Eight cases of locally acquired, mosquito-transmitted (i.e., autochthonous) Plasmodium vivax malaria, which has not been reported in the United States since 2003, were reported to CDC from state health departments in Florida and Texas during May 18-July 17, 2023. As of August 4, 2023, case surveillance, mosquito surveillance and control activities, and public outreach and education activities continue in both states. U.S. clinicians need to consider a malaria diagnosis in patients with unexplained fever, especially in areas where autochthonous malaria has been recently reported, although the risk for autochthonous malaria in the United States remains very low. Prompt diagnosis and treatment of malaria can prevent severe disease or death and limit ongoing transmission to local Anopheles mosquitoes and other persons. Preventing mosquito bites and controlling mosquitoes at home can prevent mosquitoborne diseases, including malaria. Before traveling internationally to areas with endemic malaria, travelers should consult with a health care provider regarding recommended malaria prevention measures, including potentially taking malaria prophylaxis. Malaria is a nationally notifiable disease; continued reporting of malaria cases to jurisdictional health departments and CDC will also help ensure robust surveillance to detect and prevent autochthonous malaria in the United States.

South Texas is recognized as a potential area for the emergence and re-emergence of mosquito-borne diseases due to recent circulation of Zika, chikungunya, and dengue viruses. During 2017, high Aedes aegypti abundance found in the city of Brownsville, TX, in combination with the previous year's local transmission of Zika virus, triggered the activation of the Texas Department of State Health Services Emergency Mosquito Control Contingency Contract. A contract with the Clarke Environmental and Mosquito Control was a response to control Ae. aegypti, using a ground-based wide-area larvicide spray (WALS™) containing Bacillus thuringiensis israelensis. The WALS application was evaluated through a field-based bioassay and by comparing surveillance data pre- and post-WALS application. The WALS application bioassay demonstrated that the larvicide was effective up to 60 m into the target properties. Additionally, the number of Ae. aegypti captured in traps decreased in the WALS intervention areas compared with the untreated control areas, with an estimated 29% control.

Obesity is a common, complex, and often persistent chronic disease associated with serious health and social consequences if not treated.1 Yet, despite the disease’s complexity, treatment of obesity can be successful.2–4 The current and long-term health of 14.4 million children and adolescents is affected by obesity,5,6 making it one of the most common pediatric chronic diseases in the United States.5,7,8 | | Obesity has long been stigmatized as a reversible consequence of personal choices but has, in reality, complex genetic, physiologic, socioeconomic, and environmental contributors. An increased understanding of the impact of social determinants of health (SDoHs) on the chronic disease of obesity—along with heightened appreciation of the impact of the chronicity and severity of obesity-related comorbidities—has enabled broader and deeper understanding of the complexity of both obesity risk and treatment.9,10

You have in your hands, or at your fingertips, the first edition of the American Academy of Pediatrics clinical practice guideline for evaluation and management of children and adolescents with overweight and obesity. Putting together this guideline was no small task, and the Academy is grateful to the efforts of all the professionals who contributed to the production of this document. This work is a true testament to their passion and dedication to combatting childhood and adolescent overweight and obesity.

In November and December 2016, an outbreak of locally transmitted Zika occurred in Brownsville, TX. The Texas Department of State Health Services requested for a Centers for Disease Control and Prevention (CDC) Epi Aid, and as part of that Epi Aid a team of CDC entomologists was deployed in January 2017. The mission was to improve mosquito-based arbovirus surveillance and evaluate the possibility of continuing local Zika virus (ZIKV) transmission in the city. The mosquito-based arbovirus surveillance program was expanded from 4 to 40 BG-Sentinel traps evenly distributed throughout the city. Over a 2-wk period, 15 mosquito species were detected; the most abundant species were Culex quinquefasciatus, Aedes aegypti, and Ae. albopictus, which accounted for 66.7%, 16.2%, and 5.7% of the total mosquito collection, respectively. The relative abundance of Ae. aegypti (1.0 mosquitoes/trap/day) and Ae. albopictus (0.4 mosquitoes/trap/day) was very low and unlikely to initiate and/or sustain ZIKV transmission. Zika virus was not detected in the mosquitoes collected, suggesting no or extremely low ZIKV transmission at that time.

