Sickle cell disease in Indian tribal population: Findings of a multi-centre Indian SCD registry.

BACKGROUND: Sickle cell disease (SCD) registries provide crucial real-world data on demographics, epidemiology, healthcare, patient outcomes, and treatment efficacy. This paper presents findings from the Indian SCD Registry (ISCDR) on clinical manifestations, crisis episodes, disease management, and healthcare utilization in patients with SCD from 12 primary health centres (PHCs) in six tribal districts of India. METHODS: The ISCDR was introduced along with a three-tier screening process. Its Android-based application incorporates two electronic case report forms for patient data collection over one year. This paper presents a year's data from the ISCDR's 324 patients with SCD. RESULTS: Patients with SCD, aged one to 65 years, exhibited varied clinical manifestations. Most patients (85.2 %) were unaware of their SCD status before enrolling in ISCDR. Moderate to severe anaemia was prevalent (66.05 % and 30.56 %, respectively). Pain was a common complaint (80.86 %; CI: 76.17-85.00), while symptoms of stroke included sudden severe headaches (34.57 %; CI: 29.40-40.02). Common splenic sequestration symptoms included stomach pain (42.90 %; CI: 37.44-48.49) and abdominal tenderness (13.27 %; CI: 9.77-17.46), as a sign. Healthcare utilization was high, with 96.30 % receiving treatment and 83.64 % consuming hydroxyurea. Hospitalization occurred for 38.27 % (CI: 32.95-43.81), and 12.04 % (CI: 8.70-16.09) had blood transfusion during last year. CONCLUSIONS: ISCDR serves as a dynamic digital database on SCD epidemiology, clinical aspects, treatment and healthcare utilization. Notably, many patients lacked prior awareness of their SCD status, underscoring the need for improved awareness and care management. Integrating the registry into the national programme can streamline treatment implementation, prioritize management approaches, and optimize individual benefits.

To leave no one behind: Assessing utilization of maternal newborn and child health services by all the 13 particularly vulnerable tribal groups (PVTGs) of Odisha, India.

BACKGROUND: Indigenous tribal people experience lower coverage of maternal, newborn and child healthcare (MNCH) services worldwide, including in India. Meanwhile, Indian tribal people comprise a special sub-population who are even more isolated, marginalized and underserved, designated as particularly vulnerable tribal groups (PVTGs). However, there is an extreme paucity of evidence on how this most vulnerable sub-population utilizes health services. Therefore, we aimed to estimate MNCH service utilization by all the 13 PVTGs of the eastern Indian state of Odisha and compare that with state and national rates. METHODS: A total of 1186 eligible mothers who gave birth to a live child in last 5 years, were interviewed using a validated questionnaire. The weighted MNCH service utilization rates were estimated for antenatal care (ANC), intranatal care (INC), postnatal care (PNC) and immunization (for 12-23-month-old children). The same rates were estimated for state (n = 7144) and nationally representative samples (n = 176 843) from National Family Health Survey-5. RESULTS: The ANC service utilization among PVTGs were considerably higher than national average except for early pregnancy registration (PVTGs 67% versus national 79.9%), and 5 ANC components (80.8% versus 82.3%). However, their institutional delivery rates (77.9%) were lower than averages for Odisha (93.1%) and India (90.1%). The PNC and immunization rates were substantially higher than the national averages. Furthermore, the main reasons behind greater home delivery in the PVTGs were accessibility issues (29.9%) and cultural barriers (23.1%). CONCLUSION: Ours was the first study of MNCH service utilization by PVTGs of an Indian state. It is very pleasantly surprising to note that the most vulnerable subpopulation of India, the PVTGs, have achieved comparable or often greater utilization rates than the national average, which may be attributable to overall significantly better performance by the Odisha state. However, PVTGs have underperformed in terms of timely pregnancy registration and institutional delivery, which should be urgently addressed.

Development, validation & pilot testing of a questionnaire to assess healthcare seeking behaviour, healthcare service utilization & out-of-pocket expenditure of Particularly Vulnerable Tribal Groups of Odisha, India.

