Secondary Dengue Infection Research Articles

Marmosets (Callithrix jacchus) as a non-human primate model for evaluation of candidate dengue vaccines: induction and maintenance of specific protective immunity against challenges with clinical isolates.

Dengue virus (DENV) is one of the major infectious diseases in tropical regions and approximately half of the world population is at risk of infection. Vaccines would offer an effective control measure against this disease. We previously reported on the utility of marmosets as an animal model for studying primary and secondary dengue infections. Infected marmosets consistently develop viraemia and antibody kinetics that reflect those of patients with dengue. Thus, it is important to determine the utility of marmosets as an animal model for demonstrating vaccine efficacy. In this study, marmosets were inoculated with candidate vaccine and parent strains and challenged with a clinical DENV strain. The viraemia and antibody kinetics in these marmosets were determined. Marmosets consistently develop lower viraemia with an attenuated vaccine strain. During secondary challenge, the IgM response was delayed, whereas the IgG levels rose rapidly, indicating a secondary antibody response. The neutralizing activities against the homotypic serotype were high; all marmosets were protected against viraemia following secondary inoculation. The viraemia markers and antibody responses were consistent with those of human DENV infection and vaccinees. These results demonstrate the utility of marmosets as an animal model for the study of vaccine efficacy.

Dengvaxia sensitizes seronegatives to vaccine enhanced disease regardless of age.

During a large scale clinical efficacy trial of the Sanofipasteur live-attenuated tetravalent dengue vaccine (Dengvaxia), features of hospitalized disease accompanying dengue infections in placebo recipients were closely similar to those in vaccinated children. However, the age specific hospitalization curves for these two populations differed. The curve for children vaccinated at ages 2-16 years closely resembled the 1981 age specific hospitalization rate curve for Cuban children infected with DENV 2 who were sensitized by a prior DENV 1 infection. The corresponding age specific hospitalization curve for placebos experiencing heterotypic secondary dengue infections peaked at age, 9-11 years. These differing epidemiological features support the conclusion that antibody dependent enhanced (ADE) dengue disease occurred in seronegatives who were sensitized by vaccine. As hospitalizations continue to occur in all age groups Dengvaxia consumers should be warned that sensitized vaccinated seronegatives will experience enhanced dengue disease into the forseeable future.

Detection of Virus-Antibody Immune Complexes in Secondary Dengue Virus Infection.

It has been reported that virus-antibody immune complexes formed during secondary dengue virus infection are associated with increased disease severity. Here, we describe the details of a plaque titration method that uses FcγR -expressing BHK cells to detect and quantify infectious virus-immune complexes and a quantitative real-time PCR method for the quantification of virus genome in patients with secondary dengue infection. These methods detect both viruses in free-form and in immune complexes in patients with dengue infection, and are useful for determining viremia levels and patterns that better reflect in vivo conditions.

Asymptomatic dengue infection in adults of major cities of Pakistan.

To determine the asymptomatic dengue infection in adults of Pakistani population. This study was conducted in five major cities (Islamabad, Karachi, Lahore, Multan, and Peshawar) of Pakistan. A total of 5 230 adults aged 18 years and above without a history of dengue fever at any point in their life were enrolled from participating laboratories. Those who were confirmed for dengue previously were excluded. Of the total, 62.6% (n = 3 276) were male with an average age of 34.6 years. Participants were briefed about the objectives of the study, and written consent was obtained to perform dengue IgG test using enzyme linked immunosorbent assay. The brief information related to age, gender and area was also taken on proforma. Overall 32.3% (n = 1 691) was having asymptomatic dengue infection which was 67.5% (n = 756) in Karachi followed by 39.1% (n = 391) in Islamabad, 29.9% (n = 316) in Lahore and 21% (n = 228) in Peshawar and none from Multan. More males were affected with asymptomatic dengue infection than females. The asymptomatic dengue infection was significantly higher in different cities; however, there was no significant difference with respect to age groups. The asymptomatic dengue infection is higher in cities i.e. Karachi, Islamabad and Lahore which are at risk of developing secondary dengue infections. There is a need of awareness among the public about secondary dengue infection.

