Medicine Public Health, Environmental and Occupational Health

Mosquito-borne diseases and control

Description

This cluster of papers focuses on the global impact of arboviral diseases, particularly Zika virus and dengue. It covers epidemiology, neurological manifestations such as microcephaly and Guillain-Barré Syndrome, vaccine development, and strategies for vector control.

Keywords

Arboviral Diseases; Zika Virus; Dengue; Mosquito-borne; Epidemiology; Microcephaly; Vaccine Development; Flaviviruses; Vector Control; Neurological Manifestations

In the early 2015, several cases of patients presenting symptoms of mild fever, rash, conjunctivitis and arthralgia were reported in the northeastern Brazil. Although all patients lived in a dengue … In the early 2015, several cases of patients presenting symptoms of mild fever, rash, conjunctivitis and arthralgia were reported in the northeastern Brazil. Although all patients lived in a dengue endemic area, molecular and serological diagnosis for dengue resulted negative. Chikungunya virus infection was also discarded. Subsequently, Zika virus (ZIKV) was detected by reverse transcription-polymerase chain reaction from the sera of eight patients and the result was confirmed by DNA sequencing. Phylogenetic analysis suggests that the ZIKV identified belongs to the Asian clade. This is the first report of ZIKV infection in Brazil.
We report on the development and application of a rapid assay for detecting and typing dengue viruses. Oligonucleotide consensus primers were designed to anneal to any of the four dengue … We report on the development and application of a rapid assay for detecting and typing dengue viruses. Oligonucleotide consensus primers were designed to anneal to any of the four dengue virus types and amplify a 511-bp product in a reverse transcriptase-polymerase chain reaction (PCR). First, we produced a cDNA copy of a portion of the viral genome in a reverse transcriptase reaction in the presence of primer D2 and then carried out a standard PCR (35 cycles of heat denaturation, annealing, and primer extension) with the addition of primer D1. The resulting double-stranded DNA product of the RT-PCR was typed by two methods: dot blot hybridization of the 511-bp amplified product to dengue virus type-specific probes or a second round of PCR amplification (nested PCR) with type-specific primers, yielding DNA products the unique sizes of which were diagnostic for each dengue virus serotype. The accumulated data demonstrated that dengue viruses can be accurately detected and typed from viremic human serum samples.
The alphaviruses are a genus of 26 enveloped viruses that cause disease in humans and domestic animals. Mosquitoes or other hematophagous arthropods serve as vectors for these viruses. The complete … The alphaviruses are a genus of 26 enveloped viruses that cause disease in humans and domestic animals. Mosquitoes or other hematophagous arthropods serve as vectors for these viruses. The complete sequences of the +/- 11.7-kb plus-strand RNA genomes of eight alphaviruses have been determined, and partial sequences are known for several others; this has made possible evolutionary comparisons between different alphaviruses as well as comparisons of this group of viruses with other animal and plant viruses. Full-length cDNA clones from which infectious RNA can be recovered have been constructed for four alphaviruses; these clones have facilitated many molecular genetic studies as well as the development of these viruses as expression vectors. From these and studies involving biochemical approaches, many details of the replication cycle of the alphaviruses are known. The interactions of the viruses with host cells and host organisms have been exclusively studied, and the molecular basis of virulence and recovery from viral infection have been addressed in a large number of recent papers. The structure of the viruses has been determined to about 2.5 nm, making them the best-characterized enveloped virus to date. Because of the wealth of data that has appeared, these viruses represent a well-characterized system that tell us much about the evolution of RNA viruses, their replication, and their interactions with their hosts. This review summarizes our current knowledge of this group of viruses.
Zika virus (ZIKV) is an emerging arbovirus of the Flaviviridae family, which includes dengue, West Nile, yellow fever, and Japanese encephalitis viruses, that causes a mosquito-borne disease transmitted by the … Zika virus (ZIKV) is an emerging arbovirus of the Flaviviridae family, which includes dengue, West Nile, yellow fever, and Japanese encephalitis viruses, that causes a mosquito-borne disease transmitted by the Aedes genus, with recent outbreaks in the South Pacific. Here we examine the importance of human skin in the entry of ZIKV and its contribution to the induction of antiviral immune responses. We show that human dermal fibroblasts, epidermal keratinocytes, and immature dendritic cells are permissive to the most recent ZIKV isolate, responsible for the epidemic in French Polynesia. Several entry and/or adhesion factors, including DC-SIGN, AXL, Tyro3, and, to a lesser extent, TIM-1, permitted ZIKV entry, with a major role for the TAM receptor AXL. The ZIKV permissiveness of human skin fibroblasts was confirmed by the use of a neutralizing antibody and specific RNA silencing. ZIKV induced the transcription of Toll-like receptor 3 (TLR3), RIG-I, and MDA5, as well as several interferon-stimulated genes, including OAS2, ISG15, and MX1, characterized by strongly enhanced beta interferon gene expression. ZIKV was found to be sensitive to the antiviral effects of both type I and type II interferons. Finally, infection of skin fibroblasts resulted in the formation of autophagosomes, whose presence was associated with enhanced viral replication, as shown by the use of Torin 1, a chemical inducer of autophagy, and the specific autophagy inhibitor 3-methyladenine. The results presented herein permit us to gain further insight into the biology of ZIKV and to devise strategies aiming to interfere with the pathology caused by this emerging flavivirus.Zika virus (ZIKV) is an arbovirus belonging to the Flaviviridae family. Vector-mediated transmission of ZIKV is initiated when a blood-feeding female Aedes mosquito injects the virus into the skin of its mammalian host, followed by infection of permissive cells via specific receptors. Indeed, skin immune cells, including dermal fibroblasts, epidermal keratinocytes, and immature dendritic cells, were all found to be permissive to ZIKV infection. The results also show a major role for the phosphatidylserine receptor AXL as a ZIKV entry receptor and for cellular autophagy in enhancing ZIKV replication in permissive cells. ZIKV replication leads to activation of an antiviral innate immune response and the production of type I interferons in infected cells. Taken together, these results provide the first general insights into the interaction between ZIKV and its mammalian host.
Journal Article Zika Virus (I). Isolations and serological specificity Get access G. W. A. Dick, G. W. A. Dick The National Institute for Medical Research, London, UK Search for other … Journal Article Zika Virus (I). Isolations and serological specificity Get access G. W. A. Dick, G. W. A. Dick The National Institute for Medical Research, London, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar S. F. Kitchen, S. F. Kitchen Formerly staff member of the Division of Medicine and Public Health, The Rockefeller Foundation, New York, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar A. J. Haddow A. J. Haddow aFormerly staff member of International Health Division, The Rockefeller Foundation, New York, USAbFrom the Virus Research Institute, Entebbe, Uganda Search for other works by this author on: Oxford Academic PubMed Google Scholar Transactions of The Royal Society of Tropical Medicine and Hygiene, Volume 46, Issue 5, September 1952, Pages 509–520, https://doi.org/10.1016/0035-9203(52)90042-4 Published: 01 September 1952
In 2007, physicians on Yap Island reported an outbreak of illness characterized by rash, conjunctivitis, and arthralgia. Although serum from some patients had IgM antibody against dengue virus, the illness … In 2007, physicians on Yap Island reported an outbreak of illness characterized by rash, conjunctivitis, and arthralgia. Although serum from some patients had IgM antibody against dengue virus, the illness seemed clinically distinct from previously detected dengue. Subsequent testing with the use of consensus primers detected Zika virus RNA in the serum of the patients but no dengue virus or other arboviral RNA. No previous outbreaks and only 14 cases of Zika virus disease have been previously documented.We obtained serum samples from patients and interviewed patients for information on clinical signs and symptoms. Zika virus disease was confirmed by a finding of Zika virus RNA or a specific neutralizing antibody response to Zika virus in the serum. Patients with IgM antibody against Zika virus who had a potentially cross-reactive neutralizing-antibody response were classified as having probable Zika virus disease. We conducted a household survey to estimate the proportion of Yap residents with IgM antibody against Zika virus and to identify possible mosquito vectors of Zika virus.We identified 49 confirmed and 59 probable cases of Zika virus disease. The patients resided in 9 of the 10 municipalities on Yap. Rash, fever, arthralgia, and conjunctivitis were common symptoms. No hospitalizations, hemorrhagic manifestations, or deaths due to Zika virus were reported. We estimated that 73% (95% confidence interval, 68 to 77) of Yap residents 3 years of age or older had been recently infected with Zika virus. Aedes hensilli was the predominant mosquito species identified.This outbreak of Zika virus illness in Micronesia represents transmission of Zika virus outside Africa and Asia. Although most patients had mild illness, clinicians and public health officials should be aware of the risk of further expansion of Zika virus transmission.
Dengue viruses occur as four antigenically related but distinct serotypes transmitted to humans by Aedes aegypti mosquitoes. These viruses generally cause a benign syndrome, dengue fever, in the American and … Dengue viruses occur as four antigenically related but distinct serotypes transmitted to humans by Aedes aegypti mosquitoes. These viruses generally cause a benign syndrome, dengue fever, in the American and African tropics, and a severe syndrome, dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), in Southeast Asian children. This severe syndrome, which recently has also been identified in children infected with the virus in Puerto Rico, is characterized by increased vascular permeability and abnormal hemostasis. It occurs in infants less than 1 year of age born to dengue-immune mothers and in children 1 year and older who are immune to one serotype of dengue virus and are experiencing infection with a second serotype. Dengue viruses replicate in cells of mononuclear phagocyte lineage, and subneutralizing concentrations of dengue antibody enhance dengue virus infection in these cells. This antibody-dependent enhancement of infection regulates dengue disease in human beings, although disease severity may also be controlled genetically, possibly by permitting and restricting the growth of virus in monocytes. Monoclonal antibodies show heterogeneous distribution of antigenic epitopes on dengue viruses. These epitopes serve to regulate disease: when antibodies to shared antigens partially neutralize heterotypic virus, infection and disease are dampened; enhancing antibodies alone result in heightened disease response. Further knowledge of the structure of dengue genomes should permit rapid advances in understanding the pathogenetic mechanisms of dengue.
