William L. Nicholson

A New Phlebovirus Associated with Severe Febrile Illness in Missouri

Two men from northwestern Missouri independently presented to a medical facility with fever, fatigue, diarrhea, thrombocytopenia, and leukopenia, and both had been bitten by ticks 5 to 7 days before the onset of illness. Ehrlichia chaffeensis was suspected as the causal agent but was not found on serologic analysis, polymerase-chain-reaction (PCR) assay, or cell culture. Electron microscopy revealed viruses consistent with members of the Bunyaviridae family. Next-generation sequencing and phylogenetic analysis identified the viruses as novel members of the phlebovirus genus. Although Kochs postulates have not been completely fulfilled, we believe that this phlebovirus, which is novel in the Americas, is the cause of this clinical syndrome.

Etiology of Severe Non-malaria Febrile Illness in Northern Tanzania: A Prospective Cohort Study

Introduction The syndrome of fever is a commonly presenting complaint among persons seeking healthcare in low-resource areas, yet the public health community has not approached fever in a comprehensive manner. In many areas, malaria is over-diagnosed, and patients without malaria have poor outcomes. Methods and Findings We prospectively studied a cohort of 870 pediatric and adult febrile admissions to two hospitals in northern Tanzania over the period of one year using conventional standard diagnostic tests to establish fever etiology. Malaria was the clinical diagnosis for 528 (60.7%), but was the actual cause of fever in only 14 (1.6%). By contrast, bacterial, mycobacterial, and fungal bloodstream infections accounted for 85 (9.8%), 14 (1.6%), and 25 (2.9%) febrile admissions, respectively. Acute bacterial zoonoses were identified among 118 (26.2%) of febrile admissions; 16 (13.6%) had brucellosis, 40 (33.9%) leptospirosis, 24 (20.3%) had Q fever, 36 (30.5%) had spotted fever group rickettsioses, and 2 (1.8%) had typhus group rickettsioses. In addition, 55 (7.9%) participants had a confirmed acute arbovirus infection, all due to chikungunya. No patient had a bacterial zoonosis or an arbovirus infection included in the admission differential diagnosis. Conclusions Malaria was uncommon and over-diagnosed, whereas invasive infections were underappreciated. Bacterial zoonoses and arbovirus infections were highly prevalent yet overlooked. An integrated approach to the syndrome of fever in resource-limited areas is needed to improve patient outcomes and to rationally target disease control efforts.

Emergence of a New Pathogenic Ehrlichia Species, Wisconsin and Minnesota, 2009

BACKGROUND Ehrlichiosis is a clinically important, emerging zoonosis. Only Ehrlichia chaffeensis and E. ewingii have been thought to cause ehrlichiosis in humans in the United States. Patients with suspected ehrlichiosis routinely undergo testing to ensure proper diagnosis and to ascertain the cause. METHODS We used molecular methods, culturing, and serologic testing to diagnose and ascertain the cause of cases of ehrlichiosis. RESULTS On testing, four cases of ehrlichiosis in Minnesota or Wisconsin were found not to be from E. chaffeensis or E. ewingii and instead to be caused by a newly discovered ehrlichia species. All patients had fever, malaise, headache, and lymphopenia; three had thrombocytopenia; and two had elevated liver-enzyme levels. All recovered after receiving doxycycline treatment. At least 17 of 697 Ixodes scapularis ticks collected in Minnesota or Wisconsin were positive for the same ehrlichia species on polymerase-chain-reaction testing. Genetic analyses revealed that this new ehrlichia species is closely related to E. muris. CONCLUSIONS We report a new ehrlichia species in Minnesota and Wisconsin and provide supportive clinical, epidemiologic, culture, DNA-sequence, and vector data. Physicians need to be aware of this newly discovered close relative of E. muris to ensure appropriate testing, treatment, and regional surveillance. (Funded by the National Institutes of Health and the Centers for Disease Control and Prevention.).

The increasing recognition of rickettsial pathogens in dogs and people

Dogs and people are exposed to and susceptible to infection by many of the same tick-borne bacterial pathogens in the order Rickettsiales, including Anaplasma phagocytophilum, Ehrlichia canis, E. chaffeensis, E. ewingii, Rickettsia rickettsii, R. conorii, and other spotted fever group rickettsiae. Recent findings include descriptions of novel Ehrlichia and Rickettsia species, recognition of the occurrence and clinical significance of co-infection, and increasing awareness of Rhipicephalus sanguineus-associated diseases. Newer molecular assays are available, although renewed efforts to encourage their use are needed. This review highlights the ecology and epidemiology of these diseases, and proposes avenues for future investigation.

Transmission of the Agent of Human Granulocytic Ehrlichiosis by Ixodes spinipalpis Ticks: Evidence of an Enzootic Cycle of Dual Infection with Borrelia burgdorferi in Northern Colorado

Previous work described an enzootic cycle of Borrelia burgdorferi sensu lato (hereafter referred to as B. burgdorferi) maintained by the rodent Neotoma mexicana and the tick Ixodes spinipalpis in northern Colorado. We investigated the incidence of coinfection among rodents with the agent of human granulocytic ehrlichiosis (aoHGE). aoHGE was detected in 23.5% of 119 rodent spleens examined. Biopsy results indicated that 78 (65.5%) of the 119 rodents were positive for B. burgdorferi, whereas 22 (78.5%) of the 28 animals that harbored aoHGE were also infected with B. burgdorferi. In 14 of 25 I. spinipalpis tick pools, aoHGE was detected by amplifying both the 16s rRNA and p44 gene of aoHGE. The ability of I. spinipalpis to transmit aoHGE was examined in C3H/HeJ mice. aoHGE was detected in their blood 5 days after I. spinipalpis infestation. This study confirms that both B. burgdorferi and aoHGE can be transmitted by I. spinipalpis ticks and that there is a high incidence of coinfection in rodents, predominantly Peromyscus maniculatus and N. mexicana, that inhabit the foothills of northern Colorado.

