Descripción del Primer Brote de Dengue en la Ciudad de Santo Tomé, Corrientes, 2016 / Description of the First Dengue Outbreak in the City of Santo Tomé, Corrientes, 2016

Argentina sufrió diferentes brotes de dengue en las regiones más cálidas durante el verano de 2016. En la ciudad de Santo Tomé (Corrientes) se produjo el primer brote. En este marco, el objetivo del trabajo fue evaluar la distribución temporal y espacial de los casos de dengue en Santo Tomé, así como las acciones adoptadas para interrumpir la transmisión. MÉTODOS: Los casos sospechosos fueron detectados por el personal sanitario, se confirmaron las muestras por análisis serológico y se georreferenció cada caso positivo, que fue clasificado como autóctono o importado. Las acciones de prevención fueron: bloqueo larval; control focal y rociado espacial; evaluación de larvicidas; descacharrado; charlas, capacitaciones y asamblea barrial. RESULTADOS: De 148 pacientes sospechosos se confirmaron 52 entre las semanas epidemiológicas 3 y 22. La cepa circulante fue DENV 1. El 46% (24/52) de los casos fueron autóctonos y se concentraron en el barrio Sarmiento. El 21% (140/655) de las viviendas presentaron criaderos de culícidos, de los cuales el 84% (210/251) resultó positivo para Ae. aegypti. DISCUSIÓN: Santo Tomé tuvo todas las condiciones para que se registrara el brote de dengue: población susceptible, presencia del vector y arribo de casos importados. Si bien la distribución de casos fue homogénea durante todo el brote, en el barrio Sarmiento se vio una clara circulación viral, que pudo ser controlada mediante una tarea interdisciplinaria de acción y prevención

Climate Change, Health and Mosquito-Borne Diseases: Trends and Implications to the Pacific Region.

Climate change is known to affect Pacific Island nations in a variety of ways. One of them is by increasing the vulnerability of human health induced by various climate change impacts, which pose an additional burden to the already distressed health systems in the region. This paper explores the associations between climate change and human health on the one hand, and outlines some of the health care challenges posed by a changing climate on the other. In particular, it describes the links between climate variations and the emergence of climate-sensitive infectious diseases, such as the mosquito-borne diseases dengue, chikungunya, and Zika. The paper also presents a summary of the key findings of the research initiatives Climate Change and Prevalence Study of ZIKA Virus Diseases in Fiji and the findings from the World Mosquito Program as two examples of public health action in the Pacific region.

Unbiased Metagenomic Sequencing for Pediatric Meningitis in Bangladesh Reveals Neuroinvasive Chikungunya Virus Outbreak and Other Unrealized Pathogens.

