Burden of dengue, leishmaniasis and lymphatic filariasis in India and its states from 1990-2019: Analysis from the Global Burden of Disease study (GBD 2019).

Vector-borne diseases such as dengue, leishmaniasis, and lymphatic filariasis, constitute significant sources of illness, disability, and mortality among the poor and vulnerable in many countries around the world, including India. Based on the global burden of diseases, injuries, and risk factors study 2019, we analyse the burden of dengue, leishmaniasis, and lymphatic filariasis, in India from 1990 to 2019. Over this period, there was a reduction in the burden of lymphatic filariasis and leishmaniasis. Notably, dengue emerged as the most common vector-borne disease, exhibiting high fatality rate above 15 years of age and the highest DALY within 15-49 age group. Additionally, dengue cases surged substantially between 1990 and 2019. Leishmaniasis related mortality and DALY declined in the year 2019 compared to the year 1990, with high mortality and DALY in the 0-49-year-old age group. For lymphatic filariasis, DALY was more pronounce among those in the 15-49-year age group, which underwent reduction in 2019. Males had a higher burden in other vector-borne diseases than females, although females had a slightly elevated dengue burden. These findings highlight the evolving epidemiological trends related to vector-borne diseases in India, over the last three decades and underline the critical significance of sustained efforts for the elimination and control of vector-borne diseases.

Prevalence of soil-transmitted helminth infections in HIV patients: a systematic review and meta-analysis.

Soil-transmitted Helminth (STH) infections have been found associated with people living with human immunodeficiency virus (HIV) but little is known about the overall burden of STH coinfection in HIV patients. We aimed to assess the burden of STH infections among HIV patients. Relevant databases were systematically searched for studies reporting the prevalence of soil-transmitted helminthic pathogens in HIV patients. Pooled estimates of each helminthic infection were calculated. The odds ratio was also determined as a measure of the association between STH infection and the HIV status of the patients. Sixty-one studies were finally included in the meta-analysis, consisting of 16,203 human subjects from all over the world. The prevalence of Ascaris lumbricoides infection in HIV patients was found to be 8% (95% CI 0.06, 0.09), the prevalence of Trichuris trichiura infection in HIV patients was found to be 5% (95% CI 0.04, 0.06), the prevalence of hookworm infection in HIV patients was found to be 5% (95% CI 0.04, 0.06), and prevalence of Strongyloides stercoralis infection in HIV patients was found to be 5% (95% CI 0.04, 0.05). Countries from Sub-Saharan Africa, Latin America & Caribbean and Asia were identified with the highest burden of STH-HIV coinfection. Our analysis indicated that people living with HIV have a higher chance of developing Strongyloides stercoralis infections and decreased odds of developing hookworm infections. Our findings suggest a moderate level of prevalence of STH infections among people living with HIV. The endemicity of STH infections and HIV status both are partially responsible for the burden of STH-HIV coinfections.

A meta-analysis on the prevalence of Taenia solium and Taenia saginata infections in India.

Tapeworm infections in humans are considered to be a significant public health menace. Despite its public health importance, the data on tapeworm infection remains fragmented and underutilised. The present study reviews the overall burden and distribution of taeniasis and cysticercosis caused by Taenia solium and Taenia saginata in India by conducting a systematic review of the scientific literature based on Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Data from 19 eligible articles were analysed and the prevalence of T. solium-associated taeniasis/cysticercosis was found to be 11.06% (95% confidence interval [CI] 6.856 to 16.119) and the prevalence of T. saginata-associated taeniasis was found to be 4.7% (95% CI 3.301 to 6.301). This systematic review and meta-analysis provides a comprehensive analysis of the available literature on tapeworm infections and assesses the burden of Taenia infection from India, identifying areas of high prevalence requiring active surveillance and public health interventions.

Prevalence of Pregnancy Associated Malaria in India.

