Ronald Rosenberg

Xanthurenic Acid Induces Gametogenesis in Plasmodium, the Malaria Parasite

A small, heat stable chromophore extracted from mosquitoes has recently been implicated as the signal that induces mating of Plasmodium, the malaria parasite. We have used high resolution electrospray mass spectrometry to determine that this gamete activation factor (GAF) has a m/z = 205.0450, suggesting a molecular species composition of C10H7NO4. Xanthurenic acid (XA), a product of tryptophan catabolism, was determined to have an elemental composition, ultraviolet absorbance maxima, and mass spectrum consistent with those characteristics of GAF. XA activated gametogenesis of Plasmodium gallinaceum and P. falciparum in vitro at concentrations lower than 0.5 μm in saline buffered to pH 7.4. A structural analog of XA, kynurenic acid (C10H6NO3), also activated gametogenesis but only at higher concentrations and with less effect. We propose that XA is GAF. This is the first evidence that XA has induction activity.

Malaria: some considerations regarding parasite productivity

The complicated life cycle of Plasmodium is characterized by proliferative stages in each of its hosts--mosquito and vertebrate--that are interrupted by restrictive steps as it moves from one to the other. Productivity at each stage affects not only pathology but also the probability for successful transmission. This Opinion article briefly assesses what is known about productivity at each step and attempts, with limited success, to put each in the context of an entire cycle, sporozoite to sporozoite.

Search strategy has influenced the discovery rate of human viruses

A widely held concern is that the pace of infectious disease emergence has been increasing. We have analyzed the rate of discovery of pathogenic viruses, the preeminent source of newly discovered causes of human disease, from 1897 through 2010. The rate was highest during 1950–1969, after which it moderated. This general picture masks two distinct trends: for arthropod-borne viruses, which comprised 39% of pathogenic viruses, the discovery rate peaked at three per year during 1960–1969, but subsequently fell nearly to zero by 1980; however, the rate of discovery of nonarboviruses remained stable at about two per year from 1950 through 2010. The period of highest arbovirus discovery coincided with a comprehensive program supported by The Rockefeller Foundation of isolating viruses from humans, animals, and arthropod vectors at field stations in Latin America, Africa, and India. The productivity of this strategy illustrates the importance of location, approach, long-term commitment, and sponsorship in the discovery of emerging pathogens.

Fatal Spotted Fever Rickettsiosis, Kenya

We report a fatal case of rickettsiosis in a woman from the United States living in Kenya, who had a history of tick exposure. Immunohistochemical staining of skin, kidney, and liver demonstrated spotted fever group rickettsiae. The clinical findings, severity, and fatal outcome are most consistent with Rickettsia conorii infection.

Detecting the emergence of novel, zoonotic viruses pathogenic to humans

RNA viruses, with their high potential for mutation and epidemic spread, are the most common class of pathogens found as new causes of human illness. Despite great advances made in diagnostic technology since the 1950s, the annual rate at which novel virulent viruses have been found has remained at 2–3. Most emerging viruses are zoonoses; they have jumped from mammal or bird hosts to humans. An analysis of virus discovery indicates that the small number of novel viruses discovered annually is an artifact of inadequate surveillance in tropical and subtropical countries, where even established endemic pathogens are often misdiagnosed. Many of the emerging viruses of the future are already infecting humans but remain to be uncovered by a strategy of disease surveillance in selected populations.

Vector-borne infections.

Infections with vector-borne pathogens are a major source of emerging diseases. The ability of vectors to bridge spatial and ecologic gaps between animals and humans increases opportunities for emergence. Small adaptations of a pathogen to a vector can have profound effects on the rate of transmission to humans.

Vital Signs: Trends in Reported Vectorborne Disease Cases - United States and Territories, 2004-2016.

Introduction Vectorborne diseases are major causes of death and illness worldwide. In the United States, the most common vectorborne pathogens are transmitted by ticks or mosquitoes, including those causing Lyme disease; Rocky Mountain spotted fever; and West Nile, dengue, and Zika virus diseases. This report examines trends in occurrence of nationally reportable vectorborne diseases during 2004–2016. Methods Data reported to the National Notifiable Diseases Surveillance System for 16 notifiable vectorborne diseases during 2004–2016 were analyzed; findings were tabulated by disease, vector type, location, and year. Results A total 642,602 cases were reported. The number of annual reports of tickborne bacterial and protozoan diseases more than doubled during this period, from >22,000 in 2004 to >48,000 in 2016. Lyme disease accounted for 82% of all tickborne disease reports during 2004–2016. The occurrence of mosquitoborne diseases was marked by virus epidemics. Transmission in Puerto Rico, the U.S. Virgin Islands, and American Samoa accounted for most reports of dengue, chikungunya, and Zika virus diseases; West Nile virus was endemic, and periodically epidemic, in the continental United States. Conclusions and Implications for Public Health Practice Vectorborne diseases are a large and growing public health problem in the United States, characterized by geographic specificity and frequent pathogen emergence and introduction. Differences in distribution and transmission dynamics of tickborne and mosquitoborne diseases are often rooted in biologic differences of the vectors. To effectively reduce transmission and respond to outbreaks will require major national improvement of surveillance, diagnostics, reporting, and vector control, as well as new tools, including vaccines.

Genomic characterization of Zika virus isolated from Indonesia

Zika virus (ZIKV) JMB-185 strain was isolated from a febrile patient in Jambi, Indonesia in 2014. To understand its genetic characteristics, we performed whole genome sequencing using the Ion Torrent PGM platform on the supernatant of the first passage. The phylogenetic analysis showed that the isolate was not closely related to the Brazilian ZIKV associated with microcephaly or isolates from the recent Singapore Zika outbreak. Molecular evolution analysis indicated that JMB-185 strain may have been circulating in the Southeast Asia region, including Indonesia since 2000. We observed high nucleotide sequence identity between Indonesia, Thailand, Singapore, and American strains although unique amino acid substitutions were also observed. This report provides information on the genomic characteristics of Indonesian ZIKV which may be used for further studies.

Threat from Emerging Vectorborne Viruses.

The earliest members of genus Homo were surely bedeviled by blood-feeding arthropods, some of which doubtless carried zoonotic pathogens. However, the phenomenon of vectorborne human epidemic disease began only after humans began building settlements 15,000 years ago (1). Settlements offered pathogens not only host density but also opportunities for their vertebrate reservoirs and arthropod vectors to cohabit with us. Epidemic Yersinia pestis (the Medieval Black Death) was only possible because black rats (Rattus rattus), the host of the vector flea, had become extraordinarily successful at living off human garbage and nesting in our buildings.

Isolation and complete genome analysis of neurotropic dengue virus serotype 3 from the cerebrospinal fluid of an encephalitis patient

Although neurological manifestations associated with dengue viruses (DENV) infection have been reported, there is very limited information on the genetic characteristics of neurotropic DENV. Here we describe the isolation and complete genome analysis of DENV serotype 3 (DENV-3) from cerebrospinal fluid of an encephalitis paediatric patient in Jakarta, Indonesia. Next-generation sequencing was employed to deduce the complete genome of the neurotropic DENV-3 isolate. Based on complete genome analysis, two unique and nine uncommon amino acid changes in the protein coding region were observed in the virus. A phylogenetic tree and molecular clock analysis revealed that the neurotropic virus was a member of Sumatran-Javan clade of DENV-3 genotype I and shared a common ancestor with other isolates from Jakarta around 1998. This is the first report of neurotropic DENV-3 complete genome analysis, providing detailed information on the genetic characteristics of this virus.