Deciphering drug discovery and microbial pathogenesis research in tuberculosis during the two decades of postgenomic era using entity mining approach.

We examined literature on Mycobacterium tuberculosis (Mtb) subsequent to its genome release, spanning years 1999-2020. We employed scientometric mapping, entity mining, visualization techniques, and PubMed and PubTator databases. Most popular keywords, most active research groups, and growth in quantity of publications were determined. By gathering annotations from the PubTator, we determined direction of research in the areas of drug hypersensitivity, drug resistance (AMR), and drug-related side effects. Additionally, we examined the patterns in research on Mtb metabolism and various forms of tuberculosis, including skin, brain, pulmonary, extrapulmonary, and latent tuberculosis. We discovered that 2011 had the highest annual growth rate of publications, at 19.94%. The USA leads the world in publications with 18,038, followed by China with 14,441, and India with 12,158 publications. Studies on isoniazid and rifampicin resistance showed an enormous increase. Non-tuberculous mycobacteria also been the subject of more research in effort to better understand Mtb physiology and as model organisms. Researchers also looked at co-infections like leprosy, hepatitis, plasmodium, HIV, and other opportunistic infections. Host perspectives like immune response, hypoxia, and reactive oxygen species, as well as comorbidities like arthritis, cancer, diabetes, and kidney disease etc. were also looked at. Symptomatic aspects like fever, coughing, and weight loss were also investigated. Vitamin D has gained popularity as a supplement during illness recovery, however, the interest of researchers declined off late. We delineated dominant researchers, journals, institutions, and leading nations globally, which is crucial for aligning ongoing and evolving landscape of TB research efforts. Recognising the dominant patterns offers important information about the areas of focus for current research, allowing biomedical scientists, clinicians, and organizations to strategically coordinate their efforts with the changing priorities in the field of tuberculosis research.

Unusual presentations of a severe type 2 leprosy reaction mimicking sepsis induced by helminth infection.

We describe an unusual case of type 2 leprosy reaction (T2R) with septic shock-like features induced by helminth infection in a 31-year-old Moluccan male patient with a history of completed treatment of WHO multidrug therapy (MDT)-multibacillary (MB) regimen 2 years before admission. During the course of illness, the patient had numerous complications, including septic shock, anemia, and disseminated intravascular coagulation (DIC). Nevertheless, antibiotic therapies failed to give significant results, and the source of infection could not be identified. Helminth infection was subsequently revealed by endoscopic examination followed by parasitological culture. Resolution of symptoms and normal level of organ function-specific markers were resolved within 3 days following anthelmintic treatment. This report demonstrated the challenge in the diagnosis and treatment of severe T2R. Given that helminth infections may trigger severe T2R that mimics septic shock, health professionals need to be aware of this clinical presentation, especially in endemic regions of both diseases.

Opportunistic tropical infections in immunosuppressed patients.

Autoimmune and autoinflammatory diseases are associated with severe morbidity, and represent an impactful health and economic burden worldwide. The treatment of these diseases can include a course with detrimental side effects. Immunosuppression increases the risk of opportunistic infections, but in some cases, the abrupt discontinuation of these medications can result in immune reconstitution inflammatory syndrome. Special attention must be directed to endemic tropical infections, such as leishmaniasis, Chagas disease, malaria, arbovirosis, yellow fever, leprosy, paracoccidioidomycosis, disseminated strongyloidiasis, and ectoparasitosis. These endemic diseases of developing countries can be considered as possible emerging diseases in developed regions partially because of environmental factors and migration. In the present article, we aim to review the evidence-based aspects of the most important opportunistic tropical infections in immunosuppressed patients. We also aim to review the important aspects of vaccination, chemical prophylaxis, and treatment for these infections in people with medication-induced immunosuppression.

