<i>In vitro</i> susceptibility of Gabonese wild isolates of 
<i>Plasmodium falciparum</i> to artemether, and comparison with 
chloroquine, quinine, halofantrine and amodiaquine

Pradines, Bruno; Mamfoumbi, Modeste Mabika; Parzy, Daniel; Medang, M. Owono; Lebeau, Catherine; Mbina, J. R. Mourou; Doury, J. C.; Kombila, Maryvonne

doi:10.1017/s0031182098003400

Cited by 32 publications

(29 citation statements)

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“…12 The in vivo efficacy of amodiaquine has been demonstrated in other countries in central Africa, in spite of its in vitro cross-resistance with chloroquine. 13,14 In the present study, an association between P. malariae carriage and P. falciparum infection rate (at initiation of the study) or reinfection delay (during the follow-up) was observed. At enrollment, children infected with P. malariae presented more often with a P. falciparum infection and usually exhibited higher parasite densities than the other children, although the differences were not significant (both P Ͻ 0.07).…”

Section: Discussionsupporting

confidence: 52%

Factors influencing resistance to reinfection with Plasmodium falciparum.

Domarle

Migot-Nabias²,

Mvoukani³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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Abstract. A treatment-reinfection study design was used to investigate the relationships between host immunologic and/or genetic factors and resistance to reinfection with Plasmodium falciparum. Sixty-one children in Gabon were enrolled in a cross-sectional study to measure the prevalence of each human plasmodial species. All were given amodiaquine for radical cure of parasites, and 40 were subsequently followed-up for 30 weeks. Successive blood smears were examined to measure the delay of reappearance in blood of asexual stages of P. falciparum parasites. Presence of infection during the cross-sectional survey was associated with male sex, non-deficient glucose-6-phosphate dehydrogenase activity, plasma interleukin-10 level, and anti-LSA-Rep antibody concentration. Resistance to reinfection was related to the presence of anti-LSA-J antibodies, and the absence of anti-LSA-Rep antibodies. Moreover, P. malariae-infected subjects were usually co-infected with P. falciparum, and were also more rapidly reinfected with P. falciparum after treatment, compared with those without P. malariae infection.Most studies aimed to investigate the protection against Plasmodium falciparum malaria have used malaria attacks as criteria.1,2 However, these criteria require long and precise follow-up of the populations because malaria attacks occur rarely, even in hyperendemic areas where children who present more than 2 malaria attacks per year are rare. 3 Moreover, such criteria mainly investigate protection against blood stages of the parasite and do not allow the assessment of protection against the pre-erythrocytic stages. The existence of such protection is shown by the fact that only a small proportion part of infective bites leads to the appearance of parasites in the peripheral blood. 4 Similarly, the prevalence rates of blood parasite infections following antimalarial treatment are extremely lower than presumed in view of the number of infective bites from mosquitoes. 5 In this context, effector mechanisms may be directed against the sporozoites, the liver stages, or both. Protection against the sporozoites may result from a specific humoral response because it has been demonstrated for the antibody directed to the repetitive epitope (NANP) 3 from the circumsporozoite (CS) protein. 6 Antibody targeted against liver-stage antigens may also contribute to the reduction of the emergence of P. falciparum from the liver. The plasma levels of Th1-type and Th2-type cytokines are also thought to play a major role in individual levels of protection. To evaluate the level of protection against the sporozoite and liver stages of the parasite, we first performed a cross-sectional study to assess the parasitologic status of children living in Gabon, an area hyperendemic for malaria. All children then received a curative antimalarial treatment and were enrolled in a longitudinal follow-up to measure their delay of reinfection by natural challenge. Relationships between the immunologic factors and the infection rate at the beginning of the s...

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Section: Discussionsupporting

confidence: 52%

Factors influencing resistance to reinfection with Plasmodium falciparum.

Domarle

Migot-Nabias²,

Mvoukani³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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“…However, molecules considered as promising antimalarial drugs (pyronaridine and artemisinin derivatives) showed in vitro cross-resistance with chloroquine, quinine, amodiaquine, and halofantrine. 24,25 The relationship between in vitro and in vivo resistance depends not only on this but also on the level of resistance and the coefficients of correlation (r) and determination (r2). A positive correlation between the responses of 2 antimalarial drugs suggests in vitro cross-resistance but does not necessarily imply in vivo cross-resistance.…”

Section: Discussionmentioning

confidence: 99%

Antibiotics for prophylaxis of Plasmodium falciparum infections: in vitro activity of doxycycline against Senegalese isolates.

