Upregulation of S100A8 in peripheral blood mononuclear cells from patients with depression treated with SSRIs: a pilot study.

BACKGROUND: Major depressive disorder (MDD) affects more than 350 million people worldwide, and there is currently no laboratory test to diagnose it. This pilot study aimed to identify potential biomarkers in peripheral blood mononuclear cells (PBMCs) from MDD patients. METHODS: We used tandem mass tagging coupled to synchronous precursor selection (mass spectrometry) to obtain the differential proteomic profile from a pool of PBMCs from MDD patients and healthy subjects, and quantitative PCR to assess gene expression of differentially expressed proteins (DEPs) of our interest. RESULTS: We identified 247 proteins, of which 133 had a fold change ≥ 2.0 compared to healthy volunteers. Using pathway enrichment analysis, we found that some processes, such as platelet degranulation, coagulation, and the inflammatory response, are perturbed in MDD patients. The gene-disease association analysis showed that molecular alterations in PBMCs from MDD patients are associated with cerebral ischemia, vascular disease, thrombosis, acute coronary syndrome, and myocardial ischemia, in addition to other conditions such as inflammation and diabetic retinopathy. CONCLUSIONS: We confirmed by qRT-PCR that S100A8 is upregulated in PBMCs from MDD patients and thus could be an emerging biomarker of this disorder. This report lays the groundwork for future studies in a broader and more diverse population and contributes to a deeper characterization of MDD.

Defining operational research priorities to improve malaria control and elimination in sub-Saharan Africa: results from a country-driven research prioritization setting process.

BACKGROUND: In order to reignite gains and accelerate progress toward improved malaria control and elimination, policy, strategy, and operational decisions should be derived from high-quality evidence. The U.S. President's Malaria Initiative (PMI) Insights project together with the Université Cheikh Anta Diop of Dakar, Senegal, conducted a broad stakeholder consultation process to identify pressing evidence gaps in malaria control and elimination across sub-Saharan Africa (SSA), and developed a priority list of country-driven malaria operational research (OR) and programme evaluation (PE) topics to address these gaps. METHODS: Five key stakeholder groups were engaged in the process: national malaria programmes (NMPs), research institutions in SSA, World Health Organization (WHO) representatives in SSA, international funding agencies, and global technical partners who support malaria programme implementation and research. Stakeholders were engaged through individual or small group interviews and an online survey, and asked about key operational challenges faced by NMPs, pressing evidence gaps in current strategy and implementation guidance, and priority OR and PE questions to address the challenges and gaps. RESULTS: Altogether, 47 interviews were conducted with 82 individuals, and through the online survey, input was provided by 46 global technical partners. A total of 33 emergent OR and PE topics were identified through the consultation process and were subsequently evaluated and prioritized by an external evaluation committee of experts from NMPs, research institutions, and the WHO. The resulting prioritized OR and PE topics predominantly focused on generating evidence needed to close gaps in intervention coverage, address persistent challenges faced by NMPs in the implementation of core strategic interventions, and inform the effective deployment of new tools. CONCLUSION: The prioritized research list is intended to serve as a key resource for informing OR and PE investments, thereby ensuring future investments focus on generating the evidence needed to strengthen national strategies and programme implementation and facilitating a more coordinated and impactful approach to malaria operational research.

Prevalence and factors associated with skin-to-skin contact (SSC) practice: findings from a population-based cross-sectional survey in 10 selected districts of Bangladesh.

BACKGROUND: Skin-to-skin contact (SSC) practice improves newborn survival and child development through preventing hypothermia in newborns, improving early initiation of breastfeeding practice, and strengthening mother-child bonding. Despite having numerous benefits, it is one of the least practiced interventions in low and middle-income countries (1 to 74%). In Bangladesh, the prevalence of SSC was 26% in 2014. In this study, we aimed to estimate the prevalence of SSC in the study districts and identify factors that facilitate or inhibit SSC practice so that context-specific recommendations can be made to advance the use of this intervention. METHODS: We used baseline household survey data of USAID's MaMoni MNCSP project conducted in 10 districts of Bangladesh in 2019. Our analysis included 13,695 recently delivered women (RDW) with a live birth outcome. Our primary outcome was the mother's reported practice of SSC. We examined various antepartum, intrapartum, newborn, and sociodemographic factors associated with SSC using a multivariable generalized linear model. Our findings were reported using adjusted Prevalence Risk Ratios (aPRRs) and 95% Confidence Intervals (CIs). RESULTS: Overall, 28% of RDW reported practicing SSC across the 10 surveyed districts. Our multivariable analysis showed that public facility delivery (aPRR 2.01; 95%CI: 1.80, 2.26), private facility delivery (aPRR 1.23; 95%CI: 1.06, 1.42) and ≥ 4 antenatal care (ANC) visits at least one from a medically trained provider (MTP) (aPRR 1.17; 95%CI: 1.03, 1.26) had a significant positive association with SSC practice. Caesarean section (aPRR 0.64; 95%CI: 0.56, 0.73) had a significant negative association with SSC practice compared to vaginal births. We also found a significant positive association of SSC practice with mothers' who perceived the birth size of their baby to be small, mothers with a higher education level (≥10 years), and mothers from households in the highest wealth quintile. CONCLUSIONS: The prevalence of SSC is very low in the surveyed districts of Bangladesh. Considering the factors associated with SSC, relevant stakeholders need to increase their efforts on improving ANC and facility delivery coverages as well as improving SSC practice in the facilities especially after caesarean deliveries. Countries with a high burden of home deliveries, also need to emphasize community-based interventions and increasing coverage of skilled birth attendance for improving this life-saving intervention.

