SARS-CoV-2: Molecular Structure, Pathogenesis, Potential Therapeutic Targets, and Immune Response of the Infected Subject.

Background: The pathogenic mechanisms and immune response of COVID-19 are far from clear. Through a documentary review of literature, the authors describe virological and molecular aspects of SARS-CoV-2, the intimate mechanisms of cell infection, and potential therapeutic targets. They also analyze the characteristics of immune response of the infected subject. Objectives: Objectives of this study are to describe the state of knowledge on virological data, molecular and physiopathogenic mechanisms of SARS-CoV-2, with a view to a better understanding of the therapeutic targets, as well as the immune response of the infected subject. Methodology. This documentary review is a compilation of several meta-analyses, consistent with the methodology described in the PRISMA statement on literature data on SARS-CoV-2, published between March 22 and August 14, 2020 (Moher et al.). The search engines used for the selection of articles were as follows: PubMed, Google Scholar, Global Health, and WHO reports. Papers of interest were those addressing virological and molecular data on SARS-CoV-2, therapeutic aspects of COVID-19, and immunity of the infected subject. Of the 617 eligible papers, 417 could be retained after removing the duplicates. Ultimately, only 50 articles were retained for final evaluation. The data collected allowed the development of a two-armed model around the physiopathological aspects and potential therapeutic targets, as well as aspects of host immunity, respectively. The model was then compared to data from the HIV literature. Conclusion: Reported data could contribute to a better understanding of molecular mechanisms of cellular infection by SARS-CoV-2 as well as to a more easy explanation of the action of pharmacological agents used for the treatment, while elucidating intimate mechanisms of the immunity of infected subject.

Pulmonary embolism: epidemiological data and diagnosis in Kinshasa hospitals.

BACKGROUND: Pulmonary embolism (PE) is common but difficult to diagnose. OBJECTIVE: To describe the epidemiological, clinical and paraclinical characteristics of PE in Kinshasa hospitals. METHOD: This was a retrospective study in 158 cases with suspected PE. RESULTS: The prevalence of PE was 37% among cases with suspicion of the disease. Male sex was predominant (55%). The mean age was 55 ± 15 years. The main risk factors were obesity (53%), immobilisation (43%) and surgery (14%). The main symptoms were dyspnoea (98%), cough (59%), chest pain (43%) and unilateral limb pain (36%). Tachypnoea (88%), tachycardia (53%) and signs of deep-vein thrombosis (36%) were the main clinical presentations. Lung examination was normal in 55% of the patients. PE prevalence in the 'PE likely' category based on the Wells score was 53%. Levels of D-dimers were elevated in all patients. Sinus tachycardia (72%), S1Q3T3 pattern (30%) and T-wave inversion in V1-V4 (34%) were the main electrocardiographic abnormalities. Chest X-ray was normal in 30% of patients. Right ventricular pressure overload was detected in 58% of patients who had access to echocardiography. Computed tomography pulmonary angiography was performed in 65% of patients. All patients were treated with anticoagulants; no cases received thrombolytics. Patients who died (7%) were all in class III-V according to the Pulmonary Embolism Severity Index prognostic score. CONCLUSION: PE is common in Kinshasa, with characteristics similar to those reported in the literature.

Echoendoscopie digestive diagnostique et interventionnelle à la clinique Marie-Yvette de Kinshasa (RDC) : Résultats d'une série préliminaire prospective

