Effective Strategy For Elimination Research Articles

Genetic surveillance reveals low, sustained malaria transmission with clonal replacement in Sao Tome and Principe.

Despite efforts to eliminate malaria in Sao Tome and Principe (STP), cases have recently increased. Understanding residual transmission structure is crucial for developing effective elimination strategies. This study collected surveillance data and generated amplicon sequencing data from 980 samples between 2010 and 2016 to examine the genetic structure of the parasite population. The mean multiplicity of infection (MOI) was 1.3, with 11% polyclonal infections, indicating low transmission intensity. Temporal trends of these genetic metrics did not align with incidence rates, suggesting that changes in genetic metrics may not straightforwardly reflect changes in transmission intensity, particularly in low transmission settings where genetic drift and importation have a substantial impact. While 88% of samples were genetically linked, continuous turnover in genetic clusters and changes in drug-resistance haplotypes were observed. Principal component analysis revealed some STP samples were genetically similar to those from Central and West Africa, indicating possible importation. These findings highlight the need to prioritize several interventions such as targeted interventions against transmission hotspots, reactive case detection, and strategies to reduce the introduction of new parasites into this island nation as it approaches elimination. This study also serves as a case study for implementing genetic surveillance in a low transmission setting.

Elimination of uranium pollution from coastal nuclear power plant by marine microorganisms: Capability and mechanism

Uranium is one of the sensitive radionuclides in the wastewater of nuclear powers. Due to the fact that nuclear powers are mainly located in coastal areas, the elimination of uranium (U(VI)) pollution from coastal nuclear power is ultimately rely on marine microorganisms. The fixing of U(VI) on V. alginolyticus surface or converting it into sediments is an effective elimination strategy for U(VI) pollution. In this work, typical marine microorganism V. alginolyticus was used to evaluate the elimination of U(VI) pollution by marine microorganisms. Effects of solution conditions (such as pH, temperature, and bacterium concentrations) on the physicochemical properties and elimination capabilities of V. alginolyticus were studied in detail. FT-IR, XPS and XRD results reveal that COOH, NH2, OH and PO4 on V. alginolyticus were main functional groups for U(VI) elimination and formed (UO2)3(PO4)2·H2O. The elimination of U(VI) by V. alginolyticus includes two stages of adsorption and biomineralization. The theoretical maximum adsorption capacity (Cs,max) of V. alginolyticus for U(VI) can reach up to 133 mg/g at pH 5 and 298 K, and the process reached equilibrium in 3 h. Results show that V. alginolyticus play important role in the elimination of U(VI) pollution in seawater.

Oxalate homeostasis.

Oxalate homeostasis is maintained through a delicate balance between endogenous sources, exogenous supply and excretion from the body. Novel studies have shed light on the essential roles of metabolic pathways, the microbiome, epithelial oxalate transporters, and adequate oxalate excretion to maintain oxalate homeostasis. In patients with primary or secondary hyperoxaluria, nephrolithiasis, acute or chronic oxalate nephropathy, or chronic kidney disease irrespective of aetiology, one or more of these elements are disrupted. The consequent impairment in oxalate homeostasis can trigger localized and systemic inflammation, progressive kidney disease and cardiovascular complications, including sudden cardiac death. Although kidney replacement therapy is the standard method for controlling elevated plasma oxalate concentrations in patients with kidney failure requiring dialysis, more research is needed to define effective elimination strategies at earlier stages of kidney disease. Beyond well-known interventions (such as dietary modifications), novel therapeutics (such as small interfering RNA gene silencers, recombinant oxalate-degrading enzymes and oxalate-degrading bacterial strains) hold promise to improve the outlook of patients with oxalate-related diseases. In addition, experimental evidence suggests that anti-inflammatory medications might represent another approach to mitigating or resolving oxalate-induced conditions.

