Priorities and Future of Diagnosis of Emerging Viral Diseases
Pradip V. Fulmali, MSc
Viral Disease Biology Program
Rajiv Gandhi Center for Biotechnology
Trivandrum – 695014, Kerala, India
Email: pradipfulmali@gmail.com
Mumps is an acuteinfectious disease caused by the mumps virus, which is a member ofthe paramyxoviridae family. Mumps (epidemic parotitis) is an acutecommunicable disease characterized by the painful enlargement of thesalivary glands, particularly the parotid glands. Neurologic andocular manifestations of mumps are well documented but seldom appearconcomitantly.29-32 Meningitis and mild meningoencephalitis are the most frequentcomplications of mumps in children. The epidemiology of mumps inIndia is not well understood. Despite the availability of aneffective vaccine, it continues to occur in epidemic proportions,with significant morbidity in the pediatric age group.33 The clinical diagnosis of mumps is made on the basis of the presenceof acute unilateral or bilateral parotitis. Laboratory confirmationof mumps infection is achieved through the isolation of IgM-specificantibodies to mumps virus in acute-phase serum samples, mumps virusin cell culture, or RNA of the mumps virus by RT-PCR.
WN virus has beenreported to cause mild, febrile illness in southern India.34 Severe WN encephalitis has been documented in the pediatric andelderly populations of the Kolar region of Karnataka (during 1977,1978, and 1981) and Dibrugarh region of Assam (during 2008).Serological tests confirmed the diagnosis in these cases as WN fever,and the WN virus was isolated from human clinical specimens.35 Additionally, febrile illness in epidemic form and clinically overtencephalitis cases has been documented in the Udaipur area ofRajasthan and Buldhana, Marathwada, and Khandesh districts ofMaharashtra.36 Neutralizing antibodies specific to the WN virus have been detectedin about 20–30% of human serum samples collected from TamilNadu, Karnataka, Andhra Pradesh, Maharashtra, Gujarat, MadhyaPradesh, Orissa, and Rajasthan.37 All these studies indicate continuous WN virus activity in India.However, in most areas, JE and WN viruses coexist, and these casesremain undiagnosed because of the lack of virus-specific diagnostictests.
DV is one of themost prevalent viral species in India. It causes dengue, which has aclinical presentation ranging from a self-limiting disease to moresevere forms, such as dengue hemorrhagic fever (DHF) and dengue shocksyndrome (DSS). Acute febrile encephalopathy (AFE) is a common causeof childhood hospital admission in many parts of India. Theassociation of DV with neurological conditions, such as encephalitis,myelitis, mononeuropathies, acute disseminated encephalomyelitis, andGuillain–Barré syndrome has been documented.38-40 The frequency of dengue in patients with encephalitis, assessed onthe basis of the presence of anti-dengue IgM in the serum, has beenshown to range from 5% to 20% .41Thepathogenesis of the neurological manifestations is not clearlydefined, but some reports have attributed it to the encephalopathypresent in severe cases of DHF. Encephalopathy/encephalitis-likecomplications have also been recently documented in DV infections innorthern and eastern India, other Asian countries, and South America. 42,43 However, the involvement of the brain and spinal cord is uncommon inDV infection, and the prognosis is poor in patients presenting withencephalitis or myelitis.44 DV has been isolated from the blood of patients having severeneurological complications.45
Paramyxoviruses havebeen implicated in both animal and human infections. Morbillivirusesare responsible for large-scale epidemics. Fatal infection in horsesand humans was determined to be caused by a new paramyxovirus, Hendravirus (HeV) in Australia, and a closely related virus—Nipahvirus (NiV)—was responsible for fatal infections in pigs andhumans in Malaysia. Human cases of NiV and HeV virus(paramyxoviruses) infections with high mortality have been documentedin Australia, Malaysia, Singapore, India, and Bangladesh. The firstknown NiV encephalitis outbreak occurred in Siliguri region (WestBengal), India, during 2001.6 Relapse encephalitis and long-term neurological defects have beendocumented in a significant portion (~10%) of the patients recoveringfrom acute Nipah virus infection. In outbreak situations inBangladesh and India, the mortality rate rose to approximately70%.46,47 The multiple outbreaks of NiV in Bangladesh and the 2001 outbreak inWest Bengal show a continued risk for spillover infection betweenbats and humans in this region.48 Henipavirus infections are probably more widespread than currentestimations and therefore warrant intense monitoring, especially incountries where large-scale deforestation occurs.49
-
KFD was discoveredin 1957 in the Mysore forest region of south India, where 400–500persons per year are infected with the virus.50 KFD virus has been found only in monkeys, humans, and Haemaphysalisspinigera ticks in the KFD-epidemic region of south India.51 KFD antibodies have been detected in residents of north and northeastIndia, and the KFD seropositive rate is especially high amongresidents of India’s Andaman and Nicobar Islands. KFDantibodies also were detected in both human and bird sera in theChinese districts of Guangdong, Guangxi, Guizhou, Hubei, Henan,Xinjiang, and Qinghai in 1983. Recently, KFD has also been isolatedfrom humans in China.52 Considering the spread of KFD to newer areas, there is clearly a needfor developing a rapid diagnostic system for KFD. In view of thechanging ecology, the spread of KFD virus warrants attention since itcan extend to localities never affected before. Among the majorinfections of viral origin are encephalitis due to herpes simplex(HSV), Epstein–Barr virus, cytomegalovirus, or herpes zostervirus, which can be treated with special antiviral drugs.53 HSV encephalitis is a rare but extremely serious brain disease causedby HSV–1 in the pediatric population, except newborns. In about70% of infant HSV encephalitis, the disease occurs when a latentHSV–2 virus is activated. When left untreated, HSV encephalitisis fatal in over 70% of the cases in India. Each year, about 2,100cases of encephalitis are reported from the USA, while the exactincidence of encephalitis in India is not known. Therefore, there isa need to develop sensitive and specific diagnostic tests for theearly detection of the herpes group of viruses.