Background A chikungunya virus outbreak of unprecedented magnitude is currently ongoing in Indian Ocean territories. In Réunion Island, this alphavirus has already infected about one-third of the human population. The … Background A chikungunya virus outbreak of unprecedented magnitude is currently ongoing in Indian Ocean territories. In Réunion Island, this alphavirus has already infected about one-third of the human population. The main clinical symptom of the disease is a painful and invalidating poly-arthralgia. Besides the arthralgic form, 123 patients with a confirmed chikungunya infection have developed severe clinical signs, i.e., neurological signs or fulminant hepatitis. Methods and Findings We report the nearly complete genome sequence of six selected viral isolates (isolated from five sera and one cerebrospinal fluid), along with partial sequences of glycoprotein E1 from a total of 127 patients from Réunion, Seychelles, Mauritius, Madagascar, and Mayotte islands. Our results indicate that the outbreak was initiated by a strain related to East-African isolates, from which viral variants have evolved following a traceable microevolution history. Unique molecular features of the outbreak isolates were identified. Notably, in the region coding for the non-structural proteins, ten amino acid changes were found, four of which were located in alphavirus-conserved positions of nsP2 (which contains helicase, protease, and RNA triphosphatase activities) and of the polymerase nsP4. The sole isolate obtained from the cerebrospinal fluid showed unique changes in nsP1 (T301I), nsP2 (Y642N), and nsP3 (E460 deletion), not obtained from isolates from sera. In the structural proteins region, two noteworthy changes (A226V and D284E) were observed in the membrane fusion glycoprotein E1. Homology 3D modelling allowed mapping of these two changes to regions that are important for membrane fusion and virion assembly. Change E1-A226V was absent in the initial strains but was observed in >90% of subsequent viral sequences from Réunion, denoting evolutionary success possibly due to adaptation to the mosquito vector. Conclusions The unique molecular features of the analyzed Indian Ocean isolates of chikungunya virus demonstrate their high evolutionary potential and suggest possible clues for understanding the atypical magnitude and virulence of this outbreak.
The mosquito Aedes (Stegomyia) albopictus (Skuse) (Diptera: Culicidae), originally indigenous to South-east Asia, islands of the Western Pacific and Indian Ocean, has spread during recent decades to Africa, the mid-east, … The mosquito Aedes (Stegomyia) albopictus (Skuse) (Diptera: Culicidae), originally indigenous to South-east Asia, islands of the Western Pacific and Indian Ocean, has spread during recent decades to Africa, the mid-east, Europe and the Americas (north and south) after extending its range eastwards across Pacific islands during the early 20th century. The majority of introductions are apparently due to transportation of dormant eggs in tyres. Among public health authorities in the newly infested countries and those threatened with the introduction, there has been much concern that Ae. albopictus would lead to serious outbreaks of arbovirus diseases (Ae. albopictus is a competent vector for at least 22 arboviruses), notably dengue (all four serotypes) more commonly transmitted by Aedes (Stegomyia) aegypti (L.). Results of many laboratory studies have shown that many arboviruses are readily transmitted by Ae. albopictus to laboratory animals and birds, and have frequently been isolated from wild-caught mosquitoes of this species, particularly in the Americas. As Ae. albopictus continues to spread, displacing Ae. aegypti in some areas, and is anthropophilic throughout its range, it is important to review the literature and attempt to predict whether the medical risks are as great as have been expressed in scientific journals and the popular press. Examination of the extensive literature indicates that Ae. albopictus probably serves as a maintenance vector of dengue in rural areas of dengue-endemic countries of South-east Asia and Pacific islands. Also Ae. albopictus transmits dog heartworm Dirofilaria immitis (Leidy) (Spirurida: Onchocercidae) in South-east Asia, south-eastern U.S.A. and both D. immitis and Dirofilaria repens (Raillet & Henry) in Italy. Despite the frequent isolation of dengue viruses from wild-caught mosquitoes, there is no evidence that Ae. albopictus is an important urban vector of dengue, except in a limited number of countries where Ae. aegypti is absent, i.e. parts of China, the Seychelles, historically in Japan and most recently in Hawaii. Further research is needed on the dynamics of the interaction between Ae. albopictus and other Stegomyia species. Surveillance must also be maintained on the vectorial role of Ae. albopictus in countries endemic for dengue and other arboviruses (e.g. Chikungunya, EEE, Ross River, WNV, LaCrosse and other California group viruses), for which it would be competent and ecologically suited to serve as a bridge vector.
Abstract In December 2013, during a Zika virus (ZIKV) outbreak in French Polynesia, a patient in Tahiti sought treatment for hematospermia, and ZIKV was isolated from his semen. ZIKV transmission … Abstract In December 2013, during a Zika virus (ZIKV) outbreak in French Polynesia, a patient in Tahiti sought treatment for hematospermia, and ZIKV was isolated from his semen. ZIKV transmission by sexual intercourse has been previously suspected. This observation supports the possibility that ZIKV could be transmitted sexually.
Chikungunya virus (CHIKV) is an emerging arbovirus associated with several recent large-scale epidemics. The 2005-2006 epidemic on Reunion island that resulted in approximately 266,000 human cases was associated with a … Chikungunya virus (CHIKV) is an emerging arbovirus associated with several recent large-scale epidemics. The 2005-2006 epidemic on Reunion island that resulted in approximately 266,000 human cases was associated with a strain of CHIKV with a mutation in the envelope protein gene (E1-A226V). To test the hypothesis that this mutation in the epidemic CHIKV (strain LR2006 OPY1) might influence fitness for different vector species, viral infectivity, dissemination, and transmission of CHIKV were compared in Aedes albopictus, the species implicated in the epidemic, and the recognized vector Ae. aegypti. Using viral infectious clones of the Reunion strain and a West African strain of CHIKV, into which either the E1-226 A or V mutation was engineered, we demonstrated that the E1-A226V mutation was directly responsible for a significant increase in CHIKV infectivity for Ae. albopictus, and led to more efficient viral dissemination into mosquito secondary organs and transmission to suckling mice. This mutation caused a marginal decrease in CHIKV Ae. aegypti midgut infectivity, had no effect on viral dissemination, and was associated with a slight increase in transmission by Ae. aegypti to suckling mice in competition experiments. The effect of the E1-A226V mutation on cholesterol dependence of CHIKV was also analyzed, revealing an association between cholesterol dependence and increased fitness of CHIKV in Ae. albopictus. Our observation that a single amino acid substitution can influence vector specificity provides a plausible explanation of how this mutant virus caused an epidemic in a region lacking the typical vector. This has important implications with respect to how viruses may establish a transmission cycle when introduced into a new area. Due to the widespread distribution of Ae. albopictus, this mutation increases the potential for CHIKV to permanently extend its range into Europe and the Americas.
Clinical and serologic evidence indicate that 2 American scientists contracted Zika virus infections while working in Senegal in 2008. One of the scientists transmitted this arbovirus to his wife after … Clinical and serologic evidence indicate that 2 American scientists contracted Zika virus infections while working in Senegal in 2008. One of the scientists transmitted this arbovirus to his wife after his return home. Direct contact is implicated as the transmission route, most likely as a sexually transmitted infection.
Dengue and chikungunya are increasing global public health concerns due to their rapid geographical spread and increasing disease burden. Knowledge of the contemporary distribution of their shared vectors, Aedes aegypti … Dengue and chikungunya are increasing global public health concerns due to their rapid geographical spread and increasing disease burden. Knowledge of the contemporary distribution of their shared vectors, Aedes aegypti and Aedes albopictus remains incomplete and is complicated by an ongoing range expansion fuelled by increased global trade and travel. Mapping the global distribution of these vectors and the geographical determinants of their ranges is essential for public health planning. Here we compile the largest contemporary database for both species and pair it with relevant environmental variables predicting their global distribution. We show Aedes distributions to be the widest ever recorded; now extensive in all continents, including North America and Europe. These maps will help define the spatial limits of current autochthonous transmission of dengue and chikungunya viruses. It is only with this kind of rigorous entomological baseline that we can hope to project future health impacts of these viruses.
Abstract To evaluate transmission dynamics, we exposed 25 bird species to West Nile virus (WNV) by infectious mosquito bite. We monitored viremia titers, clinical outcome, WNV shedding (cloacal and oral), … Abstract To evaluate transmission dynamics, we exposed 25 bird species to West Nile virus (WNV) by infectious mosquito bite. We monitored viremia titers, clinical outcome, WNV shedding (cloacal and oral), seroconversion, virus persistence in organs, and susceptibility to oral and contact transmission. Passeriform and charadriiform birds were more reservoir competent (a derivation of viremia data) than other species tested. The five most competent species were passerines: Blue Jay (Cyanocitta cristata), Common Grackle (Quiscalus quiscula), House Finch (Carpodacus mexicanus), American Crow (Corvus brachyrhynchos), and House Sparrow (Passer domesticus). Death occurred in eight species. Cloacal shedding of WNV was observed in 17 of 24 species, and oral shedding in 12 of 14 species. We observed contact transmission among four species and oral in five species. Persistent WNV infections were found in tissues of 16 surviving birds. Our observations shed light on transmission ecology of WNV and will benefit surveillance and control programs.