Malaria in pregnancy is a major public health concern. It results in impaired maternal health and adversely effects fetal and perinatal outcomes. The present systematic review was conducted to assess the prevalence, distribution and adverse pregnancy outcomes in malaria infected females in India. A comprehensive search and review of PubMed and Web of Science based on PRISMA guidelines was carried out to find articles reporting prevalence of malaria in pregnant women from India. Data from 16 studies were analyzed and prevalence of malaria among pregnant women in India was found to be 11.4 % (95 % CI: 7.3, 16.3). Prevalence of malaria among asymptomatic and symptomatic pregnant women was found to be 10.62% (95% CI: 6.05, 16.23) and 13.13% (95% CI: 7.2, 20.52), respectively. P. falciparum and P. vivax were both reported with in the same population. The geospatial distribution of malaria in pregnancy spanned over nine very populous states of India. The review also reported severe maternal and perinatal outcomes. Given the seriousness of malaria in pregnant women and its effects on the fetus and new-born, a stringent district wise guideline for early detection and prophylaxis in regions identified in this review will help in its better control.

Prevalence of Amoebiasis and Associated Complications in India: A Systematic Review.

PURPOSE: Intestinal protozoan parasites are responsible for diarrheal diseases causing significant morbidity and mortality. Entamoeba histolytica is the principle protozoan parasite associated with diarrheal infections. The infection is often associated with inaccessibility to clean drinking water and poor sanitary conditions in low- and middle-income countries including India. A comprehensive systematic review was performed to evaluate a reliable nationwide estimate for prevalence and geographic distribution of amoebiasis in India and the complications associated with it. METHODS: We used the PRISMA guidelines to perform a systematic review and meta-analysis of articles published between the year 2001-2020. Two English language databases PubMed and Web of Science were searched to achieve relevant studies. RESULTS: Initial searches resulted in 467 studies out of which 64 eligible articles involving data from 289,659 human subjects from 12 states and 4 union territories were included in the final analysis. Prevalence of amoebiasis ranged from 3-23% in asymptomatic population, 0.64-11% in symptomatic patients and 1-17.5% in HIV-infected patients. Highest prevalence was seen in Tamil Nadu, Andaman Nicobar Island and North East India. Extra intestinal invasion of Entamoeba histolytica leading to complications such as amoebic liver abscess, amoebic colitis, colonic perforation and ameboma were also reported. Such complications have the potential to increase healthcare burden and may prove to be fatal. CONCLUSION: Amoebiasis remains a significant public health issue in India responsible for diarrheal diseases causing significant morbidity and mortality. Entamoeba histolytica is the principle protozoan parasite associated with amoebiasis. Public health efforts should be directed towards its control and better diagnostic methods should be employed for distinguishing between pathogenic and non-pathogenic species of Entamoeba.

Global prevalence and distribution of coinfection of malaria, dengue and chikungunya: a systematic review.

BACKGROUND: Malaria, Dengue and Chikungunya are vector borne diseases with shared endemic profiles and symptoms. Coinfections with any of these diseases could have fatal outcomes if left undiagnosed. Understanding the prevalence and distribution of coinfections is necessary to improve diagnosis and designing therapeutic interventions. METHODS: We have carried out a systematic search of the published literature based on PRISMA guidelines to identify cases of Malaria, Dengue and Chikungunya coinfections. We systematically reviewed the literature to identify eligible studies and extracted data regarding cases of coinfection from cross sectional studies, case reports, retrospective studies, prospective observational studies and surveillance reports. RESULTS: Care full screening resulted in 104 publications that met the eligibility criteria and reported Malaria/Dengue, Dengue/Chikungunya, Malaria/Chikungunya and Malaria/Dengue/Chikungunya coinfections. These coinfections were spread over six geographical locations and 42 different countries and are reported more frequently in the last 15 years possibly due to expanding epidemiology of Dengue and Chikungunya. Few of these reports have also analysed distinguishing features of coinfections. Malaria/Dengue coinfections were the most common coinfection followed by Dengue/Chikungunya, Malaria/Chikungunya and Malaria/Dengue/Chikungunya coinfections. P. falciparum and P. vivax were the commonest species found in cases of malaria coinfections and Dengue serotype-4 commonest serotype in cases of dengue coinfections. Most studies were reported from India. Nigeria and India were the only two countries from where all possible combinations of coinfections were reported. CONCLUSION: We have comprehensively reviewed the literature associated with cases of coinfections of three important vector borne diseases to present a clear picture of their prevalence and distribution across the globe. The frequency of coinfections presented in the study suggests proper diagnosis, surveillance and management of cases of coinfection to avoid poor prognosis of the underlying etiology.

