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Between October, 2013, and April, 2014, French Polynesia experienced the largest Zika virus outbreak ever described at that time. During the same period, an increase in Guillain-Barré syndrome was reported, suggesting a possible association between Zika virus and Guillain-Barré syndrome. We aimed to assess the role of Zika virus and dengue virus infection in developing Guillain-Barré syndrome. In this case-control study, cases were patients with Guillain-Barré syndrome diagnosed at the Centre Hospitalier de Polynésie Française (Papeete, Tahiti, French Polynesia) during the outbreak period. Controls were age-matched, sex-matched, and residence-matched patients who presented at the hospital with a non-febrile illness (control group 1; n=98) and age-matched patients with acute Zika virus disease and no neurological symptoms (control group 2; n=70). Virological investigations included RT-PCR for Zika virus, and both microsphere immunofluorescent and seroneutralisation assays for Zika virus and dengue virus. Anti-glycolipid reactivity was studied in patients with Guillain-Barré syndrome using both ELISA and combinatorial microarrays. 42 patients were diagnosed with Guillain-Barré syndrome during the study period. 41 (98%) patients with Guillain-Barré syndrome had anti-Zika virus IgM or IgG, and all (100%) had neutralising antibodies against Zika virus compared with 54 (56%) of 98 in control group 1 (p<0·0001). 39 (93%) patients with Guillain-Barré syndrome had Zika virus IgM and 37 (88%) had experienced a transient illness in a median of 6 days (IQR 4–10) before the onset of neurological symptoms, suggesting recent Zika virus infection. Patients with Guillain-Barré syndrome had electrophysiological findings compatible with acute motor axonal neuropathy (AMAN) type, and had rapid evolution of disease (median duration of the installation and plateau phases was 6 [IQR 4–9] and 4 days [3–10], respectively). 12 (29%) patients required respiratory assistance. No patients died. Anti-glycolipid antibody activity was found in 13 (31%) patients, and notably against GA1 in eight (19%) patients, by ELISA and 19 (46%) of 41 by glycoarray at admission. The typical AMAN-associated anti-ganglioside antibodies were rarely present. Past dengue virus history did not differ significantly between patients with Guillain-Barré syndrome and those in the two control groups (95%, 89%, and 83%, respectively). This is the first study providing evidence for Zika virus infection causing Guillain-Barré syndrome. Because Zika virus is spreading rapidly across the Americas, at risk countries need to prepare for adequate intensive care beds capacity to manage patients with Guillain-Barré syndrome. Labex Integrative Biology of Emerging Infectious Diseases, EU 7th framework program PREDEMICS. and Wellcome Trust.

Dengue is a re-emerging neglected disease of major public health importance. This review highlights important considerations for dengue disease in Africa, including epidemiology and underestimation of disease burden in African countries, issues with malaria misdiagnosis and co-infections, and potential evidence of genetic protection from severe dengue disease in populations of African descent. The findings indicate that dengue virus prevalence in African countries and populations may be more widespread than reported data suggests, and that the Aedes mosquito vectors appear to be increasing in dissemination and number. Changes in climate, population, and plastic pollution are expected to worsen the dengue situation in Africa. Dengue misdiagnosis is also a problem in Africa, especially due to the typical non-specific clinical presentation of dengue leading to misdiagnosis as malaria. Finally, research suggests that a protective genetic component against severe dengue exists in African descent populations, but further studies should be conducted to strengthen this association in various populations, taking into consideration socioeconomic factors that may contribute to these findings. The main takeaway is that Africa should not be overlooked when it comes to dengue, and more attention and resources should be devoted to this disease in Africa.

