Involvement of dual serotypes during a severe dengue outbreak in Wadi area, Nagpur district, Maharashtra 2017.

BACKGROUND & OBJECTIVES: An outbreak of dengue-like illness was reported from Wadi area within the Nagpur Municipal Corporation during September-October 2017 with five deaths. Major symptoms reported were high fever (103-106 oF), acute joint pains, myalgia, drowsiness, breathlessness, etc. An investigation was conducted to confirm the etiological agent, its characterization and the vectors involved in the outbreak. METHODS: Serological analysis was conducted to detect dengue (DEN)/chikungunya IgM antibodies in 158 sera samples. Nested-PCR was carried out to serotype eight ELISA positive samples. Adult and larval mosquito collections were conducted in the affected areas to determine species composition and mosquito density. RESULTS: Dengue IgM antibodies were detected in 44 sera samples. Molecular typing revealed involvement of DEN-2 and DEN-3 serotypes. Dengue hemorrhagic fever symptoms were observed in two patients. Aedes aegypti breeding was found rampant with Breteu index and house index ranging from 23 to 70 and 17 to 56, respectively. Major breeding habitats encountered were, used tyres, cement tanks and refrigerator trays. INTERPRETATION & CONCLUSION: Clinical symptoms, detection of anti-DEN IgM antibodies in high number of samples and heavy breeding of Ae. aegypti confirmed it was a dengue outbreak.

A case report of dengue haemorrhagic fever during the peripartum period: challenges in management and a case of vertical dengue transmission.

BACKGROUND: Incidence of Dengue infection is on the increase in Sri Lanka with it being associated with significant maternal and neonatal morbidity in pregnancy. CASE PRESENTATION: A 33-year-old pregnant woman at 38 weeks of gestation, presented with acute onset of fever, was later diagnosed with Dengue illness. Due to the emergence of warning symptoms and signs and rapidly dropping platelet count, the baby was delivered by urgent caesarian section. She went into the critical phase during the postoperative period and due to concealed bleeding, required blood transfusion. On the 5th day of life, the neonate was also diagnosed with possible dengue by vertical transmission and required blood and PLT transfusions for recovery. CONCLUSIONS: This case report illustrates how a high index of suspicion, early diagnosis, close monitoring, timely intervention and critical consideration of physiological changes of pregnancy when interpreting clinical situation, led to achieving a successful outcome.

Preventive and therapeutic challenges in combating Zika virus infection: are we getting any closer?

The neuroteratogenic nature of Zika Virus (ZIKV) infection has converted what would have been a tropical disease into a global threat. Zika is transmitted vertically via infected placental cells especially in the first and second trimesters. In the developing central nervous system (CNS), ZIKV can infect and induce apoptosis of neural progenitor cells subsequently causing microcephaly as well as other neuronal complications in infants. Its ability to infect multiple cell types (placental, dermal, and neural) and increased environmental stability as compared to other flaviviruses (FVs) has broadened the transmission routes for ZIKV infection from vector-mediated to transmitted via body fluids. To further complicate the matters, it is genetically similar (about 40%) with the four serotypes of dengue virus (DENV), so much so that it can almost be called a fifth DENV serotype. This homology poses the risk of causing cross-reactive immune responses and subsequent antibody-dependent enhancement (ADE) of infection in case of secondary infections or for immunized individuals. All of these factors complicate the development of a single preventive vaccine candidate or a pharmacological intervention that will completely eliminate or cure ZIKV infection. We discuss all of these factors in detail in this review and conclude that a combinatorial approach including immunization and treatment might prove to be the winning strategy.

[Hemorrhagic dengue and vertical transmission to the newborn: a case report and literature review]. / Dengue materno de tipo hemorrágico con trasmisión vertical al neonato: reporte de un caso y revisión de la bibliografía.

