scholarly journals Population pharmacogenomics: an update on ethnogeographic differences and opportunities for precision public health

2021 ◽  
Author(s):  
Yitian Zhou ◽  
Volker M. Lauschke
Keyword(s):  
Public Health ◽  
Drug Targets ◽  
Drug Disposition ◽  
Drug Hypersensitivity ◽  
Sub Saharan Africa ◽  
Loss Of Function ◽  
Drug Induced ◽  
Landscape Complexity ◽  
Precision Public Health ◽  
Stratified Care

AbstractBoth safety and efficacy of medical treatment can vary depending on the ethnogeographic background of the patient. One of the reasons underlying this variability is differences in pharmacogenetic polymorphisms in genes involved in drug disposition, as well as in drug targets. Knowledge and appreciation of these differences is thus essential to optimize population-stratified care. Here, we provide an extensive updated analysis of population pharmacogenomics in ten pharmacokinetic genes (CYP2D6, CYP2C19, DPYD, TPMT, NUDT15 and SLC22A1), drug targets (CFTR) and genes involved in drug hypersensitivity (HLA-A, HLA-B) or drug-induced acute hemolytic anemia (G6PD). Combined, polymorphisms in the analyzed genes affect the pharmacology, efficacy or safety of 141 different drugs and therapeutic regimens. The data reveal pronounced differences in the genetic landscape, complexity and variant frequencies between ethnogeographic groups. Reduced function alleles of CYP2D6, SLC22A1 and CFTR were most prevalent in individuals of European descent, whereas DPYD and TPMT deficiencies were most common in Sub-Saharan Africa. Oceanian populations showed the highest frequencies of CYP2C19 loss-of-function alleles while their inferred CYP2D6 activity was among the highest worldwide. Frequencies of HLA-B*15:02 and HLA-B*58:01 were highest across Asia, which has important implications for the risk of severe cutaneous adverse reactions upon treatment with carbamazepine and allopurinol. G6PD deficiencies were most frequent in Africa, the Middle East and Southeast Asia with pronounced differences in variant composition. These variability data provide an important resource to inform cost-effectiveness modeling and guide population-specific genotyping strategies with the goal of optimizing the implementation of precision public health.

Molecular characterization of SARS-CoV-2

2020 ◽  
Vol 20 ◽  
Author(s):  
Miribane Dërmaku-Sopjani ◽  
Mentor Sopjani
Keyword(s):  
Public Health ◽  
Drug Targets ◽  
Virus Genome ◽  
Health Crisis ◽  
Public Health Crisis ◽  
Therapeutic Drugs ◽  
New Public Health ◽  
New Public ◽  
And Function

Abstract:: The coronavirus disease 2019 (COVID-19) is currently a new public health crisis threatening the world. This pandemic disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus has been reported to be originated in bats and by yet unknown intermediary animals were transmitted to humans in China 2019. The SARSCoV- 2 spreads faster than its two ancestors the SARS-CoV and Middle East respiratory syndrome coronavirus (MERSCoV) but has reduced fatality. At present, the SARS-CoV-2 has caused about a 1.16 million of deaths with more than 43.4 million confirmed cases worldwide, resulting in a serious threat to public health globally with yet uncertain impact. The disease is transmitted by inhalation or direct contact with an infected person. The incubation period ranges from 1 to 14 days. COVID-19 is accompanied by various symptoms, including cough, fatigue. In most people the disease is mild, but in some other people, such as in elderly and people with chronic diseases, it may progress from pneumonia to a multi-organ dysfunction. Many people are reported asymptomatic. The virus genome is sequenced, but new variants are reported. Numerous biochemical aspects of its structure and function are revealed. To date, no clinically approved vaccines and/or specific therapeutic drugs are available to prevent or treat the COVID-19. However, there are reported intensive researches on the SARSCoV- 2 to potentially identify vaccines and/or drug targets, which may help to overcome the disease. In this review, we discuss recent advances in understanding the molecular structure of SARS-CoV-2 and its biochemical characteristics.

