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BACKGROUND: The ongoing COVID-19 pandemic has had a significant impact worldwide, with an incommensurable social and economic burden. The rapid development of safe and protective vaccines against this disease is a global priority. CoronaVac is a vaccine prototype based on inactivated SARS-CoV-2, which has shown promising safety and immunogenicity profiles in pre-clinical studies and phase 1/2 trials in China. To this day, four phase 3 clinical trials are ongoing with CoronaVac in Brazil, Indonesia, Turkey, and Chile. This article reports the safety and immunogenicity results obtained in a subgroup of participants aged 18 years and older enrolled in the phase 3 Clinical Trial held in Chile. METHODS: This is a multicenter phase 3 clinical trial. Healthcare workers aged 18 years and older were randomly assigned to receive two doses of CoronaVac or placebo separated by two weeks (0-14). We report preliminary safety results obtained for a subset of 434 participants, and antibody and cell-mediated immunity results obtained in a subset of participants assigned to the immunogenicity arm. The primary and secondary aims of the study include the evaluation of safety parameters and immunogenicity against SARS-CoV-2 after immunization, respectively. This trial is registered at clinicaltrials.gov ( NCT04651790 ). FINDINGS: The recruitment of participants occurred between November 27 (th) , 2020, until January 9 (th) , 2021. 434 participants were enrolled, 397 were 18-59 years old, and 37 were ≥60 years old. Of these, 270 were immunized with CoronaVac, and the remaining 164 participants were inoculated with the corresponding placebo. The primary adverse reaction was pain at the injection site, with a higher incidence in the vaccine arm (55.6%) than in the placebo arm (40.0%). Moreover, the incidence of pain at the injection site in the 18-59 years old group was 58.4% as compared to 32.0% in the ≥60 years old group. The seroconversion rate for specific anti-S1-RBD IgG was 47.8% for the 18-59 years old group 14 days post immunization (p.i.) and 95.6% 28 and 42 days p.i. For the ≥60 years old group, the seroconversion rate was 18.1%, 100%, and 87.5% at 14, 28, and 42 days p.i., respectively. Importantly, we observed a 95.7% seroconversion rate in neutralizing antibodies for the 18-59 years old group 28 and 42 days p.i. The ≥60 years old group exhibited seroconversion rates of 90.0% and 100% at 28 and 42 days p.i. Interestingly, we did not observe a significant seroconversion rate of anti-N-SARS-CoV-2 IgG for the 18-59 years old group. For the participants ≥60 years old, a modest rate of seroconversion at 42 days p.i. was observed (37.5%). We observed a significant induction of a T cell response characterized by the secretion of IFN-γ upon stimulation with Mega Pools of peptides derived from SARS-CoV-2 proteins. No significant differences between the two age groups were observed for cell-mediated immunity. INTERPRETATION: Immunization with CoronaVac in a 0-14 schedule in adults of 18 years and older in the Chilean population is safe and induces specific IgG production against the S1-RBD with neutralizing capacity, as well as the activation of T cells secreting IFN-γ, upon recognition of SARS-CoV-2 antigens. FUNDING: Ministry of Health of the Chilean Government; Confederation of Production and Commerce, Chile; Consortium of Universities for Vaccines and Therapies against COVID-19, Chile; Millennium Institute on Immunology and Immunotherapy.

BackgroundThe ongoing COVID-19 pandemic has had a significant impact worldwide, with an incommensurable social and economic burden. The rapid development of safe and protective vaccines against this disease is a global priority. CoronaVac is a vaccine prototype based on inactivated SARS-CoV-2, which has shown promising safety and immunogenicity profiles in pre-clinical studies and phase 1/2 trials in China. To this day, four phase 3 clinical trials are ongoing with CoronaVac in Brazil, Indonesia, Turkey, and Chile. This article reports the safety and immunogenicity results obtained in a subgroup of participants aged 18 years and older enrolled in the phase 3 Clinical Trial held in Chile.MethodsThis is a multicenter phase 3 clinical trial. Healthcare workers aged 18 years and older were randomly assigned to receive two doses of CoronaVac or placebo separated by two weeks (0-14). We report preliminary safety results obtained for a subset of 434 participants, and antibody and cell-mediated immunity results obtained in a subset of participants assigned to the immunogenicity arm. The primary and secondary aims of the study include the evaluation of safety parameters and immunogenicity against SARS-CoV-2 after immunization, respectively. This trial is registered at clinicaltrials.gov (NCT04651790).FindingsThe recruitment of participants occurred between November 27th, 2020, until January 9th, 2021. 434 participants were enrolled, 397 were 18-59 years old, and 37 were ≥60 years old. Of these, 270 were immunized with CoronaVac, and the remaining 164 participants were inoculated with the corresponding placebo. The primary adverse reaction was pain at the injection site, with a higher incidence in the vaccine arm (55.6%) than in the placebo arm (40.0%). Moreover, the incidence of pain at the injection site in the 18-59 years old group was 58.4% as compared to 32.0% in the ≥60 years old group. The seroconversion rate for specific anti-S1-RBD IgG was 47.8% for the 18-59 years old group 14 days post immunization (p.i.) and 95.6% 28 and 42 days p.i. For the ≥60 years old group, the seroconversion rate was 18.1%, 100%, and 87.5% at 14, 28, and 42 days p.i., respectively. Importantly, we observed a 95.7% seroconversion rate in neutralizing antibodies for the 18-59 years old group 28 and 42 days p.i. The ≥60 years old group exhibited seroconversion rates of 90.0% and 100% at 28 and 42 days p.i. Interestingly, we did not observe a significant seroconversion rate of anti-N-SARS-CoV-2 IgG for the 18-59 years old group. For the participants ≥60 years old, a modest rate of seroconversion at 42 days p.i. was observed (37.5%). We observed a significant induction of a T cell response characterized by the secretion of IFN-γ upon stimulation with Mega Pools of peptides derived from SARS-CoV-2 proteins. No significant differences between the two age groups were observed for cell-mediated immunity.InterpretationImmunization with CoronaVac in a 0-14 schedule in adults of 18 years and older in the Chilean population is safe and induces specific IgG production against the S1-RBD with neutralizing capacity, as well as the activation of T cells secreting IFN-γ, upon recognition of SARS-CoV-2 antigens.FundingMinistry of Health of the Chilean Government; Confederation of Production and Commerce, Chile; Consortium of Universities for Vaccines and Therapies against COVID-19, Chile; Millennium Institute on Immunology and Immunotherapy.

