An atlas of human vector-borne microbe interactions reveals pathogenicity mechanisms.

Vector-borne diseases are a leading cause of death worldwide and pose a substantial unmet medical need. Pathogens binding to host extracellular proteins (the "exoproteome") represents a crucial interface in the etiology of vector-borne disease. Here, we used bacterial selection to elucidate host-microbe interactions in high throughput (BASEHIT)-a technique enabling interrogation of microbial interactions with 3,324 human exoproteins-to profile the interactomes of 82 human-pathogen samples, including 30 strains of arthropod-borne pathogens and 8 strains of related non-vector-borne pathogens. The resulting atlas revealed 1,303 putative interactions, including hundreds of pairings with potential roles in pathogenesis, including cell invasion, tissue colonization, immune evasion, and host sensing. Subsequent functional investigations uncovered that Lyme disease spirochetes recognize epidermal growth factor as an environmental cue of transcriptional regulation and that conserved interactions between intracellular pathogens and thioredoxins facilitate cell invasion. In summary, this interactome atlas provides molecular-level insights into microbial pathogenesis and reveals potential host-directed targets for next-generation therapeutics.

Pathogen prospecting of museums: Reconstructing malaria epidemiology.

Malaria is a disease of global significance. Ongoing changes to the earth's climate, antimalarial resistance, insecticide resistance, and socioeconomic decline test the resilience of malaria prevention programs. Museum insect specimens present an untapped resource for studying vector-borne pathogens, spurring the question: Do historical mosquito collections contain Plasmodium DNA, and, if so, can museum specimens be used to reconstruct the historical epidemiology of malaria? In this Perspective, we explore molecular techniques practical to pathogen prospecting, which, more broadly, we define as the science of screening entomological museum specimens for human, animal, or plant pathogens. Historical DNA and pathogen prospecting provide a means of describing the coevolution of human, vector, and parasite, informing the development of insecticides, diagnostics, therapeutics, and vaccines.

Malaria: influence of Anopheles mosquito saliva on Plasmodium infection.

Malaria is caused by Plasmodium protozoa that are transmitted by anopheline mosquitoes. Plasmodium sporozoites are released with saliva when an infected female mosquito takes a blood meal on a vertebrate host. Sporozoites deposited into the skin must enter a blood vessel to start their journey towards the liver. After migration out of the mosquito, sporozoites are associated with, or in proximity to, many components of vector saliva in the skin. Recent work has elucidated how Anopheles saliva, and components of saliva, can influence host-pathogen interactions during the early stage of Plasmodium infection in the skin. Here, we discuss how components of Anopheles saliva can modulate local host responses and affect Plasmodium infectivity. We hypothesize that therapeutic strategies targeting mosquito salivary proteins can play a role in controlling malaria and other vector-borne diseases.

Neurological manifestations of Flaviviridae, Togaviridae, and Peribunyaviridae as vector-borne viruses.

Vector-borne viruses pose a significant health problem worldwide, as they are transmitted to humans through the bite of infected arthropods such as mosquitoes and ticks. In recent years, emerging and re-emerging vector-borne diseases have gained attention as they can cause a wide spectrum of neurological manifestations. The neurological manifestations of vector-borne viruses encompass a board spectrum of clinical manifestations, ranging from mild and self-limiting symptoms to severe and life-threatening conditions. Common neurological complications include viral encephalitis, acute flaccid paralysis, aseptic meningitis, and various neuromuscular disorders. The specific viruses responsible for these neurological sequelae vary by geographic region and include Orthoflavivirus nilense, Zika virus, dengue virus, chikungunya virus, Japanese encephalitis virus, and tick-borne encephalitis virus. This review focuses on the pathogenesis of these neurologic complications and highlights the mechanisms by which vector-borne viruses invade the central nervous system and trigger neuroinflammatory responses. Diagnostic challenges and strategies for early detection of neurological manifestations are discussed, emphasising the importance of clinical suspicion and advanced laboratory testing.

Discovering disease-causing pathogens in resource-scarce Southeast Asia using a global metagenomic pathogen monitoring system.

SignificanceMetagenomic pathogen sequencing offers an unbiased approach to characterizing febrile illness. In resource-scarce settings with high biodiversity, it is critical to identify disease-causing pathogens in order to understand burden and to prioritize efforts for control. Here, metagenomic next-generation sequencing (mNGS) characterization of the pathogen landscape in Cambodia revealed diverse vector-borne and zoonotic pathogens irrespective of age and gender as risk factors. Identification of key pathogens led to changes in national program surveillance. This study is a "real world" example of the use of mNGS surveillance of febrile individuals, executed in-country, to identify outbreaks of vector-borne, zoonotic, and other emerging pathogens in a resource-scarce setting.

Alarming Trends in Dengue Incidence and Mortality in Bangladesh.

