Undiagnosed hypertension and associated factors among adults in the urban field practice area of AIIMS Raipur: A community-based screening survey.

Introduction: Undiagnosed hypertension (HTN) increases the risk of severe consequences such as chronic kidney disease (CKD), hypertensive retinopathy, heart failure, and stroke. Population-based screening can be used to expose the hidden diseased mass with active disease. Thus, a screening survey was conducted to estimate the proportion of people with HTN among apparently healthy adults of age ≥30 years residing at the urban field practice area (UHTC) of AIIMS, Raipur, and also determine the predictors of undiagnosed HTN among the study participants. Methodology: This was a community-based cross-sectional study conducted over 2 months duration in the Ramnagar area, which comes under the urban field practice area of AIIMS Raipur using the STEPS tool is an acronym of study tool provided by WHO i.e. STEPwise approach to NCD risk factor surveillance consisting of three steps viz. questionnaire for behavioural risk factors, physical measurements and biochemical measurements. Results: In this study, 24.2% (95%, confidence interval [CI]: 20.1-28.2) of participants screened positive for HTN. The proportion of males who screened positive for HTN was 28.8% (95% CI: 22.6-35), whereas the proportion of females who screened positive for HTN was 19.6% (95% CI: 14.3-25). In this study, elderly (>60 years), male gender, daily tobacco use, greater waist circumference (male >90 cm and female >80 cm), and daily salt intake of more than 5 g were found to have higher odds of having HTN. Conclusion: The prevalence of undiagnosed HTN in the UHTC of AIIMS Raipur was quite high.

Investigation of an acute surge of COVID-19 associated mucormycosis (CAM) cases reported to a tertiary health care institution in Bihar, India.

Introduction: Acute surge in coronavirus disease-2019 (COVID)-associated mucormycosis (CAM) cases was reported during mid-May 2021, which was later declared an epidemic in various states of India including Bihar. Objective: We carried out a rapid investigation of CAM cases to describe the epidemiological and clinical profiles and find plausible predictors to guide the initiation of public health actions. Methods: A team of public health specialists contacted all the CAM cases reported to our hospital to collect relevant information using a case-investigation-form. In addition, the team visited the Flu Clinic and Ear, Nose, and Throat (ENT) outpatient department (OPD) to capture CAM cases on daily basis during the period of the acute surge of CAM cases. Results: About 88% of 130 CAM cases reported during the period of the acute surge were in the advanced stage of mucormycosis. The majority of the CAM cases were younger (less than 60 years) [76.2%], diabetics [65.4%], un-vaccinated [86.9%], and had used steroids for management of COVID-19 [64.6%]. Other findings of public health importance were summarized and possible public health actions were recommended for the prevention of outbreaks in future. Conclusion: Optimum management of diabetes including screening for each COVID case, rational use of steroids only when necessary, strict adherence to COVID appropriate behavior by health professionals as well as the public, increasing COVID vaccine coverage, CAM awareness, and setting up a CAM surveillance mechanism may be the key to prevent and control CAM outbreaks in future.

Literature review of rheumatoid arthritis in India.

AIM: Rheumatoid arthritis (RA) can lead to severe disability. This literature review assessed the descriptive epidemiology, comorbidities and extra-articular manifestations, functioning abilities and quality of life, and treatment patterns of RA patients in India. METHOD: A literature review of all observational studies published from 1985 to 2012 was conducted using MEDLINE and Embase. Quantitative and qualitative findings were summarized. RESULTS: Twenty-eight studies were identified for data extraction. Seven described the descriptive epidemiology of RA, 14 described comorbidities and extra-articular manifestations, nine described the functioning abilities and quality of life among patients, and 10 provided information on treatments. CONCLUSION: This review is confined to studies with small sample sizes, cross-sectional designs, and/or clinical settings that may not be representative of the entire Indian population. There is a need for more robust studies, as conclusions for the entire Indian RA population cannot be drawn from only the current observational studies.

Janibacter hoylei sp. nov., Bacillus isronensis sp. nov. and Bacillus aryabhattai sp. nov., isolated from cryotubes used for collecting air from the upper atmosphere.