The burden of meningitis in low-and-middle-income countries remains significant, but the infectious causes remain largely unknown, impeding institution of evidence-based treatment and prevention decisions. We conducted a validation and application study of unbiased metagenomic next-generation sequencing (mNGS) to elucidate etiologies of meningitis in Bangladesh. This RNA mNGS study was performed on cerebrospinal fluid (CSF) specimens from patients admitted in the largest pediatric hospital, a World Health Organization sentinel site, with known neurologic infections (n = 36), with idiopathic meningitis (n = 25), and with no infection (n = 30), and six environmental samples, collected between 2012 and 2018. We used the IDseq bioinformatics pipeline and machine learning to identify potentially pathogenic microbes, which we then confirmed orthogonally and followed up through phone/home visits. In samples with known etiology and without infections, there was 83% concordance between mNGS and conventional testing. In idiopathic cases, mNGS identified a potential bacterial or viral etiology in 40%. There were three instances of neuroinvasive Chikungunya virus (CHIKV), whose genomes were >99% identical to each other and to a Bangladeshi strain only previously recognized to cause febrile illness in 2017. CHIKV-specific qPCR of all remaining stored CSF samples from children who presented with idiopathic meningitis in 2017 (n = 472) revealed 17 additional CHIKV meningitis cases, exposing an unrecognized meningitis outbreak. Orthogonal molecular confirmation, case-based clinical data, and patient follow-up substantiated the findings. Case-control CSF mNGS surveys can complement conventional diagnostic methods to identify etiologies of meningitis, conduct surveillance, and predict outbreaks. The improved patient- and population-level data can inform evidence-based policy decisions.IMPORTANCE Globally, there are an estimated 10.6 million cases of meningitis and 288,000 deaths every year, with the vast majority occurring in low- and middle-income countries. In addition, many survivors suffer from long-term neurological sequelae. Most laboratories assay only for common bacterial etiologies using culture and directed PCR, and the majority of meningitis cases lack microbiological diagnoses, impeding institution of evidence-based treatment and prevention strategies. We report here the results of a validation and application study of using unbiased metagenomic sequencing to determine etiologies of idiopathic (of unknown cause) cases. This included CSF from patients with known neurologic infections, with idiopathic meningitis, and without infection admitted in the largest children's hospital of Bangladesh and environmental samples. Using mNGS and machine learning, we identified and confirmed an etiology (viral or bacterial) in 40% of idiopathic cases. We detected three instances of Chikungunya virus (CHIKV) that were >99% identical to each other and to a strain previously recognized to cause systemic illness only in 2017. CHIKV qPCR of all remaining stored 472 CSF samples from children who presented with idiopathic meningitis in 2017 at the same hospital uncovered an unrecognized CHIKV meningitis outbreak. CSF mNGS can complement conventional diagnostic methods to identify etiologies of meningitis, and the improved patient- and population-level data can inform better policy decisions.

Dengue fever and chikungunya virus infections: identification in travelers in Uganda - 2017.

Arboviruses are (re-) emerging viruses that cause significant morbidity globally. Clinical manifestations usually consist of a non-specific febrile illness that may be accompanied by rash, arthralgia and arthritis and/or with neurological or hemorrhagic syndromes. The broad range of differential diagnoses of other infectious and non-infectious etiologies presents a challenge for clinicians. While knowledge of the geographic distribution of pathogens and the current epidemiological situation, incubation periods, exposure risk factors and vaccination history can help guide the diagnostic approach, the non-specific and variable clinical presentation can delay final diagnosis. This case report summarizes the laboratory-based findings of three travel-related cases of arbovirus infections in Uganda. These include a patient from Bangladesh with chikungunya virus infection and two cases of dengue fever from Ethiopia. Early detection of travel-imported cases by public health laboratories is important to reduce the risk of localized outbreaks of arboviruses such as dengue virus and chikungunya virus. Because of the global public health importance and the continued risk of (re-) emerging arbovirus infections, specific recommendations following diagnosis by clinicians should include obtaining travel histories from persons with arbovirus-compatible illness and include differential diagnoses when appropriate.

A global model for predicting the arrival of imported dengue infections.

With approximately half of the world's population at risk of contracting dengue, this mosquito-borne disease is of global concern. International travellers significantly contribute to dengue's rapid and large-scale spread by importing the disease from endemic into non-endemic countries. To prevent future outbreaks and dengue from establishing in non-endemic countries, knowledge about the arrival time and location of infected travellers is crucial. We propose a network model that predicts the monthly number of dengue-infected air passengers arriving at any given airport. We consider international air travel volumes to construct weighted networks, representing passenger flows between airports. We further calculate the probability of passengers, who travel through the international air transport network, being infected with dengue. The probability of being infected depends on the destination, duration and timing of travel. Our findings shed light onto dengue importation routes and reveal country-specific reporting rates that have been until now largely unknown. This paper provides important new knowledge about the spreading dynamics of dengue that is highly beneficial for public health authorities to strategically allocate the often limited resources to more efficiently prevent the spread of dengue.

Spatially Adjusted Time-varying Reproductive Numbers: Understanding the Geographical Expansion of Urban Dengue Outbreaks.

