Nora Mamani

Rotavirus-associated medical visits and hospitalizations in South America: a prospective study at three large sentinel hospitals.

Background. Knowledge of the impact of rotavirus-associated disease on the health care systems of South America can aid in defining strategies for diagnosis, management and prevention. Up to date information on the impact of rotavirus disease in South America is scarce. Aim. To determine prospectively the impact of rotavirus disease as a cause of medical visits and hospitalizations at three large sentinel pediatric hospitals in Argentina, Chile and Venezuela. Methods. A 2-year prospective surveillance for rotavirus-associated medical visits and hospitalizations was conducted during 1997 through 1998 at three large sentinel public hospitals, one each in Argentina, Chile and Venezuela. A common surveillance protocol was implemented at the three sites, and a representative number of nonbloody diarrhea stool samples from children <36 months of age were tested for rotavirus by enzyme-linked immunosorbent assay. Results. For our target age group, acute diarrhea-associated medical visits/hospitalizations represented 4%/2%, 5%/6% and 9%/13% of all medical visits/all hospitalizations at the Argentinean, Chilean and Venezuelan sites, respectively (P < 0.001 for difference among the three sites). Rotavirus detection rates among a total of 5801/1256 medical visit/hospitalization diarrhea stool samples tested were 39%/71% in Argentina, 34%/47% in Chile and 29%/38% in Venezuela (P < 0.01 by chi square for difference among the three sites). Rotavirus was associated with a mean of 1.5, 1.8 and 3% of total medical visits and 1.6, 2.8 and 5% of hospitalizations among children <36 months of age at the Argentinean, Chilean and Venezuelan sites, respectively. Seasonality was evident for medical visits at all three sites (although less striking in Chile) with peak activity occurring between November and May. Rotavirus-associated hospitalizations had a marked peak in Venezuela, represented largely by short stays, but not in Argentina and Chile. Conclusions. Rotavirus was a significant cause of medical visits at all three sentinel sites. Rotavirus caused less hospitalizations than previously reported in Argentina and Chile. On the basis of our findings we estimate that ∼106 000/21 000, 48 000/8000 and 98 000/31 000 rotavirus-associated medical visits/hospitalizations occur yearly in Argentina, Chile and Venezuela, respectively.

Human Caliciviruses Are a Significant Pathogen of Acute Sporadic Diarrhea in Children of Santiago, Chile

Human caliciviruses (HuCVs) are increasingly recognized as common pathogens that cause acute sporadic diarrhea in children; however, regional antigenic and genetic diversity complicate detection techniques. Stool samples from children seeking medical attention in 2 outpatient clinics, a large emergency department, and 2 hospital wards were evaluated for HuCVs by reverse transcription-polymerase chain reaction, using primers based on a conserved sequence of the polymerase region of a previously sequenced Chilean strain. HuCVs were detected in 53 (8%) of 684 children 1 month to 5 years of age (mean, 13 months). Detection occurred year-round without a clear seasonal peak, and detection frequency declined from 16% in 1997 to 2% in 1999. The decline may have been due to a change in virus genotype. HuCVs are a significant pathogen of acute sporadic diarrhea in Chilean children, and continuous characterization of genetic diversity will be crucial for appropriate detection.

A third gyrovirus species in human faeces.

Until 2011 the genus Gyrovirus in the family Circoviridae consisted of a single virus (Chicken anemia virus or CAV) causing a common immunosuppressive disease in chickens when a second gyrovirus (HGyV) was reported on the skin of 4 % of healthy humans. HGyV is very closely related to a recently described chicken gyrovirus, AGV2, suggesting that they belong to the same viral species. During a viral metagenomic analysis of 100 human faeces from children with diarrhoea in Chile we identified multiple known human pathogens (adenoviruses, enteroviruses, astroviruses, sapoviruses, noroviruses, parechoviruses and rotaviruses) and a novel gyrovirus species we named GyV3 sharing <63 % similarity with other gyrovirus proteins with evidence of recombination with CAV in its UTR. Gyroviridae consensus PCR revealed a high prevalence of CAV DNA in diarrhoea and normal faeces from Chilean children and faeces of USA cats and dogs, which may reflect consumption of CAV-infected/vaccinated chickens. Whether GyV3 can infect humans and/or chickens requires further studies.

Novel Recombinant Norovirus Causing Outbreaks of Gastroenteritis in Santiago, Chile

ABSTRACT Capsid and polymerase (RdRp) genes of 13 norovirus outbreak strains from Chile were compared. The genes sequences were discordant for five strains, and recombination was confirmed for two of them by amplification of a 1,360-bp gene segment containing a fragment of both genes. These strains belonged to a novel genogroup by RdRp sequence and to genogroup GII/3 by capsid sequence. Determining the clinical and epidemiological impact of human calicivirus recombination will require future studies.

