Infection With Strongyloides Stercoralis Among Children In Urban Slums Of Kibera In Nairobi, Kenya

Background: Strongyloidiasis is an intestinal parasitic infection with poorly-defined geographical Endemicity in Africa. It is a Soil-Transmitted Helminths (STH) infection caused by Strongyloides stercoralis and Strongyloides fuelleborni. Aim: To investigate the prevalence of Strongyloides infection among children living in an urban slum in Nairobi, Kenya. Likewise, to assess it's association with other soil - transmitted Helminths. Methodology and Findings: We used the recently-developed Ss-NIE-1-antibody ELISA assay for Strongyloides to evaluate Sera collected during a 2012 study of Soil Transmitted Helminth infection prevalence among children in the Kibera slum of Nairobi, Kenya. A total of 745 samples from School Age Children (SAC) and Pre-school-age children (PSAC) were tested; eight (1.1%) were positive for Strongyloides. Infection was equally common among SAC and PSAC. No association was found between infection with Strongyloides and infection with other Soil Transmitted Helminths. Conclusion: Strongyloides is a rare infection among children living in the urban slum of Kibera. Similar evaluation of exposure to Strongyloides stercoralis across different age groups and environmental, geographical features in Africa are warranted. Keywords: Strongyloides, children, Keny

Correction: Whole-blood expression of inflammasome- and glucocorticoid-related mRNAs correctly separates treatment-resistant depressed patients from drug-free and responsive patients in the BIODEP study

We have corrected this Article post-publication, because Dr. Cattaneo’s affiliation details were originally incorrect (she was affiliated with three institutions but is in fact only linked to one: Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia). These changes reflect in both the PDF and HTML versions of this Article

Correction: Whole-blood expression of inflammasome- and glucocorticoid-related mRNAs correctly separates treatment-resistant depressed patients from drug-free and responsive patients in the BIODEP study.

We have corrected this Article post-publication, because Dr. Cattaneo's affiliation details were originally incorrect (she was affiliated with three institutions but is in fact only linked to one: Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia). These changes reflect in both the PDF and HTML versions of this Article

Whole-blood expression of inflammasome- and glucocorticoid-related mRNAs correctly separates treatment-resistant depressed patients from drug-free and responsive patients in the BIODEP study

Funder: DH | National Institute for Health Research (NIHR); doi: https://doi.org/10.13039/501100000272Abstract: The mRNA expression signatures associated with the ‘pro-inflammatory’ phenotype of depression, and the differential signatures associated with depression subtypes and the effects of antidepressants, are still unknown. We examined 130 depressed patients (58 treatment-resistant, 36 antidepressant-responsive and 36 currently untreated) and 40 healthy controls from the BIODEP study, and used whole-blood mRNA qPCR to measure the expression of 16 candidate mRNAs, some never measured before: interleukin (IL)-1-beta, IL-6, TNF-alpha, macrophage inhibiting factor (MIF), glucocorticoid receptor (GR), SGK1, FKBP5, the purinergic receptor P2RX7, CCL2, CXCL12, c-reactive protein (CRP), alpha-2-macroglobulin (A2M), acquaporin-4 (AQP4), ISG15, STAT1 and USP-18. All genes but AQP4, ISG15 and USP-18 were differentially regulated. Treatment-resistant and drug-free depressed patients had both increased inflammasome activation (higher P2RX7 and proinflammatory cytokines/chemokines mRNAs expression) and glucocorticoid resistance (lower GR and higher FKBP5 mRNAs expression), while responsive patients had an intermediate phenotype with, additionally, lower CXCL12. Most interestingly, using binomial logistics models we found that a signature of six mRNAs (P2RX7, IL-1-beta, IL-6, TNF-alpha, CXCL12 and GR) distinguished treatment-resistant from responsive patients, even after adjusting for other variables that were different between groups, such as a trait- and state-anxiety, history of childhood maltreatment and serum CRP. Future studies should replicate these findings in larger, longitudinal cohorts, and test whether this mRNA signature can identify patients that are more likely to respond to adjuvant strategies for treatment-resistant depression, including combinations with anti-inflammatory medications

CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice

Neuroinflammation and microglial activation are significant processes in Alzheimer’s disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes in association with Alzheimer’s disease, and experimental data have demonstrated microglial proliferation as a significant component of the neuropathology. In this study, we tested the efficacy of the selective CSF1R inhibitor JNJ-40346527 (JNJ-527) in the P301S mouse tauopathy model. We first demonstrated the anti-proliferative effects of JNJ-527 on microglia in the ME7 prion model, and its impact on the inflammatory profile, and provided potential CNS biomarkers for clinical investigation with the compound, including pharmacokinetic/pharmacodynamics and efficacy assessment by TSPO autoradiography and CSF proteomics. Then, we showed for the first time that blockade of microglial proliferation and modification of microglial phenotype leads to an attenuation of tau-induced neurodegeneration and results in functional improvement in P301S mice. Overall, this work strongly supports the potential for inhibition of CSF1R as a target for the treatment of Alzheimer’s disease and other tau-mediated neurodegenerative diseases

Inflammatory biomarkers in Alzheimer's disease plasma

Introduction:Plasma biomarkers for Alzheimer’s disease (AD) diagnosis/stratification are a“Holy Grail” of AD research and intensively sought; however, there are no well-established plasmamarkers.Methods:A hypothesis-led plasma biomarker search was conducted in the context of internationalmulticenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL;259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed.Results:Ten analytes showed significant intergroup differences. Logistic regression identified five(FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APOε4 adjusted, optimally differentiated AD andCTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI(AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Twoanalytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71).Discussion:Plasma markers of inflammation and complement dysregulation support diagnosis andoutcome prediction in AD and MCI. Further replication is needed before clinical translatio

Experiences of a community-based lymphedema management program for lymphatic filariasis in Odisha State, India: An analysis of focus group discussions with patients, families, community members and program volunteers

Author Summary Around the world 68 million people are infected with lymphatic filariasis (LF), a mosquito-borne disease caused by filarial worms. The parasite can damage patients' lymphatic systems causing pain, infections and swollen limbs, known as lymphedema or, in more advanced stages, elephantiasis. Lymphedema management programs can help patients to deal with the physical and emotional effects of lymphedema and elephantiasis. We held a total of 24 focus groups to discuss the experiences of people with lymphedema in Odisha State, India who participate in such a program. Discussions were held with patients, family members of patients, community members and program volunteers. Significant social, physical and economic difficulties were described by patients and family members, including marriage-related issues, social stigma, and lost workdays. However, the positive impacts of the lymphedema management program were also emphasized, and many family and community members indicated that community members were accepting of patients and had some improved understanding of the cause of the disease. People were able to hold both a 'scientific' and a 'traditional' understanding of LF at the same time. The financial hardships that people described highlight the need for improved economic opportunities for lymphedema-affected patients. Support programs based in the community also have clear social and emotional benefits. There is an urgent need to scale up LF management programs to reduce the suffering of people affected by LF

A Delphi consultation to assess indicators of readiness to provide quality health facility-based lymphoedema management services.

BACKGROUND:The World Health Organization (WHO) in collaboration with partners is developing a toolkit of resources to guide lymphatic filariasis (LF) morbidity management and disability prevention (MMDP) implementation and evaluation. Direct health facility inspection is the preferred method for documenting the readiness of a country programme to provide quality lymphoedema management services, one of the three MMDP criteria used to demonstrate the elimination of LF as a public health problem. METHODOLOGY/PRINCIPAL FINDINGS:As component of tool development, a Delphi consultation was implemented to gain consensus on six proposed domains and fourteen proposed tracer indicators to measure national programme readiness to provide quality health facility-based lymphoedema management services. A seven-point Likert-type scale was used to rank the importance of proposed domains and tracer indicators. Consensus for inclusion of the indicator was defined a priori as 70% or more of respondents ranking the proposed indicator in the top three tiers (5-7). Purposive sampling was used to select 43 representative experts including country representatives, programme implementers, and technical experts. A 55.8% response rate (n = 24) was achieved for the survey. Analysis of the responses demonstrated that consensus for inclusion had been reached for all proposed domains including trained staff (mean = 6.9, standard deviation (SD) = 0.34), case management and education materials (mean = 6.1, SD = 0.65), water infrastructure (mean = 6.3, SD = 0.81), medicines and commodities (mean = 6.3, SD = 0.69), patient tracking system (mean = 6.3, SD = 0.85), and staff knowledge (mean = 6.5, SD = 0.66). SIGNIFICANCE:The Delphi consultation provided an efficient and structured method for gaining consensus among lymphatic filariasis experts around key lymphoedema management quality indicators. The results from this analysis were used to refine the indicators included within the direct inspection protocol tool to ensure its ability to assess health facility readiness to provide quality lymphoedema management services

