Dengue In Infants Research Articles

Infant Dengue a 10-Year Experience from a Tertiary Center in South India.

Dengue remains a major problem in the tropics. Several Asian countries have reported an increasing trend in the proportion of infants with dengue fever. However, most studies are limited to case reports or small case series from isolated outbreaks. We planned this study to look at clinico-laboratory profile, outcome, and predictors of severity in a large cohort of infants over a decade. Electronic medical records of infants admitted at a tertiary center of South India, with laboratory confirmed dengue infection between 2009 and 2019 were reviewed. Diagnosis was based on detection of NS-1 antigen and/or immunoglobulin M antibody against DENV(dengue virus) or positive DENV RNA polymerase chain reaction in infants presenting with acute febrile illness and clinical features consistent with dengue. Of 395 children with dengue admitted during study period, 99 (25%) were infants. A cyclical incidence pattern was noted, with higher cases in alternate years. Fever (99%) was most common, followed by gastrointestinal symptoms (vomiting, diarrhea-28%) and upper respiratory symptoms (cough, coryza-22%). Fifty-three infants had severe dengue, and 39 had shock. Fourteen children had multiorgan dysfunction syndrome, and 13 died. Infants with severe dengue were older than those with nonsevere disease, had lower serum albumin and greater frequency of severe thrombocytopenia, and had coagulopathy. On multivariable analysis, low serum albumin predicted development of severe dengue [P = 0.003, odds ratio 12.4 (95% confidence interval: 2.42-63.7)]. Dengue in infants may be challenging to recognize because of its undifferentiated presentation, with gastrointestinal and upper respiratory symptoms that are similar to other viral illness. Severe dengue is common in this sample, and lower serum albumin at presentation was predictive of severe disease.

Clinical profile of Dengue infection in infants a tertiary teaching hospital experience

Background: Dengue viral infection caused by arthropod borne flavivirus has become endemic worldwide. India contributes to a tune of 20% of global burden. The clinical manifestation ranging from benign dengue fever (DF) to life threatening dengue hemorrhagic fever (DHF)/ dengue shock syndrome (DSS), has varied nonspecific features in infants. study was undertaken during our peak dengue season to know the clinical profile and outcome of dengue viral infection in infants.Methods: This is a prospective observational study. All infants with features suggestive/ clinical suspicion of dengue were enrolled with parental consent. Their demographic detail, history, clinical features were collected, categorised and treated according to WHO 2012 dengue guidelines.Results: A total of 86 infants were enrolled. Male female ratio was 2.44:1. Majority of infants were in Category B (63.9%) Fever being the most common presentation, Gastrointestinal and Respiratory symptoms, CNS manifestation like convulsion/ altered sensorium was noticed in 3.4% cases. Majority of cases were in critical phase (80%), recovery phase with fluid overloaded (edema) features were present in 7% cases. Thrombocytopenia was seen in all infants. Infants in Category C needed ionotropes, ventilator support and blood products, whereas those in other two categories did not. Recovery was seen in 94.25% and mortality was 4.6%.Conclusions: This study highlights the varied presentation of dengue in infants and to have a high index of clinical suspicion for dengue in infants presenting with nonspecific symptoms, for effective care of this dynamic disease.

Epidemiology of Dengue Among Children Aged < 18 Months-Puerto Rico, 1999-2011.