Symptomatic and Asymptomatic Rotavirus and Norovirus Infections During Infancy in a Chilean Birth Cohort

Background: Rotavirus and more recently norovirus have been recognized as 2 of the most common causes of acute diarrhea in children. Comparative analysis of these infections in a birth cohort has not been performed and can provide relevant insight on clinical and viral behaviors. Methods: Mother-infant pairs from middle-low socioeconomic background living in the Metropolitan Region of Chile are being followed for 18 months in 2 outpatient clinics. Infants are evaluated monthly for asymptomatic excretion of rotavirus and norovirus and during acute diarrhea episodes (ADE) for rotavirus, norovirus, and bacterial enteropathogens. Severity of ADE is evaluated using the Vesikari score. Results: Between July 1, 2006 and September 1, 2008 a total of 198 children were followed for a mean of 15.7 months. Asymptomatic rotavirus and norovirus infections were detected in 1.3% and 8% of 2278 stool samples compromising 14% and 57% of infants, respectively. Incidence of ADE was approximately 0.8 for the first year of life and approximately 0.6 for the 13 to 18 month age group. Rotavirus and norovirus were detected in 15% and 18% of 145 ADE evaluated. Mean Vesikari score was 10.4 and 7.4 for rotavirus and norovirus respectively (P = 0.01) and severity was not associated with age of patients for either virus. Reinfections were more common for norovirus asymptomatic episodes: 44% versus 19% (P = 0.01) and borderline for symptomatic episodes: 40% versus 11% (P = 0.08). Rotavirus genotype G9P8 and norovirus genogroup II (GII) predominated although most asymptomatic episodes for both viruses were nontypable. None of 19 symptomatic GII norovirus infections had a previous documented GII infection compared with 10 of 31 asymptomatic GII infections (OR = 0. 95% CL = 0, 0.59; P = 0.008). Conclusions: Children had suffered a mean of approximately 1.4 ADE by 18 months of age of which 15% and 18% were caused by rotavirus and norovirus, respectively. In general rotavirus infections were more severe than norovirus infections and for both viruses severity was not related to age. Norovirus reinfections were significantly more common than rotavirus reinfections but for GII norovirus a primary infection seems to confer protection against clinically significant reinfections.

Seroprevalence of Norwalk Virus and Mexico Virus in Chilean Individuals: Assessment of Independent Risk Factors for Antibody Acquisition

Norwalk virus (NV) and Mexico (MX) virus represent distinct genetic clusters within the same genus of human caliciviruses (CVs), a major cause of diarrhea in adults. The magnitude and potential risk factors of human CV infection in populations from Santiago and Punta Arenas, Chile, were assessed. Individuals (n = 1,864) gave a blood sample and answered a questionnaire during a household survey. Sera were tested for antibody to NV and MX virus with use of recombinant capsid antigens. Overall, NV and MX virus seroprevalence rates were 83% and 91% in Santiago vs. 67% and 90% in Punta Arenas, respectively (P < .001 for NV virus). Lower socioeconomic status and increasing age were risk factors for infection with both viruses (P < .001). Consumption of seafood, consumption of vegetables, and child care center attendance were population risk factors for infection, but the association of a factor with a virus depended on the city. Prevention of human CV infections will require individual assessment in different communities.

Prospective characterization of norovirus compared with rotavirus acute diarrhea episodes in chilean children.