Frequency of Dengue virus Infection among Febrile Patients of Lahore

BACKGROUND: Dengue virus infection is one of the major global public health problems. The infection usually occurs with clinical manifestations ranging from an asymptomatic or mild febrile illness as classical dengue fever to the potentially life-threatening illness, dengue hemorrhagic fever and dengue shock syndrome. The objective of the current study was to observe the frequency and diagnosis of primary or secondary dengue viral infection among individuals in Lahore city, Pakistan.METHODS: Study subjects were identified for the presence of dengue diagnostic markers including NS1 antigen, IgM and IgG antibody. The dengue specific antigen NS1 was detected by immonochromatography, while dengue specific antibodies (IgM and IgG) were measured through ELISA.RESULTS: Total 98 (56%) out of 175 febrile cases were found infected by dengue virus. From total 98 confirmed dengue cases, NS1 antigen was detected in 59 (60.20%), IgM antibodies were present in 74 (75.51%) and IgG antibodies were detected in 40 (40.81%) individuals. Statistical analysis reveals correlation of NS1 antigen and IgM antibody among dengue patients with significant P-value (P < 0.01). Results indicated that 58 (59%) were infected by primary infection and 40 (41%) were infected by secondary infection. The most effected age group was 21-30 years (51.02%) and least effected age group was <10 years (3.06%). Males were observed higher in number 61 (62%) as compare to females 37 (38%). Overall, the frequency of dengue virus infections were 56% among undifferentiated febrile patients in Lahore city, Pakistan.CONCLUSION: Dengue is found endemic in city population with increased incidence in monsoon and post monsoon. Constant vigilance of patients and dengue vector control awareness programs among public and health care officials could support in combating dengue.

Stage-Structured Transmission Model Incorporating Secondary Dengue Infection

In this paper, a non-linear stage-structured model has been formulated to study the effects of primary/secondary dengue infection on children and adults. It is assumed that a proportion of susceptible children have been previously infected by a serotype asymptomatically. After recovery from asymptomatic infection, the immunity is developed for the particular serotype but they remain susceptible to heterologous serotypes. These children may get secondary infection when exposed to a different serotype. The model has two equilibrium states. Global/local stability of equilibrium states have been discussed. The stability of disease-free state changes at $$R_0=1$$ . Applying the center manifold theory, the existence of forward bifurcation is possible. This concludes that the primary/secondary infection in children as well as in adults population could be eradicated for $$R_0<1$$ . Numerical results are used to explore the global behavior of disease-free/endemic state for choice of arbitrary initial conditions.

Clinical and Laboratory Profile of Dengue Viral Infections in and around Mangalore, India

Background: Dengue (DEN) is being recognised as the world’s major emerging tropical disease. Clinically, DEN may resemble other infections such as malaria, leptospirosis, and typhoid, and thus, laboratory investigations are required for definitive diagnosis. Secondary DEN infection, caused most often by dengue virus (DENV) serotypes 2 and 3, is known to present with severe disease manifestations. This study was undertaken to examine the clinical and laboratory profile of DEN viral infections and to determine the circulating serotypes in and around Mangalore, India. Materials and Methods: Serum samples from 285 clinically suspected cases of DEN in and around Mangalore between September 2013 and January 2014 were processed for detection of DEN IgM and IgG antibodies and nonstructural 1 (NS1) antigen using commercial ELISA kits. Detection of DEN viral RNA and serotyping was done by multiplex real-time reverse-transcriptase polymerase chain reaction (RT-PCR). The clinical and haematological profiles of the patients were analysed. Results: Serum samples from 83 (29%) patients were positive for DEN NS1 antigen and/or IgM antibodies. 33 (45%) out of 73 serum samples processed by multiplex real-time RT-PCR were positive for DEN viral RNA. DEN-1, -2 and -3 were the serotypes identified in this study. Fever was the most common presenting symptom followed by myalgia/arthralgia. Majority of the patients had thrombocytopaenia. Conclusion: Early detection of DEN can be achieved effectively using NS1 ELISA and IgM capture ELISA. Circulating DENV serotypes should be closely monitored for prevention of fatal outcomes in secondary infections.

Increased sensitivity of NS1 ELISA by heat dissociation in acute dengue 4 cases

BackgroundDengue is an acute febrile illness considered the major arboviral disease in terms of morbidity, mortality, economic impact and dissemination worldwide. Brazil accounts for the highest notification rate, with circulation of all four dengue serotypes. The NS1 antigen is a dengue highly conserved specific soluble glycoprotein essential for viral replication and viability that can be detected 0 to 18 days from the onset of fever (peak first 3 days). It induces a strong humoral response and is known as a complement-fixing antigen. Lower NS1 test sensitivity occurs in secondary dengue infections probably due to immune complex formation impairing antigen detection by ELISA.MethodsWe compared the sensitivity of NS1 ELISA in heat dissociated and non-dissociated samples from 156 RT-PCR confirmed acute dengue-4 cases from 362 prospectively enrolled patients.ResultsSecondary infections accounted for 83.3% of cases. NS1 ELISA was positive in 42.5% and indeterminate in 10.2% of dengue-4 cases. After heat dissociation, 7 negative and 16 indeterminate samples turned positive, increasing the overall test sensitivity to 57.7%.ConclusionsAlthough it is time consuming and requires the use of specific laboratory equipment, NS1 ELISA combined with heat dissociation could be a slightly better alternative for triage in suspected dengue cases.

