scholarly journals Characterisation of factors contributing to the performance of nonwoven fibrous matrices as substrates for adenovirus vectored vaccine stabilisation

2020 ◽  
Author(s):  
Pawan Dulal ◽  
Adam A Walters ◽  
Nicholas Hawkins ◽  
Tim DW Claridge ◽  
Katarzyna Kowal ◽  
...  

AbstractThe global network of fridges and freezers known as the “cold chain” can account for a significant proportion of the total cost of vaccination and is susceptible to failure. Cost-efficient techniques to enhance stability of vaccines could prevent such losses and improve vaccination coverage, particularly in low income countries. We have previously reported a novel, potentially less expensive thermostabilisation approach using a combination of simple sugars and glass micro-fibrous matrix, achieving an excellent recovery of vaccines after storage at supraphysiological temperatures. This matrix is, however, prone to fragmentation and currently not suitable for clinical translation.Here, we report an investigation of alternative, potentially GMP compatible, fibrous matrices. A number of commercially-available matrices permitted good protein recovery, quality of sugar glass and moisture content of the dried product but did not achieve the thermostabilisation performance of the original glass fibre matrix. We therefore further investigated physical and chemical characteristics of the glass fibre matrix and its components. Our investigation shows that the polyvinyl alcohol present in the glass fibre matrix assists vaccine stability. This finding enabled us to develop a custom-produced matrix with encouraging performance, as an initial step towards a biocompatible matrix for clinical translation. We discuss the path to transfer of the technology into clinical use, including potential obstacles.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pawan Dulal ◽  
Robabeh Gharaei ◽  
Adam J. Berg ◽  
Adam A. Walters ◽  
Nicholas Hawkins ◽  
...  

AbstractAdenovirus vectors offer a platform technology for vaccine development. The value of the platform has been proven during the COVID-19 pandemic. Although good stability at 2–8 °C is an advantage of the platform, non-cold-chain distribution would have substantial advantages, in particular in low-income countries. We have previously reported a novel, potentially less expensive thermostabilisation approach using a combination of simple sugars and glass micro-fibrous matrix, achieving excellent recovery of adenovirus-vectored vaccines after storage at temperatures as high as 45 °C. This matrix is, however, prone to fragmentation and so not suitable for clinical translation. Here, we report an investigation of alternative fibrous matrices which might be suitable for clinical use. A number of commercially-available matrices permitted good protein recovery, quality of sugar glass and moisture content of the dried product but did not achieve the thermostabilisation performance of the original glass fibre matrix. We therefore further investigated physical and chemical characteristics of the glass fibre matrix and its components, finding that the polyvinyl alcohol present in the glass fibre matrix assists vaccine stability. This finding enabled us to identify a potentially biocompatible matrix with encouraging performance. We discuss remaining challenges for transfer of the technology into clinical use, including reliability of process performance.


Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 520
Author(s):  
Roberto Cárcamo-Calvo ◽  
Carlos Muñoz ◽  
Javier Buesa ◽  
Jesús Rodríguez-Díaz ◽  
Roberto Gozalbo-Rovira

Rotavirus is the leading cause of severe acute childhood gastroenteritis, responsible for more than 128,500 deaths per year, mainly in low-income countries. Although the mortality rate has dropped significantly since the introduction of the first vaccines around 2006, an estimated 83,158 deaths are still preventable. The two main vaccines currently deployed, Rotarix and RotaTeq, both live oral vaccines, have been shown to be less effective in developing countries. In addition, they have been associated with a slight risk of intussusception, and the need for cold chain maintenance limits the accessibility of these vaccines to certain areas, leaving 65% of children worldwide unvaccinated and therefore unprotected. Against this backdrop, here we review the main vaccines under development and the state of the art on potential alternatives.


PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255807
Author(s):  
Haydee Miranda-Ortiz ◽  
Edith A. Fernández-Figueroa ◽  
Erika B. Ruíz-García ◽  
Anallely Muñoz-Rivas ◽  
Alejandra Méndez-Pérez ◽  
...  

