The contamination of arsenic in surface water and groundwater across different regions of the world is caused due to both natural and anthropogenic origins. Arsenic in drinking water sources causes several adverse effects in humans. Worldwide, more than 230 million people are exposed to arsenic, including approximately 180 million people in South Asia. The contamination of groundwater has been identified as a significant threat to the well-being of individuals. Prolonged and excessive consumption of inorganic arsenic in drinking water has resulted in gastrointestinal disorders, respiratory effects, arsenicosis, and immunotoxicity. The toxic effects of arsenic contamination may ultimately lead to the manifestation of fatal illnesses such as skin and various types of cancers. Moreover, chronic arsenic exposure in visceral leishmaniasis-endemic regions may contribute to altered immune responses and reduced treatment effectiveness in affected patients. The high health risk of arsenic contamination highlights the urgent need to minimize arsenic contamination from drinking water sources. In this review, the authors summarize the major sources of arsenic contamination in water, health impacts and its remediation methods.
Oncogenic viruses, including Epstein-Barr virus (EBV), Human Papillomavirus (HPV), Kaposi's Sarcoma-Associated Herpesvirus (KSHV), Hepatitis B Virus (HBV), Merkel Cell Polyomavirus (MCPyV), Human T-cell Lymphotropic Virus (HTLV-1), and Hepatitis C Virus (HCV), are significant contributors to cancer development, each through distinct mechanisms. EBV is recognised for its association with cancers such as Burkitt lymphoma and nasopharyngeal carcinoma. High-risk types of HPV are primarily connected to cervical cancer. KSHV plays a crucial role in the development of Kaposi's sarcoma, especially among individuals with compromised immune systems. Both HBV and HCV are implicated in liver cancer due to chronic infections and resultant inflammation. MCPyV is linked to aggressive skin cancers, while HTLV-1 can lead to leukemia and various neurological complications. Collectively, these viruses account for approximately 20% of all cancers globally, providing valuable insights into cancer pathogenesis and potential treatment avenues. Effective management of these viruses includes the use of vaccines such as Gardasil for HPV and antiviral medications for HBV and HCV. Treatment options for cancers associated with EBV, KSHV, and MCPyV encompass targeted therapies and surgical interventions. Preventive measures emphasise vaccination, safe practices to curb virus transmission, routine screenings, and maintaining a healthy lifestyle. Ongoing research and public health initiatives are vital for enhancing prevention and treatment strategies, particularly in high-risk and resource-limited settings. By deepening our understanding of these viruses, we can improve the development of targeted therapies and strive to reduce the global burden of cancer.
BACKGROUND:Treatment regimens and clinical outcomes for post-kala-azar dermal leishmaniasis (PKDL) vary across South Asia and Eastern Africa. We evaluated the skin target site pharmacokinetics (PK) of miltefosine, liposomal amphotericin B (LAmB) and paromomycin and associated pharmacodynamics (PD) on skin parasite reduction and lesion healing, to determine PK/PD factors driving regional differences in clinical outcomes. METHODS:In South Asia, participants (n = 126) received LAmB alone or with miltefosine. In Eastern Africa, participants (n = 110) received LAmB or paromomycin with miltefosine. Skin drug concentrations were compared to the in vitro EC50 of Leishmania donovani to assess PK target attainment, then correlated with skin parasite load and lesion score to evaluate pharmacokinetic-pharmacodynamic (PK-PD) relationships. RESULTS:Antileishmanial drug distribution varied in skin. Miltefosine showed the highest skin-to-plasma ratio, with medians of 1.19 (IQR: 0.78-1.88) in South Asia vs. 1.58 (1.1-2.08) in Eastern Africa (P < 0.05). Combining paromomycin or LAmB with miltefosine improved PK target attainment and reduced variability. In South Asia, macular or mixed (macular and papular/nodular) lesions predominated (93%) and were associated with ≥6-fold higher baseline parasite load and lesion score versus Eastern Africa, where papular and maculopapular lesions were more common (97%). By treatment end, parasite loads dropped ≥99% in both regions, with ≤7% above the transmission threshold. Lesion scores decreased by 11% in South Asia and 93% in Eastern Africa. CONCLUSIONS:Similar skin PK target attainment and relative parasite reduction were achieved for all regimens. Regional differences in parasite load and lesion score at baseline and lesion healing rates, suggest disease presentation is the primary factor affecting clinical outcomes.
