§<p>age of 21 cases is missing.</p>†<p>Having 1 mixed, 1 P. vivax.</p>‡&l... more §<p>age of 21 cases is missing.</p>†<p>Having 1 mixed, 1 P. vivax.</p>‡<p>Having 2 mixed.</p>††<p>Having 3 mixed, 1 P. vivax.</p>‡‡<p>Having 1 mixed, 1 P. vivax.</p><p>¥ Having 2 mixed.</p><p># Having 3 mixed, 1 P. vivax.</p><p>+ve: Positive for malaria; Pf: <i>Plasmodium falciparum</i>; Pv: <i>Plasmodium vivax</i>; Mixed: <i>P. falciparum</i> + <i>P. vivax</i>; SPR: Slide Positivity rate; SFR: Slide Falciparum Rate; Pf%: <i>P. falciparum</i> percentage; Complicated malaria: Cerebral and Severe malaria both); CM: Cerebral malaria; SM: Severe malaria.</p><p>Age and sex wise prevalence of malaria among suspected malaria cases at tertiary health care hospital in Bastar, Chhattisgarh, Central India.</p
Background & objectives: Malaria is a major public health problem in many States of the country, ... more Background & objectives: Malaria is a major public health problem in many States of the country, particularly, in Madhya Pradesh where both Plasmodium vivax and P. falciparum are endemic. Although many studies have been conducted to investigate risk factors for malaria, but only a few have examined household and socio-economic risk factors. The present study was, therefore, undertaken to explore the relationship of different socio-demographic, socio-economic and behavioural risk factors with malaria prevalence in tribal areas of Madhya Pradesh, India. Methods: This study was undertaken in all 62 villages of Bargi Primary Health Centre from May 2005 to June 2008. These villages comprised 7117 households with an average family size of five members. Fortnightly fever surveys were conducted in all villages to assess prevalence of malaria infection in the community. The distinct univariate and multivariate logistic regression models were fitted on the data set. Results: The important soc...
The American Journal of Tropical Medicine and Hygiene, 2008
A study on the clinicoepidemiology of cerebral malaria (CM) and mild malaria (MM) among adults an... more A study on the clinicoepidemiology of cerebral malaria (CM) and mild malaria (MM) among adults and children attending NSCB medical college hospital Jabalpur and civil hospital Maihar, Satna, in central India was undertaken. Of 1,633 patients, 401 were Plasmodium falciparum and 18 P. vivax. Of 401, 199 CM patients and 112 MM patients were enrolled. Severe complications among CM patients were jaundice (26%), acute renal failure (22%), respiratory distress (22%), severe malaria anemia (18%), hypotension (17%), hepatic encephalopathy (7.0%), and hematuria (5%). Among CM cases, seizures and severe malaria anemia were significantly higher in children (P < 0.0001) compared with adults, whereas jaundice (P < 0.0025), acute renal failure (P < 0.0001), and hematuria (P Յ 0.05) were significantly higher among adults. Mortality was high among adults with multiple organ failures. Overall case fatality rate was 21%. Neurologic sequelae at discharge from the hospital were 3%, whereas at follow-up, only 1% had persistent neurologic sequelae.
RTS,S is the most advanced malaria vaccine candidate, currently under phase-III clinical trials i... more RTS,S is the most advanced malaria vaccine candidate, currently under phase-III clinical trials in Africa. This Plasmodium falciparum vaccine contains part of the central repeat region and the complete C-terminal T cell epitope region (Th2R and Th3R) of the circumsporozoite protein (CSP). Since naturally occurring polymorphisms at the vaccine candidate loci are critical determinants of the protective efficacy of the vaccines, it is imperative to investigate these polymorphisms in field isolates. In this study we have investigated the genetic diversity at the central repeat, C-terminal T cell epitope (Th2R and Th3R) and N-terminal T cell epitope regions of the CSP, in P. falciparum isolates from Madhya Pradesh state of India. These isolates were collected through a 5-year prospective study aimed to develop a well-characterized field-site for the future evaluation of malaria vaccine in India. Our results revealed that the central repeat (63 haplotypes, n = 161) and C-terminal Th2R/Th3R epitope (24 haplotypes, n = 179) regions were highly polymorphic, whereas N-terminal non-repeat region was less polymorphic (5 haplotypes, n = 161) in this population. We did not find any evidence of the role of positive natural selection in maintaining the genetic diversity at the Th2R/Th3R regions of CSP. Comparative analysis of the Th2R/Th3R sequences from this study to the global isolates (n = 1160) retrieved from the GenBank database revealed two important points. First, the majority of the sequences (,61%, n = 179) from this study were identical to the Dd2/Indochina type, which is also the predominant Th2R/Th3R haplotype in Asia (,59%, n = 974). Second, the Th2R/Th3R sequences in Asia, South America and Africa are geographically distinct with little allele sharing between continents. In conclusion, this study provides an insight on the existing polymorphisms in the CSP in a parasite population from India that could potentially influence the efficacy of RTS,S vaccine in this region.