Contexte et objectif. L?Echo-endoscopie est une technique qui associe l?endoscopie et l?échographie intra-cavitaire. Elle permet ainsi d?examiner la cavité, la paroi des organes, ainsi que l?environnement péri-pariétal. Son intérêt dans la recherche et la caractérisation des lésions est évidente, notamment en cancérologie. Cette technique est très peu réalisée en Afrique subsaharienne. L?objectif était de décrire les trouvailles de l?écho-endoscopie digestive. Méthodes. Nous avons réalisé une étude transversale sur l?écho-endoscopie digestive, entre janvier et avril 2017, à la Clinique Marie-Yvette de Kinshasa. Les paramètres d?intérêts comprenaient : les caractéristiques sociodémo-graphiques, les indications de l?écho-endoscopie digestive, le type d?EDI et les pathologies macroscopiques et microscopiques diagnostiquées.Résultats. 38 patients ont été enrôlés. Il y avait 22 hommes (57,9%) et 16 femmes (42,1%), soit un sex-ratio H/F de 1,4 soit 14H/10F). Leur âge moyen était de 58,7±18,6 ans (extrêmes de 16 à 89 ans).Les indications les plus fréquentes de l?écho-endoscopie étaient : un ictère obstructif dans 13 cas sur 38 ; (soit 34,2%), une masse abdominale palpable dans 12 cas (31,6%), un amaigrissement dans 12 cas (31,6%), une douleur de l?hypochondre droit dans 9 cas (23,7%), bilan d?extension de lésion anorectale dans 5 cas (3,2%).Les diagnostics les plus fréquents étaient : foie hétérogène (9 cas ; 23,7% des cas), calcul de bas cholédoque (6 cas ; 15,8%), tumeur céphalo-pancréatique (5cas ; 13,2%), calculs de la vésicule biliaire (4cas ; 10,5%), TIPMP (3 cas ; 7,9%). 15 patients sur 38, soit 39,5% des cas, ont bénéficié d?une cyto-ponction (écho-endoscopie interventionnelle).Les diagnostics histologiques (tableau 1) plus fréquemment retenus étaient un adénocarcinome du pancréas (5 cas ; 13,2% des cas), une hépatite virale (3 cas ; 7,9%), une cirrhose du foie (2cas ; 5,3%), un carcinome du foie (2 cas ; 5,3%), et un fragment non contributif (1 cas ; 2,6%).Conclusion : La présente étude montre la faisabilité de l?écho-endoscopie diagnostique et interventionnelle à Kinshasa (RDC). Les indications les plus fréquentes étaient bilio-pancréatiques et cancérologiques

Ebola virus outbreaks in Africa: past and present.

Ebola haemorrhagic fever (EHF) is a zoonosis affecting both human and non-human primates (NHP). Outbreaks in Africa occur mainly in the Congo and Nile basins. The first outbreaks of EHF occurred nearly simultaneously in 1976 in the Democratic Republic of the Congo (DRC, former Zaire) and Sudan with very high case fatality rates of 88% and 53%, respectively. The two outbreaks were caused by two distinct species of Ebola virus named Zaire ebolavirus (ZEBOV) and Sudan ebolavirus (SEBOV). The source of transmission remains unknown. After a long period of silence (1980-1993), EHF outbreaks in Africa caused by the two species erupted with increased frequency and new species were discovered, namely Côte d'Ivoire ebolavirus (CIEBOV) in 1994 in the Ivory Coast and Bundibugyo ebolavirus (BEBOV) in 2007 in Uganda. The re-emergence of EHF outbreaks in Gabon and Republic of the Congo were concomitant with an increase in mortality amongst gorillas and chimpanzees infected with ZEBOV. The human outbreaks were related to multiple, unrelated index cases who had contact with dead gorillas or chimpanzees. However, in areas where NHP were rare or absent, as in Kikwit (DRC) in 1995, Mweka (DRC) in 2007, Gulu (Uganda) in 2000 and Yambio (Sudan) in 2004, the hunting and eating of fruit bats may have resulted in the primary transmission of Ebola virus to humans. Human-to-human transmission is associated with direct contact with body fluids or tissues from an infected subject or contaminated objects. Despite several, often heroic field studies, the epidemiology and ecology of Ebola virus, including identification of its natural reservoir hosts, remains a formidable challenge for public health and scientific communities.