A Novel Approach to Depression Care: Efficacy of an Adapted Interpersonal Therapy in a Large, Urban Primary Care Setting.

The Collaborative Care Model (CoCM), in which social workers, primary care physicians, and a consulting psychiatrist work as a team, is an established approach to the treatment of common mental health conditions in primary care settings. Following implementation of a CoCM depression care program at our hospital-based academic primary care practice, we observed a low rate of retention with the use of problem solving therapy/behavioral activation (PST/BA). Our aim in this study was to evaluate the effectiveness of interpersonal psychotherapy (IPT), an evidence-based, flexible strategy that focuses on the relationship between depression and interpersonal challenges, compared to PST/BA. In 2015, most patients enrolled in our CoCM received PST/BA. In 2016, most patients received IPT. Patients who were enrolled and discharged from our CoCM depression care program in the years 2015 and 2016 and received either PST/BA or IPT, were included. Our primary measure was the difference in change in PHQ-9 score between the PST/BA and the IPT groups. Secondary outcomes included the difference in the change in GAD-7 score and measures of glycemic and blood pressure control between the two groups. Two hundred thirty four patients were included in our analysis. One hundred sixty five received PST/BA and 69 received IPT. There was no difference between groups in baseline demographics or measures of depression, anxiety, presence of hypertension, or presence of prediabetes/diabetes. Our primary analysis demonstrated a greater decrease in PHQ-9 score in patients receiving IPT (9.93) compared to those receiving PST/BA (5.41) (p < 0.0001). The proportion of patients achieving a clinical response (PHQ-9 < 10) was also greater in the IPT group (71%) compared to the PST/BA group (44%). In a CoCM depression care program, IPT was a more effective strategy in improving depression symptoms as measured by PHQ-9 scores than PST/BA.

Evaluating malaria programmes in moderate- and low-transmission settings: practical ways to generate robust evidence.

BACKGROUND: Many countries have made substantial progress in scaling-up and sustaining malaria intervention coverage, leading to more focalized and heterogeneous transmission in many settings. Evaluation provides valuable information for programmes to understand if interventions have been implemented as planned and with quality, if the programme had the intended impact on malaria burden, and to guide programmatic decision-making. Low-, moderate-, and heterogeneous-transmission settings present unique evaluation challenges because of dynamic and targeted intervention strategies. This paper provides illustration of evaluation approaches and methodologies for these transmission settings, and suggests how to answer evaluation questions specific to the local context. METHODS: The Roll Back Malaria Monitoring and Evaluation Reference Group formed a task force in October 2017 to lead development of this framework. The task force includes representatives from National Malaria Programmes, funding agencies, and malaria research and implementing partners. The framework builds on existing guidance for process and outcome evaluations and impact evaluations specifically in high transmission settings. RESULTS: The theory of change describes how evaluation questions asked by national malaria programmes in different contexts influence evaluation design. The transmission setting, existing stratification, and data quality and availability are also key considerations. The framework is intended for adaption by countries to their local context, and use for evaluation at sub-national level. Confirmed malaria incidence is recommended as the primary impact indicator due to its sensitivity to detect changes in low-transmission settings. It is expected that process evaluations provide sufficient evidence for programme monitoring and improvement, while impact evaluations are needed following adoption of new mixes of interventions, operational strategies, tools or policies, particularly in contexts of changing malaria epidemiology. Impact evaluations in low-, moderate-, or heterogeneous-transmission settings will likely use plausibility designs, and methods highlighted by the framework include interrupted time series, district-level dose-response analyses, and constructed control methods. Triangulating multiple data sources and analyses is important to strengthen the plausibility argument. CONCLUSIONS: This framework provides a structure to assist national malaria programmes and partners to design evaluations in low-, moderate- or heterogeneous-transmission settings. Emphasizing a continuous cycle along the causal pathway linking process evaluation to impact evaluation and then programmatic decision-making, the framework provides practical guidance in evaluation design, analysis, and interpretation to ensure that the evaluation meets national malaria programme priority questions and guides decision-making at national and sub-national levels.