Comportamiento de los estados reaccionales de la lepra en la proviencia Camagïeu. Cuba / No disponible

Se realizó un estudio observacional descriptivo prospectivo con el objetivo de caracterizar el comportamiento de los estados reaccionales de la lepra en la provincia Camagüey, en el período comprendido del 1ero de Abril del 2014 al 30 de Marzo de 2015. El universo de estudio estuvo constituido por todos los pacientes con diagnóstico de estados reaccionales. La mayoría de los pacientes se encontraban en las edades de 40 años y más, con predominio del sexo masculino. El eritema nudoso leproso se presentó con mayor frecuencia. La mitad de los enfermos presentó la reacción leprótica en el primer semestre de diagnosticada la enfermedad y las formas clínicas leves fueron las de mayor incidencia. La totalidad de los pacientes presentó malestar general. Las caries dentales y la faringo- amigdalitis estreptocóccica fueron las enfermedades asociadas más frecuentes. La afectación psicológica se presentó en más de la mitad de los enfermos. Las reacciones lepróticas fueron causa de discapacidad en más de la cuarta parte de los pacientes. La totalidad de ellos fue tratada según lo normado en el Programa Nacional de Control de la lepra en Cuba, y solo un enfermo presentó efecto adverso

A prospective, observational, descriptive study was carried out to characterize the behavior of leprosy reactive states in the province of Camagüey during the period from April 1, 2015 to March 30, 2016. The aim of the study was to evaluate all of the patients with a diagnosis of reactional states (leprosy reactions). The majority of the patients were in the ages of 40 years and above and the majority were male. Erythema nodosum leprosum was the most frequent episode. Half of the patients presented the leprosy reaction in the first semester after diagnosis of the disease and the mild clinical forms presented the highest incidence of reactions. All patients presented general malaise. Dental caries and streptococcal pharyngitis were the most common associated diseases. Psychological involvement occurred in more than half of the patients and leprosy reactions were the cause of disability in more than a quarter of patients. All of them were treated as recommended in the National Leprosy Control Program in Cuba, and only one patient had an adverse effect

Aspectos clínicos y aislamientos de micobacterias ambientales en muestras pulmonares y extrapulmonares / Clinical aspects and the isolation of environmental mycobacteria in pulmonary and extrapulmonary samples

Las infecciones provocadas por micobacterias atípicas, micobacterias no tuberculosas y más recientemente denominadas micobacterias ambientales u oportunistas, en los últimos tiempos desempeñan un papel preponderante en el diagnóstico clínico. Estas especies se relacionan generalmente con estados de inmuno depresión del paciente. En este trabajo se estudiaron 136 cepas aisladas de pacientes con sintomatología específica tanto pulmonar como extrapulmonar, incluidos aquellos infectados por el virus de la inmunodeficiencia humana (VIH), éstas fueron estudiadas e identificadas en el Laboratorio Nacional de Referencia e Investigaciones de Tuberculosis, Lepra y Micobacterias, durante el período de enero de 2011 a diciembre de 2012. Es importante destacar que el 72.79% de los aislamientos eran procedentes de pacientes VIH positivos. El total de las cepas aisladas fue analizado según la clasificación establecida por Runyon; los grupos encontrados con mayor frecuencia fueron el III y el IV; por especie, las de mayor porcentaje de aislamiento fueron las del complejo Mycobacterium avium-intracellulare, Mycobacterium malmoense, Mycobacterium fortuitum y Mycobacterium chelonae, respectivamente. Estos estudios son de gran importancia diagnóstica en los laboratorios de micobacteriología, pues de esta forma se puede llegar a conocer cuáles son las especies micobacterianas predominantes en la población,y lograr establecer una vigilancia sobre este tipo de infecciones, particularmente en pacientes inmunodeficientes, los que pueden ser origen de una peligrosa diseminación de la enfermedad...

Histopathological study of cutaneous manifestations in HIV and AIDS patients.

