Differential expression of mycobacterial antigen MPT64, apoptosis and inflammatory markers in multinucleated giant cells and epithelioid cells in granulomas caused by Mycobacterium tuberculosis

The development of granulomas is a major histopathological feature of tuberculosis. Very little information is available concerning the physiology and functions of different cell types in the tuberculous granulomas. The aim of this study was to compare the epithelioid cells (ECs) and multinucleated giant cells (MGCs) in the granulomas caused by Mycobacterium tuberculosis complex organisms. Lymph node biopsies from 30 cases of lymphadenitis were studied for expression of the secreted mycobacterial protein MPT64, caspase 3 as a marker of apoptosis, apoptosis-related proteins (Fas Ligand, Fas and Bax) and inflammatory cytokines (interleukin-10, transforming growth factor-β (TGF-β), tumour necrosis factor-α and interferon-γ) by immunohistochemistry. MGCs more often contained M. tuberculosis secretory antigen MPT64 (p < 0.001) and expressed more TGF-β (p = 0.004) than ECs. The total number of apoptotic MGCs was higher than the number of apoptotic ECs (p = 0.04). Interestingly, there was a significant negative correlation between apoptosis and MPT64 expression in MGCs (r = −0.569, p = 0.003), but not in ECs, implying that the heavy antigen load would lead to inhibition of apoptosis in these cells. When compared with ECs, higher percentage of MGCs expressed Fas Ligand and Fas (p < 0.004). The role of MGCs may thus be different from surrounding ECs and these cells by virtue of higher mycobacterial antigen load, more TGF-β and reduced apoptosis may contribute towards persistence of infection

Social psychiatry and psychiatric epidemiology functional impairment among people with severe and enduring mental disorder in rural Ethiopia: a cross-sectional study

Purpose: Evidence regarding functional impairment in people with severe mental disorders (SMD) is sparse in low and middle-income countries. The aim of this study was to identify factors associated with functional impairment in people with enduring SMD in a rural African setting. Methods: A cross-sectional study was conducted at the baseline of a health service intervention trial. A total of 324 participants were recruited from an existing communityascertained cohort of people with SMD (n= 218), and attendees at the Butajira General Hospital psychiatric clinic (n= 106). Inclusion criteria defined people with SMD who had ongoing need for care: those who were on psychotropic medication, currently symptomatic or had a relapse in the preceding two years. The World Health Organization Disability Assessment schedule (WHODAS-2.0) and the Butajira Functioning Scale (BFS), were used to assess functional impairment. Multivariable negative binomial regression models were fitted to investigate the association between demographic, socio-economic and clinical characteristics, and functional impairment. Results: Increasing age, being unmarried, rural residence, poorer socio-economic status, symptom severity, continuous course of illness, medication side effects and internalized stigma were associated with functional impairment across self reported and caregiver responses for both the WHODAS and the BFS. Diagnosis per se was not associated consistently with functional impairment. Conclusion: To optimize functioning in people with chronic SMD in this setting, services need to target residual symptoms, poverty, medication side effects and internalized stigma. Testing the impact of community interventions to promote recovery will be useful. Advocacy for more tolerable treatment options is warranted

Impact of district mental health care plans on symptom severity and functioning of patients with priority mental health conditions: the Programme for Improving Mental Health Care (PRIME) cohort protocol

Background: The Programme for Improving Mental Health Care (PRIME) sought to implement mental health care plans (MHCP) for four priority mental disorders (depression, alcohol use disorder, psychosis and epilepsy) into routine primary care in five low- and middle-income country districts. The impact of the MHCPs on disability was evaluated through establishment of priority disorder treatment cohorts. This paper describes the methodology of these PRIME cohorts. Methods: One cohort for each disorder was recruited across some or all five districts: Sodo (Ethiopia), Sehore (India) , Chitwan (Nepal), Dr. Kenneth Kaunda (South Africa) and Kamuli (Uganda), comprising 17 treatment cohorts in total (N = 2182). Participants were adults residing in the districts who were eligible to receive mental health treatment according to primary health care staff, trained by PRIME facilitators as per the district MHCP. Patients who screened positive for depression or AUD and who were not given a diagnosis by their clinicians (N = 709) were also recruited into comparison cohorts in Ethiopia, India, Nepal and South Africa. Caregivers of patients with epilepsy or psychosis were also recruited (N = 953), together with or on behalf of the person with a mental disorder, depending on the district. The target sample size was 200 (depression and AUD), or 150 (psychosis and epilepsy) patients initiating treatment in each recruiting district. Data collection activities were conducted by PRIME research teams. Participants completed follow-up assessments after 3 months (AUD and depression) or 6 months (psychosis and epilepsy), and after 12 months. Primary outcomes were impaired functioning, using the 12-item World Health Organization Disability Assessment Schedule 2.0 (WHODAS), and symptom severity, assessed using the Patient Health Questionnaire (depression), the Alcohol Use Disorder Identification Test (AUD), and number of seizures (epilepsy). Discussion: Cohort recruitment was a function of the clinical detection rate by primary health care staff, and did not meet all planned targets. The cross-country methodology reflected the pragmatic nature of the PRIME cohorts: while the heterogeneity in methods of recruitment was a consequence of differences in health systems and MHCPs, the use of the WHODAS as primary outcome measure will allow for comparison of functioning recovery across sites and disorders