Prevalence and distribution of soil-transmitted helminth infections in India.

BACKGROUND: Understanding the prevalence of soil-transmitted helminth infections is necessary to plan control strategies and focus on highly endemic regions for preventive chemotherapy and improved sanitation facilities. India is known to be endemic for soil-transmitted helminth infections. METHODS: To understand the prevalence, spatial distribution and identify high-risk zones, a systematic search of published literature was carried out based on PRISMA guidelines from the year 2000 to 2015. RESULTS: A careful screening of the identified literature yielded 39 studies that reported the prevalence of soil-transmitted helminth infections from 19 different states of India. Ascaris lumbricoides was the most prevalent parasite. Higher than 50% prevalence was reported from six states. Nearly 90% studies reported the prevalence of more than one parasite species in the same sample population. CONCLUSION: This is the first study to comprehensively review the literature associated with soil-transmitted helminth infections from India giving a clear idea of its prevalence, distribution and high endemic areas.

Anti-diabetic potential of Catharanthus roseus Linn. and its effect on the glucose transport gene (GLUT-2 and GLUT-4) in streptozotocin induced diabetic wistar rats.

BACKGROUND: Catharanthus roseus is an important Ayurvedic medication in traditional medicine. It is potentially used in countries like India, South Africa, China and Malaysia for the healing of diabetes mellitus. Although, the molecular mechanisms behind this effect are yet to be exclusively explored. Due to the great antidiabetic and hyperlipidemic potential of c. roseus, we hypothesized that the insulin mimetic effect of ethanolic extract of c. roseus might add to glucose uptake through improvement in the expression of genes of the glucose transporter (GLUT) family messenger RNA (mRNA) in liver. METHODS: STZ-induced diabetic rats treated by ethanolic extract of c. roseus 100 mg/kg and 200 mg/kg; and one group treated with Metformin (100 mg/kg). After final administration of treatment of 4 weeks, blood samples were collected under fasting conditions, and the body weights (BWs) were measured. Total RNA from liver was extracted with the Qiagen RNEasy Micro kit (GERMANY) as described in the manufacturer's instructions. First-strand complementary DNA (cDNA) was synthesized at 40 °C by priming with oligo-dT12-18 (Invitrogen, USA) and using Super ScriptII reverse transcriptase according to the protocol provided by the manufacturer (Invitrogen, USA). Real-time polymerase chain reaction (PCR) amplifications for GLUT-4 (gene ID: 25139) were conducted using Light-Cycler 480 (Roche, USA) with the SyBr® I nucleic acid stain (Invitrogen, USA) according to the manufacturer's instructions. Polymerase chain reaction products of ß-actin primer gene were used as an internal standard. RESULTS: The proposed study was framed to look at the antidiabetic efficacy of ethanolic extract of c. roseus and an expression of GLUT-2 and GLUT-4 gene in streptozotocin induced diabetic wistar rats. The doses were administered orally at a rate of 100 and 200 mg/kg and detrain the glucose transport system in liver for 4 weeks. The observed results showed a good positive correlation between intracellular calcium and insulin release levels in isolated islets of Langerhans. The supplementation of ethanolic extract of c. roseus significantly amplified the expression of GLUT gene mRNA by Real Time PCR in liver of diabetic rats. CONCLUSIONS: We conclude that the observed antidiabetic effect of c. roseus on STZ induced diabetes was a result of complex mechanisms of GLUT gene mRNA expression. The findings are very encouraging and greatly advocate its candidature for the design of a novel herbal drug to cure deadly diabetes.