OBJECTIVE: To describe the case of a patient with term pregnancy and infection with hemorrhagic dengue and vertical transmission to the newborn. CLINICAL CASE: Thirty-two year old patient with pregnancy at 38 weeks was admitted with fever 2 days earlier (38 degrees C). During her stay she continued with fever of 39 degrees C and platelets of 85,000/mm3. Serology for dengue NS1 antigen was reported positive. Labor was induced getting a new-born, male, 3,220 g, who breathed and cried at birth. During the postpartum period continued with fever, malaise, retro-ocular pain, generalized rash in upper and lower limbs, bleeding gums and petechial on the soft palate and thrombocytopenia of 5,000/mm3, later. At 8 days of stay, platelet concentration increased to 42,000/mm3 without requiring platelet concentrates and she was discharged after ten days in hospital with platelets of 94,000/mm3. The 4th day of extra-uterine live (EUL), neonate shows generalized rash over the trunk; The 5th day starts with 38 degrees C fever and thrombocytopenia (78,000/mm3). Dengue serological tests reported positive for Ag NS1 and negative for Abs IgM and IgG. Neonate was admitted to NICU, he continued with a decrease in platelet of 14,000/mm3- and ecchymotic areas by pressure and veno-punction sites. Four platelet concentrates were transfused. At 10th day of EUL platelet count was reported with 387,000/mm3. CONCLUSIONS: In an endemic area, such as Sinaloa state, in a pregnant woman with fever and thrombocytopenia, we should be alert to possibility of a DV infection and its complications. Although rare, such as this case, infection can be transmitted to fetus (vertical transmission) and produce a primary congenital dengue, even in its severe hemorrhagic types.

Female-specific flightless phenotype for mosquito control.

Dengue and dengue hemorrhagic fever are increasing public health problems with an estimated 50-100 million new infections each year. Aedes aegypti is the major vector of dengue viruses in its range and control of this mosquito would reduce significantly human morbidity and mortality. Present mosquito control methods are not sufficiently effective and new approaches are needed urgently. A "sterile-male-release" strategy based on the release of mosquitoes carrying a conditional dominant lethal gene is an attractive new control methodology. Transgenic strains of Aedes aegypti were engineered to have a repressible female-specific flightless phenotype using either two separate transgenes or a single transgene, based on the use of a female-specific indirect flight muscle promoter from the Aedes aegypti Actin-4 gene. These strains eliminate the need for sterilization by irradiation, permit male-only release ("genetic sexing"), and enable the release of eggs instead of adults. Furthermore, these strains are expected to facilitate area-wide control or elimination of dengue if adopted as part of an integrated pest management strategy.

Severe perinatal dengue hemorrhagic fever in a low birth weight infant.

A 31-year-old Hmong (Thai hilltribe) multiparous (G5P2) female with dengue hemorrhagic fever delivered a low birth weight male infant at 34 weeks estimated gestational age. The mother had fever for a total of 6 days, along with hepatomegaly, hepatic dysfunction and thrombocytopenia. Serology showed acute secondary dengue infection. She had no serious complications. The infant (birth weight 1,850 grams) developed a fever 140 hours postpartum of 37.8 degrees C for one day, then developed drowsiness, poor feeding and apnea. Hepatomegaly, thrombocytopenia, hepatic dysfunction and moderate coagulopathy were detected, with consequential shock and anemia due to gastrointestinal and pulmonary hemorrhage. Vigorous treatment with mechanical ventilation, packed red cells (PRC), fresh frozen plasma (FFP) and platelet concentrate transfusions were given and the child recovered successfully and commenced breast-feeding. At six months of age the child's growth and development were normal except for an impaired hearing screening test.

[Dengue as haemorrhagic fever]. / Denga jako goraczka krwotoczna.

Dengue virus is distributed in tropical and subtropical regions and transmitted by mosquitoes of the genus Aedes. In September 2010 two cases of indigenous dengue fever were diagnosed in metropolitan France for the first time and next DENV infection was diagnosed in a German traveler returning from a trip to Croatia. The Aedes albopictus mosquitoes were found in several European countries (for example in greenhouses in Netherlands). The indigenous DENV infections in Europe are rare diseases, probably acquired after bites of infected mosquitoes imported by airplanes from endemic areas. Nonspecific symptoms including: fever (up to 39 degrees C), chills, arthralagia, headache, myalgia and abnormalities in laboratory tests such as: thrombocytopaenia, leukopaenia and liver tests cause problems with differential diagnosis ofhematologic and hepatologic syndromes. The most serious complications are associated with dengue shock syndrome with mortality rate of 50%.

