Thiravat Hemachudha
Chulalongkorn University, Medicine, Faculty Member
Over the past 10 years, new techniques and protocols have been proposed for rabies diagnosis, especially in humans. However, the reported number of laboratory-con-firmed human rabies cases remains limited and underestimates the real... more
Over the past 10 years, new techniques and protocols have been proposed for rabies diagnosis, especially in humans. However, the reported number of laboratory-con-firmed human rabies cases remains limited and underestimates the real impact of this neglected zoonotic disease, particularly in enzo-epizootic areas of Asia and Africa [1]. The regular reporting of diagnostic data through the structures of the World Orga-nization for Animal Health and the World Health Organization (WHO) (using the RABNET network, for example), together with the importance of the status of rabies as a notifiable disease in all countries, remain
Human coronavirus HKU1 (HCoV-HKU1) was first detected in a patient with viral pneumonia from Hong Kong in 2004. Here, we report the first complete genome sequence of HCoV-HKU1 from Thailand, obtained from a nonill person who worked in a... more
Human coronavirus HKU1 (HCoV-HKU1) was first detected in a patient with viral pneumonia from Hong Kong in 2004. Here, we report the first complete genome sequence of HCoV-HKU1 from Thailand, obtained from a nonill person who worked in a bat cave.
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The association between patch metrics and roosting site (n = 31) suitability of Lyle’s flying fox (Pteropus lylei) in 26 Central Eastern and Western provinces of Thailand was quantified. Land use classes with 90-m resolution were... more
The association between patch metrics and roosting site (n = 31) suitability of Lyle’s flying fox (Pteropus lylei) in 26 Central Eastern and Western provinces of Thailand was quantified. Land use classes with 90-m resolution were identified based on various vegetation and land cover types to calculate patch metrics using FRAGSTATS. Then, Maximum Entropy Modeling (MaxEnt) was performed using patch metrics covariates to produce a predictive potential distribution map. The results indicated that patch contiguity (contiguity index, 63.7%), patch area (29.3%), and patch shape complexity (shape index, 5.7%) are the most influential patch metrics, all of which have negative effects on roosting site suitability. In total, 13,222 small patches were considered highly suitable patches, with a mean area of 0.921 ± 0.698 (SD) ha, which accounted for 122,090 ha (2.04%) of the study area. Roosting sites predicted from the model were consistently associated with occurrences of roosting sites observ...
Research Interests: Geography and Contiguity
George M. Baer died this year in Mexico City at the aged of 72 years old. He was our mentor when we started intensive research on rabies pathogenicity and control in Bangkok some time in the early 1980s. He introduced the young Thai... more
George M. Baer died this year in Mexico City at the aged of 72 years old. He was our mentor when we started intensive research on rabies pathogenicity and control in Bangkok some time in the early 1980s. He introduced the young Thai scientists to the international rabies community. He then remained a friend and advisor to the “Mad Dog Gang” in Bangkok. Dr. Baer was born in London of German refugee parents and educated at Cornell University in the United States where he received his Doctor of Veterinary Medicine degree in 1959. This was followed by completion of the US-CDC Clinical Epidemiology Training Program where he eventually became the chief of the rabies division.
Pre- as well as post-exposure prophylaxis plays an important role in controlling the number of deaths associated with human rabies. Rabies vaccines, classically injected intramuscularly, are now also administered by intradermal (ID)... more
Pre- as well as post-exposure prophylaxis plays an important role in controlling the number of deaths associated with human rabies. Rabies vaccines, classically injected intramuscularly, are now also administered by intradermal (ID) route. Vaccines to be administered by the ID route should meet the same quality, safety and efficacy specifications as vaccines for intramuscular (IM) use. The aim of this paper is to provide information based on publicly available data regarding the ID use of rabies vaccines and to identify potential needs for further analysis of the potency, immunogenicity and effectiveness of rabies vaccines administered by this route. A first literature search, focused on the immunogenicity of rabies vaccines given by ID route, identified 338 publications in the period 1997-2018, 40 of which were included in our analyses. A second search investigating the effectiveness of ID vaccination resulted in 371 hits for the period 2007-2018, of which 13 suitable publications were retained. The immunogenicity of current rabies vaccines was analyzed in 3 ways: proportion of subjects reaching the antibody threshold of 0.5 IU/ml after ID vaccination, relationship between potency and immunogenicity of the vaccine given intradermally, and comparison of antibody responses after IM or ID vaccination. Overall, vaccines administered intradermally were found immunogenic. Post-exposure prophylaxis by ID route appeared at least as immunogenic as by IM regimens. By contrast, ID pre-exposure prophylaxis trended towards lower antibody titers than IM vaccination, but the observation was not associated with any clinical relevance. Vaccine effectiveness was assessed by investigating survival after exposure. Data from more than 30,000 patients who sought rabies post-exposure prophylaxis did not indicate that current vaccines administered by ID route lack efficacy. These results support current recommendations for ID vaccination against rabies. However, published data on ID performance were associated with significant weaknesses that future research should better address.