Clinical and Laboratory Diagnosis of Dengue Virus Infection

Infection with any of the 4 dengue virus serotypes results in a diverse range of symptoms, from mild undifferentiated fever to life-threatening hemorrhagic fever and shock. Given that dengue virus infection elicits such a broad range of clinical symptoms, early and accurate laboratory diagnosis is essential for appropriate patient management. Virus detection and serological conversion have been the main targets of diagnostic assessment for many years, however cross-reactivity of antibody responses among the flaviviruses has been a confounding issue in providing a differential diagnosis. Furthermore, there is no single, definitive diagnostic biomarker that is present across the entire period of patient presentation, particularly in those experiencing a secondary dengue infection. Nevertheless, the development and commercialization of point-of-care combination tests capable of detecting markers of infection present during different stages of infection (viral nonstructural protein 1 and immunoglobulin M) has greatly simplified laboratory-based dengue diagnosis. Despite these advances, significant challenges remain in the clinical management of dengue-infected patients, especially in the absence of reliable biomarkers that provide an effective prognostic indicator of severe disease progression. This review briefly summarizes some of the complexities and issues surrounding clinical dengue diagnosis and the laboratory diagnostic options currently available.

A Study on Gene Expression Profile of Endogenous Antioxidant Enzymes: CAT, MnSOD and GPx in Dengue Patients.

Dengue is an arthropod-borne threat among tropical countries. Currently no effective means to treat the virus or to predict which patient will develop the severe form of the disease. Recently the relationship between oxidative/antioxidative response and dengue pathogenesis was suggested. Based on this the present study has analysed the expression of endogenous antioxidant genes: Catalase (CAT), Superoxide dismutase (MnSOD) and Glutathione peroxidase in patients with dengue compared to other febrile illness (OFI) and healthy controls. The study enrolled 88 dengue confirmed patients comprising 56 were patients with non-severe dengue, and 32 were severe dengue cases, 31 were patients with OFI, and 63 healthy controls were also involved. Peripheral blood mononuclear cells isolated from patients and controls during the day of admission and from the available cases on the day of defervescence were used to estimate the transcript levels by quantitative PCR. The expression levels of all the three genes were found to be down-regulated throughout the course of dengue infection (p<0.05) and OFI cases compared to healthy controls. Within dengue group, no significant difference was observed in any of the parameters between severe and non-severe cases. Interestingly, a significant down-regulation of MnSOD expression was recorded in secondary dengue infection compared to primary during admission (p<0.05). It was found that all the down-regulated study genes have positively correlated in all dengue cases during the day of admission (p<0.01). But during defervescence, the same was found only between CAT and MnSOD. Down-regulated endogenous antioxidant enzymes during dengue infection could be the possible rationale of oxidative stress reported in dengue disease earlier. The present study markers could not distinguish dengue from OFI cases and severe from non-severe dengue cases. Mechanism of down-regulation has to be explored further which will pave the way for the therapeutic target in dengue disease.

Evaluation of Non-Structural Protein-1(NS1) positive patients of 2013 dengue outbreak in Khyber Pakhtunkhwa, Pakistan.

