Cost-effectiveness of artemisinin-naphthoquine versus artemether-lumefantrine for the treatment of uncomplicated malaria in Papua New Guinean children.

BACKGROUND: A recent randomized trial showed that artemisinin-naphthoquine (AN) was non-inferior to artemether-lumefantrine (AL) for falciparum malaria and superior for vivax malaria in young Papua New Guinean children. The aim of this study was to compare the cost-effectiveness of these two regimens. METHODS: An incremental cost-effectiveness analysis was performed using data from 231 children with Plasmodium falciparum and/or Plasmodium vivax infections in an open-label, randomized, parallel-group trial. Recruited children were randomized 1:1 to receive once daily AN for 3 days with water or twice daily AL for 3 days given with fat. World Health Organisation (WHO) definitions were used to determine clinical/parasitological outcomes. The cost of transport between the home and clinic, plus direct health-care costs, served as a basis for determining each regimen's incremental cost per incremental treatment success relative to AL by Day 42 and its cost per life year saved. RESULTS: In the usual care setting, AN was more effective for the treatment of uncomplicated malaria in children aged 0.5-5.9 years. AL and AN were equally efficacious for the treatment of falciparum malaria, however AN had increased anti-malarial treatment costs per patient of $10.46, compared with AL. AN was the most effective regimen for treatment of vivax malaria, but had increased treatment costs of $14.83 per treatment success compared with AL. CONCLUSIONS: Whilst AN has superior overall efficacy for the treatment of uncomplicated malaria in PNG children, AL was the less costly regimen. An indicative extrapolation estimated the cost per life year saved by using AN instead of AL to treat uncomplicated malaria to be $12,165 for girls and $12,469 for boys (discounted), which means AN may not be cost-effective and affordable for PNG at current cost. However, AN may become acceptable should it become WHO prequalified and/or should donated/subsidized drug supply become available.

Atovaquone + proguanil: new preparation. Second-line antimalarial combination.

(1) Quinine, halofantrine and mefloquine are effective treatments for most cases of uncomplicated Plasmodium falciparum malaria. (2) The choice of drug for prevention of P. falciparum malaria in highly endemic regions depends on the risk of chloroquine resistance, and possibly mefloquine resistance. The reference treatments are the chloroquine + proguanil combination, and mefloquine. (3) Marketing authorisation has been granted in France for the atovaquone + proguanil combination, in curative and preventive treatment of P. falciparum malaria. (4) The efficacy of the atovaquone + proguanil combination in uncomplicated malaria is similar to that of other treatments. Some strains of malaria seem to have reduced sensitivity. (5) The atovaquone + proguanil combination is also effective as prophylaxis, but there are no clinical trials showing whether it is equivalent to or better than other preventive treatments in non immune travellers. (6) According to the French licensing terms, atovaquone + proguanil prophylaxis can be stopped 7 days after leaving an endemic area, rather than 3-4 weeks with other drugs. This recommendation is based on weak evidence: mainly on theoretical arguments and on the absence of clinical malaria in some patients with evidence of P. falciparum infection. (7) The atovaquone + proguanil combination is less effective against other Plasmodium species (P. malariae, P. ovale and P. vivax). Chloroquine remains the reference treatment for these forms of malaria, which do not carry a risk of serious complications. (8) There were few adverse events in people taking the atovaquone + proguanil combination during clinical trials. During curative treatment, this combination caused more nausea and vomiting than reference treatments, while, in the prophylactic setting, it had slightly fewer adverse effects than the chloroquine + proguanil combination or mefloquine alone. But the drop out rate was not significantly different between treatment groups. (9) Atovaquone should be taken with food, to improve absorption. (10) The atovaquone + proguanil combination is expensive and is not refunded in France. In contrast, curative treatment with quinine is cheap, and is fully refunded. (11) Mefloquine and quinine remain the treatments of choice for uncomplicated malaria where there is chloroquine resistance. The atovaquone + proguanil combination is useful if mefloquine and quinine are contraindicated; unlike halofantrine, this combination does not carry the risk of serious drug interactions. In the prophylactic setting, the lack of experience with atovaquone means it should only be used as a second line option, after mefloquine, for short-term prophylaxis in areas with a high prevalence of chloroquine resistance.

Prophylaxis for human immunodeficiency virus-related Pneumocystis carinii pneumonia: using simulation modeling to inform clinical guidelines.

BACKGROUND: Human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART) have experienced a dramatic decrease in Pneumocystis carinii pneumonia (PCP), necessitating reassessment of clinical guidelines for prophylaxis. METHODS: A simulation model of HIV infection was used to estimate the lifetime costs and quality-adjusted life expectancy (QALE) for alternative CD4 cell count criteria for stopping primary PCP prophylaxis in patients with CD4 cell count increases receiving HAART and alternative agents for second-line PCP prophylaxis in those intolerant of trimethoprim-sulfamethoxazole (TMP/SMX). The target population was a cohort of HIV-infected patients in the United States with initial CD4 cell counts of 350/microL who began PCP prophylaxis after their first measured CD4 lymphocyte count less than 200/microL. Data were from randomized controlled trials and other published literature. RESULTS: For patients with CD4 cell count increases during HAART, waiting to stop prophylaxis until the first observed CD4 cell count was greater than 300/microL prevented 9 additional cases per 1000 patients and cost $9400 per quality-adjusted life year (QALY) gained compared with stopping prophylaxis at 200/microL. For patients intolerant of TMP/SMX, using dapsone increased QALE by 2.7 months and cost $4500 per QALY compared with no prophylaxis. Using atovaquone rather than dapsone provided only 3 days of additional QALE and cost more than $1.5 million per QALY. CONCLUSIONS: Delaying discontinuation of PCP prophylaxis until the first observed CD4 cell count greater than 300/microL is cost-effective and provides an explicit "PCP prophylaxis stopping criterion." In TMP/SMX-intolerant patients, dapsone is more cost-effective than atovaquone.

Lariam's legacy.

The most-prescribed malaria drug could produce psychiatric side effects in more than one-quarter of all travelers who take it.

Estimating the cost effectiveness of atovaquone versus intravenous pentamidine in the treatment of mild-to-moderate Pneumocystis carinii pneumonia.

Pneumocystis carinii pneumonia (PCP) is the most common severe opportunistic infection, and one of the most costly, among people with AIDS. Over 50% of patients experience toxic effects of the major anti-PCP medications- cotrimoxazole (trimethoprim-sulfamethoxazole) and pentamidine. Recently, the US Food and Drug Administration approved a new oral drug therapy, atovaquone, as an alternative to pentamidine for the treatment of people with mild-to-moderate PCP who are intolerant of cotrimoxazole. We developed a decision tree model to estimate the costs and cost effectiveness of atovaquone therapy compared with intravenous pentamidine therapy for cotrimoxazole-intolerant patients with mild-to-moderate PCP. Clinical outcomes were based on data from a phase III trial comparing the 2 medications. Our economic outcomes were based on treatment algorithms derived from discharge data, published reports and the clinical judgement of the co-authors. We estimate the total expected cost of treating a patient for an episode of PCP with atovaquone to be $US3990 compared with $US6545 for pentamidine under our baseline scenario (1995 dollars). Our decision model also provides insight into the large cost-savings benefits of treating mild-to-moderate PCP on an outpatient basis.