Supramolecular assemblies of a newly developed indole derivative for selective adsorption and photo-destruction of perfluoroalkyl substances

Per-/polyfluoroalkyl substances (PFASs) contamination has caused worldwide health concerns, and increased demand for effective elimination strategies. Herein, we developed a new indole derivative decorated with a hexadecane chain and a tertiary amine center (named di-indole hexadecyl ammonium, DIHA), which can form stable nanospheres (100–200 nm) in water via supramolecular assembly. As the DIHA nanospheres can induce electrostatic, hydrophobic and van der Waals interactions (all are long-ranged) that operative cooperatively, in addition to the nano-sized particles with large surface area, the DIHA nanocomposite exhibited extremely fast adsorption rates (in seconds), high adsorption capacities (0.764–0.857 g g−1) and selective adsorption for perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), outperformed the previous reported high-end PFASs adsorbents. Simultaneously, the DIHA nanospheres can produce hydrated electron (eaq−) when subjected to UV irradiation, with the virtue of constraining the photo-generated eaq− and the adsorbed PFOA/PFOS molecules entirely inside the nanocomposite. As such, the UV/DIHA system exhibits extremely high degradation/defluorination efficiency for PFOA/PFOS, even under ambient conditions, especially with the advantages of low chemical dosage requirement (μM level) and robust performance against environmental variables. Therefore, it is a new attempt of using supramolecular approach to construct an indole-based nanocomposite, which can elegantly combine adsorption and degradation functions. The novel DIHA nanoemulsion system would shed light on the treatment of PFAS-contaminated wastewater.

Plasmodium vivax gametocytes and transmission.

Malaria elimination means cessation of parasite transmission. At present, the declining malaria incidence in many countries has made elimination a feasible goal. Transmission control has thus been placed at the center of the national malaria control programs. The efficient transmission of Plasmodium vivax from humans to mosquitoes is a key factor that helps perpetuate malaria in endemic areas. A better understanding of transmission is crucial to the success of elimination efforts. Biological delineation of the parasite transmission process is important for identifying and prioritizing new targets of intervention. Identification of the infectious parasite reservoir in the community is key to devising an effective elimination strategy. Here we describe the fundamental characteristics of P. vivax gametocytes - the dynamics of their production, longevity, and the relationship with the total parasitemia - as well as recent advances in the molecular understanding of parasite sexual development. In relation to malaria elimination, factors influencing the human infectivity and the current evidence for a role of asymptomatic carriers in transmission are presented.

A mathematical model by route of transmission and fibrosis progression to estimate undiagnosed individuals with HCV in different Italian regions

BackgroundAlthough an increase in hepatitis C virus (HCV) prevalence from Northern to Southern Italy has been reported, the burden of asymptomatic individuals in different Italian regions is currently unknown.MethodsA probabilistic approach, including a Markov chain for liver disease progression, was applied to estimate current HCV viraemic burden. The model defined prevalence by geographic area using an estimated annual historical HCV incidence by age, treatment rate, and migration rate from the Italian National database. Viraemic infection by age group was estimated for each region by main HCV transmission routes of individuals for stage F0–F3 (i.e. patients without liver cirrhosis and thus potentially asymptomatic) and F4 (patients with liver cirrhosis, thus potentially symptomatic).ResultsBy January 2020, it was estimated that there were 409,184 Italian individuals with HCV (prevalence of 0.68%; 95% CI: 0.54–0.82%), of which 300,171 (0.50%; 95% CI: 0.4–0.6%) were stage F0–F3. Considering all individuals with HCV in stage F0–F3, the geographical distributions (expressed as the proportion of HCV infected individuals by macroarea within the overall estimated number of F0–F3 individuals and prevalence values, expressed as the percentage of individuals with HCV versus the overall number of individuals for each macroarea) were as follows: North 42.1% (0.45%; 95% CI: 0.36–0.55%), Central 24.1% (0.61%; 95% CI: 0.48–0.74%), South 23.2% (0.50%; 95% CI: 0.4–0.61%), and the Isles 10.6% (0.49%; 95% CI: 0.39–0.59%). The population of people who inject drugs accounted for 50.4% of all individuals infected (F0–F3). Undiagnosed individuals (F0–F3) were ~ 15 years younger (⁓ 50 years) compared with patients with stage F4 (⁓ 65 years), with similar age distributions across macroareas. In contrast to what has been reported on HCV epidemiology in Italy, an increasing trend in the proportion of potentially undiagnosed individuals with HCV (absolute number within the F0–F3) from South (23.2%) to North (42.1%) emerged, independent of similar regional prevalence values.ConclusionThis targeted approach, which addresses the specific profile of undiagnosed individuals, is helpful in planning effective elimination strategies by region in Italy and could be a useful methodology for other countries in implementing their elimination plans.

