ABSTRACT
We conducted a case-control study to examine associations between parasite infection, including protozoa infection, and tuberculosis (TB) in children in Lima, Peru. We enrolled 189 matched-pairs. In multivariable conditional logistic regression analyses, Blastocystis hominis infection (rate ratio = 0.30, 95% confidence interval = 0.14-0.64, P = 0.002) was strongly associated with a lower risk of TB. We observed a statistically significant inverse linear dose-response relationship between Blastocystis hominis infection and TB. These findings should be confirmed in future prospective studies.
Subject(s)
Amebiasis/epidemiology , Blastocystis Infections/epidemiology , Entamoebiasis/epidemiology , Giardiasis/epidemiology , Protozoan Infections/epidemiology , Tuberculosis/epidemiology , Amebiasis/complications , Blastocystis Infections/complications , Blastocystis hominis/isolation & purification , Case-Control Studies , Child , Child, Preschool , Endolimax/isolation & purification , Entamoeba/isolation & purification , Entamoebiasis/complications , Female , Giardia lamblia/isolation & purification , Giardiasis/complications , Humans , Logistic Models , Male , Multivariate Analysis , Peru , Protozoan Infections/complications , Risk Factors , Tuberculosis/complications , Tuberculosis/parasitologyABSTRACT
BACKGROUND: Helminthiasis and tuberculosis (TB) coincide geographically and there is much interest in exploring how concurrent worm infections might alter immune responses against bacilli and might necessitate altered therapeutic approaches. A DNA vaccine that codifies heat shock protein Hsp65 from M. leprae (DNAhsp65) has been used in therapy during experimental tuberculosis. This study focused on the impact of the co-existence of worms and TB on the therapeutic effects of DNAhsp65. METHODOLOGY/PRINCIPAL FINDINGS: Mice were infected with Toxocara canis or with Schistosoma mansoni, followed by coinfection with M. tuberculosis and treatment with DNAhsp65. While T. canis infection did not increase vulnerability to pulmonary TB, S. mansoni enhanced susceptibility to TB as shown by higher numbers of bacteria in the lungs and spleen, which was associated with an increase in Th2 and regulatory cytokines. However, in coinfected mice, the therapeutic effect of DNAhsp65 was not abrogated, as indicated by colony forming units and analysis of histopathological changes. In vitro studies indicated that Hsp65-specific IFN-gamma production was correlated with vaccine-induced protection in coinfected mice. Moreover, in S. mansoni-coinfected mice, DNA treatment inhibited in vivo TGF-beta and IL-10 production, which could be associated with long-term protection. CONCLUSIONS/SIGNIFICANCE: We have demonstrated that the therapeutic effects of DNAhsp65 in experimental TB infection are persistent in the presence of an unrelated Th2 immune response induced by helminth infections.
Subject(s)
Schistosomiasis mansoni/microbiology , Toxocariasis/microbiology , Tuberculosis Vaccines/immunology , Tuberculosis/parasitology , Vaccines, DNA/immunology , Analysis of Variance , Animals , Bacterial Proteins/genetics , Chaperonin 60/genetics , Disease Models, Animal , Female , Helminths , Interferon-gamma , Interleukins/metabolism , Lung/metabolism , Mice , Mice, Inbred BALB C , Nitrites/metabolism , Schistosoma mansoni , Schistosomiasis mansoni/immunology , Th1 Cells/metabolism , Toxocara canis , Tuberculosis/drug therapy , Tuberculosis/immunology , Tuberculosis/prevention & control , Tuberculosis Vaccines/pharmacology , Vaccines, DNA/pharmacologyABSTRACT
Mycobacterium tuberculosis and helminth infections coincide geographically and are classically described as TH1 and TH2 pathologies. There is much interest in exploring how concurrent worm infections might alter immune responses to mycobacterial infection. To explore this issue, mice were infected with Toxocara canis and co-infected with M. tuberculosis. Mice infected with M. tuberculosis had high numbers of neutrophils and mononuclear cells within the alveolar spaces, with increased parenchymal interferon (IFN)-gamma levels. However, in Toxocara-infected mice we detected increased eosinophil numbers in bronchoalveolar lavage fluid (BALF) and increased parenchymal levels of interleukin (IL)-5. In co-infected mice the BALF demonstrated enhanced eosinophil influx with decreased neutrophil and mononuclear cell accumulation. However, co-infected mice had similar mycobacterial proliferation in their lungs accompanied by similar histopathological changes and similar cytokine/nitric oxide production compared with Mycobacterium-only-infected mice. Our results suggest that T. canis infection does not necessarily lead to increased susceptibility to pulmonary tuberculosis.
