Govindakarnavar Arunkumar

Hand, foot and mouth disease (HFMD): emerging epidemiology and the need for a vaccine strategy

Hand, foot, and mouth disease (HFMD) is a contagious viral disease and mainly affects infants and young children. The main manifestations are fever, vesicular rashes on hand, feet and buttocks and ulcers in the oral mucosa. Usually, HFMD is self-limiting, but a small proportion of children may experience severe complications such as meningitis, encephalitis, acute flaccid paralysis and neurorespiratory syndrome. Historically, outbreaks of HFMD were mainly caused by two enteroviruses: the coxsackievirus A16 (CV-A16) and the enterovirus 71 (EV-A71). In the recent years, coxsackievirus A6 and coxsackievirus A10 have been widely associated with both sporadic cases and outbreaks of HFMD worldwide, particularly in India, South East Asia and Europe with an increased frequency of neurological complications as well as mortality. Currently, there is no pharmacological intervention or vaccine available for HFMD. A formalin-inactivated EV-A71 vaccine has completed clinical trial in several Asian countries. However, this vaccine cannot protect against other major emerging etiologies of HFMD such as CV-A16, CV-A6 and CV-A10. Therefore, the development of a globally representative multivalent HFMD vaccine could be the best strategy.

Acute flaccid paralysis due to West nile virus infection in adults: A paradigm shift entity

Three cases of acute flaccid paralysis (AFP) with preceding fever are described. One patient had a quadriparesis with a florid meningoencephalitic picture and the other two had asymmetric flaccid paralysis with fasciculations at the onset of illness. Magnetic resonance imaging in two cases showed prominent hyperintensitities in the spinal cord and brainstem with prominent involvement of the grey horn (polio-myelitis). Cerebrospinal fluid (CSF) polymerase chain reaction was positive for West Nile virus (WNV) in the index patient. All three cases had a positive WNV immunoglobulin M antibody in serum/CSF and significantly high titer of WNV neutralizing antibody in serum, clearly distinguishing the infection from other Flaviviridae such as Japanese encephalitis. WNV has been recognized in India for many decades; however, AFP has not been adequately described. WNV is a flavivirus that is spread by Culex mosquitoes while they take blood meals from humans and lineage 1 is capable of causing a devastating neuro-invasive disease with fatal consequences or severe morbidity. We describe the first three laboratory confirmed cases of WNV induced AFP from Kerala and briefly enumerate the salient features of this emerging threat.

Influenza virus neuraminidase (NA): a target for antivirals and vaccines

Influenza, the most common infectious disease, poses a great threat to human health because of its highly contagious nature and fast transmissibility, often leading to high morbidity and mortality. Effective vaccination strategies may aid in the prevention and control of recurring epidemics and pandemics associated with this infectious disease. However, antigenic shifts and drifts are major concerns with influenza virus, requiring effective global monitoring and updating of vaccines. Current vaccines are standardized primarily based on the amount of hemagglutinin, a major surface antigen, which chiefly constitutes these preparations along with the varying amounts of neuraminidase (NA). Anti-influenza drugs targeting the active site of NA have been in use for more than a decade now. However, NA has not been approved as an effective antigenic component of the influenza vaccine because of standardization issues. Although some studies have suggested that NA antibodies are able to reduce the severity of the disease and induce a long-term and cross-protective immunity, a few major scientific issues need to be addressed prior to launching NA-based vaccines. Interestingly, an increasing number of studies have shown NA to be a promising target for future influenza vaccines. This review is an attempt to consolidate studies that reflect the strength of NA as a suitable vaccine target. The studies discussed in this article highlight NA as a potential influenza vaccine candidate and support taking the process of developing NA vaccines to the next stage.