Crowdsourcing Covid-19 signals in sub-Saharan Africa: Leveraging digital contributor networks for participatory surveillance of Covid-19 symptoms and deaths (Preprint)

2020 ◽  
Author(s):  
Ngozi A Erondu ◽  
Sagal A Ali ◽  
Mohamed Ali ◽  
Schadrac C Agbla
Keyword(s):  
Public Health ◽  
Sub Saharan Africa ◽  
Specific Information ◽  
Surveillance Systems ◽  
Health Seeking ◽  
African Countries ◽  
Cross Sectional Survey ◽  
Local Networks ◽  
The World ◽  
Sub Saharan

BACKGROUND In sub-Saharan Africa, underreporting of cases and deaths has been attributed to various factors including, weak disease surveillance, low health-seeking behaviour of flu like symptoms, and stigma of Covid-19. There is evidence that SARS-CoV-2 spread mimics transmission patterns of other countries across the world. Since the Covid-19 pandemic has changed the way research can be conducted and in light of restrictions on travel and risks to in-person data collection, innovative approaches to collecting data must be considered. Nearly 50% of Africa’s population is a unique mobile subscriber and it is one of the fastest growing smart-phone marketplaces in the world; hence, mobile phone platforms should be considered to monitor Covid-19 trends in the community. OBJECTIVE We demonstrate the use of digital contributor platforms to survey individuals about cases of flu-like symptoms and instances of unexplained deaths in Ethiopia, Kenya, Nigeria, Somalia, and Zimbabwe. METHODS Rapid cross-sectional survey of individuals with severe flu and pneumonia symptoms and unexplained deaths in Ethiopia, Kenya, Nigeria, Somalia and Zimbabwe RESULTS Using a non-health specific information platform, we found COVID-19 signals in five African countries, specifically: •Across countries, nearly half of the respondents (n=739) knew someone who had severe flu or pneumonia symptoms in recent months. •One in three respondents from Somalia and one in five from Zimbabwe respondents said they knew more than five people recently displaying flu and/or pneumonia symptoms. •In Somalia there were signals that a large number of people might be dying outside of health facilities, specifically in their homes or in IDP or refugee camps. CONCLUSIONS Existing digital contributor platforms with local networks are a non-traditional data source that can provide information from the community to supplement traditional government surveillance systems and academic surveys. We demonstrate that using these distributor networks to for community surveys can provide periodic information on rumours but could also be used to capture local sentiment to inform public health decision-making; for example, these insights could be useful to inform strategies to increase confidence in Covid19 vaccine. As Covid-19 continues to spread somewhat silently across sub-Saharan Africa, regional and national public health entities should consider expanding event-based surveillance sources to include these systems.

scholarly journals COVID-19 pandemic: the implications of the natural history, challenges of diagnosis and management for care in sub-Saharan Africa

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Lawrence Omo-Aghoja ◽  
Emuesiri Goodies Moke ◽  
Kenneth Kelechi Anachuna ◽  
Adrian Itivere Omogbiya ◽  
Emuesiri Kohworho Umukoro ◽  
...  
Keyword(s):  
Public Health ◽  
Natural History ◽  
Low Income ◽  
Sub Saharan Africa ◽  
Low Income Countries ◽  
Diagnosis And Management ◽  
Severe Acute Respiratory Infection ◽  
Identification Technique ◽  
Sub Saharan ◽  
Policies And Programs

