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1.
BMC Health Serv Res ; 23(1): 705, 2023 Jun 29.
Article in English | MEDLINE | ID: mdl-37386431

ABSTRACT

BACKGROUND: In 2017, Liberia became one of the first countries in the African region to develop and implement a national strategy for integrated case management of Neglected Tropical Diseases (CM-NTDs), specifically Buruli ulcer, leprosy, lymphatic filariasis morbidities, and yaws. Implementing this plan moves the NTD program from many countries' fragmented (vertical) disease management. This study explores to what extent an integrated approach offers a cost-effective investment for national health systems. METHODS: This study is a mixed-method economic evaluation that explores the cost-effectiveness of the integrated CM-NTDs approach compared to the fragmented (vertical) disease management. Primary data were collected from two integrated intervention counties and two non-intervention counties to determine the relative cost-effectiveness of the integrated program model vs. fragmented (vertical) care. Data was sourced from the NTDs program annual budgets and financial reports for integrated CM-NTDs and Mass Drug Administration (MDA) to determine cost drivers and effectiveness. RESULTS: The total cost incurred by the integrated CM-NTD approach from 2017 to 2019 was US$ 789,856.30, with the highest percentage of costs for program staffing and motivation (41.8%), followed by operating costs (24.8%). In the two counties implementing fragmented (vertical) disease management, approximately US$ 325,000 was spent on the diagnosis of 84 persons and the treatment of twenty-four persons suffering from NTDs. While 2.5 times as much was spent in integrated counties, 9-10 times more patients were diagnosed and treated. CONCLUSIONS: The cost of a patient being diagnosed under the fragmented (vertical) implementation is five times higher than integrated CM-NTDs, and providing treatment is ten times as costly. Findings indicate that the integrated CM-NTDs strategy has achieved its primary objective of improved access to NTD services. The success of implementing an integrated CM-NTDs approach in Liberia, presented in this paper, demonstrates that NTD integration is a cost-minimizing solution.


Subject(s)
Case Management , Delivery of Health Care , Infections , Neglected Diseases , West African People , Humans , Black People/statistics & numerical data , Budgets , Case Management/economics , Case Management/statistics & numerical data , Cost-Benefit Analysis , Liberia/epidemiology , Neglected Diseases/economics , Neglected Diseases/therapy , Cost-Effectiveness Analysis , Infections/economics , Infections/therapy , Delivery of Health Care, Integrated/economics , Delivery of Health Care, Integrated/statistics & numerical data , Tropical Medicine/economics , Tropical Medicine/statistics & numerical data , Health Services Accessibility/economics , Health Services Accessibility/statistics & numerical data , Delivery of Health Care/economics , Delivery of Health Care/statistics & numerical data , West African People/statistics & numerical data
2.
Immunology ; 165(1): 44-60, 2022 01.
Article in English | MEDLINE | ID: mdl-34716913

ABSTRACT

Cytokines are considered vital mediators of the immune system. Down- or upregulation of these mediators is linked to several inflammatory and pathologic situations. IL-26 is referred to as an identified member of the IL-10 family and IL-20 subfamily. Due to having a unique cationic structure, IL-26 exerts diverse functions in several diseases. Since IL-26 is mainly secreted from Th17, it is primarily considered a pro-inflammatory cytokine. Upon binding to its receptor complex (IL-10R1/IL-20R2), IL-26 activates multiple signalling mediators, especially STAT1/STAT3. In cancer, IL-26 induces IL-22-producing cells, which consequently decrease cytotoxic T-cell functions and promote tumour growth through activating anti-apoptotic proteins. In hypersensitivity conditions such as rheumatoid arthritis, multiple sclerosis, psoriasis and allergic disease, this cytokine functions primarily as the disease-promoting mediator and might be considered a biomarker for disease prognosis. Although IL-26 exerts antimicrobial function in infections such as hepatitis, tuberculosis and leprosy, it has also been shown that IL-26 might be involved in the pathogenesis and exacerbation of sepsis. Besides, the involvement of IL-26 has been confirmed in other conditions, including graft-versus-host disease and chronic obstructive pulmonary disease. Therefore, due to the multifarious function of this cytokine, it is proposed that the underlying mechanism regarding IL-26 function should be elucidated. Collectively, it is hoped that the examination of IL-26 in several contexts might be promising in predicting disease prognosis and might introduce novel approaches in the treatment of various diseases.


