Blood meals from 'dead-end' vertebrate hosts enhance transmission potential of malaria-infected mosquitoes.

Ingestion of an additional blood meal(s) by a hematophagic insect can accelerate development of several vector-borne parasites and pathogens. Most studies, however, offer blood from the same vertebrate host species as the original challenge (for e.g., human for primary and additional blood meals). Here, we show a second blood meal from bovine and canine hosts can also enhance sporozoite migration in Anopheles stephensi mosquitoes infected with the human- and rodent-restricted Plasmodium falciparum and P. berghei, respectively. The extrinsic incubation period (time to sporozoite appearance in salivary glands) showed more consistent reductions with blood from human and bovine donors than canine blood, although the latter's effect may be confounded by the toxicity, albeit non-specific, associated with the anticoagulant used to collect whole blood from donors. The complex patterns of enhancement highlight the limitations of a laboratory system but are nonetheless reminiscent of parasite host-specificity and mosquito adaptations, and the genetic predisposition of An. stephensi for bovine blood. We suggest that in natural settings, a blood meal from any vertebrate host could accentuate the risk of human infections by P. falciparum: targeting vectors that also feed on animals, via endectocides for instance, may reduce the number of malaria-infected mosquitoes and thus directly lower residual transmission. Since endectocides also benefit animal health, our results underscore the utility of the One Health framework, which postulates that human health and well-being is interconnected with that of animals. We posit this framework will be further validated if our observations also apply to other vector-borne diseases which together are responsible for some of the highest rates of morbidity and mortality in socio-economically disadvantaged populations.

Multifaceted Role of Nanomaterials in Modulating In Vitro Seed Germination, Plant Morphogenesis, Metabolism and Genetic Engineering.

The agricultural practices of breeding, farm management and cultivation have improved production, to a great extent, in order to meet the food demands of a growing population. However, the newer challenges of climate change, global warming, and nutritional quality improvement will have to be addressed under a new scenario. Plant biotechnology has emerged as a reliable tool for enhancing crop yields by protecting plants against insect pests and metabolic engineering through the addition of new genes and, to some extent, nutritional quality improvement. Plant tissue culture techniques have provided ways for the accelerated clonal multiplication of selected varieties with the enhanced production of value-added plant products to increase modern agriculture. The in vitro propagation method has appeared as a pre-eminent approach for the escalated production of healthy plants in relatively shorter durations, also circumventing seasonal effects. However, there are various kinds of factors that directly or indirectly affect the efficiency of in vitro regeneration like the concentration and combination of growth regulators, variety/genotype of the mother plant, explant type, age of seedlings and other nutritional factors, and elicitors. Nanotechnology as one of the latest and most advanced approaches in the material sciences, and can be considered to be very promising for the improvement of crop production. Nanomaterials have various kinds of properties because of their small size, such as an enhanced contact surface area, increased reactivity, stability, chemical composition, etc., which can be employed in plant sciences to alter the potential and performance of plants to improve tissue culture practices. Implementing nanomaterials with in vitro production procedures has been demonstrated to increase the shoot multiplication potential, stress adaptation and yield of plant-based products. However, nanotoxicity and biosafety issues are limitations, but there is evidence that implies the promotion and further exploration of nanoparticles in agriculture production. The incorporation of properly designed nanoparticles with tissue culture programs in a controlled manner can be assumed as a new pathway for sustainable agriculture development. The present review enlists different studies in which treatment with various nanoparticles influenced the growth and biochemical responses of seed germination, as well as the in vitro morphogenesis of many crop species. In addition, many studies suggest that nanoparticles can be useful as elicitors for elevating levels of important secondary metabolites in in vitro cultures. Recent advancements in this field also depict the suitability of nanoparticles as a promising carrier for gene transfer, which show better efficiency than traditional Agrobacterium-mediated delivery. This review comprehensively highlights different in vitro studies that will aid in identifying research gaps and provide future directions for unexplored areas of research in important crop species.

Characterisation of OXA-48-like carbapenemases in Escherichia coli and Klebsiella pneumoniae from North India.

