Varied Prevalence of Antimalarial Drug Resistance Markers in Different Populations of Newly Arrived Refugees in Uganda.

Newly arrived refugees offer insights into malaria epidemiology in their countries of origin. We evaluated asymptomatic refugee children within 7 days of arrival in Uganda from South Sudan and the Democratic Republic of Congo (DRC) in 2022 for parasitemia, parasite species, and Plasmodium falciparum drug resistance markers. Asymptomatic P. falciparum infections were common in both populations. Coinfection with P. malariae was more common in DRC refugees. Prevalences of markers of aminoquinoline resistance (PfCRT K76T, PfMDR1 N86Y) were much higher in South Sudan refugees, of antifolate resistance (PfDHFR C59R and I164L, PfDHPS A437G, K540E, and A581G) much higher in DRC refugees, and of artemisinin partial resistance (ART-R; PfK13 C469Y and A675V) moderate in both populations. Prevalences of most mutations differed from those seen in Ugandans attending health centers near the refugee centers. Refugee evaluations yielded insights into varied malaria epidemiology and identified markers of ART-R in 2 previously little-studied countries.

Sex-Linked Differences in Malaria Risk Across the Lifespan.

Despite the high burden of malaria worldwide, there is surprisingly scarce research on sex-based differences in malaria outside of pregnancy. A more thorough understanding of sexual dimorphism in malaria, and what underlies these sex-based differences, could elucidate the underlying mechanisms driving malaria pathogenesis and has the potential to inform malaria control efforts, including new vaccines. This review summarizes our current understanding of sex-based differences in the epidemiology of malaria across the lifespan, potential sex- or gender-based mechanisms driving these differences, and the knowledge gaps that need to be addressed.

Prevent Acute Chest Syndrome checklist (PACScheck): A quality improvement initiative to reduce acute chest syndrome.

BACKGROUND: Acute chest syndrome (ACS) is a life-threatening complication of sickle cell disease (SCD). The Prevent Acute Chest Syndrome checklist (PACScheck) was created to drive appropriate ordering of opioids, incentive spirometry (IS), intravenous fluids (IVF), evaluation of oxygen desaturation, and bronchodilator use. OBJECTIVES: Decrease the development of ACS by 5% in a hospitalized pediatric SCD population. METHODS: A multidisciplinary team conducted a quality improvement (QI) project between April 2020 and August 2021 on an inpatient pediatric hematology unit. At-risk hospitalizations were patients with SCD who did not have ACS upon hospital admission. PACScheck was implemented and weekly run charts assessed documentation. Process control (p) charts, geometric control (g) charts, and chi-square tests assessed checklist process measures pre- and post-PACScheck. G chart assessed the number of encounters between ACS events. RESULTS: A total of 483 at-risk hospitalizations were identified in the 12 months prior and 363 during the study period. A g chart demonstrated that fewer encounters developed ACS during PACScheck. A p chart demonstrated that IS documentation increased during PACScheck. A run chart of PACScheck documentation demonstrated a median of 100% documentation at least once per hospitalization during the last six months of the intervention. CONCLUSION: Development of ACS can be reduced by implementing a best-practices checklist (PACScheck) on an inpatient pediatric hematology unit with a multidisciplinary team.

Retention of discharge instructions using an interdisciplinary model for at-risk children with cancer: A quality improvement initiative.

PURPOSE: We sought to improve caregiver retention of critical initial hospital discharge instructions using a multidisciplinary, team-based intervention for newly diagnosed pediatric cancer patients at high risk for unfavorable outcomes. MATERIALS AND METHODS: A multidisciplinary team of pediatric residents, nurses, social workers, pharmacists and hematology/oncology faculty implemented practices to optimize teaching of key discharge material as part of four Plan-Do-Study-Act intervention cycles. An 11-question survey distributed at the first post-discharge clinic visit assessed the efficacy of the intervention, as defined by caregiver retention of critical home instructions. RESULTS: Thirty-nine caregivers of pediatric cancer patients in an urban academic tertiary-care children's hospital took part in this project. Overall retention of key discharge information was greater in the post-intervention cohort compared to the baseline cohort (median total scores: 89 and 63, respectively; p = .001). Improvements in the proportions of correct responses post-intervention were also observed across all subject matters: from 0.57 to 0.88 for fever guidelines (p = .059), from 0.71 to 0.78 for signs of sepsis (p = .65), from 0.57 to 1.00 for accurate choice of on-call number (p = .004), and from 0.71 to 0.94 for antiemetic management (p = .14). CONCLUSION: Initiation of our comprehensive cancer-specific program to improve caregiver retention of discharge instructions at the first post-hospitalization clinic visit has been successful and sustainable. This project demonstrated that a multi-disciplinary collaborative team effort increases caregiver retention of critical health information, and this has potential to lead to improved outcomes for patients.