A community-based cervical cancer screening program in Alappuzha district of Kerala using camp approach.

Background:Cervical cancer is a major cause of preventable cancer related death in women, particularly in middle-income developing countries. Screening of cervical pre-cancer by cytology remains an effective strategy for prevention of mortality. However, there is paucity of community-based studies in Kerala. The aim of this study was to determine the prevalence of cervical precancerous lesions and to study the associated epidemiological factors through camp approach.Materials and Methods:A cross–sectional study was carried out among women in Alappuzha district, Kerala, by conducting community-based screening camps covering all the panchayaths from February 2017 to January 2019.Statistical Analysis Used:Descriptive statistics including mean for continuous variables and frequency along with their percentage for categorical variables were determined. Pearson’s Chi-square test was used to determine the strength of the association between variables. Statistical significance was set at P value less than 0.05.Results:Out of 5241 women screened, majority (62.9%) were in the reproductive age group (31–50 years) with mean age of 47.1 ± 10.3 years. The prevalence of precancerous lesions of cervix was 6.37%, which consisted of low-grade squamous intraepithelial lesion (LSIL) in 2.2%, high-grade squamous intraepithelial lesion (HSIL) in 0.5% and Carcinoma-in-situ in 0.2%. Risk factors that had significant association with cervical precancerous lesions were lower education status, genital infections, early marriage age and high parity.Conclusion:Well planned community-based screening programs can help to identify the exact prevalence of cervical pre-cancer in a region and the associated epidemiological factors leading to formulation of effective elimination strategies.

Comparison of polymerase chain reaction, microscopy, and rapid diagnostic test in malaria detection in a high burden state (Odisha) of India

ABSTRACT Precise identification of Plasmodium species is critical in malaria control and elimination. Despite several shortcomings, microscopy and rapid diagnostic test (RDT) continue to be the leading diagnostic methods. Polymerase chain reaction (PCR) is the most sensitive method but its dependency on advanced laboratory and skilled workers limits its use. Here, we compared the diagnostic performance of microscopy, RDT, and PCR in clinically suspected patients from a high malaria burden state (Odisha) of India. The diagnostic performance (sensitivity, specificity, positive predictive value, and negative predictive value) of all three methods was compared using microscopy and PCR as the gold standard. PCR identified 323 (76.5 %) positive cases out of 422 samples, whereas microscopy and RDT identified only 272 (64.4 %) and 266 (63.0 %) positive cases, respectively. The sensitivity of RDT and microscopy for detecting malaria and P. falciparum cases was >80% compared to that by PCR. However, the sensitivity in identifying P. vivax (57.0 %) and a mixture of P. falciparum and P. vivax (18.0 %) was poor. We highlight application of PCR in malaria diagnosis and its benefits in reducing the transmission. This emphasizes the need for incorporation of molecular diagnostic approaches for effective elimination strategies.

Investigation of the effects of various stress factors on biofilms and planktonic bacteria in cooling tower model system.