Background & objectives: Assessing healthcare seeking behaviour (HSB), healthcare utilization and related out-of-pocket expenditures of Particularly Vulnerable Tribal Groups (PVTGs) of India through a prism of the health system may help to achieve equitable health outcomes. Therefore, this comprehensive study was envisaged to examine these issues among PVTGs of Odisha, India. However, there exists no validated questionnaire to measure these variables among PVTGs. Therefore, a study questionnaire was developed for this purpose and validated. Methods: Questionnaire was constructed in four phases: questionnaire development, validity assessment, pilot testing and reliability assessment. Nine domain experts face validated questionnaire in two rounds, followed by a single round of quantitative content validity. Next, the questionnaire was pretested in three rounds using cognitive interviews and pilot-tested among 335 and 100 eligible individuals for the two sections healthcare seeking behaviour (HSB-Q) and maternal and child healthcare service utilization (MCHSU-Q). Internal consistency reliability was assessed for de novo HSB-Q. Results: On two rounds of expert-driven face validity, 55 items were eliminated from 200 items. Questionnaire showed moderate to high content validity (item-level content validity index range: 0.78 to 1, scale-level content validity index/universal agreement: 0.73; scale-level content validity index/average: 0.96 and multirater kappa statistics range: 0.6 to 1). During the pre-test, items were altered until saturation was achieved. Pilot testing helped to refine interview modalities. The Cronbach alpha and McDonald's omega assessing internal consistency of HSB-Q were 0.8 and 0.85, respectively. Interpretation & conclusions: The questionnaire was found to be valid and reliable to explore healthcare seeking behaviour, maternal and child healthcare utilization and related out-of-pocket expenditure incurred by PVTGs of Odisha, India.

To what extent classic socio-economic determinants explain trends of anaemia in tribal and non-tribal women of reproductive age in India? Findings from four National Family Heath Surveys (1998-2021).

BACKGROUND: Despite unprecedented socio-economic growth experienced by Indians in the past few decades, and a long history of anti-anaemia public health measures, prevalence of anaemia in Indian non-pregnant women of reproductive age group (NPWRA) has not declined. This warrants a firm understanding of what explains the anaemia situation over time, preferably by sub-populations. Therefore, we aimed to examine the trends of anaemia in tribal NPWRA (least privileged) and compare with the trends in the NPWRA of general caste (most privileged) between 1998 to 2021. Additionally, the study also explored explanation of any decline and tribal/general narrowing of these trends. METHODS: We studied four rounds of National Family Health Survey (1998-99, 2005-06, 2015-16, 2019-21). We examined the trend of anaemia (haemoglobin < 12 g/dl) and its possible determinants in tribal and general NPWRA and estimated the portion of "decline" and "narrowing" that could be explained by the underlying and intermediate determinants (wealth, education, residence, parity and food security) using multiple logistic regression. RESULTS: The distribution of determinants improved over 23 years in both the groups but more in tribals. But anaemia either remained unchanged or increased in both except 7.1 points decline in tribals between 2006-2016, leading also to 7 points narrowing of tribal/general gap. The modest attenuation of beta coefficients representing the change of anaemia prevalence (log of odds) in tribals from -0.314(-0.377, -0.251) to -0.242(-0.308, -0.176) after adjustment with determinants could explain only 23% of the decline. Similarly, only 7% of the narrowing of the tribal/general anaemia gap could be explained. CONCLUSIONS: The structural determinants wealth, education, food security, parity and urban amenities improved immensely in India but anaemia did not decline in this 23-year period. This implies that the "usual suspects" - the structural determinants are not the main drivers of anaemia in the country. The main driver may be absolute and/or functional deficiency status of micronutrients including iron attributable to inadequate uptake and absorption of these elements from Indian diets; and therefore, their effects are noticeable in every socio-economic stratum of India. Future research for aetiologies and new interventions for anaemia alleviation in India may focus on these factors.

Indian sickle cell disease registry for surveillance and patient management: Development and implementation.

In India, sickle cell disease (SCD) predominantly occurs in indigenous (tribal) people, who are about 104 million. However, screening and diagnosis seldom happen. This situation necessitates developing a comprehensive SCD care model, including a registry. This paper describes the development and implementation of the Indian SCD registry (ISCDR) in six tribal-dominated districts of India. The ISCDR was created in two components-(i) an Android-based mobile/tablet application, (ii) a dashboard/admin panel for patients' data management and retrieval. Data capture involves two electronic case report forms (CRF), that is, the primary form (CRF-1) and the repeat visit form (CRF-2). CRF-1 is completed as soon as the patient is found positive and captures the patient's information, including medical history, diagnosis, symptoms, precipitating factors, hospitalisation history and treatment received. Issues related to quality, security and data-sharing were addressed. After the screening system was functional, ISCDR was initiated. In 12 months, data of 324 SCD patients and 1771 carriers were entered. The study demonstrates the feasibility of establishing an SCD registry in India. It collects systematic longitudinal data on SCD patients, which are essential for programme planning and management. Further, it is feasible to scale up and integrate with other health management databases.

