Meeting for the development of action plans toward the interruption of transmission and elimination of leprosy in the Region of the Americas. Antigua, Guatemala, 9–11 July 2024. Meeting report

From 9 to 11 July 2024, a meeting on leprosy elimination was held in Antigua, Guatemala, bringing together experts in leprosy management and program coordinators from 14 countries across the Americas. Organized by the Pan American Health Organization (PAHO) with the support of the World Health Organization, the meeting aimed to address the critical challenge of interrupting transmission and eliminating leprosy in the Region. During the event, participants reviewed the progress made in implementing the Road Map for Neglected Tropical Diseases 2021–2030 and achieving the objectives of PAHO’s Disease Elimination Initiative. Key strategies were discussed, including the use of tools such as the Leprosy Elimination Monitoring Tool and the Leprosy Program and Transmission Assessment, which help track progress toward interrupting transmission and eliminating the disease. Workshops emphasized the importance of developing national action plans tailored to the specific needs of each country to ensure an effective elimination process. The event fostered collaboration among participating countries, reaffirming a joint commitment to achieving the milestones for leprosy elimination in the Americas. The outcomes of this meeting are expected to influence the regional approach to interrupting transmission and eliminating leprosy, highlighting the need for a clear vision and coordinated efforts to advance the elimination not only of leprosy but also of other neglected tropical diseases.

Reunión para elaborar planes de acción a fin de interrumpir la transmisión y eliminar la lepra en la Región de las Américas. Antigua (Guatemala), del 9 al 11 de julio del 2024. Informe de la reunión

La Reunión sobre Lepra en Guatemala, celebrada del 9 al 11 de julio de 2024, reunió a expertos internacionales en salud, representantes gubernamentales y coordinadores de programas para discutir el estado actual de los esfuerzos de control de la lepra y explorar formas innovadoras de abordar la enfermedad. Organizado por la OPS y apoyado por las autoridades sanitarias nacionales, el evento fue un acontecimiento clave en la búsqueda de soluciones para los desafíos pendientes en la eliminación de la lepra en América Latina. Durante los tres días de la reunión, los participantes participaron en una serie de talleres, presentaciones y discusiones colaborativas centradas en el fortalecimiento de los sistemas de vigilancia, la mejora del acceso al diagnóstico y tratamiento, y el alcance a las comunidades marginadas. Uno de los temas principales fue la necesidad de enfoques integrados en la atención médica que prioricen el diagnóstico temprano y el tratamiento continuo para prevenir la discapacidad y el estigma asociados a la lepra. El evento también destacó la importancia de mantener la voluntad política y asegurar fondos a largo plazo para apoyar los programas nacionales de lepra. En particular, representantes de varios países de América Latina compartieron sus experiencias con intervenciones exitosas basadas en la comunidad, enfatizando la importancia del protagonismo local en los esfuerzos de control de la lepra. Además de compartir mejores prácticas y casos de éxito, la reunión sirvió como plataforma para desarrollar un plan de acción adaptado a las necesidades específicas de la región. Este plan destaca la colaboración entre gobiernos, organizaciones no gubernamentales y comunidades locales, así como la necesidad de continuar innovando en el tratamiento y la vigilancia. Se espera que los resultados de esta reunión tengan un impacto significativo en la lucha contra la lepra en América Latina, ofreciendo una renovada esperanza y determinación para eliminar esta enfermedad como una preocupación de salud pública de una vez por todas.

Lepra infantil en Buenos Aires. Reporte de cuatro casos / Childhood leprosy in Buenos Aires: four cases report

La lepra infantil, aquella que afecta a niños de hasta 14 años, se caracteriza por la demora en su diagnóstico, ya que habitualmente es confundida con otras dermatosis. Su presencia en un niño es un indicador epidemiológico relevante, dado que señala la transmisión activa de la enfermedad. Presentamos 4 pacientes de entre 5 y 14 años asistidos en un hospital público de la Ciudad de Buenos Aires. Dos pacientes presentaron lepra borderline tuberculoide; uno, lepra lepromatosa; y otra, lepra indeterminada. La Organización Mundial de la Salud facilita la terapéutica para la población entre 10 y 14 años, pero no contempla a los menores de 10 años. Esta dificultad implica adecuar la dosis y la forma farmacéutica a cada paciente menor de la edad referida. Finalmente, es de destacar que el diagnóstico de los pacientes llevó al diagnóstico y tratamiento de la enfermedad en convivientes adultos.