Acute encephalitis syndrome (AES) is a major public health concern in India, especially in Muzaffarpur, Bihar, as outbreaks of this neurological disorder have brought on significant morbidity and mortality. It is usually characterized by sudden fever, seizures, confusion, and altered mental status in children along with infectious agents, environmental factors, and malnutrition. It is evident during litchi harvest (April-June), affecting malnourished children from poor families. Among 622 AES cases from May till July 2019; a significant majority were found to have higher mortality and morbidity indices among female Scheduled Caste children. Access barriers in the social and cultural context delayed health care in the event of morbidity. Earlier speculation about associating litchi intake was set aside as most of affected children stayed far from orchards. Clinically, it manifests with fever starting suddenly associated with seizures, altered sensorium, hypoglycemia, hyponatremia, and elevated biomarkers CPK, LDH, and ammonia. High humidity and inadequate mosquito net use are linked. However, these observational studies could not show laboratory evidence of vectors of Japanese encephalitis. Priorities in action include strengthening surveillance, nutrition, education, and better health care access.
Background:: Visceral leishmaniasis is a vector-borne immune-related disease that manifests mainly by lowering of immune protective T-helper-1 cells and onset of diseasepromoting T-helper-2 cells therefore the treatment of visceral leishmaniasis depends on boosting the immune status of the host. Methods:: In this study, two traditional medicinal plants Withania somnifera and Tinospora cordifolia were selected, and their whole plant extracts were used for treating visceral leishmaniasisinfected BALB/c mice. Observing the case of immune suppression and balance of Th-1/Th-2 dichotomy during visceral leishmaniasis in mind, the efficacy of these combined herbal drugs against visceral leishmaniasis infected mice was evaluated by monitoring the restoration of Thelper- 1 type protective immune response. Results:: To evaluate the effectiveness of these drugs against visceral leishmaniasis, reactive nitrogen species and reactive oxygen species were measured. Biochemical parameters were also performed from blood serum samples during this study, and normalized results were obtained in visceral leishmaniasis-infected mice treated with Withania somnifera and Tinospora cordifolia subgroup. The Amphotericin B treated subgroup was considered as standard positive control during the experiment. Conclusion:: A combination of herbal drugs resulted in a successful clearance of Leishmania parasite as well as increased immune protective T-helper-1 cells, suggesting these drugs as efficient antileishmanial agents.
Background:It is well recognized that parents play a central role in making decisions for their children. Understanding willingness of parents to vaccinate their children against COVID-19 is important as it helps to develop effective strategies for maximizing vaccination coverage. We aimed to evaluate parental acceptance regarding COVID-19 vaccination for children between 6 and 12 years of age in India. Methods:A mixed-method study (March-September 2023) employed a structured questionnaire and in-depth interviews with parents of school-going and non-school-going children across five purposively selected Indian states. Multistage random sampling was used for districts, schools, and students, while convenience sampling was applied for qualitative data. Multivariable logistic regression assessed factors influencing parental acceptance of COVID-19 vaccination, and qualitative analysis identified barriers and facilitators. Results:A total of 2017 parents participated in the study. The overall parental acceptance to vaccinate their children against COVID-19 was 76.4%. Multivariate logistic regression analysis showed that parents who were literate (p = 0.004), not vaccinated against COVID-19 (p = 0.012), had less than or equal to four family members (p < 0.001) and a history of COVID-19 infection in the family (p = 0.036) were less likely to accept the COVID-19 vaccine for their children. Key barriers to vaccination included uncertainty over the protection provided by the vaccine, fear about side effects, and misconceptions about the vaccine whereas belief in the vaccine, perceived severity of COVID-19 disease, and bundling with routine vaccination were the key facilitators. Conclusion:These findings highlight the importance of increasing adult COVID-19 vaccination. Developing policies focusing on parents with higher literacy, staying in smaller families, and previous COVID-19 infection among family members will help to increase the vaccine uptake among children. Interventions for the integration of these vaccines with routine immunization or availability at schools may help in increasing COVID-19 vaccine acceptance.