Dengue, a mosquito-borne viral illness caused by dengue virus types (DENV)-1 to DENV-4, is endemic in Puerto Rico. Severe dengue usually occurs in individuals previously infected with DENV or among infants born to previously infected mothers. To describe clinical features of dengue in infants, we retrospectively characterized dengue patients aged < 18 months reported to the Passive Dengue Surveillance System (PDSS) during 1999–2011. To determine frequency of signs, symptoms, and disease severity, case report forms and medical records were evaluated for patients who tested positive for dengue by reverse transcriptase polymerase chain reaction or anti-DENV immunoglobulin Menzyme-linked immunosorbent assay. Of 4,178 reported patients aged < 18 months, 813 (19%) were laboratory positive. Of these, most had fever (92%), rash (53%), bleeding manifestations (52%), and thrombocytopenia (52%). Medical records were available for 145 (31%) of 472 hospitalized patients, of which 40% had dengue, 23% had dengue with warning signs, and 33% had severe dengue. Mean age of patients with severe dengue was 8 months. Anti-DENV immunoglobulin G (IgG) titers were not statistically different in patients with (50%) and without (59%) severe dengue. In this study, one-third of DENV-infected infants met the severe dengue case definition. The role of maternal anti-DENV IgG in development of severe disease warrants further study in prospective cohorts of mother-infant pairs.

Epidemiology of Infant Dengue Cases Illuminates Serotype-Specificity in the Interaction between Immunity and Disease, and Changes in Transmission Dynamics.

BackgroundInfants born to dengue immune mothers acquire maternal antibodies to dengue. These antibodies, though initially protective, decline during the first year of life to levels thought to be disease enhancing, before reaching undetectable levels. Infants have long been studied to understand the interaction between infection and disease on an individual level.Methods/FindingsConsidering infants (cases <1 year old) as a unique group, we analyzed serotype specific dengue case data from patients admitted to a pediatric hospital in Bangkok, Thailand. We show differences in the propensity of serotypes to cause disease in individuals with dengue antibodies (infants and post-primary cases) and in individuals without dengue antibodies (primary cases). The mean age of infant cases differed among serotypes, consistent with previously observed differential waning of maternal antibody titers by serotype. We show that trends over time in epidemiology of infant cases are consistent with those observed in the whole population, and therefore with trends in the force of infection.Conclusions/SignificanceInfants with dengue are informative about the interaction between antibody and the dengue serotypes, confirming that in this population DENV-2 and DENV-4 almost exclusively cause disease in the presence of dengue antibody despite infections occurring in others. We also observe differences between the serotypes in the mean age in infant cases, informative about the interaction between waning immunity and disease for the different serotypes in infants. In addition, we show that the mean age of infant cases over time is informative about transmission in the whole population. Therefore, ongoing surveillance for dengue in infants could provide useful insights into dengue epidemiology, particularly after the introduction of a dengue vaccine targeting adults and older children.

Incidence of Severe Dengue in Infants in Paraguay

Introduccion: Identificar grupo etario con riesgo de Dengue Grave (DG) dentro del grupo de lactantes, podria evitar hospitalizaciones innecesarias. Objetivo: Determinar la incidencia de DG en lactantes hospitalizados durante la epidemia 2013. Materiales y Metodos: Diseno de cohorte retrospectivo, se incluyeron todos los ninos menores de un ano con Fiebre Dengue confirmado por serologia. Resultados: De 60 lactantes, 82% fueron menores de 6 meses de edad. 15 (25%) evolucionaron a DG, 3 presentaron shock sin fuga capilar, uno fue diagnosticado de miocarditis y otro hepatitis. Los ninos con DG tenian ≤ 6 meses (RR= 1.4 IC 1.2–1.4p = 0.02). Durante el seguimiento 34 (56,6%) desarrollaron signos de alarma, 15 clasificaron como DG, 19 (31,6%) fueron de alta como DSA. Ingresaron en fase febril (DG: 2.6 ±1.3 dias versus DNG: 2.1±1.2 p: 0.14). La fuga capilar se produjo entre el dia 4-5 de la enfermedad (media 4.6 DS ±0.7). Los ninos con DG tuvieron mas signos de shock temprano (66.7% versus 18.2% RR= 1.9 IC= 1.1–3.3 p <0.001) y algun signo de alarma (RR=1.8 IC 1.3-2.4 p < 0.001), mas plaquetopenia en el dia 5° (86.6% versus 33.3% RR= 1.7 IC= 1.2- 2.4 p < 0.001), niveles mas elevados de transaminasas (33.3 % versus 2.2 % RR= 1.5 IC= 1–2.2 p = 0.006) e hipoalbuminemia (2.6 ±0.48 versus 3.6 ±0.49 p <0.001). Requirieron mas bolos de cristaloides (100% versus 33.3% RR= 2 IC= 1.4-2.8 p <0.001), hidratacion parenteral (93.3% versus 46.5% RR= 1.6 IC= 1.2 - 2.1 p= 0.001), soporte vasoactivo y transfusiones con hemoderivados. Conclusiones : Se observa tendencia de mayor riesgo de la enfermedad en menores con edad igual o menor a 6 meses.

