First Molecular Evidence of Emerging Lophomonas Pathogen Among Patients Suspected of Having Pulmonary Tuberculosis in Mazandaran Province, Northern Iran.

PURPOSE: Lophomoniasis is a chronic protozoan respiratory disease in humans with main clinical symptoms such as chronic cough, productive sputum, breath shortness, and occasionally hemoptysis. Differentiation diagnosis of lophomoniasis from tuberculosis (TB) and asthma is crucial. METHODS: In this study, 210 participants with suspected TB referred to tuberculosis laboratories in Mazandaran province, northeastern Iran, were enrolled during 2021. All patients showed low grade fever, chronic cough or sputum on referral. Sputum specimens were collected from the participants, and Lophomonas DNA was detected through a conventional genus-specific polymerase chain reaction (PCR). RESULTS: Out of 210 participants, 67 (31.9%) had Lophomonas spp., infection, 38 (18.1%) had TB (Smear and culture-positive), and 20 (9.5%) had both TB and Lophomonas co-infection. CONCLUSION: Based on our results, a relatively high occurrence of Lophomonas infection was found among patients suspected of having TB. Accordingly, due to the high similarity of clinical symptoms between both pulmonary diseases, it is highly recommended to accurately and early diagnose the parasite in the sputum specimen.

Parasitic infections in Malaysian aborigines with pulmonary tuberculosis: a comparative cross-sectional study.

The geographical distribution of tuberculosis (TB) overlaps with various parasitic infections. Uncovering the characteristics of coinfecting parasites that potentially affect the host susceptibility to TB is pertinent as it may provide input to current TB therapeutic and prophylactic measures. The present study was aimed at examining the types of parasitic infections in TB patients and healthy TB contacts (HC) in Orang Asli, Malaysian aborigines, who dwelled in the co-endemic areas. Stool and serum samples were collected from Orang Asli who fulfilled the selection criteria and provided written informed consents. Selected parasitic infections in the two study groups were determined by stool examination and commercial serum antibody immunoassays. The prevalence of parasitic infections in TB and HC participants were 100% (n = 82) and 94.6% (n = 55) respectively. The parasitic infections comprised toxocariasis, trichuriasis, amoebiasis, toxoplasmosis, hookworm infection, ascariasis, strongyloidiasis, and brugian filariasis, in decreasing order of prevalence. Overall, helminth or protozoa infection did not show any significant association with the study groups. However, when the species of the parasite was considered, individuals exposed to trichuriasis and toxoplasmosis showed significant odds reduction (odds ratio (OR) 0.338; 95% confidence interval (CI) 0.166, 0.688) and odds increment (OR 2.193; 95% CI 1.051, 4.576) to have active pulmonary TB, respectively. In conclusion, trichuriasis and toxoplasmosis may have distinct negative and positive associations respectively with the increase of host susceptibility to TB.

Helminth-induced arginase-1 exacerbates lung inflammation and disease severity in tuberculosis.

Parasitic helminth worms, such as Schistosoma mansoni, are endemic in regions with a high prevalence of tuberculosis (TB) among the population. Human studies suggest that helminth coinfections contribute to increased TB susceptibility and increased rates of TB reactivation. Prevailing models suggest that T helper type 2 (Th2) responses induced by helminth infection impair Th1 immune responses and thereby limit Mycobacterium tuberculosis (Mtb) control. Using a pulmonary mouse model of Mtb infection, we demonstrated that S. mansoni coinfection or immunization with S. mansoni egg antigens can reversibly impair Mtb-specific T cell responses without affecting macrophage-mediated Mtb control. Instead, S. mansoni infection resulted in accumulation of high arginase-1-expressing macrophages in the lung, which formed type 2 granulomas and exacerbated inflammation in Mtb-infected mice. Treatment of coinfected animals with an antihelminthic improved Mtb-specific Th1 responses and reduced disease severity. In a genetically diverse mouse population infected with Mtb, enhanced arginase-1 activity was associated with increased lung inflammation. Moreover, in patients with pulmonary TB, lung damage correlated with increased serum activity of arginase-1, which was elevated in TB patients coinfected with helminths. Together, our data indicate that helminth coinfection induces arginase-1-expressing type 2 granulomas, thereby increasing inflammation and TB disease severity. These results also provide insight into the mechanisms by which helminth coinfections drive increased susceptibility, disease progression, and severity in TB.