Abstract Background Coronavirus disease (COVID-19) is a severe acute respiratory infection which has afflicted virtually almost all nations of the earth. It is highly transmissible and represents one of the most serious pandemics in recent times, with the capacity to overwhelm any healthcare system and cause morbidity and fatality. Main content The diagnosis of this disease is daunting and challenging as it is dependent on emerging clinical symptomatology that continues to increase and change very rapidly. The definitive test is the very expensive and scarce polymerase chain reaction (PCR) viral identification technique. The management has remained largely supportive and empirical, as there are no officially approved therapeutic agents, vaccines or antiviral medications for the management of the disease. Severe cases often require intensive care facilities and personnel. Yet there is paucity of facilities including the personnel required for diagnosis and treatment of COVID-19 in sub-Saharan Africa (SSA). It is against this backdrop that a review of key published reports on the pandemic in SSA and globally is made, as understanding the natural history of a disease and the documented responses to diagnosis and management is usually a key public health strategy for designing and improving as appropriate, relevant interventions. Lead findings were that responses by most nations of SSA were adhoc, paucity of public health awareness strategies and absence of legislations that would help enforce preventive measures, as well as limited facilities (including personal protective equipment) and institutional capacities to deliver needed interventions. Conclusion COVID-19 is real and has overwhelmed global health care system especially low-income countries of the sub-Sahara such as Nigeria. Suggestions for improvement of healthcare policies and programs to contain the current pandemic and to respond more optimally in case of future pandemics are made herein.

scholarly journals Climate Change and Health Preparedness in Africa: Analysing Trends in Six African Countries

2021 ◽  
Vol 18 (9) ◽  
pp. 4672
Author(s):  
Samuel Kwasi Opoku ◽  
Walter Leal Filho ◽  
Fudjumdjum Hubert ◽  
Oluwabunmi Adejumo
Keyword(s):  
Public Health ◽  
Climate Change ◽  
South Africa ◽  
Human Health ◽  
Health Systems ◽  
Health Professionals ◽  
Health Problems ◽  
Sub Saharan Africa ◽  
Basic Knowledge ◽  
African Countries

Climate change is a global problem, which affects the various geographical regions at different levels. It is also associated with a wide range of human health problems, which pose a burden to health systems, especially in regions such as Africa. Indeed, across the African continent public health systems are under severe pressure, partly due to their fragile socioeconomic conditions. This paper reports on a cross-sectional study in six African countries (Ghana, Nigeria, South Africa, Namibia, Ethiopia, and Kenya) aimed at assessing their vulnerabilities to climate change, focusing on its impacts on human health. The study evaluated the levels of information, knowledge, and perceptions of public health professionals. It also examined the health systems’ preparedness to cope with these health hazards, the available resources, and those needed to build resilience to the country’s vulnerable population, as perceived by health professionals. The results revealed that 63.1% of the total respondents reported that climate change had been extensively experienced in the past years, while 32% claimed that the sampled countries had experienced them to some extent. Nigerian respondents recorded the highest levels (67.7%), followed by Kenya with 66.6%. South Africa had the lowest level of impact as perceived by the respondents (50.0%) when compared with the other sampled countries. All respondents from Ghana and Namibia reported that health problems caused by climate change are common in the two countries. As perceived by the health professionals, the inadequate resources reiterate the need for infrastructural resources, medical equipment, emergency response resources, and technical support. The study’s recommendations include the need to improve current policies at all levels (i.e., national, regional, and local) on climate change and public health and to strengthen health professionals’ skills. Improving the basic knowledge of health institutions to better respond to a changing climate is also recommended. The study provides valuable insights which may be helpful to other nations in Sub-Saharan Africa.

scholarly journals Advancing precision public health using human genomics: examples from the field and future research opportunities

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Megan C. Roberts ◽  
Alison E. Fohner ◽  
Latrice Landry ◽  
Dana Lee Olstad ◽  
Amelia K. Smit ◽  
...  
Keyword(s):  
Public Health ◽  
Precision Medicine ◽  
Behavioral Science ◽  
Public Health Research ◽  
Future Research ◽  
Human Genomics ◽  
Precision Public Health ◽  
Genomics Research ◽  
Health Initiatives ◽  
Public Health Initiatives

