Background: Dengue is a growing problem both in its geographical spread and in its intensity, and yet current global distribution remains highly uncertain. Challenges in diagnosis and diagnostic methods as well as highly variable national health systems mean no single data source can reliably estimate the distribution of this disease. As such, there is a lack of agreement on national dengue status among international health organisations. Here we bring together all available information on dengue occurrence using a novel approach to produce an evidence consensus map of the disease range that highlights nations with an uncertain dengue status. Methods/Principal Findings: A baseline methodology was used to assess a range of evidence for each country. In regions where dengue status was uncertain, additional evidence types were included to either clarify dengue status or confirm that it is unknown at this time. An algorithm was developed that assesses evidence quality and consistency, giving each country an evidence consensus score. Using this approach, we were able to generate a contemporary global map of national-level dengue status that assigns a relative measure of certainty and identifies gaps in the available evidence. Conclusion: The map produced here provides a list of 128 countries for which there is good evidence of dengue occurrence, including 36 countries that have previously been classified as dengue-free by the World Health Organization and/or the US Centers for Disease Control. It also identifies disease surveillance needs, which we list in full. The disease extents and limits determined here using evidence consensus, marks the beginning of a five-year study to advance the mapping of dengue virus transmission and disease risk. Completion of this first step has allowed us to produce a preliminary estimate of population at risk with an upper bound of 3.97 billion people. This figure will be refined in future work.

/pdf/refining-the-global-spatial-limits-of-dengue-virus-f8emry0wk5.pdf

Refining the global spatial limits of dengue virus transmission by evidence-based consensus

For dengue viruses 1 to 4 (DENV1-4), a specific range of antibody titer has been shown to enhance viral replication in vitro and severe disease in animal models. Although suspected, such antibody-dependent enhancement of severe disease has not been shown to occur in humans. Using multiple statistical approaches to study a long-term pediatric cohort in Nicaragua, we show that risk of severe dengue disease is highest within a narrow range of preexisting anti-DENV antibody titers. By contrast, we observe protection from all symptomatic dengue disease at high antibody titers. Thus, immune correlates of severe dengue must be evaluated separately from correlates of protection against symptomatic disease. These results have implications for studies of dengue pathogenesis and for vaccine development, because enhancement, not just lack of protection, is of concern.

https://science.sciencemag.org/content/sci/358/6365/929.full.pdf

Antibody-dependent enhancement of severe dengue disease in humans

Dengue is a major international public health concern and the number of outbreaks has escalated greatly. Human migration, international trade and travel are constantly introducing new vectors and pathogens into novel geographic areas. Of particular interest is the extent to which dengue virus (DENV) infections are subclinical or inapparent. Not only may such infections contribute to the global spread of DENV by human migration, but also seroprevalence rates in naive populations may be initially high despite minimal numbers of detectable clinical cases. As the probability of severe disease is increased in secondary infections, populations may thus be primed, with serious public health consequences following introduction of a new serotype. In addition, pre-existing immunity from inapparent infections may affect vaccine uptake and the ratio of clinically apparent to inapparent infection could affect the interpretation of vaccine trials. We performed a literature search for inapparent DENV infections and provide an analytical review of their frequency and associated risk factors. Inapparent rates were highly variable, but “inapparent” was the major outcome of infection in all prospective studies. Differences in the epidemiological context and type of surveillance account for much of the variability in inapparent infection rates. However, one particular epidemiological pattern was shared by four longitudinal cohort studies: the rate of inapparent DENV infections was positively correlated with the incidence of disease the previous year, strongly supporting an important role for short-term heterotypic immunity in determining the outcome of infection. Primary and secondary infections were equally likely to be inapparent. Knowledge of the extent to which viruses from inapparent infections are transmissible to mosquitoes is urgently needed. Inapparent infections need to be considered for their impact on disease severity, transmission dynamics, and vaccine efficacy and uptake.

https://hal-pasteur.archives-ouvertes.fr/pasteur-01161861/document

Epidemiological risk factors associated with high global frequency of inapparent dengue virus infections.

Respiratory syncytial virus is the most common respiratory virus infection in early childhood, causing a wide range of illness from mild colds to life-threatening croup, bronchiolitis and pneumonia that may require intensive care. Exactly which parameters contribute to the seasonality of RSV (and other respiratory viruses, such as influenza) and their comparative significance are the subject of ongoing intensive debate. This review article summarises the specific contributions and correlations between the incidence of RSV and various climate parameters. This systematic review of the literature specifically focuses on these climate associations and have been stratified by study site latitudes: tropical (0-23.5°N or S), subtropical (23.5-40°N or S) and temperate latitudes (>40°N or S). Correlations between RSV incidence and temperature and relative humidity are particularly variable and inconsistent amongst the tropical regions. In subtropical and temperate regions, RSV incidence is more consistently positively correlated with lower temperatures and higher relative humidity. Although there is some variation with the diagnostic methods used in these studies, most used immunofluorescent viral antigen testing to diagnose RSV infection. Statistically, most studies used some form of regression analysis, which assumes no dependence between data taken at different time points. A few used the autoregressive integrated moving average approach, which may be more realistic for an infectious agent as the total number of cases usually evolves in a time-dependent manner during a typical seasonal epidemic.

