2012
|
Journal Articles
|
| Johanna H Kattenberg, Christian M Tahita, Inge A J Versteeg, Halidou Tinto, Maminata Traoré-Coulibaly, Henk D F H Schallig, Petra F Mens Antigen persistence of rapid diagnostic tests in pregnant women
in Nanoro, Burkina Faso, and the implications for the diagnosis
of malaria in pregnancy (Journal Article) In: Trop. Med. Int. Health, vol. 17, no. 5, pp. 550–557, 2012. @article{Kattenberg2012-hg,
title = {Antigen persistence of rapid diagnostic tests in pregnant women
in Nanoro, Burkina Faso, and the implications for the diagnosis
of malaria in pregnancy},
author = {Johanna H Kattenberg and Christian M Tahita and Inge A J Versteeg and Halidou Tinto and Maminata Traor\'{e}-Coulibaly and Henk D F H Schallig and Petra F Mens},
year = {2012},
date = {2012-05-01},
journal = {Trop. Med. Int. Health},
volume = {17},
number = {5},
pages = {550--557},
publisher = {Wiley},
abstract = {OBJECTIVES: To evaluate persistence of several Plasmodium
antigens in pregnant women after treatment and compare
diagnostics during treatment follow-up. METHODS: Thirty-two pregnant women (N = 32) with confirmed malaria infection by a
histidine-rich protein 2 (HRP2)-based rapid diagnostic test
(RDT) and microscopy were followed for 28 days after
artemisinin-based combination therapy (ACT). A Plasmodium
lactate dehydrogenase (pLDH)-based RDT and two ELISAs based on
the detection of dihydrofolate reductase-thymidylate synthase
(DHFR-TS) and haeme detoxification protein (HDP) were compared
with each other and to RT-PCR at each visit. RESULTS: The mean
visit number (95% confidence interval) on which the HRP2-based
RDT was still positive after treatment was 3.4 (2.7-4.1) visits
with some patients still positive at day 28. This is
significantly later than the pLDH-based RDT [0.84 (0.55-1.1)],
microscopy (median 1, range 1-3), DHFR-TS-ELISA [1.7 (1.1-2.3)]
and RT-PCR (median 2, range 1-5) (P < 0.05), but not
significantly later than HDP-ELISA [2.1 (1.6-2.7)]. Lower
gravidity and higher parasite density at day 0 resulted in
significantly longer positive results with most tests (P <
0.05). CONCLUSIONS: HRP2 can persist up to 28 days after ACT
treatment; therefore, this test is not suitable for treatment
follow-up in pregnant women and can generate problems when using
this test during intermittent preventive treatment (IPTp).
DHFR-TS is less persistent than HRP2, making it a potentially
interesting target for diagnosis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVES: To evaluate persistence of several Plasmodium
antigens in pregnant women after treatment and compare
diagnostics during treatment follow-up. METHODS: Thirty-two pregnant women (N = 32) with confirmed malaria infection by a
histidine-rich protein 2 (HRP2)-based rapid diagnostic test
(RDT) and microscopy were followed for 28 days after
artemisinin-based combination therapy (ACT). A Plasmodium
lactate dehydrogenase (pLDH)-based RDT and two ELISAs based on
the detection of dihydrofolate reductase-thymidylate synthase
(DHFR-TS) and haeme detoxification protein (HDP) were compared
with each other and to RT-PCR at each visit. RESULTS: The mean
visit number (95% confidence interval) on which the HRP2-based
RDT was still positive after treatment was 3.4 (2.7-4.1) visits
with some patients still positive at day 28. This is
significantly later than the pLDH-based RDT [0.84 (0.55-1.1)],
microscopy (median 1, range 1-3), DHFR-TS-ELISA [1.7 (1.1-2.3)]
and RT-PCR (median 2, range 1-5) (P < 0.05), but not
significantly later than HDP-ELISA [2.1 (1.6-2.7)]. Lower
gravidity and higher parasite density at day 0 resulted in
significantly longer positive results with most tests (P <
0.05). CONCLUSIONS: HRP2 can persist up to 28 days after ACT
treatment; therefore, this test is not suitable for treatment
follow-up in pregnant women and can generate problems when using
this test during intermittent preventive treatment (IPTp).
DHFR-TS is less persistent than HRP2, making it a potentially
interesting target for diagnosis. |
| Ronnatrai Rueangweerayut, Aung Pyae Phyo, Chirapong Uthaisin, Yi Poravuth, Tran Quang Binh, Halidou Tinto, Louis K Pénali, Neena Valecha, Nong Thi Tien, Salim Abdulla, Isabelle Borghini-Fuhrer, Stephan Duparc, Chang-Sik Shin, Lawrence Fleckenstein, Pyronaridine-Artesunate Study Team Pyronaridine-artesunate versus mefloquine plus artesunate for
malaria (Journal Article) In: N. Engl. J. Med., vol. 366, no. 14, pp. 1298–1309, 2012. @article{Rueangweerayut2012-is,
title = {Pyronaridine-artesunate versus mefloquine plus artesunate for
malaria},
author = {Ronnatrai Rueangweerayut and Aung Pyae Phyo and Chirapong Uthaisin and Yi Poravuth and Tran Quang Binh and Halidou Tinto and Louis K P\'{e}nali and Neena Valecha and Nong Thi Tien and Salim Abdulla and Isabelle Borghini-Fuhrer and Stephan Duparc and Chang-Sik Shin and Lawrence Fleckenstein and Pyronaridine-Artesunate Study Team},
year = {2012},
date = {2012-04-01},
journal = {N. Engl. J. Med.},
volume = {366},
number = {14},
pages = {1298--1309},
abstract = {BACKGROUND: Pyronaridine-artesunate is an artemisinin-based
combination therapy under evaluation for the treatment of
Plasmodium falciparum and P. vivax malaria. METHODS: We conducted
a phase 3, open-label, multicenter, noninferiority trial that
included 1271 patients between 3 and 60 years of age from Asia
(81.3%) or Africa (18.7%) with microscopically confirmed,
uncomplicated P. falciparum malaria. Patients underwent
randomization for treatment with a fixed-dose combination of 180
mg of pyronaridine and 60 mg of artesunate or with 250 mg of
mefloquine plus 100 mg of artesunate. Doses were calculated
according to body weight and administered once daily for 3 days.
RESULTS: Pyronaridine-artesunate was noninferior to mefloquine
plus artesunate for the primary outcome: adequate clinical and
parasitologic response in the per-protocol population on day 28,
corrected for reinfection with the use of
polymerase-chain-reaction (PCR) genotyping. For this outcome,
efficacy in the group receiving pyronaridine-artesunate was
99.2% (743 of 749 patients; 95% confidence interval [CI], 98.3
to 99.7) and that in the group receiving mefloquine plus
artesunate was 97.8% (360 of 368 patients; 95% CI, 95.8 to
99.1), with a treatment difference of 1.4 percentage points (95% CI, 0.0 to 3.5; P=0.05). In the intention-to-treat population,
efficacy on day 42 in the group receiving pyronaridine-artesunate
was 83.1% (705 of 848 patients; 95% CI, 80.4 to 85.6) and that
in the group receiving mefloquine plus artesunate was 83.9% (355
of 423 patients; 95% CI, 80.1 to 87.3). In Cambodia, where there
were 211 study patients, the median parasite clearance time was
prolonged for both treatments: 64 hours versus 16.0 to 38.9 hours
in other countries (P<0.001, on the basis of Kaplan-Meier
estimates). Kaplan-Meier estimates of the recrudescence rate in
the intention-to-treat population in Cambodia until day 42 were
higher with pyronaridine-artesunate than with mefloquine plus artesunate (10.2% [95% CI, 5.4 to 18.6] vs. 0%; P=0.04 as
calculated with the log-rank test), but similar for the other
countries combined (4.7% [95% CI, 3.3 to 6.7] and 2.8% [95% CI, 1.5 to 5.3], respectively; P=0.24). Elevated levels of
aminotransferases were observed in those receiving
pyronaridine-artesunate. Two patients receiving mefloquine plus
artesunate had seizures. CONCLUSIONS: Fixed-dose
pyronaridine-artesunate was efficacious in the treatment of
uncomplicated P. falciparum malaria. In Cambodia, extended
parasite clearance times were suggestive of in vivo resistance to
artemisinin. (Funded by Shin Poong Pharmaceutical Company and the
Medicines for Malaria Venture; ClinicalTrials.gov number,
NCT00403260.).},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Pyronaridine-artesunate is an artemisinin-based
combination therapy under evaluation for the treatment of
Plasmodium falciparum and P. vivax malaria. METHODS: We conducted
a phase 3, open-label, multicenter, noninferiority trial that
included 1271 patients between 3 and 60 years of age from Asia
(81.3%) or Africa (18.7%) with microscopically confirmed,
uncomplicated P. falciparum malaria. Patients underwent
randomization for treatment with a fixed-dose combination of 180
mg of pyronaridine and 60 mg of artesunate or with 250 mg of
mefloquine plus 100 mg of artesunate. Doses were calculated
according to body weight and administered once daily for 3 days.