Tuberculosis is the leading cause of death globally that is due to a single pathogen, and up to a fifth of patients with tuberculosis in high-incidence countries are children younger than 16 years. Unfortunately, the diagnosis of childhood tuberculosis is challenging because the disease is often paucibacillary and it is difficult to obtain suitable specimens, causing poor sensitivity of currently available pathogen-based tests. Chest radiography is important for diagnostic evaluations because it detects abnormalities consistent with childhood tuberculosis, but several limitations exist in the interpretation of such results. Therefore, other imaging methods need to be systematically evaluated in children with tuberculosis, although current data suggest that when available, cross-sectional imaging, such as CT, should be considered in the diagnostic evaluation for tuberculosis in a symptomatic child. Additionally, much of the understanding of childhood tuberculosis stems from clinical specimens that might not accurately represent the lesional biology at infection sites. By providing non-invasive measures of lesional biology, advanced imaging tools could enhance the understanding of basic biology and improve on the poor sensitivity of current pathogen detection systems. Finally, there are key knowledge gaps regarding the use of imaging tools for childhood tuberculosis that we outlined in this Personal View, in conjunction with a proposed roadmap for future research.

• COVID-19 patients may have persistently positive RT-PCRs for as many as 9 weeks. • Some are being required to continue in isolation until they have negative results. • SARS-CoV-2 qualitative RT-PCR does not distinguish infectious from noninfectious. • Quantitative RT-PCRs and immunoassays are better markers of infectivity period. • Social isolation can have economic, physical, psychological, and social effects.

Over the past 15 years, and despite many difficulties, significant progress has been made to advance child and adolescent tuberculosis (TB) care. Despite increasing availability of safe and effective treatment and prevention options, TB remains a global health priority as a major cause of child and adolescent morbidity and mortality—over one and a half million children and adolescents develop TB each year. A history of the global public health perspective on child and adolescent TB is followed by 12 narratives detailing challenges and progress in 19 TB endemic low and middle-income countries. Overarching challenges include: under-detection and under-reporting of child and adolescent TB; poor implementation and reporting of contact investigation and TB preventive treatment services; the need for health systems strengthening to deliver effective, decentralized services; and lack of integration between TB programs and child health services. The COVID-19 pandemic has had a significant negative impact on case detection and treatment outcomes. Child and adolescent TB working groups can address country-specific challenges to close the policy–practice gaps by developing and supporting decentral ized models of care, strengthening clinical and laboratory diagnosis, including of multidrug-resistant TB, providing recommended options for treatment of disease and infection, and forging strong collaborations across relevant health sectors.

Latin America accounts for roughly one-quarter of global COVID-19 cases and one-third of deaths. Health inequalities in the region lead to barriers regarding the best use of diagnostic tests during the pandemic. There is a need for a simplified guideline in the region that takes into consideration the available health resources, international guidelines, medical literature, and local expertise. Nine experts from different Latin American countries developed a simplified algorithm for COVID-19 diagnosis in the region, using a modified Delphi method. Twenty-four questions related to diverse diagnostic settings were initially proposed, followed by an extensive discussion of the literature and experts’ experience. According to time from close contact or symptom onset, the algorithm considers three different timeframes (≤7 days, 8–13 days, and ≥14 days) and discusses diagnostic options for each one. SARS-CoV-2 real-time reverse transcription polymerase chain reaction (rRT-PCR) continues to be the diagnostic test of choice from Day 1 to Day 14 after symptom onset or close contact, although antigen testing may be used in high-prevalence settings or in particular situations (such as from Day 0 to Days 5–7 of symptom onset). Antibody assays may be used for diagnostic confirmation, mainly after Day 14, if there is an epidemiological or individual need. If the clinical suspicion is very high, but other tests are negative, these assays may be used as an adjunct to decision-making from Days 8–13. The proposed algorithm is intended to be used as a support for COVID-19 diagnosis decision-making in Latin America.

