Priority Diseases Research Articles

A protocol for a living mapping review of global research funding for infectious diseases with a pandemic potential – PANDEMIC PACT

The COVID CIRCLE initiative Research Project Tracker by UKCDR and GloPID-R and associated living mapping review (LMR) showed the importance of sharing and analysing data on research at the point of funding to improve coordination during a pandemic. This approach can also help with research preparedness for outbreaks and hence our new programme the Pandemic Preparedness: Analytical Capacity and Funding Tracking Programme (Pandemic PACT) has been established. The LMR described in this protocol will provide an open, accessible, near-real-time overview of the funding landscape for a wide range of infectious disease and pandemic preparedness research using a rich database. The underpinning database will feed into an online funding tracking dashboard, with visualisations and advanced exploration features. The database is the expansion of the previous UKCDR and GloPID-R COVID-19 Research Project database with addition of the priority diseases from the WHO Blueprint list plus initial additions of pandemic influenza, mpox and plague. We have captured as much information as possible about grants and their outputs and ensured that our metadata and database is aligned to the FAIR (findable, accessible, interoperable and reproducible) principles by design. Prior to the public release, the data are processed by researchers and supported with artificial intelligence to create a curated data product. We anticipate that the database, this associated LMR and online funding tracking dashboard, will be a useful resource for funders, policy makers and researchers. In the future, our work will inform a more coordinated approach to research funding by providing evidence and data, including identification of gaps in funding allocation with a particular focus on low- and middle-income countries.

Estimating the health effects of COVID-19-related immunisation disruptions in 112 countries during 2020–30: a modelling study

There have been declines in global immunisation coverage due to the COVID-19 pandemic. Recovery has begun but is geographically variable. This disruption has led to under-immunised cohorts and interrupted progress in reducing vaccine-preventable disease burden. There have, so far, been few studies of the effects of coverage disruption on vaccine effects. We aimed to quantify the effects of vaccine-coverage disruption on routine and campaign immunisation services, identify cohorts and regions that could particularly benefit from catch-up activities, and establish if losses in effect could be recovered. For this modelling study, we used modelling groups from the Vaccine Impact Modelling Consortium from 112 low-income and middle-income countries to estimate vaccine effect for 14 pathogens. One set of modelling estimates used vaccine-coverage data from 1937 to 2021 for a subset of vaccine-preventable, outbreak-prone or priority diseases (ie, measles, rubella, hepatitis B, human papillomavirus [HPV], meningitis A, and yellow fever) to examine mitigation measures, hereafter referred to as recovery runs. The second set of estimates were conducted with vaccine-coverage data from 1937 to 2020, used to calculate effect ratios (ie, the burden averted per dose) for all 14 included vaccines and diseases, hereafter referred to as full runs. Both runs were modelled from Jan 1, 2000, to Dec 31, 2100. Countries were included if they were in the Gavi, the Vaccine Alliance portfolio; had notable burden; or had notable strategic vaccination activities. These countries represented the majority of global vaccine-preventable disease burden. Vaccine coverage was informed by historical estimates from WHO-UNICEF Estimates of National Immunization Coverage and the immunisation repository of WHO for data up to and including 2021. From 2022 onwards, we estimated coverage on the basis of guidance about campaign frequency, non-linear assumptions about the recovery of routine immunisation to pre-disruption magnitude, and 2030 endpoints informed by the WHO Immunization Agenda 2030 aims and expert consultation. We examined three main scenarios: no disruption, baseline recovery, and baseline recovery and catch-up. We estimated that disruption to measles, rubella, HPV, hepatitis B, meningitis A, and yellow fever vaccination could lead to 49 119 additional deaths (95% credible interval [CrI] 17 248-134 941) during calendar years 2020-30, largely due to measles. For years of vaccination 2020-30 for all 14 pathogens, disruption could lead to a 2·66% (95% CrI 2·52-2·81) reduction in long-term effect from 37 378 194 deaths averted (34 450 249-40 241 202) to 36 410 559 deaths averted (33 515 397-39 241 799). We estimated that catch-up activities could avert 78·9% (40·4-151·4) of excess deaths between calendar years 2023 and 2030 (ie, 18 900 [7037-60 223] of 25 356 [9859-75 073]). Our results highlight the importance of the timing of catch-up activities, considering estimated burden to improve vaccine coverage in affected cohorts. We estimated that mitigation measures for measles and yellow fever were particularly effective at reducing excess burden in the short term. Additionally, the high long-term effect of HPV vaccine as an important cervical-cancer prevention tool warrants continued immunisation efforts after disruption. The Vaccine Impact Modelling Consortium, funded by Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation. For the Arabic, Chinese, French, Portguese and Spanish translations of the abstract see Supplementary Materials section.

