Role of BCG and Measles vaccination in protection against COVID-19 infection and severity of the disease: A pilot case-control study

Background: The role of BCG and MMR/Measles vaccination in reducing the burden of COVID-19 has been based on ecological data mostly. We planned this explorative pilot case-control study to understand the role of vaccination with Bacillus Calmette朑uerin (BCG) and measles administered as part of MMR vaccine on COVID 19. Methodology: A case-control study was conducted in AIIMS Patna during December 2020 and January 2021. A total of 100 COVID-19 patients confirmed by RT-PCR test were taken as cases, and for each case, age and gender-matched SARS-COV-2 negative individual was taken as control. A study tool containing a pre-tested semi-structured questionnaire was used. Results: The unadjusted odds of COVID-19 were found to be significantly higher among BCG vaccinated [1.88(1.03-4.4)] and MMR vaccinated individuals [5.06(2.34-10.90]. BCG vaccine was not found to have an independent effect on COVID-19 after adjusting for tobacco use, MMR vaccination status, unprotected contact with SARS-COV-2 positive patients, and co-morbidities. But Measles vaccine was found to independently increase the risk of COVID-19 [AOR: 4.505(1.8-11.3)]. Conclusion: BCG vaccination status was not found to be an independent predictor of COVID-19. Further studies with large sample size and better study design (cohort, randomized trials) need to be conducted.

A study on estimate of Iodine Deficiency Disorders and adequacy of Iodized Salt Consumption in Begusarai district of Bihar, India

Background: Iodine Deficiency Disorder is major public health problem causing increased perinatal mortality, mental retardation and goiter and all these morbidities are preventable. Most effective and inexpensive mode to prevent IDD is consumption of iodized salt. Objectives: To estimate the proportion of households using adequately iodized salt in Begusarai district, to assess the knowledge of households on consumption and storage of salt and to estimate Total Goitre Rate (TGR). Material and Methods: Community- based cross sectional study carried out on 412 household from 30 cluster in Begusarai district using cluster sampling technique. Children (6-12 years) were examined clinically for goitre status and sample of household salt was collected for testing iodine content. Iodine content estimation was done both quantitatively by titration and qualitatively by MBI kit. Statistical analysis was performed using SPSS version 22. Result: The respondents were mainly female (92.8%) of mean age 34 years. Three- fifth (61.6%) participants used packaged crushed salt for cooking purpose, followed by packaged crystal (30.5%). Only 12.1 % of the respondents gave affirmative answer for presence of label and logo. Storage of salt in container with lid was 78.5%. The proportion of household using adequately iodized salt was 78%. The sensitivity MBI kit was 61% and the Total goiter rate was 9.3%. Conclusion: The Begusarai district falls in mild public health problem for IDD as TGR is more than 5% and even after many decades of effort towards achieving an adequately salt iodization of more than 90%, it is 79% only.

Assessment of Cold Chain System for Routine Immunization of Primary Health centres of the Bhojpur district of Bihar

Background: Immunization is an important among activity in the Public Health Services. The vaccines are highly temperature sensitive and vaccine potency once lost cannot be restored. A well-managed cold chain will increase the efficiency of immunization and reduce vaccine wastage. An assessment of cold chain system for vaccine storage was done in the all PHCs of the study area. Aims & Objectives: To evaluate the cold chain practices, with particular reference to assessing the availability of cold chain equipment, vaccine storage practices, monitoring of cold chain in primary health centres (PHCs) of Bhojpur district. Material & Methods: A cross-sectional study was conducted at all the cold chain points of 14 PHCs of Bhojpur district during January to May 2015. A predesigned, pretested checklist was used by the trained investigators during their visits. The information was evaluated on the basis of important components related to the cold chain points. Results: All the PHCs had a dedicated cold chain room with sufficient number of cold chain equipment. Consolidated effective vaccine management score for cold chain points of 8 (57.1%) PHCs were average (60-79%). None of the PHCs have satisfactory score (≥ 80%). Vaccine storage practice and availability of complete RI micro-plan were found satisfactory at 12 (85.7%) PHCs. Maintenance of cold chain equipment were satisfactory at 10 (71%) PHCs. But, temperature monitoring. (5) (35.7%) and waste disposal related to routine immunization 3 (21.4%) PHCs were disappointing. Conclusion: The primary health centres had average performance related to the cold chain system, which is a matter of concern warranting for the cold chain monitoring. We recommend supportive supervision as the key measures in improvement of cold chain system.