Background Plasmodium falciparum infection causes cerebral malaria (CM) in a subset of patients w... more Background Plasmodium falciparum infection causes cerebral malaria (CM) in a subset of patients with anti-malarial treatment protecting only about 70% to 80% of patients. Why a subset of malaria patients develops CM complications, including neurological sequelae or death, is still not well understood. It is believed that host immune factors may modulate CM outcomes and there is substantial evidence that cellular immune factors, such as cytokines, play an important role in this process. In this study, the potential relationship between the antibody responses to the merozoite surface protein (MSP)-1 complex (which consists of four fragments namely: MSP-183, MSP-130, MSP-138 and MSP-142), MSP-636 and MSP-722 and CM was investigated. Methods Peripheral blood antibody responses to recombinant antigens of the two major allelic forms of MSP-1 complex, MSP-636 and MSP-722 were compared between healthy subjects, mild malaria patients (MM) and CM patients residing in a malaria endemic region ...
Biomarkers have been used to diagnose and prognosticate the progress and outcome of many chronic ... more Biomarkers have been used to diagnose and prognosticate the progress and outcome of many chronic diseases such as neoplastic and non communicable diseases. However, only recently did the field of malaria research move in the direction of actively identifying biomarkers that can accurately discriminate the severe forms of malaria. Malaria continues to be a deadly disease, killing close to a million people (mostly children) every year. One life-threatening complication of malaria is cerebral malaria (CM). Studies carried out in Africa have demonstrated that even with the best treatment, as high as 15–30% of CM patients die and about 10–24% of CM survivors suffer short-or long-term neurological impairment. The transition from mild malaria to CM can be sudden and requires immediate intervention. Currently, there is no biological test available to confirm the diagnosis of CM and its complications. It is hoped that development of biomarkers to identify CM patients and potential risk for a...
Treatment of Plasmodium falciparum is complicated by the emergence and spread of parasite resista... more Treatment of Plasmodium falciparum is complicated by the emergence and spread of parasite resistance to many of the first-line drugs used to treat malaria. Antimalarial drug resistance has been associated with specific point mutations in several genes, suggesting that these single nucleotide polymorphisms can be useful in tracking the emergence of drug resistance. In India, P. falciparum infection can manifest itself as asymptomatic, mild, or severe malaria, with or without cerebral involvement. We tested whether chloroquine- and antifolate drug-resistant genotypes would be more commonly associated with cases of cerebral malaria than with cases of mild malaria in the province of Jabalpur, India, by genotyping the dhps , dhfr , pfmdr-1 , and pfcrt genes using pyrosequencing, direct sequencing, and real-time PCR. Further, we used microsatellites surrounding the genes to determine the origins and spread of the drug-resistant genotypes in this area. Resistance to chloroquine was essenti...
Tau is a microtubule-associated protein (MAP) that is abundant in the axonal part of neurons of t... more Tau is a microtubule-associated protein (MAP) that is abundant in the axonal part of neurons of the central nervous system. Previous studies among African children and Vietnamese adults suffering from cerebral malaria (CM) showed the pathological significance of measuring circulatory total Tau levels. A pilot investigation was carried out to better characterise neurological pathogenesis among severe malaria patients in Central India. Serum levels of total human Tau (pg/ml) were measured by ELISA following manufacturer guidelines among hospital admitted P. falciparum malaria patients classified with different degree of severity (mild malaria = MM, non-cerebral severe malaria = NCSM, cerebral malaria survivors = CM-S and cerebral malaria nonsurvivors = CM-NS) using WHO, 2000 definitions, including healthy controls (HC) enroled from the hospital's blood bank. Categorical and numerical variables were analysed by applying appropriate statistical test using Stata 11.0 software. A total of 139 subjects (14 HC, 25 MM, 29 NCSM, 44 CM-S and 27 CM-NS) were included in this preliminary investigation. Serum levels of total human Tau were detected in 0% HC, 4.0% MM, 20.7% NCSM, 43.2% CM-S and 48.2% CM-NS patients. Compared to MM, percent Tau detection was significantly higher among severe malaria patients (p = 0.001). Further, compared to NCSM,% Tau detection was significantly higher in CM-S patients (Chi 2 = 3.9, p = 0.048) & CM-NS patients (Chi 2 = 4.7, p = 0.030). Percent Tau detection was also significantly higher among severe malaria cases presenting with multiple complications compared to those without multiple complications (p = 0.006). ROC analysis of serum Tau levels (pg/ml) revealed a fair AUC value (0.75) to distinguish CM-NS group (but not CM-S) from NCSM group. In conclusion, serum percent detection of total human Tau is associated with axonal damage among patients with different degree of P. falciparum malaria severity in Central India.
HC – healthy controls, MM – mild malaria, CMS – cerebral malaria survivors, CMNS – cerebral malar... more HC – healthy controls, MM – mild malaria, CMS – cerebral malaria survivors, CMNS – cerebral malaria non-survivors. Box plots represent medians and 25and 75percentiles. Bars mark the 10and 90percentiles, and outliers are plotted as points. MM versus CMS and CMNS: *** p < 0.05, $$$ p < 0.0045 bonferroni adjustment (alpha = 0.05/11), CMS versus CMNS: +++ p < 0.05, ### p < 0.0045 bonferroni adjustment (alpha = 0.05/11).<b>Copyright information:</b>Taken from "Plasma IP-10, apoptotic and angiogenic factors associated with fatal cerebral malaria in India"http://www.malariajournal.com/content/7/1/83Malaria Journal 2008;7():83-83.Published online 19 May 2008PMCID:PMC2405803.
