ABSTRACT
It has been demonstrated that continuous exposure to amodiaquine (AQ) alone elicits <i>in vitro</i> antischistosomal activities at concentrations of 1 - 10 µg/ml. However, orally administered drugs reach a peak blood concentration within one or two hours and then gradually decrease. The blood concentration does not remain at a constant level over several days as <i>in vitro</i> concentration of continuous drug exposure. <i>In vitro</i> activities by one day exposure to AQ better reflect the actual antischistosomal activities after oral administration than those elicited by continuous exposure.The objective of the present study is to compare the antischistosomal potential of one-day exposure to AQ with that to praziquantel (PZQ), a current antischistosomal drug. <i>Schistosoma mansoni</i> adult worm pairs were incubated with 0 (control), 1, 2, 5 and 10 µg/ml AQ as well as 0.01, 0.02, 0.05 and 0.1 µg/ml PZQ for the first day, and were subsequently incubated in drug-free media for a period of 14 days. The one-day exposure to AQ significantly reduced the daily egg output of the worm pairs at 1 - 10 µg/ml. The inhibitory effect on egg production continued at 5 and 10 µg/ml but proved temporary at 1 and 2 µg/ml. Furthermore, AQ-induced specific morphological alterations (severe swelling and/or localization of hemozoin) were observed in the worms at 5 and 10 µg/ml. The AQ-specific appearance of the male worms gradually faded during subsequent incubation in drug-free media, although the female worms showed elongation. Meanwhile, PZQ inhibited the egg output of adult worm pairs at concentrations of 0.01 - 0.1 µg/ml during exposure. The inhibitory effect on egg production continued at 0.05 and 0.1 µg/ml but proved temporary at 0.01 and 0.02 µg/ml. Furthermore, PZQ induced a visible contraction and shortening of the male and female worms at 0.05 and 0.1 µg/ml during exposure, but the PZQ-specific alterations quickly disappeared during subsequent incubation in drug-free media. To our knowledge, this is the first report showing that one-day exposure to AQ inhibits the egg production of adult worm pairs at 1 - 10 µg/ml and induces specific morphological alterations in the worms at 5 and 10 µg/ml. The present findings have important implications for the evaluation of the therapeutic effects of both AQ monotherapy and combination therapy with artesunate on schistosomiasis in clinical field trials.
ABSTRACT
It has been demonstrated that continuous exposure to amodiaquine (AQ) alone elicits <i>in vitro</i> antischistosomal activities at concentrations of 1–10 μg/ml. However, orally administered drugs reach a peak blood concentration within one or two hours and then gradually decrease. The blood concentration does not remain at a constant level over several days as <i>in vitro</i> concentration of continuous drug exposure. <i>In vitro</i> activities by one day exposure to AQ better reflect the actual antischistosomal activities after oral administration than those elicited by continuous exposure.The objective of the present study is to compare the antischistosomal potential of one-day exposure to AQ with that to praziquantel (PZQ), a current antischistosomal drug. <i>Schistosoma mansoni</i> adult worm pairs were incubated with 0 (control), 1, 2, 5 and 10 μg/ml AQ as well as 0.01, 0.02, 0.05 and 0.1 μg/ml PZQ for the first day, and were subsequently incubated in drug-free media for a period of 14 days. The one-day exposure to AQ significantly reduced the daily egg output of the worm pairs at 1–10 μg/ml. The inhibitory effect on egg production continued at 5 and 10 μg/ml but proved temporary at 1 and 2 μg/ml. Furthermore, AQ-induced specific morphological alterations (severe swelling and/or localization of hemozoin) were observed in the worms at 5 and 10 μg/ml. The AQ-specific appearance of the male worms gradually faded during subsequent incubation in drug-free media, although the female worms showed elongation. Meanwhile, PZQ inhibited the egg output of adult worm pairs at concentrations of 0.01–0.1 μg/ml during exposure. The inhibitory effect on egg production continued at 0.05 and 0.1 μg/ml but proved temporary at 0.01 and 0.02 μg/ml. Furthermore, PZQ induced a visible contraction and shortening of the male and female worms at 0.05 and 0.1 μg/ml during exposure, but the PZQ-specific alterations quickly disappeared during subsequent incubation in drug-free media. To our knowledge, this is the first report showing that one-day exposure to AQ inhibits the egg production of adult worm pairs at 1–10 μg/ml and induces specific morphological alterations in the worms at 5 and 10 μg/ml. The present findings have important implications for the evaluation of the therapeutic effects of both AQ monotherapy and combination therapy with artesunate on schistosomiasis in clinical field trials.