Vector density and the control of kala-azar in Bihar, India

Bihar, India has been in the grip of kala-azar for many years. Its rampant and severe spread has made life miserable in most parts of the state. Such conditions require a comprehensive understanding of this affliction. The numbers coming out of the districts prone to the disease in the north and south Ganges have provided us with several startling revelations, as there are striking uniformities on both sides, including similar vegetation, water storage facilities, house construction and little change in risk factors. The northern areas have been regularly sprayed with DDT since 1977, but eradication of the disease appears to be a distant dream. In 2007 alone, there were as many as 37,738 cases in that region. In contrast, the southern districts of Patna and Nalanda have never had the disease in its epidemic form and endemic disease has been present in only some pockets of the two districts. In those cases, two rounds of spraying with DDT had very positive results, with successful control and no new established foci. In addition, an eleven-year longitudinal study of the man hour density and house index for the vector Phlebotomus argentipes demonstrated that they were quite high in Patna and Nalanda and quite low in north Bihar. Given these facts, an attempt has been made to unravel the role of P. argentipes saliva (salivary gland) in the epidemiology of kala-azar. It was determined that patchy DDT spraying should be avoided for effective control of kala-azar.

Aggressive angiomyxoma in men.

Aggressive angiomyxoma is an uncommon neoplasm that preferentially involves the pelvic and perianal regions of reproductive age females. These tumors are rare in men and merit a wider recognition in male urologic pathology. We report a case of a 65 year old male who presented with a swelling in the left perineal region since 2 years which gradually increased in size to 10 x 10 x 8 cms. CT scan revealed a well defined lobulated heterogenous minimally enhancing mass in the left ischiorectal fossa extending upto the subcutaneous plane. Microscopically stellate to spindle shaped cells arranged in a loose myxoid stroma with numerous thin to thick walled vessels were seen. There was no evidence of pleomorphism, hyperchromatism or mitotic activity. This case is reported because of its rarity in males. It is a benign tumor and requires a wide excisional surgery.

Magnitude of unresponsiveness to sodium stibogluconate in the treatment of visceral leishmaniasis in Bihar.

BACKGROUND: The Indian government proposes to eliminate kala-azar, which has been a serious public health problem in Bihar. This study aimed to assess the magnitude of unresponsiveness to sodium stibogluconate in the treatment of new cases of visceral leishmaniasis and to identify the associated factors. METHODS: Patients with clinically and parasitologically confirmed visceral leishmaniasis (n = 182) who had received no prior treatment, were enrolled for the study. The patients were treated with sodium stibogluconate (20 mg/kg body weight; upper limit 850 mg), intramuscularly for 30 days. The vital parameters and side-effects, if any, were monitored. Patients who developed toxicity during treatment were excluded from the study but were given rescue treatment with liposomal amphotericin B. All patients who completed the treatment were followed up for 6 months. RESULTS: Unresponsiveness to sodium stibogluconate at the end of treatment was 43%. It was higher in women (48%) compared to men (40%). A significant association was observed between unresponsiveness and level of endemicity (p = 0.0002), large spleen size (p = 0.04) and immune response (migration inhibition factor) (p = 0.00002). At the end of 6 months' follow up, 27% of patients relapsed, giving a total unresponsiveness rate of 58%. CONCLUSION: Unresponsiveness to sodium stibogluconate is a serious problem in the management of patients with visceral leishmaniasis. In patients with factors associated with nonresponse to sodium stibogluconate, alternative drugs such as miltefosine or amphotericin B should be considered as first-line drugs.

Epidemiological, clinical & pharmacological study of antimony-resistant visceral leishmaniasis in Bihar, India.

BACKGROUND & OBJECTIVES: Sodium antimony gluconate (SAG) is reported to be losing its efficacy in Bihar as a first line drug for treatment of visceral leishmaniasis (VL). Concerned with the increasing incidence of antimony-resistant VL patients in Bihar, we undertook an epidemiological, clinical and pharmacological study to formulate a scientific basis for choosing a suitable first line drug for VL. METHODS: Consecutive, fresh and parasitologically confirmed patients of VL from different geographical areas of Bihar were considered for inclusion in the study. Parasites isolated from patients were tested in vitro to assess their response to sodium antimony gluconate (SAG) to 20 microg/ml, response to 20 mg/kg of SAG for 5 days in experimentally induced VL in BALB/c mice from those isolates, and response to SAG in patients treated with SAG for 28 days. Similarly response in culture (1 microg/ml) to amphotericin B (AMB) of all 282 isolates, (1 mg/kg body wt for 20 days) in patients and infected BALB/c mice (1 mg/kg body wt for 5 days) was determined. Antimony levels of plasma were determined at 2, 8 and 24 h after intramuscular injection of SAG. Patients unwilling for SAG treatment or relapsed after SAG treatment and withdrawn from SAG group because of toxicity were treated with AMB. Plasma antimony levels were estimated by atomic absorption spectrometer. RESULTS: Though antimony sensitive and resistant patient were distributed in all 14 districts of Bihar studied, there was a significant variation from district to district. Of the 123 patients included in the SAG treatment group, 19 were withdrawn due to development of toxicity and 2 died; 178 patients were treated with AMB. No patient in AMB group developed any toxicity or died. Only 47 (46%) of 102 patients, 106 (37.6%) of 282 infected macrophages, 90 (52.9%) of 170 experimental infections were cured with SAG. Mc Nemar's test on paired comparisons showed statistical significance difference (P<0.01) between infected macrophage and experimental infection. AMB cured all patients, infected mice and cleared parasites from all isolates. INTERPRETATION & CONCLUSION: Antimony resistant strains of L. donovani were wide spread over different geographical areas in Bihar. SAG cured lesser percentage of VL cases clinically compared to AMB and should be replaced by AMB as a first line drug.