Subject(s)
Disease Susceptibility , Interleukins/genetics , Interleukins/metabolism , Animals , Cytokines/genetics , Cytokines/metabolism , Gene Expression Regulation , Humans , Infections/etiology , Infections/metabolism , Infections/pathology , Inflammation/etiology , Inflammation/metabolism , Inflammation/pathology , Interleukins/chemistry , Neoplasms/etiology , Neoplasms/metabolism , Neoplasms/pathology , Organ Specificity/genetics , Organ Specificity/immunology , Protein Transport , Signal Transduction , Structure-Activity Relationship
3.
Front Immunol ; 12: 702552, 2021.
Article in English | MEDLINE | ID: mdl-34335615

ABSTRACT

Availability of highly parallelized immunoassays has renewed interest in the discovery of serology biomarkers for infectious diseases. Protein and peptide microarrays now provide a rapid, high-throughput platform for immunological testing and validation of potential antigens and B-cell epitopes. However, there is still a need for tools to prioritize and select relevant probes when designing these arrays. In this work we describe a computational method called APRANK (Antigenic Protein and Peptide Ranker) which integrates multiple molecular features to prioritize potentially antigenic proteins and peptides in a given pathogen proteome. These features include subcellular localization, presence of repetitive motifs, natively disordered regions, secondary structure, transmembrane spans and predicted interaction with the immune system. We trained and tested this method with a number of bacteria and protozoa causing human diseases: Borrelia burgdorferi (Lyme disease), Brucella melitensis (Brucellosis), Coxiella burnetii (Q fever), Escherichia coli (Gastroenteritis), Francisella tularensis (Tularemia), Leishmania braziliensis (Leishmaniasis), Leptospira interrogans (Leptospirosis), Mycobacterium leprae (Leprae), Mycobacterium tuberculosis (Tuberculosis), Plasmodium falciparum (Malaria), Porphyromonas gingivalis (Periodontal disease), Staphylococcus aureus (Bacteremia), Streptococcus pyogenes (Group A Streptococcal infections), Toxoplasma gondii (Toxoplasmosis) and Trypanosoma cruzi (Chagas Disease). We have evaluated this integrative method using non-parametric ROC-curves and made an unbiased validation using Onchocerca volvulus as an independent data set. We found that APRANK is successful in predicting antigenicity for all pathogen species tested, facilitating the production of antigen-enriched protein subsets. We make APRANK available to facilitate the identification of novel diagnostic antigens in infectious diseases.


Subject(s)
Antigens/analysis , Antigens/immunology , Computer Simulation , Infections/immunology , Computational Biology/methods , Humans , Proteome
4.
Hautarzt ; 71(3): 251-254, 2020 Mar.
Article in German | MEDLINE | ID: mdl-31950208

ABSTRACT

In his both highly amusing and thrilling story Roald Dahl describes an adventure of his fictive uncle Oswald Hendryk Cornelius, a snobby Englishman and womanizer, suffering from delusional anxiety of infections and hygienic compulsions. Forced by the breakdown of his car in the Sinai desert, he accepts the invitation of a noble Arab to spend the night in his palace, situated like a mirage in the middle of the desert. Oswald is plagued by erotic obsessions at the sight of the beautiful wife as well as the likewise beautiful daughter. The night rewards him with the desired amorous adventure but without knowing with whom he had spent the night. Oswald's satisfaction changes to pure horror when, the next morning, the owner of the house reveals that the visitor during the night was neither his wife nor daughter.


Subject(s)
Anxiety , Delusions , Hygiene , Infections , Phobic Disorders , Anxiety Disorders , Humans , Male
5.
Sci Transl Med ; 11(511)2019 09 25.
Article in English | MEDLINE | ID: mdl-31554740