The oxacillinase-48 (OXA-48)-like carbapenemases are class D ß-lactamases and increasingly reported in Enterobacterial species. The detection of these carbapenemases is challenging and little information is available on the epidemiology and plasmid characteristics of OXA-48-like carbapenemase producers. We detected the presence of OXA-48-like carbapenemases in 500 clinical isolates of Escherichia coli and Klebsiella pneumoniae, followed by detection of other carbapenemases, extended spectrum ß-lactamases (ESBLs) and 16S rRNA methyltransferases in OXA-48 producers. Clonal relatedness was studied using pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). Finally, plasmid characterisation was performed through conjugation experiment, S1-PFGE and Southern hybridisation. Around 40% of E. coli and K. pneumoniae isolates harboured OXA-48-like ß-lactamases. Two OXA-48 allele variants, OXA-232 and OXA-181 were detected in our study. OXA-48 producers co-harbored diverse drug-resistant genes belonging to other classes of carbapenemases, ESBLs and 16S rRNA methyltransferases. OXA-48-like carbapenemase producers exhibited high clonal diversity. Bla OXA-48 carrying plasmids were conjugative, untypable and their size was ~ 45 kb and ~ 104.5 kb in E. coli and K. pneumoniae respectively. In conclusion, OXA-48-like carbapenemases have emerged as major cause of carbapenem resistance in Enterobacteriaceae and probably still being under reported. Strict surveillance and adequate detection methods are needed to prevent the dissemination of OXA-48-like carbapenemases.

Outbreak of colistin resistant, carbapenemase (bla NDM, bla OXA-232) producing Klebsiella pneumoniae causing blood stream infection among neonates at a tertiary care hospital in India.

Infections caused by multi-drug resistant Klebsiella pneumoniae are a leading cause of mortality and morbidity among hospitalized patients. In neonatal intensive care units (NICU), blood stream infections by K. pneumoniae are one of the most common nosocomial infections leading to poor clinical outcomes and prolonged hospital stays. Here, we describe an outbreak of multi-drug resistant K. pneumoniae among neonates admitted at the NICU of a large tertiary care hospital in India. The outbreak involved 5 out of 7 neonates admitted in the NICU. The antibiotic sensitivity profiles revealed that all K. pneumoniae isolates were multi-drug resistant including carbapenems and colistin. The isolates belonged to three different sequence types namely, ST-11, ST-16 and ST-101. The isolates harboured carbapenemase genes, mainly bla NDM-1, bla NDM-5 and bla OXA-232 besides extended-spectrum ß-lactamases however the colistin resistance gene mcr-1, mcr-2 and mcr-3 could not be detected. Extensive environmental screening of the ward and healthcare personnel led to the isolation of K. pneumoniae ST101 from filtered incubator water, harboring bla NDM-5, bla OXA-232 and ESBL genes (bla CTX-M) but was negative for the mcr genes. Strict infection control measures were applied and the outbreak was contained. This study emphasizes that early detection of such high-risk clones of multi-drug resistant isolates, surveillance and proper infection control practices are crucial to prevent outbreaks and further spread into the community.

Elicitor mediated enhancement of shoot biomass and lupeol production in Hemidesmus indicus (L.) R. Br. ex. Schult. and Tylophora indica (Burm. F.) Merrill using yeast extract and salicylic acid.

Hemidesmus indicus (L.) R. Br. ex Schult. and Tylophora indica (Burm. F.) Merrill shoot cultures were treated with different concentrations of yeast extract (YE; 25-200 mg/L) and salicylic acid (SA; 50-200 µM), and their effect on lupeol production was assessed. The maximum dry weight (DW) biomass was recorded when H. indicus shoots were treated with SA (50 µM) and T. indica shoots with YE (200 mg/L). Highest lupeol yield (335.40 ± 0.04 µg/g DW) was obtained in H. indicus shoots after treatment with 50 µM of SA for 3 weeks. Whereas in T. indica, maximum lupeol content (584.26 ± 8.14 µg/g DW) was recorded by giving treatment with 25 µM of SA for 6 weeks.

Bacterial coinfections in COVID: Prevalence, antibiotic sensitivity patterns and clinical outcomes from a tertiary institute of Northern India.

