[Acute disseminated encephalomyelitis due to Mycoplasma pneumoniae in a previously healthy boy]. / Encefalomielitis aguda diseminada por Mycoplasma pneumoniae en un niño previamente sano.

We present here the case of a previously healthy 5 year-old boy hospitalized in an intensive care unit due to tonic-clonic seizures focused on the face and right side of the body, and axillary temperature of 37.4°C. Common bacterial and viral etiology was ruled out through studies of cerebrospinal fluid (CSF) samples. Mycoplasma pneumoniae was suspected by a positive immunofluorescence serum test for IgM class antibodies. Finally, with a brain biopsy, M. pneumoniae was confirmed by polymerase chain reaction (PCR) and acute disseminated encephalomyelitis by pathological anatomy. The patient was treated with clarithromycin and had an uneventful evolution. At least to our knowledge, this is the first case in which M. pneumoniae DNA was detected by PCR in a brain biopsy.

Systematic review and meta-analysis of respiratory syncytial virus infection epidemiology in Latin America.

Respiratory syncytial virus (RSV) is a frequent cause of acute respiratory infection and the most common cause of bronchiolitis in infants. The aim of this systematic review and meta-analysis was to obtain a comprehensive epidemiological picture of the data available on disease burden, surveillance, and use of resources in Latin America. Pooled estimates are useful for cross-country comparisons. Data from published studies reporting patients with probable or confirmed RSV infection in medical databases and gray literature were included from 74 studies selected from the 291 initially identified. When considering all countries, the largest pooled percentage RSV in low respiratory tract infection patients was found in the group between 0 and 11 months old, 41.5% (95% CI 32.0­51.4). In all countries, percentages were increasingly lower as older children were included in the analyses. The pooled percentage of RSV in LRTIs in the elderly people was 12.6 (95% CI 4.2­24.6). The percentage of RSV infection in hospitalized newborns was 40.9% (95% CI 28.28­54.34). The pooled case fatality ratio for RSV infection was 1.74% (95% CI 1.2­2.4) in the first 2 years of life. The average length of stay excluding intensive care unit admissions among children with risk factors for severe disease was 12.8 (95% CI 8.9­16.7) days, whereas it averaged 7.3 (95% CI 6.1/8.5) days in otherwise healthy children.We could conclude that infants in their first year of age were the most vulnerable population. To our knowledge, this is the first systematic review on RSV disease burden and use of health resources in Latin America.

Pediatric hospitalizations associated with 2009 pandemic influenza A (H1N1) in Argentina.

BACKGROUND: While the Northern Hemisphere experiences the effects of the 2009 pandemic influenza A (H1N1) virus, data from the recent influenza season in the Southern Hemisphere can provide important information on the burden of disease in children. METHODS: We conducted a retrospective case series involving children with acute infection of the lower respiratory tract or fever in whom 2009 H1N1 influenza was diagnosed on reverse-transcriptase polymerase-chain-reaction assay and who were admitted to one of six pediatric hospitals serving a catchment area of 1.2 million children. We compared rates of admission and death with those among age-matched children who had been infected with seasonal influenza strains in previous years. RESULTS: Between May and July 2009, a total of 251 children were hospitalized with 2009 H1N1 influenza. Rates of hospitalization were double those for seasonal influenza in 2008. Of the children who were hospitalized, 47 (19%) were admitted to an intensive care unit, 42 (17%) required mechanical ventilation, and 13 (5%) died. The overall rate of death was 1.1 per 100,000 children, as compared with 0.1 per 100,000 children for seasonal influenza in 2007. (No pediatric deaths associated with seasonal influenza were reported in 2008.) Most deaths were caused by refractory hypoxemia in infants under 1 year of age (death rate, 7.6 per 100,000). CONCLUSIONS: Pandemic 2009 H1N1 influenza was associated with pediatric death rates that were 10 times the rates for seasonal influenza in previous years.

