Paranoid psychosis related to mefloquine antimalarial prophylaxis.

Mefloquine is an important antimalarial drug for treatment and prophylaxis of chloroquine-resistant malaria. Its use has been associated with neuropsychiatric side-effects. We report a case of paranoid psychosis associated with mefloquine occurring in a remote part of Papua New Guinea. Adverse reactions and contraindications are discussed. This case underlines the importance of awareness of neuropsychiatric side-effects with mefloquine use and of taking a careful psychiatric history before prescribing mefloquine.

Randomized comparison of intramuscular artemether and intravenous quinine in adult, Melanesian patients with severe or complicated, Plasmodium falciparum malaria in Papua New Guinea.

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.

Cell-mediated immunity in HIV seronegative patients recovered from Cryptococcus neoformans var. gattii meningitis.

Cell-mediated immunity was assessed in 37 HIV seronegative healthy patients cured of Cryptococcus neoformans var. gattii meningitis and compared with matched controls using a multitest device which simultaneously injects seven standardized common antigens intradermally. Responses in patients and controls were similar: however, male patients had significantly higher compound (average) scores than controls (P = 0.041). Male scores were higher than female scores in both patient (P = 0.002) and control (P = 0.017) groups. In eight patients with acute cryptococcal meningitis, seven were anergic to challenge with 5 IU of tuberculin on admission. Two of these patients had positive reactions after treatment. Three of four patients tested prior to treatment with the multitest device were anergic to all seven antigens but all three survivors showed improved responsiveness following cure. These data suggest that patients are immunosuppressed on presentation (due to overwhelming var. gattii infection) but that following cure, cell-mediated immunity improves to its premorbid state. A transient state of immunosuppression prior to the development of the disease cannot be excluded.

The effect of corticosteroids on visual loss in Cryptococcus neoformans var. gattii meningitis.

In Papua New Guinea visual loss is a frequent sequal to Cryptococcus neoformans var. gattii meningitis in immunocompetent patients. We have previously postulated that visual loss may occur as a result of the immunological response to infection around the optic nerve. This retrospective study set out to explore the effect of corticosteroids on visual outcome. Sixteen patients received varying doses of corticosteroid (mainly 100-250 mg of hydrocortisone daily for the prevention of febrile reactions to amphotericin) and 10 received anticryptococcal therapy alone. Visual deterioration occurred less frequently in those treated with corticosteroids (2/16 [12.5%] vs. 7/10 [70%], P = 0.007), blindness was less frequent (1/16 [5.3%] vs. 5/10 [50%], P = 0.018), and in 3 patients vision improved. Corticosteroids may have a role in preventing or halting visual loss in C. neoformans var. gattii meningitis in immunocompetent patients.

Visual loss in immunocompetent patients with Cryptococcus neoformans var. gattii meningitis.

In Papua New Guinea cryptococcal meningitis occurs predominantly in immunocompetent patients in whom Cryptococcus neoformans var, gattii is implicated in 95% of cases. Ocular complications are common. We have reviewed ophthalmic findings in 82 immunocompetent patients and have attempted to identify those features of the disease that predict an unfavourable visual outcome. Visual loss occurred in 52.6% of survivors and was associated with optic atrophy following optic disc swelling in 60.9%. Progression of disc swelling to optic atrophy was predicted by the presence of an abducens palsy (P = 0.049) and cerebrospinal fluid (CSF) cryptococcal antigen titres > 1:1024 (P = 0.036). Raised intracranial pressure (defined as opening CSF pressure > or = 300 mm on admission) was not associated with visual loss. Vision deteriorated in 17.3% of patients despite anticryptococcal therapy and in 3.7% it followed curative therapy. The high rate of visual loss in immunocompetent patients with C. neoformans var. gattii infection contrasts with others' experience of immunosuppressed patients with C. neoformans var. neoformans infection, in whom visual loss was rare. This difference may reflect immune mediated optic nerve dysfunction in C. neoformans var. gattii meningitis caused by either compression due to arachnoid adhesions or oedema and inflammatory cell-mediated damage.

Electrocardiographic abnormalities in patients bitten by taipans (Oxyuranus scutellatus canni) and other elapid snakes in Papua New Guinea.

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.

Cryptococcus neoformans in Papua New Guinea: a common pathogen but an elusive source.

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.

Symptomatic human immunodeficiency virus (HIV) infection in Papua New Guinea.

