Hepatitis C virus infection in a tertiary care hospital in Mumbai, India: Identification of a mixed and novel genotype

Purpose: Hepatitis C virus (HCV) is a leading cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). HCV being a ribonucleic acid virus has considerable sequence variability. Assessment of viral load and genotype is necessary for designing treatment strategies and monitoring for viral resistance among HCV-infected cases. HCC is the most common form of liver cancer, often occurring in people with chronic hepatitis B or C. We undertook this study to observe genotype distribution of the virus in HCV patients from Mumbai. Materials and Methods: Between January 2017 and December 2017, the study was conducted on 120 chronic hepatitis outpatients from a tertiary care hospital, Mumbai, after obtaining ethics approval. All these diagnosed cases of HCV were subjected to molecular diagnosis in a research institute, Mumbai, by real-time polymerase chain reaction-based techniques. Results: Males were more preponderant than females with HCV infection, and the highest number of HCV-infected cases was observed in the age group of 41–50 years. Genotype 3 (n = 70; 58.3%) accounted for the highest number of cases followed by genotypes 1b (n = 29; 24.2%) and then 1a (n = 14; 11.7%). Mixed genotypes 1b + 3 and individual genotype 4 were found in two cases each (1.7%). A total of three samples (2.5%) were found with untypeable genotype. Conclusion: The major HCV genotype observed was 3 which is difficult to treat with direct-acting antivirals, owing to the more rapid progression of liver disease, increased rates of steatosis (non-alcoholic fatty liver disease), a higher risk for cancer (HCC). We believe this study is the first one to address the prevalence of mixed genotypes and untypeable genotype from India.

Dengue presenting as Acute Liver Failure A case report

Background: Dengue is the most common arboviral illness in humans. It is transmitted by mosquitoes of the genus Aedes, which are widely distributed in subtropical and tropical countries. The dengue virus has four related but antigenically distinct serotypes: DENV-1, DENV-2, DENV-3, and DENV-4. Many patients with dengue experience a prodrome of chills and facial flushing, which may last for 2-3 days. Other symptoms may include headache, retro-orbital pain, severe myalgias, nausea and vomiting, maculopapular or macular confluent rash over the thorax with islands of skin sparing, weakness, altered taste sensation, anorexia, sore throat, hemorrhagic manifestations (e.g. petechiae, bleeding gums, epistaxis and hematuria) and lymphadenopathy. The incubation period is 3-14 days. Criteria for the diagnosis of dengue hemorrhagic fever, according to the World Health Organization (WHO), are as follows: Fever, Hemorrhagic manifestations (e.g. hemoconcentration, thrombocytopenia, and positive tourniquet test), Circulatory failure, such as signs of vascular permeability (e.g. hypoproteinemia, effusions) and Hepatomegaly. Aim: To know the atypical manifestations of Dengue such as acute liver failure, seizures and encephalopathy. Material and methods: Study material obtained from Columbia Asia hospital Patiala along with all the records and detailed history of the patient. The study was carried out in Intensive Care Unit of the hospital where the patient was admitted. Observation and conclusion: In our case, patient presented with Dengue Hemorrhagic Fever. He developed acute liver failure which was considered to be due to dengue infection as antigen for the same was positive and other viral markers were negative. Acute liver failure manifested in the form of raised liver enzymes, coagulopathy, and encephalopathy. Dengue can lead to mild to moderate elevation of liver enzymes but complication of acute liver failure is rare.

Antiviral activity of crude extracts of Eugenia jambolana Lam. against highly pathogenic avian influenza (H5N1) virus.