A mRNA Vaccine for Crimean-Congo Hemorrhagic Fever Virus Expressing Non-Fusion GnGc Using NSm Linker Elicits Unexpected Immune Responses in Mice.

Crimean-Congo hemorrhagic fever (CCHF), caused by Crimean-Congo Hemorrhagic virus (CCHFV), is listed in the World Health Organization's list of priority diseases. The high fatality rate in humans, the widespread distribution of CCHFV, and the lack of approved specific vaccines are the primary concerns regarding this disease. We used microfluidic technology to optimize the mRNA vaccine delivery system and demonstrated that vaccination with nucleoside-modified CCHFV mRNA vaccines encoding GnNSmGc (vLMs), Gn (vLMn), or Gc (vLMc) induced different immune responses. We found that both T-cell and B-cell immune responses induced by vLMc were better than those induced by vLMn. Interestingly, immune responses were found to be lower for vLMs, which employed NSm to link Gn and Gc for non-fusion expression, compared to those for vLMc. In conclusion, our results indicated that NSm could be a factor that leads to decreased specific immune responses in the host and should be avoided in the development of CCHFV vaccine antigens.

Monitoring Access to Child Medicines: Introducing a Standardized Set of Age-Appropriate Medicines.

Monitoring access to pediatric medicines as part of the Sustainable Development Goal (SDG) agenda for 2030 requires surveying age-appropriate medicines. This study aimed to develop tracer sets of essential age-appropriate medicines for use in SDG indicator 3.b.3 or in conjunction with other methodologies for monitoring access to medicines. Two sets of medicines were developed, one for young children (1 month to 5 years) and one for school-aged children (5-12 years). Priority diseases were selected based on the global burden of disease and linked to active ingredients of first choice according to treatment guidelines and the World Health Organization (WHO) Model List of Essential Medicines for Children (EMLc). To ensure clinical relevance, the Delphi technique was employed to identify areas of (dis)agreement among clinical pediatric experts. During two consultation rounds, experts were invited to indicate (dis)agreement. Five experts per age group were largely in agreement with the initial selections, but various therapeutic alternatives were suggested for addition. A second consultation round with five experts did not lead to major adjustments. The final sets included 26 treatment options for both groups. Specific age-appropriate formulations were selected from the WHO EMLc 2023. These two globally representative tracer sets of medicines consider the particular needs of children and could aid countries in the critical monitoring of accessibility to pediatric medicines.

Optimising diagnosis and management of kidney disease: an implementation trial of a clinical decision support system future health today

BackgroundChronic kidney disease affects more than 10% of the world’s population and is a non-communicable disease of global concern and priority. There is a significant implementation gap between best practice guideline recommendations and current kidney disease management. Previous research has shown the need to partner with primary care to improve education, collaboration, and kidney disease awareness. This implementation trial will explore use of an innovative clinical decision support software, Future Health Today, to improve screening, diagnosis, and management of kidney disease in primary care. The program will be supported by tertiary care outreach services. The primary aim is to test the hypothesis that the Future Health Today implementation program will improve screening, diagnosis, and management of kidney disease. Secondary aims are to evaluate primary care satisfaction and broader health service impacts.MethodsThis pre-post implementation trial using an interrupted time series design will evaluate the clinical and service outcomes of Future Health Today, using a mixed methods study in twenty general practices with an estimated population size of 150,000. Deidentified patient data will be extracted from participating practices to examine the primary aims of the study. Surveys and semi-structured interviews with general practice will inform secondary hypotheses. Data linkage between primary care and tertiary care data will examine the broader health service impacts.DiscussionThis investigator driven trial will assess the impact of Future Health Today software coupled with education and clinical outreach support. Investigators hypothesise that there will be improvement in appropriate screening, diagnosis, and management of kidney disease. This program has the potential to be scaled more broadly.Trial RegistrationAustralian New Zealand Clinical Trial Registry: ACTRN12623001096640.