Childhood leprosy, which affects children up to 14 years old, is characterized by a delay in diagnosis since it is usually confused with other dermatoses. Its presence in a child is a relevant epidemiological indicator since it signals active disease transmission. We present 4 patients between 5 and 14 years old who attended a public hospital in Buenos Aires ­two patients with borderline tuberculoid leprosy, one with lepromatous leprosy, and one with indeterminate leprosy.The World Health Organization provides therapy for people between 10 and 14 but does not consider children under 10. This difficulty implies adapting the dosage and pharmaceutical form to each patient under this age. Finally, it should be noted that the diagnosis of the patients led to the diagnosis and treatment of the disease in adult cohabitants.

Patulin inhibition of specific apple microbiome members uncovers Hanseniaspora uvarum as a potential biocontrol agent.

Penicillium expansum is a major postharvest pathogen of apples, causing loss in fruits through tissue damage, as well as in apple products due to contamination with the mycotoxin patulin. During infections, patulin is a cultivar-dependent virulence factor that facilitates apple lesion development. Patulin also has characterized antimicrobial activity and is important for inhibiting other competitive phytopathogens, but the role of this inhibitory activity has not been investigated in the context of the apple microbiome. In our current study, we isolated 68 apple microbiota and characterized their susceptibility to P. expansum extracts. We found Gram-negative bacteria and Basidiomycete yeast to demonstrate largely patulin-specific growth inhibition compared to Gram-positive and Ascomycete isolates. From co-cultures, we identified a Hanseniaspora and Gluconobacter pairing that reduced P. expansum biomass and found that Hanseniaspora uvarum alone is sufficient to reduce apple disease progression in vivo. We investigated possible mechanisms of H. uvarum biocontrol activity and found modest inhibition on apple puree plates, as well as a trend toward lower patulin levels at the wound site. Active biocontrol activity required live yeast, which also were effective in controlling Botrytis cinerea apple infections. Lastly, we explored the breadth of H. uvarum biocontrol activity with over 30 H. uvarum isolates and found consistent inhibition of P. expansum apple disease.

The Publication and Historical Significance of Modern Chinese Medical Reports.

Unlike Western medical journals such as The Lancet which focused on Western-centric medical cases, Medical Reports analyzed medical and sanitary issues in East Asia, including China, Korea, and Japan and sought solutions to these problems. Medical Reports, a medical project initiated by the Chinese Maritime Customs Service (CMCS) in 1871, aimed to compile reference materials on the health conditions and diseases in ports. It was launched by the British Inspector General Robert Hart, who appointed the British Shanghai Customs Surgeon R. Alexander Jameson as the editor. Beginning in the 1860s, the British-led CMCS began expanding its reach from major cities to border areas, western regions, Taiwan Island, and Hainan Island, as well as territories beyond Qing Dynasty, such as Seoul, Busan, Incheon, Hong Kong, and Macau. This expansion required multinational cooperation, leading to the participation of Customs Surgeons, medical missionaries, and military doctors from ten countries, including the UK, the United States, France, China, Germany, Canada, Portugal, Norway, the Netherlands, and Australia, in the Medical Reports project. The Medical Reports were directly tied to the medical and sanitary initiatives in that community. They were authored by Customs Surgeons from a country with substantial regional influence. An analysis of the authors' nationalities, primary research focuses, and the relationship between the customs regions they covered revealed a statistically significant correlation. Even after Robert Koch discovered bacteria in the late nineteenth century, the miasma theory remained dominant, and most British doctors in India did not acknowledge the possibility that diseases could be caused by parasites. Despite this conservative historical context, the Medical Reports featured progressive research, including studies on leprosy based on germ theory and studies that actively embraced the emerging theory that parasites could be the cause of certain illnesses. In this process, the relatively unknown young physician named Patrick Manson, while working at the CMCS for 13 years, significantly advanced his medical knowledge by publishing numerous studies on filaria in the Medical Reports. His work led to the groundbreaking discovery that mosquitoes transmit infectious diseases. These research achievements pioneered the field of tropical medicine, a discipline that had not been established even in the extensive colonial holdings of France and Britain in tropical regions. Manson's work for the Medical Reports significantly advanced human efforts to prevent and respond to infectious diseases.