RESULTS: Pyronaridine-artesunate was noninferior to mefloquine
plus artesunate for the primary outcome: adequate clinical and
parasitologic response in the per-protocol population on day 28,
corrected for reinfection with the use of
polymerase-chain-reaction (PCR) genotyping. For this outcome,
efficacy in the group receiving pyronaridine-artesunate was
99.2% (743 of 749 patients; 95% confidence interval [CI], 98.3
to 99.7) and that in the group receiving mefloquine plus
artesunate was 97.8% (360 of 368 patients; 95% CI, 95.8 to
99.1), with a treatment difference of 1.4 percentage points (95% CI, 0.0 to 3.5; P=0.05). In the intention-to-treat population,
efficacy on day 42 in the group receiving pyronaridine-artesunate
was 83.1% (705 of 848 patients; 95% CI, 80.4 to 85.6) and that
in the group receiving mefloquine plus artesunate was 83.9% (355
of 423 patients; 95% CI, 80.1 to 87.3). In Cambodia, where there
were 211 study patients, the median parasite clearance time was
prolonged for both treatments: 64 hours versus 16.0 to 38.9 hours
in other countries (P<0.001, on the basis of Kaplan-Meier
estimates). Kaplan-Meier estimates of the recrudescence rate in
the intention-to-treat population in Cambodia until day 42 were
higher with pyronaridine-artesunate than with mefloquine plus artesunate (10.2% [95% CI, 5.4 to 18.6] vs. 0%; P=0.04 as
calculated with the log-rank test), but similar for the other
countries combined (4.7% [95% CI, 3.3 to 6.7] and 2.8% [95% CI, 1.5 to 5.3], respectively; P=0.24). Elevated levels of
aminotransferases were observed in those receiving
pyronaridine-artesunate. Two patients receiving mefloquine plus
artesunate had seizures. CONCLUSIONS: Fixed-dose
pyronaridine-artesunate was efficacious in the treatment of
uncomplicated P. falciparum malaria. In Cambodia, extended
parasite clearance times were suggestive of in vivo resistance to
artemisinin. (Funded by Shin Poong Pharmaceutical Company and the
Medicines for Malaria Venture; ClinicalTrials.gov number,
NCT00403260.). |
| Innocent Valea, Halidou Tinto, Maxime K Drabo, Lieven Huybregts, Hermann Sorgho, Jean-Bosco Ouedraogo, Robert T Guiguemde, Jean Pierre Geertruyden, Patrick Kolsteren, Umberto D’Alessandro, FSP/MISAME Group An analysis of timing and frequency of malaria infection during
pregnancy in relation to the risk of low birth weight, anaemia
and perinatal mortality in Burkina Faso (Journal Article) In: Malar. J., vol. 11, no. 1, pp. 71, 2012. @article{Valea2012-pp,
title = {An analysis of timing and frequency of malaria infection during
pregnancy in relation to the risk of low birth weight, anaemia
and perinatal mortality in Burkina Faso},
author = {Innocent Valea and Halidou Tinto and Maxime K Drabo and Lieven Huybregts and Hermann Sorgho and Jean-Bosco Ouedraogo and Robert T Guiguemde and Jean Pierre Geertruyden and Patrick Kolsteren and Umberto D'Alessandro and FSP/MISAME Group},
year = {2012},
date = {2012-03-01},
journal = {Malar. J.},
volume = {11},
number = {1},
pages = {71},
publisher = {Springer Nature},
abstract = {BACKGROUND: A prospective study aiming at assessing the effect
of adding a third dose sulphadoxine-pyrimethamine (SP) to the
standard two-dose intermittent preventive treatment for pregnant
women was carried out in Hounde, Burkina Faso, between March
2006 and July 2008. Pregnant women were identified as earlier as
possible during pregnancy through a network of home visitors,
referred to the health facilities for inclusion and followed up
until delivery. METHODS: Study participants were enrolled at
antenatal care (ANC) visits and randomized to receive either two
or three doses of SP at the appropriate time. Women were visited
daily and a blood slide was collected when there was fever (body
temperature > 37.5°C) or history of fever. Women were encouraged
to attend ANC and deliver in the health centre, where the
new-born was examined and weighed. The timing and frequency of
malaria infection was analysed in relation to the risk of low
birth weight, maternal anaemia and perinatal mortality. RESULTS:
Data on birth weight and haemoglobin were available for 1,034
women. The incidence of malaria infections was significantly
lower in women having received three instead of two doses of SP.
Occurrence of first malaria infection during the first or second
trimester was associated with a higher risk of low birth weight: incidence rate ratios of 3.56 (p < 0.001) and 1.72 (p = 0.034),
respectively. After adjusting for possible confounding factors,
the risk remained significantly higher for the infection in the first trimester of pregnancy (adjusted incidence rate ratio = 2.0},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: A prospective study aiming at assessing the effect
of adding a third dose sulphadoxine-pyrimethamine (SP) to the
standard two-dose intermittent preventive treatment for pregnant
women was carried out in Hounde, Burkina Faso, between March
2006 and July 2008. Pregnant women were identified as earlier as
possible during pregnancy through a network of home visitors,
referred to the health facilities for inclusion and followed up
until delivery. METHODS: Study participants were enrolled at
antenatal care (ANC) visits and randomized to receive either two
or three doses of SP at the appropriate time. Women were visited
daily and a blood slide was collected when there was fever (body
temperature > 37.5°C) or history of fever. Women were encouraged
to attend ANC and deliver in the health centre, where the
new-born was examined and weighed. The timing and frequency of
malaria infection was analysed in relation to the risk of low
birth weight, maternal anaemia and perinatal mortality. RESULTS:
Data on birth weight and haemoglobin were available for 1,034
women. The incidence of malaria infections was significantly
lower in women having received three instead of two doses of SP.
Occurrence of first malaria infection during the first or second
trimester was associated with a higher risk of low birth weight: incidence rate ratios of 3.56 (p < 0.001) and 1.72 (p = 0.034),
respectively. After adjusting for possible confounding factors,
the risk remained significantly higher for the infection in the first trimester of pregnancy (adjusted incidence rate ratio = 2.0 |
2011
|
Journal Articles
|
| S Clinical Trials Partnership RTS, Selidji Todagbe Agnandji, Bertrand Lell, Solange Solmeheim Soulanoudjingar, José Francisco Fernandes, Béatrice Peggy Abossolo, Cornelia Conzelmann, Barbara Gaelle Nfono Ondo Methogo, Yannick Doucka, Arnaud Flamen, Benjamin Mordmüller, Saadou Issifou, Peter Gottfried Kremsner, Jahit Sacarlal, Pedro Aide, Miguel Lanaspa, John J Aponte, Arlindo Nhamuave, Diana Quelhas, Quique Bassat, Sofia Mandjate, Eusébio Macete, Pedro Alonso, Salim Abdulla, Nahya Salim, Omar Juma, Mwanajaa Shomari, Kafuruki Shubis, Francisca Machera, Ali Said Hamad, Rose Minja, Ali Mtoro, Alma Sykes, Saumu Ahmed, Alwisa Martin Urassa, Ali Mohammed Ali, Grace Mwangoka, Marcel Tanner, Halidou Tinto, Umberto D’Alessandro, Hermann Sorgho, Innocent Valea, Marc Christian Tahita, William Kaboré, Sayouba Ouédraogo, Yara Sandrine, Robert Tinga Guiguemdé, Jean Bosco Ouédraogo, Mary J Hamel, Simon Kariuki, Chris Odero, Martina Oneko, Kephas Otieno, Norbert Awino, Jackton Omoto, John Williamson, Vincent Muturi-Kioi, Kayla F Laserson, Laurence Slutsker, Walter Otieno, Lucas Otieno, Otsyula Nekoye, Stacey Gondi, Allan Otieno, Bernhards Ogutu, Ruth Wasuna, Victorine Owira, David Jones, Agnes Akoth Onyango, Patricia Njuguna, Roma Chilengi, Pauline Akoo, Christine Kerubo, Jesse Gitaka, Charity Maingi, Trudie Lang, Ally Olotu, Benjamin Tsofa, Philip Bejon, Norbert Peshu, Kevin Marsh, Seth Owusu-Agyei, Kwaku Poku Asante, Kingsley Osei-Kwakye, Owusu Boahen, Samuel Ayamba, Kingsley Kayan, Ruth Owusu-Ofori, David Dosoo, Isaac Asante, George Adjei, George Adjei, Daniel Chandramohan, Brian Greenwood, John Lusingu, Samwel Gesase, Anangisye Malabeja, Omari Abdul, Hassan Kilavo, Coline Mahende, Edwin Liheluka, Martha Lemnge, Thor Theander, Chris Drakeley, Daniel Ansong, Tsiri Agbenyega, Samuel Adjei, Harry Owusu Boateng, Theresa Rettig, John Bawa, Justice Sylverken, David Sambian, Alex Agyekum, Larko Owusu, Francis Martinson, Irving Hoffman, Tisungane Mvalo, Portia Kamthunzi, Ruthendo Nkomo, Albans Msika, Allan Jumbe, Nelecy Chome, Dalitso Nyakuipa, Joseph Chintedza, W Ripley Ballou, Myriam Bruls, Joe Cohen, Yolanda Guerra, Erik Jongert, Didier Lapierre, Amanda Leach, Marc Lievens, Opokua Ofori-Anyinam, Johan Vekemans, Terrell Carter, Didier Leboulleux, Christian Loucq, Afiya Radford, Barbara Savarese, David Schellenberg, Marla Sillman, Preeti Vansadia First results of phase 3 trial of RTS,S/AS01 malaria vaccine
in African children (Journal Article) In: N. Engl. J. Med., vol. 365, no. 20, pp. 1863–1875, 2011. @article{RTSS_Clinical_Trials_Partnership2011-gv,
title = {First results of phase 3 trial of RTS,S/AS01 malaria vaccine
in African children},
author = {S Clinical Trials Partnership RTS and Selidji Todagbe Agnandji and Bertrand Lell and Solange Solmeheim Soulanoudjingar and Jos\'{e} Francisco Fernandes and B\'{e}atrice Peggy Abossolo and Cornelia Conzelmann and Barbara Gaelle Nfono Ondo Methogo and Yannick Doucka and Arnaud Flamen and Benjamin Mordm\"{u}ller and Saadou Issifou and Peter Gottfried Kremsner and Jahit Sacarlal and Pedro Aide and Miguel Lanaspa and John J Aponte and Arlindo Nhamuave and Diana Quelhas and Quique Bassat and Sofia Mandjate and Eus\'{e}bio Macete and Pedro Alonso and Salim Abdulla and Nahya Salim and Omar Juma and Mwanajaa Shomari and Kafuruki Shubis and Francisca Machera and Ali Said Hamad and Rose Minja and Ali Mtoro and Alma Sykes and Saumu Ahmed and Alwisa Martin Urassa and Ali Mohammed Ali and Grace Mwangoka and Marcel Tanner and Halidou Tinto and Umberto D'Alessandro and Hermann Sorgho and Innocent Valea and Marc Christian Tahita and William Kabor\'{e} and Sayouba Ou\'{e}draogo and Yara Sandrine and Robert Tinga Guiguemd\'{e} and Jean Bosco Ou\'{e}draogo and Mary J Hamel and Simon Kariuki and Chris Odero and Martina Oneko and Kephas Otieno and Norbert Awino and Jackton Omoto and John Williamson and Vincent Muturi-Kioi and Kayla F Laserson and Laurence Slutsker and Walter Otieno and Lucas Otieno and Otsyula Nekoye and Stacey Gondi and Allan Otieno and Bernhards Ogutu and Ruth Wasuna and Victorine Owira and David Jones and Agnes Akoth Onyango and Patricia Njuguna and Roma Chilengi and Pauline Akoo and Christine Kerubo and Jesse Gitaka and Charity Maingi and Trudie Lang and Ally Olotu and Benjamin Tsofa and Philip Bejon and Norbert Peshu and Kevin Marsh and Seth Owusu-Agyei and Kwaku Poku Asante and Kingsley Osei-Kwakye and Owusu Boahen and Samuel Ayamba and Kingsley Kayan and Ruth Owusu-Ofori and David Dosoo and Isaac Asante and George Adjei and George Adjei and Daniel Chandramohan and Brian Greenwood and John Lusingu and Samwel Gesase and Anangisye Malabeja and Omari Abdul and Hassan Kilavo and Coline Mahende and Edwin Liheluka and Martha Lemnge and Thor Theander and Chris Drakeley and Daniel Ansong and Tsiri Agbenyega and Samuel Adjei and Harry Owusu Boateng and Theresa Rettig and John Bawa and Justice Sylverken and David Sambian and Alex Agyekum and Larko Owusu and Francis Martinson and Irving Hoffman and Tisungane Mvalo and Portia Kamthunzi and Ruthendo Nkomo and Albans Msika and Allan Jumbe and Nelecy Chome and Dalitso Nyakuipa and Joseph Chintedza and W Ripley Ballou and Myriam Bruls and Joe Cohen and Yolanda Guerra and Erik Jongert and Didier Lapierre and Amanda Leach and Marc Lievens and Opokua Ofori-Anyinam and Johan Vekemans and Terrell Carter and Didier Leboulleux and Christian Loucq and Afiya Radford and Barbara Savarese and David Schellenberg and Marla Sillman and Preeti Vansadia},