ABSTRACT

Variants in the leucine-rich repeat kinase-2 (LRRK2) gene are associated with Parkinson's disease, leprosy, and Crohn's disease, three disorders with inflammation as an important component. Because of its high expression in granulocytes and CD68-positive cells, LRRK2 may have a function in innate immunity. We tested this hypothesis in two ways. First, adult mice were intravenously inoculated with Salmonella typhimurium, resulting in sepsis. Second, newborn mouse pups were intranasally infected with reovirus (serotype 3 Dearing), which induced encephalitis. In both mouse models, wild-type Lrrk2 expression was protective and showed a sex effect, with female Lrrk2-deficient animals not controlling infection as well as males. Mice expressing Lrrk2 carrying the Parkinson's disease-linked p.G2019S mutation controlled infection better, with reduced bacterial growth and longer animal survival during sepsis. This gain-of-function effect conferred by the p.G2019S mutation was mediated by myeloid cells and was abolished in animals expressing a kinase-dead Lrrk2 variant, p.D1994S. Mouse pups with reovirus-induced encephalitis that expressed the p.G2019S Lrrk2 mutation showed increased mortality despite lower viral titers. The p.G2019S mutant Lrrk2 augmented immune cell chemotaxis and generated more reactive oxygen species during virulent infection. Reovirus-infected brains from mice expressing the p.G2019S mutant Lrrk2 contained higher concentrations of α-synuclein. Animals expressing one or two p.D1994S Lrrk2 alleles showed lower mortality from reovirus-induced encephalitis. Thus, Lrrk2 alleles may alter the course of microbial infections by modulating inflammation, and this may be dependent on the sex and genotype of the host as well as the type of pathogen.


Subject(s)
Alleles , Infections/enzymology , Infections/genetics , Inflammation/genetics , Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics , Sex Characteristics , Animals , Brain/pathology , Brain/virology , Chemotaxis , Encephalitis/virology , Female , Humans , Infections/immunology , Infections/pathology , Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/deficiency , Leukocytes/enzymology , Male , Mice, Inbred C57BL , Mutation/genetics , Reactive Oxygen Species/metabolism , Reoviridae/physiology , Salmonella typhimurium/growth & development , Sepsis/microbiology , Survival Analysis , alpha-Synuclein/metabolism
7.
Nat Immunol ; 17(9): 1046-56, 2016 09.
Article in English | MEDLINE | ID: mdl-27478939

ABSTRACT

Single-nucleotide variations in C13orf31 (LACC1) that encode p.C284R and p.I254V in a protein of unknown function (called 'FAMIN' here) are associated with increased risk for systemic juvenile idiopathic arthritis, leprosy and Crohn's disease. Here we set out to identify the biological mechanism affected by these coding variations. FAMIN formed a complex with fatty acid synthase (FASN) on peroxisomes and promoted flux through de novo lipogenesis to concomitantly drive high levels of fatty-acid oxidation (FAO) and glycolysis and, consequently, ATP regeneration. FAMIN-dependent FAO controlled inflammasome activation, mitochondrial and NADPH-oxidase-dependent production of reactive oxygen species (ROS), and the bactericidal activity of macrophages. As p.I254V and p.C284R resulted in diminished function and loss of function, respectively, FAMIN determined resilience to endotoxin shock. Thus, we have identified a central regulator of the metabolic function and bioenergetic state of macrophages that is under evolutionary selection and determines the risk of inflammatory and infectious disease.


Subject(s)
Arthritis, Juvenile/genetics , Crohn Disease/genetics , Infections/genetics , Leprosy/genetics , Macrophages/immunology , Proteins/genetics , Shock, Septic/genetics , Adenosine Triphosphate/metabolism , Animals , Bacteriolysis , Cells, Cultured , Energy Metabolism , Fatty Acid Synthase, Type I/metabolism , Genetic Predisposition to Disease , Humans , Inflammasomes/metabolism , Intracellular Signaling Peptides and Proteins , Lipid Metabolism/genetics , Mice , Mice, Inbred C57BL , Mice, Knockout , NADPH Oxidases/metabolism , Oxidation-Reduction , Polymorphism, Single Nucleotide , Risk
8.
Infectio ; 18(4): 135-142, sep.-dic. 2014. tab
Article in English | LILACS, COLNAL | ID: lil-734991

