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OBJECTIVE: We assessed the impact of political conflict (Boko Haram) on tuberculosis (TB) case noti?cations in Adamawa State in North-east Nigeria. DESIGN: A retrospective analysis of TB case notifications from TB registers (2010-2016) to describe changes in TB notification, sex and age ratios by the degree of conflict by local government area. SETTING: Adamawa State. PARTICIPANTS: 21?076 TB cases notified. RESULTS: 21?076 cases (62% male) were noti?ed between 2010 and 2016, of which 19 604 (93%) were new TB cases. Areas affected by conflict in 2014 and 2015 had decreased case notification while neighbouring areas reported increased case notifications. The male to female ratio of TB cases changed in areas in conflict with more female cases being notified. The young and elderly (1-14 and >65 years old) had low notifications in all areas,with a small increase in case notifications during the years of conflict. CONCLUSION: TB case notifications decreased in conflict areas and increased in areas without conflict. More males were notified during peace times and more female cases were reported from areas in conflict. Young and elderly populations had decreased case notifications but experienced a slight increase during the conflict years. These changes are likely to reflect population displacement and a dissimilar effect of conflict on the accessibility of services. TB services in conflict areas deserve further study to identify resilient approaches that could reach affected populations., BMJ open, 10(9), art.no.e035263; 2020

There is no definitive predictor of dengue severity, and this has led to a very large number of unnecessary hospitalizations worldwide. Although mast cell mediators are believed to a play role in dengue severity, the lack of precise kinetic data demands further research on early predictors. We enrolled 111 patients with confirmed dengue and 85 with “other febrile illness” (OFI) in a hospital-based prospective study in Vietnam. Dengue patients were classified as level 1, 2, or 3 based on the clinical intervention received. Blood samples were collected from each patient every day (pre- and post-defervescence) and after discharge. Plasma chymase, total IgE, and dengue-specific IgE were measured. Dengue-specific IgE levels showed an increasing trend during the course of illness and remained high even at post-discharge, although no significant difference was observed among severity levels. Total IgE showed no such trend. The specific IgE/total IgE ratio (S/T ratio) remained constantly higher in level 3 patients compared to other levels, with a significant difference at some time points. The S/T ratio of acute phase samples (before defervescence) tended to increase with increasing severity (level 1 < 2 < 3), and was significantly higher in level 3 patients than in level 1 and OFI patients. As an early predictor of severity allowing level 3 patients to be distinguished from other dengue patients, the S/T ratio achieved a sensitivity of 75% and specificity of 68%. We describe the kinetic profiles of IgEs, their ratio, and chymase levels at different severity levels. The S/T ratio was found to be associated with dengue severity, suggesting that it could potentially be used as an early predictor of severity.

The increasing resistance of malaria to drugs raise the need to new antimalarial agents. Antiplasmodial herbs and their active compounds are the most promising source the new antimalarial agents. This study aimed to identify the medicinal plants with very good in vitro antiplasmodial activities, with half-maximal inhibitory concentration (IC50)≤1μg/ml, and to determine trends in the process of screening their antiplasmodial activities. A total of 58 reports published in the English language were retrieved from the bibliographical databases. Screening and data extraction were performed by two independent reviewers. The herbs were categorized as very good, good, moderate and inactive if the IC50 values were 1-5μg/ml and >5μg/ml respectively. We documented 752 medicinal plants belonging to 254 genera. The majority of the plants were reported from Africa followed by Asia. The traditional use for malaria treatment was the most common reason for the selection of the plants for investigation. About 80% of the plants experimented were reported to be inactive. Among plants identified as having very good to good antiplasmodial crude extracts are Harungana madagascariensis, Quassia africana, and Brucea javanica, while Picrolemma spruce, Aspidosperma vargasi, Aspidosperma desmanthum, and Artemisia annua were reported to have individual compound isolates with very good antiplasmodial activities. In conclusion, the number of plant species assessed so far is still small compared with the stock in nature's plant library. A mechanism of systematically approaching and exploring the untouched plant genera needs to be designed.

