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Trop Med Int Health. 1 January 2008; Volume 13 (Issue 1); DOI:10.1111/j.1365-3156.2007.01978.x
Guthmann JP, Pittet A, Lesage A, Imwong M, Lindegardh N, et al.
Trop Med Int Health. 1 January 2008; Volume 13 (Issue 1); DOI:10.1111/j.1365-3156.2007.01978.x
OBJECTIVE: To assess the efficacy of chloroquine in the treatment of Plasmodium vivax malaria in in Dawei District, southern Myanmar. METHODS: Enrolled patients at Sonsinphya clinic >6 months of age were assessed clinically and parasitologically every week for 28 days. To differentiate new infections from recrudescence, we genotyped pre- and post-treatment parasitaemia. Blood chloroquine was measured to confirm resistant strains. RESULTS: Between December 2002 and April 2003, 2661 patients were screened, of whom 252 were included and 235 analysed. Thirty-four per cent (95% CI: 28.1-40.6) of patients had recurrent parasitaemia and were considered treatment failures. 59.4% of these recurrences were with a different parasite strain. Two (0.8%) patients with recurrences on day 14 had chloroquine concentrations above the threshold of 100 ng/ml and were considered infected with chloroquine resistant parasites. 21% of failures occurred during the first 3 weeks of follow-up: early recurrence and median levels of blood chloroquine comparable to those of controls suggested P. vivax resistance. CONCLUSIONS: Plasmodium vivax resistance to chloroquine seems to be emerging in Dawei, near the Thai-Burmese border. While chloroquine remains the first-line drug for P. vivax infections in this area of Myanmar, regular monitoring is needed to detect further development of parasite resistance.
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Trop Med Int Health. 1 April 2006; Volume 11 (Issue 4); DOI:10.1111/j.1365-3156.2006.01580.x
Rolland E, Checchi F, Pinoges LLP, Balkan S, Guthmann JP, et al.
Trop Med Int Health. 1 April 2006; Volume 11 (Issue 4); DOI:10.1111/j.1365-3156.2006.01580.x
OBJECTIVE: To compare the cost-effectiveness of malaria treatment based on presumptive diagnosis with that of malaria treatment based on rapid diagnostic tests (RDTs). METHODS: We calculated direct costs (based on experience from Ethiopia and southern Sudan) and effectiveness (in terms of reduced over-treatment) of a free, decentralised treatment programme using artesunate plus amodiaquine (AS + AQ) or artemether-lumefantrine (ART-LUM) in a Plasmodium falciparum epidemic. Our main cost-effectiveness measure was the incremental cost per false positive treatment averted by RDTs. RESULTS: As malaria prevalence increases, the difference in cost between presumptive and RDT-based treatment rises. The threshold prevalence above which the RDT-based strategy becomes more expensive is 21% in the AS + AQ scenario and 55% in the ART-LUM scenario, but these thresholds increase to 58 and 70%, respectively, if the financing body tolerates an incremental cost of 1 euro per false positive averted. However, even at a high (90%) prevalence of malaria consistent with an epidemic peak, an RDT-based strategy would only cost moderately more than the presumptive strategy: +29.9% in the AS + AQ scenario and +19.4% in the ART-LUM scenario. The treatment comparison is insensitive to the age and pregnancy distribution of febrile cases, but is strongly affected by variation in non-biomedical costs. If their unit price were halved, RDTs would be more cost-effective at a malaria prevalence up to 45% in case of AS + AQ treatment and at a prevalence up to 68% in case of ART-LUM treatment. CONCLUSION: In most epidemic prevalence scenarios, RDTs would considerably reduce over-treatment for only a moderate increase in costs over presumptive diagnosis. A substantial decrease in RDT unit price would greatly increase their cost-effectiveness, and should thus be advocated. A tolerated incremental cost of 1 euro is probably justified given overall public health and financial benefits. The RDTs should be considered for malaria epidemics if logistics and human resources allow.
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Ann Trop Med Parasitol. 1 September 2002; Volume 96 (Issue 6); DOI:10.1179/000349802125001654
Guthmann JP, Kasparian S, Phetsouvanh R, Nathan N, Garcia MG, et al.