Evaluation of a facility-based inspection tool to assess lymphedema management services in Vietnam.

Assuring availability of services for patients with lymphedema is required for countries to be validated as having achieved elimination of lymphatic filariasis (LF). A direct inspection protocol (DIP) tool, designed to measure the readiness to provide quality lymphedema management services, has recently been developed. The DIP tool includes 14 indicators across six quality themes: trained staff, case management and education materials, water infrastructure, medicines and commodities, patient tracking system, and staff knowledge. We evaluated the use of the tool in Vietnam, where data were needed to inform validation efforts. To apply the tool in Vietnam, we compiled a list of 219 commune health stations (CHS) with known lymphedema patients and conducted a cross-sectional survey in 32 CHS; including 24 in Red River Delta region, 2 in the North Central region, and 6 in the South Central Coast region. The mean facility score, calculated by assigning 1 point per indicator, was 8.8 of 14 points (63%, range 4[29%]-13[93%]). Percentage of surveyed facilities with staff trained in last two years was 0%; availability of lymphedema management guidelines (56%); availability of information, education, and communication materials (16%); reliable improved water infrastructure (94%); availability of antiseptics (81%), antifungals (44%), analgesics or anti-inflammatories (97%), antibiotics (94%); supplies for lymphedema and acute attack management (100%); lymphedema patients recorded in last 12 months (9%); staff knowledge about lymphedema signs/symptoms (63%), lymphedema management strategies (72%), signs/symptoms of acute attacks (81%), and acute attack management strategies (75%). The tool allowed standardized assessment of readiness to provide quality services. Lack of trained health staff, limited patient tracking, and depletion of education materials were identified as challenges and addressed by the national program. Survey data were included in the validation dossier, providing evidence necessary for WHO to validate Vietnam as having eliminated lymphatic filariasis in 2018

Assessment of factors related to individuals who were never treated during mass drug administration for lymphatic filariasis in Ambon City, Indonesia.

BackgroundOne challenge to achieving Lymphatic filariasis (LF) elimination is the persistent coverage-compliance gap during annual mass drug administration (MDA) and the risk of ongoing transmission among never treated individuals. Our analysis examined factors associated with individuals who were never treated during MDA.MethodsData were derived from two cross-sectional surveys conducted in Waihaong and Air Salobar Health Center in 2018 and 2019. We analyzed information from 1915 respondents aged 18 years or above. The study outcome was individuals who self-reported never treatment during any round of MDA. All potential predictors were grouped into socio-demographic, health system, therapy and individual factors. Logistic regression analyses were used to examine factors associated with never treatment in any year of MDA.ResultsNearly half (42%) of respondents self-reported they were never treated during any round of MDA. Factors associated with increased odds of never treatment were respondents working in formal sectors (aOR = 1.75, p = 0.040), living in the catchment area of Waihaong Health Center (aOR = 2.33, p = 0.029), and those perceiving the possibility of adverse events after swallowing LF drugs (aOR = 2.86, pConclusionsEfforts to reassure community members about adverse events, specific instructions on how to take LF drugs, and improving awareness that MDA participation is part of one's contribution to promoting community health are essential drivers for uptake with LF drugs during MDA