St. Louis encephalitis virus (SLEV) is a flavivirus that circulates in an enzootic cycle between birds and mosquitoes and can also infect humans to cause febrile disease and sometimes encephalitis. Although SLEV is endemic to the United States, no activity was detected in California during the years 2004 through 2014, despite continuous surveillance in mosquitoes and sentinel chickens. In 2015, SLEV-positive mosquito pools were detected in Maricopa County, Arizona, concurrent with an outbreak of human SLEV disease. SLEV-positive mosquito pools were also detected in southeastern California and Nevada in summer 2015. From 2016 to 2018, SLEV was detected in mosquito pools throughout southern and central California, Oregon, Idaho, and Texas. To understand genetic relatedness and geographic dispersal of SLEV in the western United States since 2015, we sequenced four historical genomes (3 from California and 1 from Louisiana) and 26 contemporary SLEV genomes from mosquito pools from locations across the western US. Bayesian phylogeographic approaches were then applied to map the recent spread of SLEV. Three routes of SLEV dispersal in the western United States were identified: Arizona to southern California, Arizona to Central California, and Arizona to all locations east of the Sierra Nevada mountains. Given the topography of the Western United States, these routes may have been limited by mountain ranges that influence the movement of avian reservoirs and mosquito vectors, which probably represents the primary mechanism of SLEV dispersal. Our analysis detected repeated SLEV introductions from Arizona into southern California and limited evidence of year-to-year persistence of genomes of the same ancestry. By contrast, genetic tracing suggests that all SLEV activity since 2015 in central California is the result of a single persistent SLEV introduction. The identification of natural barriers that influence SLEV dispersal enhances our understanding of arbovirus ecology in the western United States and may also support regional public health agencies in implementing more targeted vector mitigation efforts to protect their communities more effectively.

The N-linked glycosylation motif at amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV) is linked to enhanced murine neuroinvasiveness, avian pathogenicity and vector competence. Naturally occurring isolates with altered E protein glycosylation patterns have been observed in WNV isolates; however, the specific effects of these polymorphisms on avian host pathogenesis and vector competence have not been investigated before. In the present study, amino acid polymorphisms, NYT, NYP, NYF, SYP, SYS, KYS and deletion (A'DEL), were reverse engineered into a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses. These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus. The NYS and NYT glycosylated viruses showed higher viral replication, pH and temperature sensitivity than NYP, NYF, SYP, SYS, KYS and A'DEL viruses in vitro. Interestingly, in vivo results demonstrated asymmetric effects in avian and mosquito competence that were independent of the E-protein glycosylation status. In AMCRs and HOSPs, all viruses showed comparable viremias with the exception of NYP and KYS viruses that showed attenuated phenotypes. Only NYP showed reduced vector competence in both Cx. quinquefasciatus and Cx. tarsalis. Glycosylated NYT exhibited similar avian virulence properties as NYS, but resulted in higher mosquito oral infectivity than glycosylated NYS and nonglycosylated, NYP, NYF, SYP and KYS mutants. These data demonstrated that amino acid polymorphisms at E154/156 dictate differential avian host and vector competence phenotypes independent of E-protein glycosylation status.

The Togaviridae is a family of small, enveloped viruses with single-stranded, positive-sense RNA genomes of 10-12 kb. Within the family, the genus Alphavirus includes a large number of diverse species, while the genus Rubivirus includes the single species Rubella virus. Most alphaviruses are mosquito-borne and are pathogenic in their vertebrate hosts. Many are important human and veterinary pathogens (e.g. chikungunya virus and eastern equine encephalitis virus). Rubella virus is transmitted by respiratory routes among humans. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of the Togaviridae, which is available at www.ictv.global/report/togaviridae.