The immune response to tuberculosis infection in the setting of Helicobacter pylori and helminth infections.

We screened 176 healthy, adult (aged 18-55 years) US refugees from tuberculosis (TB)-endemic countries to evaluate whether cytokine responses to latent TB infection (LTBI) are modified in the setting of concurrent H. pylori and helminth infection. As measured by the Quantiferon-TB GOLD interferon-γ release assay, a total 38 (22%) subjects had LTBI, of which 28 (74%) also were H. pylori seropositive and/or helminth infected. Relative to ten subjects with LTBI only, 16 subjects with concurrent H. pylori infection had significantly elevated levels of IFN-γ, and nine subjects with both H. pylori and helminth infection had significantly elevated levels of IFN-γ, IL-2, IL-13, and IL-5. H. pylori is associated with enhanced IFN-γ responses to TB, even in the setting of concurrent helminth infection. Efficacy of TB vaccines may vary with the co-existence of these three infections in the developing world.

Malaria infections do not compromise vaccine-induced immunity against tuberculosis in mice.

BACKGROUND: Given the considerable geographic overlap in the endemic regions for malaria and tuberculosis, it is probable that co-infections with Mycobacterium tuberculosis and Plasmodium species are prevalent. Thus, it is quite likely that both malaria and TB vaccines may be used in the same populations in endemic areas. While novel vaccines are currently being developed and tested individually against each of these pathogens, the efficacy of these vaccines has not been evaluated in co-infection models. To further assess the effectiveness of these new immunization strategies, we investigated whether co-infection with malaria would impact the anti-tuberculosis protection induced by four different types of TB vaccines in a mouse model of pulmonary tuberculosis. PRINCIPAL FINDINGS: Here we show that the anti-tuberculosis protective immunity induced by four different tuberculosis vaccines was not impacted by a concurrent infection with Plasmodium yoelii NL, a nonlethal form of murine malaria. After an aerogenic challenge with virulent M. tuberculosis, the lung bacterial burdens of vaccinated animals were not statistically different in malaria infected and malaria naïve mice. Multi-parameter flow cytometric analysis showed that the frequency and the median fluorescence intensities (MFI) for specific multifunctional T (MFT) cells expressing IFN-γ, TNF-α, and/or IL-2 were suppressed by the presence of malaria parasites at 2 weeks following the malaria infection but was not affected after parasite clearance at 7 and 10 weeks post-challenge with P. yoelii NL. CONCLUSIONS: Our data indicate that the effectiveness of novel TB vaccines in protecting against tuberculosis was unaffected by a primary malaria co-infection in a mouse model of pulmonary tuberculosis. While the activities of specific MFT cell subsets were reduced at elevated levels of malaria parasitemia, the T cell suppression was short-lived. Our findings have important relevance in developing strategies for the deployment of new TB vaccines in malaria endemic areas.

El comportamiento de la tuberculosis pulmonar: características sociodemográficas, clínicas-bacteriológicas y de evaluacion del tratamiento. Un estudio en el Hospital de Neumonología Dr. Gumersindo Sayago de Santiago del Estero años 2000-2007 / The behavior of pulmonary tuberculosis: sociodemographic, clinical-bacteriological evaluation and treatment. A study of Pneumology Hospital Dr. Gumersindo Sayago de Santiago del Estero

