The first three reported cases of Sporothrix brasiliensis cat-transmitted sporotrichosis outside South America.

An epidemic of cat-transmitted sporotrichosis caused by Sporothrix brasiliensis has emerged as a major public health threat in Brazil in recent decades. We report the first three cases of cat-transmitted sporotrichosis caused by Sporothrix brasiliensis outside South America, and the first ever cases of cat-transmitted sporotrichosis in the United Kingdom. We outline the public health implications and outbreak response and encourage clinicians and veterinarians worldwide to be vigilant for sporotrichosis in cats and cat owners.

Recent advances in understanding the human host immune response in tuberculous meningitis.

Tuberculous meningitis (TBM), the most severe form of tuberculosis, causes death in approximately 25% cases despite antibiotic therapy, and half of survivors are left with neurological disability. Mortality and morbidity are contributed to by a dysregulated immune response, and adjunctive host-directed therapies are required to modulate this response and improve outcomes. Developing such therapies relies on improved understanding of the host immune response to TBM. The historical challenges in TBM research of limited in vivo and in vitro models have been partially overcome by recent developments in proteomics, transcriptomics, and metabolomics, and the use of these technologies in nested substudies of large clinical trials. We review the current understanding of the human immune response in TBM. We begin with M. tuberculosis entry into the central nervous system (CNS), microglial infection and blood-brain and other CNS barrier dysfunction. We then outline the innate response, including the early cytokine response, role of canonical and non-canonical inflammasomes, eicosanoids and specialised pro-resolving mediators. Next, we review the adaptive response including T cells, microRNAs and B cells, followed by the role of the glutamate-GABA neurotransmitter cycle and the tryptophan pathway. We discuss host genetic immune factors, differences between adults and children, paradoxical reaction, and the impact of HIV-1 co-infection including immune reconstitution inflammatory syndrome. Promising immunomodulatory therapies, research gaps, ongoing challenges and future paths are discussed.

Investigating competencies needed by European-trained doctors in rural South African hospitals.

BACKGROUND: Many European-trained doctors (ETDs) recruited to work in rural district hospitals in South Africa have insufficient generalist competencies for the range of practice required. Africa Health Placements recruits ETDs to work in rural hospitals in Africa. Many of these doctors feel inadequately prepared. The Stellenbosch University Ukwanda Centre for Rural Health is launching a Postgraduate Diploma in Rural Medicine to help prepare doctors for such work. AIM: To determine the competencies gap for ETDs working in rural district hospitals in South Africa to inform the curriculum of the PG Dip (Rural Medicine). SETTING: Rural district hospitals in South Africa. METHODS: Nine hospitals in the Eastern Cape, KwaZulu-Natal and Mpumalanga were purposefully selected by Africa Health Placements as receiving ETDs. An online survey was developed asking about the most important competencies and weaknesses for ETDs when working rurally. The clinical manager and any ETDs currently working in each hospital were invited to complete the survey. RESULTS: Surveys were completed by 19 ETDs and five clinical managers. The top clinical competencies in relation to 10 specific domains were identified. The results also indicate broader competencies required, specific skills gaps, the strengths that ETDs bring to South Africa and how ETDs prepare themselves for working in this context. CONCLUSION: This study identifies the important competency gaps among ETDs and provides useful direction for the diploma and other future training initiatives. The diploma faculty must reflect on these findings and ensure the curriculum is aligned with these gaps.

Investigating competencies needed by European-trained doctors in rural South African hospitals

