Burden of Cerebral Malaria in Central India (2004–2007)

Jain, Vidhan; Nagpal, Avinash C.; Joel, Pradeep K.; Shukla, Man Mohan; Singh, Mrigendra P.; Gupta, Rajaneesh; Dash, A. P.; Mishra, Saroj K.; Udhayakumar, Venkatachalam; Stiles, Jonathan K.; Singh, Neeru

doi:10.4269/ajtmh.2008.79.636

Cited by 40 publications

(41 citation statements)

References 24 publications

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“…In India, CM is often associated with MOD, including malarial ARF (26). In this study, 31% of SM patients had more than two damaged organs, and ARF was the second most common cause of SM (see Fig.…”

Section: Discussionmentioning

confidence: 93%

Multifaceted Role of Heme during Severe Plasmodium falciparum Infections in India

et al. 2015

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f Several immunomodulatory factors are involved in malaria pathogenesis. Among them, heme has been shown to play a role in the pathophysiology of severe malaria in rodents, but its role in human severe malaria remains unclear. Circulating levels of total heme and its main scavenger, hemopexin, along with cytokine/chemokine levels and biological parameters, including hemoglobin and creatinine levels, as well as transaminase activities, were measured in the plasma of 237 Plasmodium falciparum-infected patients living in the state of Odisha, India, where malaria is endemic. All patients were categorized into well-defined groups of mild malaria, cerebral malaria (CM), or severe noncerebral malaria, which included acute renal failure (ARF) and hepatopathy. Our results show a significant increase in total plasma heme levels with malaria severity, especially for CM and malarial ARF. Spearman rank correlation and canonical correlation analyses have shown a correlation between total heme, hemopexin, interleukin-10, tumor necrosis factor alpha, gamma interferon-induced protein 10 (IP-10), and monocyte chemotactic protein 1 (MCP-1) levels. In addition, canonical correlations revealed that heme, along with IP-10, was associated with the CM pathophysiology, whereas both IP-10 and MCP-1 together with heme discriminated ARF. Altogether, our data indicate that heme, in association with cytokines and chemokines, is involved in the pathophysiology of both CM and ARF but through different mechanisms.

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Section: Discussionmentioning

confidence: 93%

Multifaceted Role of Heme during Severe Plasmodium falciparum Infections in India

et al. 2015

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“…This study utilized samples collected from a hospital study to assess the neurological deficits associated with CM patients in India. The study details have been reported previously (18,19). Here we provide brief details about the study site and study populations.…”

Section: Methodsmentioning

confidence: 99%

Evidence of Selective Sweeps in Genes Conferring Resistance to Chloroquine and Pyrimethamine in Plasmodium falciparum Isolates in India

Mixson‐Hayden

Jain

McCollum

et al. 2010

Antimicrob Agents Chemother

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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 essentially fixed, with 95% of the isolates harboring the pfcrt K76T mutation. Resistant genotypes of dhfr, dhps, and pfmdr-1 were found in 94%, 17%, and 77% of the isolates, respectively. Drugresistant genotypes were equally likely to be associated with cerebral malaria as with mild malaria. We found evidence of a selective sweep in pfcrt and, to a lesser degree, in dhfr, indicating high levels of resistance to chloroquine and evolving resistance to pyrimethamine. Microsatellites surrounding pfcrt indicate that the resistant genotypes (SVMNT) were most similar to those found in Papua New Guinea.

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“…Both Plasmodium vivax and P. falciparum are prevalent in this area, and P. falciparum transmission occurs primarily during the monsoon and post-monsoon seasons (July-January). Previous studies revealed that malaria is present in all age groups, with the highest prevalence occurring in children between 8-14 years of age [42,67].…”

Section: Study Sitesmentioning

confidence: 99%

“…The characteristics of randomly selected subjects are described in Table 1. These subjects were selected from a subset of a prospective study conducted in India [41,42]. The main complications in CM patients but absent in HC and MM were seizure (CMS 46%, CMNS 67%) and renal failure (CMS 19%, CMNS 17%).…”

Section: Patient Characteristicsmentioning

confidence: 99%

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CXCL4 and CXCL10 Predict Risk of Fatal Cerebral Malaria

et al. 2011

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Abstract. 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 shortand 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.

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Burden of Cerebral Malaria in Central India (2004–2007)

Cited by 40 publications

References 24 publications

Multifaceted Role of Heme during Severe Plasmodium falciparum Infections in India

Multifaceted Role of Heme during Severe Plasmodium falciparum Infections in India

Evidence of Selective Sweeps in Genes Conferring Resistance to Chloroquine and Pyrimethamine in Plasmodium falciparum Isolates in India

CXCL4 and CXCL10 Predict Risk of Fatal Cerebral Malaria

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