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ABSTRACTIn the age of a pandemic, such as the ongoing one caused by SARS-CoV-2, the world faces limited supply of tests, PPE and reagents, and factories are struggling to meet the growing demands. This study aimed to evaluate the efficacy... more
ABSTRACTIn the age of a pandemic, such as the ongoing one caused by SARS-CoV-2, the world faces limited supply of tests, PPE and reagents, and factories are struggling to meet the growing demands. This study aimed to evaluate the efficacy of pooling specimen 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 specimens were pooled for testing, containing either one or two known positive specimen of varying viral concentrations. Pooling specimens did not affect the sensitivity of detecting SARS-CoV-2, and the PCR cycle threshold (Ct) between testing of pooling specimen and subsequent individual testing was not significantly different using paired t-test. This study also identified cost savings garnered from pooling of specimen for testing at 4 differing prevalence rates, ranging from 0.1-10%. Pooling specimens to test for COVID-19 infection in low prevalence areas or in low risk popul...
Background The incidence of autoimmune encephalitis has risen globally. There are two general categories of disease-associated antibodies that can be tested for: neuronal surface and intracellular. However, testing both groups of... more
Background The incidence of autoimmune encephalitis has risen globally. There are two general categories of disease-associated antibodies that can be tested for: neuronal surface and intracellular. However, testing both groups of autoantibodies are costly. This study aims to identify differences between groups by comparing clinical presentations, radiological findings and CSF profile of patients, and determine if any parameters are indicative of one group of autoantibodies over another. Additionally, we aim to report the local incidence of less common groups of disease-associated antibodies as well. Methods Seventy-seven records of autoimmune encephalitis/encephalomyelitis patients admitted to King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between October 2010 and February 2017 were reviewed. Patients with infections or those with classic central nervous system demyelinating features were excluded. Results Of 77 patients, 40% presented with neuronal surface antibodies and ...
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Rabies is a life-threatening neglected tropical disease: tens of thousands of cases are reported annually in endemic countries (mainly in Africa and Asia), although the actual numbers are most likely underestimated. Rabies is a zoonotic... more
Rabies is a life-threatening neglected tropical disease: tens of thousands of cases are reported annually in endemic countries (mainly in Africa and Asia), although the actual numbers are most likely underestimated. Rabies is a zoonotic disease that is caused by infection with viruses of the Lyssavirus genus, which are transmitted via the saliva of an infected animal. Dogs are the most important reservoir for rabies viruses, and dog bites account for >99% of human cases. The virus first infects peripheral motor neurons, and symptoms occur after the virus reaches the central nervous system. Once clinical disease develops, it is almost certainly fatal. Primary prevention involves dog vaccination campaigns to reduce the virus reservoir. If exposure occurs, timely post-exposure prophylaxis can prevent the progression to clinical disease and involves appropriate wound care, the administration of rabies immunoglobulin and vaccination. A multifaceted approach for human rabies eradicatio...