ABSTRACT

Antecedentes: Las infecciones por micobacterias no tuberculosas (MNT) se describen en los últimos años con mayor frecuencia, especialmente en pacientes con inmunosupresión y en pacientes tratados por procedimientos estéticos. Las MNT incluyen especies del género Mycobacterium , diferentes del complejo Mycobacterium tuberculosis y Mycobacterium leprae . Objetivo: Describir las características demográficas y clínicas de pacientes hospitalizados con infecciones por MNT. Metodología: Estudio descriptivo retrospectivo. Resultados: De 187 pacientes con infección por micobacterias documentadas por cultivo, 17 (9,1%) tuvieron infección por MNT. Edad promedio de 38,4 ± 19,2 años. El 58,82% fueron hombres. Las principales comorbilidades fueron VIH/sida (41,17%), diabetes mellitus (23,53%), enfermedad renal crónica (17,64%), terapia inmunosupresora (17,64%) y neoplasias (17,64%). En los coinfectados con VIH el recuento de CD4 fue <50 en 85,71%. Las especies más frecuentes fueron complejo M. avium (CMA) 35,29%, M. abscessus (17,65%) y M. chelonae (11,76%). Las formas de infección fueron: diseminada (35,29%), pulmonar (23,53%), piel y tejidos blandos (17,64%) y gastrointestinal (11,76%). Estancia promedio de 22,1 días; un 23,53% requirió atención en UCI. La mortalidad general fue 23,53%. Conclusión: Las infecciones por MNT causan una serie de condiciones patológicas, los pacientes inmunocomprometidos son la población de mayor riesgo y las formas diseminada y pulmonar,las más frecuentes. La sospecha temprana así como la toma de muestras adecuadas y el uso de métodos diagnósticos apropiados son indispensables para su diagnóstico oportuno y tratamiento adecuado.


Background: Nontuberculous mycobacteria (NTM) infections has been described more frequently in recent years, especially in immunosuppression conditions and after cosmetic surgical procedures. The NTM include species of the genus Mycobacterium , other than Mycobacterium tuberculosis complex and Mycobacterium leprae. Objective: To describe the demographic and clinical characteristics of Colombian in-patientswith NTM infections. Methodology: A retrospective descriptive study. Results: In 187 patients with culture- confirmed mycobacterial infection, 17 (9,1%) had NTM.The mean age was 38,4 ± 19,2 and 58,82% were men. Major comorbidities were: HIV/AIDS(41,1%), diabetes mellitus (23,5%), chronic renal disease (17,6%), immunosuppressive therapy(17,6%) and neoplasms (17,6%). In patients co-infected with HIV, CD4 count was <50 in 85,7%.The most frequent species were M. avium complex (MAC) in 35,2%, M. abscessus in 17,6% and M. chelonae in 11,7%. Infections were disseminated (35,2%), pulmonary (23,5%), skin and soft tissue (17,6%) and in gastrointestinal system (11,7%). The average hospital stay was 22,1 day sand 23,5% required intensive care unit. Overall mortality was 23,5%. Conclusion: MNT infections cause a number of pathological conditions, being more frequent in immunocompromised patients. The disseminated and pulmonary forms were the most common. Early clinical suspicion and appropriate samples and diagnostic assays, are crucial for early diagnosis and treatment.


Subject(s)
Humans , Male , Adult , Mycobacterium Infections, Nontuberculous , HIV , Immunosuppression Therapy , Colombia , Hospitals , Infections , Mycobacterium Infections, Nontuberculous , Neoplasms
9.
Salud(i)ciencia (Impresa) ; 21(1): 40-44, Nov.2014. tab
Article in Spanish | LILACS | ID: lil-790940

ABSTRACT

Las infecciones provocadas por micobacterias atípicas, micobacterias no tuberculosas y más recientemente denominadas micobacterias ambientales u oportunistas, en los últimos tiempos desempeñan un papel preponderante en el diagnóstico clínico. Estas especies se relacionan generalmente con estados de inmuno depresión del paciente. En este trabajo se estudiaron 136 cepas aisladas de pacientes con sintomatología específica tanto pulmonar como extrapulmonar, incluidos aquellos infectados por el virus de la inmunodeficiencia humana (VIH), éstas fueron estudiadas e identificadas en el Laboratorio Nacional de Referencia e Investigaciones de Tuberculosis, Lepra y Micobacterias, durante el período de enero de 2011 a diciembre de 2012. Es importante destacar que el 72.79% de los aislamientos eran procedentes de pacientes VIH positivos. El total de las cepas aisladas fue analizado según la clasificación establecida por Runyon; los grupos encontrados con mayor frecuencia fueron el III y el IV; por especie, las de mayor porcentaje de aislamiento fueron las del complejo Mycobacterium avium-intracellulare, Mycobacterium malmoense, Mycobacterium fortuitum y Mycobacterium chelonae, respectivamente. Estos estudios son de gran importancia diagnóstica en los laboratorios de micobacteriología, pues de esta forma se puede llegar a conocer cuáles son las especies micobacterianas predominantes en la población,y lograr establecer una vigilancia sobre este tipo de infecciones, particularmente en pacientes inmunodeficientes, los que pueden ser origen de una peligrosa diseminación de la enfermedad...


