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Hospitalization criteria in imported falciparum malaria [correspondence]
The definitive version is available at www3.interscience.wiley.co
Tuberculous meningitis: does lowering the treatment threshold result in many more treated patients?
The definitive version is available at www3.interscience.wiley.comOBJECTIVE: To determine how many more patients would be treated when lowering the treatment threshold for tuberculous meningitis. METHODS: From 1989 to 2004 findings of patients with symptoms lasting more than 1 week and inflammatory changes of cerebrospinal fluid (CSF) were collected. Several models of latent class analysis were tested. Cumulative numbers of cases were plotted against different cut-offs for post-test probability. RESULTS: In a cohort of 232 patients the prevalence of tuberculous meningitis (TBM) was estimated at 79.8% (95% CI. 67,0-88,1); probabilities above 80% were reached in 73% of patients. Lowering this threshold from 80% to 20% would add 14% more patients to be treated, for a total of 87%. A further lowering of the threshold to 5% would imply 5% more patients to be treated, bringing the cumulative number to 92%. The difference of lowering the threshold from 80% to 5% was 19%. CONCLUSION: In this setting, at least 75% of patients showing suggestive symptoms for more than a week and CSF changes very probably had TBM. The number of patients that should be treated does not increase linearly when lowering the threshold
Efficient in vitro expansion of human immunodeficiency virus (HIV)-specific t-cell responses by gag mRNA-electroporated dendritic cells from treated and untreated HIV type 1-infected individuals
Developing an immunotherapy to keep human immunodeficiency virus type 1 (HIV-1) replication suppressed while discontinuing highly active antiretroviral therapy (HAART) is an important challenge. In the present work, we evaluated in vitro whether dendritic cells (DC) electroporated with gag mRNA can induce HIV-specific responses in T cells from chronically infected subjects. Monocyte-derived DC, from therapy-naïve and HAART-treated HIV-1-seropositive subjects, that were electroporated with consensus codon-optimized HxB2 gag mRNA efficiently expanded T cells, secreting gamma interferon (IFN-gamma) and interleukin 2 (IL-2), as well as other cytokines and perforin, upon restimulation with a pool of overlapping Gag peptides. The functional expansion levels after 1 week of stimulation were comparable in T cells from HAART-treated and treatment-naïve patients and involved both CD4(+) and CD8(+) T cells, with evidence of bifunctionality in T cells. Epitope mapping of p24 showed that stimulated T cells had a broadened response toward previously nondescribed epitopes. DC, from HAART-treated subjects, that were electroporated with autologous proviral gag mRNA equally efficiently expanded HIV-specific T cells. Regulatory T cells did not prevent the induction of effector T cells in this system, whereas the blocking of PD-L1 slightly increased the induction of T-cell responses. This paper shows that DC, loaded with consensus or autologous gag mRNA, expand HIV-specific T-cell responses in vitro
Infection à Mycobacterium ulcerans traitée par Rifater, Pyrazynamide, Myambutol associés à la chirurgie; à propos d'un cas avec un recul de six ans
The author reports a case of pleuritis associated with a large homolateral Buruli thorax ulcer in a nine-year old female patient, in the Democratic Republic of Congo. Smears on Ziehl-Neelsen revealed acid-alcohol-resistant bacilli. The pathological histology confirmed a Mycobacterium ulcerans infection (Buruli ulcer). The treatment was surgical (excision-dressing-grafting) associated to antibiotic therapy (Rifater, Pyrazynamide, and Myambutol). After six years of follow up, no relapse was observed
Could clinical audit improve the diagnosis of pulmonary tuberculosis in Cuba, Peru and Bolivia?
