Iatrogenic prion infection.
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Biomedical subjects
Publications and source records attributed to I F Laurenson.
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A HIV-positive patient presented with cryptococcal meningitis that was not detected by cerebrospinal fluid (CSF) latex antigen and direct microscopy. The diagnosis was confirmed by culture of the CSF and subsequent urine culture, both of which yielded an apparently acapsular strain of Cryptococcus neoformans. After 19 months the patient relapsed and capsulated yeasts were observed on this occasion on direct microscopy of the CSF. The latex antigen test was strongly positive. Culture again yielded an apparently acapsular isolate. Retrospective culture of all isolates obtained from this patient in sterile CSF resulted in the formation of capsules. This was confirmed by the requirement of normal non heat inactivated serum for neutrophil-cryptococcus attachment to occur in vitro. Although antigen and direct microscopy are frequently relied upon to diagnose cryptococcal meningitis, a negative result does not exclude the condition.
An open-label, randomized, controlled trial was used to compare the safety and efficacy of intramuscular artemether (a loading dose of 3.2 mg/kg, followed by 1.6 mg/kg daily for 4 days) and intravenous quinine (a loading dose of 20 mg quinine dihydrochloride/kg, followed first by 10 mg/kg every 8 h, each injection taking 4 h, for at least 48 h, and then oral quinine for a total of 7 days) in the management of strictly defined severe/complicated malaria in Melanesian adults. Four (12%) of the 33 patients who enrolled and completed follow-up died (one of the 15 who received artemether and three of the 18 who received quinine). Overall, cerebral malaria was uncommon (6%) whilst jaundice was common (76%). The time taken to clear 50% of parasites was less in those treated with artemether (median = 8 h; range = 2-24 h) than in the patients given quinine (median = 14 h; range = 2-25 h; P = 0.05). Temperature defervescence was also quicker in those treated with artemether (median = 32 hours; range = 20-112 h) than in those in the quinine group (median = 48 h; range = 28-88 h; P = 0.034). Hypoglycaemia was not observed in any patient treated with artemether but complicated therapy in 11 (79%) of the 14 patients given quinine who had not had pre-treatment spontaneous hypoglycaemia. No serious adverse effects were attributable to artemether. The Plasmodium falciparum infections observed during the 1 month of follow-up, in three patients who had received artemether and two who had been given quinine, were probably due to recrudescence. Plasmodium vivax parasitaemias were also observed during follow-up, in one or two patients in each treatment group. Artemether appears safe in Melanesian adults and is probably as effective as intravenous quinine in the treatment of severe or complicated falciparum malaria.
Severe falciparum malaria usually occurs in children, but also occurs in nonimmune migrants or partially immune adults in areas of unstable transmission. We have studied prospectively 70 adult patients with strictly defined severe malaria from the south coast of Papua New Guinea where malaria transmission is not intense. Only 19 (27.1%) were migrants from areas where malaria transmission does not occur; many other patients were periurban dwellers who had become infected after visits to their home villages. The most common clinical features were jaundice or hepatic dysfunction, impaired consciousness, renal failure, cerebral malaria, and anemia. Hypoglycemia was common following treatment with quinine. The overall case fatality rate was 18.6%; renal failure and cerebral malaria in particular were associated with a poor outcome. Reduction in mortality might be achieved by aggressive therapy of renal failure with earlier institution of dialysis; the use of preventive measures for immigrants or urban dwellers returning to high transmission areas might reduce the incidence of this dangerous disease.
The case records of 23 patients who presented over a 5-year period with a diagnosis of pyogenic liver abscess were reviewed. Ascending cholangitis was implicated in nine cases, seven of which were associated with underlying malignancy. Haematogenous spread via the portal route accounted for five cases. Primary treatment included percutaneous abscess drainage in 15 patients. Whereas nine of the 11 patients with benign underlying pathology were managed successfully, the four with malignant biliary obstruction did not survive. Only one of the 23 patients who presented with hepatic abscess required surgical intervention. Percutaneous abscess drainage combined with appropriate antibiotic therapy is an effective means of managing hepatic abscess, but there remains a substantial overall mortality rate resulting from the increasing incidence of malignant biliary obstruction as a cause of this condition.
