis/imunologia , Tuberculose/prevenção & controle , Animais , Carga Bacteriana , Coinfecção , Citocinas/metabolismo , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/microbiologia , Viabilidade Microbiana , Fagocitose , Fenótipo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/microbiologia , Tuberculose/imunologia , Tuberculose/microbiologia , Vacinas contra a Tuberculose/imunologia , Deficiência de Vitamina D/imunologiaRESUMO
BACKGROUND: Although the burden of infectious diseases seems to be decreasing in developed countries, few national studies have measured the total incidence of these diseases. We aimed to develop and apply a robust systematic method for monitoring the epidemiology of serious infectious diseases. METHODS: We did a national epidemiological study with all hospital admissions for infectious and non-infectious diseases in New Zealand from 1989 to 2008, to investigate trends in incidence and distribution by ethnic group and socioeconomic status. We extended a recoding system based on the ninth revision of international classification of diseases (ICD-9) to the tenth revision (ICD-10), and applied this to data for hospital admissions from the New Zealand Ministry of Health, National Minimum Dataset. We filtered results to account for changes in health-care practices over time. Acute overnight admissions were the events of interest. FINDINGS: Infectious diseases made the largest contribution to hospital admissions of any cause. Their contribution increased from 20·5% of acute admissions in 1989-93, to 26·6% in 2004-08. We noted clear ethnic and social inequalities in infectious disease risk. In 2004-08, the age-standardised rate ratio was 2·15 (95% CI 2·14-2·16) for Maori (indigenous New Zealanders) and 2·35 (2·34-2·37) for Pacific peoples compared with the European and other group. The ratio was 2·81 (2·80-2·83) for the most socioeconomically deprived quintile compared with the least deprived quintile. These inequalities have increased substantially in the past 20 years, particularly for Maori and Pacific peoples in the most deprived quintile. INTERPRETATION: These findings support the need for stronger prevention efforts for infectious diseases, and reinforce the need to reduce ethnic and social inequalities and to address disparities in broad social determinants such as income levels, housing conditions, and access to health services. Our method could be adapted for infectious disease surveillance in other countries. FUNDING: New Zealand Ministry of Health, New Zealand Health Research Council.
Assuntos
Doenças Transmissíveis/epidemiologia , Hospitalização/estatística & dados numéricos , Doenças Transmissíveis/etnologia , Acessibilidade aos Serviços de Saúde , Hospitalização/tendências , Humanos , Incidência , Havaiano Nativo ou Outro Ilhéu do Pacífico/estatística & dados numéricos , Nova Zelândia/epidemiologia , Classe SocialRESUMO
BACKGROUND: The increasing frequency and intensity of dengue outbreaks in endemic and non-endemic countries requires a rational, evidence based response. To this end, we aimed to collate the experiences of a number of affected countries, identify strengths and limitations in dengue surveillance, outbreak preparedness, detection and response and contribute towards the development of a model contingency plan adaptable to country needs. METHODS: The study was undertaken in five Latin American (Brazil, Colombia, Dominican Republic, Mexico, Peru) and five in Asian countries (Indonesia, Malaysia, Maldives, Sri Lanka, Vietnam). A mixed-methods approach was used which included document analysis, key informant interviews, focus-group discussions, secondary data analysis and consensus building by an international dengue expert meeting organised by the World Health Organization, Special Program for Research and Training in Tropical Diseases (WHO-TDR). RESULTS: Country information on dengue is based on compulsory notification and reporting ("passive surveillance"), with laboratory confirmation (in all participating Latin American countries and some Asian countries) or by using a clinical syndromic definition. Seven countries additionally had sentinel sites with active dengue reporting, some also had virological surveillance. Six had agreed a formal definition of a dengue outbreak separate to seasonal variation in case numbers. Countries collected data on a range of warning signs that may identify outbreaks early, but none had developed a systematic approach to identifying and responding to the early stages of an outbreak. Outbreak response plans varied in quality, particularly regarding the early response. The surge capacity of hospitals with recent dengue outbreaks varied; those that could mobilise additional staff, beds, laboratory support and resources coped best in comparison to those improvising a coping strategy during the outbreak. Hospital outbreak management plans were present in 9/22 participating hospitals in Latin-America and 8/20 participating hospitals in Asia. CONCLUSIONS: Considerable variation between countries was observed with regard to surveillance, outbreak detection, and response. Through discussion at the expert meeting, suggestions were made for the development of a more standardised approach in the form of a model contingency plan, with agreed outbreak definitions and country-specific risk assessment schemes to initiate early response activities according to the outbreak phase. This would also allow greater cross-country sharing of ideas.