Log median levels (pg/ml) of eighteen (18) biomarkers [IFN-γ, TNF-α, MIP-1α, IL-1β, IL-2, RANTES,... more Log median levels (pg/ml) of eighteen (18) biomarkers [IFN-γ, TNF-α, MIP-1α, IL-1β, IL-2, RANTES, IL-4, IL-5, G-CSF, IL-6, IL-9, Eotaxin, IL-12 (p70), IL-13, GM-CSF, IL-15, IL-17 and MCP-1 (MCAF)]. Biomarkers were quantified via Luminex™ from blood samples collected from patients at time of admission. HC – healthy controls, MM – mild malaria, CMS – cerebral malaria survivors, CMNS – cerebral malaria non-survivors. Box plots represent medians and 25and 75percentiles. Bars mark the 10and 90percentiles, and outliers are plotted as points. HC versus MM, CMS, and CMNS: *** p < 0.05, $$$ p < 0.0045 bonferroni adjustment (alpha = 0.05/18)<b>Copyright information:</b>Taken from "Plasma IP-10, apoptotic and angiogenic factors associated with fatal cerebral malaria in India"http://www.malariajournal.com/content/7/1/83Malaria Journal 2008;7():83-83.Published online 19 May 2008PMCID:PMC2405803.
Tropical Medicine & International Health, 2013
We report for the first-time detection of Plasmodium ovale in central India. From 2010, all hospi... more We report for the first-time detection of Plasmodium ovale in central India. From 2010, all hospitalised suspected malaria cases at the malaria clinic of the Regional Medical Research Centre for Tribals in Bastar district, central India, were screened. Plasmodium species were identified by microscopy and species-specific nested PCR of 18s rRNA. Of 256 enrolled cases of confirmed P. falciparum malaria by microscopy, P. ovale infection was detected in three cases (1.2%) by PCR and sequencing. Of these three cases, one had cerebral malaria and another had severe malaria anaemia. In both of these cases, P. ovale infection was mixed with P. falciparum, while in third case the infection was mixed with both P. falciparum and P. vivax. Phylogenetic analysis revealed that these isolates showed closed homology with West African genotypes. All three hospitalised patients were originally residents of remote inaccessible forest villages and never moved out of their residence. This finding also has implications in malaria control and elimination as P. ovale causes relapses. This study highlights the need of molecular diagnosis of malaria species for appropriate treatment and control.
Background Plasmodium falciparum in a subset of patients can lead to cerebral malaria (CM), a maj... more Background Plasmodium falciparum in a subset of patients can lead to cerebral malaria (CM), a major contributor to malaria-associated mortality. Despite treatment, CM mortality can be as high as 30%, while 10% of survivors of the disease may experience short- and long-term neurological complications. The pathogenesis of CM is mediated by alterations in cytokine and chemokine homeostasis, inflammation as well as vascular injury and repair processes although their roles are not fully understood. The hypothesis for this study is that CM-induced changes in inflammatory, apoptotic and angiogenic factors mediate severity of CM and that their identification will enable development of new prognostic markers and adjunctive therapies for preventing CM mortalities. Methods Plasma samples (133) were obtained from healthy controls (HC, 25), mild malaria (MM, 48), cerebral malaria survivors (CMS, 48), and cerebral malaria non-survivors (CMNS, 12) at admission to the hospital in Jabalpur, India. P...
Cerebral malaria (CM) is one of the most severe forms of P. falciparum infection, with an associa... more Cerebral malaria (CM) is one of the most severe forms of P. falciparum infection, with an associated high case-fatality rate. Angiopoietins (ANG-1 and ANG-2) are important biomarkers of endothelial activation and dysfunction. This study was carried out in Maharani Hospital and associated Medical College, Jagdalpur, CG, Central India from 2010 to 2014. Based on the treatment recovery patterns, cases (n = 65) were classified as mild malaria with rapid recovery (MM-RR), n= 14; non-cerebral severe malaria with moderately fast recovery (NCSM-MFR), n= 9; CM survivors with slow recovery (CMS-SR), n= 36 and deteriorated CM non-survivors (Det-CMNS), n= 6. Plasma levels (pg/ml) of ANG-1 and ANG-2 were measured by ELISA in all the samples at the time of hospital admission and 48 hours of treatment. Levels were also measured in available samples at the third time point (time of discharge for survivors or 72 hours post-treatment in fatal cases). Data analysis was done by appropriate statistical tests using Stata 11.0 and SPSS 25.0 software. At the time of admission, ANG-2 and ratios of ANG-2/ANG-1 significantly distinguished Det-CMNS cases from MM-RR and NCSM-MFR cases with good AUC scores (0.8-0.9). Further, Det-CMNS cases could also be distinguished from MM-RR, NCSM-MFR, and CMS-SR cases by ANG-2 (AUC scores 0.9) and ratios of ANG-2/ANG-1 (AUC: 0.8-0.9) at 48 hours of treatment. Paired analysis of sequential measurement of angiopoietins revealed that compared to admission levels, the ratios of ANG-2/ANG-1 significantly declined 48 hours after treatment in MM-RR (p= 0.041), NCSM-MFR (p= 0.050), and CMS-SR (p= 0.0002) cases but not in cases of Det-CMNS (p= 0.916). In conclusion, plasma levels of ANG-2 and ratios of ANG-2/ANG-1 may serve as good biomarkers to distinguish the malaria severity at the time of hospital admission and recovery patterns upon treatment in Central India.