One hundred sixty-six patients with enzyme immunoassay-proven bites by taipans (Oxyuranus scutellatus canni) were studied in Port Moresby, Papua New Guinea. One hundred thirty-nine (84%) showed clinical evidence of envenoming: local signs were trivial, but most developed hemostatic disorders and neurotoxicity. The blood of 77% of the patients was incoagulable and 35% bled spontaneously, usually from the gums. Fifty-one per cent had microscopic hematuria. Neurotoxic signs (ptosis, ophthalmoplegia, bulbar paralysis, and peripheral muscular weakness) developed in 85%. Endotracheal intubation was required in 42% and mechanical ventilation in 37%. Electrocardiographic abnormalities (sinus bradycardia and septal T wave inversion) were found in 52% of a group of 69 unselected patients. Specific antivenom raised against Australian taipan venom was effective in stopping spontaneous systemic bleeding and restoring blood coagulability but, in most cases, it neither reversed nor prevented the evolution of paralysis even when given within a few hours of the bite. However, early antivenom treatment was associated statistically with decreased incidence and severity of neurotoxic signs. The low case fatality rate of 4.3% is attributable mainly to the use of mechanical ventilation, a technique rarely available in Papua New Guinea. Earlier use of increased doses of antivenoms of improved specificity might prove more effective.
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To determine if reactive oxygen metabolites have a pathogenic role in Helicobacter pylori (H pylori) related gastroduodenal disease, this study measured their production in antral mucosal biopsy specimens. Two related chemiluminescence techniques were used comparing H pylori positive (n = 105) and negative patients (n = 64) with a similar spectrum of macroscopic disease. After chemiluminescence assays, biopsy specimens were graded histologically. Increased luminol dependent chemiluminescence (detecting reactive oxygen metabolites through peroxidase catalysed reactions) was found in H pylori positive patients (median photon emission = 6.4 x 10(3)/min/mg wet weight (95% confidence intervals 3.6 to 9.9)) but not H pylori negative cases (-0.9 (-1.3 to -0.6)) (p = 0.0001). Similar results were found using lucigenin (which reacts directly with oxygen metabolites, particularly superoxide): (H pylori positive 0.9 (0.1 to 3.2); H pylori negative -1.2 (-3.4 to -0.6)) (p = 0.0003). Chemiluminescence was greater in H pylori positive compared with negative tissue when samples were grouped by equivalent macroscopic or microscopic damage. This difference was in part accounted for by a greater neutrophil infiltration in the H pylori positive mucosa, but when biopsy specimens with equivalent neutrophil infiltration could be compared directly, positive specimens gave greater chemiluminescence than negative. Smoking, drugs, and alcohol consumption had no independent effect. It is concluded that excess mucosal reactive oxygen metabolite production is associated with H pylori gastric antral infection and may be an important pathogenic mechanism. There is no evidence for reactive oxygen metabolite participation in the pathogenesis of gastric mucosal injury in cases unrelated to H pylori infection.