The association between aids related stigma and major depressive disorder among HIV-positive individuals in Uganda

BACKGROUND: Major depressive disorder in people living with HIV/AIDS (PLWHA) is common and may be associated with a number of factors, including AIDS-related stigma, decreased CD4 levels, increased opportunistic infections and sociodemographic variables. The extent to which AIDS-related stigma is associated with major depressive disorder among PLWHA has not been well studied in sub-Saharan Africa. The objective of this study was to examine the associations between major depressive disorder, AIDS-related stigma, immune status, and sociodemographic variables with the aim of making recommendations that can guide clinicians. METHODS: We assessed 368 PLWHA for major depressive disorder, as well as for potentially associated factors, including AIDS-related stigma, CD4 levels, presence of opportunistic infections, and sociodemographic variables. RESULTS: The prevalence of major depressive disorder was 17.4%, while 7.9% of the participants had AIDS related stigma. At multivariable analysis, major depressive disorder was significantly associated with AIDS-related stigma [OR = 1.65, CI (1.20-2.26)], a CD4 count of ≥200 [OR 0.52 CI (0.27-0.99)], and being of younger age [0.95, CI (0.92-0.98). CONCLUSIONS: Due to the high burden of major depressive disorder, and its association with AIDS related stigma, routine screening of PLWHA for both conditions is recommended. However, more research is required to understand this association

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Reaction of rice cultivars to a virulent rice yellow mottle virus strain in Uganda

Rice ( Oryza spp.) has long been an important food staple for many traditional rice growing communities. Key developments in efforts to improve rice production such as the development of NERICA varieties have been widely recognised. Nonetheless, emerging diseases such as the Rice Yellow Mottle Virus sobemovirus (RYMV) undermine dissemination of new technologies and sustained productivity of the crop. The RYMV is highly variable and several resistance-breaking strains have been identified. Appropriate sources of resistance to RYMV should be identified and characterised in order to pyramid genes for both complete and partial resistance. In this study, reaction of nine (9) rice cultivars to RYMV virulent strain in Uganda was determined. Four upland and three lowland NERICA varieties, an O. Sativa lowland variety, Gigante and IR64 were observed. Isolates of RYMV were collected from three "hot-spots" in Uganda (Lira, Luweero and Iganga). The isolate from Iganga was most virulent on RYMV susceptible cultivar (IR64), and thus used to constitute study treatment evaluated in the study. Cultivars were potted and raised in a screenhouse experiment arranged in a randomised complete block design (RCBD) with three replicates. Significant differences for relative area under disease progress curve (RAUDPC) (P≤0.01) were detected among the cultivars. Similarly, significant positive correlations (P≤0.05) were observed between mean disease score and percentage reduction in grain weight and between percentage grain weight and reduction in plant height. Susceptible cultivars were characterised based on premature death, and significantly reduced grain weight and plant height (P≤0.01 and P≤0.05), respectively. These results demonstrated the aggressive nature of the specific RYMV strain, and provided evidence with regard to the importance of grain weight and plant height in evaluating RYMV disease resistance.Le riz ( Oryza spp.) a été depuis longtemps un aliment de base pour plusieurs communautés cultivatrices de riz. Les développements-clés dans l’effort d’améliorer la production rizicole, tel que le développement des variétés NERICA, ont été largement reconnus. Néanmoins, l’apparition des maladies telle que le virus de la panachure jaune de type sobemovirus contraint la dissémination des nouvelles technologies et la productivité soutenue de la culture. Le virus de la panachure jaune du riz est très variable et plusieurs souches virulentes ont été identifiées. De sources appropriées de résistance à la maladie de la panichure jaune du riz devront être identifiées et caractérisées afin de pyramider les gènes pour une résistance complete et/ou partielle. Dans cette étude, la réaction de 9 cultivars de riz au virus virulent de la panachure jaune en Ouganda était déterminée. Quatre variétés NERICA de montagne et trois variétés NERICA des bas-fonds, ainsi qu’une variété des bas-fonds de type O. sativa, Gigante et IR64, étaient observées. Les isolats du virus de la panachure jaune du riz étaient collectés des “zones dangereuses” de l’Ouganda, notamment Lira, Luwero et Iganga. L’isolat de l’Iganga était le plus virulent au cultivar IR64 susceptible au virus de la panachure jaune et donc était utilisé pour constituer le traitement évalué dans cette étude. Les cultivars étaient cultivés en pots dans une serre et arranges en blocs aléatoires complets avec trois répétitions. Des différences significatives pour la surface relative sous la courbe progressive de la maladie (P≤0.01) étaient détectées parmi les cultivars. De façon similaire, des corrélations positives significatives (P≤0.05) étaient observées entre les moyennes des cotations de la maladie et le pourcentage de réduction du poids des grains, et entre le pourcentage du poids des grains et la réduction de la hauteur de plant. Les cultivars susceptibles étaient caractérisés sur base de la mort prématurée, et la réduction significative du poids des grains et la hauteur de plant (P≤0.01 et P≤0.05), respectivement. Ces résultats ont démontré la nature aggressive du virus de la panachure jaune et fournissent l’ évidence de l’omportance du poids en grains et la hauteur de plants dans l’évaluation de la résistance à la maladie de la panachure jaune du riz