Background & objectives: Malaria is a major public health problem in many states of the country, ... more Background & objectives: Malaria is a major public health problem in many states of the country, particularly, in Madhya Pradesh where both Plasmodium vivax and P. falciparum are endemic. Although many studies have been conducted to investigate risk factors for malaria, but only a few have examined household and socio-economic risk factors. The present study was, therefore, undertaken to explore the relationship of different socio-demographic, socio-economic and behavioural risk factors with malaria prevalence in tribal areas of Madhya Pradesh, India. Methods: This study was undertaken in all 62 villages of Bargi Primary Health Centre from May 2005 to June 2008. These villages comprised 7117 households with an average family size of five members. fortnightly fever surveys were conducted in all villages to assess prevalence of malaria infection in the community. The distinct univariate and multivariate logistic regression models were fitted on the data set. Results: The important soc...
The risk factors for cerebral malaria (CM) and the wide variation in clinical manifestations of m... more The risk factors for cerebral malaria (CM) and the wide variation in clinical manifestations of malaria are poorly understood. Recent studies indicate that interferon gamma inducible chemokine, CXCL10, is a strong predictor of both human and experimental cerebral malaria. Increased plasma and cerebrospinal fluid levels of CXCL10 were tightly associated with fatal CM in Indian and Ghanaian patients. In the present study, we hypothesized that in a subset of malaria patients, CM susceptibility is associated with variation in CXCL10 expression. We determined whether polymorphisms in the CXCL10 gene promoter region played a role in the clinical status of malaria patients and addressed the genetic basis of CXCL10 expression during malaria infection. Following extensive bioinformatics analyses, two reported single nucleotide polymorphisms in the CXCL10 promoter (2135G.A [rs56061981] and 21447A.G [rs4508917]) were identified among 66 CM and 69 non-CM Indian patients using PCR-restriction fragment length polymorphism assay. Individuals with the 21447(A/G) genotype were susceptible to CM (adjusted odds ratio [AOR] = 2.60, 95% CI = 1.51-5.85, p = 0.021). In addition, individuals with the 21447(A/G) genotype had significantly higher plasma CXCL10 levels than individuals with the 21447(A/A) genotype. Stratifying patients according to gender, the observed association of CM with over expression of CXCL10 were more pronounced in males than in female patients (AOR = 5.47, 95% CI = 1.34-22.29, p = 0.018). Furthermore, 2135G.A polymorphism conferred a decreased risk of CM among males (AOR = 0.19, 95% CI = 0.05-0.78, p = 0.021). Polymorphisms in the CXCL10 gene promoter sequence were associated with increased CXCL10 production, which is linked to severity of CM. These results suggest that the 21447A.G polymorphism in CXCL10 gene promoter could be partly responsible for the reported variation underlying severity of CM outcomes particularly in males.
Plasmodium falciparum in a subset of patients can lead to a diffuse encephalopathy known as cereb... more Plasmodium falciparum in a subset of patients can lead to a diffuse encephalopathy known as cerebral malaria (CM). Despite treatment, mortality caused by CM can be as high as 30% while 10% of survivors of the disease may experience short-and long-term neurological complications. The pathogenesis of CM involves alterations in cytokine and chemokine expression, local inflammation, vascular injury and repair processes. These diverse factors have limited the rate of discovery of prognostic predictors of fatal CM. Identification of reliable early predictors of CM severity will enable clinicians to adjust this risk with appropriate management of CM. Recent studies revealed that elevated levels of CXCL10 expression in cerebrospinal fluid and peripheral blood plasma independently predicted severe and fatal CM. CXCR3, a promiscuous receptor of CXCL10, plays an important role in pathogenesis of mouse model of CM. In this study the role of corresponding CXCR3 ligands (CXCL11, CXCL10, CXCL9 & CXCL4) in fatal or severe CM was evaluated by comparing their levels in 16 healthy control (HC), 26 mild malaria (MM), 26 cerebral malaria survivors (CMS) and 12 non-survivors (CMNS) using enzyme linked immunosorbent assay (ELISA). Levels of CXCL4 and CXCL10 were significantly elevated in CMNS patients (p < 0.05) when compared with HC, MM and CMS. Elevated plasma levels of CXCL10 and CXCL4 were tightly associated with CM mortality. Receiver Operating Characteristic (ROC) curve analysis revealed that CXCL4 and CXCL10 can discriminate CMNS from MM (p < 0.0001) and CMS (p < 0.0001) with an area under the curve (AUC) = 1. These results suggest that CXCL4 and CXCL10 play a prominent role in pathogenesis of CM associated death and may be used as functional or surrogate biomarkers for predicting CM severity.
Background The mechanisms underlying the pathogenesis of cerebral malaria (CM) syndrome are not w... more Background The mechanisms underlying the pathogenesis of cerebral malaria (CM) syndrome are not well understood. Previous studies have shown a strong association of inflammatory chemokines, apoptotic markers and angiogenic molecules with CM ...
Background The mechanisms underlying the pathogenesis of cerebral malaria (CM) syndrome are not w... more Background The mechanisms underlying the pathogenesis of cerebral malaria (CM) syndrome are not well understood. Previous studies have shown a strong association of inflammatory chemokines, apoptotic markers and angiogenic molecules with CM ...
