Norovirus in children under 2 years of age: an epidemiological study in Panama during the COVID-19 pandemic.

Introduction: Norovirus infection is a common cause of acute gastroenteritis (AGE). Surveillance activities are important to aid investigation into effective norovirus control strategies, including vaccination. Here, we report ancillary findings related to the incidence, prevalence, and etiology of AGE caused by norovirus in Panama after adjustment of study methodology to comply with national coronavirus disease 2019 (COVID-19) mandates. Methods: In January 2020, children aged <2 years began enrolling into an epidemiological study in Panama to estimate the burden of norovirus in preparation for evaluating upcoming prevention strategies. This included an observational, longitudinal, community-based AGE surveillance study and a hospital-based AGE surveillance study. For the longitudinal study, healthy children aged 5-18 months were enrolled from January 6 through March 23, 2020, with a follow-up of approximately 6 months. The last participant was contacted on September 23, 2020. For the hospital-based study, starting on January 21, 2020, children aged <2 years who were admitted to the Hospital del Niño Dr. José Renán Esquivel in Panama City due to AGE were evaluated. The last sample was collected on September 29, 2020. Collected stool samples were tested for norovirus as well as astrovirus, sapovirus, and various enteropathogens. Unfortunately, this study was disrupted by the subsequent implementation of disease transmission control procedures for the COVID-19 pandemic, and the study methodology was revised to comply with COVID-19 mandates. Results: In the longitudinal surveillance cohort [N = 400 (Chiriquí, n = 239; Panama, n = 161)], a total of 185 AGE episodes were documented (Chiriquí, n = 85; Panama, n = 100) resulting in an overall AGE incidence of 11.6 (95% CI: 9.99-13.4) episodes per 100 child-months. The norovirus-related AGE incidence was 0.3 (95% CI: 0.10-0.73) episodes per 100 child-months (5/185 AGE episodes) and the prevalence of norovirus was 4.6% (13/282 stool samples collected). In the hospital-based surveillance cohort, at least one pathogen was detected in 50% of samples (44/88 stool samples collected) and norovirus prevalence was 6.8% (6/88 stool samples collected). Discussion: This report demonstrates how the occurrence of the COVID-19 pandemic hindered the conduct of clinical trials. However, this also created unique research opportunities to investigate the potential impact of pandemic control measures on the etiology of infectious diarrheal disease.

Clinical and epidemiological characteristics of Madariaga and Venezuelan equine encephalitis virus infections.

Madariaga virus (MADV) and Venezuelan equine encephalitis virus (VEEV) are emerging arboviruses affecting rural and remote areas of Latin America. However, there are limited clinical and epidemiological reports available, and outbreaks are occurring at an increasing frequency. We addressed this gap by analyzing all the available clinical and epidemiological data of MADV and VEEV infections recorded since 1961 in Panama. A total of 168 of human alphavirus encephalitis cases were detected in Panama from 1961 to 2023. Here we describe the clinical signs and symptoms and epidemiological characteristics of these cases, and also explored signs and symptoms as potential predictors of encephalitic alphavirus infection when compared to those of other arbovirus infections occurring in the region. Our results highlight the challenges clinical diagnosis of alphavirus disease in endemic regions with overlapping circulation of multiple arboviruses.

Detection of parechovirus A in respiratory, gastrointestinal, and neurological clinical samples of pediatric patients from Panama (2014-2015).

Parechovirus A (PeV-A, Parechovirus, Picornaviridae) are human pathogens associated with mild to severe gastrointestinal and respiratory diseases in young children. While several studies have investigated the association of PeV-A with human disease, little is known about its epidemiology or detection in Latin America. Between the years 2014 and 2015, a total of 200 samples were collected from Panamanian pediatric patients aged < 16 years old exhibiting symptoms associated with respiratory (n = 64), gastrointestinal (n = 68), or neurological (n = 68) diseases. These samples were gathered from patients who had previously received negative diagnoses for the main respiratory viruses, rotavirus, and neurological viruses like herpes virus, enterovirus, and cytomegalovirus. The presence of PeV-A was analyzed by real time RT-PCR.Eight positive PeV-A infections (4.0%, 95% CI: 1.7 to 7.7) were detected: two in respiratory samples (3.0%, 95% CI: 0.3 to 10.8), five in gastrointestinal samples (7.3%, 95% CI: 2.4 to 16.3), and one in cerebrospinal fluid (1.5%, 95% CI: 1.4 to 7.9). The study provides evidence of PeV-A circulation in Panama and the data collectively, remarked on the importance of considering PeV-A in the Panamanian pediatric diagnostic landscape, especially when conventional testing for more common viruses yields negative results.

Detection of Leishmania RNA Virus 1 in Leishmania (Viannia) panamensis Isolates, Panama.