Accidents d'exposition au sang chez les professionnels de sante a l'Hopital Biamba Marie Mutombo

Contexte : Les accidents d'exposition au sang (AES) constituent un des risques les plus importants auxquels font face les professionnels de sante. Lors d'un AES; bien que de nombreux pathogenes puissent etre transmis; les virus induisant un portage chronique en cas de contamination dominent le risque; et justifient a eux seuls; les mesures de prevention et de prophylaxie post-exposition. Il s'agit du VIH; des Virus des hepatites B et C. Cependant; l'ampleur reelle du probleme n'est pas connue dans notre pays; la Republique Democratique du Congo (RDC). Objectif : Evaluer la frequence des AES chez les professionnels de sante de l'Hopital Biamba Marie Mutombo; en decrire les caracteristiques et determiner les categories professionnelles les plus concernees. Methode : Une enquete transversale a ete menee au mois d'Aout 2009 et reprenant les AES survenus au cours des 12 derniers mois a l'HOPITAL BIAMBA MARIE MUTOMBO de Kinshasa. Une fiche d'enquete a ete utilisee; sollicitant les informations generales sur le professionnel ainsi que les accidents de blessures et la projection du sang ou d'un autre liquide biologique survenus a l'hopital au cours de l'annee derniere. Resultats : Parmi les 219 professionnels enquetes; seuls 24des participants etaient informes sur les risques encourus par l'exposition aux pathogenes sanguins. 40ont declare avoir eu au moins une blessure accidentelle et 16une eclaboussure d'un liquide biologique au cours de l'annee derniere. Les Infirmiers ont reporte le plus grand nombre d'accidents (piqures et projections de liquides biologiques). Les AES ont ete plus dus aux aiguilles avant l`acte professionnel. Conclusion : Pres de 50des AES pouvaient etre evites par des mesures simples; malheureusement pas toujours connues des professionnels de sante

Effets de la rehabilitation sur les indicateurs de sante cardiorespiratoire aux cliniques Universitaires de Kinshasa

Cette etude transversale a recherche l'impact des techniques simples de rehabilitation cardiorespiratoire sur l'evolution clinique des patients BPCO (n = 25) ou souffrant de cardiopathie hypertensive (n = 11). A l'aide d'un test de chi-carre et d'un test de Freedman; l'impact d'un programme de rehabilitation de 6 mois a ete evalue sur l'evolution des symptomes et de certaines donnees de l'examen physique.les parametres d'interet ont ete enregistres en 4 etapes selon un chronogramme preetabli. Nos resultats ont montre : une nette amelioration des symptomes des le 3eme mois (dyspnee; toux; expectorations); une reduction significative de la frequence respiratoire du repos et du pouls; une reduction precoce de la pression diastolique moyenne et plus tardive de la pression thoracique et de l'indice de masse corporelle. Cette enquete montre l'interet des techniques simples de rehabilitation cardiorespiratoire pendant au moins trois mois; dans la prise en charge des affections chroniques cardiorespiratoires

Prevalence de la transmission perinatale du VIH sous prophylaxie a la Nevirapine a Kinshasa

La transmission verticale du VIH est la cause principale de l'infection pediatrique par le VIH. Plusieurs schemas d'antiretroviraux (ARV) sont utilises dans les programmes de Prevention de la Transmission de la Mere a l'Enfant (PTME) ; allant de la dose unique prophylactique a base de la Nevirapine (NVP); a l'utilisation des Antiretroviraux a Haute Activite Therapeutique (HAART). Dans cette etude nous cherchons a determiner la prevalence de la transmission perinatale du VIH sous monotherapie a la Nevirapine utilisee dans la PTME en Republique Democratique du Congo (RDC). La charge virale a ete dosee par PCR-RNA chez 147 meres seropositives consentantes ainsi que chez leurs enfants. Un premier prelevement de sang veineux a ete effectue a l'entree en salle de travail; un deuxieme a l'accouchement; chez les meres. Concernant les enfants; un prelevement a ete effectue au cordon ombilical et un autre entre 6 et 10 semaines de vie ex utero. De 146 echantillons de sang du cordon; 21 n'ont pas ete analyses; car alteres. Les particules virales ont ete retrouvees dans 19/125 echantillons preleves a la naissance; soit 15;20. Lors du 2ieme prelevement; cette charge virale est devenue indetectable chez 17/19. Seuls 80 enfants ont ete retrouves pour ce deuxieme prelevement. En definitif 67 enfants ont eu des analyses effectuees successivement sur les prelevements du cordon et sur ceux pratiques entre 6 et 10 semaines apres la naissance et 11 etaient infectes; soit 16;40(IC a 95: 8;50-27;50).Ces donnees sont les premieres rapportees en RDC