The use of saliva for the diagnosis of SARS-CoV-2 has shown to be a good alternative to nasopharyngeal swabs (NPS), since it permits self-collection, avoids the exposure of healthy persons to infected patients, reduces waiting times, eliminates the need of personal protective equipment and is non-invasive. Yet current saliva testing is still expensive due to the need of specialized tubes containing buffers to stabilize the RNA of SARS-CoV-2 and inactivate the virus. These tubes are expensive and not always accessible in sufficient quantities. We now developed an alternative saliva testing method, using TRIzol for extraction, viral inactivation, and storage of SARS-CoV-2 RNA, combined with RT-qPCR, which was comparable in its performance to NPS. Paired saliva samples and NPS were taken from 15 asymptomatic healthcare workers and one patient with SARS-CoV-2. Further 13 patients with SARS-CoV-2 were only saliva-tested. All the tests were performed according to CDC 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel. Saliva (4 mL) was taken in sterile 50 mL tubes, 1.5 mL TRIzol were added and mixed. Our results show that 5 μL of saliva RNA extracted with TRIzol allow for an adequate detection of the virus in patients positive for SARS-CoV-2 and was equally sensitive to NPS in TRIzol. We conclude that saliva testing using TRIzol is a recommendable method for diagnosis of SARS-CoV-2 since it has several advantages over currently used saliva tests: it can be done with normal sterile tubes, does not need cold-chain handling, is stable at room temperature, is non-invasive and less costly, making it more accessible for low-income countries. Cheaper saliva testing using TRIzol is especially relevant for low-income countries to optimize diagnosis and help define quarantine durations for families, healthcare workers, schools, and other public workplaces, thus decreasing infections and mortality caused by SARS-CoV-2.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Sofia Ottaru ◽  
Mariam M. Mirambo ◽  
Rogatus Kabyemera ◽  
Benson R. Kidenya ◽  
Mwanaisha Seugendo ◽  
...  

Background. Toxoplasma gondii infection during pregnancy is associated with serious neonatal complications, including hydrocephalus. In many high-income countries, T. gondii screening and treatment during the antenatal period are routinely carried out to prevent associated complications, whereas in most low-income countries, there is no routine screening of T. gondii during pregnancy. Despite the parasite being common in Tanzania, there is a paucity of information on the prevalence of T. gondii and cranial ultrasound patterns among children with hydrocephalus. Methods. An analytical cross-sectional hospital-based study involving 125 infants with hydrocephalus attending the Bugando Medical Centre (BMC) was conducted between May 2017 and February 2018. Sociodemographic and other relevant information was collected using a pretested data collection tool. Venous blood samples were collected, and sera were used for the detection of specific T. gondii antibodies by indirect enzyme-linked immunosorbent assay (ELISA) as per manufacturer’s instructions. Data were analysed using STATA version 13 software. Results. The mean age of enrolled children was 4.8±3.5 months. Out of 125 infants with hydrocephalus, 29 (23.2%, 95% CI: 21-36) were seropositive for T. gondii-specific IgG antibodies. By multiple generalized linear model analysis, being male (aRR=1.1, 95% CI: 0.9–1.5, p=0.049), higher birth order (aRR=1.2, 95% CI: 1.0–1.5, p=0.023), consumption of fish meat (aRR=1.6, 95% CI: 1.2–2.3, p=0.003), and using other methods of cooking meat than boiling (aRR=1.7, 95% CI: 1.1–2.5, p=0.015) were independent risk factors for T. gondii IgG seropositivity. Obstructive hydrocephalus was significantly more common among T. gondii-seronegative infants compared to IgG-seropositive infants (31.3% [30/96] vs. 13.8% [4/29]; p=0.049). Conclusions. A significant proportion of infants with nonobstructive hydrocephalus are T. gondii IgG seropositive, and this is predicted by male gender, increase of birth order, consuming fish, and using other methods of cooking meat than boiling. These facts highlight the importance of continuing health education for pregnant women regarding T. gondii transmission and the need to follow-up their infants so that appropriate counselling and management can be provided.