Biofilm is a microbial population which live in a self-produced extracellular polymeric matrix by attaching to surfaces. Biofilms consist of different different types of organisms such as bacteria, fungi, protozoa, etc. Many biofilms that develop in nature consist of more than one type of organism. Biofilms protect bacteria from adverse conditions such as temperature fluctuation and disinfectants. The aim of this study was to determine the effective elimination strategies for combating biofilm and planktonic bacteria in cooling tower model system using different decontamination / disinfection techniques. In this study, 14week-old biofilms were treated with temperatures of 4°C, 65°C; pH of 3, 11; 2 and 10mg/l chlorine, 2 and 10mg/l monochloramine; hypotonic salt (0.01% NaCl) and hypertonic salt (3% NaCl) solution. For enumeration, number of aerobic heterotrophic bacteria was determined by conventional culture method, number of live bacteria was determined by LIVE/DEAD viability kit, CTC-DAPI and Alamar blue staining methods. Temperature of 65°C, pH of 3, 10mg/l monochloramine and hypertonic salt solution were the most effective parameters for decontamination of biofilm and planktonic bacteria. Biofilm bacteria in the circulating water system were significantly more resistant than planktonic bacteria against stress factors. When the numbers of epifluorescence microscopy and conventional culture technique were compared, significantly higher number of live bacteria were detected using epifluorescence microscopy. Bacteria enter the viable but non-culturable phase by loosing their culturability under stress conditions. For this reason, the conventional culture method should be supported by different techniques to get more realistic numbers.

Serum indoxyl sulfate concentrations associate with progression of chronic kidney disease in children.

The uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (pCS) accumulate in patients with chronic kidney disease (CKD) as a consequence of altered gut microbiota metabolism and a decline in renal excretion. Despite of solid experimental evidence for nephrotoxic effects, the impact of uremic toxins on the progression of CKD has not been investigated in representative patient cohorts. In this analysis, IS and pCS serum concentrations were measured in 604 pediatric participants (mean eGFR of 27 ± 11 ml/min/1.73m2) at enrolment into the prospective Cardiovascular Comorbidity in Children with CKD study. Associations with progression of CKD were analyzed by Kaplan-Meier analyses and Cox proportional hazard models. During a median follow up time of 2.2 years (IQR 4.3–0.8 years), the composite renal survival endpoint, defined as 50% loss of eGFR, or eGFR <10ml/min/1.73m2 or start of renal replacement therapy, was reached by 360 patients (60%). Median survival time was shorter in patients with IS and pCS levels in the highest versus lowest quartile for both IS (1.5 years, 95%CI [1.1,2.0] versus 6.0 years, 95%CI [5.0,8.4]) and pCS (1.8 years, 95%CI [1.5,2.8] versus 4.4 years, 95%CI [3.4,6.0]). Multivariable Cox regression disclosed a significant association of IS, but not pCS, with renal survival, which was independent of other risk factors including baseline eGFR, proteinuria and blood pressure. In this exploratory analysis we provide the first data showing a significant association of IS, but not pCS serum concentrations with the progression of CKD in children, independent of other known risk factors. In the absence of comorbidities, which interfere with serum levels of uremic toxins, such as diabetes, obesity and metabolic syndrome, these results highlight the important role of uremic toxins and accentuate the unmet need of effective elimination strategies to lower the uremic toxin burden and abate progression of CKD.

Reveal a hidden highly toxic substance in biochar to support its effective elimination strategy

With the aim to develop optimized biochar with minimal contaminants, it is important significance to broaden the understanding of biochar. Here, we disclose for the first time, a highly toxic substance (metal cyanide, MCN, such as KCN or NaCN) in biochar. The cyanide ion (CN−) content in biochar can be up to 85,870 mg/kg, which is determined by the inherent metal content and type in the biomass with K and Na increasing and Ca, Mg and Fe decreasing its formation. Density functional theory (DFT) analysis shows that unstable alkali oxygen-containing metal salts such as K2CO3 can induce an N rearrangement reaction to produce for example, KOCN. The strong reducing character of the carbon matrix further converts KOCN to KCN, thus resulting biochar with high risk. However, the stable Mg, Ca and Fe salts in biomass cannot induce an N rearrangement reaction due to their high binding energies. We therefore propose that high valent metal chloride salts such as FeCl3 and MgCl2 could be used to inhibit the production of cyanide via metal interactive reaction. These findings open a new point of view on the potential risk of biochar and provide a mitigation solution for biochar’s sustainable application.