Crude extracts of leaves and bark of E. jambolana were tested for antiviral activity against highly pathogenic avian influenza virus (H5N1) by CPE reduction assay in three different layouts to elucidate virucidal, post-exposure and pre-exposure antiviral activity of the extracts. The cold and hot aqueous extracts of bark and hot aqueous extract of leaves of E. jambolana showed significant virucidal activity (100% inhibition) which was further confirmed in virus yield reduction assay (~98 to 99% reduction) and by egg based in ovo assay. The selective index (CC50/EC50) of hot aqueous extract (248) and cold aqueous extract (43.5) of bark of E. jambolana showed their antiviral potential against H5N1 virus. The significant virucidal activity of leaves and bark of E. jambolana merits further investigation as it may provide alternative antiviral agent for managing avian influenza infections in poultry farms and potential avian-human transmission.

Impact of mass supplementation of vitamin A.

OBJECTIVE: To study the impact of mass supplementation of Vitamin A solution on morbidity due to diarrhea, Acute respiratory infection (ARI) and xerophthalmia. METHODS: The two rounds of age specific mass distribution of Vitamin A solution were undertaken during January 2000 and December 2000 respectively covering 27,642 (98.7%) and 31,762 (88.0%) children respectively out of total beneficiaries in two round of PPI in Chandigarh. A random sample of 276 children from intervention area and 252 children from control area in the age group of 1-5 yr were followed up on monthly basis for morbidity pattern for a period of nine mth. The morbidity pattern for intervention and control area children was compared to see the impact of mass supplementation of Vitamin A solution. RESULTS: The average annual episodes of diarrhea in intervention children were lower (3.9 per yr) as compared to control children (5.2 per yr) although difference was not statistically significant (P>0.05) except in initial month. The average annual episodes of ARI in intervention children were lower (5.1 per yr) as compared to Control children (6.0 per yr) although difference was not significant (P>0.05) except in initial first mth. There was significant decline in vitamin A deficiency (VAD) as no case of Bitot's spot was found in intervention children as compared to control children where the prevalence of Bitot's spot ranged from 4.3-5.08% during different visits. The mortality rate was found to be higher in control children with a death rate of 8 per 1000 children during the study period as compared to intervention children where no death was recorded. CONCLUSION: It is concluded that mass supplementation of vitamin A led to significant reduction in xerophthalmia and decline in mortality in the intervention area as compared to control area.

Validity of verbal autopsy in determining causes of adult deaths.

A verbal autopsy (VA) questionnaire, which had an open-ended description of the deceased's illness followed by a series of close-ended questions on specific symptoms and signs, was used by three trained field workers to interview relatives of the deceased who had died in a Chandigarh hospital in previous year. The sensitivity and specificity of the cause of death assigned by physician from the verbal autopsy was calculated against the cause of death derived from the hospital records. Of the 262 verbal autopsies, 60% were males and 23% belonged to rural area. Specificity of VA cause of death was high (>95%) for all broad cause groups except cardiovascular (79%) diseases. Sensitivity was highest for injuries (85%) and it was in the range of 60% to 65% for circulatory diseases, neoplasms, and infectious diseases. Sensitivity was low (20% to 40%) for respiratory, digestive and endocrine diseases. Cause specific proportionate mortality for major cause groups by the VA were statistically similar to the causes of deaths derived from the hospital records (p>0.05). Therefore, VA can be used for determining causes of adult deaths.

Evaluation of cold chain system in Chandigarh during PPI campaign 2001-2002.

OBJECTIVE: To evaluate the maintenance of cold chain system (CCS) in intensified pulse polio immunization (IPPI) programme, during December 2001 and January 2002 in Union Territory (UT) Chandigarh. MATERIALS & METHODS: A Cross sectional time bound study was conducted in seven centres, where OPV vials were stored prior to IPPI and 20 IPPI Booths in UT, Chandigarh. Booths were selected by stratified random sampling technique. The status of cold chain equipments was assessed at headquarter of IPPI, 6 regional (distribution) centres, 20 IPPI posts and 5 house to house teams. RESULTS: The cold chain sickness rate was found to be 9.7% in January, 2002. There were reports of breakdown of cold chain maintenance due to defective plugs and sockets, faults in thermostat, leakage of gas. But all vaccine samples picked up randomly were reported potent, as per the test reports provided by Central Research Institute (CRI), Kasauli during the period of study. OBSERVATION & DISCUSSION: Temperature charting and cold chain maintenance was found satisfactory, but necessity of improvement, specially regarding the handling of vaccines by the female health worker. Lids of vaccine carriers not closed tightly, frequent opening of lids during immunization, direct exposure of vaccine to atmospheric temperature, keeping the vaccine vial in hand or pocket. More emphasis is to be given on maintenance of cold chain system in orientation training programme of all Health functionaries before the Intensified Pulse Polio Immunization (IPPI) programme.

