Spotted fever rickettsiosis in South Africa: Evaluation of laboratory diagnostic capacity and interlaboratory comparison of serological testing

Background. Spotted fever rickettsiosis, also known as tick bite fever (TBF), is a common infectious disease in South Africa (SA). Although the diagnosis of TBF is often based on clinical grounds only, laboratory testing is important to confirm the diagnosis and can contribute to case management in the light of a myriad of differential diagnoses, and in complicated cases.Objectives. To report on the availability and scope of laboratory tests for investigating suspected cases of TBF in SA, and the outcome of an inter-laboratory comparison (ILC) conducted for serological tests.Methods. A self-administered questionnaire was circulated to major pathology laboratories in SA to determine what TBF tests they offered for TBF investigation. In addition, a clinical panel was provided to willing laboratories in order to perform an ILC of the serological tests.Results. Serological tests for TBF were available from five laboratories serving both the private and state medical sectors in SA. There was no standardised testing platform or result interpretation across the different laboratories. Polymerase chain reaction (PCR) tests were less frequently available, and not available to state-operated facilities. The outcome of the ILC indicated varied performance and interpretation of serological results for TBF.Conclusions. Laboratory investigation for TBF is routinely and widely available in SA. Both serological and PCR-based methods were varied, and the lack of standardisation and interpretation of tests needs to be addressed to improve the overall quality of TBF diagnosis in SA. The utility of ILC to identify problem areas in serological testing for TBF is highlighted, and laboratories in SA are encouraged to use it to improve the quality of testing. Â

The values and risks of an Intergovernmental Panel for One Health to strengthen pandemic prevention, preparedness, and response

The COVID-19 pandemic has shown the need for better global governance of pandemic prevention, preparedness, and response (PPR) and has emphasised the importance of organised knowledge production and uptake. In this Health Policy, we assess the potential values and risks of establishing an Intergovernmental Panel for One Health (IPOH). Similar to the Intergovernmental Panel on Climate Change, an IPOH would facilitate knowledge uptake in policy making via a multisectoral approach, and hence support the addressing of infectious disease emergence and re-emergence at the human-animal-environment interface. The potential benefits to pandemic PPR include a clear, unified, and authoritative voice from the scientific community, support to help donors and institutions to prioritise their investments, evidence-based policies for implementation, and guidance on defragmenting the global health system. Potential risks include a scope not encompassing all pandemic origins, unclear efficacy in fostering knowledge uptake by policy makers, potentially inadequate speed in facilitating response efforts, and coordination challenges among an already dense set of stakeholders. We recommend weighing these factors when designing institutional reforms for a more effective global health system

Rabies, Still Neglected after 125 Years of Vaccination

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Rabies-Related Knowledge and Practices Among Persons At Risk of Bat Exposures in Thailand

Rabies is a fatal encephalitis caused by lyssaviruses. Evidence of lyssavirus circulation has recently emerged in Southeast Asian bats. We surveyed persons regularly exposed to bats and bat habitats in Thailand to assess rabies‐related knowledge and practices. Targeted groups included guano miners, bat hunters, game wardens, and residents/personnel at Buddhist temples where mass bat roosting occurs. Of the 106 people interviewed, 11 (10%) identified bats as a source of rabies. History of a bat bite/scratch was reported by 29 (27%), and 38 (36%) expressed either that they would do nothing or that they did not know what they would do in response to a bat bite. Guano miners were less likely than other groups to indicate animal bites as a mechanism of transmission (68% vs. 90%, p=0.03) and were less likely to say they would respond appropriately to a bat bite or scratch (61% vs. 27%, p=0.003). These findings indicate a need for educational outreach in Thailand to raise awareness of bat rabies, promote exposure prevention, and ensure health‐seeking behaviors for bat‐inflicted wounds, particularly among at‐risk groups

In Vitro and In Vivo Isolation and Characterization of Duvenhage Virus

A fatal human case of Duvenhage virus (DUVV) infection in a Dutch traveller who had returned from Kenya was reported in 2007. She exhibited classical symptoms of rabies encephalitis with distinct pathological findings. In the present study we describe the isolation and characterization of DUVV in vitro and its passage in BALB/c mice. The virus proved to be neuroinvasive in both juvenile and adult mice, resulting in about 50% lethality upon peripheral infection. Clinical signs in infected mice were those of classical rabies. However, the distribution of viral antigen expression in the brain differed from that of classical rabies virus infection and neither inclusion bodies nor neuronal necrosis were observed. This is the first study to describe the in vitro and in vivo isolation and characterization of DUVV

A Step Forward in Molecular Diagnostics of Lyssaviruses – Results of a Ring Trial among European Laboratories

