BackgroundBringing reliable and accurate tuberculosis (TB) diagnosis closer to patients is a key priority for global TB control. Molbio Diagnostics have developed the Truenat point-of-care molecular assays for detection of TB and rifampicin (RIF) resistance.MethodsWe conducted a prospective multicentre diagnostic accuracy study at 19 primary health care centres and seven reference laboratories in Peru, India, Ethiopia and Papua New Guinea to estimate the diagnostic accuracy of the point-of-care Truenat MTB, MTB Plus and MTB-RIF Dx assays for pulmonary TB using culture and phenotypic drug susceptibility testing as the reference standard, compared to Xpert MTB/RIF or Ultra.ResultsOf 1807 enrolled participants with TB signs/symptoms, 24% were culture positive for Mycobacterium tuberculosis, of which 15% were RIF-resistant. In microscopy centres, the pooled sensitivity of Truenat MTB and Truenat MTB Plus was 73% [95% CI: 67, 78] and 80% [95% CI: 75, 84], respectively. Among smear-negative specimens, sensitivities were 36% [95% CI: 27, 47] and 47% [95% CI: 37, 58], respectively. Sensitivity of Truenat MTB-RIF was 84% [95% CI: 62, 95]. Truenat assays showed high specificity. Head-to-head comparison in the central reference laboratories suggested that the Truenat assays have similar performance to Xpert MTB/RIF.ConclusionWe found performance of Molbio's Truenat MTB, MTB plus and MTB-RIF Dx assays to be comparable to that of the Xpert MTB/RIF assay. Performing the Truenat tests in primary health care centres with very limited infrastructure was feasible. These data supported the development of a WHO policy recommendation of the Molbio assays.

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Background Bartonella bacilliformis is the aetiological agent of Carrión's disease, a biphasic and highly lethal illness formerly restricted to the South American Andes that is now spreading to adjacent areas. Reliable serodiagnostic approaches and vaccines are urgently needed. In this study, we aimed to identify immunodominant proteins of B bacilliformis and to establish novel and reliable serodiagnostic tools. MethodsWe used a reverse vaccinology approach in combination with an analysis of heterologous genomic expression libraries to identify immunodominant proteins, on the basis of the genome sequences of B bacilliformis strains KC583 and KC584. Antigens were screened with serum samples collected from Peruvian patients with B bacilliformis infections and from German healthy blood donors without history of travel to South America. We further analysed immunoreactive proteins of B bacilliformis with immunoblotting and line blots. We used selected target proteins to develop a diagnostic ELISA. To assess the performance of this ELISA, we did receiver operating characteristic analyses to assess the area under the curve, cutoff values, sensitivities, and specificities with 95% CIs. FindingsWe used serum samples obtained between Dec 23, 1990, and May 5, 2018, from 26 Peruvian patients with B bacilliformis infections and serum samples taken between Aug 28 and Aug 31, 2020, from 96 healthy German blood donors. 21 potentially immunodominant proteins were identified and recombinantly expressed, and their reactivity was assessed with immunoblotting and line blots. Of these 21 antigens, 14 were found to be immunoreactive. By using serum samples of Peruvian patients with Carrión's disease and of healthy German blood donors, we identified three antigens (porin B, autotransporter E, and hypothetical protein B) as suitable immunodominant antigens, and we applied them in a diagnostic ELISA using two different antigen combinations (porin B plus autotransporter E and porin B plus autotransporter E plus hypothetical protein B). For the combination of porin B and autotransporter E, with optical density measured at 450 nm (OD 450 ) cutoff value of 0•29, sensitivity was 80•8% (95% CI 60•7-93•5) and specificity was 94•8% (88•3-98•3) for all Peruvian patient samples. For a combination of porin B, autotransporter E, and hypothetical protein B, with an OD 450 cutoff of 0•34, sensitivity was 76•9% (56•4-91•0) and specificity was 93•8% (86•9-97•7) for all Peruvian patient samples. Interpretation This novel ELISA could represent a useful serodiagnostic tool for future epidemiological studies of B bacilliformis in endemic areas. Additionally, the immunodominant antigens we have identified could provide a first basis for future vaccine development to prevent the highly lethal Carrión's disease. Funding DRUID (Novel Drug Targets against Poverty-Related and Neglected Tropical Infectious Diseases) Initiative and Robert Koch Institute.