Mendelian susceptibility to mycobacterial disease is a rare clinical condition characterized by a predisposition to infectious diseases caused by poorly virulent mycobacteria. Other infections such as salmonellosis and candidiasis are also reported. The purpose of this article is to describe a young boy affected with various infectious diseases caused by Mycobacterium tuberculosis complex, Salmonella sp, Klebsiella pneumonie, Citrobacter sp., and Candida sp, complicated with severe enteropathy and transient hypogammaglobulinemia. We reviewed medical records and performed flow cytometry staining for lymphocyte populations, lymphocyte proliferation in response to PHA, and intracellular IFN-γ production in T cell PHA blasts in the patient and a healthy control. Sanger sequencing was used to confirm the genetic variants in the patient and relatives. Genetic analysis revealed a bi-allelic mutation in IL12RB1 (C291Y) resulting in complete IL-12Rβ1 deficiency. Functional analysis demonstrated the lack of intracellular production of IFN-γ in CD3+ T lymphocytes from the patient in response to rhIL-12p70. To our knowledge, this is the third patient with MSMD due to IL-12Rβ1 deficiency complicated with enteropathy and hypogammaglobulinemia and the first case of this disease to be described in Colombia.

HIV pre-exposure prophylaxis (PrEP) is underutilized among Hispanics, women, and low-income individuals. To better understand PrEP barriers in this population, questionnaires were administered to 500 patients attending public health clinics in southern Arizona which provide family planning and sexually transmitted infections care. Sixty-three percent believed that they had no risk of HIV infection. When asked “Before today, did you know that there was a pill that can prevent HIV infection?” 80% of persons answered no. Among women, 88% answered no to this question. As expected, individuals with a higher perceived HIV risk (OR 1.76) or one HIV risk factor (OR 5.85) had a higher probability of knowledge. Among survey participants 87% would take a daily pill, 91% would visit a health-care provider every 3 months, and 92% would have laboratory testing every 3 months. Fifty-four percent would not be afraid or embarrassed if friends or family knew they were taking PrEP. Seventy-two percent would take PrEP despite temporary nausea. Sixty-two percent would pay ≥ $40 every 3 months for PrEP. Lack of knowledge, rather than patient attitudes, is the more important barrier to wider utilization of PrEP among individuals, especially women, attending public health clinics in Southern Arizona. Future efforts need to focus on education and access to PrEP in underserved populations including women and Hispanics.

Setting: Numerous knowledge gaps hamper the prevention and treatment of childhood drug-resistant tuberculosis (TB). Identifying research priorities is vital to inform and develop strategies to address this neglected problem. Objective: To systematically identify and rank research priorities in childhood drug-resistant TB. Design: Adapting the Child Health and Nutrition Research Initiative (CHNRI) methodology, we compiled 53 research questions in four research areas, then classified the questions into three research types. We invited experts in childhood drug-resistant TB to score these questions through an online survey. Results: A total of 81 respondents participated in the survey. The top-ranked research question was to identify the best combination of existing diagnostic tools for early diagnosis. Highly ranked treatment-related questions centred on the reasons for and interventions to improve treatment outcomes, adverse effects of drugs and optimal treatment duration. The prevalence of drug-resistant TB was the highest-ranked question in the epidemiology area. The development type questions that ranked highest focused on interventions for optimal diagnosis, treatment and modalities for treatment delivery. Conclusion: This is the first effort to identify and rank research priorities for childhood drug-resistant TB. The result is a resource to guide research to improve prevention and treatment of drug-resistant TB in children.

A healthy 16-year-old girl born and raised in Tucson, AZ, had screening and confirmatory testing revealing Chagas disease; clinical evaluation established that she had the indeterminate form of chronic Chagas disease with evidence of likely autochthonous transmission. Trypanosoma cruzi DNA was detected by conventional polymerase chain reaction in Triatoma rubida captured at her home.

The Arizona Department of Health Services identified unusually high levels of influenza activity and severe complications during the 2015–2016 influenza season leading to concerns about potential increased disease severity compared with prior seasons. We estimated state-level burden and severity to compare across three seasons using multiple data sources for community-level illness, hospitalisation and death. Severity ratios were calculated as the number of hospitalisations or deaths per community case. Community influenza-like illness rates, hospitalisation rates and mortality rates in 2015–2016 were higher than the previous two seasons. However, ratios of severe disease to community illness were similar. Arizona experienced overall increased disease burden in 2015–2016, but not increased severity compared with prior seasons. Timely estimates of state-specific burden and severity are potentially feasible and may provide important information during seemingly unusual influenza seasons or pandemic situations.

Childhood tuberculosis contributes significantly to the global tuberculosis disease burden but remains challenging to diagnose due to inadequate methods of pathogen detection in paucibacillary pediatric samples and lack of a child-specific host biomarker to identify disease. Accurately diagnosing tuberculosis in children is required to improve case detection, surveillance, healthcare delivery, and effective advocacy. In May 2014, the National Institutes of Health convened a workshop including researchers in the field to delineate priorities to address this research gap. This blueprint describes the consensus from the workshop, identifies critical research steps to advance this field, and aims to catalyze efforts toward harmonization and collaboration in this area.