year = {2011},
date = {2011-11-01},
journal = {N. Engl. J. Med.},
volume = {365},
number = {20},
pages = {1863--1875},
publisher = {New England Journal of Medicine (NEJM/MMS)},
abstract = {BACKGROUND: An ongoing phase 3 study of the efficacy, safety,
and immunogenicity of candidate malaria vaccine RTS,S/AS01 is
being conducted in seven African countries. METHODS: From March
2009 through January 2011, we enrolled 15,460 children in two
age categories--6 to 12 weeks of age and 5 to 17 months of
age--for vaccination with either RTS,S/AS01 or a non-malaria
comparator vaccine. The primary end point of the analysis was
vaccine efficacy against clinical malaria during the 12 months
after vaccination in the first 6000 children 5 to 17 months of
age at enrollment who received all three doses of vaccine
according to protocol. After 250 children had an episode of
severe malaria, we evaluated vaccine efficacy against severe
malaria in both age categories. RESULTS: In the 14 months after
the first dose of vaccine, the incidence of first episodes of
clinical malaria in the first 6000 children in the older age
category was 0.32 episodes per person-year in the RTS,S/AS01
group and 0.55 episodes per person-year in the control group,
for an efficacy of 50.4% (95% confidence interval [CI], 45.8
to 54.6) in the intention-to-treat population and 55.8% (97.5%
CI, 50.6 to 60.4) in the per-protocol population. Vaccine
efficacy against severe malaria was 45.1% (95% CI, 23.8 to
60.5) in the intention-to-treat population and 47.3% (95% CI,
22.4 to 64.2) in the per-protocol population. Vaccine efficacy
against severe malaria in the combined age categories was 34.8%
(95% CI, 16.2 to 49.2) in the per-protocol population during an
average follow-up of 11 months. Serious adverse events occurred
with a similar frequency in the two study groups. Among children
in the older age category, the rate of generalized convulsive
seizures after RTS,S/AS01 vaccination was 1.04 per 1000 doses
(95% CI, 0.62 to 1.64). CONCLUSIONS: The RTS,S/AS01 vaccine
provided protection against both clinical and severe malaria in
African children. (Funded by GlaxoSmithKline Biologicals and the
PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov
number, NCT00866619 .).},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: An ongoing phase 3 study of the efficacy, safety,
and immunogenicity of candidate malaria vaccine RTS,S/AS01 is
being conducted in seven African countries. METHODS: From March
2009 through January 2011, we enrolled 15,460 children in two
age categories–6 to 12 weeks of age and 5 to 17 months of
age–for vaccination with either RTS,S/AS01 or a non-malaria
comparator vaccine. The primary end point of the analysis was
vaccine efficacy against clinical malaria during the 12 months
after vaccination in the first 6000 children 5 to 17 months of
age at enrollment who received all three doses of vaccine
according to protocol. After 250 children had an episode of
severe malaria, we evaluated vaccine efficacy against severe
malaria in both age categories. RESULTS: In the 14 months after
the first dose of vaccine, the incidence of first episodes of
clinical malaria in the first 6000 children in the older age
category was 0.32 episodes per person-year in the RTS,S/AS01
group and 0.55 episodes per person-year in the control group,
for an efficacy of 50.4% (95% confidence interval [CI], 45.8
to 54.6) in the intention-to-treat population and 55.8% (97.5%
CI, 50.6 to 60.4) in the per-protocol population. Vaccine
efficacy against severe malaria was 45.1% (95% CI, 23.8 to
60.5) in the intention-to-treat population and 47.3% (95% CI,
22.4 to 64.2) in the per-protocol population. Vaccine efficacy
against severe malaria in the combined age categories was 34.8%
(95% CI, 16.2 to 49.2) in the per-protocol population during an
average follow-up of 11 months. Serious adverse events occurred
with a similar frequency in the two study groups. Among children
in the older age category, the rate of generalized convulsive
seizures after RTS,S/AS01 vaccination was 1.04 per 1000 doses
(95% CI, 0.62 to 1.64). CONCLUSIONS: The RTS,S/AS01 vaccine
provided protection against both clinical and severe malaria in
African children. (Funded by GlaxoSmithKline Biologicals and the
PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov
number, NCT00866619 .). |
| Zeno Bisoffi, Sodiomon B Sirima, Filip Meheus, Claudia Lodesani, Federico Gobbi, Andrea Angheben, Halidou Tinto, Bouma Neya, Klara Van den Ende, Annalisa Romeo, Jef Van den Ende Strict adherence to malaria rapid test results might lead to a
neglect of other dangerous diseases: a cost benefit analysis
from Burkina Faso (Journal Article) In: Malar. J., vol. 10, no. 1, pp. 226, 2011. @article{Bisoffi2011-dn,
title = {Strict adherence to malaria rapid test results might lead to a
neglect of other dangerous diseases: a cost benefit analysis
from Burkina Faso},
author = {Zeno Bisoffi and Sodiomon B Sirima and Filip Meheus and Claudia Lodesani and Federico Gobbi and Andrea Angheben and Halidou Tinto and Bouma Neya and Klara Van den Ende and Annalisa Romeo and Jef Van den Ende},
year = {2011},
date = {2011-08-01},
journal = {Malar. J.},
volume = {10},
number = {1},
pages = {226},
publisher = {Springer Nature},
abstract = {BACKGROUND: Malaria rapid diagnostic tests (RDTs) have generally
been found reliable and cost-effective. In Burkina Faso, the
adherence of prescribers to the negative test result was found
to be poor. Moreover, the test accuracy for malaria-attributable
fever (MAF) is not the same as for malaria infection. This paper
aims at determining the costs and benefits of two competing
strategies for the management of MAF: presumptive treatment for
all or use of RDTs. METHODS: A cost benefit analysis was carried
out using a decision tree, based on data previously obtained,
including a randomized controlled trial (RCT) recruiting 852
febrile patients during the dry season and 1,317 in the rainy
season. Cost and benefit were calculated using both the real
adherence found by the RCT and assuming an ideal adherence of
90% with the negative result. The main parameters were
submitted to sensitivity analysis. RESULTS AND DISCUSSION: At
real adherence, the test-based strategy was dominated. Assuming
ideal adherence, at the value of 525 € for a death averted, the
total cost of managing 1,000 febrile children was 1,747 vs.
1,862 € in the dry season and 1,372 vs. 2,138 in the rainy
season for the presumptive vs. the test-based strategy. For
adults it was 2,728 vs. 1,983 and 2,604 vs. 2,225, respectively.
At the subsidized policy adopted locally, assuming ideal
adherence, the RDT would be the winning strategy for adults in
both seasons and for children in the dry season.At sensitivity
analysis, the factors most influencing the choice of the better
strategy were the value assigned to a death averted and the
proportion of potentially severe NMFI treated with antibiotics
in patients with false positive RDT results. The test-based
strategy appears advantageous for adults if a satisfactory
adherence could be achieved. For children the presumptive
strategy remains the best choice for a wide range of scenarios.
CONCLUSIONS: For RDTs to be preferred, a positive result should
not influence the decision to treat a potentially severe NMFI
with antibiotics. In the rainy season the presumptive strategy
always remains the better choice for children.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Malaria rapid diagnostic tests (RDTs) have generally
been found reliable and cost-effective. In Burkina Faso, the
adherence of prescribers to the negative test result was found
to be poor. Moreover, the test accuracy for malaria-attributable
fever (MAF) is not the same as for malaria infection. This paper
aims at determining the costs and benefits of two competing
strategies for the management of MAF: presumptive treatment for
all or use of RDTs. METHODS: A cost benefit analysis was carried
out using a decision tree, based on data previously obtained,
including a randomized controlled trial (RCT) recruiting 852
febrile patients during the dry season and 1,317 in the rainy
season. Cost and benefit were calculated using both the real
adherence found by the RCT and assuming an ideal adherence of
90% with the negative result. The main parameters were
submitted to sensitivity analysis. RESULTS AND DISCUSSION: At
real adherence, the test-based strategy was dominated. Assuming
ideal adherence, at the value of 525 € for a death averted, the
total cost of managing 1,000 febrile children was 1,747 vs.
1,862 € in the dry season and 1,372 vs. 2,138 in the rainy
season for the presumptive vs. the test-based strategy. For
adults it was 2,728 vs. 1,983 and 2,604 vs. 2,225, respectively.
At the subsidized policy adopted locally, assuming ideal
adherence, the RDT would be the winning strategy for adults in
both seasons and for children in the dry season.At sensitivity
analysis, the factors most influencing the choice of the better
strategy were the value assigned to a death averted and the
proportion of potentially severe NMFI treated with antibiotics
in patients with false positive RDT results. The test-based
strategy appears advantageous for adults if a satisfactory
adherence could be achieved. For children the presumptive
strategy remains the best choice for a wide range of scenarios.
CONCLUSIONS: For RDTs to be preferred, a positive result should
not influence the decision to treat a potentially severe NMFI
with antibiotics. In the rainy season the presumptive strategy
always remains the better choice for children. |
| Christine Swysen, Johan Vekemans, Myriam Bruls, Sunny Oyakhirome, Chris Drakeley, Peter Kremsner, Brian Greenwood, Opokua Ofori-Anyinam, Brenda Okech, Tonya Villafana, Terrell Carter, Barbara Savarese, Adriano Duse, Andrea Reijman, Charlotte Ingram, John Frean, Bernhards Ogutu, Clinical Trials Partnership Committee Development of standardized laboratory methods and quality
processes for a phase III study of the RTS, S/AS01
candidate malaria vaccine (Journal Article) In: Malar. J., vol. 10, no. 1, pp. 223, 2011. @article{Swysen2011-lr,
title = {Development of standardized laboratory methods and quality
processes for a phase III study of the RTS, S/AS01
candidate malaria vaccine},
author = {Christine Swysen and Johan Vekemans and Myriam Bruls and Sunny Oyakhirome and Chris Drakeley and Peter Kremsner and Brian Greenwood and Opokua Ofori-Anyinam and Brenda Okech and Tonya Villafana and Terrell Carter and Barbara Savarese and Adriano Duse and Andrea Reijman and Charlotte Ingram and John Frean and Bernhards Ogutu and Clinical Trials Partnership Committee},
year = {2011},
date = {2011-08-01},
journal = {Malar. J.},
volume = {10},
number = {1},
pages = {223},
publisher = {Springer Nature},
abstract = {BACKGROUND: A pivotal phase III study of the RTS,S/AS01 malaria
candidate vaccine is ongoing in several research centres across
Africa. The development and establishment of quality systems was
a requirement for trial conduct to meet international regulatory
standards, as well as providing an important capacity
strengthening opportunity for study centres. METHODS:
Standardized laboratory methods and quality assurance processes
were implemented at each of the study centres, facilitated by
funding partners. RESULTS: A robust protocol for determination
of parasite density based on actual blood cell counts was set up
in accordance with World Health Organization recommendations.