Ann Trop Med Parasitol. 1 September 2002; Volume 96 (Issue 6); DOI:10.1179/000349802125001654
To assess the local efficacy of chloroquine for the treatment of acute, uncomplicated, Plasmodium falciparum malaria, children and adults from Sekong province (an area of Laos with a low intensity of transmission) were tested in a 28-day, in-vivo study. Complete data were collected from 88 of the 102 subjects enrolled between October 1999 and September 2000. After genotypic analysis to distinguish recrudescing infections from re-infections, 35 (39.7%, with a 95% confidence interval of 29.5%-50.7%) of these 88 patients were considered treatment failures. These results seriously question the use of chloroquine as the first-line treatment for P. falciparum malaria in the study area.
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Trans R Soc Trop Med Hyg. 1 March 2008; Volume 102 (Issue 3); DOI:10.1016/j.trstmh.2007.10.015
Alberti KP, Guthmann JP, Fermon F, Nargaye KD, Grais RF
Trans R Soc Trop Med Hyg. 1 March 2008; Volume 102 (Issue 3); DOI:10.1016/j.trstmh.2007.10.015
Inadequate evaluation of vaccine coverage after mass vaccination campaigns, such as used in national measles control programmes, can lead to inappropriate public health responses. Overestimation of vaccination coverage may leave populations at risk, whilst underestimation can lead to unnecessary catch-up campaigns. The problem is more complex in large urban areas where vaccination coverage may be heterogeneous and the programme may have to be fine-tuned at the level of geographic subunits. Lack of accurate population figures in many contexts further complicates accurate vaccination coverage estimates. During the evaluation of a mass vaccination campaign carried out in N'Djamena, the capital of Chad, Lot Quality Assurance Sampling was used to estimate vaccination coverage. Using this method, vaccination coverage could be evaluated within smaller geographic areas of the city as well as for the entire city. Despite the lack of accurate population data by neighbourhood, the results of the survey showed heterogeneity of vaccination coverage within the city. These differences would not have been identified using a more traditional method. The results can be used to target areas of low vaccination coverage during follow-up vaccination activities.
Journal Article > ResearchFull Text
Am J Trop Med Hyg. 1 July 2006; Volume 75 (Issue 1); 143-145.
Guthmann JP, Cohuet S, Rigutto C, Fortes F, Saraiva N, et al.
Am J Trop Med Hyg. 1 July 2006; Volume 75 (Issue 1); 143-145.
In April 2004, 137 children 6-59 months of age with uncomplicated Plasmodium falciparum (Pf) malaria (Caala, Central Angola) were randomized to receive either artemether-lumefantrine (Coartem) or artesunate + amodiaquine (ASAQ). After 28 days of follow-up, there were 2/61 (3.2%) recurrent parasitemias in the Coartem group and 4/64 (6.2%) in the ASAQ group (P = 0.72), all classified as re-infections after PCR genotyping (cure rate = 100% [95%CI: 94-100] in both groups). Only one patient (ASAQ group) had gametocytes on day 28 versus five (Coartem) and three (ASAQ) at baseline. Compared with baseline, anemia was significantly improved after 28 days of follow-up in both groups (Coartem: from 54.1% to 13.4%; ASAQ: from 53.1% to 15.9%). Our findings are in favor of a high efficacy of both combinations in Caala. Now that Coartem has been chosen as the new first-line anti-malarial, the challenge is to insure that this drug is available and adequately used.
Journal Article > ResearchFull Text
Malar J. 23 August 2009; Volume 8 (Issue 1); 203.; DOI:10.1186/1475-2875-8-203
Zwang J, Olliaro PL, Barennes H, Bonnet MMB, Brasseur P, et al.
Malar J. 23 August 2009; Volume 8 (Issue 1); 203.; DOI:10.1186/1475-2875-8-203
BACKGROUND: Artesunate and amodiaquine (AS&AQ) is at present the world's second most widely used artemisinin-based combination therapy (ACT). It was necessary to evaluate the efficacy of ACT, recently adopted by the World Health Organization (WHO) and deployed over 80 countries, in order to make an evidence-based drug policy.