The basic reproductive number (R0) is a fundamental measure used to quantify the transmission potential of an epidemic in public health practice. However, R0 cannot reflect the time-varying nature of an epidemic. A time-varying effective reproductive number Rt can provide more information because it tracks the subsequent evolution of transmission. However, since it neglects individual-level geographical variations in exposure risk, Rt may smooth out interpersonal heterogeneous transmission potential, obscure high-risk spreaders, and hence hamper the effectiveness of control measures in spatial dimension. Therefore, this study proposes a new method for quantifying spatially adjusted (time-varying) reproductive numbers that reflects spatial heterogeneity in transmission potential among individuals. This new method estimates individual-level effective reproductive numbers (Rj) and a summarized indicator for population-level time-varying reproductive number (Rt). Data from the five most severe dengue outbreaks in southern Taiwan from 1998-2015 were used to demonstrate the ability of the method to highlight early spreaders contributing to the geographic expansion of dengue transmission. Our results show spatial heterogeneity in the transmission potential of dengue among individuals and identify the spreaders with the highest Rj during the epidemic period. The results also reveal that super-spreaders are usually early spreaders that locate at the edges of the epidemic foci, which means that these cases could be the drivers of the expansion of the outbreak. Therefore, our proposed method depicts a more detailed spatial-temporal dengue transmission process and identifies the significant role of the edges of the epidemic foci, which could be weak spots in disease control and prevention.

A favorable outcome of dengue hemorrhagic fever despite poor prognostic indices: a case report with a mix of classic and unusual clinical and laboratory features.

The report describes a 32-year-old man with dengue hemorrhagic fever presenting with acute onset high-grade intermittent fever with chills and rigors, headache, myalgia, abdominal pain, and vomiting. His laboratory results revealed neutrophilia, thrombocytopenia, microscopic hematuria, and a markedly elevated D-dimer. While on admission, he developed diarrhea, hypertension, and respiratory symptoms which evolved into respiratory distress with low oxygen saturation, eventually warranting his admission to the Intensive Care Unit (ICU). Despite his adverse prognostic indices, the patient made an uneventful recovery with conservative management after 16 days of admission. Thus illustrating how aggressive management could influence the outcome of dengue illness.

Social capital is associated with lower mosquito vector indices: secondary analysis from a cluster randomised controlled trial of community mobilisation for dengue prevention in Mexico.

BACKGROUND: Control of the Aedes aegypti mosquito is central to reducing the risk of dengue, zika, chikungunya, and yellow fever. Randomised controlled trials, including the Camino Verde trial in Mexico and Nicaragua, demonstrate the convincing impact of community mobilisation interventions on vector indices. These interventions might work through building social capital but little is known about the relationship between social capital and vector indices. METHODS: A secondary analysis used data collected from 45 intervention clusters and 45 control clusters in the impact survey of the Mexican arm of the Camino Verde cluster randomised controlled trial. Factor analysis combined responses to questions about aspects of social capital to create a social capital index with four constructs, their weighted averages then combined into a single scale. We categorised households as having high or low social capital based on their score on this scale. We examined associations between social capital and larval and pupal vector indices, taking account of the effects of other variables in a multivariate analysis. We report associations as odds ratios and 95% confidence intervals. RESULTS: The four social capital constructs were involvement, participation, investment, and communication. Among the 10,112 households, those in rural communities were much more likely to have a high social capital score (OR 4.51, 95% CIca 3.26-6.26). Households in intervention sites had higher social capital, although the association was not significant at the 5% level. Households with high social capital were more likely to be negative for larvae or pupae (OR 1.38, 95% CIca 1.12-1.69) and for pupae specifically (OR 1.37, 95% CIca 1.08-1.74). There was interaction between intervention status and social capital; in multivariate analysis, a combined variable of intervention/high social capital remained associated with larvae or pupae (ORa l.56, 95% CIca 1.19-2.04) and with pupae specifically (ORa 1.65, 95% CIca 1.20-2.28). CONCLUSION: This is the first report of an association of high social capital with low vector indices. Our findings support the idea that the Camino Verde community mobilisation intervention worked partly through an interaction with social capital. Understanding such interactions may help to maximise the impact of future community mobilisation interventions.

Re-introduction of dengue virus serotype 2 in the state of Rio de Janeiro after almost a decade of epidemiological silence.