Zika virus (ZIKV) is a mosquito-borne flavivirus first isolated in Uganda from a sentinel monkey in 1947. Mosquito and sentinel animal surveillance studies have demonstrated that ZIKV is endemic to … Zika virus (ZIKV) is a mosquito-borne flavivirus first isolated in Uganda from a sentinel monkey in 1947. Mosquito and sentinel animal surveillance studies have demonstrated that ZIKV is endemic to Africa and Southeast Asia, yet reported human cases are rare, with <10 cases reported in the literature. In June 2007, an epidemic of fever and rash associated with ZIKV was detected in Yap State, Federated States of Micronesia. We report the genetic and serologic properties of the ZIKV associated with this epidemic.
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 … 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.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.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.
SUMMARY Dengue fever, a very old disease, has reemerged in the past 20 years with an expanded geographic distribution of both the viruses and the mosquito vectors, increased epidemic activity, … SUMMARY Dengue fever, a very old disease, has reemerged in the past 20 years with an expanded geographic distribution of both the viruses and the mosquito vectors, increased epidemic activity, the development of hyperendemicity (the cocirculation of multiple serotypes), and the emergence of dengue hemorrhagic fever in new geographic regions. In 1998 this mosquito-borne disease is the most important tropical infectious disease after malaria, with an estimated 100 million cases of dengue fever, 500,000 cases of dengue hemorrhagic fever, and 25,000 deaths annually. The reasons for this resurgence and emergence of dengue hemorrhagic fever in the waning years of the 20th century are complex and not fully understood, but demographic, societal, and public health infrastructure changes in the past 30 years have contributed greatly. This paper reviews the changing epidemiology of dengue and dengue hemorrhagic fever by geographic region, the natural history and transmission cycles, clinical diagnosis of both dengue fever and dengue hemorrhagic fever, serologic and virologic laboratory diagnoses, pathogenesis, surveillance, prevention, and control. A major challenge for public health officials in all tropical areas of the world is to devleop and implement sustainable prevention and control programs that will reverse the trend of emergent dengue hemorrhagic fever.
In late summer 1999, an outbreak of human encephalitis occurred in the northeastern United States that was concurrent with extensive mortality in crows (Corvus species) as well as the deaths … In late summer 1999, an outbreak of human encephalitis occurred in the northeastern United States that was concurrent with extensive mortality in crows (Corvus species) as well as the deaths of several exotic birds at a zoological park in the same area. Complete genome sequencing of a flavivirus isolated from the brain of a dead Chilean flamingo (Phoenicopterus chilensis), together with partial sequence analysis of envelope glycoprotein (E-glycoprotein) genes amplified from several other species including mosquitoes and two fatal human cases, revealed that West Nile (WN) virus circulated in natural transmission cycles and was responsible for the human disease. Antigenic mapping with E-glycoprotein-specific monoclonal antibodies and E-glycoprotein phylogenetic analysis confirmed these viruses as WN. This North American WN virus was most closely related to a WN virus isolated from a dead goose in Israel in 1998.
Viremia titers in serial plasma samples from 168 children with acute dengue virus infection who were enrolled in a prospective study at 2 hospitals in Thailand were examined to determine … Viremia titers in serial plasma samples from 168 children with acute dengue virus infection who were enrolled in a prospective study at 2 hospitals in Thailand were examined to determine the role of virus load in the pathogenesis of dengue hemorrhagic fever (DHF). The infecting virus serotype was identified for 165 patients (DEN-1, 46 patients; DEN-2, 47 patients; DEN-3, 47 patients, DEN-4, 25 patients). Patients with DEN-2 infections experienced more severe disease than those infected with other serotypes. Eighty-one percent of patients experienced a secondary dengue virus infection that was associated with more severe disease. Viremia titers were determined for 41 DEN-1 and 46 DEN-2 patients. Higher peak titers were associated with increased disease severity for the 31 patients with a peak titer identified (mean titer of 107.6 for those with dengue fever vs. 108.5 for patients with DHF, P = .01). Increased dengue disease severity correlated with high viremia titer, secondary dengue virus infection, and DEN-2 virus type.
An unexpected upsurge in diagnosis of fetal and pediatric microcephaly has been reported in the Brazilian press recently. Cases have been diagnosed in nine Brazilian states so far. By 28 … An unexpected upsurge in diagnosis of fetal and pediatric microcephaly has been reported in the Brazilian press recently. Cases have been diagnosed in nine Brazilian states so far. By 28 November 2015, 646 cases had been reported in Pernambuco state alone. Although reports have circulated regarding the declaration of a state of national health emergency, there is no information on the imaging and clinical findings of affected cases. Authorities are considering different theories behind the 'microcephaly outbreak', including a possible association with the emergence of Zika virus disease within the region, the first case of which was detected in May 20151. Zika virus is a mosquito-borne disease closely related to yellow fever, dengue, West Nile and Japanese encephalitis viruses2. It was first identified in 1947 in the Zika Valley in Uganda and causes a mild disease with fever, erythema and arthralgia. Interestingly, vertical transmission to the fetus has not been reported previously, although two cases of perinatal transmission, occurring around the time of delivery and causing mild disease in the newborns, have been described3. We have examined recently two pregnant women from the state of Paraiba who were diagnosed with fetal microcephaly and were considered part of the 'microcephaly cluster' as both women suffered from symptoms related to Zika virus infection. Although both patients had negative blood results for Zika virus, amniocentesis and subsequent quantitative real-time polymerase chain reaction4, performed after ultrasound diagnosis of fetal microcephaly and analyzed at the Oswaldo Cruz Foundation, Rio de Janeiro, Brazil, was positive for Zika virus in both patients, most likely representing the first diagnoses of intrauterine transmission of the virus. The sequencing analysis identified in both cases a genotype of Asian origin. In Case 1, fetal ultrasound examination was performed at 30.1 weeks' gestation. Head circumference (HC) was 246 mm (2.6 SD below expected value) and weight was estimated as 1179 g (21st percentile). Abdominal circumference (AC), femur length (FL) and transcranial Doppler were normal for gestational age as was the width of the lateral ventricles. Anomalies were limited to the brain and included brain atrophy with coarse calcifications involving the white matter of the frontal lobes, including the caudate, lentostriatal vessels and cerebellum. Corpus callosal and vermian dysgenesis and enlarged cisterna magna were observed (Figure 1). In Case 2, fetal ultrasound examination was performed at 29.2 weeks' gestation. HC was 229 mm (3.1 SD below expected value) and estimated fetal weight was 1018 g (19th percentile). AC was below the 3rd percentile but FL was normal. The cerebral hemispheres were markedly asymmetric with severe unilateral ventriculomegaly, displacement of the midline, thinning of the parenchyma on the dilated side, failure to visualize the corpus callosum and almost complete disappearance or failure to develop the thalami. The pons and brainstem were thin and continuous with a non-homogeneous small mass at the position of the basal ganglia. Brain calcifications were more subtle than in Case 1 and located around the lateral ventricles and fourth ventricle. Both eyes had cataracts and intraocular calcifications, and one eye was smaller than the other (Figure 2). In the meantime, in Paraiba state, six children diagnosed with Zika virus were born to mothers who were apparently symptomatic during pregnancy, all of them with neonatal HC below the 10th percentile. Fetal neurosonograms showed two cases with cerebellar involvement and three with brain calcifications. One had severe arthrogryposis. Intrauterine infections affecting the brain are relatively rare; cytomegalovirus (CMV), toxoplasmosis, herpes virus, syphilis and rubella are well known vectors of fetal disease. Among the Flaviviruses there have been only isolated reports linking West Nile encephalitis virus to fetal brain insults5. The presence of calcifications was suggestive of an intrauterine infection but severe damage of the cerebellum, brainstem and thalami is rarely associated with intrauterine infection. Both cases showed some similarities to CMV cases but with a more severe and destructive pattern and they lacked the nodules characteristic of toxoplasmosis. Interestingly, the reported case of fetal West Nile virus infection has similar characteristics5. It is difficult to explain why there have been no fetal cases of Zika virus infection reported until now but this may be due to the underreporting of cases, possible early acquisition of immunity in endemic areas or due to the rarity of the disease until now. As genomic changes in the virus have been reported6, the possibility of a new, more virulent, strain needs to be considered. Until more cases are diagnosed and histopathological proof is obtained, the possibility of other etiologies cannot be ruled out. As with other intrauterine infections, it is possible that the reported cases of microcephaly represent only the more severely affected children and that newborns with less severe disease, affecting not only the brain but also other organs, have not yet been diagnosed. If patients diagnosed in other states are found to be seropositive for Zika virus, this represents a severe health threat that needs to be controlled expeditiously. The Brazilian authorities reacted rapidly by declaring a state of national health emergency. As there is no known medical treatment for this disease, a serious attempt will be needed to eradicate the mosquito and prevent the spread of the disease to other Brazilian states and across the border7.