Genetic variants of MICB and PLCE1 and associations with non-severe dengue.

BackgroundA recent genome-wide association study (GWAS) identified susceptibility loci for dengue shock syndrome (DSS) at MICB rs3132468 and PLCE1 rs3740360. The aim of this study was to define the extent to which MICB (rs3132468) and PLCE1 (rs3740360) were associated with less severe clinical phenotypes of pediatric and adult dengue.Methods3961 laboratory-confirmed dengue cases and 5968 controls were genotyped at MICB rs3132468 and PLCE1 rs3740360. Per-allele odds ratios (OR) with 95% confidence intervals (CI) were calculated for each patient cohort. Pooled analyses were performed for adults and paediatrics respectively using a fixed effects model.ResultsPooled analysis of the paediatric and adult cohorts indicated a significant association between MICB rs3132468 and dengue cases without shock (OR = 1.15; 95%CI: 1.07 – 1.24; P = 0.0012). Similarly, pooled analysis of pediatric and adult cohorts indicated a significant association between dengue cases without shock and PLCE1 rs3740360 (OR = 0.92; 95%CI: 0.85 – 0.99; P = 0.018). We also note significant association between both SNPs (OR = 1.48; P = 0.0075 for MICB rs3132468 and OR = 0.75, P = 0.041 for PLCE1 rs3740360) and dengue in infants.DiscussionThis study confirms that the MICB rs3132468 and PLCE1 rs3740360 risk genotypes are not only associated with DSS, but are also associated with less severe clinical phenotypes of dengue, as well as with dengue in infants. These findings have implications for our understanding of dengue pathogenesis.

Dengue in infants: an overview

Dengue virus (DV) infection causes either a benign syndrome, dengue fever, or a severe syndrome, dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS), that is characterized by systemic capillary leakage, thrombocytopaenia and hypovolaemic shock. DHF/DSS occur mainly due to secondary infection by a heterotype DV infection in children and adults but in infants even primary infection by DV causes DHF/DSS. Clinical manifestations of DHF/DSS are more significantly associated with death in infants compared with older children. Vertical transmission of DV and anti-DV IgG has been well reported and is responsible for the pathogenesis of DV disease and its manifestations in infants. The complex pathogenesis of DHF/DSS during primary dengue in infants, with multiple age-related confounding factors, offers unique challenges to investigators. Dengue in infants is not often studied in detail due to practical limitations, but looking at the magnitude of DHF/DSS in infants and the unique opportunities this model provides, there is a need to focus on this problem. This paper reviews existing knowledge on this aspect of DV infection and the challenges it provides.

Clinical and Virological Features of Dengue in Vietnamese Infants

BackgroundInfants account for a small proportion of the overall dengue case burden in endemic countries but can be clinically more difficult to manage. The clinical and laboratory features in infants with dengue have not been extensively characterised.Methodology/Principal FindingsThis prospective, cross-sectional descriptive study of infants hospitalized with dengue was conducted in Vietnam from November 2004 to December 2007. More than two-thirds of 303 infants enrolled on clinical suspicion of dengue had a serologically confirmed dengue virus (DENV) infection. Almost all were primary dengue infections and 80% of the infants developed DHF/DSS. At the time of presentation and during hospitalization, the clinical signs and symptoms in infants with dengue were difficult to distinguish from those with other febrile illnesses, suggesting that in infants early laboratory confirmation could assist appropriate management. Detection of plasma NS1 antigen was found to be a sensitive marker of acute dengue in infants with primary infection, especially in the first few days of illness.Conclusions/SignificanceCollectively, these results provide a systematic description of the clinical features of dengue in infants and highlight the value of NS1 detection for diagnosis.

