Profile and course of cardiovascular morbidity and mortality in Conakry. Apropos of 268 cases seen at the Cardiology Department of the Ignace-Deen University Hospital 1986-1987

Over a period of two years (1986-1987), the authors have studied the morbidity and mortality of various cardiovascular diseases in a hospital population of 268 patients. By comparing it with a previous similar study conducted over 5 years (1981-1985), they have reached the following conclusions: the prevalence of the main nosological groups is equivalent (H.B.P., rheumatoid valvulopathies, chronic pulmonary heart, ischemic cardiopathies; severity of the valvulopathies and their prognosis which raise social and medical problems especially that of cardiac surgery, still inexistent in Guinea; increased prevalence of diseases such as hypertension and rheumatoid valvulopathies. They suggest early screening, especially for rheumatoid valvulopathies and hypertension, which cause major social problems because of their complications. Besides, it would be desirable that visits at regular intervals be made mandatory in schools and universities and at preemployment examinations and in all SMI (?) centers in the country.     

Efficacy, safety, and selection of molecular markers of drug resistance by two ACTs in Mali

We conducted a randomized single-blinded trial comparing the efficacy and safety of artesunate (AS) + amodiaquine (AQ, 3 days) versus AS (3 days) + sulfadoxine-pyrimethamine (SP, single dose) versus AS monotherapy (5 days) in Southern Mali. Uncomplicated malaria cases were followed for 28 days. Molecular markers of drug resistance were determined. After identification of recrudescences by genotyping, both artemisinin-based combination therapies (ACTs) reached nearly 100% efficacy at Day 14 and Day 28 versus 98.3% and 96.5% for AS, respectively (P > 0.05). AS + SP significantly selected DHFR and DHPS mutations associated with sulfadoxine and pyrimethamine resistance (P < 0.001), and AS + AQ equally selected PfCRT and PfMDR1 point mutations associated with chloroquine and AQ resistance (P < 0.001). No significant adverse event attributable to any of the study drugs was found. The ACTs were efficacious and safe, but the selection of markers for resistance to the partner drugs raises concerns over their lifespan in areas of intense malaria transmission.     

Repeated artemisinin-based combination therapies in a malaria hyperendemic area of Mali: efficacy, safety, and public health impact

Artemisinin-based combination therapies (ACTs) are the first-line treatment of uncomplicated malaria. The public health benefit and safety of repeated administration of a given ACT are poorly studied. We conducted a randomized trial comparing artemether-lumefantrine, artesunate plus amodiaquine (AS+AQ) and artesunate plus sulfadoxine-pyrimethamine (AS+SP) in patients 6 months of age and older with uncomplicated malaria in Mali from July 2005 to July 2007. The patient received the same initial treatment of each subsequent uncomplicated malaria episode except for treatment failures where quinine was used. Overall, 780 patients were included. Patients in the AS+AQ and AS+SP arms had significantly less risk of having malaria episodes; risk ratio (RR) = 0.84 (P = 0.002) and RR = 0.80 (P = 0.001), respectively. The treatment efficacy was similar and above 95% in all arms. Although all drugs were highly efficacious and well tolerated, AS+AQ and AS+SP were associated with less episodes of malaria.     

L’apport de l’imagerie dans le diagnostic de la tuberculose uro-génitale (TUG): Une analyse de 4 observations et revue de la littérature

Tuberculosis (TB) of the urinary tract represents a secondary location of the disease. Its diagnosis is based on bacteriologic examination, but the chance of demonstrating the Koch bacillus in the urine is rare. This underlines the importance of imaging in the diagnosis and subsequent medical treatment of the disease. We report four cases where radiologic imaging in association with clinical and epidemiological findings raised the suspicion of genito-urinary TB. Only in one case was urine culture positive for the Koch bacillus. In the other three patients with negative cultures, histopathological examination of the resected specimens revealed tuberculous lesions. This shows the importance of radiology for early diagnosis and treatment of genito-urinary TB.     

Contribution à l’étude de la mortalité dans un service d’urologie: Le cas du service d’urologie du CHU de Cocody d’Abidjan de 2000 à 2006

Objective

To analyze the incidence and main causes of mortality in the Department of Urology of the University Hospital of Cocody.

Patients and Methods

This retrospective analysis included 117 patients who died in the Department of Urology of the University Hospital of Cocody between April 2000 and December. Based on the data collected from the patient files, the hospital registry and the death certificates we studied the frequency and causes of death.

Results

The overall mortality rate was 10.1% with a male-to-female sex ratio of 14:1. The patients’ mean age was 63.4 (range 18–94) years. The main cause of death was cancer (87.5%). Cancer of the prostate which was the second most frequent reason for consultation after benign prostatic hyperplasia was the commonest cause of death encountered in 62.4% of the patients, followed by bladder and renal cancer with 16,2% and 6%, respectively. Prostatic adenoma (52%) was the most frequent and urethral stricture (8%) the third most frequent reason for hospitalization and led to death in 3.4% and 4.3%, respectively. Moreover, death mainly occurred in the second half of the month (53.9%) and during the night (57.3%).

