A Case Series on Spotted Fever and Typhus Fever Seropositivity at National Center for Disease Control and Epidemiological Perspective.

Background: The rickettsioses, except for typhus fever and scrub typhus (ST), were not really recognized as distinct clinical entities until the early 20th century. Only when specific rickettsial serologic testing was introduced in the 1940s could the precise etiologies of various rickettsial diseases (RDs) be determined with certainty. Although ST is a well- recognized zoonotic disease entity, but non-scrub typhus rickettsial infection like spotted fever group and typhus group are not well studied in India and are still underestimated. Methods: We report cases who had shown seropositivity of spotted fever and typhus fever RD in IgM and IgG ELISA whose samples were referred from various hospitals of Delhi/National Capital Region in which clinicians had strong suspicion of rickettsiosis other than ST or Weil-Felix test found positive for any of the OX2, 19, and K antigens. Results: We reported 18 cases of SFG and TGRD with mostly cases presented with fever followed by hepato-intestinal symptoms. Conclusion: The vast variability and nonspecific presentation of rickettsiosis in spotted and typhus fever at times have often made it difficult to diagnose clinically. Prompt antibiotic therapy shortens the course of the disease, lowers the risk of complications, and in turn, reduces morbidity and mortality owing to RDs. There is a distinct need for physicians and health care workers at all levels of care in India to be aware of the clinical features, available diagnostic tests and their interpretation, and the therapy for these infections.

Case Report: An Atypical Case of Post-Kala-Azar Dermal Leishmaniasis with Ulcers and Verrucous Lesions: Clinical and Therapeutic Implications.

About 75% cases of post-kala-azar dermal leishmaniasis (PKDL) occur in India. Although the classic description of PKDL is the progression from initial hypopigmented macular lesions to papules to plaques and nodular lesions, atypical morphologies are also seen and are easily missed or misdiagnosed. We report a case of a 27-year-old man who presented to us with multiple acral ulcers and verrucous lesions for 5 years. A diagnosis of PKDL was made based on slit skin smear, histopathology, and quantitative polymerase chain reaction. The patient was given combination therapy with four doses of liposomal amphotericin B and miltefosine 50 mg twice daily for 45 days. In this report, we discuss unusual morphologies of PKDL, the pathway to the diagnosis, and the therapeutic options available along with their efficacy.

Human anthrax in India in recent times: A systematic review & risk mapping.

The disease anthrax occurs generally in herbivores and the causative organism (Bacillus anthracis) infects humans who come in contact with infected animals or their products. The persistence of anthrax spores for decades and its lethality contribute to its biowarfare potential. We conducted this systematic review along with risk mapping to investigate the spatio-temporal distribution, clinico-epidemiological, socio-behavioural and programmatic issues pertaining to anthrax in India over the last two decades. Peer reviewed quantitative and qualitative studies and grey literature comprising weekly reports of the 'Integrated Disease Surveillance Program' (IDSP), were accessed for extracting data. IDSP data were used for geo-referencing of the villages of anthrax cases; Pseudo-absence was generated to fit a Bayesian Additive Regression Trees (BART) model to develop anthrax risk map. The case fatality rate of cutaneous anthrax ranged from 2% to 38%, while the gastrointestinal and inhalational types were 100% fatal. Our synthesis revealed that human anthrax outbreaks in India were clustered around the eastern coastal regions. The states of Odisha, West Bengal, Andhra Pradesh and Jharkhand reported maximum number of outbreaks. Odisha reported a maximum number of 439 human anthrax cases since 2009, of which Koraput district contributed to 200 cases (46%). While handling or consumption of infected animal product were proximal drivers of these events, poverty, lack of awareness, traditional beliefs and local practices served as facilitatory factors. Other structural determinants were wild life-livestock interface, historical forest loss, soil pH, soil-water balance, organic carbon content, temperature, rainfall and humidity. The programmatic issues identified through this review were lack of active surveillance, non-availability of diagnostic facility at the periphery, delayed reporting, absence of routine livestock vaccination and lack of adequate veterinary services. Interventions based on One-health approach in the country merit immediate policy and program attention; high risk zones for anthrax identified during present investigation, should be prioritized.