Strengthening Health System and Community Mobilization for Sickle Cell Disease Screening and Management among Tribal Populations in India: An Interventional Study.

Sickle cell disease (SCD) affects 5% of the global population, with over 300,000 infants born yearly. In India, 73% of those with the sickle hemoglobin gene belong to indigenous tribes in remote regions lacking proper healthcare. Despite the prevalence of SCD, India lacked state-led public health programs until recently, leaving a gap in screening and comprehensive care. Hence, the Indian Council of Medical Research conducted implementation research to address this gap. This paper discusses the development and impact of the program, including screening and treatment coverage for SCD in tribal areas. With a quasi-experimental design, this study was conducted in six tribal-dominated districts in three phases - formative, intervention, and evaluation. The intervention included advocacy, partnership building, building the health system's capacity and community mobilization, and enabling the health systems to screen and manage SCD patients. The capacity building included improving healthcare workers' skills through training and infrastructure development of primary healthcare (PHC) facilities. The impact of the intervention is visible in terms of people's participation (54%, 76% and 93% of the participants participated in some intervention activities, underwent symptomatic screening and demanded the continuity of the program, respectively), and improvement in SCD-related knowledge of the community and health workers (with more than 50% of net change in many of the knowledge-related outcomes). By developing screening and treatment models, this intervention model demonstrated the feasibility of SCD care at the PHC level in remote rural areas. This accessible approach allows the tribal population in India to routinely seek SCD care at their local PHCs, offering great convenience. Nevertheless, additional research employing rigorous methodology is required to fine-tune the model. National SCD program may adopt this model, specifically for community-level screening and management of SCD in remote and rural areas.

Molecular surveillance of anti-malarial drug resistance genes in Plasmodium falciparum isolates in Odisha, India.

BACKGROUND: Despite significant progress in eliminating malaria from the state of Odisha, India, the disease is still considered endemic. Artesunate plus sulfadoxine-pyrimethamine (AS + SP) has been introduced since 2010 as first-line treatment for uncomplicated Plasmodium falciparum malaria. This study aimed to investigate the prevalence of mutations associated with resistance to chloroquine (CQ), sulfadoxine-pyrimethamine (SP), and artesunate (ART) in P. falciparum parasites circulating in the state. METHODS: A total of 239 isolates of P. falciparum mono infection were collected during July 2018-November 2020 from the four different geographical regions of the state. Genomic DNA was extracted from 200 µL of venous blood and amplified using nested polymerase chain reaction. Mutations on gene associated with CQ (Pfcrt and Pfmdr1) were assessed by PCR amplification and restriction fragment length polymorphism, artemisinin (Pfk13) gene by DNA sequencing and SP (Pfdhfr and Pfdhps) genes by allele-specific polymerase chain reaction (AsPCR). RESULTS: The point mutation in Pfcrt (K76T) was detected 2.1%, in Pfmdr1 (N86Y) 3.4%, and no mutations were found in Pfkelch13 propeller domain. Prevalence of Pfdhfr, Pfdhps and Pfhdfr-Pfdhps (two locus) gene mutations were 50.43%, 47.05% and 49.79% respectively. The single, double, triple and quadruple point mutations in Pfdhfr gene was 11.2%, 8.2%, 17.2% and 3.4% while, in Pfdhps gene was 10.9%,19.5%, 9.5% and 2.7% respectively. Of the total 13 haplotypes found in Pfdhfr, 8 were detected for the first time in the state and of the total 26 haplotypes found in Pfdhps, 7 were detected for the fisrt time in the state. The linked quintuple mutation Pfdhfr (N51I-C59R-S108N)-Pfdhps (A437G-K540E) responsible for clinical failure (RIII level of resistance) of SP resistance and A16V-S108T mutation in Pfdhfr responsible for cycloguanil was absent. CONCLUSION: The study has demonstrated a low prevalence of CQ resistance alleles in the study area. Despite the absence of the Pfkelch13 mutations, high prevalence of Pfdhfr and Pfdhps point mutations undermine the efficacy of SP partner drug, thereby threatening the P. falciparum malaria treatment policy. Therefore, continuous molecular and in vivo monitoring of ACT efficacy is warranted in Odisha.