Improving environmental conditions of a slum in Chandigarh by an awareness campaign.

An intervention project, in the form of an environmental awareness campaign was conducted in a slum of Chandigarh with a population of about 40,000, from December 1998-April 1999. The activities enforced during this campaign included focus group discussions with general public and mothers, household visit by medical students, distribution of literature, use of mass media by involving local residents, primary child care workers, teachers and school children. Evaluation of this campaign was carried out in May 1999 and compared with the baseline data obtained from a survey done in 1997. The study revealed that the method of storing water in covered buckets and utensils had improved significantly from 14.3% and 4.7% in the baseline survey to 35.2% (P < 0.001) and 16.2% (P < 0.01) respectively. Refuse disposal in the community bin and own bin had significantly improved to 22.2% (P < 0.001) and 19% (P < 0.01) from 8.4% and 11.2% respectively in the baseline survey. 51.2% of the residents using own bins disposed the refuse finally into the community bin. The use of community latrines had significantly increased among males (50.0%), females (47.7%) and children (41.2%) after intervention as compared to 32.8%, 32.5% and 16.7% respectively as found in the baseline survey (P < 0.001) and similarly open defaecation had significantly reduced among them. Further the study shows that the awareness regarding diarrhoea as hazard of unsafe water had improved significantly from 28.7% in baseline survey to 55.6% after intervention (P < 0.001). Knowledge of the residents regarding hazards of refuse disposal in the open and open defaecation had also improved significantly. Simple environmental awareness campaign can change the knowledge and behavioural practices of slum dwellers and could be a model for launching similar projects in other slums of India and other developing countries.

Adrenergic involvement in the locus ceruleus and adjoining regions in the facilitation of predatory attack behavior as induced by hypothalamic stimulation in cats.

The present study was carried out in five cats which did not attack the rats spontaneously. Predatory attack on an anaesthetized rat was elicited by electrical stimulation of extreme lateral regions of hypothalamus. These sites were stimulated at a current strength from 300-700 microa to evoke a predatory attack on an anaesthetized rat. The attack was accompanied by minimal affective display such as alertness, pupillary dilatation, and culminated in beck biting at higher current strength. A scoring system allowed the construction of stimulus response curves, which remained fairly constant when repeated over a period of 3-4 weeks. Microinfusions of norepineprine and clonidine in 4.0 and 5.0 microg dose respectively in locus ceruleus and adjoining tegmental fields facilitated the predatory attack and there was a significant reduction in the threshold current strength for the elicitation of affective and somatomotor components. Microinfusions of yohimbine, an alpha-2 blocker, in 5 microg dose completely blocked the predatory attach response as indicated by an increase in the threshold current strength for the affective components. The somatomotor components were completely inhibited and could not be elicited even when the current strength was increased to 1000 microA. The predatory attack behavior remained completely inhibited for almost two hours following microinfusion of yohimbine. During this period, the animal was extremely drowsy and reacted very slowly even to a painful stimulus such as pinching of tail. Microinfusions of propranalol (beta-blocker), practalol (beta-1 blocker), prazosin (alpha-1 antagonist), propylene glycol as well as saline in similar volumes (0.5 microl) as control failed to produce any blocking effect, thus indicating the involvement of alpha-2 adrenoceptive mechanisms in the modulation of predatory attack in this region of midbrain. The facilitatory effects of norepinephrine and clonidine were significant at P<0.01 and P<0.05 respectively with Wilcoxon's signed rank test. The inhibitory effects of yohimbine were significant at P<0.05. The present study indicates the involvement of alpha-2 adrenoceptive mechanisms in the facilitation of hypothalamically elicited predatory attack.