Operationalising health systems thinking: a pathway to high effective coverage.

BACKGROUND: The global health community has recognised the importance of defining and measuring the effective coverage of health interventions and their implementation strength to monitor progress towards global mortality and morbidity targets. Existing health system models and frameworks guide thinking around these measurement areas; however, they fall short of adequately capturing the dynamic and multi-level relationships between different components of the health system. These relationships must be articulated for measurement and managed to effectively deliver health interventions of sufficient quality to achieve health impacts. Save the Children's Saving Newborn Lives programme and EnCompass LLC, its evaluation partner, developed and applied the Pathway to High Effective Coverage as a health systems thinking framework (hereafter referred to as the Pathway) in its strategic planning, monitoring and evaluation. METHODS: We used an iterative approach to develop, test and refine thinking around the Pathway. The initial framework was developed based on existing literature, then shared and vetted during consultations with global health thought leaders in maternal and newborn health. RESULTS: The Pathway is a robust health systems thinking framework that unpacks system, policy and point of intervention delivery factors, thus encouraging specific actions to address gaps in implementation and facilitate the achievement of high effective coverage. The Pathway includes six main components - (1) national readiness; (2) system structures; (3) management capacity; (4) implementation strength; (5) effective coverage; and (6) impact. Each component is comprised of specific elements reflecting the range of facility-, community- and home-based interventions. We describe applications of the Pathway and results for in-country strategic planning, monitoring of progress and implementation strength, and evaluation. CONCLUSIONS: The Pathway provides a cohesive health systems thinking framework that facilitates assessment and coordinated action to achieve high coverage and impact. Experiences of its application show its utility in guiding strategic planning and in more comprehensive and effective monitoring and evaluation as well as its potential adaptability for use in other health areas and sectors.

Are new national malaria strategic plans informed by the previous ones? A comprehensive assessment of sub-Saharan African countries from 2001 to present.

BACKGROUND: New national malaria strategic plans (NMSPs) should build upon the achievements and challenges identified during the implementation of previous plans, but there is limited research on the transition process between NMSPs. This study aims to fill this gap through an assessment of NMSPs across sub-Saharan Africa. METHODS: The study reviewed the two most recent NMSPs for selected sub-Saharan African countries. Targets for six core malaria indicators were extracted from each NMSP and compared to the coverage achieved according to corresponding population-based surveys completed near the end of the NMSP term. Implementation challenges and proposed solutions identified through the NMSP analysis were documented. The current NMSP was reviewed to determine whether proposed solutions had been integrated into the strategy. RESULTS: Twenty-two countries in sub-Saharan Africa were included in the assessment. Of the 135 verified targets, only 4 were achieved. No country reached more than one of the six targets assessed in each NMSP. Despite this low success rate, only four of the 22 countries lowered a subsequent target, with most setting the next target at an equal or greater level. Most NMSPs identified solutions to address implementation challenges faced, but the solutions were not always fully incorporated in the new strategy. CONCLUSIONS: The results show a disconnect between NMSPs. Most targets were set according to global goals rather than the individual country's previous achievements and limitations. This indicates a need to revise the NMSP development process to guide programmes in defining targets based on their country context and incorporate strategies to address challenges identified in the previous NMSP. This will allow countries to set and meet achievable targets as they work toward global goals.

Caregiver exposure to malaria social and behaviour change messages can improve bed net use among children in an endemic country: secondary analysis of the 2015 Nigeria Malaria Indicator Survey.

BACKGROUND: To reduce the malaria burden in Nigeria, the National Malaria Strategic Plan (NMSP) 2014‒2020 calls for the scale-up of prevention and treatment interventions, including social and behaviour change (SBC). SBC interventions can increase awareness and improve the demand for and uptake of malaria interventions. However, there is limited evidence supporting the implementation of SBC interventions to improve key malaria behaviours, such as insecticide-treated bed net (ITN) use, among children in Nigeria. METHODS: Using data from 2015 Nigeria Malaria Indicator Survey, this study used multiple logistic regression to assess the relationship between caregiver exposure to malaria messages and ITN use among children under five. RESULTS: Caregiver exposure to ITN-related messages was significantly associated with ITN use among children under five (odds ratio [OR] = 1.63, p < 0.001). CONCLUSIONS: The results suggest that caregiver exposure to topic-specific SBC messages improves the use of ITNs among children. Given these results, Nigeria should strive to scale up SBC interventions to help increase ITN use among children in line with the objectives of the NMSP. Further evidence is needed to determine which SBC interventions are the most effective and scalable in Nigeria.