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Sub-passaging of QS-05, a street rabies virus (RABV) isolate, in non-neuronal cells resulted in a virus with higher pathogenicity, QS-BHK-P7. Four full-length cDNA plasmids were constructed and the corresponding recombinant viruses were... more
Sub-passaging of QS-05, a street rabies virus (RABV) isolate, in non-neuronal cells resulted in a virus with higher pathogenicity, QS-BHK-P7. Four full-length cDNA plasmids were constructed and the corresponding recombinant viruses were recovered: rQS-05, rQS-BHK-P7 and rQS05-2475G/rQS-BHK-P7-2475A (made by switching of intergenic P-M between these two backbones). rQS-BHK-P7-2475 A virus had eight instead of seven adenosines in its poly(A) sequence. Interestingly, mutant viruses with 6 or 8 adenosines infected more neuroblastoma cells than their parental ones. Mice that were infected intracerebrally and intramuscularly with rQS05-2475G and rQS-BHK-P7 exhibited highest mortality. However, mice infected with rQS-BHK-P7-2475AA had the shortest survival time. This study demonstrates that modifications in the non-coding region may play a role in determining the virulence of RABV.
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Research Interests: Magnetic Resonance Imaging, Image Analysis, Brain, Humans, Female, and 15 moreMale, PARALYSIS, Rabies, Clinical Sciences, Aged, Middle Aged, Image Enhancement, Adult, Brachial Plexus, Disease Progression, Nuclear Magnetic Resonance Imaging, Encephalitis, Neurosciences, Neurologic Examination, and Macho
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Background: Acquired myasthenia gravis (MG) is the most common neuromuscular junction disorder. Acetylcholine receptor (AChR) antibody is found in the majority of MG. Objective: Describe and compare the clinical manifestations of MG... more
Background: Acquired myasthenia gravis (MG) is the most common neuromuscular junction disorder. Acetylcholine receptor (AChR) antibody is found in the majority of MG. Objective: Describe and compare the clinical manifestations of MG patients with and without the presence of serum AChR antibody. Material and method: Between 2009 and 2010, 90 cases with MG, treated at the adult neurology service of King Chulalongkorn Memorial Hospital were consecutively recruited. Serum AChR antibody was measured by enzyme linked immunosorbent assay. Result of 0.45 nmole per liter or over is considered positive. Patients were divided into two groups based on serological status. Demographic data and clinical parameters were recorded and compared. Results: Mean age was 47.5 +/- 15.6 years. Sixty-eight (75.5%) were female. Twenty-two (24.4%) had ocular MG and sixty-eight (75.6%) had generalized MG. Mean age of onset was 40.9 +/- 15.2 years. Sixty-seven (74.4%) were AChR antibody positive and twenty-three (25.6%) were AChR antibody negative. Limb/ocular-limb weakness was more commonly found in AChR antibody positive (p = 0.12) while pure ocular weakness was significantly found in AChR antibody negative (p = 0.006*). Myasthenic crisis (MC) tended to develop in AChR antibody positive (p = 0.06). Numbers of patients with moderate to severe weakness were significantly higher in AChR antibody positive (p = 0.04*). Thymic pathology was found in 72.3% of thymectomized AChR antibody positive patients. None of thymectomized seronegative patients had abnormal thymus. Good response to acetylcholine esterase inhibitors was more frequent in AChR antibody positive patients (p = 0.009*). Immunotherapy and thymectomy (p = 0.001*) were more frequently provided in AChR antibody positive patients. Conclusion: AChR antibody positive MG manifested more severe, generalized weakness with frequent MC. Abnormal thymic histopathology was more frequently found in AChR antibody positive MG. Response to ACEI was better in AChR antibody positive group. However overall outcomes of both groups were favorable without any difference.
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Encephalitis and polyneuritis occurring after rabies vaccination are believed to be immunologically mediated. We studied antibody responses to neural antigens in 36 patients with major neurologic complications, 25 with minor... more
Encephalitis and polyneuritis occurring after rabies vaccination are believed to be immunologically mediated. We studied antibody responses to neural antigens in 36 patients with major neurologic complications, 25 with minor complications, and 39 with no complications after immunization with a brain-derived, Semple rabies vaccine. Patients with major complications had significantly elevated levels of antibody to brain white matter as compared with the other groups (P less than 0.001). Assays for antibody to selected central nervous system antigens showed that high levels of serum and cerebrospinal fluid antibody to myelin basic protein correlated with the presence of major neurologic complications (both central and peripheral nervous systems). The level of antibody to cerebroside correlated best with the number of injections of vaccine, but like antibody to myelin basic protein, the antibody to cerebroside was present in the cerebrospinal fluid of patients with major complications. Some patients with major complications also had antibodies directed to the gangliosides GD1b and GT1b. No antibodies to myelin-associated glycoprotein were detected in any of the samples. These data implicate myelin basic protein as an encephalitogen in these autoimmune diseases of the human nervous system, but suggest that immune responses to cerebroside and certain gangliosides may have an augmentative role in severe disease.