Enkephalinergic involvement in substantia nigra in the modulation of hypothalamically-induced predatory attack behavior.

The present study was carried out in five cats which did not attack the rats spontaneously. Predatory attack on an anaesthetized rat was elicited by electrical stimulation of lateral hypothalamus at a mean current strength of 650 microA. The attack was accompanied by minimal affective display and culminated in neck biting. Microinfusions of DAME (delta-alanine methionine enkephaline) in 500 ng dose in substantia nigra facilitated the predatory attack and there was a significant reduction in the threshold current strength for affective display as well as somatomotor components. Microinfusions of naloxone, an opioid antagonist in 1.0 microg dose when DAME effect was at its peak reversed the facilitatory effects and the threshold returned to the control levels within 10 minutes of naloxone infusion at the same locus. Microinfusions of naloxone alone in similar dosage completely blocked the predatory attack response as indicated by an increase in the threshold current strength for somatomotor as well as affective display components. The somatomotor were completely inhibited and could not be elicited even when the current strength was increased to 1000 microA. Control injections of saline in similar volumes (0.5 microl) failed to produce any response Microinfusions of naloxone in lower dose (250 ng) failed to produce any blocking effect. These findings indicate that hypothalamically elicited predatory attack is facilitated by enkephalinergic mechanisms operating at the midbrain level.

Mass supplementation of vitamin A linked to National Immunization Day.

OBJECTIVE: Main objectives were to assess the feasibility of linking vitamin A delivery with National Immunization Days (NIDs) and to see the impact on xerophthalmia. METHODS: An Intervention study of mass distribution of vitamin A solution was undertaken to control widespread xerophthalmia prevalent in children living in about 26 slums of Chandigarh in the year 2000. Two rounds of mass distribution of Vitamin A solution covering 27642 and 31762 children in 1-5 years of age in first and second rounds, respectively, were undertaken. The findings of second round and post evaluation after intervention are presented here. An additional team of two persons per pulse polio immunization (PPI) centre delivered age specific doses of vitamin A solution through 98 centres and operational problems were recorded. PPI staff provided the supervision and PPI tally sheets were used. RESULTS: The programme achieved a vitamin A coverage rate of 99% in first round and 88% in second round. Only two parents refused vitamin A solution. No side effect or cases of toxicity due to vitamin A were reported by health institutions in the area or in a stratified random sample of 101 children. There was a significant decline (13.4%) in xerophthalmia after two rounds of mass distribution (P < .001). The strategy to deliver vitamin A was successfully integrated into NID's and appeared to achieve a significant decline in xerophthalmia. CONCLUSION: Linking of vitamin A distribution with PPI could be a basis for launching similar initiatives in other areas of India and other countries where xerophthalmia is a public health problem.

Measles outbreak in a Periurban area of Chandigarh: need for improving vaccine coverage and strengthening surveillance.

OBJECTIVE: An outbreak of measles was investigated in the periurban areas of Chandigarh Union Territory, during the months of December 1998 to February 1999. Mainly the children below 15 years of age were affected. The children of migrant labourers belonging to the neighbouring states of Uttar Pradesh and Bihar constituted the majority of population in the area under study. They belonged to lower socio economic status with low immunization coverage. METHODS: A total of 2968 houses were surveyed for epidemiological investigations in the areas of colony No. 5, Ramdarbar, Palsora and Pandit colony of Kajheri, covering a population of 14,601 and 7.3% (216/2968) of families were affected in the outbreak. RESULTS: Two hundred and eighty three cases of measles were reported with an attack rate of 4.5% and male to female ratio of (M:F) 5.3%:3.6%. Among the measles cases, 48.8% had received measles vaccination. The outbreak was investigated by detecting measles specific IgG/IgM antibodies either in acute or convalescent serum samples or both. Due to inadequate surveillance system and containment measures, the outbreak was in full swing during the winter months. Measles related complications were reported in 31.1% cases (i.e. diarrhoea in 15.2% and Pneumonia is 7.1%). CONCLUSION: Following smallpox and guinea worm eradication, WHO's next thrust, is on eradication of poliomyelitis and measles. Hence, strengthening of disease surveillance as well as vaccination policies are mandatory to achieve disease control in these areas.