METHODS: An individual patient data (IPD) analysis was conducted on efficacy outcomes in 26 clinical studies in sub-Saharan Africa using the WHO protocol with similar primary and secondary endpoints.
RESULTS: A total of 11,700 patients (75% under 5 years old), from 33 different sites in 16 countries were followed for 28 days. Loss to follow-up was 4.9% (575/11,700). AS&AQ was given to 5,897 patients. Of these, 82% (4,826/5,897) were included in randomized comparative trials with polymerase chain reaction (PCR) genotyping results and compared to 5,413 patients (half receiving an ACT). AS&AQ and other ACT comparators resulted in rapid clearance of fever and parasitaemia, superior to non-ACT. Using survival analysis on a modified intent-to-treat population, the Day 28 PCR-adjusted efficacy of AS&AQ was greater than 90% (the WHO cut-off) in 11/16 countries. In randomized comparative trials (n = 22), the crude efficacy of AS&AQ was 75.9% (95% CI 74.6-77.1) and the PCR-adjusted efficacy was 93.9% (95% CI 93.2-94.5). The risk (weighted by site) of failure PCR-adjusted of AS&AQ was significantly inferior to non-ACT, superior to dihydroartemisinin-piperaquine (DP, in one Ugandan site), and not different from AS+SP or AL (artemether-lumefantrine). The risk of gametocyte appearance and the carriage rate of AS&AQ was only greater in one Ugandan site compared to AL and DP, and lower compared to non-ACT (p = 0.001, for all comparisons). Anaemia recovery was not different than comparator groups, except in one site in Rwanda where the patients in the DP group had a slower recovery.
CONCLUSION: AS&AQ compares well to other treatments and meets the WHO efficacy criteria for use against falciparum malaria in many, but not all, the sub-Saharan African countries where it was studied. Efficacy varies between and within countries. An IPD analysis can inform general and local treatment policies. Ongoing monitoring evaluation is required.
METHODS: An individual patient data (IPD) analysis was conducted on efficacy outcomes in 26 clinical studies in sub-Saharan Africa using the WHO protocol with similar primary and secondary endpoints.
RESULTS: A total of 11,700 patients (75% under 5 years old), from 33 different sites in 16 countries were followed for 28 days. Loss to follow-up was 4.9% (575/11,700). AS&AQ was given to 5,897 patients. Of these, 82% (4,826/5,897) were included in randomized comparative trials with polymerase chain reaction (PCR) genotyping results and compared to 5,413 patients (half receiving an ACT). AS&AQ and other ACT comparators resulted in rapid clearance of fever and parasitaemia, superior to non-ACT. Using survival analysis on a modified intent-to-treat population, the Day 28 PCR-adjusted efficacy of AS&AQ was greater than 90% (the WHO cut-off) in 11/16 countries. In randomized comparative trials (n = 22), the crude efficacy of AS&AQ was 75.9% (95% CI 74.6-77.1) and the PCR-adjusted efficacy was 93.9% (95% CI 93.2-94.5). The risk (weighted by site) of failure PCR-adjusted of AS&AQ was significantly inferior to non-ACT, superior to dihydroartemisinin-piperaquine (DP, in one Ugandan site), and not different from AS+SP or AL (artemether-lumefantrine). The risk of gametocyte appearance and the carriage rate of AS&AQ was only greater in one Ugandan site compared to AL and DP, and lower compared to non-ACT (p = 0.001, for all comparisons). Anaemia recovery was not different than comparator groups, except in one site in Rwanda where the patients in the DP group had a slower recovery.
CONCLUSION: AS&AQ compares well to other treatments and meets the WHO efficacy criteria for use against falciparum malaria in many, but not all, the sub-Saharan African countries where it was studied. Efficacy varies between and within countries. An IPD analysis can inform general and local treatment policies. Ongoing monitoring evaluation is required.
Journal Article > ResearchFull Text
J Clin Microbiol. 1 June 2009; Volume 47 (Issue 6); 1931-3.; DOI:10.1128/JCM.02245-08.