We detected Leishmania RNA virus 1 (LRV1) in 11 isolates of Leishmania (Viannia) panamensis collected during 2014-2019 from patients from different geographic areas in Panama. The distribution suggested a spread of LRV1 in L. (V.) panamensis parasites. We found no association between LRV1 and an increase in clinical pathology.

Case Report: First Confirmed Case of Coinfection of SARS-CoV-2 With Choclo orthohantavirus.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a major international public health concern. The World Health Organization (WHO) declared the pandemic of coronavirus disease 2019 (COVID-19) on March 11, 2020. In Panama, the first SARS-CoV-2 infection was confirmed on March 9, 2020, and the first fatal case associated to COVID-19 was reported on March 10. This report presents the case of a 44-year-old female who arrived at the hospital with a respiratory failure, five days after the first fatal COVID-19 case, and who was living in a region where hantavirus pulmonary syndrome cases caused by Choclo orthohantavirus (CHOV), are prevalent. Thus, the clinical personnel set a differential diagnosis to determine a respiratory disease caused by the endemic CHOV or the new pandemic SARS-CoV-2. This case investigation describes the first coinfection by SARS-CoV-2 and CHOV worldwide. PCR detected both viruses during early stages of the disease and the genomic sequences were obtained. The presence of antibodies was determined during the patient's hospitalization. After 23 days at the intensive care unit, the patient survived with no sequelae, and antibodies against CHOV and SARS-CoV-2 were still detectable 12 months after the disease. The detection of the coinfection in this patient highlights the importance, during a pandemic, of complementing the testing and diagnosis of the emergent agent, SARS-CoV-2, with other common endemic respiratory pathogens and other zoonotic pathogens, like CHOV, in regions where they are of public health concern.

SARS-CoV-2 reinfection with a virus harboring mutation in the Spike and the Nucleocapsid proteins in Panama.

We report a case of reinfection by SARS-CoV-2 with the second virus harboring amino acid changes in the Spike protein (141-143del, D215A, ins215AGY, L452R, D614G), orf1a, helicase, orf3a, and Nucleocapside. The virus associated with the reinfection, from an endemic lineage containing the S:L452R immune escape mutation, was circulating in Panama at the time.

Early Transmission Dynamics, Spread, and Genomic Characterization of SARS-CoV-2 in Panama.

We report an epidemiologic analysis of 4,210 cases of infection with severe acute respiratory syndrome coronavirus 2 and genetic analysis of 313 new near-complete virus genomes in Panama during March 9-April 16, 2020. Although containment measures reduced R0 and Rt, they did not interrupt virus spread in the country.

Genotypes of human metapneumovirus circulating during 2010-2012 in children from Panama.

Human metapneumovirus (HMPV) is a common causative agent of severe respiratory tract infections in children under 5 years old, the elderly and immunocompromised patients, being responsible for 5-15% of all viral respiratory infections requiring hospitalization. Though HMPV was included in the surveillance program for respiratory viruses in 2010, its genotype distribution remains unknown. Herein, 45 positive samples to HMPV from children ≤5 years old were characterized by phylogenetic analysis based on N gene sequence. Results showed the co-circulation of four sub-lineages: A2a (8.8%), A2b (55.5%), B1 (15.6%), and B2 (20%), demonstrating the genetic heterogeneity of HMPV circulating in Panamá.

Genetic variability of human respiratory syncytial virus group B in Panama reveals a novel genotype BA14.

In Panama, human respiratory syncytial virus (HRSV) is responsible of 20-40% of acute respiratory infections in children under 5 years old. Currently, little is known about the genetic variability of HRSV in Central America and the Caribbean. Recently, we reported the genetic variability of HRSV-A, however; no studies on HRSV-B in Panama have been described yet. In this study, 24 sequences of Panamanian HRSV-B, from children (<5 years) with acute respiratory infections (ARI), collected from July 2008 to November 2012 were analyzed. All sequences share the characteristic 60-nt duplication of the BA strains. Six Panamanian strains grouped with the BA10 genotype and 12 samples clustered together in a separate monophyletic clade with an aLRT support value of 0.92 and an intra-group p-distance less than 0.07. This fulfills the criteria to consider a new genotype in HRSV, which we named BA14 genotype. Another six strains remain unclassified, but closely related to BA9, BA11, or the new BA14 genotypes, according to their genetic p-distance. Different amino acid substitutions in the Panamanian HRSV-B strains were observed, some previously described and others found only on Panamanian strains. This study contributes to the knowledge of the genetic variability and evolution of HRSV in Central America.

Detection of human bocavirus type 1 infection in Panamanian children with respiratory illness.

