Scrub Typhus: Re-emerging Public Health Problem in India

Scrub Typhus is emerging as an important cause of fever of unknown origin and needs to be differentiated from other causes of febrile illnesses. During March to June 2014, a systematic search on ‘Scrub typhus’ was conducted to determine epidemiology and factors causing re-emergence of this disease in India. Scrub typhus is an acute, febrile, infectious illness caused by Orientia tsutsugamushi, transmitted to humans through bites of the trombiculid mites. The infection can range from a mild, self-limiting disease to a fatal illness in 35-50% of cases, with multi-organ dysfunction, if not promptly diagnosed and appropriately treated. The reports of the disease were rare for several decades, but currently a clear re-emergence has been documented from several states in India. This resurgence may be attributed to changes in the human behavior-unplanned urbanization, deforestation and rapid transport leading to displacement of vectors as well the rodents from one place to another. There is an urgent need for awareness generation among the medical and para-medical professionals especially at the peripheral levels. Standard treatment guidelines for timely diagnosis and treatment of Scrub Typhus should be available, especially in rural areas, where the disease remains undiagnosed, and this should be in accordance with the facilities available at sub-centers, PHCs, and CHCs. Active surveillance of rickettsial diseases is required to be carried out to know exact magnitude and distribution of the disease

Normal Puerperium

Puerperium is the time following delivery during which pregnancy-induced maternal anatomical and physiological changes return to the nonpregnant state. Puerperium period of 6 weeks can be divided into: (a) immediate – within 24 hours (b) early – up to 7 days (c) remote – up to 6 weeks. The puerperal effects are seen in all organs and particularly in reproductive organs. Infection and haemorrhage are the common postpartum complications. Post partum care is very important. Advice on exclusive breast feeding and contraception is also mandatory after every childbirth

Three-year review of a capacity building pilot for a sustainable regional network on food, nutrition and health systems education in India.

BACKGROUND: In Kolkata (India), there are high rates of malnourished children (45.9%) under the age of three, impacting growth, organ development, function, and cognition. Mothers have a major role to play during this crucial development stage, with research showing nutrition knowledge, attitudes and practices (KAP) of mothers are important determinants of childhood malnutrition. AIMS: To document 3 years of capacity building towards a sustainable nutrition education network in Kolkata, India, while assessing the ability to perform data collection in the form of needs assessments, impact assessments and capacity reviews. METHODS: Descriptive review and analysis of engagement and impact from 3 years of work by the NNEdPro Global Centre for Nutrition and Health, initiating locally led nutrition education interventions. Mapping to the Indian National Nutrition Strategy was also performed to review adherence to nationwide priorities surrounding nutrition and determine the wider application potential of the network. RESULTS: Two simultaneous projects were taken forward by a team of local healthcare professionals and student champions. Project 1-medical college workshops for medical student nutrition education with added focus on underserved populations, Project 2-preparation for a 'Mobile Teaching Kitchen' (MTK) in marginalised communities to empower local women as nutrition educators.Data collection methods used for analysing markers of impact and sustainability were semi-structured interviews of the community members, and KAP questionnaires to assess response to educational sessions. CONCLUSION: With local support it is possible to create and sustain fieldwork for an extended period with meaningful outputs and impact. This initiative demonstrates that it is possible to use healthcare professionals, students and volunteers with low-intensity training and a low-cost approach to produce action research with considerable impact and results in rapid, reliable and robust manner

CD38: an ecto-enzyme with functional diversity in T cells

CD38, a nicotinamide adenine dinucleotide (NAD)+ glycohydrolase, is considered an activation marker of T lymphocytes in humans that is highly expressed during certain chronic viral infections. T cells constitute a heterogeneous population; however, the expression and function of CD38 has been poorly defined in distinct T cell compartments. We investigated the expression and function of CD38 in naïve and effector T cell subsets in the peripheral blood mononuclear cells (PBMCs) from healthy donors and people with HIV (PWH) using flow cytometry. Further, we examined the impact of CD38 expression on intracellular NAD+ levels, mitochondrial function, and intracellular cytokine production in response to virus-specific peptide stimulation (HIV Group specific antigen; Gag). Naïve T cells from healthy donors showed remarkably higher levels of CD38 expression than those of effector cells with concomitant reduced intracellular NAD+ levels, decreased mitochondrial membrane potential and lower metabolic activity. Blockade of CD38 by a small molecule inhibitor, 78c, increased metabolic function, mitochondrial mass and mitochondrial membrane potential in the naïve T lymphocytes. PWH exhibited similar frequencies of CD38+ cells in the T cell subsets. However, CD38 expression increased on Gag-specific IFN-γ and TNF-α producing cell compartments among effector T cells. 78c treatment resulted in reduced cytokine production, indicating its distinct expression and functional profile in different T cell subsets. In summary, in naïve cells high CD38 expression reflects lower metabolic activity, while in effector cells it preferentially contributes to immunopathogenesis by increasing inflammatory cytokine production. Thus, CD38 may be considered as a therapeutic target in chronic viral infections to reduce ongoing immune activation