A community based study on haemoglobinopathies and G6PD deficiency among particularly vulnerable tribal groups in hard-to-reach malaria endemic areas of Odisha, India: implications on malaria control.

BACKGROUND: Haemoglobinopathies and G6PD deficiency are inherited disorders found mostly in malaria-endemic areas among different tribal groups of India. However, epidemiological data specific to Particularly Vulnerable Tribal Groups (PVTGs), important for planning and implementing malaria programmes, is limited. Therefore, the present community-based study aimed to assess the prevalence of haemoglobinopathies and G6PD deficiency among the 13 PVTGs found in the state of Odisha, reporting the maximum malaria cases in the country. METHODS: This cross-sectional study was conducted from July 2018 to February 2019 in 12 districts, home to all 13 PVTGs, in an estimated sample size of 1461, selected two-stage sampling method. Detection of haemoglobinopathies was done by the variant analyser. Screening of G6PD deficiency was carried out using DPIP method followed by quantification using spectrophotometry. The PCR-RFLP technology was used to determine variant of G6PD deficiency and haplotype analysis of sickle cell, while ARMS-PCR and GAP-PCR was used for detecting the mutation pattern in ß-thalassaemia and α-thalassaemia respectively. The diagnosis of malaria was done by Pf-PAN RDT as point of care, followed by nPCR for confirmation and Plasmodium species identification. RESULTS: The prevalence of sickle cell heterozygotes (AS) was 3.4%, sickle cell homozygous (SS) 0.1%, ß-thalassaemia heterozygotes 0.3%, HbS/ß-thalassaemia compound heterozygote 0.07%, HbS-α-thalassaemia 2.1%, G6PD deficiency 3.2% and malaria 8.1%. Molecular characterization of ßS revealed the presence of Arab-Indian haplotype in all HbS cases and IVS 1-5 G → C mutation in all ß-thalassaemia cases. In case of α-thal, αα/α-3.7 gene deletion was most frequent (38%), followed by αα/α-4.2 (18%) and α-3.7/α-3.7 (4%). The frequency of G6PD Orissa (131C → G) mutation was found to be 97.9% and G6PD Mediterranean (563C → T) 2.1%. Around 57.4% of G6PD deficient individuals and 16% of the AS were found to be malaria positive. CONCLUSION: The present study reveals wide spread prevalence of sickle cell anaemia, α-thalassaemia, G6PD deficiency and malaria in the studied population. Moderate to high prevalence of G6PD deficiency and malaria warrants G6PD testing before treating with primaquine (PQ) for radical cure of Plasmodium vivax. Screening and counselling for HbS is required for the PVTGs of Odisha.

Neglected malaria parasites in hard-to-reach areas of Odisha, India: implications in elimination programme.

BACKGROUND: Information on the foci of Plasmodium species infections is essential for any country heading towards elimination. Odisha, one of the malaria-endemic states of India is targeting elimination of malaria by 2030. To support decision-making regarding targeted intervention, the distribution of Plasmodium species infections was investigated in hard-to-reach areas where a special malaria elimination drive, namely Durgama Anchalare Malaria Nirakaran (DAMaN) began in 2017. METHODS: A cross-sectional survey was conducted in 2228 households during July to November 2019 in six districts, to evaluate the occurrence of Plasmodium species. The species were identified by polymerase chain reaction (PCR) followed by sequencing, in case of Plasmodium ovale. RESULTS: Of the 3557 blood specimens tested, malaria infection was detected in 282 (7.8%) specimens by PCR. Of the total positive samples, 14.1% were P. ovale spp. and 10.3% were Plasmodium malariae infections. The majority of P. ovale spp. (75.8%) infections were mixed with either Plasmodium falciparum and/or Plasmodium vivax and found to be distributed in three geophysical regions (Northern-plateau, Central Tableland and Eastern Ghat) of the State, while P. malariae has been found in Northern-plateau and Eastern Ghat regions. Speciation revealed occurrence of both Plasmodium ovale curtisi (classic type) and Plasmodium ovale wallikeri (variant type). CONCLUSIONS: In the present study a considerable number of P. ovale spp. and P. malariae were detected in a wide geographical areas of Odisha State, which contributes around 40% of the country's total malaria burden. For successful elimination of malaria within the framework of national programme, P. ovale spp. along with P. malariae needs to be incorporated in surveillance system, especially when P. falciparum and P. vivax spp. are in rapid decline.