Background and objectives Modulation of the immune reaction is essential in the development of various diseases, including dengue's “Cytokine Tsunami”, an increase in vascular permeability with concomitant severe vascular leakage. We aim to identify the role of T-helper (Th) cells, Th2 and Th7, with their related cytokines in dengue pathogenesis. Material and methods Nine electronic databases and manual search were applied to detect available publications. A meta-analysis using a fixed- or random-effect model was performed to measure standardized mean difference (SMD) with 95% confidence interval (CI). The National Institute of Health (NIH) tools for observational cohort, cross-sectional, and case-control studies were used to examine the risk of bias. The protocol was recorded in PROSPERO with CRD42017060230. Results A total of 38 articles were found including 19 case-control, 11 cross-sectional and 8 prospective cohort studies. We indicated that Th2 cytokines (IL-4, IL-6, IL-8) and Th17 cytokine (IL-17) in dengue patients were notably higher than in a healthy control group in acute phase (SMD = 1.59, 95% CI [0.68, 2.51], p = 0.001; SMD = 1.24, 95% CI [0.41, 2.06], p = 0.003; SMD = 1.13, 95% CI [0.61, 1.66], p Conclusions This study provides evidence of the significant roles of IL-4, IL-6, IL-8, IL-10 and IL-17 in the pathogenesis of developing a severe reaction in dengue fever. However, to fully determine the association of Th cytokines with dengue, it is necessary to perform further studies to assess kinetic levels during the duration of the illness.

BACKGROUND: The National Program for Chagas disease was implemented in Bolivia in 2006, and it greatly decreased the number of infections through vector control. Subsequently, a treatment regimen of benznidazole (BNZ) was started in seropositive school-age children living in certified vector control areas. METHODS AND FINDINGS: We conducted a 12-month follow-up study and seven blood samples were taken during and after the treatment. Serology, conventional diagnostic PCR (cPCR) and quantitative Real-time PCR (qPCR) were performed. Plasma Th1/Th2/Th17 cytokines levels were also determined. Approximately 73 of 103 seropositive children complied with BNZ, with three interruptions due to side effects. To evaluate each individual's treatment efficacy, the cPCR and qPCR values during the final 6 months of the follow-up period were observed. Among 57 children who completed follow-up, 6 individuals (11%) showed both cPCR(+) and qPCR(+) (non reactive), 24 (42%) cPCR(-) but qPCR(+) (ambiguous) and 27 (47%) cPCR(-) and qPCR(-) (reactive). Within 14 Th1/Th2/Th17 cytokines, IL-17A showed significantly higher levels in seropositive children before the treatment compared to age-matched seronegative children and significantly decreased to the normal level one-year after. Moreover, throughout the follow-up study, IL-17A levels were positively co-related to parasite counts detected by qPCR. At the 12 months' time point, IL-17A levels of non-reactive subjects were significantly higher than either those of reactive or ambiguous subjects suggesting that IL-17A might be useful to determine the reactivity to BNZ treatment. CONCLUSIONS: Plasma levels of IL-17A might be a bio-marker for detecting persistent infection of T. cruzi and its chronic inflammation., PLoS neglected tropical diseases, 13(9), e0007715; 2019

BackgroundChagas disease (CD), typically confined to the Latin America (LA) region, is emerging as a global health problem. In Japan, as in the rest of world, the under-diagnose rate of CD is alarmingly high. Various studies have highlighted the importance of informed knowledge in the seeking behavior. Educational integrative activities, with consideration for socio-cultural factors, can help increase the knowledge of the participants. There has been no studies that analyze the difference in knowledge, before and after these educational activities. This study aimed to qualitatively and quantitatively investigate the knowledge, behavior and attitude toward CD among LA migrants in Japan and to evaluate the effectiveness of the community educational activity in increasing knowledge of CD.MethodologyThis cross-sectional study involved two questionnaires to analyze the knowledge of the LA migrant participants before and after the community activity (CA) in four cities in Japan (Oizumi, Suzuka, Hadano, and Nagoya).Principal FindingsA total of 75 participants were enrolled, predominantly Bolivians from hyperendemic areas. The baseline knowledge of CD was low. However, most of them were familiar with the disease although less than 10% of them had been tested for CD before. Living in Japan for more than 10 years and previously being tested for CD were the factors associated with better knowledge. The conducted CA significantly improved the knowledge of the participants. They associated the term “Chagas” mostly with fear and concern. In contrast to other studies, the level of stigmatization was low. The barriers in care seeking behavior were language, migration process and difficulties to access to the healthcare system.ConclusionEducational activities with integrative approach are useful to increase knowledge of CD. The activity brings the possibility to explore not only the level of knowledge, but also to reveal the experience and to understand the needs of the people at risk.Author SummaryThough the incident rate of Chagas disease (CD) has fallen, more than 7 million people are affected worldwide. The CD prevalence is under-estimated because just 1% of these affected people can access to the diagnosis and treatment. This situation is maintaining mainly for the lack of implication of socio-cultural factors in the interventions to decrease the burden of the disease. Educational activities with integral approach are useful to increase the knowledge of the people at risk. People that have being tested for CD before or living in Japan for more than 10 years have better knowledge about the disease, suggesting the importance of knowledge in the seeking behavior. The authors recommend the implementation of educational activities with integral approach as a strategy to improves the knowledge of Chagas disease among Latin America migrants in Japan.