Visceral leishmaniasis (VL) is a vector-borne disease that progress mainly by lowering of immune protective cells Th1 and the appearance of cells Th2 that promote illness therefore the treatment of this disease relies on improving the immune condition of the host. Currently used treatment options of VL are Amphotericin B (AmB) and its liposomal formulation i.e., Ambisome. But these treatment options are not safe as these drugs have many side effects and limitations like hepatotoxicity, nephrotoxicity, VL relapse and PKDL conversion. This has prompted the search for alternative treatment options amongst herbal drugs; Thus, This study investigated Tinospora cordifolia and Withania somnifera's antileishmanial potentia, either in combination or alone. In vivo experiments demonstrated a substantial decrease in BALB/c mice in the spleen parasitic burden. Moreover, the treatment effectively modulated immune response of the host, leading to Th1 polarization, crucial for eliminating Leishmania donovani. This method not only targets the parasite but also fortifies the immune system, offering a safer, cost-effective alternative to current therapies for Visceral leishmaniasis, which are often limited by toxicity and resistance.
Lipid metabolism plays a decisive role in host-pathogen interactions and immune regulation, with apolipoproteins (Apo) being central to this process. However, their role in leishmaniasis remains unexplored. Herein, we deliberate the immunoregulatory function of ApoA1 during Leishmania donovani infection using THP-1-derived macrophages alone and in combination with T lymphocytes derived from human PBMC. We found low serum ApoA1 levels in active VL and PKDL than in healthy controls. It was shown that direct interaction of ApoA1 with ABCA1 (ATP-binding cassette transporter A1) on macrophages promotes cholesterol efflux, reflected by increased HDL levels and reduced total cellular cholesterol. This phenomenon was associated with reduced Leishmania infectivity and its downstream signaling in macrophages, i.e., downregulation of PPAR-γ and the endoplasmic reticulum-stress marker CHOP. Additionally, ApoA1 in the presence of extracellular HDL slightly promoted macrophage polarization towards M1, as indicated by increased expression of IL-12 and iNOS2 or nitric oxide production, alongside reduced expression of M2 phenotype-associated markers, including IL-10 and arginase. In co-culture with PBMC-derived T-cells, ApoA1-primed macrophages facilitated Th1 polarization, as demonstrated by increased IFN-γ and STAT1, and indirectly by reduced expression of Th2-specific markers (GATA-3 and IL-4). Overall, these results implicate ApoA1 as a vital immunomodulatory factor and potential therapeutic target in leishmaniasis.
BACKGROUND:Leishmaniasis continues to pose a significant global health challenge, exacerbated by the increasing resistance to current therapeutic agents such as miltefosine and amphotericin B. This growing resistance highlights the urgent need for alternative treatment strategies. In this context, phytomedicine has emerged as a promising avenue for novel antileishmanial therapies. In our previous study, the crude extract derived from neem (Azadirachta indica) leaves exhibited notable antileishmanial activity. Subsequent analysis using LC-MS/MS enabled the identification of bioactive constituents within the active fraction, including azadiradione (AZD), a drug with potential therapeutic effects unexplored against leishmaniasis. RESULTS:AZD exhibited dose-dependent growth inhibition along with structural disruption and DNA fragmentation in promastigotes with an IC50 of 17.09 μM. In silico docking and simulation with AZD identified Leishmania peroxidases (e.g., ascorbate peroxidase and tryparedoxin peroxidase) as probable molecular targets, with subsequent downregulation of their expression confirmed in vitro. The CC50 on human macrophages (MФs) and EC50 on intracellular amastigotes were determined as 56.32 μM and 11.67 μM for AZD, respectively. The dose-dependent reduction in MФs' infectivity demonstrates the drug potential of AZD against the pathogenic stage of Leishmania. However, the selectivity index (SI) of AZD was calculated as 4.83, indicating a moderate Leishmania-specific drug potential of AZD. The decrease in IL-10, IL-1β, and arginase expression and the increase in IL-12 and iNOS expression reinforce the immunoregulatory potential of AZD in favour of the host. Further investigations are required to optimize the dosage and improve the selectivity of AZD before proposing it for the treatment of Leishmania infection. CONCLUSION:This study demonstrated the novel findings related to the drug potential of AZD with defined Leishmania targets and host protective cytokine response. Studies on animal models may deliver further insights into its therapeutic potential.