Intravitam Diagnosis of Rabies in Patients with Acute Encephalitis: A Study of Two Cases.

Rabies is one of the oldest known zoonotic diseases. Rhabdovirus, an RNA virus belonging to the genus Lyssavirus and family Rhabdoviridae, causes rabies. Rabies diagnosis is challenging as the rabies virus remains confined to neurons after the initial animal bite. It largely remains immune-evasive until the infection reaches the central nervous system. The bottleneck in rabies diagnosis remains the non-availability of technical expertise and failure to collect an appropriate sample. The laboratory confirmation of rabies in both antemortem and postmortem samples is important. The samples were tested for anti-rabies antibodies using quantitative ELISA. In this report, two case studies are presented to demonstrate the suitability of ELISA for the intra vitam diagnosis of rabies using cerebrospinal fluid (CSF) as a diagnostic sample. The interpretation of serology results for both vaccinated and unvaccinated individuals has been discussed in detail, which has helped to confirm the antemortem diagnosis of rabies. In this report, we observed that ELISA can be a viable alternative for anti-rabies antibody detection in CSF and can be used as a viable alternative to more technically challenging tests, such as Rapid Fluorescent Focus Inhibition Test (RFFFIT) and Immunofluorescence Assays (IFA).

Rabies Outbreak in the Urban Area of Delhi: An Investigation Report and One Health Perspective for Outbreak Management.

Rabies is a global problem and is endemic in India. Rabies cases occur throughout the year, and the majority of cases are associated with dog bites. We report a rabies outbreak investigation in an urban area of Delhi conducted by our multidisciplinary team, and its role in proactively controlling a rabies outbreak by concerted efforts and timely advice to various stakeholders using a "One Health Approach." A veterinary care NGO from Delhi picked up a suspected rabid stray dog and submitted a brain sample for diagnosis of rabies, as they had received information from a resident of the locality about an unprovoked animal bite incident involving a girl (category III bite) and close contact of two more stray dogs living in the vicinity of the suspected rabid dog. The laboratory diagnosis of rabies in the suspected dog brain sample was confirmed by using Fluorescence Antibody Test (FAT). A multi-expert investigation team with expertise in medicine, microbiology, veterinary sciences, laboratory diagnosis, and public health was constituted to investigate the outbreak. The timely, adequate, and appropriate anti-rabies management initiated for the animal bite victims in this incident could prevent rabies. Proactive involvement of multiple stakeholders and knowledge attributes and practice of local residents could prevent human rabies. As there were no further reports of dog bites from the area, the chain of rabies transmission in that area could be controlled. The presented work is a classical case scenario where concerted efforts of all stakeholders achieved effective control and prevention of rabies by adopting the "One Health approach".

Rabies can be a disease of puppyhood.

This brief report documents an interesting and a rare case of 10 week old male puppy who suddenly showed a change in his behavior (irritable, agitated, anorexic, and refusing feeds), bitten six humans, and was laboratory-confirmed as died due to rabies (Rapid antigen test and reverse transcriptase polymerase chain reaction positive for rabies at the National Rabies Reference Laboratory, WHO collaborating Centre for Rabies Epidemiology, Centre for Arboviral and Zoonotic Diseases, National Centre for Disease Control, Delhi). All animal bite victims were timely provided postexposure prophylaxis for rabies who had shown sufficient seroconversion by IgG antirabies antibody using enzyme linked immunoassay (ELISA) and have been reported healthy. This case report reinforces the role of veterinarians/primary care physicians for strong suspicion of rabies encephalitis in puppies with behavioral or neurologic abnormalities and timely/appropriate rabies immunization of the animal bite victims. Shreds of evidence also focus that rabies in puppies younger than 3 months of age is grave and the risk of human beings contracting rabies from young puppies is of public health importance because of fatal consequences. Continuing medical education for primary care physicians and veterinarians, and outreach community public awareness campaigns should be regularly done to promote knowledge of pre-exposure/post-exposure prophylaxis, preventive measures, and animal bite management.

Utility of smear examination, culture, and serological tests in the diagnosis of visceral leishmaniasis/post-kala-azar dermal leishmaniasis at National Centre for Disease Control, Delhi.

