Epidemiology of scrub typhus and other rickettsial infections (2018-22) in the hyper-endemic setting of Mizoram, North-East India.

BACKGROUND: In the past decade, scrub typhus cases have been reported across India, even in regions that had no previous history of the disease. In the North-East Indian state of Mizoram, scrub typhus cases were first recorded only in 2012. However, in the last five years, the state has seen a substantial increase in the scrub typhus and other rickettsial infections. As part of the public health response, the Mizoram Government has integrated screening and line listing of scrub typhus and other rickettsial infections across all its health settings, a first in India. Here we detail the epidemiology of scrub typhus and other rickettsial infections from 2018-2022, systematically recorded across the state of Mizoram. METHODOLOGY/PRINCIPAL FINDINGS: The line-listed data positive for scrub typhus and other rickettsial infections identified by rapid immunochromatographic test and/or Weil-Felix test from 2018-22 was used for the analysis. During this period, 22,914 cases of rickettsial infections were recorded, out of which 19,651 were scrub typhus cases. Aizawl is the worst affected, with 10,580 cases (46.17%). The average incidence of rickettsial infections is 3.54 cases per 1000 persons-year, and the case fatality rate is 0.35. Only ∼2% of the reported scrub typhus cases had eschar. Multivariate logistic regression analysis indicate patients with eschar (aOR = 2.5, p<0.05), occupational workers [farmers (aOR:3.9), businessmen (aOR:1.8), construction workers (aOR:17.9); p<0.05], and children (≤10 years) (aOR = 5.4, p<0.05) have higher odds of death due to rickettsial infections. CONCLUSION: The integration of systematic surveillance and recording of rickettsial diseases across Mizoram has shed important insights into their prevalence, morbidity, and mortality. This study underscores the importance of active surveillance of rickettsial infections across India, as the burden could be substantially higher, and is probably going undetected.

Seroprevalence of scrub typhus and other rickettsial diseases among the household rodents of Mizoram, North-East India.

In the last decade, scrub typhus, a zoonotic disease has emerged as a major health concern in Mizoram, a North-East Indian state that shares international borders with Myanmar and Bangladesh. Mizoram is a biodiversity hotspot and >85% of the state is under forest cover, which provides an ideal ecological niche for the rodents and mites to transmit scrub typhus and other rickettsial infections. Using the Weil-Felix test, a serosurvey of household rodents from 41 villages spread across all the 11 districts in Mizoram was undertaken to gather important insights on their role in disease transmission. Furthermore, the chigger and flea indexes were calculated from the captured rodents. The 163 rodents captured belonged to five species; the highest numbers were from Rattus tanezumi (87), followed by Rattus rattus (41), Mus musculus (17), Suncus murinus (16), and Bandicota bengalensis (2). The rickettsial seropositivity of the captured rodents was 66.26% (108 out of 163 were positive). Among the 163 rodents, sera of 75 (46.01%), 61 (37.42%), and 73 (44.78%) were reactive to OXK, OX19, and OX2 antigens, respectively. The chigger and flea index were 17.92 and 0.16, respectively. Overall, the study has given important insights into the risk of multiple rickettsial infections that household rodents could transmit in Mizoram. These findings indicate the need for the urgent implementation of effective rodent control strategies in Mizoram.

Cisplatin- and dietary ascorbic acid-mediated changes in the mitochondria of Dalton's lymphoma-bearing mice.