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Combined active and passive immunization has been established to be an optimal strategy for rabies post-exposure prophylaxis (PEP). Prompt administration of vaccine and rabies immunoglobulin (RIG) can reliably prevent the disease.... more
Combined active and passive immunization has been established to be an optimal strategy for rabies post-exposure prophylaxis (PEP). Prompt administration of vaccine and rabies immunoglobulin (RIG) can reliably prevent the disease. However, RIG is unavailable and unaffordable in the majority of cases. On the basis of a model experiment using hamsters, we demonstrated that vaccine injection at the wound site in the same manner as administration of RIG provided protective efficacy that was not inferior to the current optimal PEP, a combination of vaccination and RIG. Further study is needed to determine whether it can replace the use of RIG.
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Research Interests: Thailand, Adolescent, Humans, Female, Male, and 5 morePrednisolone, Aged, Middle Aged, Adult, and Ophthalmoplegia
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Enterovirus infections are important causes of a sepsis-like syndromes in infants under 3 months of age. Most enterovirus infected patients presented with fever without localizing signs and rashes. Detection of enterovirus RNA by NASBA in... more
Enterovirus infections are important causes of a sepsis-like syndromes in infants under 3 months of age. Most enterovirus infected patients presented with fever without localizing signs and rashes. Detection of enterovirus RNA by NASBA in serum and/or CSF represents a rapid method for the diagnosis of enterovirus infection in infants presenting with a sepsis-like syndrome.
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Rabies post exposure treatment and rapid diagnosis in an endemic area requires skillful and an experienced medical staff and veterinary specialists. A software program was introduced in 2000 as a tool to diagnose rabies based on clinical... more
Rabies post exposure treatment and rapid diagnosis in an endemic area requires skillful and an experienced medical staff and veterinary specialists. A software program was introduced in 2000 as a tool to diagnose rabies based on clinical symptoms and signs of suspicious dogs where veterinarian service and other laboratory diagnostic options are not immediately available. It is easily accessed from the website: www.soonak.com/rabies.
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Sera from 26 patients with major neurologic complications, 19 patients with minor complications and 23 patients with no complications induced by Semple rabies vaccine were assayed for neutralizing antibody to rabies virus. Seroconversion... more
Sera from 26 patients with major neurologic complications, 19 patients with minor complications and 23 patients with no complications induced by Semple rabies vaccine were assayed for neutralizing antibody to rabies virus. Seroconversion to the protective level (greater than or equal to 0.5 IU/ml) was found in 21 of 22 patients (95%) with major complications, and in 7 of 19 (37%) with minor complications, occurring during the first 14 days of vaccination. This was in contrast to 42% (5/12) seroconversion in uncomplicated recipients after 14 daily injections. After initiation of dexamethasone treatment, 13 of 18 patients with major complications showed a diminution in their rabies antibody levels on day 4 or 7.
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Antibodies to HTLV-I were assayed in sera of 9 patients with progressive myelopathy, 11 with multiple sclerosis, 5 with myopathy and in 10 HIV-seropositive intravenous heroin abusers. Clinical features in 9 cases with progressive... more
Antibodies to HTLV-I were assayed in sera of 9 patients with progressive myelopathy, 11 with multiple sclerosis, 5 with myopathy and in 10 HIV-seropositive intravenous heroin abusers. Clinical features in 9 cases with progressive myelopathy were not different from those previously described in tropical spastic paraparesis associated with HTLV-I infection. No detectable HTLV-1 antibody was found in the sera of any of the 35 patients studied.