2019 ◽  
Vol 2019 ◽  
pp. 1-5 ◽  
Author(s):  
Elieza Chibwe ◽  
Vitus Silago ◽  
Edwin Kajoro ◽  
Muhsin Juma ◽  
Emmanuel Mkumbo ◽  
...  

Background. Hepatitis B and hepatitis C viruses (HBV and HCV) are life-threatening infections of public health importance due to their association with cirrhosis and hepatocellular carcinoma. Despite HBV being moderately endemic in many low-income countries, there is no routine HBV vaccination among child bearing aged women making them at risk of transmitting infections to the foetus during pregnancy. This study investigated the seroprevalence of antihepatitis B surface antibodies (anti-HBs) and HCV antibodies among pregnant women in Mwanza city to provide data that can be used in devising preventive strategies. Methods. A cross-sectional hospital-based study involving 339 pregnant women was conducted between June and July 2017. Data were collected using structured data collection tool. Detection of anti-HBs was performed using enzyme immunoassay while qualitative rapid immunochromatographic tests were employed to detect HCV antibodies. Data was analyzed by using STATA version 13. Results. The mean age of the study participants was 25.6±5.8 years. The prevalence of anti-HBs was 85/339 (25.1%, 95% CI: 20.4-29.6) while that of HCV antibodies was 1/333 (0.3%, 95% CI: 0.1-0.4). By univariate logistic regression analysis, increase in age (OR: 1.04, 95% CI: 1.00-1.09, P=0.03), unknown HIV status (OR: 0.3, 95% CI: 0.11-0.79, P=0.035), and multigravidity (OR: 2.12, 95% CI: 1.18-3.8, P=0.038) were significantly associated with anti-HBs seropositivity. Conclusion. A significant proportion of pregnant women have anti-HBs while the seroprevalence of HCV is low among pregnant women in the city of Mwanza. Routine screening of HBV among pregnant women coupled with appropriate management should be emphasized in developing countries. Further studies to determine seroprevalence of HCV are recommended across the country.


2021 ◽  
Author(s):  
Caitlin L. Maikawa ◽  
Joseph L. Mann ◽  
Aadithya Kannan ◽  
Catherine M. Meis ◽  
Ben S. Ou ◽  
...  

ABSTRACTThere are 150 million people with diabetes worldwide who require insulin replacement therapy and the prevalence of diabetes is rising fastest in middle and low-income countries. Current formulations require costly refrigerated transport and storage to prevent loss of insulin integrity. This study shows the development of simple “drop-in” amphiphilic copolymer excipients to maintain formulation integrity, bioactivity, pharmacokinetics and pharmacodynamics for over 6 months when subjected to severe stressed aging conditions that cause current commercial formulation to fail in under 2 weeks. Further, when these copolymers are added to Humulin R (Eli Lilly) in original commercial packaging they prevent insulin aggregation for up to 4 days at 50 °C compared to less than 1 day for Humulin R alone. These copolymers demonstrate promise as simple formulation additives to increase the cold chain resilience of commercial insulin formulations, thereby expanding global access to these critical drugs for treatment of diabetes.


AppliedChem ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 4-13
Author(s):  
Aswin Doekhie ◽  
Rajeev Dattani ◽  
Yun-Chu Chen ◽  
Francoise Koumanov ◽  
Karen J. Edler ◽  
...  