Decades of cholera in Odisha, India (1993-2015): lessons learned and the ways forward.

Cholera is one of the major public health problems in the state of Odisha, India since centuries. The current paper is a comprehensive report on epidemiology of cholera in Odisha, which was documented from 1993. PubMed and Web of Knowledge were searched for publications reporting cholera in Odisha during the period 1993-2015. The search was performed using the keywords 'Odisha' and/or 'Orissa' and 'Cholera'. In addition, manual search was undertaken to find out relevant papers. During the study period, a total of 37 cholera outbreaks were reported with an average of >1.5 cholera outbreaks per year and case fatality ratio was 0.3%. Vibrio cholerae O1 Ogawa serotype was the major causative agent in most of the cholera cases. The recent studies demonstrated the prevalence of V. cholerae O1, El Tor variants carrying ctxB1, ctxB7 and Haitian variant tcpA allele associated with polymyxin B sensitivity and these variants are replacing the proto type El Tor. The first report of variant ctxB7 in Odisha during super-cyclone 1999 predicted its emergence and subsequent spread causing cholera outbreaks. The prevalence of multidrug-resistant V. cholerae at different time periods created alarming situation. The efficacy trial of oral cholera vaccine (OCV, Shanchol) in a public health set-up in Odisha has shown encouraging results which should be deployed for community level vaccination among the vulnerable population. This paper has taken an effort to disseminate the valuable information of epidemiology of cholera that will influence the policy-makers and epidemiologists for constant surveillance in other parts of Odisha, India and around the globe.

Identification of population of bacteria from culture negative surgical site infection patients using molecular tool.

BACKGROUND: Managing surgical site infections, with negative culture report in routine diagnosis is a common dilemma in microbiology accounting more than 30% worldwide. The present study attempted to identify the presence of bacterial spp. if any in wound aspirates/swabs of culture negative surgical site infections of hospitalised patients using molecular tools. METHODS: Ninety-seven patients with post-operative SSI whose wound swabs/aspirate were negative in the conventional aerobic culture after 72 h of incubation were analysed by 16S rRNA gene specific broad range PCR. The amplified DNA fragments were sequenced by Sanger DNA sequencing method and homology of the sequence were matched using NCBI BLAST (NCBI, USA) RESULTS: Of the 97 patients, 16S rRNA based broad range PCR assay could identify the presence of bacterial pathogen in 53(54.63%) cases, of which 29 isolates were supposed to be of viable but non-culturable bacteria (VBNC), 07 were of obligatory anaerobes and 13 were of unculturable bacteria, 04 were with poly bacterial infections. CONCLUSIONS: Our study highlights the usefulness of PCR assay in detecting the presence of any VBNC, anaerobes and unculturable bacteria in SSI patients regardless of how well the bacteria may or may not grow in culture. Measures should be taken to use anaerobic culture system and PCR diagnosis along with conventional culture to detect the VBNC and unculturable bacteria where Gram stain is positive for better patient care.

Scrub typhus associated acute kidney injury: An emerging health problem in Odisha, India.

BACKGROUND & OBJECTIVES: Acute kidney injury associated with scrub typhus is an emerging health problem in the tropics including India. This study intended to find out the incidence, clinical outcome, cytokine response and genotypes of Orientia tsutsugamushi associated with AKI patients in Odisha, a state in eastern India. METHODS: Acute febrile illness or history of acute fever with various degrees of kidney involvement admitted to SCB Medical College Hospital, Cuttack were included in the study. A detailed demographic characteristics and clinical features were recorded with pre-tested questionnaire at the time of admission. Scrub Typhus was detected by 'IgM ELISA' test (OD > 0.5) and PCR. Routine urine, haematological and biochemical tests were performed. Genotyping of the Orientia tsutsugamushi was done using 56-kDa gene for Orientia species and phylogenetic tree by neighbor-joining method. The plasma level of the IFN-γ (pro-inflammatory cytokine) and IL10 (anti-inflammatory) were measured by commercially available ELISA kit. The statistical analysis was performed using Graph Pad Prism software (version 4). RESULTS: Out of 140 acute febrile illness or history of acute febrile illness patients with AKI admitted to hospital, 32.14% were confirmed to be scrub typhus positive; eschar was seen in 17.8% of them. Of the total scrub typhus positive cases, 24.4% were having multi organ dysfunction. Majority of the AKI patients (60%) were in the "failure" category under RIFLE criteria. The mortality rate was 20.0%. Risk of dialysis requirement and mortality increases with RIFLE classification. "Karp" was the predominant circulating genotype. IFN-γ and IL10 level was high among the scrub typhus associated AKI patients. INTERPRETATION & CONCLUSION: The study shows a high incidence of scrub typhus associated AKI and high case fatality rate. Hence, emphasis should be given on differential diagnosis. RIFLE classification is applicable with increment risk of dialysis requirement and death. An in-depth study is required to determine the role of O. tsutsugamuchi KARP strain and INF-γ/ IL-10 in disease severity so as to identify a prognostic marker.