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Despite increases in our understanding of rabies pathogenesis, it remains an inevitably fatal disease. Lack of awareness, low level of political commitment to rabies control, and failure to recognize and correlate clinical, laboratory,... more
Despite increases in our understanding of rabies pathogenesis, it remains an inevitably fatal disease. Lack of awareness, low level of political commitment to rabies control, and failure to recognize and correlate clinical, laboratory, and neuroimaging features contribute to continuing deaths. Clinical symptomatology, once believed to be unique, may be variable, even in patients associated with lyssaviruses of the same genotype. This article discusses virus transport, the role of virus and host response mechanisms in relation to protean clinical manifestations, and mechanisms responsible for relative intactness of consciousness in human rabies. Differential involvement of the anterior horn cell in furious rabies and the peripheral nerve in paralytic rabies is summarized. Escape mechanisms from host defenses explain why a fatal outcome is unavoidable regardless of therapy. Neuroprotective treatment, using a coma-induction regimen, proves not to be beneficial. Survival of patients wit...
Rabies virus preferentially involves brainstem, thalamus and spinal cord in human furious and paralytic rabies beginning in the early stage of illness. Nevertheless, rabies patient remains alert until the pre-terminal phase. Weakness of... more
Rabies virus preferentially involves brainstem, thalamus and spinal cord in human furious and paralytic rabies beginning in the early stage of illness. Nevertheless, rabies patient remains alert until the pre-terminal phase. Weakness of extremities develops only when furious rabies patient becomes comatose; whereas peripheral nerve dysfunction is responsible for weakness in paralytic rabies. Evidence of apoptosis and mitochondrial outer membrane permeabilization in brain and spinal cord of 10 rabies patients was examined and these findings were correlated with the presence of rabies virus antigen. Although apoptosis was evident in most of the regions, cytochrome c leakage was relatively absent in spinal cord of nearly all patients despite the abundant presence of rabies virus antigen. Such finding was also noted in brainstem of 5 patients. Cell death in human rabies may be delayed in spinal cord and the reticular activating system, such as brainstem, thus explaining absence of weakn...
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Rabies is readily diagnosed when it presents as the classic furious form. Paralytic and atypical forms can pose significant problems in diagnosis. Catastrophic incidents included 7 organ transplant recipients who died of rabies recently... more
Rabies is readily diagnosed when it presents as the classic furious form. Paralytic and atypical forms can pose significant problems in diagnosis. Catastrophic incidents included 7 organ transplant recipients who died of rabies recently in United States and Germany. Although rabies remains top in the lists of differential diagnosis of encephalitis in rabies endemic area, its complication may divert physicians from making a relevant management. We encountered an unusual case of paralytic rabies who presented with spontaneous pneumomediastinum. A young male presented with fever and dysphagia. There was a history of fluctuating consciousness and aerophobia but they were absent or could not be demonstrated at the time of admission. He exhibited subcutaneous chest wall emphysema and was found to have pneumomediastinum which resulted in surgical intervention. He developed paralysis followed by seizures during postoperative period. Diagnosis was confirmed by demonstration of rabies RNA in ...
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Five male mature dogs with normal sex organs and normal pre-study semen evaluation received intratesticular injections of a sterile solution of balanced zinc gluconate. Semen without sperm could be collected on days 26, 30, 35 and 51 from... more
Five male mature dogs with normal sex organs and normal pre-study semen evaluation received intratesticular injections of a sterile solution of balanced zinc gluconate. Semen without sperm could be collected on days 26, 30, 35 and 51 from 4 dogs. The dogs achieved penile erection but no ejaculation before these days. There were no significant adverse effects and no change in the dog behavior during the time that they were observed. Histopathological findings documented virtually complete fibrosis of seminiferous tubules and Leydig cells on days 60 and 75. This preliminary study concludes that balanced zinc gluconate may be used to sterilize dogs.