Background: Rotavirus and more recently noroviruses are recognized as main causes of moderate to severe acute diarrhea episodes (ADE) in children ≤5 years of age. Comparing epidemiologic and clinical features of norovirus to rotavirus ADE will aid in the decision-making process required to develop norovirus vaccines. Methods: Surveillance for ADE occurring in children ≤5 years of age was implemented in the emergency department (ED) and ward of a large hospital in Santiago and Valparaiso, and in 4 outpatient clinics in Santiago. A stool sample was obtained within 48 hours of consultation for rotavirus detection by enzyme-linked immunosorbent assay and noroviruses by enzyme-linked immunosorbent assay or reverse transcription polymerase chain reaction. For ED and hospital rotavirus and norovirus ADE parents were instructed to monitor clinical findings associated with severity until the end of the episode. The 20-point Vesikari score was used to determine disease severity. Results: Between July 2006 and October 2008 rotavirus and noroviruses were detected in 331 (26%) and 224 (18%) of 1913 ADE evaluated. The proportion of rotavirus-positive samples in hospital ward, ED, and outpatient clinic was 40%, 26% to 30%, and 13% compared with 18%, 17% to 19%, and 14% for noroviruses. Mean age and 25%–75% interquartile interval of children with rotavirus and norovirus ADE were remarkably similar, 15.6 months (9–20), and 15.5 months (9–19), respectively. Rotavirus cases displayed an autumn-winter peak followed 2 to 3 months later by the norovirus peak. The mean (interquartile) for the Vesikari score was 12.9 (11–15) and 11.9 (9–14.5) for rotavirus (N = 331) and norovirus (N = 224) ADE, respectively, P = 0.003. Compared with norovirus, rotavirus ADE were more common in the 11 to 16 severity score interval (P = 0.006), had a higher maximum stool output in a given day (P = 0.01) and more frequent fever (P < 0.0001). Duration of diarrhea, presence, duration and intensity of vomiting, and intensity of fever did not differ between viruses. Mixed rotavirus and norovirus infections were uncommon (<1%) and not clinically more severe. Clinical severity of ADE in young infants was similar for rotavirus and lower (P = 0.03) for noroviruses compared with older children. Conclusion: Noroviruses are a significant cause of moderate to severe endemic ADE in Chilean children. Although significantly less severe than rotavirus as a group, most norovirus episodes were moderate to severe clinically. An effective norovirus vaccine would be of significant additional benefit to the current rotavirus vaccine in decreasing disease burden associated with ADE.

Caliciviruses and foodborne gastroenteritis, Chile.

Human caliciviruses caused 45% of 55 gastroenteritis outbreaks occurring in Santiago, Chile, during 2000–2003. Outbreaks affected ≤99 persons, occurred most commonly in the home, and were associated with seafood consumption. Thirteen outbreak strains sequenced were noroviruses, including 8 GII, 2 GI, and 3 belonging to a novel genogroup.

Impact of Rotavirus Infections on Outpatient Clinic Visits in Chile

Background: Incorporation of new rotavirus vaccines into national programs of developing countries will rely on well-designed cost-effective analysis based on accurate assessment of disease burden. For Chile, rotavirus disease burden is determined mostly by outpatient clinic and emergency room visits and by hospitalizations. We previously estimated a yearly incidence of 8000 and 53,000 hospitalizations and emergency room visits respectively for children ≤3 years of age. Objective: The objective of this study was to quantify the impact of rotavirus as a cause of outpatient clinic visits. Methods: A prospective surveillance protocol between the Health Ministry and the University of Chile in 11 outpatient clinics from 6 regions included reporting of all acute diarrhea cases in children <5 years of age and collection of a stool sample for the first 5 children per week. Results: A total of 5217 acute diarrhea episodes requiring an outpatient medical visit for a total assigned population of 41,927 children <5 years of age were reported from August 1, 2004, to October 30, 2005, in the 11 clinics. A total of 179 rotavirus positive samples were detected from 1313 stools collected for an overall positivity of 13.6% (95% confidence limit: 11.8–15.6%). Rotavirus outpatient visits occurred during all 15 months without a clear seasonal predominance and peaked between 6 months and 2 years of age. G4 types predominated during the 15-month period. Conclusions: For Chilean children ≤3 years of age, a yearly estimate of 11,658 to 16,305 outpatient medical visits need to be added to previous disease burden estimates.

Persistent and Transient Helicobacter pylori Infections in Early Childhood

BACKGROUND Helicobacter pylori, the main cause of peptic ulcer disease and gastric cancer in adult populations, is generally acquired during the first years of life. Infection can be persistent or transient and bacterial and host factors determining persistence are largely unknown and may prove relevant for future disease. METHODS Two cohorts of healthy Chilean infants (313 total) were evaluated every 3 months for 18-57 months to determine pathogen- and host-factors associated with persistent and transient infection. RESULTS One-third had at least one positive stool ELISA by age 3, with 20% overall persistence. Persistent infections were acquired at an earlier age, associated with more household members, decreased duration of breastfeeding, and nonsecretor status compared to transient infections. The cagA positive strains were more common in persistent stools, and nearly 60% of fully characterized persistent stool samples amplified cagA/vacAs1m1. Persistent children were more likely to elicit a serologic immune response, and both infection groups had differential gene expression profiles, including genes associated with cancer suppression when compared to healthy controls. CONCLUSIONS These results indicate that persistent H. pylori infections acquired early in life are associated with specific host and/or strain profiles possibly associated with future disease occurrence.