BACKGROUND:Multiple organisms infect the host simultaneously in the case of coinfection. This study intended to determine the prevalence of viral hepatitis B in HIV/Asymptomatic VL co-infected patients and to identify the HBV genotype circulating in these patients in Bihar, India. METHODS:There were 96 archived samples with co-infection with HIV and asymptomatic VLpositivity included in this study. A real-time PCR test was performed to measure the load of HBV DNA, and a chemiluminescent immunoassay was performed to determine the level of HBsAg. RESULTS:Our study evaluated HIV and AVL co-infected patients with two coexisting genotypes of HBV and observed the expression of the B, C, and D genotypes. HBsAg levels correlated directly with HBV DNA levels in almost every case. CONCLUSION:For a better understanding of this disease, authors need approaches and strategies for improving the current diagnostic techniques, as well as studies focusing on vector control procedures and other operational tools.
Introduction: Dengue virus is considered an important mosquito-borne virus that currently poses a major health risk and belongs to the Flaviviridae family. The study was conducted to estimate the NS1 antigen and anti- dengue IgM antibody-based prevalence of dengue infection in Patna, Bihar and also to investigate the association of seasonal variation along with the gender-specific prevalence also. Methods: The study involved collection, classification, and analysis of laboratory-based data of blood sample a period of 5 years with reference to dengue infection. Results: During this period a total 7415 samples were referred to the laboratory for screening from different hospitals. Then data were analysed to determine the NS1 and IgM based prevalence against dengue virus. A total of 29.77% were found positive for NS1 and 21.71% were found positive for IgM. Further 64.17% males and 35.82% females were found NS1 positive. Similarly, 66.52 males and 33.48 females were found positive for IgM. Most of the dengue infection was reported in the post monsoon season. Conclusions: So, from study we can conclude that serological testing for presumptive identification of dengue infections is useful for prevention and monitoring the prevalence. Furthermore, a concerted effort is needed to create regional awareness among people in this area.
Scrub typhus is a disease caused by the bacteria Orientia tsutsugamushi, spread primarily by chiggers, which are larval mites. These mites are commonly found in Southeast Asia, including countries like India, Indonesia, and Thailand. The disease is often hard to diagnose because its symptoms—fever, headache, muscle pain, and stomach issues—are similar to other illnesses. A key sign of scrub typhus is an “eschar,” a sore that appears at the bite site. Without treatment, which typically involves antibiotics like doxycycline or azithromycin, the disease can lead to severe complications such as sepsis, shock, and multi-organ failure, with a high mortality rate. Scrub typhus has been documented in various regions, with historical records dating back to the 19th century in China. Despite advances in treatment regimen since World War II, no vaccine is available. Diagnostic methods include serological tests and PCR techniques to detect the bacteria. Preventive measures focus on avoiding areas where chiggers are prevalent and using insect repellent. Even if the scrub typhus fever has been reported from regions such as Japan to northern Australia and the Arabian Peninsula, Indian people from different parts are suffering from this endemic disease and doxycycline has become the drug of choice for the treatment of scrub typhus fever. Clinical diagnosis of scrub typhus and research related to this endemic disease must be assorted as the scrub typhus may become resistant to the current treatment regimen.
The rubella virus (RUV), cytomegalovirus (CMV), and herpes simplex virus (HSV) cause mild illness in immune-competent individuals, pregnant women, and fetus/newborns. The study estimated the prevalence of RUV, CMV, and HSV infection based on IgM antibody levels, and also investigated the association of seasonal variation.
Japanese Encephalitis Virus (JEV) is a flavivirus transmitted by mosquitoes and one of the foremost causes of viral encephalitis infection in Asia, predominantly occurring in children in rural areas. Initially isolated in Japan in 1924, JEV is largely spread by Culex mosquitoes, notably Culex tritaeniorhynchus and Culex gelidus, breeding in paddy fields. The virus has a zoonotic cycle with pigs as amplifying hosts and ardeid birds as reservoirs. JEV outbreaks reach their peak during the monsoon months (July–September). Severe encephalitis may occur with manifestations such as fever, vomiting, seizures, paralysis, and coma. The case fatality rate is approximately 30 %, and survivors can have long-term neurological complications. JEV invades the central nervous system by crossing the blood-brain barrier, causing neuroinflammation and neuronal damage. Diagnosis is made with serological tests and molecular tests. JEV is endemic in India, Nepal, China, Myanmar, Vietnam, and other Asian nations. In India, 1000–2500 cases occur each year, with underreporting suspected. Bihar is a focused area, with Muzaffarpur district having a high incidence. Control is based on vaccination and vector control. Four vaccines are available, but limited coverage underscores the necessity for increased immunization and surveillance.