Syndromic surveillance during 2022 Uganda Martyrs' commemoration.

Mass gatherings frequently include close, prolonged interactions between people, which presents opportunities for infectious disease transmission. Over 20,000 pilgrims gathered at Namugongo Catholic and Protestant shrines to commemorate 2022 Uganda Martyr's Day. We described syndromes suggestive of key priority diseases particularly COVID-19 and viral hemorrhagic fever (VHF) among visiting pilgrims during May 25-June 5, 2022. We conducted a survey among pilgrims at the catholic and protestant shrines based on signs and symptoms for key priority diseases: COVID-19 and VHF. A suspected COVID-19 case was defined as acute respiratory illness (temperature greater 37.5°C and at least one sign/symptom of respiratory infection such as cough or shortness of breath) whereas a suspected VHF case was defined as fever >37.5°C and unexplained bleeding among pilgrims who visited Namugongo Catholic and Protestant shrines from May 25 to June 5, 2022. Pilgrims were sampled systematically at entrances and demarcated zonal areas to participate in the survey. Additionally, we extracted secondary data on pilgrims who sought emergency medical services from Health Management Information System registers. Descriptive analysis was conducted to identify syndromes suggestive of key priority diseases. Among 1,350 pilgrims interviewed, 767 (57%) were female. The mean age was 37.9 (±17.9) years. Nearly all pilgrims 1,331 (98.6%) were Ugandans. A total of 236 (18%) reported ≥1 case definition symptom and 42 (3%) reported ≥2 symptoms. Thirty-nine (2.9%) were suspected COVID-19 cases and three (0.2%) were suspected VHF cases from different regions of Uganda. Among 5,582 pilgrims who sought medical care from tents, 628 (11.3%) had suspected COVID-19 and one had suspected VHF. Almost one in fifty pilgrims at the 2022 Uganda Martyrs' commemoration had at least one symptom of COVID-19 or VHF. Intensified syndromic surveillance and planned laboratory testing capacity at mass gatherings is important for early detection of public health emergencies that could stem from such events.

Mortality Associated with Priority Diseases in Flood-Affected Areas Using District Health Information System (DHIS2) During September-December 2022: Pakistan Experience.

To quantify the burden of communicable diseases and characterize the most reported infections during public health emergency of floods in Pakistan. The study's design is a descriptive trend analysis. The study utilized the disease data reported to District Health Information System (DHIS2) for the 12 most frequently reported priority diseases under the Integrated Disease Surveillance and Response (IDSR) system in Pakistan. In total, there were 1,532,963 suspected cases during August to December 2022 in flood-affected districts (n = 75) across Pakistan; Sindh Province reported the highest number of cases (n = 692,673) from 23 districts, followed by Khyber Pakhtunkhwa (KP) (n = 568,682) from 17 districts, Balochistan (n = 167,215) from 32 districts, and Punjab (n = 104,393) from 3 districts. High positivity was reported for malaria (79,622/201,901; 39.4%), followed by acute diarrhea (non-cholera) (23/62; 37.1%), hepatitis A and E (47/252; 18.7%), and dengue (603/3245; 18.6%). The crude mortality rate was 11.9 per 10 000 population (1824/1,532,963 [deaths/cases]). The study identified acute respiratory infection, acute diarrhea, malaria, and skin diseases as the most prevalent diseases. This suggests that preparedness efforts and interventions targeting these diseases should be prioritized in future flood response plans. The study highlights the importance of strengthening the IDSR as a Disease Early Warning System through the implementation of the DHIS2.