The Asian/American genotype of dengue virus serotype 2 (DENV-2) has been introduced in Brazil through the state of Rio de Janeiro around 1990, and since then it has been spreading and evolving, leading to several waves of dengue epidemics throughout the country that cause a major public health problem. Of particular interest has been the epidemic of 2008, whose highest impact was evidenced in the state of Rio de Janeiro, with a higher number of severe cases and mortality rate, compared to previous outbreaks. Interestingly, no circulation of DENV-2 was witnessed in this region during the preceding 9-year period. By early 2010, phylogenetic analysis of the 2008 epidemic strain revealed that the outbreak was caused by a new viral lineage of the Asian/American genotype, which was pointed as responsible for the outbreak severity as well. The same scenario is repeating in 2019 in this state; however, only a few cases have been detected yet. To provide information that helps to the understanding of DENV-2 dynamics in the state of Rio de Janeiro, and thereafter contribute to public health control and prevention actions, we employed phylogenetic studies combined with temporal and dynamics geographical features to determine the origin of the current viral strain. To this effect, we analyzed a region of 1626 nucleotides entailing the Envelope/NS1 viral genes. Our study reveals that the current strain belongs to the same lineage that caused the 2008 outbreak, however, it is phylogenetically distant from any Brazilian strain identified so far. Indeed, it seemed to be originated in Puerto Rico around 2002 and has been introduced into the state in late 2018. Taking into account that no DENV-2 case was reported over the last decade in the state (representing a whole susceptible children generation), and the fact that a new viral strain may be causing current dengue infections, these results will be influential in strengthening dengue surveillance and disease control, mitigating the potential epidemiological consequences of virus spread.

Clinical Profiles of Dengue Fever Patients, during an Outbreak.

BACKGROUND: Dengue fever (DF) has become a major public health concern globally. It is an infection caused by a virus of the family Flaviviridae, with five serotypes (DENV 1-5). Recent years have seen an increase in the prevalence of the disease in Pakistan. The current study was carried out to evaluate the clinical features, laboratory findings and demographic information of the patients reported during the dengue outbreak in Multan of Pakistan in 2015. METHODS: The hospital documentation-based data of confirmed DF cases were collected for the 6 months period from a Tertiary Care Hospital in Multan, Pakistan. The patients were labeled as confirmed on the basis of NS1 and IgM positivity by ELISA. The data collected were analyzed using SPSS. RESULTS: Overall, 361 patients were investigated (78.67% males and 21.33% females), with maximum infection rate in the age group of 18-35yr (50.41%). Mean hospital stay was 2.64d (SD 1.2), while mean fever duration was 5.27 (SD 1.57). Outbreak occurred during the months from Jul-Dec, while maximum patients were reported in Oct (287). No mortality was reported, and all patients recovered. CONCLUSION: Better management practices and timely reporting can reduce the risk factors associated with the disease.

Molecular and phylogenetic analysis of the dengue strains circulating in Odisha, India.

Dengue has emerged as a major public health challenge in terms of both changing clinical pattern and epidemiological features. The state of Odisha reported first dengue epidemic in the year 2010 and this continued each year in epidemic form during post monsoon period gradually becoming an endemic phenomenon. Present study depicts the changing epidemiological and clinical pattern of dengue with reference to its serotypes and genotypes. The study included 5320 suspected dengue cases from different health facilities of the state during 2010-2017. Dengue NS1 antigen and IgM antibody was done through ELISA. Serotyping was done through RTPCR by amplifying a part of core-pre-membrane gene (CprM) followed by sequencing and phylogenetic analysis. Dengue IgM antibody in 17.7% cases and NS1 antigen in 53.20% cases was detected. Dengue serotype 2 (DEN-2) was the only serotype detected in 2010 and 2011 where as all four serotypes 1, 2, 3, 4 were detected in 2012-2017, DEN-2 being dominant but in 2017 DEN-3 was found to be dominant. Phylogenetic analysis revealed genotype IV of DEN-2 and genotype III of DEN-1 and DEN-3 circulating in this region. In 6 cases involvement of DEN-2 in clinically evident encephalitis cases is an important observation in this region and needs public health attention. High prevalence of dengue was observed without any previous reported outbreaks in the state with increased number of cases from 2010 to 2012 affecting both urban and rural areas. High incidence in 2012 was due to co-circulation of more than one serotype which continued in the following years. Severity in some cases was associated with mixed infection but in most cases it was mild indicating the endemic nature of the virus in most parts of Odisha.