Background: Considerable progress has been made in dengue management, however the lack of appropriate predictors of severity has led to huge number of unwanted admissions mostly decided on the grounds of warning signs. Apoptosis related mediators,among others, are known to correlate with severe dengue (SD) although no predictive validity is established. The objective of this study was to investigate the association of plasma cell-free DNA (cfDNA) with SD, and evaluate its prognostic value in SD prediction at acute phase. Methods: This was a hospital-based prospective cohort study conducted in Vietnam.All the recruited patients were required to be admitted to the hospital and were strictly monitored for various laboratory and clinical parameters(including progression to SD) until discharged. Plasma samples collected during acute phase (6-48 h before defervescence) were used to estimate the level of cfDNA. Results: Of the 61 dengue patients,SD patients (n = 8)developed shock syndrome in 4.8 days (95% CI 3.7-5.4) after the fever onset. Plasma cfDNA levels before the defervescence of SD patients were significantly higher than the non-SD group (p = 0.0493). From the receiver operating characteristic (ROC) curve analysis, a cut-off of > 36.9 ng/mL was able to predict SD with a good sensitivity (87.5%), specificity (54.7%), and area under the curve (AUC) (0.72, 95% CI 0.55-0.88; p = 0.0493).Conclusions: Taken together, these findings suggest that cfDNA could serve as a potential prognostic biomarker of SD. Studies with cfDNA kinetics and its combination with other biomarkers and clinical parameters would further improve the diagnostic ability for SD., Annals of Clinical Microbiology and Antimicrobials, 18(1), art.no.10; 2019

The objective was to assess the immunoequivalence and protective efficacy of the novel, relatively safe dendrigraft poly-l-lysine-based nanoparticle formulation in comparison to the non-degradable polyethylenimine-based system. Groups of 6-week-old female C57BL/6 mice were immunized three times biweekly. Each mouse received 100 µg of the Plasmodium yoelii GPI8p-transamidase PyTAM formulated with nanoball that consisted of PyTAM/PEI/γ-PGA or PyTAM/DGL/γ-PGA and their respective nanoparticle-coated blank vector controls. Two weeks after the last immunization, the humoral responses and cellular immune response were assessed. The survival and parasitemia were evaluated in each group challenged intraperitoneally with 106 of a lethal strain of P. yoelii 17XL-parasitized red blood cells. Mice immunized with PyTAM/PEI/γ-PGA or PyTAM/DGL/γ-PGA showed similar survival rates, humoral responses and T helper 1 pro-inflammatory cellular immune responses in vivo and ex vivo. In particular, the PyTAM/DGL/γ-PGA formulation showed a significant increase in conventional dendritic cells in the spleen, which were consistently associated with high interleukin-12 production, the driver of the T helper 1 response. We show that the substitution of non-degradable polyethylenimine with the biodegradable dendrigraft poly-l-lysine in the nanoparticle formulation is immunoequivalent and elicits protective immunity against the lethal strain of P. yoelii. Therefore, this new gene-delivery vehicle with a good safety profile presents an exciting prospect for application in vaccination strategies.

