Rabies 2007: perspective from Asia.

Rabies remains a public health problem in many parts of the less developed world. Much is known about the virology, pathophysiology, epidemiology, and methods for control but this knowledge is not applied in many countries. Thailand has been on the frontline of efforts to conduct research in rabies for almost a century, starting with Dr. Leopold Robert from the Institute Pasteur of Paris. He was invited by the Thai King in 1913 to develop a research and production facility for rabies vaccine and snake antivenins which later became the Queen Saovabha Memorial Institute. Thai physicians, scientists and nurses, jointly with some notable expatriate colleagues, were then responsible for major advances in rabies vaccine development, rational application of preand postexposure prophylaxis and better understanding of immunology and pathophysiology of this dread disease. They not only discovered new scientific principles but also cost-benefit methods for their application and set the foundation for the work conducted in Thailand during the next two decades. Many concepts developed by Thai scientists have been incorporated into WHO and US-CDC rabies management guidelines. This is an overview of significant developments during the past two decades [1-8].

A prospective study of enterovirus infection in Thai infants presenting as sepsis.

Objective: To study prospectively the prevalence, clinical presentations and laboratory findings of enterovirus (EV) infection in infants under 3 months of age who present as a sepsis-like syndrome. Method: All infants less than 3 month of age admitted as a sepsis-like syndrome to King Chulalongkorn Memorial Hospital between April 2003 and February 2004 were included. Patients who were immunocompromised or who had been admitted for longer than 14 days before developing symptoms were excluded. A detailed history, physical and laboratory findings were recorded and analyzed. Specimens of blood and cerebrospinal fluid were tested for enteroviruses using Nucleic Acid Sequence-Based Amplification (NASBA). Patients were followed to determine the clinical outcome and duration of hospitalization. Results: Of 56 infants, thirty-six were admitted to the pediatric wards and 20 had been hospitalized since birth in the neonatal intensive care unit (NICU) or nursery wards. Enterovirus infection was diagnosed in 13 (36.1 %) of the patients admitted to the pediatric wards and none in the group of NICU/nursery patients. The most common clinical presentations were high grade fever (92 %), rashes (77 %) and lethargy (54 %) as compared to fever (78.3 %), poor feeding (60.9 %) and lethargy (56.5 %) in the EV negative group. Ten (76.9 %) of the enterovirus positive infants had evidence of central nervous system (CNS) involvement as evidenced by the presence of EV RNA in cerebrospinal fluid (CSF) or CSF pleocytosis plus EV RNA in blood and/or CSF. Nevertheless, CSF pleocytosis was found in only 7 infants (53.8 %). Average duration of illness was 3.2 days as compared to 3.5 days in the nonenteroviral group with similar clinical features. All enterovirus positive patients had an uncomplicated recovery. Ten (76.9 %) received parenteral antibiotics for a mean of 5 days (versus 4.8 days in enterovirus negative group). The average length of stay was 8.1 days as compared to 15 days in enterovirus negative group. Conclusion: 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.

Computer based program for rapid canine rabies diagnosis.

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.

[Bat lyssavirus in Thailand]

A study of bat lyssavirus survey was done in Thailand from 2001 to 2003. A total of 932 bats of 11 species were captured in 8 provinces for blood collection and testing for neutralizing antibodies against rabies virus (RABV), Australian bat lyssavirus (ABLV) and broader panel of other lyssaviruses (Irkut, Aravan and Khujand). All Thai bat samples were negative to RABV Sixteen samples of 394 with sufficient volume of serum had detectable neutralizing antibodies against Irkut, Aravan, Khujand and ABL viruses. Another 13 samples were also found to have antibody to ABLV. However, due to insufficient volume, further analysis to other lyssaviruses could not be performed. Nevertheless, this showed that the prevalence of lyssavirus infection in Thai bats could be as high as 7.3% (29/396). The present study showed that natural occurrence of lyssavirus antibodies found in Thai bats were related to newer putative lyssavirus genotype(s) other than those previously described. These data also suggest that several lyssaviruses are in circulation throughout Thailand as well as other Asian countries, such as in the Philippines, Central Asia, and in certain parts of Russia. The present study and preparation of this article was supported by grants from the Thailand Research Fund and the National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Thailand.

[Rabies diagnosis in human]

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 nucleic acid amplification method is often used as a diagnostic test due to its good sensitivity and specificity and can be applied to wide varieties of specimens. Accurate data on rabies statistics contribute to the success in control and prevention of rabies.

Intratesticular injection of a balanced zinc solution for permanent sterilization of dogs.

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.

Rabies and dog population control in Thailand: success or failure?

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 this survey, approximately 110,000 of the dogs living in Bangkok were considered to be ownerless (stray or feral), whereas the remainder was believed to be owned or were community dogs. Nevertheless, it has not been known how many of the latter group can be accessible or are in compliance with local rabies control regulations. When the dog population statistics collected in 1999 are compared to an earlier survey conducted in 1992, the stray dog population appears to have almost tripled in size in Bangkok over the eight year

Paradigm shift in rabies control: a system approach.

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.