Estimating the proportion of vaccine-induced hospitalized dengue cases among Dengvaxia vaccinees in the Philippines.

Background: Dengvaxia was used in the Philippines to vaccinate 9-10-year-old school children, living in areas highly endemic for dengue. After about 830,000 had received at least 1 of 3 recommended doses, risks of enhanced disease in dengue-naïve vaccinees were reported. Methods: We used Phase 3 trial data to derive the proportions of cases of hospitalised and severe dengue that might have been prevented by the Philippines vaccination programme and, among those cases that may occur in vaccinees, what proportions are likely to arise in those who were seropositive or seronegative for dengue at the time of first vaccination and what proportion in the latter group may be enhanced disease attributable to the vaccine. Results: Assuming about 15% of vaccinees were dengue naïve at vaccination and the effects of the vaccine are independent of the number of doses received, we estimate that, in the 5 years following vaccination, the number of cases of severe disease in the vaccinated population will be reduced by about 70%. Among vaccinees who do develop severe disease, about half the cases will be due to vaccine breakthrough in seropositive vaccinees, and about a quarter will be excess cases in seronegative vaccinees that will have occurred as a consequence of vaccination. Conclusions: Overall, the Philippine dengue vaccination programme will likely prevent a substantial number of severe dengue cases and, among those that do occur, the majority are likely to be breakthrough disease in seropositive vaccinees and a minority attributable to the excess risk of enhanced disease in seronegative vaccinees.

Considering Genomic and Immunological Correlates of Protection for a Dengue Intervention.

Over three billion are at risk of dengue infection with more than 100 million a year presenting with symptoms that can lead to deadly haemorrhagic disease. There are however no treatments available and the only licensed vaccine shows limited efficacy and is able to enhance the disease in some cases. These failures have mainly been due to the complex pathology and lack of understanding of the correlates of protection for dengue virus (DENV) infection. With increasing data suggesting both a protective and detrimental effect for antibodies and CD8 T-cells whilst having complex environmental dynamics. This review discusses the roles of genomic and immunological aspects of DENV infection, providing both a historical interpretation and fresh discussion on how this information can be used for the next generation of dengue interventions.

Clinical and epidemiologic characteristics associated with dengue during and outside the 2016 outbreak identified in health facility-based surveillance in Ouagadougou, Burkina Faso.

BACKGROUND: In Africa, the magnitude of dengue virus (DENV) transmission is largely unknown. In Burkina Faso, several outbreaks have been reported and data are often based on findings from outbreak investigations. METHODS: To better understand dengue epidemiology and clinical characteristics in Burkina Faso, a fever surveillance study was conducted among patients aged 1-55 years, who presented with non-malarial febrile illness at five primary healthcare facilities in Ouagadougou, Burkina Faso from December 2014 to February 2017, encompassing a 3-month dengue outbreak in September-November 2016. Acute and convalescent blood samples were collected within an interval of 10-21 days between visits. Acute samples were tested with dengue rapid diagnostic tests (RDT) and a selected subset with RT-PCR, and all acute/convalescent samples with IgM/IgG ELISA. RESULTS: Among 2929 non-malarial febrile patients, 740 (25%) were dengue-positive based on RT-PCR and/or IgM/IgG ELISA; 428 out of 777 patients (55%) and 312 out of 2152 (14%) were dengue-positive during outbreak and non-outbreak periods, respectively. There were 11% (316/2929) and 4% (129/2929) patients showing positive for NS1 and IgM, on the RDT, respectively. DENV 2 predominated during the outbreak, whereas DENV 3 predominated before the outbreak. Only 25% of dengue-positive cases were clinically diagnosed with suspected dengue. The odds of requiring observation for ≤3 days (versus routine outpatient care) were 11 times higher among dengue-positive cases than non-dengue cases. In adjusted analyses, dengue-positivity was associated with rash and retro-orbital pain (OR = 2.6 and 7.4, respectively) during the outbreak and with rash and nausea/vomiting (OR = 1.5 and 1.4, respectively) during the non-outbreak period. CONCLUSION: Dengue virus is an important pathogen in Burkina Faso, accounting for a substantial proportion of non-malarial fevers both during and outside outbreak, but is only infrequently suspected by clinicians. Additional longitudinal data would help to further define characteristics of dengue for improved case detection and surveillance.