Cisplatin treatment caused a significant increase in the life span of ascites Dalton's lymphoma (DL) Tumor-bearing (TB) mice. However, as compared to cisplatin (CP) alone, combination treatment with ascorbic acid plus CP resulted in better therapeutic efficacy against murine DL. Cisplatin treatment of TB mice resulted in the appearance of thickened and irregular arrangement of mitochondrial cristae in the liver, kidney and DL tumor cells. Combination treatment of the hosts with ascorbic acid and CP lessened deformities in the mitochondria of liver and kidney, while in tumor cells, this increased the formation of vacuoles and disruption in mitochondrial cristae. Cisplatin treatment decreased the succinate dehydrogenase (SDH) activity in the mitochondria of kidney and DL cells and combination treatment caused further decrease in SDH activity in kidney and DL cells during 24-48 h of treatment. After CP treatment, the protein content in the mitochondria of these tissues decreased, and during combination treatment, it showed significant improvement. Mitochondrial lipid peroxidation (LPO) increased in these tissues after CP treatment. However, combination treatment significantly decreased mitochondrial LPO in liver and kidney but increased in DL cells. This increase in mitochondrial LPO in DL cells and decrease in liver and kidney could play an important role in the antitumor activity of combination treatment and at the same time reduce CP-induced toxicity in the host. However, further study may be desirable to explore some aspects of the mechanism(s) involved in these changes in mitochondria.

Cyclophosphamide and ascorbic acid-mediated ultrastructural and biochemical changes in Dalton's lymphoma cells in vivo.

Cyclophosphamide, an antineoplastic drug effective against a wide variety of cancers is cytotoxic to normal cells also. Ascorbic acid (vitamin C) at higher concentrations possesses cytotoxic effects and it can also enhance the cytotoxicity of 5-fluorouracil in a dose-dependent manner in mouse lymphoma. In the present study, effect of cyclophosphamide treatment alone and in combination with ascorbic acid in vivo on the ultrastructure and some biochemical changes in Dalton's lymphoma tumor cells were investigated. Cyclophosphamide treatment causes disappearance of cell membrane processes, thickening and reduction in the number of mitochondrial cristae as well as the manifestation of rounded shape of mitochondria. The combination treatment with ascorbic acid plus cyclophosphamide caused further changes in tumor cells showing disintegration in the cell surface membrane, disruption in the nuclear membrane and roundish mitochondria with reduction and disruption in the mitochondrial cristae. The observed ascorbic acid plus cyclophosphamide-mediated decrease in reduced glutathione (GSH) in tumor cells may play an important role in the antitumor activity of cyclophosphamide by weakening cellular antioxidant-mediated defense mechanism, thereby increasing tumor cell's susceptibility to cell death. The cyclophosphamide-mediated decrease in lactate dehydrogenase activity in tumor cells and simultaneous increase in ascites supernatant may possibly indicate alteration in the membrane permeability of tumor cells for lactate dehydrogenase as well as tumor cell injury. Further investigation should determine detailed mechanism(s) involved in cyclophosphamide-induced ultrastructural and biochemical changes in tumor cells.

Structural and biochemical changes in mitochondria after cisplatin treatment of Dalton's lymphoma-bearing mice.

Cisplatin treatment of tumor-bearing mice and analysis of ultrastructural features of mitochondria in the kidney and Dalton's lymphoma cells showed the appearance of more roundish mitochondria with thickened membranes. It also caused the reduction in the number and irregularity in the shape of cristae and formation of vacuoles in the mitochondria. After cisplatin treatment, decreased level of protein, succinate dehydrogenase activity, and increased level of lipid peroxidation were noted in Dalton's lymphoma tumor cells and kidney. Cisplatin-mediated decrease in SDH activity, GSH level and an increase in LPO in the mitochondria of kidney could play an important role to produce nephrotoxicity. However, in DL cells, decrease in cellular GSH could be noteworthy than mt-GSH, along with decrease in SDH activity and increase in LPO in the cisplatin-mediated anticancer activity. These changes could play an important role to produce both the cisplatin-mediated effects i.e. anticancer activity and nephrotoxicity. Cisplatin-induced biochemical and ultrastructural changes in mitochondria after cisplatin treatment should be an important factor in the development of biochemical injury in mitochondria and affecting the overall metabolism in the cells. The findings from the present studies indicate multilevel effect of cisplatin in the cells and do support the earlier view that mitochondria could be a critical target in cisplatin-mediated anticancer activity and toxicity in the hosts.