Nivedita Gupta

Hypertension: salt restriction, sodium homeostasis, and other ions.

Salt is composed of Sodium Chloride (NaCl) which in body water becomes essential electrolytes, viz., Sodium (Na⁺) and Chloride (Cl⁻) ions, including in the blood and other extracellular fluids (ECF). Na⁺ ions are necessary cations in muscle contractions and their depletion will effect all the muscles in body including smooth muscle contraction of blood vessels, a fact which is utilized in lowering the blood pressure. Na⁺ ions also hold water with them in the ECF. Na⁺ homeostasis in body is maintained by thirst (water intake), kidneys (urinary excretion) and skin (sweating). In Na⁺ withdrawal, body tries to maintain homeostasis as far as possible. However, in certain conditions (e.g., during exercise, intake of drugs and in disorders causing Syndrome of Inappropriate Anti Diuretic Hormone Secretion (SIADH), diuretics, diarrhea) coupled with moderate or severe dietary salt restriction (anorexia nervosa), hyponatremia can get precipitated. Hyponatremia is one end point in the spectrum of disorders caused by severe Na⁺ depletion whereas in moderate depletion it can cause hypohydration (or less total body water) and lower urinary volume (U v ). Moreover, salt sensitivity varies in various populations leading to different responses in relation to dietary Na⁺ intake. Diabetes and Hypertension often co-exist but Na⁺ withdrawal in salt sensitive subjects worsens diabetes though hypertension gets better and reverse occurs in salt loading. Therefore, Na⁺ or salt restriction may be non-physiological. In hypertensive subjects other alternatives to Na⁺ withdrawal could be Potassium (K⁺) and Calcium (Ca⁺²) supplementation. Further studies are required to monitor safety/side effects of salt restriction.

Acute encephalitis syndrome in Gorakhpur, Uttar Pradesh, India – Role of scrub typhus

With reference to the recent communication to this Journal by Ranjan and colleagues, it is notable that outbreaks of acute encephalitis syndrome (AES) with high fatality have been occurring in Gorakhpur division, Uttar Pradesh, India since several years. These outbreaks occur during rainy season, peak during AugusteSeptember and predominantly affect children aged 14 years. Annually, approximately 1500e2000 AES patients get admitted to BRD Medical College (BRDMC), Gorakhpur the only tertiary care hospital in the region, with a case-fatality of 20e25%. In the past, AES patients have been investigated for viral and non-viral etiologies including Japanese encephalitis (JE), herpes simplex, enteroviruses, Chandipura, measles, mumps, dengue, varicella, Parvovirus, West Nile, malaria, and typhoid. 4 However, except for a small contribution (<10%) from JE, the etiology of AES has largely remained unknown. We investigated AES patients to explore role of scrub typhus (ST). We enrolled 370 AES patients (defined as acute onset of fever and change in mental status and/or new onset of seizures, excluding simple febrile seizures) and 109 patients of acute febrile illness (AFI; defined as fever of 2 weeks duration, without localizable signs) admitted at BRDMC during SeptembereOctober 2015 (Table 1). Blood samples were collected from these patients (1 ml in EDTA, 2 ml in plain tube without anticoagulant for serum). EDTA blood was centrifuged; buffy coat was applied on four spots of Whatman FTA classic card (GE Healthcare, UK) and air-dried. DNA was extracted from one spot using Qiagen protocol. A quantitative real-time PCR for 47 kDa gene was performed using primers, probes and protocol described by Jiang et al. and validated by Kim et al. A cycle threshold value 38 was considered positive. All samples were tested in duplicate and ST positives were repeat-tested. DNA quality and sample integrity was tested by performing RNase P qPCR. Sera were tested for IgM antibodies against Orientia tsutsugamushi (OT) using commercial ELISA (Scrub Typhus Detect, InBios International Inc., Seattle, USA). In the absence of any data about

Scrub Typhus as a Cause of Acute Encephalitis Syndrome, Gorakhpur, Uttar Pradesh, India

Outbreaks of acute encephalitis syndrome (AES) have been occurring in Gorakhpur Division, Uttar Pradesh, India, for several years. In 2016, we conducted a case–control study. Our findings revealed a high proportion of AES cases with Orientia tsutsugamushi IgM and IgG, indicating that scrub typhus is a cause of AES.