Subject(s)
Humans , HIV , Opportunistic Infections , Nontuberculous Mycobacteria , Mycobacterium avium Complex , Infections
11.
J Hand Surg Am ; 39(8): 1636-45, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25070033

ABSTRACT

Chronic infections of the hand are uncommon, and a high index of suspension is required for their early diagnosis. These can be grouped based on the microorganism. Mycobacterial infections include tuberculosis, atypical mycobacterial infections, and leprosy. Other bacterial infections include actinomycosis, cat-scratch disease, syphilis, tularemia, bacillary angiomatosis, and actinomycetoma. Fungal infections may be classified as cutaneous (affecting the skin, the paronychia or nail plate), subcutaneous (mainly lymphocutaneous sporotrichosis and dermatiaceous infections), and deep fungal infections. Each type of deep fungal infection has a "classic" presentation and this is emphasized. Finally, common chronic viral infections of the hand include warts and orf.


Subject(s)
Hand , Infections , Chronic Disease , Hand/microbiology , Hand/virology , Humans , Infections/diagnosis , Infections/microbiology , Infections/therapy , Infections/virology
12.
Arch Pathol Lab Med ; 138(6): 745-53, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24878014

ABSTRACT

CONTEXT: The sinonasal tract is frequently affected by a variety of nonneoplastic inflammatory disease processes that are often multifactorial in their etiology but commonly have a molecular genetic component. OBJECTIVE: To review the molecular genetics of a variety of nonneoplastic inflammatory diseases of the sinonasal tract. DATA SOURCES: Inflammatory lesions of the sinonasal tract can be divided into 3 main categories: (1) chronic rhinosinusitis, (2) infectious diseases, and (3) autoimmune diseases/vasculitides. The molecular diagnosis and pathways of a variety of these inflammatory lesions are currently being elucidated and will shed light on disease pathogenesis and treatment. CONCLUSIONS: The sinonasal tract is frequently affected by inflammatory lesions that arise through complex interactions of environmental, infectious, and genetic factors. Because these lesions are all inflammatory in nature, the molecular pathology surrounding them is most commonly due to upregulation and down-regulation of genes that affect inflammatory responses and immune regulation.


Subject(s)
Nose Diseases/genetics , Aspirin/adverse effects , Autoimmune Diseases/genetics , Autoimmune Diseases/immunology , Churg-Strauss Syndrome/genetics , Churg-Strauss Syndrome/immunology , Granulomatosis with Polyangiitis/genetics , Granulomatosis with Polyangiitis/immunology , Humans , Infections/genetics , Infections/immunology , Leishmaniasis/genetics , Leishmaniasis/immunology , Leprosy/genetics , Leprosy/immunology , Mycoses/genetics , Mycoses/immunology , Nose Diseases/immunology , Rhinitis/genetics , Rhinitis/immunology , Rhinoscleroma/genetics , Rhinoscleroma/immunology , Sarcoidosis/genetics , Sarcoidosis/immunology , Sinusitis/genetics , Sinusitis/immunology , Vasculitis/genetics , Vasculitis/immunology
13.
Article in English | LILACS, VETINDEX | ID: biblio-1484589

ABSTRACT

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, a microorganism that usually affects skin and nerves. Although it is usually well-controlled by multidrug therapy (MDT), the disease may be aggravated by acute inflammatory reaction episodes that cause permanent tissue damage particularly to peripheral nerves. Tuberculosis is predominantly a disease of the lungs; however, it may spread to other organs and cause an extrapulmonary infection. Both mycobacterial infections are endemic in developing countries including Brazil, and cases of coinfection have been reported in the last decade. Nevertheless, simultaneous occurrence of perianal cutaneous tuberculosis and erythema nodosum leprosum is very rare, even in countries where both mycobacterial infections are endemic.


