Retrospective case series describing the efficacy, safety and cost-effectiveness of a vial-sharing programme for canakinumab treatment for paediatric patients with cryopyrin-associated periodic syndrome

Background Cryopyrin-associated periodic syndrome (CAPS) is a rare autoinflammatory disease, caused by gain of function mutation in NLRP3 resulting in excess production of interleukin-1 (IL-1). Canakinumab is a human monoclonal antibody against Interleukin-1 beta (IL-1β), licensed for the treatment of CAPS. The objective of the study was to describe the feasibility and cost-effectiveness of a canakinumab vial-sharing programme for paediatric patients with CAPS. Method Retrospective case series and clinical service description of a national specially commissioned CAPS clinic at Great Ormond Street Hospital (GOSH). Effectiveness was assessed using a CAPS disease activity score (DAS) and serum amyloid A protein (SAA). Adverse events were collected to determine safety. The number of canakinumab vials saved was considered when investigating the cost-effectiveness of vial-sharing. Results Nineteen/20 (95%) of our paediatric patients achieved minimally active clinical disease activity with canakinumab monotherapy; and 75% achieved both minimally active clinical disease and serological remission using a pre-specified definition based on the CAPS DAS and SAA level. Canakinumab was well tolerated, with only one child developing an infection requiring hospitalisation during the study. Canakinumab vial sharing resulted in 117 vials of canakinumab saved over a 24-month period, equating to a direct drug-related cost saving of £1,385,821, and a conservative estimated 5-year cost-saving of £3,464,552.50. Conclusion We provide further evidence for the effectiveness and safety of canakinumab in children with CAPS, and highlight the cost-effectiveness of a vial-sharing programme for this high cost medicine. We suggest that this could have important implications for the delivery of other high cost medicines used in paediatric practice

Prioritization of zoonoses for multisectoral, One Health collaboration in Somalia, 2023

Background: The human population of Somalia is vulnerable to zoonoses due to a high reliance on animal husbandry. This disease risk is exacerbated by relatively low income (poverty) and weak state capacity for health service delivery in the country as well as climate extremes and geopolitical instability in the region. To address this threat to public health efficiently and effectively, it is essential that all sectors have a common understanding of the priority zoonotic diseases of greatest concern to the country. Methods: Representatives from human, animal (domestic and wildlife), agriculture, and environmental health sectors undertook a multisectoral prioritization exercise using the One Health Zoonotic Disease Prioritization (OHZDP) tool developed by the United States CDC. The process involved: reviewing available literature and creating a longlist of zoonotic diseases for potential inclusion; developing and weighting criteria for establishing the importance of each zoonoses; formulating categorical questions (indicators) for each criteria; scoring each disease according to the criteria; and finally ranking the diseases based on the final score. Participants then brainstormed and suggested strategic action plans to prevent, and control prioritized zoonotic diseases. Results: Thirty-three zoonoses were initially considered for prioritization. Final criteria for ranking included: 1) socioeconomic impact (including sensitivity) in Somalia; 2) burden of disease in humans in Somalia); 3) availability of intervention in Somalia; 4) environmental factors/determinants; and 5) burden of disease in animals in Somalia. Following scoring of each zoonotic disease against these criteria, and further discussion of the OHZDP tool outputs, seven priority zoonoses were identified for Somalia: Rift Valley fever, Middle East respiratory syndrome, anthrax, trypanosomiasis, brucellosis, zoonotic enteric parasites (including Giardia and Cryptosporidium), and zoonotic influenza viruses. Conclusions: The final list of seven priority zoonotic diseases will serve as a foundation for strengthening One Health approaches for disease prevention and control in Somalia. It will be used to: shape improved multisectoral linkages for integrated surveillance systems and laboratory networks for improved human, animal, and environmental health; establish multisectoral public health emergency preparedness and response plans using One Health approaches; and enhance workforce capacity to prevent, control and respond to priority zoonotic diseases

Data-driven malaria prevalence prediction in large densely populated urban holoendemic sub-Saharan West Africa

Over 200 million malaria cases globally lead to half-million deaths annually. The development of malaria prevalence prediction systems to support malaria care pathways has been hindered by lack of data, a tendency towards universal "monolithic" models (one-size-fits-all-regions) and a focus on long lead time predictions. Current systems do not provide short-term local predictions at an accuracy suitable for deployment in clinical practice. Here we show a data-driven approach that reliably produces one-month-ahead prevalence prediction within a densely populated all-year-round malaria metropolis of over 3.5 million inhabitants situated in Nigeria which has one of the largest global burdens of P. falciparum malaria. We estimate one-month-ahead prevalence in a unique 22-years prospective regional dataset of > 9 × 10^{4} participants attending our healthcare services. Our system agrees with both magnitude and direction of the prediction on validation data achieving MAE ≤ 6 × 10^{-2}, MSE ≤ 7 × 10^{-3}, PCC (median 0.63, IQR 0.3) and with more than 80% of estimates within a (+ 0.1 to - 0.05) error-tolerance range which is clinically relevant for decision-support in our holoendemic setting. Our data-driven approach could facilitate healthcare systems to harness their own data to support local malaria care pathways

Predicting effective pro-apoptotic antileukaemic drug combinations using cooperative dynamic BH3 profiling