Ankle syndesmotic ligaments avulsion fractures: incidence in adult population.

BACKGROUND: Distal tibiofibular syndesmosis injury is often associated with ankle fractures in adults. Injuries to the anterior/posterior inferior tibiofibular ligament (AITFL/PITFL) may present as a mid-substance tear or as an avulsion at insertion. Tibial and fibular avulsion of the AITFL is known as Tillaux fracture and Wagstaffe fracture, respectively. Tibial avulsion of the PITFL is referred to as a Volkmann fracture, and fibular avulsion of the PITFL is still undefined and has not been reported yet. The aim of this study is to summarize the incidence of these four avulsions, that is, tibial and fibular avulsions of the AITFL and PITFL. METHOD: Radiography and computed tomography (CT) imaging data of all adult patients with ankle fractures treated at our hospital between November 2010 and March 2023 were retrospectively analyzed. All ankle fractures were classified according to the Weber-AO and Lauge-Hansen classification systems by two experienced radiologists and two surgeons. The incidence of the four avulsions of the AITFL/PITFL was determined. RESULTS: In total, 1,770 ankle fractures in 1,758 patients were included in this study. The total incidence of avulsions at the four insertions of the AITFL/PITFL (occurring at one, two, or three insertions) was found to be 26.3% (465/1,770). Volkmann fracture had the highest incidence (19.9%, 353/1,770), and it was followed by Tillaux fracture (5.3%, 93/1,770), Wagstaffe fracture (3.3%, 59/1,770), and fibular avulsion of the PITFL (0.5%, 8/1,770). It is noteworthy that fibular avulsion of the PITFL has been reported here for the first time. The incidence of avulsion at one insertion was 23.6% (418/1770) and 2.7% (47/1770) at multiple insertions. CONCLUSION: In adult ankle fractures, avulsion occurs at the four insertions of the AITFL/PITFL in more than 25% of patients. The tibial insertion of the PITFL had the highest incidence of avulsion among the four insertions, while the fibular insertion of the PITFL had the lowest. The four types of avulsions can be isolated or in association with other avulsions. Future research studies on these four types of avulsion fractures would help in accurate diagnosis, decision-making and treatment of ankle Syndesmosis injuries. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Cellular and molecular determinants of bacterial burden in leprosy granulomas revealed by single-cell multimodal omics.