Background: The protective or pathogenic role of T lymphocytes during the acute phase of dengue virus (DENV) infection has not been fully understood despite its importance in immunity and vaccine development . Objectives: This study aimed to clarify the kinetics of T lymphocyte subsets during the clinical course of acute dengue patients. Study design: In this hospital-based cohort study, 59 eligible Vietnamese dengue patients were recruited and admitted. They were investigated and monitored for T cell subsets and a panel of clinical and laboratory parameters every day until discharged and at post-discharge from the hospital. Results: We described for the first time the kinetics of T cell response during the clinical course of DENV infection. Severe cases showed significantly lower levels of effector CD8+ T cells compared to mild cases at day ?1 (p = 0.017) and day 0 (p = 0.033) of defervescence. After defervescence, these cell counts in severe cases increased rapidly to equalize with the levels of mild cases. Our results also showed a decline in total CD4+ T, Th1, Th1/17 cells during febrile phase of dengue patients compared to normal controls or convalescent phase. On the other hand, Th2 cells increased during DENV infection until convalescent phase. Cytokines such as interferon-γ, IL-12p70, IL-5, IL-23, IL-17A showed tendency to decrease on day 0 and 1 compared with convalescence and only IL-5 showed significance indicating the production during acute phase was not systemic.Conclusion: With a rigorous study design, we uncovered the kinetics of T cells in natural DENV infection. Decreased number of effector CD8+ T cells in the early phase of infection and subsequent increment after defervescence day probably associated with the T cell migration in DENV infection., Frontiers in Immunology, 11, art.no.1980; 2020

Oxidosqualene cyclase (OSC), a membrane-associated protein, is a key enzyme of sterol biosynthesis. Here we report a novel assay for OSC, involving reaction in aqueous solution, NMR quantification in organic solvent, and factor analysis of spectra. We evaluated one known and three novel inhibitors on OSC of Trypanosoma cruzi, a parasite causative of Chagas disease, and compared their effects on human OSC for selectivity. Among them, one novel inhibitor showed a significant parasiticidal activity.

There is still urgent need for a vaccine against schistosomiasis, especially in Schistosoma japonicum endemic areas where even a vaccine that will interrupt zoonotic transmission will be potentially effective as an intervention tool. We had developed a novel nanoparticle gene delivery system, which has proven efficacious in gene transfection to target immune cells with complementary adjuvant effect and high protective efficacy in several diseases. Here, we applied this nanoparticle system in combination with S. japonicum glutathione S-transferase (SjGST) DNA vaccine to show the immunogenicity and anti-fecundity effect of the nanoparticle coated vaccine formulation against murine schistosomiasis. The nanoparticle-coated DNA vaccine formulation induced desired immune responses. In comparison with the nanoparticle coated empty vector, it produced significantly increased antigen-specific humoral response, T-helper 1 polarized cytokine environment, higher proportion of IFN-γ producing CD4(+) T-cells and the concomitant decrease in IL-4 producing CD4(+) T-cells. Although there was no effect on worm burden, we recorded a marked reduction in tissue egg burden. There was up to 71.3% decrease in tissue egg burden and 55% reduction in the fecundity of female adult worms. Our data showed that SjGST DNA vaccine, delivered using the nanoparticle gene delivery system, produced anti-fecundity effect on female adult schistosomes as previously described by using conventional subunit vaccine with adjuvant, proving this DNA vaccine formulation as a promising candidate for anti-pathology and transmission blocking application.

Introduction: Dengue is a viral disease that spreads rapidly in the tropic and subtropic regions of the world and causes 22,000 deaths annually. In 2009, the World Health Organization (WHO) released a new classification of dengue infections, which divided them into three categories: dengue without warning sign (D), dengue with warning sign (DWS), and severe dengue (SD). However, researchers have been using different criteria to define persistent vomiting; therefore, we aimed to evaluate the ability of the number of vomiting times in early prediction of SD development among D/DWS patients. Method: A hospital-based cohort study was conducted in Ben Tre-south of Vietnam. We enrolled confirmed dengue patients with D and DWS at admission. The final classification was determined on the discharged day for every patient based on the classification of WHO 2009 without using vomiting symptom, using the receiver operating characteristic (ROC) curve to evaluate the ability of the number of vomiting times in early prediction of SD development among D/DWS patients. Result: The prevalence of vomiting symptom was higher in SD group than D/DWS group (92 versus 46 %, p = 0.006), and the median of the number of vomiting times was higher in SD group than D/DWS group (2.5 versus 0, p = 0.001). To distinguish SD from D/DWS, the ROC curve of the number of vomiting episodes showed that the area under the curve was 0.77; with the cut point of two, the sensitivity and specificity were 92 and 52 %, respectively. Conclusion: The number of vomiting times could be a good clinical sign which can early predict SD from the group of D/DWS. We suggest the definition of persistent vomiting should be vomiting two times or more per day., Tropical Medicine and Health, 44, 14; 2016