Currently,enteroviruses are posing a global health concern and cause a widespectrum of diseases that includes myocarditis and pericarditis,exanthems and enanthems, conjunctivitis, and meningitis. Theassociation of a few enteroviruses has been identified with human CNSinfections leading to fatal neurological disease. Enteroviruses alsocause seasonal aseptic meningitis and meningoencephalitis in younginfants. Recently, the association of enterovirus 76 has beenrecognized in 30% of the encephalitis cases in northern India.54 In spite of the best efforts, more than 70% of the cases of viralencephalitis remain undiagnosed and pose a challenge to bothclinicians and virologists. However, except the JE virus, other viralagents associated with the remaining 70% of the encephalitic caseshave not been characterized because of the lack of specific andsensitive diagnostic techniques. Rapid and specific diagnosis of theinfectious agent in emergency situations assists the clinician inmonitoring the patients, which would help decrease the morbidity andmortality.
Different viraldiagnostic assays and their limitations
With the largenumber of tests available for the detection of infectious agentsaffecting humans, it is often not recognized that most of these testsare indirect. For infections caused by agents such as hepatitis Cvirus (HCV), hepatitis B virus (HBV), human immunodeficiency virus(HIV), or other agents of viral or bacterial origin, commonly usedtests determine the presence of specific antibodies produced by thepatient’s immune system in response to the infectious agent.These tests are useful for blood screening and, to a limited extent,as diagnostic tools, but because they offer only an indirect measureof infection, they do not clarify whether the infection is past orcurrent or whether there is a response to the therapy. Anantibody-based test can also miss a recent infection, becausegenerally, it may take several days to weeks for the immune system tomount an antibody response to the infectious agent. This can beespecially dangerous if the infectious agent rapidly spreads in thepatient or if the blood from an apparently healthy but recentlyinfected person (with HIV or HCV) is used for blood transfusion.
A new generation oftests has been developed to directly measure the concentration of theinfectious agent within the patient’s sample. These testsdetect the presence of nucleic acids (the genetic material) of theinfections agents in the blood or other samples from the patient. Twomajor methods have been developed and accepted for detection ofinfectious agents in patient samples. The most common is thepolymerase chain reaction (PCR), which uses an enzymatic reaction toamplify specific nucleic acid sequences from the infectious agent ifthey are present in the sample.55-60
Latest Articles
Emerging and re-emerging infectious diseases in Kerala
R. Sajith Kumar and Edited by Prathiksha
Emerging and reemerging infectious diseases pose a threat to the stability of nations worldwide due to their adverse effects on health and development. Factors for the emergence/re-emergence of infectious diseases are complex and interrelated...
Scrub Typhus presenting as Atypical Pneumonia
Sajan Christopher, K. Sreekanthan
Scrub typhus is being increasingly reported in India. It is highly endemic in suburban regions of Thiruvananthapuram. It should be considered in the differential diagnosis of patients with acute febrile illness
Commentary
Towards a paradigm shift in rabies treatment
Ramkumar Hariharan
The almost fairy tale-like story of 15-year old Jeanna Giese, who became a medical first in 2004, by surviving rabies without any post-exposure prophylaxis, has sparked renewed interest and enthusiasm in the treatment of this fatal disease. The completely novel medical protocol that was used to treat Giese was crafted by Dr Rodney Willoughby and his team at the Children’s Hospital in Wisconsin...
Infectious Diseases – An Ayurvedic Perspective
R. B. Hosamani
The nature being the mother of mankind has always had soothing effect. But in the process of learning for his comfort man has neglected the untoward effects on nature.
Pictorial Commentary
Cerebral Rabies
S. K. Shankar,
Anita Mahadevan,
M.S. Suja
A sixteen year old male presented with acute onset of paresthesias
Cerebral Malaria
K.P. Aravindan
Autopsied brain of a guest worker from Orissa seen through the microscope. The delicate branching capillaries