Turning science into health solutions: KEMRI’s challenges as Kenya’s health product pathfinder

BACKGROUND: A traditional pathway for developing new health products begins with public research institutes generating new knowledge, and ends with the private sector translating this knowledge into new ventures. But while public research institutes are key drivers of basic research in sub-Saharan Africa, the private sector is inadequately prepared to commercialize ideas that emerge from these institutes, resulting in these institutes taking on the role of product development themselves to alleviate the local disease burden. In this article, the case study method is used to analyze the experience of one such public research institute: the Kenya Medical Research Institute (KEMRI). DISCUSSION: Our analysis indicates that KEMRI's product development efforts began modestly, and a manufacturing facility was constructed with a strategy for the facility's product output which was not very successful. The intended products, HIV and Hepatitis B diagnostic kits, had a short product life cycle, and an abrupt change in regulatory requirements left KEMRI with an inactive facility. These problems were the result of poor innovation management capacity, variability in domestic markets, lack of capital to scale up technologies, and an institutional culture that lacked innovation as a priority.However, KEMRI appears to have adapted by diversifying its product line to mitigate risk and ensure continued use of its manufacturing facility. It adopted an open innovation business model which linked it with investors, research partnerships, licensing opportunities, and revenue from contract manufacturing. Other activities that KEMRI has put in place over several years to enhance product development include the establishment of a marketing division, development of an institutional IP policy, and training of its scientists on innovation management. SUMMARY: KEMRI faced many challenges in its attempt at health product development, including shifting markets, lack of infrastructure, inadequate financing, and weak human capital with respect to innovation. However, it overcame them through diversification, partnerships and changes in culture. The findings could have implications for other research institutes in Sub-Saharan Africa seeking to develop health products. Such institutes must analyze potential demand and uptake, yet be prepared to face the unexpected and develop appropriate risk-mitigating strategies

Composition of the Essential Oil of Clausena Suffruticosa Leaf and Evaluation of its Antimicrobial and Cytotoxic Activities

Purpose: To investigate the essential oil content of Clausena suffruticosa leaf for its in-vitro antibacterial, antifungal and cytotoxic activities.Methods: The essential oil of Clausena suffruticosa leaf was extracted by hydrodistillation using a modified Clevenger-type apparatus and was analyzed by GC-MS using electron impact ionization method. Antibacterial, antifungal and cytotoxic screenings were made by disc diffusion technique,poisoned food technique and brine shrimp lethality bioassay, respectively. Minimum inhibitory concentration (MIC) of the oil was determined by measuring the zone of inhibition, with tetracycline as reference standard. Fluconazole served as standard in the antifungal assessment.Results: A total of twenty two compounds, of which Estragole, Anethole and â-Ocimene were the major ones, were found in the essential oil of C. suffruticosa. The oil showed higher antibacterial activity against Shigella flexneri than the reference, tetracycline (p < 0.05). Significant activity (p < 0.001) against other Gram-positive microbes - Staphylococcus aureus, Bacillus subtilis, Bacillus cereus, Bacillus polymyxa and Bacillus megaterium – was also observed. However, Gram-negative bacteria -Salmonella typhi, Shigella flexneri, Proteus mirabilis and Escherichia coli. Klebsiella pneumoniae and Shigella sonnei - showed no sensitivity to the oil. In the antifungal assay, the oil exhibited greater activity (p < 0.001) against Aspergillus ochraceus than the reference, fluconazole, Inhibition of other fungal strains tested was also statistically significant (p < 0.001). The lethal concentration (LC50) of the oil against brine shrimp was 41.2 ìg/ml in the cytotoxic assay.Conclusion: It is evident that the essential oil of C. suffruticosa is a potent antimicrobial and cytotoxic agent that should be further evaluated.Keywords: Clausena suffruticosa, Essential oil, Cytotoxicity, Antimicrobial, Brine shrim

Drug resistance in Plasmodium falciparum from the Chittagong Hill Tracts, Bangladesh.

OBJECTIVE: To assess the efficacy of antimalarial treatment and molecular markers of Plasmodium falciparum resistance in the Chittagong Hill Tracts of Bangladesh. METHODS: A total of 203 patients infected with P. falciparum were treated with quinine 3 days plus sulphadoxine/pyrimethamine (SP) combination therapy, and followed up during a 4-week period. Blood samples collected before treatment were genotyped for parasite mutations related to chloroquine (pfcrt and pfmdr1 genes) or SP resistance (dhfr and dhps). RESULTS: Of 186 patients who completed follow-up, 32 patients (17.2%) failed to clear parasitaemia or became positive again within 28 days after treatment. Recurring parasitaemia was related to age (chi(2) = 4.8, P < 0.05) and parasite rates on admission (t = 3.1, P < 0.01). PCR analysis showed that some of these cases were novel infections. The adjusted recrudescence rate was 12.9% (95% CI 8.1-17.7) overall, and 16.6% (95% CI 3.5-29.7), 15.5% (95% CI 8.3-22.7) and 6.9% (95% CI 0.4-13.4) in three age groups (<5 years, 5-14, > or =15). The majority of infections carried mutations associated with chloroquine resistance: 94% at pfcrt and 70% at pfmdr. Sp-resistant genotypes were also frequent: 99% and 73% of parasites carried two or more mutations at dhfr and dhps, respectively. The frequency of alleles at dhfr, dhps and pfmdr was similar in cases that were successfully treated and those that recrudesced. CONCLUSIONS: The clinical trial showed that quinine 3-days combined to SP is still relatively effective in the Chittagong Hill Tracts. However, if this regimen is continued to be widely used, further development of SP resistance and reduced quinine sensitivity are to be expected. The genotyping results suggest that neither chloroquine nor SP can be considered a reliable treatment for P. falciparum malaria any longer in this area of Bangladesh