Dengue, an acute febrile disease caused by dengue virus (DENV) infection, is endemic to Indonesia. During early 2020, an outbreak of severe dengue occurred in Maumere, East Nusa Tenggara province, a region with low dengue endemicity with limited data on the characteristics of the circulating DENV. By 18 March 2020, 1396 cases were reported with 14 fatalities. Investigation was conducted to understand the cause and characteristics of the outbreak. Sera were collected from 133 patients with dengue-like symptoms through random sampling at TC Hillers Hospital, Maumere during outbreak between February and June 2020. Dengue was confirmed using NS1 and/or RT-PCR detection. Serological status was determined using IgG/IgM ELISA and plaque reduction neutralization test (PRNT). DENV serotyping and genome sequencing were performed to identify the DENV serotype and genotype. We recruited suspected dengue patients attending the hospital during the outbreak. Dengue was confirmed in 72.2% (96/133), while 18.8% (25/133) were diagnosed as probable dengue. Children under 18 years old accounted for 85.1% (103/121) of dengue cases. Severe dengue accounted for 94.2% (81/86) of cases. Secondary infections made up 92.6% (112/121) of cases. Serotyping detected 87.3% (62/71) as DENV-3, 7.0% (5/71) as DENV-4, 2.8% (2/71) as DENV-1, and 2.8% (2/71) as DENV-2. Phylogenetic analysis revealed close evolutionary relationship of Maumere DENV to viruses from other Indonesian regions, especially Bali and Kupang. PRNT on DENV-3 secondary infections patients detected the presence of DENV-2 and DENV-4 neutralizing antibodies. The severe dengue outbreak in Maumere is caused by DENV-3 introduced from nearby islands. The high proportion of secondary infections likely contributes to the severity of the disease. The high percentage of anti-dengue neutralizing antibodies for multiple serotypes and the high proportion of anti-dengue IgG in young children suggests a history of dengue transmission with a high infection rate in the area.

Pakistan has been an endemic country for dengue virus since 1994, with a significant increase in cases reported in 2022 largely due to heavy rainfall and flooding. All four serotypes of the dengue virus (DENV) are present in Pakistan, with DENV 1 and DENV 2 being the most prevalent. The current study aims to explore the clinical presentations and features of dengue fever in a tertiary care hospital. We enrolled and studied 349 cases of suspected and confirmed dengue presenting for care at the Aga Khan University Hospital in Karachi between June 2021 and November 2023. Collected data on cases included clinical symptoms and laboratory results including qRT-PCR and serotype characterization. The majority of subjects enrolled (75%) had mild disease without warning signs, while 11% exhibited warning signs, 1.4% had severe dengue, and 12.6% had no dengue diagnosis. Patients with severe dengue (SD) had significantly higher levels of liver enzymes (AST and ALT) compared to those with non-severe dengue (NSD) (AST; p = 0.024 and ALT; p = 0.047). Additionally, a higher grade of thrombocytopenia was significantly associated with hospitalization (p = 0.0008), and prolonged illness (p = 0.03). Both Platelet (p < 0.0001) and WBC counts (p = 0.001) were significantly lower in dengue PCR-positive patients in comparison to Dengue PCR-negative. Among those tested for dengue serotypes, DENV 1 (34%) and DENV 2 (45%) emerged as the predominant serotypes, with mixed infections accounting for 17%. The sensitivity of q-RT PCR was found to be 87.25% and the specificity of 68.35%. qRT-PCR detected 43.5% of cases with viral fever initially screened negative by IgM or NS1. The epidemiology of dengue fever during a widespread outbreak in 2022 showed a predominance of DENV 1 and DENV 2 serotypes with milder phenotype of viral illness. Screening with rapid tests requires further confirmation by molecular assay in cases with dengue and dengue-like illness. The sensitivity of q-RT PCR using gold standard.

