Persistent West Nile virus infection in the golden hamster: studies on its mechanism and possible implications for other flavivirus infections

Golden hamsters (Mesocricetus auratus) experimentally infected with West Nile virus (WNV) developed chronic renal infection and persistent shedding of virus in urine for up to 8 months, despite initial rapid clearance of virus from blood and the timely appearance of high levels of specific neutralizing antibodies. Infectious WNV could be recovered by direct culture of their urine and by cocultivation of kidney tissue for up to 247 days after initial infection. Only moderate histopathologic changes were observed in the kidneys or brain of the chronically infected hamsters, although WNV antigen was readily detected by immunohistochemistry within epithelium, interstitial cells, and macrophages in the distal renal tubules. Comparison of WNV isolates from serial urine samples from individual hamsters over several months indicated that the virus underwent both genetic and phenotypic changes during persistent infection. These findings are similar to previous reports of persistent infection with tickborne encephalitis and Modoc viruses.     

Bacterial enteric infections and vaccine development.

There is a great need for effective vaccines against the major bacterial enteropathogens. Bacterial enteric infections resulting in diarrhea, dysentery, or enteric fever constitute a huge public health problem, with more than a billion episodes of disease and several million deaths annually in developing countries. Diarrhea caused by a bacterial enteric infection is also the commonest illness experienced by international travellers. Studies of pathogenesis have established the importance of specific ligand-receptor interactions between the enteropathogens and the intestinal epithelium, resulting in attachment and colonization of the bacteria and production of disease through either invasive mechanisms or production of toxins. Studies of protective immune mechanisms have emphasized the importance of secretory IgA antibodies and mucosal memory for protection against noninvasive, enterotoxigenic infections such as cholera and ETEC diarrhea and also drawn attention to the possible protective role of IFN-gamma production by intestinal T cells in these secretory diarrheas. In invasive dysenteric and enteric-fever infections caused by such organisms as Shigella and Salmonella, optimal protection may depend on a combination of mucosal and systemic immunity. On the basis of this knowledge, several new vaccines have been developed and proved to be efficacious in large field tests. These include an oral killed B-WC vaccine and a killed WC-alone vaccine against cholera, and both a live attenuated oral vaccine (Ty21a) and an injectable Vi antigen vaccine against typhoid fever. In addition, a killed oral ETEC vaccine and live attenuated oral Shigella vaccines have begun to be tested in phase 1 and phase 2 studies in humans. The properties of the new vaccines against bacterial enteric infections give promise that these vaccines should be useful both in control programs in developing countries and for immunoprophylaxis against travellers' diarrhea.     

Oral vaccination against enteric bacterial infections: An overview

Summary The present situation and the future prospects for the use of oral vaccines against the major enteric diseases typhoid fever, shigellosis and cholera are discussed in this paper. No significant protection could be demonstrated for oral inactivated whole-cell vaccines. In contrast, an oral live vaccine based on the attenuatedSalmonella typhi strain Ty 21a was highly efficacious in volunteer challenge studies and in a controlled field trial. Two attenuated strains are presently being tested in volunteer studies as candidate vaccines against shigellosis; one usesS. typhi Ty 21a and the otherEscherichia coli K-12 as the carrier for shigella antigens. Experimental challenge studies in volunteers showed that recovery from clinical cholera confers solid and long-lasting protection. The goal of present research is to develop a vaccine that mimics the events of clinical cholera without causing disease.

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Orale Impfstoffe gegen enterale Bakterieninfektionen; eine Übersicht

Zusammenfassung Es werden die gegenwärtigen Möglichkeiten und Aussichten für die Verwendung oraler Impfstoffe gegen die wichtigsten enteralen Bakterieninfektionen Typhus, Dysenterie und Cholera besprochen. Orale Impfstoffe gegen Typhus, bestehend aus inaktivierten Bakterien, sind unwirksam. Demgegenüber erwies sich ein oraler Lebendimpfstoff, basierend auf dem attenuiertenSalmonella typhi Stamm Ty 21a, in klinischen Belastungsversuchen und in Feldversuchen als sehr wirksam. Gegenwärtig werden in Freiwilligen zwei attenuierte Stämme als mögliche Kandidaten für einen Lebendimpfstoff gegen Shigellose getestet; der eine benütztS. typhi Ty 21a und der andereEscherichia coli K-12 als Träger für Shigella Schutzantigene. Belastungsversuche in Freiwilligen haben gezeigt, daß eine überstandene Cholera-Erkrankung einen guten und langdauernden Schutz hinterläßt. Das Ziel gegenwärtiger Forschung ist, einen Impfstoff zu entwickeln, der möglichst nahe die Ereignisse einer Cholera-Infektion nachahmt, jedoch ohne deren Symptome auszulösen.

