Dengue virus serotype did not contribute to clinical severity or mortality in Taiwan's largest dengue outbreak in 2015.

BACKGROUND: Dengue virus serotype 2 (DENV-2) was the major serotype in the 2015 dengue outbreak in Taiwan, while DENV-1 and DENV-3 were dominant between 2005 and 2014. We aimed to investigate whether DENV-2 contributed to disease severity and mortality in the outbreak in Kaohsiung city, Taiwan. METHODS: We collected serum samples from dengue patients to detect the presence of DENV and determine the serotypes by using quantitative reverse transcription-polymerase chain reaction. Our cohorts comprised 105 DENV-1-infected cases and 1,550 DENV-2-infected cases. Demographic data, DENV serotype, and comorbidities were covariates for univariate and multivariate analyses to explore the association with severity and mortality. RESULTS: The results suggested that DENV-1 persisted and circulated, while DENV-2 was dominant during the dengue outbreak that occurred between September and December 2015. However, DENV-2 did not directly contribute to either severity or mortality. Aged patients and patients with diabetes mellitus (DM) or moderate to severe chronic kidney disease (CKD) had a higher risk of developing severe dengue. The mortality of dengue patients was related to a higher Charlson comorbidity index score and severe dengue. Among DENV-2-infected patients and older patients, preexisting anti-dengue IgG, DM, and moderate to severe CKD were associated with severe dengue. Moreover, female sex and severe dengue were associated with a significantly higher risk of death. CONCLUSIONS: Our findings highlight the importance of timely serological testing in elderly patients to identify potential secondary infections and focus on the meticulous management of elderly patients with DM or moderate to severe CKD to reduce dengue-related death.

Maternal and peri-natal outcomes of dengue fever with special emphasis on vertical transmission.

OBJECTIVE: To investigate the maternal and peri-natal outcomes of dengue infection and frequency of dengue immunoglobulin G positivity in pregnant women along with pregnancy outcomes. Method: The observational two-phase study was conducted from 2012 to 2015 in Lahore, Pakistan. In phase 1, pregnant women who had acute dengue fever were prospectively and retrospectively enrolled from 4 tertiary care hospitals. Demographic data, clinical/laboratory parameters and maternal/foetal outcomes were recorded for each subject. In the second phase, normal pregnant women with no current or past history of dengue fever were enrolled from Gynaecology Department of Shaikh Zayed Hospital, Lahore, to determine the frequency of dengue immunoglobulin G positivity and pregnancy outcome. Data was analysed using SPSS 20. RESULTS: Of the 12 subjects in phase 1, 10(83.3%) were prospective cases and 2(16.6%) were retrospective. The overall mean age was 26.3±5.4 years, 7(58.3%) were in 2nd and 5(41.6%) were in 3rd trimester of pregnancy. Among the 4(33.3%) women at gestational age ≥33 weeks, 3(75%) had poor foetal outcome. In the second phase, there were 127 women with a mean age of 27.4±4.3 years. Among them, 38(29.9%) women were in the 2nd and 89(70.1%) were in the 3rd trimester. Dengue immunoglobulin G positivity was found in 65(51.2%) cases, but poor maternal or foetal outcome was not found in such women. CONCLUSIONS: Acute dengue fever at late term resulted in adverse foetal outcomes. Frequency of dengue immunoglobulin G positivity was high among pregnant women, but it was not associated with adverse outcomes.

Seropositivity among Blood Samples Drawn from Suspected Dengue Cases at a Tertiary Care Centre of Nepal: A Descriptive Cross-sectional Study.