Evaluation of cholinesterase level in an endemic population exposed to malathion suspension formulation as a vector control measure

The manuscript describes a study on the blood cholinesterase (ChE) level in an exposed population at different interval of time after spraying with malathion suspension (SRES) use for kala-azar vector control in an endemic area of Bihar, India. The toxicity of a 5 percent malathion formulation in the form of a slow release emulsified suspension (SRES) was assessed by measuring serum ChE levels in spraymen and in the exposed population.The study showed a significant decrease in ChE levels in the spraymen (p < 0.01) after one week of spraying and in exposed population one week and one month after of spraying (p < 0.01), but was still within the normal range of ChE concentration, one year after spraying, the ChE concentration in the exposed population was the same as prior to spraying (p > 0.01). On no occasion was the decrease in ChE level alarming. A parallel examination of the clinical status also showed the absence of any over toxicity or any behavioural changes in the exposed population. Hence, it may be concluded that 5 percent malathion slow release formulation, SRES, is a safe insecticide for use as a vector control measure in endemic areas of kala-azar in Bihar, India so long as good personal protection for spraymen is provided to minimize absorption and it can substitute the presently used traditional DDT spray.

Effect of immunization with lipid associated polysaccharide antigen and anti CD-2 antibodies on class II MHC expression and cellular immune response in BALB/C mice infected with Leishmania donovani.

In a bid to characterize the antigens and immunization mechanisms which may be used to produce a protective response against L. donovani, role of lipid associated polysaccharide (LPS) antigen and whole antigen was evaluated. BALB/C mice were immunized with whole or LPS antigen in combination with one of three putative adjuvents (anti CD-2 antibody/FIA/0.85% Saline). LPS antigen emulsified in anti CD-2 antibody was found to induce significant antibodies in mice on day 28 against challenge with lethal dose of L. donovani. Immunoprophylactic properties of LPS and whole antigen was investigated on day 40 through cytokine elicitation (IL-2), MIF) in culture supernatants of spleen cells, but before that MHC-II expressed on macrophage was studied. The LPS antigen in combination with anti CD-2 antibody was found to be most immuno-reactive inducing higher MHC-II expression on macrophages which was associated with substantial rise in the level of MIF and IL-2. It coincided with decline in antibody titre in 100% mice immunized with LPS antigen while Leishmania injected as whole antigen failed to induce specific macrophage and T-cell response with all the above formulations. We surmise from our data that lipid associated polysaccharide antigen linked to anti CD-2 antibody has potential for eliciting protective immunity against Leishmania.

A randomized clinical trial of low dosage combination of pentamidine and allopurinol in the treatment of antimony unresponsive cases of visceral leishmaniasis.

OBJECTIVES: A randomized clinical trial of low dosage combination of pentamidine and allopurinol was carried out with objectives to assess the efficacy and toxicity as compared to full dosage of pentamidine in antimony unresponsive visceral leishmaniasis (VL) patients. METHODS: Using a randomized control clinical trial, a total of 158 antimony unresponsive patients of VL were randomly allocated into two treatment groups. Patients in one group (n=80) received half the dosage of pentamidine i.e. 2 mg/kg body weight by IM route on alternate day and allopurinol in dose of 15 mg/kg body weight in three divided dosages for 30 days; patients in the second group (n=78) received pentamidine in dose of 4 mg/kg body weight by IM route on alternate day for 15 injections in 30 days. The efficacy and safety of the two regimens were compared. RESULTS: Apparent cure i.e. clinical and pathological cure at the end of therapy, in 78 (97.5%) and 67 (86%), and ultimate cure i.e. clinical and parasitological cure at the end of follow-up of six months, in 73 (91.25%) and 58 (74.35%) patients was observed in the combination regimen and single regimen group respectively. The difference of the ultimate cure between two groups of the patients was statistically significant (p < 0.01). In single regimen group, 11 (14%) patients showed primary unresponsiveness (with no response during treatment) and nine (13%) relapse (after six months of follow-up) respectively, where as in combination regimen group, two (2.5%) patients showed primary unresponsiveness and five (6.4%) relapse respectively. By the end of the treatment, the incidence of injection-related toxicity, such as rigor and fever, was same in both groups. No hyperglycemia was observed in combination therapy probably due to reduced dose of pentamidine and three patients in single regimen developed hyperglycemia and one of them developed irreversible hyperglycemia. CONCLUSIONS: The study showed that the combination of pentamidine (half dose) and allopurinol is more effective in achieving ultimate cure with an added advantage of reduced toxicity in unresponsive cases as compared to full pentamidine dose.

