Missed opportunities in the prevention and diagnosis of pediatric tuberculosis: a scoping review.

OBJECTIVES: Identify potential barriers, delays, and missed opportunities in the prevention and diagnosis of childhood TB. METHODS: Scoping review according to the PRISMA extension. The definitions considered for the selection followed the acronym PCC where the population (P) is children under 18 years of age with TB disease, the concept (C) refers to missed opportunities for prevention and diagnosis, and context (C) is defined as a diagnosis of TB disease. The authors searched systematically in the databases; VHL/Lilacs, Medline via PubMed, Cochrane, Scopus, and Web of Science, without date or language limitation. RESULTS: Seven studies were included. In developed countries, with low disease burden, the main shortcoming is the delay in diagnosing bacilliferous adults in contact with young children. This problem is concentrated in the portion of the population with socioeconomic vulnerability. In underdeveloped countries, with a high burden of disease, the biggest challenge is tracking children who come into contact with bacilliferous patients. CONCLUSIONS: There are still many missed opportunities in the prevention and diagnosis of childhood TB. The positive legacy of the COVID-19 pandemic should be taken advantage of and the encouragement of scientific development in the management of infectious diseases should be taken.

Global RNAseq of ocular cells reveals gene dysregulation in both asymptomatic and with Congenital Zika Syndrome infants exposed prenatally to Zika virus.

In 2015, Brazil reported an outbreak identified as Zika virus (ZIKV) infection associated with congenital abnormalities. To date, a total of 86 countries and territories have described evidence of Zika infection and recently the appearance of the African ZIKV lineage in Brazil highlights the risk of a new epidemic. The spectrum of ZIKV infection-induced alterations at both cellular and molecular levels is not completely elucidated. Here, we present for the first time the gene expression responses associated with prenatal ZIKV infection from ocular cells. We applied a recently developed non-invasive method (impression cytology) which use eye cells as a model for ZIKV studies. The ocular profiling revealed significant differences between exposed and control groups, as well as a different pattern in ocular transcripts from Congenital Zika Syndrome (CZS) compared to ZIKV-exposed but asymptomatic infants. Our data showed pathways related to mismatch repair, cancer, and PI3K/AKT/mTOR signaling and genes probably causative or protective in the modulation of ZIKV infection. Ocular cells revealed the effects of ZIKV infection on primordial neuronal cell genes, evidenced by changes in genes associated with embryonic cells. The changes in gene expression support an association with the gestational period of the infection and provide evidence for the resulting clinical and ophthalmological pathologies. Additionally, the findings of cell death- and cancer-associated deregulated genes raise concerns about the early onset of other potential pathologies including the need for tumor surveillance. Our results thus provide direct evidence that infants exposed prenatally to the Zika virus, not only with CZS but also without clinical signs (asymptomatic) express cellular and molecular changes with potential clinical implications.

Tuberculose intratorácica na forma pseudotumoral e óssea como manifestação de doença granulomatosa crônica / Intrathoracic tuberculosis in the pseudotumoral and bone form as a manifestation of chronic granulomatous disease

A doença granulomatosa crônica (DGC) é um erro inato da imunidade de fagócitos, e ocorre em decorrência de mutações que afetam componentes da enzima NADPH oxidase. Os pacientes são suceptíveis a infecções graves e letais por fungos e bactérias. O objetivo deste trabalho é relatar o caso de um lactente com DGC que apresentou manifestação clínica de tuberculose (TB) intratorácica na forma pseudotumoral e óssea iniciada no período neonatal. O diagnóstico de DGC foi realizado através do teste de DHR e, após o início da profilaxia com sulfametoxazoltrimetroprima e itraconazol, o paciente manteve-se estável clinicamente. A mãe e a irmã também apresentaram DHR alterados, a análise genética revelou uma mutação ligada ao X no exon 2 do gene CYBB c.58G>A, levando uma alteração em G20R. É fundamental que o diagnóstico seja realizado o mais precocemente possível, a fim de instituir as orientações aos familiares e tratamento adequado, reduzindo assim complicações infecciosas e melhorando prognóstico.

Chronic granulomatous disease (CGD) is an inborn error of phagocyte immunity and occurs as a resulto f mutations that affect components of the NADPH oxidase enzyme. Patients are susceptible to serious and lethal fungal and bacterial infections. The aim of this paper is to report a case an infant with CGD who presented clinical manifestations of intrathoracic tuberculosis (TB) in the pseudotumoral and bone form, which started in the neonatal period. The diagnosis of CGD was performed using the DHR test and, after starting prophylaxis with sulfamethoxazole-trimethoprim and itraconazole, the patient remained clinically stable. The mother and sister also had altered DHR, genetic analysis revealed an X-linked mutation in exon 2 of the CYBB gene c.58G>A, leading to an alteration in G20R. It is essential that the diagnosis is made as early as possible, in order to establish guidelines for Family members and adequate treatment, thus reducing infectious complications and improving prognosis.

Serum Proteomics Reveals Alterations in Protease Activity, Axon Guidance, and Visual Phototransduction Pathways in Infants With In Utero Exposure to Zika Virus Without Congenital Zika Syndrome.