La tuberculosis está reconocida como uno de los principales problemas de salud pública en la mayoría de los países del mundo y en la actualidad considerada como enfermedad emergente. Por ello se decidió estudiar el comportamiento de la tuberculosis pulmonar en el Hospital Neumonólogico “Gumersindo Sayago” de la provincia de Santiago del Estero.El estudio es descriptivo, prospectivo y longitudinal. La población la conforman 840 casos y es de carácter intencional y estadística. Se describen las variables Independientes (edad, sexo, residencia) y Dependientes (Motivo de Consulta, Bacteriología, Evaluación por Cohortes) Se manejo fuentes secundarias, recopilando los datos en una matriz realizada en Microsoft, presentados en tablas simples y de doble entrada, gráficos aritméticos y mapas semaforizados elaborados en Office 2003, Microsoft Word y Excel y para la exposición en Power Point. La investigación comprende 8 años, y se obtuvieron los siguientes resultados en ese periodo: Resultaron del sexo masculino el 56 por ciento y el 44 por ciento femenino.La edad más afectada fue de los 55 a 59 años con 96 casos, seguido de 50 a 54 con 86 casos. El mayor registro fue en departamento capital (293), seguido por Banda (189) y los departamentos Robles y Río Hondo en el interior.Los centros urbanos tuvieron un 67.7 por ciento de los registros en relación al 32.2 por ciento identificados en la población rural. En la Clasificación Bacteriológica, tuvo confirmación etiológica el 74 por ciento de los casos, predominando el Examen Directo ante el Cultivo (+), un 24 por ciento resulto (-) y un 2 por ciento no se realizó. En Motivo de Consulta, los Sintomáticos Respiratorios alcanzaron el 97, 4 por ciento, Contacto 0,6 por ciento, Examen de Salud 1,9 y Otros 0,1En la Evaluación del Tratamiento se identifica un 73 por ciento de Éxito, 16 por ciento de Abandono, 6 por ciento Fallecidos y Trasladados el 5 por ciento.

Are intestinal helminths risk factors for developing active tuberculosis?

OBJECTIVES: To determine the prevalence of intestinal helminth infections in active tuberculosis patients and their healthy household contacts and to assess its association with active TB in an area endemic for both types of infections. METHODS: Smear-positive pulmonary TB patients and healthy household contacts were tested for intestinal helminths using direct microscopy and the formol-ether concentration techniques. Three consecutive stool samples were examined before the start of TB chemotherapy. Sputum microscopy was done using the sodium hypochlorite concentration techniques. Participants were also tested for HIV by commercial sandwich enzyme linked immunosorbent assay. RESULTS: The study population consisted of 230 smear-positive TB patients and 510 healthy household contacts. The prevalence of intestinal helminths was 71% in patients and 36% in controls. HIV seroprevalence was significantly higher in patients than in controls (46.7%vs. 11.6%, P < 0.001). Conditional logistic regression analysis showed a strong association between TB and intestinal helminth infection (OR = 4.2, 95% CI 2.7-5.9, P < 0.001), and between TB and HIV infection (OR = 7.8, 95% CI 4.8-12.6, P < 0.0001). The odds of being a TB patient increased with the number of helminth species per person: in individuals with mono-infection it was 4.3 (95% CI 2.8-6.8); in people infected with two species was 4.7 (95% CI 2.5-8.7), and in patients infected with three or more helminths was 12.2 (3.9-52.6). CONCLUSION: Intestinal helminth infection may be one of the risk factors for the development of active pulmonary TB in addition to HIV infection. This finding may have important implications in the control of TB in helminth endemic areas of the world.

Distribution of IFN-gamma, IL-4 and TNF-alpha protein and CD8 T cells producing IL-12p40 mRNA in human lung tuberculous granulomas.

