Assessment of the direct hospital cost of medical care for patients hospitalized for a stroke in Gabon.

While the incidence of stroke is increasing in developing countries, resulting in an extremely high economic burden, very few costing studies have been carried out to date. This study aims to measure the direct hospital costs of stroke management in Gabon. The study adopts a retrospective approach, based on a review of patient records in the Neurology and Cardiology Departments of the University Hospital of Libreville (CHUL) between January 2018 and December 2019. It focuses on all patients received for stroke at the CHUL during the study period, regardless of the outcome, analyzing direct hospital costs. Three hundred and thirteen (313) patients were admitted during the period in question, 72.52% in neurology and 27.48% in cardiology. The average age was 58.44 (±13.73 years). Fifty-six percent (56.23%) had health coverage. Ischemic stroke was more common than hemorrhagic stroke, at 79.55% and 20.45%, respectively. The average expenditure per patient was estimated at 619,633 CFA francs (€944.62). From the point of view of social security coverage, the average out-of-pocket expense per patient was 147,140 CFA francs (€224.31), for a reimbursement of 422,883 CFA francs (€644.68). The average direct cost of stroke is very high for both patients and administrations. This argues for the implementation of prevention programs for the disease. The results of this study may be useful for work on the efficiency of such programs.

Detecting antibiotic resistance genes in anthropogenically impacted streams and rivers.

Streams and rivers are widely impacted by human activities ranging from hydrological modifications to point and nonpoint pollution. Among the pollutants that enter lotic ecosystems are pharmaceuticals and personal care products, including antibiotics, that may play a role in the occurrence of antibiotic resistance genes (ARGs). Oftentimes, ARGs are detected based on culturing of bacteria or by using quantitative polymerase chain reaction; the limitations of these methods create barriers to our understanding. Use of more exhaustive methods, such as metagenomics, may overcome some of these barriers. The public health and ecological impacts of ARGs may be profound but are largely understudied. Antibiotic resistance is a growing concern for public health.

Evaluation of the intention to use the electronic medical record (EMR) by health professionals in healthcare facilities of Libreville and Owendo in Gabon.

Introduction: Health systems in several countries have integrated information and communication technologies into their operations. Electronic medical records (EMRs) are at the core of patient care. The working of these EMRs requires their acceptance and use by medical and paramedical personnel. The objective of this study was to empirically evaluate the intention of health professionals to use these EMRs. Materials and Methods: A questionnaire on the intention of health professionals to use the EMR was developed following a Likert scale. The survey was done via in-person interviews of health professionals in major health facilities in the cities of Libreville and Owendo in Gabon. The technology acceptance model (TAM) was tested using a step-down logistic regression analysis to identify the main factors explaining the intention of health professionals to use the EMR. Results: A total of 218 health professionals responded to the questionnaire. Thirty-eight percent (38%) of respondents were male. The average age was 41.33 years (±8.98 years) and the average length of service at work in the system was 12.02 years (±8.47 years). The integrated model showed that the intention to use the EMR was significantly associated with the perceived usefulness, the subjective standard, and experience. No socio-demographic variables explained the intention to use the EMR. Conclusion: The perceived ease, familiarity with the computer, and motivation are not associated with the intention to use the EMR. Actions should be taken to raise awareness and train health professionals to motivate them to accept and use EMRs in their medical practices.

From Real-world Individuals' Data to National Health Indicators: Multiphase Pilot Study in Gabon.

BACKGROUND: Achieving health goals requires informed decision-making supported by transparent, reliable, and relevant health information. This helps decision makers, such as health managers, to better understand the functioning of their health system and improve their ability to respond quickly to health demands. To achieve this, the health system needs to be supported by a digitized decision-making information system. In Sub-Saharan African countries, inadequate digital infrastructure, including limited internet connectivity and insufficient access to appropriate computer software, makes it difficult to collect, process, and analyze data for health statistics. The processing of data is done manually in this case; however, this situation affects the quality of the health statistics produced and compromises the quality of health intervention choices in these countries. OBJECTIVE: This study aimed to describe the conceptual approach of a data production and dissemination platform model proposed and implemented in Gabon. More precisely, it aimed to present the approach applied for the multidimensional analysis of the data production and dissemination process in the existing information system and present the results of an evaluation of the proposed model implemented in a real context. METHODS: The research was carried out in 3 phases. First, a platform was designed and developed based on the examination of the various data production and indicator generation procedures. Then, the platform was implemented in chosen health facilities in Gabon. Finally, a platform evaluation was carried out with actual end users. RESULTS: A total of 14 users with 12 years of average experience in health data management were interviewed. The results show that the use of the proposed model significantly improved the completeness, timeliness, and accuracy of data compared with the traditional system (93% vs 12%, P<.001; 96% vs 18%, P<.001; and 100% vs 18%, P<.001; respectively). CONCLUSIONS: The proposed model contributes significantly to the improvement of health data quality in Gabon.

