scholarly journals Generation of Simian Rotavirus Reassortants with VP4- and VP7-Encoding Genome Segments from Human Strains Circulating in Africa Using Reverse Genetics

Viruses ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 201 ◽  
Author(s):  
Alexander Falkenhagen ◽  
Corinna Patzina-Mehling ◽  
Ashish K. Gadicherla ◽  
Amy Strydom ◽  
Hester G. O’Neill ◽  
...  
Keyword(s):  
Cell Culture ◽  
Disease Burden ◽  
Reverse Genetics ◽  
Sub Saharan Africa ◽  
Rotavirus A ◽  
Virus Particles ◽  
Rotavirus Vaccines ◽  
Human Rotavirus ◽  
Sub Saharan ◽  
Infants And Young Children

Human rotavirus A (RVA) causes acute gastroenteritis in infants and young children. The broad use of two vaccines, which are based on RVA strains from Europe and North America, significantly reduced rotavirus disease burden worldwide. However, a lower vaccine effectiveness is recorded in some regions of the world, such as sub-Saharan Africa, where diverse RVA strains are circulating. Here, a plasmid-based reverse genetics system was used to generate simian RVA reassortants with VP4 and VP7 proteins derived from African human RVA strains not previously adapted to cell culture. We were able to rescue 1/3 VP4 mono-reassortants, 3/3 VP7 mono-reassortants, but no VP4/VP7 double reassortant. Electron microscopy showed typical triple-layered virus particles for the rescued reassortants. All reassortants stably replicated in MA-104 cells; however, the VP4 reassortant showed significantly slower growth compared to the simian RVA or the VP7 reassortants. The results indicate that, at least in cell culture, human VP7 has a high reassortment potential, while reassortment of human VP4 from unadapted human RVA strains with simian RVA seems to be limited. The characterized reassortants may be useful for future studies investigating replication and reassortment requirements of rotaviruses as well as for the development of next generation rotavirus vaccines.

scholarly journals Endemic foot and mouth disease: pastoral in-herd disease dynamics in sub-Saharan Africa

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
I. McLachlan ◽  
G. Marion ◽  
I. J. McKendrick ◽  
T. Porphyre ◽  
I. G. Handel ◽  
...  
Keyword(s):  
Disease Burden ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Sub Saharan Africa ◽  
Herd Level ◽  
Population Turnover ◽  
Foot And Mouth ◽  
Sub Saharan ◽  
Multiple Strains ◽  
Reduced Risk

AbstractFoot and mouth disease (FMD) burden disproportionally affects Africa where it is considered endemic. Smallholder livestock keepers experience significant losses due to disease, but the dynamics and mechanisms underlying persistence at the herd-level and beyond remain poorly understood. We address this knowledge gap using stochastic, compartmental modelling to explore FMD virus (FMDV) persistence, outbreak dynamics and disease burden in individual cattle herds within an endemic setting. Our analysis suggests repeated introduction of virus from outside the herd is required for long-term viral persistence, irrespective of carrier presence. Risk of new disease exposures resulting in significant secondary outbreaks is reduced by the presence of immune individuals giving rise to a period of reduced risk, the predicted duration of which suggests that multiple strains of FMDV are responsible for observed yearly herd-level outbreaks. Our analysis suggests management of population turnover could potentially reduce disease burden and deliberate infection of cattle, practiced by local livestock keepers in parts of Africa, has little effect on the duration of the reduced risk period but increases disease burden. This work suggests that FMD control should be implemented beyond individual herds but, in the interim, herd management may be used to reduced FMD impact to livestock keepers.

scholarly journals The relative importance and stability of disease burden causes over time: summarizing regional trends on disease burden for 290 causes over 28 years

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Henry Dyson ◽  
Raf Van Gestel ◽  
Eddy van Doorslaer
Keyword(s):  
Disease Burden ◽  
Respiratory Infections ◽  
Sub Saharan Africa ◽  
Regional Trends ◽  
Disability Adjusted Life ◽  
Life Years ◽  
Causes Of Disease ◽  
Sub Saharan ◽  
Disease Study ◽  
Over Time

