The sensitivity of Plasmodium falciparum to chloroquine and amodiaquine in Ibadan, Nigeria

An extended in vivo test of the sensitivity of Plasmodium falciparum to antimalarial drugs in Nigerian children showed no evidence of resistance to chloroquine and amodiaquine. However, the results of a small number of in vitro tests suggest a decreased sensitivity of the parasite to chloroquine when compared with the results of earlier studies in the same locality.     

Assessment of chloroquine sensitivity of Plasmodium falciparum in Choluteca, Honduras

During an outbreak of urban malaria in Choluteca, Honduras, the response of local isolates of Plasmodium falciparum to chloroquine was assessed. The 7-day WHO alternative standard field test was used together with three in vitro tests: the Rieckmann macro- and micromethods and a new 48-hour test which underwent its first field trial in this study. No chloroquine resistance was found in in vivo tests in 10 patients or in the in vitro tests on blood samples from 6 patients.     

Revaluation of chloroquine therapeutic efficacy on children with uncomplicated Plasmodium falciparum malaria in eastern Ivory Coast (1999-2002)

OBJECTIVE: A prospective study was made from November 1999 to May 2002 in order to revaluate the therapeutic efficacy of chloroquine in pediatric Plamodium falciparum malaria in Ivory Coast. DESIGN: This study was included in the national Plasmodium falciparum-susceptibility supervision program. Two hundred and fifty-six out of 594 patients from six to 59 months of age were included. Chloroquine was administered in accordance with the standard 14 day WHO protocol; i.e. administered dose of 25 mg/kg, in split doses, over three days. RESULTS: Two hundred and forty-seven patients completed the treatment. Among these, 217 presented with adequate clinical response (87.8%). The percentage of therapeutic failure was 12.2% with 12 early cases of therapeutic failure and 18 late cases of therapeutic failure. Chloroquine was more efficacious in Agnibilékrou (11.3% of therapeutic failure), Bondoukou (10.4%), and Tanda (10%), than in Abengourou (16.4%). Parasitic reduction on patients with resistant Plasmodium was superior to 90%, from day 0 to day 3. The risk of therapeutic failure was significantly linked to patient age. CONCLUSION: Considering these results, the authors suggest that the first-line treatment with chloroquine must be continued for uncomplicated malaria in humans.     

A network RER rooted on in vitro readout assays of Plasmodium falciparum sensitivity to chloroquine in the Indian Ocean Region

Chloroquine has been used as a first line drug to treat uncomplicated malaria cases during the last five decades in Madagascar and in the Comoros Union. The four plasmodial species known to infect humans occur on Madagascar Island. Chloroquine-resistant malaria cases, sometimes only suspected from presumptive malaria cases, have been reported in both countries. Thus, to redefine a strategy and a policy to cure malaria, there is a need to get relevant and updated data. In December 1999, the Madagascan Ministry of Health and the Institut Pasteur de Madagascar formed a network named RER for malaria resistance surveillance. In 2000 and 2001, 18 study sites (17 throughout Madagascar and 1 in Comoros) joined this network. Health-care workers were trained mainly for malaria diagnosis through the use of blood smear examination and for malaria case management. To alleviate the lack of competent medical teams within the health centres, and for technical and logistic reasons, as part of the network activities, it was decided to start with in vitro tests to assess the sensitivity of P.falciparum isolates to chloroquine by means of the isotopic method. Parasitized blood samples were collected from consenting patients. P.falciparum isolates were more predominant (989/1,036). Out of the 564 tests done, 432 (76.6%) could be assessed. Results demonstrated that 94.3% (381/404) of the Madagascan P.falciparum isolates were susceptible to chloroquine. In contrast, chloroquine-resistant isolates were prevalent in Comoros (8/28). The network set-up is presented. The usefulness of the in vivo approach and of the in vitro investigations (chemosusceptibility test and screening of mutations accounting for resistance to chloroquine) to monitor the emergence and the dissemination of chloroquine-resistant parasites is discussed.     

Evidence of increased chloroquine sensitivity in Thai isolates of Plasmodium falciparum

Sensitivity of Thai isolates of Plasmodium falciparum to chloroquine collected over the years 1978-1986 was measured by two methods: (i) by growth of previously cultured isolates for 72 h in presence of drug, and (ii) by the WHO standard in vitro microtest. During this period there were signs of a gradual increase in drug sensitivity, coinciding with the withdrawal of chloroquine for treatment of falciparum malaria in Thailand.     

The in vivo sensitivity of Plasmodium falciparum to chloroquine and to sulphadoxine-pyrimethamine combination in Ibadan,Nigeria

Fifty-eight Nigerian children with Plasmodium falciparum malaria were allocated randomly into two groups and treated with either chloroquine (25 mg/kg over three days) or Fansidar (35 mg sulphadoxine (+ $\text{1}\text{20}$ pyrimethamine) per kg single dose)). They were observed for 28 days during which blood films were examined periodically for malaria parasites.Asexual forms of P. falciparum, which were present in the blood films of all the patients in both groups before commencing treatment, disappeared rapidly from the blood so that by the fourth day after starting treatment no parasites were seen in the blood films. The blood films thereafter remained negative in both groups throughout the rest of the 28-day observation period. The rate of fever clearance was also similar in both groups. The study did not show resistance to Fansidar or to chloroquine. There is therefore, at present, no case for the indiscriminate use of Fansidar on the basis of suspected chloroquine resistance.     