A subnational profiling analysis reveals regional differences as the main predictor of ITN ownership and use in Nigeria.

BACKGROUND: To reduce the malaria burden in Nigeria, the country is scaling up prevention and treatment interventions, especially household ownership and use of insecticide-treated nets (ITNs). Nevertheless, large gaps remain to achieve the goals of the National Malaria Strategic Plan 2014-2020 of universal access to ITNs and their increased use. To inform the targeting of intervention strategies and to maximize impact, the authors conducted a sub-national profiling of household ITN ownership and use in the general population to identify key predictors of ITN ownership and use, and the sub-groups that are at higher risk of low ITN coverage and use. METHODS: The authors conducted a secondary analysis of data from the 2015 Nigeria Malaria Indicator Survey. Using the Chi square automatic interaction detector (CHAID) and multiple logistic regression analysis, the authors examined the key predictors of ITN ownership and use in the general population throughout Nigeria. RESULTS: The CHAID models identified region of the country as the best predictor of household ownership of at least one ITN and its use in the general population, with higher ownership and use observed in the northern regions. The odds of a household owning an ITN were five times greater in the North West region compared with the North Central region (odds ratio [OR] = 5.47, 95% confidence interval [CI] 4.46-6.72, p < 0.001). The odds of ITN use were two times greater for those living in the North West region compared with the North Central region (OR = 2.04, 95% CI 1.73-2.41, p < 0.001). Other significant predictors were household size, head of household education level, household wealth quintile, and place of residence. The CHAID gain index results identified households in the South West, North Central and South Central regions with low ITN ownership, and the general population in the South South, South East and North Central regions with low ITN use. CONCLUSIONS: This study reveals regional differences in ITN ownership and use in Nigeria. Therefore, the findings from this analysis provide evidence that could inform the NMEP to better target future campaign and routine distribution of ITNs, to achieve universal access and increased use by 2020 in Nigeria.

Alterations in the Levels of Growth Factors in Adolescents with Major Depressive Disorder: A Longitudinal Study during the Treatment with Fluoxetine.

Major depressive disorder (MDD) has a prevalence of 5% in adolescents. Several studies have described the association between the inflammatory response and MDD, but little is known about the relationship between MDD and growth factors, such as IL-7, IL-9, IL-17A, VEGF, basic FGF, G-CSF, and GM-CSF. It must be appointed that there are scarce reports on growth factors in adolescents with MDD and even fewer with a clinical follow-up. In this work, we evaluated the levels of growth factors (IL-7, IL-9, IL-17A, VEGF, basic FGF, G-CSF, and GM-CSF) in MDD adolescents and the clinical follow-up during eight weeks of treatment with fluoxetine. Methods. All patients were diagnosed according to the DSM-IV-TR, and the severity of the symptoms was evaluated using the Hamilton Depression Rating Scale (HDRS). Growth factors IL-7, IL-9, IL-17A, VEGF, basic FGF, G-CSF, and GM-CSF were quantified by cytometric bead array using serum samples from 22 adolescents with MDD and 18 healthy volunteers. Results. All patients showed clinical improvement since the fourth week of pharmacological treatment according to the HDRS. Considerably higher levels of IL-7, IL-9, IL-17A, VEGF, basic FGF, G-CSF, and GM-CSF were detected in MDD adolescents as compared to healthy volunteers. A significant but temporal decrease was detected in basic FGF, G-CSF, and GM-CSF at week four of fluoxetine administration. Conclusions. To the best of our knowledge, this is the first report to show alterations in the levels of growth factors, such as IL-7, IL-9, IL-17A, VEGF, basic FGF, G-CSF, and GM-CSF in MDD adolescents during eight weeks of clinical follow-up. These disturbances might be involved in the physiopathology of MDD since such growth factors have been proven to participate in the neural development and correct functioning of the CNS; therefore, subtle alterations in it may contribute to MDD.

Inflammatory Profiles in Depressed Adolescents Treated with Fluoxetine: An 8-Week Follow-up Open Study.