Molecular Docking Study of Pramipexole Derivatives as Radiopharmaceutical Candidates for Brain Imaging

Neurodegenerative diseases are a global priority disease. According to the World Health Organization (WHO), it is estimated that by 2050, there will be 152 million people with neurodegenerative diseases. Currently, the method used for brain imaging is PET/CT, with the most widely used radiopharmaceutical being 18F-FDG [7,8]. 18F-FDG is used to determine brain glucose metabolism, however the 18F-FDG does not have a specific receptor. Pramipexole compounds can cross the blood-brain barrier and have high specificity for dopamine receptors. By modifying and labelling the structure of pramipexole derivatives, it is expected to obtain pramipexole derivatives with a good affinity to the dopamine receptor. In order to reduce the risk of failure, radiation hazard, and research funds, in this research, a molecular docking study was carried out using the targeted docking method between dopamine receptor proteins and 22 pramipexole derivatives using AutoDock 4, GaussView software for structure preparation, Gaussian software for energy calculation, and Biovia Discovery Studio for structure visualization. The experimental results showed that the free binding energy of pramipexole derivatives for the dopamine receptor was obtained in the range of -2.81 to -5.84 kcal/mol. The best free binding energy value was obtained for compound PD-7, with a free binding energy value of -5.84 kcal/mol, while the RMSD value obtained was 0.6 A°, and amino acid residues that interacted with compound PD-7 among others: Leu347, Leu343, Tyr198, Leu199, Glu202, Phe201, and Val203 with hydrophobic and hydrogen bond interactions. The PD-7 compound was labeled using the radioisotope iodine-131 based on the free binding energy value. From the experimental results, compound 131I-PD-7 showed a free binding energy value of -4.66 kcal/mol and interacts with the similar amino acid residues as compound PD-7. These results indicate that the compound 131I-PD-7 is a potential candidate to be studied further as a radiopharmaceutical candidate for brain imaging.

The evolution of Kenya's animal health surveillance system and its potential for efficient detection of zoonoses.

Animal health surveillance systems in Kenya have undergone significant changes and faced various challenges throughout the years. In this article, we present a comprehensive overview of the Kenya animal health surveillance system (1944 to 2024), based on a review of archived documents, a scoping literature review, and an examination of past surveillance assessments and evaluation reports. The review of archived documents revealed key historical events that have shaped the surveillance system. These include the establishment of the Directorate of Veterinary Services in 1895, advancements in livestock farming, the implementation of mandatory disease control interventions in 1944, the growth of veterinary services from a section to a ministry in 1954, the disruption caused by the Mau Mau insurrection from 1952 to 1954, which led to the temporary halt of agriculture in certain regions until 1955, the transition of veterinary clinical services from public to private, and the progressive privatization plan for veterinary services starting in 1976. Additionally, we highlight the development of electronic surveillance from 2003 to 2024. The scoping literature review, assessments and evaluation reports uncovered several strengths and weaknesses of the surveillance system. Among the strengths are a robust legislative framework, the adoption of technology in surveillance practices, the existence of a formal intersectoral coordination platform, the implementation of syndromic, sentinel, and community-based surveillance methods, and the presence of a feedback mechanism. On the other hand, the system's weaknesses include the inadequate implementation of strategies and enforcement of laws, the lack of standard case definitions for priority diseases, underutilization of laboratory services, the absence of formal mechanisms for data sharing across sectors, insufficient resources for surveillance and response, limited integration of surveillance and laboratory systems, inadequate involvement of private actors and communities in disease surveillance, and the absence of a direct supervisory role between the national and county veterinary services. To establish an effective early warning system, we propose the integration of surveillance systems and the establishment of formal data sharing mechanisms. Furthermore, we recommend enhancing technological advancements and adopting artificial intelligence in surveillance practices, as well as implementing risk-based surveillance to optimize the allocation of surveillance resources.

The Current Pathogenicity and Potential Risk Evaluation of Marburg Virus to Cause Mysterious "Disease X"-An Update on Recent Evidences.