OBJECTIVES: Most human immunodeficiency virus (HIV)-infected patients develop various skin diseases. These skin manifestations not only act as markers but also reflect the patient's underlying immune status. Investigating CD4 counts is costly and not always possible. Thus, the potential value to be gained by using skin manifestations as predictors of low CD4 counts and disease progression should be explored. The present study attempted to correlate the association of various cutaneous disorders found in HIV patients with CD4 and CD8 counts, the CD4 : CD8 ratio and stage of HIV infection. METHODS: This was a prospective study involving 61 patients who were HIV-positive and demonstrated skin lesions. Punch biopsies of skin were taken for histopathological diagnosis. CD4 and CD8 T cell counts were performed. RESULTS: The study sample included a majority of male patients, most of whom were aged 21-40 years. Pruritic papular dermatitis was the most common skin manifestation, followed by molluscum contagiosum, eosinophilic folliculitis, and Hansen's disease. Most of the lesions were associated with CD4 counts of <220/µl (n = 38). All skin lesions associated with HIV or acquired immune deficiency syndrome (AIDS) showed a CD4 : CD8 ratio of <0.50. CONCLUSIONS: The study findings demonstrate an inverse relationship between CD4 counts and the occurrence of skin lesions. The majority of lesions were associated with stage 3 or stage 4 infection. Thus, specific cutaneous manifestations can be considered as good clinical indicators for predicting underlying immune status in resource-poor countries.

Multiple rare opportunistic and pathogenic fungi in persistent foot skin infection.

Persistent superficial skin infection caused by multiple fungi is rarely reported. Recently, a number of fungi, both opportunistic and persistent in nature were isolated from the foot skin of a 24-year old male in Malaysia. The fungi were identified as Candida parapsilosis, Rhodotorula mucilaginosa, Phoma spp., Debaryomyces hansenii, Acremonium spp., Aureobasidium pullulans and Aspergillus spp., This is the first report on these opportunistic strains were co-isolated from a healthy individual who suffered from persistent foot skin infection which was diagnosed as athlete's foot for more than 12 years. Among the isolated fungi, C. parapsilosis has been an increasingly common cause of skin infections. R. mucilaginosa and D. hansenii were rarely reported in cases of skin infection. A. pullulans, an emerging fungal pathogen was also being isolated in this case. Interestingly, it was noted that C. parapsilosis, R. mucilaginosa, D. hansenii and A. pullulans are among the common halophiles and this suggests the association of halotolerant fungi in causing persistent superficial skin infection. This discovery will shed light on future research to explore on effective treatment for inhibition of pathogenic halophiles as well as to understand the interaction of multiple fungi in the progress of skin infection.

[Nontuberculous mycobacterial infections of the lung]. / Atypische Mykobakteriose der Lunge.

Nontuberculous mycobacterium (NTM) species are mycobacterial species other than those belonging to the Mycobacterium tuberculosis complex and M. leprae. NTM are generally free-living organisms that are ubiquitous in the environment. Pulmonary disease, especially in older persons with and without underlying lung disease, is caused primarily by M. avium complex (MAC) and M. kansasii. The symptoms and signs of MAC lung disease are variable and not specific, but include cough, malaise, weakness, dyspnoea, chest discomfort and occasionally hemoptoe. Two major clinical presentations include disease in those with underlying lung disease, primarily white, middle-aged or elderly men - often alcoholics and/or smokers with underlying chronic obstructive lung disease, patients in whom MAC develops in areas of prior bronchiectasis, and patients with cystic fibrosis; and those without known underlying lung disease, including non-smoking women over age 50 who have interstitial patterns on chest radiography. M. kansasii infections are endemic in cities with infected tap water. Symptoms of the M. kansasii lung disease resemble to tuberculosis. M. abszessus is the most pathogenic rapid growing Mycobacterium which causes pulmonary infection. The American Thoracic Society and Infectious Disease Society of America's diagnostic criteria for nontuberculous mycobacterial pulmonary infections include both imaging studies consistent with pulmonary disease and recurrent isolation of mycobacteria from sputum or isolated from at least one bronchial wash in a symptomatic patient. For treatment of MAC lung disease we recommend depending on severity and susceptibility testing a three to four drug treatment with a macrolide, rifampicin and ethambutol and for M. kansasii a treatment with Isoniazid, rifampicin and ethambutol. Surgical management only plays a role in rare and special cases. Treatment should be continued until sputum cultures are consecutively negative for at least one year.

Secondary leprosy infection in a patient with psoriasis during treatment with infliximab.