Nutritional status of pre-school children in an integrated child development service (ICDS) block of Chandigarh.

Nutritional status of 1286 pre-school children selected by a stratified random sampling and residing in urban, rural and slum areas of Chandigarh was assessed by weight for age criteria by making domicilliary visits. The overall prevalence of protein energy mulnutrition (PEM) was found to be 51.6% while 65.4%, 26.3%, 5.3% and 3% of children had grades I, II, II and IV PEM, respectively. The prevalence of malnutrition significantly increased with increase in age till 3rd year, then started declining (P<0.001). The prevalence of PEMwas significantly higher among Integrated Child Development Service (ICDS) beneficiaries (53.8%) than non-ICDS beneficiaries (46.9%); P<0.05. More attention and better impetus are required to be given to improve the nutritional status of pre-school children in Chandigarh.

Interconversion of free sugars in relation to activities of enzymes catalyzing synthesis and cleavage of sucrose in growing stem tissues of sorghum.

Free sugar interconversion and activities of soluble acidic (pH 4.8) and neutral (pH 7.5) invertases, sucrose synthase (synthesis) and sucrose phosphate synthase were investigated in the growing nodes and internodes of sorghum (Sorghum vulgare). The results were substantiated with incorporation of 14C from supplied sucrose and hexoses into endogenous sugars of these stem tissues. With the advancement in plant growth, the content of total free sugars in apical nodes and internodes increased till 70 DAS (flowering stage) followed by a decline. In the corresponding basal tissues, the sugar build-up continued even beyond this stage of plant growth. Compared with basal stem tissues, the apical ones contained high activities of soluble invertases and a low proportion amongst free sugars of sucrose. The activities of sucrose-hydrolyzing enzymes were higher as compared with those of sucrose-synthesizing ones in both nodes and internodes and with the growth of plant, the activity of neutral invertase increased in these tissues. More 14C from supplied sucrose and hexoses appeared in extracted sugars from cut discs of apical nodes and internodes in comparison with their basal counterparts. 14C from supplied sucrose appeared in glucose, fructose and from supplied hexoses appeared in sucrose. The results suggest that in apical nodes and internodes, where a rapid cell division and cell expansion occur, sucrose is obligatorily inverted to meet the increased requirement of hexoses and there is a compartmentalized synthesis and cleavage of sucrose in the nodes and internodes of growing sorghum plant.

Rapid assessment and delivery of Vitamin A to slum children by using National Immunization Day in Chandigarh.

This study was done with the objective to see the feasibility of using National Immunization Days (NIDs) for rapid assessment, and delivery of Vitamin A solution to about 27,600 children dwelling in 26 slums in Union Territory of Chandigarh. The assessment of Vitamin A deficiency (VAD) was done in a stratified random sample of 1304 children during third round of Intensified Pulse Polio Immunization (IPPI) and delivery of Vitamin A solution was done during fourth round of IPPI in 1999-2000 covering 27,642 children in the age group of 1-5 years. An additional team of two persons per centre delivered age specific doses of Vitamin A solution through 72 centres and operational problems were recorded. IPPI staff provided supervision and same tally sheets as of IPPI were used. The prevalence rate of VAD was 24.6%, with conjunctival xerosis, bitot's spot and corneal xerosis as 23.7%, 0.6% and 0.2% respectively. 27,275 (98.7%) children out of 27,642 were administered Vitamin A solution, with no major operational problem. Only five parents (0.01%) refused Vitamin A solution. No case of side effect or toxicity due to Vitamin-A was reported. The strategy to assess and deliver Vitamin A during NID's was found to be feasible and successful and could be a basis for launching similar initiatives in other areas of India and other countries where VAD is a public health problem.