Preparation of Antigens 561; Preparation of Sera 567; Preparation of Erythrocytes 568; Chemical Reagents 569; Technique of HA and HI Tests 570; HA Titrations 571; HI Tests 572; References 573During … Preparation of Antigens 561; Preparation of Sera 567; Preparation of Erythrocytes 568; Chemical Reagents 569; Technique of HA and HI Tests 570; HA Titrations 571; HI Tests 572; References 573During the past few years, the methods for conducting hemagglutination (HA) and hemagglutination-inhibition (HI) tests with arthropod-borne (arbor) viruses have undergone a number of modifications, directed toward simplification and improvement as well as extension of the tests to include a larger number of arbor viruses. Accordingly, it seems desirable at this time to bring together, in one publication rather than in a series of papers, a description of the procedures currently in use in The Rockefeller Foundation Virus Laboratories. Some of the procedures were initially developed elsewhere; of those developed in this laboratory, most aspects have not been previously reported.It was stated by Hallauer (1946) that he had obtained a hemagglutinating antigen from viscerotropic but not from neurotropic strains of yellow fever.
A widespread epidemic of Zika virus (ZIKV) infection was reported in 2015 in South and Central America and the Caribbean. A major concern associated with this infection is the apparent … A widespread epidemic of Zika virus (ZIKV) infection was reported in 2015 in South and Central America and the Caribbean. A major concern associated with this infection is the apparent increased incidence of microcephaly in fetuses born to mothers infected with ZIKV. In this report, we describe the case of an expectant mother who had a febrile illness with rash at the end of the first trimester of pregnancy while she was living in Brazil. Ultrasonography performed at 29 weeks of gestation revealed microcephaly with calcifications in the fetal brain and placenta. After the mother requested termination of the pregnancy, a fetal autopsy was performed. Micrencephaly (an abnormally small brain) was observed, with almost complete agyria, hydrocephalus, and multifocal dystrophic calcifications in the cortex and subcortical white matter, with associated cortical displacement and mild focal inflammation. ZIKV was found in the fetal brain tissue on reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay, with consistent findings on electron microscopy. The complete genome of ZIKV was recovered from the fetal brain.
Zika virus (ZIKV) has been linked to central nervous system malformations in fetuses. To characterize the spectrum of ZIKV disease in pregnant women and infants, we followed patients in Rio … Zika virus (ZIKV) has been linked to central nervous system malformations in fetuses. To characterize the spectrum of ZIKV disease in pregnant women and infants, we followed patients in Rio de Janeiro to describe clinical manifestations in mothers and repercussions of acute ZIKV infection in infants.
In late August 1999, an unusual cluster of cases of meningoencephalitis associated with muscle weakness was reported to the New York City Department of Health. The initial epidemiologic and environmental … In late August 1999, an unusual cluster of cases of meningoencephalitis associated with muscle weakness was reported to the New York City Department of Health. The initial epidemiologic and environmental investigations suggested an arboviral cause.
Summary The Zika virus has spread rapidly in the Americas since its first identification in Brazil in early 2015. Prenatal Zika virus infection has been linked to adverse pregnancy and … Summary The Zika virus has spread rapidly in the Americas since its first identification in Brazil in early 2015. Prenatal Zika virus infection has been linked to adverse pregnancy and birth outcomes, most notably microcephaly and other serious brain anomalies. To determine whether Zika virus infection during pregnancy causes these adverse outcomes, we evaluated available data using criteria that have been proposed for the assessment of potential teratogens. On the basis of this review, we conclude that a causal relationship exists between prenatal Zika virus infection and microcephaly and other serious brain anomalies. Evidence that was used to support this causal relationship included Zika virus infection at times during prenatal development that were consistent with the defects observed; a specific, rare phenotype involving microcephaly and associated brain anomalies in fetuses or infants with presumed or confirmed congenital Zika virus infection; and data that strongly support biologic plausibility, including the identification of Zika virus in the brain tissue of affected fetuses and infants. Given the recognition of this causal relationship, we need to intensify our efforts toward the prevention of adverse outcomes caused by congenital Zika virus infection. However, many questions that are critical to our prevention efforts remain, including the spectrum of defects caused by prenatal Zika virus infection, the degree of relative and absolute risks of adverse outcomes among fetuses whose mothers were infected at different times during pregnancy, and factors that might affect a woman’s risk of adverse pregnancy or birth outcomes. Addressing these questions will improve our ability to reduce the burden of the effects of Zika virus infection during pregnancy.
Abstract Zika virus (ZIKV) has recently caused a pandemic disease, and many cases of ZIKV infection in pregnant women resulted in abortion, stillbirth, deaths and congenital defects including microcephaly, which … Abstract Zika virus (ZIKV) has recently caused a pandemic disease, and many cases of ZIKV infection in pregnant women resulted in abortion, stillbirth, deaths and congenital defects including microcephaly, which now has been proposed as ZIKV congenital syndrome. This study aimed to investigate the in situ immune response profile and mechanisms of neuronal cell damage in fatal Zika microcephaly cases. Brain tissue samples were collected from 15 cases, including 10 microcephalic ZIKV-positive neonates with fatal outcome and five neonatal control flavivirus-negative neonates that died due to other causes, but with preserved central nervous system (CNS) architecture. In microcephaly cases, the histopathological features of the tissue samples were characterized in three CNS areas (meninges, perivascular space, and parenchyma). The changes found were mainly calcification, necrosis, neuronophagy, gliosis, microglial nodules, and inflammatory infiltration of mononuclear cells. The in situ immune response against ZIKV in the CNS of newborns is complex. Despite the predominant expression of Th2 cytokines, other cytokines such as Th1, Th17, Treg, Th9, and Th22 are involved to a lesser extent, but are still likely to participate in the immunopathogenic mechanisms of neural disease in fatal cases of microcephaly caused by ZIKV.
Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) in the genus Flavivirus and the family Flaviviridae. ZIKV was first isolated from a nonhuman primate in 1947 and from mosquitoes in … Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) in the genus Flavivirus and the family Flaviviridae. ZIKV was first isolated from a nonhuman primate in 1947 and from mosquitoes in 1948 in Africa, and ZIKV infections in humans were sporadic for half a century before emerging in the Pacific and the Americas. ZIKV is usually transmitted by the bite of infected mosquitoes. The clinical presentation of Zika fever is nonspecific and can be misdiagnosed as other infectious diseases, especially those due to arboviruses such as dengue and chikungunya. ZIKV infection was associated with only mild illness prior to the large French Polynesian outbreak in 2013 and 2014, when severe neurological complications were reported, and the emergence in Brazil of a dramatic increase in severe congenital malformations (microcephaly) suspected to be associated with ZIKV. Laboratory diagnosis of Zika fever relies on virus isolation or detection of ZIKV-specific RNA. Serological diagnosis is complicated by cross-reactivity among members of the Flavivirus genus. The adaptation of ZIKV to an urban cycle involving humans and domestic mosquito vectors in tropical areas where dengue is endemic suggests that the incidence of ZIKV infections may be underestimated. There is a high potential for ZIKV emergence in urban centers in the tropics that are infested with competent mosquito vectors such as Aedes aegypti and Aedes albopictus.
The literature on severe West Nile virus (WNV) neuroinvasive disease (WNND) in patients treated with anti-CD20 therapies is limited. We systematically characterize cases of WNND in the tertiary academic UCHealth … The literature on severe West Nile virus (WNV) neuroinvasive disease (WNND) in patients treated with anti-CD20 therapies is limited. We systematically characterize cases of WNND in the tertiary academic UCHealth system. A retrospective cohort (January 2016 to January 2024) of patients with a validated diagnosis of WNND and anti-CD20 medication use was identified with electronic medical record query followed by individual chart review. We identified 25 patients; multiple sclerosis was the most common indication for anti-CD20 therapy in 13 patients (52%). Twenty-one patients (84%) presented with meningoencephalitis. CSF WNV IgM was positive in 5 of 21 patients (24%) who were tested while 13 of 14 tested patients (93%) had positive reverse-transcription PCR (RT-PCR) findings in the CSF. MRI demonstrated anomalies associated with WNND in 12 of 23 patients (52%) with available imaging. Intensive care unit admission was required in 8 patients (32%), and 12 patients (48%) were treated with intravenous immunoglobulin. Worsening of ≥1 point from pre-WNV baseline modified Rankin Scale (mRS) score to the 90-day postdischarge mRS score was seen in 18 patients (75%). Two patients (8%) died by 90 days. WNND leads to disability accrual in patients on B cell-depleting anti-CD20 therapies. Utilization of RT-PCR is important in optimizing diagnosis in this patient population because of limited sensitivity of the WNV-IgM testing commonly used in the general population.
Background Dengue is a significant global health threat, transmitted by mosquitoes and influenced by multiple factors. A comprehensive analysis of the impact of these factors on dengue at a global … Background Dengue is a significant global health threat, transmitted by mosquitoes and influenced by multiple factors. A comprehensive analysis of the impact of these factors on dengue at a global scale is helpful for better understanding and effective control of dengue epidemics. Methods This study employed machine learning techniques to develop a global predictive model for forecasting annual dengue cases. A wide range of multi-source features, including historical cases, population, climate, air travel, forest, anemia, vector, serotype and socioeconomic features, were comprehensively considered. The impact of these features was revealed using the SHAP (Shapley Additive Explanations) framework. Results The global multi-variable model outperformed the baseline model, indicating the importance of considering multiple factors. Among the multi-source features, historical cases contribute the most, at about 73.63%. Risk factors associated to dengue were identified, including the occurrence of Aedes mosquitoes, changes in the predominant serotype, and the prevalence of anemia. Feature contribution pattern was different between hyperendemic and non-hyperendemic regions. In hyperendemic regions, historical cases and population were found to contribute more significantly, emphasizing the role of population immunity in dengue dynamics. Conclusions Dengue is influenced by a wide range of multi-source factors, and prevention and control measures should be specifically designed while taking into account regional differences for effective control of dengue.