Abstract Background Since the Global Burden of Disease study (GBD) has become more comprehensive, data for hundreds of causes of disease burden, measured using Disability Adjusted Life Years (DALYs), have become increasingly available for almost every part of the world. However, undergoing any systematic comparative analysis of the trends can be challenging given the quantity of data that must be presented. Methods We use the GBD data to describe trends in cause-specific DALY rates for eight regions. We quantify the extent to which the importance of ‘major’ DALY causes changes relative to ‘minor’ DALY causes over time by decomposing changes in the Gini coefficient into ‘proportionality’ and ‘reranking’ indices. Results The fall in regional DALY rates since 1990 has been accompanied by generally positive proportionality indices and reranking indices of negligible magnitude. However, the rate at which DALY rates have been falling has slowed and, at the same time, proportionality indices have tended towards zero. These findings are clearest where the focus is exclusively upon non-communicable diseases. Notably, large and positive proportionality indices are recorded for sub-Saharan Africa over the last decade. Conclusion The positive proportionality indices show that disease burden has become less concentrated around the leading causes over time, and this trend has become less prominent as the DALY rate decline has slowed. The recent decline in disease burden in sub-Saharan Africa is disproportionally driven by improvements in DALY rates for HIV/AIDS, as well as for malaria, diarrheal diseases, and lower respiratory infections.

Rotavirus

2021 ◽  
Author(s):  
Sultan Mahmood
Keyword(s):  
Rna Virus ◽  
Sub Saharan Africa ◽  
Oral Rehydration ◽  
Degree Of Protection ◽  
Rotavirus Vaccines ◽  
Increased Risk ◽  
Hygiene Measures ◽  
Primary Means ◽  
Sub Saharan ◽  
Health System Responsiveness

Rotavirus is a double-stranded RNA virus that causes vomiting and diarrhea among children under 5 years. The main cause of mortality from rotavirus gastroenteritis (RVGE) is dehydration if not corrected appropriately with oral rehydration salts (ORS). Though the prevalence of RVGE is similar across countries and socio-economic groups, the higher mortality in Sub-Saharan Africa and South Asia is presumably due to poor awareness and poor health system responsiveness rather than poor hygiene. Enzyme immunoassays are the most commonly used tools for diagnosis of RVGE from stool samples. ORS and zinc remain the mainstay of treatment. Water, sanitation and hygiene measures did not appear to be very effective leaving vaccination among young children as the primary means of prevention. 4 WHO prequalified live attenuated, oral vaccines are available with different efficacy in high- versus low-mortality countries. There is a high degree of protection in countries with low RV mortality, and lower protection in countries with high RV morbidity and more fatalities. Rotavirus vaccines were associated with intussusception, though larger trials failed to establish increased risk in vaccinated groups compared to placebo recipients.

scholarly journals Surveillance of Human Rotavirus in Wuhan, China (2011–2019): Predominance of G9P[8] and Emergence of G12

Pathogens ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 810
Author(s):  
Xuan Zhou ◽  
Yuan-Hong Wang ◽  
Bei-Bei Pang ◽  
Nan Chen ◽  
Nobumichi Kobayashi
Keyword(s):  
Etiologic Agent ◽  
Genetic Characteristics ◽  
Predominant Genotype ◽  
Rotavirus A ◽  
Epidemic Season ◽  
Human Rotavirus ◽  
Stool Specimens ◽  
Virus Strains ◽  
Nsp3 Gene ◽  
Infants And Young Children