Comprehensive preclinical evaluation of human-derived anti-poly-GA antibodies in cellular and animal models of C9ORF72 disease

Hexanucleotide G4C2 repeat expansions in the C9ORF72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Dipeptide repeat proteins (DPRs) generated by translation of repeat-containing RNAs show toxic effects in vivo as well as in vitro and are key targets for therapeutic intervention. We generated human antibodies that bind DPRs with high affinity and specificity. Anti-GA antibodies engaged extra- and intracellular poly-GA and reduced aggregate formation in a poly-GA over-expressing human cell line. However, antibody treatment in human neuronal cultures synthesizing exogenous poly-GA resulted in the formation of large extracellular immune complexes and did not affect accumulation of intracellular poly-GA aggregates. Treatment with antibodies was also shown to directly alter the morphological and biochemical properties of poly-GA and to shift poly-GA/antibody complexes to more rapidly sedimenting ones. These alterations were not observed with poly-GP and have important implications for accurate measurement of poly-GA levels including the need to evaluate all centrifugation fractions and disrupt the interaction between treatment antibodies and poly-GA by denaturation. Targeting poly-GA and poly-GP in two mouse models expressing G4C2 repeats by systemic antibody delivery for up to 16 months was well-tolerated and led to measurable brain penetration of antibodies. Long term treatment with anti-GA antibodies produced improvement in an open field movement test in aged C9ORF72450 mice. However, chronic administration of anti-GA antibodies in AAV-(G4C2)149 mice was associated with increased levels of poly-GA detected by immunoassay and did not significantly reduce poly-GA aggregates or alleviate disease progression in this model. Significance Immunotherapy has been proposed for neurodegenerative disorders including Alzheimer’s or Parkinson’s diseases. Recent reports using antibodies against poly-GA or active immunization suggested similar immunotherapy in ALS/FTD caused by repeat expansion in the C9ORF72 gene (1, 2). Here, we systematically characterized human antibodies against multiple DPR species and tested the biological effects of antibodies targeting poly-GA in different cellular and mouse models. Target engagement was shown in three independent cellular models. Anti-GA antibodies reduced the number of intracellular poly-GA aggregates in human T98G cells but not in cultured human neurons. Whereas chronic anti-GA treatment in BAC C9ORF72450 mice did not impact poly-GA levels and modestly improved one behavioral phenotype, poly-GA levels detected by immunoassays were increased and disease progression was unaltered in AAV-(G4C2)149 mice

Women′s health: Beyond reproductive years

With changing demographic profile India has more older women than men as life expectancy for women is 67.57 as against 65.46 for men. Gender differences in the aging process reflect biological, economic, and social differences. Both social and health needs of the older women are unique and distinctive as they are vulnerable. The social problems revolve around widowhood, dependency, illiteracy and lack of awareness about the policies and programmes from which they can benefit. Among the medical problems, vision (cataract) and degenerative joint disease top the list, followed by neurological problems. Lifestyle diseases form another single-most important group of health problems in the elderly women. The risk of cardiovascular disease doubles with the outcome being poorer than men. The most common causes of death among women above the age of 60 years are stroke, ischemic heart disease and COPD. Hypertensive heart disease and lower respiratory tract infections contribute to mortality in these women. Common malignancies viz. Cervical, breast and uterus in women are specific to them and account for a sizeable morbidity and mortality. In a study done at Lady Hardinge medical college in Delhi, Hypertension (39.6%) and obesity (12-46.8%) were very common in postmenopausal women. Half or more women had high salt and fat intake, low fruit and vegetable intake and stress. There is a need to recognize the special health needs of the women beyond the reproductive age, to be met through strengthening and reorienting the public health services at all levels starting from primary health care to secondary till tertiary care level with adequate referral linkages. All policies and programs need to have a gender perspective. At present there is lack of sensitization and appropriate training of the health personnel in dealing with the needs of elderly. Women too need to be aware to adopt healthy lifestyle and seek timely care