[Laboratory tests in the diagnosis of feral herd infections].

Immunological laboratory tests play an important role in establishing the depth of extent of this or that infectious disease. Scheduled immunological monitoring (serological screening) is made to find out whether there are antibodies (Abs) against the causative agents of individual feral herd infections. The immunological examination is aimed at detecting Abs against the pathogens of infectious diseases of bacterial (Ixodes tick-borne borrelioses, tularemia, leptospiroses, human granulocytic anaplasmosis), viral (hemorrhagic fever with renal syndrome, tick-borne viral encephalitis, West Nile fever), and rickettsial (Q-fever) etiologies. The performed serological screening could yield data on the practically widespread of hemorrhagic fever with renal syndrome in the Ulyanovsk Region and show high rates of Abs to Ixodes tick-borne borrelioses (5.75), coxiellosis (3.7%), and human granulocytic anaplasmosis (4.3%).

Dengue hemorrhagic fever - A systemic literature review of current perspectives on pathogenesis, prevention and control.

BACKGROUND: Dengue is an arboviral disease caused by dengue virus. Symptomatic dengue infection causes a wide range of clinical manifestations, from mild dengue fever (DF) to potentially fatal disease, such as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). We conducted a literature review to analyze the risks of DHF and current perspectives for DHF prevention and control. METHODS: According to the PRISMA guidelines, the references were selected from PubMed, Web of Science and Google Scholar database using search strings containing a combination of terms that included dengue hemorrhagic fever, pathogenesis, prevention and control. Quality of references were evaluated by independent reviewers. RESULTS: DHF was first reported in the Philippines in 1953 and further transmitted to the countries in the region of South-East Asia and Western Pacific. Plasma leakages is the main pathophysiological hallmark that distinguishes DHF from DF. Severe plasma leakage can result in hypovolemic shock. Various factors are thought to impact disease presentation and severity. Virus virulence, preexisting dengue antibodies, immune dysregulation, lipid change and host genetic susceptibility are factors reported to be correlated with the development of DHF. However, the exact reasons and mechanisms that triggers DHF remains controversial. Currently, no specific drugs and licensed vaccines are available to treat dengue disease in any of its clinical presentations. CONCLUSION: This study concludes that antibody-dependent enhancement, cytokine dysregulation and variation of lipid profiles are correlated with DHF occurrence. Prompt diagnosis, appropriate treatment, active and continuous surveillance of cases and vectors are the essential determinants for dengue prevention and control.

Distribution of dengue virus types in Aedes aegypti in dengue endemic districts of Rajasthan, India.

BACKGROUND & OBJECTIVE: Dengue haemorrhagic fever (DHF) is the major cause of sustained morbidity/ mortality among human cases of dengue in dengue endemic areas of Rajasthan. Screening of mosquitoes collected from disease endemic settings and typing the virus could provide significant epidemiological information for prospective risk of DHF. We therefore carried out a study on different dengue virus types as occurring in field collected Aedes aegypti mosquitoes from four dengue endemic districts of Rajasthan, India. METHODS: Adult Ae. aegypti were collected from the human dwellings of urban, peri-urban and rural settings of four dengue endemic districts of Rajasthan, India. The field collected adults were fed on 4 per cent glucose solution and kept in the laboratory for 3-4 days. The adult field collected Ae. aegypti, were subjected to indirect fluorescence antibody test (IFAT) following standard procedure. Commercially acquired monoclonal antibodies against DEN types 1, 2, 3 and 4 were used. The remnants of IFA test subjected mosquitoes were made into viral suspension which was inoculated into the cell culture medium and mouse brain to confirm the presence of virus as shown by IFA test. RESULTS: Of the 498 adult Ae. aegypti tested, 78 (15.6%) were positive by IFA test. Among urban areas, desert area (Jodhpur) showed highest (21.6%) mosquito infectivity followed by 7.1 per cent in forest and river area (Kota) and least (3.2%) in semi-arid area (Jaipur). Among rural settings also, desert area showed maximum (25.0%) natural infection in mosquitoes followed by rural setting-1 of semi-arid area (24.1%). Among urban setting of desert area, all the four dengue types viz., DEN-1, 2, 3 and 4 were detected. In semi-arid area, urban settings showed presence of DEN-3, whereas among rural settings, rural-1 showed all the four DEN types, rural-2 showed DEN-1 and DEN-3, rural-4 showed DEN-3 and DEN-4, and rural-3 showed no mosquito infections. In forest and river area, among urban settings only, three DEN types, 1, 2 and 4 were observed. INTERPRETATION & CONCLUSION: In desert and semi-arid areas of Rajasthan, where people possess tendency of over- and sustained storage of domestic water, present observations on occurrence of all four dengue virus types may have important bearing on the epidemiology of DHF in the area.