BACKGROUND: Which cell populations that determine the fate of bacteria in infectious granulomas remain unclear. Leprosy, a granulomatous disease with a strong genetic predisposition, caused by Mycobacterium leprae infection, exhibits distinct sub-types with varying bacterial load and is considered an outstanding disease model for studying host-pathogen interactions. METHODS: We performed single-cell RNA and immune repertoire sequencing on 11 healthy controls and 20 patients with leprosy, and integrated single-cell data with genome-wide genetic data on leprosy. Multiplex immunohistochemistry, and in vitro and in vivo infection experiments were conducted to confirm the multimodal omics findings. FINDINGS: Lepromatous leprosy (L-LEP) granulomas with high bacterial burden were characterised by exhausted CD8+ T cells, and high RGS1 expression in CD8+ T cells was associated with L-LEP. By contrast, tuberculoid leprosy (T-LEP) granulomas with low bacterial burden displayed enrichment in resident memory IFNG+ CD8+ T cells (CD8+ Trm) with high GNLY expression. This enrichment was potentially attributable to the communication between IL1B macrophages and CD8+ Trm via CXCL10-CXCR3 signalling. Additionally, IL1B macrophages in L-LEP exhibited anti-inflammatory phenotype, with high APOE expression contributing to high bacterial burden. Conversely, IL1B macrophages in T-LEP were distinguished by interferon-γ induced GBP family genes. INTERPRETATION: The state of IL1B macrophages and functional CD8+ T cells, as well as the relationship between them, is crucial for controlling bacterial persistence within granulomas. These insights may indicate potential targets for host-directed immunotherapy in granulomatous diseases caused by mycobacteria and other intracellular bacteria. FUNDING: The Key research and development program of Shandong Province (2021LCZX07), Natural Science Foundation of Shandong Province (ZR2023MH046), Youth Science Foundation Cultivation Funding Plan of Shandong First Medical University (Shandong Academy of Medical Sciences) (202201-123), National Natural Science Foundation of China (82471800, 82230107, 82273545, 82304039), the China Postdoctoral Science Foundation (2023M742162), Shandong Province Taishan Scholar Project (tspd20230608), Joint Innovation Team for Clinical & Basic Research (202410), Central guidance for local scientific and technological development projects of Shandong Province (YDZX2023058).

Triple Infectious Syndrome: Pulmonary Tuberculosis and HIV in a Case of Pure Neuritic Leprosy With Underlying Diabetes Mellitus.

Pulmonary tuberculosis (PTB), human immunodeficiency virus (HIV), and leprosy are of public health importance, as all three diseases are communicable and contribute to disease burden in society. Co-infection with these three entities is extremely rare but leads to significant mortality and morbidity. We report a case that highlights the diagnostic challenges and therapeutic management of a patient who was diagnosed with pure neuritic leprosy on multibacillary-multidrug therapy (MB-MDT) and subsequently co-diagnosed with PTB and HIV. The patient was started on anti-tubercular therapy and anti-retroviral therapy for treatment under India's national health programs, which play a major role in treating those of low socioeconomic status. The optimization of these therapeutic drugs is quite challenging during treatment due to potential drug interactions and toxicities. High clinical suspicion is required to rule out PTB before initiating rifampicin-containing MB-MDT, which can lead to rifampicin-resistant TB and screening for HIV. As there is a social stigma associated with these patients, they require good psychological support during and after treatment.

Applying the Techniques of Materials Science towards an Understanding of the Process of Canine Intervertebral Disc Degeneration.

Intervertebral disc degeneration in dogs occurs in an accelerated way and involves calcification, which is associated with disc herniation or extrusion. The degenerative process is complex and involves the transformation of collagen fibres, loss of proteoglycans and notochord cells and a reduction in water content; however, how these processes are linked to future disc extrusion remains unknown. We have employed techniques including Fourier Transform Infra-red Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Uniaxial Compression Loading and Atomic Force Microscopy (AFM) in an attempt to gain a greater understanding of the degenerative process and its consequences on the physical properties of the disc. FTIR verified by TEM demonstrated that calcium phosphate exists in an amorphous state within the disc and that the formation of crystalline particles of hydroxyapatite occurs prior to disc extrusion. AFM identified crystalline agglomerates consistent with hydroxyapatite as well as individual collagen fibres. SEM enabled the identification of regions rich in calcium, phosphorous and oxygen and allowed the visualization of the topographical landscape of the disc. Compression testing generated stress/strain curves which will facilitate investigation into disc stiffness. Ongoing work is aimed at identifying potential areas of intervention in the degenerative process as well as further characterizing the role of calcification in disc extrusion.

Implications of drug resistance in leprosy: disease course, reactions and the use of novel drugs.