Pradines

Spiegel²,

Rogier³

et al. 2000

The American Journal of Tropical Medicine and Hygiene

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Abstract. The in vitro activities of doxycycline, chloroquine, quinine, amodiaquine, artemether, pyrimethamine, and cycloguanil were evaluated against Plasmodium falciparum isolates from Senegal (Dielmo and Ndiop), using an isotopic, micro, drug susceptibility test. The 71 50% inhibitory concentration (IC 50 ) values for doxycycline ranged from 0.7 to 108.0 M and the geometric mean IC 50 for the 71 isolates was 11.3 M (95% confidence interval ϭ 9.5-13.4 M). The activity of doxycycline did not differ significantly (P ϭ 0.0858) between the chloroquine-susceptible isolates and the chloroquine-resistant isolates. There was no in vitro correlation between the responses to doxycycline and those to artemether, chloroquine, quinine, amodiaquine, pyrimethamine, and cycloguanil, suggesting no in vitro cross-resistance among these drugs. Potency was increased by prolonged exposure. In 96-hr incubations, the activity of doxycycline was 4-5-fold more increased than in 48-hr incubations. The in vitro activity of doxycycline against intraerythrocytic stages of multidrug-resistant P. falciparum, its action against the preerythrocytic forms, the lack of correlation between the responses in vitro of P. falciparum to doxycycline and the other antimalarial drugs, and its original potential site of action are factors that favor its use as antimalarial drug.The current options for reducing the morbidity and mortality of malaria are chemoprophylaxis and chemotherapy. Therefore, the increasing prevalence of strains of Plasmodium falciparum resistant to chloroquine and other antimalarial drugs poses a serious problem for control of malaria.

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“…In the two laboratories, the in vitro protocol for drug sensitivity assays was based on [ 3 H]hypoxanthine incorporation (9) with the same protocol and the same culture media (11,19,25). They were conducted in triplicate in flatbottomed 96-well plates using Albumax II as the protein source instead of human serum (19,25).…”

Section: Methodsmentioning

confidence: 99%

“…They were conducted in triplicate in flatbottomed 96-well plates using Albumax II as the protein source instead of human serum (19,25). Drug stock (1 mg ⅐ ml…”

Section: Methodsmentioning

confidence: 99%

Differential Association of Plasmodium falciparum Na ⁺ /H ⁺ Exchanger Polymorphism and Quinine Responses in Field- and Culture-Adapted Isolates of Plasmodium falciparum

Bertaux

Briolant

Ferdig

et al. 2011

Antimicrob Agents Chemother

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Plasmodium falciparum isolates with decreased susceptibility to quinine are increasingly being found in malaria patients. Mechanisms involved in this resistance are not yet understood. Several studies claim that alongside mutations in the Pfcrt and Pfmdr1 genes, the Pfnhe-1 Na ؉ /H ؉ exchanger polymorphism plays a role in decreasing susceptibility. However, conflicting results on the link between the Pfnhe-1 gene and quinine resistance arise from field-and culture-adapted isolates. We tested the association between Pfnhe-1, Pfcrt, and Pfmdr1 polymorphisms in field-and culture-adapted isolates from various countries with their in vitro susceptibility to quinine. Field isolates presented a higher diversity of the Pfnhe-1 microsatellite sequence than culture-adapted isolates. In culture-adapted isolates but not in field isolates, mutations in the Pfcrt and Pfmdr1 genes, as well as a higher number of DNNND repeats in the Pfnhe-1 gene, were associated with a higher 50% inhibitory concentration (IC 50 ) of quinine. Furthermore, most of the culture-adapted isolates with more than one DNNND repeat in the Pfnhe-1 gene also harbored mutated Pfcrt and Pfmdr1 genes with an apparent cumulative effect on quinine susceptibility. This study supports the involvement of the Pfnhe-1 gene in the modulation of the in vitro quinine response when associated with mutated Pfcrt and Pfmdr1 genes. Culture adaptation could be responsible for selection of specific haplotypes of these three genes. Methods used for drug testing might thus influence the association between Pfnhe-1 polymorphism and quinine susceptibility. However, we do not exclude the possibility that in particular settings, Pfnhe-1 polymorphism can be used as a molecular marker for surveillance of quinine resistance.

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In vitro susceptibility of Gabonese wild isolates of Plasmodium falciparum to artemether, and comparison with chloroquine, quinine, halofantrine and amodiaquine

Cited by 32 publications

References 0 publications

Factors influencing resistance to reinfection with Plasmodium falciparum.

Factors influencing resistance to reinfection with Plasmodium falciparum.

Antibiotics for prophylaxis of Plasmodium falciparum infections: in vitro activity of doxycycline against Senegalese isolates.

Differential Association of Plasmodium falciparum Na ⁺ /H ⁺ Exchanger Polymorphism and Quinine Responses in Field- and Culture-Adapted Isolates of Plasmodium falciparum

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In vitro susceptibility of Gabonese wild isolates of Plasmodium falciparum to artemether, and comparison with chloroquine, quinine, halofantrine and amodiaquine

Cited by 32 publications

References 0 publications

Factors influencing resistance to reinfection with Plasmodium falciparum.

Factors influencing resistance to reinfection with Plasmodium falciparum.

Antibiotics for prophylaxis of Plasmodium falciparum infections: in vitro activity of doxycycline against Senegalese isolates.

Differential Association of Plasmodium falciparum Na + /H + Exchanger Polymorphism and Quinine Responses in Field- and Culture-Adapted Isolates of Plasmodium falciparum

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Differential Association of Plasmodium falciparum Na ⁺ /H ⁺ Exchanger Polymorphism and Quinine Responses in Field- and Culture-Adapted Isolates of Plasmodium falciparum