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Estimation of the spread and advancement of Plasmodium falciparum artemisinin-resistant parasites can be done by probing polymorphisms in the kelch (Pfk13) domain (a validated molecular marker). This study aimed to provide baseline information for future artemisinin surveillance by analyzing the k13-propeller domain in P. falciparum field isolates collected from 24 study areas in 14 malaria hot spots of Odisha (previously Orissa) during July 2018-January 2019. A total of 178 P. falciparum mono infections were assessed. An 849-base pair fragment encoding the Pfk13 propeller was amplified by nested polymerase chain reaction and sequenced in both directions (PCR). After DNA alignment with the 3D7 reference sequence, all samples were found to be wild type. It can be anticipated that malaria public health is not under direct threat in Odisha relating to ART resistance. [ABSTRACT FROM AUTHOR]

Estimation of the spread and advancement of Plasmodium falciparum artemisinin-resistant parasites can be done by probing polymorphisms in the kelch (Pfk13) domain (a validated molecular marker). This study aimed to provide baseline information for future artemisinin surveillance by analyzing the k13-propeller domain in P. falciparum field isolates collected from 24 study areas in 14 malaria hot spots of Odisha (previously Orissa) during July 2018-January 2019. A total of 178 P. falciparum mono infections were assessed. An 849-base pair fragment encoding the Pfk13 propeller was amplified by nested polymerase chain reaction and sequenced in both directions (PCR). After DNA alignment with the 3D7 reference sequence, all samples were found to be wild type. It can be anticipated that malaria public health is not under direct threat in Odisha relating to ART resistance. [ABSTRACT FROM AUTHOR]

Background: Current Global Program to Eliminate Lymphatic Filariasis (GPELF) that prohibits pregnant mothers and children below two years of age from coverage targeted interruption of transmission after 5–6 rounds of annual mass drug administration (MDA). However, after more than 10 rounds of MDA in India the target has not been achieved, which poses challenge to the researchers and policy makers. Several studies have shown that in utero exposure to maternal filarial infections plays certain role in determining the susceptibility and disease outcome in children. But the mechanism of which has not been studied extensively. Therefore the present study was undertaken to understand the mechanism of immune modulation in children born to filarial infected mother in a MDA ongoing area. Methodology and principal finding: To our knowledge this is the first study to conduct both cellular and humoral immunological assays and follow up the children until older age in a W bancrofti endemic area,where the microfilariae (Mf) rate has come down to <1% after 10 rounds of MDA. A total 57 (32: born to infected, 25: born to uninfected mother) children were followed up. The infection status of children was measured by presence of Mf and circulating filarial antigen (CFA) assay. Filaria specific IgG1, IgG2, IgG3 and IgG4 responses were measured by ELISA. Plasma level of IL-10 and IFN-γ were evaluated by using commercially available ELISA kit. The study reveals a high rate of acquisition of filarial infection among the children born to infected mother compared to uninfected mothers. A significantly high level of IgG1 and IgG4 was observed in children born to infected mother, whereas high level of IgG3 was marked in children born to uninfected mother. Significantly high level of IL-10 positively correlated with IgG4 have been observed in infected children born to infected mother, while high level of IFN-γ positively correlated with IgG3 was found in infection free children born to mother free from infection at the time of pregnancy. Moreover a negative correlation between IL-10and IFN-γ has been observed only among the infected children born to infected mother. Significance conclusion: The study shows a causal association between maternal filarial infection and impaired or altered immune response in children more susceptible to filarial infection during early childhood. As lymphatic damage that commences in childhood during asymptomatic stage has major implications from public health point of view, understanding maternal programming of the newborn immune system could provide a basis for interventions promoting child health by implementing MDA campaigns towards all women of childbearing age and young children in achieving the target of global elimination of LF. [ABSTRACT FROM AUTHOR]

