In vitro effects of amodiaquine on paired Schistosoma mansoni adult worms at concentrations of less than 5 µg/mL

In this study, the in vitro effects of amodiaquine (AQ) monotherapy on the egg output of paired adult Schistosoma mansoni worms and their survival during in vitro culture were assessed. In addition, the gross morphological alterations of male and female worms caused by AQ were visually observed under a dissecting microscope. AQ significantly reduced the daily egg output of paired adult S. mansoni worms following incubation for 14 days at 1-5 µg/mL, but not at 0.5 µg/mL, compared with the control group. AQ also reduced the survival of male and female worms at concentrations of 2 and 5 µg/mL, respectively. Moreover, exposure to 5 µg/mL AQ caused severe swelling and/or localisation of black content in the body of all male and female worms within one or two days of incubation; subsequently, shrinkage in the male worms and elongation in the female worms were observed. The initial morphological alterations caused by AQ occurred along the intestinal tract of the male and female worms. To our knowledge, this is the first study to report not only the efficacy of AQ at concentrations lower than 5 µg/mL on paired adult S. mansoni worms, but also the effects of AQ on the intestinal tracts of worms in in vitro culture.

Susceptibility of Colombian Plasmodium falciparum isolates to 4-aminoquinolines and the definition of amodiaquine resistance in vitro

There are wide variations in the threshold used to define in vitro resistance of Plasmodium falciparum to amodiaquine (AQ), probably due to differences in methodology and interpretation. In vitro susceptibility data of Colombian P. falciparum strains to AQ and N-desethylamodiaquine is used to illustrate the need to standardized methodologies and compare inhibitory concentrations, instead of resistant/susceptible phenotypes, when studying the mechanisms of resistance to AQ and monitoring drug susceptibility trends in the field.

In vitro sensitivity of Plasmodium falciparum to eight antimalarials in China-Myanmar and China-Lao PDR border areas.

In 1991-1995 by using the Rieckmann in vitro micro-method, susceptibilities of Plasmodium falciparum to eight antimalarials in the China-Lao PDR and China-Myanmar border areas were tested. The resistant rates of P. falciparum to chloroquinine were 95.0%-100%; IC50 114-240nmol/l. P. falciparum resistant rates to amodiaquine resistance accounted for 83.5%-100%, IC50 52-72nmol/l. All cases were sensitive to quinine, IC50 470-608nmol/l. P. falciparum isolates from the Lao PDR frontier were highly sensitive to artesunate, dihydroartemisinin, and arteether. Resistant rates from other areas were 0-11%. P. falciparum from China-Myanmar and Lao PDR border areas were also sensitive to mefloquine, IC50 68-88nmol/l. A longitudinal survey of the sensitivity of P. falciparum in vivo on the China-Lao PDR border showed that the average defervescent time of falciparum malaria was treated by pyronaridine increased from 32.7 +/- 16.0 hours during 1984-85 to 56.2 +/- 27.4 hours in 1995; the recrudescence rate rose up from 15.2% to 37.5%. The results monitored in vitro showed that all cases assessed in 1988 for response to pyronaridine were sensitive, but 36.4% of cases had emerging resistance, IC50 increased from 13nmol/l to 40 nmol/l. The above results suggested that P. falciparum in these areas has expressed resistance to chloroquine and amodiaquine. However, the parasites are still sensitive to artemisinin, pyronaridine, mefloquine, quinine, but with a declining sensitivities.

Estudos "in vitro" dos níveis de resistência do Plasmodium falciparum a drogas, de 1983 a 1986 / In vitro studies of the levels of resistance to drugs of Plasmodium falciparum, from 1983 to 1986

Foram realizados 171 testes de sensibilidade (microtécnica) com cepas de Plasmodium falciparum da Regiäo Amazónica brasileira para cloroquina, mefloquina, amodiaquina e quinino. Os testes tiveram duraçäo de 24 horas com as drogas preparadas na hora de realizaçäo de cada teste. Os resultados mostraram elevada resistência a cloroquina (83%) e sensibilidade em quase a totalidade das amostras testadas para mefloquina (97,7%). Para amodiaquina e quinino observou-se sensibilidade em 51,0% e 56,5% das cepas, respectivamente. Este estudo demonstra a emergência de um possível foco de resistência do Plasmodium falciparum a mefloquina, em Tucuruí

In vitro drug response of Plasmodium falciparum in the Philippines: increased resistance to amodiaquine.

A long term study was carried out at San Lazaro Hospital, Manila, Philippines, monitoring the in vitro response of Plasmodium falciparum to chloroquine, amodiaquine, mefloquine, and quinine. The in vitro effective dose giving 50% inhibition of schizogony was: 0.68 X 10(-6) M/liter blood for chloroquine; 0.18 X 10(-6) for amodiaquine; 0.2 X 10(-6) for mefloquine; and 1.12 X 10(-6) for quinine. The percent of isolates determined to be resistant in vitro was 85.2% for chloroquine, and 1.2% for both mefloquine and quinine. These figures were relatively unchanged over the course of 3 years studied. The in vitro resistance rate to amodiaquine increased from 5.1% in 1982 to 22.2% in 1984.