Profil et evolution de la resistance primaire de Mycobacterium tuberculosis aux antituberculeux dans deux centres de traitement a Kinshasa

"Objectif : Determiner la frequence; le profil et l'evolution de la resistance primaire aux antituberculeux parmi des sujets seropositifs et seronegatifs pour le VIH traites dans deux centres de Kinshasa. Methodes : Les expectorations des sujets eligibles ont ete ensemencees sur milieu de Lowenstein Jensen et la sensibilite des souches aux antituberculeux usuels testee selon la technique des proportions de Canetti et al. (7). La resistance globale a un ou plusieurs antituberculeux etait de 42et la comparaison des donnees entre sujets VIH+ et VIH- a ete effectuee a l'aide du test de Chi-carre ou du test exact de Fisher selon le cas. Resultats : Sur 161 souches isolees de Mycobacterium tuberculosis; 68 (42) se sont revelees resistantes a au moins un de quatre antituberculeux testes. La monoresistance a ete plus marquee pour la streptomycine (30;4) et l'Isoniazide (19;9). La frequence la plus faible a ete observee pour la rifampicine (5). Le profil de la resistance globale n'a pas montre de difference significative entre sujets VIH+ et VIH- (45""vs 40; p=0;505) tandis que la resistance isolee est apparue plus marquee pour les sujets VIH+ pour tous les antituberculeux testes hormis l'ethambutol La multiresistance (MDR-TB) a ete observee pour 8 souches (5). Conclusion : Le taux de resistance primaire a au moins un antituberculeux et la presence de la multiresistance justifient l'extension de la surveillance au reste du pays en vue de definir les strategies adequates de riposte. L'impact du VIH sur la resistance merite d'etre etudie dans des series plus grandes."

[Primary resistance of Mycobacterium tuberculosis to anti-tuberculosis drugs in Kinshasa, (DRC)]. / Résistance primaire de Mycobacterium tuberculosis aux anti-tuberculeux à Kinshasa, République Démocratique du Congo.

In a descriptive cross-sectional study carried out in Kinshasa between July 2003 and January 2004, we determined the prevalence of the primary resistance of M. tuberculosis to first-line anti-tuberculosis drugs. The antibiogram was performed with the proportion method on 301 isolats from patients who all had a first episode of pulmonary tuberculosis with positive microscopy (TPM+) and who had not received any anti-tuberculosis treatment before. The primary resistance rate reached 43.5%; it reached 31.6% in 1990. The multi-drug-resistance rate (MDR-TB) notified as resistant to both rifamicine and isoniazide rose to 5.3%. This rate of primary resistance is among the highest in Africa. The emergence of the resistant strains and specially the multi-drug-resistant strains (MDR-TB) in Kinshasa requires a regular assessment of these phenomena which threaten seriously the implementation of the national tuberculosis control programme.

Prevalence of symptoms of asthma, rhinitis and eczema in 13- to 14-year-old children in Africa: the International Study of Asthma and Allergies in Childhood Phase III.