Scrub Typhus as an Etiology of Acute Febrile Illness in Gorakhpur, Uttar Pradesh, India, 2016

Seasonal outbreaks of acute encephalitis syndrome (AES) with high mortality occur every year in Gorakhpur region of Uttar Pradesh, India. Earlier studies indicated the role of scrub typhus as the important etiology of AES in the region. AES cases were hospitalized late in the course of their illness. We established surveillance for acute febrile illness (AFI) (fever ≥ 4 days duration) in peripheral health facilities in Gorakhpur district to understand the relative contribution of scrub typhus. Of the 224 patients enrolled during the 3-month period corresponding to the peak of AES cases in the region, about one-fifth had immunoglobulin M (IgM) antibodies against Orientia tsutsugamushi. Dengue and leptospira accounted for 8% and 3% of febrile illness cases. Treating patients with AFI attending the peripheral health facilities with doxycycline could prevent development of AES and thereby reduce deaths due to AES in Gorakhpur region.

Mapping dengue cases through a national network of laboratories, 2014-2015

Dengue fever, a mosquito-borne viral disease, is a major public health problem globally1. It has been estimated that more than 390 million dengue infections occur every year, of which 96 million manifest clinically2,3. India contributes to about a third of global burden of apparent dengue infections2,3. As per India’s Integrated Disease Surveillance Programme, more than 100 dengue outbreaks were reported in 20154. Good laboratory-based disease surveillance is essential for early detection of dengue outbreaks and implementation of effective preventive and control measures1.

Burden of bacterial meningitis in India: Preliminary data from a hospital based sentinel surveillance network

Background Worldwide, acute bacterial meningitis is a major cause of high morbidity and mortality among under five children, particularly in settings where vaccination for H. influenzae type b, S. pneumoniae and N. meningitidis is yet to be introduced in the national immunization programs. Estimation of disease burden of bacterial meningitis associated with these pathogens can guide the policy makers to consider inclusion of these newer vaccines in the immunization programs. A network of hospital based sentinel surveillance was established to generate baseline data on the burden of bacterial meningitis among children aged less than 5 years in India and to provide a platform for impact assessment following introduction of the Pentavalent and Pneumococcal Conjugate Vaccines (PCV). Methods During surveillance carried out in select hospitals across India in 2012–2013, information regarding demographics, immunization history, clinical history, treatment details and laboratory investigations viz. CSF biochemistry, culture, latex agglutination and PCR was collected from children aged 1 to 59 months admitted with suspected bacterial meningitis. Results A total of 3104 suspected meningitis cases were enrolled from 19,670 children admitted with fever at the surveillance hospitals. Of these, 257 cases were confirmed as cases of meningitis. They were due to S. pneumoniae (82.9%), H. influenzae type b (14.4%) and N. meningitidis (2.7%). Highest prevalence (55.3%) was observed among children 1 to 11 months. Antimicrobial susceptibility testing revealed considerable resistance among S. pneumoniae isolates against commonly used antibiotics such as cotrimoxazole, erythromycin, penicillin, and cefotaxime. More commonly prevalent serotypes of S. pneumoniae in circulation included 6B, 14, 6A and 19F. More than 90% of serotypes identified were covered by Pneumococcal Conjugate Vaccine 13. Conclusions We observed that S. pneumoniae was the commonest cause of bacterial meningitis in hospitalized children under five years of age in India. Continued surveillance is expected to provide valuable information and trends in future, to take an informed decision on introduction of pneumococcal vaccination in Universal Immunization Programme in India and will also eventually help in post-vaccination impact evaluation.