§<p>age of 21 cases is missing.</p>†<p>Having 1 mixed, 1 P. vivax.</p>‡&l... more §<p>age of 21 cases is missing.</p>†<p>Having 1 mixed, 1 P. vivax.</p>‡<p>Having 2 mixed.</p>††<p>Having 3 mixed, 1 P. vivax.</p>‡‡<p>Having 1 mixed, 1 P. vivax.</p><p>¥ Having 2 mixed.</p><p># Having 3 mixed, 1 P. vivax.</p><p>+ve: Positive for malaria; Pf: <i>Plasmodium falciparum</i>; Pv: <i>Plasmodium vivax</i>; Mixed: <i>P. falciparum</i> + <i>P. vivax</i>; SPR: Slide Positivity rate; SFR: Slide Falciparum Rate; Pf%: <i>P. falciparum</i> percentage; Complicated malaria: Cerebral and Severe malaria both); CM: Cerebral malaria; SM: Severe malaria.</p><p>Age and sex wise prevalence of malaria among suspected malaria cases at tertiary health care hospital in Bastar, Chhattisgarh, Central India.</p
Background & objectives: Malaria is a major public health problem in many States of the country, ... more Background & objectives: Malaria is a major public health problem in many States of the country, particularly, in Madhya Pradesh where both Plasmodium vivax and P. falciparum are endemic. Although many studies have been conducted to investigate risk factors for malaria, but only a few have examined household and socio-economic risk factors. The present study was, therefore, undertaken to explore the relationship of different socio-demographic, socio-economic and behavioural risk factors with malaria prevalence in tribal areas of Madhya Pradesh, India. Methods: This study was undertaken in all 62 villages of Bargi Primary Health Centre from May 2005 to June 2008. These villages comprised 7117 households with an average family size of five members. Fortnightly fever surveys were conducted in all villages to assess prevalence of malaria infection in the community. The distinct univariate and multivariate logistic regression models were fitted on the data set. Results: The important soc...
The American Journal of Tropical Medicine and Hygiene, 2008
A study on the clinicoepidemiology of cerebral malaria (CM) and mild malaria (MM) among adults an... more A study on the clinicoepidemiology of cerebral malaria (CM) and mild malaria (MM) among adults and children attending NSCB medical college hospital Jabalpur and civil hospital Maihar, Satna, in central India was undertaken. Of 1,633 patients, 401 were Plasmodium falciparum and 18 P. vivax. Of 401, 199 CM patients and 112 MM patients were enrolled. Severe complications among CM patients were jaundice (26%), acute renal failure (22%), respiratory distress (22%), severe malaria anemia (18%), hypotension (17%), hepatic encephalopathy (7.0%), and hematuria (5%). Among CM cases, seizures and severe malaria anemia were significantly higher in children (P < 0.0001) compared with adults, whereas jaundice (P < 0.0025), acute renal failure (P < 0.0001), and hematuria (P Յ 0.05) were significantly higher among adults. Mortality was high among adults with multiple organ failures. Overall case fatality rate was 21%. Neurologic sequelae at discharge from the hospital were 3%, whereas at follow-up, only 1% had persistent neurologic sequelae.
RTS,S is the most advanced malaria vaccine candidate, currently under phase-III clinical trials i... more RTS,S is the most advanced malaria vaccine candidate, currently under phase-III clinical trials in Africa. This Plasmodium falciparum vaccine contains part of the central repeat region and the complete C-terminal T cell epitope region (Th2R and Th3R) of the circumsporozoite protein (CSP). Since naturally occurring polymorphisms at the vaccine candidate loci are critical determinants of the protective efficacy of the vaccines, it is imperative to investigate these polymorphisms in field isolates. In this study we have investigated the genetic diversity at the central repeat, C-terminal T cell epitope (Th2R and Th3R) and N-terminal T cell epitope regions of the CSP, in P. falciparum isolates from Madhya Pradesh state of India. These isolates were collected through a 5-year prospective study aimed to develop a well-characterized field-site for the future evaluation of malaria vaccine in India. Our results revealed that the central repeat (63 haplotypes, n = 161) and C-terminal Th2R/Th3R epitope (24 haplotypes, n = 179) regions were highly polymorphic, whereas N-terminal non-repeat region was less polymorphic (5 haplotypes, n = 161) in this population. We did not find any evidence of the role of positive natural selection in maintaining the genetic diversity at the Th2R/Th3R regions of CSP. Comparative analysis of the Th2R/Th3R sequences from this study to the global isolates (n = 1160) retrieved from the GenBank database revealed two important points. First, the majority of the sequences (,61%, n = 179) from this study were identical to the Dd2/Indochina type, which is also the predominant Th2R/Th3R haplotype in Asia (,59%, n = 974). Second, the Th2R/Th3R sequences in Asia, South America and Africa are geographically distinct with little allele sharing between continents. In conclusion, this study provides an insight on the existing polymorphisms in the CSP in a parasite population from India that could potentially influence the efficacy of RTS,S vaccine in this region.
