Detection of Hantavirus during the COVID-19 Pandemic, Arizona, USA, 2020.

We identified 2 fatal cases of persons infected with hantavirus in Arizona, USA, 2020; 1 person was co-infected with SARS-CoV-2. Delayed identification of the cause of death led to a public health investigation that lasted ≈9 months after their deaths, which complicated the identification of a vector or exposure.

Soft Tick Relapsing Fever - United States, 2012-2021.

Soft tick relapsing fever (STRF) (also known as tickborne relapsing fever) is a rare infection caused by certain Borrelia spirochetes and transmitted to humans by soft-bodied Ornithodoros ticks. In the United States, acquisition of STRF is commonly associated with exposure to rustic cabins, camping, and caves. Antibiotic treatment is highly effective for STRF, but without timely treatment, STRF can result in severe complications, including death. No nationally standardized case definition for STRF exists; however, the disease is reportable in 12 states. This report summarizes demographic and clinical information for STRF cases reported during 2012-2021 from states where STRF is reportable. During this period, 251 cases were identified in 11 states. The median annual case count was 24. Most patients with STRF (55%) were hospitalized; no fatalities were reported. The geographic distribution and seasonal pattern of STRF have remained relatively constant since the 1990s. Persons should avoid rodent-infested structures and rodent habitats, such as caves, in areas where STRF is endemic. STRF surveillance, prevention, and control efforts would benefit from a standardized case definition and increased awareness of the disease among the public and clinicians.

"Sniffing" out SARS-CoV-2 in Arizona working dogs: an exploratory serosurvey.

Susceptibility to and infection with SARS-CoV-2 in companion animals has been well-documented throughout the COVID-19 pandemic. Surveillance for the virus in dogs has largely been focused on household pets; however, other canine populations may also be impacted. We partnered with a local veterinary hospital with a high working dog patient volume to conduct viral and neutralizing antibody testing in working dogs and identify potential risk factors in the dog's work and home environments. Surveillance of SARS-CoV-2 in law enforcement and security working dogs in Arizona found 24.81% (32/129) of dogs to be seropositive. Thirteen dogs presenting with clinical signs or with reported exposure to COVID-19 in the 30 days prior to sample collection were also tested by PCR; all samples were negative. 90.7% (n = 117) of dogs were reported to be asymptomatic or have no change in performance at the time of sampling. Two dogs (1.6%) had suspected anosmia as reported by their handlers; one of which was seropositive. Known exposure to the dog's COVID-19 positive handler or household member was identified as a significant risk factor. Demographics factors including sex, altered status, and type of work were not associated with canine seropositivity. Further work is warranted to understand the impact of SARS-CoV-2 and other infectious diseases in working dogs.

Unprecedented Outbreak of West Nile Virus - Maricopa County, Arizona, 2021.

West Nile virus (WNV) is a mosquitoborne disease primarily transmitted through bites of infected Culex species mosquitos (1). In the United States, WNV is the leading domestically acquired arboviral disease; it can cause severe illness affecting the brain and spinal cord with an associated case fatality rate of 10% (2,3). On September 2, 2021, Maricopa County Environmental Services Department, Vector Control Division (MCESD-VCD) notified the Maricopa County Department of Public Health (MCDPH) and the Arizona Department of Health Services (ADHS) that the WNV vector index (VI), a measure of infected Culex mosquitoes, was substantially elevated. By that date, at least 100 WNV cases had already been reported among Maricopa County residents to MCDPH by health care providers and laboratories. Within 2 weeks, the VI reached its highest ever recorded level (53.61), with an associated tenfold increase in the number of human disease cases. During 2021, a total of 1,487 human WNV cases were identified; 956 (64.3%) patients had neuroinvasive disease, and 101 (6.8%) died. MCESD-VCD conducted daily remediation efforts to mitigate elevated VI and address mosquito-related complaints from residents (i.e., large numbers of outdoor mosquitoes from an unknown source and unmaintained swimming pools potentially breeding mosquitoes). MCDPH increased outreach to the community and providers through messaging, education events, and media. This was the largest documented focal WNV outbreak in a single county in the United States (4). Despite outreach efforts to communities and health care partners, clinicians and patients reported a lack of awareness of the WNV outbreak, highlighting the need for public health agencies to increase prevention messaging to broaden public awareness and to ensure that health care providers are aware of recommended testing methods for clinically compatible illnesses.