Herbal plants and plant preparations as remedial approach for viral diseases

Herbal plants, plant preparations and phytoconstituents have proved useful in attenuating infectious conditions and were the only remedies available, till the advent of antibiotics (many being of plant origin themselves). Among infectious diseases, viral diseases in particular, remain the leading cause of death in humans globally. A variety of phytoconstituents derived from medicinal herbs have been extensively studied for antiviral activity. Based on this rationale, an online search was performed, which helped to identify a large number of plant species harboring antiviral molecules. These herbal sources have been reported individually or in combinations across a large number of citations studied. Activities against rabies virus, Human immunodeficiency virus, Chandipura virus, Japanese Encephalitis Virus, Enterovirus, Influenza A/H1N1 and other influenza viruses were discovered during the literature search. This review includes all such plant species exhibiting antiviral properties. The review also encompasses composition and methodologies of preparing various antiviral formulations around the globe. An elaborate section on the formulations filed for patent registration, along with non-patented formulations, has also been included in this article. To conclude, herbal sources provide researchers enormous scope to explore and bring out viable alternatives against viral diseases, considering non-availability of suitable drug candidates and increasing resistance to existing drug molecules for many emerging and re-emerging viral diseases.

Possible non-sexual modes of transmission of human papilloma virus

There is strong evidence to suggest vertical and horizontal modes of transmission of human papilloma virus (HPV), an established etiologic agent of cervical cancer. Infants, children, and adults can acquire both high‐risk and low‐risk infections by birth or by close contact even though HPV is mainly transmitted sexually. A thorough review of the literature was performed to assess the possible non‐sexual modes of transmission of HPV.

Pitfalls and optimal approaches to diagnose melioidosis.

Melioidosis is a severe and fatal infectious disease in the tropics and subtropics. It presents as a febrile illness with protean manifestation ranging from chronic localized infection to acute fulminant septicemia with dissemination of infection to multiple organs characterized by abscesses. Pneumonia is the most common clinical presentation. Because of the wide range of clinical presentations, physicians may often misdiagnose and mistreat the disease for tuberculosis, pneumonia or other pyogenic infections. The purpose of this paper is to present common pitfalls in diagnosis and provide optimal approaches to enable early diagnosis and prompt treatment of melioidosis. Melioidosis may occur beyond the boundaries of endemic areas. There is no pathognomonic feature specific to a diagnosis of melioidosis. In endemic areas, physicians need to expand the diagnostic work-up to include melioidosis when confronted with clinical scenarios of pyrexia of unknown origin, progressive pneumonia or sepsis. Radiological imaging is an integral part of the diagnostic workup. Knowledge of the modes of transmission and risk factors will add support in clinically suspected cases to initiate therapy. In situations of clinically highly probable or possible cases where laboratory bacteriological confirmation is not possible, applying evidence-based criteria and empirical treatment with antimicrobials is recommended. It is of prime importance that patients undergo the full course of antimicrobial therapy to avoid relapse and recurrence. Early diagnosis and appropriate management is crucial in reducing serious complications leading to high mortality, and in preventing recurrences of the disease. Thus, there is a crucial need for promoting awareness among physicians at all levels and for improved diagnostic microbiology services. Further, the need for making the disease notifiable and/or initiating melioidosis registries in endemic countries appears to be compelling.

Detection of genital HPV infection using urine samples: a population based study in India

BACKGROUND Cervical cancer is the second commonest cancer among Indian women and its association with human papilloma virus (HPV) is well established. This preventable cancer accounts for the maximum number of cancer related deaths among rural Indian women. Unlike in developed countries there are no organized cervical cancer screening programmes in India due to lack of resources and manpower. OBJECTIVE To detect genital HPV infection using urine samples among asymptomatic rural women in the age group of 18-65 years. MATERIALS AND METHODS The study area chosen was Perdoor village in Udupi Taluk, Karnataka State and all the women in the age group of 18-65 years formed the study cohort. A cross sectional study was conducted by house visits and 1,305 women were enrolled in the study. After taking written informed consent a data sheet was filled and early stream random urine samples were collected, transported to a laboratory at 4OC and aliquoted. Samples were tested using nested HPV PCR with PGMY09/11 and GP5+/6+ primers. Positive cases were genotyped by sequence analysis. RESULTS Study participants included 1,134 sexually active and 171 unmarried women with a mean age at marriage of 22.1 (SD=3.9) years. Study area showed high female literacy rate of 86.6%. Five urine samples tested positive for HPV DNA (0.4%). CONCLUSIONS We found very low genital HPV infection rate among women from monogamous community. This is the first major population based study carried out among asymptomatic rural women to detect genital HPV infectio from Karnataka using urine samples.