Evaluation of direct costs associated with the management of clinical stage of malaria in children under five years old in Gabon.

BACKGROUND: Malaria is one of the leading causes of morbidity and mortality in African countries. It is one of the leading causes of hospital visits and hospitalization in pediatric wards for children under 5 years old. Interestingly however, the economic burden of this disease remains unknown in these endemic countries including Gabon. The purpose of this study is to assess the direct hospital cost for the management of malaria in children under 5 years old at the Libreville University Hospital Centre (CHUL, Centre Hospitalier Universitaire de Libreville) in Gabon. METHODS: This research work is a retrospective study using a comprehensive review of medical records of patients seen at the CHUL over a two-year period extending from January 2018 through December 2019. The study focused on children under 5 years old, admitted for malaria in the paediatric ward of the CHUL. The analysis targeted specifically direct hospital costs, which excluded salary and wages of health care workers. The monetary currency used in this study was the CFA francs, as that currency is the one used in Central Africa (as reference, 1 Euro = 656 CFA francs). RESULTS: For the set timeframe, 778 patient records matched the study criteria. Thus, out of 778 admitted patients, 58.4% were male while 41.5% were female. Overall, the average age was 13.2 months (± 13.8 months). The total cost incurred by the hospital for the management of these 778 malaria patients was 94,922,925 CFA francs (144,699.58 €), for an average expense per patient topping at 122,008 CFA francs (185.99 €). The highest expenditure items were hospitalizations (44,200,000 CFA francs, 67,378.1 €), followed by drugs (26,394,425 CFA francs, 40,235.4 €) and biomedical examinations (14,036,000 CFA francs, 21,396.34 €). CONCLUSION: The financial burden for managing malaria in the paediatric ward seems to be very high, not only for the hospital, but also for families in spite of the government medical insurance coverage in some cases. These findings bring new insights as to the urgency to develop policies that foster preventive initiatives over curative approaches in the management of malaria in children in endemic countries.

Advances in epidermal growth factor receptor specific immunotherapy: lessons to be learned from armed antibodies.

The epidermal growth factor receptor (EGFR) has been recognized as an important therapeutic target in oncology. It is commonly overexpressed in a variety of solid tumors and is critically involved in cell survival, proliferation, metastasis, and angiogenesis. This multi-dimensional role of EGFR in the progression and aggressiveness of cancer, has evolved from conventional to more targeted therapeutic approaches. With the advent of hybridoma technology and phage display techniques, the first anti-EGFR monoclonal antibodies (mAbs) (Cetuximab and Panitumumab) were developed. Due to major limitations including host immune reactions and poor tumor penetration, these antibodies were modified and used as guiding mechanisms for the specific delivery of readily available chemotherapeutic agents or plants/bacterial toxins, giving rise to antibody-drug conjugates (ADCs) and immunotoxins (ITs), respectively. Continued refinement of ITs led to deimmunization strategies based on depletion of B and T-cell epitopes or substitution of non-human toxins leading to a growing repertoire of human enzymes capable of inducing cell death. Similarly, the modification of classical ADCs has resulted in the first, fully recombinant versions. In this review, we discuss significant advancements in EGFR-targeting immunoconjugates, including ITs and recombinant photoactivable ADCs, which serve as a blueprint for further developments in the evolving domain of cancer immunotherapy.