Burkholderia pseudomallei Laboratory Exposure, Arizona, USA.

We describe an incidental Burkholderia pseudomallei laboratory exposure in Arizona, USA. Because melioidosis cases are increasing in the United States and B. pseudomallei reservoirs have been discovered in the Gulf Coast Region, US laboratory staff could be at increased risk for B. pseudomallei exposure.

Epidemiologic and Clinical Characteristics of Monkeypox Cases - United States, May 17-July 22, 2022.

Monkeypox, a zoonotic infection caused by an orthopoxvirus, is endemic in parts of Africa. On August 4, 2022, the U.S. Department of Health and Human Services declared the U.S. monkeypox outbreak, which began on May 17, to be a public health emergency (1,2). After detection of the first U.S. monkeypox case), CDC and health departments implemented enhanced monkeypox case detection and reporting. Among 2,891 cases reported in the United States through July 22 by 43 states, Puerto Rico, and the District of Columbia (DC), CDC received case report forms for 1,195 (41%) cases by July 27. Among these, 99% of cases were among men; among men with available information, 94% reported male-to-male sexual or close intimate contact during the 3 weeks before symptom onset. Among the 88% of cases with available data, 41% were among non-Hispanic White (White) persons, 28% among Hispanic or Latino (Hispanic) persons, and 26% among non-Hispanic Black or African American (Black) persons. Forty-two percent of persons with monkeypox with available data did not report the typical prodrome as their first symptom, and 46% reported one or more genital lesions during their illness; 41% had HIV infection. Data suggest that widespread community transmission of monkeypox has disproportionately affected gay, bisexual, and other men who have sex with men and racial and ethnic minority groups. Compared with historical reports of monkeypox in areas with endemic disease, currently reported outbreak-associated cases are less likely to have a prodrome and more likely to have genital involvement. CDC and other federal, state, and local agencies have implemented response efforts to expand testing, treatment, and vaccination. Public health efforts should prioritize gay, bisexual, and other men who have sex with men, who are currently disproportionately affected, for prevention and testing, while addressing equity, minimizing stigma, and maintaining vigilance for transmission in other populations. Clinicians should test patients with rash consistent with monkeypox,† regardless of whether the rash is disseminated or was preceded by prodrome. Likewise, although most cases to date have occurred among gay, bisexual, and other men who have sex with men, any patient with rash consistent with monkeypox should be considered for testing. CDC is continually evaluating new evidence and tailoring response strategies as information on changing case demographics, clinical characteristics, transmission, and vaccine effectiveness become available.§.

Genomic investigation of a household SARS-CoV-2 disease cluster in Arizona involving a cat, dog, and pet owner.

Arizona's COVID-19 and Pets Program is a prospective surveillance study being conducted to characterize how SARS-CoV-2 impacts companion animals living in households with SARS-CoV-2-positive individuals. Among the enrolled pets, we identified a SARS-CoV-2-infected cat and dog from the same household; both animals were asymptomatic but had close contact with the symptomatic and SARS-CoV-2-positive owner. Whole genome sequencing of animal and owner specimens revealed identical viral genomes of the B.1.575 lineage, suggesting zoonotic transmission of SARS-CoV-2 from human to at least one pet. This is the first report of the B.1.575 lineage in companion animals. Genetically linking SARS-CoV-2 between people and animals, and tracking changes in SARS-CoV-2 genomes is essential to detect any cross-species SARS-CoV-2 transmission that may lead to more transmissible or severe variants that can affect humans. Surveillance studies, including genomic analyses of owner and pet specimens, are needed to further our understanding of how SARS-CoV-2 impacts companion animals.

Understanding Mosquito Surveillance Data for Analytic Efforts: A Case Study.

Mosquito surveillance data can be used for predicting mosquito distribution and dynamics as they relate to human disease. Often these data are collected by independent agencies and aggregated to state and national level portals to characterize broad spatial and temporal dynamics. These larger repositories may also share the data for use in mosquito and/or disease prediction and forecasting models. Assumed, but not always confirmed, is consistency of data across agencies. Subtle differences in reporting may be important for development and the eventual interpretation of predictive models. Using mosquito vector surveillance data from Arizona as a case study, we found differences among agencies in how trapping practices were reported. Inconsistencies in reporting may interfere with quantitative comparisons if the user has only cursory familiarity with mosquito surveillance data. Some inconsistencies can be overcome if they are explicit in the metadata while others may yield biased estimates if they are not changed in how data are recorded. Sharing of metadata and collaboration between modelers and vector control agencies is necessary for improving the quality of the estimations. Efforts to improve sharing, displaying, and comparing vector data from multiple agencies are underway, but existing data must be used with caution.