Virological surveillance and antiviral resistance of human influenza virus in Argentina, 2005-2008.

OBJECTIVE: To describe the virological characteristics of the influenza strains circulating in Argentina in 2005-2008 and to assess the prevalence of antiviral resistance. METHODS: On the basis of their geographical spread and prevalence, influenza A and B isolates grown in Madin-Darby canine kidney cells were selected after antigenic and genomic characterization to be analyzed for antiviral resistance by enzymatic assay and pyrosequencing. Amantadine susceptibility was evaluated by pyrosequencing for known resistance markers on 45 strains of influenza A. Susceptibility to oseltamivir and zanamivir was evaluated by enzymatic assay of 67 influenza A and 46 influenza B strains, some of which were further analyzed by sequencing the neuraminidase gene. RESULTS: Resistance to amantadine was observed only on A(H3N2) strains (29/33); all of them carried the mutation S31N in their M2 sequence. Oseltamivir resistance was observed in 12 (34.3%) of the 35 A(H1N1) strains from 2008; all of them carried the mutation H275Y in their neuraminidase sequence. All these viruses remained sensitive to zanamivir. CONCLUSIONS: This study describes a high incidence of amantadine-resistant influenza A(H3N2) viruses since 2006 and an unprecedented increase in oseltamivir resistance detected only in influenza A(H1N1) viruses isolated in 2008. Influenza A and B viruses were more sensitive to oseltamivir than to zanamivir, and influenza A viruses were more sensitive to both neuraminidase inhibitors than the influenza B viruses. The national data generated and analyzed in this study may help increase knowledge about influenza antiviral drug resistance, which is a problem of global concern.

Timing of respiratory syncytial virus and influenza epidemic activity in five regions of Argentina, 2007-2016.

BACKGROUND: Within-country differences in the timing of RSV and influenza epidemics have not been assessed in Argentina, the eighth largest country in the world by area. OBJECTIVE: We aimed to compare seasonality for RSV and influenza both nationally and in each of the five regions to inform Argentina's prevention and treatment guidelines. METHOD: The Argentine National Laboratories and Health Institutes Administration collected respiratory specimens from clinical practices, outbreak investigations, and respiratory virus surveillance in 2007-2016; these were tested using immunofluorescence or RT-PCR techniques. We calculated weekly percent positive (PP) and defined season onset as >2 consecutive weeks when PP exceeded the annual mean for the respective year and region. Median season measures (onset, offset and peak) and the established mean method were calculated for each virus. RESULTS: An annual median 59 396 specimens were tested for RSV and 60 931 for influenza; 21-29% tested positive for RSV and 2-7% for influenza. National RSV activity began in April; region-specific start weeks varied by 7 weeks. Duration of RSV activity did not vary widely by region (16-18 weeks in duration). National influenza activity started in June; region-specific start weeks varied by 3 weeks. Duration of influenza epidemic activity varied more by region than that of RSV (7-13 weeks in duration). CONCLUSION: In Argentina, RSV and influenza activity overlapped during the winter months. RSV season tended to begin prior to the influenza season, and showed more variation in start week by region. Influenza seasons tended to vary more in duration than RSV seasons.

[Influenza associated excess mortality in Argentina: 1992-2002]. / Exceso de mortalidad asociada a influenza en Argentina: 1992-2002.

OBJECTIVE: To describe the effect of influenza on mortality in Argentina, from 1992 to 2002. METHOD: In order to fulfill this objective, influenza associated excess mortality was determined by the application of ARIMA method to mortality data for pneumonia and influenza and for all causes. RESULTS: Excess mortality was only detected during subtype A/H3N2 seasons. The model yielded about 31,240 excess mortality for all causes. Pneumonia deaths contributed in about 15%. Approximately 80-95% of pneumonia and influenza excess mortality was restricted to persons > 64 years old. CONCLUSIONS: These estimations show that the virus circulation has had an important influence on mortality, increasing the number of deaths, especially in elderly population. The aging of the population reinforces the need of preventing strategies, including vaccination programs with high coverage in elderly population.