Automated equipment including haematology and biochemistry
analyzers were put in place with standard methods for bedside
testing of glycaemia, base excess and lactacidaemia. Facilities
for X-rays and basic microbiology testing were also provided or
upgraded alongside health care infrastructure in some centres.
External quality assurance assessment of all major laboratory
methods was established and method qualification by each
laboratory demonstrated. The resulting capacity strengthening
has ensured laboratory evaluations are conducted locally to the
high standards required in clinical trials. CONCLUSION: Major
efforts by study centres, together with support from
collaborating parties, have allowed standardized methods and
robust quality assurance processes to be put in place for the
phase III evaluation of the RTS, S/AS01 malaria candidate
vaccine. Extensive training programmes, coupled with continuous
commitment from research centre staff, have been the key
elements behind the successful implementation of quality
processes. It is expected these activities will culminate in
healthcare benefits for the subjects and communities
participating in these trials. TRIAL REGISTRATION:
Clinicaltrials.gov NCT00866619.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: A pivotal phase III study of the RTS,S/AS01 malaria
candidate vaccine is ongoing in several research centres across
Africa. The development and establishment of quality systems was
a requirement for trial conduct to meet international regulatory
standards, as well as providing an important capacity
strengthening opportunity for study centres. METHODS:
Standardized laboratory methods and quality assurance processes
were implemented at each of the study centres, facilitated by
funding partners. RESULTS: A robust protocol for determination
of parasite density based on actual blood cell counts was set up
in accordance with World Health Organization recommendations.
Automated equipment including haematology and biochemistry
analyzers were put in place with standard methods for bedside
testing of glycaemia, base excess and lactacidaemia. Facilities
for X-rays and basic microbiology testing were also provided or
upgraded alongside health care infrastructure in some centres.
External quality assurance assessment of all major laboratory
methods was established and method qualification by each
laboratory demonstrated. The resulting capacity strengthening
has ensured laboratory evaluations are conducted locally to the
high standards required in clinical trials. CONCLUSION: Major
efforts by study centres, together with support from
collaborating parties, have allowed standardized methods and
robust quality assurance processes to be put in place for the
phase III evaluation of the RTS, S/AS01 malaria candidate
vaccine. Extensive training programmes, coupled with continuous
commitment from research centre staff, have been the key
elements behind the successful implementation of quality
processes. It is expected these activities will culminate in
healthcare benefits for the subjects and communities
participating in these trials. TRIAL REGISTRATION:
Clinicaltrials.gov NCT00866619. |
| Raffaella Ravinetto, Anne Buvé, Tinto Halidou, Pascal Lutumba, Ambrose Talisuna, Mohammad Juffrie, Umberto D’Alessandro, Marleen Boelaert Double ethical review of North-South collaborative clinical
research: hidden paternalism or real partnership? (Journal Article) In: Trop. Med. Int. Health, vol. 16, no. 4, pp. 527–530, 2011. @article{Ravinetto2011-tb,
title = {Double ethical review of North-South collaborative clinical
research: hidden paternalism or real partnership?},
author = {Raffaella Ravinetto and Anne Buv\'{e} and Tinto Halidou and Pascal Lutumba and Ambrose Talisuna and Mohammad Juffrie and Umberto D'Alessandro and Marleen Boelaert},
year = {2011},
date = {2011-04-01},
journal = {Trop. Med. Int. Health},
volume = {16},
number = {4},
pages = {527--530},
publisher = {Wiley},
abstract = {Despite their universal character, the ethical principles
governing clinical research need to be translated into
procedures and practices, which will vary among countries and
regions because of differences in local cultural norms and in
the available resources. Double ethical review, by which a
research protocol is submitted for ethical clearance both in the
country or countries where the research takes place and in the
country of the sponsor or funding agency, will then help ensure
that all relevant perspectives are taken into account. In
addition, a geographically and culturally close ethics committee
can do a much better informed and comprehensive assessment of
the respective skills of the clinical sites and of the sponsor.
But the practical implementation of double ethical review can
bring significant difficulties and delays, especially in
multi-site and multi-country researches. Currently, most ethics
committees do not proactively seek communication with others
evaluating the same research protocol in different
socio-economical and cultural contexts, so in practice there is
no mutual learning process. Proactive communication would help
to build collaborative partnership among ethical bodies,
promoting common practices and resolving conflicting opinions.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Despite their universal character, the ethical principles
governing clinical research need to be translated into
procedures and practices, which will vary among countries and
regions because of differences in local cultural norms and in
the available resources. Double ethical review, by which a
research protocol is submitted for ethical clearance both in the
country or countries where the research takes place and in the
country of the sponsor or funding agency, will then help ensure
that all relevant perspectives are taken into account. In
addition, a geographically and culturally close ethics committee
can do a much better informed and comprehensive assessment of
the respective skills of the clinical sites and of the sponsor.
But the practical implementation of double ethical review can
bring significant difficulties and delays, especially in
multi-site and multi-country researches. Currently, most ethics
committees do not proactively seek communication with others
evaluating the same research protocol in different
socio-economical and cultural contexts, so in practice there is
no mutual learning process. Proactive communication would help
to build collaborative partnership among ethical bodies,
promoting common practices and resolving conflicting opinions. |
2010
|
Journal Articles
|
| Innocent Valea, Halidou Tinto, Maxime K Drabo, Lieven Huybregts, Marie-Claire Henry, Dominique Roberfroid, Robert T Guiguemde, Patrick Kolsteren, Umberto D’Alessandro, FSP/MISAME Group Intermittent preventive treatment of malaria with
sulphadoxine-pyrimethamine during pregnancy in Burkina Faso:
effect of adding a third dose to the standard two-dose regimen
on low birth weight, anaemia and pregnancy outcomes (Journal Article) In: Malar. J., vol. 9, no. 1, pp. 324, 2010. @article{Valea2010-af,
title = {Intermittent preventive treatment of malaria with
sulphadoxine-pyrimethamine during pregnancy in Burkina Faso:
effect of adding a third dose to the standard two-dose regimen
on low birth weight, anaemia and pregnancy outcomes},
author = {Innocent Valea and Halidou Tinto and Maxime K Drabo and Lieven Huybregts and Marie-Claire Henry and Dominique Roberfroid and Robert T Guiguemde and Patrick Kolsteren and Umberto D'Alessandro and FSP/MISAME Group},
year = {2010},
date = {2010-11-01},
journal = {Malar. J.},
volume = {9},
number = {1},
pages = {324},
publisher = {Springer Nature},
abstract = {BACKGROUND: Intermittent preventive treatment with
sulphadoxine-pyrimethamine (IPTp-SP) is being implemented in
most malaria endemic countries as a standard two-doses regimen
as it reduces the risk of low birth weight (LBW) and the
prevalence of maternal anaemia. Nevertheless, where the risk of
infection close to delivery is high because of intense
transmission, a third IPTp-SP dose may further reduce the
negative effects of malaria on pregnancy outcome. METHODS:
Pregnant women in the 2nd or 3rd trimester were randomized to
receive either 2 (SP2) or 3 doses (SP3) of SP. Trained field
workers paid home visits to the women for drug administration
according to a predefined drug delivery schedule. Women were
encouraged to attend their scheduled ANC visits and to deliver
at the health facilities where the new-born was weighed. The
prevalence of LBW (<2500 g), severe anaemia (Hb < 8 g/dL) and
premature birth was analysed using intention-to-treat (ITT) and
per-protocol (PP) analysis. RESULTS: Data from 1274 singleton
pregnancies were analysed (641 in the SP3 and 633 in the SP2
group). The uptake of the intervention appeared to be low.
Though the prevalence of LBW in both intervention groups was similar (adjusted Incident Rate Rati},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Intermittent preventive treatment with
sulphadoxine-pyrimethamine (IPTp-SP) is being implemented in
most malaria endemic countries as a standard two-doses regimen
as it reduces the risk of low birth weight (LBW) and the
prevalence of maternal anaemia. Nevertheless, where the risk of
infection close to delivery is high because of intense
transmission, a third IPTp-SP dose may further reduce the
negative effects of malaria on pregnancy outcome. METHODS:
Pregnant women in the 2nd or 3rd trimester were randomized to
receive either 2 (SP2) or 3 doses (SP3) of SP. Trained field
workers paid home visits to the women for drug administration
according to a predefined drug delivery schedule. Women were
encouraged to attend their scheduled ANC visits and to deliver
at the health facilities where the new-born was weighed. The
prevalence of LBW (<2500 g), severe anaemia (Hb < 8 g/dL) and
premature birth was analysed using intention-to-treat (ITT) and
per-protocol (PP) analysis. RESULTS: Data from 1274 singleton
pregnancies were analysed (641 in the SP3 and 633 in the SP2
group). The uptake of the intervention appeared to be low.