Phase I of the International Study of Asthma and Allergies in Childhood has provided valuable information regarding international prevalence patterns and potential risk factors in the development of asthma, allergic rhinoconjunctivitis and eczema. However, in Phase I, only six African countries were involved (Algeria, Tunisia, Morocco, Kenya, South Africa and Ethiopia). Phase III, conducted 5-6 years later, enrolled 22 centres in 16 countries including the majority of the centres involved in Phase I and new centres in Morocco, Tunisia, Democratic Republic of Congo, Togo, Sudan, Cameroon, Gabon, Reunion Island and South Africa. There were considerable variations between the various centres of Africa in the prevalence of the main symptoms of the three conditions: wheeze (4.0-21.5%), allergic rhinoconjunctivitis (7.2-27.3%) and eczema (4.7-23.0%). There was a large variation both between countries and between centres in the same country. Several centres, including Cape Town (20.3%), Polokwane (18.0%), Reunion Island (21.5%), Brazzaville (19.9%), Nairobi (18.0%), Urban Ivory Coast (19.3%) and Conakry (18.6%) showed relatively high asthma symptom prevalences, similar to those in western Europe. There were also a number of centres showing high symptom prevalences for allergic rhinoconjunctivitis (Cape Town, Reunion Island, Brazzaville, Eldoret, Urban Ivory Coast, Conakry, Casablanca, Wilays of Algiers, Sousse and Eldoret) and eczema (Brazzaville, Eldoret, Addis Ababa, Urban Ivory Coast, Conakry, Marrakech and Casablanca).

Bronchial responsiveness in active steelworkers.

Coke-oven workers are exposed to dust and irritant gases. Therefore they are at risk of developing lung diseases including chronic bronchitis. Nonspecific bronchial hyperresponsiveness (BHR) has been advocated as a potential risk factor predisposing to the development of chronic bronchitis. In a previous study, we showed that prevalence of BHR was higher in retired coke-oven workers than in retired blast furnace workers. The present study was carried out to determine the prevalence of BHR in active steelworkers. Thus, 137 coke-oven workers and 150 blast furnace workers underwent clinical examination, a standardized questionnaire for the study of respiratory symptoms, pulmonary function testing and methacholine aerosol challenge. The study demonstrates a higher prevalence and degree of BHR [provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (PC20) < or = 8 mg x mL(-1)] in coke-oven workers than in blast furnace workers (31.4 versus 6.7%; p<0.001). Moreover, the frequency of respiratory symptoms and basal bronchial obstruction were greater among coke-oven workers with BHR in nonresponders. The basal maximum expiratory flow from 25-75% of forced vital capacity and the respiratory symptoms were correlated with bronchial responsiveness. The lack of correlation observed between BHR and the intensity of smoking or years spent in coke-oven environment may be explained by the high proportion of smokers, the worker turnover in the steel plant, and the "healthy worker effect". In conclusion, the higher prevalence and degree of bronchial hyperresponsiveness in coke-oven workers suggests that coke-oven pollutants are more intense irritants than those that escape from blast furnaces.

Usefulness of induced sputum analysis in pulmonary diseases.

In this study, we analysed the cellular component of induced sputum in healthy control subjects (n = 30), asthmatics (n = 44), patients suffering from COPD (n = 15), pulmonary tuberculosis (PTB) (n = 14) and healthy steel workers (HSW) (n = 14). Sputum was induced by inhalation of hypertonic saline (NaCl 5%) for 20 min. When compared to the healthy control group, all the disease groups as well as the one of healthy steelworkers exhibited significantly higher total sputum cell counts. Analysis of the differential cell counts showed that there was a significant increase in % eosinophils in asthmatics, in % neutrophils in COPD, asthmatics, tuberculosis and healthy steelworkers and in % lymphocytes in pulmonary tuberculosis. Our study illustrates the feasibility and the possible clinical application of induced sputum analysis in several pulmonary diseases and shows how this technique could be useful in assessing airway inflammatory processes in subjects exposed to industrial pollutants.