Gender difference in the incidence of malaria diagnosed at public health facilities in Uganda.

BACKGROUND: Routine malaria surveillance data in Africa primarily come from public health facilities reporting to national health management information systems. Although information on gender is routinely collected from patients presenting to these health facilities, stratification of malaria surveillance data by gender is rarely done. This study evaluated gender difference among patients diagnosed with parasitological confirmed malaria at public health facilities in Uganda. METHODS: This study utilized individual level patient data collected from January 2020 through April 2021 at 12 public health facilities in Uganda and cross-sectional surveys conducted in target areas around these facilities in April 2021. Associations between gender and the incidence of malaria and non-malarial visits captured at the health facilities from patients residing within the target areas were estimated using poisson regression models controlling for seasonality. Associations between gender and data on health-seeking behaviour from the cross-sectional surveys were estimated using poisson regression models controlling for seasonality. RESULTS: Overall, incidence of malaria diagnosed per 1000 person years was 735 among females and 449 among males (IRR = 1.72, 95% CI 1.68-1.77, p < 0.001), with larger differences among those 15-39 years (IRR = 2.46, 95% CI 2.34-2.58, p < 0.001) and over 39 years (IRR = 2.26, 95% CI 2.05-2.50, p < 0.001) compared to those under 15 years (IRR = 1.46, 95% CI 1.41-1.50, p < 0.001). Female gender was also associated with a higher incidence of visits where malaria was not suspected (IRR = 1.77, 95% CI 1.71-1.83, p < 0.001), with a similar pattern across age strata. These associations were consistent across the 12 individual health centres. From the cross-sectional surveys, females were more likely than males to report fever in the past 2 weeks and seek care at the local health centre (7.5% vs. 4.7%, p = 0.001) with these associations significant for those 15-39 years (RR = 2.49, 95% CI 1.17-5.31, p = 0.018) and over 39 years (RR = 2.56, 95% CI 1.00-6.54, p = 0.049). CONCLUSIONS: Females disproportionately contribute to the burden of malaria diagnosed at public health facilities in Uganda, especially once they reach childbearing age. Contributing factors included more frequent visits to these facilities independent of malaria and a higher reported risk of seeking care at these facilities for febrile illnesses.

LLIN Evaluation in Uganda Project (LLINEUP2)-Factors associated with coverage and use of long­lasting insecticidal nets following the 2020-21 national mass distribution campaign: a cross-sectional survey of 12 districts.

BACKGROUND: In 2020-2021, long-lasting insecticidal nets (LLINs) were distributed nationwide in Uganda during the COVID-19 pandemic. A cross-sectional survey was conducted in 12 districts to evaluate the impact of the campaign 1-5 months after LLIN distribution. METHODS: During April-May 2021, households were randomly selected from target areas (1-7 villages) surrounding 12 government-run health facilities established as Malaria Reference Centres; at least 50 households were enrolled per cluster. Outcomes included household ownership of LLINs distributed through the universal coverage campaign (UCC) (at least one UCC LLIN), adequate coverage of UCC LLINs (at least one UCC LLIN per 2 residents), and use of LLINs (resident slept under a LLIN the previous night). Multivariate logistic regression models were used to identify household- and individual-level factors associated with outcomes, controlling for clustering around health facilities. RESULTS: In total, 634 households, with 3342 residents and 1631 bed-nets, were included. Most households (93.4%) owned at least 1 UCC LLIN, but only 56.8% were adequately covered by UCC LLINs. In an adjusted analysis, the factor most strongly associated with adequate coverage by UCC LLINs was fewer household residents (1-4 vs 7-14; adjusted odds ratio [aOR] 12.96, 95% CI 4.76-35.26, p < 0.001; 5-6 vs 7-14 residents; aOR 2.99, 95% CI 1.21-7.42, p = 0.018). Of the 3166 residents of households that owned at least one UCC LLIN, only 1684 (53.2%) lived in adequately covered households; 89.9% of these used an LLIN the previous night, compared to 1034 (69.8%) of 1482 residents living in inadequately covered households. In an adjusted analysis, restricted to residents of inadequately covered households, LLIN use was higher in children under-five than those aged 5-15 years (aOR 3.04, 95% CI 2.08-4.46, p < 0.001), and higher in household heads than distantly-related residents (aOR 3.94, 95% CI 2.38-6.51, p < 0.001). CONCLUSIONS: Uganda's 2021-21 campaign was successful, despite the COVID-19 pandemic. In future campaigns, strategies should be adopted to ensure high LLIN coverage, particularly for larger households. A better understanding of the drivers of LLIN use within households is needed to guide future interventions, educational messages, and behaviour change communication strategies; school-aged children and distantly-related residents appear vulnerable and could be targeted.