Subject(s)
Animals , Leprosy/pathology , Infections , Mycobacterium leprae , Review Literature as Topic
14.
Nutr. hosp ; 29(1): 26-36, ene. 2014. ilus, tab
Article in English | IBECS | ID: ibc-120553

ABSTRACT

La lepra es una enfermedad infecciosa crónica causada por el Mycobacterium leprae, un bacilo intracelular de transmisión aérea. La enfermedad afecta la piel y los nervios periféricos y causa secuelas neurológicas. El bacilo se multiplica lentamente en el hospedador y posiblemente la enfermedad ocurre por el mal funcionamiento de la respuesta inmunitaria del hospedador. Esta revisión aborda el papel de algunos micronutrientes específicos en la respuesta inmunitaria, tales como las vitaminas A, D, E, C, el cinc y el selenio, detallando sus mecanismos de acción en las enfermedades infecciosas y en la lepra. La respuesta inmunitaria a los patógenos libera sustancias nocivas que producen lesión tisular. Esta revisión también aborda cómo una menor cantidad de antioxidantes puede contribuir a un aumento del estrés oxidativo y a complicaciones de las enfermedades infecciosas y la lepra. Puesto que los micronutrientes poseen un efecto regulador de la respuesta inmunitaria innata y adaptativa, es importante un equilibrio perfecto de sus concentraciones para mejorar la respuesta inmunitaria frente a los patógenos (AU)


Leprosy is a chronic infectious disease caused by Mycobacterium leprae, an intracellular bacillus of airborne transmission. The disease affects the skin and peripheral nerves and can cause neurological sequelae. The bacillusmultiplies slowly in the host and the disease probably occurs due to malfunctioning in host immune response. This review addresses the role of some specific micronutrients in the immune response, such as Vitamins A, D, E, C, Zinc and Selenium, detailing their mechanisms of actions in infectious diseases, and in leprosy. The immune response to pathogens releases harmful substances, which lead to tissue damage. This review discusses how a decreased level of antioxidants may contribute to an increased oxidative stress and complications of infectious diseases and leprosy. As the nutrients have a regulatory effect in the innate and adaptative immune responses, a perfect balance in their concentrations is important to improve the immune response against the pathogens (AU)


Subject(s)
Humans , Micronutrients/pharmacokinetics , Leprosy/diet therapy , Adaptive Immunity/immunology , Immunity, Innate/immunology , Oxidative Stress/physiology , Antioxidants/pharmacokinetics , Infections/immunology , Ascorbic Acid/pharmacokinetics , Zinc/pharmacokinetics , Selenium/pharmacokinetics , Vitamin D/pharmacokinetics
15.
Brain Behav Immun ; 35: 169-75, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24075848

ABSTRACT

Cytokine gene variants are known to influence both infectious disease susceptibility and harm-avoidant behaviors, suggesting that these risk variants may be pleiotropically linked to instinctual disease-avoidant traits. The gamma-interferon (IFNG) +874 T>A polymorphism (rs2430561) is an ideal candidate gene variant for immune-behavioral studies. It is a functional SNP, regulating IFNG mRNA expression; it is known to modulate serotonergic activity and is therefore capable of modifying behavior; and it has previously been associated with increased susceptibility to malaria, tuberculosis, leprosy and Chagas disease. We hypothesized that the infectious disease-high-risk IFNG +874 A-allele would be associated with four personality traits previously reported as behavioral defenses against infection: Harm Avoidance (HA), Extraversion (E), Exploratory Excitability (Exp E), and Openness to Experience (O). We tested this hypothesis in a sample of 168 healthy university students from Southern California genotyped for IFNG +874 T>A and evaluated by the Temperament and Character Inventory-Revised (TCI-R) and the NEO Five-Factor Inventory (NEO-FFI). We found that the infectious disease-high-risk IFNG +874 A-allele was associated with increased HA (P=0.001) and decreased E (P=0.030) and Exp E (P=0.030). These findings suggest that the IFNG +874 A gene variant is linked both to infectious disease susceptibility and to proactive behavioral defenses that reduce infection risk in healthy subjects.