Changes in cytokine levels in major depression and during treatment have been reported in adults. However, few studies have examined cytokine levels in an adolescent sample despite this being a common age of onset. Methods. We measured proinflammatory (IL-2, IFN-γ, IL-1ß, TNF-α, IL-6, IL-12, and IL-15) and anti-inflammatory (IL-4, IL-5, IL-13, IL-1Ra, and IL-10) cytokine serum levels in 22 adolescents with major depression and 18 healthy volunteers. Cytokines were measured by multiplex bead-based immunoassays at baseline, and 4 and 8 weeks after commencement of fluoxetine administration in the clinical group. Results. Compared to healthy volunteers, adolescents with major depression at baseline showed significant increases in all pro- and anti-inflammatory cytokines, except IL-1Ra and IL-10. Significant changes were observed in fluoxetine treatment compared to baseline: proinflammatory cytokines IFN-γ, IL-1ß, TNF-α, IL-6, IL-12, and IL-15 were decreased only at week 4 whereas IL-2 was increased only at week 8; anti-inflammatory cytokines IL-4 and IL-5 were increased at week 8 while IL-1Ra was reduced only at week 4. There were no significant correlations between cytokine levels and symptomatic improvement in HDRS. Discussion. The results suggest a significant interplay between cytokine levels, the depressive state, and the stage of treatment with an SSRI. To the best of our knowledge, this is the first report in depressed adolescents with elevated IL-12, IL-13, and IL-15 levels. Further studies are necessary to clarify the role and mechanisms of altered cytokine levels in the pathogenesis and physiopathology of major depressive disorder.

Treating depression in an urban primary care setting: Introducing an adapted therapeutic approach to improve behavioral health engagement in primary care.

Depression is common in patients attending primary care clinics especially for those in socioeconomically disadvantaged urban neighborhoods. A number of behavioral health collaborative care models exist to screen, assess, and treat patients within primary care clinics. This paper discusses the implementation of a behavioral health care program using the Improving Mood Promoting Access to Collaborative Treatment (IMPACT) model within an urban primary care clinic setting in New York City, that serves a large population of ethnically diverse and socioeconomically disadvantaged patients. While elements of the structured IMPACT model in the clinic were effective, the therapeutic approaches did not always meet the needs of all the patients. Therefore, the article describes the challenges this program faced and highlights how the IMPACT model was modified to meet the specific needs of the patients by using an adapted version of Interpersonal Psychotherapy as an alternative psychosocial intervention to the traditional Problem Solving Treatment psychosocial treatment in IMPACT.

A systematic review and synthesis of the strengths and limitations of measuring malaria mortality through verbal autopsy.

BACKGROUND: Lack of valid and reliable data on malaria deaths continues to be a problem that plagues the global health community. To address this gap, the verbal autopsy (VA) method was developed to ascertain cause of death at the population level. Despite the adoption and wide use of VA, there are many recognized limitations of VA tools and methods, especially for measuring malaria mortality. This study synthesizes the strengths and limitations of existing VA tools and methods for measuring malaria mortality (MM) in low- and middle-income countries through a systematic literature review. METHODS: The authors searched PubMed, Cochrane Library, Popline, WHOLIS, Google Scholar, and INDEPTH Network Health and Demographic Surveillance System sites' websites from 1 January 1990 to 15 January 2016 for articles and reports on MM measurement through VA. INCLUSION CRITERIA: article presented results from a VA study where malaria was a cause of death; article discussed limitations/challenges related to measurement of MM through VA. Two authors independently searched the databases and websites and conducted a synthesis of articles using a standard matrix. RESULTS: The authors identified 828 publications; 88 were included in the final review. Most publications were VA studies; others were systematic reviews discussing VA tools or methods; editorials or commentaries; and studies using VA data to develop MM estimates. The main limitation were low sensitivity and specificity of VA tools for measuring MM. Other limitations included lack of standardized VA tools and methods, lack of a 'true' gold standard to assess accuracy of VA malaria mortality. CONCLUSIONS: Existing VA tools and methods for measuring MM have limitations. Given the need for data to measure progress toward the World Health Organization's Global Technical Strategy for Malaria 2016-2030 goals, the malaria community should define strategies for improving MM estimates, including exploring whether VA tools and methods could be further improved. Longer term strategies should focus on improving countries' vital registration systems for more robust and timely cause of death data.

Women Serum Concentrations of the IL-10 Family of Cytokines and IFN-γ Decrease from the Third Trimester of Pregnancy to Active Labor.