Relationships between test positivity rate, total laboratory confirmed cases of malaria, and malaria incidence in high burden settings of Uganda: an ecological analysis.

BACKGROUND: Malaria surveillance is critical for monitoring changes in malaria morbidity over time. National Malaria Control Programmes often rely on surrogate measures of malaria incidence, including the test positivity rate (TPR) and total laboratory confirmed cases of malaria (TCM), to monitor trends in malaria morbidity. However, there are limited data on the accuracy of TPR and TCM for predicting temporal changes in malaria incidence, especially in high burden settings. METHODS: This study leveraged data from 5 malaria reference centres (MRCs) located in high burden settings over a 15-month period from November 2018 through January 2020 as part of an enhanced health facility-based surveillance system established in Uganda. Individual level data were collected from all outpatients including demographics, laboratory test results, and village of residence. Estimates of malaria incidence were derived from catchment areas around the MRCs. Temporal relationships between monthly aggregate measures of TPR and TCM relative to estimates of malaria incidence were examined using linear and exponential regression models. RESULTS: A total of 149,739 outpatient visits to the 5 MRCs were recorded. Overall, malaria was suspected in 73.4% of visits, 99.1% of patients with suspected malaria received a diagnostic test, and 69.7% of those tested for malaria were positive. Temporal correlations between monthly measures of TPR and malaria incidence using linear and exponential regression models were relatively poor, with small changes in TPR frequently associated with large changes in malaria incidence. Linear regression models of temporal changes in TCM provided the most parsimonious and accurate predictor of changes in malaria incidence, with adjusted R2 values ranging from 0.81 to 0.98 across the 5 MRCs. However, the slope of the regression lines indicating the change in malaria incidence per unit change in TCM varied from 0.57 to 2.13 across the 5 MRCs, and when combining data across all 5 sites, the R2 value reduced to 0.38. CONCLUSIONS: In high malaria burden areas of Uganda, site-specific temporal changes in TCM had a strong linear relationship with malaria incidence and were a more useful metric than TPR. However, caution should be taken when comparing changes in TCM across sites.

Impact of COVID-19 on routine malaria indicators in rural Uganda: an interrupted time series analysis.

