Diagnostic Images of Pulmonary Alveolar Microlithiasis: A Rare, Autosomal Recessive Disorder.

Pulmonary alveolar microlithiasis (PAM) is a genetic lung disorder that is characterized by the accumulation of calcium phosphate deposits in the alveolar spaces of the lung. PAM is discovered incidentally on radiographs performed for other purposes, and the typical disease course is characterized by slowly progressive respiratory failure over decades. Treatment remains supportive. A 62-year-old woman presented in the emergency department with dyspnoea and fatigue. On physical examination she had crackles on pulmonary auscultation and digital clubbing. A CT scan of the chest showed multiple high-density areas throughout the lung parenchyma, suggesting the presence of alveolar microlithiasis. This CT finding is the typical radiological presentation of PAM, while the hallmark presentation is clinical-radiological dissociation. LEARNING POINTS: Pulmonary alveolar microlithiasis (PAM) is a rare genetic lung disorder resulting in accumulation of calcium phosphate deposits in the alveoli.The typical radiological presentation of PAM is the classic 'sandstorm' appearance in the lung.The key to diagnosis of this disease is clinical-radiological dissociation.

Protective effect of exclusive breastfeeding and effectiveness of maternal vaccination in reducing pertussis-like illness

Abstract Objective: To assess the protective effect of exclusive breastfeeding and the effectiveness of maternal vaccination in reducing pertussis-like illness. Method: This was a case-control study conducted in sentinel hospitals for pertussis in Recife between July 2016 and July 2018. Cases included children aged under six months with symptoms compatible with pertussis (pertussis-like illness). Controls included children aged under six months, living in the metropolitan region of Recife with no diagnosis of pertussis-like illness and matched by the same hospital and birth date. Results: Seventy-three cases and 194 controls were included. The diagnosis of pertussis-like illness was predominantly clinical (97,2%). Amongst the main symptoms, paroxysmal cough was observed in 95.89% of cases and vomiting in 53.4%. There were 29 hospitalized cases and no deaths. Out of the 73 cases, 47 were born to mothers vaccinated against pertussis during pregnancy, and the mothers of 144 of the 194 controls had been vaccinated. The protective effect of breastfeeding was of 74% (95% CI;38%, 89%). Children younger than six months, who were exclusively breastfed and with mothers vaccinated against pertussis during pregnancy were 5 times less likely to develop pertussis-like illness, corresponding to a protection of 79% (95% CI;31%, 94%). The effectiveness of maternal vaccination against pertussis-like illness in children under six months was low (27%) and not statistically significant (CI 95%; −34% a 60%). Conclusions: Exclusive breastfeeding protects children under six months from pertussis-like illness and may be enhanced when associated with maternal vaccination. These strategies should be encouraged because they also protect against pertussis-like illnesses.

Protective effect of exclusive breastfeeding and effectiveness of maternal vaccination in reducing pertussis-like illness.

OBJECTIVE: To assess the protective effect of exclusive breastfeeding and the effectiveness of maternal vaccination in reducing pertussis-like illness. METHOD: This was a case-control study conducted in sentinel hospitals for pertussis in Recife between July 2016 and July 2018. Cases included children aged under six months with symptoms compatible with pertussis (pertussis-like illness). Controls included children aged under six months, living in the metropolitan region of Recife with no diagnosis of pertussis-like illness and matched by the same hospital and birth date. RESULTS: Seventy-three cases and 194 controls were included. The diagnosis of pertussis-like illness was predominantly clinical (97,2%). Amongst the main symptoms, paroxysmal cough was observed in 95.89% of cases and vomiting in 53.4%. There were 29 hospitalized cases and no deaths. Out of the 73 cases, 47 were born to mothers vaccinated against pertussis during pregnancy, and the mothers of 144 of the 194 controls had been vaccinated. The protective effect of breastfeeding was of 74% (95% CI;38%, 89%). Children younger than six months, who were exclusively breastfed and with mothers vaccinated against pertussis during pregnancy were 5 times less likely to develop pertussis-like illness, corresponding to a protection of 79% (95% CI;31%, 94%). The effectiveness of maternal vaccination against pertussis-like illness in children under six months was low (27%) and not statistically significant (CI 95%; -34% a 60%). CONCLUSIONS: Exclusive breastfeeding protects children under six months from pertussis-like illness and may be enhanced when associated with maternal vaccination. These strategies should be encouraged because they also protect against pertussis-like illnesses.

Lyme aortitis.

A 72-year-old man was admitted with complaints of sudden-onset oppressive precordial pain radiating to the back for 1 hour. He had hypotension, peripheral cyanosis and cold extremities. An initial assessment was done and acute coronary syndrome was excluded. After the patient was admitted, he developed fever and increased levels of inflammatory markers. Data obtained from CT angiography and transoesophageal echocardiogram revealed diffuse parietal thickening of the arch and the descending thoracic aorta, as well as dilatation of the aortic root and the proximal ascending aorta. In addition, the test for Borrelia burgdorferi was positive, and the patient was diagnosed with Lyme vasculitis of the thoracic aorta. He was treated with doxycycline for 3 weeks. Two months later, the patient exhibited a Stanford type A aortic dissection (clinically stable), which was treated by prosthesis replacement. The patient has remained asymptomatic for 1 year after the episode, performing his routine daily activities.

A DNA vaccine against yellow fever virus: development and evaluation.