Purpose: Bacterial coinfections are a leading cause of morbidity and mortality during viral infections including corona virus disease (COVID-19). The COVID-19 pandemic has highlighted the need to comprehend the complex connection between bacterial and viral infections. During the current pandemic, systematic testing of the COVID-19 patients having bacterial coinfections is essential to choose the correct antibiotics for treatment and prevent the spread of antimicrobial resistance (AMR). This study was planned to study the prevalence, demographic parameters, comorbidities, antibiotic sensitivity patterns, and outcomes in hospitalized COVID-19 patients with bacterial coinfections. Material and Methods: The COVID-19 patients having bacterial coinfections were selected for the study and analyzed for the prevalence, antibiotic sensitivities, comorbidities, and clinical outcomes. The bacterial isolates were identified and the antibiotic susceptibility testing was performed according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Results: Of the total 1,019 COVID-19 patients screened, 5.2% (n = 53) demonstrated clinical signs of bacterial coinfection. Escherichia coli were the most common isolate followed by Pseudomonas aeruginosa and Klebsiella spp. among the gram-negative bacterial infections. Coagulase-negative Staphylococcus species (CONS) and Staphylococcus aureus were most common among the gram-positive bacterial infections. The antibiotic sensitivity profiling revealed that colistin (99%), imipenem (78%), and fosfomycin (95%) were the most effective drugs against the gram-negative isolates while vancomycin (100%), teicoplanin (99%), and doxycycline (71%) were most potent against the gram-positive isolates. The analysis of the clinical parameters and outcomes revealed that among the COVID-19 patients with bacterial coinfections, the mortality rate was higher (39%) than the control group (17%) (P-value < 0.001). Conclusion: This study reveals the significantly increased rates of bacterial coinfections among COVID-19 patients which may lead to an increase in mortality. This study will guide the physicians at the primary level on the rational and correct usage of antibiotics in such COVID cases. Hence, systematic testing of COVID-19 patients with bacterial coinfections is the need of the hour to decrease the mortality rate and limit the spread of AMR.

Gastrointestinal helminths increase Bordetella bronchiseptica shedding and host variation in supershedding.

Co-infected hosts, individuals that carry more than one infectious agent at any one time, have been suggested to facilitate pathogen transmission, including the emergence of supershedding events. However, how the host immune response mediates the interactions between co-infecting pathogens and how these affect the dynamics of shedding remains largely unclear. We used laboratory experiments and a modeling approach to examine temporal changes in the shedding of the respiratory bacterium Bordetella bronchiseptica in rabbits with one or two gastrointestinal helminth species. Experimental data showed that rabbits co-infected with one or both helminths shed significantly more B. bronchiseptica, by direct contact with an agar petri dish, than rabbits with bacteria alone. Co-infected hosts generated supershedding events of higher intensity and more frequently than hosts with no helminths. To explain this variation in shedding an infection-immune model was developed and fitted to rabbits of each group. Simulations suggested that differences in the magnitude and duration of shedding could be explained by the effect of the two helminths on the relative contribution of neutrophils and specific IgA and IgG to B. bronchiseptica neutralization in the respiratory tract. However, the interactions between infection and immune response at the scale of analysis that we used could not capture the rapid variation in the intensity of shedding of every rabbit. We suggest that fast and local changes at the level of respiratory tissue probably played a more important role. This study indicates that co-infected hosts are important source of variation in shedding, and provides a quantitative explanation into the role of helminths to the dynamics of respiratory bacterial infections.

HPLC and GC/MS analysis of Prunus ulmifolia Franch. (syn. Aflatunia ulmifolia (Franch.) Vassilcz.) leaves growing in South-Eastern Kazakhstan.

Prunus ulmifolia Franch. (Rosaceae) was investigated for its phytochemical composition from South-Eastern Kazakhstan for the first time. HPLC analysis confirmed rutin (0.88%) in ethanol extract, and the extract also exhibited antioxidant activity. The GC/MS analysis identified total 44 components from main groups e.g. oxygenated monoterpenes (51.06%), oxygenated sesquiterpenes (20.33%), non-terpene derivatives (18.71%), and sesquiterpene hydrocarbons (7.89%), and the maximum content was of acyclic alcoholic monoterpenoid citronellol (36.58%). The hierarchical cluster analysis (HCA) from previous reports and present study was used to demonstrate the variations between essential oil compositions in different Prunus species. It formed three main clusters, cluster I consisted of species with benzaldehyde as dominant component. Cluster II included plants with benzaldehyde as secondary component, and cluster III was of P. ulmifolia in which benzaldehyde was not detected. Further, the essential oil was assessed for cytotoxic and antimicrobial activities too, and it showed better cytotoxic but poor antimicrobial activities.