INTRODUCTION: The cases of dengue fever have been reported more frequently in Nepal these days. The aim of this study was to find the prevalence of seropositivity among blood samples drawn from suspected dengue cases at a tertiary care centre of Nepal. METHODS: A descriptive cross-sectional study was conducted at a tertiary care hospital from 1st June 2017 to 31st October 2018 after getting approval from the Institutional Review Committee (Reference number: 23/2016). A total of 537 suspected dengue patients were selected for the study using convenience sampling. These dengue positive sera were assayed for their reactivity with Immunoglobulin M and Immunoglobulin G present in sera and synthetic peptides of dengue virus by enzyme linked immunosorbent assay. Data was entered and analysed in Microsoft Excel 2016. Point estimate at 95% Confidence Interval was calculated along with frequency, percentage, mean and standard deviation. RESULTS: Among 537 suspected dengue cases, the seropositivity for dengue was found in 124 (23.09%) (19.52-26.65 at 95% Confidence Interval) of the serum. CONCLUSIONS: The present study revealed that dengue was more prevalent in our setting compared to similar studies. All the synthetic peptides showed reactivity with dengue-positive sera with maximum reactivity shown by RR2 peptide. In dengue-positive sera, RR2 peptide of dengue virus identified more Immunoglobulin M than Immunoglobulin G.

Severity of dengue illness and presence of anti DV IgG in serum of laboratory confirmed dengue cases.

BACKGROUND & OBJECTIVES: Presence of dengue is reported from India since 1960s. Secondary dengue infection may be more severe than primary, hence, distinction between primary and secondary dengue is essential. A way to detect secondary dengue is demonstration of anti DV IgG in patients' serum. In this study we explored the association of dengue severity with anti DV IgG positivity. METHODS: Laboratory confirmed cases of dengue (positive for anti DV IgM/ NS-1 Antigen/ DV -RNA), presenting to the hospital within 7 days of illness, were consecutively enrolled for a period of one month (September 1-30, 2018) and were tested for anti DV IgG in their serum. All PCR positive samples were serotyped. Cases positive for anti-dengue IgG were labeled as secondary cases. Clinical details were collected to assess the severity of illness. Association of dengue severity with anti DV IgG positivity was calculated. RESULTS: Of the 128 dengue positive cases, 89 (69.5%) were anti DV IgM positive, 72 (56.3%) were Dengue NS-1 positives and 37 (28.9%) were DV-RNA positive. Only 39 (30.5%) cases were having detectable anti-dengue IgG in their serum (secondary dengue). Anti-dengue IgM positivity was significantly higher in secondary dengue cases. No association of anti DV IgG positivity was seen with severity of dengue illness. INTERPRETATION & CONCLUSION: No association of IgG positivity with severity of illness was seen. D4 serotype is first time reported from Uttar Pradesh, India.

Dengue epidemic in Malaysia: urban versus rural comparison of dengue immunoglobulin G seroprevalence among Malaysian adults aged 35-74 years.

BACKGROUND: A periodic serosurvey of dengue seroprevalence is vital to determine the prevalence of dengue in countries where this disease is endemic. This study aimed to determine the prevalence of dengue immunoglobulin G (IgG) seropositivity among healthy Malaysian adults living in urban and rural areas. METHODS: A total of 2598 serum samples (1417 urban samples, 1181 rural samples) were randomly collected from adults ages 35-74 y. The presence of the dengue IgG antibody and neutralising antibodies to dengue virus (DENV) 1-4 was determined using enzyme-linked immunosorbent assay and the plaque reduction neutralisation test assay, respectively. RESULTS: The prevalence of dengue IgG seropositivity was 85.39% in urban areas and 83.48% in rural areas. The seropositivity increased with every 10-y increase in age. Ethnicity was associated with dengue seropositivity in urban areas but not in rural areas. The factors associated with dengue seropositivity were sex and working outdoors. In dengue IgG-positive serum samples, 98.39% of the samples had neutralising antibodies against DENV3, but only 70.97% of them had neutralising antibodies against DENV4. CONCLUSION: The high seroprevalence of dengue found in urban and rural areas suggests that both urban and rural communities are vital for establishing and sustaining DENV transmission in Malaysia.

Primary Dengue Infection in Patients Requiring Hospitalization During an Outbreak in a Low Incidence Mexican Region.

