HIV and depression in a primary care clinic in Johannesburg, South Africa

As rapidly expanding HIV care and treatment programs are implemented in sub-Saharan Africa, maintaining engagement in HIV care is proving to be a significant operational challenge. Depression is highly prevalent among HIV-infected people in sub-Saharan Africa and predicts a range of poor HIV-related clinical outcomes including faster disease progression and increased morbidity and mortality. Depression is strongly associated with non-adherence to anti-retroviral treatment (ART), and may also impact engagement in HIV care. Recognizing and treating depression among HIV-infected patients seeking care in primary health care settings, where most HIV testing and treatment takes place, could increase access to mental health services and may help to target patients at risk for negative outcomes. An observational study was conducted between September 2012 and April 2013 among 1683 randomly selected adult patients undergoing routine, opt-out HIV counseling and testing (HCT) at Witkoppen Health and Welfare Center (WHWC), a high-HIV burden primary care clinic in Johannesburg, South Africa. Patients were screened for depression immediately prior to HCT using the Patient Health Questionnaire-9 (PHQ-9), a 9-item brief screening tool administered by lay health workers. A subset of 400 patients was included in a blinded diagnostic validation study of the PHQ-9 (Aim 1). Sensitivity and specificity of the PHQ-9 were calculated with the Mini International Neuropsychiatric Interview (MINI) as the reference standard, and receiver operating characteristic (ROC) curve analyses were performed. Patients who tested positive for HIV were followed and linkage to care, defined as returning to WHWC within 3 months to obtain a CD4 count result, was assessed (Aim 2). Among patients who collected a CD4 count, ART initiation within 3 months was assessed. Multivariable Poisson regression with a robust variance estimator was used to assess the association between depression and linkage to care or ART initiation. Nearly all patients completed depression screening and 82% (n=1386) subsequently tested for HIV. Of the patients who tested for HIV and were of unknown HIV status prior to testing, 26% (n=340) were found to be HIV-infected. Nearly a quarter of all patients (22%) were depressed. Similar to other studies, depression was more common among patients who tested positive for HIV compared to those who tested negative for HIV (30.3% versus 19.7%, p<0.0001). In the validation sample included in Aim 1, the prevalence of depression was 11.8% and one-third of participants tested positive for HIV. Using the standard cut-off score of &#8805;10, the PHQ-9 demonstrated a sensitivity of 78.7% (95% CI: 64.3-89.3) and specificity of 83.4% (95% CI: 79.1-87.2) for identifying major depressive disorder. The area under the ROC curve was 0.88 (95% CI: 0.83-0.92). Test characteristics did not vary by HIV status or language and in sensitivity analyses, reference test bias associated with the MINI appeared unlikely. The PHQ-9 was easily implemented by lay health workers. The instrument performed reasonably well and may be a useful depression screening tool in high HIV-burden sub-Saharan African primary health care settings. Of the HIV-infected patients included in Aim 2, 30% were depressed. The proportion who linked to care was 80% among depressed patients and 73% among patients who were not depressed (Risk ratio: 1.08; 95% confidence interval: 0.96, 1.23). Of the participants who linked to care, 81% initiated ART within 3 months in both depressed and not depressed groups (Risk ratio: 0.99; 95% confidence interval: 0.86, 1.15). Conducting this study in a clinic-based population may have selected for patients who are high-utilizers of health care and unlikely to be at high risk for loss to HIV care. These unexpected results highlight the importance of population selection and the timing of HIV testing relative to depression screening when studying the complex relationship between depression and engagement in HIV care.Doctor of Philosoph

Chemokine receptor CCR5 promotes leukocyte trafficking to the brain and survival in West Nile virus infection

The molecular immunopathogenesis of West Nile virus (WNV) infection is poorly understood. Here, we characterize a mouse model for WNV using a subcutaneous route of infection and delineate leukocyte subsets and immunoregulatory factors present in the brains of infected mice. Central nervous system (CNS) expression of the chemokine receptor CCR5 and its ligand CCL5 was prominently up-regulated by WNV, and this was associated with CNS infiltration of CD4+ and CD8+ T cells, NK1.1+ cells and macrophages expressing the receptor. The significance of CCR5 in pathogenesis was established by mortality studies in which infection of CCR5−/− mice was rapidly and uniformly fatal. In the brain, WNV-infected CCR5−/− mice had increased viral burden but markedly reduced NK1.1+ cells, macrophages, and CD4+ and CD8+ T cells compared with WNV-infected CCR5+/+ mice. Adoptive transfer of splenocytes from WNV-infected CCR5+/+ mice into infected CCR5−/− mice increased leukocyte accumulation in the CNS compared with transfer of splenocytes from infected CCR5−/− mice into infected CCR5−/− mice, and increased survival to 60%, the same as in infected CCR5+/+ control mice. We conclude that CCR5 is a critical antiviral and survival determinant in WNV infection of mice that acts by regulating trafficking of leukocytes to the infected brain