Identification of cholera hotspots in Zambia: A spatiotemporal analysis of cholera data from 2008 to 2017.

The global burden of cholera is increasing, with the majority (60%) of the cases occurring in sub-Saharan Africa. In Zambia, widespread cholera outbreaks have occurred since 1977, predominantly in the capital city of Lusaka. During both the 2016 and 2018 outbreaks, the Ministry of Health implemented cholera vaccination in addition to other preventative and control measures, to stop the spread and control the outbreak. Given the limitations in vaccine availability and the logistical support required for vaccination, oral cholera vaccine (OCV) is now recommended for use in the high risk areas ("hotspots") for cholera. Hence, the aim of this study was to identify areas with an increased risk of cholera in Zambia. Retrospective cholera case data from 2008 to 2017 was obtained from the Ministry of Health, Department of Public Health and Disease Surveillance. The Zambian Central Statistical Office provided district-level population data, socioeconomic and water, sanitation and hygiene (WaSH) indicators. To identify districts at high risk, we performed a discrete Poisson-based space-time scan statistic to account for variations in cholera risk across both space and time over a 10-year study period. A zero-inflated negative binomial regression model was employed to identify the district level risk factors for cholera. The risk map was generated by classifying the relative risk of cholera in each district, as obtained from the space-scan test statistic. In total, 34,950 cases of cholera were reported in Zambia between 2008 and 2017. Cholera cases varied spatially by year. During the study period, Lusaka District had the highest burden of cholera, with 29,080 reported cases. The space-time scan statistic identified 16 districts to be at a significantly higher risk of having cholera. The relative risk of having cholera in these districts was significantly higher and ranged from 1.25 to 78.87 times higher when compared to elsewhere in the country. Proximity to waterbodies was the only factor associated with the increased risk for cholera (P<0.05). This study provides a basis for the cholera elimination program in Zambia. Outside Lusaka, the majority of high risk districts identified were near the border with the DRC, Tanzania, Mozambique, and Zimbabwe. This suggests that cholera in Zambia may be linked to movement of people from neighboring areas of cholera endemicity. A collaborative intervention program implemented in concert with neighboring countries could be an effective strategy for elimination of cholera in Zambia, while also reducing rates at a regional level.

Prospects and restraints of green roofs for high-rise buildings in Sri Lanka

PurposeGreen roofs are acknowledged as a method to substitute greenery washed out by the urbanization. They provide many ecological and sustainable benefits of greenery; reduce the adverse effects of high-rise building constructions. Though this concept is more popular across many countries over the past few decades, still, implementation of this technology in Sri Lanka is new and scant. Hence, the purpose of this paper is to identify and analyze the potential of green roofs in high-rise buildings in Sri Lanka.Design/methodology/approachThe data collection was conducted through expert interviews and questionnaire survey. Expert interviews were carried out to validate the prospects and restraints identified through literature review to the Sri Lankan context and analyzed using content analysis. Questionnaire survey identified the most significant prospects and restraints using descriptive statistics and paired sample t-test. Purposive sampling was used to select participants.FindingsReduction of air pollution, aesthetical appearance, thermal benefits and energy savings, reduction of an urban heat island effect, the addition of points in the green rating system are the top most significant prospects that need to be highlighted in promoting green roof systems in Sri Lankan high rises. Less space allocation on rooftops, lack of technical competence and lack of awareness and research are restraints that need most effective elimination strategies to encourage green roof systems.Originality/valueThe first identified and quantified prospects and restraints for green roof system in Sri Lankan high-rise buildings can be utilized by the government, donors, multi-lateral agencies to promote the sustainable development in Sri Lanka and this knowledge could be used in different scale awareness programs. The value of this paper is such that the paper discusses the links of green roofs with the other facets of sustainability. The new legal reforms and amendments in Sri Lanka could potentially be pending with findings of this study.