Correlations between climate factors and incidence--a contributor to RSV seasonality

Dengue viruses cause more human morbidity and mortality than any other arthropod-borne virus. Dengue prevention relies mainly on vector control; however, the failure of traditional methods has promoted the development of novel entomological approaches. Although use of the intracellular bacterium wolbachia to control mosquito populations was proposed 50 years ago, only in the past decade has its use as a potential agent of dengue control gained substantial interest. Here, we review evidence that supports a practical approach for dengue reduction through field release of wolbachia-infected mosquitoes and discuss the additional studies that have to be done before the strategy can be validated and implemented. A crucial next step is to assess the efficacy of wolbachia in reducing dengue virus transmission. We argue that a cluster randomised trial is at this time premature because choice of wolbachia strain for release and deployment strategies are still being optimised. We therefore present a pragmatic approach to acquiring preliminary evidence of efficacy through various complementary methods including a prospective cohort study, a geographical cluster investigation, virus phylogenetic analysis, virus surveillance in mosquitoes, and vector competence assays. This multipronged approach could provide valuable intermediate evidence of efficacy to justify a future cluster randomised trial.

/pdf/assessing-the-epidemiological-effect-of-wolbachia-for-dengue-4q4jlardts.pdf

Assessing the epidemiological effect of wolbachia for dengue control

https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(14)64508-0/pdf

Regular pattern of respiratory syncytial virus and rotavirus infections and relation to weather in Stockholm, 1984-1993

The etiology of acute respiratory tract infection and its association with diarrhea was analyzed in 135 hospitalized children less than three years of age with mainly respiratory symptoms in two pediatric hospitals in Honduras and El Salvador. Etiologic diagnoses were performed on nasopharyngeal samples by tissue culture and immunofluorescence, including a search for the presence of respiratory virus-specific immunoglobulin A antibodies. Fecal samples were subjected to electron microscopy and tissue culture. The majority (83%) of the children (65% boys and 35% girls) were less than 12 months old and 45% were less than four months old. In 63 (47%) patients, at least one viral infection of the respiratory tract was identified. Respiratory syncytial virus (RSV) or the respective IgA antibodies were found in 43 (32%) patients, influenza A and B viruses in 29 (21%) patients, adenovirus in four patients, and enterovirus in two patients. Twenty (15%) patients had two or more viral agents. An association between RSV cases and environmental temperature was established. In 124 fecal samples, we identified four cases with astrovirus, seven with nonpolio enterovirus, and eight with adenovirus, but only three cases with rotavirus. Diarrhea was present in 55 (45%) of the patients. There was a statistically significant association between diarrhea and cases with RSV. This was shown to be associated with antibiotic treatment.

Respiratory infection and iatrogenic diarrhea in Honduras and El Salvador during the 1991-1992 season.

Cutaneous amebiasis is the least common clinical form of human amebiasis in Mexico, sexual amebiasis was only occasionally observed before the late 1980s. However, in the last few decades, most of the documented cases of cutaneous amebiasis from around the world are sexually transmitted. We present two cases of sexually transmitted genital amebiasis. The molecular characterization of the Entamoeba species in the affected tissues underlines the importance of an etiological diagnosis using specific and sensitive techniques that avoid the rapid destruction of tissues and the irreversible sequelae to the anatomy and function of the affected organs. In addition, for those interested in the study of the human-amoebic disease relationship and its epidemiology, the detection of a new, mixed infection in an invasive case of amebiasis reveals new perspectives in the study of the extraordinarily complex host-parasite relationship in amebiasis.

/pdf/cutaneous-amebiasis-the-importance-of-molecular-diagnosis-of-59trzvxcdb.pdf

Cutaneous Amebiasis: The Importance of Molecular Diagnosis of an Emerging Parasitic Disease

Traditional study designs do not identify acute asymptomatic or pre-symptomatic dengue virus (DENV) infections, thus limiting our understanding of immunologic and viral factors that modulate infection outcome. In the 2006 and 2007 dengue seasons, we conducted a pilot index cluster study in Managua, Nicaragua, in which 442 persons living within 50 meters of 22 index cases identified through an ongoing pediatric cohort study were evaluated for DENV infection. Post-enrollment and pre-enrollment DENV infections were confirmed in 12 (2.7%) and 19 (4.3%) contacts, respectively. Five (42%) post-enrollment infections were asymptomatic, and DENV-2 was identified in 9 (75%) infections. Phylogenetic analysis with full-length DENV genomic sequence from contacts, index cases, and cohort dengue cases indicated focal transmission and infection outside the local area. We demonstrate the feasibility of identification of acute asymptomatic and pre-symptomatic cases in urban Latin America, the first report of such a study in the Americas, and identify age and concomitant immunity to DENV of contacts as a key factor in index cluster study design.

Index Cluster Study of Dengue Virus Infection in Nicaragua

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Regular pattern of respiratory syncytial virus and rotavirus infections and relation to weather in Stockholm, 1984-1993

Respiratory infection and iatrogenic diarrhea in Honduras and El Salvador during the 1991-1992 season.

Cutaneous Amebiasis: The Importance of Molecular Diagnosis of an Emerging Parasitic Disease

Index Cluster Study of Dengue Virus Infection in Nicaragua