Plasma C3c in immune-mediated neurological diseases: a preliminary report

Plasma C3c levels were examined in 56 patients with immune (27) and non-immune (29) mediated neurological diseases by crossed immunoelectrophoresis. Plasma samples were collected during the active phase of illness in both groups, usually within 7 days of admission. 11 patients (4 Guillain-Barré Syndrome-GBS, 3 chronic inflammatory demyelinating polyneuropathy-CIDP, 4 myasthenia gravis-MG) had their plasma saved sequentially during the active and the recovery phase. Plasma C3c levels were elevated in the group with immune mediated diseases when compared with those of non-immune mediated diseases. The sensitivity and specificity of C3c as a diagnostic test for immune mediated neurological diseases were 61.4 and 100% respectively with a positive and negative predictive value of 100 and 41%. the C3c levels in plasma correlated well with disease severity in MG and GBS patients. Such a correlation was also evident in all CIDP patients except one that had persistent elevation in the presence of clinical improvement. Results suggest that the plasma C3c level may be useful for differentiating immune from non-immune mediated neurological diseases. Plasma C3c may also be used for monitoring disease severity, particularly in myasthenia gravis.     

Immunologic study of human encephalitic and paralytic rabies. Preliminary report of 16 patients

Lymphocyte proliferation tests to rabies antigen and myelin basic protein were performed on peripheral blood lymphocytes from nine patients with the encephalitic form and on seven with the paralytic form of human rabies. Six of the nine patients with encephalitis had proliferative responses to rabies antigen, whereas all of the patients with paralysis had no response. Two patients in each group also had a proliferative response to myelin basic protein. The myelin basic protein-reactive patients had a more rapidly fatal disease than the non-reactive patients. This preliminary study suggests that host immune responses may influence the clinical manifestations and course in human rabies.     

Sequence analysis of rabies virus in humans exhibiting encephalitic or paralytic rabies

Two distinct clinical patterns, encephalitic (furious) and paralytic (dumb), have been recognized in human rabies. It has been postulated that different rabies virus variants associated with particular vectors may be responsible for these different clinical manifestations. Analysis of the glycoprotein (G), nucleoprotein (N), and phosphoprotein (P) genes of rabies viruses from 2 human cases of encephalitic rabies and from 2 human cases of paralytic rabies demonstrated only minor nucleotide differences. Deduced amino-acid patterns of the N protein were identical in both human and canine samples that came from the same geographic location, regardless of the clinical form. All differences in amino-acid patterns of the G protein were found outside the ectodomain, in either the signal peptide or the transmembrane and endodomains. None of the amino-acid differences of the P protein was within the interactive site with dynein. These findings support the concept that clinical manifestations of rabies are not explained solely by the associated rabies virus variant.     

Evaluating the efficiency of specimen pooling for PCR-based detection of COVID-19

In the age of a pandemic, such as the ongoing one caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the world faces a limited supply of tests, personal protective equipment, and factories and supply chains are struggling to meet the growing demands. This study aimed to evaluate the efficacy of specimen pooling for testing of SARS-CoV-2 virus, to determine whether costs and resource savings could be achieved without impacting the sensitivity of the testing. Ten previously tested nasopharyngeal and throat swab specimens by real-time polymerase chain reaction (PCR), were pooled for testing, containing either one or two known positive specimens of varying viral concentrations. Specimen pooling did not affect the sensitivity of detecting SARS-CoV-2 when the PCR cycle threshold (Ct) of original specimen was lower than 35. In specimens with low viral load (Ct > 35), 2 of 15 pools (13.3%) were false negative. Pooling specimens to test for Coronavirus Disease 2019 infection in low prevalence (≤1%) areas or in low risk populations can dramatically decrease the resource burden on laboratory operations by up to 80%. This paves the way for large-scale population screening, allowing for assured policy decisions by governmental bodies to ease lockdown restrictions in areas with a low incidence of infection, or with lower-risk populations.     

Bat Nipah virus, Thailand

Surveillance for Nipah virus (NV) was conducted in Thailand's bat population. Immunoglobulin G antibodies to NV were detected with enzyme immunoassay in 82 of 1,304 bats. NV RNA was found in bat saliva and urine. These data suggest the persistence of NV infection in Thai bats.     

Rabies control in South and Southeast Asia

We have the knowledge and tools to eliminate the threat of canine rabies but this disease, nevertheless, remains a public health threat in many parts of the world. Lack of motivation by governments, cultural issues and inadequate funding remain barriers. This is amazing since the number of human rabies deaths worldwide is greater than that from polio, meningococcal meningitis, Japanese encephalitis, yellow fever, SARS, bird flue and other scourges that attract more attention. Safe and effective vaccines are now widely available. Reduced dose effective and less expensive post-exposure vaccination regimens have helped eliminate nerve tissue vaccines in Thailand, Philippines and Sri Lanka. India and Pakistan, the major users of dangerous nerve tissue derived Semple type vaccine, are now considering following suite. Immediate wound care and prompt use of a potent vaccine will save a majority of infected persons. Rabies immunoglobulin, injected into and around bite wounds, provides added safety for the severely exposed. The high cost of rabies immunoglobulin and tissue culture vaccines are remaining barriers, but new manufacturers and the use of intradermal vaccination schedules can reduce costs. Ultimately, it is the need to control rabies in dogs that must occupy most of our attention. The tools are available, but attitudes must change before they can be applied. There have been many new developments since publication of the last WHO rabies expert committee report in 1992 (new version in print)] and we will address those that have practical applicability.     

Transmission dynamics of rabies virus in Thailand: Implications for disease control

Background  

In Thailand, rabies remains a neglected disease with authorities continuing to rely on human death statistics while ignoring the financial burden resulting from an enormous increase in post-exposure prophylaxis. Past attempts to conduct a mass dog vaccination and sterilization program have been limited to Bangkok city and have not been successful. We have used molecular epidemiology to define geographic localization of rabies virus phylogroups and their pattern of spread in Thailand.     

Rabies encephalitis following fox bite--histological and immunohistochemical evaluation of lesions caused by virus

Rabies caused by fox bite is uncommon, most cases being caused by bite of rabid dogs (95%). We report a 45-year-old lady with rabies encephalomyelitis caused by bite of a rabid wild fox (Vulpes vulpes), a species prevalent in the Deccan plateaus of Central India. Though foxes are known to be susceptible to rabies, literature on the pathological changes caused by fox bite rabies in humans is scarce. Unlike the mild histological alterations described in canine rabies, a florid encephalitic process evolved in fox bite rabies, in our case, with intense microglial reaction, neuronophagia and perivascular inflammatory infiltrates despite clinical manifestation as a paralytic rabies. Immunostaining using polyclonal antibodies to the rabies viral nucleocapsid antigen and to the whole virion demonstrated high viral load within neurons with extensive spread along dendritic arborization and axonal tracts. Genomic sequence analysis demonstrated close homology with canine virus strain with only minor variations.