Labor is regarded as increased myometrial activity with a regular contractility pattern. At this final stage of pregnancy, myometrial quiescence is lost, accompanied by altered immune homeostasis. It is well known that the interleukin (IL)-10 family of cytokines modulates immunological responses mainly in epithelial cells, including the endometrium. To investigate their inflammatory profile during labor, we performed a longitudinal study in a group of healthy pregnant women (n = 20) with uncomplicated pregnancies in the third trimester of pregnancy and during active labor. Blood was sampled from pregnant women in the third trimester (gestational age 32-38 weeks, mean 36 ± 2 weeks) and during active labor (39-41 weeks of gestation, mean 40 ± 1 weeks). Serum levels of several cytokines were measured using multiplex immunoassays for both stages, indicating that the concentrations of IL-10, IL-20, IL-22, IL-28A, and interferon (IFN)-γ were significantly decreased during active labor in comparison with third-trimester levels (p < 0.05). Our analysis did not find significant correlations between IL-10, IL-20, IL-22, IL-28A, and IFN-γ levels and gestational age. However, our data suggest that the systemic downregulation of several members of the IL-10 family of cytokines plays an important role in the activation of myometrial smooth cells associated with uterine contractions during active labor. Downregulation of this IL-10 family of cytokines seems to coincide with the well-reported functional progesterone withdrawal during labor. Likewise, lower plasma IFN-γ concentrations may indicate a role for IFN-γ in active labor.

Strengthening individual capacity in monitoring and evaluation of malaria control programmes to streamline M&E systems and enhance information use in malaria endemic countries.

BACKGROUND: Malaria control interventions in most endemic countries have intensified in recent years and so there is a need for a robust monitoring and evaluation (M&E) system to measure progress and achievements. Providing programme and M&E officers with the appropriate skills is a way to strengthen malaria's M&E systems and enhance information use for programmes' implementation. This paper describes a recent effort in capacity strengthening for malaria M&E in sub-Saharan Africa (SSA). METHODS: From 2010 to 2014, capacity-strengthening efforts consisted of organizing regional in-person workshops for M&E of malaria programmes for Anglophone and Francophone countries in SSA in collaboration with partners from Ghana and Burkina Faso. Open-sourced online courses were also available in English. A post-workshop assessment was conducted after 5 years to assess the effects of these regional workshops and identify gaps in capacity. RESULTS: The regional workshops trained 181 participants from 28 countries from 2010 to 2014. Trained participants were from ministries of health, national malaria control and elimination programmes, non-governmental organizations, and development partners. The average score (%) for participants' knowledge tests increased from pretest to posttest for Anglophone workshops (2011: 59 vs. 76, 2012: 41 vs. 63, 2013: 51 vs. 73; 2014: 50 vs. 74). Similarly, Francophone workshop posttest scores increased, but were lower than Anglophone due to higher scores at pretest. (2011: 70 vs. 76, 2012: 74 vs. 79, 2013: 61 vs. 68; 2014: 64 vs. 75). Results of the post-workshop assessment revealed that participants retained practical M&E knowledge and skills for malaria programs, but there is a need for a module on malaria surveillance adapted to the pre-elimination context. CONCLUSION: The workshops were successful because of the curriculum content, facilitation quality, and the engagement of partner institutions with training expertise. Results from the post-workshop assessment will guide the curriculum's development and restructuring for the next phase of workshops. Country-specific malaria M&E capacity needs assessments may also inform this process as countries reduce malaria burden.

Malaria prevalence and use of control measures in an area with persistent transmission in Senegal.

INTRODUCTION: In Senegal, the widespread use of vector control measures has resulted in a significant reduction in the malaria burden and led the country to consider the possibility of elimination. Given this shift and changing context, it is important to characterize the malaria burden across all age groups to guide decision-making on programmatic interventions to interrupt transmission and ultimately eradicate the disease. In Senegal, there is a lack of information on malaria prevalence among certain populations, particularly among adolescents and adults. This study sought to assess the magnitude of malaria infections in all age groups, as well as malaria associated factors in an area of persistent transmission in Senegal. METHODS: A cross-sectional household survey was conducted in four health posts (Khossanto, Mamakhona, Diakhaling and Sambrambougou), of the health district of Saraya, in November 2021, among individuals over 6 months of age. Households were selected using multistage sampling. Consented participants were screened for malaria parasites by microscopic examination of blood smears, and hemoglobin levels were measured using the Hemocue HB 301TM analyzer. Socio-demographic information of the participants, household heads, household assets, and information on ownership and use of preventive measures were collected using a structured questionnaire. Weighted generalized mixed effects logistic regression model was used to identify factors associated with microscopically confirmed malaria infection. RESULTS: A total of 1759 participants were enrolled in the study. Overall, about 21% of participants were classified as having Plasmodium infection; children aged 5-10 years old (26.6%), adolescents aged 10-19 years old (24.7%), and children under five years of age (20.5%) had higher rates of infection compared to adults (13.5%). Plasmodium falciparum accounted for 99.2% of the malaria infections, and most infections (69%) were asymptomatic. Around one-third of study participants had anemia (hemoglobin level <11.0 g/dl), with under five children bearing the highest burden (67.3%). Multivariate analysis showed that the odds of having a malaria infection were around 2 times higher among participants in Khossanto compared to Diakhaling (aOR = 1.84, 95% CI:1.06-3.20). Participants aged 5-9 years were more likely to have malaria infection compared to under five children (aOR = 1.40, 95% CI:1.02-1.91). Factors associated with anemia were P. falciparum infection (aOR = 1.36, p = 0.027), females (aOR = 2.16, p = 0.000), under-five age group (aOR = 13.01, p = 0.000). CONCLUSION: Malaria burden was considerable among adolescents and under ten children living in an area of persistent transmission, with adolescents more commonly presenting as asymptomatic. Interventions tailored to this specific group of the population are needed to better control the disease and reduce its burden.