In 2015, ZIKV infection attracted international attention during an epidemic in the Americas, when neurological disorders were reported in infants who had their mothers exposed to ZIKV during pregnancy. World Health Organization (WHO) epidemiological data show that 5 to 15% of neonates exposed to ZIKV in the uterus have complications included in abnormalities related to Congenital Zika Syndrome (CZS). The risk of complications after birth is not well documented, however, clinical evidence shows that 6% of infants exposed to ZIKV during pregnancy have complications present at birth, and this rate rises to 14% when medical monitoring is performed in all exposed infants, regardless of birth condition. Thus, the evaluation and monitoring of all exposed infants are of foremost importance as the development of late complications has been increasingly supported by clinical evidence. The identification of changes in protein profile of infants exposed to ZIKV without CZS could provide valuable findings to better understand molecular changes in this cohort. Here, we use a shotgun-proteomics approach to investigate alterations in the serum of infants without CZS symptoms but exposed to intrauterine ZIKV (ZIKV) compared to unexposed controls (CTRL). A complex pattern of differentially expressed proteins was identified, highlighting the dysregulation of proteins involved in axon orientation, visual phototransduction, and global protease activity in children exposed to ZIKV without CZS. These data support the importance of monitoring children exposed to ZIKV during gestation and without early CZS symptoms. Our study is the first to assess molecular evidence of possible late disorders in children victims of the ZIKV outbreak in the Americas. We emphasize the importance of medical monitoring of symptomatic and asymptomatic children, as apparently unexplained late neurological and eye disorders may be due to intrauterine ZIKV exposure.

Cellular Imprinting Proteomics Assay: A Novel Method for Detection of Neural and Ocular Disorders Applied to Congenital Zika Virus Syndrome.

Congenital Zika syndrome was first described due to increased incidence of congenital abnormalities associated with Zika virus (ZIKV) infection. Since the eye develops as part of the embryo central nervous system (CNS) structure, it becomes a specialized compartment able to display symptoms of neurodegenerative diseases and has been proposed as a noninvasive approach to the early diagnosis of neurological diseases. Ocular lesions result from defects that occurred during embryogenesis and can become apparent in newborns exposed to ZIKV. Furthermore, the absence of microcephaly cannot exclude the occurrence of ocular lesions and other CNS manifestations. Considering the need for surveillance of newborns and infants with possible congenital exposure, we developed a method termed cellular imprinting proteomic assay (CImPA) to evaluate the ocular surface proteome specific to infants exposed to ZIKV during gestation compared to nonexposure. CImPA combines surface cells and fluid capture using membrane disks and a large-scale quantitative proteomics approach, which allowed the first-time report of molecular alterations such as neutrophil degranulation, cell death signaling, ocular and neurological pathways, which are associated with ZIKV infection with and without the development of congenital Zika syndrome, CZS. Particularly, infants exposed to ZIKV during gestation and without early clinical symptoms could be detected using the CImPA method. Lastly, this methodology has broad applicability as it could be translated in the study of several neurological diseases to identify novel diagnostic biomarkers. Data are available via ProteomeXchange with identifier PXD014038.

Nasopharyngeal carriage, serotype distribution and antimicrobial resistance of Streptococcus pneumoniae among children from Brazil before the introduction of the 10-valent conjugate vaccine.

BACKGROUND: Streptococcus pneumoniae remains a major cause of childhood morbidity and mortality worldwide. Nasopharyngeal colonization plays an important role in the development and transmission of pneumococcal diseases, and infants and young children are considered to be the main reservoir of this pathogen. The aim of this study was to evaluate the rates and characteristics associated with nasopharyngeal carriage, the distribution of serotypes and the antimicrobial resistance profiles of Streptococcus pneumoniae among children in a large metropolitan area in Brazil before the introduction of the 10-valent pneumococcal conjugate vaccine. METHODS: Between March and June 2010, nasopharyngeal swabs were collected from 242 children aged <6 years attending one day care center and the emergency room of a pediatric hospital. Pneumococcal isolates were identified by conventional methods and serotypes were determined by a sequential multiplex PCR assay and/or the Quellung reaction. The antimicrobial susceptibilities of the pneumococci were assessed by the disk diffusion method. MICs for erythromycin and penicillin were also performed. Erythromycin resistance genes were investigated by PCR. RESULTS: The overall colonization rate was 49.2% and it was considerably higher among children in the day care center. Pneumococcal carriage was more common among day care attenders and cohabitants with young siblings. The most prevalent serotypes were 6B, 19F, 6A, 14, 15C and 23F, which accounted for 61.2% of the isolates. All isolates were susceptible to clindamycin, levofloxacin, rifampicin and vancomycin. The highest rate of non-susceptibility was observed for sulphamethoxazole-trimethoprim (51.2%). Penicillin non-susceptible pneumococci (PNSP) accounted for 27.3% of the isolates (MICs of 0.12-4 µg/ml). Penicillin non-susceptibility was strongly associated with serotypes 14 and 23F. Hospital attendance and the presence of respiratory or general symptoms were frequently associated with PNSP carriage. The two erythromycin-resistant isolates (MICs of 2 and 4 µg/ml) belonged to serotype 6A, presented the M phenotype and harbored the mef(A/E) gene. CONCLUSIONS: Correlations between serotypes, settings and penicillin non-susceptibility were observed. Serotypes coverage projected for the 10-valent pneumococcal conjugate vaccine was low (45.5%), but pointed out the potential reduction of PNSP nasopharyngeal colonization by nearly 20%.

Congenital toxoplasmosis infection in an infant born to an HIV-1-infected mother

We report the occurrence of congenital toxoplasmosis in an infant born to an HIV infected mother who had high anti-toxoplasma IgG and negative IgM at nine weeks of gestation. We briefly review available literature and discuss the possible mechanisms of transmission of congenital toxoplasmosis among HIV infected pregnant women.

Congenital toxoplasmosis infection in an infant born to an HIV-1-infected mother.

We report the occurrence of congenital toxoplasmosis in an infant born to an HIV infected mother who had high anti-toxoplasma IgG and negative IgM at nine weeks of gestation. We briefly review available literature and discuss the possible mechanisms of transmission of congenital toxoplasmosis among HIV infected pregnant women.