Introduction: A range of assays have been developed to detect specific antileishmanial antibody, such as rK 39 immunochromatographic test (ICT), KE 16 ICT, ELISA test, and indirect immunofluorescent antibody test (IFAT), which play a crucial role in serological diagnosis of visceral leishmaniasis (VL). However, limited published reports are available on the utility of serological test (IFAT test/rk 39), smear examination, and culture in the diagnosis of VL and post-kala-azar dermal leishmaniasis (PKDL) in our country. Materials and Methods: We present utility of serological test (IFAT test/rK 39), smear examination for Leishmania donovani (LD) bodies, and culture in 2589 samples from 2294 VL/PKDL suspected patients (January 2009-December 2019) tested in Centre for Arboviral and Zoonotic diseases, National Centre for Disease Control, New Delhi, India, for laboratory diagnosis of VL/PKDL. Results: A total of 80/553 (14.4%) cases were confirmed of VL (74/522 cases by demonstration of LD bodies in bone marrow smear examination, 5/12 in splenic smear examination 1/19 by culture) and 4/21 (19.0%) cases were confirmed of PKDL (demonstration of LD bodies in slit skin smear examination. In our study 197/1368 (14.4%) cases were diagnosed positive by IFAT, 34/646 (5.2%) cases by rk 39 ICT for VL/PKDL by demonstration of specific antileishmanial antibodies. Conclusion: As the goal of elimination of VL as a public health problem is approaching, apart from serological tests such as rk 39 and IFAT, direct methods of detection such as (parasitic demonstration in BM smear, culture, and molecular tests) for Leishmania may play a crucial role for achieving a correct diagnosis and treatment. We also concluded that IFAT though not field-friendly, its optimal use as an adjunct test with BM smear in all stages of infections may be required. Further rk39 is a simple, reliable, noninvasive, and field-friendly test for diagnosis VL, especially in endemic areas.

Association between the physical activity and metabolic syndrome in residents of a foot-hill area in India.

BACKGROUND AND AIMS: Physical inactivity, has been linked to development of metabolic syndrome, which increases the risk of developing cardiovascular disease. Aim of the study was to assess the level of physical activity and it's association with prevalence of metabolic syndrome and oxidative stress in a semiurban foothill population of India. METHODS: Participants (n = 288), >18 years of age were enrolled. Their demographics and clinical details were recorded. Fasting plasma glucose, triglycerides, cholesterol and erythrocyte glutathione peroxidase activity were measured. Physical activity was estimated using Global Physical Activity Questionnaire and converted into metabolic equivalent in minutes per week. RESULTS: 37.5% of study population was found to be physically active, with more males (43.3%) being active than females (23.3%). Inactivity was associated with higher triglycerides levels in males and with higher hip circumference, diastolic blood pressure, triglycerides and fasting plasma glucose in females. No significant difference was found in the oxidative stress, indicated by decreased glutathione peroxidase activity, between active and inactive persons or persons with normal and increased body mass index. CONCLUSIONS: There is a high prevalence of physical inactivity in this region of India, with prevalence of physical inactivity higher is females as compared to males. No significant co-relation was found between the levels of activity and components of metabolic syndrome and oxidative stress in the study population.

Nipah Virus Disease: Recent Perspective and One Health Approach.