Three novel bacterial strains, PVAS-1(T), B3W22(T) and B8W22(T), were isolated from cryotubes used to collect air samples at altitudes of between 27 and 41 km. Based on phenotypic characteristics, chemotaxonomic features, DNA-DNA hybridization with the nearest phylogenetic neighbours and phylogenetic analysis based on partial 16S rRNA gene sequences (PVAS-1(T), 1196 nt; B3W22(T), 1541 nt; B8W22(T), 1533 nt), the three strains were identified as representing novel species, and the names proposed are Janibacter hoylei sp. nov. (type strain PVAS-1(T) =MTCC 8307(T) =DSM 21601(T) =CCUG 56714(T)), Bacillus isronensis sp. nov. (type strain B3W22(T) =MTCC 7902(T) =JCM 13838(T)) and Bacillus aryabhattai sp. nov. (type strain B8W22(T) =MTCC 7755(T) =JCM 13839(T)).

Kinetics of T cell cytokine gene expression in gerbils after a primary subcutaneous Brugia pahangi infection.

The majority of patients infected with lymphatic filariae are microfilaremic but tend to manifest little obvious pathology because of the infections. Data collected from the Mongolian gerbil-Brugia spp. model for human lymphatic filariasis suggest this experimental animal model system most closely represents this patient group and will be useful in studying immunological parameters associated with chronic infections. This article reports the quantitation of interleukin (IL)-4, IL-5, IL-10, IL-13, and interferon (IFN)-gamma messenger RNA (mRNA) in gerbils after a primary subcutaneous infection with Brugia pahangi. Chronically infected gerbils showed elevated IL-4 in all tissues, compared with earlier time points, linking this Th2 cytokine to the downregulation of responsiveness, which develops in gerbils and humans. Both IL-5 and IL-13 mRNA expression were transient in all tissues. The peak in IL-5 at 14-28 days postinfection reflects the peak of peripheral eosinophilia observed in B. pahangi-infected gerbils. Little IFN-gamma mRNA was reported from chronically infected gerbils. The data collected thus far suggest that the expression profile of many of the measured cytokines in B. pahangi-infected gerbils reflects what is seen in an important subset of humans infected with lymphatic filariae, the microfilaremic, asymptomatic patient.

Profiling the cellular immune response to multiple Brugia pahangi infections in a susceptible host.

Human lymphatic filariasis is caused primarily by Brugia malayi and Wuchereria bancroffi. Unraveling this disease is complex, as people living in endemic areas exhibit a vast array of clinical states and immune responses. The Mongolian gerbil (Meriones unguiculatus)-B. pahangi model of human lymphatic filariasis has provided much information on immune parameters associated with filarial infection. Prior investigations in our laboratory have shown that gerbils closely mimic a subset of patients classified as microfilaremic but asymptomatic, a group that comprises the majority of people living in endemic areas. Worm recovery data suggest that gerbils carrying current B. pahangi infections do not show any resistance to subsequent subcutaneous B. pahangi infections. The aim of the present studies was to investigate the T cell cytokine response in gerbils receiving multiple infections of B. pahangi as a means of mimicking the conditions experienced by people in endemic areas. The T cell cytokine profile generated by multiply infected gerbils was not different from that previously generated by gerbils infected only once with B. pahangi. Gerbils infected multiple times with B. pahangi showed a transient increase in IL-5, which corresponded to the increased eosinophil levels previously reported from multiply infected gerbils. Chronically infected gerbils showed elevated IL-4 mRNA levels, as has been reported from gerbils infected only once with B. pahangi. Chronic infections were also associated with a state of immune hyporesponsiveness, as determined by the characterization of lymphatic thrombi and lymphoproliferation of spleen and renal lymph node cells to worm antigen.

Soft tissue rheumatism.

Soft tissue rheumatism includes disorders of tendons and their sheaths, ligaments, bursae, joint capsules, muscles, fasciae and others. Inflammatory signs or systemic manifestations may be lacking in these disorders. Fibrositis, bursitis, tenosynovitis, myositis are some of the common types of soft tissue rheumatism. The disorders can be classified broadly into two groups ie, diffuse and local. Proper history taking and performing detailed examination are very important in arriving at diagnosis. Management includes pain relief by suitable measures. In fibromyalgia diffuse musculoskeletal pain is observed having at least 11 or 18 tender points involving upper and lower body bilaterally.