Effect of aqueous extracts of Ficus vogeliana Miq and Tieghemella africana Pierre in 7,12-Dimethylbenz(a)anthracene -induced skin cancer in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Skin cancer is the most common form of cancer responsible for considerable morbidity and mortality. Tieghemella africana and Ficus vogeliana are used in traditional medicine to treat cancers. AIM OF THE STUDY: Therefore, the aim of this study was to investigate the antioxidant, antiangiogenic and anti-tumor activities of these plant extracts. MATERIALS AND METHODS: To achieve it, phytochemical screening, antioxidant activity and antiangiogenic activity were assessed. Thereafter, the anti-tumor activity was determined using skin tumorigenesis induced by 7,12-dimethylbenz[a]anthracene. RESULTS: The phytochemical result analysis showed that both plant extracts were rich in polyphenols, alkaloids and terpene compounds and possessed good antioxidant activity based on DPPH radical scavenging (IC50 = 9.70 µg/mL and 4.60 µg/mL and AAI values of 5.20 and 10.88) and strong total antioxidant capacity (115.44 VtCE (mg)/g of dry plant extract and 87.37 VtCE (mg)/g of dry plant extract, respectively). Additionally, both plant extracts possessed antiangiogenic activities (IC50 = 53.43 µg/mL and 92.68 µg/mL, respectively), which correlated with significant antitumor activities when using 35 mg/kg (65.02% and 77.54%) and 70 mg/kg of extracts (81.07% and 88.18%). CONCLUSIONS: In summary, this study illustrates the promising usage of Tieghemella africana and Ficus vogeliana plant extracts in treating skin cancer. However, further characterization of the extracts must be performed to isolate the most active anticancer compound.

Impact of knowledge, attitudes, and sociocultural factors on school enrollment of children with epilepsy in Gabon.

PURPOSE: Perceptions, beliefs and culture influence attitude towards epilepsy in sub-Saharan Africa. Misconceptions on epilepsy contribute to the persistence of negative attitudes in children with epilepsy particularly on their school enrollment. The aim of the study was to assess knowledge, attitudes, and sociocultural factors affecting schooling of children with epilepsy in Gabon. METHODS: Teachers and health workers from two urban and four rural localities of Gabon were assessed using a self-administered questionnaire. RESULTS: Overall 1310 subjects filled the survey questionnaire, including 813 teachers and 497 health workers. Knowledge on risk factors and suggestive signs of childhood epilepsy were globally poor. Misconceptions on etiology of epilepsy were significant with contagiousness (27.5%) and demonic possession (16.0%) representing the major prevalent idea about the origin of epilepsy in children. Attitudes of teachers and health workers towards schooling of children with epilepsy were positive (85.0%). However, more than half recommended enrollment of these children in specialized school programs. In multivariate analysis, education level (OR = 1.40; 95% confidence interval 1.01-1.81) and marital status (OR = 1.62; 95% confidence interval 1.18-2.22) were sociocultural factors likely to affect chances of school enrollment of children with epilepsy. CONCLUSION: Understanding the influence of socio-cultural factors surrounding school enrollment of children with epilepsy could enhance public awareness campaigns about epilepsy and to improve school integration of these children.

Distribution and co-occurrence of antibiotic and metal resistance genes in biofilms of an anthropogenically impacted stream.

Urban stream biofilms are potential hotspots for resistomes and antibiotic resistance genes (ARGs). Biofilm communities that harbor resistance genes may be influenced by contaminant input (e.g., metals and antibiotics) from urban drainage (i.e., Wastewater Treatment Plant effluent and stormwater runoff); understanding the ecology of these communities and their resistome is needed. Given the potential importance of the co-occurrence of ARGs and metal resistance genes (MRGs), we investigated the spatial and temporal distribution of three ARGs (tetracycline [tetW] and sulfonamides [sulI and sulII]), four MRGs (lead [pbrT], copper [copA], and cadmium/cobalt/zinc [czcA and czcC]) via quantitative PCR and biofilm bacterial community composition via MiSeq 16S sequencing at four time points along an urbanization gradient (i.e., developed, agriculture, and forested sites) in a stream's watershed. Our results revealed that ARG and MRG abundances were significantly affected by land use-time interaction, with greater resistance abundances occurring in more urban locations during particular times of the year. It was also observed that changes in ARG and MRG profiles were influenced by differences in community composition among land use types, and that these differences were in response to changes in stream physicochemical parameters (pH, redox, temperature, nutrient availability, and metal concentration) that were driven by sub-watershed land use. Moreover, the dynamics between ARGs and MRGs within these communities correlated strongly and positively with one another. Taken altogether, our results demonstrate that changes in environmental properties due to human activity may drive the ARG-MRG profiles of biofilm communities by modulating community structure over time and space.