The World Health Organization (WHO) defined Disease X as an upcoming disease with the potential to cause a pandemic. Pathogen X is responsible for Disease X. Marburg virus disease (MVD) is one of the diseases from the priority disease list published by WHO. Marburg virus is a filamentous, negative-sense RNA virus that belongs to the same filovirus family as the lethal Ebola virus. Since the first discovery of this virus in 1967, 17 outbreaks occurred sporadically till 2023. Rousettus aegyptiacus acts as the natural reservoir of the virus. With an average incubation period of 5 to 10 days, its first target is the mononuclear phagocytic system cells. It is highly contagious and can be easily transmitted from animal to human and human to human via direct contact with blood or body fluid, feces, and semen of the infected host. Although Marburg disease has a high case fatality rate of close to 90%, unfortunately, there is no approved vaccines or treatments are available. The most recent outbreak of Marburg virus in Equatorial Guinea and Tanzania in 2023 caused an alert for global health. However, based on the last global pandemic of COVID-19 and the sudden re-emerging of monkeypox around the world, we can assume that the Marburg virus has the potential to cause a global pandemic. Our modern world depends on globalization, which helps the virus transmission among countries. The Marburg virus can easily be transmitted to humans by fruit bats of the Pteropodidae family. This virus causes severe hemorrhagic disease, and there are no specific vaccines and treatments available to combat it. Therefore, community engagement and early supportive care for patients are keys to successfully controlling MVD.

Establishing self-sustaining vaccine manufacturing ecosystems: Africa’s priority diseases

Establishing self-sustaining vaccine manufacturing ecosystems: Africa’s priority diseases

Management of diseases in a ruminant livestock production system: a participatory appraisal of the performance of veterinary services delivery, and utilization in Ghana

IntroductionSustainable livestock production remains crucial for attainment of food security globally and for safeguarding the livelihoods of many households in low- and –middle income countries. However, the high prevalence of infectious livestock diseases, coupled with inadequate provision and adoption of effective control measures, leads to reduced livestock productivity, increased animal mortalities, and emergence of antimicrobial resistant pathogens. This study sought to assess the management strategies employed by farmers for priority diseases affecting their animals and the utilization and performance of veterinary services.MethodsWe conducted the study in three districts, namely, Mion, Pru East, and Kwahu Afram Plains South Districts, which represent the main livestock production belts in Ghana. We used questionnaires in surveys, to collect pertinent data from 350 ruminant livestock farmers and 13 professional veterinary officers (VOs) in the study districts. Additionally, we conducted seven focus group discussions (FGDs) with 65 livestock farmers in the study districts. The survey data was analyzed, and we describe the distribution of the priority livestock diseases, the disease management strategies employed, and the performance of veterinary services in Ghana. We also analyzed the raw FGD transcript texts deductively based on the study objectives. To validate findings across the different datasets, we used triangulation.ResultsAlmost all the farmers (98%) reared small ruminants, with about 25% also rearing cattle. The main priority livestock diseases identified includes pestes-des-petits-ruminants and mange infection in sheep and goats, as well as contagious bovine pleuropneumonia and foot-and-mouth-disease in cattle. We found that majority (82%) of the farmers relied on treatment, while only 20% opted for vaccination services. Additionally, the veterinary system in Ghana did not adequately regulate the antimicrobial medications employed by farmers to manage diseases. Thus, in most of the cases, the medicines applied by farmers were not useful for the target diseases. Although our findings show the farmers perceived VOs to perform highly compared to informal providers on most of the attributes evaluated including medicine availability and quality, treatment effectiveness, advisory services, service affordability, and competence, only 33% utilized VOs services. The majority of the farmers (51%) used the services of informal providers, who were better in proximity and popularity with farmers.ConclusionsThe livestock sector in Ghana faces a substantial challenge due primarily to vaccine-preventable diseases. Even though VOs demonstrated superior performance on key veterinary service performance indicators, their services are underutilized by livestock farmers. Additionally, the absence of regulatory oversight by the veterinary system over antimicrobials utilized in animal production contributes to their misapplication by livestock farmers, posing a considerable risk to both public health and food security. It is thus imperative to introduce new initiatives that enhance the uptake of animal vaccines and better antimicrobial stewardship to ensure sustainable livestock production.