Suppression of dengue transmission by application of integrated vector control strategies at sero-positive GIS-based foci.

A serological survey of primary school children from six schools in Chachoengsao Province, Thailand, was performed at the end of the peak of dengue transmission. GIS analysis of sero-positive cases was carried out to determine transmission foci. Vector control implementation was conducted in the foci and also within 100 meters around the foci in the treated areas by community participation in collaboration with the local government. Vector control strategies included source reduction together with the use of screen covers, a combination of Bacillus thuringiensis subsp. israelensis and Mesocyclops thermocyclopoides, and lethal ovitraps. Implementation of vector control strategies in the foci was continued until the end of the rainy season. Vector control effectiveness was monitored using entomological, serological, and clinical parameters. Results showed a significant reduction of dengue vectors as well as a decrease in sero-positive children and clinical cases in treated areas when compared with untreated areas.

Clinical and laboratory features that distinguish dengue from other febrile illnesses in endemic populations.

OBJECTIVE: Clinicians in resource-poor countries need to identify patients with dengue using readily-available data. The objective of this systematic review was to identify clinical and laboratory features that differentiate dengue fever (DF) and/or dengue haemorrhagic fever (DHF) from other febrile illnesses (OFI) in dengue-endemic populations. METHOD: Systematic review of the literature from 1990 to 30 October 2007 including English publications comparing dengue and OFI. RESULTS: Among 49 studies reviewed, 34 did not meet our criteria for inclusion. Of the 15 studies included, 10 were prospective cohort studies and five were case-control studies. Seven studies assessed all ages, four assessed children only, and four assessed adults only. Patients with dengue had significantly lower platelet, white blood cell (WBC) and neutrophil counts, and a higher frequency of petechiae than OFI patients. Higher frequencies of myalgia, rash, haemorrhagic signs, lethargy/prostration, and arthralgia/joint pain and higher haematocrits were reported in adult patients with dengue but not in children. Most multivariable models included platelet count, WBC, rash, and signs of liver damage; however, none had high statistical validity and none considered changes in clinical features over the course of illness. CONCLUSIONS: Several individual clinical and laboratory variables distinguish dengue from OFI; however, some variables may be dependent on age. No published multivariable model has been validated. Study design, populations, diagnostic criteria, and data collection methods differed widely across studies, and the majority of studies did not identify specific aetiologies of OFIs. More prospective studies are needed to construct a valid and generalizable algorithm to guide the differential diagnosis of dengue in endemic countries.

A two-age-classes dengue transmission model.

In this paper, we discuss a two-age-classes dengue transmission model with vaccination. The reason to divide the human population into two age classes is for practical purpose, as vaccination is usually concentrated in one age class. We assume that a constant rate of individuals in the child-class is vaccinated. We analyze a threshold number which is equivalent to the basic reproduction number. If there is an undeliberate vaccination to infectious children, which worsens their condition as the time span of being infectious increases, then paradoxically, vaccination can be counter productive. The paradox, stating that vaccination makes the basic reproduction number even bigger, can occur if the worsening effect is greater than a certain threshold, a function of the human demographic and epidemiological parameters, which is independent of the level of vaccination. However, if the worsening effect is to increase virulence so that one will develop symptoms, then the vaccination is always productive. In both situations, screening should take place before vaccination. In general, the presence of class division has obscured the known rule of thumb for vaccination.

A predictive model for Dengue Hemorrhagic Fever epidemics.

