Gerhard Dobler

Chikungunya Fever in Travelers: Clinical Presentation and Course

BACKGROUND An outbreak of chikungunya virus infection emerged in the southwest Indian Ocean islands in 2005, spread out to India, and resulted in an ongoing outbreak that has involved >1.5 million patients, including travelers who have visited these areas. METHODS Our study investigated 69 travelers who developed signs and symptoms compatible with chikungunya fever after returning home from countries involved in the epidemic. Twenty cases of infection that were confirmed by serological analysis, polymerase chain reaction, and/or cell culture were investigated. RESULTS All patients experienced flulike symptoms with fever and joint pain. No serious complications were observed, but 69% of the patients had persistent arthralgia for >2 months, and 13% had it for >6 months. Viral RNA could be detected in blood samples using reverse-transcriptase polymerase chain reaction in 4 of 4 patients who presented to a health care facility during their first week of illness, and the virus was successfully isolated from blood samples obtained from 2 of these patients. Chikungunya virus-specific immunoglobulin M and/or immunoglobulin G antibodies were detected in all patients. However, initial testing of serum samples yielded negative results for 3 of 5 patients during the first week. CONCLUSIONS Chikungunya fever must be considered in travelers who develop fever and arthritis after traveling to areas affected by an ongoing epidemic. Related arthritis mainly affects smaller joints and often persists for extended periods. Serological testing may have negative results during the first week of the disease; diagnosis using polymerase chain reaction appears to be more reliable during this time. Travelers to areas of epidemicity should be informed of the risk of infection and of adequate preventive measures, such as protection against mosquitos.

Emergence of zoonotic arboviruses by animal trade and migration

Arboviruses are transmitted in nature exclusively or to a major extend by arthropods. They belong to the most important viruses invading new areas in the world and their occurrence is strongly influenced by climatic changes due to the life cycle of the transmitting vectors. Several arboviruses have emerged in new regions of the world during the last years, like West Nile virus (WNV) in the Americas, Usutu virus (USUV) in Central Europe, or Rift Valley fever virus (RVFV) in the Arabian Peninsula. In most instances the ways of introduction of arboviruses into new regions are not known. Infections acquired during stays in the tropics and subtropics are diagnosed with increasing frequency in travellers returning from tropical countries, but interestingly no attention is paid on accompanying pet animals or the hematophagous ectoparasites that may still be attached to them. Here we outline the known ecology of the mosquito-borne equine encephalitis viruses (WEEV, EEEV, and VEEV), WNV, USUV, RVFV, and Japanese Encephalitis virus, as well as Tick-Borne Encephalitis virus and its North American counterpart Powassan virus, and will discuss the most likely mode that these viruses could expand their respective geographical range. All these viruses have a different epidemiology as different vector species, reservoir hosts and virus types have adapted to promiscuous and robust or rather very fine-balanced transmission cycles. Consequently, these viruses will behave differently with regard to the requirements needed to establish new endemic foci outside their original geographical ranges. Hence, emphasis is given on animal trade and suitable ecologic conditions, including competent vectors and vertebrate hosts.

Rickettsia spp. in wild small mammals in Lower Bavaria, South-Eastern Germany.

So far, data on the natural cycle of rickettsiae of the tick-borne spotted fever group (SFG) in Central Europe are barely available. Some studies showed the occurrence of different Rickettsia species in their arthropod vectors, but it is unclear which animals might have any kind of reservoir function. This survey was therefore set up to provide information on the occurrence of SFG rickettsiae in small mammals in Germany. A total of 124 rodents and insectivores were collected over a period of 3 years in Lower Bavaria, South-Eastern Germany. Screening for Rickettsia antibodies was performed using immunofluorescence with Rickettsia conorii and R. helvetica slides, and the comparability of sera and body fluids (transudates) was investigated in these assays. Further, real-time polymerase chain reaction (PCR) was used for screening of Rickettsial DNA in rodents and insectivores. Ear versus liver tissue was compared to evaluate the more suitable tissue for detection of specific DNA. Further, a new PCR targeting the 18S ribosomal nucleic acid was established as internal control. The results indicated that transudates are a sufficient alternative to proof infection in cases where no sera are available. Rickettsial DNA, that is, Rickettsia felis and R. helvetica, was found in seven animals with the ears proving to be a proper choice for PCR. Statistical analyses revealed that the presence of ectoparasites and the body size positively correlated with the occurrence of rickettsial DNA. Overall, our study suggests that rodents and other small mammals may act as reservoir hosts for Rickettsia. However, with the course of infection and its transmission in wild animals still unknown, further investigations are needed to better understand the natural cycle of SFG rickettsiae.