Tumor necrosis factor α antagonists are proven to be effective for the treatment of chronic inflammatory conditions, such as psoriasis. A major concern for patients is the risk of acquiring granulomatous infectious diseases caused by the immunosuppressive effects of the drugs. We report a 60-year-old man with psoriasis who underwent infliximab treatment for 2 years and developed secondary leprosy, presenting extensive erythematous and infiltrated plaques on the trunk and limbs with loss of sensitivity (thermal, pain and tactile). The skin lesion biopsy showed perivascular epithelioid granulomas, nodular dermal aggregates of foamy macrophages and bundles of acid-fast bacilli. The clinical picture associated with histopathologic evaluation suggested borderline lepromatous leprosy. Before infliximab treatment, the patient had a positive tuberculin skin test and underwent chemoprophylaxis treatment for latent tuberculosis. Although the tuberculin reactivity suggests a strong correlation with a latent Mycobacterium tuberculosis infection, the possibility of infections by other mycobacteria, such as Mycobacterium leprae, should not be discarded.

[Cutaneous and soft skin infections due to non-tuberculous mycobacteria]. / Infecciones cutáneas y de partes blandas por micobacterias no tuberculosas.

The frequency of isolation as well as the number of species of non-tuberculous mycobacteria (NTM) has increased in the last years. Nearly every pathogenic species of NTM may cause skin and soft tissue infections, but rapidly growing mycobacteria (Mycobacterium fortuitum, Mycobacterium chelonae and Mycobacterium abscessus), Mycobacterium marinum and Mycobacterium ulcerans are the most commonly involved. Many of these cutaneous mycobacteriosis, such as rapidly growing mycobacteria, M. marinum, Mycobacterium avium complex, Mycobacterium kansasii or Mycobacterium xenopi are world-wide distributed. In contrast, some others have a specific geographical distribution. This is the case of M. ulcerans, which causes a cutaneous diseases endemic of Central and West Africa (Buruli ulcer) and Australia (Bairnsdale ulcer), being the third mycobacterial infection after tuberculosis and leprosy. Cutaneous mycobacteriosis usually appear either after contact of traumatic or surgical wounds with water or other contaminated products, or, secondarily, as a consequence of a disseminated mycobacterial disease, especially among immunosuppressed patients. For an early diagnosis, it is necessary to maintain a high degree of suspicion in patients with chronic cutaneous diseases and a history of trauma, risk exposure and negative results of conventional microbiological studies. In general, individualized susceptibility testing is not recommended for most NTM infections, except for some species, and in case of therapeutic failure. Treatment includes a combination of different antimicrobial agents, but it must be taken into account that NTM are resistant to conventional antituberculous drugs. Severe cases or those with deep tissues involvement could also be tributary of surgical resection.

Incidência de tuberculose em indivíduos co-infectados HIV-hanseníase / Incidence of tuberculosis in patients co-infected with HIV-leprosy