Though the prevalence of LBW in both intervention groups was similar (adjusted Incident Rate Rati |
| Zeno Bisoffi, Sodiomon B Sirima, Joris Menten, Cristian Pattaro, Andrea Angheben, Federico Gobbi, Halidou Tinto, Claudia Lodesani, Bouma Neya, Maria Gobbo, Jef Van den Ende Accuracy of a rapid diagnostic test on the diagnosis of malaria
infection and of malaria-attributable fever during low and high
transmission season in Burkina Faso (Journal Article) In: Malar. J., vol. 9, no. 1, pp. 192, 2010. @article{Bisoffi2010-jd,
title = {Accuracy of a rapid diagnostic test on the diagnosis of malaria
infection and of malaria-attributable fever during low and high
transmission season in Burkina Faso},
author = {Zeno Bisoffi and Sodiomon B Sirima and Joris Menten and Cristian Pattaro and Andrea Angheben and Federico Gobbi and Halidou Tinto and Claudia Lodesani and Bouma Neya and Maria Gobbo and Jef Van den Ende},
year = {2010},
date = {2010-07-01},
journal = {Malar. J.},
volume = {9},
number = {1},
pages = {192},
publisher = {Springer Nature},
abstract = {BACKGROUND: Malaria management policies currently recommend that
the treatment should only be administered after laboratory
confirmation. Where microscopy is not available, rapid
diagnostic tests (RDTs) are the usual alternative. Conclusive
evidence is still lacking on the safety of a test-based strategy
for children. Moreover, no formal attempt has been made to
estimate RDTs accuracy on malaria-attributable fever. This study
aims at estimating the accuracy of a RDT for the diagnosis of
both malaria infection and malaria - attributable fever, in a
region of Burkina Faso with a typically seasonal malaria
transmission pattern. METHODS: Cross-sectional study. SUBJECTS:
all patients aged > 6 months consulting during the study
periods. Gold standard for the diagnosis of malaria infection
was microscopy. Gold standard for malaria-attributable fever was
the number of fevers attributable to malaria, estimated by
comparing parasite densities of febrile versus non-febrile
subjects. EXCLUSION CRITERIA: severe clinical condition needing
urgent care. RESULTS: In the dry season, 186/852 patients with
fever (22%) and 213/1,382 patients without fever (15%) had a
Plasmodium falciparum infection. In the rainy season, this
proportion was 841/1,317 (64%) and 623/1,669 (37%),
respectively. The attributable fraction of fever to malaria was
11% and 69%, respectively. The RDT was positive in 113/400
(28.3%) fever cases in the dry season, and in 443/650 (68.2%)
in the rainy season. In the dry season, the RDT sensitivity and
specificity for malaria infection were 86% and 90%
respectively. In the rainy season they were 94% and 78%
respectively. In the dry season, the RDT sensitivity and
specificity for malaria-attributable fever were 94% and 75%,
the positive predictive value (PPV) was 9% and the negative
predictive value (NPV) was 99.8%. In the rainy season the test
sensitivity for malaria-attributable fever was 97% and
specificity was 55%. The PPV ranged from 38% for adults to
82% for infants, while the NPV ranged from 84% for infants to
over 99% for adults. CONCLUSIONS: In the dry season the RDT has
a low positive predictive value, but a very high negative
predictive value for malaria-attributable fever. In the rainy
season the negative test safely excludes malaria in adults but
not in children.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Malaria management policies currently recommend that
the treatment should only be administered after laboratory
confirmation. Where microscopy is not available, rapid
diagnostic tests (RDTs) are the usual alternative. Conclusive
evidence is still lacking on the safety of a test-based strategy
for children. Moreover, no formal attempt has been made to
estimate RDTs accuracy on malaria-attributable fever. This study
aims at estimating the accuracy of a RDT for the diagnosis of
both malaria infection and malaria – attributable fever, in a
region of Burkina Faso with a typically seasonal malaria
transmission pattern. METHODS: Cross-sectional study. SUBJECTS:
all patients aged > 6 months consulting during the study
periods. Gold standard for the diagnosis of malaria infection
was microscopy. Gold standard for malaria-attributable fever was
the number of fevers attributable to malaria, estimated by
comparing parasite densities of febrile versus non-febrile
subjects. EXCLUSION CRITERIA: severe clinical condition needing
urgent care. RESULTS: In the dry season, 186/852 patients with
fever (22%) and 213/1,382 patients without fever (15%) had a
Plasmodium falciparum infection. In the rainy season, this
proportion was 841/1,317 (64%) and 623/1,669 (37%),
respectively. The attributable fraction of fever to malaria was
11% and 69%, respectively. The RDT was positive in 113/400
(28.3%) fever cases in the dry season, and in 443/650 (68.2%)
in the rainy season. In the dry season, the RDT sensitivity and
specificity for malaria infection were 86% and 90%
respectively. In the rainy season they were 94% and 78%
respectively. In the dry season, the RDT sensitivity and
specificity for malaria-attributable fever were 94% and 75%,
the positive predictive value (PPV) was 9% and the negative
predictive value (NPV) was 99.8%. In the rainy season the test
sensitivity for malaria-attributable fever was 97% and
specificity was 55%. The PPV ranged from 38% for adults to
82% for infants, while the NPV ranged from 84% for infants to
over 99% for adults. CONCLUSIONS: In the dry season the RDT has
a low positive predictive value, but a very high negative
predictive value for malaria-attributable fever. In the rainy
season the negative test safely excludes malaria in adults but
not in children. |
2009
|
Journal Articles
|
| Quique Bassat, Modest Mulenga, Halidou Tinto, Patrice Piola, Steffen Borrmann, Clara Menéndez, Michael Nambozi, Innocent Valéa, Carolyn Nabasumba, Philip Sasi, Antonella Bacchieri, Marco Corsi, David Ubben, Ambrose Talisuna, Umberto D’Alessandro Dihydroartemisinin-piperaquine and artemether-lumefantrine for
treating uncomplicated malaria in African children: a
randomised, non-inferiority trial (Journal Article) In: PLoS One, vol. 4, no. 11, pp. e7871, 2009. @article{Bassat2009-xq,
title = {Dihydroartemisinin-piperaquine and artemether-lumefantrine for
treating uncomplicated malaria in African children: a
randomised, non-inferiority trial},
author = {Quique Bassat and Modest Mulenga and Halidou Tinto and Patrice Piola and Steffen Borrmann and Clara Men\'{e}ndez and Michael Nambozi and Innocent Val\'{e}a and Carolyn Nabasumba and Philip Sasi and Antonella Bacchieri and Marco Corsi and David Ubben and Ambrose Talisuna and Umberto D'Alessandro},
year = {2009},
date = {2009-11-01},
journal = {PLoS One},
volume = {4},
number = {11},
pages = {e7871},
publisher = {Public Library of Science (PLoS)},
abstract = {BACKGROUND: Artemisinin combination therapies (ACTs) are
currently the preferred option for treating uncomplicated
malaria. Dihydroartemisinin-piperaquine (DHA-PQP) is a promising
fixed-dose ACT with limited information on its safety and
efficacy in African children. METHODOLOGY/PRINCIPAL FINDINGS:
The non-inferiority of DHA-PQP versus artemether-lumefantrine
(AL) in children 6-59 months old with uncomplicated P.
falciparum malaria was tested in five African countries (Burkina
Faso, Kenya, Mozambique, Uganda and Zambia). Patients were
randomised (2:1) to receive either DHA-PQP or AL.
Non-inferiority was assessed using a margin of -5% for the
lower limit of the one-sided 97.5% confidence interval on the
treatment difference (DHA-PQP vs. AL) of the day 28 polymerase
chain reaction (PCR) corrected cure rate. Efficacy analysis was
performed in several populations, and two of them are presented
here: intention-to-treat (ITT) and enlarged per-protocol (ePP).
1553 children were randomised, 1039 receiving DHA-PQP and 514
AL. The PCR-corrected day 28 cure rate was 90.4% (ITT) and
94.7% (ePP) in the DHA-PQP group, and 90.0% (ITT) and 95.3%
(ePP) in the AL group. The lower limits of the one-sided 97.5%
CI of the difference between the two treatments were -2.80% and
-2.96%, in the ITT and ePP populations, respectively. In the
ITT population, the Kaplan-Meier estimate of the proportion of
new infections up to Day 42 was 13.55% (95% CI:
11.35%-15.76%) for DHA-PQP vs 24.00% (95% CI:
20.11%-27.88%) for AL (p<0.0001). CONCLUSIONS/SIGNIFICANCE:
DHA-PQP is as efficacious as AL in treating uncomplicated
malaria in African children from different endemicity settings,
and shows a comparable safety profile. The occurrence of new
infections within the 42-day follow up was significantly lower
in the DHA-PQP group, indicating a longer post-treatment
prophylactic effect. TRIAL REGISTRATION: Controlled-trials.com
ISRCTN16263443.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Artemisinin combination therapies (ACTs) are
currently the preferred option for treating uncomplicated
malaria. Dihydroartemisinin-piperaquine (DHA-PQP) is a promising
fixed-dose ACT with limited information on its safety and
efficacy in African children. METHODOLOGY/PRINCIPAL FINDINGS:
The non-inferiority of DHA-PQP versus artemether-lumefantrine
(AL) in children 6-59 months old with uncomplicated P.
falciparum malaria was tested in five African countries (Burkina
Faso, Kenya, Mozambique, Uganda and Zambia). Patients were
randomised (2:1) to receive either DHA-PQP or AL.
Non-inferiority was assessed using a margin of -5% for the
lower limit of the one-sided 97.5% confidence interval on the
treatment difference (DHA-PQP vs. AL) of the day 28 polymerase
chain reaction (PCR) corrected cure rate. Efficacy analysis was
performed in several populations, and two of them are presented
here: intention-to-treat (ITT) and enlarged per-protocol (ePP).
1553 children were randomised, 1039 receiving DHA-PQP and 514
AL. The PCR-corrected day 28 cure rate was 90.4% (ITT) and
94.7% (ePP) in the DHA-PQP group, and 90.0% (ITT) and 95.3%
(ePP) in the AL group. The lower limits of the one-sided 97.5%
CI of the difference between the two treatments were -2.80% and
-2.96%, in the ITT and ePP populations, respectively. In the
ITT population, the Kaplan-Meier estimate of the proportion of
new infections up to Day 42 was 13.55% (95% CI:
11.35%-15.76%) for DHA-PQP vs 24.00% (95% CI:
20.11%-27.88%) for AL (p<0.0001). CONCLUSIONS/SIGNIFICANCE:
DHA-PQP is as efficacious as AL in treating uncomplicated
malaria in African children from different endemicity settings,
and shows a comparable safety profile. The occurrence of new
infections within the 42-day follow up was significantly lower
in the DHA-PQP group, indicating a longer post-treatment
prophylactic effect. TRIAL REGISTRATION: Controlled-trials.com
ISRCTN16263443. |
| Zeno Bisoffi, Bienvenu Sodiomon Sirima, Andrea Angheben, Claudia Lodesani, Federico Gobbi, Halidou Tinto, Jef Van den Ende Rapid malaria diagnostic tests vs. clinical management of
malaria in rural Burkina Faso: safety and effect on clinical
decisions. A randomized trial (Journal Article) In: Trop. Med. Int. Health, vol. 14, no. 5, pp. 491–498, 2009. @article{Bisoffi2009-zh,
title = {Rapid malaria diagnostic tests vs. clinical management of
malaria in rural Burkina Faso: safety and effect on clinical
decisions. A randomized trial},
author = {Zeno Bisoffi and Bienvenu Sodiomon Sirima and Andrea Angheben and Claudia Lodesani and Federico Gobbi and Halidou Tinto and Jef Van den Ende},
year = {2009},
date = {2009-05-01},
journal = {Trop. Med. Int. Health},
volume = {14},
number = {5},
pages = {491--498},
publisher = {Wiley},
abstract = {OBJECTIVES: To assess if the clinical outcome of patients
treated after performing a Rapid Diagnostic Test for malaria
(RDT) is at least equivalent to that of controls (treated
presumptively without test) and to determine the impact of the
introduction of a malaria RDT on clinical decisions. METHODS:
Randomized, multi-centre, open clinical trial in two arms in
2006 at the end of the dry and of the rainy season in 10
peripheral health centres in Burkina Faso: one arm with use of
RDT before treatment decision, one arm managed clinically.