BACKGROUND: In March 2020, the government of Uganda implemented a strict lockdown policy in response to the COVID-19 pandemic. Interrupted time series analysis (ITSA) was performed to assess whether major changes in outpatient attendance, malaria burden, and case management occurred after the onset of the COVID-19 epidemic in rural Uganda. METHODS: Individual level data from all outpatient visits collected from April 2017 to March 2021 at 17 facilities were analysed. Outcomes included total outpatient visits, malaria cases, non-malarial visits, proportion of patients with suspected malaria, proportion of patients tested using rapid diagnostic tests (RDTs), and proportion of malaria cases prescribed artemether-lumefantrine (AL). Poisson regression with generalized estimating equations and fractional regression was used to model count and proportion outcomes, respectively. Pre-COVID trends (April 2017-March 2020) were used to predict the'expected' trend in the absence of COVID-19 introduction. Effects of COVID-19 were estimated over two six-month COVID-19 time periods (April 2020-September 2020 and October 2020-March 2021) by dividing observed values by expected values, and expressed as ratios. RESULTS: A total of 1,442,737 outpatient visits were recorded. Malaria was suspected in 55.3% of visits and 98.8% of these had a malaria diagnostic test performed. ITSA showed no differences between observed and expected total outpatient visits, malaria cases, non-malarial visits, or proportion of visits with suspected malaria after COVID-19 onset. However, in the second six months of the COVID-19 time period, there was a smaller mean proportion of patients tested with RDTs compared to expected (relative prevalence ratio (RPR) = 0.87, CI (0.78-0.97)) and a smaller mean proportion of malaria cases prescribed AL (RPR = 0.94, CI (0.90-0.99)). CONCLUSIONS: In the first year after the COVID-19 pandemic arrived in Uganda, there were no major effects on malaria disease burden and indicators of case management at these 17 rural health facilities, except for a modest decrease in the proportion of RDTs used for malaria diagnosis and the mean proportion of malaria cases prescribed AL in the second half of the COVID-19 pandemic year. Continued surveillance will be essential to monitor for changes in trends in malaria indicators so that Uganda can quickly and flexibly respond to challenges imposed by COVID-19.

Within-household clustering of genetically related Plasmodium falciparum infections in a moderate transmission area of Uganda.

BACKGROUND: Evaluation of genetic relatedness of malaria parasites is a useful tool for understanding transmission patterns, but patterns are not easily detectable in areas with moderate to high malaria transmission. To evaluate the feasibility of detecting genetic relatedness in a moderate malaria transmission setting, relatedness of Plasmodium falciparum infections was measured in cohort participants from randomly selected households in the Kihihi sub-county of Uganda (annual entomological inoculation rate of 27 infectious bites per person). METHODS: All infections detected via microscopy or Plasmodium-specific loop mediated isothermal amplification from passive and active case detection during August 2011-March 2012 were genotyped at 26 microsatellite loci, providing data for 349 samples from 230 participants living in 80 households. Pairwise genetic relatedness was calculated using identity by state (IBS). RESULTS: As expected, genetic diversity was high (mean heterozygosity [He] = 0.73), and the majority (76.5 %) of samples were polyclonal. Despite the high genetic diversity, fine-scale population structure was detectable, with significant spatiotemporal clustering of highly related infections. Although the difference in malaria incidence between households at higher (mean 1127 metres) versus lower elevation (mean 1015 metres) was modest (1.4 malaria cases per person-year vs. 1.9 per person-year, respectively), there was a significant difference in multiplicity of infection (2.2 vs. 2.6, p = 0.008) and, more strikingly, a higher proportion of highly related infections within households (6.3 % vs. 0.9 %, p = 0.0005) at higher elevation compared to lower elevation. CONCLUSIONS: Genetic data from a relatively small number of diverse, multiallelic loci reflected fine scale patterns of malaria transmission. Given the increasing interest in applying genetic data to augment malaria surveillance, this study provides evidence that genetic data can be used to inform transmission patterns at local spatial scales even in moderate transmission areas.

Impact of Microscopic and Submicroscopic Parasitemia During Pregnancy on Placental Malaria in a High-Transmission Setting in Uganda.

BACKGROUND: Placental malaria is a major cause of adverse birth outcomes. However, data are limited on the relationships between longitudinal measures of parasitemia during pregnancy and placental malaria. METHODS: Data came from 637 women enrolled in a randomized controlled trial of intermittent preventive treatment of malaria in pregnancy (IPTp) from Uganda. Plasmodium falciparum parasitemia was assessed using microscopy and ultrasensitive quantitative PCR at intervals of 28 days from 12 to 20 weeks gestation through delivery. Multivariate analysis was used to measure associations between characteristics of parasitemia during pregnancy and the risk of placental malaria based on histopathology. RESULTS: Overall risk of placental malaria was 44.6%. None of the 34 women without parasitemia detected during pregnancy had evidence of placental malaria. Increasing proportion of interval assessments with parasitemia and higher parasite densities were independently associated with an increased risk of placental malaria. Higher gravidity and more effective IPTp were associated with a decreased risk of placental malaria. Women with parasitemia only detected before the third trimester still had an increased risk of placental malaria. CONCLUSIONS: The frequency, density, and timing of parasitemia are all important risk factors for placental malaria. Interventions should target the prevention of all levels of parasitemia throughout pregnancy.