High Seroprevalence of Rift Valley Fever and Evidence for Endemic Circulation in Mbeya Region, Tanzania, in a Cross-Sectional Study

Background The Rift Valley fever virus (RVFV) is an arthropod-borne phlebovirus. RVFV mostly causes outbreaks among domestic ruminants with a major economic impact. Human infections are associated with these events, with a fatality rate of 0.5–2%. Since the virus is able to use many mosquito species of temperate climates as vectors, it has a high potential to spread to outside Africa. Methodology/Principal Findings We conducted a stratified, cross-sectional sero-prevalence survey in 1228 participants from Mbeya region, southwestern Tanzania. Samples were selected from 17,872 persons who took part in a cohort study in 2007 and 2008. RVFV IgG status was determined by indirect immunofluorescence. Possible risk factors were analyzed using uni- and multi-variable Poisson regression models. We found a unique local maximum of RVFV IgG prevalence of 29.3% in a study site close to Lake Malawi (N = 150). The overall seroprevalence was 5.2%. Seropositivity was significantly associated with higher age, lower socio-economic status, ownership of cattle and decreased with distance to Lake Malawi. A high vegetation density, higher minimum and lower maximum temperatures were found to be associated with RVFV IgG positivity. Altitude of residence, especially on a small scale in the high-prevalence area was strongly correlated (PR 0.87 per meter, 95% CI = 0.80–0.94). Abundant surface water collections are present in the lower areas of the high-prevalence site. RVF has not been diagnosed clinically, nor an outbreak detected in the high-prevalence area. Conclusions RVFV is probably circulating endemically in the region. The presence of cattle, dense vegetation and temperate conditions favour mosquito propagation and virus replication in the vector and seem to play major roles in virus transmission and circulation. The environmental risk-factors that we identified could serve to more exactly determine areas at risk for RVFV endemicity.

Characterization of a sandfly fever Sicilian virus isolated during a sandfly fever epidemic in Turkey

BACKGROUND Phleboviruses cause sandfly fever but isolates are rare. OBJECTIVES To analyse samples from concurrent outbreaks of suspected sandfly fever in the Mediterranean provinces of Adana, Izmir and the central province of Ankara, Turkey. STUDY DESIGN Samples from acute cases were analysed by immunofluorescence assay (IFA). Virus isolation was attempted and pyrosequencing performed. RESULTS In IFA 38% of 106 samples tested scored IgM positive for sandfly fever Sicillian virus (SFSV), 12% for SFSV/sandfly fever Cyprus Virus (SFCV) and only 4% for SFCV. A sandfly fever Sicilian type virus designated sandfly fever Turkey virus (SFTV) was isolated. The S-segment sequence of SFTV had a homology of 98% to that of SFCV. The M-segment sequence showed a 91.1% homology to the only SFSV sequence available. The L-segment sequence showed a homology of 58% and 60.3% to Toscana virus and Rift Valley Fever virus sequences, a partial 201nt sequence showed 95.5% homology to the SFSV Sabin strain. CONCLUSION A new phlebovirus related to sandfly fever Sicilian virus, SFTV was isolated and characterized from acute patient material. The sandfly fever Sicilian virus activity seems to be changing in Turkey. Entomological studies are needed.

Isolation and molecular characterization of a tick-borne encephalitis virus strain from a new tick-borne encephalitis focus with severe cases in Bavaria, Germany.

Tick-borne encephalitis (TBE) is the most important viral infection transmitted by ticks in Central Europe. In Germany, where TBE was classified as a notifiable disease in 2001, a highly variable number of clinically apparent human cases was reported in the last few years, ranging from the lowest number of 238 in 2007 to a maximum of 546 in 2006. The dynamics of the virus and its vector tick remain poorly understood. We investigated a highly active TBE focus in south-eastern Germany where from 2003 to 2008 a total of 9 clinical human cases was diagnosed. Three out of these 9 cases were fatal indicating an unusually high mortality rate possibly due to a highly virulent TBEV strain. From 2005 till 2008, 2150 Ixodes ricinus ticks were collected and tested for the presence of TBE virus. Five TBEV-positive ticks were detected by real-time RT-PCR. A viable virus strain was isolated from one of the positive ticks sampled in 2005. This is the first TBE virus isolate from a tick in Germany for 30 years. Sequencing of the full-length genome of this virus strain (AS33) revealed 2 unique amino acid substitutions in the envelope protein known to play a role in the pathogenicity of TBE virus. Amplification of the envelope gene using 2 TBEV-PCR-positive ticks from 2006 also showed these particular mutations indicating that this TBE virus strain was present in at least 2 consecutive years. The entire sampling area was divided into smaller sectors for the exact location of TBEV-positive ticks. Virus-positive ticks were found to be randomly distributed throughout the investigated focus, which is used as recreational area by the local people.