Data Integration - Challenges, Techniques and Future Directions: A Comprehensive Study

Objectives: This paper studies various query reformulation techniques, which are used to convert the intermediate schema to the targeted schema. The techniques such as Ontology based information integration and data integration languages are also reviewed. Methods/Statistical Analysis: This paper discusses the techniques used for data integration and also to resolve inconsistencies from the integrated data. Data integration techniques mainly focusing on integration of data in several levels and applying independent or unified query over the data available. Findings: Analysis of various techniques done in the paper has led to the identification of several shortcomings and scope for improvements in the available techniques. This identified research directions includes vertical enhancement of wrappers by utilizing a single unified wrapper for all the data sources. Optimizing the queries depending on the data source is also another major requirement to provide efficient and faster results reducing the data retrieval latencies. The paper also advocates other research directions that include identifying duplicates from the retrieved data and performing effective elimination strategies to reduce space consumption. Identifying conflicts and applying strategies to eliminate conflicts is another major area with a huge scope for improvement. Application/Improvements: The comprehensive survey also recommends further works in the area of data integration techniques.

Biofilm formation by Salmonella Typhimurium and Staphylococcus aureus on stainless steel under either mono- or dual-species multi-strain conditions and resistance of sessile communities to sub-lethal chemical disinfection

Intercellular interactions encountered within and between different bacterial species are believed to play key roles in both biofilm formation and antimicrobial resistance. In this study, Salmonella Typhimurium and Staphylococcus aureus (3 strains per species) were left to form biofilms on stainless steel coupons incubated at 20 °C for 144 h (i.e. 6 days), in periodically renewable growth medium, under either mono- or dual-species conditions. Subsequently, the developed sessile communities were exposed for 6 min to sub-lethal concentrations of: (i) benzalkonium chloride (BC, 50 ppm), (ii) sodium hypochlorite (NaClO, 10 ppm), or (iii) peroxyacetic acid (PAA, 10 ppm). The dominance of each strain in the mono- and dual-species biofilm communities, both before and after disinfection, was monitored by pulsed field gel electrophoresis (PFGE). Results revealed that dual-species conditions led to a significant (ca. 10-fold) reduction in the number of sessile cells for both species, compared to mono-species ones, with interspecies interactions however found to not exert any significant effect on the disinfection resistance of each species as a whole. However, PFGE analysis revealed that the different strains here employed behaved differently with regard to biofilm formation and disinfection resistance, with this effect to be also strongly dependent on the culture conditions (mono-/dual-species) and the disinfectant applied. Such results expand our knowledge on multi-species biofilms formed by foodborne pathogenic bacteria and could hopefully be helpful in our efforts to develop effective elimination strategies and thus improve food safety.

Tumor growth accelerated by chemotherapy-induced senescent cells is suppressed by treatment with IL-12 producing cellular vaccines.

Standard-of-care chemo- or radio-therapy can induce, besides tumor cell death, also tumor cell senescence. While senescence is considered to be a principal barrier against tumorigenesis, senescent cells can survive in the organism for protracted periods of time and they can promote tumor development. Based on this emerging concept, we hypothesized that elimination of such potentially cancer-promoting senescent cells could offer a therapeutic benefit. To assess this possibility, here we first show that tumor growth of proliferating mouse TC-1 HPV-16-associated cancer cells in syngeneic mice becomes accelerated by co-administration of TC-1 or TRAMP-C2 prostate cancer cells made senescent by pre-treatment with the anti-cancer drug docetaxel, or lethally irradiated. Phenotypic analyses of tumor-explanted cells indicated that the observed acceleration of tumor growth was attributable to a protumorigenic environment created by the co-injected senescent and proliferating cancer cells rather than to escape of the docetaxel-treated cells from senescence. Notably, accelerated tumor growth was effectively inhibited by cell immunotherapy using irradiated TC-1 cells engineered to produce interleukin IL-12. Collectively, our data document that immunotherapy, such as the IL-12 treatment, can provide an effective strategy for elimination of the detrimental effects caused by bystander senescent tumor cells in vivo.

