Safety and Reactogenicity of Canarypox ALVAC-HIV (vCP1521) and HIV-1 gp120 AIDSVAX B/E Vaccination in an Efficacy Trial in Thailand

A prime-boost vaccination regimen with ALVAC-HIV (vCP1521) administered intramuscularly at 0, 4, 12, and 24 weeks and gp120 AIDSVAX B/E at 12 and 24 weeks demonstrated modest efficacy of 31.2% for prevention of HIV acquisition in HIV-uninfected adults participating in a community-based efficacy trial in Thailand.Reactogenicity was recorded for 3 days following vaccination. Adverse events were monitored every 6 months for 3.5 years, during which pregnancy outcomes were recorded. Of the 16,402 volunteers, 69% of the participants reported an adverse event any time after the first dose. Only 32.9% experienced an AE within 30 days following any vaccination. Overall adverse event rates and attribution of relatedness did not differ between groups. The frequency of serious adverse events was similar in vaccine (14.3%) and placebo (14.9%) recipients (p = 0.33). None of the 160 deaths (85 in vaccine and 75 in placebo recipients, p = 0.43) was assessed as related to vaccine. The most common cause of death was trauma or traffic accident. Approximately 30% of female participants reported a pregnancy during the study. Abnormal pregnancy outcomes were experienced in 17.1% of vaccine and 14.6% (p = 0.13) of placebo recipients. When the conception occurred within 3 months (estimated) of a vaccination, the majority of these abnormal outcomes were spontaneous or elective abortions among 22.2% and 15.3% of vaccine and placebo pregnant recipients, respectively (p = 0.08). Local reactions occurred in 88.0% of vaccine and 61.0% of placebo recipients (p<0.001) and were more frequent after ALVAC-HIV than AIDSVAX B/E vaccination. Systemic reactions were more frequent in vaccine than placebo recipients (77.2% vs. 59.8%, p<0.001). Local and systemic reactions were mostly mild to moderate, resolving within 3 days.The ALVAC-HIV and AIDSVAX B/E vaccine regimen was found to be safe, well tolerated and suitable for potential large-scale use in Thailand.ClinicalTrials.govNCT00223080

Lung flukes (paragonimiasis)

Paragonimiasis is an infection by flukes of the genus Paragonimus, with foci of disease in Asia, Africa, and Central and South America. Humans acquire infection by eating metacercariae in improperly cooked freshwater crabs or crayfish. Acute inflammatory and allergic symptoms are rarely serious and usually resolve spontaneously. Chronic manifestations may be (1) pulmonary—most remarkably with a chronic, productive cough with jam-like, brownish-red sputum; and (2) extrapulmonary—most importantly in the central nervous system, often presenting with seizures. Diagnosis is by demonstrating ova in sputum, stool, or pleural fluid. Serology can be used to support the diagnosis, especially in extrapulmonary paragonimiasis. Treatment with praziquantel is almost always effective. Prevention is by health education and the mass treatment of infected people in an endemic area....</p

Therapeutic effects of antivenom supplemented by antithrombin III in rats experimentally envenomated with Russell's viper (Daboia russelli siamensis) venom

The effects of equine antivenom and antithrombin III (AT-III) on the coagulopathy induced by Russell's viper venom (RVV, Daboia russelli siamensis) were investigated in the rat. After taking blood samples from the femoral vein for determination of simple blood clotting time and AT-III activity, all anaesthetized rats received an intramuscular injection of venom (2 micrograms/g). Treatment (antivenom or AT-III or both) was given intravenously through another femoral vein 30 min after venom injection. All untreated rats (n = 7) developed AT-III depletion (< 70%) [mean (S.D.)] 70 (36) min, and incoagulable blood 85 (53) min after venom injection. Supplementation with AT-III (either 0.25 U/g or 0.5 U/g) had no effect on the RVV induced coagulopathy (n = 20). Treatment with antivenom alone (10 micrograms/g) reduced the incidence of abnormal clotting significantly (8/15, 53%) (P = 0.03). When antivenom was given in combination with AT-III (0.5 U/g), abnormal clotting was prevented in all but one animal (1/15, 7%) (P = 0.007). AT-III activity declined progressively in all rats which developed non-clotting blood. These results suggest that coagulopathy in Russell's viper envenoming is associated with activation of coagulation and consumption of AT-III. Antivenom can prevent coagulopathy, but its neutralizing activity is augmented significantly by AT-III supplementation

Therapeutic Responses to Different Antimalarial Drugs in Vivax Malaria

ABSTRACT The therapeutic responses to the eight most widely used antimalarial drugs were assessed in 207 adult patients with Plasmodium vivax malaria. This parasite does not cause marked sequestration, so parasite clearance can be used as a direct measure of antimalarial activity. The activities of these drugs in descending order were artesunate, artemether, chloroquine, mefloquine, quinine, halofantrine, primaquine, and pyrimethamine-sulfadoxine (PS). Therapeutic responses to PS were poor; parasitemias did not clear in 5 of the 12 PS-treated patients, whereas all the other patients made an initial recovery. Of 166 patients monitored for ≥28 days, 35% had reappearance of vivax malaria 11 to 65 days later and 7% developed falciparum malaria 5 to 21 days after the start of treatment. There were no significant differences in the times taken for vivax malaria reappearance among the different groups except for those given mefloquine and chloroquine, in which all vivax malaria reappearances developed &gt;28 days after treatment, suggesting suppression of the first relapse by these slowly eliminated drugs. There was no evidence of chloroquine resistance. The antimalarial drugs vary considerably in their intrinsic activities and stage specificities of action. </jats:p