Factors Influencing Graduate Program Choice Among Undergraduate Women

Context: Despite equal enrollment proportions in MD and PhD programs, there are fewer women than men in MD-PhD programs and academic medicine. Factors important in degree program selection, including the perception of gender disparities, among undergraduate students were characterized. Methods: In 2017, pre-health students at four public North Carolina universities were invited to participate in an online survey regarding career plans, decision factors, and perceptions of gender disparities in MD, PhD and MD-PhD pathways. The authors characterized factors important to program selection, and evaluated the association of intended graduate program with perceived gender disparities using Fisher’s exact tests. Results: Among the n=186 female survey participants, most were white (54%) and intended MD, PhD, and/or MD-PhD programs (52%). Sixty percent had heard of MD-PhD programs, over half had no research experience, and half were considering but uncertain about pursuing a research career. The most common factors influencing degree program choice were perceived competitiveness as an applicant, desired future work environment, and desire for patient interaction. Twenty-five percent of students considering MD, PhD, and MD-PhD programs stated that perceived gender disparities during training for those degrees will influence their choice of program, however intended degree was not statistically associated with perceived gender disparities. Discussion: Perceived gender disparities may influence choice of graduate training program but are not among the top factors. Perceived competitiveness as an applicant is an important career consideration among undergraduate women. Strategies to increase awareness of MD-PhD programs, to encourage women to consider all training paths for which they are qualified are needed. Keywords: Education, Graduate; Sexism; Career Choice; Biomedical Research/education; Female What is known: Though men and women are nearly equally represented in MD-only and PhD-only programs, women are underrepresented in MD-PhD programs, which train physician-scientists. Prior studies have shown gender is not associated with rates of attrition from MD-PhD programs or differences in academic preparation, research interest, or research experience, suggesting enrollment differences by gender may be due to fewer women applying to MD-PhD programs. Gender parity in the physician-scientist workforce is critical to equitably serving a diverse patient population. What this study adds: This study is the first to examine the role of gender disparities in the career choices of undergraduate women. Given the moderate familiarity with MD-PhD training and lack of research experience among respondents, increased awareness of MD-PhD programs and expanded research opportunities may help undergraduates make informed career choices. This may increase women MD-PhD applicants, creating a more balanced physician-scientist workforce to address the needs of patients from all backgrounds

Promoting Latinx health equity through community-engaged policy and practice reforms in North Carolina

IntroductionThe Latinx Advocacy Team &amp; Interdisciplinary Network for COVID-19 (LATIN-19) is a unique multi-sector coalition formed early in the COVID-19 pandemic to address the multi-level health inequities faced by Latinx communities in North Carolina.MethodsWe utilized the National Institute on Minority Health and Health Disparities (NIMHD) Research Framework to conduct a directed content analysis of 58 LATIN-19 meeting minutes from April 2020 through October 2021. Application of the NIMHD Research Framework facilitated a comprehensive assessment of complex and multidimensional barriers and interventions contributing to Latinx health while centering on community voices and perspectives.ResultsCommunity interventions focused on reducing language barriers and increasing community-level access to social supports while policy interventions focused on increasing services to slow the spread of COVID-19.DiscussionOur study adds to the literature by identifying community-based strategies to ensure the power of communities is accounted for in policy reforms that affect Latinx health outcomes across the U.S. Multisector coalitions, such as LATIN-19, can enable the improved understanding of underlying barriers and embed community priorities into policy solutions to address health inequities

