The accuracy of an electronic nose to diagnose tuberculosis in patients referred to an expert centre.

INTRODUCTION: An electronic nose (eNose) device has shown a high specificity and sensitivity to diagnose or rule out tuberculosis (TB) in the past. The aim of this study was to evaluate its performance in patients referred to INERAM. METHODS: Patients aged ≥15 years were included. A history, physical examination, chest radiography (CRX) and microbiological evaluation of a sputum sample were performed in all participants, as well as a 5-minute breath test with the eNose. TB diagnosis was preferably established by the gold standard and compared to the eNose predictions. Univariate and multivariate logistic regression analyses were performed to assess potential risk factors for erroneous classification results by the eNose. RESULTS: 107 participants with signs and symptoms of TB were enrolled of which 91 (85.0%) were diagnosed with TB. The blind eNose predictions resulted in an accuracy of 50%; a sensitivity of 52.3% (CI 95%: 39.6-64.7%) and a specificity of 36.4% (CI 95%: 12.4-68.4%). Risk factors for erroneous classifications by the eNose were older age (multivariate analysis: OR 1.55, 95% CI 1.10-2.18, p = 0.012) and antibiotic use (multivariate analysis: OR 3.19, 95% CI 1.06-9.66, p = 0.040). CONCLUSION: In this study, the accuracy of the eNose to diagnose TB in a tertiary referral hospital was only 50%. The use of antibiotics and older age represent important factors negatively influencing the diagnostic accuracy of the eNose. Therefore, its use should probably be restricted to screening in high-risk communities in less complex healthcare settings.

Exploring the "Latin American Mediterranean" family and the RDRio lineage in Mycobacterium tuberculosis isolates from Paraguay, Argentina and Venezuela.

BACKGROUND: The Latin American & Mediterranean (LAM) spoligotype family is one of the most successful genotype of Mycobacterium tuberculosis worldwide and particularly prevalent in South-America. Within this family, a sublineage named Region of Difference Rio (RDRio) was reported initially in Brazil and is characterized by a genomic deletion of about 26.3 kb. This lineage seems to show a specific adaptation to the Euro-Latin American population. In this context, we sought to evaluate the LAM family and the presence of the RDRio genotype in samples from three Latin American countries including Paraguay, Venezuela and Argentina. To detect LAM strains reliably we applied a typing scheme using spoligotyping, 12 loci MIRU-VNTR, the Ag85C103 SNP and the regions of difference RDRio and RD174. IS6110-RFLP results were also used when available. RESULTS: Genotyping of 413 M. tuberculosis isolates from three Latin-American countries detected LAM (46%) and the ill-defined T clade (16%) as the most frequent families. The highest clustering rate was detected in the sample population from the city of Caracas in Venezuela. We observed considerable differences in the presence of the RDRio lineage, with high frequency in Caracas-Venezuela (55%) and low frequency in Buenos Aires-Argentina (11%) and Paraguay (10%). The molecular markers (RD174, Ag85C103, MIRU02-MIRU40 signature) of the RDRio lineage were essentially confirmed. For the LAM family, the most polymorphic loci were MIRU40, MIRU31, MIRU10, MIRU26, MIRU16 and the least polymorphic MIRU24, MIRU20, MIRU04, MIRU23. CONCLUSIONS: Our results suggest a differential adaptation of LAM-sublineages in neighboring populations and that RDRio strains spread regionally with different rates of distribution. The Ag85C SNP and RDs (RD174, RDRio) tested in this study can in fact facilitate molecular epidemiological studies of LAM strains in endemic settings and low-income countries.

The potential of a portable, point-of-care electronic nose to diagnose tuberculosis.

INTRODUCTION: Tuberculosis (TB) is the leading cause of death due to an infectious disease worldwide. Especially in low-income countries, new diagnostic techniques that are accessible, inexpensive and easy-to-use, are needed to shorten transmission time and initiate treatment earlier. OBJECTIVE: We conducted a study with a handheld, point-of-care electronic nose (eNose) device to diagnose TB through exhaled breath. SETTING: This study includes a total of 110 patients and visitors of an expert centre of respiratory diseases in Asunción, Paraguay. TB diagnosis was established by culture of Mycobacterium tuberculosis complex and compared with the eNose results in two phases. RESULTS: The calibration phase, including only culture confirmed TB cases versus healthy people, demonstrated a sensitivity and specificity of 91% and 93% respectively. The confirmation phase, including all participants, showed a sensitivity of 88% and a specificity of 92%. The eNose showed high acceptance rate among participants, and was easy to operate. CONCLUSION: The eNose resulted in a powerful technique to differentiate between healthy people and TB patients. Its comfort, speed and usability promise great potential in vulnerable groups, in remote areas and hospital settings to triage patients with suspicion of TB.