Quantification of PCR amplification products of Brugia HhaI repeat DNA using a semiautomated Q-PCR system.

The sensitive, rapid and species-specific diagnosis of Brugia infections in humans or animal models is important in determining the level of parasitemia and the efficacy of chemotherapy or vaccinations. The HhaI family of highly repeated DNA sequences from Brugia have been useful in polymerase chain reaction (PCR)-based diagnosis of brugian filarial infections in blood samples and in mosquitoes. A PCR assay was developed using a biotinylated primer, a non-biotinylated primer and a species-specific chemiluminescent probe [tris[2,2'bipyridine] ruthenium (II) chelate, TBR] to detect PCR amplified Hhal family repeats. Individual blood samples from jirds infected with Brugia malayi or B. pahangi and with different levels of microfilaremia were tested in this assay. Known concentrations of Brugia DNA and DNA from the blood of uninfected control jirds were used as positive and negative controls, respectively. The PCR products generated by this method were analyzed using a semi-automated quantitative (Q)-PCR system. The levels of parasite DNA can be calculated from the luminosity units generated. Significant amounts of parasite DNA were detected in blood samples from infected jirds, and these values were correlated with the levels of microfilaremia. In contrast, reductions in circulating microfilaria following treatment with ivermectin correlated with low levels of measurable DNA. Using this system, we were also able to detect HhaI repeat DNA in the spleens of B. pahangi- infected jirds at 56 days post-infection when circulating microfilariae were not readily detectable. The results indicate that the species-specific Hhal Q-PCR detection and quantification method is rapid and sensitive, is useful in the detection of Brugia DNA in blood and other tissues and is suited for use in clinical settings because it does not require radioactive isotopes and gel-based protocols.

Identification and localization of glutathione S-transferase as a potential target enzyme in Brugia species.

Brugia filarial nematodes are pathogenic lymphatic-dwelling parasites that, like other helminths, may modify the host's defense mechanisms by a major detoxification process involving glutathione-binding proteins such as glutathione S-transferases (GSTs). In the present study, soluble extracts of third-stage larvae, adult male and female worms, microfilariae of either B. pahangi or B. malayi or the adult worm excretory-secretory products of B. malayi were used to determine GST activity. These extracts and affinity-purified fractions of B. pahangi adult worms had a specific enzymatic activity when 1-chloro-2,4-dinitrobenzene was used as a substrate. The observance of this enzyme in all life cycle stages of Brugia spp. demonstrates its ubiquitous nature. Lavage of intraperitoneally infected jirds, but not that of uninfected jirds, also showed increased enzymatic activity, suggesting that GST is secreted in vivo. Soluble proteins of both Brugia spp. were strongly recognized by antibodies in sera from rabbits immunized with affinity-purified native GST of Onchocerca volvulus. Immunohistochemical studies localized these proteins in adult worms, demonstrating cross-reactivity between the GST of these two filarial nematodes. The effect of this enzyme on the motility and viability of adult worms, microfilariae, and larvae was tested in vitro using a battery of known GST inhibitors. Of all those tested, ethacrynic acid, N-ethylmalemide, 4-nitropyridine-oxide, or 1-chloro-2,4-dinitrobenzene at micromolar concentrations reduced the viability and motility of microfilariae, third-stage larvae, and adult worms. These results suggest that Brugia GSTs are major metabolic enzymes and may play an important role in the parasite's survival.

Transglutaminase activity in equine strongyles and its potential role in growth and development.