Background: Children born from filarial infected mothers are comparatively more susceptible to filarial infection than the children born to uninfected mothers. But the mechanism of such increased susceptibility to infection in early childhood is not exactly known. Several studies have shown the association of active filarial infection with T cell hypo-responsiveness which is mediated by regulatory T cells (Tregs). Since the Tregs develop in the thymus from CD4+ CD25hi thymocytes at an early stage of the human fetus, it can be hypothesized that the maternal infection during pregnancy affects the development of Tregs in children at birth as well as early childhood. Hence the present study was designed to test the hypothesis by selecting a cohort of pregnant mothers and children born to them subsequently in a filarial endemic area of Odisha, India. Methodology and Principal finding: A total number of 49 pregnant mothers and children born to them subsequently have been followed up (mean duration 4.4 years) in an area where the microfilariae (Mf) rate has come down to <1% after institution of 10 rounds of annual mass drug administration (MDA). The infection status of mother, cord and children were assessed through detection of microfilariae (Mf) and circulating filarial antigen (CFA). Expression of Tregs cells were measured by flow cytometry. The levels of IL-10 were evaluated by using commercially available ELISA kit. A significantly high level of IL-10 and Tregs have been observed in children born to infected mother compared to children of uninfected mother at the time of birth as well as during early childhood. Moreover a positive correlation between Tregs and IL-10 has been observed among the children born to infected mother. Significance: From these observations we predict that early priming of the fetal immune system by filarial antigens modulate the development of Tregs, which ultimately scale up the production of IL-10 in neonates and creates a milieu for high rate of acquisition of infection in children born to infected mothers. The mechanism of susceptibility and implication of the results in global elimination programme of filariasis has been discussed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Prevention of β thalassaemia implies knowledge of the molecular spectrum occurring in the population at risk. This knowledge is necessary, especially when a prevention protocol is applied to a multiethnic population. For this purpose, we carried out molecular analysis of 431 β thalassaemia subjects belonging to tribal (aboriginal) and non-tribal communities of Orissa, a part of peninsular India and found six types of mutation (four previously unreported and two reported). Molecular analysis of β gene mutation showed that out of 431 β thalassaemia cases (265 β thalassaemia traits, 64 β thalassaemia major, 47 haemoglobin E-β thalassaemia, 55 haemoglobin S-β thalassaemia cases), 71% of cases (n=306) showed the IVS I-5(G→C) mutation, 12% of cases (n=52) showed FS 41/42(-CTTT), 7% of cases (n=30) showed CD 15(G→A), 4·8% of cases (n=21) showed CD 30 (G→C), 3% of cases (n=13) showed FS 8/9 (+G), and 2% of cases (n=9) showed IVSI-1(G→T). The tribal populations possess only the IVS I-5(G→C) mutation whereas the non-tribal groups possess the FS 41/42(-CTTT), FS 8/9 (+G), IVS I-1(G→T), CD30(G→C) and IVS I-5(G→C) mutations. Among the non-tribal communities, Muslims did not have the IVS I-1 (G→T) mutation. Clinically, anaemia was mild to moderate in β thalassaemia trait and was found to be associated with the majority of abnormalities such as pyrexial episodes, fatigue, headache, lethargy and pallor. However, there were no differences in the incidence of clinical abnormalities between tribal and non-tribal populations and also among the different molecular variants of β gene. This is the first report from Orissa on the prevalence of different molecular variants of β thalassaemia. The clinical presentation of β thalassaemia trait cases and their variation from other population have been discussed with reference to the different genetic variants. [ABSTRACT FROM AUTHOR]

Prevention of β thalassemia requires knowledge of the molecular spectrum occurring in the population at risk. This knowledge is particularly necessary when prevention control is applied to a multiethnic population. For this purpose, we are analyzing different populations of Orissa (India). During the study we encountered a β thalassemia major patient (a child) who was doubly heterozygous for IVS I-5(G→C) and codon 15(G→A) alleles where codon 15(G→A) was for the first time found in the father of the patient. Also, the patient showed severe clinical abnormalities because of the severe nature of these β thalassemia alleles. This will provide further insights into β globin gene regulation and the genotype–phenotype relationship. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