Epidemiology and distribution of tick-borne encephalitis.

SummaryTick-borne encephalitis (TBE) is the main tick-borne virus infection in Eurasia. It is prevalent across the entire continent from Japan to France and occurs in endemic foci. Expansion of prevalence in areas including northern Russia, Sweden, and Finland has been observed in recent years. Ticks are the most important vectors and may transmit the TBE virus to animals and humans. TBE can also be transmitted to humans in milk containing the virus. TBE has been implicated as a travel-acquired illness and there are isolated reports of its occurrence in countries outside the known areas of prevalence. Therefore, TBE should be included in the differential diagnosis for all central nervous system diseases inside or outside endemic areas.ZusammenfassungDie Frühsommer-Meningoenzephalitis (FSME) ist die medizinisch wichtigste durch Zecken übertragene Virusinfektion in Eurasien. Ihr Verbreitungsgebiet reicht von Japan im Osten Asiens bis nach Frankreich im Westen Europas. In den zurückliegenden Jahren wurde ein Ausweitung der Verbreitungsgebiete in nördlicher Richtung in Nord-Russland, Schweden und Finnland beobachtet. Zecken spielen die wichtigste Rolle in der Übertragung des FSME-Virus auf Mensch und Tier. Allerdings kann die Infektion auch durch Virus-haltige Milch erfolgen. Die FSME spielt eine zunehmende Rolle in der Reisemedizin. Erkrankungsfälle treten in Regionen außerhalb der bekannten FSME-Verbreitungsgebiete auf. Daher sollte die FSME grundsätzlich bei allen entzündlichen Erkrankungen des Zentralen Nervensystems differenzialdiagnostisch ausgeschlossen werden.

Tick-borne encephalitis virus in dogs - is this an issue?

The last review on Tick-borne encephalitis (TBE) in dogs was published almost ten years ago. Since then, this zoonotic tick-borne arbovirus has been geographically spreading and emerging in many regions in Eurasia and continues to do so. Dogs become readily infected with TBE virus but they are accidental hosts not capable to further spread the virus. They seroconvert upon infection but they seem to be much more resistant to the clinical disease than humans. Apart from their use as sentinels in endemic areas, however, an increasing number of case reports appeared during the last decade thus mirroring the rising public health concerns. Owing to the increased mobility of people travelling to endemic areas with their companion dogs, this consequently leads to problems in recognizing and diagnosing this severe infection in a yet non-endemic area, simply because the veterinarians are not considering TBE. This situation warrants an update on the epidemiology, clinical presentation and possible preventions of TBE in the dog.

Fleas as parasites of the family Canidae.

Historically, flea-borne diseases are among the most important medical diseases of humans. Plague and murine typhus are known for centuries while the last years brought some new flea-transmitted pathogens, like R. felis and Bartonella henselae. Dogs may play an essential or an accidental role in the natural transmission cycle of flea-borne pathogens. They support the growth of some of the pathogens or they serve as transport vehicles for infected fleas between their natural reservoirs and humans. More than 15 different flea species have been described in domestic dogs thus far. Several other species have been found to be associated with wild canids. Fleas found on dogs originate from rodents, birds, insectivores and from other Carnivora. Dogs therefore may serve as ideal bridging hosts for the introduction of flea-borne diseases from nature to home. In addition to their role as ectoparasites they cause nuisance for humans and animals and may be the cause for severe allergic reactions.

Genetic characterization of Tribec virus and Kemerovo virus, two tick-transmitted human-pathogenic Orbiviruses

We determined the complete genome sequences of Tribeč virus (TRBV) and Kemerovo virus (KEMV), two tick-transmitted Orbiviruses that can cause diseases of the central nervous system and that are currently classified into the Great Island virus serogroup. VP2 proteins of TRBV and KEMV show very low sequence similarity to the homologous VP4 protein of tick-transmitted Great Island virus (GIV). The new sequence data support previous serological classification of these Orbiviruses into the Kemerovo serogroup, which is different from the Great Island virus serogroup. Genome segment 9 of TRBV and KEMV encodes several overlapping ORFs in the +1 reading frame relative to VP6(Hel). A co-phylogenetic analysis indicates a host switch from insect-borne Orbiviruses toward Ixodes species, which is in disagreement with previously published data.