Transglutaminases (E.C. 2.3.3.13) are a family of Ca(2+)-dependent enzymes that stabilize protein structure by catalyzing the formation of isopeptide bonds. A novel form of transglutaminase has been identified and characterized that seem to play an important role in growth, development, and molting in adult and larval stages of filarial nematodes. The aim of this study was to identify the ubiquitous nature of this enzyme in other nematodes and to measure its significance to larval growth, molting, and development. For this purpose, equine Strongylus spp. were used. Activity of this enzyme was identified in extracts of larvae and adults of Strongylus vulgaris, S. edentatus, Parascaris equorum and Cylicocyclus insigne. The significance of transglutaminase in the early growth and development of Strongylus vulgaris, S. edentatus and S. equinus was tested by adding specific inhibitors, monodansylcadaverine (MDC) or cystamine (CS), to in vitro cultures of third (L3) and fourth stage larvae (L4). The viability, molting and growth of these nematode species were affected by both inhibitors. Cystamine promoted abnormal development of Strongylus edentatus L3, resulting in an aberrant expansion of the anterior end. Addition of these inhibitors to cultures of L4 also reduced growth of the three species. The results indicated that transglutaminase is present in a wide array of nematode parasites and may be important in growth and development of their larval stages.

Granulomatous inflammatory response to recombinant filarial proteins of Brugia species.

The lymphatic inflammatory response in Brugia-infected jirds peaks early during primary infections and then decreases in severity as judged by the numbers of lymph thrombi present within these vessels. Antigen-specific hypersensitivity reactions in these animals was measured by a pulmonary granulomatous inflammatory response (PGRN) induced by somatic adult worm antigen (SAWA)-coated beads, and by cellular proliferative responses of renal lymph node cells. The kinetics of these responses temporally correspond to lymphatic lesion formation. The importance of any single antigen to the induction of this inflammatory response has not been elucidated. In this study, the PGRN was used to measure the cellular immune response to four recombinant filarial proteins during the course of a primary B. pahangi infection. These proteins were BpL4, glycoprotein (glutathione peroxidase) gp29, heat shock protein (hsp) 70, and filarial chitinase. All were fusion proteins of maltose-binding protein (MBP). Control beads included those coated with diethanolamine (DEA), SAWA, or MBP. The measurements of PRGN were made at 14, 28, 56, and > 150 days postinfection (PI) in infected jirds, in jirds sensitized with SAWA, and in uninfected jirds. The secretory homolog of glutathione peroxidase gp29 was the only recombinant protein tested that induced a significantly greater PGRN (P < 0.05) than controls. This was seen at 28 days PI. These observations indicate that gp29 may be part of the worm antigen complex that induces an early inflammatory response, a response similar to that observed with SAWA. These studies indicate that this approach is useful in investigating the functional ability of specific proteins in the induction and down-regulation of immune-mediated inflammatory responses elicited by filarial parasites. Absence of a granulomatous response to the other recombinant proteins used may be related to the nature and sensitivity of the assay used or the character of recombinant proteins tested.

Effect of gamma radiation on Brugia L3 development in vivo and the kinetics of granulomatous inflammation induced by these parasites.

Previous studies have shown that the downregulation of parasite-specific cellular immune response in Brugia-infected jirds requires viable worms but is not dependent on microfilariae (MF) for either induction or maintenance of this phenomenon. To clarify further which life cycle stages induce filarial hyporesponsiveness, jirds were infected intraperitoneally with third stage larvae (L3) exposed to 0, 15, 25, 35, 45, or 90 krad of gamma radiation to differentially alter L3 development. Necropsies were performed at 7, 14, 28, and 118 days postinoculation (DPI). The degree of parasite development, intraperitoneal inflammation, and pulmonary granulomatous inflammation (PGRN) to parasite antigen-coated beads embolized in the lungs were monitored at the time of necropsy. Parasite survival and worm lengths were inversely related to the irradiation dose. Gamma radiation at 35, 45, or 90 krad prevented larval molt to the adult stage. Some parasites irradiated with 15 or 25 krad developed beyond fourth stage larvae (L4) to infertile adult females. The PGRN peaked at 14 DPI in all infected groups. Downregulation of the PGRN occurred after 14 DPI in groups that received nonirradiated L3 or L3 irradiated with 15 krad. No significant decrease of the PGRN occurred in groups that received parasites irradiated with more than 15 krad. Significant peritoneal inflammation as indicated by an increase in macrophages occurred only in jirds that received nonirradiated L3. These data demonstrate the importance of the adult stages in inducing downmodulation in the absence of MF and suggest that the L4 may also play a role in the induction of this phenomenon. An alternate conclusion is that parasite burden and not developmental stage is important in the induction of this hyporesponsive state.