Culture of Clinical Specimens Reveals Extensive Diversity of Legionella pneumophila Strains in Arizona.

Between 2000 and 2017, a total of 236 Legionella species isolates from Arizona were submitted to the CDC for reference testing. Most of these isolates were recovered from bronchoalveolar lavage specimens. Although the incidence of legionellosis in Arizona is less than the overall U.S. incidence, Arizona submits the largest number of isolates to the CDC for testing compared to those from other states. In addition to a higher proportion of culture confirmation of legionellosis cases in Arizona than in other states, all Legionellapneumophila isolates are forwarded to the CDC for confirmatory testing. Compared to that from other states, a higher proportion of isolates from Arizona were identified as belonging to L. pneumophila serogroups 6 (28.2%) and 8 (8.9%). Genome sequencing was conducted on 113 L. pneumophila clinical isolates not known to be associated with outbreaks in order to understand the genomic diversity of strains causing legionellosis in Arizona. Whole-genome multilocus sequence typing (wgMLST) revealed 17 clusters of isolates sharing at least 99% identical allele content. Only two of these clusters contained isolates from more than one individual with exposure at the same facility. Additionally, wgMLST analysis revealed a group of 31 isolates predominantly belonging to serogroup 6 and containing isolates from three separate clusters. Single nucleotide polymorphism (SNP) and pangenome analysis were used to further resolve genome sequences belonging to a subset of isolates. This study demonstrates that culture of clinical specimens for Legionella spp. reveals a highly diverse population of strains causing legionellosis in Arizona which could be underappreciated using other diagnostic approaches.IMPORTANCE Culture of clinical specimens from patients with Legionnaires' disease is rarely performed, restricting our understanding of the diversity and ecology of Legionella Culture of Legionella from patient specimens in Arizona revealed a greater proportion of non-serogroup 1 Legionellapneumophila isolates than in other U.S. isolates examined. Disease caused by such isolates may go undetected using other diagnostic methods. Moreover, genome sequence analysis revealed that these isolates were genetically diverse, and understanding these populations may help in future environmental source attribution studies.

Dengue Knowledge, Attitudes, and Practices Among Arizona Health Care Providers, 2014-2015.

Background: Detection of local dengue transmission requires an aware and engaged medical community, as health care providers are the front line of public health surveillance. To assess the knowledge, attitude, and practice about dengue, an online survey was distributed among Arizona health care providers during 2014 and 2015. Materials and Methods: The survey consisted of a total of 10 knowledge, attitude, and practice questions divided as follows: 5 knowledge questions, 2 attitude questions, and 3 practice questions. The link to the Qualtrics survey was distributed through the Arizona Health Alert Network to a total of 4582 e-mail addresses, of which 335 participants opened the survey, and 196 completed and submitted their responses. Results: Less than half the respondents reported choosing the right dengue diagnostic test (40.4%) or understanding the epidemiology of dengue in Arizona (40.9%). Slightly more than half the respondents reported frequently asking for travel history (59%), and three-fourth of them would notify the local health department on suspicion of a dengue patient (76.1%). Survey score was associated with providers specialized in infectious diseases (1.88, 95% CI: 0.42-3.33, p = 0.01), medical doctors or doctors of osteopathic medicine (1.82, 95% CI: 0.98-2.65, p < 0.0001), and respondents who reported to have heard about the increase in dengue cases in Sonora (Mexico) in fall 2014 (1.51, 95% CI: 0.67-2.34, p = 0.0005), indicating better survey performance. Conclusions: These results indicate that education for health care providers on dengue should be improved particularly among general practice noninfectious disease providers who might be the first point of care for dengue patients. Findings suggest that additional training on clinical management, asking travel history, and notifying the local health department on suspicion of a dengue patient are needed.

Comparing ownership and use of bed nets at two sites with differential malaria transmission in western Kenya.