Leprosy remains a significant neglected tropical disease despite the goal of elimination having been achieved in various endemic nations over the past two decades. Reactional episodes complicate the disease course, resulting in deformities and disability. The main aim of treatment is to kill Mycobacterium leprae and decrease the bacterial load, which could help prevent further bacilli transmission. A major concern in breaking the chain of transmission and possibly for recurrent reactions is the role of drug-resistant bacilli. Though some data is available on the background prevalence of drug resistance in leprosy, there is a paucity of studies that look for resistance specifically in leprosy reactions. Administration of long-term steroids or immunosuppressants for chronic and recurrent responses in the presence of drug resistance has the twin effect of perpetuating the multiplication of resistant bacilli and encouraging the dissemination of leprosy. The increasing trend of prescribing second-line drugs for leprosy or type 2 reactions without prior assessment of drug resistance can potentially precipitate a severe public health problem as this can promote the development of resistance to second-line drugs as well. A comprehensive multicenter study, including drug resistance surveillance testing in cases of reactions, is necessary, along with the current measures to stop the spread of leprosy. Here, we have detailed the history of drug resistance in leprosy, given pointers on when to suspect drug resistance, described the role of resistance in reactions, methods of resistance testing, and the management of resistant cases with second-line therapy.

Thermothelomyces thermophilus exo- and endo-glucanases as tools for pathogenic E. coli biofilm degradation.

The escalating prevalence of drug-resistant pathogens not only jeopardizes the effectiveness of existing treatments but also increases the complexity and severity of infectious diseases. Escherichia coli is one the most common pathogens across all healthcare-associated infections. Enzymatic treatment of bacterial biofilms, targeting extracellular polymeric substances (EPS), can be used for EPS degradation and consequent increase in susceptibility of pathogenic bacteria to antibiotics. Here, we characterized three recombinant cellulases from Thermothelomyces thermophilus: a cellobiohydrolase I (TthCel7A), an endoglucanase (TthCel7B), and a cellobiohydrolase II (TthCel6A) as tools for hydrolysis of E. coli and Gluconacetobacter hansenii biofilms. Using a design mixture approach, we optimized the composition of cellulases, enhancing their synergistic activity to degrade the biofilms and significantly reducing the enzymatic dosage. In line with the crystalline and ordered structure of bacterial cellulose, the mixture of exo-glucanases (0.5 TthCel7A:0.5 TthCel6A) is effective in the hydrolysis of G. hansenii biofilm. Meanwhile, a mixture of exo- and endo-glucanases is required for the eradication of E. coli 042 and clinical E. coli biofilms with significantly different proportions of the enzymes (0.56 TthCel7B:0.44 TthCel6A and 0.6 TthCel7A:0.4 TthCel7B, respectively). X-ray diffraction pattern and crystallinity index of E. coli cellulose are comparable to those of carboxymethyl cellulose (CMC) substrate. Our results illustrate the complexity of E. coli biofilms and show that successful hydrolysis is achieved by a specific combination of cellulases, with consistent recurrence of TthCel7B endoglucanase.

Molecular Identification of Mycobacterium leprae in the Leprosy Patients.

BACKGROUND: Several discoveries about leprosy indicate that Mycobacterium leprae transmission mainly occurs by inhalation, and the nose is a major port of entry and exit. Molecular probes have shown certain potential for the detection and identification of M. leprae in patients. The aim of this study was to identify M. leprae in nasal swab specimens using polymerase chain reaction (PCR)-based assays followed by gene sequencing methods. This observational study examines 64 anterior nasal swab samples taken from pretreatment leprosy patients, on-treatment and completed leprosy treatment in Bulukumba, South Sulawesi, Indonesia. METHODS: samples were analyzed by molecular detection methods according to the standard methods at the Clinical Microbiology Laboratory of Hasanuddin University. Descriptive statistics were utilized to summarize patient demographics and outcomes. RESULTS: This study uses PCR to detect the M. leprae deoxyribonucleic acid (DNA) from nasal swab specimens. Data were collected from 64 patients with a percentage of male patients 51.54%. Based on the age category, the group 45-46 years was the most frequent (39.05%). PCR detection proline-rich antigen gene of a 531 bp DNA fragment from M. leprae, was positive in eight patients, and they were multibacillary. Furthermore, PCR was positive in 5 (31.25%) of 16 new leprosy patients, 2 (8.69%) of 23 on-treatment patients, and 1 (4%) of 25 treatment completed patients. Based on the results of the phylogenetic tree and analysis of 8 positive results detected by M. leprae from leprosy patients, almost all samples have a level of similarity, except for sample Ua7. CONCLUSIONS: M. leprae cannot grow in vitro, so molecular diagnostic tools were used to confirm the disease. This study predominantly of males with the age above 45 years of age being the most common. Eight M. leprae were positive from nasal swab leprosy patients. The sequencing findings provide insight into the genetic diversity of the genus M. leprae, so it is necessary to consider the detection of whole-genome sequence.