Assuntos
Dengue/epidemiologia , Surtos de Doenças , Ásia/epidemiologia , Medicina Baseada em Evidências , Humanos , América Latina/epidemiologia , Modelos Estatísticos , Vigilância da População/métodos , Medição de RiscoRESUMO
OBJECTIVES: Recently published guidelines on the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections recommend against administering vancomycin by continuous infusion on the basis of insufficient studies comparing this with intermittent infusion. We compared outcomes of patients treated with continuous infusion and intermittent infusion of vancomycin. PATIENTS AND METHODS: Data for outpatients treated with continuous infusion and intermittent infusion of vancomycin were compared utilizing rates of clinical failure defined as the need for unplanned re-admission, change of antibiotics or extension of therapy. RESULTS: A total of 244 patients met the inclusion criteria, with 188 receiving continuous infusion and 56 intermittent infusion of vancomycin. The endpoint occurred in 21.3% and 30.4% of those receiving continuous infusion and intermittent infusion, respectively (relative risk 0.701, 95% CI 0.432-1.136, Pâ=â0.159). Patient characteristics differed slightly between the two groups; however, logistic regression to adjust for differences in age, co-morbidity, subtherapeutic levels and prosthetic devices did not substantially alter this result. CONCLUSIONS: No difference in rates of clinical failure of continuous infusion and intermittent infusion of vancomycin was observed in this outpatient cohort.
Assuntos
Assistência Ambulatorial/métodos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/tratamento farmacológico , Vancomicina/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Infecções Estafilocócicas/microbiologia , Falha de Tratamento , Adulto JovemRESUMO
Background: Matrix metalloproteinase (MMP) activity has an important role in lung cavitary formation occurred in pulmonary tuberculosis (TB). Low number and viability of CD4 + T-lymphocytes in patients with TB/HIV co-infection leads to impaired neutrophils production, causing further impaired MMPs production. Objective: To explore association of neutrophils and lymphocytes count to MMP-8 and MMP-9 among pulmonary TB patients with cavitary lesion and HIV co-infection. Methods: We conducted a cross-sectional study using a purposive sampling technique among patients with non-cavitary TB (n = 50), cavitary TB (n = 50) and TB/HIV (n = 27). Complete blood count was examined, including neutrophils and lymphocytes count. MMP-8 and MMP-9 were measured from plasma samples using ELISA method. Statistical analysis was conducted to determine the relation between neutrophils, lymphocytes and MMPs. Result: MMP-8 and MMP-9 were positively correlated with neutrophils, but not to lymphocytes in all groups. Neutrophils, lymphocytes, and MMP-9 were significantly lower in TB/HIV co-infection, whereas MMP-8 was higher compared to new pulmonary TB. Interestingly, in cavitary TB, low lymphocytes were significantly correlated with higher level of MMP-8 and larger extent of lung affected. Conclusion: MMP-8 and MMP-9 are associated with neutrophil count, suggesting that neutrophils contribute significantly to their secretion. MMP-8 is significantly higher in TB/HIV co-infection and extent of lung damage in cavitary TB with lower lymphocyte count. This study suggests that lower lymphocyte level is related to higher neutrophil orchestrated inflammation, leading to tissue destruction.
RESUMO
In the battle for control of coronavirus disease-19 (COVID-19), we have few weapons. Yet contact tracing is among the most powerful. Contact tracing is the process by which public-health officials identify people, or contacts, who have been exposed to a person infected with a pathogen or another hazard. For all its power, though, contact tracing yields a variable level of success. One reason is that contact tracing's ability to break the chain of transmission is only as effective as the proportion of contacts who are actually traced. In part, this proportion turns on the quality of the information that infected people provide, which makes human memory a crucial part of the efficacy of contact tracing. Yet the fallibilities of memory, and the challenges associated with gathering reliable information from memory, have been grossly underestimated by those charged with gathering it. We review the research on witnesses and investigative interviewing, identifying interrelated challenges that parallel those in contact tracing, as well as approaches for addressing those challenges.
Assuntos
COVID-19/diagnóstico , Busca de Comunicante/métodos , Memória , Saúde Pública/métodos , Humanos , SARS-CoV-2RESUMO
Community transmission of influenza A pandemic (H1N1) 2009 was followed by high rates of hospital admissions in the Wellington region of New Zealand, particularly among Maori and Pacific Islanders. These findings may help health authorities anticipate the effects of pandemic (H1N1) 2009 in other communities.