BACKGROUND: Challenges persist in ensuring access to and optimal use of long-lasting, insecticidal bed nets (LLINs). Factors associated with ownership and use may differ depending on the history of malaria and prevention control efforts in a specific region. Understanding how the cultural and social-environmental context of bed net use may differ between high- and low-risk regions is important when identifying solutions to improve uptake and appropriate use. METHODS: Community forums and a household, cross-sectional survey were used to collect information on factors related to bed net ownership and use in western Kenya. Sites with disparate levels of transmission were selected, including an endemic lowland area, Miwani, and a highland epidemic-prone area, Kapkangani. Analysis of ownership was stratified by site. A combined site analysis was conducted to examine factors associated with use of all available bed nets. Logistic regression modelling was used to determine factors associated with ownership and use of owned bed nets. RESULTS: Access to bed nets as the leading barrier to their use was identified in community forums and cross-sectional surveys. While disuse of available bed nets was discussed in the forums, it was a relatively rare occurrence in both sites. Factors associated with ownership varied by site. Education, perceived risk of malaria and knowledge of individuals who had died of malaria were associated with higher bed net ownership in the highlands, while in the lowlands individuals reporting it was easy to get a bed net were more likely to own one. A combined site analysis indicated that not using an available bed net was associated with the attitudes that taking malaria drugs is easier than using a bed net and that use of a bed net will not prevent malaria. In addition, individuals with an unused bed net in the household were more likely to indicate that bed nets are difficult to use, that purchased bed nets are better than freely distributed ones, and that bed nets should only be used during the rainy season. CONCLUSION: Variations in factors associated with ownership should be acknowledged when constructing messaging and distribution campaigns. Despite reports of bed nets being used for other purposes, those in the home were rarely unused in these communities. Disuse seemed to be related to beliefs that can be addressed through education programmes. As mass distributions continue to take place, additional research is needed to determine if factors associated with LLIN ownership and use change with increasing availability of LLIN.

The availability and consistency of dengue surveillance data provided online by the World Health Organization.

BACKGROUND: The use of high quality disease surveillance data has become increasingly important for public health action against new threats. In response, countries have developed a wide range of disease surveillance systems enabled by technological advancements. The heterogeneity and complexity of country data systems have caused a growing need for international organizations such as the World Health Organization (WHO) to coordinate the standardization, integration, and dissemination of country disease data at the global level for research and policy. The availability and consistency of currently available disease surveillance data at the global level are unclear. We investigated this for dengue surveillance data provided online by the WHO. METHODS AND FINDINGS: We extracted all dengue surveillance data provided online by WHO Headquarters and Regional Offices (RO's). We assessed the availability and consistency of these data by comparing indicators within and between sources. We also assessed the consistency of dengue data provided online by two example countries (Brazil and Indonesia). Data were available from WHO for 100 countries since 1955 representing a total of 23 million dengue cases and 82 thousand deaths ever reported to WHO. The availability of data on DengueNet and some RO's declined dramatically after 2005. Consistency was lacking between sources (84% across all indicators representing a discrepancy of almost half a million cases). Within sources, data at high spatial resolution were often incomplete. CONCLUSIONS: The decline of publicly available, integrated dengue surveillance data at the global level will limit opportunities for research, policy, and advocacy. A new financial and operational framework will be necessary for innovation and for the continued availability of integrated country disease data at the global level.

Knowledge, attitudes and practices of malaria control among communities from the health district of Forécariah in the Republic of Guinea, West Africa.

BACKGROUND & OBJECTIVES: Malaria is the leading cause of death in children under 5-yr of age in the Republic of Guinea. This study aimed at investigating the knowledge, attitudes and practices of malaria control in urban and rural communities in Guinea in order to better target future health interventions. METHODS: A cross-sectional survey of 200 randomly selected households was conducted in an urban site and in three rural villages within the health district of Forιcariah using two semi-structured questionnaires. RESULTS: Only 18.5% of the respondents were aware of the role of mosquitoes in the transmission of malaria in both urban and rural households. Mosquito nets were identified as a malaria prevention method by 11.5% of the participants and only 8.5% of the respondents mentioned stagnant water as a potential mosquito breeding site. Households' heads were more aware of mosquito control methods, with 56 and 42% of the respondents recognizing that bednets or insecticidal coils can protect from mosquitoes, respectively. Despite the limited knowledge of malaria transmission and prevention, 55% of the households owned at least one long-lasting insecticide-treated net (LLIN) and 79% of the net-owning households slept under a net/LLIN the night before the survey. INTERPRETATION & CONCLUSION: In order to maximize the benefits of malaria control strategies, health education should be implemented, building on the higher awareness of mosquito control methods and stressing the role of vectors in transmitting the disease.