Rotaviruses are a major etiologic agent of gastroenteritis in infants and young children worldwide. To learn the shift of genotypes and genetic characteristics of Rotavirus A (RVA) causing diarrhea in children and adults, a hospital-based surveillance of rotavirus was conducted in Wuhan, China from June 2011 through May 2019, and representative virus strains were phylogenetically analyzed. Among a total of 6733 stool specimens collected from both children and adults with acute gastroenteritis, RVA was detected in 25.5% (1125/4409) and 12.3% (285/2324) of specimens, respectively. G9P[8] was the most common genotype (74.5%), followed by G1P[8] (8.7%), G2P[4] (8.4%), and G3P[8] (7.3%), with G9P[8] increasing rapidly during the study period. The predominant genotype shifted from G1P[8] to G9P[8] in 2012–2013 epidemic season. G12P[6] strain RVA/Human-wt/CHN/Z2761/2019/G12P[6] was detected in April 2019 and assigned to G12-P[6]-I1-R1-C1-M1-A1-N1-T2-E1-H1 genotypes. Phylogenetic analysis revealed that VP7, VP4, VP6, VP3, NSP1, NSP2, and NSP5 genes of Z2761 clustered closely with those of Korean G12P[6] strain CAU_214, showing high nucleotide identities (98.0–98.8%). The NSP3 gene of Z2761 was closely related to those of G2P[4] and G12P[6] rotaviruses in Asia. All the eleven gene segments of Z2761 kept distance from those of cocirculating G9P[8], G1P[8], and G3P[8] strains detected in Wuhan during this study period. This is the first identification of G12 rotavirus in China. It is deduced that Z2761 is a reassortant having DS-1-like NSP3 gene in the background of G12P[6] rotavirus genetically close to CAU_214.

scholarly journals Acquired Immunity to Malaria

2009 ◽  
Vol 22 (1) ◽  
pp. 13-36 ◽  
Author(s):  
Denise L. Doolan ◽  
Carlota Dobaño ◽  
J. Kevin Baird
Keyword(s):  
Plasmodium Falciparum ◽  
High Risk ◽  
Immune Status ◽  
Severe Disease ◽  
Sub Saharan Africa ◽  
Acquired Immunity ◽  
Sub Saharan ◽  
High Risk Infants ◽  
Induced Immunity ◽  
Infants And Young Children

SUMMARY Naturally acquired immunity to falciparum malaria protects millions of people routinely exposed to Plasmodium falciparum infection from severe disease and death. There is no clear concept about how this protection works. There is no general agreement about the rate of onset of acquired immunity or what constitutes the key determinants of protection; much less is there a consensus regarding the mechanism(s) of protection. This review summarizes what is understood about naturally acquired and experimentally induced immunity against malaria with the help of evolving insights provided by biotechnology and places these insights in the context of historical, clinical, and epidemiological observations. We advocate that naturally acquired immunity should be appreciated as being virtually 100% effective against severe disease and death among heavily exposed adults. Even the immunity that occurs in exposed infants may exceed 90% effectiveness. The induction of an adult-like immune status among high-risk infants in sub-Saharan Africa would greatly diminish disease and death caused by P. falciparum. The mechanism of naturally acquired immunity that occurs among adults living in areas of hyper- to holoendemicity should be understood with a view toward duplicating such protection in infants and young children in areas of endemicity.

scholarly journals Microbial exposure drives polyclonal expansion of innate γδ T cells immediately after birth

2020 ◽  
Vol 117 (31) ◽  
pp. 18649-18660 ◽  
Author(s):  
Sarina Ravens ◽  
Alina S. Fichtner ◽  
Maike Willers ◽  
Dennis Torkornoo ◽  
Sabine Pirr ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Γδ T Cells ◽  
Sub Saharan Africa ◽  
T Cell Subsets ◽  
Γδ T Cell ◽  
Microbial Exposure ◽  
Sub Saharan ◽  
Next Generation Sequencing Ngs ◽  
Infants And Young Children

Starting at birth, the immune system of newborns and children encounters and is influenced by environmental challenges. It is still not completely understood how γδ T cells emerge and adapt during early life. Studying the composition of T cell receptors (TCRs) using next-generation sequencing (NGS) in neonates, infants, and children can provide valuable insights into the adaptation of T cell subsets. To investigate how neonatal γδ T cell repertoires are shaped by microbial exposure after birth, we monitored the γ-chain (TRG) and δ-chain (TRD) repertoires of peripheral blood T cells in newborns, infants, and young children from Europe and sub-Saharan Africa. We identified a set ofTRGandTRDsequences that were shared by all children from Europe and Africa. These were primarily public clones, characterized by simple rearrangements of Vγ9 and Vδ2 chains with low junctional diversity and usage of non-TRDJ1gene segments, reminiscent of early ontogenetic subsets of γδ T cells. Further profiling revealed that these innate, public Vγ9Vδ2+T cells underwent an immediate TCR-driven polyclonal proliferation within the first 4 wk of life. In contrast, γδ T cells using Vδ1+and Vδ3+TRDrearrangements did not significantly expand after birth. However, different environmental cues may lead to the observed increase of Vδ1+and Vδ3+TRDsequences in the majority of African children. In summary, we show how dynamic γδ TCR repertoires develop directly after birth and present important differences among γδ T cell subsets.