Comparison of the reservoir competence of medium-sized mammals and Peromyscus leucopus for Anaplasma phagocytophilum in Connecticut.

In the northeastern United States, Anaplasma phagocytophilum, the agent of human granulocytic ehrlichiosis (HGE), is transmitted by the tick vector Ixodes scapularis. The white-footed mouse Peromyscus leucopus is a competent reservoir for this agent, but the reservoir competence of non-Peromyscus hosts of I. scapularis has not been studied. Here, we report data confirming reservoir competence of medium-sized mammals for A. phagocytophilum. Raccoons, Virginia opossums, gray squirrels, and striped skunks were live-trapped in June-August of 1998-1999 at two locations in Connecticut. Captured animals were kept for several days at the laboratory in wire-mesh cages over water to allow naturally attached ticks to drop off. Samples of blood and serum were taken from each animal prior to its release at the site of capture. Engorged ticks collected from each animal were allowed to molt. Resulting I. scapularis nymphs and adults were tested for the presence of A. phagocytophilum DNA by polymerase chain reaction, as were the blood samples from the animals. A. phagocytophilum DNA was detected in the blood of >10% of the raccoons tested. Raccoons, opossums, squirrels, and skunks produced adult I. scapularis infected with the agent of HGE. Prevalence of infection was the highest in adult ticks fed as nymphs upon raccoons (23%) and the lowest in those fed upon skunks and opossums (5-7%). The agent was present in nymphal I. scapularis fed as larvae upon raccoons and squirrels, but not in ticks fed upon skunks or opossums. We also tested the ability of I. scapularis to transmit A. phagocytophilum to laboratory-reared white-footed mice after acquiring it from medium-sized mammals. Ticks that acquired the agent from raccoons and squirrels successfully transmitted it to mice. Thus, raccoons and gray squirrels are reservoir-competent for the agent of HGE-they become naturally infected, and are capable of transmitting the infection to feeding ticks.

Human Granulocytic Ehrlichiosis in Europe: Clinical and Laboratory Findings for Four Patients from Slovenia

Febrile illnesses following a tick bite in patients from Slovenia were evaluated for an ehrlichial etiology. A case of acute human granulocytic ehrlichiosis (HGE) was confirmed by seroconversion to the HGE agent or molecular identification of ehrlichial organisms. Acute infection with the HGE agent was confirmed in four patients. None of the patients had detectable antibodies to the HGE agent at their first visit, but polymerase chain reaction analysis was positive for three patients. All four patients subsequently seroconverted to the HGE agent as shown by high titers of antibody. Clinical features and laboratory findings were similar to those in reports from the United States, although the disease course was relatively mild in the Slovenian cases. All patients recovered rapidly and without sequelae, although only two received antibiotic therapy (of whom only one was treated with doxycycline). HGE is an emerging tick-borne disease in the United States and should now be included in the differential diagnosis of febrile illnesses occurring after a tick bite in Europe.

Primary Isolation of Ehrlichia chaffeensis from Patients with Febrile Illnesses: Clinical and Molecular Characteristics

Ehrlichia chaffeensis was sought among patients with a history of tick exposure and fever, and the accuracy of other diagnostic tests was compared with that of primary isolation. Among the 38 patients enrolled, E. chaffeensis was isolated from the blood of 7 (18%) and from cerebrospinal fluid specimens of 2 of these 7. All 7 patients also were positive by polymerase chain reaction (PCR) of blood, and 6 patients developed diagnostic titers of antibody to E. chaffeensis. The isolates were characterized by molecular analysis of the 16S rRNA gene, the 120-kDa protein gene, and the variable-length PCR target (VLPT) of E. chaffeensis. On the basis of the 120-kDa and VLPT genotypes, the cerebrospinal fluid and blood isolates from the same patients were identical. This study demonstrates that both PCR and culture of blood for E. chaffeensis have high diagnostic yields. More frequent isolation of E. chaffeensis from patients with infection should further our understanding of the pathogenesis of this infection.

Bartonella sp. Bacteremia in Patients with Neurological and Neurocognitive Dysfunction

ABSTRACT We detected infection with a Bartonella species (B. henselae or B. vinsonii subsp. berkhoffii) in blood samples from six immunocompetent patients who presented with a chronic neurological or neurocognitive syndrome including seizures, ataxia, memory loss, and/or tremors. Each of these patients had substantial animal contact or recent arthropod exposure as a potential risk factor for Bartonella infection. Additional studies should be performed to clarify the potential role of Bartonella spp. as a cause of chronic neurological and neurocognitive dysfunction.

Rickettsia parkeri Rickettsiosis, Argentina.

Rickettsia parkeri, a recently identified cause of spotted fever rickettsiosis in the United States, has been found in Amblyomma triste ticks in several countries of South America, including Argentina, where it is believed to cause disease in humans. We describe the clinical and epidemiologic characteristics of 2 patients in Argentina with confirmed R. parkeri infection and 7 additional patients with suspected R. parkeri rickettsiosis identified at 1 hospital during 2004–2009. The frequency and character of clinical signs and symptoms among these 9 patients closely resembled those described for patients in the United States (presence of an inoculation eschar, maculopapular rash often associated with pustules or vesicles, infrequent gastrointestinal manifestations, and relatively benign clinical course). Many R. parkeri infections in South America are likely to be misdiagnosed as other infectious diseases, including Rocky Mountain spotted fever, dengue, or leptospirosis.