A Large-Scale Dataset of Search Interests Related to Disease X Originating from Different Geographic Regions

The World Health Organization (WHO) added Disease X to their shortlist of blueprint priority diseases to represent a hypothetical, unknown pathogen that could cause a future epidemic. During different virus outbreaks of the past, such as COVID-19, Influenza, Lyme Disease, and Zika virus, researchers from various disciplines utilized Google Trends to mine multimodal components of web behavior to study, investigate, and analyze the global awareness, preparedness, and response associated with these respective virus outbreaks. As the world prepares for Disease X, a dataset on web behavior related to Disease X would be crucial to contribute towards the timely advancement of research in this field. Furthermore, none of the prior works in this field have focused on the development of a dataset to compile relevant web behavior data, which would help to prepare for Disease X. To address these research challenges, this work presents a dataset of web behavior related to Disease X, which emerged from different geographic regions of the world, between February 2018 and August 2023. Specifically, this dataset presents the search interests related to Disease X from 94 geographic regions. These regions were chosen for data mining as these regions recorded significant search interests related to Disease X during this timeframe. The dataset was developed by collecting data using Google Trends. The relevant search interests for all these regions for each month in this time range are available in this dataset. This paper also discusses the compliance of this dataset with the FAIR principles of scientific data management. Finally, an analysis of this dataset is presented to uphold the applicability, relevance, and usefulness of this dataset for the investigation of different research questions in the interrelated fields of Big Data, Data Mining, Healthcare, Epidemiology, and Data Analysis with a specific focus on Disease X.

Documenting the development, adoption and pre-ebola implementation of Liberia’s integrated disease surveillance and response (IDSR) strategy

BackgroundIn the immediate aftermath of a 14-year civil conflict that disrupted the health system, Liberia adopted the internationally recommended integrated disease surveillance and response (IDSR) strategy in 2004. Despite this, Liberia was among the three West African countries ravaged by the worst Ebola epidemic in history from 2014 to 2016. This paper describes successes, failures, strengths, and weaknesses in the development, adoption, and implementation of IDSR following the civil war and up until the outbreak of Ebola, from 2004 to early 2014.MethodsWe reviewed 112 official Government documents and peer-reviewed articles and conducted 29 in-depth interviews with key informants from December 2021 to March 2022 to gain perspectives on IDSR in the post-conflict and pre-Ebola era in Liberia. We assessed the core and supportive functions of IDSR, such as notification of priority diseases, confirmation, reporting, analysis, investigation, response, feedback, monitoring, staff training, supervision, communication, and financial resources. Data were triangulated and presented via emerging themes and in-depth accounts to describe the context of IDSR introduction and implementation, and the barriers surrounding it.ResultsDespite the adoption of the IDSR framework, Liberia failed to secure the resources—human, logistical, and financial—to support effective implementation over the 10-year period. Documents and interview reports demonstrate numerous challenges prior to Ebola: the surveillance system lacked key components of IDSR including laboratory testing capacity, disease reporting, risk communication, community engagement, and staff supervision systems. Insufficient financial support and an abundance of vertical programs further impeded progress. In-depth accounts by donors and key governmental informants demonstrate that although the system had a role in detecting Ebola in Liberia, it could not respond effectively to control the disease.ConclusionOur findings suggest that post-war, Liberia’s health system intended to prioritize epidemic preparedness and response with the adoption of IDSR. However, insufficient investment and systems development meant IDSR was not well implemented, leaving the country vulnerable to the devastating impact of the Ebola epidemic.

Healthcare provider-targeted mobile applications to diagnose, screen, or monitor communicable diseases of public health importance in low- and middle-income countries: A systematic review.

Communicable diseases remain a leading cause of death and disability in low- and middle-income countries (LMICs). mHealth technologies carry considerable promise for managing these disorders within resource-poor settings, but many existing applications exclusively represent digital versions of existing guidelines or clinical calculators, communication facilitators, or patient self-management tools. We thus systematically searched PubMed, Web of Science, and Cochrane Central for studies published between January 2007 and October 2019 involving technologies that were mobile phone- or tablet-based; able to screen for, diagnose, or monitor a communicable disease of importance in LMICs; and targeted health professionals as primary users. We excluded technologies that digitized existing paper-based tools or facilitated communication (i.e., knowledge-based algorithms). Extracted data included disease category, pathogen type, diagnostic method, intervention purpose, study/target population, sample size, study methodology, development stage, accessory requirement, country of development, operating system, and cost. Given the search timeline, studies involving COVID-19 were not included in the analysis. Of 13,262 studies identified by the screen, 33 met inclusion criteria. 12% were randomized clinical trials (RCTs), with 58% of publications representing technical descriptions. 62% of studies had 100 or fewer subjects. All studied technologies involved diagnosis or screening steps; none addressed the monitoring of infections. 52% focused on priority diseases (HIV, malaria, tuberculosis), but only 12% addressed a neglected tropical disease. Although most reported studies were priced under 20USD at time of publication, two thirds of the records did not yet specify a cost for the study technology. We conclude that there are only a small number of mHealth technologies focusing on innovative methods of screening and diagnosing communicable diseases potentially of use in LMICs. Rigorous RCTs, analyses with large sample size, and technologies assisting in the monitoring of diseases are needed.