Knowledge, Attitude and Practice Concerning Human Papilloma Virus Infection and its Health Effects among Rural Women, Karnataka, South India

BACKGROUND Cervical cancer is one of the commonest cancers among women all over the world. The association of cervical cancer with human papilloma virus (HPV) is well established. Knowledge about the causal relationship between HPV and cervical cancer is important to make appropriate, evidence-based health care choices. In this context we conducted a community based study among women about the knowledge, attitude and practice about HPV infections and their health effects. MATERIALS AND METHODS A cross sectional interview based house to house survey was conducted with a validated data collection tool covering sociodemographic factors, knowledge, attitude and practice about HPV and its health effects, among 1020 women from a rural village, Perdoor, in Udupi district, Karnataka, India in 2013-14. RESULTS The mean age of participants was 38.9 years (SD=12.6). Study participants showed a high literacy rate (85.7%). Only 2.4% of sexually exposed women had undergone Pap smear testing. Partners of 4.4%women had undergone circumcision and they belonged to the Muslim community. Male condom usage was reported by 26 women (2.6%). However, none of the participants had heard of HPV and its health effects. CONCLUSIONS This community based study found complete ignorance about HPV among rural South Indian women in spite of a high literacy level.

Global human papilloma virus vaccine implementation: An update

Human papillomavirus (HPV) infections continue to be one of the most common sexually transmitted infections worldwide. The oncogenic potential of this virus was well established in anogenital malignancies and oropharyngeal cancers. Even though a fall in cervical cancer rates has been reported worldwide, the subsequent rise in HPV‐associated head and neck cancers among men and women have been reported from developed countries, necessitating the vaccination of adolescent boys as well. The objective of this narrative review is to provide an update on the current status of HPV vaccination worldwide. This will be helpful for clinicians in counseling parents and guardians as this vaccine mainly targets sexually naïve preadolescents. An electronic search of the databases was carried out to retrieve information concerning HPV vaccine implementation between July 2006 and 2017, with special emphasis on the current viewpoints, controversies and ethical issues. Globally, 74 countries have implemented the HPV vaccine in the national immunization schedule, and this vaccine is listed as an essential medicine by WHO. About 60% of the low‐ and lower–middle‐income countries have implemented the vaccine with financial assistance from Gavi and WHO. The HPV vaccine is a safe vaccine with no serious adverse effects as per the data available from developed nations as well as low/lower middle/upper middle‐income countries. However, long‐term follow‐up is essential to substantiate the impact of the vaccination programs in cancer prevention.

Genetic analysis of neuraminidase gene of influenza A(H1N1)pdm09 virus circulating in Southwest India from 2009 to 2012

Genetic analysis of neuraminidase gene sequences in 23 archived isolates of influenza A(H1N1)pdm09 virus, isolated during the 2009–2012 influenza seasons, was carried out to determine the genetic variability. Amino acid substitutions were observed at the rates of 0.3–0.7% per year. The catalytic site consisting of 8 functional and 11 framework residues were found conserved in 20 isolates and mutated in three (E228G, E278G, and N295T) isolates. To the best of our knowledge the three catalytic site mutants observed in our study have not been reported elsewhere to date. Similarly, mutations in the antigenic sites (K217E, K254E, V267A, and D451E except I263V) are discussed for the first time through this article. The effect of these mutations on drug and antibody binding were analyzed using biochemical and structural studies. Detailed studies on the neuraminidase gene are sparse and our study may serve as an appropriate platform to gain insights about the evolution of influenza virus, thereby facilitating drugs/vaccines design and development. J. Med. Virol. 89:202–212, 2017.