Streamlining sporozoite isolation from mosquitoes by leveraging the dynamics of migration to the salivary glands.

BACKGROUND: Sporozoites isolated from the salivary glands of Plasmodium-infected mosquitoes are a prerequisite for several basic and pre-clinical applications. Although salivary glands are pooled to maximize sporozoite recovery, insufficient yields pose logistical and analytical hurdles; thus, predicting yields prior to isolation would be valuable. Preceding oocyst densities in the midgut is an obvious candidate. However, it is unclear whether current understanding of its relationship with sporozoite densities can be used to maximize yields, or whether it can capture the potential density-dependence in rates of sporozoite invasion of the salivary glands. METHODS: This study presents a retrospective analysis of Anopheles stephensi mosquitoes infected with two strains of the rodent-specific Plasmodium berghei. Mean oocyst densities were estimated in the midguts earlier in the infection (11-15 days post-blood meal), with sporozoites pooled from the salivary glands later in the infection (17-29 days). Generalized linear mixed effects models were used to determine if (1) mean oocyst densities can predict sporozoite yields from pooled salivary glands, (2) whether these densities can capture differences in rates of sporozoite invasion of salivary glands, and (3), if the interaction between oocyst densities and time could be leveraged to boost overall yields. RESULTS: The non-linear effect of mean oocyst densities confirmed the role of density-dependent constraints in limiting yields beyond certain oocyst densities. Irrespective of oocyst densities however, the continued invasion of salivary glands by the sporozoites boosted recoveries over time (17-29 days post-blood meal) for either parasite strain. CONCLUSIONS: Sporozoite invasion of the salivary glands over time can be leveraged to maximize yields for P. berghei. In general, however, invasion of the salivary glands over time is a critical fitness determinant for all Plasmodium species (extrinsic incubation period, EIP). Thus, delaying sporozoite collection could, in principle, substantially reduce dissection effort for any parasite within the genus, with the results also alluding to the potential for changes in sporozoites densities over time to modify infectivity for the next host.

Burden of tyrosine kinase inhibitor failure in Chinese chronic myeloid leukemia patients: a systematic literature review.

Aim: To conduct a systematic literature review of real-world evidence on the burden of tyrosine kinase inhibitor (TKI) failure in Chinese patients with chronic myeloid leukemia (CML). Methods: We identified 155 references in Chinese- and English-language journals from 2001 to 2021. Results: The age-adjusted mortality rate in Chinese CML patients was decreasing. Imatinib treatment had a higher annual treatment failure risk than nilotinib (0.199 vs 0.041). Patients with TKI treatment failure tended to be young (median: 38.6 years), have progressive disease (44.3%) and harbor BCR-ABL1 mutations (51.6%). The disease burden of TKI treatment failure included reduced health outcomes and increased health resource utilization and costs. Conclusion: CML relapse cases could continuously rise in China due to increasing TKI treatment failure over extended survival.

Trends of drug resistance to the commonly used antibiotics to combat the COVID-19 pandemic: Experience from a super-speciality institute of Northern India.