Relevance of direct agglutination test in seroepidemiological survey of Kala-azar in epidemic foci of Bihar.

The performance of direct agglutination test (DAT) was evaluated under field conditions in three endemic districts of Bihar. In three villages of these districts, 197 households were surveyed with a population of 1167 individuals. Out of 1167 individuals, 603 were clinically examined for VL and blood samples of each examined individual were collected for DAT. The proportion of DAT positivity in both males (32.33%) and females (32.94%) was statistically not significant (p > 0.05). The proportion of DAT positivity in all age groups was observed to be similar (p > 0.05). The GMRT was observed highest in active VL cases. Out of 20 DAT positive individuals having fever, 5 were examined parasitologically (bone marrow aspiration) and in three cases positivity was observed. This showed the relevance of DAT in early diagnosis of visceral leishmaniasis and usefulness of DAT in field conditions.

Scope and efficacy of complex radiofrequency ablation.

Radiofrequency ablation is an effective treatment for various tachycardias. In some patients undergoing radiofrequency ablation, there are additional complexities. Of 254 consecutive patients (161 males, 93 females, aged 38 +/- 15 years) who underwent radiofrequency ablation, two groups were identified. Patients with structural heart disease, multiple accessory pathways, multifocal idiopathic ventricular tachycardia, parahisian accessory pathways, and multiple mechanisms of tachycardia were considered as complex radiofrequency ablation (Group I) and the remaining as non-complex radiofrequency ablation (Group II). There were 23 patients in Group I. The overall success rate was not different in the two groups: 20/23 (87%) vs 208/231 (90%) in groups I and II, respectively. The procedure and fluoroscopy time (212 +/- 91 min vs 136 +/- 45 min; p = 0.0001; and 55 +/- 31 min vs 31 +/- 21 min; p = 0.001, respectively) were significantly longer in Group I. There was a higher recurrence rate in Group I (6/20, 30% vs 20/208, 9.6%; p = 0.02); repeat radiofrequency ablation was successfully performed in four patients with recurrence in Group I. Complications were rare in both the groups. There was no mortality. Thus radiofrequency ablation in complex situations was effective, though more demanding than non-complex radiofrequency ablation and associated with higher recurrence.

Codon usage in the prototype baculovirus--Autographa californica nuclear polyhedrosis virus.

The overall codon usage profile of Autographa californica nuclear polyhedrosis virus (AcNPV) was analyzed, using UWGCG sequence analysis software package from the known protein coding gene sequences available in GenBank Release 72. The analysis revealed that although only 45% of the codon used by AcNPV have G/C at wobble base position, 15 out of 20 AcNPV codons over-utilized for their given amino acids has G/C at the wobble position indicating a possible selection of these codons. The differences in codon usage profile were studied using a parameter called D squared value, calculated with the aid of CORRESPOND program of UWGCG software package. While most of the codon usage profile of the individual genes was very similar to the overall AcNPV codon usage profile (D squared value less than 1.5), there were notable differences (D-squared value greater than 1.5). These genes were polh, p10, ub, sod, gp41, core, 25k, 39k, ie-n, etm, ets most of which, interestingly, belonged to late or very late class and were expressed relatively more efficiently. The two highly expressed genes of AcNPV, polh and the p10, differ from the overall AcNPV codon usage profile with respect to at least nine amino acids (Val, Ala, Ser, Lys, Ile, Thr, Leu, Phe, Arg). Our findings that the two highly expressed late genes polh and p10 utilize a codon usage profile different from the early genes have important implications.

Field trial of an ecological approach for the control of Phlebotomus argentipes using mud & lime plaster.

A pilot study for the control of Ph. argentipes, a known vector of kala-azar in India, was carried out using an ecological approach. Of the 15 houses selected for the study 10, including the cattle sheds and latrines, were plastered with a mixture of mud and lime, up to a height of 1.22 m taking care to seal all cracks and crevices. The remaining five houses were left unplastered and were considered as control areas. The pre-treatment and post-treatment resting densities of the sandfly were monitored both in treated and untreated houses. A sudden drop in the sandfly density was noticed in the treated houses, whereas there was no significant reduction in the check houses, suggesting an effective control.