     

HIV and malaria: interactions and implications

PURPOSE OF REVIEW: This review summarizes accumulating evidence of interactions between HIV and malaria and implications related to prevention and treatment of coinfection. RECENT FINDINGS: HIV-infected persons are at increased risk for clinical malaria; the risk is greatest when immune suppression is advanced. Adults with advanced HIV may be at risk for failure of malaria treatment, especially with sulfa-based therapies. Malaria is associated with increases in HIV viral load that, while modest, may impact HIV progression or the risk of HIV transmission. Cotrimoxazole prophylaxis greatly reduces the risk of malaria in people with HIV; the risk can be further reduced with antiretroviral treatment and the use of insecticide treated mosquito nets. Increased numbers of doses of intermittent preventive treatment during pregnancy can reduce the risk of placental malaria in women with HIV. SUMMARY: Interactions between malaria and HIV have important public health implications. People with HIV should use cotrimoxazole and insecticide treated mosquito nets. Malaria prevention is particularly important for pregnant women with HIV, although more information is needed about the best combination of strategies for prevention. In people with HIV, malaria diagnoses should be confirmed, highly effective drugs should be used for treatment, and possible drug interactions should be considered.     

肠道微生物群对炎症性肠病的影响

古语说,为了解整体首先必须了解其组成部分.这同样适用于对人的胃肠道研究.正如生物学中大多数领域,我们已经积累了关于该系统分化和特异性的大量知识.从大体解剖到分子生物学,我们在组织、细胞和亚细胞水平对于肠道的功能和工作过程有了较为详细的了解.虽然已将现有的遗传调节和生物化学技术应用于人类研究,至今仍然只见树木不见森林.在以宿主为中心的工作重点中,仍然未能充分认识最小组成部分的作用,即我们常驻的微生物.     

Nosocomial infections—A 1980 view: Progress,priorities and prognosis

Following a brief historic perspective, this review highlights the progress that has been made in the field of nosocomial infections in the past decade. Scientific progress has been made in a few efficacy studies, the determinative role of the host, concepts of immunoincompetence, emerging pathogens, such as Legionnella pneumophila, the epidemiology of antimicrobial drug resistance and concepts of chemoprophylaxis. Major advances have been made in preventing a few specific nosocomial infections such as hepatitis B. The evolving roles of infection control practitioners and hospital epidemiologists represent important progress in meeting manpower needs. Major failures of the past decade include the continuing absence of an acceptable scientific basis for infection control, the lack of standards for hospital infection control and the consequent inability to carry out effective education. Major challenges in the 1980s will be to determine what is effective and what is not in infection control activities, and to focus control activities and recommendations more sharply.     

Burden of meningitis and other severe bacterial infections of children in africa: implications for prevention.

Apart from meningococcal disease in the sub-Saharan meningitis belt, the incidence and impact of life-threatening bacterial diseases in children across Africa have not been quantified. The clinical and epidemiological data on pneumococcal, Haemophilus influenzae type b (Hib), and other forms of bacterial meningitis, as well as data on other severe bacterial infections throughout the continent were scrutinized. Pneumococci were the leading causative agents of nonepidemic meningitis and other bacteremic diseases, followed by Hib. Meningococcal diseases were less common. Mortality rates associated with pneumococcal, Hib, and meningococcal meningitis were 549 (45%) of 1211 patients, 389 (29%) of 1352 patients, and 104 (8%) of 1236 patients, respectively; sequelae occurred in 50%, 40%, and 10% of cases. At 0-4 years of age, the estimated incidences of Hib meningitis and all classic Hib diseases were 70 and 100 cases per 100,000 population per year, accounting for approximately 90,000 and 120,000 cases per year, respectively. Including older age groups and, especially, nonbacteremic Hib pneumonia in the estimates of Hib disease in Africa increased the overall numbers manifold; the numbers of pneumococcal infections were even greater. The only realistic way to combat these severe infections efficaciously would be through widespread vaccination, starting with Hib conjugates.     

Prevalence of cryptosporidium among patients with acute enteric infection

Twelve hundred faecal samples from patients suspected of acute enteric infection were examined for Cryptosporidium oocysts by means of a modified Ziehl-Neelsen technique. Smears prepared from the formol-ether sediment of 400 faecal samples were compared with those made directly from faeces. The numbers of positive patients were identical, but the diagnosis was easier to make with smears prepared from sediment. Cryptosporidia were found in 21 samples and after correction for duplicates the net result was 16 cases (2%) of cryptosporidiosis diagnosed among 800 patients. Except in one case Cryptosporidium was the only pathogen found. Fourteen patients had diarrhoea while excreting the parasite. All the patients recovered spontaneously within 3 weeks. Nine of them had recently travelled abroad; for three others, infected calves may possibly have been the source of infection. Carriers were not found among 120 persons without gastro-intestinal symptoms.     

Sexually transmitted enteric and rectal infections in homosexual men

Intestinal infections represent a major health problem in homosexual men. The spectrum of potential pathogens includes classic sexually transmitted pathogens, enteric bacterial and protozoan pathogens, and a wide range of opportunistic infections seen in patients with human immunodeficiency virus (HIV) infections. Diagnosis and treatment of these infections must be comprehensive, including a full microbiologic evaluation, assessment of the immuno-competence of the patient, and repeat examination following completion of therapy.