Successful eradication or control of prevailing infectious diseases is linked to vaccine efficacy, stability, and distribution. The majority of protein-based vaccines are transported at fridge (2–8 °C) temperatures, cold chain, to retain potency. However, this has been shown to be problematic. Proteins are inherently susceptible to thermal fluctuations, occurring during transportation, causing them to denature. This leads to ineffective vaccines and an increase in vaccine-preventable diseases, especially in low-income countries. Our research utilises silica to preserve vaccines at room temperature, removing the need for cold chain logistics. The methodology is based upon sol–gel chemistry in which soluble silica is employed to encapsulate and ensilicate vaccine proteins. This yields a protein-loaded silica nanoparticle powder which is stored at room temperature and subsequently released using a fast chemical process. We have previously shown that tetanus toxin C fragment (TTCF) ensilication is a diffusion-limited cluster aggregation (DLCA)-based process using time-resolved small-angle x-ray scattering (SAXS). Here, we present our expanded investigation on the modularity of this system to further the understanding of ensilication via time-resolved SAXS. Our results show that variations in the ensilication process could prove useful in the transition from batch to in-flow manufacturing of ensilicated nanoparticles.


Author(s):  
Davor Petrović ◽  
Vida Čulić ◽  
Zofia Swinderek-Alsayed

AbstractJoubert syndrome (JS) is a rare congenital, autosomal recessive disorder characterized by a distinctive brain malformation, developmental delay, ocular motor apraxia, breathing abnormalities, and high clinical and genetic heterogeneity. We are reporting three siblings with JS from consanguineous parents in Syria. Two of them had the same homozygous c.2172delA (p.Trp725Glyfs*) AHI1 mutation and the third was diagnosed prenatally with magnetic resonance imaging. This pathogenic variant is very rare and described in only a few cases in the literature. Multinational collaboration could be of benefit for the patients from undeveloped, low-income countries that have a low-quality health care system, especially for the diagnosis of rare diseases.


2013 ◽  
pp. 121-136
Author(s):  
Duong Pham Bao

The objective of this article is to review the development of the rural financial system in Vietnam in recent years, especially, after Doi moi. There are two opposite schools of thought in the literature on rural credit policies in developing countries. One is the conventional supply-side (government-led) approach while the other is called “a new paradigm” that emphasizes the importance of the viability of financial providers and the well functioning of rural credit markets. Conventional theories of rural finance contend that rural finance in low-income countries is generally accompanied by many failures. Contrary to these theories, rural finance in Vietnam does not encounter the above-mentioned failures so far. Up to the present time, it is progressing well. Using a supply-side approach, methodologically, this study reviews the development of the rural financial system in Vietnam. The significance of this study is to challenge the extreme view of dichotomizing between the old and the new credit paradigms. Analysis in this study contends that a rural financial market that, (1) is initiated and spurred by government; (2) operates principally under market mechanisms; and (3) is strongly supported by rural organizations (semi-formal/informal institutions) can progress stably and well. Therefore, the extremely dichotomizing approach must be avoided.


EMJ Radiology ◽  
2020 ◽  

Retained foreign bodies have become very rare in countries where the safety rules in the operating theatre are very rigorous and follow precise guidelines. There are low-income countries where hospital structures are precarious, in which the implementation of surgical safety rules has only been effective recently. Surgical teams in these countries are not yet well trained in the observance of the guidelines concerning swab count, meaning that textilomas are not uncommon. Abdominal textiloma may be asymptomatic, or present serious gastrointestinal complications such as bowel obstruction, perforation, or fistula formation because of misdiagnosis. It may mimic abscess formation in the early stage or soft tissue masses in the chronic stage. This case report presents a 27-year-old female who underwent an emergency laparotomy in a rural surgical centre for an ectopic pregnancy. Two months later, a swelling had appeared on the left side of her abdomen, gradually increasing in size, which was not very painful but caused digestive discomfort and asthenia. Intermittent fever was described and treated with antibiotics. The patient was referred to a better equipped centre to benefit from a CT scan. A textiloma was strongly suspected on the CT but a left colic mass was not excluded. Laparotomy confirmed the diagnosis of textiloma and the postoperative course was uneventful. Prevention rules must be strengthened in these countries where patients can hardly bear the costs of iterative surgeries for complications that are avoidable.


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