Brugia pahangi: differential induction and regulation of jird inflammatory responses by life-cycle stages.

It has been hypothesized that different life-cycle stages of filarial nematodes induce different host responses. This concept was examined in the Brugia pahangi-jird model of lymphatic filariasis by measuring the kinetics of inflammatory responses to parasite antigens following intraperitoneal inoculation of different life-cycle stages. For this purpose, viable female or male worms, L3, L4, or microfilarial stage, were used. Dead worms served as controls. Worm and microfilarial burdens, pulmonary granulomatous inflammation (PGRN) to soluble adult worm antigen (SAWA)-coated beads, and peritoneal eosinophil and macrophage numbers were assessed at different days post-inoculation. All jirds inoculated with any of these life-cycle stages developed an early PGRN to SAWA which was later significantly reduced. Only viable worms induced down-regulation of the PGRN response. These results indicate that the hyporesponsive state is induced and maintained by all life-cycle stages. Also, the degree of granulomatous response was influenced by worm burden, with larger worm burdens inducing lower initial levels of PGRN to SAWA. Peritoneal inflammatory responses differed from the systemic response in that numbers of macrophages increased with time and microfilarial accumulation. No correlation was observed between peritoneal inflammatory responses measured by eosinophil and macrophage numbers and PGRN to SAWA.

Adoptive transfer of granulomatous inflammation to Brugia antigens in jirds.

Brugia pahangi infections of jirds (Meriones unguiculatus) produce a granulomatous inflammatory response within the lymphatic vessels. Granulomas that form around beads coated with soluble adult antigens embolized in the lungs have been used to measure this response. Similar lesions were observed in naive jirds receiving lymph node cells and splenocytes from animals with acute infections. This was not the case with cells from chronically infected jirds that were hyporesponsive to implanted antigen-coated beads. Passively transferred immune sera collected during the acute and chronic periods of infection did not transfer this response. Lymph node cells but not splenocytes obtained from chronically infected jirds induced a down regulation of this response in animals during the acute period. These results indicate that this inflammatory response in the jird is cell mediated and that adoptive transfer in jirds is feasible. The induction of the down-regulated state may also be mediated by cells, but not serum factors.

Effect of Brugia malayi on the growth and proliferation of endothelial cells in vitro.

Athymic mice (C3H/HeN) parasitized by Brugia malayi develop massively dilated lymphatics. The lymphatic endothelial lining is perturbed, and numerous mononuclear and giant cells are closely apposed to the endothelium. The hyperplastic endothelial cells and low opening pressure of the lymphatics suggest abnormal multiplication of these cells may be important in the dilation. We studied the in vitro growth rate of human umbilical vein endothelial cells cultured with adult worms and microfilariae of B. malayi. The tetrazolium salt reduction assays were used to quantify possible direct mitogenic or inhibitory effects. The growth factor-induced proliferation of endothelial cells was significantly suppressed by 44-51% on day 1, 46-81% on day 3, and 45-79% on day 5 in cultures containing adult female worms, which had greater suppressor activity on endothelial cell proliferation than male worms, microfilariae, or soluble adult worm extract. Culture supernatant containing female worm excretory-secretory products significantly inhibited the growth and multiplication of cells, suggesting that adult female worms release antigens or proteins that have inhibitory activity on growth factors necessary for endothelial cell proliferation in vitro. Excess human recombinant epidermal growth factor and bovine brain extract partly reversed the inhibitory activity of worms in culture and restored the endothelial cell proliferation when incubated with worm culture supernatant. Indomethacin and BW 775Hcl failed to restore normal endothelial proliferation in the presence of female worms, suggesting that parasite-derived prostanoids and cyclooxygenase products did not cause the inhibition. Lymph from dilated lymphatics, but not serum from infected mice, increased the proliferation of cells in vitro. Together, these data demonstrate that excretory-secretory products of B. malayi parasites suppress vascular endothelial proliferation in vitro. Furthermore, increases in the number of these cells in vitro in the presence of lymph suggest that parasite-induced host factors may be important in modulating the degree of proliferation.