[Severe acute respiratory syndrome. The public health laboratory in a global emergency]. / Síndrome respiratorio agudo grave. El laboratorio de salud pública frente a una emergencia global.

By the end of year 2002 there was an outbreak of atypical pneumonia in Southeast Asia which soon spread to other continents. This new severe acute respiratory syndrome (SARS) was produced by a novel coronavirus. Due to the severity of the situation and risk of introduction of this pathology in our country, the need to arrange specific laboratory diagnostic tests arose. Classic techniques, such as the electron microscopy and molecular biology test such as retrotranscription followed by the polymerase chain reaction (RT-PCR) were implemented. The araldit included cells infected with bovine coronavirus which allowed the viral particles to be visualized easily but it took more time in comparison with the negative staining of free particles from viral cultures. RT-PCR was able to detect RNA of isolated viruses from cases in Hong Kong and Germany.

RSV molecular characterization and specific antibody response in young children with acute lower respiratory infection.

The presence of respiratory syncytial virus (RSV) in nasopharyngeal aspirates (NPA) were studied in 254 hospitalized Argentinean children with acute lower respiratory infection tract (ALRI). The specific humoral immune response and partial sequences of the G protein gene were studied in a subset of 22 children with RSV confirmed infection. The RSV IgM detection and the RSV IgG titration were made by immunofluorescence assay (IFA) in pairs of sera. The partial RSV G gene sequences were obtained by an RT-PCR amplification directly from de NPAs. RSV was present in 44.5% of the children. The RSV IgM was detected in 22.7 and 68.8% of the first and second sera, respectively. The IgG geometric mean titers of the acute and convalescent sera were 8 and 589. The RSV IgG titration was able to define 86.4% of the RSV confirmed cases. The percentage of coincidence between RSV IgM detection in the second sera and diagnosis by RSV IgG titration was 72.7% and no significant differences were observed. The nucleotide sequence of one group A and three group B viruses were identified. The first one was related with circulating viruses in Madrid, Montevideo and Mozambique during 1992, 1989 and 1999, respectively. The three sequences identified as group B viruses were closely related with circulating viruses in 1998 from South Africa and Canada during 1999 and 2000. The data obtained in our study provide the first approach at the molecular level (nucleotide) of the RSV circulating strains in Argentina and the lack of genotype patterns previously determined make necessary a continuous molecular surveillance in order to contribute to the understanding of the behavior of this virus in our community.

Antigenic and genomic relation between human influenza viruses that circulated in Argentina in the period 1995-1999 and the corresponding vaccine components.

BACKGROUND: The analysis of epidemic influenza virus has been focused on antigenic and genomic characterization of the hemagglutinin (HA) glycoprotein in order to detect new variants for the recommendation of the vaccine strains in each season. Since October 1998, WHO organized a second meeting to evaluate the vaccine formula for the southern hemisphere. OBJECTIVES: (a) Present the antigenic and genomic characterization of influenza strains obtained from the Argentina surveillance network, (b) compare between strains collected in Argentina and other countries with the vaccine formula strains used in each season. STUDY DESIGN: Influenza strains were collected during a 5-year period (1995-1999). Initially, laboratory diagnosis was done by immunofluorescence (IF) assay on clinical samples, followed by viral isolation in Madin-Darby canine kidney (MDCK) cells. The isolates were characterized antigenically by hemagglutination-inhibition (HI) assay with post-infection ferret antisera. The genomic characterization consisted on RT-PCR followed by sequencing of the HA1 portion of the HA gene. The comparison between reference and circulating strains was analyzed by the construction of phylogenetic trees. RESULTS: The H3N2 circulating strains matched the corresponding vaccine component only in 1999, the first year when a vaccine recommended specifically for the southern hemisphere was used. Besides, H1N1 circulating strains matched the corresponding vaccine component only in 1998. Regarding to influenza B, only in 1995, the circulating strains showed no match to the B vaccine component. CONCLUSIONS: The results showed the usefulness of an intensified influenza laboratory surveillance to access the correct vaccine and the importance of having the necessary tools to characterize the circulating strains.