Background: Dengue manifestations can range from subclinical to fatal. The study of factors that influence dengue's clinical severity can provide information to potentially limit or predict severe cases. Secondary infection (SI) with a different dengue serotype has been recognized as an important determinant of severity. However, severe dengue (SD) manifestations, including shock, can happen during primary infection (PI) too and the mechanisms involved are less understood. To characterize the severe manifestations associated to PI, we distinguished between primary and secondary dengue cases in hospitalized patients from a region of low and recent dengue incidence in central Mexico. This region can serve as a model for dengue's behavior as it spreads to new areas worldwide. Methods: Dengue-specific immunoglobulin M (IgM) and IgG concentrations were measured in the serum of 78 hospitalized patients with dengue hemorrhagic fever, and their ratios were used to discriminate between PI and SI, as recommended by World Health Organization. Clinical and laboratory manifestations were compared between PI and SI. Results and Conclusions: PI was detected in 23% of hospitalized dengue cases, a proportion similar to that reported in high-incidence regions in Mexico. PI was more frequent in 16- to 40-year-olds, and was absent in patients older than 60 years. Only dengue with warning signs and SD were present in the studied population of hospitalized patients, and case frequency decreased with clinical severity both in PI and SI groups. No significant differences in demographics, laboratory tests, or symptoms were found between PI and SI, which illustrates that cases requiring hospitalization during outbreaks can be severe, even if they are PI. This information can help plan for sanitary contingencies in places where dengue is recently emergent and numerous PI cases are expected. The mechanisms involved in PI clinical severity need to be studied further.

Duration of immunity in recipients of two doses of 17DD yellow fever vaccine.

Antibody levels following yellow fever vaccination (YFV) decrease considerably with time, leaving a substantial proportion of single-dose recipients seronegative after 10 years. Little is known about the persistence of immunity after two or more doses of the vaccine. This study was designed to verify the current immune status of adults who had received two or more doses of YFV. A cross-sectional study assessed the immune status for yellow fever according to time since the latest YFV: second dose at 30-45 days (reference group), 1-5 years, 6-9 years and 10 years or more; and three or more doses. Volunteers had their vaccination cards checked and were interviewed before having a blood sample drawn for titration of neutralizing YF antibodies, and being tested for dengue IgG. The proportion seropositive (titer ≥ 1:50) and the geometric mean titers (GMT) were compared among the subgroups of time since the latest YFV. Participants (n = 323) were predominantly female (80.5%) and had a median age of 34 years (range 18-76). In the reference group (n = 99), 69% were seropositive before the second dose. After revaccination, the proportions seropositive (95% C.I.) were 100% (96-100%) in the reference subgroup, 90% (83-95%) in the 1-5 year subgroup (n = 109), 86% (77-92%) in the 6-9 year subgroup (n = 92) and 86% (57-98%) in the 10+ years subgroup (n = 14). Only 9 participants with more than 2 previous doses of YFV were eligible for the study, and 8 of them were seropositive. Sociodemographic variables, age at vaccination and previous dengue infection did not confound the association of seropositivity to time since the last YFV. The results support the need of booster doses of the YFV to maintain antibody levels consistent with protection, and indicate that a small proportion of individuals may need more than two doses, provided that priority is given to primovaccination of all susceptibles.

High Seroprevalence of Dengue Virus Infection in Blood Donors From Delhi: A Single Centre Study.