Raised circulating von Willebrand factor is a recognised marker of vascular injury. To evaluate the role of vascular injury in the pathogenesis of inflammatory bowel disease, serum von Willebrand factor in Crohn's disease, ulcerative colitis, confirmed bacterial diarrhoea, and healthy subjects was measured. von Willebrand factor values were raised in 9/14 patients (p = 0.007) with active Crohn's disease, 15/28 (p = 0.0004) with inactive Crohn's disease, 16/23 (p = 0.0003) with active ulcerative colitis, 9/27 (p = 0.04) with inactive ulcerative colitis, and 15/17 (p = 0.0001) patients with bacterial diarrhoea. Serum von Willebrand factor was unrelated to disease activity in Crohn's disease but was significantly raised in active (p = 0.02) compared with inactive ulcerative colitis. In contrast to controls, the detection of von Willebrand factor from inflammatory bowel disease sera and that from fractured endothelial cells was significantly inhibited by the reducing agent, dithiothreitol, suggesting the presence of an additional dithiothreitol sensitive form of the molecule derived from injured endothelial cells in inflammatory bowel disease. That serum von Willebrand factor is raised in quiescent as well as active Crohn's disease is compatible with the proposal that vascular injury is a fundamental abnormality in this disorder. The raised von Willebrand factor values in active inflammatory bowel disease and bacterial diarrhoea could be caused by either vascular injury, occurring secondary to bowel inflammation, or to an acute phase response resulting from endothelial cell stimulation by mediators released during the inflammatory process. Raised circulating von Willebrand factor could contribute to the increased risk of thrombosis associated with active inflammatory bowel disease.
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Eleven cases of cryptococcal meningitis were diagnosed and biotyped from September 1991 to August 1992 in Papua New Guinea (PNG). Seven isolates were Cryptococcus neoformans var. gattii from paediatric and adult patients, one with diabetes mellitus and 4 were C. neoformans var. neoformans from adults, of whom 2 had human immunodeficiency virus type 1 (HIV-1) infection, and one each had tuberculosis and Plasmodium vivax malaria. Significant clinical findings were headache, fever, meningism, vomiting, photophobia, papilloedema and cranial nerve lesions. Five patients (45.5%) died; 3 of these were adults with var. gattii and 2 were men with both var. neoformans and HIV-1 infections. This prospective tropical study documents the emergence of C. neoformans var. neoformans in patients with HIV-1 infection in a country where previously var. gattii had predominated in the immunocompetent. There has been no earlier report of cryptococcosis in an HIV-1 seropositive patient in PNG. Despite presumed exposure to both varieties of C. neoformans, var. gattii infections had been most frequent. As HIV-1 spreads, the proportion of hosts infected with var. neoformans may rise. The course of meningitis caused by the 2 varieties of C. neoformans may differ, with mortality in the tropics remaining particularly high. In PNG the environmental source of C. neoformans remains elusive.
Envenoming by a number of species of snake may affect the myocardium or cause electrocardiographic changes; several different mechanisms have been proposed. In a prospective study of snake bite in Papua New Guinea, electrocardiographic changes were observed in 36 of 69 patients (52%) envenomed by the taipan (Oxyuranus scutellatus), 2 of 6 (33%) envenomed by death adders (Acanthophis sp.) and one envenomed by the brown snake (Pseudonaja textilis). Septal T wave inversion and bradycardias, including atrioventricular block, were the commonest abnormalities. There was no haemodynamic deterioration. The cause of these changes is uncertain; only 2 of 24 patients (8.3%) with electrocardiographic changes had markedly elevated plasma concentrations of cardiac troponin T, a sensitive and specific marker of myocardial damage. This suggests that myocardial damage is uncommon following bites by these species. Electrocardiographic abnormalities are most likely to have been caused by a direct toxic effect of a venom component upon cardiac myocyte function; in taipan bites, taicatoxin, a calcium channel blocker, might be responsible.
Around Port Moresby, Papua New Guinea (PNG), the annual incidence of cryptococcal meningitis is estimated to be up to 42.8 per million population; Cryptococcus neoformans var. gattii is the predominant causative agent. In Australia and California, environmental isolations have established an ecological association of C. neoformans var. gattii with Eucalyptus camaldulensis, E. tereticornis, and more recently E. rudis and E. gomphcephala. In PNG few E. camaldulensis survive experimental planting, E. tereticornis is endemic and there are no records of planting of the non-endemic E. rudis and E. gomphcephela. Despite extensive sampling of eucalypt-associated and other sources, we were unable to identify the ecological niche of C. neoformans var. gattii and neoformans in this region.
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