Rabies is a lethal and notifiable zoonotic disease for which diagnostics have to meet the highest standards. In recent years, an evolution was especially seen in molecular diagnostics with a wide variety of different detection methods published. Therefore, a first international ring trial specifically designed on the use of reverse transcription polymerase chain reaction (RT-PCR) for detection of lyssavirus genomic RNA was organized. The trial focussed on assessment and comparison of the performance of conventional and real-time assays. In total, 16 European laboratories participated. All participants were asked to investigate a panel of defined lyssavirus RNAs, consisting of Rabies virus (RABV) and European bat lyssavirus 1 and 2 (EBLV-1 and -2) RNA samples, with systems available in their laboratory. The ring trial allowed the important conclusion that conventional RT-PCR assays were really robust assays tested with a high concordance between different laboratories and assays. The real-time RT-PCR system by Wakeley et al. (2005) in combination with an intercalating dye, and the combined version by Hoffmann and co-workers (2010) showed good sensitivity for the detection of all RABV samples included in this test panel. Furthermore, all used EBLV-specific assays, real-time RT-PCRs as well as conventional RT-PCR systems, were shown to be suitable for a reliable detection of EBLVs. It has to be mentioned that differences were seen in the performance between both the individual RT-PCR systems and the laboratories. Laboratories which used more than one molecular assay for testing the sample panel always concluded a correct sample result. Due to the markedly high genetic diversity of lyssaviruses, the application of different assays in diagnostics is needed to achieve a maximum of diagnostic accuracy. To improve the knowledge about the diagnostic performance proficiency testing at an international level is recommended before using lyssavirus molecular diagnostics e.g. for confirmatory testing

Lack of Marburg virus transmission from experimentally infected to susceptible in-contact Egyptian fruit bats

Egyptian fruit bats (Rousettus aegyptiacus) were inoculated subcutaneously (n = 22) with Marburg virus (MARV). No deaths, overt signs of morbidity, or gross lesions was identified, but microscopic pathological changes were seen in the liver of infected bats. The virus was detected in 15 different tissues and plasma but only sporadically in mucosal swab samples, urine, and fecal samples. Neither seroconversion nor viremia could be demonstrated in any of the in-contact susceptible bats (n = 14) up to 42 days after exposure to infected bats. In bats rechallenged (n = 4) on day 48 after infection, there was no viremia, and the virus could not be isolated from any of the tissues tested. This study confirmed that infection profiles are consistent with MARV replication in a reservoir host but failed to demonstrate MARV transmission through direct physical contact or indirectly via air. Bats develop strong protective immunity after infection with MARV.This work was supported by the National Institute for Communicable Diseases.http://jid.oxfordjournals.orgam2016Paraclinical Science

Henipavirus RNA in African Bats

BACKGROUND: Henipaviruses (Hendra and Nipah virus) are highly pathogenic members of the family Paramyxoviridae. Fruit-eating bats of the Pteropus genus have been suggested as their natural reservoir. Human Henipavirus infections have been reported in a region extending from Australia via Malaysia into Bangladesh, compatible with the geographic range of Pteropus. These bats do not occur in continental Africa, but a whole range of other fruit bats is encountered. One of the most abundant is Eidolon helvum, the African Straw-coloured fruit bat. METHODOLOGY/PRINCIPAL FINDINGS: Feces from E. helvum roosting in an urban setting in Kumasi/Ghana were tested for Henipavirus RNA. Sequences of three novel viruses in phylogenetic relationship to known Henipaviruses were detected. Virus RNA concentrations in feces were low. CONCLUSIONS/SIGNIFICANCE: The finding of novel putative Henipaviruses outside Australia and Asia contributes a significant extension of the region of potential endemicity of one of the most pathogenic virus genera known in humans

Vaccination against Human Influenza A/H3N2 Virus Prevents the Induction of Heterosubtypic Immunity against Lethal Infection with Avian Influenza A/H5N1 Virus

Annual vaccination against seasonal influenza viruses is recommended for certain individuals that have a high risk for complications resulting from infection with these viruses. Recently it was recommended in a number of countries including the USA to vaccinate all healthy children between 6 and 59 months of age as well. However, vaccination of immunologically naïve subjects against seasonal influenza may prevent the induction of heterosubtypic immunity against potentially pandemic strains of an alternative subtype, otherwise induced by infection with the seasonal strains. Here we show in a mouse model that the induction of protective heterosubtypic immunity by infection with a human A/H3N2 influenza virus is prevented by effective vaccination against the A/H3N2 strain. Consequently, vaccinated mice were no longer protected against a lethal infection with an avian A/H5N1 influenza virus. As a result H3N2-vaccinated mice continued to loose body weight after A/H5N1 infection, had 100-fold higher lung virus titers on day 7 post infection and more severe histopathological changes than mice that were not protected by vaccination against A/H3N2 influenza. The lack of protection correlated with reduced virus-specific CD8+ T cell responses after A/H5N1 virus challenge infection. These findings may have implications for the general recommendation to vaccinate all healthy children against seasonal influenza in the light of the current pandemic threat caused by highly pathogenic avian A/H5N1 influenza viruses