Risperidone Decreases Expression of Serotonin Receptor-2A (5-HT2A) and Serotonin Transporter (SERT) but Not Dopamine Receptors and Dopamine Transporter (DAT) in PBMCs from Patients with Schizophrenia.

Dopamine and serotonin receptors and transporters play an essential role in the pathophysiology of schizophrenia; changes in their expression have been reported in neurons and leukocytes. Each antipsychotic induces a unique pattern in leukocyte function and phenotype. However, the use of polytherapy to treat schizophrenia makes it challenging to determine the specific effects of risperidone on peripheral blood mononuclear cells (PBMCs). The aim of this study was to evaluate the changes in the expression of D3, D5, DAT, 5-HT2A, and SERT in PBMCs from healthy volunteers (HV), drug-naive patients with schizophrenia (PWS), drug-free PWS, and PWS treated with risperidone for up to 40 weeks using quantitative PCR. Our study revealed elevated mRNA levels of D3, DAT, 5-HT2A, and SERT in unmedicated PWS. Treatment with risperidone led to a reduction only in the expression of 5-HT2A and SERT. Furthermore, we observed a moderate correlation between 5-HT2A expression and the positive and negative syndrome scale (PANSS), as well as SERT expression and PANSS scale. We also found a moderate correlation between 5-HT2A and SERT expression and the positive subscale. The duration of risperidone consumption had a significant negative correlation with the expression of 5-HT2A and SERT. Our study introduces the measurement of 5-HT2A and SERT expression in PBMCs as a useful parameter for assessing the response to risperidone in PWS.

Concomitant Treatment with Doxycycline and Rifampicin in Balb/c Mice Infected with Brucella abortus 2308 Fails to Reduce Inflammation and Motor Disability.

Brucellosis is an infection widely distributed around the world, and in some countries it is considered a public health problem. Brucellosis causes insidious symptoms that make it difficult to diagnose. Infection can also trigger chronic pain and neuropsychiatric complications. Antibiotics are not always effective to eradicate infection, contributing to chronicity. We aimed to investigate the effects of antibiotic treatment on proinflammatory cytokines, neurotransmitters, corticosterone, and behavior in a murine model of infecrion of B. abortus strain 2308. Four study groups were created: (a) control; (b) antibiotic control; (c) infected with B. abortus 2308; and (d) infected and treated with rifampicin and doxycycline. We determined B. abortus 2308 colony-forming units (CFUs), the count of dendritic cells, and macrophages in the spleen; serum levels of cytokines and corticosterone; levels of serotonin, dopamine, epinephrine, and norepinephrine in the brain; and equilibrium, physical strength, anxiety, and hopelessness tests. The infected and treated mice group was compared with the control and infected mice to assess whether treatment is sufficient to recover neuroimmunoendocrine parameters. Our results showed that despite the treatment of brucellosis with rifampicin and doxycycline, antibiotic-treated mice showed a persistence of B. abortus 2308 CFUs, an increased count in macrophage number, and higher circulating levels of corticosterone. Furthermore, the levels of IL-12, IL-6, and TNF-α remained higher. We found a decrease in muscular strength and equilibrium concomitant to changes in neurotransmitters in the hippocampus, cerebellum, and frontal cortex. Our data suggest that the remaining bacterial load after antibiotic administration favors inflammatory, neurochemical, and behavioral alterations, partly explaining the widespread and paradoxical symptomatology experienced by patients with chronic brucellosis.

Imipramine Administration in Brucella abortus 2308-Infected Mice Restores Hippocampal Serotonin Levels, Muscle Strength, and Mood, and Decreases Spleen CFU Count.