Purpose: Coronavirus disease 2019 (COVID-19) is purely a viral illness which is not affected by the usage of antibiotics, but the risk of development of secondary bacterial infections during the course of respiratory illness or hospitalisation has led to a surge of antibiotic use. Anti-microbial resistance has taken an upward trend to some of the commonly used or over-used antibiotics. The present study was planned to focus on the trends of resistance rates noticed for the common antibiotics, namely, doxycycline, azithromycin, and so on, before and after the advent of this pandemic. Material and Methods: The study was conducted at a tertiary care hospital of North India with 2000 samples, 1000 samples between March 2019 and March 2020 before the COVID pandemic and 1000 samples between April 2020 and April 2021 after the advent of the pandemic. Identification and zones for doxycycline and erythromycin were interpreted as per Clinical and Laboratory Standards Institute guidelines. Results: Among the various samples, pus/aspirated fluids were in majority (47%), followed by blood (29%), respiratory specimens (18%), and urine (6%). On stratifying the various pathogens associated with the treatment of doxycycline and erythromycin, Staphylococcus species were the predominant ones in almost 82% of the cases, followed by Enterococcus (12%) and Streptococcus (6%) species. For doxycycline, the overall sensitivity was noted to be 46% in the year 2019-20 and 31% in the year 2020-21, whereas for erythromycin, the sensitivity was seen as 39% in 2019-20 and dropped down to 26% in 2020-21. Conclusions: The authors noted a dip in the overall sensitivity towards doxycycline and azithromycin. This finding clearly indicates the increasing rates of antibiotic resistance in a developing country such as India during these COVID times. A proper anti-microbial stewardship programme during these times will help to de-escalate the increasing resistance rates and will prove to be of great help to the primary care physicians.

Complete genome sequence of an extensively drug-resistant Pseudomonas aeruginosa ST773 clinical isolate from North India.

OBJECTIVES: Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen causing a wide range of community- and hospital-acquired infections. Here we report the complete genome sequence of an extensively drug-resistant (XDR) P. aeruginosa strain (PA790) in order to understand the antibiotic resistance genes (ARGs) harboured by such a strain. METHODS: Whole-genome sequencing (WGS) was performed using Illumina HiSeq and Nanopore MinION platforms. Genome assembly was performed using Unicycler v.0.4.8. The genome was annotated using the NCBI Prokaryotic Genome Annotation Pipeline (PGAP). In silico predictions were fulfilled using curated bioinformatics tools. RESULTS: Pseudomonas aeruginosa PA790 was classified as XDR and belongs to sequence type 773 (ST773). The complete genome size is 6 932 250 bp with a G+C content of 66.02% and a BUSCO (Benchmarking Universal Single-Copy Orthologs) score of 100. Strain PA790 harboured 12 different ARGs conferring resistance to eight different classes of antibiotics. It was identified as the nineteenth ST773 strain among 5785 whole-genome sequences of P. aeruginosa available in the NCBI database. CONCLUSION: Pseudomonas aeruginosa PA790 belongs to ST773 and was identified as the nineteenth such isolate to be submitted to NCBI and the first complete ST773 genome from India. The WGS data with multiple ARGs of P. aeruginosa PA790 (ST773) will aid in understanding the evolution and phylogeny of such high-risk clones and provide a solid basis for further research on XDR strains.

Genetic Characterisation of Colistin Resistant Klebsiella pneumoniae Clinical Isolates From North India.

Background: Increasing use of colistin has led to the world-wide emergence of mobile colistin resistant gene (mcr). The present study aimed to identify and characterise mcr and other drug-resistant genes in colistin resistant Klebsiella pneumoniae clinical isolates. Methods: Twenty-two colistin resistant K. pneumoniae were analysed for mcr and other drug-resistant genes, efflux pumps, and virulence genes, and for their biofilm forming ability. Pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) were performed for all mcr-1 positive isolates. S1-PFGE and Southern hybridisation were performed for localisation of mcr-1 and blaNDM. Results: Nineteen colistin resistant K. pneumoniae harboured mcr-1 and 3 had mgrB disruption. All isolates harboured blaOXA-48-type and ESBL genes; eight strains (five with mcr-1 and three with mgrB disruption) co-harboured blaNDM. Efflux pumps genes AcrAB and mdtK were detected in all 22 and tol-C in 21 isolates. Virulence-related genes entB and irp-1 were detected in all 22, mrkD in 20, and fimH-1 in 18 isolates; 11 isolates were strong biofilm producers. PFGE clustered mcr-1 positive isolates into eight groups based on ≥90% similarity; MLST revealed diverse sequence types, predominant being ST-15 (n = 4) and ST-16 (n = 4). Both mcr-1 and blaNDM were localised on plasmid and chromosome; mcr-1 was present on IncFII type and blaNDM on IncFIB and IncA/C type plasmids. Conclusions: Colistin resistance in K. pneumoniae was predominantly mediated by mcr-1. Co-existence of colistin, carbapenem, and other drug-resistant genes along with efflux pumps indicates towards enormous genomic plasticity in K. pneumoniae with ability to emerge as super-spreader of drug-resistance.