Background Plasmodium falciparum infection causes cerebral malaria (CM) in a subset of patients w... more Background Plasmodium falciparum infection causes cerebral malaria (CM) in a subset of patients with anti-malarial treatment protecting only about 70% to 80% of patients. Why a subset of malaria patients develops CM complications, including neurological sequelae or death, is still not well understood. It is believed that host immune factors may modulate CM outcomes and there is substantial evidence that cellular immune factors, such as cytokines, play an important role in this process. In this study, the potential relationship between the antibody responses to the merozoite surface protein (MSP)-1 complex (which consists of four fragments namely: MSP-183, MSP-130, MSP-138 and MSP-142), MSP-636 and MSP-722 and CM was investigated. Methods Peripheral blood antibody responses to recombinant antigens of the two major allelic forms of MSP-1 complex, MSP-636 and MSP-722 were compared between healthy subjects, mild malaria patients (MM) and CM patients residing in a malaria endemic region ...
Biomarkers have been used to diagnose and prognosticate the progress and outcome of many chronic ... more Biomarkers have been used to diagnose and prognosticate the progress and outcome of many chronic diseases such as neoplastic and non communicable diseases. However, only recently did the field of malaria research move in the direction of actively identifying biomarkers that can accurately discriminate the severe forms of malaria. Malaria continues to be a deadly disease, killing close to a million people (mostly children) every year. One life-threatening complication of malaria is cerebral malaria (CM). Studies carried out in Africa have demonstrated that even with the best treatment, as high as 15–30% of CM patients die and about 10–24% of CM survivors suffer short-or long-term neurological impairment. The transition from mild malaria to CM can be sudden and requires immediate intervention. Currently, there is no biological test available to confirm the diagnosis of CM and its complications. It is hoped that development of biomarkers to identify CM patients and potential risk for a...
Treatment of Plasmodium falciparum is complicated by the emergence and spread of parasite resista... more Treatment of Plasmodium falciparum is complicated by the emergence and spread of parasite resistance to many of the first-line drugs used to treat malaria. Antimalarial drug resistance has been associated with specific point mutations in several genes, suggesting that these single nucleotide polymorphisms can be useful in tracking the emergence of drug resistance. In India, P. falciparum infection can manifest itself as asymptomatic, mild, or severe malaria, with or without cerebral involvement. We tested whether chloroquine- and antifolate drug-resistant genotypes would be more commonly associated with cases of cerebral malaria than with cases of mild malaria in the province of Jabalpur, India, by genotyping the dhps , dhfr , pfmdr-1 , and pfcrt genes using pyrosequencing, direct sequencing, and real-time PCR. Further, we used microsatellites surrounding the genes to determine the origins and spread of the drug-resistant genotypes in this area. Resistance to chloroquine was essenti...
Tau is a microtubule-associated protein (MAP) that is abundant in the axonal part of neurons of t... more Tau is a microtubule-associated protein (MAP) that is abundant in the axonal part of neurons of the central nervous system. Previous studies among African children and Vietnamese adults suffering from cerebral malaria (CM) showed the pathological significance of measuring circulatory total Tau levels. A pilot investigation was carried out to better characterise neurological pathogenesis among severe malaria patients in Central India. Serum levels of total human Tau (pg/ml) were measured by ELISA following manufacturer guidelines among hospital admitted P. falciparum malaria patients classified with different degree of severity (mild malaria = MM, non-cerebral severe malaria = NCSM, cerebral malaria survivors = CM-S and cerebral malaria nonsurvivors = CM-NS) using WHO, 2000 definitions, including healthy controls (HC) enroled from the hospital's blood bank. Categorical and numerical variables were analysed by applying appropriate statistical test using Stata 11.0 software. A total of 139 subjects (14 HC, 25 MM, 29 NCSM, 44 CM-S and 27 CM-NS) were included in this preliminary investigation. Serum levels of total human Tau were detected in 0% HC, 4.0% MM, 20.7% NCSM, 43.2% CM-S and 48.2% CM-NS patients. Compared to MM, percent Tau detection was significantly higher among severe malaria patients (p = 0.001). Further, compared to NCSM,% Tau detection was significantly higher in CM-S patients (Chi 2 = 3.9, p = 0.048) & CM-NS patients (Chi 2 = 4.7, p = 0.030). Percent Tau detection was also significantly higher among severe malaria cases presenting with multiple complications compared to those without multiple complications (p = 0.006). ROC analysis of serum Tau levels (pg/ml) revealed a fair AUC value (0.75) to distinguish CM-NS group (but not CM-S) from NCSM group. In conclusion, serum percent detection of total human Tau is associated with axonal damage among patients with different degree of P. falciparum malaria severity in Central India.
HC – healthy controls, MM – mild malaria, CMS – cerebral malaria survivors, CMNS – cerebral malar... more HC – healthy controls, MM – mild malaria, CMS – cerebral malaria survivors, CMNS – cerebral malaria non-survivors. Box plots represent medians and 25and 75percentiles. Bars mark the 10and 90percentiles, and outliers are plotted as points. MM versus CMS and CMNS: *** p < 0.05, $$$ p < 0.0045 bonferroni adjustment (alpha = 0.05/11), CMS versus CMNS: +++ p < 0.05, ### p < 0.0045 bonferroni adjustment (alpha = 0.05/11).<b>Copyright information:</b>Taken from "Plasma IP-10, apoptotic and angiogenic factors associated with fatal cerebral malaria in India"http://www.malariajournal.com/content/7/1/83Malaria Journal 2008;7():83-83.Published online 19 May 2008PMCID:PMC2405803.