Geographic distribution of livestock-associated Staphylococcus aureus in the United States.

Sampling for livestock-associated Staphylococcus aureus (LA-SA) in the United States is haphazard. The diversity of LA-S. aureus in the U.S. appears to be greater than in other countries. We review the epidemiology of LA-S. aureus in U.S. pigs, occupationally-exposed individuals, and environmental samples to assess the diversity and abundance of U.S. LA-S. aureus.

Antimycobacterial drugs currently in Phase II clinical trials and preclinical phase for tuberculosis treatment.

INTRODUCTION: In 2010, about 8.8 million new cases of tuberculosis were recorded and 1.1 million people died of tuberculosis worldwide. Although numbers are in decrease since 2006, tuberculosis still represents a global issue and a major public health threat, due to appearance of multidrug-resistant and extensively drug-resistant tuberculosis cases. Although anti-tuberculosis drugs currently used are effective against tuberculosis, they present however more and more limits, especially in treating complex cases of tuberculosis, increasing therefore the need to develop new tools and approaches to treat tuberculosis today. AREAS COVERED: In this review, we describe anti-tuberculosis drugs in Phase II clinical trials and in preclinical phase that are likely to play a crucial role in the management of tuberculosis cases in a near future. SQ109, TMC207, nitroimidazoles, and oxazolidinones are currently in Phase II clinical trials while BDM31343, SQ641, CPZEN-45, RBx 8700, DC-159a, and BTZ043 are in preclinical phase. CONCLUSION: These drugs, alone or in different combinations represent a promising future for the treatment of tuberculosis. Continual conjugative efforts between governments and private organizations worldwide are essential for building new strategies for discovery and the development of new anti-tuberculosis drugs.

Structure of the DNA-binding domain of the response regulator PhoP from Mycobacterium tuberculosis.

The PhoP-PhoR two-component signaling system from Mycobacterium tuberculosis is essential for the virulence of the tubercle bacillus. The response regulator, PhoP, regulates expression of over 110 genes. In order to elucidate the regulatory mechanism of PhoP, we determined the crystal structure of its DNA-binding domain (PhoPC). PhoPC exhibits a typical fold of the winged helix-turn-helix subfamily of response regulators. The structure starts with a four-stranded antiparallel beta-sheet, followed by a three-helical bundle of alpha-helices, and then a C-terminal beta-hairpin, which together with a short beta-strand between the first and second helices forms a three-stranded antiparallel beta-sheet. Structural elements are packed through a hydrophobic core, with the first helix providing a scaffold for the rest of the domain to pack. The second and third helices and the long, flexible loop between them form the helix-turn-helix motif, with the third helix being the recognition helix. The C-terminal beta-hairpin turn forms the wing motif. The molecular surfaces around the recognition helix and the wing residues show strong positive electrostatic potential, consistent with their roles in DNA binding and nucleotide sequence recognition. The crystal packing of PhoPC gives a hexamer ring, with neighboring molecules interacting in a head-to-tail fashion. This packing interface suggests that PhoPC could bind DNA in a tandem association. However, this mode of DNA binding is likely to be nonspecific because the recognition helix is partially blocked and would be prevented from inserting into the major groove of DNA. Detailed structural analysis and implications with respect to DNA binding are discussed.

Structure of EthR in a ligand bound conformation reveals therapeutic perspectives against tuberculosis.

Mycobacterium tuberculosis EthR is a repressor of ethA, a gene encoding a mono-oxygenase required for the activation of the prodrug ethionamide. Here we describe the X-ray crystal structure of EthR, a homodimer with an entirely helical structure showing similarities to TetR family members. Each monomer contained a fortuitous ligand identified as hexadecyl octanoate. The crystal structure of EthR purified in M. smegmatis revealed the presence of a comparable ligand. The binding of hexadecyl octanoate to EthR induces a conformational state incompatible with repressor function, which should lead to ethA derepression and consequently to an increased sensitivity to ethionamide and other thioamides. A related, more hydrophilic ketone was found to exhibit synergistic antimycobacterial effects when tested together with ethionamide, indicating that this strategy may help reduce the dosage of potent antibacterial compounds that otherwise are too toxic to be used as first-line drugs.