Review on Pest Des Petits Ruminants Virus and its Socioeconomic Impact in Small Ruminants

Peste Des Petits Ruminants (PPR) are a highly contagious viral disease that mainly affects sheep and goats. It belongs to the genus Morbillivirus in the family Paramyxoviridae. Today, this disease is considered a cause of mortality and morbidity in many countries of the world. The disease occurs south of the Sahara Desert and north of the equator in Africa, most of the Middle East, and parts of Asia, including the Indian subcontinent. It is transmitted by aerosols during close contact between animals, mainly through sneezing and coughing. The disease is characterized by high fever, discharge from the eyes and nose, pneumonia, necrosis and gastrointestinal tract leading to foul smelling diarrhoea. Diagnosis can be made based on clinical, pathological and epizootological findings. This has significant economic implications for food security and livelihoods. Therefore, PPR is considered one of the most damaging animal diseases in Africa, the Middle East and Asia, and is also one of the priority diseases listed in the FAO-OIE Global Framework for the Progressive Control of Trans boundary Animal Diseases. Peste des Petits ruminants are common in Ethiopia due to economic losses due to reduced production, death, abortion and cost of disease control. There is no specific treatment for PPR. However, drugs that control bacterial and parasitic complications may reduce mortality. For surveillance purposes, circular vaccination and/or vaccination of high-risk populations may also be useful. Therefore, eradication of PPR is done through a combination of quarantine, movement control, cleaning and disinfection of infected areas and vaccination.

A review of new challenges and solutions to the timely and effective implementation of clinical research responses to high priority diseases of epidemic and pandemic potential: A scoping review protocol

Background: Conducting and implementing clinical research response during pandemic and epidemic diseases outbreaks are often fraught with challenges due to their unprecedented nature. In previous research, challenges to the implementation of clinical research responses during pandemic and epidemic outbreaks were identified and solutions suggested. While the emergence of the Covid-19 pandemic has, on one hand, highlighted new and unresolved challenges, several novel solutions such as the Randomised Evaluation of Covid-19 Therapy (RECOVERY) trial were also implemented and reported in the literature. This scoping review, therefore, aims to synthesise and update solutions to the barriers affecting the implementation of clinical research responses during new, emerging or re-emerging diseases of pandemic and epidemic potential, to further inform strategies that would enhance pandemic and epidemic preparedness and response. Methods: This scoping review will be conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analysis- Extension for Scoping Reviews (PRISMA-ScR). Search will be conducted in six scientific databases: Ovid MEDLINE, Ovid Global Health, OVID PsycINFO, Ovid Embase, Scopus Epistemonikos, and complemented by a grey literature search in Google Scholar. Terms related to clinical trial, high consequence infectious diseases and the PEARLES domains will be used in the search. Two reviewers will independently screen retrieved articles in Rayyan software. Descriptive data of studies will be extracted into a pre-developed Microsoft Excel template while qualitative data related to the PEARLES solutions or barriers will be coded in NVivo. Results will be synthesised thematically and presented in a narrative style. Conclusions: This scoping review will synthesise new and updated solutions to the PEARLES challenges encountered during the implementation of clinical research responses to high consequence epidemics and pandemics. Furthermore, it will examine how challenges and proposed solutions identified prior to the emergence of Covid-19 have been addressed and tested in real time.

'It doesn't happen how you think, it is very complex!' Reconciling stakeholder priorities, evidence, and processes for zoonoses prioritisation in India.