First laboratory confirmation on the existence of Zika virus disease in India

• After WHO declaration of Zika threat, a surveillance program was conducted under the initiative of Department of Health research/ Indian council of Medical Research, Ministry of Health, India using Virology Research and Diagnostic Laboratories (VRDL) network.

Comparison of two commercial ELISA kits for detection of rubella specific IgM and IgG antibodies

Enzyme linked immunosorbent assay (ELISA) plays an important role in laboratory confirmation of congenital rubella syndrome (CRS), postnatal rubella and seroprevalence studies in different populations. Variation of results are documented for samples tested by different commercial kits. The Enzygnost rubella ELISA, widely used in the WHO network, is expensive and not readily available. In the present study, performance of the Euroimmun ELISA was compared to the Enzygnost ELISA for detection of rubella specific IgM and IgG antibodies. Two hundred and eighty five serum samples collected from suspected CRS patients identified through a recently initiated surveillance for CRS at six sentinel hospitals and 435 serum samples from a serosurvey of pregnant women from these sites, were available for testing of rubella specific IgM and IgG antibodies respectively. Qualitative agreement (concordance percentage and Cohen’s Kappa coefficient -κ) was evaluated for both IgM and IgG assays. Bland – Altman plots were used to assess the difference in quantitative agreement for IgG titers. Good qualitative agreement between the two ELISA kits was observed for detection of both anti rubella IgM (94.7% agreement and k of 0.86) and IgG (96.3% agreement and k of 0.84). Sensitivity and specificity of Euroimmun assays compared to Enzygnost was 100% and 93.1% for IgM and 95.9% and 100% for IgG respectively. Bland – Altman analysis for paired quantitative results of rubella specific IgG yielded a mean difference of 0.781 IU/ml with majority of values (97.1%) within ± 2 SD of the mean difference. Euroimmun ELISA provided on an average, higher titers as compared to Enzygnost. Our study findings suggest that Euroimmun ELISA may be considered for detection of rubella specific IgM in suspected CRS cases and rubella specific IgG in surveillance studies.

Acute Encephalitis Syndrome in Eastern Uttar Pradesh, India: Changing Etiological Understanding

Seasonal outbreaks of acute encephalitis syndrome (AES) with high case fatality have been occurring in Gorakhpur division in Eastern Uttar Pradesh, India, for more than three decades. Japanese encephalitis virus (JEV) accounted for <10% of AES cases, while the etiology of the remaining cases remained largely unknown. Investigations conducted during the 2014 and 2015 outbreaks indicated Orientia tsutsugamushi (Haruo Hayashi 1920) (Norio Ogata 1929) Tamura et al. 1995 (Rickettsiales: Rickettsiaceae) as the etiology in about 60% of AES cases. Hospital-based surveillance studies indicated that about one-fifth of the patients with acute febrile illness were due to scrub typhus. Further studies are required to identify the etiology of about a third of AES cases that test negative for scrub typhus, JEV, or dengue.

Epidemiology of Hepatitis A and Hepatitis E Based on Laboratory Surveillance Data—India, 2014–2017

Hepatitis A and hepatitis E viruses (HAV and HEV) are the most common etiologies of viral hepatitis in India. To better understand the epidemiology of these infections, laboratory surveillance data generated during 2014-2017, by a network of 51 virology laboratories, were analyzed. Among 24,000 patients tested for both HAV and HEV, 3,017 (12.6%) tested positive for HAV, 3,865 (16.1%) for HEV, and 320 (1.3%) for both HAV and HEV. Most (74.6%) HAV patients were aged ≤ 19 years, whereas 76.9% of HEV patients were aged ≥ 20 years. These laboratories diagnosed 12 HAV and 31 HEV clusters, highlighting the need for provision of safe drinking water and improvements in sanitation. Further expansion of the laboratory network and continued surveillance will provide data necessary for informed decision-making regarding introduction of hepatitis-A vaccine into the immunization program.