Attenuated yellow fever (YF) virus 17D/17DD vaccines are the only available protection from YF infection, which remains a significant source of morbidity and mortality in the tropical areas of the world. The attenuated YF virus vaccine, which is used worldwide, generates both long-lasting neutralizing antibodies and strong T-cell responses. However, on rare occasions, this vaccine has toxic side effects that can be fatal. This study presents the design of two non-viral DNA-based antigen formulations and the characterization of their expression and immunological properties. The two antigen formulations consist of DNA encoding the full-length envelope protein (p/YFE) or the full-length envelope protein fused to the lysosomal-associated membrane protein signal, LAMP-1 (pL/YFE), aimed at diverting antigen processing/presentation through the major histocompatibility complex II precursor compartments. The immune responses triggered by these formulations were evaluated in H2b and H2d backgrounds, corresponding to the C57Bl/6 and BALB/c mice strains, respectively. Both DNA constructs were able to induce very strong T-cell responses of similar magnitude against almost all epitopes that are also generated by the YF 17DD vaccine. The pL/YFE formulation performed best overall. In addition to the T-cell response, it was also able to stimulate high titers of anti-YF neutralizing antibodies comparable to the levels elicited by the 17DD vaccine. More importantly, the pL/YFE vaccine conferred 100% protection against the YF virus in intracerebrally challenged mice. These results indicate that pL/YFE DNA is an excellent vaccine candidate and should be considered for further developmental studies.

Membrane and envelope virus proteins co-expressed as lysosome associated membrane protein (LAMP) fused antigens: a potential tool to develop DNA vaccines against flaviviruses

Vaccination is the most practical and cost-effective strategy to prevent the majority of the flavivirus infection to which there is an available vaccine. However, vaccines based on attenuated virus can potentially promote collateral side effects and even rare fatal reactions. Given this scenario, the developent of alternative vaccination strategies such as DNA-based vaccines encoding specific flavivirus sequences are being considered. Endogenous cytoplasmic antigens, characteristically plasmid DNA-vaccine encoded, are mainly presented to the immune system through Major Histocompatibility Complex class I - MHC I molecules. The MHC I presentation via is mostly associated with a cellular cytotoxic response and often do not elicit a satisfactory humoral response. One of the main strategies to target DNA-encoded antigens to the MHC II compartment is expressing the antigen within the Lysosome-Associated Membrane Protein (LAMP). The flavivirus envelope protein is recognized as the major virus surface protein and the main target for neutralizing antibodies. Different groups have demonstrated that co-expression of flavivirus membrane and envelope proteins in mammalian cells, fused with the carboxyl-terminal of LAMP, is able to induce satisfactory levels of neutralizing antibodies. Here we reviewed the use of the envelope flavivirus protein co-expression strategy as LAMP chimeras with the aim of developing DNA vaccines for dengue, West Nile and yellow fever viruses.

A vacinação é a estratégia mais prática e o melhor custo-benefício para prevenir a maioria das infecções dos flavivirus, para os quais existe vacina disponível. Entretanto, as vacinas baseadas em vírus atenuados podem potencialmente promover efeitos colaterais e, mais raramente, reações fatais. Diante deste cenário, o desenvolvimento de estratégias alternativas de vacinação, como vacinas baseadas em DNA codificando seqüências específicas dos flavivirus, está sendo considerado. Antí-genos citoplasmáticos endógenos, caracteristicamente codificados por vacinas de DNA plasmidial, são majoritariamente apresentados ao sistema imune através de moléculas do Complexo Maior de Histocompatibilidade de classe I - MHC I. A via de apresentação MHC I é mais associada à resposta celular citotóxica e, frequentemente, não elicita uma resposta humoral satisfatória. Uma das principais estratégias para direcionar antígenos codificados pelas vacinas de DNA para o compartimento MHC II é expressar estes antígenos dentro da Proteína de Associação à Membrana Lisossomal (LAMP). A proteína do envelope dos flavivirus é reconhecidamente a principal proteína de superfície viral e o principal alvo para anticorpos neutralizantes. Diferentes grupos têm demonstrado que a co-expressão das proteínas de membrana e do envelope dos flavivirus em células de mamíferos, fusionada com a porção carboxi-terminal de LAMP, é capaz de induzir níveis satisfatórios de anticorpos neutralizantes. Neste trabalho revisamos a estratégia de co-expressão da proteína do envelope dos flavivírus, como quimeras de LAMP, com o objetivo de desenvolver vacinas de DNA contra a febre do Oeste do Nilo, dengue e febre amarela.

Membrane and envelope virus proteins co-expressed as lysosome associated membrane protein (LAMP) fused antigens: a potential tool to develop DNA vaccines against flaviviruses.

Vaccination is the most practical and cost-effective strategy to prevent the majority of the flavivirus infection to which there is an available vaccine. However, vaccines based on attenuated virus can potentially promote collateral side effects and even rare fatal reactions. Given this scenario, the development of alternative vaccination strategies such as DNA-based vaccines encoding specific flavivirus sequences are being considered. Endogenous cytoplasmic antigens, characteristically plasmid DNA-vaccine encoded, are mainly presented to the immune system through Major Histocompatibility Complex class I - MHC I molecules. The MHC I presentation via is mostly associated with a cellular cytotoxic response and often do not elicit a satisfactory humoral response. One of the main strategies to target DNA-encoded antigens to the MHC II compartment is expressing the antigen within the Lysosome-Associated Membrane Protein (LAMP). The flavivirus envelope protein is recognized as the major virus surface protein and the main target for neutralizing antibodies. Different groups have demonstrated that co-expression of flavivirus membrane and envelope proteins in mammalian cells, fused with the carboxyl-terminal of LAMP, is able to induce satisfactory levels of neutralizing antibodies. Here we reviewed the use of the envelope flavivirus protein co-expression strategy as LAMP chimeras with the aim of developing DNA vaccines for dengue, West Nile and yellow fever viruses.