Global gridded temperature data sets (GGTDs) differ in data sources, quality control, generation methods, and spatial-temporal resolution, introducing observational uncertainty. This uncertainty is critical not only for studies on current … Global gridded temperature data sets (GGTDs) differ in data sources, quality control, generation methods, and spatial-temporal resolution, introducing observational uncertainty. This uncertainty is critical not only for studies on current climate conditions but also for future climate change projections, where observational data sets are used for bias correction and downscaling of global climate model (GCM) outputs. It is hence essential to ensure that reference data sets accurately represent the true climate state and span a sufficiently long period to filter out internal variability. The selection of appropriate GGTDs is hence a crucial yet often overlooked factor in research that examines the impact of climate variability and change on vector-borne diseases such as yellow fever (YF), a climate-sensitive arboviral disease endemic to tropical regions of Africa and South America. In this study, we evaluated four GGTDs, namely the Berkeley Earth Surface Temperatures (BEST), the Climatic Research Unit Time-Series (CRUTS), the fifth-generation atmospheric reanalysis of the global climate from the European Centre for Medium-Range Weather Forecasts (ECMWF), ERA5, and its land-focused derivative, ERA5Land, for health-related impact research, specifically examining YF transmission in South America. Each data set was evaluated via grid-based analysis and validated against national weather station data, focusing on Brazil and Colombia, where YF outbreak risk remains. While reanalysis generally outperformed lower-resolution products, ERA5 demonstrated a slight advantage over ERA5Land despite the latter’s higher spatial resolution. Most importantly, our findings show that substantial differences among GGTDs affected the spatial representation of climate change indices, bioclimatic variables, and spatially aggregated temperature estimates at the administrative (AD) unit level, with substantial variations in the latter translating into markedly different estimates of key disease transmission parameters. In Colombia, admin-level temperature inputs differing by more than 6 ∘ C led to differences of about 0.2 in simulated reproduction numbers generated within a dynamic compartmental YF modeling framework.
A study published by Teerasarntipan et al in the World Journal of Gastroenterology provides valuable insights into prognostic scoring for acute liver failure and in-hospital mortality in patients with dengue-induced … A study published by Teerasarntipan et al in the World Journal of Gastroenterology provides valuable insights into prognostic scoring for acute liver failure and in-hospital mortality in patients with dengue-induced severe hepatitis. Their findings validate the model for end-stage liver disease score as the most reliable predictor while demonstrating the utility of the simpler Easy Albumin-Bilirubin score. Despite these findings, current prognostic models face limitations in real-world clinical applications. This letter discusses the strengths and weaknesses of current prognostic models, proposes future directions for improving prognostic accuracy and clinical implementations. This letter also broadens the horizons of prognostic models for liver dysfunction caused by other viral infections.
Sarah Crunkhorn | Nature Reviews Drug Discovery
Introduction Several multiplex and singleplex PCR systems exist for the detection of Dengue(DENV), Zika(ZIKV), and Chikungunya(CHIKV) viruses; however, their performance characteristics in East Africa remain unassessed. In this study, we … Introduction Several multiplex and singleplex PCR systems exist for the detection of Dengue(DENV), Zika(ZIKV), and Chikungunya(CHIKV) viruses; however, their performance characteristics in East Africa remain unassessed. In this study, we investigated the TaqMan® Arbovirus Triplex Kit, which allows for the simultaneous identification of CHIKV, DENV, and ZIKV viruses in serum samples and singleplex assays, including the RealStar® Chikungunya RT-PCR Kit 2.0, RealStar® Dengue RT-PCR Kit 3.0, and RealStar® Zika Virus RT-PCR Kit 1.0. Methods We used Clinical Laboratory Improvement validation methods and residual specimens sourced from DENV, CHIKV, and ZIKV outbreaks, from Kenya, Brazil, and the Democratic Republic of Congo(DRC) in March 2024. Quality control was ensured through Quality Control for Medical diagnostics (QCMD) commercial positive panels. Gold standard results were established through consensus from multiple kits, including the TaqMan® Arbovirus Triplex Kit, Illumina viral surveillance panel (Illumina VSP), and Altona singleplex kit. Data were analyzed using R to determine specificity, sensitivity, negative predictive value (NPV), positive predictive value (PPV), and diagnostic odds ratio, with probit analysis employed to evaluate the limit of detection. Results The TaqMan® Arbovirus Kit showed sensitivity exceeding 95% for all three virus targets: 97.98% for DENV, and 100% for both CHIKV and ZIKV. Simillarly, the RealStar® RT-PCR Kits exhibited sensitivities: 93.94% for CHIKV, 90.91% for DENV, and 100% for ZIKV. All kits demonstrated specificity above 99%, with a positive predictive value (PPV) over 99% and a negative predictive value (NPV) exceeding 97%. Probit analysis revealed that the TaqMan® Arbovirus Kit also had a lower detection limit compared to the RealStar kit for all tested viruses. Conclusion The TaqMan® Arbovirus Kit provides multiplex capabilities and performance similar to the RealStar® CHIKV, DENV, and ZIKV RT-PCR Kits. Consequently, these kits can be used interchangeably for detecting DENV, CHIKV, and ZIKV viruses in outbreak situations.
Yellow fever (YF) is an acute hemorrhagic zoonotic disease that causes severe liver damage, renal failure, and hemorrhagic shock. No antiviral treatment is available; thus, vaccination is a critical preventive … Yellow fever (YF) is an acute hemorrhagic zoonotic disease that causes severe liver damage, renal failure, and hemorrhagic shock. No antiviral treatment is available; thus, vaccination is a critical preventive measure. Although the World Health Organization (WHO) revised the guidelines regarding the need for booster vaccination for YF with the rationale that a single vaccination provides sufficient long-term immunogenicity, no studies have evaluated long-term immunity in Japanese adults who received a single dose of YF vaccine. This study evaluated the long-term persistence of immunogenicity in Japanese adults vaccinated with the YF vaccine. This observational study enrolled Japanese adults who received a single YF vaccination &gt;5 years previously. Blood samples were collected after confirming eligibility for the study. The serum levels of anti-yellow fever virus (YFV)-neutralizing antibodies were measured using the 50% plaque reduction neutralization test (PRNT50). The 65 participants comprised 35 males and 30 females, with a median age at vaccination of 34 years. The time between YF vaccination and registration was between 5 and 26 years. All participants remained seropositive even after a long time. Statistical analysis showed no correlation between the time elapsed since YF vaccination and PRNT50. Our results indicate that a single dose of YF vaccine provides adequate long-term immunity in Japanese adults and that booster vaccinations are not routinely required. These findings strongly aid in the development of travel medicine guidelines and the optimization of vaccination strategies by reducing the usage of medical resources and simplifying the health requirements for travelers.
Dengue is caused by the four serotypes of dengue virus (DENV-1-4) and poses a significant global public health challenge, with an estimated 100–400 million infections annually. Severe dengue manifestations, such … Dengue is caused by the four serotypes of dengue virus (DENV-1-4) and poses a significant global public health challenge, with an estimated 100–400 million infections annually. Severe dengue manifestations, such as Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS), are influenced by immune responses, particularly during secondary infections with different serotypes. Antibody-dependent enhancement (ADE) of DENV infection is a critical mechanism in dengue immunopathogenesis, underscoring the need for comprehensive evaluation of antibody responses. Traditional cell lines used for DENV propagation exhibit variability and present logistical challenges for assessing non-neutralizing antibody functions. Here, we report the establishment of a stable CEM-NK R cell line expressing DC-SIGN, designated CEM2001, capable of supporting continuous infection with all four DENV serotypes. These cell lines allow for continuous DENV infection, enabling detailed immunoassays to evaluate serotype-specific and cross-reactive non-neutralizing antibody responses. Our approach offers a significant advancement in dengue research, providing a consistent and reliable system to study DENV immune responses and supporting future efforts to develop and evaluate dengue therapeutics and vaccines.
<title>Abstract</title> <bold>Background</bold> Malaria and its related vector-borne diseases, including dengue, chikungunya, and measles, among the parasitic diseases, are significant contributors to the estimated 95% deaths occurring in Africa where various … <title>Abstract</title> <bold>Background</bold> Malaria and its related vector-borne diseases, including dengue, chikungunya, and measles, among the parasitic diseases, are significant contributors to the estimated 95% deaths occurring in Africa where various factors such as ecosystem, fragile health systems, and climate conditions are favorable to species of mosquitoes transmitting the malaria parasite and have been a serious obstacle to socio-economic development across Africa. Understanding the shared predictors of these diseases can help prioritize public health interventions and resource allocation. However, cross-disease vulnerability modeling in the African context remains understudied, especially using integrated environmental and social indicators. <bold>Methods</bold> This research proposes developing a predictive framework that aims to address this challenge by identifying African countries that are highly vulnerable to multiple disease outbreaks, using malaria as a baseline for assessing susceptibility to dengue, chikungunya, and measles. To achieve this objective, we compiled data from 40 African countries across 10 variables capturing climatic, demographic, and healthcare system features. Analytical techniques included descriptive statistics, Random Forest, Lasso regression, Hotspot Analysis, Principal Component Analysis (PCA), and the construction of a novel Cross-Disease Vulnerability Index (CDVI). <bold>Results</bold> The analysis revealed highly vulnerable clusters in Central, Southern, and Western Africa. Our random forest achieved a classification accuracy of 87.5%, and the lasso regression achieved a coefficient of determination of 84.67%, highlighting rainfall, urbanization, population under age 15, and population density as the most influential predictors of vulnerability. The CDVI strongly correlated with actual malaria burdens (ρ = +0.72, p &lt; 0.0028), indicating a significant association of malaria and cross-disease vulnerability. <bold>Conclusion</bold> This study highlights the importance of integrating cross-modeling in identifying multiple diseases proves to be a crucial factor in strengthening early warning systems. Health Organizations, policymakers, and other researchers should prioritize countries, including Botswana, Eswatini, Namibia, Gabon, and Equatorial Guinea, which have high CDVI scores for epidemic readiness initiatives.