Evaluation of the solitary pulmonary nodule by positron emission tomography imaging.

Current noninvasive imaging methods are not sufficiently reliable for accurate detection of malignancy in most solitary pulmonary nodules (SPNs). Positron emission tomography (PET) using 18-fluorodeoxyglucose (FDG), showing increased FDG uptake and retention in malignant cells, has proved useful to differentiate malignant from benign tissue and could, therefore, contribute to the evaluation of the SPN. We performed a prospective study of 50 patients referred to the Pneumology Department with unclear diagnoses of SPN after conventional radiological screening. PET study was performed on each subject before an invasive procedure was proposed. Thirty three patients had a malignant nodule and 17 had a benign nodule. The mean size of malignant nodule was 3 cm (range 1.5-4.5 cm). All showed a marked increase in 18-FDG uptake. The mean size of benign nodule was 1.8 cm (range 0.5-3.5 cm). PET imaging showed the absence of 18-FDG uptake and correctly identified 15 of 17 benign nodules. There was two false-positive cases with a moderate increase in 18-FDG uptake (1 postprimary tuberculosis; and 1 anthracosilicotic nodule with nonspecific inflammation). At present, the sensitivity and specificity of the method are 100 and 88%, respectively. The positive and negative predictive values of PET imaging for SPNs are 94 and 100%, respectively. Our preliminary results demonstrate that PET-FDG imaging is a noninvasive technique, which appears highly accurate in differentiating malignant SPN from benign SPN.

Changes in bronchial responsiveness, circulating leucocytes and ex vivo cytokine production by blood monocytes after PAF inhalation in allergic asthmatics.

We investigated the effects of inhaled platelet-activating factor (PAF) on methacholine bronchial responsiveness, circulating leucocyte counts, and ex vivo tumour necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1) production from blood monocytes in eight allergic asthmatics. Bronchial responsiveness was defined as the provocative concentration of methacholine causing a 20% decrease in forced expiratory volume in one second (PC20). Circulating leucocytes were counted by means of an automatic haemocytometer, and cytokines were measured with specific immunoassays. The different variables were measured before and 4, 24, 48, 72 and 168 h after a PAF (225 micrograms), a lyso-PAF (225 micrograms) and a saline bronchial challenge. When compared with lyso-PAF and saline, inhalation of PAF resulted in a significant decrease in PC20 over a period of one week. Two falls in bronchial responsiveness were identified, the first by 4 h and the second beginning 48 h and reaching a maximum by 168 h. The increases in spontaneous TNF alpha and IL-1 production which occurred during the week after both PAF, lyso-PAF and saline, did not differ significantly. Likewise, the changes in circulating neutrophil counts, characterized by a transient rise by 4 h after PAF and lyso-PAF but not saline, followed by a fall by 24 h and a persistent decrease until 168 h, were not significantly different after PAF, lyso-PAF and saline. On the other hand, in comparison with lyso-PAF and saline, inhaled PAF caused a significant protracted augmentation in circulating eosinophil counts, which was maximal by 48 h but did not correlate with the delayed decline in PC20.(ABSTRACT TRUNCATED AT 250 WORDS)

[Asthma and nonspecific bronchial hyperreactivity]. / Asthme et hyperréactivité bronchique non spécifique.

Bronchial hyperresponsiveness is a hallmark of asthma although it can also be present, to a lesser extent, in other diseases. The level of bronchial responsiveness depends on immuno-inflammatory processes modifying the functional status of airway smooth muscle as well as the structure of the bronchial wall. The responsiveness toward a direct constricting pharmacological agent is poorly correlated to the one toward an indirect constricting agent or a physical stimulus which cause airway obstruction through a more complex mechanism. Transversal studies show a relationship between the severity of asthma and the level of methacholine airway responsiveness. Long term treatment with corticoids can reduce the bronchial hyperresponsiveness of asthmatics.