RESUMO Objetivo: Descrever os desfechos de pacientes com síndrome do desconforto respiratório agudo associada à influenza subtipo H1N1 grave tratados com oxigenação por membrana extracorpórea. Métodos: Trata-se de revisão retrospectiva de uma coorte de pacientes oriunda de um único centro, constituída por adultos com síndrome do desconforto respiratório agudo relacionada com influenza subtipo H1N1 e tratados com oxigenação venovenosa por membrana extracorpórea durante a temporada de inverno no hemisfério norte de 2013/2014. Resultados: Dez pacientes receberam oxigenação venovenosa por membrana extracorpórea para tratamento de influenza subtipo H1N1 entre janeiro de 2013 e março de 2014. Sete deles foram transferidos para nosso centro visando à utilização de oxigenação por membrana extracorpórea dentro de um período de 72 horas após o início da ventilação mecânica. A idade mediana foi de 40 anos, sendo 30% dos pacientes do sexo feminino. O valor mediano da proporção entre pressão parcial de oxigênio e fração inspirada de oxigênio foi de 62,5, sendo o escore RESP mediano de 6. Três pacientes receberam inalação de óxido nítrico e quatro utilizaram posição prona como tratamento de resgate antes de ser iniciada a oxigenação por membrana extracorpórea. A duração mediana da ventilação mecânica foi de 22 dias (variação de 14 - 32). O tempo mediano de permanência na unidade de terapia intensiva foi de 27 dias (variação de 14 - 39). O tempo mediano de permanência no hospital foi de 29,1 dias (variação de 16,0 - 46,9). Ocorreram complicações não importantes de sangramento em seis dos dez pacientes. Oito dos dez pacientes sobreviveram até a alta hospitalar. Conclusão: Os sobreviventes eram relativamente jovens e tiveram alta com boas condições funcionais, o que salienta os anos de vida ajustados pela qualidade que foram salvos. Nossa experiência demonstra que mesmo um programa ainda relativamente novo de oxigenação por membrana extracorpórea pode desempenhar um papel importante, e proporcionar resultados excelentes para os pacientes mais graves. ABSTRACT Objective: This report aimed to describe the outcomes of the patients with severe H1N1 associated acute respiratory distress syndrome who were treated with extracorporeal membrane oxygenation therapy. Methods: This retrospective review analyzed a single-center cohort of adult patients with H1N1-related acute respiratory distress syndrome who were managed with veno-venous extracorporeal membrane oxygenation during the winter of 2013/2014. Results: A total of 10 patients received veno-venous extracorporeal membrane oxygenation for H1N1 influenza between January 2013 and March 2014. Seven patients were transferred to our center for extracorporeal membrane oxygenation consideration (all within 72 hours of initiating mechanical ventilation). The median patient age was forty years, and 30% were female. The median arterial oxygen partial pressure to fraction of inspired oxygen ratio was 62.5, and the median RESP score was 6. Three patients received inhaled nitric oxide, and four patients were proned as rescue therapy before extracorporeal membrane oxygenation was initiated. The median duration of mechanical ventilation was twenty-two days (range, 14 - 32). The median length of stay in the intensive care unit was twenty-seven days (range, 14 - 39). The median hospital length of stay was 29.1 days (range, 16.0 - 46.9). Minor bleeding complications occurred in 6 of 10 patients. Eight of the ten patients survived to hospital discharge. Conclusion: The survivors were relatively young and discharged with good functional status (i.e., enhancing quality-adjusted life-years-saved). Our experience shows that even a relatively new extracorporeal membrane oxygenation program can play an important role in that capacity and provide excellent outcomes for the sickest patients.

This report aimed to describe the outcomes of the patients with severe H1N1 associated acute respiratory distress syndrome who were treated with extracorporeal membrane oxygenation therapy.This retrospective review analyzed a single-center cohort of adult patients with H1N1-related acute respiratory distress syndrome who were managed with veno-venous extracorporeal membrane oxygenation during the winter of 2013/2014.A total of 10 patients received veno-venous extracorporeal membrane oxygenation for H1N1 influenza between January 2013 and March 2014. Seven patients were transferred to our center for extracorporeal membrane oxygenation consideration (all within 72 hours of initiating mechanical ventilation). The median patient age was forty years, and 30% were female. The median arterial oxygen partial pressure to fraction of inspired oxygen ratio was 62.5, and the median RESP score was 6. Three patients received inhaled nitric oxide, and four patients were proned as rescue therapy before extracorporeal membrane oxygenation was initiated. The median duration of mechanical ventilation was twenty-two days (range, 14 - 32). The median length of stay in the intensive care unit was twenty-seven days (range, 14 - 39). The median hospital length of stay was 29.1 days (range, 16.0 - 46.9). Minor bleeding complications occurred in 6 of 10 patients. Eight of the ten patients survived to hospital discharge.The survivors were relatively young and discharged with good functional status (i.e., enhancing quality-adjusted life-years-saved). Our experience shows that even a relatively new extracorporeal membrane oxygenation program can play an important role in that capacity and provide excellent outcomes for the sickest patients.Descrever os desfechos de pacientes com síndrome do desconforto respiratório agudo associada à influenza subtipo H1N1 grave tratados com oxigenação por membrana extracorpórea.Trata-se de revisão retrospectiva de uma coorte de pacientes oriunda de um único centro, constituída por adultos com síndrome do desconforto respiratório agudo relacionada com influenza subtipo H1N1 e tratados com oxigenação venovenosa por membrana extracorpórea durante a temporada de inverno no hemisfério norte de 2013/2014.Dez pacientes receberam oxigenação venovenosa por membrana extracorpórea para tratamento de influenza subtipo H1N1 entre janeiro de 2013 e março de 2014. Sete deles foram transferidos para nosso centro visando à utilização de oxigenação por membrana extracorpórea dentro de um período de 72 horas após o início da ventilação mecânica. A idade mediana foi de 40 anos, sendo 30% dos pacientes do sexo feminino. O valor mediano da proporção entre pressão parcial de oxigênio e fração inspirada de oxigênio foi de 62,5, sendo o escore RESP mediano de 6. Três pacientes receberam inalação de óxido nítrico e quatro utilizaram posição prona como tratamento de resgate antes de ser iniciada a oxigenação por membrana extracorpórea. A duração mediana da ventilação mecânica foi de 22 dias (variação de 14 - 32). O tempo mediano de permanência na unidade de terapia intensiva foi de 27 dias (variação de 14 - 39). O tempo mediano de permanência no hospital foi de 29,1 dias (variação de 16,0 - 46,9). Ocorreram complicações não importantes de sangramento em seis dos dez pacientes. Oito dos dez pacientes sobreviveram até a alta hospitalar.Os sobreviventes eram relativamente jovens e tiveram alta com boas condições funcionais, o que salienta os anos de vida ajustados pela qualidade que foram salvos. Nossa experiência demonstra que mesmo um programa ainda relativamente novo de oxigenação por membrana extracorpórea pode desempenhar um papel importante, e proporcionar resultados excelentes para os pacientes mais graves.