Leishmaniasis in the middle East: incidence and epidemiology.

Leishmaniasis is a major health problem worldwide, with several countries reporting cases of leishmaniasis resulting in loss of human life or a lifelong stigma because of bodily scars. The Middle East is endemic for cutaneous leishmaniasis, with countries like Syria reporting very high incidence of the disease. Despite several countries establishing national control programs for containing the sandfly vector and treatment of infection, the disease continues to spread. In addition to the endemicity of the region for leishmaniasis, the Middle East has seen a great deal of human migration either for earning of livelihood or due to political upheaval in the region. These factors contribute to the spread and proliferation of the causative species Leishmania and its sandfly host. This review discusses the current epidemiological scenario in Iraq, Syria, Saudi Arabia, and Jordan, emphasizing the number of cases reported, vector species, Leishmania species, and treatment available. The data is primarily from WHO reports for each country and current and old literature.

Distinct assembly profiles of HLA-B molecules.

MHC class I polymorphisms are known to influence outcomes in a number of infectious diseases, cancers, and inflammatory diseases. Human MHC class I H chains are encoded by the HLA-A, HLA-B, and HLA-C genes. These genes are highly polymorphic, with the HLA-B locus being the most variable. Each HLA class I protein binds to a distinct set of peptide Ags, which are presented to CD8(+) T cells. HLA-disease associations have been shown in some cases to link to the peptide-binding characteristics of individual HLA class I molecules. In this study, we show that polymorphisms at the HLA-B locus profoundly influence the assembly characteristics of HLA-B molecules and the stabilities of their peptide-deficient forms. In particular, dependence on the assembly factor tapasin is highly variable, with frequent occurrence of strongly tapasin-dependent or independent allotypes. Several polymorphic HLA-B residues located near the C-terminal end of the peptide are key determinants of tapasin-independent assembly. In vitro refolded forms of tapasin-independent allotypes assemble more readily with peptides compared to tapasin-dependent allotypes that belong to the same supertype, and, during refolding, reduced aggregation of tapasin-independent allotypes is observed. Paradoxically, in HIV-infected individuals, greater tapasin-independent HLA-B assembly confers more rapid progression to death, consistent with previous findings that some HLA-B allotypes shown to be tapasin independent are associated with rapid progression to multiple AIDS outcomes. Together, these findings demonstrate significant variations in the assembly of HLA-B molecules and indicate influences of HLA-B-folding patterns upon infectious disease outcomes.

T cell ageing: effects of age on development, survival & function.

Age associated decline of the immune system continues to be a major health concern. All components of innate and adaptive immunity are adversely affected to lesser or greater extent by ageing resulting in an overall decline of immunocompetence. As a result in the aged population, there is increased susceptibility to infection, poor responses to vaccination, and increased incidence of autoreactivity. There is an increasing focus on the role of T cells during ageing because of their impact on the overall immune responses. A steady decline in the production of fresh naïve T cells, more restricted T cell receptor (TCR) repertoire and weak activation of T cells are some of the effects of ageing. In this review we summarize our present understanding of the effects of ageing on naïve CD4 T cells and potential approaches for therapeutic interventions to restore protective immunity in the aged population.

Voltage gated calcium channels negatively regulate protective immunity to Mycobacterium tuberculosis.