High proportions of pfhrp2 gene deletion and performance of HRP2-based rapid diagnostic test in Plasmodium falciparum field isolates of Odisha.

BACKGROUND: With the documentation of cases of falciparum malaria negative by rapid diagnostic tests (RDT), though at low frequency from natural isolates in a small pocket of Odisha, it became absolutely necessary to investigate the status of HRP-2 based RDT throughout the state and in different seasons of the year. METHODS: Suspected individuals were screened for malaria infection by microscopy and RDT in 25/30 districts of Odisha, India. Discrepancies in results were confirmed by PCR. False negative RDT samples for Plasmodium falciparum mono-infection were evaluated for detection of HRP2 antigen in ELISA and genotyped for pfhrp2, pfhrp3 and their flanking genes. Multiplicity of infection was ascertained based on msp1 and msp2 genotyping and parasitaemia level was determined by microscopy. RESULTS: Of the total 1058 patients suspected for malaria, 384 were microscopically confirmed for P. falciparum mono-infection and RDT failure was observed in 58 samples at varying proportion in different regions of the state. The failure in detection was due to undetectable level of HRP-2. Although most of these samples were screened during rainy season (45/345), significantly high proportion (9/17) of RDT negative samples were obtained during the summer compared to rainy season (P = 0.0002; OR = 7.5). PCR genotyping of pfhrp2 and pfhrp3 in RDT negative samples showed 38/58 (65.5) samples to be pfhrp2 negative and 24/58 (41.4) to be pfhrp3 negative including dual negative in 17/58 (29.3). Most of the RDT negative samples (39/58) were with single genotype infection and high proportions of pfhrp2 deletion (7/9) was observed in summer. No difference in parasitaemia level was observed between RDT positive and RDT negative patients. CONCLUSION: High prevalence of parasites with pfhrp2 deletion including dual deletions (pfhrp2 and pfhrp3) is a serious cause of concern, as these patients could not be given a correct diagnosis and treatment. Therefore, HRP2-based RDT for diagnosing P. falciparum infection in Odisha is non-reliable and must be performed in addition to or replaced by other appropriate diagnostic tools for clinical management of the disease.

Association of angiotensin-converting enzyme and angiotensin-converting enzyme-2 gene polymorphisms with essential hypertension in the population of Odisha, India.

BACKGROUND: Hypertension is a serious health issue worldwide and essential hypertension, which includes 90-95% of the cases, is influenced by both genetic and environmental factors. Identification of these factors may help in control of this disease. The Insertion/Deletion (I/D) polymorphism in Angiotensin-Converting Enzyme (ACE) gene and rs2106809 (C > T) polymorphism in Angiotensin-Converting Enzyme 2 (ACE2) gene have been reported to be associated with essential hypertension in different populations. AIM: To investigate the association of ACE I/D and ACE2 rs2106809 polymorphisms with essential hypertension in the population of Odisha, an eastern Indian state. SUBJECTS AND METHODS: A total of 246 hypertensives (159 males and 87 females) and 274 normotensives (158 males and 116 females) were enrolled in the study. Detailed anthropometric data, tobacco, alcohol and food habits were recorded and 2 ml of venous blood was collected for biochemical and genetic analysis. RESULTS: The DD genotype of ACE and TT genotype of ACE2 were significantly high among female hypertensives, while T allele of ACE2 was linked to male hypertensives. In the male population, alcohol was also identified as a potential risk factor. CONCLUSION: Among females, ACE I/D and ACE2 rs2106809 polymorphisms, while among males, ACE2 rs2106809 polymorphism and alcohol consumption are associated with essential hypertension in the study population.

