Sequential dysregulated plasma levels of angiopoietins (ANG-2 and ratios of ANG-2/ANG-1) are associated with malaria severity and mortality among hospital admitted cases in South Bastar Region of Chhattisgarh, Central India.

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.

Serum levels of total human Tau associated with axonal damage among severe malaria patients in Central India.

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 non-survivors = 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 (Chi2 = 3.9, p = 0.048) & CM-NS patients (Chi2 = 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.

Burden of complicated malaria in a densely forested Bastar region of Chhattisgarh State (Central India).

BACKGROUND: A prospective study on severe and complicated malaria was undertaken in the tribal dominated area of Bastar division, Chhattisgarh (CG), Central India, with an objective to understand the clinical epidemiology of complicated malaria in patients attending at a referral hospital. METHODS: Blood smears, collected from the general medicine and pediatric wards of a government tertiary health care facility located in Jagdalpur, CG, were microscopically examined for malaria parasite from July 2010 to December 2013. The Plasmodium falciparum positive malaria cases who met enrollment criteria and provided written informed consent were enrolled under different malaria categories following WHO guidelines. PCR was performed to reconfirm the presence of P.falciparum mono infection among enrolled cases. Univariate and multivariate logistic regression analysis was done to identify different risk factors using STATA 11.0. RESULTS: A total of 40,924 cases were screened for malaria. The prevalence of malaria and P.falciparum associated complicated malaria (severe and cerebral both) in the hospital was 6% and 0.81%, respectively. P.falciparum malaria prevalence, severity and associated mortality in this region peaked at the age of > 4-5 years and declined with increasing age. P.falciparum malaria was significantly more prevalent in children than adults (P < 0.00001). Among adults, males had significantly more P.falciparum malaria than females (P < 0.00001). Case fatality rate due to cerebral malaria and severe malaria was, respectively, 32% and 9% among PCR confirmed mono P.falciparum cases. Coma was the only independent predictor of mortality in multivariate regression analysis. Mortality was significantly associated with multi-organ complication score (P = 0.0003). CONCLUSION: This study has revealed that the pattern of morbidity and mortality in this part of India is very different from earlier reported studies from India. We find that the peak morbidity and mortality in younger children regardless of seasonality. This suggests that this age group needs special care for control and clinical management.