Background: Many European-trained doctors (ETDs) recruited to work in rural district hospitals in South Africa have insufficient generalist competencies for the range of practice required. Africa Health Placements recruits ETDs to work in rural hospitals in Africa. Many of these doctors feel inadequately prepared. The Stellenbosch University Ukwanda Centre for Rural Health is launching a Postgraduate Diploma in Rural Medicine to help prepare doctors for such work. Aim: To determine the competencies gap for ETDs working in rural district hospitals in South Africa to inform the curriculum of the PG Dip (Rural Medicine). Setting: Rural district hospitals in South Africa. Methods: Nine hospitals in the Eastern Cape, KwaZulu-Natal and Mpumalanga were purposefully selected by Africa Health Placements as receiving ETDs. An online survey was developed asking about the most important competencies and weaknesses for ETDs when working rurally. The clinical manager and any ETDs currently working in each hospital were invited to complete the survey. Results: Surveys were completed by 19 ETDs and five clinical managers. The top clinical competencies in relation to 10 specific domains were identified. The results also indicate broader competencies required, specific skills gaps, the strengths that ETDs bring to South Africa and how ETDs prepare themselves for working in this context. Conclusion: This study identifies the important competency gaps among ETDs and provides useful direction for the diploma and other future training initiatives. The diploma faculty must reflect on these findings and ensure the curriculum is aligned with these gaps

Cytomegalovirus Retinitis Screening and Treatment in Human Immunodeficiency Virus Patients in Malawi: A Feasibility Study.

BACKGROUND: Cytomegalovirus retinitis is a treatable cause of blindness in people with human immunodeficiency virus (HIV) typically with CD4 counts <50 cells/mm3. Diagnosis is with indirect fundoscopy, and treatment is with intravitreal ganciclovir injections or systemic therapy. However, diagnosis and treatment are not widely available in Malawi, which has an adult HIV prevalence estimated at 10.6%. This study aimed to establish the prevalence of cytomegalovirus retinitis among people with HIV in Malawi and the feasibility of screening. METHODS: Patients with CD4 counts <200 cells/mm3 were examined from 2 HIV clinics in Lilongwe and the main government hospital. Data were collected on antiretroviral therapy, ocular symptoms, and visual acuity. Fundoscopy was performed to investigate for features of cytomegalovirus retinitis. Retinal photographs were reviewed by an ophthalmologist. Patients diagnosed with cytomegalovirus retinitis were offered weekly ganciclovir injections, because systemic treatment was not available. RESULTS: Five of the 102 people with HIV screened had cytomegalovirus retinitis (4.9%). All affected patients had CD4 counts <50 cells/mm3 (mean, 15 cells/mm3; range, 3-22 cells/mm3). Visual acuity was unhelpful in identifying those with cytomegalovirus retinitis. Symptomatically, only blurred vision was useful. Two patients consented to treatment, 1 of which improved but relapsed after defaulting. CONCLUSIONS: Cytomegalovirus retinitis screening based on CD4 count is essential to early recognition because visual acuity and symptoms are unreliable. Cytomegalovirus retinitis is a significant yet neglected public health issue in Malawi. Oral valganciclovir is essential to reduce blindness and mortality in those diagnosed but is not yet available. Further screening and advocacy are needed.

Small molecule inhibition of p38 MAP kinase extends the replicative life span of human ATR-Seckel syndrome fibroblasts.

Ataxia-telangiectasia and rad3 (ATR)-related Seckel syndrome is associated with growth retardation and premature aging features. ATR-Seckel fibroblasts have a reduced replicative capacity in vitro and an aged morphology that is associated with activation of stress-associated p38 mitogen-activated protein kinase and phosphorylated HSP27. These phenotypes are prevented using p38 inhibitors, with replicative capacity restored to the normal range. However, this stressed phenotype is retained in telomerase-immortalized ATR-Seckel fibroblasts, indicating that it is independent of telomere erosion. As with normal fibroblasts, senescence in ATR-Seckel is bypassed by p53 abrogation. Young ATR-Seckel fibroblasts show elevated levels of p21(WAF1), p16(INK4A), phosphorylated actin-binding protein cofilin, and phosphorylated caveolin-1, with small molecule drug inhibition of p38 reducing p16(INK4A) and caveolin-1 phosphorylation. In conclusion, ATR-Seckel fibroblasts undergo accelerated aging via stress-induced premature senescence and p38 activation that may underlie certain clinical features of Seckel syndrome, and our data suggest a novel target for pharmacological intervention in this human syndrome.