India has targeted elimination of lymphatic filariasis (LF) through mass drug administration (MDA) by 2027. Mapping of LF endemic areas is a priority for implementation of MDA. Current national LF remapping tool for unsurveyed/uncertain districts, have many limitations. The WHO has recommended a sensitive and rapid remapping protocol (Mini-TAS), that needs validation in Indian setting. Hence, in the present study a comparative assessment of these two protocols (national protocol vs Mini-TAS) was undertaken in two non-MDA districts of Odisha, with unknown filarial endemicity but reporting chronic cases. Purposive sampling was done in five top sites based on filarial case count as per the national protocol. Random 30 cluster survey was done by conducting school based Mini-TAS, Microfilariae (Mf) survey among adults (>10 years) in villages/wards with schools and Molecular Xenomonitoring (MX) of infection in vectors. Costing by activity and items of the surveys was acomplished using itemized cost menu. In Kalahandi, one of the five purposive sampling sites showed Mf prevalence above threshold (> 1%). But except Mini-TAS neither MX nor house-hold Mf survey among adults could detect the infection above the threshold. While in Balangir, Mf prevalence in all purposive sampling sites,Mini-TAS, Mf prevalence among adult and MX were above the respective thresholds confirming endemicity of LF in the district. The per sample cost of purposive sampling for Mf was the lowest INR 41, followed by adult Mf sampling INR 93. Mini-TAS and MX were expensive with INR 659 and 812 respectively. The study demonstrates that though all the sampling methods could detect filarial infection above the threshold in high-risk areas, Mini-TAS could only detect infection in low-risk areas. Therefore, in the national programme Mini-TAS can be used as a decision-making tool to determine whether to exclude/ include a district having uncertain endemicity for MDA. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To describe the development and implementation of a population-based screening programme for sickle cell disease (SCD) implemented in 12 SCD-endemic and tribal-dominated primary/community health centres (PHCs/CHCs) across six districts of India. Setting: India reports a huge burden of SCD, especially among indigenous (tribal) communities. However, there is no state-led SCD programme in many places, and systematic screening is absent. This situation necessitates developing a model of population screening. Methods: This programme was meant to screen all people and was carried out in three tiers. The first tier was a symptomatic survey carried out by community health workers. Regular health workers then screened those referred by sickle cell solubility test at sub-health centres as the second tier. The third tier was confirmation by haemoglobin electrophoresis at PHCs/CHCs. Communities were mobilised and prepared to accept the screening. Capacity building of health facilities was ensured through training and supply of equipment and material. Results: Initial observation based on six months' data revealed that out of the 110,754 tribal population of 12 PHCs/CHCs, 8418 (7.6%) were identified in the symptomatic survey. Subsequently, 9416 people, including the above 8418, underwent the solubility test, and 2607 (27.7%) were found to be positive. Of these, 1978 (78.9%) underwent electrophoresis. About 64.2% were found to be positive for sickle haemoglobin (233 (18.4%) SCD and 1036 (81.6%) SCD trait). Conclusions: The study demonstrates the feasibility of establishing a population-based screening programme in the primary health care system. It is easy to implement in tribal habitations as part of the proposed national SCD/haemoglobinopathies programme. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 β-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%, β-thalassaemia heterozygotes 0.3%, HbS/β-thalassaemia compound heterozygote 0.07%, HbS-α-thalassaemia 2.1%, G6PD deficiency 3.2% and malaria 8.1%. Molecular characterization of βS revealed the presence of Arab-Indian haplotype in all HbS cases and IVS 1–5 G → C mutation in all β-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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Parasite growth within the erythrocyte causes dramatic alterations of host cell which on one hand facilitates nutrients acquisition from extracellular environment and on other hand contributes to the symptoms of severe malaria. The current paper focuses on interactions between the Plasmodium parasite and its metabolically highly reduced host cell, the natural selection of numerous polymorphisms in the genes encoding hemoglobin and other erythrocyte proteins. [ABSTRACT FROM AUTHOR]

Five hundred and 20 cases (279 males; 241 females), referred for anemia, with a wide age range, from different parts of the state of Orissa, India, were investigated to evaluate the extent of the prevalence of hemoglobinopathies (sickle cell disorders and thalassemias) by analyzing the associated hemoglobin (Hb) profiles, Hb genotypes, as well as the clinical and hematological parameters. We found sickle cell trait (Hb AS) in 131 cases (62 males; 69 females), homozygous sickle cell anemia in 49 cases (34 males; 15 females) and Hb S-β thalassemia (S-β-thal) in 17 cases (nine males; eight females). There were also 46 cases (32 males; 14 females) of β-thal major, 103 cases (51 males; 52 females) of β-thal trait, six cases (four males; two females) of Hb E trait [β26(B8)Glu→Lys; GAG→AAG] , and 17 cases (12 males; five females) of Hb E-β- thal (E-β-thal). A large proportion of these anomalies were found among the general caste people rather than among the tribal population which constitutes 22% of the total population in this state. Hb E was found mainly in higher castes like Khandayat and Karan, residing in the coastal region of Orissa. This study provides comprehensive data on the spectrum of hemoglobinopathies in this state. [ABSTRACT FROM AUTHOR]

