Arbovirus isolations from mosquitoes collected during and after the 1982-1983 epizootic of western equine encephalitis in Argentina

Mosquitoes were collected in Santa Fe and Rio Negro provinces, Argentina, in 1982-1983 during a western equine encephalitis (WEE) epizootic. Totals of 153,084 mosquitoes from Santa Fe Province and 484 from Rio Negro Province were tested for virus in 2,351 pools. Seventeen virus strains were isolated, all from Santa Fe collections, as follows: 4 WEE, 6 Venezuelan equine encephalitis, 1 St. Louis encephalitis, 2 Antequera, 1 Maguari, 1 Melao, 1 new vesiculovirus (Calchaqui), and 1 Gamboa. The WEE virus isolates were from Aedes albifasciatus, Anopheles albitarsis, Mansonia species, and Psorophora pallescens. Collections during the spring and summer (1983-1984) following the epizootic yielded 49,707 mosquitoes from Santa Fe, 15,961 from Rio Negro, and 2,019 from Chubut provinces. Twenty-two virus strains were isolated, all from Santa Fe mosquitoes, as follows: 3 strains of SLE virus and 19 strains of Turlock (TUR) virus. All but one of the TUR virus isolates appear to have come from mosquitoes that engorged on a viremic chicken following entry into a bait trap. The vector relationships of each virus isolated during and after the WEE epizootic are discussed.     

Growth characteristics of the chimeric Japanese encephalitis virus vaccine candidate, ChimeriVax-JE (YF/JE SA14--14--2), in Culex tritaeniorhynchus, Aedes albopictus, and Aedes aegypti mosquitoes

The Japanese encephalitis (JE) virus vaccine candidate, ChimeriVax-JE, which consists of a yellow fever (YF) 17D virus backbone containing the prM and E genes from the JE vaccine strain JE SA14--14--2, exhibits restricted replication in non-human primates, producing only a low-level viremia following peripheral inoculation. Although this reduces the likelihood that hematophagous insects could become infected by feeding on a vaccinated host, it is prudent to investigate the replication kinetics of the vaccine virus in mosquito species that are known to vector the viruses from which the chimera is derived. In this study ChimeriVax-JE virus was compared to its parent viruses, as well as to wild-type JE virus, for its ability to replicate in Culex tritaeniorhynchus, Aedes albopictus, and Aedes aegypti mosquitoes. Individual mosquitoes were exposed to the viruses by oral ingestion of a virus-laden blood meal or by intrathoracic (IT) virus inoculation. ChimeriVax-JE virus did not replicate following ingestion by any of the three mosquito species. Additionally, replication was not detected after IT inoculation of ChimeriVax-JE in the primary JE virus vector, Cx. tritaeniorhynchus. ChimeriVax-JE exhibited moderate growth following IT inoculation into Ae. aegypti and Ae. albopictus, reaching titers of 3.6-5.0 log(10) PFU/mosquito. There was no change in the virus genotype associated with replication in mosquitoes. Similar results were observed in mosquitoes of all three species that were IT inoculated or had orally ingested the YF 17D vaccine virus. In contrast, all mosquitoes either IT inoculated with or orally fed wild-type and vaccine JE viruses became infected, reaching maximum titers of 5.4-7.3 log(10) PFU/mosquito. These results indicate that ChimeriVax-JE virus is restricted in its ability to infect and replicate in these mosquito vectors. The low viremia caused by ChimeriVax-JE in primates and poor infectivity for mosquitoes are safeguards against secondary spread of the vaccine virus.     

Use of cyclical etidronate and prevention of non-vertebral fractures

This study examined the effects of cyclical etidronate, when used in routine clinical practice, on the prevention of fracture. Information was obtained from 550 general practices in the UK that provide their medical records to the General Practice Research Database. A total of 7977 patients taking cyclical etidronate treatment and 7977 age-, sex- and practice-matched control patients with a diagnosis of osteoporosis were analysed. People taking cyclical etidronate had a significantly reduced risk of non-vertebral fracture (by 20%) and of hip fracture (by 34%) relative to the osteoporosis control patients. The relative risk of non-vertebral fracture was 0.80 (95% confidence interval 0.70-0.92), that of hip fracture 0.66 (0.51-0.85) and that of wrist fracture 0.81 (0.58-1.14). When fracture incidence rates were compared between the two groups, the rate of non-vertebral, hip and wrist fracture decreased significantly (P < 0.05) with increasing etidronate exposure. The results of this study complement and extend clinical observations supporting the anti-fracture efficacy of cyclical etidronate therapy.      

Clonal diseases of large granular lymphocytes [see comments]

Three distinct clinical syndromes occur in patients with increased numbers of circulating LGL. Patients with T-LGL leukemia have clonal proliferations of CD3+ LGL typically associated with chronic neutropenia and autoimmune features. NK-LGL leukemia is characterized by clonal CD3- LGL proliferation with an acute clinical presentation marked by massive hepatosplenomegaly and systemic illness. However, most patients with increased numbers of CD3- LGL do not have clinical features of NK-LGL leukemia and have a chronic clinical course. X- linked gene analyses have supported a polyclonal LGL lymphocytosis in this syndrome. Further studies are needed to determine whether clonal progression can occur in these patients.     