Summary Background Multidrug-resistant tuberculosis threatens to reverse recent reductions in global tuberculosis incidence. Although children younger than 15 years constitute more than 25% of the worldwide population, the global incidence of multidrug-resistant tuberculosis disease in children has never been quantified. We aimed to estimate the regional and global annual incidence of multidrug-resistant tuberculosis in children. Methods We developed two models: one to estimate the setting-specific risk of multidrug-resistant tuberculosis among child cases of tuberculosis, and a second to estimate the setting-specific incidence of tuberculosis disease in children. The model for risk of multidrug-resistant tuberculosis among children with tuberculosis needed a systematic literature review. We multiplied the setting-specific estimates of multidrug-resistant tuberculosis risk and tuberculosis incidence to estimate regional and global incidence of multidrug-resistant tuberculosis disease in children in 2010. Findings We identified 3403 papers, of which 97 studies met inclusion criteria for the systematic review of risk of multidrug-resistant tuberculosis. 31 studies reported the risk of multidrug-resistant tuberculosis in both children and treatment-naive adults with tuberculosis and were used for evaluation of the linear association between multidrug-resistant disease risk in these two patient groups. We identified that the setting-specific risk of multidrug-resistant tuberculosis was nearly identical in children and treatment-naive adults with tuberculosis, consistent with the assertion that multidrug-resistant disease in both groups reflects the local risk of transmitted multidrug-resistant tuberculosis. After application of these calculated risks, we estimated that around 999 792 (95% CI 937 877–1 055 414) children developed tuberculosis disease in 2010, of whom 31 948 (25 594–38 663) had multidrug-resistant disease. Interpretation Our estimates underscore that many cases of tuberculosis and multidrug-resistant tuberculosis disease are not being detected in children. Future estimates can be refined as more and better tuberculosis data and new diagnostic instruments become available. Funding US National Institutes of Health, the Helmut Wolfgang Schumann Fellowship in Preventive Medicine at Harvard Medical School, the Norman E Zinberg Fellowship at Harvard Medical School, and the Doris and Howard Hiatt Residency in Global Health Equity and Internal Medicine at the Brigham and Women's Hospital.

The accurate diagnosis of tuberculosis (TB) in children remains challenging. A myriad of common childhood diseases can present with similar symptoms and signs, and differentiating between exposure and infection, as well as infection and disease can be problematic. The paucibacillary nature of childhood TB complicates bacteriological confirmation and specimen collection is difficult. In most instances intrathoracic TB remains a clinical diagnosis. TB infection and disease represent a dynamic continuum from TB exposure with/without infection, to subclinical/incipient disease, to non-severe and severe disease. The clinical spectrum of intrathoracic TB in children is broad, and the classification of clinical, radiological, endoscopic, and laboratory findings into recognized clinical syndromes allows a more refined diagnostic approach in order to minimize both under- and over-diagnosis. Bacteriological confirmation can be improved significantly by collecting multiple, high-quality specimens from the most appropriate source. Mycobacterial testing should include traditional smear microscopy and culture, as well as nucleic acid amplification testing. A systematic approach to the child with recent exposure to TB, or with clinical and radiological findings compatible with this diagnosis, should allow pragmatic classification as TB exposure, infection, or disease to facilitate timely and appropriate management. It is important to also assess risk factors for TB disease progression and to undertake follow-up evaluations to monitor treatment response and ongoing evidence supporting a TB, or alternative, diagnosis. Electronic supplementary material The online version of this article (doi:10.1186/s41479-016-0023-9) contains supplementary material, which is available to authorized users.