ABSTRACT
It has become difficult in recent years to conduct the direct feeding of mosquitoes on animals because of ethical considerations related to animal experimentation. Thus, the artificial feeding of mosquitoes on blood meals is an important technique in studies on the oral infection of mosquitoes to agents. Since Rutledge <I>et al.</I> (1964) devised the artificial membrane-feeding technique, several artificial membrane-feeding methods have been developed to increase the feeding rates of mosquitoes on blood meals. The purpose of the present study is to develop a simple and convenient device for the artificial feeding of mosquitoes. We designed a device using Kimwipe®, a coverglass, the lid of a plastic dish and a 50 ml Erlenmeyer flask. The efficacy was assessed by the infection rate of mosquitoes to <I>Brugia pahangi</I> microfilariae (MF) derived from the peritoneal cavity of Mongolian jirds. Immediately after the feeding of mosquitoes on MF by the new device, the MF infection rate of mosquitoes was 50 - 81%. On day 14 post-feeding, 51 - 94% of mosquitoes harbored third-stage infective larvae. The components needed to construct the device for artificial feeding of mosquitoes are generally available in laboratories. Furthermore, no elaborate modification of materials is necessary in making the feeding device. Therefore, this simple and convenient artificial feeding device promises to be applicable for experimental infection of mosquitoes not only with <I>B. pahangi </I>MF but also with other agents such as malaria and viruses.
ABSTRACT
Some field trials have already demonstrated the high antischistosomal potential of combination therapies using Artesunate (ART) and current antimalarial drugs (Boulanger <I>et al.,</I> 2007; Mohamed <I>et al.,</I> 2009; Sissoko <I>et al.,</I> 2009). The antischistosomal effects of these drugs are noteworthy, especially when they are used for the treatment of malaria in schistosomiasis endemic areas. However, the antischistosomal effects of Amodiaquine (AQ), Primaquine (PQ), Chloroquine (CQ) and Pyrimethamine (Py) have never been assessed by <I>in vitro</I> incubation. The objective of the present study is to assess the <I>in vitro</I> effects of current antimalarial drugs on the egg productivity of adult worm pairs of <I>S. mansoni</I> and their survival times. The effect of the current antimalarial drugs Mefloquine (MQ), quinine (QN), AQ, PQ, CQ, Sulfadiazine (Sf) and Py on the egg output of adult worm pairs of <I>Schistosoma mansoni</I> and their survival times during <I>in vitro</I> culture were assessed at a concentration of 10 Μg⁄ml. AQ, PQ, CQ and Py significantly inhibited the daily egg output of paired female worms at a concentration of 10 Μg⁄ml during the 1 or 2-day <I>in vitro</I> cultivation. However, QN and Sf did not significantly affect the daily egg output during the 8-day incubation. One-day exposure to MQ killed all paired male and female adult worms. AQ and PQ significantly decreased the survival of both paired male and female worms during the 14-day incubation, but QN, CQ, Py and Sf did not exert any similar effect. The present result is consistent with an assessment of the antischistosomal effects of artemisinin-based combination therapy in malaria and schistosomiasis co-endemic areas.
ABSTRACT
A cross-sectional survey of 327 Japanese short-term travelers (≤3 weeks) arriving in Bangkok, Thailand was conducted to assess the incidence of travelers’ diarrhea (TD) as well as their symptoms and treatment-seeking behaviors. The incidence of the first episode of TD (FTD) was ascertained retrospectively by questionnaire. Reported by 69 travelers, FTD clustered within the first 8 days of arrival in Thailand, and the incidence rate varied from 2% to 8% with the highest incidence on the third day.<BR> Cumulative probability of FTD was 19% for those arriving in Thai directly from Japan, 42 % for those arriving via Southeast Asia, and 25% for those arriving via other regions at Day 7 by the Kaplan-Meier survival analysis. Log rank test revealed a higher FTD risk for travelers arriving via other Southeast Asian countries than for those arriving directly from Japan (<I>P</I> < 0.005). Of all the 69 FTD episodes, 33% had classic TD defined as ≥3 unformed stools per 24 hours with at least one accompanying symptom, 49% had moderate TD defined as ≤2 unformed stools with at least one additional symptom or more unformed stools without additional symptoms, and 17% had mild TD defined as with ≤ 2 unformed stools without additional symptoms. Cumulative probability of FTD at Day 7 was 12% for classic TD, 25% for classic plus moderate TD and 30% for all the TD. More than 38% of travelers with diarrhea took medicine brought from Japan. Among travelers with classic TD, 35% bought medicine in Thailand, whereas 47-50% of travelers with moderate and mild TD took only rest without any treatment.