Blood pressure normalizing effect of Talahridaya marma therapy: A case report.

Ancient Ayurvedic literature described 107 vital regions of the body and considered them as a seat of prana (life force) and collectively termed them as marma. The applied aspect of this concept, marma chikitsa or marma therapy, is gaining popularity as it is being practiced by many clinicians in which these marma are stimulated in different ways to treat different diseases. Hypertension is one of the major disorders affecting majority of the world population. Inspite of available antihypertensive therapies, the hypertensive population of not only the older age group, but also of that of young adults is increasing. Blood pressure normalising effect of marma therapy is observed by clinicians practicing marma therapy due to its holistic effect on the body. Clinical data regarding efficacy of this therapy is very sparse and hence, its application in different diseases remained unexplored till date. This case report is of a young hypertensive male whose blood pressure significantly improved with Talahridaya marma therapy. This patient was detected with raised blood pressure on repetitive examinations. The volunteer was subjected to Talahridayamarma therapy where his classical Talahridaya marma point on left upper limb was physically stimulated in controlled way for 10 days and the patient was also taught to perform the therapy on himself. The blood pressure was recorded, both before and after giving the therapy on each day. The volunteer showed significant improvement in his blood pressure recordings.

Sex, age, and parental harmonic convergence behavior affect the immune performance of Aedes aegypti offspring.

Harmonic convergence is a potential cue, female mosquitoes use to choose male mates. However, very little is known about the benefits this choice confers to offspring performance. Using Aedes aegypti (an important vector of human disease), we investigated whether offspring of converging parental pairs showed differences in immune competence compared to offspring derived from non-converging parental pairs. Here we show that harmonic convergence, along with several other interacting factors (sex, age, reproductive, and physiological status), significantly shaped offspring immune responses (melanization and response to a bacterial challenge). Harmonic convergence had a stronger effect on the immune response of male offspring than on female offspring. Further, female offspring from converging parental pairs disseminated dengue virus more quickly than offspring derived from non-converging parental pairs. Our results provide insight into a wide range of selective pressures shaping mosquito immune function and could have important implications for disease transmission and control.

Logistic regression analysis of environmental and other variables and incidences of tuberculosis in respiratory patients.

The objective of this study was to examine the association of 14 variables with TB in respiratory patients. The variables included: urban/rural, persons in 1200 sqft area, TB in family, crowding, smoking (family member), gender, age, education, smoking, workplace, kitchen location, cooking fuel, ventilation, and kerosene uses. Eight hundred respiratory patients were tested for sputum positive pulmonary TB; 500 had TB and 300 did not. An analysis of the unadjusted odds ratio (UOR) and adjusted OR (AOR) was undertaken using logistic regression to link the probability of TB incidences with the variables. There was an inconsistency in the significance of variables using UOR and AOR. A subset model of 4 variables (kerosene uses, ventilation, workplace, and gender) based on significant AOR was adjudged acceptable for estimating the probability of TB incidences. Uses of kerosene (AOR 2.62 (1.95, 3.54)) consistently related to incidences of TB. It was estimated that 50% reduction in kerosene uses could reduce the probability of TB by 13.29% in respiratory patients. The major recommendation was to replace kerosene uses from households with a supply of clean fuel like liquid petroleum or natural gas and rural electrification.

A framework for PM2.5 constituents-based (including PAHs) emission inventory and source toxicity for priority controls: A case study of Delhi, India.