Persistent Parasitemia Despite Dramatic Reduction in Malaria Incidence After 3 Rounds of Indoor Residual Spraying in Tororo, Uganda.

BACKGROUND: Indoor residual spraying of insecticide (IRS) has been associated with reductions in the incidence of malaria, but its impact on malaria parasitemia is unclear. METHODS: We followed 469 participants from August 2011 to May 2016 in Tororo, Uganda, a historically high malaria transmission setting. Three rounds of IRS with bendiocarb were implemented from December 2014 to December 2015. Symptomatic malaria episodes were identified by passive surveillance. Parasitemia was identified by active surveillance every 1-3 months using microscopy and Plasmodium falciparum-specific loop-mediated isothermal amplification. RESULTS: IRS was associated with a significant decline in the incidence of symptomatic malaria irrespective of age (episodes per person per year declined from 3.98 to 0.13 in children aged <5 years, 2.30 to 0.15 in children aged 5-10 years, and 0.41 to 0 in adults; P < .001 for all). IRS significantly reduced the prevalence of parasitemia, but the prevalence remained high (pre-IRS to post-third round: 58.5% to 11.3% in children aged <5 years, 73.3% to 23.7% in children aged 5-10 years, and 52.2% to 15.4% in adults; P < .001 for all). CONCLUSIONS: Although IRS was associated with significant reductions in the incidence of malaria and prevalence of parasitemia, a proportion of the population remained parasitemic, providing a potential reservoir for malaria transmission.

"Tuberculosis in advanced HIV infection is associated with increased expression of IFNγ and its downstream targets".

BACKGROUND: Tuberculosis (TB) is the major cause of death in Human Immunodeficiency Virus (HIV)-infected individuals. However, diagnosis of TB in HIV remains challenging particularly when HIV infection is advanced. Several gene signatures and serum protein biomarkers have been identified that distinguish active TB from latent infection. Our study was designed to assess if gene expression signatures and cytokine levels would distinguish active TB in advanced HIV. METHODS: We conducted a case-control study of whole blood RNA-Seq and plasma cytokine/chemokine analysis in HIV-infected with CD4+ T cell count of ≤ 100 cells/µl, with and without active TB. Next, the overlap of the differentially expressed genes (DEG) with the published signatures was performed and then receiver operator characteristic (ROC) analysis was done on small gene discriminators to determine their performance in distinguishing TB in advanced HIV. ELISA was performed on plasma to evaluate cytokine and chemokine levels. RESULTS: Hierarchical clustering of the transcriptional profiles showed that, in general, HIV-infected individuals with TB (TB-HIV) clustered separately from those without TB. IPA indicated that the TB-HIV signature was characterized by an increase in inflammatory signaling pathways. Analysis of overlaps between DEG in our data set with published TB signatures revealed that significant overlap was seen with one TB signature and one TB-IRIS signature. ROC analysis revealed that transcript levels of FcGR1A (AUC = 0.85) and BATF2 (AUC = 0.82), previously reported as consistent single gene classifiers of active TB irrespective of HIV status, performed successfully even in advanced HIV. Plasma protein levels of IFNγ, a stimulator of FcGR1A and BATF2, and CXCL10, also up-regulated by IFNγ, accurately classified active TB (AUC = 0.98 and 0.91, respectively) in advanced HIV. Neither of these genes nor proteins distinguished between TB and TB-IRIS. CONCLUSIONS: Gene expression of FcGR1A and BATF2, and plasma protein levels of IFNγ and CXCL10 have the potential to independently detect TB in advanced HIV. However, since other lung diseases were not included in this study, these final candidates need to be validated as specific to TB in the advanced HIV population with TB.

Performance of loop-mediated isothermal amplification assay in the diagnosis of pulmonary tuberculosis in a high prevalence TB/HIV rural setting in Uganda.