India, a persistently significant contributor to the global malaria burden, rolled out several anti-malaria interventions at the national and state level to control and recently, to eliminate the disease. Odisha, the eastern Indian state with the highest malaria burden experienced substantial gains shown by various anti-malaria initiatives implemented under the National Vector-borne Disease Control Programme (NVBDCP). However, recalcitrant high-transmission "pockets" of malaria persist in hard-to-reach stretches of the state, characterised by limited access to routine malaria surveillance and the forested hilly topography favouring unbridled vector breeding. The prevalence of asymptomatic malaria in such pockets serves as perpetual malaria reservoir, thus hindering its elimination. Therefore, a project with the acronym DAMaN was initiated since 2017 by state NVBDCP, targeting locally identified high endemic 'pockets' in 23 districts. DAMaN comprised biennial mass screening and treatment, provisioning of long-lasting insecticidal net (LLIN) and behavioural change communication. Subsequently, to inform policy, assessment of DAMaN was conceived that aims to estimate the coverage of the various components of the project; the prevalence of malaria, even at sub-patent level especially among pregnant/lactating women and children; and its impact on malaria incidence. A survey of DAMaN beneficiaries will measure coverage; and knowledge and practices related to LLIN; along with collection of blood specimens from a probability sample. A multi-stage stratified clustered sample of 2228 households (~33% having pregnant/lactating women) will be selected from 6 DAMaN districts. Routine DAMaN project data (2017–2018) and NVBDCP data (2013–2018) will be extracted. Rapid Diagnostic Test, Polymerase Chain Reaction and blood smear microscopy will be conducted to detect malarial parasitemia. In addition to measuring DAMaN's coverage and malarial prevalence in DAMaN pockets, its impact will be estimated using pre-post differences and Interrupted Time Series analysis using 2017 as the "inflection" point. The assessment may help to validate the unique strategies employed by DAMaN. [ABSTRACT FROM AUTHOR]

Sickle cell disease (SCD) is one of the major public health problems in the world. In India, the burden of SCD is comparatively high in socio-economically disadvantaged tribal communities. Though efficacious interventions are available to manage SCD, they are not reaching to these communities and no comprehensive programme is in place in the health care system. Therefore, the Indian Council of Medical Research has initiated a nation-wide study to develop an effective intervention model for SCD patients in tribal areas through the government health care system. This intervention includes increasing awareness and preparing the communities for accessing the government health care system for SCD care, and improving the capacity of the primary health care systems including the training of the health care providers on prevention and management of SCD. The study adopted a quasi-experimental design with pre-vs. post-intervention comparisons of outcome variables within the interventional groups and with the control group. The study will be implemented in 6 districts which are endemic for SCD, spread across different geographical zones of India. In each district, four primary health centre (PHC) areas which are predominantly inhabited by tribal population will be selected. Of these four PHC areas, two will be selected randomly for implementing the intervention and the remaining two will be the control area. Information necessary for development and implementation of the intervention will be gathered during formative research, by using both quantitative and qualitative research methods. Intervention with an inclusive partnership and community mobilization will be implemented. The major steps in the implementation of intervention are partnership building with various health and non-health partners including the community. Capacity building and strengthening is another important component to enable the primary health facilities to screen and manage SCD patients. Primarily, sub-health centres and primary healthcare centres will be equipped with appropriate SCD screening techniques. All doctors in the system will be trained in advanced treatment and management issues. To improve the community's awareness and readiness, community mobilization activities will be conducted. An impact evaluation will be carried out at the end of the intervention by comparing the improvement of SCD management in intervention PHCs to that of the control PHCs. However, the process evaluation and necessary mid-term corrections will be made throughout the intervention period. Thus, an intervention model in terms of its suitability, replicability and sustainability for the tribal population will be developed and tested. The findings of this study are more suitable to use during advocacy and to replicate the model by the state health departments. This study develops and places an appropriate referral system for SCD patients at the PHC level. Improving the community's access to health care, improving the quality of care in government health centres and raising awareness among tribal communities are crucial to achieving through innovation. Taken together, these innovations would significantly contribute to better access to health care and management of the SCD patients of underserved tribal population. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Global Program to Eliminate Lymphatic Filariasis (GPELF) launched by WHO aims to eliminate the disease by 2020. To achieve the goal annual mass drug administration (MDA) with diethylcarbamazine (DEC) plus albendazole (ABZ) has been introduced in all endemic countries. The current policy however excludes pregnant mothers and children below two years of age from MDA. Since pregnancy and early childhood are critical periods in determining the disease outcome in older age, the present study was undertaken to find out the influence of maternal filarial infection at the time of pregnancy on the susceptibility outcome of children born in a community after implementation of MDA for the first time. Methodology and Principal Findings: The participants in this cohort consists of pregnant mothers and their subsequently born children living in eight adjacent villages endemic for filarial infections, in Khurda District, Odisha, India, where MDA has reduced microfilariae (Mf) rate from 12% to 0.34%. Infection status of mother and their children were assessed by detection of Mf as well as circulating filarial antigen (CFA) assay. The present study reveals a high rate of acquiring filarial infection by the children born to infected mother than uninfected mothers even though Mf rate has come down to < 1% after implementation of ten rounds of MDA. Significance: To attain the target of eliminating lymphatic filariasis the current MDA programme should give emphasis on covering the women of child bearing age. Our study recommends incorporating supervised MDA to Adolescent Reproductive and Sexual Health Programme (ARSH) to make the adolescent girls free from infection by the time of pregnancy so as to achieve the goal. [ABSTRACT FROM AUTHOR]