Background: Nipah virus (NiV) first emerged in 1998 in Malaysia, causing an outbreak of respiratory illness and encephalitis in pigs. Pig-to-human transmission of NiV associated with severe febrile encephalitis was described, and it was thought to occur through close contact with infected animals. The first outbreak was reported in India in Siliguri, West Bengal in 2001 followed by Nadia, West Bengal and adjoining areas of Bangladesh in 2007, where an intermediate animal host was not identified, suggesting bat-to-human and human-to-human transmissions. Although it is extremely difficult to document the spillover event and ascertain crossing of trans-natural boundaries by bats and bringing new viruses in an unexposed population, efforts for source identification are important to understand the epidemiology of disease. As the disease transcends beyond one species and has shown to infect humans, it therefore requires the 'One Health approach' in which multiple sectors coordinate and work together to achieve better public health outcomes. Objective: We summarize the re-emergence and response of the Nipah virus outbreaks (NiVD) in Kerala, India, about 1800 kms away, a decade later in 2018 and 2019. The paper recapitulates involvement of various stakeholders from the Ministry of Health and Family Welfare, Directorate of Health Research, Indian Council of Agricultural Research, State Health Department, State Animal Husbandry, District Administration, and multidisciplinary response mechanism during the NiVD outbreaks of 2018 and 2019. Methods: Information was collected from the Press Information Bureau (PIB), media/weekly alerts from the Integrated Disease Surveillance Programme (IDSP), news articles from print and electronic media, newsletters, advisories from the National Centre for Disease Control (NCDC), Disease Outbreak News (DON), World Health Organization (WHO), and published papers from various stakeholders. Findings & Conclusion: The evidence of NiV in humans and bats, with samples collected from the outbreak sites, was laboratory confirmed. The multidisciplinary response mechanisms during the 2018 outbreak helped in further understanding the importance of the One Health approach for systemic and streamlined response utilizing existing surveillance systems. This was of utmost help in the subsequent outbreak of the disease that occurred during 2019, wherein there was no documented spread of disease from the index case and no mortality was observed. This success reiterates the need for institutionalizing the involvement and cooperation of various departments and organizations during public health emergencies, especially of Zoonotic diseases, using the One Health approach.

Chronicle down memory lane: India's sixty years of plague experience.

BACKGROUND: This perspective documents the historical aspects of outbreaks of plague of last six decades, establishment of plague surveillance network in India with detailed insights about its activities and recent developments requiring focus on plague surveillance. Human plague was reported in Mulbagal area of Karnataka in 1966-67 only to re-emerge in the country in 1994 in Beed district (Maharashtra) and subsequently in Surat (Gujarat). Later Plague outbreak has been reported in the year 2002 with index case from Village Hatkoti, Shimla District in Himachal Pradesh. The last outbreak reported from India was in 2004 from Village Dangaud, Uttarkashi District in Uttarakhand followed by a period of quiescent since last 17 years. OBJECTIVES: During the last few decades, at least three geographical areas experienced outbreaks of plague after silent period of 28 years. We recapitulate the response mechanism for containing outbreaks during the last three outbreaks of plague held in Maharashtra & Gujarat (1994), Himachal Pradesh (2002) and Uttarakhand (2004). We also document the Plague surveillance network of India and its activities which is a comprehensive surveillance system comprising of rodent, flea, canine and human surveillance whose foundation was started in 1964. The recent developments of last decade in terms of revised Human plague surveillance case definitions, Plague surveillance sites, vector control, novel diagnostics and vaccines in our country are also mentioned. CONCLUSION: The thrust areas in control of plague outbreak are early detection and isolation of cases, timely effective antibiotic treatment, chemoprophylaxis to contacts, strengthening of surveillance system and massive IEC campaign in infected areas. Yersinia pestis (causative agent of Plague) also being an important bioterrorism agent, clinicians need to pay special attention to diagnose and microbiologists must be provided skilled training for laboratory confirmation to this pestilential disease for effective and timely management.

The missing pieces in the jigsaw and need for cohesive research amidst coronavirus infectious disease 2019 global response.

Identifying the research needs and gaps amidst this COVID-19 travelling across the countries is absolutely important for finely improving on the way we think and act. The natural history of the disease as well as viral shedding in different stages of clinical illness needs to be known which helps in triaging the patients in hospital settings. Animal and environmental interface need to be studied for defining the high-risk situations. Transmission dynamics in community or hospital and defining the laboratory criteria for the case confirmation will be most crucial. Gene sequencing and validation and, suitable use of molecular based tests such as real-time polymerase chain reaction (qRT-PCR) should be clearly evaluated for diagnosis and/ or surveillance. The movement control strategy must be defined to prevent secondary transmission in healthcare as well as in community settings. Repurposing of drug molecules is an elegant strategy to develop therapeutics in the case of pandemics quickly. Unproven practices and treatment protocols should invite critical scrutiny on the basis of ethics. Socioeconomic status of the community is also an important determinant for the compliance and sustainable public health measures.