Background & Objective:Dengue infection is an arthropod borne disease caused by Dengue virus in humans. Dengue virus infection has more potential to produce severe form of the disease with more severe symptoms. Proper diagnosis of dengue fever is very important for its safe management. The objective of this study was to evaluate the non structural protein-1 (NS1) positive parameter for identification of dengue fever by using ELISA from 2013 dengue outbreak in Khyber Pakhtunkhwa.Methods:It was a cross sectional study conducted among 384 patients tested for dengue admitted to different hospitals of Khyber Pakhtunkhwa April to December 2013 with symptoms related to classical dengue fever. Written informed consent was taken from 100 NS1 positive diagnosed patients, and 3 to 5 ml blood sample was collected for confirmation through ELISA testing. ELISA test for dengue IgG and IgM was performed two time in order to confirm the dengue cases. Data was entered and analyzed by using SPSS version 16.Result:The study performed on 100 NS1 positive samples of patients, admitted to hospitals with symptoms related to classical dengue fever, indicated that after performing the IgM and IgG capture ELISA test only 76 samples were actually found positive for dengue. The rest of the 24 samples were found negative for both IgM and IgG capture ELISAs. The study also revealed that 90.8 % patients had primary dengue infection and 35.5% patients had secondary dengue infection. Most patients were between the age of 10-20 years (26%), among them19.7% were having primary dengue infection. Among 10-20 years of age 50% female patients were false dengue patients.Conclusion:About 24 % NSI protein positive samples were found negative for both IgM and IgG capture ELISAs showed that NS1protein positivity does not confirm actual dengue infection.

Serodiagnosis of asymptomatic dengue infection.

Dengue virus (DENV) is a mosquito-transmitted virus that is expanding across the world. The incidence of dengue infection, especially severe disease, has been increasing. DENV consist of 4 serotypes of single stranded RNA viruses (D1-D4) in the genus Flavivirus, family Flaviviridae. Majority of dengue infections are asymptomatic cases, which cause difficulty in disease control and are important in dengue surveillance. There is still no gold standard to diagnose asymptomatic dengue infection. Plaque reduction neutralization test (PRNT) has been developed for many purposes such as immunological study, clinical study, vaccine trial and is currently the most sensitive and specific method for serological surveillance. However, PRNT shows some degree of cross reaction among different dengue serotypes especially secondary dengue infection cases and to other flaviviruses. Moreover, various modification since the beginning make PRNT lack of inter-laboratory standardization which is an important issue. This paper discusses the important of asymptomatic dengue infection and its diagnostic method.

Drivers of Inter-individual Variation in Dengue Viral Load Dynamics.

Dengue is a vector-borne viral disease of humans that endemically circulates in many tropical and subtropical regions worldwide. Infection with dengue can result in a range of disease outcomes. A considerable amount of research has sought to improve our understanding of this variation in disease outcomes and to identify predictors of severe disease. Contributing to this research, patterns of viral load in dengue infected patients have been quantified, with analyses indicating that peak viral load levels, rates of viral load decline, and time to peak viremia are useful predictors of severe disease. Here, we take a complementary approach to understanding patterns of clinical manifestation and inter-individual variation in viral load dynamics. Specifically, we statistically fit mathematical within-host models of dengue to individual-level viral load data to test virological and immunological hypotheses explaining inter-individual variation in dengue viral load. We choose between alternative models using model selection criteria to determine which hypotheses are best supported by the data. We first show that the cellular immune response plays an important role in regulating viral load in secondary dengue infections. We then provide statistical support for the process of antibody-dependent enhancement (but not original antigenic sin) in the development of severe disease in secondary dengue infections. Finally, we show statistical support for serotype-specific differences in viral infectivity rates, with infectivity rates of dengue serotypes 2 and 3 exceeding those of serotype 1. These results contribute to our understanding of dengue viral load patterns and their relationship to the development of severe dengue disease. They further have implications for understanding how dengue transmissibility may depend on the immune status of infected individuals and the identity of the infecting serotype.

The value of IgG to IgM ratio in predicting secondary dengue infection

Background The determination of primary or secondary dengueinfection using hemagglutination inhibition (HI) test is time-con-suming. The IgG to IgM ratio which can be obtained earlier wasused by several studies to differentiate secondary from primaryinfection, but they still reported various cut-off points.Objective To find the diagnostic value and best cut off point ofIgG to IgM ratio for predicting secondary dengue infection.Methods This was a prospective study carried out between July2003 and June 2004. Children with suspected dengue hemor-rhagic fever (DHF) were tested for HI during acute and convales-cent phase. The IgG and IgM titer were examined during the acutephase using ELISA method.Results Sixty-two children were recruited, 48 with secondary in-fection and 14 with primary infection. The prevalence of second-ary infection was 77%. The best cut off point of the IgG to IgM ratioto predict secondary infection was &gt;1.1 with sensitivity of 87.5%,specificity 92.9%, likelihood ratio 12.3, and post test probability97.7%.Conclusion The IgG to IgM ratio of &gt;1.1 is a good predictor forsecondary infection

Severity of Plasma Leakage Is Associated With High Levels of Interferon γ-Inducible Protein 10, Hepatocyte Growth Factor, Matrix Metalloproteinase 2 (MMP-2), and MMP-9 During Dengue Virus Infection.

