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.

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.

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.