Essential hypertension which accounts 90–95% of the total hypertension cases is affected by both genetic and environmental factors. This study was undertaken to investigate the association of aldosterone synthase C-344T, angiotensin II type I receptor A1166C and 11-β hydroxysteroid dehydrogenase type 2 G534A polymorphisms with essential hypertension in the population of Odisha, India. A total of 246 hypertensive subjects (males, 159; females, 87) and 274 normal healthy individuals (males, 158; females, 116) were enrolled in this study based on the inclusion and exclusion criteria. Analysis of genetic and biochemical data revealed that in this population the CT and TT genotypes of aldosterone synthase C-344T polymorphism, frequency of alcohol consumption and aldosterone levels were significantly high among the total as well as male hypertensives, while the AC and CC genotypes of angiotensin II type I receptor A1166C polymorphism were significantly high among the total as well as female hypertensives. High density lipoprotein levels were higher in male hypertensives. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Microparticles (MPs) resulting from vesiculation of different cell types in Plasmodium falciparum infection correlate with the level of proinflammatory cytokine TNF that may thereby determine the disease severity. Using TruCount tube based flow cytometric method for the exact quantification of MP and enzyme linked immunosorbent assay for the measurement of TNF, we conducted a hospital based case control study on P. falciparum malaria patients to scrutinize and infer the link between the two. In 52 cerebral malaria (CM), 21 multi-organ-dysfunction (MOD), 12 non cerebral severe malaria (NCSM) and 43 uncomplicated malaria patients, the MP level was found to be significantly elevated in febrile malaria patients compared to healthy controls and a striking decrease in MP level was observed with the clearance of the P. falciparum infection in the patients upon follow-up. The lowering of the parasite density with the level of plasma TNF and the positive correlation of the cytokine with the cell derived MPs and negative correlation with the respective cell count in human malaria patients suggests that TNF may be a key stimulant to the cells resulting in the release of MPs in malaria infection. [Copyright &y& Elsevier]

Abstract: In the absence of definite marker for artemisinin (ART) resistance, molecular monitoring of its partner drug sulfadoxine pyrimethamine (SP) in artemisinin based combination therapy (ACTs) together with chloroquine (CQ) for which ART is negatively correlated, may predict the effectiveness of ACT. We analyzed 201 Plasmodium falciparum field isolates for drug resistance markers for CQ (pfcrt and pfmdr1), pyrimethamine (pfdhfr) and sulfadoxine (pfdhps). Our study reveals high prevalence and non-random association of resistant mutants (K76T and N86Y) of CQ markers (pfcrt and pfmdr1). The predominance of highly resistant pfdhfr genotypes for SP with intragenic and intergenic pair-wise linkage disequilibrium between single nucleotide polymorphisms of resistant mutants of pfdhfr (C59R and S108N) and pfdhps (S436A, A437G, K540E) warn on further inclusion of SP in ACT. These findings suggest the replacement of SP in ACT with alternative partner drug for better efficacy. [Copyright &y& Elsevier]