Dengue virus infection typically causes mild dengue fever, but, in severe cases, life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) occur. The pathophysiological hallmark of DHF and DSS is plasma leakage that leads to enhanced vascular permeability, likely due to a cytokine storm. Ninety patients with dengue during 2010-2012 in Singapore were prospectively recruited and stratified according to their disease phase, primary and secondary infection status, and disease severity, measured by plasma leakage. Clinical parameters were recorded throughout the disease progression. The levels of various immune mediators were quantified using comprehensive multiplex microbead-based immunoassays for 46 immune mediators. Associations between clinical parameters and immune mediators were analyzed using various statistical methods. Potential immune markers, including interleukin 1 receptor antagonist, interferon γ-inducible protein 10, hepatocyte growth factor, soluble p75 tumor necrosis factor α receptor, vascular cell adhesion molecule 1, and matrix metalloproteinase 2, were significantly associated with significant plasma leakage. Secondary dengue virus infections were also shown to influence disease outcome in terms of disease severity. This study identified several key markers for exacerbated dengue pathogenesis, notably plasma leakage. This will allow a better understanding of the molecular mechanisms of DHF and DSS in patients with dengue.

Impact of dengue virus (DENV) co-infection on clinical manifestations, disease severity and laboratory parameters.

BackgroundThe co-circulation of 4 DENV serotypes in geographically expanding area, has resulted in increasing occurrence of DENV co-infections. However, studies assessing the clinical impact of DENV co-infections have been scarce and have involved small number of patients. This study explores the impact of DENV co-infection on clinical manifestations and laboratory parameters.MethodsThis retrospective study involved consecutive hospitalized patients with non-structural protein 1 (NS1) antigen positivity during an outbreak (Jan to April 2014). Multiplex RT-PCR was performed directly on NS1 positive serum samples to detect and determine the DENV serotypes. All PCR-positive serum samples were inoculated onto C6/36 cells. Multiplex PCR was repeated on the supernatant of the first blind passage of the serum-infected cells. Random samples of supernatant from the first passage of C6/36 infected cells were subjected to whole genome sequencing. Clinical and laboratory variables were compared between patients with and without DENV co-infections.ResultsOf the 290 NS1 positive serum samples, 280 were PCR positive for DENV. Medical notes of 262 patients were available for analysis. All 4 DENV serotypes were identified. Of the 262 patients, forty patients (15.3 %) had DENV co-infections: DENV-1/DENV-2(85 %), DENV-1/DENV-3 (12.5 %) and DENV-2/DENV-3 (2.5 %). Another 222 patients (84.7 %) were infected with single DENV serotype (mono-infection), with DENV- 1 (76.6 %) and DENV- 2 (19.8 %) predominating. Secondary dengue infections occurred in 31.3 % patients. Whole genome sequences of random samples representing DENV-1 and DENV-2 showed heterogeneity amongst the DENVs.Multivariate analysis revealed that pleural effusion and the presence of warning signs were significantly higher in the co-infected group, both in the overall and subgroup analysis. Diarrhoea was negatively associated with co-infection. Additionally, DENV-2 co-infected patients had higher frequency of patients with severe thrombocytopenia (platelet count < 50,000/mm3), whereas DENV-2 mono-infections presented more commonly with myalgia. Elevated creatinine levels were more frequent amongst the co-infected patients in univariate analysis. Haemoconcentration and haemorrhagic manifestations were not higher amongst the co-infected patients. Serotypes associated with severe dengue were: DENV-1 (n = 9), DENV-2 (n = 1), DENV-3 (n = 1) in mono-infected patients and DENV-1/DENV-2 (n = 5) and DENV-1/DENV-3 (n = 1) amongst the co-infected patients.ConclusionDENV co-infections are not uncommon in a hyperendemic region and co-infected patients are skewed towards more severe clinical manifestations compared to mono-infected patients.

Evaluation of Commercially Available Assays for Diagnosis of Acute Dengue in Schoolchildren During an Epidemic Period in Medellin, Colombia.