[Community-acquired pneumonia in patients in 2 hospital populations]. / Neumonía adquirida en la comunidad en dos poblaciones hospitalarias.

Patients hospitalized with community acquired pneumonia were studied prospectively in two hospitals located in the surroundings of Buenos Aires city. Fifty two patients from General Hospital Manuel Belgrano (HMB) were included from March 1998 to February 1999 and 23 patients from Hospital Dr A. Cetrangolo (HCET) for respiratory disease, were included from June 2000 to May 2001. Patients with lung tuberculosis, lung neoplasia and HIV infection were excluded. Clinical background, signs and symptoms were recorded. Microbiological examinations performed included bacteria, respiratory viruses and mycobacteria. Studies for "atypical" bacteria (Chlamydia spp., Coxiella burnetii, Mycoplasma pneumoniae and Legionella spp.) were carried out by serological methods. No differences in age and gender were observed between both groups. Most frequently observed comorbidities in the HMB group included COPD, diabetes and cardiac failure while in the HCET group these were COPD, asthma and lung fibrosis. Etiology was established in 48% and 65.2% of the patients in the first and second group, respectively. Most frequent agents were Mycoplasma pneumoniae, Streptococcus pneumoniae, influenza A and Legionella spp.; the last one was detected in 12% of the patients. Most of these patients were from HMB and presented a good outcome. Mortality was similar in both groups (13.3%). In the HBM group it was related to the presence of comorbidities in 7 out of 8 cases, and in the HCET group it was a consequence of the worsening of their chronic respiratory failure.

Antigenic and genomic characterization of human influenza A and B viruses circulating in Argentina after the introduction of influenza A(H1N1)pdm09.

This study was conducted as part of the Argentinean Influenza and other Respiratory Viruses Surveillance Network, in the context of the Global Influenza Surveillance carried out by the World Health Organization (WHO). The objective was to study the activity and the antigenic and genomic characteristics of circulating viruses for three consecutive seasons (2010, 2011 and 2012) in order to investigate the emergence of influenza viral variants. During the study period, influenza virus circulation was detected from January to December. Influenza A and B, and all current subtypes of human influenza viruses, were present each year. Throughout the 2010 post-pandemic season, influenza A(H1N1)pdm09, unexpectedly, almost disappeared. The haemagglutinin (HA) of the A(H1N1)pdm09 viruses studied were segregated in a different genetic group to those identified during the 2009 pandemic, although they were still antigenically closely related to the vaccine strain A/California/07/2009. Influenza A(H3N2) viruses were the predominant strains circulating during the 2011 season, accounting for nearly 76 % of influenza viruses identified. That year, all HA sequences of the A(H3N2) viruses tested fell into the A/Victoria/208/2009 genetic clade, but remained antigenically related to A/Perth/16/2009 (reference vaccine recommended for this three-year period). A(H3N2) viruses isolated in 2012 were antigenically closely related to A/Victoria/361/2011, recommended by the WHO as the H3 component for the 2013 Southern Hemisphere formulation. B viruses belonging to the B/Victoria lineage circulated in 2010. A mixed circulation of viral variants of both B/Victoria and B/Yamagata lineages was detected in 2012, with the former being predominant. A(H1N1)pdm09 viruses remained antigenically closely related to the vaccine virus A/California/7/2009; A(H3N2) viruses continually evolved into new antigenic clusters and both B lineages, B/Victoria/2/87-like and B/Yamagata/16/88-like viruses, were observed during the study period. The virological surveillance showed that the majority of the circulating strains during the study period were antigenically related to the corresponding Southern Hemisphere vaccine strains except for the 2012 A(H3N2) viruses.