A statistical model for predicting monthly Dengue Hemorrhagic Fever (DHF) cases from the city of Makassar is developed and tested. The model uses past and present DHF cases, climate and meteorological observations as inputs. These inputs are selected using a stepwise regression method to predict future DHF cases. The model is tested independently and its skill assessed using two skill measures. Using the selected variables as inputs, the model is capable of predicting a moderately-severe epidemic at lead times of up to six months. The most important input variable in the prediction is the present number of DHF cases followed by the relative humidity three to four months previously. A prediction 1-6 months in advance is sufficient to initiate various activities to combat DHF epidemic. The model is suitable for warning and easily becomes an operational tool due to its simplicity in data requirement and computational effort.

Descriptive epidemiology of dengue transmission in Uttar Pradesh.

We report epidemiology of dengue infection as revealed through a hospital based surveillance for dengue infection over a 3 year period in Lucknow, U.P., India. In 2003-2005, children with acute febrile encephalopathy (AFE) and in 2005-2006, children with acute undifferentiated febrile illness (AUFI) were enrolled. IgM antibodies to dengue were tested by ELISA in acute serum. A total of 118/563 (20.9%) patients tested positive for dengue antibodies. Dengue transmission occurred round the year in the Lucknow region with peak in postmonsoon season and occurred equally in rural and urban areas. All the surrounding districts were affected, with no distinct high prevalence areas.

[Dengue vaccines].

Dengue is the most important mosquito borne virus infection in the tropics. Based on the effects of global warming, it is expected that dengue epidemic areas will further expand in the next decades unless effective and affordable vaccines are made available soon. At the moment, several vaccine developers have utilized live-attenuated live tetravalent vaccines and two of them have already completed phase two trials. However, the risk of antibody-dependent enhancement infection is not well elucidated and thus further and careful evaluation of the safety on proposed candidate vaccines are essential. At the moment, Bill and Melinda Gates Foundation strongly support the vaccine development through the Pediatric Dengue Vaccine Initiative.

Climate variability and dengue hemorrhagic fever in Southeast Sulawesi Province, Indonesia.

To determine the association of climatic factors and dengue hemorrhagic fever and to develop the prediction approach of future dengue transmission. The study used totally monthly dengue hemorrhagic fever cases at Health Office Kendari, Southeast Sulawesi, Indonesia. Monthly meteorological data, consisting of temperature, rainfall, and humidity, was obtained from the Meteorology, Climatology and Geophysics Agency in Kendari district. All data analysis, including Spearman and Poisson distribution, was carried out in R Studio (version 3.3.2) utilizing the R statistical language version 2.15. The highest rate of dengue hemorrhagic fever cases was found in January, February, and March. Temperature averages at lag 2 (p = 0.53, p < 0.0001), lag 3 (p = 0.59, p < 0.0001), and lag 4 (p = 0.41, p < 0.01)) correlated with the incident rate of DHF. The average temperature at lag 2 was found to have a positive impact on the incidence of DHF by Poisson function. This study provides preliminary evidence of the influence of climatic factors on dengue transmission.

Assessment of benefits and risks associated with dengue vaccination at the individual and population levels: a dynamic modeling approach.

BACKGROUND: A case-cohort study, using a novel assay and data from three dengue vaccine efficacy trials, highlighted differences in vaccination outcomes according to baseline serostatus. Based on these results, we explored, with a model, the benefits and risks associated with vaccination. RESEARCH DESIGN AND METHODS: Parameters of a previously developed transmission model were estimated with subject-level data from a case-cohort study. The model was used to assess vaccination outcomes for a range of transmission settings over 5-30 years, with or without indirect protection. MAIN OUTCOME MEASURES: Symptomatic dengue cases, dengue hospitalizations, and severe dengue cases. RESULTS: The model is consistent with previous results indicating a transitory period at increased risk for dengue-seronegative vaccine recipients (setting-dependent duration) and long-term benefits for dengue-seropositive recipients. At the population level, benefits to seropositive individuals over 10 years outweighed the risk to those seronegative in moderate to high transmission settings (≥50% seropositivity at age 9), especially in high transmission settings (no excess hospitalizations in dengue-seronegative for ≥80% seropositivity at age 9). Results were more favorable when longer time horizons or indirect protection were considered. CONCLUSIONS: Results indicate a public health benefit associated with dengue vaccination especially in high-transmission settings, even with the initial excess risks to dengue-seronegative patients which diminish over time.