A simple mass-based emission inventory (EI) of PM2.5 alone does not provide the information on the toxicity of the sources, as not all PM2.5 particles are equally toxic. The PM2.5 EI should have three inter-linked versions (i) mass-based, (ii) constituent-based and (iii) source toxicity-based. A framework (applied to the city of Delhi) to prepare constituent and source toxicity-based EI was developed. Mass emission of twelve sources was estimated for 89 constituents. The USEPA's CompTox database was used to estimate threshold concentration for the constituents of PM2.5 for carcinogenic, chronic and acute health effects. A product of mass emission of the constituent and inverse of its threshold concentration provides an assessment of toxicity of the source. Toxicity was not linearly associated with the mass emission. Road dust, vehicles, coal, dung, wood and coal power plant showed the highest toxicity as presence of metals Cr, Co, Cd, and As make these sources disproportionately more toxic. Among PAHs, Dibenzo (ah)anthracene, showed the highest cancer risk with its 98% emission from vehicles. The soft options replacing wood, crop, coal and dung with LPG, elimination of diesel power generation, burning of waste were simple and effective measures to reduce chronic toxicity by about 40%.

External disturbances impact helminth-host interactions by affecting dynamics of infection, parasite traits, and host immune responses.

External perturbations, such as multispecies infections or anthelmintic treatments, can alter host-parasite interactions with consequences on the dynamics of infection. While the overall profile of infection might appear fundamentally conserved at the host population level, perturbations can disproportionately affect components of parasite demography or host responses, and ultimately impact parasite fitness and long-term persistence.We took an immuno-epidemiological approach to this reasoning and examined a rabbit-helminth system where animals were trickle-dosed with either one or two helminth species, treated halfway through the experiment with an anthelmintic and reinfected one month later following the same initial regime. Parasite traits (body length and fecundity) and host immune responses (cytokines, transcription factors, antibodies) were quantified at fixed time points and compared before and after drug treatment, and between single and dual infections.Findings indicated a resistant host phenotype to Trichostrongylus retortaeformis where abundance, body length, and fecundity were regulated by a protective immune response. In contrast, Graphidium strigosum accumulated in the host and, while it stimulated a clear immune reaction, many genes were downregulated both following reinfection and in dual infection, suggestive of a low host resistance.External perturbations affected parasite fecundity, including body length and number of eggs in utero, more significantly than abundance; however, there was no consistency in the parasite-immune relationships.Disentangling the processes affecting parasite life history, and how they relate to host responses, can provide a better understanding of how external disturbances impact disease severity and transmission, and how parasites strategies adjust to secure persistence at the host and the population level.

Field Relevant Variation in Ambient Temperature Modifies Density-Dependent Establishment of Plasmodium falciparum Gametocytes in Mosquitoes.

The relationship between Plasmodium falciparum gametocyte density and infections in mosquitoes is central to understanding the rates of transmission with important implications for control. Here, we determined whether field relevant variation in environmental temperature could also modulate this relationship. Anopheles stephensi were challenged with three densities of P. falciparum gametocytes spanning a ~10-fold gradient, and housed under diurnal/daily temperature range ("DTR") of 9°C (+5°C and -4°C) around means of 20, 24, and 28°C. Vector competence was quantified as the proportion of mosquitoes infected with oocysts in the midguts (oocyst rates) or infectious with sporozoites in the salivary glands (sporozoite rates) at peak periods of infection for each temperature to account for the differences in development rates. In addition, oocyst intensities were also recorded from infected midguts and the overall study replicated across three separate parasite cultures and mosquito cohorts. While vector competence was similar at 20 DTR 9°C and 24 DTR 9°C, oocyst and sporozoite rates were also comparable, with evidence, surprisingly, for higher vector competence in mosquitoes challenged with intermediate gametocyte densities. For the same gametocyte densities however, severe reductions in the sporozoite rates was accompanied by a significant decline in overall vector competence at 28 DTR 9°C, with gametocyte density per se showing a positive and linear effect at this temperature. Unlike vector competence, oocyst intensities decreased with increasing temperatures with a predominantly positive and linear association with gametocyte density, especially at 28 DTR 9°C. Oocyst intensities across individual infected midguts suggested temperature-specific differences in mosquito susceptibility/resistance: at 20 DTR 9°C and 24 DTR 9°C, dispersion (aggregation) increased in a density-dependent manner but not at 28 DTR 9°C where the distributions were consistently random. Limitations notwithstanding, our results suggest that variation in temperature could modify seasonal dynamics of infectious reservoirs with implications for the design and deployment of transmission-blocking vaccines/drugs.