BACKGROUND: Smear microscopy lacks sensitivity especially in HIV co-infection, resulting in undiagnosed tuberculosis (TB) and high mortality. The loop-mediated isothermal amplification (TB-LAMP) assay can be staged with minimal infrastructure, is rapid, low cost and detection can be with the naked eye. We assessed feasibility and performance of Eiken TB-LAMP test at point-of-need in TB diagnosis in a high prevalence TB/HIV rural setting in Uganda. METHODS: From October 2013-February 2014, TB-LAMP testing was performed on sputum specimens from outpatient presumptive TB adults at a district hospital and two low-level health centers in Kiboga District where smear microscopy is the available routine diagnostic option. TB-LAMP was performed by a technician after a week of training in the district hospital. The technician had no prior experience in the technology. Samples from the low-level health centers were transported to the district hospital for TB-LAMP. RESULTS: Of the 233 presumptive TB (126 at hospital); 113 (48.5%) were HIV-infected; 129 (55%) male; median age 40 (IQR 30-53). Compared to MTB culture, overall sensitivity and specificity of TB-LAMP were 55.4% (95 CI 44.1-66.3) and 98.0% (95 CI 94.3-99.6) respectively. Among HIV-infected participants, TB-LAMP sensitivity and specificity were 52.3% (95 CI 36.7-67.5%) and 97.1% (95 CI 89.9-99.6) respectively; and 24.4% (95% CI 12.9-39.5) and 98.6% (95% CI 95.1-99.8) respectively among smear-negatives. TB-LAMP sensitivity and specificity were 62.2% (95% CI 44.8-77.5) and 97.8% (95% CI 92.1-99.7) in the hospital setting where central testing occurred compared to 50.0% (95% CI 34.9-65.1) and 98.4% (95% CI 91.2-100) respectively in low-level health centers where specimens were transported centrally. CONCLUSIONS: In this high prevalence TB/HIV rural setting, TB-LAMP performs better than conventional smear microscopy in diagnosis of MTB among presumptive TB patients although the sensitivity is lower than that reported by the World Health Organization. TB-LAMP can easily be performed following a short training period and in absence of sophisticated infrastructure and expertise.

Entrapment as a mediator of suicide crises.

BACKGROUND: Prior research has validated the construct of a suicide crisis syndrome (SCS), a specific psychological state that precedes and may precipitate suicidal behavior. The feeling of entrapment is a central concept of the SCS as well as of several other recent models of suicide. However, its exact relationship with suicidality is not fully understood. In efforts to clarify the exact role of entrapment in the suicidal process, we have examined if entrapment mediates the relationship of other components of the SCS, including ruminative flooding, panic-dissociation, fear of dying and emotional pain, with suicidal ideation (SI) in recently hospitalized psychiatric inpatients. METHODS: The Suicide Crisis Inventory (SCI) and Beck Scale for Suicidal Ideation (BSS) were administered to 200 high-risk adult psychiatric inpatients hospitalized following SI or suicide attempt, assessing SCS and SI levels at admission, respectively. The possible mediation effects of entrapment on the relationship between the other components of the SCS and SI at admission were evaluated. RESULTS: Entrapment significantly and fully mediated the relationship of ruminative flooding, panic-dissociation, and fear of dying with SI, with no direct relationships between these variables and SI reaching statistical significance. Further, no reverse mediation relationships between these variables and SI were found, indicating that the mediation effects of entrapment were unidirectional. While entrapment did mediate the association between emotional pain and SI, the direct relationship between emotional pain and SI was also significant. Moreover, in reverse mediational analysis, emotional pain was a partial mediator of the relationship between entrapment and SI. CONCLUSION: Entrapment and emotional pain may have a more direct association with SI than the other components of the SCS, including ruminative flooding, panic-dissociation, and fear of dying, the effects of which are mediated by the former. This suggests entrapment and emotional pain may represent key symptomatic targets for intervention in acutely suicidal individuals. Further research is needed to determine the relationship of these constructs to suicidal behavior.

Prediction of suicidal behavior in high risk psychiatric patients using an assessment of acute suicidal state: The suicide crisis inventory.