INTRODUCTION: The risk of transfusion transmitted dengue has been increasingly recognized. Blood donors in an endemic area like Delhi may serve as a potential vehicle for transmission of the infection. Moreover, prevalence of infection in them would be representative of the true picture of dengue in a population. AIM: To determine the prevalence of dengue virus infection in blood donors in a tertiary care centre. MATERIALS AND METHODS: A total of 200 blood donors were recruited in the study after obtaining informed consent in the Institute of Liver and Biliary Sciences, New Delhi in July and August 2012. Data regarding clinical and demographic characteristics was collected using a preformed questionnaire. Blood samples obtained were subjected to anti-dengue IgM and IgG ELISA as well as semi-nested Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) for dengue RNA. RESULTS: Of the study subjects, most were men (97%) with a median age of 28 years (range 19-51 years). Anti-dengue IgG was positive in 116 cases (58%) while IgM was seen in 27cases (13.5%). Of them, in 25 (12.5%) cases both IgG and IgM were positive, while only two (1%) cases tested positive for IgM alone. None of the blood donors were found to be viremic on screening using Nested RT-PCR. A clear increase of IgG seroprevalence with age was evident. No difference in the seroprevalence rates in urban vs. rural areas was seen. CONCLUSION: High seroprevalence of dengue infection was seen in healthy asymptomatic blood donors. Though evidence of acute infection was found in some, none were found to be viremic. Larger studies are required to quantify the risk and provide strong evidence for policies to be made.

Nuevas evidencias en la susceptibilidad a la infección por dengue asociadas al polimorfismo HH del receptor FcgRIIa / New evidence in the susceptibility to dengue infection associated to HH polymorphism of FcgRlla receptor

Introducción: las variantes polimórficas del receptor FcgR IIa han sido asociadas con la susceptibilidad a padecer diferentes enfermedades infecciosas. Recientemente se reportó la asociación entre el polimorfismo de este receptor y la susceptibilidad a padecer la fiebre hemorrágica por dengue. Objetivos: explorar si la asociación a la susceptibilidad o protección de las variantes homocigóticas del receptor, pudieran estar relacionadas además, con los títulos de IgG y la exposición a diferente número de infecciones. Métodos: se hizo un estudio de tipo analítico retrospectivo a individuos infectados por virus dengue 4 en Ciudad de La Habana durante la epidemia de 2006, que se contactaron en 2008. Se reclutó un total de 97 individuos, de los cuales 68 habían padecido fiebre dengue y 29 fiebre hemorrágica de dengue.Se les extrajo una muestra de 10 mL de sangre total en anticoagulante que se empleó en el aislamiento de ADN. Se determinó el polimorfismo genético del receptor FcgRIIa, los títulos de anticuerpos totales IgG anti-dengue y el antecedente de infección por dengue. Resultados: se evidenció, de modo interesante, una relación directamente proporcional y muy significativa (p< 0,0001) entre los altos títulos de IgG anti-dengue con el número de infecciones padecidas. Este comportamiento fue característico en los individuos con la variante homocigótica HH. Conclusiones: al parecer, en aquellos individuos con polimorfismo para el receptor FcgRIIa-H/H podría haber una tendencia a la no eliminación de los anticuerpos IgG a través del FcgRIIa, la cual está asociada con el número de infecciones.

Introduction: polymorphic variants of FcgRIIa receptor have been associated to susceptibility to develop several infectious diseases. The relationship between the polymorphism of this receptor and the susceptibility to dengue hemorrhagic fever was recently reported. Objectives: to explore whether the association of the homocygotic variants of the receptor to susceptibility to or protection from a disease could be also related with the IgG antibody titters and the exposure to a number of infections. Methods: a retrospective analytical study was performed on individuals who had been infected with the dengue virus 4 during the 2006 epidemic in the City of Havana and were tracked down in 2008. A total number of 97 individuals were recruited of whom 68 had suffered dengue fever and 29 had had dengue hemorrhagic fever. A 10 mL blood sample was taken from each of them and then placed in EDTA anticoagulant for DNA isolation and 5ml placed in dry tubes to obtain serum. The genetic polymorphism of FcgRlla receptor, the total anti-dengue IgG antibody titers and the antecedent of dengue infection were determined. Results: it was interesting to note that there was very significant direct relation (p< 0.0001) between high anti-dengue IgG antibodies titers and the number of infections suffered by these people. This behaviour was present in those individuals with the HH homocygotic variant. Conclusion: it seems that those individuals with polymorphism in FCgRlla-H/H receptor would tend to non-elimination of IgG antibodies through this receptor, which is associated to the number of infections suffered by the individual.