Abstract: The complement receptor 1 (CR1/CD35) protein acts as the major rosetting receptor in Plasmodium falciparum infection and several genetic variants of CR1 gene have been shown to be associated with quantitative expression of erythrocyte CR1 (E-CR1) level. However, CR1 level and gene polymorphisms exhibit differences in clinical manifestation of malaria in regions of varying disease endemicity. The result of the present study which analyzed three SNPs (intron 27 HindIIIA>T, exon 22 3650 A>G, and exon 33 5507 C>G) of the CR1 gene in Orissa, a hyperendemic state in eastern-India showed that a significantly increased risk for cerebral malaria (CM) was associated with AA genotype of both intron 27 and exon 22 when compared with mild, severe malaria anemia (SMA) and CM+SMA group respectively. Further, the overall haplotype analysis for all the three loci showed predominantly two major haplotypes ‘AAC’ coding for higher expression of CR1 and ‘TGG’ haplotype coding for low expression of CR1 level with the former haplotype being significantly associated with CM (P value<0.00619 after Bonferroni correction) compared to mild malaria. The ‘TGG’ haplotype was proportionately more in SMA cases compared to mild malaria though statistically not significant. These findings suggest that the mild malaria group had an intermediate level of E-CR1 and extremely low or high levels of CR1 can cause severity in malaria. Further large scale studies in different endemic regions are needed to explain the epidemiological differences between E-CR1 expression and clinical manifestation of malaria which may contribute to the understanding of malaria pathogenesis. [Copyright &y& Elsevier]

Abstract: To explore the hypothesis that angiotensin II may play a role in the susceptibility to cerebral malaria (CM), we performed a genetic association study of malaria patients in Orissa, India analyzing three SNPs (ACE2 C→T, iNOS C→T, eNOS Glu→Asp) and two I/D polymorphisms (ACE I/D and IL-4 B1/B2). Our results showed that the ‘D’ allele of ACE I/D polymorphism, responsible for increased Ang II production had a significant association with mild malaria and the ACE2 C→T substitution had gender specific effect of possibly reduced expression of ACE2 in presence of ‘T’ allele in women leading to increased level of Ang II and hence protection against CM. Combined genotype analysis of eNOS Glu→Asp substitution responsible for increased NO production in Plasmodium falciparum infected individuals and ACE I/D polymorphism also showed stronger association of (Glu-Asp+Asp-Asp/ID+DD) genotypes with mild malaria (P <0.0001). Whether by its antiplasmodial activity and/or by some unknown mechanisms, Ang II protects from susceptibility to cerebral malaria remains to be investigated. These genetic findings may contribute to the understanding of malaria pathogenesis. [Copyright &y& Elsevier]

Abstract: The role of nitric oxide (NO) in the pathogenesis of cerebral malaria is controversial. Of the three isoforms of nitric oxide synthases (NOS), though iNOS expression is the major source of NO level in vivo, nNOS is the main isoform constitutively expressed in the neural tissues. However, there has been no investigation of the role of polymorphisms of the nNOS gene in the etiology of cerebral malaria. We have analyzed two single nucleotide polymorphisms (SNPs) of nNOS gene (−84G→A and 276C→T), responsible for decreased basal transcriptional activity, in 200 patients with mild Plasmodium falciparum malaria and 170 patients with cerebral malaria. Our results showed a significant association of AG genotype (OR=1.83, 95%CI=1.19–2.78, P =0.007) and AA genotype (OR=3.86, 95%CI=1.42–10.5, P =0.007) of nNOS −84G→A substitution with cerebral malaria. Interestingly, when the nNOS variant genotypes were combined together for analysis, a significantly increased risk of cerebral malaria was associated with −84(AG+AA)/276(CT+TT) genotype (OR=2.59, 95%CI=1.46–4.60, P =0.0016) and −84(AG+AA)/276(CC) genotype (OR=1.89, 95%CI=1.08–3.32, P =0.0334). The −84A seems to be a putative risk allele on the susceptibility to cerebral malaria and low nitric oxide production might have contributed to the development of cerebral malaria. [Copyright &y& Elsevier]

A correction to the article "Aldosterone synthase C-344T, angiotensin II type 1 receptor A1166C and 11-β hydroxysteroid dehydrogenase G534A gene polymorphisms and essential hypertension in the population of Odisha, India" that was published in a previous issue of the periodical is presented.