Systematic review of sub-microscopic P. vivax infections: prevalence and determining factors.

BackgroundSub-microscopic (SM) Plasmodium infections represent transmission reservoirs that could jeopardise malaria elimination goals. A better understanding of the epidemiology of these infections and factors contributing to their occurrence will inform effective elimination strategies. While the epidemiology of SM P. falciparum infections has been documented, that of SM P. vivax infections has not been summarised. The objective of this study is to address this deficiency.Methodology/Principal FindingsA systematic search of PubMed was conducted, and results of both light microscopy (LM) and polymerase chain reaction (PCR)-based diagnostic tests for P. vivax from 44 cross-sectional surveys or screening studies of clinical malaria suspects were analysed. Analysis revealed that SM P. vivax is prevalent across different geographic areas with varying transmission intensities. On average, the prevalence of SM P. vivax in cross-sectional surveys was 10.9%, constituting 67.0% of all P. vivax infections detected by PCR. The relative proportion of SM P. vivax is significantly higher than that of the sympatric P. falciparum in these settings. A positive relationship exists between PCR and LM P. vivax prevalence, while there is a negative relationship between the proportion of SM P. vivax and the LM prevalence for P. vivax. Amongst clinical malaria suspects, however, SM P. vivax was not identified.Conclusions/SignificanceSM P. vivax is prevalent across different geographic areas, particularly areas with relatively low transmission intensity. Diagnostic tools with sensitivity greater than that of LM are required for detecting these infection reservoirs. In contrast, SM P. vivax is not prevalent in clinical malaria suspects, supporting the recommended use of quality LM and rapid diagnostic tests in clinical case management. These findings enable malaria control and elimination programs to estimate the prevalence and proportion of SM P. vivax infections in their settings, and develop appropriate elimination strategies to tackle SM P. vivax to interrupt transmission.

Epidemiological Modeling of Bovine Brucellosis in India.

The study objective is to develop an epidemiological model of brucellosis transmission dynamics among cattle in India and to estimate the impact of different prevention and control strategies. The prevention and control strategies are test-and-slaughter, transmission rate reduction, and mass vaccination. We developed a mathematical model based on the susceptible-infectious-recovered epidemic model to simulate brucellosis transmission dynamics, calibrated to the endemically stable levels of bovine brucellosis prevalence of cattle in India. We analyzed the epidemiological benefit of different rates of reduced transmission and vaccination. Test-and-slaughter is an effective strategy for elimination and eradication of brucellosis, but socio-cultural constraints forbid culling of cattle in India. Reducing transmission rates lowered the endemically stable levels of brucellosis prevalence correspondingly. One-time vaccination lowered prevalence initially but increased with influx of new susceptible births. While this epidemiological model is a basic representation of brucellosis transmission dynamics in India and constrained by limitations in surveillance data, this study illustrates the comparative epidemiological impact of different bovine brucellosis prevention and control strategies.