Primary endpoint: persistence of fever at day 4. Secondary
endpoints: frequency of malaria treatment and of antibiotic
treatment. RESULTS: A total of 852 febrile patients were
recruited in the dry season and 1317 febrile patients in the
rainy season, and randomized either to be submitted to RDT
(P_RTD) or to be managed presumptively (P_CLIN). In both
seasons, no significant difference was found between the two
randomized groups in the frequency of antimalarial treatment,
nor of antibiotic prescription. In the dry season, 80.8% and
79.8% of patients with a negative RDT were nevertheless
diagnosed and treated for malaria, and so were 85.0% and 82.6%
negative patients in the rainy season. In the rainy season only,
both diagnosis and treatment of other conditions were
significantly less frequent in RDT positive vs. negative patients (48.3% vs. 61.4% and 46.2% vs. 59.9},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVES: To assess if the clinical outcome of patients
treated after performing a Rapid Diagnostic Test for malaria
(RDT) is at least equivalent to that of controls (treated
presumptively without test) and to determine the impact of the
introduction of a malaria RDT on clinical decisions. METHODS:
Randomized, multi-centre, open clinical trial in two arms in
2006 at the end of the dry and of the rainy season in 10
peripheral health centres in Burkina Faso: one arm with use of
RDT before treatment decision, one arm managed clinically.
Primary endpoint: persistence of fever at day 4. Secondary
endpoints: frequency of malaria treatment and of antibiotic
treatment. RESULTS: A total of 852 febrile patients were
recruited in the dry season and 1317 febrile patients in the
rainy season, and randomized either to be submitted to RDT
(P_RTD) or to be managed presumptively (P_CLIN). In both
seasons, no significant difference was found between the two
randomized groups in the frequency of antimalarial treatment,
nor of antibiotic prescription. In the dry season, 80.8% and
79.8% of patients with a negative RDT were nevertheless
diagnosed and treated for malaria, and so were 85.0% and 82.6%
negative patients in the rainy season. In the rainy season only,
both diagnosis and treatment of other conditions were
significantly less frequent in RDT positive vs. negative patients (48.3% vs. 61.4% and 46.2% vs. 59.9 |
| Innocent Valéa, Halidou Tinto, Madi Nikiema, Lawrence Yamuah, Noel Rouamba, Maxime Drabo, Robert T Guiguemde, Umberto d’Alessandro Performance of OptiMAL-IT compared to microscopy, for malaria
detection in Burkina Faso (Journal Article) In: Trop. Med. Int. Health, vol. 14, no. 3, pp. 338–340, 2009. @article{Valea2009-ip,
title = {Performance of OptiMAL-IT compared to microscopy, for malaria
detection in Burkina Faso},
author = {Innocent Val\'{e}a and Halidou Tinto and Madi Nikiema and Lawrence Yamuah and Noel Rouamba and Maxime Drabo and Robert T Guiguemde and Umberto d'Alessandro},
year = {2009},
date = {2009-03-01},
journal = {Trop. Med. Int. Health},
volume = {14},
number = {3},
pages = {338--340},
publisher = {Wiley},
abstract = {OBJECTIVE: To compare the performance of OptiMAL-IT, a rapid
diagnostic test for malaria, with that of microscopy in Burkina
Faso. METHOD: Finger-prick blood samples of 464 children
attending hospital for suspected malaria were tested for malaria
by microscopy and OptiMAL-IT. RESULTS: The sensitivity and specificity of OptiMAL-IT were 98.7% (CI 95% = 97.6-99.8) and 96.2% (CI 95% = 94.3-98.1) respectively, with a high positive
likelihood ratio (25.97). CONCLUSION: OptiMAL-IT can be
considered a good method to diagnose malaria in Burkina Faso,
particularly in remote areas with little or no access to
microscopy services.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE: To compare the performance of OptiMAL-IT, a rapid
diagnostic test for malaria, with that of microscopy in Burkina
Faso. METHOD: Finger-prick blood samples of 464 children
attending hospital for suspected malaria were tested for malaria
by microscopy and OptiMAL-IT. RESULTS: The sensitivity and specificity of OptiMAL-IT were 98.7% (CI 95% = 97.6-99.8) and 96.2% (CI 95% = 94.3-98.1) respectively, with a high positive
likelihood ratio (25.97). CONCLUSION: OptiMAL-IT can be
considered a good method to diagnose malaria in Burkina Faso,
particularly in remote areas with little or no access to
microscopy services. |
2008
|
Journal Articles
|
| Richard L Culleton, Toshihiro Mita, Mathieu Ndounga, Holger Unger, Pedro V L Cravo, Giacomo M Paganotti, Nobuyuki Takahashi, Akira Kaneko, Hideaki Eto, Halidou Tinto, Corine Karema, Umberto D’Alessandro, Virgilio Rosário, Takatoshi Kobayakawa, Francine Ntoumi, Richard Carter, Kazuyuki Tanabe Failure to detect Plasmodium vivax in West and Central Africa by
PCR species typing (Journal Article) In: Malar. J., vol. 7, no. 1, pp. 174, 2008. @article{Culleton2008-pj,
title = {Failure to detect Plasmodium vivax in West and Central Africa by
PCR species typing},
author = {Richard L Culleton and Toshihiro Mita and Mathieu Ndounga and Holger Unger and Pedro V L Cravo and Giacomo M Paganotti and Nobuyuki Takahashi and Akira Kaneko and Hideaki Eto and Halidou Tinto and Corine Karema and Umberto D'Alessandro and Virgilio Ros\'{a}rio and Takatoshi Kobayakawa and Francine Ntoumi and Richard Carter and Kazuyuki Tanabe},
year = {2008},
date = {2008-09-01},
journal = {Malar. J.},
volume = {7},
number = {1},
pages = {174},
publisher = {Springer Nature},
abstract = {BACKGROUND: Plasmodium vivax is estimated to affect 75 million
people annually. It is reportedly absent, however, from west and
central Africa due to the high prevalence of the Duffy negative
phenotype in the indigenous populations. Despite this,
non-African travellers consistently return to their own
countries with P. vivax malaria after visiting this region. An
attempt was made, therefore, to detect the presence of P. vivax
parasites in blood samples collected from the indigenous
populations of west and central Africa. METHODS: Parasite
species typing (for all four human malaria parasites) was
carried out by PCR on 2,588 blood samples collected from
individuals from nine African malaria-endemic countries.
RESULTS: Most infections (98.5%) were Plasmodium falciparum,
Plasmodium malariae was identified in 8.5% of all infections,
and Plasmodium ovale in 3.9%. The prevalence of both parasites
varied greatly by country. Only one case of P. vivax was
detected from Sao Tome, an island off the west coast of Africa,
confirming the scarcity of this parasite in Africa. CONCLUSION:
The prevalence of P. vivax in local populations in sub-Saharan
Africa is very low, despite the frequent identification of this
parasite in non-African travellers.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Plasmodium vivax is estimated to affect 75 million
people annually. It is reportedly absent, however, from west and
central Africa due to the high prevalence of the Duffy negative
phenotype in the indigenous populations. Despite this,
non-African travellers consistently return to their own
countries with P. vivax malaria after visiting this region. An
attempt was made, therefore, to detect the presence of P. vivax
parasites in blood samples collected from the indigenous
populations of west and central Africa. METHODS: Parasite
species typing (for all four human malaria parasites) was
carried out by PCR on 2,588 blood samples collected from
individuals from nine African malaria-endemic countries.
RESULTS: Most infections (98.5%) were Plasmodium falciparum,
Plasmodium malariae was identified in 8.5% of all infections,
and Plasmodium ovale in 3.9%. The prevalence of both parasites
varied greatly by country. Only one case of P. vivax was
detected from Sao Tome, an island off the west coast of Africa,
confirming the scarcity of this parasite in Africa. CONCLUSION:
The prevalence of P. vivax in local populations in sub-Saharan
Africa is very low, despite the frequent identification of this
parasite in non-African travellers. |
| Halidou Tinto, Lougué Guekoun, Issaka Zongo, Robert Tinga Guiguemdé, Umberto D’Alessandro, Jean Bosco Ouédraogo Chloroquine-resistance molecular markers (Pfcrt T76 and
Pfmdr-1 Y86) and amodiaquine resistance in Burkina Faso (Journal Article) In: Trop. Med. Int. Health, vol. 13, no. 2, pp. 238–240, 2008. @article{Tinto2008-bs,
title = {Chloroquine-resistance molecular markers (Pfcrt T76 and
Pfmdr-1 Y86) and amodiaquine resistance in Burkina Faso},
author = {Halidou Tinto and Lougu\'{e} Guekoun and Issaka Zongo and Robert Tinga Guiguemd\'{e} and Umberto D'Alessandro and Jean Bosco Ou\'{e}draogo},
year = {2008},
date = {2008-02-01},
journal = {Trop. Med. Int. Health},
volume = {13},
number = {2},
pages = {238--240},
publisher = {Wiley},
abstract = {We investigated the relationship between the two main molecular
markers for chloroquine resistance (Pfcrt T76 and Pfmdr-1 Y86)
and the clinical efficacy of amodiaquine in Burkina Faso. Before
treatment, the prevalence of Pfcrt T76, Pfmdr-1 Y86 or both
mutations in the same infection was significantly higher in
patients who experienced a recrudescence than in those who
successfully responded to the treatment. Therefore, these two
molecular markers could be useful in monitoring amodiaquine
resistance, particularly in countries where this drug is used in
combination with artesunate as first- or second-line treatment.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We investigated the relationship between the two main molecular
markers for chloroquine resistance (Pfcrt T76 and Pfmdr-1 Y86)
and the clinical efficacy of amodiaquine in Burkina Faso. Before
treatment, the prevalence of Pfcrt T76, Pfmdr-1 Y86 or both
mutations in the same infection was significantly higher in
patients who experienced a recrudescence than in those who
successfully responded to the treatment. Therefore, these two
molecular markers could be useful in monitoring amodiaquine
resistance, particularly in countries where this drug is used in
combination with artesunate as first- or second-line treatment. |
2007
|
Journal Articles
|
| Halidou Tinto, Jean Bosco Ouédraogo, Issaka Zongo, Chantal Overmeir, Eric Marck, Tinga Robert Guiguemdé, Umberto D’Alessandro Sulfadoxine-pyrimethamine efficacy and selection of Plasmodium
falciparum DHFR mutations in Burkina Faso before its
introduction as intermittent preventive treatment for pregnant
women (Journal Article) In: Am. J. Trop. Med. Hyg., vol. 76, no. 4, pp. 608–613, 2007. @article{Tinto2007-yx,
title = {Sulfadoxine-pyrimethamine efficacy and selection of Plasmodium
falciparum DHFR mutations in Burkina Faso before its
introduction as intermittent preventive treatment for pregnant
women},
author = {Halidou Tinto and Jean Bosco Ou\'{e}draogo and Issaka Zongo and Chantal Overmeir and Eric Marck and Tinga Robert Guiguemd\'{e} and Umberto D'Alessandro},
year = {2007},
date = {2007-04-01},
journal = {Am. J. Trop. Med. Hyg.},
volume = {76},
number = {4},
pages = {608--613},
publisher = {American Society of Tropical Medicine and Hygiene},
abstract = {Sulfadoxine-pyrimethamine efficacy was determined with a 28-day
follow-up in 97 children between 6 months and 15 years of age.