Dengue is a viral infection transmitted by mosquitoes of the Aedes genus, responsible for millions of cases each year. In Benin, several outbreaks have been reported, particularly in Abomey-Calavi, where … Dengue is a viral infection transmitted by mosquitoes of the Aedes genus, responsible for millions of cases each year. In Benin, several outbreaks have been reported, particularly in Abomey-Calavi, where the first dengue-related death was recorded in 2019. In the absence of a specific treatment, vector control remains the primary preventive measure. However, the emergence of insecticide resistance, notably through kdr mutations, could compromise its effectiveness. This study aims to identify the dengue virus serotypes circulating in the commune of AbomeyCalavi and to assess the frequency of kdr mutations V410L, V1016G, V1016I, F1534C, and S989P in Aedes aegypti and Aedes albopictus mosquitoes. Mosquitoes were collected in August 2024 from four arrondissement Togba, Calavi, Akassato, and Godomey through morning and afternoon spraying. After morphological identification, molecular analyses were conducted to detect the viral serotypes and kdr mutations. A total of 218 Aedes mosquitoes were collected, with a predominance of Aedes aegypti (68.8%) compared to Aedes albopictus (31.2%). The overall dengue positivity rate was 23.39% (95%CI: 17.9 - 29.6). The most frequent serotype was DENV-3 (12.4%), followed by DENV-2 (6.9%), DENV-1 (5%), and DENV-4 (0.09%). Six mosquitoes were co-infected with two serotypes, including three with DENV-1 and DENV-4. kdr mutations were detected in both species, with frequencies of 45% for V1016G, 44% for S989P, 40% for F1534C, 22% for V410L, and 19% for V1016I. Four mosquitoes carried three simultaneous mutations, while twenty-two carried two. Two mosquitoes co-infected with two serotypes also carried two different mutations. These results highlight the active circulation of the dengue virus and the presence of kdr mutations in Aedes mosquitoes in Abomey-Calavi. However, no significant association was observed between dengue infection and kdr mutations, and their distribution was independent of the viral serotype. These findings emphasize the need for regular monitoring of kdr mutations to adapt vector control strategies and limit the spread of dengue.
Abstract BACKGROUND Larval control is crucial for managing mosquito arbovirus vectors. Quality control (QC) data from insecticide‐based interventions are rarely exploited to assess the effectiveness of biocides in the field. … Abstract BACKGROUND Larval control is crucial for managing mosquito arbovirus vectors. Quality control (QC) data from insecticide‐based interventions are rarely exploited to assess the effectiveness of biocides in the field. This study aims to: (i) evaluate the outcomes of large‐scale catch basin treatments with diflubenzuron (DFB) and Bacillus thuringiensis var. israelensis and B . ( Lysinibacillus ) sphaericus (Bti + Bs) on immature stages of Aedes albopictus and Culex pipiens , with reference to critical variables, such as the intervals between catch basin treatments and inspections; and (ii) identify areas of repeated treatment failures. RESULTS More than 30 000 catch basins were inspected from 2019 to 2021 for mosquito immature stages after treatment with DFB and Bti + Bs in 461 municipalities in north‐east Italy. Overall, 5% of catch basins revealed the presence of live L3–L4 larvae and/or pupae. Model results showed opposite associations between percentages of positive catch basins treated with the two larvicides and the intervals between treatments and inspections, likely because of the different modes of action; i.e., a negative association following DFB treatments (day 7/day 21: Ae. Albopictus , 7%–4%; Cx . pipiens , 8%–4%), and a positive association following Bti + Bs treatments for Ae. albopictus (day 7/day 21: 2%–13%). Spatial analysis revealed repeated DFB treatment failures against Cx. pipiens in the area of the Venice lagoon, where the highest frequencies of alleles associated with DFB resistance have been reported. CONCLUSION The results show that, despite unavoidable limitations, high‐quality area‐wide databases from multi‐year QC activities of public mosquito control interventions may allow general conclusions to be reached (such as shortening the intervals between Bti + Bs treatments) accounting for real‐world heterogeneities that cannot be achieved experimentally. © 2025 The Author(s). Pest Management Science published by John Wiley &amp; Sons Ltd on behalf of Society of Chemical Industry.
Malaria continues to pose a significant health challenge, particularly in low-resource settings (LRS), where access to reliable and timely diagnostics is often limited. In this context, point-of-care (POC) in vitro … Malaria continues to pose a significant health challenge, particularly in low-resource settings (LRS), where access to reliable and timely diagnostics is often limited. In this context, point-of-care (POC) in vitro diagnostics (IVDs) play a key role in supporting early detection and treatment. The aim of this scoping review was to better understand the landscape of malaria IVD technologies, with the aim of identifying both their strengths and limitations to guide and accelerate the development of POC diagnostics suitable for endemic regions and LRS. To support this analysis, the ASSURED (Affordability, Sensitivity, Specificity, User-friendliness, Rapidity, Equipment-free, Deliverability) criteria were applied to rank each technology in terms of its potential for POC applications in LRS. A literature search was conducted in PubMed and Web of Science for original research articles on malaria POC diagnostic devices published in English over the last 20 years (2003-2023). Records were screened based on eligibility criteria. For each paper, we identified biomarkers, biological specimens used, analytical methods, and readout technologies. Each record was ranked from low to high for its compatibility with the seven ASSURED criteria and for the Technology Readiness Level. The final dataset included 118 records. Of the methods considered, immunoassays were the most frequently reported (41.5%), followed by loop-mediated isothermal amplification (LAMP, 22.8%), polymerase chain reaction (PCR, 6.7%) and optical microscopy (4.2%). The limit of detection was highest for LAMP and PCR. Biomarkers employed for diagnosis included the Plasmodium parasite, parasite protein antigens and hemozoin. Blood was the most commonly employed biological specimen (76.2%), followed by urine and saliva (5.1%). Despite a focus on malaria IVDs for POC applications, only 8% of the records mentioned ASSURED criteria, with most studies manifesting low compatibility with the criteria. Although meeting the ASSURED criteria remains challenging, microscopy is still the gold standard because of its diagnostic accuracy. Recent developments in low-cost, high-magnification lenses and innovative manufacturing techniques have enabled the production of microscopy devices in LRS. Combined with advancements in image processing and shape recognition through machine learning, there is strong potential for intellectual and economic investments to enhance microscopy for POC malaria diagnostics.
Zika virus (ZIKV) infection of neuronal cells leads to endoplasmic reticulum (ER) stress, which is one of the key causes of neuronal damage. However, how ZIKV mediates ER stress has … Zika virus (ZIKV) infection of neuronal cells leads to endoplasmic reticulum (ER) stress, which is one of the key causes of neuronal damage. However, how ZIKV mediates ER stress has not been fully understood. Here, we observed that ZIKV infection of astrocytes elevated Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) expression, increased intracellular Ca2+ concentration, and upregulated ER stress-related genes. SERCA2 was identified to regulate Ca2+ homeostasis and ER stress during ZIKV infection through both knockdown and overexpression of SERCA2 in astrocytes. Furthermore, ZIKV NS2A interacted with SERCA2 and increased the expression of SERCA2, disrupted Ca2+ homeostasis, and induced ER stress in astrocytes. After the knockdown of SERCA2 expression, Ca2+ homeostasis and ER stress were significantly mitigated in astrocytes expressing NS2A. Additionally, pTMS1-2 and pTMS4-5 of NS2A interacted with SERCA2 and regulated Ca2+ homeostasis and ER stress. ZIKV infection of the brains of BALB/c neonatal mice also elevated expression of SERCA2 and ER stress-related genes. Furthermore, SERCA2 expression facilitated ZIKV replication. These results suggested that ZIKV NS2A mediates ER stress through its interaction with SERCA2, providing new insights into the pathogenic mechanism of ZIKV and the development of anti-ZIKV therapies. Zika virus (ZIKV) infection induces intracellular Ca2+ imbalance and endoplasmic reticulum (ER) stress. However, the molecular mechanisms involved in it remain unknown. Here we reported, for the first time, that ZIKV infection increased the expression of Sarco/endoplasmic reticulum Ca2+-ATPase 2 (SERCA2), which plays a crucial role in regulating Ca2+ homeostasis and ER stress. Furthermore, ZIKV NS2A was found to interact with SERCA2, contributing to the regulation of Ca2+ homeostasis and ER stress during ZIKV infection. And ZIKV NS2A pTMS1-pTMS2 and pTMS4-pTMS5 were the specific sites that interacted with SERCA2. These findings elucidate that the interaction between NS2A and SERCA2 is responsible for the regulation of the upstream signaling pathway of ER stress mediated by ZIKV infection. Additionally, the expression of SERCA2 promoted ZIKV proliferation, indicating that SERCA2 may serve as a potential target for anti-ZIKV therapies.