Algumas doenças micobacterianas são mais comuns no curso da infecção pelo HIV, como a tuberculose (TB) e afecções pelo complexo Mycobacterium avium e outras menos evidentes como a hanseníase. Visto haver homologia entre a carga genética do M. tuberculosis e do M. leprae, supomos poder observar alguma interferência na incidência de tuberculose (TB) em pacientes co-infectados HIV-hanseniase. O objetivo deste estudo é avaliar a incidência de tuberculose (TB) em pacientes co-infectados HIV-hanseníase acompanhados na FIOCRUZ, Rio de Janeiro. Trata-se de um estudo retrospectivo de todos os casos de co-infecção HIV-hanseníase atendidos na FIOCRUZ, Rio de Janeiro, de janeiro/1990 a outubro/2007. Desenvolvemos um protocolo padrão para a coleta dos dados demográficos, clínicos, imunológicos e histopatológicos; enfatizando os períodos de tratamento com corticóides e a incidência de doenças oportunistas do diagnóstico da hanseníase ao término do tratamento com poliquimioterapia (PQT) específica. A incidência de TB foi calculada pelo número de caso por pessoa-tempo. Dos 41 pacientes selecionados, 78 por cento tinham a forma paucibacilar da hanseníase. O diagnóstico de AIDS foi estabelecido em 90,2 por cento dos casos no momento diagnóstico da hanseníase. A maioria (66,7 por cento) das reações hansênicas ocorreu antes do início da PQT e em 75 por cento dos pacientes, durante o uso de terapia anti-retroviral. As reações hansênicas foram controladas com corticoterapia em 86,4 por cento dos casos por tempo médio de 214 dias. Observamos a incidência de 02 pneumocistoses, 02 neurotoxoplasmoses, 01 isosporíase, 04 casos de tuberculose (01 pulmonar e 03 disseminadas) e 01 caso suspeito de tuberculose pulmonar que perdemos o seguimento. Apenas 01 caso de tuberculose disseminada e 01 de neurotoxoplasmose foram diagnosticados durante corticoterapia. Durante a PQT incidência de tuberculose foi de 13,8 casos (IC: 0,27 – 27,31) por 1.000 pessoas/ mês, no período pré-tratamento da hanseníase a incidência foi de 5,05 casos (IC: 0,62 – 9,48) por 1.000 pessoas/ mês e no pós-PQT a incidência foi de 0,5 casos (IC: 3,93 – 4,93) por 1.000 pessoas/ mês. A incidência de TB no período durante o a PQT (durante a tri-infecção) foi o dobro do período pré-hanseníase e 20 vezes maior que a incidência de TB no período pós-PQT. Apesar dos dados não serem estatisticamente significativos, consideramos esses dados importantes pelo alto valor da incidência. Este estudo não observou aumento da ocorrência de tuberculose ou outras infecções oportunistas durante o uso de corticoterapia em doses imunossupressivas.

HIV and tuberculosis: partners in crime.

BACKGROUND: Tuberculosis is the commonest infection detected in HIV-infected individuals worldwide. AIM: The aim of this study is to describe the clinical, bacteriologic and radiological spectrum of tuberculosis (TB) in the setting of human immunodeficiency virus (HIV) infection in a tertiary care centre in Mumbai. METHODS: A total of 8640 HIV-infected individuals were screened for tuberculosis routinely from January 1998 to December 2003, using clinical examination, chest X-ray and abdominal ultrasonography, sputum smears for acid-fast bacilli (AFB) and culture on Lowenstein-Jensen medium. RESULTS: TB was detected in 8078 (93.5%) patients of whom 3393 (42%) had pulmonary, 3514 (43.5%) had extrapulmonary TB and 1171 (14.5%) had disseminated disease. One thousand two hundred thirty eight patients (36.5%) showed AFB in sputum, while 1154 (34%) showed growth on culture medium and 4174 had radiographic involvement. In 781 (67%) individuals disseminated disease coexisted with pulmonary involvement. All 8078 coinfected patients were treated with anti-TB therapy (ATT), of whom 6422 patients (79.5%) showed one or more adverse events. Gastritis was the commonest complaint followed by hepatitis and skin rashes. ATT resistance was detected in 482 individuals. CONCLUSION: Tuberculosis is the commonest opportunistic infection (OI) in HIV positive patients in India, showing a higher prevalence of extrapulmonary and disseminated TB and adverse events due to ATT. Early recognition of concurrent OIs and their adequate treatment and prophylaxis is essential.

Fatal disseminated strongyloidiasis in patients on immunosuppressive therapy: report of two cases.

Disseminated strongyloidiasis is a rare manifestation in patients on immunosuppressive drugs. We report two cases of fatal disseminated Strongyloides stercoralis infestation. The first was in a patient of pemphigus vulgaris who developed an exacerbation of symptoms, one year after diagnosis and was given intravenous dexamethasone and azathioprine and in the third week of hospitalization developed features of septicemia, respiratory failure and petechial hemorrhages which were proven to be due to disseminated strongyloidiasis. The second patient was diagnosed to have stage IV diffuse large cell type of non-Hodgkin lymphoma and after the second cycle of chemotherapy, developed generalized symptoms of septicemia, respiratory failure, purpuric macules and patches. This was also proven to be disseminated strongyloidiasis.