Expression Pattern of Estrogen Receptor Alpha and Progesterone Receptor in Gallbladder Carcinoma and Their Association with Clinicopathological Parameters and Overall Survival.

BACKGROUND: Gallbladder cancer (GBC) is a highly aggressive malignant tumor with a poor prognosis. Despite being first described two centuries ago, there are no targeted therapies available beyond conventional cytotoxic therapy. Epidemiological studies have shown that the incidence of gallbladder cancer is higher in females than males. This suggests that the gallbladder may be a female sex hormone-responsive organ, and these hormones might be involved in the pathogenesis of gallbladder cancer. Therefore, we aimed to analyze the expression of ERα and PR in GBC and correlate their expression with clinicopathological variables and overall survival. PATIENTS AND METHODS: A total of 235 histopathologically diagnosed GBC cases were included in this hospital-based cross-sectional study. Clinicopathological data were collected, and the expression of ERα and PR was evaluated by immunohistochemistry. RESULTS: The mean age of this study population was 55.47 ± 8.45 with range 28-87 years. Females were predominated over male with a male-to-female ratio of 1:3.5. Positive nuclear expression of the ERα and PR was found in 13 (5.5%) and eight (3.4%) cases, respectively. Apart from nuclear staining, cytoplasmic expression of ERα and PR was found in three (1.2%) and 31 (13.2%) cases, respectively. Higher percentage of positive nuclear expression of ER was found in < 50 years age (p value = 0.04), parity > 4 (p value = 0.02), advanced pT stage (T3) (p value = 0.01), lymphovascular invasion (p value = 0.02), and liver invasion (p value = 0.04) which were statistically significant. Higher percentage of PR expression was also observed in < 50 years age (p value = 0.01), and tumor associated with gallstone (p value = 0.04). There was no significant correlation between cytoplasmic expression of ER, PR, and clinicopathological variables. In multivariate analysis, there was no significant correlation between ER or PR positive expression and overall survival. CONCLUSION: Although nuclear expression of ERα was significantly associated with progressive disease factors but the positive expression was found in very small percentage of GBC cases. So anti-hormone therapy might be an option in patient with ER α positive gallbladder carcinoma.

Development and implementation of a strategy for early diagnosis and management of scrub typhus: an emerging public health threat.

Scrub typhus, caused by Orientia tsutsugamushi, is a re-emerging zoonotic disease in the tropics with considerable morbidity and mortality rates. This disease, which is mostly prevalent in rural areas, remains underdiagnosed and underreported because of the low index of suspicion and non-specific clinical presentation. Limited access to healthcare, diagnostics, and treatment in rural settings further makes it challenging to distinguish it from other febrile illnesses. While easily treatable, improper treatment leads to severe forms of the disease and even death. As there is no existing public health program to address scrub typhus in India, there is an urgent need to design a program and test its effectiveness for control and management of the disease. With this backdrop, this implementation research protocol has been developed for a trial in few of the endemic "pockets" of Odisha, an eastern Indian state that can be scalable to other endemic areas of the country, if found effective. The main goal of the proposed project is to include scrub typhus as a differential diagnosis of fever cases in every tier of the public health system, starting from the community level to the health system, for the early diagnosis among suspected cases and to ensure that individuals receive complete treatment. The current study aimed to describe the protocol of the proposed Scrub Typhus Control Program (STCP) in detail so that it can receive valuable views from peers which can further strengthen the attempt.

Malnutrition and Anemia Among Particularly Vulnerable Tribal Groups of Odisha, India: Needs for Context-Specific Intervention.

Background: As undernutrition and anemia persist to be prevalent in India, the socioeconomically disadvantaged groups continue to take the greater brunt. Odisha is home to the largest number of particularly vulnerable tribal groups (PVTGs) in India. The study aimed to provide a comprehensive report on the undernutrition and anemia status of all the PVTGs of Odisha. Methods: A community-based cross-sectional study was conducted among (N = 1461, 683 males and 779 females) 13 PVTGs spread across 12 districts of Odisha from August 2018 to February 2019. Results: Among the under-five children, the prevalence of underweight was observed in 75.26%, stunting in 55.42%, and wasting in 60.00% and all forms of undernutrition were higher among girls. Among children and adolescents belonging to the age group of 5 to 19 years, the prevalence of thinness was 46.7%. In individuals above the age of 20, the prevalence of underweight among males was 37.7% and females was 44.3% and severe anemia was present in 36.5% of females and 35.8% of males. Women in the reproductive age have a higher prevalence of anemia. Conclusion: The study shows that undernutrition and anemia remain high in the PVTGs, especially among the under-five children and women in the reproductive age. As the country heads toward fulfilling Sustainable Development Goals (SDG) by 2030, national and state health policies need to be designed and implemented, giving special focus to these vulnerable groups.

