Scaling up public mental health care in Sub-Saharan Africa: insights from infectious disease.

INTRODUCTION: Models estimate that the disability burden from mental disorders in Sub-Saharan Africa (SSA) will more than double in the next 40 years. Similar to HIV, mental disorders are stigmatized in many SSA settings and addressing them requires community engagement and long-term treatment. Yet, in contrast to HIV, the public mental healthcare cascade has not been sustained, despite robust data on scalable strategies. We draw on findings from our International AIDS Society (IAS) 2020 virtual workshop and make recommendations for next steps in the scale up of the SSA public mental healthcare continuum. DISCUSSION: Early HIV surveillance and care cascade targets are discussed as important strategies for HIV response in SSA that should be adopted for mental health. Advocacy, including engagement with civil society, and targeted economic arguments to policymakers, are reviewed in the context of HIV success in SSA. Parallel opportunities for mental disorders are identified. Learning from HIV, communication of strategies that advance mental health care needs in SSA must be prioritized for broad global audiences. CONCLUSIONS: The COVID-19 pandemic is setting off a colossal escalation of global mental health care needs, well-publicized across scientific, media, policymaker, and civil society domains. The pandemic highlights disparities in healthcare access and reinvigorates the push for universal coverage. Learning from HIV strategies, we must seize this historical moment to improve the public mental health care cascade in SSA and capitalize on the powerful alliances ready to be forged. As noted by Ambassador Goosby in our AIDS 2020 workshop, 'The time is now'.

Anatomy of the posterior caudal lobe of the cerebellum and the eminentia granularis posterior in a mormyrid fish.

The cerebellum of mormyrid fish is of interest for its large size and unusual histology. The mormyrid cerebellum, as in all ray-finned fishes, has three subdivisions--valvula, corpus, and caudal lobe. The structures of the mormyrid valvula and corpus have been examined previously, but the structure of the mormyrid caudal lobe has not been studied. The mormyrid caudal lobe includes a posterior caudal lobe associated with the electrosense and an anterior caudal lobe associated with lateral line and eighth nerve senses. In this article we describe cellular elements of the posterior caudal lobe and of the eminentia granularis posterior (EGp) in the mormyrid fish Gnathonemus petersii. The EGp gives rise to the parallel fibers of the posterior caudal lobe. We used intracellular injection of biocytin, extracellular injection of biotinylated dextran amine, and immunohistochemistry with antibodies to gamma-aminobutyric acid, inositol triphosphate receptor I, calretinin, and Zebrin II. The histological structure of the posterior caudal lobe is markedly irregular in comparison to that of the corpus and the valvula, and a tight modular organization of cerebellar elements is less apparent here. Most Purkinje cell bodies are in the middle of the molecular region. Their dendrites are only roughly oriented in the sagittal plane, extend both ventrally and dorsally, and branch irregularly. Climbing fibers terminate only on smooth dendrites near the soma. Most Purkinje cell axons terminate locally on eurydendroid cells that project outside the cortex. The results provide an additional variant to the already large set of different cerebellar and cerebellum-like structures.

The role of gamma delta T cells in airway epithelial injury and bronchial responsiveness after chlorine gas exposure in mice.

BACKGROUND: Acute exposure to chlorine (Cl2) gas causes epithelial injury and airway dysfunction. gammadelta T cells are present in the mucosal surface of the airways and may contribute to the injury/repair response of the epithelium. METHODS: C57Bl/6J (wild type) and TCR-delta-/- mice exposed to Cl2 (400 ppm) for 5 minutes underwent measurements of airway responses to i.v. methacholine (MCh) at 1, 3, and 5 days after exposure. Bronchoalveolar lavage was performed to determine epithelial and leukocyte counts, and protein content. Tissue repair was assessed by proliferating cell nuclear antigen (PCNA) immunoreactivity and by expression of keratinocyte growth factor (KGF) mRNA by real-time PCR. RESULTS: Wild type mice developed a greater degree of airway hyperresponsiveness to MCh at 1 day post exposure to Cl2 compared with TCR-delta-/- mice. Epithelial cell counts in BAL after Cl2 exposure were greater in TCR-delta-/- mice, but macrophages showed a later peak and granulocyte numbers were lower in TCR-delta-/- than in wild type mice. Both groups had increased levels of total protein content in BAL after Cl2 exposure that resolved after 3 and 5 days, respectively. Epithelial proliferating cell nuclear antigen staining was increased at 1 and 3 days post exposure and was similar in the two groups. KGF mRNA was constitutively expressed in both groups and did not increase significantly after Cl2 but expression was lower in TCR-delta-/- mice. CONCLUSION: The severity of airway epithelial injury after Cl2 is greater in TCR-delta-/- mice but the inflammatory response and the change in airway responsiveness to methacholine are reduced. The rates of epithelial regeneration are comparable in both groups.

Cell morphology and circuitry in the central lobes of the mormyrid cerebellum.

The cerebellum of mormyrid electric fish is large and unusually regular in its histological structure. We have examined the morphology of cellular elements in the central lobes of the mormyrid cerebellum. We have used intracellular injection of biocytin to determine the morphology of cells with somas in the cortex, and we have used extracellular placement of anterograde tracers in the inferior olive to label climbing fibers. Our results confirm previous Golgi studies and extend them by providing a more complete description of axonal trajectories. Most Purkinje cells in mormyrids and other actinopterygian fishes are interneurons that terminate locally in the cortex on efferent neurons that are equivalent to cerebellar nucleus cells in mammals. We confirm the markedly sagittal distribution of the fan-like dendrites of Purkinje cells, efferent cells, and molecular layer interneurons. We show that Purkinje cell axons extend further than was previously thought in the sagittal plane. We show that climbing fibers are distributed in narrow sagittal strips and that these fibers terminate exclusively in the ganglionic layer below the molecular layer where parallel fibers terminate. Our results together with those of others show that the central lobes of the mormyrid cerebellum, similar to the mammalian cerebellum, are composed of sagittally oriented modules made up of Purkinje cells, climbing fibers, molecular layer interneurons, and cerebellar efferent cells (cerebellar nucleus cells in mammals) that Purkinje cells inhibit. This modular organization is more apparent and more sharply defined in the mormyrid than in the mammal.

Chlorine-induced injury to the airways in mice.

Exposure to chlorine gas (Cl2) causes occupational asthma that we hypothesized occurs through the induction of airway inflammation and airway hyperresponsiveness by oxidative damage. Respiratory mechanics and airway responsiveness to methacholine were assessed in A/J mice 24 hours after a 5-minute exposure to 100, 200, 400, or 800 ppm Cl2 and 2 and 7 days after inhalation of 400 ppm Cl2. Airway responsiveness was higher 24 hours after 400 and 800 ppm Cl2. Responsiveness after inhalation of 400 ppm Cl2 returned to normal by 2 days but was again elevated at 7 days. Airway epithelial loss, patchy alveolar damage, proteinaceous exudates, and inflammatory cells within alveolar walls were observed in animals exposed to 800 ppm Cl2. Macrophages, granulocytes, epithelial cells, and nitrate/nitrite levels increased in lung lavage fluid. Increased inducible nitric oxide synthase expression and oxidation of lung proteins were observed. Epithelial cells and alveolar macrophages from mice exposed to 800 ppm Cl2 stained for 3-nitrotyrosine residues. Inhibition of inducible nitric oxide synthase with 1400W (1 mg/kg) abrogated the Cl2-induced changes in responsiveness. We conclude that chlorine exposure causes functional and pathological changes in the airways associated with oxidative stress. Inducible nitric oxide synthase is involved in the induction of changes in responsiveness to methacholine.