Assuntos
Vírus da Influenza A Subtipo H1N1 , Influenza Humana/epidemiologia , Havaiano Nativo ou Outro Ilhéu do Pacífico/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Surtos de Doenças/estatística & dados numéricos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Adulto JovemRESUMO
Rothia aeria is a recently described Gram-positive rod from the family Micrococcaceae. An elderly woman with rheumatoid arthritis and dental abscesses who was undergoing immunosuppression had R. aeria isolated from synovial fluid. This report characterizes this rare organism and contributes to the literature on its pathogenicity and likely oral source.
Assuntos
Infecções por Actinomycetales/diagnóstico , Bacteriemia/diagnóstico , Micrococcaceae/isolamento & purificação , Líquido Sinovial/microbiologia , Infecções por Actinomycetales/tratamento farmacológico , Infecções por Actinomycetales/microbiologia , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Artrite Reumatoide/complicações , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Cárie Dentária/complicações , Feminino , Humanos , Testes de Sensibilidade Microbiana , Micrococcaceae/efeitos dos fármacos , Micrococcaceae/genética , Técnicas de Amplificação de Ácido Nucleico , Fenótipo , RNA Ribossômico 16S/genética , Articulação do OmbroRESUMO
AIMS: We aimed to determine the effectiveness of surveillance using testing for SARS-CoV-2 to identify an outbreak arising from a single case of border control failure in a country that has eliminated community transmission of COVID-19: New Zealand. METHODS: A stochastic version of the SEIR model CovidSIM v1.1 designed specifically for COVID-19 was utilised. It was seeded with New Zealand population data and relevant parameters sourced from the New Zealand and international literature. RESULTS: For what we regard as the most plausible scenario with an effective reproduction number of 2.0, the results suggest that 95% of outbreaks from a single imported case would be detected in the period up to day 36 after introduction. At the time point of detection, there would be a median number of five infected cases in the community (95% range: 1-29). To achieve this level of detection, an ongoing programme of 5,580 tests per day (1,120 tests per million people per day) for the New Zealand population would be required. The vast majority of this testing (96%) would be of symptomatic cases in primary care settings and the rest in hospitals. CONCLUSIONS: This model-based analysis suggests that a surveillance system with a very high level of routine testing is probably required to detect an emerging or re-emerging SARS-CoV-2 outbreak within five weeks of a border control failure in a nation that had previously eliminated COVID-19. Nevertheless, there are plausible strategies to enhance testing yield and cost-effectiveness and potential supplementary surveillance systems such as the testing of town/city sewerage systems for the pandemic virus.
Assuntos
Simulação por Computador , Infecções por Coronavirus/epidemiologia , Monitoramento Epidemiológico , Pneumonia Viral/epidemiologia , Betacoronavirus , COVID-19 , Busca de Comunicante , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/transmissão , Hospitais , Humanos , Nova Zelândia/epidemiologia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/transmissão , Atenção Primária à Saúde , Quarentena , SARS-CoV-2RESUMO
BACKGROUND: OraQuick® is a rapid test with high specificity demonstrated in non-dengue endemic settings. However, reports of false positive OraQuick® results suggest poor specificity in the context of dengue fever. OBJECTIVES: To assess the specificity of OraQuick® for HIV-1/2 in patients with dengue fever. STUDY DESIGN: In a study performed across two Singapore hospitals, adult participants meeting WHO 2009 criteria for probable dengue (fever >37.5 °C plus two other clinical or haematological criteria) were identified at hospital outpatient clinics from April 2012 to July 2013. Eligible participants were asked for informed consent to complete a questionnaire on HIV risk factors, as well as HIV testing by OraQuick®, fourth-generation EIA and NAAT. Dengue testing was by Dengue Duo NS1Ag + Ab Combo kits. Confirmed dengue was defined as NS1-positive and probable dengue as IgM-positive. RESULTS: Of 152 eligible patients, 82 consented to inclusion in the study. Fifty-two of these had dengue; 43 confirmed and 9 probable cases. All patients with dengue had a negative OraQuick® result, negative EIA and undetectable HIV-1 RNA, corresponding to a specificity of 100 %. CONCLUSIONS: OraQuick® has high specificity in the context of dengue infection. It can be used to diagnose HIV-associated illness as a cause of fever in dengue endemic settings.