Independent pathways can transduce the life-cycle differentiation signal in Trypanosoma brucei.

African trypanosomes cause disease in humans and livestock, generating significant health and welfare problems throughout sub-Saharan Africa. When ingested in a tsetse fly bloodmeal, trypanosomes must detect their new environment and initiate the developmental responses that ensure transmission. The best-established environmental signal is citrate/cis aconitate (CCA), this being transmitted through a protein phosphorylation cascade involving two phosphatases: one that inhibits differentiation (TbPTP1) and one that activates differentiation (TbPIP39). Other cues have been also proposed (mild acid, trypsin exposure, glucose depletion) but their physiological relevance and relationship to TbPTP1/TbPIP39 signalling is unknown. Here we demonstrate that mild acid and CCA operate through TbPIP39 phosphorylation, whereas trypsin attack of the parasite surface uses an alternative pathway that is dispensable in tsetse flies. Surprisingly, glucose depletion is not an important signal. Mechanistic analysis through biophysical methods suggests that citrate promotes differentiation by causing TbPTP1 and TbPIP39 to interact.

Investigating mammalian tyrosine phosphatase inhibitors as potential 'piggyback' leads to target Trypanosoma brucei transmission.

African trypanosomiasis is a neglected tropical disease affecting humans and animals across 36 sub-Saharan African countries. We have investigated the potential to exploit a 'piggyback' approach to inhibit Trypanosoma brucei transmission by targeting the key developmental regulator of transmission, T. brucei protein tyrosine phosphatase 1. This strategy took advantage of the extensive investment in inhibitors for human protein tyrosine phosphatase 1B, a key target for pharmaceutical companies for the treatment of obesity and diabetes. Structural predictions for human and trypanosome tyrosine phosphatases revealed the overall conservation of important functional motifs, validating the potential for exploiting cross specific compounds. Thereafter, nineteen inhibitors were evaluated; seventeen from a protein tyrosine phosphatase 1B-targeted inhibitor library and two from literature analysis - oleanolic acid and suramin, the latter of which is a front line drug against African trypanosomiasis. The compounds tested displayed similar inhibitory activities against the human and trypanosome enzymes, mostly behaving as noncompetitive inhibitors. However, their activity against T. brucei in culture was low, necessitating further chemical modification to improve their efficacy and specificity. Nonetheless, the results validate the potential to explore a 'piggyback' strategy targeting T. brucei protein tyrosine phosphatase 1 through exploiting the large pharmacological investment in therapies for obesity targeting protein tyrosine phosphatase 1B.

A novel phosphatase cascade regulates differentiation in Trypanosoma brucei via a glycosomal signaling pathway.

In the mammalian bloodstream, the sleeping sickness parasite Trypanosoma brucei is held poised for transmission by the activity of a tyrosine phosphatase, TbPTP1. This prevents differentiation of the transmissible "stumpy forms" until entry into the tsetse fly, whereupon TbPTP1 is inactivated and major changes in parasite physiology are initiated to allow colonization of the arthropod vector. Using a substrate-trapping approach, we identified the downstream step in this developmental signaling pathway as a DxDxT phosphatase, TbPIP39, which is activated upon tyrosine phosphorylation, and hence is negatively regulated by TbPTP1. In vitro, TbPIP39 promotes the activity of TbPTP1, thereby reinforcing its own repression, this being alleviated by the trypanosome differentiation triggers citrate and cis-aconitate, generating a potentially bistable regulatory switch. Supporting a role in signal transduction, TbPIP39 becomes rapidly tyrosine-phosphorylated during differentiation, and RNAi-mediated transcript ablation in stumpy forms inhibits parasite development. Interestingly, TbPIP39 localizes in glycosomes, peroxisome-like organelles that compartmentalize the trypanosome glycolytic reactions among other enzymatic activities. Our results invoke a phosphatase signaling cascade in which the developmental signal is trafficked to a unique metabolic organelle in the parasite: the glycosome. This is the first characterized environmental signaling pathway targeted directly to a peroxisome-like organelle in any eukaryotic cell.