BACKGROUND: Human Immunodeficiency Virus (HIV) infection was first detected in Papua New Guinea (PNG) in 1987. By August 1995 a total of 323 persons had been diagnosed as HIV antibody positive nationwide and seroprevalence rates were climbing. This study was prompted by a lack of data on the clinical syndromes associated with HIV infection in Melanesian adults. AIMS: To describe the clinical and epidemiological features of symptomatic HIV infection in adult Melanesians. METHODS: A largely retrospective study of patients was admitted to the medical wards of the Port Moresby general hospital between January 1990 and September 1995. Clinical records of patients with antibody to HIV were studied and clinical, laboratory and epidemiological data were recorded. RESULTS: Seventy patients were studied and the majority were young, urban dwelling adults from a variety of social groups. The sex distribution was even. Common clinical syndromes associated with HIV infection were chronic diarrhoea (47.8%), wasting (94.2%) and oropharyngeal candidiasis (68.7%). Tuberculosis was suspected in 68.6% and cryptococcal meningitis was detected in 8.6% including one patient with Cryptococcus. neoformans var. gattii infection. There was a high mortality (53%) in patients admitted to hospital. CONCLUSIONS: Patients with HIV infection in PNG present to hospital late in their disease course. Clinical syndromes are similar to those observed in Africa and mortality on first admission is high. The major mode of transmission is heterosexual and sexually transmitted diseases and promiscuity are probably important factors in facilitating spread.

Clinical manifestations of HIV infection in Melanesian adults.

PIP: By mid-1995, a total of 308 HIV cases had been reported in Papua New Guinea. The majority (74%) of these cases were diagnosed in Port Moresby. This article describes the clinical characteristics of HIV infection in 67 adults who presented to Port Moresby General Hospital in 1990-95. The median age at presentation was 27 years in men and 28 years in women, with an equal distribution of cases by sex. The major presenting symptoms were wasting and weight loss exceeding 10% of body weight (94%), chronic diarrhea (47%), prolonged fever (77%), and oropharyngeal candidiasis (66%). Pulmonary tuberculosis was diagnosed on the basis of chest X-ray and history in 37 patients (56%), but only 3 had sputum positive for acid-fast bacilli. Anemia was present in 75%. 65 patients (97%) fulfilled the World Health Organization criteria for AIDS. The inpatient mortality rate in this series was 43%, and 13 of these 29 patients died within a month of their first presentation.^ieng

Severe and complicated falciparum malaria in Melanesian adults in Papua New Guinea.

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.

Predictors of outcome in Cryptococcus neoformans var. gattii meningitis.

In Papua New Guinea, Cryptococcus neoformans var. gattii meningitis has a high fatality rate even in immunocompetent patients. Our retrospective study attempted to identify marker of poor prognosis. Of 88 immunocompetent patients, 30 (34.1%) died, usually soon after admission, and mortality was higher in men (p = 0.025) and older patients (p = 0.039). Death was associated with altered consciousness (p < 0.001), a history of convulsions prior to treatment (p = 0.002) and a maximum systolic blood pressure of > 150 mmHg (p = 0.017). These data suggest that death results from raised intracranial pressure and subsequent tentorial herniation. However, CSF opening pressure measured on admission was raised in 29/36 (81%) patients and did not predict outcome. In survivors, relapse was uncommon and was not predicted by discharge serum cryptococcal antigen titres, which were frequently raised on completion of therapy in asymptomatic patients. Mortality may be reduced if efforts are made to lower intracranial pressure in those patients who present with markers of poor prognosis.

Meningitis caused by Cryptococcus neoformans var. gattii and var. neoformans in Papua New Guinea.

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.

Neurotoxicity, anticoagulant activity and evidence of rhabdomyolysis in patients bitten by death adders (Acanthophis sp.) in southern Papua New Guinea.

Thirty-two patients with enzyme-immunoassay-proven death adder (Acanthophis sp.) bites were studied in Port Moresby, Papua New Guinea. Eighteen were envenomed; local signs were rare and none had incoagulable blood, but all except one had signs of neurotoxicity. Five (27.7%) envenomed patients required intubation and ventilation. One patient developed renal failure, previously undescribed following death adder bites. Laboratory investigations showed mild prolongation of prothrombin and partial thromboplastin times in some patients. In vitro studies showed that the venom contains anticoagulant activity, but does not cause fibrinogenolysis. In contrast to taipan envenoming, neurotoxicity did not progress after antivenom administration, and there was reversal of neurotoxicity, evident within 6 h, in three severely envenomed patients treated less than 12 h after the bite. One patient treated with antivenom and anticholinesterases had the most dramatic response to treatment; the optimum management of bites by this species may include prompt treatment with both antivenom and anticholinesterases in addition to effective first aid.

Neuromuscular effects of Papuan Taipan snake venom.