Subject(s)
Mycobacterium tuberculosis/immunology , Th1 Cells/immunology , Th2 Cells/immunology , Toxocara canis/immunology , Toxocariasis/immunology , Tuberculosis/immunology , Animals , Bronchoalveolar Lavage Fluid/parasitology , Cytokines/immunology , Disease Susceptibility/immunology , Disease Susceptibility/microbiology , Female , Lung/pathology , Mice , Mice, Inbred BALB C , Mycobacterium tuberculosis/genetics , Nitric Oxide/chemistry , Nitric Oxide/metabolism , Spleen/immunology , Toxocariasis/microbiology , Tuberculosis/parasitologyABSTRACT
The impact of intestinal helminth infection on Mycobacterium tuberculosis (MTB)-specific immune responses during active tuberculosis (TB) is not known. We investigated the role of intestinal helminth infection in anti-MTB immunity by evaluating both cellular phenotype and cytokine profiles in patients with TB and patients with concomitant TB and intestinal helminth infection (TB + Helm) during TB therapy. Twenty-seven per cent of TB patients enrolled for the study were co-infected with at least one intestinal helminth. At baseline, absolute frequencies of leucocytes, monocytes and eosinophils from TB and TB + Helm patients differed from healthy subjects. Concomitant intestinal helminth infection in TB + Helm patients had a negative impact (P < 0.05) on absolute frequencies of CD3(+), CD4(+), CD8(+), natural killer (NK) T and CD4(+) CD25(high) T cell subsets when compared to either TB patients or healthy controls. Differences in CD4(+) T cell frequencies were accompanied by lower interferon (IFN)-gamma and elevated and sustained interleukin (IL)-10 levels in whole blood (WB) cultures from TB + Helm compared to TB patients. In addition to a depressed anti-MTB immunity, TB + Helm patients also presented with more severe radiological pulmonary disease, with a significant difference (P = 0.013) in the number of involved lung zones at the end of TB treatment. The above data may indicate that concomitant intestinal helminth infection in patients with newly diagnosed TB skews their cytokine profile toward a T helper 2 response, which could favour persistent MTB infection and a more protracted clinical course of the disease.
Subject(s)
Antitubercular Agents/therapeutic use , Helminthiasis/immunology , Intestinal Diseases, Parasitic/immunology , Mycobacterium tuberculosis , Tuberculosis/drug therapy , Tuberculosis/immunology , Adolescent , Adult , Case-Control Studies , Female , Flow Cytometry , Helminthiasis/microbiology , Humans , Immunophenotyping , Interferon-gamma/immunology , Interleukin-10/immunology , Interleukin-5/immunology , Intestinal Diseases, Parasitic/microbiology , Leukocytes/immunology , Male , Statistics, Nonparametric , Tuberculosis/parasitologyABSTRACT
Emergence of multi-drug resistance (MDR) Mycobacterium tuberculosis isolates constitutes a threat to public health worldwide. This study aimed at acquiring first epidemiological data for Guyana. Thirty-six M. tuberculosis isolates from patients of the Georgetown Chest Clinic were subjected to susceptibility testing on solid agar and in broth media. Resistance to at least one first-line drug was observed in 8 (22.2 percent, 95 percent confidence interval 8.3 -36.1 percent) and simultaneous resistance to rifampicin and isoniazid (MDR) in 4 (11.1 percent, 95 percent confidence interval 0.6-21.6 percent) of the 36 isolates. The risk of infection with resistant isolates was significantly related to earlier antituberculosis therapy (P=0.040). These data indicate a high proportion of resistant M.tuberculosis isolates in Guyana and call for the implementation of control strategies based on an improved laboratory diagnosis of TB(AU)
Subject(s)
Humans , Tuberculosis/diagnosis , Tuberculosis/parasitology , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Multidrug-Resistant/prevention & control , Tuberculosis, Multidrug-Resistant/parasitology , Mycobacterium tuberculosis , Drug Resistance, Bacterial/immunology , Guyana , Drug Resistance, Multiple/immunology , Caribbean RegionABSTRACT
Respecto al Programa de la Campaña Nacional Contra la Tuberculosis Bovina, corresponde a la Secretaría de Agricultura y Recursos Hidráulicos, a través de la Dirección General de Salud Animal, la instrumentación legal, la elaboración de normas y procedimientos, así como el control, supervisión administrativa, evaluación epizootiológica, económica y verificación de la calidad de la tuberculina empleada. En relación a los procedimientos, se mencionan los criterios que han de seguirse en: diagnóstico de la situación de la tuberculosis bovina; promoción y control; y, erradicación. En lo que concierne a la certificación y revalidación de hatos libres, se establecen: requisistos para la certificación de hato libre; pruebas diagnósticas; reactores positivos y sospechosos; cuarentena; cancelación del certificado; control de los animales en hatos registrados; requisitos para la revalidación de hatos libres; suspensión de la certificación de hato libre; exportación de ganado de carne; y, corrales de acopio. En cuanto al uso e interpretación de las pruebas de tuberculina, se deben tener en cuenta: las instrucciones para la realización de las pruebas de tuberculina (equipo, identificación, facilidades para el manejo de ganado, sitio de aplicación de la tuberculina, técnica de aplicación, observaciones, procedimiento para registrar y reportar los resultados y archivo de pruebas); pruebas aprobadas de tuberculina (anocaudal, simple o cervical, doble comparativa y excepciones); procedimientos especiales en hatos de alto riesgo; investigación en animales concurrentes (aves, cerdos, cabras, gatos y perros); e, investigación en humanos. Por otra parte, se proporciona una "guía técnica para el Programa de la Campaña Nacional para el Control y Erradicación de la Brucelosis", misma que está integrada por los siguientes apartados: términos empleados; disposiciones generales; procedimiento de aplicación en bovinos; procedimiento de aplicación en caprinos y bovinos; disposiciones generales en zonas de erradicación; y, procedimientos de vigilancia