Mycobacterium tuberculosis modulates levels and activity of key intracellular second messengers to evade protective immune responses. Calcium release from voltage gated calcium channels (VGCC) regulates immune responses to pathogens. In this study, we investigated the roles of VGCC in regulating protective immunity to mycobacteria in vitro and in vivo. Inhibiting L-type or R-type VGCC in dendritic cells (DCs) either using antibodies or by siRNA increased calcium influx in an inositol 1,4,5-phosphate and calcium release calcium activated channel dependent mechanism that resulted in increased expression of genes favoring pro-inflammatory responses. Further, VGCC-blocked DCs activated T cells that in turn mediated killing of M. tuberculosis inside macrophages. Likewise, inhibiting VGCC in infected macrophages and PBMCs induced calcium influx, upregulated the expression of pro-inflammatory genes and resulted in enhanced killing of intracellular M. tuberculosis. Importantly, compared to healthy controls, PBMCs of tuberculosis patients expressed higher levels of both VGCC, which were significantly reduced following chemotherapy. Finally, blocking VGCC in vivo in M. tuberculosis infected mice using specific antibodies increased intracellular calcium and significantly reduced bacterial loads. These results indicate that L-type and R-type VGCC play a negative role in M. tuberculosis infection by regulating calcium mobilization in cells that determine protective immunity.

Protective immunity to Mycobacterium tuberculosis infection by chemokine and cytokine conditioned CFP-10 differentiated dendritic cells.

BACKGROUND: Dendritic cells (DCs) play major roles in mediating immune responses to mycobacteria. A crucial aspect of this is the priming of T cells via chemokines and cytokines. In this study we investigated the roles of chemokines RANTES and IP-10 in regulating protective responses from Mycobacterium tuberculosis (M. tb) 10 kDa Culture Filtrate Protein-10 (CFP-10) differentiated DCs (CFP10-DCs). METHODS AND FINDINGS: Infection of CFP10-DCs with mycobacteria down-modulated RANTES and IP-10 levels. Pathway specific microarray analyses showed that in addition to RANTES and IP-10, mycobacteria infected CFP10-DCs showed reduced expression of many Th1 promoting chemokines and chemokine receptors. Importantly, T cells co-cultured with RANTES and IP-10 conditioned CFP10-DCs mediated killing of mycobacteria from infected macrophages. Similarly, T cells recruited by RANTES and IP-10 conditioned CFP10-DCs mediated significant killing of mycobacteria from infected macrophages. IFN-gamma treatment of CFP10-DCs restored RANTES and IP-10 levels and T cells activated by these DCs mediated significant killing of virulent M. tb inside macrophages. Adoptive transfer of either RANTES and IP-10 or IL-12 and IFN-gamma conditioned CFP10-DCs cleared an established M. tb infection in mice. The extent of clearance was similar to that obtained with drug treatment. CONCLUSIONS: These results indicate that chemokine and cytokine secretion by DCs differentiated by M. tb antigens such as CFP-10 play major roles in regulating protective immune responses at sites of infection.

Mycobacterium tuberculosis and dendritic cells: recognition, activation and functional implications.

The highly complex nature of interactions of Mycobacterium tuberculosis with cells of the immune system has puzzled researchers the world-over in understanding the pathogenesis and immunology associated with tuberculosis (TB). This has contributed to the delay in development of effective vaccine(s) for TB. Several excellent studies have provided only a glimpse of the kind and degree of immune responses elicited following infection by mycobacteria. Preferred entry via respiratory route results in the capture of mycobacteria by alveolar macrophages that eventually become their long-term hosts. Since the pathogen is rarely cleared this has resulted in the human population serving as a large reservoir for mycobacteria. Owing to their unique ability to prime naïve and memory T cells, dendritic cells (DCs) play important and indispensable roles in the initiation and maintenance of protective immune responses following infection. The kind of immune response initiated by DCs with respect to mycobacteria determines the character of immune responses mounted by the host against the pathogen. The profile of cytokines and chemokines secreted as a result of infection of DCs by mycobacteria further plays an important role in defining the course of infection. This minireview attempts to highlight key interactions of mycobacteria with dendritic cells. We discus the uptake of mycobacteria by DCs followed by DC activation and the spectrum of immune responses initiated by infected/activated DCs, followed by numerous ways the pathogen has devised to subvert protective responses.