Background Increases in human population size, dengue vector-density and human mobility cause rapid spread of dengue virus in Indonesia. We investigated the changes in dengue haemorrhagic fever (DHF) incidence in Indonesia over a 45-year period and determined age-specific trends in annual DHF incidence. Methods Using an on-going nationwide dengue surveillance program starting in 1968, we evaluated all DHF cases and related deaths longitudinally up to 2013. Population demographics were used to calculate annual incidence and case fatality ratios (CFRs). Age-specific data on DHF available from 1993 onwards were used to assess trends in DHF age-distribution. Time-dependency of DHF incidence and CFRs was assessed using the Cochrane-Armitage trend test. Results The annual DHF incidence increased from 0.05/100,000 in 1968 to ~ 35-40/100,000 in 2013, with superimposed epidemics demonstrating a similar increasing trend with the highest epidemic occurring in 2010 (85.70/100,000; p < 0.01). The CFR declined from 41% in 1968 to 0.73% in 2013 (p < 0.01). Mean age of DHF cases increased during the observation period. Highest incidence of DHF was observed among children aged 5 to 14 years up to 1998, but declined thereafter (p < 0.01). In those aged 15 years or over, DHF incidence increased (p < 0.01) and surpassed that of 5 to 14 year olds from 1999 onwards. Conclusions Incidence of DHF over the past 45 years in Indonesia increased rapidly with peak incidence shifting from young children to older age groups. The shifting age pattern should have consequences for targeted surveillance and prevention.

Dengue contributes a significant burden on global public health and economies. In Africa, the burden of dengue virus (DENV) infection is not well described. This review was undertaken to determine the prevalence of dengue and associated risk factors. A literature search was done on PubMed/MEDLINE, Scopus, Embase, and Google Scholar databases to identify articles published between 1960 and 2020. Meta-analysis was performed using a random-effect model at a 95% confidence interval, followed by subgroup meta-analysis to determine the overall prevalence. Between 1960 and 2020, 45 outbreaks were identified, of which 17 and 16 occurred in East and West Africa, respectively. Dengue virus serotype 1 (DENV-1) and DENV-2 were the dominant serotypes contributing to 60% of the epidemics. Of 2211 cases reported between 2009 and 2020; 1954 (88.4%) were reported during outbreaks. Overall, the prevalence of dengue was 29% (95% CI: 20–39%) and 3% (95% CI: 1–5%) during the outbreak and non-outbreak periods, respectively. Old age (6/21 studies), lack of mosquito control (6/21), urban residence (4/21), climate change (3/21), and recent history of travel (3/21) were the leading risk factors. This review reports a high burden of dengue and increased risk of severe disease in Africa. Our findings provide useful information for clinical practice and health policy decisions to implement effective interventions.

Dengue is a major public health issue worldwide and severe dengue (SD) is life threatening. It is critical to triage patients with dengue infection in the early stage. However, there is limited knowledge on early indicators of SD. The objective of this study is to identify risk factors for the prognosis of SD and try to find out some potential predictive factors for SD from dengue fever (DF) in the early of infection. The PubMed, Cochrane Library and Web of Science databases were searched for relevant studies from June 1999 to December 2020. The pooled odds ratio (OR) or standardized mean difference (SMD) with 95% confidence intervals (CI) of identified factors was calculated using a fixed or random effect model in the meta-analysis. Tests for heterogeneity, publication bias, subgroup analyses, meta-regression, and a sensitivity analysis were further performed. A total of 6,848 candidate articles were retrieved, 87 studies with 35,184 DF and 8,173 SD cases met the eligibility criteria. A total of 64 factors were identified, including population and virus characteristics, clinical symptoms and signs, laboratory biomarkers, cytokines, and chemokines; of these factors, 34 were found to be significantly different between DF and SD, while the other 30 factors were not significantly different between the two groups after pooling the data from the relevant studies. Additionally, 9 factors were positive associated with SD within 7 days after illness when the timing subgroup analysis were performed. Practical factors and biomarkers for the identification of SD were established, which will be helpful for a prompt diagnosis and early effective treatment for those at greatest risk. These outcomes also enhance our knowledge of the clinical manifestations and pathogenesis of SD.