Oxidized Bacterial Cellulose Membranes Immobilized with Papain for Dressing Applications: Physicochemical and In Vitro Biological Properties.

This research consolidates our group's advances in developing a therapeutic dressing with innovative enzymatic debridement, focusing on the physicochemical and in vitro biological properties of papain immobilized in wet oxidized bacterial cellulose (OxBC-Papain) dressing. OxBC membranes were produced with Komagataeibacter hansenii oxidized with NaIO4, and papain was immobilized on them. They were characterized in terms of enzyme stability (over 100 days), absorption capacity, water vapor transmission (WVT), hemocompatibility, cytotoxicity, and cell adhesion. The OxBC-Papain membrane showed 68.5% proteolytic activity after 100 days, demonstrating the benefit of using the OxBC wet membrane for papain stability. It had a WVT rate of 678 g/m2·24 h and cell viability of 99% and 86% for L929 and HaCat cells, respectively. The membranes exhibited non-hemolytic behavior and maintained 26% clotting capacity after 1 h. The wet OxBC-Papain membrane shows significant potential as a natural biomolecule-based therapeutic dressing for wound care, offering efficient debridement, moisture maintenance, exudate absorption, gas exchange, and hemostasis without cytotoxic effects or cell adhesion to the dressing. Further research, especially using in vivo models, is needed to assess its efficacy in inducing epithelialization. This study advances stomatherapy knowledge, providing a cost-effective solution for enzymatic debridement in healthcare.

Leprosy Presenting With Scleroderma and Cataract: A Clinical Conundrum.

Leprosy, a chronic infectious disease caused by Mycobacterium leprae, even though treatable, remains a significant public health problem. It mainly impacts the skin, peripheral nerves, mucosa of the upper respiratory tract, and the eyes. In this case report, we present the case of a 64-year-old female with numerous hypopigmented patches with loss of sensations, madarosis, resorption of toes and digits, skin tightening, and diminution of vision. The skin over the hands exhibited thickening, leading to functional impairments that influenced both manual dexterity and mobility. The diagnosis of this unique case, showing a complex triad of lepromatous leprosy, scleroderma, and sclerotic cataract, was confirmed by clinical evaluation, skin biopsies, serological tests, and ophthalmic examination. Following this, the patient underwent dexamethasone-cyclophosphamide pulse therapy and multidrug treatment to halt the disease progression, prevent further disability, and reduce transmission. The case management addressed the issue of overlapping symptoms and conditions to provide appropriate care and cure to the patient. Public health initiatives under the National Leprosy Eradication Programme play an important role in promoting early diagnosis, effective treatment, and community empowerment, working toward a future where leprosy is no longer a threat to public health by preventing disability, reducing transmission, and combating the social stigma associated with it.

Prevalence and associated risk factors of Mycoplasma genitalium infection in women in Western Cameroon: A cross sectional study.