Subject(s)
Avoidance Learning/physiology , Genetic Predisposition to Disease/genetics , Infections/genetics , Interferon-gamma/physiology , Adult , Character , Female , Genetic Association Studies , Genetic Predisposition to Disease/psychology , Humans , Infections/immunology , Infections/psychology , Interferon-gamma/genetics , Interferon-gamma/immunology , Male , Middle Aged , Personality/genetics , Personality/physiology , Personality Inventory , Polymorphism, Single Nucleotide/genetics , Polymorphism, Single Nucleotide/physiology , Temperament , Young Adult
16.
PLoS One ; 8(11): e81047, 2013.
Article in English | MEDLINE | ID: mdl-24282567

ABSTRACT

BACKGROUND: Toll-like receptor 4 plays a role in pathogen recognition, and common polymorphisms may alter host susceptibility to infectious diseases. PURPOSE: To review the association of two common polymorphisms (TLR4 896A>G and TLR4 1196C>T) with infectious diseases. DATA SOURCES: We searched PubMed and EMBASE up to March 2013 for pertinent literature in English, and complemented search with references lists of eligible studies. STUDY SELECTION: We included all studies that: reported an infectious outcome; had a case-control design and reported the TLR4 896A>G and/or TLR4 1196C>T genotype frequencies; 59 studies fulfilled these criteria and were analyzed. DATA EXTRACTION: Two authors independently extracted study data. DATA SYNTHESIS: The generalized odds ratio metric (ORG) was used to quantify the impact of TLR4 variants on disease susceptibility. A meta-analysis was undertaken for outcomes reported in >1 study. Eleven of 37 distinct outcomes were significant. TLR4 896 A>G increased risk for all parasitic infections (ORG 1.59; 95%CI 1.05-2.42), malaria (1.31; 95%CI 1.04-1.66), brucellosis (2.66; 95%CI 1.66-4.27), cutaneous leishmaniasis (7.22; 95%CI 1.91-27.29), neurocysticercosis (4.39; 95%CI 2.53-7.61), Streptococcus pyogenes tonsillar disease (2.93; 95%CI 1.24-6.93) , typhoid fever (2.51; 95%CI 1.18-5.34) and adult urinary tract infections (1.98; 95%CI 1.04-3.98), but was protective for leprosy (0.36; 95%CI 0.22-0.60). TLR4 1196 C>T effects were similar to TLR4 896 A>G for brucellosis, cutaneous leishmaniasis, leprosy, typhoid fever and S. pyogenes tonsillar disease, and was protective for bacterial vaginosis in pregnancy (0.55; 95%CI 0.31-0.98) and Haemophilus influenzae tonsillar disease (0.42; 95%CI 0.17-1.00). The majority of significant associations were among predominantly Asian populations and significant associations were rare among European populations. CONCLUSIONS: Depending on the type of infection and population, TLR4 polymorphisms are associated with increased, decreased or no difference in infectious disease. This may be due to differential functional expression of TLR4, the co-segregation of TLR4 variants or a favorable inflammatory response.


Subject(s)
Genetic Predisposition to Disease , Genome-Wide Association Study , Infections/genetics , Polymorphism, Genetic , Toll-Like Receptor 4/genetics , Humans
17.
Curr Opin Neurol ; 26(5): 510-5, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23945279

ABSTRACT

PURPOSE OF REVIEW: Infectious neuropathies are heterogeneous neuropathies with multiple causes. They still represent an important world health burden and some of them have no current available therapy. RECENT FINDINGS: Leprosy incidence has decreased by 50% during the last years, but leprosy-related neuropathies still cause severe disability. The pure neuritic leprosy is a diagnostic challenge that may require nerve biopsy or nerve aspiration cytology. The treatment itself may lead to a 'reversal reaction', which further causes injuries to the nerve. HCV-related neuropathies may be related or not to the presence of cryoglobulins. The absence of vasculitis, the most frequent form is a peripheral sensory neuropathy involving small nerve fibers, and more accurately diagnosed by pain-related evoked potentials. HIV-related neuropathy has become the major neurological complication of HIV infection. Both HIV-induced neuropathy and antiretroviral toxic neuropathy are clinically indistinguishable. The existence of an isolated chronic polyneuropathy due to Borrelia burgdorferi remains highly controversial. Lastly, an active infectious ganglioneuritis caused by varicella zoster virus, producing shingles, is the most frequent infectious neuropathy in the world and may cause various neurological complications. Zoster sine herpete remains frequently undiagnosed. SUMMARY: Recent data have improved our knowledge and diagnostic tools of infectious neuropathies. Treatment of the injured nerves is not yet available, and prevention and rapid diagnosis remain the main priorities for the clinician.