AbstractPrecision public health is a relatively new field that integrates components of precision medicine, such as human genomics research, with public health concepts to help improve population health. Despite interest in advancing precision public health initiatives using human genomics research, current and future opportunities in this emerging field remain largely undescribed. To that end, we provide examples of promising opportunities and current applications of genomics research within precision public health and outline future directions within five major domains of public health: biostatistics, environmental health, epidemiology, health policy and health services, and social and behavioral science. To further extend applications of genomics within precision public health research, three key cross-cutting challenges will need to be addressed: developing policies that implement precision public health initiatives at multiple levels, improving data integration and developing more rigorous methodologies, and incorporating initiatives that address health equity. Realizing the potential to better integrate human genomics within precision public health will require transdisciplinary efforts that leverage the strengths of both precision medicine and public health.

scholarly journals Proteomic profiling of murine biliary-derived hepatic organoids and their capacity for drug disposition, bioactivation and detoxification

2021 ◽  
Author(s):  
Lawrence Howell ◽  
Rosalind E. Jenkins ◽  
Stephen Lynch ◽  
Carrie Duckworth ◽  
B. Kevin Park ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Metabolism ◽  
Rna Polymerase Ii ◽  
Liver Tissue ◽  
Drug Disposition ◽  
Multiple Drug ◽  
Proteomic Profiling ◽  
Cytochrome P450 3A ◽  
Drug Induced

AbstractHepatic organoids are a recent innovation in in vitro modeling. Initial studies suggest that organoids better recapitulate the liver phenotype in vitro compared to pre-existing proliferative cell models. However, their potential for drug metabolism and detoxification remains poorly characterized, and their global proteome has yet to be compared to their tissue of origin. This analysis is urgently needed to determine what gain-of-function this new model may represent for modeling the physiological and toxicological response of the liver to xenobiotics. Global proteomic profiling of undifferentiated and differentiated hepatic murine organoids and donor-matched livers was, therefore, performed to assess both their similarity to liver tissue, and the expression of drug-metabolizing enzymes and transporters. This analysis quantified 4405 proteins across all sample types. Data are available via ProteomeXchange (PXD017986). Differentiation of organoids significantly increased the expression of multiple cytochrome P450, phase II enzymes, liver biomarkers and hepatic transporters. While the final phenotype of differentiated organoids is distinct from liver tissue, the organoids contain multiple drug metabolizing and transporter proteins necessary for liver function and drug metabolism, such as cytochrome P450 3A, glutathione-S-transferase alpha and multidrug resistance protein 1A. Indeed, the differentiated organoids were shown to exhibit increased sensitivity to midazolam (10–1000 µM) and irinotecan (1–100 µM), when compared to the undifferentiated organoids. The predicted reduced activity of HNF4A and a resulting dysregulation of RNA polymerase II may explain the partial differentiation of the organoids. Although further experimentation, optimization and characterization is needed relative to pre-existing models to fully contextualize their use as an in vitro model of drug-induced liver injury, hepatic organoids represent an attractive novel model of the response of the liver to xenobiotics. The current study also highlights the utility of global proteomic analyses for rapid and accurate evaluation of organoid-based test systems.

scholarly journals The Search for a Schistosomiasis Vaccine: Australia’s Contribution

Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 872
Author(s):  
Donald P. McManus
Keyword(s):  
Public Health ◽  
Drug Resistance ◽  
Sub Saharan Africa ◽  
Effective Vaccine ◽  
Neglected Tropical Disease ◽  
Vaccine Research ◽  
Health Measures ◽  
Leading Role ◽  
Invaluable Tool ◽  
Sub Saharan

Schistosomiasis, a neglected tropical disease caused by parasitic flatworms of the genus Schistosoma, results in considerable human morbidity in sub-Saharan Africa, in particular, but also parts of the Middle East, South America, and Southeast Asia. The anti-schistosome drug praziquantel is efficacious and safe against the adult parasites of all Schistosoma species infecting humans; however, it does not prevent reinfection and the development of drug resistance is a constant concern. The need to develop an effective vaccine is of great importance if the health of many in the developing world is to be improved. Indeed, vaccination, in combination with other public health measures, can provide an invaluable tool to achieve lasting control, leading to schistosomiasis elimination. Australia has played a leading role in schistosomiasis vaccine research over many years and this review presents an overview of some of the significant contributions made by Australian scientists in this important area.

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