The polymerase chain reaction (PCR)-corrected treatment failure
was 8.2% and the uncorrected was 21.6%. The presence of the
dihydrofolate reductase (DHFR) and dihydropteroate synthetase
(DHPS) mutations linked to sulfadoxine-pyrimethamine resistance
before and after treatment was determined by PCR-restriction
fragment length polymorphism (RFLP) and by a fluorogenic PCR
assay. Before treatment, the prevalence of the triple DHFR
mutations was higher among the patients having had a recurrent
parasitemia (either recrudescence or new infection; 28.6% versus 9.3%), although the difference was not significant (P =
0.1). The double mutation Ala-436/Gly-437 was observed in 67%
of samples, whereas no Glu-540 mutation was found. After
treatment, the triple DHFR mutation was found in 76.2% of
patients with recurrent parasitemia, recrudescence, and new
infection alike. Such high prevalence of mutant parasites
indicates that sulfadoxine-pyrimethamine should not be used as
monotherapy.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Sulfadoxine-pyrimethamine efficacy was determined with a 28-day
follow-up in 97 children between 6 months and 15 years of age.
The polymerase chain reaction (PCR)-corrected treatment failure
was 8.2% and the uncorrected was 21.6%. The presence of the
dihydrofolate reductase (DHFR) and dihydropteroate synthetase
(DHPS) mutations linked to sulfadoxine-pyrimethamine resistance
before and after treatment was determined by PCR-restriction
fragment length polymorphism (RFLP) and by a fluorogenic PCR
assay. Before treatment, the prevalence of the triple DHFR
mutations was higher among the patients having had a recurrent
parasitemia (either recrudescence or new infection; 28.6% versus 9.3%), although the difference was not significant (P =
0.1). The double mutation Ala-436/Gly-437 was observed in 67%
of samples, whereas no Glu-540 mutation was found. After
treatment, the triple DHFR mutation was found in 76.2% of
patients with recurrent parasitemia, recrudescence, and new
infection alike. Such high prevalence of mutant parasites
indicates that sulfadoxine-pyrimethamine should not be used as
monotherapy. |
| Issaka Zongo, Grant Dorsey, Noel Rouamba, Halidou Tinto, Christian Dokomajilar, Robert T Guiguemde, Philip J Rosenthal, Jean Bosco Ouedraogo Artemether-lumefantrine versus amodiaquine plus
sulfadoxine-pyrimethamine for uncomplicated falciparum malaria
in Burkina Faso: a randomised non-inferiority trial (Journal Article) In: Lancet, vol. 369, no. 9560, pp. 491–498, 2007. @article{Zongo2007-uv,
title = {Artemether-lumefantrine versus amodiaquine plus
sulfadoxine-pyrimethamine for uncomplicated falciparum malaria
in Burkina Faso: a randomised non-inferiority trial},
author = {Issaka Zongo and Grant Dorsey and Noel Rouamba and Halidou Tinto and Christian Dokomajilar and Robert T Guiguemde and Philip J Rosenthal and Jean Bosco Ouedraogo},
year = {2007},
date = {2007-02-01},
journal = {Lancet},
volume = {369},
number = {9560},
pages = {491--498},
publisher = {Elsevier BV},
abstract = {BACKGROUND: Artemisinin-based combination regimens are widely
advocated for malarial treatment, but other effective regimens
might be cheaper and more readily available. Our aim was to
compare the risk of recurrent parasitaemia in patients given
artemether-lumefantrine with that in those given amodiaquine
plus sulfadoxine-pyrimethamine for uncomplicated malaria.
METHODS: We enrolled 521 patients aged 6 months or older with
uncomplicated falciparum malaria in Bobo-Dioulasso, Burkina
Faso. Patients were randomly assigned to receive standard doses
of either artemether-lumefantrine (261) or amodiaquine plus
sulfadoxine-pyrimethamine (260) for 3 days. Primary endpoints
were the risks of treatment failure within 28 days, either
unadjusted or adjusted by genotyping to distinguish
recrudescence from new infection. The study is registered at
controlled-trials.gov with the identifier ISRCTN54261005.
FINDINGS: Of enrolled patients, 478 (92%) completed the 28-day
study. The risk of recurrent symptomatic malaria was lowest in
the group given amodiaquine plus sulfadoxine-pyrimethamine
(1.7%vs 10.2%; risk difference 8.5%; 95% CI 4.3-12.6; p=0.0001); as was the risk of recurrent parasitaemia (4.7%vs 15.1%; 10.4%; 5.1-15.6; p=0.0002). Nearly all recurrences were
due to new infections. Recrudescences were four late treatment
failures with artemether-lumefantrine and one early treatment
failure with amodiaquine plus sulfadoxine-pyrimethamine. Both
regimens were safe and well tolerated, with pruritus more common
with amodiaquine plus sulfadoxine-pyrimethamine than with
artemether-lumefantrine. Each regimen selected for new isolates
with mutations that have been associated with decreased drug
susceptibility. INTERPRETATION: Amodiaquine plus
sulfadoxine-pyrimethamine was more effective than was
artemether-lumefantrine for the treatment of uncomplicated
malaria. For regions of Africa where amodiaquine plus
sulfadoxine-pyrimethamine continues to be effective, this less
expensive and more available regimen should be considered as an
alternative to blanket recommendations for artemisinin-based
combination treatment for malaria.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Artemisinin-based combination regimens are widely
advocated for malarial treatment, but other effective regimens
might be cheaper and more readily available. Our aim was to
compare the risk of recurrent parasitaemia in patients given
artemether-lumefantrine with that in those given amodiaquine
plus sulfadoxine-pyrimethamine for uncomplicated malaria.
METHODS: We enrolled 521 patients aged 6 months or older with
uncomplicated falciparum malaria in Bobo-Dioulasso, Burkina
Faso. Patients were randomly assigned to receive standard doses
of either artemether-lumefantrine (261) or amodiaquine plus
sulfadoxine-pyrimethamine (260) for 3 days. Primary endpoints
were the risks of treatment failure within 28 days, either
unadjusted or adjusted by genotyping to distinguish
recrudescence from new infection. The study is registered at
controlled-trials.gov with the identifier ISRCTN54261005.
FINDINGS: Of enrolled patients, 478 (92%) completed the 28-day
study. The risk of recurrent symptomatic malaria was lowest in
the group given amodiaquine plus sulfadoxine-pyrimethamine
(1.7%vs 10.2%; risk difference 8.5%; 95% CI 4.3-12.6; p=0.0001); as was the risk of recurrent parasitaemia (4.7%vs 15.1%; 10.4%; 5.1-15.6; p=0.0002). Nearly all recurrences were
due to new infections. Recrudescences were four late treatment
failures with artemether-lumefantrine and one early treatment
failure with amodiaquine plus sulfadoxine-pyrimethamine. Both
regimens were safe and well tolerated, with pruritus more common
with amodiaquine plus sulfadoxine-pyrimethamine than with
artemether-lumefantrine. Each regimen selected for new isolates
with mutations that have been associated with decreased drug
susceptibility. INTERPRETATION: Amodiaquine plus
sulfadoxine-pyrimethamine was more effective than was
artemether-lumefantrine for the treatment of uncomplicated
malaria. For regions of Africa where amodiaquine plus
sulfadoxine-pyrimethamine continues to be effective, this less
expensive and more available regimen should be considered as an
alternative to blanket recommendations for artemisinin-based
combination treatment for malaria. |
2006
|
Journal Articles
|
| Halidou Tinto, Claude Rwagacondo, Corinne Karema, Denise Mupfasoni, Waltruda Vandoren, Emmanuel Rusanganwa, Annette Erhart, Chantal Van Overmeir, Eric Van Marck, Umberto D’Alessandro In-vitro susceptibility of Plasmodium falciparum to
monodesethylamodiaquine, dihydroartemisinin and quinine in an
area of high chloroquine resistance in Rwanda (Journal Article) In: Trans. R. Soc. Trop. Med. Hyg., vol. 100, no. 6, pp. 509–514, 2006. @article{Tinto2006-iz,
title = {In-vitro susceptibility of Plasmodium falciparum to
monodesethylamodiaquine, dihydroartemisinin and quinine in an
area of high chloroquine resistance in Rwanda},
author = {Halidou Tinto and Claude Rwagacondo and Corinne Karema and Denise Mupfasoni and Waltruda Vandoren and Emmanuel Rusanganwa and Annette Erhart and Chantal Van Overmeir and Eric Van Marck and Umberto D'Alessandro},
year = {2006},
date = {2006-06-01},
journal = {Trans. R. Soc. Trop. Med. Hyg.},
volume = {100},
number = {6},
pages = {509--514},
publisher = {Oxford University Press (OUP)},
abstract = {Plasmodium falciparum in-vitro susceptibility to chloroquine
(CQ), monodesethylamodiaquine, quinine and dihydroartemisinin
was investigated in Rwandan patients with a parasitaemia of at least >or=4000/microl. The study was carried out in
November-December 2003. Dihydroartemisinin was the most potent (GM IC(50)=2.6nmol/l, 95% CI 2.2-3.2) among the drugs tested.
Resistance to chloroquine was 45% (33/74) and that to
monodesethylamodiaquine 7% (5/74). All the tested isolates were
susceptible to quinine. The mean IC(50) of
monodesethylamodiaquine, quinine and dihydroartemisinin was
significantly higher for chloroquine-resistant than for
chloroquine-sensitive strains (P<0.05). The IC(50) of each drug
was significantly and positively correlated to that of the other
three drugs (P<0.005), and this correlation was higher between CQ and monodesethylamodiaquine (r=0.8). In-vitro CQ resistance
is linked to that of the other drugs tested. Most worrying is
the positive correlation between the IC(50) of
dihydroartemisinin and the other drugs, more particularly with
CQ, suggesting an increased tolerance of the parasites to all
drugs.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Plasmodium falciparum in-vitro susceptibility to chloroquine
(CQ), monodesethylamodiaquine, quinine and dihydroartemisinin
was investigated in Rwandan patients with a parasitaemia of at least >or=4000/microl. The study was carried out in
November-December 2003. Dihydroartemisinin was the most potent (GM IC(50)=2.6nmol/l, 95% CI 2.2-3.2) among the drugs tested.