Subject(s)
Infections/complications , Peripheral Nervous System Diseases/diagnosis , Peripheral Nervous System Diseases/etiology , Biopsy/methods , Early Diagnosis , Humans , Infections/diagnosis , Inflammation/complications , Leprosy/complications , Leprosy/diagnosis , Leprosy/therapy , Peripheral Nervous System Diseases/prevention & control , Peripheral Nervous System Diseases/therapy
18.
Neurology ; 79(9): 937-40, 2012 Aug 28.
Article in English | MEDLINE | ID: mdl-22927678

ABSTRACT

BACKGROUND: Approximately one-third of refugees worldwide live in refugee camps. Selected neurologic diseases are actively reported in some refugee camps. METHODS: The United Nations High Commissioner for Refugees monitors health visits in refugee camps with the assistance of more than 25 partner organizations using standardized case definitions. Neurologic diseases were selected and searched for the years 2008 to 2011. The number of health care visits for a neurologic disease was calculated and divided by the aggregated number of reporting months available for each refugee camp ("visits per camp-month"). RESULTS: Five neurologic diseases were reported from 127 refugee camps in 19 countries. Visits for chronic, noncommunicable diseases including epilepsy (53,941 visits in 1,426 camp-months, 48% female) and cerebrovascular disease (4,028 visits in 1,333 camp-months, 51% female) far exceeded those for neurologic infectious diseases (acute flaccid paralysis/poliomyelitis, 78 visits in 3,816 camp-months, 42% female; leprosy, 74 visits in 3,816 camp-months, 66% female; meningitis, 477 visits in 3,816 camp-months, 51% female). In 2011, these diseases accounted for 31,349 visits globally with 91% of visits for epilepsy. CONCLUSIONS: Targeted programs addressing epilepsy and stroke among refugees in camps should become a priority and indicate that other chronic neurologic diseases that may be under- or misdiagnosed may also be common in refugee camps. Given that significant under-reporting is likely, our findings demonstrate the pressing need for coordinated preventive and interventional measures for epilepsy and stroke in refugee camps.


Subject(s)
Nervous System Diseases/epidemiology , Refugees/statistics & numerical data , Adolescent , Adult , Age Factors , Aged , Cerebrovascular Disorders/epidemiology , Child , Child, Preschool , Data Interpretation, Statistical , Epilepsy/epidemiology , Female , Humans , Infections/epidemiology , Leprosy/epidemiology , Male , Meningitis/epidemiology , Middle Aged , Paralysis/epidemiology , United Nations , Young Adult
19.
Nihon Hansenbyo Gakkai Zasshi ; 80(3): 301-4, 2011 Sep.
Article in Japanese | MEDLINE | ID: mdl-21941837

ABSTRACT

Human immunology and relationship between immune mechanism and infection were explained. Humoral immunity and cellular immunity collaborate properly and eliminate microorganisms. In immunocompromised host these mechanisms are broken. For prevention of healthcare associated infections, standard precausion is important basically. Additionary, according to the status of the patient, contact precaution, droplet precaution or airborne precaution should be applied.


Subject(s)
Health Personnel , Infections/immunology , Cross Infection/prevention & control , Humans , Immunity, Cellular , Immunity, Humoral , Immunocompromised Host/immunology , Infection Control , Infections/therapy
20.
J Ayub Med Coll Abbottabad ; 23(3): 149-52, 2011.
Article in English | MEDLINE | ID: mdl-23272458

ABSTRACT

Infectious diseases are influenced by where patients have lived or travelled in the past, e.g., infection with Schistosoma mekongi can be acquired during freshwater contact in Cambodia, but not in the United States. Here the infectious diseases of Khmer immigrants in the United States were studied by reviewing published reports. Thirteen case series and 9 case reports of 5,222 patients were identified. Most reports were of infections with gastrointestinal parasites (8, 36%), Plasmnodium species (3, 14%), Mycobacterium tuberculosis (3, 14%), and Mycobacterium leprae (2, 9%). Other reports included infections with Burkholderia pseudomallei, Trichinella spiralis, and Schistosoma japonicum. In conclusion, Khmer patients in the US can be infected with different gastrointestinal. parasites, different extrapulmonary forms of tuberculosis have been reported, and 2 reports of M. leprae were identified. A country-specific database for origin and current residence for Khmer and other immigrant groups providing access to specialised information may be useful for clinicians taking care of immigrants.


Subject(s)
Infections/epidemiology , Cambodia/ethnology , Emigrants and Immigrants , Humans , United States/epidemiology
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