West Nile virus (WNV) is enzootic in northern Colorado. Annual surveillance activities in Fort Collins, CO, include collecting female Culex mosquitoes and testing them for the presence of WNV RNA in order to calculate 1) Culex female abundance, 2) WNV infection rate, and 3) the vector index (VI). These entomological risk indices inform public policy regarding the need for emergency adulticiding. Currently, these are calculated on a city-wide basis. In this study, we present descriptive data from historical surveillance records spanning 2006-2013 to discern seasonal and yearly patterns of entomological risk for WNV infection. Also, we retrospectively test the hypothesis that entomological risk is correlated with human transmission risk and is heterogeneous within the City of Fort Collins. Four logistically relevant zones within the city were established and used to test this hypothesis. Zones in the eastern portion of the city consistently had significantly higher Culex abundance and VI compared with zones in the west, leading to higher entomological risk indicators for human WNV infection in the east. Moreover, the relative risk of a reported human case of WNV infection was significantly higher in the eastern zones of the city. Our results suggest that a more spatially targeted WNV management program may better mitigate human risk for WNV infection in Fort Collins, and possibly other cities where transmission is enzootic, while at the same time reducing pesticide use.

St. Louis encephalitis virus (SLEV) has shown greater susceptibility to oral infectivity than West Nile virus (WNV) in Culex mosquitoes. To identify the viral genetic elements that modulate these disparate phenotypes, structural chimeras (WNV-pre-membrane [prM] and envelope [E] proteins [prME]/SLEV.IC and SLEV-prME/WNV.IC) were constructed in which two of the structural proteins, the prM and E, were interchanged between viruses. Oral dose-response assessment with the chimeric/parental WNV and SLEV was performed to characterize the infection phenotypes in Culex mosquitoes by artificial oral blood meals. The median infectious dose required to infect 50% of Cx. quinquefasciatus with WNV was indistinguishable from that of the SLEV-prME/WNV.IC chimeric virus. Similarly, SLEV and WNV-prME/SLEV.IC virus exhibited an indistinguishable oral dose-response relationship in Cx. quinquefasciatus. Infection rates for WNV.IC and SLEV-prME/WNV.IC were significantly lower than SLEV.IC and WNV-prME/SLEV.IC infection rates. These results indicated that WNV and SLEV oral infectivities are not mediated by genetic differences within the prM and E proteins.

BACKGROUND: We have developed a manufacturing strategy that can improve the safety and genetic stability of recombinant live-attenuated chimeric dengue vaccine (DENVax) viruses. These viruses, containing the pre-membrane (prM) and envelope (E) genes of dengue serotypes 1-4 in the replicative background of the attenuated dengue-2 PDK-53 vaccine virus candidate, were manufactured under cGMP. METHODOLOGY/PRINCIPAL FINDINGS: After deriving vaccine viruses from RNA-transfected Vero cells, six plaque-purified viruses for each serotype were produced. The plaque-purified strains were then analyzed to select one stock for generation of the master seed. Full genetic and phenotypic characterizations of the master virus seeds were conducted to ensure these viruses retained the previously identified attenuating determinants and phenotypes of the vaccine viruses. We also assessed vector competence of the vaccine viruses in sympatric (Thai) Aedes aegypti mosquito vectors. CONCLUSION/SIGNIFICANCE: All four serotypes of master vaccine seeds retained the previously defined safety features, including all three major genetic loci of attenuation, small plaques, temperature sensitivity in mammalian cells, reduced replication in mosquito cell cultures, and reduced neurovirulence in new-born mice. In addition, the candidate vaccine viruses demonstrated greatly reduced infection and dissemination in Aedes aegypti mosquitoes, and are not likely to be transmissible by these mosquitoes. This manufacturing strategy has successfully been used to produce the candidate tetravalent vaccine, which is currently being tested in human clinical trials in the United States, Central and South America, and Asia.