Broadly neutralizing human antibodies against dengue virus identified by single B cell transcriptomics.

Eliciting broadly neutralizing antibodies (bNAbs) against the four dengue virus serotypes (DENV1-4) that are spreading into new territories is an important goal of vaccine design. To define bNAb targets, we characterized 28 antibodies belonging to expanded and hypermutated clonal families identified by transcriptomic analysis of single plasmablasts from DENV-infected individuals. Among these, we identified J9 and J8, two somatically related bNAbs that potently neutralized DENV1-4. Mutagenesis studies showed that the major recognition determinants of these bNAbs are in E protein domain I, distinct from the only known class of human bNAbs against DENV with a well-defined epitope. B cell repertoire analysis from acute-phase peripheral blood suggested that J9 and J8 followed divergent somatic hypermutation pathways, and that a limited number of mutations was sufficient for neutralizing activity. Our study suggests multiple B cell evolutionary pathways leading to DENV bNAbs targeting a new epitope that can be exploited for vaccine design.

Identification of highly conserved, serotype-specific dengue virus sequences: implications for vaccine design.

BACKGROUND: The sequence diversity of dengue virus (DENV) is one of the challenges in developing an effective vaccine against the virus. Highly conserved, serotype-specific (HCSS), immune-relevant DENV sequences are attractive candidates for vaccine design, and represent an alternative to the approach of selecting pan-DENV conserved sequences. The former aims to limit the number of possible cross-reactive epitope variants in the population, while the latter aims to limit the cross-reactivity between the serotypes to favour a serotype-specific response. Herein, we performed a large-scale systematic study to map and characterise HCSS sequences in the DENV proteome. METHODS: All reported DENV protein sequence data for each serotype was retrieved from the NCBI Entrez Protein (nr) Database (txid: 12637). The downloaded sequences were then separated according to the individual serotype proteins by use of BLASTp search, and subsequently removed for duplicates and co-aligned across the serotypes. Shannon's entropy and mutual information (MI) analyses, by use of AVANA, were performed to measure the diversity within and between the serotype proteins to identify HCSS nonamers. The sequences were evaluated for the presence of promiscuous T-cell epitopes by use of NetCTLpan 1.1 and NetMHCIIpan 3.2 server for human leukocyte antigen (HLA) class I and class II supertypes, respectively. The predicted epitopes were matched to reported epitopes in the Immune Epitope Database. RESULTS: A total of 2321 nonamers met the HCSS selection criteria of entropy < 0.25 and MI > 0.8. Concatenating these resulted in a total of 337 HCSS sequences. DENV4 had the most number of HCSS nonamers; NS5, NS3 and E proteins had among the highest, with none in the C and only one in prM. The HCSS sequences were immune-relevant; 87 HCSS sequences were both reported T-cell epitopes/ligands in human and predicted epitopes, supporting the accuracy of the predictions. A number of the HCSS clustered as immunological hotspots and exhibited putative promiscuity beyond a single HLA supertype. The HCSS sequences represented, on average, ~ 40% of the proteome length for each serotype; more than double of pan-DENV sequences (conserved across the four serotypes), and thus offer a larger choice of sequences for vaccine target selection. HCSS sequences of a given serotype showed significant amino acid difference to all the variants of the other serotypes, supporting the notion of serotype-specificity. CONCLUSION: This work provides a catalogue of HCSS sequences in the DENV proteome, as candidates for vaccine target selection. The methodology described herein provides a framework for similar application to other pathogens.