Prevalence of tuberculosis respiratory symptoms and associated factors in the indigenous populations of Paraguay (2012)

BACKGROUND The prevalence of respiratory symptoms and confirmed tuberculosis (TB) among indigenous groups in Paraguay is unknown. METHODS This study assessed the prevalence of respiratory symptoms, confirmed pulmonary TB, and associated socio-economic factors among indigenous Paraguayan populations. Indigenous persons residing in selected communities were included in the study. A total of 24,352 participants were interviewed at home between October and December 2012. Respiratory symptomatic individuals were defined as those with respiratory symptoms of TB. A hierarchical Poisson regression analysis was performed with four levels: individual characteristics, living conditions and environmental characteristics, source of food, and type of nutrition. FINDINGS In this study, 1,383 participants had respiratory symptoms (5.7%), but only 10 had culture-confirmed TB (41/100,000 inhabitants). The small number of cases did not allow evaluation of the risk factors for TB. Age older than 37 years was associated with a two-fold increased risk of symptoms. Female sex; family history of TB; type of housing; home heating; a lack of hunting, fishing, or purchasing food; and a lack of vegetable consumption were also associated with the presence of symptoms. A lack of cereal consumption had a protective effect. Members of the Ayoreo or Manjui ethnic groups had a three-fold increased risk of symptoms. MAIN CONCLUSION Individual characteristics, dietary habits, and belonging to specific ethnic groups were associated with respiratory symptoms.

Prevalence of tuberculosis respiratory symptoms and associated factors in the indigenous populations of Paraguay (2012).

BACKGROUND: The prevalence of respiratory symptoms and confirmed tuberculosis (TB) among indigenous groups in Paraguay is unknown. METHODS: This study assessed the prevalence of respiratory symptoms, confirmed pulmonary TB, and associated socio-economic factors among indigenous Paraguayan populations. Indigenous persons residing in selected communities were included in the study. A total of 24,352 participants were interviewed at home between October and December 2012. Respiratory symptomatic individuals were defined as those with respiratory symptoms of TB. A hierarchical Poisson regression analysis was performed with four levels: individual characteristics, living conditions and environmental characteristics, source of food, and type of nutrition. FINDINGS: In this study, 1,383 participants had respiratory symptoms (5.7%), but only 10 had culture-confirmed TB (41/100,000 inhabitants). The small number of cases did not allow evaluation of the risk factors for TB. Age older than 37 years was associated with a two-fold increased risk of symptoms. Female sex; family history of TB; type of housing; home heating; a lack of hunting, fishing, or purchasing food; and a lack of vegetable consumption were also associated with the presence of symptoms. A lack of cereal consumption had a protective effect. Members of the Ayoreo or Manjui ethnic groups had a three-fold increased risk of symptoms. MAIN CONCLUSION: Individual characteristics, dietary habits, and belonging to specific ethnic groups were associated with respiratory symptoms.

First insight into Mycobacterium tuberculosis genetic diversity in Paraguay.

BACKGROUND: We present a picture of the biodiversity of Mycobacterium tuberculosis in Paraguay, an inland South American country harboring 5 million inhabitants with a tuberculosis notification rate of 38/100,000. RESULTS: A total of 220 strains collected throughout the country in 2003 were classified by spoligotyping into 79 different patterns. Spoligopatterns of 173 strains matched 51 shared international types (SITs) already present in an updated version of SpolDB4, the global spoligotype database at Pasteur Institute, Guadeloupe. Our study contributed to the database 13 new SITs and 15 orphan spoligopatterns. Frequencies of major M. tuberculosis spoligotype lineages in our sample were as follows: Latin-American & Mediterranean (LAM) 52.3%, Haarlem 18.2%, S clade 9.5%, T superfamily 8.6%, X clade 0.9% and Beijing clade 0.5%. Concordant clustering by IS6110 restriction fragment length polymorphism (RFLP) and spoligotyping identified transmission in specific settings such as the Tacumbu jail in Asuncion and aboriginal communities in the Chaco. LAM genotypes were ubiquitous and predominated among both RFLP clusters and new patterns, suggesting ongoing transmission and adaptative evolution in Paraguay. We describe a new and successfully evolving clone of the Haarlem 3 sub-lineage, SIT2643, which is thus far restricted to Paraguay. We confirmed its clonality by RFLP and mycobacterial interspersed repetitive unit (MIRU) typing; we named it "Tacumbu" after the jail where it was found to be spreading. One-fifth of the spoligopatterns in our study are rarely or never seen outside Paraguay and one-tenth do not fit within any of the major phylogenetic clades in SpolDB4. CONCLUSION: Lineages currently thriving in Paraguay may reflect local host-pathogen adaptation of strains introduced during past migrations from Europe.