Pandemic influenza A/H1N1 2009 antibodies in the metropolitan area of Buenos Aires in Argentina.

OBJECTIVE: To estimate the infection prevalence in Buenos Aires during the outbreak of pandemic influenza A/H1N1 2009 virus (A(H1N1)pdm09). METHODS: A(H1N1)pdm09-specific antibodies were measured by hemagglutination inhibition assay in human serum samples collected 6 months after the outbreak and before the introduction of the A(H1N1)pdm09 vaccine in Argentina. Baseline levels of cross-reactive antibodies to A(H1N1)pdm09 were determined by testing 162 serum samples collected before 2009. RESULTS: The overall seroprevalence of A(H1N1)pdm09 in 150 children and 427 adults was 28.9% (95% confidence interval (CI) 25-33%), with a 58.0% prevalence in children <19 years of age and an 18.7% prevalence in adults ≥19 years of age (p<0.001). The prevalence was 43.5% in children <5 years old and 60.6% among children aged 5-18 years. The prevalence in adults declined with increasing age: 24.9% in 19-39-year-olds, 9.7% in 40-59-year-olds, and 8.1% in those ≥60 years old. The prevalence of specific A(H1N1)pdm09 antibodies was higher compared with the baseline in children (p=0.014), adolescents (p<0.001), and adults <40 years old (p=0.017). Seroprevalence in health care workers was not different from the rest of the population (13.6% vs. 19.3%, respectively; p=0.421). CONCLUSIONS: The prevalence of specific A(H1N1)pdm09 antibodies was high at 28.9%. The highest prevalence was observed in children, adolescents, and young adults.

Encefalomielitis aguda diseminada por Mycoplasma pneumoniae en un niño previamente sano / Acute disseminated encephalomyelitis due to Mycoplasma pneumoniae in a previously healthy boy

Se presenta el caso de un niño de 5 años sin antecedentes de enfermedad, que se internó en terapia intensiva por convulsiones tónico-clónicas focalizadas en la cara y en el hemicuerpo derecho, con documentación de temperatura axilar de 37,4°C. Se descartó la presencia de gérmenes comunes y la etiología viral a través de estudios de muestras de líquido cefalorraquídeo (LCR). Se sospechó la presencia de Mycoplasma pneumoniae por comprobarse inmunofluorescencia positiva en suero para anticuerpos de clase IgM. El diagnóstico se confirmó mediante la detección del ADN de dicho patógeno sobre la biopsia cerebral efectuada por el método de la reacción en cadena de la polimerasa (PCR) y una histología compatible con encefalomielitis aguda diseminada. El paciente recibió tratamiento con claritromicina y su evolución fue favorable. Al menos dentro de nuestros conocimientos, este es el primer caso en el que se detectó ADN de M. pneumoniae en una biopsia cerebral por el método de PCR.

We present here the case of a previously healthy 5 year-old boy hospitalized in an intensive care unit due to tonic-clonic seizures focused on the face and right side of the body, and axillary temperature of 37.4 °C. Common bacterial and viral etiology was ruled out through studies of cerebrospinal fluid (CSF) samples. Mycoplasma pneumoniae was suspected by a positive immunofluorescence serum test for IgM class antibodies. Finally, with a brain biopsy, M. pneumoniae was confirmed by polymerase chain reaction (PCR) and acute disseminated encephalomyelitis by pathological anatomy. The patient was treated with clarithromycin and had an uneventful evolution. At least to our knowledge, this is the first case in which M. pneumoniae DNA was detected by PCR in a brain biopsy.

Burden of influenza in Latin America and the Caribbean: a systematic review and meta-analysis.