Update on Dengue: Epidemiology, Virus Evolution, Antiviral Drugs, and Vaccine Development

Dengue virus is the most widespread geographically of the arboviruses and a major public health threat in the tropics and subtropics. Scientific advances in recent years have provided new insights about the pathogenesis of more severe disease and novel approaches into the development of antiviral compounds and dengue vaccines. Phylogenetic studies show an association between specific subtypes (within serotypes) and severity of dengue. The lack of association between maternal antibodies and development of severe dengue in infants in a recent study has called for the rethinking or refinement of the current antibody-dependent enhancement theory of dengue hemorrhagic syndrome in infancy. Such studies should stimulate new directions of research into mechanisms responsible for the development of severe dengue. The life cycle of dengue virus readily shows that virus entry and replication can be targeted by small molecules. Advances in a mouse model (AG 129 mice) have made it easier to test such antiviral compounds. The efforts to find specific dengue inhibitors are intensifying and the tools to evaluate the efficacy of new drugs are now in place for rapid translation into trials in humans. Furthermore, several dengue vaccine candidates are in development, of which the chimeric dengue/yellow fever vaccine has now entered phase 3 trials. Until the availability of a licensed vaccine, disease surveillance and vector population control remain the mainstay of dengue prevention.

Maternal Antibody and Viral Factors in the Pathogenesis of Dengue Virus in Infants

The pathogenesis of dengue in infants is poorly understood. We postulated that dengue severity in infants would be positively associated with markers of viral burden and that maternally derived, neutralizing anti-dengue antibody would have decayed before the age at which infants with dengue presented to the hospital. In 75 Vietnamese infants with primary dengue, we found significant heterogeneity in viremia and NS1 antigenemia at hospital presentation, and these factors were independent of disease grade or continuous measures of disease severity. Neutralizing antibody titers, predicted in each infant at the time of their illness, suggested that the majority of infants (65%) experienced dengue hemorrhagic fever when the maternally derived neutralizing antibody titer had declined to <1 : 20. Collectively, these data have important implications for dengue vaccine research because they suggest that viral burden may not solely explain severe dengue in infants and that neutralizing antibody is a reasonable but not absolute marker of protective immunity in infants.

DIFFERENCES IN DENGUE SEVERITY IN INFANTS, CHILDREN, AND ADULTS IN A 3-YEAR HOSPITAL-BASED STUDY IN NICARAGUA

To investigate age-related differences in dengue severity, 114 infants, 1,211 children, and 346 adults with laboratory-confirmed dengue virus (DEN) infections presenting to three hospitals in major urban centers in Nicaragua were recruited from 1999 to 2001. The age distribution of dengue cases and the circulating serotype (predominantly DEN2) were representative of national data. Similar results were obtained when either dengue hemorrhagic fever/dengue shock syndrome or its principal manifestations (vascular permeability, internal hemorrhage, marked thrombocytopenia, and/or shock) were analyzed in relation to age and immune status. The burden of disease and of severe dengue was found predominantly in infants 4-9 months of age and in children 5-9 years old, and secondary DEN infection was a risk factor for severity in children. Age-related differences were identified in the prevalence of specific clinical manifestations as well as in their association with a confirmed DEN diagnosis. This represents one of the few comprehensive studies to analyze characteristics of dengue in infants, children, and adults in the same population and highlights age-related differences in dengue severity.