Global progress towards eliminating gastrointestinal helminth infections

To highlight the gastrointestinal helminths in the context of renewed global commitment to control or eliminate neglected tropical diseases in the coming decade. Two key documents, namely the 2012 London Declaration for Neglected Tropical Diseases and the 2013 World Health Assembly resolution, emphasize the importance of mass drug administration (MDA) for controlling several key neglected tropical diseases. These documents, together with the Global Burden of Disease Study 2010, establish the major gastrointestinal helminth infections, including the soil-transmitted helminthiases - ascariasis, trichuriasis, hookworm, and strongyloidiasis - in addition to the intestinal and liver fluke infections, as some of the most important gastrointestinal infections of humankind. Current MDA approaches using single-dose albendazole or mebendazole are effective for ascariasis, less so for other soil-transmitted helminth infections. Expanded use of albendazole in combination with ivermectin would ensure improved drug efficacies against trichuriasis and strongyloidiasis. There is no effective elimination strategy for targeting hookworm and liver and intestinal fluke infections through current MDA approaches. The global community must expand current MDA efforts, while simultaneously developing additional drugs, diagnostics, and vaccines alongside better utilizing transmission dynamics and modeling, if it is to successfully meet the goals and targets established by policymakers.

Immune Inhibitory Receptors Support The Activity Of Leukemia STEM CELLS

New therapeutic strategies and targets are needed for cancer treatment. Previously we identified the immune inhibitory receptor LILRB2 as a receptor for angiopoietin-like protein 2 and supports acute myeloid leukemia (AML) development. Here, our new in silico analysis demonstrated that a large number of immune inhibitory receptors including LILRBs and LAIR1 are highly expressed on leukemia cells and their expression inversely correlates with overall survival of human AML patients (n = 186). These inhibitory receptors contain ITIMs in signaling domains and recruit phosphatases SHP-1, SHP-2, or SHIP for signaling. We focused on study the role of one of these inhibitory receptors, LAIR1.To study the potential function of LAIR1 in human leukemia, we silenced the expression of lair1 in 8 different human AML and ALL cell lines and in primary human AML cells. All the knockdown led to dramatic apoptosis of the cells in vitro and almost completely abolished leukemia development in xenograted NSG mice.To gain a deeper understanding of the mechanism by which LAIR1 supports AML development, we chose to study AML development in lair1-null mice. These mice have normal hematopoietic stem cell activity in the BM. The mice transplanted with MLL-AF9-transduced lair1-null cells developed AML drastically more slowly than controls in secondary transplantation. Mice transplanted with lair1-null AML cells had significantly decreased spleen sizes and leukemia cells. When lair1 expression was silenced, there was an approximately 90% decrease in numbers of AML stem cells (AML-SCs) -enriched YFP+Mac-1+Kit+ cells in BM than in mice transplanted with control AML cells. Importantly, the lair1-null AML cells had a 90% decrease upon the serial CFU replating, and disappeared in mice upon tertiary transplantation. These results suggest that LAIR1 sustains the stemness of AML-SCs.We further performed SHP-1 and SHP-2 rescue experiments to determine which phosphatase mediates the effects of LAIR1 in AML-SCs. The ectopic expression of SHP-1 was capable of rescuing the defective phenotype of lair1-null AML cells. This was evident in the primary and secondary plating for analysis of CFU and in the flow cytometry analysis of the hematopoietic lineages in transplanted mice. This was a surprising result; however, it was supported by the result of the in silico analysis of the relationship between SHP-1 expression and the overall survival of human AML patients (n =186).Taken together, our study marks the first step towards elucidation of the molecular mechanisms and signaling pathway by which LAIR1 supports AML-SC activity. The identification of ITIM-receptors and their downstream signaling as a potential new class of therapeutic targets may reshape our views regarding how cancer develops, how cancer stem cells differ from other cells, and how to treat this difficult disease. Our study suggests that, some leukemia stem cells express high levels of ITIM-inhibitory receptors. The current treatment (chemotherapy and kinase inhibition) may not efficiently target these cancer stem cells, because these inhibitory receptors enable the leukemia stem cells to survive the conventional therapies eventually resulting in tumor relapse. Therefore, the blockade of inhibitory receptor signaling through receptor targeting or SHP inhibition in combination with conventional therapies may prove to be an effective strategy for elimination of leukemia stem cells. Disclosures:No relevant conflicts of interest to declare.