Prevention of degradation of human polymorphonuclear leukocyte proteins by diisopropylfluorophosphate

Proteases can complicate the characterization of proteins from cells, especially human polymorphonuclear leukocytes (PMN), which contain abundant neutral proteases. We tested the ability of agents to inhibit proteolysis, with special reference to the subunit polypeptides of the contractile proteins actin, myosin, and actin-binding protein (ABP). Phenylmethylsulfonyl fluoride (PMSF), O-phenanthroline, EGTA, EDTA, N- ethylmaleimide, alone or in combinations, failed to prevent extensive proteolysis of the PMN proteins during solubilization of cells with dodecyl sulfate. These inhibitors and also alpha-1-antitrypsin and soybean trypsin inhibitor similarly could not prevent proteolysis during homogenization of cells in cold isosomolar sucrose. Treatment of PMN with greater than or equal to mM diisopropylfluorophosphate (DFP) prior to solubilization or homogenization markedly inhibited proteolysis. PMSF and DFP were equally effective in inhibiting proteolysis in PMN extracts, suggesting that the efficacy of DFP may result from its permeation of intact cells and granules before barriers are disrupted by detergents or homogenization. Treatment of PMN with DFP under conditions inhibiting proteolysis did not affect their rate of phagocytosis. We recommend the use of DFP in future studies correlating functions and protein structure of PMN.     

Emergency embolization of spontaneous ruptured hepatocellular carcinoma: Correlation between survival and Child−Pugh classification

From February 1994 to April 2000, 29 emergency gelfoam embolizations for spontaneous ruptured hepatocellular carcinoma (HCC) performed in 28 patients were retrospectively reviewed. There were 11 patients in Child's A , 11 in Child's B and six in Child's C classification of cirrhosis. The duration of the procedure, artery embolized and complications were reviewed, and the Child?Pugh classification of each patient was correlated with their mean survival period. Embolization was done in 12 right hepatic arteries, two left hepatic arteries and 15 proper hepatic arteries. In one patient, the left hepatic artery was embolized initially but the proper hepatic artery was also embolized because another subcapsular liver tumour was found after reviewing the preangiogram CT scan. The entire procedure took 40?170 min (mean = 86 min) with no periprocedural complication. Following embolization, the mean survival period for Child's A class was 218.3 days, Child's B class was 83.4 days and Child's C class was 11.0 days. Transcatheter embolization is an effective treatment to arrest bleeding in spontaneous ruptured HCC. Patients with Child's A class cirrhosis have the longest survival. Selective embolization of either the right or the left hepatic artery alone carries the potential risk of missing multifocal HCC that might not be easily appreciated during angiography.     

17D yellow fever vaccines: new insights. A report of a workshop held during the World Congress on medicine and health in the tropics, Marseille, France, Monday 12 September 2005

Yellow fever (YF) is a major health problem in endemic regions of Africa and South America. It also poses a serious health risk to travellers to areas with endemic disease. Currently, there is no effective drug treatment for YF; however, 17D YF vaccines have demonstrated high rates of effectiveness and good safety profiles. This workshop was organized to review key data and issues about YF disease and currently available 17D YF vaccines. Starting with an overview of the current disease epidemiology in Africa and South America and a review of the safety data of 17D YF vaccines, data were then presented demonstrating the genetic stability of multiple production lots of a 17D YF vaccine, the immunological responses of healthy subjects post-vaccination and the long-term immunogenicity of 17D YF vaccines. Finally, the findings of the molecular characterization of 17D YF virus sub-strains recovered from rare, fatal cases of post-vaccination serious adverse events were presented. There was unanimous agreement that current 17D YF vaccines have a highly favourable benefit-risk profile when used in persons at risk of exposure to the YF virus, and that appropriate use of 17D YF vaccines will minimize the occurrence of serious adverse events post-vaccination.     

OFLOXACIN VERSUS TRIMETHOPRIM AND CO-TRIMOXAZOLE IN THE TREATMENT OF UNCOMPLICATED URINARY TRACT INFECTION IN GENERAL PRACTICE

A large-scale, randomised, multicentre single-blind clinical trial was conducted to assess the comparative efficacy and tolerance of ofloxacin, trimethoprim and co-trimoxazole in the treatment of uncomplicated urinary tract infection in general practice. A total of 1,069 patients from 76 centres across the UK were enrolled in the study, and randomised to one of the following treatment groups: ofloxacin (200 mg od), trimethoprim (200 mg bd) or co-trimoxazole (trimethoprim 160 mg and sulphamethoxazole 800 mg bd). Each patient received five days of medication. Clinically, ofloxacin was as effective as trimethoprim and co-trimoxazole. However, the bacteriological cure rate was significantly better for ofloxacin, with eradication of the initial causative pathogen by the end of treatment in 92% of patients in the ofloxacin group, compared with 81% for trimethoprim and co-trimoxazole (P = 0.0002). There was also a lower relapse rate for ofloxacin. Ofloxacin was well tolerated: adverse events were reported by 67 (12.4%) patients in the ofloxacin group, compared with 48 (18.7%) patients in the co-trimoxazole group and 37 (13.6%) patients in the trimethoprim group. Ofloxacin can therefore be considered a suitable alternative for the treatment of uncomplicated urinary tract infection.