The transmission dynamics of the dengue disease with imperfect vaccination and re-infection are being considered &amp; analyzed. The model exhibits backward bifurcation when the basic reproduction number (R0) is less … The transmission dynamics of the dengue disease with imperfect vaccination and re-infection are being considered &amp; analyzed. The model exhibits backward bifurcation when the basic reproduction number (R0) is less than 1. However, using the Lyapunov function as well as the LaSalle Invariance Principle, it is demonstrated that with perfect vaccination and no re-infection, the DFE point is globally asymptotically stable. If R0 &gt; 1, there exists a distinct endemic equilibrium that is locally asymptotically stable. Numerical results of the model, using relevant parameter values, indicate that the increasing rate of vaccination waning resulted in the increase of infected individuals. Further numerical results suggest that the disease will continue in the community in the presence of re-infection. It also suggests that the dengue virus can be controlled effectively using the perfect vaccine. J. Bangladesh Math. Soc. 45.1 (2025) 16–31
Dengue fever, a common mosquito-borne viral illness in tropical and subtropical areas, is endemic in over one hundred countries. Recent dengue outbreaks in Bangladesh exhibited higher morbidity and a notable … Dengue fever, a common mosquito-borne viral illness in tropical and subtropical areas, is endemic in over one hundred countries. Recent dengue outbreaks in Bangladesh exhibited higher morbidity and a notable change in signs and symptoms, making the disease pattern more complicated. Yet the inadequate knowledge regarding the shifting of clinical parameters leads to inaccurate diagnoses and constrained treatment options. This study sought to assess the changing patterns of clinicopathological markers across various stages of the disease. Data were collected from 211 (137 dengue-positive and 74 dengue-negative) hospitalized patients in Chattogram, Bangladesh during the 2024 dengue outbreak. The dengue-positive patients were categorized into groups according to age, gender, and IgG status (primary or secondary infection). We evaluated the parameters throughout five stages of the disease utilizing Prism GraphPad-10. In our study, older (&gt;40 years) patients exhibited lower platelet counts over an extended period. Besides, a decrease in hematocrit and hemoglobin levels, along with an increased ESR (Erythrocyte Sedimentation Rate), NLR (Neutrophil-Lymphocyte Ratio), ALT (Alanine Transaminase), and AST (Aspartate Transaminase) was noted among older (&gt;50 years) patients. In males and females, differences in the changing patterns of platelet count, hematocrit, ALT, and AST were observed. Significant differences in many indices between IgG-negative and IgG-positive patients have been noted. Compared to IgG-negative patients, IgG-positive patients exhibited lower platelet counts and higher ESR, NLR, AST, and ALT. Interestingly, hematocrit changing patterns were similar in IgG-positive and IgG-negative patients, while the pattern for NLR was substantially different. Initial NLR was high (&gt;4) in IgG-positive patients, reducing significantly (p***=0.0001) at the following stage and lowering to 2 until the last stage, while IgG-negative patients maintained NLR around three. This research will help to elucidate the disease patterns of current dengue infections by providing significant insights into the changing clinical parameters during the period of the disease.
The dynamics of zoonotic infectious diseases with silent circulation may be imperfectly understood and monitored using passive (or reactive) epidemiological surveillance data only, highlighting the interest of quantitative methods like … The dynamics of zoonotic infectious diseases with silent circulation may be imperfectly understood and monitored using passive (or reactive) epidemiological surveillance data only, highlighting the interest of quantitative methods like modelling. West Nile virus (WNV) is a widespread mosquito-borne virus transmitted from birds to "dead-end" hosts including humans and horses, in whom it can be fatal. It was first detected in Guadeloupe, Caribbean, in 2002, although no WNV clinical case in humans nor horses had been reported on the archipelago before 2024. Undetected infections represent a risk as WNV can be transmitted via blood and organ donations. In Guadeloupe, epidemiological surveillance started in 2002 in chickens and horses and in 2015 in mosquitoes, to detect WNV and to improve knowledge on its epidemiology and dynamics. In order to reconstruct the WNV force of infection (FOI), we built a model assessing different hypotheses regarding its dynamics using serological results in respectively 1,022 and 3,649 blood samples collected from 256 horses and 317 chickens between 2002 and 2018. We fitted the model to the serological data using a Markov Chain Monte Carlo algorithm. We found that WNV FOI in Guadeloupe Island presented both within-year (seasonal) and between-years fluctuations. We identified three main episodes of WNV circulation on the island between 2002 and 2017. During years with circulation, the FOI was predicted to be highest around the months of October-November, although transmission could occur all year long. We estimated a very low weekly seroreversion rate, which is consistent with a lifelong persistence of WNV IgG antibodies in many infected individuals. To conclude, combining longitudinal serological data to a mathematical model allowed reconstructing the recurrent and silent circulation of WNV in this Caribbean island, which could improve surveillance design for better virus detection.
A country with continental dimensions like Brazil, characterized by heterogeneity of climates, biomes, natural resources, population density, socioeconomic conditions, and regional challenges, also exhibits significant spatial variation in dengue outbreaks. … A country with continental dimensions like Brazil, characterized by heterogeneity of climates, biomes, natural resources, population density, socioeconomic conditions, and regional challenges, also exhibits significant spatial variation in dengue outbreaks. This study aimed to characterize Brazilian territory based on epidemiological and climate data to determine the optimal time to guide preventive and control strategies. To achieve this, the Moving Epidemics Method (MEM) was employed to analyze dengue historical patterns using 14-year disease data (2010-2023) aggregated by the 120 Brazilian Health Macro-Regions (HMR). Statistical outputs from MEM included the mean outbreak onset, duration, and variation of these measurements, pre- and post-epidemic thresholds, and the high-intensity level of cases. Environmental data used includes mean annual precipitation, temperature, and altitude, as well as the Köppen Climate Classification of each area. A multivariate cluster analysis using the k-means algorithm was applied to MEM outputs and climate data. Four clusters/regions were identified, with the mean temperature, mean precipitation, mean outbreak onset, high-intensity level of cases, and mean altitude explaining 80% of the centroid variation among the clusters. Region 1 (North-Northwest) encompasses areas with the highest temperatures, precipitation, and early outbreak onset, in February. Region 2a (Northeast) has the lowest precipitation and a later onset, in March. Region 3 (Southeast) presents higher altitude, and early outbreak onset in February; while Region 4 (South) has a lower temperature, with onset in March. To better adjust the results, the unique Roraima state HMR state was manually classified as Region 2b (Roraima) because of its outbreak onset in July and the highest precipitation volume. The results suggested preventive and control measures should be implemented first in Regions North-Northwest and Southeast, followed by Regions Northeast, South, and Roraima, highlighting the importance of regional vector control measures based on historical and climatic patterns. Integrating these findings with monitoring systems and fostering cross-sector collaboration can enhance surveillance and mitigate future outbreaks. The proposed methodology also holds potential for application in controlling other mosquito-transmitted viral diseases, expanding its public health impact.
The objective of this study was to develop an evidence map on the strategies for preventing and controlling Aedes aegypti infestation and related viral infections. The evidence map was created … The objective of this study was to develop an evidence map on the strategies for preventing and controlling Aedes aegypti infestation and related viral infections. The evidence map was created according to the methodology of the Latin American and Caribbean Center on Health Sciences Information (BIREME). Publication searches were performed in MEDLINE/PubMed and the Virtual Health Library, filtered for systematic reviews (SRs) only. The methodological quality of the SR was accessed using the AMSTAR2 tool, and Tableau software was used to construct the evidence map. A total of 44 SRs on the prevention and control of A. aegypti infestation and related viral infections (dengue, chikungunya, Zika, and yellow fever viruses) were included in the map. The evidence map indicates 130 associations between 59 interventions and 18 outcomes. The reported interventions were categorized into 10 groups, including community/educational actions, use of repellents, immunization, individual protection, diagnostics, biological and chemical control of the vector, epidemiological surveillance, environmental actions, and combined interventions. The described outcomes were grouped as mosquito infestation, behavior change, prevention and control, immunological response, safety, and epidemiological surveillance. The elaborated map highlighted strong evidence supporting the effectiveness of vaccination, DEET repellents, community participation, chemical control of the vector, and combined housing interventions in protecting against the vector and transmitted viruses. Nonetheless, several evidence gaps remain in the knowledge of how to best prevent and control the vector and its related viral infections, underscoring the need for high-quality SRs and primary studies.
The global burden of arboviral diseases continues to rise with alarming frequency and impact [...] The global burden of arboviral diseases continues to rise with alarming frequency and impact [...]