Brucellosis infection causes non-specific symptoms such as fever, chills, sweating, headaches, myalgia, arthralgia, anorexia, fatigue, and mood disorders. In mouse models, it has been associated with increased levels of IL-6, TNF-α, and IFN-γ, a decrease in serotonin and dopamine levels within the hippocampus, induced loss of muscle strength and equilibrium, and increased anxiety and hopelessness. Imipramine (ImiP), a tricyclic antidepressant, is used to alleviate neuropathic pain. This study evaluated the effects of ImiP on Balb/c mice infected with Brucella abortus 2308 (Ba) at 14- and 28-days post-infection. Serum levels of six cytokines (IFN-γ, IL-6, TNF-α, IL-12, MCP-1. and IL-10) were assessed by FACS, while the number of bacteria in the spleen was measured via CFU. Serotonin levels in the hippocampus were analyzed via HPLC, and behavioral tests were conducted to assess strength, equilibrium, and mood. Our results showed that mice infected with Brucella abortus 2308 and treated with ImiP for six days (Im6Ba14) had significantly different outcomes compared to infected mice (Ba14) at day 14 post-infection. The mood was enhanced in the forced swimming test (FST) (p < 0.01), tail suspension test (TST) (p < 0.0001), and open-field test (p < 0.0001). Additionally, there was an increase in serotonin levels in the hippocampus (p < 0.001). Furthermore, there was an improvement in equilibrium (p < 0.0001) and muscle strength (p < 0.01). Lastly, there was a decrease in IL-6 levels (p < 0.05) and CFU count in the spleen (p < 0.0001). At 28 days, infected mice that received ImiP for 20 days (Im20Ba28) showed preservation of positive effects compared to infected mice (Ba28). These effects include the following: (1) improved FST (p < 0.0001) and TST (p < 0.0001); (2) better equilibrium (p < 0.0001) and muscle strength (p < 0.0001); (3) decreased IL-6 levels (p < 0.05); and (4) reduced CFU count in the spleen (p < 0.0001). These findings suggest the potential for ImiP to be used as an adjuvant treatment for the symptoms of brucellosis, which requires future studies.

Malaria prevention knowledge, attitudes, and practices (KAP) among adolescents living in an area of persistent transmission in Senegal: Results from a cross-sectional study.

INTRODUCTION: While malaria morbidity has sharply declined in several areas in Senegal, it remains an important problem in the southern part of the country, particularly among adolescents. Understanding adolescents' knowledge, attitudes, prevention and care-seeking practices is important to inform more targeted interventions aimed at optimizing adolescents' uptake of malaria prevention and control measures. This study assessed malaria-related knowledge, attitudes, and practices (KAP) among adolescents living in a highly persistent transmission area in Senegal. METHODS: A community-based cross-sectional survey was conducted among 391 adolescents living in the Saraya health district. A multistage random sampling technique was used to select households. An electronic questionnaire developed on Open Data Kit (ODK), was used to collect data on socio-demographic characteristics, household assets, adolescents' knowledge of malaria, as well as their attitudes with regards to malaria prevention, and care-seeking behaviors. Bivariate and multivariate analyses were performed to assess factors associated with adolescents' KAP towards malaria. RESULTS: Nearly, one-third of the participants had good knowledge of malaria (34.4%) and good practice in regards to malaria preventive measures (32.8%) while 59.0% had a positive attitude and 73.8% had good care-seeking behavior regarding malaria. Multivariate analysis revealed that a primary (aOR = 5.43, p = 0.002) or secondary level of education (aOR = 10.41, p = 0.000) was associated with good knowledge of malaria transmission, signs, and prevention measures. Male individuals had lower knowledge compared to female ones (aOR = 0.40, p = 0.001). Individuals belonging to households from the highest wealth quintile were more likely to have a positive attitude towards malaria compared to those from households in the lowest wealth quintile (aOR = 3.49, p = 0.004). The odds of positive attitude towards malaria decreased among participants with koranic and primary education level, respectively (aOR = 0.14, p = 0.005) and (aOR = 0.24, p = 0.019). A positive attitude was 1.89 more likely to be (aOR = 1.89, p = 0.026) associated with good practice of prevention measures compared to adolescents who demonstrated negative attitudes. Individuals from households in the fourth (aOR = 0.42, p = 0.024), middle (aOR = 0.34, P = 0.005), and second (aOR = 0.42, p = 0.027) wealth quintiles were less likely to use malaria prevention measures compared to those from households in the highest wealth quintile. CONCLUSION: The study revealed that adolescents, generally have poor levels of malaria knowledge and low uptake of malaria prevention and control interventions. Targeted interventions for high-risk adolescents are needed, that focus on improving their knowledge of the disease and effective preventive measures, and on increasing their access to health care services and LLINs.