Background Mycoplasma genitalium is implicated in genitourinary disorders in both men and women as a sexually transmitted infection (STI). This study aimed to ascertain the prevalence of M. genitalium and identify associated risk factors among women. Aim To investigate the prevalence of M. genitalium and identify various risk-factors associated with M. genitalium infection in women attending the clinic in Western Cameroon. Methods A cross-sectional study was conducted in hospitals from five districts of Western Cameroon on sexually active and non-menstruating women attending for antenatal, prenuptial and contraception consultations,between January 2020 and July 2020. Endocervical swabs (n = 680) were collected, and M. genitalium was detected using real-time PCR targeting the MgPa and pdhD genes. Results A total of 680 women, characterised by a mean age of 27.4 ± 7.5 years, were included in this study. The overall prevalence of the M. genitalium infection was 5.2%. Bivariate analysis revealed that having more than one sexual partner was independently associated with three times higher odds of prevalent M. genitalium infection (OR 2.9, 95% CI: 1.03-8.56). Limitation Cross-sectional design limits exploring temporal relationships with other STIs. Freezing specimens for a year until PCR testing may have compromised detection rates of M. genitalium. Conclusion This study contributes valuable data to the limited understanding of M. genitalium epidemiology. The findings may aid in the formulation of national clinical standards for testing and screening strategies, emphasising the importance of addressing associated risk factors in the targeted population.

Health worker perspectives on barriers and facilitators of tuberculosis investigation coverage among index case contacts in rural Southwestern Uganda: a qualitative study.

BACKGROUND: In 2012, the World Health Organization recommended screening and investigation of contacts of index tuberculosis patients as a strategy to accelerate detection of tuberculosis (TB) cases. Nine years after the adoption of this recommendation, coverage of TB contact investigations in Uganda remains low. The objective of this study was to examine health care providers' perceptions of factors influencing coverage of TB contact investigations in three selected rural health facilities in Mbarara district, southwestern Uganda. METHODS: This study identified provider opinions on the barriers and facilitators to implementation of TB contact investigation using the Consolidated Framework for Implementation Research. Using an exploratory qualitative study design, semi-structured interviews with 19 health workers involved in the TB program at district, health facility and community levels were conducted from April 2020 and July 2020. Analysis was conducted inductively using reflexive thematic analysis in six iterative steps: familiarizing with the data, creating initial codes, searching for themes, reviewing themes, developing theme definitions, and writing the report. RESULTS: Nineteen health care workers participated in this study which translates to a 100% response rate. These included two district TB and leprosy supervisors, five nurses, five clinical officers, six village health team members and one laboratory technician. The three themes that emerged from the analysis were intervention-related, health system and contextual factors. Health system-related barriers included inadequate or delayed government funding for the TB program, shortage of human resources, insufficient personal protective equipment, and a stock-out of supplies such as Xpert MTB cartridges. Contextual barriers included steep terrain, poverty or low income, and the stigma associated with TB and COVID-19. Facilitators comprised increased knowledge and understanding of the intervention, performance review and on-the-job training of health workers. CONCLUSIONS: This study found that most of the factors affecting TB contact investigations in this rural community were related to health system constraints such as inadequate or delayed funding and human resource shortages. This can be addressed by strengthening the foundational elements of the health system - health financing and human resources - to establish a comprehensive TB control program that will enable the efficient identification of missing TB patients.

The pattern of rpoB gene mutation of Mycobacterium tuberculosis and predictors of rifampicin resistance detected by GeneXpert MTB/RIF assay in Tanzania.

