Papers by Christian Nsanzabana
Malaria Journal, 2014
Background: The wide-scale implementation of insecticide-treated nets and indoor residual sprayin... more Background: The wide-scale implementation of insecticide-treated nets and indoor residual spraying (IRS) has contributed to a considerable decrease of malaria morbidity and mortality in sub-Saharan Africa over the last decade. Due to increasing resistance in Anopheles gambiae sensu lato mosquitoes to dichlorodiphenyl trichloroethane (DDT) and pyrethroids, alternative insecticide formulations for IRS with long-lasting residual activity are required to sustain the gains obtained in most malaria-endemic countries.
by Bernhards Ogutu, Jacques Lebras, Philippe J Guerin, Erasmus Kamugisha, Gabrielle Fröberg, Teferi Eshetu, Samuel Nsobya, Anastasia Grivoyannis, Billy Ngasala, Mehul Dhorda, Clarissa Moreira, Steffen Borrmann, Carol Sibley, Maja Malmberg, Christian Nsanzabana, and Prabin Dahal The American journal of tropical medicine and hygiene, 2014
Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the artem... more Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes are associated with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) have not been clearly defined. Individual patient data from 31 clinical trials were harmonized and pooled by using standardized methods from the WorldWide Antimalarial Resistance Network. Data for more than 7,000 patients were analyzed to assess relationships between parasite polymorphisms in pfcrt and pfmdr1 and clinically relevant outcomes after treatment with AL or ASAQ. Presence of the pfmdr1 gene N86 (adjusted hazards ratio = 4.74, 95% confidence interval = 2.29 - 9.78, P < 0.001) and increased pfmdr1 cop...
PLoS Neglected Tropical Diseases, 2011
Background: Measuring the impact of capacity strengthening support is a priority for the internat... more Background: Measuring the impact of capacity strengthening support is a priority for the international development community. Several frameworks exist for monitoring and evaluating funding results and modalities. Based on its long history of support, we report on the impact of individual and institutional capacity strengthening programmes conducted by the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) and on the factors that influenced the outcome of its Research Capacity Strengthening (RCS) activities.
Parasites & Vectors, 2010
Background: Long-lasting insecticidal nets (LLINs) are an important tool for controlling malaria.... more Background: Long-lasting insecticidal nets (LLINs) are an important tool for controlling malaria. Much attention has been devoted to determine both the effect of LLINs on the reduction of Plasmodium infection rate and on clinically-confirmed malaria cases in sub-Saharan Africa. We carried out an epidemiological study to investigate whether LLINs impact on Plasmodium prevalence rate and the proportion of clinically-confirmed malaria cases, in five villages in the district of Toumodi, central Côte d'Ivoire.
New England Journal of Medicine, 2012
Human immunodeficiency virus (HIV) protease inhibitors show activity against Plasmodium falciparu... more Human immunodeficiency virus (HIV) protease inhibitors show activity against Plasmodium falciparum in vitro. We hypothesized that the incidence of malaria in HIV-infected children would be lower among children receiving lopinavir-ritonavir-based antiretroviral therapy (ART) than among those receiving nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based ART. We conducted an open-label trial in which HIV-infected children 2 months to 5 years of age who were eligible for ART or were currently receiving NNRTI-based ART were randomly assigned to either lopinavir-ritonavir-based ART or NNRTI-based ART and were followed for 6 months to 2 years. Cases of uncomplicated malaria were treated with artemether-lumefantrine. The primary end point was the incidence of malaria. We enrolled 176 children, of whom 170 received the study regimen: 86 received NNRTI-based ART, and 84 lopinavir-ritonavir-based ART. The incidence of malaria was lower among children receiving the lopinavir-ritonavir-based regimen than among those receiving the NNRTI-based regimen (1.32 vs. 2.25 episodes per person-year; incidence-rate ratio, 0.59; 95% confidence interval [CI], 0.36 to 0.97; P=0.04), as was the risk of a recurrence of malaria after treatment with artemether-lumefantrine (28.1% vs. 54.2%; hazard ratio, 0.41; 95% CI, 0.22 to 0.76; P=0.004). The median lumefantrine level on day 7 after treatment for malaria was significantly higher in the lopinavir-ritonavir group than in the NNRTI group. In the lopinavir-ritonavir group, lumefantrine levels exceeding 300 ng per milliliter on day 7 were associated with a reduction of more than 85% in the 63-day risk of recurrent malaria. A greater number of serious adverse events occurred in the lopinavir-ritonavir group than in the NNRTI group (5.6% vs. 2.3%, P=0.16). Pruritus occurred significantly more frequently in the lopinavir-ritonavir group, and elevated alanine aminotransferase levels significantly more frequently in the NNRTI group. Lopinavir-ritonavir-based ART as compared with NNRTI-based ART reduced the incidence of malaria by 41%, with the lower incidence attributable largely to a significant reduction in the recurrence of malaria after treatment with artemether-lumefantrine. Lopinavir-ritonavir-based ART was accompanied by an increase in serious adverse events. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT00978068.).
Medical and Veterinary Entomology, 2005
The Journal of Infectious Diseases, 2010
Background. Antimalarial use is a key factor driving drug resistance and reduced treatment effect... more Background. Antimalarial use is a key factor driving drug resistance and reduced treatment effectiveness in Plasmodium falciparum malaria, but there are few formal, quantitative analyses of this process.
Antimicrobial Agents and Chemotherapy, 2011
Malaria and HIV infection are both very common in many developing countries. With the increasing ... more Malaria and HIV infection are both very common in many developing countries. With the increasing availability of therapy for HIV infection, it was of interest to determine whether antiretroviral drugs exert antimalarial effects. We therefore tested the in vitro activity of 19 antiretroviral drugs against the W2 and 3D7 strains of Plasmodium falciparum at concentrations up to 50 M. None of 5 tested nucleoside reverse transcriptase inhibitors demonstrated activity. Two nonnucleoside reverse transcriptase inhibitors, efavirenz (mean 50% inhibitory concentration [IC 50 ] of 22 to 30 M against the two strains) and etravirine (3.1 to 3.4 M), were active; nevirapine was not active. Also active were the fusion inhibitor enfuvirtide (6.2 to 7.9 M) and the entry inhibitor maraviroc (15 to 21 M). Raltegravir was not active. However, for all active drugs mentioned above, the IC 50 s were considerably greater than the concentrations achieved with standard dosing. The effects most likely to be clinically relevant were with HIV protease inhibitors. Of the tested compounds, activity was seen with lopinavir (2.7 to 2.9 M), atazanavir (3.3 to 13.0 M), saquinavir (5.0 to 12.1 M), nelfinavir (6.5 to 12.1 M), ritonavir (9.5 to 10.9 M), tipranavir (15.5 to 22.3 M), and amprenavir (28.1 to 40.8) but not darunavir. Lopinavir was active at levels well below those achieved with standard dosing of coformulated lopinavir-ritonavir. Lopinavir also demonstrated modest synergy with the antimalarial lumefantrine (mean fractional inhibitory concentration index of 0.66 for W2 and 0.53 for 3D7). Prior data showed that lopinavirritonavir also extends the pharmacokinetic exposure of lumefantrine. Thus, when used to treat HIV infection, lopinavir-ritonavir may have clinically relevant antimalarial activity and also enhance the activity of antimalarials.
American Journal of Tropical Medicine and Hygiene, 2010
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Papers by Christian Nsanzabana