Resistance to chloroquine was 45% (33/74) and that to
monodesethylamodiaquine 7% (5/74). All the tested isolates were
susceptible to quinine. The mean IC(50) of
monodesethylamodiaquine, quinine and dihydroartemisinin was
significantly higher for chloroquine-resistant than for
chloroquine-sensitive strains (P<0.05). The IC(50) of each drug
was significantly and positively correlated to that of the other
three drugs (P<0.005), and this correlation was higher between CQ and monodesethylamodiaquine (r=0.8). In-vitro CQ resistance
is linked to that of the other drugs tested. Most worrying is
the positive correlation between the IC(50) of
dihydroartemisinin and the other drugs, more particularly with
CQ, suggesting an increased tolerance of the parasites to all
drugs. |
2005
|
Journal Articles
|
| Halidou Tinto, Boroma Sanou, Jean-Claude Dujardin, Jean Bosco Ouédraogo, Chantal VAN Overmeir, Annette Erhart, Eric VAN Marck, Tinga Robert Guiguemdé, Umberto D’Alessandro Usefulness of the Plasmodium falciparum chloroquine resistance
transporter T76 genotype failure index for the estimation of
in vivo chloroquine resistance in Burkina Faso (Journal Article) In: Am. J. Trop. Med. Hyg., vol. 73, no. 1, pp. 171–173, 2005. @article{Tinto2005-vz,
title = {Usefulness of the Plasmodium falciparum chloroquine resistance
transporter T76 genotype failure index for the estimation of
in vivo chloroquine resistance in Burkina Faso},
author = {Halidou Tinto and Boroma Sanou and Jean-Claude Dujardin and Jean Bosco Ou\'{e}draogo and Chantal VAN Overmeir and Annette Erhart and Eric VAN Marck and Tinga Robert Guiguemd\'{e} and Umberto D'Alessandro},
year = {2005},
date = {2005-07-01},
journal = {Am. J. Trop. Med. Hyg.},
volume = {73},
number = {1},
pages = {171--173},
publisher = {American Society of Tropical Medicine and Hygiene},
abstract = {The prevalence of chloroquine (CQ) treatment failure and the
genotype failure index was determined in four sentinel sites in
Burkina Faso. In three sites, the genotype failure index varied
between 1.7 and 3, a result confirming the relationship between
the Plasmodium falciparum CQ resistance transporter (Pfcrt) T76
mutation and CQ resistance. In the remaining site, the genotype
failure index was unusually low, 1.1, which was significantly
different than that in the other sites (P < 0.00001). These
findings are discussed. Often but not always, the prevalence of
CQ resistance can be correctly estimated by the Pfcrt T76
genotype failure index.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The prevalence of chloroquine (CQ) treatment failure and the
genotype failure index was determined in four sentinel sites in
Burkina Faso. In three sites, the genotype failure index varied
between 1.7 and 3, a result confirming the relationship between
the Plasmodium falciparum CQ resistance transporter (Pfcrt) T76
mutation and CQ resistance. In the remaining site, the genotype
failure index was unusually low, 1.1, which was significantly
different than that in the other sites (P < 0.00001). These
findings are discussed. Often but not always, the prevalence of
CQ resistance can be correctly estimated by the Pfcrt T76
genotype failure index. |
2004
|
Journal Articles
|
| Halidou Tinto, Jean Bosco Ouédraogo, Maminata Traoré, Tinga Robert Guiguemdé Parasitological resistance of Plasmodium falciparum to
antimalarial drugs: what physicians should keep in mind (Journal Article) In: Sante, vol. 14, no. 2, pp. 69–73, 2004. @article{Tinto2004-sw,
title = {Parasitological resistance of Plasmodium falciparum to
antimalarial drugs: what physicians should keep in mind},
author = {Halidou Tinto and Jean Bosco Ou\'{e}draogo and Maminata Traor\'{e} and Tinga Robert Guiguemd\'{e}},
year = {2004},
date = {2004-04-01},
journal = {Sante},
volume = {14},
number = {2},
pages = {69--73},
abstract = {Plasmodium falciparum drug resistance has considerably modified
the attitude of physicians in terms of malaria case management.
However, a bad understanding of the resistance phenomenon can
lead to non-appropriate therapeutic and/or public health
practices. The objective of this paper was to contribute to
clarify the concept of parasitological resistance by analysing
the different types of resistance observed in vivo. We showed
through some examples that the precision of in vivo
parasitological results depends on the type of microscopical
technique used. We also showed that the classification system
into resistance levels RI, RII, and RIII does not correspond to
an increase in the resistance of the parasite itself but rather
to an increase in the proportion of the resistant strains
compared to the sensitive ones circulating in a given population.
Mutant strains are circulating in low proportions as long as
there is no selective drug pressure. They can be first detected
in vitro and, later on, when their proportion increase, they are
detected in vivo, first in non-immune subjects and later in
semi-immune subjects. Therefore, the role of the host immunity is
important in malaria drug resistance. To conclude, increasing use
of antimalarial drugs (especially in monotherapy) cannot thwart
the resistance, but rather leads to the selection of mutants
strains. As the proportion of the mutant strains increases
compared to the sensitive (wild) ones, it will reach the
microscopic detection level and then, the clinical level. It is
important that physicians involved in malaria case management
understand these notions in order to avoid non-appropriate
therapeutic decisions.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Plasmodium falciparum drug resistance has considerably modified
the attitude of physicians in terms of malaria case management.
However, a bad understanding of the resistance phenomenon can
lead to non-appropriate therapeutic and/or public health
practices. The objective of this paper was to contribute to
clarify the concept of parasitological resistance by analysing
the different types of resistance observed in vivo. We showed
through some examples that the precision of in vivo
parasitological results depends on the type of microscopical
technique used. We also showed that the classification system
into resistance levels RI, RII, and RIII does not correspond to
an increase in the resistance of the parasite itself but rather
to an increase in the proportion of the resistant strains
compared to the sensitive ones circulating in a given population.
Mutant strains are circulating in low proportions as long as
there is no selective drug pressure. They can be first detected
in vitro and, later on, when their proportion increase, they are
detected in vivo, first in non-immune subjects and later in
semi-immune subjects. Therefore, the role of the host immunity is
important in malaria drug resistance. To conclude, increasing use
of antimalarial drugs (especially in monotherapy) cannot thwart
the resistance, but rather leads to the selection of mutants
strains. As the proportion of the mutant strains increases
compared to the sensitive (wild) ones, it will reach the
microscopic detection level and then, the clinical level. It is
important that physicians involved in malaria case management
understand these notions in order to avoid non-appropriate
therapeutic decisions. |
2003
|
Journal Articles
|
| Halidou Tinto, Jean Bosco Ouédraogo, Annette Erhart, Chantal Van Overmeir, Jean-Claude Dujardin, Eric Van Marck, Tinga Robert Guiguemdé, Umberto D’Alessandro Relationship between the Pfcrt T76 and the Pfmdr-1 Y86
mutations in Plasmodium falciparum and in vitro/in vivo
chloroquine resistance in Burkina Faso, West Africa (Journal Article) In: Infect. Genet. Evol., vol. 3, no. 4, pp. 287–292, 2003. @article{Tinto2003-pn,
title = {Relationship between the Pfcrt T76 and the Pfmdr-1 Y86
mutations in Plasmodium falciparum and in vitro/in vivo
chloroquine resistance in Burkina Faso, West Africa},
author = {Halidou Tinto and Jean Bosco Ou\'{e}draogo and Annette Erhart and Chantal Van Overmeir and Jean-Claude Dujardin and Eric Van Marck and Tinga Robert Guiguemd\'{e} and Umberto D'Alessandro},
year = {2003},
date = {2003-11-01},
journal = {Infect. Genet. Evol.},
volume = {3},
number = {4},
pages = {287--292},
publisher = {Elsevier BV},
abstract = {The relationship between Pfcrt T76 and Pfmdr-1 Y86 mutations in
Plasmodium falciparum was explored in samples from patients with
uncomplicated malaria and tested in vitro and in vivo with
chloroquine (CQ) in Burkina Faso. The two mutations were
strongly related. The Pfcrt T76 mutation was found in 82% of
the samples having the Pfmdr-1 Y86 mutation too (odds ratio (OR)=4.8 [95% CI: 1.7-13.3]; P=0.002). However, only half
(16/34) of samples with Pfcrt T76 mutation had also the Pfmdr-1
Y86 mutation. The latter was apparently associated with in vitro resistance (OR=4.8 [95% CI: 1.4-16.5]; P=0.01) but such association disappeared (P=0.77) after adjusting for the
presence of the Pfcrt T76 mutation. This suggests that the
occurrence of the Pfmdr-1 Y86 mutation is dependent on that of
Pfcrt T76 mutation and could explain previous reports linking
the Pfmdr-1 Y86 mutation with CQ resistance (CQR). The isolates
carrying both the Pfcrt K76 and Pfmdr-1 N86 alleles (wild/wild
(WW)) and the single mutant Pfmdr-1 Y86 (WM) had the lowest IC50
geometric mean (GMIC50) values, while those carrying both Pfcrt
T76/Pfmdr-1 Y86 alleles (mutant/mutant (MM)), and the single
mutant Pfcrt T76 (MW) had the highest. Among pre-treatment
samples there was a strong linkage disequilibrium with an excess
of MM and WW and a deficit of single mutants (MW and WM),
suggesting that parasite fitness is higher for the former and
lower for the latter.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The relationship between Pfcrt T76 and Pfmdr-1 Y86 mutations in
Plasmodium falciparum was explored in samples from patients with
uncomplicated malaria and tested in vitro and in vivo with
chloroquine (CQ) in Burkina Faso. The two mutations were
strongly related. The Pfcrt T76 mutation was found in 82% of
the samples having the Pfmdr-1 Y86 mutation too (odds ratio (OR)=4.8 [95% CI: 1.7-13.3]; P=0.002). However, only half
(16/34) of samples with Pfcrt T76 mutation had also the Pfmdr-1
Y86 mutation. The latter was apparently associated with in vitro resistance (OR=4.8 [95% CI: 1.4-16.5]; P=0.01) but such association disappeared (P=0.77) after adjusting for the
presence of the Pfcrt T76 mutation. This suggests that the
occurrence of the Pfmdr-1 Y86 mutation is dependent on that of
Pfcrt T76 mutation and could explain previous reports linking
the Pfmdr-1 Y86 mutation with CQ resistance (CQR). The isolates
carrying both the Pfcrt K76 and Pfmdr-1 N86 alleles (wild/wild
(WW)) and the single mutant Pfmdr-1 Y86 (WM) had the lowest IC50
geometric mean (GMIC50) values, while those carrying both Pfcrt
T76/Pfmdr-1 Y86 alleles (mutant/mutant (MM)), and the single
mutant Pfcrt T76 (MW) had the highest. Among pre-treatment
samples there was a strong linkage disequilibrium with an excess
of MM and WW and a deficit of single mutants (MW and WM),
suggesting that parasite fitness is higher for the former and
lower for the latter. |