Background An estimated two billion people, over one third of the world’s population, have latent infection with Mycobacterium tuberculosis (LTBI). Patient adherence to LTBI treatment is currently poor given that individuals show no symptoms of illness and may not feel that they are at risk of developing active tuberculosis (TB). Short text messages can serve as a simple reminder to take medications and address barriers to adherence such as forgetfulness and lack of social support. Methods/design We aim to determine the feasibility and acceptability of text reminders for improving adherence in latent TB patients using a randomized controlled single-blinded trial, measuring adherence through an increase in treatment completion rates. Forty adult LTBI participants will be randomized to either text messages plus phone call reminders or phone call reminders only (usual care). Recruitment, retention, and study acceptability will be assessed as primary outcomes. Discussion This pilot study will examine the feasibility of using text messaging for increasing adherence to treatment for latent tuberculosis infection. The study will allow for evaluation of process measures and challenges and development of a model for scaling up an effectiveness trial for increasing treatment adherence. Trial registration NCT02690818 (Clinical Trials.gov) Electronic supplementary material The online version of this article (doi:10.1186/s40814-017-0128-9) contains supplementary material, which is available to authorized users.

BACKGROUND Similar to poliovirus, enterovirus type 71 (EV71) causes severe disease, including aseptic meningitis, encephalitis, acute flaccid paralysis, and acute cardiopulmonary dysfunction. Large epidemics of EV71 infection have been reported worldwide. METHODS After recognition of a cluster of cases of EV71 disease, we reviewed records of patients with EV71 disease who required hospitalization at The Children's Hospital in Denver, Colorado, from 2003 through 2005. The presence of enterovirus was detected by reverse-transcriptase polymerase chain reaction (PCR) and/or viral culture of specimens from multiple sources, and the virus was typed as EV71 using genetic sequencing. RESULTS Eight cases of EV71 disease were identified in both 2003 and 2005. Fifty-six percent of patients with EV71 disease were < or = 6 months of age (range, 4 weeks to 9 years). All 16 patients had EV71 central nervous system infection. Enterovirus PCR (EV-PCR) of cerebrospinal fluid specimens yielded positive results for only 5 (31.2%) of the 16 patients; all of these patients were < 4 months of age and had less severe disease. However, EV-PCR of upper respiratory tract specimens yielded positive results for 8 (100%) of 8 patients, and EV-PCR of lower gastrointestinal tract specimens yielded positive results for 7 (87.5%) of 8 patients. CONCLUSIONS An outbreak of neurologic EV71 disease occurred in Denver, Colorado, during 2003 and 2005. Likely, EV71 disease remains unrecognized in other parts of the United States, because EV-PCR of cerebrospinal fluid frequently yields negative results. EV-PCR of specimens from the respiratory and gastrointestinal tracts had higher diagnostic yields than did EV-PCR of cerebrospinal fluid. EV71 infection should be considered in young children presenting with aseptic meningitis, encephalitis, acute flaccid paralysis, or acute cardiopulmonary collapse. EV71 infection may be an underrecognized emerging disease in the United States.

Childhood tuberculosis contributes significantly to the global tuberculosis disease burden but remains challenging to diagnose due to inadequate methods of pathogen detection in paucibacillary pediatric samples and lack of a child-specific host biomarker to identify disease. Accurately diagnosing tuberculosis in children is required to improve case detection, surveillance, healthcare delivery, and effective advocacy. In May 2014, the National Institutes of Health convened a workshop including researchers in the field to delineate priorities to address this research gap. This blueprint describes the consensus from the workshop, identifies critical research steps to advance this field, and aims to catalyze efforts toward harmonization and collaboration in this area.

There is a lack of uniform criteria for the diagnosis and management of tuberculosis (TB) in children in Cali, Colombia. Addressing TB in children is a challenge in this setting, under both programmatic and research conditions.To facilitate the diagnostic assessment of TB in a paediatric cohort of TB household contacts.A diagnostic and management algorithm (DMA) was used to assess children exposed to adult TB cases, according to clinical and epidemiological findings and under programmatic conditions. On the basis of diagnostic tests, cases were classified as TB exposure, TB infection, suspected TB, possible TB or confirmed TB and then submitted to a management plan. This was a prospective pilot study nested within a national cohort study of the transmission dynamics of Mycobacterium tuberculosis, undertaken in Colombia during 2005-2008.During 24 months of follow-up, 54 of 217 children met the criteria for assessment by DMA, 18 of whom (33%) were considered to be TB incident cases (new TB cases among household contacts). The main clinical findings were failure to thrive and cough lasting21 days. Only one case was smear-positive and culture-confirmed TB. TB treatment was given to 16 children and they demonstrated clinical and radiographic resolution at follow-up. Conducting the study under programmatic conditions demonstrated barriers to accessing competent radiological evaluation, correct interpretation of the tuberculin skin test, and proper specimen collection.Structured assessment using DMA facilitated the detection of incident TB cases. The study identified potential barriers to addressing childhood TB in Cali.

An acquired immune deficiency due to interferon gamma (IFN-γ) autoantibodies was diagnosed in a 78-year-old Japanese man with treatment-refractory disseminated nontuberculous mycobacterial infection. In addition to standard antimycobacterial therapy, he was successfully treated with rituximab to eliminate B cells and thereby the autoantibody. Subsequently, he obtained a sustained remission from infection.

