Clinical trials of new strategies for the prevention and treatment of Plasmodium falciparum and Plasmodium vivax malaria in north eastern Papua, Indonesia.

New drug regimens are needed for effective prophylaxis and treatment of drug resistant Plasmodium falciparum and Plasmodium vivax malaria in northeastern Papua. Mefloquine and doxycycline, two standard prophylactic drugs, had high prophylactic efficacy in northeastern Papua but they have limited application for two vulnerable groups, young children and pregnant women. Azithromycin, an azalide antibiotic, had a prophylactic efficacy of 83% against P. falciparum in malaria immune Kenyans. If successful in non immunes, it would be a significant addition to the current prophylactic drugs. Chloroquine, the current first line drug in northeastern Papua, is associated with high rates of treatment failure for falciparum and vivax malaria. Cure rates might be improved by combining with chloroquine with doxycycline, two drugs that are inexpensive and widely available. Methods. Two clinical trials were conducted. (1). The prophylactic efficacy of azithromycin against P. falciparum and P. vivax was determined in a double blind, placebo-controlled trial in Indonesian adults with limited immunity. After radical cure, three hundred randomised subjects received azithromycin (n=T48, 750mg loading dose, 250mg/day), placebo (n=77), or doxycycline (n=75, 100mg/day). The end point was slide proven parasitaemia. (2). In an open trial chloroquine plus doxycycline (CQD) was compared to chloroquine or doxycycline alone for treating falciparum and vivax malaria. Eight nine falciparum patients were randomised to standard dose chloroquine (n=30), doxycycline 100 mg 12 hourly (7 days), n=20 , or chloroquine plus doxycycline (n=39) corresponding numbers for vivax patients were 23, 16, 24. Endpoints were parasite sensitivity (S) or resistance (RI, RII, and RIII) assessed by Day 28. Findings. (1). There were 58 P. falciparum and 29 P. vivax prophylaxis failures over 20 weeks. Based on incidence rates, the prophylactic efficacy of azithromycin relative to placebo was 71.6% (95% CI 50.3-83.8) against P. falciparum, and 98.9% (93.1-99.9) against P. vivax. Corresponding figures for doxycycline were 96.3% (85.4-99.6) and 98% (88.0- 99.9)

Acute asymptomatic hepatitis in a healthy normal volunteer exposed to 2 oral doses of amodiaquine and artesunate

Combination antimalarial therapy is being explored to delay development of resistance to falciparum malaria. This report describes an unexpected drug-induced hepatitis in a previously healthy young woman exposed to 2 doses of amodiaquine and artesunate. Use of these combinations should be closely monitore

Economic evaluation of a policy change from single-agent treatment for suspected malaria to artesunate-amodiaquine for microscopically confirmed uncomplicated falciparum malaria in the Oussouye District of south-western Senegal

International audienceSenegal is changing policy for case management of uncomplicated falciparum malaria, which hitherto is diagnosed clinically and treated with chloroquine or intramuscular quinine. The WHO recommends artemisinin-based combinations for treating falciparum malaria, preferably based on a parasitological diagnosis. There are no economic projections if such a policy were introduced in Senegal. We have conducted a preliminary economic assessment of such a policy change. The study took place in the chloroquine-resistant district of Oussouye in south-western Senegal. We reviewed clinic registers of the district health posts (n ¼ 5) from 1996 to 2001, and piloted artesunate combined with amodiaquine (at 4 and 10 mg/kg/day · 3 days respectively) (AS-AQ) for treating slide-proven falciparum malaria during two rainy seasons (2000 and 2001) at one health centre. These data were used to calculate current direct patient costs (clinic visit, diagnosis, drugs) of malaria treatment and project future costs for the district. The robustness of the model was tested by allowing for different drug failure rates and costs of diagnosis. During 1996-2001, the mean number of primary treatments per year was 7654 for a mean, direct cost of US$17 452 to the community. Clinical diagnosis resulted in over-treatment : 56$8150 (53% less expensive). Studies examining the public health effect and economics of deploying AS-AQ on a wider scale are underway in Senegal.Le Sénégal change de politique pour le traitement du paludisme (à falciparum) sans complication, qui est jusqu'ici diagnostiqué en clinique et traité avec de la chloroquine ou de la quinine intramusculaire. L'OMS recommande des combinaisons comprenant de l'artémisine pour traiter le paludisme à falciparum, de préférence basées sur un diagnostic parasitologique. Nous avons conduit une évaluation économique préliminaire d'un tel changement de politique. L'étude a eu lieu dans le district d'Oussouye dans le sud-ouest du Sénégal, où il y a de la résistance à la chloroquine. Nous avons repris les registres de soins des postes de santé (n= 5) de 1996 à 2001 et dans un centre de santé traité avec une combinaison artesunate amodiaquine (à 4 et 10 mg/kg/jour x 3 jours chacun) (AS-AQ) les paludismes prouvés par goutte épaisse pendant deux saisons des pluies (2000 et 2001). Les données ont été utilisées pour calculer les coûts directs par patient (consultation, diagnostic, médicament) du traitement du paludisme et projeté le coût futur pour le district. La robustesse du modèle a été testée avec différents taux d'échec des médicaments et différents coûts de diagnostic. De 1996 à 2001 le nombre moyen annuel de traitements primaires a été de 7 654 pour un coût direct annuel moyen de 17 452 US$. Le diagnostic clinique entraîne des traitements indus de 56$ (réduction de dépense de 53 %). Des études examinant les effets de santé publique et les effets économiques de déploiement du traitement AS-AQ à plus large échelle ont été entreprises au Sénégal