INTRODUCTION: Antimicrobial resistance in Mycobacterium tuberculosis (MTB) poses a significant challenge to tuberculosis (TB) management worldwide. Rifampicin resistance (RR) has been associated with the rpoB gene mutation. No study was conducted in Tanzania to determine the commonest mutation. The inconsistent findings from various studies support the need to determine whether reported mutation patterns are applicable in our setting. We determined the frequency of rpoB gene mutation and factors associated with RR, which were detected using GeneXpert MTB/RIF assay. METHODS: We conducted a retrospective cross-sectional study involving data from the National Tuberculosis and Leprosy Program database from 2020 to 2022 for cases investigated using GeneXpert MTB/RIF assay. Descriptive analysis was performed to determine the frequency of categorical variables. The chi-square test and logistic regression analysis assessed the relationship between the independent variables and outcome. The 95% confidence interval and a significance level of p<0.05 were used to assess the strength of association. RESULTS: A total of 56,004 participants had a status of MTB and RR, where 38,705/56,004 (69.11%) were males. Probe E mutation (codon 529-533), 89/219 (40.64%) was predominant. Human immunodeficiency virus (HIV)-positive patients had a higher gene mutation, 134/10601 (1.26%) than HIV-negative, 306/45016 (0.68%) (p<0.001). Patients with both pulmonary and extra-pulmonary TB had about four times greater odds of developing rifampicin resistance (AOR 3.88, 95%CI: 1.80-8.32). RR was nearly nine times higher in previously treated patients than new patients (AOR 8.66, 95% CI: 6.97-10.76). HIV-positive individuals had nearly twice the odds of developing RR than HIV-negative individuals (AOR 1.91, 95%CI: 1.51-2.42). CONCLUSION: The rate of RR was lower compared to other studies in Tanzania, with probe E mutations the most prevalent. Patients with disseminated TB, HIV co-infection and those with prior exposure to anti-TB had more risk of RR. The findings highlight the need to strengthen surveillance of multidrug-resistant TB among high risk patients.

Multiple Postoperative Lung Infections after Thymoma Surgery Diagnosed as Nontuberculous Mycobacterial Infection.

BACKGROUND: Thymomas are thymic epithelial-derived, most common primary anterior mediastinal masses. Non-tuberculous mycobacteria (NTM) are species that do not cause leprosy and belong to species outside the Mycobacterium tuberculosis complex. METHODS: With the clinical application of targeted next-generation sequencing (tNGS), we promptly confirmed a case of NTM infection combined with NTM infection after thymoma surgery, and we performed a joint literature analysis of the two diseases to improve clinicians' understanding and recognition of lung infections after thymoma surgery. RESULTS: Chest CT of both lungs showed multiple hyperdense shadows. Sputum bacterial culture and characterization detected Neisseria Dryad and Streptococcus Grass Green. The presence of Mycobacterium abscessus infection was confirmed by alveolar lavage fluid sent for second-generation macro gene sequencing. CONCLUSIONS: The body's immune function decreases after thymoma surgery. When empirical anti-infection treatment for recurrent pneumonia in the lungs is ineffective, we should be alerted to the possibility of the presence of pulmonary non-tuberculous mycobacterial infection, and next-generation sequencing should be performed promptly to arrive quickly at a diagnosis.

Trend in the epidemiological risk of leprosy in the state of Goiás-Brazil between 2010 and 2021.

OBJECTIVE: To analyze trends in epidemiological risk of leprosy in Goiás state, Brazil, and its health macro-regions, between 2010 and 2021. METHOD: This is a time series analysis of the composite leprosy epidemiological risk index in Goiás. We used cases held on the Notifiable Health Conditions Information System for calculating indicators separately and risk, classified as high, medium, low and very low. Trends were analyzed using Prais-Winsten linear regression and risk maps were produced. RESULTS: Goiás showed high leprosy endemicity (24.8 cases/100,000 inhabitants) and medium epidemiological risk between 2019 and 2021 (0.58). A stationary trend was found (annual percentage change, 0.50; 95% confidence interval, -3.04; 4.16) for risk of leprosy in Goiás as a whole and in its Central-West and Central-Southeast macro-regions. CONCLUSION: There is need for actions to reduce the epidemiological risk of leprosy, especially where its trend is stationary, this includes early screening for new cases and health education. MAIN RESULTS: Leprosy persists in Goiás state, Brazil, in an endemic form, with heterogeneous distribution. There has been a reduction in the number of municipalities with high epidemiological risk of leprosy, but challenges include active transmission and late diagnosis. IMPLICATIONS FOR SERVICES: Long-term strategies for prevention, early detection, treatment and monitoring of people with leprosy and their contacts are needed. PERSPECTIVES: It is crucial to strengthen health policies targeting leprosy in Goiás state, prioritizing continuing education and training programs for health professionals working in the entire territory.