Log median levels (pg/ml) of eighteen (18) biomarkers [IFN-γ, TNF-α, MIP-1α, IL-1β, IL-2, RANTES,... more Log median levels (pg/ml) of eighteen (18) biomarkers [IFN-γ, TNF-α, MIP-1α, IL-1β, IL-2, RANTES, IL-4, IL-5, G-CSF, IL-6, IL-9, Eotaxin, IL-12 (p70), IL-13, GM-CSF, IL-15, IL-17 and MCP-1 (MCAF)]. Biomarkers were quantified via Luminex™ from blood samples collected from patients at time of admission. HC – healthy controls, MM – mild malaria, CMS – cerebral malaria survivors, CMNS – cerebral malaria non-survivors. Box plots represent medians and 25and 75percentiles. Bars mark the 10and 90percentiles, and outliers are plotted as points. HC versus MM, CMS, and CMNS: *** p < 0.05, $$$ p < 0.0045 bonferroni adjustment (alpha = 0.05/18)<b>Copyright information:</b>Taken from "Plasma IP-10, apoptotic and angiogenic factors associated with fatal cerebral malaria in India"http://www.malariajournal.com/content/7/1/83Malaria Journal 2008;7():83-83.Published online 19 May 2008PMCID:PMC2405803.
Tropical Medicine & International Health, 2013
We report for the first-time detection of Plasmodium ovale in central India. From 2010, all hospi... more We report for the first-time detection of Plasmodium ovale in central India. From 2010, all hospitalised suspected malaria cases at the malaria clinic of the Regional Medical Research Centre for Tribals in Bastar district, central India, were screened. Plasmodium species were identified by microscopy and species-specific nested PCR of 18s rRNA. Of 256 enrolled cases of confirmed P. falciparum malaria by microscopy, P. ovale infection was detected in three cases (1.2%) by PCR and sequencing. Of these three cases, one had cerebral malaria and another had severe malaria anaemia. In both of these cases, P. ovale infection was mixed with P. falciparum, while in third case the infection was mixed with both P. falciparum and P. vivax. Phylogenetic analysis revealed that these isolates showed closed homology with West African genotypes. All three hospitalised patients were originally residents of remote inaccessible forest villages and never moved out of their residence. This finding also has implications in malaria control and elimination as P. ovale causes relapses. This study highlights the need of molecular diagnosis of malaria species for appropriate treatment and control.
Background Plasmodium falciparum in a subset of patients can lead to cerebral malaria (CM), a maj... more Background Plasmodium falciparum in a subset of patients can lead to cerebral malaria (CM), a major contributor to malaria-associated mortality. Despite treatment, CM mortality can be as high as 30%, while 10% of survivors of the disease may experience short- and long-term neurological complications. The pathogenesis of CM is mediated by alterations in cytokine and chemokine homeostasis, inflammation as well as vascular injury and repair processes although their roles are not fully understood. The hypothesis for this study is that CM-induced changes in inflammatory, apoptotic and angiogenic factors mediate severity of CM and that their identification will enable development of new prognostic markers and adjunctive therapies for preventing CM mortalities. Methods Plasma samples (133) were obtained from healthy controls (HC, 25), mild malaria (MM, 48), cerebral malaria survivors (CMS, 48), and cerebral malaria non-survivors (CMNS, 12) at admission to the hospital in Jabalpur, India. P...
Cerebral malaria (CM) is one of the most severe forms of P. falciparum infection, with an associa... more Cerebral malaria (CM) is one of the most severe forms of P. falciparum infection, with an associated high case-fatality rate. Angiopoietins (ANG-1 and ANG-2) are important biomarkers of endothelial activation and dysfunction. This study was carried out in Maharani Hospital and associated Medical College, Jagdalpur, CG, Central India from 2010 to 2014. Based on the treatment recovery patterns, cases (n = 65) were classified as mild malaria with rapid recovery (MM-RR), n= 14; non-cerebral severe malaria with moderately fast recovery (NCSM-MFR), n= 9; CM survivors with slow recovery (CMS-SR), n= 36 and deteriorated CM non-survivors (Det-CMNS), n= 6. Plasma levels (pg/ml) of ANG-1 and ANG-2 were measured by ELISA in all the samples at the time of hospital admission and 48 hours of treatment. Levels were also measured in available samples at the third time point (time of discharge for survivors or 72 hours post-treatment in fatal cases). Data analysis was done by appropriate statistical tests using Stata 11.0 and SPSS 25.0 software. At the time of admission, ANG-2 and ratios of ANG-2/ANG-1 significantly distinguished Det-CMNS cases from MM-RR and NCSM-MFR cases with good AUC scores (0.8-0.9). Further, Det-CMNS cases could also be distinguished from MM-RR, NCSM-MFR, and CMS-SR cases by ANG-2 (AUC scores 0.9) and ratios of ANG-2/ANG-1 (AUC: 0.8-0.9) at 48 hours of treatment. Paired analysis of sequential measurement of angiopoietins revealed that compared to admission levels, the ratios of ANG-2/ANG-1 significantly declined 48 hours after treatment in MM-RR (p= 0.041), NCSM-MFR (p= 0.050), and CMS-SR (p= 0.0002) cases but not in cases of Det-CMNS (p= 0.916). In conclusion, plasma levels of ANG-2 and ratios of ANG-2/ANG-1 may serve as good biomarkers to distinguish the malaria severity at the time of hospital admission and recovery patterns upon treatment in Central India.