The association between dengue incidences and provincial-level weather variables in Thailand from 2001 to 2014.

Dengue and dengue hemorrhagic pose significant burdens in many tropical countries. Dengue incidences have perpetually increased, leading to an annual (uncertain) peak. Dengue cases cause an enormous public health problem in Thailand because there is no anti-viral drug against the dengue virus. Searching for means to reduce the dengue incidences is a challenging and appropriate strategy for primary prevention in a dengue outbreak. This study constructs the best predictive model from past statistical dengue incidences at the provincial level and studies the relationships among dengue incidences and weather variables. We conducted experiments for 65 provinces (out of 77 provinces) in Thailand since there is no dengue information for the remaining provinces. Predictive models were constructed using weekly data during 2001-2014. The training set are data during 2001-2013, and the test set is the data from 2014. Collected data were separated into two parts: current dengue cases as the dependent variable, and weather variables and previous dengue cases as the independent variables. Eight weather variables are used in our models: average pressure, maximum temperature, minimum temperature, average humidity, precipitation, vaporization, wind direction, wind power. Each weather variable includes the current week and one to three weeks of lag time. A total of 32 independent weather variables are used for each province. The previous one to three weeks of dengue cases are also used as independent variables. There is a total of 35 independent variables. Predictive models were constructed using five methods: Poisson regression, negative binomial regression, quasi-likelihood regression, ARIMA(3,1,4) and SARIMA(2,0,1)(0,2,0). The best model is determined by combinations of 1-12 variables, which are 232,989,800 models for each province. We construct a total of 15,144,337,000 models. The best model is selected by the average from high to low of the coefficient of determination (R2) and the lowest root mean square error (RMSE). From our results, the one-week lag previous case variable is the most frequent in 55 provinces out of a total of 65 provinces (coefficient of determinations with a minimum of 0.257 and a maximum of 0.954, average of 0.6383, 95% CI: 0.57313 to 0.70355). The most influential weather variable is precipitation, which is used in most of the provinces, followed by wind direction, wind power, and barometric pressure. The results confirm the common knowledge that dengue incidences occur most often during the rainy season. It also shows that wind direction, wind power, and barometric pressure also have influences on the number of dengue cases. These three weather variables may help adult mosquitos to survive longer and spread dengue. In conclusion, The most influential factor for further cases is the number of dengue cases. However, weather variables are also needed to obtain better results. Predictions of the number of dengue cases should be done locally, not at the national level. The best models of different provinces use different sets of weather variables. Our model has an accuracy that is sufficient for the real prediction of future dengue incidences, to prepare for and protect against severe dengue outbreaks.

Flavivirus Cross-Reactivity to Dengue Nonstructural Protein 1 Antigen Detection Assays.

Dengue virus (DENV) and Zika virus (ZIKV) are flaviviruses of public health relevance. Both viruses circulate in the same endemic settings and acute infections generally manifest similar symptoms. This highlights the importance of accurate diagnosis for clinical management and outbreak control. One of the commonly used acute diagnostic markers for flaviviruses is nonstructural protein 1 (NS1). However, false positives due to antigenic cross-reactivity have been reported between DENV and ZIKV infections when using DENV NS1 antigen (NS1 Ag) detection assays in acute cases. Therefore, we investigated the lowest detectable virus titres and cross-reactivity of three commercial dengue NS1 Ag rapid assays and two ELISAs for different flaviviruses. Our results showed that substantially high viral titres of ZIKV, Kunjin virus (KUNV) and yellow fever virus (YFV) are required to give false-positive results when using DENV NS1 rapid detection assays. Commercial DENV NS1 ELISAs did not react with ZIKV and YFV. In comparison, tested assays detected DENV at a significantly low virus titre. Given the relatively low viral loads reported in clinical samples, our findings suggest that commercially available dengue NS1 Ag detection assays are less likely to generate false-positive results among clinical samples in areas where multiple flaviviruses cocirculate.