Snakebite is a cause of significant morbidity in Central Province, Papua New Guinea. Three adult patients with clinical evidence of neurotoxicity following envenomation by the Papuan taipan had serial neurophysiological examinations over the course of their subsequent hospitalization. All required artificial ventilation for 2.5 to 5 days. The compound muscle action potential (CMAP) amplitudes declined over the first 2 to 4 days after envenoming and then gradually increased in parallel with clinical recovery. Repetitive stimulation studies revealed a distinctive pattern of abnormality. Activation resulted in brief potentiation of the CMAP followed by significantly greater decrement than observed at rest. This effect lasted up to 30 minutes and was not altered after intravenous edrophonium. Single-fiber electromyographic recordings during the recovery phase of the illness were abnormal with marked blocking and increased jitter. All patients were able to return home.

Electrophysiological findings in patients envenomed following the bite of a Papuan taipan (Oxyuranus scutellatus canni).

Electrophysiological studies were done on patients with systemic neurotoxicity following the bite of a Papuan taipan (Oxyuranus scutellatus canni). Evoked compound muscle action potentials decreased and increased in tandem with clinical deterioration and recovery. Nerve conduction velocities did not change in envenomed patients and were consistent with control studies. Repetitive nerve stimulation studies showed decremental responses in envenomed patients with post-tetanic potentiation followed by post-tetanic exhaustion. The findings are consistent with studies in vitro which suggested that the major action of neurotoxins in Australian taipan venom is at the synapse. The observation that electrophysiological data correlate closely with the clinical condition of the patient has potential application in the assessment of interventions in the management of snake bite victims.

Failure of 3,4-diaminopyridine and edrophonium to produce significant clinical benefit in neurotoxicity following the bite of Papuan taipan (Oxyuranus scutellatus canni).

Progressive systemic neurotoxicity is a common feature in patients envenomed following the bite of a Papuan taipan (Oxyuranus scutellatus canni). Respiratory paralysis, which commonly results, accounts for considerable morbidity and mortality. Established neurotoxicity does not respond to antivenom. In this study, a combination of clinical and electrophysiological variables was used to assess the effect of edrophonium and 3,4-diaminopyridine in patients with significant neurotoxicity. Both drugs produced minor electrophysiological and clinical changes in envenomed patients. This effect was maximal when the 2 drugs were used in combination, but was insufficient to be of significant clinical benefit. Neither drug can be recommended for use in the management of Papuan taipan bite.

Snake bites by the Papuan taipan (Oxyuranus scutellatus canni): paralysis, hemostatic and electrocardiographic abnormalities, and effects of antivenom.

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.

Venom detection kits in the management of snakebite in Central province, Papua New Guinea.

The bites of six species of venomous elapid snakes in Central Province Papua New Guinea produce similar clinical syndromes. Optimal management of envenomed patients involves the use of monospecific antivenom. In this study, Venom Detection Kits (VDKs) (CSL Diagnostics, Melbourne) were used to try to make a specific diagnosis in envenomed patients at their admission. VDKs detected venom in admission bite site swabs from 39 to 46 patients (85%). Thirty-eight of these patients were shown to have been bitten by taipans. In all cases where venom was detected by the VDK, this correlated with subsequent laboratory enzyme immunoassay results. Selective use of VDKs in Central Province could allow more widespread use of monospecific antivenoms and produce considerable financial savings.

The efficacy of antivenom in the treatment of bites by the Papuan taipan (Oxyuranus scutellatus canni).

A prospective series of 156 patients systemically envenomed following the bite of a Papuan taipan (Oxyuranus scutellatus canni) were studied. All patients were treated with appropriate antivenom and clinical course and outcome were compared. The proportion of patients requiring intubation was significantly smaller, and the time to resolution of neurotoxicity and discharge from hospital significantly shorter, in patients receiving antivenom no more than 4 h after the bite. No significant difference in outcome was demonstrated between patients receiving antivenom at various times after 4 h. No difference was demonstrated in the times to restoration of coagulability between the 2 groups. The only significant difference between a small number of patients given 2 vials of antivenom and patients given a single vial at the same time after envenoming was a marginally shorter duration of intubation in those who required it. The study suggests that, to achieve significant clinical benefit in Papuan taipan bite, antivenom must be given as early as possible.

The epidemiology of snake bite in Central Province and National Capital District, Papua New Guinea.

Snake bite is an important medical problem in some areas of Papua New Guinea and appears to be most common in the Central Province and National Capital District. The overall incidence for Central Province is 215.5 per 100,000 population, but Kairuku subprovince has an incidence of 526 per 100,000, which is amongst the highest in the world. The clinical pattern of envenoming also varies within the Province, suggesting that different species of snake may be responsible for bites in different areas. Most envenomed patients are bitten during daylight on the lower limb and are rarely able to describe the snake. The mortality rate in Central Province is 7.9 per 100,000; most patients die from ventilatory failure due to severe neurotoxicity. Mortality might be reduced by increased use of compression bandaging as a first aid measure, earlier treatment with antivenom and earlier referral to hospital.