To discuss the recommendations pertaining to infants, children, and adolescents in new and updated tuberculosis (TB) guidelines that have been published since 2010 - with emphasis on those from supranational organizations.The main developments in the guidelines covered in this article are related to: novel diagnostics for TB infection, disease, and drug resistance; updated treatment regimens for childhood and drug-resistant TB (DR-TB); and primary and secondary prevention of TB disease in HIV-infected children and adolescents.These new guidelines have significant implications for improving pediatric TB care. Regarding diagnosis, current interferon-gamma release assays should not replace tuberculin skin testing, but may be complementary; a polymerase chain reaction assay has been validated for detecting Mycobacterium tuberculosis and rifampicin resistance in microscopy-negative samples, especially in HIV-infected and DR-TB suspects; and a molecular line probe assay has been validated for detecting DR-TB in microscopy-positive samples and culture isolates in DR-TB suspects. With respect to treatment, there have been certain changes in the recent World Health Organization recommendations for certain clinical syndromes, for multidrug-resistant TB disease, and for HIV/TB disease. Concerning prevention, there are new screening algorithms for case finding, and new recommendations for treating HIV-infected children with presumed TB infection and with TB disease with treatment completed (i.e., secondary prophylaxis).

Transgenic mouse models of prostate cancer provide unique opportunities to understand the molecular events in prostate carcinogenesis and for the preclinical testing of new therapies. We studied the G gamma T-15 transgenic mouse line, which contains the human fetal globin promoter linked to SV40 T antigen (Tag) and which develops androgen-independent prostate cancer. Using the immunohistochemistry of normal mouse prostates before tumor formation, we showed that the target cells of carcinogenesis in G gamma T-15 mice are located in the basal epithelial layer. We tested the efficacy of the 1,25(OH)(2)D(3) analogue, EB 1089, to chemoprevent prostate cancer in these transgenic mice. Compared with treatment with placebo, treatment with EB 1089 at three different time points before the onset of prostate tumors in mice did not prevent or delay tumor onset. However, EB 1089 significantly inhibited prostate tumor growth. At the highest dose, EB 1089 inhibited prostate tumor growth by 60% (P = 0.0003) and the growth in the number of metastases, although this dose also caused significant hypercalcemia and weight loss. We conducted several in vitro experiments to explore why EB 1089 did not prevent the occurrence of the primary tumors. EB 1089 significantly inhibited the growth of a Tag-expressing human prostate epithelial cell line, BPH-1, and an androgen-insensitive subline of LNCaP cells [which was not inhibited by 1,25(OH)(2)D(3)]. Thus, neither Tag expression nor androgen insensitivity explain the absence of chemopreventive effect. Conversely, neither 1,25(OH)(2)D(3) nor EB 1089 inhibited the growth of the normal rat prostate basal epithelial cell line NRP-152. It is likely that EB 1089 was not effective in delaying the growth of the primary tumor in G gamma T-15 transgenic mice because the target cells of carcinogenesis in these mice are located in the basal epithelial layer. We conclude that G gamma T-15 transgenic mice are a useful model for testing vitamin D-based therapies in androgen-insensitive prostate cancer but are not suitable for studies of vitamin D-based chemoprevention. The superiority of EB 1089 over 1,25(OH)(2)D(3) in the growth suppression of androgen-insensitive prostate cancer cells supports the use of EB 1089 in androgen-insensitive prostate cancer.

In Australia, tuberculosis notification rates have plateaued at a low level and disease is highly concentrated in immigrant communities where children may be affected. Many clinicians regard tuberculosis as an adult disease, hence it is rarely considered in the differential diagnosis of sick children. This paper provides a brief overview of the natural history of the disease in children to demonstrate the importance of taking a careful tuberculosis exposure history. It also provides guidance regarding the diagnosis, treatment and prevention of tuberculosis in children. The management of paediatric cases is not difficult if important differences with adult disease are carefully considered; these differences are discussed in detail.

Blood samples were obtained from six HIV-infected IV drug users attending the Indian Council for Medical Research Clinic at Imphal, the capital of Manipur state, as part of a study to analyze the sequences of the third variable region (V3) of the HIV envelope in that population. 18 sequences were obtained from the study participants, men aged 24-29 years. A fragment of the envelope gene encompassing the entire V3 loop and partial sequences from the third conserved region was sequenced, while amplifications were performed on DNA extracted directly from patient peripheral blood mononuclear cells to avoid the introduction of artifacts during cell culture. One set of viruses seems to be most closely related to a prototypical virus recovered from IV drug users in Thailand (Thai B), while the other sequences clustered more closely with a North American clade B virus (HXB). Sequences recovered from one person are rather diverse.