The definitive version is available at www3.interscience.wiley.comOBJECTIVES: To assess the effectiveness of clinical audit in improving the quality of diagnostic care provided to patients suspected of tuberculosis; and to understand the contextual factors which impede or facilitate its success. METHODS: Twenty-six health centres in Cuba, Peru and Bolivia were recruited. Clinical audit was introduced to improve the diagnostic care for patients attending with suspected TB. Standards were based on the WHO and TB programme guidelines relating to the appropriate use of microscopy, culture and radiological investigations. At least two audit cycles were completed over 2 years. Improvement was determined by comparing the performance between two six-month periods pre- and post-intervention. Qualitative methods were used to ascertain facilitating and limiting contextual factors influencing change among healthcare professionals' clinical behaviour after the introduction of clinical audit. RESULTS: We found a significant improvement in 11 of 13 criteria in Cuba, in 2 of 6 criteria in Bolivia and in 2 of 5 criteria in Peru. Twelve out of 24 of the audit criteria in all three countries reached the agreed standards. Barriers to quality improvement included conflicting objectives for clinicians and TB programmes, poor coordination within the health system and patients' attitudes towards illness. CONCLUSIONS: Clinical audit may drive improvements in the quality of clinical care in resource-poor settings. It is likely to be more effective if integrated within and supported by the local TB programmes. We recommend developing and evaluating an integrated model of quality improvement including clinical audit
Association of HIV infection and Mycobacterium ulcerans disease in Benin [research letter]
Not the final published versionWe investigated the association between Buruli ulcer and HIV by comparing the HIV-1/2 seroprevalence in a series of 426 Buruli ulcer patients and a sample of 613 residents of southern Benin. The overall HIV prevalence was 2.6% (11/426) among patients and 0.3% among controls (2/613), giving an odds ratio for the association between HIV and Buruli ulcer of 8.1 (95% confidence interval = 1.8-75; P = 0.003)
Immunopathogenesis of immune reconstitution disease in HIV patients responding to antiretroviral therapy
Purpose of review: The aim of this article is to review the most recent literature regarding the immunopathogenesis of pathogen-associated immune reconstitution disease and to discuss the role of immune activation and various effector molecules and cells such as macrophages, effector and regulatory T cells, and natural killer cells in immune reconstitution disease.
Recent findings: Many HIV patients receiving antiretroviral treatment develop immune reconstitution disease, which is characterized by exaggerated inflammatory immune responses to replicating or dead pathogens. In the majority of these cases, immune reconstitution disease is associated with restoration of pathogen-specific cellular immune responses involving CD4+ or CD8+ effector T cells. The precise conditions that trigger immune reconstitution disease have not yet been identified. Immune reconstitution disease patients have overt immune activation, which may be due to poor homeostatic control after the fast initial immune recovery in patients receiving antiretroviral therapy. Poor homeostatic control in immune reconstitution disease patients may be linked to unbalanced restoration of effector and regulatory T cells.
Summary: Although the precise mechanism of immune reconstitution disease is not well understood, it is probably related to rapid restoration of pathogen-specific immune responses and poor homeostatic control that promote exaggerated immunopathological responses, especially if viable pathogens or pathogen debris are present at high concentrations
La regionalización de los servicios de salud como una estrategia de reorganización sanitaria
OBJECTIVE: to update the topic of decentralization and regionalization associated with the performance of the health systems in order to conceptually contribute to the study of the thematic in Cuba and in other Latin American countries.
DEVELOPMENT: the non-systematic documentary review was used, and the experience accumulated for more than 4 decades by the Cuban government and the health system as regards organization and improvement of the health services to raise the population's health levels was presented. The bases, principles and lessons from these experiences of decentralization and regionalization of the health services in Cuba, which have become bases for the development of a national study, were exposed.
CONCLUSIONS: the regionalization processes favour the capacity to solve problems of the health services, starting from the consequent application of the basic principles of decentralization as a long process that allows to offering adequate levels of attention to all, to improve the quality of services, to increase the satisfaction of the population and to attain optimal levels of cost-benefit relation
Spatial targeted vector control is able to reduce malaria prevalence in the highlands of Burundi
In a highland province of Burundi, indoor residual spraying and long-lasting insecticidal net distribution were targeted in the valley, aiming also to protect the population living on the hilltops. The impact on malaria indicators was assessed, and the potential additional effect of nets evaluated. After the intervention--and compared with the control valleys--children 1-9 years old in the treated valleys had lower risks of malaria infection (odds ratio, OR: 0.55), high parasite density (OR: 0.48), and clinical malaria (OR: 0.57). The impact on malaria prevalence was even higher in infants (OR: 0.14). Using nets did not confer an additional protective effect to spraying. Targeted vector control had a major impact on malaria in the high-risk valleys but not in the less-exposed hilltops. Investment in targeted and regular control measures associated with effective case management should be able to control malaria in the highlands