Assuntos
Vírus da Dengue/isolamento & purificação , Dengue/diagnóstico , Infecções por HIV/diagnóstico , HIV/isolamento & purificação , Sorodiagnóstico da AIDS , Adulto , Idoso , Dengue/epidemiologia , Feminino , HIV/imunologia , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Kit de Reagentes para Diagnóstico , Fatores de Risco , Sensibilidade e Especificidade , Singapura/epidemiologia , Inquéritos e QuestionáriosRESUMO
New Zealand could be the first country in the world to eliminate tuberculosis (TB). We propose a TB elimination strategy based on the eight-point World Health Organization (WHO) action framework for low incidence countries. Priority actions recommended by the WHO include 1) ensure political commitment, funding and stewardship for planning and essential services; 2) address the most vulnerable and hard-to-reach groups; 3) address special needs of migrants and cross-border issues; 4) identify active TB and undertake screening for latent tuberculosis infection (LTBI) in recent TB contacts and selected high-risk groups, and provide appropriate treatment; 5) optimise the prevention and care of drug-resistant TB; 6) ensure continued surveillance, programme monitoring and evaluation and case-based data management; 7) invest in research and new tools; and 8) support global TB prevention, care and control. In New Zealand, central government needs to take greater responsibility for TB policy and programme governance. Urgent action is required to prevent TB in higher risk groups including Maori communities, and to enable immigration screening to detect and treat LTBI. Clinical services need to be supported to implement new guidelines for LTBI that enable better targeting of screening and shorter, safer treatment regimens. Access to WHO recommended treatment regimens needs to be guaranteed for drug-resistant TB. Better use of existing data could better define priority areas for action and assist in the evaluation of current control activities. Access to GeneXpert® MTB-RIF near the point of care and whole genome sequencing nationally would greatly improve clinical and public health management through early identification of drug resistance and outbreaks. New Zealand already has a world-class TB research community that could be better deployed to assist high-incidence countries through research and training.
Assuntos
Erradicação de Doenças , Tuberculose/prevenção & controle , Humanos , Programas de Rastreamento , Havaiano Nativo ou Outro Ilhéu do Pacífico , Nova Zelândia , Saúde Pública , Vigilância em Saúde Pública , Tuberculose/epidemiologia , Tuberculose/transmissãoRESUMO
Studies in IL-32 transgenic mice and in vitro suggest that IL-32 may have protective effects against Mycobacterium tuberculosis, but so far there are barely any studies in humans. We studied the role of IL-32 and its splice variants in tuberculosis (TB) in vivo and in vitro. Blood transcriptional analysis showed lower total IL-32 mRNA levels in pulmonary TB patients compared to patients with latent TB infection and healthy controls. Also, among Indonesian household contacts who were heavily exposed to an infectious TB patient, IL-32 mRNA levels were higher among those who remained uninfected compared to those who became infected with M. tuberculosis. In peripheral blood mononuclear cells from healthy donors, we found that IL-32γ, the most potent isoform, was down-regulated upon M. tuberculosis stimulation. This decrease in IL-32γ was mirrored by an increase of another splice variant, IL-32ß. Also, a higher IL-32γ/IL-32ß ratio correlated with IFN-γ production, whereas a lower ratio correlated with production of IL-1Ra, IL-6, and IL-17. These data suggest that IL-32 contributes to protection against M. tuberculosis infection, and that this effect may depend on the relative abundance of different IL-32 isoforms.
Assuntos
Processamento Alternativo , Interleucina-17/metabolismo , Interleucinas/genética , Células Th1/imunologia , Células Th17/imunologia , Tuberculose/prevenção & controle , Citocinas , Humanos , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/microbiologia , Mycobacterium tuberculosis/fisiologia , Isoformas de Proteínas , Células Th1/metabolismo , Células Th17/metabolismo , Tuberculose/genética , Tuberculose/imunologia , Tuberculose/microbiologiaRESUMO
Immunopathology contributes to high mortality in tuberculous meningitis (TBM) but little is known about the blood and cerebrospinal fluid (CSF) immune response. We prospectively characterised the immune response of 160 TBM suspects in an Indonesian cohort, including 67 HIV-negative probable or definite TBM cases. TBM patients presented with severe disease and 38% died in 6 months. Blood from TBM patients analysed by flow cytometry showed lower αßT and γδT cells, NK cells and MAIT cells compared to 26 pulmonary tuberculosis patients (2.4-4-fold, all p < 0.05) and 27 healthy controls (2.7-7.6-fold, p < 0.001), but higher neutrophils and classical monocytes (2.3-3.0-fold, p < 0.001). CSF leukocyte activation was higher than in blood (1.8-9-fold). CSF of TBM patients showed a predominance of αßT and NK cells, associated with better survival. Cytokine production after ex-vivo stimulation of whole blood showed a much broader range in TBM compared to both control groups (p < 0.001). Among TBM patients, high ex-vivo production of TNF-α, IL-6 and IL-10 correlated with fever, lymphocyte count and monocyte HLA-DR expression (all p < 0.05). TBM patients show a strong myeloid blood response, with a broad variation in immune function. This may influence the response to adjuvant treatment and should be considered in future trials of host-directed therapy.