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Rabies diagnosis in humans can be made by obtaining a history of exposure particularly to an animal bite, clinical symptoms and signs, neuroimaging such as magnetic resonance imaging (MRI) and laboratory testing. Although diagnosis made... more
Rabies diagnosis in humans can be made by obtaining a history of exposure particularly to an animal bite, clinical symptoms and signs, neuroimaging such as magnetic resonance imaging (MRI) and laboratory testing. Although diagnosis made by clinical grounds alone can be useful, this can only be limited to furious rabies. Owing to the fact that there is more than one form of rabies (furious, paralytic and atypical rabies) relying on only clinical diagnosis will undoubtedly lead to under reporting. The nonclassic or atypical rabies presents with a non specific pattern lacking pathognomomic signs as found in classic forms (furious and paralytic). A diagnosis of rabies should be considered in any patient who presents with encephalopathy of unknown cause. Diagnosis of rabies requires laboratory confirmation. MRI pattern may differentiate rabies from other viral encephalitides. Laboratory diagnosis can be used for confirmation by demonstration of viral proteins or its genomic RNA. The nucl...
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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... more
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. We analyzed 239 nucleoprotein gene sequences from animal and human brain samples collected from all over Thailand between 1998 and 2002. We then reconstructed a phylogenetic tree correlating these data with geographical information. All sequences formed a monophyletic tree of 2 distinct phylogroups, TH1 and TH2. Three subgroups were identified in the TH1 subgroup and were distributed in the middle region of the country. Eight subgroups of TH2 viruses were identified widely distributed throughout the cou...
Research Interests: Microbiology, Gene Flow, Medical Microbiology, Cats, Molecular Epidemiology, and 15 moreDogs, Phylogeny, Humans, Animals, Rabies, Population Density, Disease Control, Human Brain, Clinical Sciences, Cattle, Phylogenetic Tree, Geographic Information, Communicable disease control, Rabies Virus, and Buffaloes
Despite a success in reducing rabies deaths from almost 200 to less than 20 annually, this may not be considered a success. More than 400,000 persons required rabies post-exposure prophylaxis (PEP) in 2003, more than 4 times as many as... more
Despite a success in reducing rabies deaths from almost 200 to less than 20 annually, this may not be considered a success. More than 400,000 persons required rabies post-exposure prophylaxis (PEP) in 2003, more than 4 times as many as those in 1991 [93,641 cases in 1991; 183,815 in 1996 and 350,535 in 2001]. The number of samples submitted for testing in rabies diagnostic laboratories has been declining. However, the percent of samples that were confirmed infected with rabies during the 10 year period remained unchanged; within a range of 23 - 30% (MOPH report). Of the 6 million dogs roughly estimated to live in Thailand, there are no reliable data indicating their relative population densities or distribution patterns in various regions throughout the country. However, in a survey conducted by the Bureau of National Statistics and the Bangkok Metropolitan Administration in 1999, it was estimated that approximately 630,000 dogs dwell in Bangkok city (an area of 1 565 sq km). In thi...
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Government centered approach in rabies prevention and control has not led to rabies safe community, both in urban and rural areas. Government services and organizations should recognize that only joint collaboration among households and... more
Government centered approach in rabies prevention and control has not led to rabies safe community, both in urban and rural areas. Government services and organizations should recognize that only joint collaboration among households and community can lead to a successful rabies control mission. Dog owners should have been more actively involved in the prevention and solving of rabies problem. Promotion and support of government organizations should aim to strengthen the communities to become self reliance in diseases control and health care services. Only by strengthening community roles result in a more sustainable community disease control program.
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Whether human rabies of different forms, encephalitic (furious) and paralytic (dumb), share similar MR imaging patterns is unknown. We assessed the diagnostic value of MR imaging in both forms of the disease and compared the clinical and... more
Whether human rabies of different forms, encephalitic (furious) and paralytic (dumb), share similar MR imaging patterns is unknown. We assessed the diagnostic value of MR imaging in both forms of the disease and compared the clinical and neuroimaging findings. Three patients with paralytic and two with encephalitic rabies were examined during preserved or deteriorated levels of consciousness. Six MR examinations of the brain, three of the spinal cord, and one of the brachial plexus were performed with a 1.5-T superconducting magnet. No difference was noted between the MR findings in both clinical forms of human rabies. Nonenhancing, ill-defined, mild hyperintensity changes in the brain stem, hippocampi, hypothalami, deep and subcortical white matter, and deep and cortical gray matter were demonstrated on T2-weighted images in the noncomatose patients with rabies. Enhancement along the brachial plexus of the bitten arm was noted in one patient with encephalitic rabies who at that tim...