We established a laboratory colony of Culex pipiens mosquitoes from eggs collected in Colorado and discovered that mosquitoes in the colony are naturally infected with Culex flavivirus (CxFV), an insect-specific flavivirus. In this study we examined transmission dynamics of CxFV and effects of persistent CxFV infection on vector competence for West Nile virus (WNV). We found that vertical transmission is the primary mechanism for persistence of CxFV in Cx. pipiens, with venereal transmission potentially playing a minor role. Vector competence experiments indicated possible early suppression of WNV replication by persistent CxFV infection in Cx. pipiens. This is the first description of insect-specific flavivirus transmission dynamics in a naturally infected mosquito colony and the observation of delayed dissemination of superinfecting WNV suggests that the presence of CxFV may impact the intensity of enzootic transmission of WNV and the risk of human exposure to this important pathogen.

This study determined the transovarial transmission (TOT) potential and tissue tropisms of Culex flavivirus (CxFV), an insect-specific flavivirus, in Culex pipiens (L.). Several hundred mosquito egg rafts were collected in the field, transferred to the insectaries, reared to the fourth larval instar, and identified using morphological characteristics. Cx. pipiens were reared to adults, allowed to oviposit in individual containers, and tested for CxFV RNA by reverse transcription-polymerase chain reaction (RT-PCR) and nucleotide sequencing. Eighteen CxFV RNA-positive females were identified from 26 females that oviposited viable egg rafts. Thirty F1 adults from each positive female were individually tested by RT-PCR for CxFV RNA. Viral RNA was detected in 526 of 540 progeny, and thus, the filial infection rate was 97.4%. Because all 18 positive females produced infected offspring, the TOT prevalence was 100%. These data indicated that efficient TOT of CxFV occurs in nature. To define the tissue tropisms of CxFV, different tissues (salivary glands, ovaries, testes, head, fat bodies, and midguts) were removed from the remainder of the F1 and tested by RT-PCR for CxFV RNA. Viral RNA was detected in all tissues. Additionally, uninfected laboratory-colonized Cx. pipiens were infected with CxFV by needle inoculation, and ovaries were collected at 4, 6, 8, and 12 d postinoculation and tested for CxFV RNA by RT-PCR. Viral RNA was detected at all time points, demonstrating that CxFV infects the ovaries as early as 4 d postinoculation. Surprisingly, however, we were unable to demonstrate transovarial transmission despite the presence of viral RNA in the ovaries. Nevertheless, the experiments performed with field-infected Cx. pipiens demonstrate that TOT is an efficient mechanism by which CxFV is maintained in mosquitoes in nature.

Mosquitoes were collected in Colorado during 2006 and 2007 to examine spatial and seasonal patterns of risk for exposure to Culex vectors and West Nile virus. We used universal flavivirus primers to test pools of Culex mosquitoes for viral RNA. This led to the detection and subsequent isolation of two insect-specific flaviviruses: Culex flavivirus (CxFV), which was first described from Japan, and a novel insect flavivirus, designated Calbertado virus (CLBOV), which has also been detected in California and Canada. We recorded both viruses in Cx. tarsalis and Cx. pipiens from Colorado. Furthermore, quantitative reverse transcription polymerase chain reaction (RT-PCR) revealed the presence of CxFV RNA in Cx. pipiens eggs and larvae from a laboratory colony established in 2005 and naturally infected with CxFV, suggesting vertical transmission as a means of viral maintenance in natural Culex populations. Finally, we present phylogenetic analyses of the relationships between insect-specific flaviviruses and other selected flaviviruses.

In a previous study, a new flavivirus genome sequence was identified in Culex tarsalis mosquitoes obtained in Alberta, Canada and was shown to be genetically related to but distinct from members of the insect-specific flaviviruses. Nonstructural protein 5-encoding sequences amplified from Cx. tarsalis pools from western Canada have shown a high similarity to genome sequences of novel flaviviruses isolated from mosquitoes in California and Colorado. Despite wide distribution of this virus, designated Calbertado virus, strains demonstrate a high degree of nonstructural protein 5 nucleotide (> 90%) and amino acid (> 97%) identity. The ecology and geographic range of Calbertado virus warrants further study because it may potentially influence transmission of mosquito-borne flaviviruses, including important human pathogens such as West Nile and Saint Louis encephalitis viruses.