Study of metabolic syndrome and its risk components in patients attending tertiary care center of uttarakhand.

Metabolic syndrome is a complex of metabolic factors which includes central obesity, insulin-resistance, dyslipidemia and hypertension. Metabolic syndrome is associated with increased risk of cardiovascular disease. This study aimed to know the rate of metabolic syndrome in outpatients presenting to medicine department of our hospital and their profile. The metabolic syndrome was diagnosed using International Diabetes Federation criteria. The parameters analyzed included age, sex, blood pressure, BMI, fasting plasma glucose, HDL and triglycerides. The rate of metabolic syndrome was 21.1 % in our study. The younger population was most susceptible to metabolic derangements. Further, females were found to be affected more than males. The extremely significant parameters were deranged fasting plasma glucose, HDL, triglycerides while hypertension was found to be insignificant. Being overweight maybe a strong predictor for presence of metabolic syndrome in our region of study, and all overweight persons should be assessed and appropriately treated to prevent future cardiovascular events.

Tuberculosis and non-diabetic hyperglycemia: a challenge to public health management.

Diabetes and tuberculosis comorbidity is an emerging challenge for public health management. But the diagnostic criteria for diabetes is based on microvascular complications of diabetes and does not reflect the level of hyperglycemia which affects infectivity of Mycobacterium tuberculosis. Therefore the study protocols focussing on these comorbidities need to be reviewed.

Concomitant detection of biofilm and metallo-beta-lactamases production in gram-negative bacilli.

UNLABELLED: Carbapenems are mainstay of treating serious multidrug resistant gram-negative biofilm-based infections. However, recent emergence of metallo-beta-lactamases (MbL) producing gram-negative bacilli in different parts of world may be related to gain of virulence factors associated with biofilm production. OBJECTIVES: To explore the association of MbL and biofilm production in various gram-negative bacilli. MATERIALS AND METHODS: In this study, 110 non-repetitive ceftazidime resistant gram-negative bacilli were evaluated for biofilm and MßL production. Biofilm forming ability of isolates obtained from various specimens was tested by the tube method. Disks of ceftazidime (30 µg) and ceftazidime with ethylenediaminetetraacetic acid (30 µg + 750 µg, prepared in house) for MßL detection were used. Chi-square test was used to study the association between biofilm and MßL production. P value <0.05 was considered significant. RESULTS: 88 (80%) bacilli had shown biofilm producing ability. The association of biofilm and MßL was significant in cases of non-fermenters as compared to enterobacteriaceae members. CONCLUSION: The particular combination of virulence factors (biofilm and MßL) in bacteria may be a species specific effect which needs to be investigated at molecular level in detail. This may help in designing newer therapies based on interference with biofilm formation and thus countering clinical episodes of antibiotic resistance.

Detection of Different ß-Lactamases and their Co-existence by Using Various Discs Combination Methods in Clinical Isolates of Enterobacteriaceae and Pseudomonas spp.

BACKGROUND: Resistance to broad spectrum beta-lactams mediated by extended spectrum ß-lactamase (ESBL), AmpC, and metallobetalactamase (MBLs) enzymes are an increasing problem worldwide. The study was aimed to detect occurrence rate and to evaluate different substrates and inhibitors by disc combination method for detecting varying degree of ß-lactamase enzymes and their co-production. MATERIALS AND METHODS: A disc panel containing imipenem (IMP), IMP/EDTA, ceftazidime (CA), ceftazidime-tazobactum (CAT), CAT/cloxacillin (CLOX), ceftazidime-clavulanic acid (CAC), CAC/CLOX, cefoxitin (CN), and CN/CLOX in a single plate was used to detect presence of ESBLs, AmpC, and MBLs and/or their co-existence in 184 consecutive, nonrepetitive, clinical isolates of Enterobacteriace (n = 96) and Pseudomonas spp. (n = 88) from pus samples of hospitalized patients, resistant to 3(rd) generation cephalosporins. RESULTS: Out of a total of 96 clinical isolates of Enterobacteriaceae, 18.7, 20.8, and 27% were pure ESBL, AmpC, and MBL producers, respectively. ESBL and AmpC were co-produced by 25% isolates. Among 88 Pseudomonas spp. 38.6, 13, and 6% were pure MBL, ESBL, and AmpC producers, respectively. ESBL/AmpC and MBL/AmpC co-production was seen in 20% and 18% isolates, respectively. Among ESBL and AmpC co-producers, CA/CAC/CLOX disc combination (DC) missed 7 of the 24 ESBL producers in Enterobacteriace and 4 of the 18 ESBL in Pseudomonas spp., which were detected by CA/CAT/CLOX DC. No mechanism was detected among 8.3% Enterobacteriaceae and 2.3% Pseudomonas isolates. CONCLUSION: Diagnostic problems posed by co-existence of different classes of ß-lactamases in a single isolate could be solved by disc combination method by using simple panel of discs containing CA, CAT, CAT/CLOX, IMP, and IMP/EDTA.