Prevalence of short segments of specialized columnar epithelium in distal esophagus: association with gastroesophageal reflux.

BACKGROUND AND AIMS: Recent studies have reported high prevalence rates of short segments of specialized columnar epithelium (SCE) in the distal esophagus. The association of SCE with gastroesophageal reflux disease is not well established. We studied the prevalence and associations of short segments of SCE in the distal esophagus amongst Indians. METHODS: 271 patients (mean age 36 [14] y; 160 men) undergoing diagnostic upper gastrointestinal endoscopy were interviewed regarding symptoms of gastroesophageal reflux, and history of medications, smoking or chewing tobacco and alcohol ingestion. At endoscopy, presence and grade of esophagitis and hiatus hernia were recorded. One biopsy each was taken from the squamocolumnar junction and 2 cm proximal to it. Biopsies were stained with hematoxylin/eosin and alcian blue/periodic acid-Schiff. The pathologist was blinded to the clinical and endoscopic data. RESULTS: Short segments of SCE in the distal esophagus were present in 16/271 (6%; CI 5.03-6.97) patients. Increasing age (p<0.01), and endoscopic (p<0.01) and histologic (p<0.001) esophagitis were associated with its presence, whereas symptoms of gastroesophageal reflux, smoking, tobacco chewing, use of alcohol or non-steroidal anti-inflammatory drugs, and hiatus hernia were not. One patient with SCE had dysplasia. CONCLUSION: Prevalence of short segments of SCE in the distal esophagus amongst Indians is low and is usually associated with inflammation in the esophagus.

Epidemiology of dyspepsia in the general population in Mumbai.

BACKGROUND AND AIMS: Dyspepsia is a common complaint in the general population. The prevalence, demography and economic implications of dyspepsia in India are not known; we studied these using a detailed symptom questionnaire. METHODS: 2549 presumably healthy adults (mean age 37.2 [14.1] years; 1441 men) were interviewed. Gastrointestinal symptoms, their investigation and treatment, dietary history and history of addictions were noted. Dyspepsia was defined as abdominal fullness or upper abdominal pain present for at least one month; irritable bowel syndrome (IBS) was defined by Manning's criteria. Based on the symptom profile, subjects were divided into three broad groups: no dyspepsia (n=1695; 945 men), dyspepsia with (110; 63 men) or without (664; 382 men) IBS, and IBS alone (80; 51 men). RESULTS: 774 subjects (30.4%) had dyspepsia; the median (range) duration of symptoms was 24 (1-360) months. Abdominal fullness (n=614), abdominal pain (374), heartburn (272) and belching (271) were the most common symptoms; significant symptoms (present at least once a week) occurred in 306 subjects (12.0% of the population). More than half the subjects had symptoms suggestive of mixed type of dyspepsia; dysmotility-like dyspepsia was the next most common (n=257; 33.2%). The frequency of dyspepsia was not related to type of diet or consumption of spices. Dyspepsia was more prevalent in subjects who abused tobacco or alcohol. Three hundred and twenty-one subjects with dyspepsia (41.4%) had visited a physician for their complaints and had received treatment with antacids, acid suppressors or prokinetic drugs; 4.5% and 7.2% had undergone previous endoscopy and ultrasonography, respectively; dyspeptic subjects underwent more investigations (p<0.001) than those with IBS. CONCLUSIONS: Dyspepsia is reported by almost one-third of the population in Mumbai; significant symptoms occur in 12%. Forty percent of these subjects receive treatment and only a small number undergo endoscopy or ultrasonography.