Human West Nile virus (WNV) infection is usually asymptomatic. Less than 1% of patients develop neuroinvasive disease (WNND) which may result in permanent neurological impairment. The aim of this study … Human West Nile virus (WNV) infection is usually asymptomatic. Less than 1% of patients develop neuroinvasive disease (WNND) which may result in permanent neurological impairment. The aim of this study was to assess the functional and cognitive status of patients with WNND approximately one year after the onset of symptoms. This prospective observational cohort study involved patients with WNND. Patients’ functional and cognitive abilities one year post-infection were assessed by telephone interviews using the Modified Rankin Scale (mRS), Barthel Index, and Telephone Interview for Cognitive Status. Sixty-two participants were analyzed. All patients had encephalitis, and 7 (11.3%) also had acute flaccid paresis/paralysis (AFP). At discharge, 40 (64.5%) patients had no or minimal neurological deficit (mRS 0–1), and 14 (22.6%) were functionally dependent (mRS 3–5). One year later, 52 (83.9%) patients were functionally independent (mRS 0–2), none was severely dependent (Barthel index 0–60), and 50 (90.9%) had a Barthel index score of 91–100. Among 14 functionally dependent patients at discharge, 3 (21.4%) remained functionally dependent one year later. During the follow-up, 7 (11.3%) patients died. No significant difference was observed in the fatality rate between patients with and without AFP, mRS 3–5 at discharge, or age over 65. The most common persistent symptoms were muscle weakness, walking instability, and issues with focus and memory. Using TICS, it was found that 33/55 patients (60%) had unimpaired and 2 (3.6%) had moderately or severely impaired cognitive status. The long-term prognosis after WNV encephalitis is satisfying. The majority of patients reached functional independence and 60% had unimpaired cognitive status.
ZIKA virus (ZIKV), an emerging pathogen for which no licensed drugs or vaccines exist, has attracted global attention. ZIKV envelope protein domainIII (EDIII) can induce neutralizing antibodies with minor cross-reactive … ZIKA virus (ZIKV), an emerging pathogen for which no licensed drugs or vaccines exist, has attracted global attention. ZIKV envelope protein domainIII (EDIII) can induce neutralizing antibodies with minor cross-reactive epitopes among flaviviruses. Currently, no nanobodies against the ZIKV EDIII protein are available. In our study, 15 nanobodies were derived from a naive phage library. High-affinity and specific nanobodies of Nb-C9, Nb-D8, Nb-E3, and Nb-E5 were selected in vitro showing dissociation constants of 8.24, 6.59, 2.52, and 8.22 nM, respectively. The Nb-E3 and Nb-E5 potently neutralized strain ZIKV-GD01 with plaque reduction neutralization test (PRNT)50 values of 0.1875 and 0.0234 μg/mL, respectively. In addition, a linear epitope Z17-VGEKKITHHWHRS recognized by Nb-E5 showed potential as a candidate for the development of epitope-based vaccines. These findings may contribute to the development of a new therapeutic strategy against ZIKV infection.
Brake dust is a major component of particulate matter (PM) and enriched in potentially toxic elements (PTEs), posing a significant threat to both the environment and health especially in densely … Brake dust is a major component of particulate matter (PM) and enriched in potentially toxic elements (PTEs), posing a significant threat to both the environment and health especially in densely populated areas. In this context, an in vivo approach is essential to understand its potential negative effects. Here, we investigated the toxicity of brake dust on Aedes albopictus, a common mosquito species in urban environments. We exposed larvae to increasing concentrations of brake dust in the water (10-500 mg L-1) to evaluate: (i) effects on developmental, behavioural and morphological traits; (ii) element bioaccumulation; (iii) oxidative stress. We found a significant reduction in adult emergence rate, delayed larval growth, and morphological changes in male wing shape. At high brake dust concentrations, an increase in cannibalistic interactions among larvae was also observed. Furthermore, we demonstrated that larvae bioaccumulate elements from brake dust in different ways, with Cu, La, Ce, and Ba which were progressively bioaccumulated as brake dust concentration increased, while most other PTEs showed bioaccumulation up to 50 mg L-1, followed by a decrease at higher concentrations. The overexpression of superoxide dismutase (SOD) and catalase genes at concentrations above 50 mg L-1 indicated induction of oxidative stress response. We conclude that the toxic effects of brake dust on Ae. albopictus occurred at multiple levels, with important biological and ecological relevance. Moreover, our findings identify Ae. albopictus as a valuable model for in vivo studies on PM toxicity.
Com o passar dos tempos a dengue tornou-se a arbovirose que mais afetou humanos, caracterizada por ser uma doença infecciosa febril de etiologia viral e na maioria dos casos tem … Com o passar dos tempos a dengue tornou-se a arbovirose que mais afetou humanos, caracterizada por ser uma doença infecciosa febril de etiologia viral e na maioria dos casos tem evolução benigna, apresentando-se em duas possíveis formas clínicas: Dengue Clássica e Hemorrágica. É causada por um arbovírus, do gênero Flavivírus, sendo ele transmitido pela picada do mosquito Aedes aegypti, que se proliferam através de água parada e limpa. Esse trabalho tem como objetivo alertar a população sobre essa doença e ajudar a entender um pouco sobre seu diagnóstico. Para realização desse trabalho foram pesquisados artigos científicos relacionados ao tema diagnóstico laboratorial da dengue, utilizando-se as bases de dados on-line. Por ser uma doença com características clínicas variáveis, para o diagnóstico da dengue, é necessário o uso da análise laboratorial, para confirmação da presença do vírus. Cada exame laboratorial apresenta sua funcionalidade e sensibilidade perante ao vírus e ao sorotipo apresentado. Com o intuito de não provocar retardos nos diagnósticos, considera-se mais indicado em diagnóstico precoce o exame sorológico NS1, pela rapidez e fácil detecção logo nos primeiros dias de sintomas. Já para diferenciação dos sorotipos da dengue, podemos concluir que a PCR é considerada padrão ouro para esse diagnóstico, por ser o único exame capaz de diferenciar os quatro sorotipos.
Japanese encephalitis virus (JEV) is a mosquito-borne orthoflavivirus and a major cause of human encephalitis throughout Asia, although it is currently not reported in Europe. To assess the potential impact … Japanese encephalitis virus (JEV) is a mosquito-borne orthoflavivirus and a major cause of human encephalitis throughout Asia, although it is currently not reported in Europe. To assess the potential impact of climate change, such as increased temperatures, and the potential for native Cx. pipiens to transmit JEV genotype I in the United Kingdom (UK), we have investigated vector competence at two different temperatures. Culex pipiens f. pipiens were provided a bloodmeal containing JEV genotype I at 7.8 × 108 PFU/mL. Mosquitoes were maintained for 14 days at 21 °C or 25 °C, and rates of infection, dissemination, and transmission potential were assessed. There was no evidence for virus infection, dissemination, or potential for transmission at 21 °C. However, at 25 °C, virus infection was detected in 5 of 36 mosquitoes (13.9%). Of these, JEV disseminated to legs and wings in three specimens (3/5) and viral RNA was detected in saliva from one specimen (1/3). These data indicate that at elevated temperatures of 25 °C, UK Cx. pipiens f. pipiens could transmit JEV genotype 1.
Flaviviruses are a class of pathogenic viruses with pandemic potential which are typically transmitted via infected arthropods. In particular, Zika virus is sexually transmissible and causes congenital malformations if infection … Flaviviruses are a class of pathogenic viruses with pandemic potential which are typically transmitted via infected arthropods. In particular, Zika virus is sexually transmissible and causes congenital malformations if infection occurs during pregnancy. Although over 1.5 million people were infected during the 2015-2016 Zika outbreak, to date, there are no clinical-stage vaccines or antivirals. Herein, we report the discovery of potent inhibitors of the Zika virus NS2B-NS3 protease that also show activity against the West Nile virus NS2B-NS3 protease. Starting from a crystallographic fragment screen, we employed a pharmacophore approach coupled with high-throughput library chemistry to elaborate fragments in the active site. Potent, metabolically stable, non-covalent, non-peptidomimetic inhibitors were identified with cellular antiviral activity, with one example demonstrating excellent murine bioavailability.
Yellow fever is a mosquito-borne viral hemorrhagic fever that has caused recent outbreaks in African countries, including Ghana (2021-2022). Delayed diagnosis of yellow fever may cause increased morbidity and mortality. … Yellow fever is a mosquito-borne viral hemorrhagic fever that has caused recent outbreaks in African countries, including Ghana (2021-2022). Delayed diagnosis of yellow fever may cause increased morbidity and mortality. To improve timely detection of yellow fever, we need to better understand the factors contributing to diagnostic delays. We analyzed the diagnostic testing timeline of all suspected yellow fever cases in Ghana from 2018-2022. For these patients we calculated the days from symptom onset to specimen collection and arrival at the National Public Health and Reference Laboratory (NPHRL) for testing. We compared these times to World Health Organization (WHO) metrics. For suspected yellow fever cases, the time from symptom onset to specimen arrival had a median of 10 days (interquartile range 6-17). 5892/6345 (93%) of specimens were collected within 14 days of symptom onset, and 2653/6471 (41%) of specimens arrived within 3 days of collection (WHO metrics). Overall, we find that the timing of yellow fever testing varies among districts in Ghana. While specimens are generally collected in a timely manner, delays in specimen arrival are common. Improving specimen transport for yellow fever and/or expanded testing could lead to more timely detection of outbreaks.
Abstract We investigated West Nile cases in a Mid-Atlantic healthcare system, finding significant morbidity and mortality from neuroinvasive disease, notably among immunocompromised patients. Encephalitis was the most common complication and … Abstract We investigated West Nile cases in a Mid-Atlantic healthcare system, finding significant morbidity and mortality from neuroinvasive disease, notably among immunocompromised patients. Encephalitis was the most common complication and was associated with increased age, alcohol use disorder, immunocompromised status, and a higher Charlson Comorbidity Index.