Colonization of peripheral intravascular catheters with biofilm producing microbes: Evaluation of risk factors.

BACKGROUND: Biofilms often colonize catheters and contribute to catheter-related septicemia. However, predictors of catheter colonization by biofilms remain poorly defined. The aim of this study was to evaluate clinical factors that may be associated with biofilm colonization of catheters. MATERIALS AND METHODS: A total of 54 isolates colonizing the peripheral intravascular catheters (IVCs) were studied and their biofilm production ability was analyzed by the tube method and antimicrobial susceptibility was also done. A detailed clinical history and examination was done of each subject to know age, sex, duration of use of IVCs, site of IVCs, swelling/purulence around the IVCs, number of attempts to install the catheter, and duration of hospital stay. RESULTS: 44 (81.4%) out of 54 isolates colonizing the catheters showed biofilm formation. Biofilm formations were significantly associated with duration of hospital stay of more than 7 days [odds ratio (OR) = 6.6; 95% confidence interval (CI) = 1.3-34; P value (P) = 0.02], multiple attempts to install the catheter (OR=7; CI=1.5-31.8; P=0.01), and multidrug resistance (OR=9.5; CI=1.8 - 51.1: P=0.008). Klebsiella pneumoniae and Candida spp. comprised most of the biofilm-producing isolates. The overall susceptibility to antimicrobials was low among biofilm-producing compared to nonbiofilm-producing microbes. CONCLUSION: The results of this study suggest that evaluation of predictors of biofilm production is important in order to understand, prevent or manage biofilm colonization of IVCs.

Bacteriological and resistance profile in isolates from diabetic patients.

BACKGROUND: Diabetes mellitus has become a global epidemic illness and poses a threat for development of resistant bacterial infections. AIM: This study was aimed to know the bacteriological and resistance profile of isolates obtained from diabetic patients. MATERIALS AND METHODS: The bacterial isolates obtained from various samples of diabetic patients admitted in medicine department in 6-month period were identified and tested for antibiotic susceptibility. The extended spectrum beta-lactamases (ESßL), AmpC, and metallo-beta-lactamases (MßL) enzymes were detected in gram-negative bacilli. Methicillin, macrolide-lincosamide-streptogramin (MLS), and linezolid resistance in Staphylococcus spp. were detected. High-level aminoglycoside resistance (HLAR) in Enterococcus spp. was also tested. RESULTS: In all, 38 of 125 diabetic patients (30.4%) had bacterial infection, 18 patients had wound infections, 18 had urinary tract infections (UTIs), and 2 had respiratory tract infections. Escherichia coli among gram-negative bacteria and Staphylococcus aureus among gram-positive bacteria were the predominant pathogens. 32.5% gram-negative bacilli were AmpC producers, 37.5% were MßL producers, and 40% were ESßL producers. Methicillin and MLS resistance was found in 50% and 33.3% isolates of Staphylococcus spp., respectively. HLAR resistance was alarming in Enterococcus spp. Polymyxin among gram-negative bacteria and vancomycin for gram-positive bacteria were the last resort with highest susceptibility rates to treat infections among diabetic patients. CONCLUSION: Resistant bacterial infections in diabetic patients are common. The presence of various resistance mechanisms in isolates of our study shows that therapeutic failure can occur if empirical prescription is unsubstantiated.