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Cough assessment is central to the clinical management of respiratory diseases, including tuberculosis (TB), but strategies to objectively and unobtrusively measure cough are lacking. Acoustic epidemiology is an emerging field that uses technology to detect cough sounds and analyze cough patterns to improve health outcomes among people with respiratory conditions linked to cough. This field is increasingly exploring the potential of artificial intelligence (AI) for more advanced applications, such as analyzing cough sounds as a biomarker for disease screening. While much of the data are preliminary, objective cough assessment could potentially transform disease control programs, including TB, and support individual patient management. Here, we present an overview of recent advances in this field and describe how cough assessment, if validated, could support public health programs at various stages of the TB care cascade.

La Bartonelosis (también llamada Enfermedad de Carrión o Verruga Peruana) es una enfermedad clásica de la medicina peruana. En las últimas dos décadas se han producido nuevos conocimientos e investigacio- nes, que han roto muchos paradigmas de esta enfer- medad, los cuales son presentadas en esta revisión.

Background Diabetes mellitus (DM) patients are three times more likely to develop tuberculosis (TB) than the general population. Active TB screening in people with DM is part of a bidirectional approach. The aim of this study was to conduct pragmatic active TB screening among DM patients in four countries to inform policy. Methods DM patients were recruited in Indonesia (n=809), Peru (n=600), Romania (n=603) and South Africa (n=51). TB cases were diagnosed using an algorithm including clinical symptoms and chest X-ray. Presumptive TB patients were examined with sputum smear and culture. Results A total of 171 (8.3%) individuals reported ever having had TB (South Africa, 26%; Indonesia, 12%; Peru, 7%; Romania, 4%), 15 of whom were already on TB treatment. Overall, 14 (0.73% [95% confidence interval 0.40 to 1.23]) TB cases were identified from screening. Poor glucose control, smoking, lower body mass index, education and socio-economic status were associated with newly diagnosed/current TB. Thirteen of the 14 TB cases diagnosed from this screening would have been found using a symptom-based approach. Conclusions These data support the World Health Organization recommendation for routine symptom-based screening for TB in known DM patients in high TB-burden countries. DM patients with any symptoms consistent with TB should be investigated and diagnostic tools should be easily accessible.

BackgroundType 2 diabetes mellitus (T2DM) has been associated with infectious diseases; however, whether T2DM is associated with bacterial-resistant infections has not been thoroughly studied. We ascertained whether people with T2DM were more likely to experience resistant infections in comparison to T2DM-free individuals.MethodsSystematic review and random-effects meta-analysis. The search was conducted in Medline, Embase and Global Health. We selected observational studies in which the outcome was resistant infections (any site), and the exposure was T2DM. We studied adult subjects who could have been selected from population-based or hospital-based studies. I2 was the metric of heterogeneity. We used the Newcastle-Ottawa risk of bias scale.ResultsThe search retrieved 3370 reports, 97 were studied in detail and 61 (449 247 subjects) were selected. Studies were mostly cross-sectional or case–control; several infection sites were studied, but mostly urinary tract and respiratory infections. The random-effects meta-analysis revealed that people with T2DM were twofold more likely to have urinary tract (OR=2.42; 95% CI 1.83 to 3.20; I2 19.1%) or respiratory (OR=2.35; 95% CI 1.49 to 3.69; I2 58.1%) resistant infections. Although evidence for other infection sites was heterogeneous, they consistently suggested that T2DM was associated with resistant infections.ConclusionsCompelling evidence suggests that people with T2DM are more likely to experience antibiotic-resistant urinary tract and respiratory infections. The evidence for other infection sites was less conclusive but pointed to the same overall conclusion. These results could guide empirical treatment for patients with T2DM and infections.