Conclusion

The incidence of mortality in urology remains high and is almost exclusively related to urological cancers.     

Exosome-mediated transmission of hepatitis C virus between human hepatoma Huh7.5 cells

Recent evidence indicates there is a role for small membrane vesicles, including exosomes, as vehicles for intercellular communication. Exosomes secreted by most cell types can mediate transfer of proteins, mRNAs, and microRNAs, but their role in the transmission of infectious agents is less established. Recent studies have shown that hepatocyte-derived exosomes containing hepatitis C virus (HCV) RNA can activate innate immune cells, but the role of exosomes in the transmission of HCV between hepatocytes remains unknown. In this study, we investigated whether exosomes transfer HCV in the presence of neutralizing antibodies. Purified exosomes isolated from HCV-infected human hepatoma Huh7.5.1 cells were shown to contain full-length viral RNA, viral protein, and particles, as determined by RT-PCR, mass spectrometry, and transmission electron microscopy. Exosomes from HCV-infected cells were capable of transmitting infection to naive human hepatoma Huh7.5.1 cells and establishing a productive infection. Even with subgenomic replicons, lacking structural viral proteins, exosome-mediated transmission of HCV RNA was observed. Treatment with patient-derived IgGs showed a variable degree of neutralization of exosome-mediated infection compared with free virus. In conclusion, this study showed that hepatic exosomes can transmit productive HCV infection in vitro and are partially resistant to antibody neutralization. This discovery sheds light on neutralizing antibodies resistant to HCV transmission by exosomes as a potential immune evasion mechanism.Most tissue and cell types produce and release exosomes, a distinct population of microvesicles ranging from about 30 to 150 nm in size. Exosomes are formed in the endocytic compartment of multivesicular bodies (1) and are secreted in various body fluids under normal and pathological conditions (2, 3). Extensive studies have now implicated exosomes in many biological processes such as tissue injury and immune responses by transfer of antigens, antigen presentation (2, 4), and the shuttling of proteins, mRNAs, and microRNAs (miRNA) between cells (5). As such, it has been postulated that exosomes play a crucial role in cell communication and in the transfer of genetic information between cells (5).The role of exosomes and other secretory vesicles in the transfer of pathogen-derived antigens and virulence factors is emerging (6, 7). Whether release of vesicles from infected cells contributes to immune control and clearance of infection by the host is still not clear. For example, the HIV Gag protein recruits the outward vesicle-budding machinery of exosomes to form free virions (8). Recently, it has been shown that exosomes released from HIV-infected cells contain negative regulatory factor, which induces apoptosis of uninfected cells (9). Epstein-Barr virus-infected B cells also secrete exosomes that contain virally encoded miRNA (10). This study further demonstrates the delivery of naturally occurring functional genetic elements to neighboring cells via exosomes, indicating that viral particles or molecules associated with viral infection can be transmitted to adjacent uninfected cells via exosomes and become functional. More recently, the hepatitis A virus has shown to be able to escape humoral immunity by cloaking itself in cellular membranes on release from host cells. These virus-containing microvesicles, resembling exosomes, were shown to protect virions from antibody-mediated neutralization (11).Hepatitis C virus (HCV) infection, a leading liver disease, has been shown to have multiple routes of transmission. Apart from classical transmission by free viral particles, an antibody-resistant cell-to-cell transmission route also has been described (12). Indeed, HCV is known to evade humoral immune responses, as indicated by a lack of resistance to HCV reinfection in i.v. drug users (13), HCV reinfection during liver transplantation (14), and an ongoing difficulty of developing effective vaccines. The role of exosomes in HCV infection is still largely unknown. One earlier paper reported the presence of viral RNA in exosomes isolated from plasma of HCV-infected patients (15) but did not show exosome-mediated transmission of infection. More recent studies suggest that HCV virus assembly and release in hepatocytes may be linked to the exosome secretory pathway (16) and that hepatocyte-derived exosomes can transfer viral RNA to plasmacytoid dendritic cells, triggering their activation and IFN-α production (17). However, the role of exosomes in the cell-to-cell transmission route of HCV between hepatocytes has not been demonstrated. The aim of our study was to investigate transmission of HCV infection by hepatocyte-derived exosomes in the presence of neutralizing antibodies (nAbs) in vitro that could explain the ineffectiveness of prophylactic nAbs and agents targeting the entry of HCV into a cell. We further observe that this route of infection can generate productive viral infection.     

Incidence of and beliefs about trypanosomiasis in the Senegal River Basin.

A survey was conducted for trypanosomiasis of 10,875 persons living in 56 villages in the Senegal River Basin in Mali. The incidence of the disease was found to be 137.9/100,000. An interview survey was simultaneously undertaken in order to elucidate local beliefs about the disease. Although trypanosomiasis is recognized as a distinct disease entity once the late stage has developed, there is no knowledge of its relationship to tsetse flies. It is common knowledge that hunters who frequent riverine forest galleries and forested savanna often contract the disease. Their frequent and intense exposure to Glossina sp. is not viewed as having any relationship to their contracting the disease.