During an active surveillance study in school children in Medellin, we assessed the performance of two diagnostic strategies for dengue virus. A total of 41 patients with suspected dengue acute infection were evaluated. Diagnostic strategies consisted of one combining Panbio(®) Dengue virus IgM and IgG Capture ELISAs (enzyme-linked immunosorbent assays) with reverse transcriptase polymerase chain reaction (RT-PCR) and another using a commercial rapid SD Bioline Dengue Duo (IgG/IgM + NS1 Ag) test. These two strategies were compared with the enzyme-linked immunospot microneutralization test (ELISPOT-MNT). The sensitivity and specificity were 53.9% and 80.0% for the combination of Panbio(®) ELISAs and RT-PCR tests, and 30.8% and 73.3% for the SD Bioline Duo test, respectively. ELISPOT-MNT detected 16.4% additional cases and revealed the presence of neutralizing antibodies in all the acute samples, evidencing that they were all secondary infections. In contrast, Panbio(®) and SD Dengue Duo rapid tests only classified 23.0% and 26.9% of the cases as secondary dengue infections, respectively. Cohen's kappa coefficient and McNemar's association tests demonstrated a significant disagreement between the two diagnostic strategies and ELISPOT-MNT. Overall, these results evidence the relatively poor performances of commercial assays for the diagnosis of acute and secondary dengue infections, compared with ELISPOT-MNT, and raise concern about the accuracy of these assays for the diagnostic of dengue in endemic areas.

Immune Response to Dengue Virus Infection in Pediatric Patients in New Delhi, India--Association of Viremia, Inflammatory Mediators and Monocytes with Disease Severity.

Dengue virus, a mosquito-borne flavivirus, is a causative agent for dengue infection, which manifests with symptoms ranging from mild fever to fatal dengue shock syndrome. The presence of four serotypes, against which immune cross-protection is short-lived and serotype cross-reactive antibodies that might enhance infection, pose a challenge to further investigate the role of virus and immune response in pathogenesis. We evaluated the viral and immunological factors that correlate with severe dengue disease in a cohort of pediatric dengue patients in New Delhi. Severe dengue disease was observed in both primary and secondary infections. Viral load had no association with disease severity but high viral load correlated with prolonged thrombocytopenia and delayed recovery. Severe dengue cases had low Th1 cytokines and a concurrent increase in the inflammatory mediators such as IL-6, IL-8 and IL-10. A transient increase in CD14+CD16+ intermediate monocytes was observed early in infection. Sorting of monocytes from dengue patient peripheral blood mononuclear cells revealed that it is the CD14+ cells, but not the CD16+ or the T or B cells, that were infected with dengue virus and were major producers of IL-10. Using the Boruta algorithm, reduced interferon-α levels and enhanced aforementioned pro-inflammatory cytokines were identified as some of the distinctive markers of severe dengue. Furthermore, the reduction in the levels of IL-8 and IL-10 were identified as the most significant markers of recovery from severe disease. Our results provide further insights into the immune response of children to primary and secondary dengue infection and help us to understand the complex interplay between the intrinsic factors in dengue pathogenesis.

Early predictors to differentiate primary from secondary dengue infection in children

Aim: We aimed to analyze the early predictors to differentiate primary from secondary dengue infection and the severity of liver involvement with reference to mortality. Materials and Methods: This prospective study was conducted on 200 children having acute febrile illness between 3 months to 15 years age group. One hundred and five serologically confirmed dengue patients were included in the study and classified into primary and secondary dengue infection. Liver function tests (LFTs) and electrolytes were analyzed, and the hepatic dysfunction was correlated to the severity of the disease. Results: Of the 105 serologically confirmed dengue, 62 (59%) were primary and 43 (41%) were secondary dengue infection. Primary dengue infection was more common in Conclusion: Abnormal LFTs can be a marker to predict disease severity, but may not differentiate primary from secondary dengue infection. Occurrence of hyponatremia and thrombocytopenia may identify children likely to have secondary dengue.

Comparison of the Hemagglutination Inhibition Test and IgG ELISA in Categorizing Primary and Secondary Dengue Infections Based on the Plaque Reduction Neutralization Test.

Secondary dengue infection by heterotypic serotypes is associated with severe manifestations of disease, that is, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The World Health Organization (WHO) has recommended criteria based on the hemagglutination inhibition (HI) test to distinguish between primary and secondary dengue infections. Since the HI test has practical limitations and disadvantages, we evaluated the accuracy of WHO HI criteria and compared it with criteria based on an IgG enzyme-linked immunosorbent assay (ELISA) using a plaque reduction neutralization test (PRNT) as the gold standard. Both WHO HI criteria and IgG ELISA criteria performed strongly (16/16) in determining primary infection. However, to determine secondary infection, the IgG ELISA criteria performed better (72/73) compared to the WHO HI criteria (23/73).