Indian vaccine innovation: the case of Shantha Biotechnics

BACKGROUND: Although the World Health Organization had recommended that every child be vaccinated for Hepatitis B by the early 1980s, large multinational pharmaceutical companies held monopolies on the recombinant Hepatitis B vaccine. At a price as high as USD$23 a dose, most Indians families could not afford vaccination. Shantha Biotechnics, a pioneering Indian biotechnology company founded in 1993, saw an unmet need domestically, and developed novel processes for manufacturing Hepatitis B vaccine to reduce prices to less than$1/dose. Further expansion enabled low-cost mass vaccination globally through organizations such as UNICEF. In 2009, Shantha sold over 120 million doses of vaccines. The company was recently acquired by Sanofi-Aventis at a valuation of USD$784 million. METHODS: The case study and grounded research method was used to illustrate how the globalization of healthcare R&D is enabling private sector companies such as Shantha to address access to essential medicines. Sources including interviews, literature analysis, and on-site observations were combined to conduct a robust examination of Shantha's evolution as a major provider of vaccines for global health indications. RESULTS: Shantha's ability to become a significant global vaccine manufacturer and achieve international valuation and market success appears to have been made possible by focusing first on the local health needs of India. How Shantha achieved this balance can be understood in terms of a framework of four guiding principles. First, Shantha identified a therapeutic area (Hepatitis B) in which cost efficiencies could be achieved for reaching the poor. Second, Shantha persistently sought investments and partnerships from non-traditional and international sources including the Foreign Ministry of Oman and Pfizer. Third, Shantha focused on innovation and quality - investing in innovation from the outset yielded the crucial process innovation that allowed Shantha to make an affordable vaccine. Fourth, Shantha constructed its own cGMP facility, which established credibility for vaccine prequalification by the World Health Organization and generated interest from large pharmaceutical companies in its contract research services. These two sources of revenue allowed Shantha to continue to invest in health innovation relevant to the developing world. CONCLUSIONS: The Shantha case study underscores the important role the private sector can play in global health and access to medicines. Home-grown companies in the developing world are becoming a source of low-cost, locally relevant healthcare R&D for therapeutics such as vaccines. Such companies may be compelled by market forces to focus on products relevant to diseases endemic in their country. Sanofi-Aventis' acquisition of Shantha reveals that even large pharmaceutical companies based in the developed world have recognized the importance of meeting the health needs of the developing world. Collectively, these processes suggest an ability to tap into private sector investments for global health innovation, and illustrate the globalization of healthcare R&D to the developing world

Molecular Docking against SARS-CoV-2 Variants, Antiviral, Dynamics and Quantum Chemical Modeling of Mannopyranoside Derivatives

Researchers worldwide are prompting their hard and soul effort to develop the best possible therapeutic options to eliminate vaccination-related difficulties to effectively manage SARS-CoV-2, which is now sweeping the world. The present study was undertaken to investigate the computational properties of methyl α-D-mannopyranoside and its designed derivatives to assess their thermophysical and biochemical parameters. The PASS prediction score was reported to be 0.233&lt;Pa&lt;0.403 for antiviral, 0.473&lt;Pa&lt;0.569 for antibacterial, 0.628&lt;Pa&lt;0.680 for antifungal, and 0.242&lt;Pa&lt;0.349 for antibiotic. For this purpose, previously synthesized potential derivatives of methyl α-D-mannopyranoside were assessed with six different variants of the COVID-19 protein and docking studies by AutoDock. The highest binding affinity from the molecular docking score was obtained at -8.5 against the alpha variant (PDB ID 7EKF) in L06 against each of the SARS-CoV-2 targeted proteins. In addition, good energy values were found against the SARS-CoV-2 spike glycoprotein (PDB ID 6vxx), Omicron variant (PDB ID 7T9J) and Delta variant (PDB ID 7V8B). Although all the synthesized compounds have opposed to standard affinities, the docking scores of newly derivative compounds were found to be the highest in contrast to the alpha variant (PDB ID 7EKF) (-8.5 kcal/mol), where the standard Molnupiravir has been shown to be -6.9 kcal/mol against the alpha variant. In addition, all possible candidates for the new drug show an excellent pharmacokinetic profile, are noncarcinogenic, are highly water soluble, fulfill PASS prediction, and have drug-likeness that meets all the pharmacokinetic parameters. Therefore, this methyl-α-D-mannopyranoside and its derivatives might be useful to inhibit the mentioned COVID-19 variants as a potential drug(s) candidate