EthR, a repressor of the TetR/CamR family implicated in ethionamide resistance in mycobacteria, octamerizes cooperatively on its operator.

Ethionamide (ETH) is an important second-line antitubercular drug used for the treatment of patients infected with multidrug-resistant Mycobacterium tuberculosis. Although ETH is a structural analogue of isoniazid, only little cross-resistance to these two drugs is observed among clinical isolates. Both isoniazid and ETH are pro-drugs that need to be activated by mycobacterial enzymes to exert their antimicrobial activity. We have recently identified two M. tuberculosis genes, Rv3854c (ethA) and Rv3855 (ethR), involved in resistance to ETH. ethA encodes a protein that belongs to the Flavin-containing monooxygenase family catalysing the activation of ETH. We show here that ethR, which encodes a repressor belonging to the TetR/CamR family of transcriptional regulators, negatively regulates the expression of ethA. By the insertion of the ethA promoter region upstream of the lacZ reporter gene, overexpression of ethR in trans was found to cause a strong inhibition of ethA expression, independently of the presence of ETH in the culture media. Electrophoretic mobility shift assays indicated that EthR interacts directly with the ethA promoter region. This interaction was confirmed by DNA footprinting analysis, which, in addition, identified the EthR-binding region. Unlike other TetR/CamR members, which typically bind 15 bp operators, EthR recognises an unusually long 55 bp region suggesting multimerization of the repressor on its operator. Identification by primer-extension of the ethA transcriptional start site indicated that it is located within the EthR-binding region. Taken together, bacterial two-hybrid experiments and gel filtration assays suggested a dimerization of EthR in the absence of its operator. In contrast, surface plasmon resonance analyses showed that eight EthR molecules bind cooperatively to the 55 bp operator, which represents a novel repression mechanism for a TetR/CamR member.

In vivo interaction between the polyprenol phosphate mannose synthase Ppm1 and the integral membrane protein Ppm2 from Mycobacterium smegmatis revealed by a bacterial two-hybrid system.

Dolichol phosphate-mannose (Dol-P-Man) is a mannose donor in various eukaryotic glycosylation processes. So far, two groups of Dol-P-Man synthases have been characterized based on the way they are stabilized in the endoplasmic reticulum membrane. Enzymes belonging to the first group, such as the yeast Dpm1, are typical integral membrane proteins harboring a transmembrane segment (TMS) at their C terminus. In contrast, mammalian Dpm1, enzymes of the second group, lack the typical TMS and require the association with the small hydrophobic proteins Dpm3 to be properly stabilized in the endoplasmic reticulum membrane. In Mycobacterium tuberculosis, the Polyprenol-P-Man synthase MtPpm1 is involved in the biosynthesis of the cell wall-associated glycolipid lipoarabinomannan. MtPpm1 is composed of two domains. The C-terminal catalytic domain is homologous to eukaryotic Dol-P-Man synthases. The N-terminal domain of MtPpm1 contains six TMS that anchor the enzyme in the cytoplasmic membrane. In contrast, in Mycobacterium smegmatis, orthologs of the two domains of MtPpm1 are encoded by two distinct open reading frames, Msppm1 and Msppm2, organized as an operon. No TMS are predicted in MsPpm1, and subcellular fractionation experiments indicate that this enzyme is cytosolic when produced in Escherichia coli. Computer-assisted topology predictions and alkaline phosphatase insertions showed that MsPpm2 is an integral membrane protein. Using a recently developed bacterial two-hybrid system, it was found that MsPpm2 interacts with MsPpm1 to stabilize the synthase MsPpm1 in the bacterial membrane. This interaction is reminiscent of that of mammalian Dpm1 with Dpm3 and mimics the structure of MtPpm1 as demonstrated by the capacity of the two domains of MtPpm1 to spontaneously interact when co-expressed in E. coli.