BACKGROUND: We have developed the Suicide Crisis Inventory (SCI) to evaluate the intensity of the Suicidal Crisis Syndrome, an acute state hypothesized to precede suicide attempt. The psychometric properties of the SCI, including predictive validity for suicidal behavior (SB), were assessed. METHODS: Adult psychiatric patients (n = 201) hospitalized for high suicide risk were assessed. Logistic regression models assessed the SCI's predictive validity for SB in the 4-8 weeks following hospital discharge and its incremental predictive validity over traditional risk factors (n = 137, 64% f/u rate). Internal structure, reliability, convergent and discriminant validity, and state versus trait properties were also assessed. RESULTS: The SCI had excellent internal consistency (Cronbach's α 0.970). The SCI total score at discharge predicted short-term SB with 64% sensitivity 88% specificity (OR = 13, P = .003) at its optimal cut score. In a test of its incremental predictive validity, SCI total score at discharge improved prediction of SB over traditional risk factors (Chi-squared 5.597, P = .024, model P = .001), with AOR 2.02 (P = .030). The SCI admission versus discharge test-retest reliability and score distributions showed it to be an acute state measure. CONCLUSION: The SCI was predictive of future SB in high-risk psychiatric inpatients during the crucial weeks following their hospital discharge. Further validation in diverse patient populations is needed.

The Modular Assessment of Risk for Imminent Suicide (MARIS): A proof of concept for a multi-informant tool for evaluation of short-term suicide risk.

BACKGROUND: To date, no diagnostic tool has demonstrated clinical value for the assessment of short-term suicide risk among high-risk individuals. To this end we have developed the Modular Assessment of Risk for Imminent Suicide (MARIS), a modular patient and clinician informed risk evaluation instrument. Here we assess its predictive validity for suicidal behavior (SB) in psychiatric patients following discharge from an inpatient unit. METHODS: The MARIS and a psychological test battery were administered to 136 adult psychiatric patients hospitalized for high risk of suicide. Eighty-six participants had complete data at discharge and 59 (69.8%) were reached for follow-up. Logistic regressions were used to assess the predictive validity of the MARIS for SB over the 4-8weeks following hospital discharge and its incremental predictive validity over standard risk factors. RESULTS: Patients who exhibited SB in the period between initial assessment and follow-up had significantly higher MARIS scores. ROC analysis indicated good sensitivity and specificity of MARIS in identifying risk (OR=19). Further, MARIS total score significantly improved predictive validity by the standard risk factors when added to a model comprising global depression severity, hopelessness, and lifetime number of suicide attempts, and was the only factor that approached independent significance. CONCLUSION: The MARIS appears to be a practical and effective tool for detecting short-term suicide risk following hospital discharge, supporting the validity of modular multi-informant approach to suicide risk evaluation. Replication of these findings and further investigation of the applications of such an approach are warranted.

Clinicians' conflicting emotional responses to high suicide-risk patients-Association with short-term suicide behaviors: A prospective pilot study.

BACKGROUND: Clinician's emotional responses to patients have been recognized as potentially relating to treatment outcome, however they have received little attention in the literature on suicide risk. We examine the relationship between a novel targeted measure of clinicians' emotional responses to high-risk psychiatric inpatients and their short-term post-discharge suicide behavior. METHODS: First-year psychiatry residents' emotional responses to their patients were assessed anonymously with the novel self-report 'Therapist Response Questionnaire-Suicide Form' (TRQ-SF). Patient outcomes were assessed at 1-2months post-discharge, and post-discharge suicide outcomes were assessed with the Columbia Suicide Severity Rating Scale. Following exploratory factor analysis of the TRQ-SF, scores on the resultant factors were examined for relationships with clinical and demographic measures and post-discharge suicide behavior. RESULTS: A two-factor model fit the data, with factors reflecting dimensions of affiliation/rejection and distress/non-distress. Two items that did not load robustly on either factor had face validity for hopefulness and hopelessness and were combined as a measure along a hopefulness/hopelessness dimension. The interaction Distress×Hopefulness, reflecting a conflicting emotional response pattern, significantly predicted post-discharge suicide outcomes even after covarying for depression, entrapment, and suicidal ideation severity. CONCLUSION: Clinicians' conflicting emotional responses to high-risk patients predicted subsequent suicidal behavior, independent of traditional risk factors. Our findings demonstrate the potential clinical value of assessing such responses.

IFNγ/IL-10 co-producing cells dominate the CD4 response to malaria in highly exposed children.