The human bocavirus (HBoV) was added as a new member of the Parvoviridae family in 2005 upon its discovery in nasopharyngeal aspirates from children with respiratory infection. Recently, there has been increasing evidence of worldwide circulation of HBoV; however, in Latin America few studies have been conducted. In order to detect the circulation of HBoV in Panama, based on the National Flu Surveillance System, we developed this retrospective, cross-sectional study, from January 2011 to January 2012. Children younger than 6 years old who presented with respiratory disease were enrolled in this study. Nasopharyngeal swabs were taken in sentinel surveillance sites. Samples were tested to detect mRNA from HBoV, as well as viral RNA and DNA from others respiratory viruses. A total of 1078 patients were enrolled in this study. Overall, 44 (4.1%) of the patients presented HBoV. The most common symptoms were cough (84.6%), fever (82.1%), rhinorrhea (74.4%), and sore throat (38.5%). Less than half (45.5%) of HBoV infected patients presented with monoinfection while 54.5% of cases presented with coinfection with others respiratory viruses. Both, outpatients and inpatients were included in this study. Outpatients corresponded to 52.3% of the cases and 47.7% were inpatients. Coinfection was observed in the 50% of the inpatient cases. Phylogenetic analyses indicated that the circulating strains belonged to different clades of HBoV genotype 1. Taken together, our results support the pathogenic nature of this viral agent, especially in younger children.

Conservation of G-Protein Epitopes in Respiratory Syncytial Virus (Group A) Despite Broad Genetic Diversity: Is Antibody Selection Involved in Virus Evolution?

UNLABELLED: Worldwide G-glycoprotein phylogeny of human respiratory syncytial virus (hRSV) group A sequences revealed diversification in major clades and genotypes over more than 50 years of recorded history. Multiple genotypes cocirculated during prolonged periods of time, but recent dominance of the GA2 genotype was noticed in several studies, and it is highlighted here with sequences from viruses circulating recently in Spain and Panama. Reactivity of group A viruses with monoclonal antibodies (MAbs) that recognize strain-variable epitopes of the G glycoprotein failed to correlate genotype diversification with antibody reactivity. Additionally, no clear correlation was found between changes in strain-variable epitopes and predicted sites of positive selection, despite both traits being associated with the C-terminal third of the G glycoprotein. Hence, our data do not lend support to the proposed antibody-driven selection of variants as a major determinant of hRSV evolution. Other alternative mechanisms are considered to account for the high degree of hRSV G-protein variability. IMPORTANCE: An unusual characteristic of the G glycoprotein of human respiratory syncytial virus (hRSV) is the accumulation of nonsynonymous (N) changes at higher rates than synonymous (S) changes, reaching dN/dS values at certain sites predictive of positive selection. Since these sites cluster preferentially in the C-terminal third of the G protein, like certain epitopes recognized by murine antibodies, it was proposed that immune (antibody) selection might be driving the apparent positive selection, analogous to the antigenic drift observed in the influenza virus hemagglutinin (HA). However, careful antigenic and genetic comparison of the G glycoprotein does not provide evidence of antigenic drift in the G molecule, in agreement with recently published data which did not indicate antigenic drift in the G protein with human sera. Alternative explanations to the immune-driven selection hypothesis are offered to account for the high level of G-protein genetic diversity highlighted in this study.

High genetic diversity and predominance of Rhinovirus A and C from Panamanian hospitalized children under five years with respiratory infections.

BACKGROUND: Human Rhinoviruses (HRVs) have high genetic diversity and three species have been described: HRV-A, HRV-B, and the recently recognized HRV-C, which has been rapidly identified worldwide. FINDINGS: In the present study, we report the frequency and diversity of Human Rhinovirus (HRV) strains circulating in Panama from children hospitalized with respiratory infections. CONCLUSIONS: HRVs of species A, B and C have been identified with a predominance of HRV-A and HRV-C over HRV-B, and marked genetic diversity within each species.

Successful public health response to four cases of imported measles in Panama.

In Panama, the last endemic cases of measles occurred in 1995. In this paper, we report four cases of imported measles in three girls and one boy after they returned from a trip to Poland and Israel between 28 April and 11 May 2011. The etiologic diagnosis of the four cases was confirmed by detection of IgM antibodies against measles virus and positive polymerase chain reaction using measles-specific primers. All cases had genotype D4 with close genetic similarity to virus reported from Poland. Public health interventions included isolation of the cases in their homes and an extensive search for and vaccination of contacts of the four cases, regardless of their vaccination status. A nationwide vaccination campaign was also implemented after the first case was identified. A total of 70,950 measles vaccine doses were administered in Panama in the two months following the identification of these cases. In addition, 94,179 persons were confirmed to have their immunization schedule up-to-date and did not receive the vaccine. No secondary cases were detected in Panama in the following six months.