inter and intra‑regional differences and in(equalities) between gender and age

Publisher Copyright: © 2022. The Author(s).BACKGROUND: Tuberculosis (TB) diagnosis and treatment delays increase the period of infectiousness, making TB control difficult and increasing the fatality rates. This study aimed to determine the evolution of health care service delay (time between the patient's first contact with the health service and the diagnosis/start of treatment) and patient delay (time between onset symptoms date and the date of first contact with health services) for Pulmonary Tuberculosis (PTB) in Portugal between 2008 and 2017 across different regions, age groups and gender. METHODS: An exploratory analysis was performed, trends of both delays were studied, and 36 months forecasts were generated. We used the permutation test to test differences between groups and the Seasonal and Trend decomposition using Loess (STL) method and Autoregressive Integrated Moving Average (ARIMA) models for forecasting for both Health and Patient delays. We used data from notified PTB cases in mainland Portugal between 2008 and 2017, provided by the national surveillance system. RESULTS: Health delays remained relatively constant while patient delays increased. Females had significantly higher health delays in some regions. Individuals older than 64 had higher health delays than younger individuals, while patient delay for working-age individuals between 15 and 64 years old, presents higher patient delay. CONCLUSIONS: Forecasts presage that the upward trend of the delays is unlikely to fall in the coming years. It is important to understand the evolution of the delays and predict how these will evolve. Our understanding of the delays behaviours will contribute to better health policies and resources allocation.publishersversionpublishe

A temporal analysis on patient and health service delays in pulmonary tuberculosis in Portugal: Inter and intra‑regional differences and in(equalities) between gender and age

Background: Tuberculosis (TB) diagnosis and treatment delays increase the period of infectiousness, making TB control difficult and increasing the fatality rates. This study aimed to determine the evolution of health care service delay (time between the patient’s first contact with the health service and the diagnosis/start of treatment) and patient delay (time between onset symptoms date and the date of first contact with health services) for Pulmonary Tuberculosis (PTB) in Portugal between 2008 and 2017 across different regions, age groups and gender. Methods: An exploratory analysis was performed, trends of both delays were studied, and 36 months forecasts were generated. We used the permutation test to test differences between groups and the Seasonal and Trend decomposition using Loess (STL) method and Autoregressive Integrated Moving Average (ARIMA) models for forecasting for both Health and Patient delays. We used data from notified PTB cases in mainland Portugal between 2008 and 2017, provided by the national surveillance system. Results: Health delays remained relatively constant while patient delays increased. Females had significantly higher health delays in some regions. Individuals older than 64 had higher health delays than younger individuals, while patient delay for working-age individuals between 15 and 64 years old, presents higher patient delay. Conclusions: Forecasts presage that the upward trend of the delays is unlikely to fall in the coming years. It is important to understand the evolution of the delays and predict how these will evolve. Our understanding of the delays behaviours will contribute to better health policies and resources allocation.info:eu-repo/semantics/publishedVersio

Surveillance of the Disease Incidence and Severity of Papaya Ringspot Virus at Four Selected Districts of Bangladesh

An experiment was conducted to survey the prevalence of disease incidence and severity of Papaya ringspot virus (PRSV) at eight locations of four districts in Bangladesh. Papaya is one of the most popular fruits in the world. It suffers from several diseases including fungi, bacteria, nematodes and viruses. Among them, viral diseases are found to cause considerable yield loss, with the most important one being PRSV. The survey was conducted at three plain districts and one hill tract area from July 2016 to December 2016. During the survey period, six different symptoms were found in the selected fields and were identified as PRSV based on symptomology. These symptoms were mild mosaic (MM), mosaic (MO), severe mosaic (SM), fern leaf (FL), leaf distortion (LD) and vein clearing (VC). The highest disease incidence (36.24%) was found in BSMRAU farm in Gazipur whereas the lowest (12.04%) was found in Panchari, Khagrachari hill tract. The maximum severity (11.53%) was found in BSMRAU campus, Gazipur on the country and the lowest severity (2.50%) was found in Panchari, Khagrachari hill tract. The yield and yield contributing parameters of papaya found to be differ significantly among the surveyed area. The lowest fruit weight (324.3 gm) due to PRSV infection was recorded in BSMRAU, Gazipur while the highest fruit weight (643.6 gm) was conducted in SAU Campus, Dhaka

Sonochemical Synthesis of Cobalt Ferrite Nanoparticles

Cobalt ferrite being a hard magnetic material with high coercivity and moderate magnetization has found wide-spread applications. In this paper, we have reported the sonochemical synthesis of cobalt ferrite nanoparticles using metal acetate precursors. The ferrite synthesis occurs in three steps (hydrolysis of acetates, oxidation of hydroxides, and in situ microcalcination of metal oxides) that are facilitated by physical and chemical effects of cavitation bubbles. The physical and magnetic properties of the ferrite nano-particles thus synthesized have been found to be comparable with those reported in the literature using other synthesis techniques