Promoter polymorphisms in the ATP binding cassette transporter gene influence production of cell-derived microparticles and are highly associated with susceptibility to severe malaria in humans.

Microparticle (MP) efflux is known to be mediated by the ABCA1 protein, and the plasma level of these cell-derived MPs is elevated considerably during human malarial infection. Therefore, two polymorphisms at positions -477 and -320 in the promoter of the ABCA1 gene were genotyped and tested for association with the plasma MP level in four groups of malaria patients segregated according to the clinical severity, i.e., cerebral malaria (CM), multiorgan dysfunction (MOD), noncerebral severe malaria, and uncomplicated malaria (UM). The TruCount tube-based flow cytometric method was used for the exact quantification of different cell-derived MPs in patients. Polymorphisms in the ABCA1 gene promoter were analyzed by use of the PCR/two-primer-pair method, followed by restriction fragment length polymorphism, in 428 malaria patients. The level of circulating plasma MPs was significantly higher in febrile patients with Plasmodium falciparum infection, especially in CM patients compared to healthy individuals. The homozygous wild-type -477 and -320 genotype was observed to be significantly higher in patients with severe malaria. These patients also showed marked increases in the plasma MP numbers compared to UM patients. We report here for the first time an association of ABCA1 promoter polymorphisms with susceptibility to severe malaria, especially to CM and MOD, indicating the protective effect of the mutant variant of the polymorphism. We hypothesize that the -477T and -320G polymorphisms affect the downregulation of MP efflux and may be a predictor of organ complication during P. falciparum malarial infections.

An unusual case series of synchronous primary malignancies: Carcinoma gallbladder with renal cell carcinoma, carcinoma gallbladder with carcinoma colon, carcinoma gallbladder with carcinoma breast.

ABSTRACT: Synchronous primary cancers are very rare. Due to their low incidence rate and insidious onset, they may be easily overlooked or misdiagnosed. In addition, there is currently no international consensus for their clinical diagnosis and treatment. Three exceedingly unusual synchronous primary malignancies, carcinoma gallbladder with renal cell carcinoma, carcinoma gallbladder with carcinoma colon, and carcinoma gallbladder with carcinoma breast, are presented here. Together with their clinical presentation, therapeutic options and outcomes are also presented. Curative radical surgery of each particular tumor, along with postoperative chemotherapy or radiotherapy improves disease-free survival.

Impact of Sub-patent Malaria During Pregnancy on Birth-Weight in Odisha, India: Time-to-Event Analysis of Prospective Longitudinal Follow-Up of a Survey.

OBJECTIVE: The current study aimed to estimate prevalence of malaria infection, especially sub-patent infection, in pregnant women residing in high malaria-endemic, hard-to-reach pockets of the Indian state of Odisha; and also measure its impact on birth-weight of their new-borns. METHOD: A time-to-event analysis of prospective longitudinal follow-up study nested within a cross-sectional survey of people residing in high malaria-endemic six districts of Odisha was conducted during July-November 2019. Malaria status in pregnant mothers was categorized as malaria free; sub-patent, and patent. Hazards Ratio (HR) of low birth-weight (LBW; birth-weight < 2500 gms) was estimated in these three categories (n = 308) adjusted for residence (block), gravida, caste, age and gestational age at testing. RESULTS: 50.3% pregnant women had sub-patent malaria infection, 3.9% had patent infection. In fully adjusted model, hazards ratio of LBW was 3.76 (95% CI 1.12, 12.64, p = 0.032) in pregnant women with patent infection and 1.82 (95% CI 0.87, 3.81, p = 0.109) in women with sub-patent infection when compared to no malaria group. CONCLUSION: The study showed that half of the pregnant women in high-endemic pockets had sub-patent infection which posed deleterious influence on birth-weight of their new-borns. The study thereby flags the prevalence of sub-patent infection as a public health concern, because sub-patent infection in pregnant mothers may persist as a "silent" reservoir, with the potential to derail the malaria control program, especially when the country plans malaria elimination by 2030.