scholarly journals Screening of Viral Pathogens from Pediatric Ileal Tissue Samples after Vaccination

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Laura Hewitson ◽  
James B. Thissen ◽  
Shea N. Gardner ◽  
Kevin S. McLoughlin ◽  
Margaret K. Glausser ◽  
...  
Keyword(s):  
Porcine Circovirus ◽  
Recent Infection ◽  
Viral Pathogens ◽  
Tissue Samples ◽  
Rotavirus A ◽  
Microbial Detection ◽  
Rotavirus Vaccines ◽  
Detection Technology ◽  
Human Rotavirus ◽  
Ileal Tissue

In 2010, researchers reported that the two US-licensed rotavirus vaccines contained DNA or DNA fragments from porcine circovirus (PCV). Although PCV, a common virus among pigs, is not thought to cause illness in humans, these findings raised several safety concerns. In this study, we sought to determine whether viruses, including PCV, could be detected in ileal tissue samples of children vaccinated with one of the two rotavirus vaccines. A broad spectrum, novel DNA detection technology, the Lawrence Livermore Microbial Detection Array (LLMDA), was utilized, and confirmation of viral pathogens using the polymerase chain reaction (PCR) was conducted. The LLMDA technology was recently used to identify PCV from one rotavirus vaccine. Ileal tissue samples were analyzed from 21 subjects, aged 15–62 months. PCV was not detected in any ileal tissue samples by the LLMDA or PCR. LLMDA identified a human rotavirus A from one of the vaccinated subjects, which is likely due to a recent infection from a wild type rotavirus. LLMDA also identified human parechovirus, a common gastroenteritis viral infection, from two subjects. Additionally, LLMDA detected common gastrointestinal bacterial organisms from theEnterobacteriaceae,Bacteroidaceae, andStreptococcaceaefamilies from several subjects. This study provides a survey of viral and bacterial pathogens from pediatric ileal samples, and may shed light on future studies to identify pathogen associations with pediatric vaccinations.

scholarly journals Disease Burden of Group B Streptococcus Among Infants in Sub-Saharan Africa

2016 ◽  
Vol 35 (9) ◽  
pp. 933-942 ◽  
Author(s):  
Anushua Sinha ◽  
Louise B. Russell ◽  
Sara Tomczyk ◽  
Jennifer R. Verani ◽  
Stephanie J. Schrag ◽  
...  
Keyword(s):  
Disease Burden ◽  
Group B Streptococcus ◽  
Sub Saharan Africa ◽  
Sub Saharan ◽  
Group B

scholarly journals Disease burden and the role of pharmacogenomics in African populations

2017 ◽  
Vol 2 ◽  
Author(s):  
K. L. Mpye ◽  
A. Matimba ◽  
K. Dzobo ◽  
S. Chirikure ◽  
A. Wonkam ◽  
...  
Keyword(s):  
Disease Burden ◽  
Individual Variability ◽  
Sub Saharan Africa ◽  
Drug Side Effects ◽  
Quality Healthcare ◽  
Therapeutic Drugs ◽  
African Populations ◽  
The Status ◽  
Sub Saharan

Background.The burden of communicable and non-communicable diseases in Sub-Saharan Africa poses a challenge in achieving quality healthcare. Although therapeutic drugs have generally improved health, their efficacy differs from individual to individual. Variability in treatment response is mainly because of genetic variants that affect the pharmacokinetics and pharmacodynamics of drugs.Method.The intersection of disease burden and therapeutic intervention is reviewed, and the status of pharmacogenomics knowledge in African populations is explored.Results.The most commonly studied variants with pharmacogenomics relevance are discussed, especially in genes coding for enzymes that affect the response to drugs used for HIV, malaria, sickle cell disease and cardiovascular diseases.Conclusions.The genetically diverse African population is likely to benefit from a pharmacogenomics-based healthcare approach, especially with respect to reduction of drug side effects, and separation of responders and non-responders leading to optimized drug choices and doses for each patient.

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