Bangladesh is currently experiencing the country's largest and deadliest dengue outbreak on record. This year's outbreak has been characterized by an early seasonal surge in cases, rapid geographic spread, and a high fatality rate. The alarming trends in dengue incidence and mortality this year is an urgent wake-up call for public health policymakers and researchers to pay closer attention to dengue dynamics in South Asia, to strengthen the surveillance system and diagnostic capabilities, and to develop tools and methods for guiding strategic resource allocation and control efforts.

Biology, Ecology, and Management of the Potato Psyllid, Bactericera cockerelli (Hemiptera: Triozidae), and Zebra Chip Disease in Potato.

The potato psyllid, Bactericera cockerelli (Sulc) (Hemiptera: Triozidae), transmits the pathogen "Candidatus liberibacter solanacearum" (Lso), the putative causal agent of zebra chip disease (ZC). ZC is a disease of potato that reduces yield and quality and has disrupted integrated pest management programs in parts of the Americas and New Zealand. Advances in our understanding of the ecological factors that influence ZC epidemiology have been accelerated by the relatively recent identification of Lso and motivated by the steady increase in ZC distribution and the potential for devastating economic losses on a global scale. Management of ZC remains heavily reliant upon insecticides, which is not sustainable from the standpoint of insecticide resistance, nontarget effects on natural enemies, and regulations that may limit such tools. This review synthesizes the literature on potato psyllids and ZC, outlining recent progress, identifying knowledge gaps, and proposing avenues for further research on this important pathosystem of potatoes.

Plasmodium parasitophorous vacuole membrane protein Pfs16 promotes malaria transmission by silencing mosquito immunity.

With rising cases for the first time in years, malaria remains a significant public health burden. The sexual stage of the malaria parasite infects mosquitoes to transmit malaria from host to host. Hence, an infected mosquito plays an essential role in malaria transmission. Plasmodium falciparum is the most dominant and dangerous malaria pathogen. Previous studies identified a sexual stage-specific protein 16 (Pfs16) localized to the parasitophorous vacuole membrane. Here, we elucidate the function of Pfs16 during malaria transmission. Our structural analysis identified Pfs16 as an alpha-helical integral membrane protein with one transmembrane domain connecting to two regions across parasitophorous vacuole membrane. ELISA assays showed that insect cell-expressed recombinant Pfs16 (rPfs16) interacted with Anopheles gambiae midguts, and microscopy found that rPfs16 was bound to midgut epithelial cells. Transmission-blocking assays demonstrated that polyclonal antibodies against Pfs16 significantly reduced the number of oocysts in mosquito midguts. However, on the contrary, feeding rPfs16 increased the number of oocysts. Further analysis revealed that Pfs16 reduced the activity of mosquito midgut caspase 3/7, a key enzyme in the mosquito Jun-N-terminal kinase immune pathway. We conclude that Pfs16 facilitates parasites to invade mosquito midguts by actively silencing the mosquito's innate immunity through its interaction with the midgut epithelial cells. Therefore, Pfs16 is a potential target to control malaria transmission.

The plasmid-encoded members of paralogous gene family 52 are dispensable to the enzootic cycle of Borrelia burgdorferi.

Lyme disease, the leading vector-borne disease in the United States and Europe, develops after infection with Borrelia burgdorferi sensu lato bacteria. Transmission of the spirochete from the tick vector to a vertebrate host requires global changes in gene expression that are controlled, in part, by the Rrp2/RpoN/RpoS alternative sigma factor cascade. Transcriptional studies defining the B. burgdorferi RpoS regulon have suggested that RpoS activates the transcription of paralogous family 52 (PFam52) genes. In strain B31, PFam52 genes (bbi42, bbk53, and bbq03) encode a set of conserved hypothetical proteins with >89% amino acid identity that are predicted to be surface-localized. Extensive homology among members of paralogous families complicates studies of protein contributions to pathogenicity as the potential for functional redundancy will obfuscate findings. Using a sequential mutagenesis approach, we generated clones expressing a single PFam52 paralog, as well as a strain deficient in all three. The single paralog expressing strains were used to confirm BBI42, BBK53, and BBQ03 surface localization and RpoS regulation. Surprisingly, the PFam52-deficient strain was able to infect mice and complete the enzootic cycle similar to the wild-type parental strain. Indeed, the presence of numerous pseudogenes that contain frameshifts or internal stop codons among the PFam52 genes suggests that they may be subjected to gene loss in B. burgdorferi's reduced genome. Alternatively, the lack of phenotype might reflect the limitations of the experimental mouse infection model.

Francisella tularensis Bone and Joint Infections: United States, 2004-2023.

Tularemia is caused by the highly infectious bacterium Francisella tularensis, which is recognized as a Tier 1 bioterrorism agent. Tularemia has a range of recognized clinical manifestations, but fewer than 20 bone or joint infections from 6 countries have been reported in the literature to date. This series includes 13 cases of F. tularensis septic arthritis or osteomyelitis in the United States during 2004-2023 and describes exposures, clinical presentation, diagnosis, and outcomes for this rare but severe form of tularemia. Clinicians should consider F. tularensis in patients with compatible exposures or a history of joint replacement or immunosuppression.