In order to examine the immune response at the site of pathology in tuberculosis, we analysed cytokines present in lung granulomas, their associations with each other and with caseous necrosis as well as the phenotype of the cellular infiltrate. Paraffin-embedded tissue from the lungs of seven patients with pulmonary tuberculosis was analysed by immunohistochemistry and in situ hybridization to detect interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and interleukin-4 (IL-4) proteins and IL-12p40 mRNA. All seven patients had granulomas staining positive for IFN-gamma, TNF-alpha and IL-12p40, but only four stained positive for IL-4. Cells with the morphology of lymphocytes, macrophages and giant cells expressed TNF-alpha, IFN-gamma and IL-4 protein. Furthermore, CD68-positive myeloid cells expressed IL-12p40 mRNA, as expected, but a subset of CD3-positive lymphocytes also expressed this mRNA. These lymphocytes producing IL-12p40 also stained positive for CD8 but not CD4. A total of 141 granulomas were scored for the presence or absence of cytokine or necrosis and two major associations were identified. The first association was between IFN-gamma and IL-12, with 76% of granulomas staining positive for both cytokines. Unexpectedly, those granulomas positive for IL-4 were always positive for IFN-gamma. The second association was between TNF-alpha and caseous necrosis, where all necrotic granulomas were TNF-alpha positive. This association was modulated by IL-4. Therefore, heterogeneity of cellular infiltrate and cytokine expression is observed between adjacent granulomas in the same patient.

Effect of deworming on human T cell responses to mycobacterial antigens in helminth-exposed individuals before and after bacille Calmette-Guérin (BCG) vaccination.

The protective efficacy of BCG vaccination against pulmonary tuberculosis (TB) is highly variable in different populations. The reason remains to be elucidated. This study aims to investigate the possible effect of intestinal helminths on the immune response to PPD in naturally immunized or BCG-vaccinated humans. The study population was assessed for helminthic infection and those found to be positive were randomly assigned to either an albendazole treatment group or a control group who received a placebo. The immune response to PPD was compared between the two groups. In addition, subjects who were tuberculin skin test-negative in both groups were BCG vaccinated and later on tested for PPD-specific responses. Albendazole induced elimination/or reduction in intestinal worms resulting in a significant improvement in T cell proliferation and in interferon-gamma production by peripheral blood mononuclear cells (PBMC) stimulated with PPD. Moreover, BCG vaccination significantly improved PPD-specific immune responses in the treated group but not in the placebo group. The differences in the in vivo skin test responses were not significant. The data show that cellular immune responses to PPD are reduced in persons with concurrent helminthic infections, perhaps reflecting a lowered resistance to mycobacterial infections. This could explain, at least in part, the reduced efficacy of BCG against TB in helminth-endemic areas of the world.

[Experimental models of combined tuberculosis-opisthorchiasis pathology]. / Eksperimental'nye modeli sochetannoi patologii tuberkulez--opistorkhoz.

An experimental model of the combined course of tuberculosis and opisthorchiasis is presented in the following variants: pulmonary tuberculosis-chronic opisthorchiasis, acute and chronic opisthorchiasis in combination with tuberculosis contamination, BCG and opisthorchiasis. Specific changes in the combined pathology are shown which differ from those that accompany each of the nosological forma. Data obtained in bacteriologic, parasitologic, immunologic and pathomorphologic studies were used to describe characteristic features of the models. The results obtained allow a suggestion that parasitocenosis of mycobacteria and Opisthorchis organisms has an influence on the pathogenesis, clinical picture, diagnosis, treatment, epidemiology and prevention of tuberculosis-opisthorchiasis combined pathology.

Pulmonary schistosomiasis resembling acute pulmonary tuberculosis.

Pulmonary involvement of schistosomiasis is usually characterized by a miliary mottling or diffuse nodular infiltrates. In most cases, pulmonary involvement is associated with an apparent clinical involvement of other organs. This report describes a 35 yr old patient who developed a cavity, a parenchymatous infiltrate and hilar adenopathy in association with pulmonary schistosomiasis. Schistosoma eggs were demonstrated in transbronchial biopsies from the lung. Pulmonary involvement of schistosomiasis is reviewed and atypical features are discussed, which may lead to diagnostic difficulties, particularly compared to tuberculosis.