Dengue is a global epidemic causing over 100 million cases annually. The clinical symptoms range from mild fever to severe hemorrhage and shock, including some fatalities. The current paradigm is that these severe dengue cases occur mostly during secondary infections due to antibody-dependent enhancement after infection with a different dengue virus serotype. India has the highest dengue burden worldwide, but little is known about disease severity and its association with primary and secondary dengue infections. To address this issue, we examined 619 children with febrile dengue-confirmed infection from three hospitals in different regions of India. We classified primary and secondary infections based on IgM:IgG ratios using a dengue-specific enzyme-linked immunosorbent assay according to the World Health Organization guidelines. We found that primary dengue infections accounted for more than half of total clinical cases (344 of 619), severe dengue cases (112 of 202) and fatalities (5 of 7). Consistent with the classification based on binding antibody data, dengue neutralizing antibody titers were also significantly lower in primary infections compared to secondary infections ( P  ≤ 0.0001). Our findings question the currently widely held belief that severe dengue is associated predominantly with secondary infections and emphasizes the importance of developing vaccines or treatments to protect dengue-naive populations. In an analysis of severe dengue cases in a cohort of children in India, more than half could be attributed to primary rather than secondary infection, suggesting that primary dengue infections might also contribute substantially to severe disease burden.

Establishing reliable early warning models for severe dengue cases is a high priority to facilitate triage in dengue-endemic areas and optimal use of limited resources. However, few studies have identified the complex interactive relationship between potential risk factors and severe dengue. This research aimed to assess the potential risk factors and detect their high-order combinative effects on severe dengue. A structured questionnaire was used to collect detailed dengue outbreak data from eight representative hospitals in Dhaka, Bangladesh, in 2019. Logistic regression and machine learning models were used to examine the complex effects of demographic characteristics, clinical symptoms, and biochemical markers on severe dengue. A total of 1,090 dengue cases (158 severe and 932 non-severe) were included in this study. Dyspnoea (Odds Ratio [OR] = 2.87, 95% Confidence Interval [CI]: 1.72 to 4.77), plasma leakage (OR = 3.61, 95% CI: 2.12 to 6.15), and hemorrhage (OR = 2.33, 95% CI: 1.46 to 3.73) were positively and significantly associated with the occurrence of severe dengue. Classification and regression tree models showed that the probability of occurrence of severe dengue cases ranged from 7% (age >12.5 years without plasma leakage) to 92.9% (age ≤12.5 years with dyspnoea and plasma leakage). The random forest model indicated that age was the most important factor in predicting severe dengue, followed by education, plasma leakage, platelet, and dyspnoea. The research provides new evidence to identify key risk factors contributing to severe dengue cases, which could be beneficial to clinical doctors to identify and predict the severity of dengue early.

Background Severe dengue is a life-threatening complication; rapid identification of these cases, followed by adequate management is crucial to improve the clinical prognosis. Therefore, this study aimed to identify risk factors and predictors of severe dengue. Methods A literature search for studies reporting risk factors of severe dengue among individuals with dengue virus infection was conducted in PubMed, Scopus and Web of Science database from inception to December 31, 2020. Pooled odds ratios ( ORs ) for patients’ demographic characteristics, co-morbidities, and warning signs were estimated using an inverse variance heterogeneity model. Results We included 143 articles in the meta-analysis from a total of 13 090 articles retrieved from the literature search. The risk factors of severe dengue were: being a child [ OR  = 1.96; 95% confidence interval ( CI ): 1.22–3.13], secondary infection ( OR  = 3.23; 95% CI : 2.28–4.57), and patients with pre-existing diabetes ( OR  = 2.88; 95% CI : 1.72–4.81) and renal disease ( OR  = 4.54; 95% CI : 1.55–13.31). Warning signs strongly associated with severe disease were increased haematocrit with a concurrent decrease in platelet count ( OR  = 5.13; 95% CI : 1.61–16.34), abdominal pain ( OR  = 2.00; 95% CI : 1.49–2.68), lethargy ( OR  = 2.73; 95% CI : 1.05–7.10), vomiting ( OR  = 1.80; 95% CI : 1.43–2.26), hepatomegaly ( OR  = 5.92; 95% CI : 3.29–10.66), ascites ( OR  = 6.30; 95% CI : 3.75–10.60), pleural effusion ( OR  = 5.72; 95% CI : 3.24–10.10) and melena ( OR  = 4.05; 95% CI : 1.64–10.00). Conclusions Our meta-analysis identified children, secondary infection, diabetes and renal disease(s) as important predictors of severe dengue. Our finding also supports the predictive ability of the WHO warning signs to identify severe dengue. These findings are useful for clinicians to identify severe dengue for management and timely interventions.