Spatiotemporal Epidemiology of Oropouche Fever, Brazil, 2015-2024.

We assessed the spatiotemporal dynamics of Oropouche fever in Brazil during 2015-2024. We found the number of cases substantially increased during that period, particularly in the Amazon region. Our findings underscore the need for improved surveillance and public health measures in response to the disease's potential spread beyond endemic areas.

Oropouche Fever, Cuba, May 2024.

Phylogenetic analyses showed that the virus responsible for a May 2024 Oropouche fever outbreak in Cuba was closely related to viruses from Brazil in 2023. Pools of Ceratopogonidae spp. biting midges and Culex quinquefasciatus mosquitoes were positive for Oropouche viral RNA. No cases were severe. Virus extension to new areas may increase case numbers and severity.

Emergence of Dengue Virus Serotype 2 Cosmopolitan Genotype, Colombia.

Using Oxford Nanopore technologies and phylogenetic analyses, we sequenced and identified the cosmopolitan genotype of dengue virus serotype 2 isolated from 2 patients in the city of Villavicencio, Meta department, Colombia. This identification suggests the emergence of this genotype in the country, which warrants further surveillance to identify its epidemic potential.

Borrelia turicatae from Ticks in Peridomestic Setting, Camayeca, Mexico.

We conducted surveillance studies in Sinaloa, Mexico, to determine the circulation of tick-borne relapsing fever spirochetes. We collected argasid ticks from a home in the village of Camayeca and isolated spirochetes. Genomic analysis indicated that Borrelia turicatae infection is a threat to those living in resource-limited settings.

Fatal West Nile Virus Infection in Horse Returning to United Kingdom from Spain, 2022.

We report fatal West Nile virus (WNV) infection in a 7-year-old mare returning to the United Kingdom from Spain. Case timeline and clustering of virus sequence with recent WNV isolates suggest that transmission occurred in Andalusía, Spain. Our findings highlight the importance of vaccination for horses traveling to WNV-endemic regions.

Evidence of Zika Virus Reinfection by Genome Diversity and Antibody Response Analysis, Brazil.

We generated 238 Zika virus (ZIKV) genomes from 135 persons in Brazil who had samples collected over 1 year to evaluate virus persistence. Phylogenetic inference clustered the genomes together with previously reported ZIKV strains from northern Brazil, showing that ZIKV has been remained relatively stable over time. Temporal phylogenetic analysis revealed limited within-host diversity among most ZIKV-persistent infected associated samples. However, we detected unusual virus temporal diversity from >5 persons, uncovering the existence of divergent genomes within the same patient. All those patients showed an increase in neutralizing antibody levels, followed by a decline at the convalescent phase of ZIKV infection. Of interest, in 3 of those patients, titers of neutralizing antibodies increased again after 6 months of ZIKV infection, concomitantly with real-time reverse transcription PCR re-positivity, supporting ZIKV reinfection events. Altogether, our findings provide evidence for the existence of ZIKV reinfection events.

High Prevalence of Echinostoma mekongi Infection in Schoolchildren and Adults, Kandal Province, Cambodia.

A high prevalence of Echinostoma mekongi infection (13.9%; 260/1,876) was found among schoolchildren and adults in Kandal Province, Cambodia, by fecal examination, worm expulsion, and molecular analysis of cox1 and nd1 genes. The source of infection was consumption of Pila sp. snails, a finding confirmed morphologically and molecularly.

Delayed Diagnosis of Locally Acquired Lyme Disease, Central North Carolina, USA.

Healthcare providers in North Carolina, USA, have limited experience diagnosing and managing Lyme disease because few cases occur annually statewide. We outline the prolonged diagnostic course for a patient with locally acquired Lyme disease in North Carolina. This case highlights the need for greater awareness and professional education.

Reemergence of Oropouche Virus in the Americas and Risk for Spread in the United States and Its Territories, 2024.

Oropouche virus has recently caused outbreaks in South America and the Caribbean, expanding into areas to which the virus was previously not endemic. This geographic range expansion, in conjunction with the identification of vertical transmission and reports of deaths, has raised concerns about the broader threat this virus represents to the Americas. We review information on Oropouche virus, factors influencing its spread, transmission risk in the United States, and current status of public health response tools. On the basis of available data, the risk for sustained local transmission in the continental United States is considered low because of differences in vector ecology and in human-vector interactions when compared with Oropouche virus-endemic areas. However, more information is needed about the drivers for the current outbreak to clarify the risk for further expansion of this virus. Timely detection and control of this emerging pathogen should be prioritized to mitigate disease burden and stop its spread.

Autochthonous Human Babesiosis Caused by Babesia venatorum, the Netherlands.

Severe babesiosis with 9.8% parasitemia was diagnosed in a patient in the Netherlands who had previously undergone splenectomy. We confirmed Babesia venatorum using PCR and sequencing. B. venatorum was also the most prevalent species in Ixodes ricinus ticks collected around the patient's home. Our findings warrant awareness for severe babesiosis in similar patients.