The BH3-only apoptosis agonists BAD and NOXA target BCL-2 and MCL-1 respectively and co-operate to induce apoptosis. On this basis, therapeutic drugs targeting BCL-2 and MCL-1 might have enhanced activity if used in combination. We identified anti-leukaemic drugs sensitising to BCL-2 antagonism and drugs sensitising to MCL-1 antagonism using the technique of dynamic BH3 profiling, whereby cells were primed with drugs to discover whether this would elicit mitochondrial outer membrane permeabilisation in response to BCL-2-targeting BAD-BH3 peptide or MCL-1-targeting MS1-BH3 peptide. We found that a broad range of anti-leukaemic agents–notably MCL-1 inhibitors, DNA damaging agents and FLT3 inhibitors–sensitise leukaemia cells to BAD-BH3. We further analysed the BCL-2 inhibitors ABT-199 and JQ1, the MCL-1 inhibitors pladienolide B and torin1, the FLT3 inhibitor AC220 and the DNA double-strand break inducer etoposide to correlate priming responses with co-operative induction of apoptosis. ABT-199 in combination with pladienolide B, torin1, etoposide or AC220 strongly induced apoptosis within 4 hours, but the MCL-1 inhibitors did not co-operate with etoposide or AC220. In keeping with the long half-life of BCL-2, the BET domain inhibitor JQ1 was found to downregulate BCL-2 and to prime cells to respond to MS1-BH3 at 48, but not at 4 hours: prolonged priming with JQ1 was then shown to induce rapid cytochrome C release when pladienolide B, torin1, etoposide or AC220 were added. In conclusion, dynamic BH3 profiling is a useful mechanism-based tool for understanding and predicting co-operative lethality between drugs sensitising to BCL-2 antagonism and drugs sensitising to MCL-1 antagonism. A plethora of agents sensitised cells to BAD-BH3-mediated mitochondrial outer membrane permeabilisation in the dynamic BH3 profiling assay and this was associated with effective co-operation with the BCL-2 inhibitory compounds ABT-199 or JQ1

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

Investment in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing in Africa over the past year has led to a major increase in the number of sequences that have been generated and used to track the pandemic on the continent, a number that now exceeds 100,000 genomes. Our results show an increase in the number of African countries that are able to sequence domestically and highlight that local sequencing enables faster turnaround times and more-regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and illuminate the distinct dispersal dynamics of variants of concern-particularly Alpha, Beta, Delta, and Omicron-on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve while the continent faces many emerging and reemerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Magnetic Resonance Imaging Findings and Their Association with Electroencephalographic Data in Children with Epilepsy at Tertiary Care Hospital in Mogadishu Somalia

Abdinasir Mohamed Elmi,1 Abdiwahid Ahmed Ibrahim,2 Mohamed Sheikh Hassan,2,3 Faisal Abdi Osoble Osman,1 Cihan Çelik,1 Abdikadir Mohamed Dirie,1 Ismail Gedi Ibrahim1 1Radiology Department, Mogadishu Somali Turkish Training and Research Hospital, Mogadishu, Somalia; 2Neurology Department, Mogadishu Somali Turkish Training and Research Hospital, Mogadishu, Somalia; 3Faculty of Medicine and Surgery, Mogadishu University, Mogadishu, SomaliaCorrespondence: Abdinasir Mohamed Elmi, Radiology Department, Mogadishu Somali Turkish Training and Research Hospital, Mogadishu, Somalia, Email [email protected]: Epilepsy is a neurological disorder characterized by abnormal, fast, synchronous neuronal discharge from the cerebral cortex. This abnormal excitation of the brain is usually short and self-limiting and can last anywhere from a few seconds to a few minutes. Neuroimaging and electroencephalography (EEG) are two widely used techniques to differentiate, verify, or exclude the diagnosis of epilepsy. The study aims to identify the frequency of EEG and MRI abnormalities in pediatric epilepsy and their correlations, aiming to improve diagnostic and treatment methods for these children.Materials and Methods: In this cross-sectional retrospective study, we evaluated pediatric patients aged 0– 18 years who visited the Neurology Polyclinic between July 2022 and July 2023, were diagnosed with epilepsy in accordance with the ILAE 2014 epilepsy guidelines, and had undergone neuroimaging at the hospital’s radiology department. Demographic information and clinical data, including the patient’s age, gender, history of trauma, and congenital infection, were assessed. In all patients, a surface electroencephalogram (EEG) and brain magnetic resonance imaging (MRI) were performed.Results: Our study recruited 102 pediatric patients aged between 0– 18 years, including 63 (61.8%) boys and 39 (37.2%) girls. An electroencephalogram (EEG) and MRI study have been done on all patients. An abnormal EEG study was seen in 79 (77.45%) participants, and an abnormal MRI was noted in 45 (44.1%) patients. The EEG and MRI were both abnormal in 34 cases (33.3%). The study found no significant correlation between magnetic resonance imaging and electroencephalographic findings (P =0.779).Conclusion: We observed multiple abnormalities on neuroimaging in pediatric epileptic patients. Even though our sample size was small, our results demonstrated that there is no statistically significant relationship between EEG and MRI results.Keywords: pediatric epilepsy, electroencephalography, magnetic resonance imagin