Merens A, Guerin PJ, Guthmann JP, Nicand E
J Clin Microbiol. 1 June 2009; Volume 47 (Issue 6); 1931-3.; DOI:10.1128/JCM.02245-08.
Biological samples collected in refugee camps during an outbreak of hepatitis E were used to compare the accuracy of hepatitis E virus RNA amplification by real-time reverse transcription-PCR (RT-PCR) for sera and dried blood spots (concordance of 90.6%). Biological profiles (RT-PCR and serology) of asymptomatic individuals were also analyzed.
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Trop Med Int Health. 1 April 2004; Volume 9 (Issue 4); DOI:10.1111/j.1365-3156.2004.01217.x
Checchi F, Piola P, Kosack CS, Ardizzoni E, Klarkowski DB, et al.
Trop Med Int Health. 1 April 2004; Volume 9 (Issue 4); DOI:10.1111/j.1365-3156.2004.01217.x
We report below an in vivo antimalarial efficacy study conducted in 2002 in Bundi Bugyo, a district of western Uganda housing a large displaced population. We tested sulfadoxine-pyrimethamine (SP), amodiaquine (AQ) and the combination chloroquine plus SP (CQ + SP). A total of 268 children with uncomplicated Plasmodium falciparum malaria were followed-up for 28 days according to WHO recommendations, with PCR genotyping to distinguish late recrudescences from re-infections. PCR-adjusted failure proportions at day 28 were 37.0% (34/92, 95% CI 27.1-47.7) in the SP group, 20.6% (14/68, 95% CI 11.7-32.1) in the AQ group and 22.8% (18/79, 95% CI 14.1-33.6) in the CQ + SP group. Early failures were particularly frequent in the SP group (15.2%). Clearance of gametocytes was slower in the SP and CQ + SP groups than in the AQ group. This study suggests that, in Bundi Bugyo, CQ + SP (Uganda's first-line regimen) will need to be replaced by a more efficacious regimen. Across Uganda, the deployment of SP containing combinations may not be a feasible long-term strategy. For Bundi Bugyo, we recommend a combination of artesunate and AQ. Our study also confirms previous findings that resistance is considerably underestimated by 14-day follow-ups. Antimalarial policy decisions should therefore be based on 28-day studies, with PCR adjustment to distinguish re-infections.
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PLOS Med. 5 August 2008; Volume 5 (Issue 8); DOI:10.1371/journal.pmed.0050169
Guthmann JP, Checchi F, van den Broek IVF, Balkan S, Van Herp M, et al.
PLOS Med. 5 August 2008; Volume 5 (Issue 8); DOI:10.1371/journal.pmed.0050169
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Trop Med Int Health. 1 September 2004; Volume 9 (Issue 9); DOI:10.1111/j.1365-3156.2004.01290.x
Stivanello E, Cavailler P, Cassano F, Omar SV, Kariuki D, et al.
Trop Med Int Health. 1 September 2004; Volume 9 (Issue 9); DOI:10.1111/j.1365-3156.2004.01290.x
To provide advice on the rational use of antimalarial drugs, Médecins Sans Frontières conducted a randomized, an open label efficacy study in Kajo Keji, an area of high transmission of malaria in southern Sudan. The efficacy of chloroquine (CQ), sulphadoxine-pyrimethamine (SP) and amodiaquine (AQ) were measured in a 28-day in vivo study, with results corrected by PCR genotyping. Of 2010 children screened, 115 children aged 6-59 months with uncomplicated Plasmodium falciparum malaria were randomized into each group to receive a supervised course of treatment. Of these, 114, 103 and 111 were analysed in the CQ, SP and AQ groups, respectively. The overall parasitological failure rates at day 28 were 93.9% [95% confidence interval (CI) 87.3-97.3] for CQ, 69.9% (95% CI 60.0-78.3) for SP, and 25.2% (95% CI 17.7-34.5) for AQ. These results provide important missing data on antimalarial drug efficacy in southern Sudan. They indicate that none of the drugs could be used in monotherapy and suggest that even in combination with artemisinin, cure rates might not be efficacious enough. We recommend a combination of artemether and lumefantrine as first-line treatment for uncomplicated P. falciparum malaria cases in Kajo Keji county.