Background & objectives: Malaria is a major public health problem in many states of the country, ... more Background & objectives: Malaria is a major public health problem in many states of the country, particularly, in Madhya Pradesh where both Plasmodium vivax and P. falciparum are endemic. Although many studies have been conducted to investigate risk factors for malaria, but only a few have examined household and socio-economic risk factors. The present study was, therefore, undertaken to explore the relationship of different socio-demographic, socio-economic and behavioural risk factors with malaria prevalence in tribal areas of Madhya Pradesh, India. Methods: This study was undertaken in all 62 villages of Bargi Primary Health Centre from May 2005 to June 2008. These villages comprised 7117 households with an average family size of five members. fortnightly fever surveys were conducted in all villages to assess prevalence of malaria infection in the community. The distinct univariate and multivariate logistic regression models were fitted on the data set. Results: The important soc...
The risk factors for cerebral malaria (CM) and the wide variation in clinical manifestations of m... more The risk factors for cerebral malaria (CM) and the wide variation in clinical manifestations of malaria are poorly understood. Recent studies indicate that interferon gamma inducible chemokine, CXCL10, is a strong predictor of both human and experimental cerebral malaria. Increased plasma and cerebrospinal fluid levels of CXCL10 were tightly associated with fatal CM in Indian and Ghanaian patients. In the present study, we hypothesized that in a subset of malaria patients, CM susceptibility is associated with variation in CXCL10 expression. We determined whether polymorphisms in the CXCL10 gene promoter region played a role in the clinical status of malaria patients and addressed the genetic basis of CXCL10 expression during malaria infection. Following extensive bioinformatics analyses, two reported single nucleotide polymorphisms in the CXCL10 promoter (2135G.A [rs56061981] and 21447A.G [rs4508917]) were identified among 66 CM and 69 non-CM Indian patients using PCR-restriction fragment length polymorphism assay. Individuals with the 21447(A/G) genotype were susceptible to CM (adjusted odds ratio [AOR] = 2.60, 95% CI = 1.51-5.85, p = 0.021). In addition, individuals with the 21447(A/G) genotype had significantly higher plasma CXCL10 levels than individuals with the 21447(A/A) genotype. Stratifying patients according to gender, the observed association of CM with over expression of CXCL10 were more pronounced in males than in female patients (AOR = 5.47, 95% CI = 1.34-22.29, p = 0.018). Furthermore, 2135G.A polymorphism conferred a decreased risk of CM among males (AOR = 0.19, 95% CI = 0.05-0.78, p = 0.021). Polymorphisms in the CXCL10 gene promoter sequence were associated with increased CXCL10 production, which is linked to severity of CM. These results suggest that the 21447A.G polymorphism in CXCL10 gene promoter could be partly responsible for the reported variation underlying severity of CM outcomes particularly in males.
Plasmodium falciparum in a subset of patients can lead to a diffuse encephalopathy known as cereb... more Plasmodium falciparum in a subset of patients can lead to a diffuse encephalopathy known as cerebral malaria (CM). Despite treatment, mortality caused by CM can be as high as 30% while 10% of survivors of the disease may experience short-and long-term neurological complications. The pathogenesis of CM involves alterations in cytokine and chemokine expression, local inflammation, vascular injury and repair processes. These diverse factors have limited the rate of discovery of prognostic predictors of fatal CM. Identification of reliable early predictors of CM severity will enable clinicians to adjust this risk with appropriate management of CM. Recent studies revealed that elevated levels of CXCL10 expression in cerebrospinal fluid and peripheral blood plasma independently predicted severe and fatal CM. CXCR3, a promiscuous receptor of CXCL10, plays an important role in pathogenesis of mouse model of CM. In this study the role of corresponding CXCR3 ligands (CXCL11, CXCL10, CXCL9 & CXCL4) in fatal or severe CM was evaluated by comparing their levels in 16 healthy control (HC), 26 mild malaria (MM), 26 cerebral malaria survivors (CMS) and 12 non-survivors (CMNS) using enzyme linked immunosorbent assay (ELISA). Levels of CXCL4 and CXCL10 were significantly elevated in CMNS patients (p < 0.05) when compared with HC, MM and CMS. Elevated plasma levels of CXCL10 and CXCL4 were tightly associated with CM mortality. Receiver Operating Characteristic (ROC) curve analysis revealed that CXCL4 and CXCL10 can discriminate CMNS from MM (p < 0.0001) and CMS (p < 0.0001) with an area under the curve (AUC) = 1. These results suggest that CXCL4 and CXCL10 play a prominent role in pathogenesis of CM associated death and may be used as functional or surrogate biomarkers for predicting CM severity.
Background The mechanisms underlying the pathogenesis of cerebral malaria (CM) syndrome are not w... more Background The mechanisms underlying the pathogenesis of cerebral malaria (CM) syndrome are not well understood. Previous studies have shown a strong association of inflammatory chemokines, apoptotic markers and angiogenic molecules with CM ...
Background The mechanisms underlying the pathogenesis of cerebral malaria (CM) syndrome are not w... more Background The mechanisms underlying the pathogenesis of cerebral malaria (CM) syndrome are not well understood. Previous studies have shown a strong association of inflammatory chemokines, apoptotic markers and angiogenic molecules with CM ...
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