OBJECTIVE: Influenza causes severe morbidity and mortality. This systematic review aimed to assess the incidence, etiology, and resource usage for influenza in Latin America and the Caribbean. DESIGN: Meta-analytic systematic review. Arcsine transformations and DerSimonian Laird random effects model were used for meta-analyses. SETTING: A literature search from 1980 to 2008 in MEDLINE, Cochrane Library, EMBASE, LILACS, Ministries of Health, PAHO, proceedings, reference lists, and consulting experts. SAMPLE: We identified 1092 references, of which 31 were finally included, in addition to influenza surveillance reports. We also used information from the 10 reports from the collaborative group for epidemiological surveillance of influenza and other respiratory virus (GROG), and information retrieved from the WHO global flu database FLUNET. MAIN OUTCOME MEASURES: Incidence, percentage of influenza specimens out of the total received by influenza centers and resource-use outcomes. RESULTS: A total of 483 130 specimens of patients with influenza were analyzed. Meta-analysis showed an annual rate of 36 080 (95%CI 28 550 43 610) influenza-like illness per 100 000 persons-years. The percentage of influenza out of total specimens received by influenza centers ranged between 4.66% and 15.42%, with type A the most prevalent, and A subtype H3 predominating. The mean length of stay at hospital due to influenza ranged between 5.8 12.9 days, total workdays lost due to influenza-like illnesses were 17 150 days, and the mean direct cost of hospitalization was US$575 per laboratory-confirmed influenza case. CONCLUSIONS: Our data show that seasonal influenza imposes a high morbidity and economic burden to the region. However, the vaccine-uptake rate has been low in this region. Population-based cohort studies are required to improve the knowledge about incidence and resource utilization, which would inform healthcare authorities for decision making.

Effects of two commonly found strains of influenza A virus on developing dopaminergic neurons, in relation to the pathophysiology of schizophrenia.

Influenza virus (InfV) infection during pregnancy is a known risk factor for neurodevelopment abnormalities in the offspring, including the risk of schizophrenia, and has been shown to result in an abnormal behavioral phenotype in mice. However, previous reports have concentrated on neuroadapted influenza strains, whereas increased schizophrenia risk is associated with common respiratory InfV. In addition, no specific mechanism has been proposed for the actions of maternal infection on the developing brain that could account for schizophrenia risk. We identified two common isolates from the community with antigenic configurations H3N2 and H1N1 and compared their effects on developing brain with a mouse modified-strain A/WSN/33 specifically on the developing of dopaminergic neurons. We found that H1N1 InfV have high affinity for dopaminergic neurons in vitro, leading to nuclear factor kappa B activation and apoptosis. Furthermore, prenatal infection of mothers with the same strains results in loss of dopaminergic neurons in the offspring, and in an abnormal behavioral phenotype. We propose that the well-known contribution of InfV to risk of schizophrenia during development may involve a similar specific mechanism and discuss evidence from the literature in relation to this hypothesis.

Addition of the immunostimulatory oligonucleotide IMT504 to a seasonal flu vaccine increases hemagglutinin antibody titers in young adult and elder rats, and expands the anti-hemagglutinin antibody repertoire.

Flu vaccines are partially protective in infants and elder people. New adjuvants such as immunostimulatory oligonucleotides (ODNs) are strong candidates to solve this problem, because a combination with several antigens has demonstrated effectiveness. Here, we report that IMT504, the prototype of a major class of immunostimulatory ODNs, is a potent adjuvant of the influenza vaccine in young adult and elderly rats. Flu vaccines that use virosomes or whole viral particles as antigens were combined with IMT504 and injected in rats. Young adult and elderly animals vaccinated with IMT504-adjuvated preparations reached antibody titers 20-fold and 15-fold higher than controls, respectively. Antibody titers remained high throughout a 120 day-period. Animals injected with the IMT504-adjuvated vaccine showed expansion of the anti-hemagglutinin antibody repertoire and a significant increase in the antibody titer with hemagglutination inhibition capacity when confronted to viral strains included or not in the vaccine. This indicates that the addition of IMT504 in flu vaccines may contribute to the development of significant cross-protective immune response against shifted or drifted flu strains.