Infections due to toxigenic strains of Streptococcus pyogenes have been associated with toxic shock syndrome. The portal of entry for streptococci is associated with skin, mucous membranes, or subcutaneous lesions, or occasionally, the upper or lower respiratory tract. The clinical spectrum of the streptococcal toxic shock syndrome (STSS) may range from mild illness characterized by local pain and fever to severe disease including hemodynamic instability, organ failure, and death. Clinical manifestations include local muscle pain, high fever, hypotension, and skin rash, which may rapidly progress to involve respiratory, renal, hepatic, and hematologic systems. Streptococcal pyrogenic exotoxin A (SPE A), a superantigen, has been implicated in the pathogenesis of this syndrome. SPE A is a inducer of the synthesis of cytokines, including tumor necrosis factor (TNF)alpha and beta; TNF is responsible for most of the clinical manifestations of STSS. The treatment of STSS is primarily supportive. Therapy is directed at removing the focus of streptococcal infection if feasible and eliminating any residual toxigenic streptococci with antibiotics in conjunction with correcting hemodynamic and organ dysfunction. Additional therapeutic modalities in the treatment of STSS would theoretically attempt to neutralize the toxins or the cytokines released as a consequence of the streptococcal toxins. Intravenous immunoglobulin (IVIG) has been reported to have beneficial effects in the management of STSS, – 9 and has been proposed as an agent to ameliorate these events. We describe a case of a patient with severe STSS, whose illness was lessened with conventional measures and adjunctive IVIG.

Twenty-seven cases of histologically proven carcinoma of the male breast were reviewed and compared with 2,387 cases of mammary carcinoma in women. Men were significantly older than women at the time of diagnosis and more often reported trauma to the breast. They also had a higher incidence of local advancement which was not associated with a longer delay in seeking treatment. No sex specific difference in survival was found when relative survival was determined for all cases from the first sign of disease, and men appeared to be no less curable than women when treated with radical mastectomy for comparable stages of the disease. Men with advanced disease frequently benefited by hormone and endocrine manipulation and one had an unprecedented response to androgen therapy.

Objetivo Determinar los conocimientos, actitudes, prácticas y educación relacionados con Tuberculosis, así como la reactividad a la prueba cutánea de tuberculina de estudiantes de último año de una facultad de salud. Método Se realizó un estudio transversal utilizando un cuestionario diseñado y validado por los investigadores para indagar los conocimientos, actitudes, prácticas y educación relacionados con tuberculosis en 193 estudiantes de último año de los programas de medicina, enfermería, odontología, fisioterapia, fonoaudiología, terapia ocupacional, laboratorio clínico y atención pre-hospitalaria. Se realizó la prueba cutánea de tuberculina en 153 de los encuestados. Resultados Aunque la mayoría de los encuestados calificaron como suficiente la educación recibida sobre tuberculosis, los resultados sobre conocimientos no apoyan esta percepción: 35,2 % de los estudiantes no identificaron apropiadamente los factores de riesgo para tuberculosis nosocomial, solo 33,7 % conocían la incidencia de tuberculosis en el país y un 1,6 % de los encuestados identificó apropiadamente el tratamiento de primera línea para tuberculosis. En cuanto a las prácticas, un 50 % de los encuestados admitió que realizaría la atención de un paciente con tuberculosis sin máscara de alta eficiencia. De acuerdo a la prueba cutánea de tuberculina, 35 % de los estudiantes tenía tuberculosis latente. Conclusiones Los resultados indican que existen oportunidades para mejorar la educación que reciben los estudiantes de esta facultad con respecto a la tuberculosis, además es necesario mejorar las medidas de protección en los contextos en que se llevan a cabo las prácticas de los estudiantes para reducir el riesgo de conversión. Objective To determine tuberculosis (TB) knowledge, attitudes, practices, education and Tuberculin Skin Test (TST) positivity among Colombian health professions students in their last year of study. Methods A cross-sectional study was conducted using a self-reported questionnaire about TB knowledge, attitudes, practices and education with 193 students of medicine, nursing, dentistry, physical therapy, speech and language therapy, occupational therapy, clinical laboratory studies and emergency care. A TST was performed on 153 of the students. Results Although most of survey respondents perceived the TB education they received to be "sufficient", the results regarding their knowledge of TB do not support such perceptions: 35.2% of participants did not identify TB risk factors, 33.7 % of participants identified Colombian TB incidence, and only 1.6 % identified appropriate initial treatment for TB. In regards to practices, 50 % of respondents admitted that they would take care of a patient without a high efficiency mask. The TST was positive in 35 % of participants. Conclusions Our results show that there are opportunities to improve TB education in this health faculty, there is also a need to improve safety practices in the facilities where students work in order to reduce their risk of conversion.

Fifteen squamous cell carcinomas of the skin, termed inadequately excised by the pathologist, were aggravated by lack of patient cooperation or availability. If there was no prophylactic treatment, a recurrence rate of about 50% and an ultimate patient mortality of about 25% from uncontrolled cancer was observed. Prophylactic retreatment with reexcision or radiotherapy before the appearance of clinical recurrence in 24 patients significantly reduced these failures.

Epidermoid carcinomas of the lower extremity are infrequent tumors and references in the literature are inconsistent regarding prognosis and etiology. Some authors consider them slow growing and late to metastasize,3,5,8while others regard these lesions are more malignant than other skin cancer.7 Material Among 31,200 consecutive admissions to the Ellis Fischel State Cancer Hospital, 26 (0.09%) had epidermoid carcinoma and nine (0.03%) had carcinomas in situ of the lower extremities. The 26 invasive cancers were subdivided into group 1, containing 13 cancers that arose primarily from the skin of the leg without any antecedent benign condition being recognized, and group 2, containing 13 invasive cancers arising at the site of a recognized antecedent benign lesion. Eight carcinomas in situ fell in group 1 and one in group 2. Various characteristics of the cancers and hosts are given in Tables 1-5 and Fig 1, serving as a basis for