Bacterial infections in Lilongwe, Malawi: aetiology and antibiotic resistance

<p>Abstract</p> <p>Background</p> <p>Life-threatening infections present major challenges for health systems in Malawi and the developing world because routine microbiologic culture and sensitivity testing are not performed due to lack of capacity. Use of empirical antimicrobial therapy without regular microbiologic surveillance is unable to provide adequate treatment in the face of emerging antimicrobial resistance. This study was conducted to determine antimicrobial susceptibility patterns in order to inform treatment choices and generate hospital-wide baseline data.</p> <p>Methods</p> <p>Culture and susceptibility testing was performed on various specimens from patients presenting with possible infectious diseases at Kamuzu Central Hospital, Lilongwe, Malawi.</p> <p>Results</p> <p>Between July 2006 and December 2007 3104 specimens from 2458 patients were evaluated, with 60.1% from the adult medical service. Common presentations were sepsis, meningitis, pneumonia and abscess. An etiologic agent was detected in 13% of patients. The most common organisms detected from blood cultures were <it>Staphylococcus aureus</it>, <it>Escherichia </it><it>coli</it>, Salmonella species and <it>Streptococcus pneumoniae</it>, whereas <it>Streptococcus pneumoniae </it>and <it>Cryptococcus neoformans </it>were most frequently detected from cerebrospinal fluid. <it>Haemophilus influenzae </it>was rarely isolated. Resistance to commonly used antibiotics was observed in up to 80% of the isolates while antibiotics that were not commonly in use maintained susceptibility.</p> <p>Conclusions</p> <p>There is widespread resistance to almost all of the antibiotics that are empirically used in Malawi. Antibiotics that have not been widely introduced in Malawi show better laboratory performance. Choices for empirical therapy in Malawi should be revised accordingly. A microbiologic surveillance system should be established and prudent use of antimicrobials promoted to improve patient care.</p

A Role for Fetal Hemoglobin and Maternal Immune IgG in Infant Resistance to Plasmodium falciparum Malaria

In Africa, infant susceptibility to Plasmodium falciparum malaria increases substantially as fetal hemoglobin (HbF) and maternal immune IgG disappear from circulation. During the first few months of life, however, resistance to malaria is evidenced by extremely low parasitemias, the absence of fever, and the almost complete lack of severe disease. This resistance has previously been attributed in part to poor parasite growth in HbF-containing red blood cells (RBCs). A specific role for maternal immune IgG in infant resistance to malaria has been hypothesized but not yet identified.We found that P. falciparum parasites invade and develop normally in fetal (cord blood, CB) RBCs, which contain up to 95% HbF. However, these parasitized CB RBCs are impaired in their binding to human microvascular endothelial cells (MVECs), monocytes, and nonparasitized RBCs--cytoadherence interactions that have been implicated in the development of high parasite densities and the symptoms of malaria. Abnormal display of the parasite's cytoadherence antigen P. falciparum erythrocyte membrane protein-1 (PfEMP-1) on CB RBCs accounts for these findings and is reminiscent of that on HbC and HbS RBCs. IgG purified from the plasma of immune Malian adults almost completely abolishes the adherence of parasitized CB RBCs to MVECs.Our data suggest a model of malaria protection in which HbF and maternal IgG act cooperatively to impair the cytoadherence of parasitized RBCs in the first few months of life. In highly malarious areas of Africa, an infant's contemporaneous expression of HbC or HbS and development of an immune IgG repertoire may effectively reconstitute the waning protective effects of HbF and maternal immune IgG, thereby extending the malaria resistance of infancy into early childhood

Probability of major depression diagnostic classification using semi-structured vs. fully structured diagnostic interviews

Background: Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification. Aims: To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics. Method: Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analyzed. Binomial Generalized Linear Mixed Models were fit. Results: 17,158 participants (2,287 major depression cases) from 57 primary studies were analyzed. Among fully structured interviews, odds of major depression were higher for the MINI compared to the Composite International Diagnostic Interview (CIDI) [OR (95% CI) = 2.10 (1.15-3.87)]. Compared to semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores 6) as having major depression [OR (95% CI) = 3.13 (0.98-10.00)], similarly likely for moderate-level symptoms (PHQ-9 scores 7-15) [OR (95% CI) = 0.96 (0.56-1.66)], and significantly less likely for high-level symptoms (PHQ-9 scores 16) [OR (95% CI) = 0.50 (0.26-0.97)]. Conclusions: The MINI may identify more depressed cases than the CIDI, and semi- and fully structured interviews may not be interchangeable methods, but these results should be replicated