Although evidence suggests that T cells are critical for immunity to malaria, reliable T cell correlates of exposure to and protection from malaria among children living in endemic areas are lacking. We used multiparameter flow cytometry to perform a detailed functional characterization of malaria-specific T cells in 78 four-year-old children enrolled in a longitudinal cohort study in Tororo, Uganda, a highly malaria-endemic region. More than 1800 episodes of malaria were observed in this cohort, with no cases of severe malaria. We quantified production of IFNγ, TNFα, and IL-10 (alone or in combination) by malaria-specific T cells, and analyzed the relationship of this response to past and future malaria incidence. CD4(+) T cell responses were measurable in nearly all children, with the majority of children having CD4(+) T cells producing both IFNγ and IL-10 in response to malaria-infected red blood cells. Frequencies of IFNγ/IL10 co-producing CD4(+) T cells, which express the Th1 transcription factor T-bet, were significantly higher in children with ≥2 prior episodes/year compared to children with <2 episodes/year (P<0.001) and inversely correlated with duration since malaria (Rho = -0.39, P<0.001). Notably, frequencies of IFNγ/IL10 co-producing cells were not associated with protection from future malaria after controlling for prior malaria incidence. In contrast, children with <2 prior episodes/year were significantly more likely to exhibit antigen-specific production of TNFα without IL-10 (P = 0.003). While TNFα-producing CD4(+) T cells were not independently associated with future protection, the absence of cells producing this inflammatory cytokine was associated with the phenotype of asymptomatic infection. Together these data indicate that the functional phenotype of the malaria-specific T cell response is heavily influenced by malaria exposure intensity, with IFNγ/IL10 co-producing CD4(+) T cells dominating this response among highly exposed children. These CD4(+) T cells may play important modulatory roles in the development of antimalarial immunity.

IFNγ Responses to Pre-erythrocytic and Blood-stage Malaria Antigens Exhibit Differential Associations With Past Exposure and Subsequent Protection.

BACKGROUND: The malaria-specific T-cell response is believed to be important for protective immunity. Antimalarial chemoprevention may affect this response by altering exposure to malaria antigens. METHODS: We performed interferon γ (IFNγ) ELISpot assays to assess the cellular immune response to blood-stage and pre-erythrocytic antigens longitudinally from 1 to 3 years of age in 196 children enrolled in a randomized trial of antimalarial chemoprevention in Tororo, Uganda, an area of high transmission intensity. RESULTS: IFNγ responses to blood-stage antigens, particularly MSP1, were frequently detected, strongly associated with recent malaria exposure, and lower in those adherent to chemoprevention compared to nonadherent children and those randomized to no chemoprevention. IFNγ responses to pre-erythrocytic antigens were infrequent and similar between children randomized to chemoprevention or no chemoprevention. Responses to blood-stage antigens were not associated with subsequent protection from malaria (aHR 0.96, P = .83), but responses to pre-erythrocytic antigens were associated with protection after adjusting for prior malaria exposure (aHR 0.52, P = .009). CONCLUSIONS: In this high transmission setting, IFNγ responses to blood-stage antigens were common and associated with recent exposure to malaria but not protection from subsequent malaria. Responses to pre-erythrocytic antigens were uncommon, not associated with exposure but were associated with protection from subsequent malaria.

Attitudes of acceptability and lack of condemnation toward suicide may be predictive of post-discharge suicide attempts.

BACKGROUND: Suicide attempts (SA) after psychiatric hospitalization continue to be a major cause of morbidity. Implicit measures may enhance our ability to assess suicide risk. In this context, we describe the first use of the Suicide Opinion Questionnaire (SOQ) to identify post-discharge suicide attempters. METHODS: Adult psychiatric inpatients admitted for suicidality (N = 91) were administered a battery of measures including the SOQ, and forty were reached and reassessed for SA at two months post-discharge. Exploratory factor analysis (EFA) on items associated with suicidality was performed to identify latent constructs. Linear discriminant analysis (LDA) was used to optimize factor combination for suicide identification. Results were compared with explicit measures of suicidality, and logistic regression was used to control for other risk factors. Finally, a simplified 9-item scale was derived from the results and its performance compared to that of the linear discriminant function. RESULTS: Twenty items differed between patients with and without SA at intake or follow-up. EFA on these identified two factors: suicide attempters indicated greater acceptability and less moral condemnation of suicide. The LDA-derived discriminant function and 9-item scale was significantly sensitive and specific for post-discharge SA. CONCLUSIONS: Attitudes of acceptability and lack of condemnation toward suicide may constitute an implicit measure of suicidality that could contribute to risk assessment in a high-risk population.