Why do some zoonotic diseases receive priority from health policy decision-makers and planners whereas others receive little attention? By leveraging Shiffman and Smith's political prioritisation framework, our paper advances a political economy of disease prioritisation focusing on four key components: the strength of the actors involved in the prioritisation, the power of the ideas they use to portray the issue, the political contexts in which they operate, and the characteristics of the issue itself (e.g., overall burdens, severity, cost-effective interventions). These components afford a nuanced characterisation of how zoonotic diseases are prioritised for intervention and highlight the associated knowledge gaps affecting prioritisation outcomes. We apply this framework to the case of zoonoses management in India, specifically to identify the factors that shape disease prioritisation decision-making and outcomes. We conducted 26 semi-structured interviews with national, state and district level health policymakers, disease managers and technical experts involved in disease surveillance and control in India. Our results show pluralistic interpretation of risks, exemplified by a disconnect between state and district level actors on priority diseases. The main factors identified as shaping prioritisation outcomes were related to the nature of the zoonoses problem (the complexity of the zoonotic disease, insufficient awareness and lack of evidence on disease burdens and impacts) as well as political, social, cultural and institutional environments (isolated departmental priorities, limited institutional authority, opaque funding mechanisms), and challenges in organisation leadership for cross-sectoral engagement. The findings highlight a compartmentalised regulatory system for zoonoses where political, social, cultural, and media factors can influence disease management and prioritisation. A major policy window is the institutionalisation of One Health to increase the political priority for strengthening cross-sectoral engagement to address several challenges, including the creation of effective institutions to reconcile stakeholder priorities and prioritisation processes.

Efficacy of microbicidal actives and formulations for inactivation of Lassa virus in suspension

The World Health Organization’s R&D Blueprint list of priority diseases for 2022 includes Lassa fever, signifying the need for research and development in emergency contexts. This disease is caused by the arenavirus Lassa virus (LASV). Being an enveloped virus, LASV should be susceptible to a variety of microbicidal actives, although empirical data to support this expectation are needed. We evaluated the virucidal efficacy of sodium hypochlorite, ethanol, a formulated dual quaternary ammonium compound, an accelerated hydrogen peroxide formulation, and a p-chloro-m-xylenol formulation, per ASTM E1052-20, against LASV engineered to express green fluorescent protein (GFP). A 10-μL volume of virus in tripartite soil (bovine serum albumin, tryptone, and mucin) was combined with 50 μL of disinfectant in suspension for 0.5, 1, 5, or 10 min at 20–25 °C. Neutralized test mixtures were quantified by GFP expression to determine log10 reduction. Remaining material was passaged on Vero cells to confirm absence of residual infectious virus. Input virus titers of 6.6–8.0 log10 per assay were completely inactivated by each disinfectant within 1–5 min contact time. The rapid and substantial inactivation of LASV suggests the utility of these microbicides for mitigating spread of infectious virus during Lassa fever outbreaks.

Investigating the Efficacy and Safety of Diacerein in the Management of Knee Osteoarthritis with reference to its conventional management.

Designated as a "priority disease" by World Health Organization, Osteoarthritis is the most common chronic rheumatic disease. Providing a proper treatment for Osteoarthritis is still a major public health challenge. Diacerein has been proposed as a slow acting, symptom modifying or even disease modifying drug used in Osteoarthritis having a risk-benefit ratio far better than conventionally used drugs. However, the evidence of efficacy and safety of use of Diacerein in Osteoarthritis is yet to be explored. Hence, this study attempted to investigate the efficacy and safety of Diacerein in the management of knee osteoarthritis. This is an analytical cohort study comparing Diacerein with Non-steroidal anti-inflammatory drugs for two months in the management of knee OA. Efficacy was assessed by scores of Lysholm Knee Scoring Scale, Knee injury and Osteoarthritis Outcome Score - Physical Function Short form and Western Ontario and McMaster Universities Osteoarthritis Index. After two months of treatment, the post- treatment scores were significantly superior to the baseline scores in both the treatment groups (p<0.001). There were no significant differences among the post-treatment scores in two different treatment groups (p>0.05). Discoloration of urine and gastritis were the frequently reported adverse effects in Diacerein treatment group and Non-steroidal anti-inflammatory drugs treatment group respectively. Our findings have shown Diacerein is as effective as Non-steroidal anti-inflammatory drugs in treating knee OA patients. Diacerein was generally well tolerated, with a good safety profile. These findings indicate the need for further studies with experimental study design in larger scale.