Economic evaluation of a policy change from single-agent treatment for suspected malaria to artesunate-amodiaquine for microscopically confirmed uncomplicated falciparum malaria in the Oussouye District of south-western Senegal

International audienceSenegal is changing policy for case management of uncomplicated falciparum malaria, which hitherto is diagnosed clinically and treated with chloroquine or intramuscular quinine. The WHO recommends artemisinin-based combinations for treating falciparum malaria, preferably based on a parasitological diagnosis. There are no economic projections if such a policy were introduced in Senegal. We have conducted a preliminary economic assessment of such a policy change. The study took place in the chloroquine-resistant district of Oussouye in south-western Senegal. We reviewed clinic registers of the district health posts (n ¼ 5) from 1996 to 2001, and piloted artesunate combined with amodiaquine (at 4 and 10 mg/kg/day · 3 days respectively) (AS-AQ) for treating slide-proven falciparum malaria during two rainy seasons (2000 and 2001) at one health centre. These data were used to calculate current direct patient costs (clinic visit, diagnosis, drugs) of malaria treatment and project future costs for the district. The robustness of the model was tested by allowing for different drug failure rates and costs of diagnosis. During 1996-2001, the mean number of primary treatments per year was 7654 for a mean, direct cost of US$17 452 to the community. Clinical diagnosis resulted in over-treatment : 56$8150 (53% less expensive). Studies examining the public health effect and economics of deploying AS-AQ on a wider scale are underway in Senegal.Le Sénégal change de politique pour le traitement du paludisme (à falciparum) sans complication, qui est jusqu'ici diagnostiqué en clinique et traité avec de la chloroquine ou de la quinine intramusculaire. L'OMS recommande des combinaisons comprenant de l'artémisine pour traiter le paludisme à falciparum, de préférence basées sur un diagnostic parasitologique. Nous avons conduit une évaluation économique préliminaire d'un tel changement de politique. L'étude a eu lieu dans le district d'Oussouye dans le sud-ouest du Sénégal, où il y a de la résistance à la chloroquine. Nous avons repris les registres de soins des postes de santé (n= 5) de 1996 à 2001 et dans un centre de santé traité avec une combinaison artesunate amodiaquine (à 4 et 10 mg/kg/jour x 3 jours chacun) (AS-AQ) les paludismes prouvés par goutte épaisse pendant deux saisons des pluies (2000 et 2001). Les données ont été utilisées pour calculer les coûts directs par patient (consultation, diagnostic, médicament) du traitement du paludisme et projeté le coût futur pour le district. La robustesse du modèle a été testée avec différents taux d'échec des médicaments et différents coûts de diagnostic. De 1996 à 2001 le nombre moyen annuel de traitements primaires a été de 7 654 pour un coût direct annuel moyen de 17 452 US$. Le diagnostic clinique entraîne des traitements indus de 56$ (réduction de dépense de 53 %). Des études examinant les effets de santé publique et les effets économiques de déploiement du traitement AS-AQ à plus large échelle ont été entreprises au Sénégal

Avian influenza--a review for doctors in travel medicine.

First identified in humans in Hong Kong, influenza A/H5N1, known commonly as avian influenza, has caused human disease in 15 countries around the world. Although the current number of confirmed patients is tiny compared to seasonal and the recently emerged H1N1 'swine' influenza, H5N1 remains a candidate for the next highly pathogenic influenza pandemic. Currently, H5N1 has very limited ability to spread from person-to-person but this may change because of mutation or reassortment with other influenza viruses leading to an influenza pandemic with high mortality. If this occurs travellers are likely to be affected and travel medicine doctors will need to consider avian influenza in returning febrile travellers. The early clinical features may be dismissed easily as 'the flu' resulting in delayed treatment. Treatment options are limited. Oral oseltamivir alone has been the most commonly used drug but mortality remains substantial, up to 80% in Indonesia. Intravenous peramivir has been filed for registration and IV zanamivir is being developed. This review will focus on the epidemiological and clinical features of influenza A/H5N1 avian influenza and will highlight aspects relevant to travel medicine doctors