In vitro assessment of sensitivity of Plasmodium falciparum to chloroquine and mefloquine in Ghana

An in vitro study of sensitivity of Plasmodium falciparum to chloroquine and mefloquine in Ghana is described. Results of 60 short-term cultures from 36 patients are evaluated. No sign of chloroquine resistance was found as all microtests showed complete inhibition of maturation at a level of 0.8 X 10(-6) M. For mefloquine schizont maturation was seen at higher levels of the drug. However, the estimated EC99, with 2.2830 X 10(-6) M is probably within the range of sensitivity.     

Plasmodium falciparum: sensitivity to chloroquine in vivo in three ecological zones in Ghana.

4690 children aged 6-15 years in 5 urban and 4 rural communities in 3 ecological zones in Ghana were screened from June 1988 to December 1990 to provide suitable candidates for the World Health Organization standard in vivo test for susceptibility of Plasmodium falciparum to chloroquine. 1880 (40.1%) had parasitaemia, mostly (83.7-98.6%) due to P. falciparum infection. Of the 626 in vivo tests performed, 570 (91.1%) showed sensitivity to chloroquine and 56 (8.9%) responses were classified as resistant to chloroquine at RI (5.1%) and RII (3.8%). The resistance responses were commonest (17.1-22.7%) in the coastal zone, followed by the savanna zone (8.6-10.0%), and lowest in the forest zone (3.1-6.3%). The RII responses occurred mainly in communities in the coastal zone. There was no RIII resistance in any zone. The pattern of RI (early) and RII responses of P. falciparum to chloroquine in this study suggested an increase in sensitivity, or a reduction in resistance, of P. falciparum to chloroquine from the coast to the forest and northern savanna zones, and from the urban to the rural communities in each zone in Ghana.     

Sensitivity of Plasmodium falciparum to chloroquine in Busia District,Kenya

Individuals infected with Plasmodium falciparum were randomly divided into two groups; one group was treated with a single dose of 10 mg chloroquine base per kg. body-weight and the other with 25 mg base of chloroquine per kg body-weight given over three days, followed by an observation period of seven days. By Day 3 of observation complete parasite clearance had occurred in all the 125 triple dose recipients and 113 of 114 (99·1%) of those who had the single dose.94·4% of 36 isolates tested in vitro by the macrotechnique were sensitive to drug concentration of 0.75 nmol/ml blood or less. One isolate was relatively less sensitive and required a concentration of chloroquine of 1·50 nmol/ml to inhibit schizont growth. However, the same isolate responded well to 25 mg base of chloroquine. These findings have demonstrated that, at present, isolates of P. falciparum in Busia District are sensitive to a standard dose of 10 mg chloroquine base and there is no reason therefore to resort to alternative antimalaria drugs. These should be reserved for special cases only.     

Amodiaquine fails to cure chloroquine resistant Plasmodium falciparum in the Punjab

We evaluated amodiaquine as a replacement drug for treating falciparum malaria in an area of Pakistani Punjab where chloroquine-resistant Plasmodium falciparum has recently emerged. Amodiaquine appeared to be 4 to 8 times more effective than chloroquine when P. falciparum isolates were tested in vitro. However, the recrudescence rate was greater than 50% after oral treatment with 20 mg/kg amodiaquine given over two successive days. This lack of therapeutic response from amodiaquine may have been due to selection of resistant parasites in the villages where the study was performed through extensive use of chloroquine for presumptive malaria treatment during the preceding 18 months. We conclude that amodiaquine is not a suitable replacement for chloroquine for treating falciparum malaria in our study area despite in vitro sensitivity data suggesting that it would be efficacious. Baseline in vitro sensitivity to mefloquine is also reported.     

Changes in the resistance of Plasmodium falciparum to chloroquine in Hainan, China.

In 1979, in view of the widespread resistance of Plasmodium falciparum to chloroquine in the island of Hainan, China, it use as an antimalarial was suspended throughout the island. A longitudinal survey of the chloroquine-sensitivity of P. falciparum was carried out over the period 1981-91 to investigate whether its resistance had changed from the 1979 level. In-vitro assays were carried out every 2-3 years, while in-vivo tests were performed annually over the period 1981-83 and also in 1991. Resistance to chloroquine declined progressively after its use had stopped. The in-vitro tests indicated that the rate of chloroquine-resistant P. falciparum was 97.9% in 1981, but dropped to 60.9% in 1991 (P < 0.001). The mean concentration of chloroquine for complete inhibition of schizont formation was 10.4 pmol/microliters in 1981, but decreased to 3.0 pmol/microliters in 1991 (P < 0.001). The proportion of samples taken from malaria cases that required high concentrations ( > 6.4 pmol/microliters) of chloroquine for complete inhibition of schizont formation was 83.3% in 1981, but only 17.4% in 1991 (P < 0.001); at low concentrations ( > 1.6 pmol/microliters), the corresponding proportions increased from 4.2% in 1981 to 60.8% in 1991 (P < 0.001). In the 4-week in-vivo test, the rate of chloroquine-resistant P. falciparum decreased from 84.2% in 1981 to 40% in 1991 (P < 0.001). RII + RIII cases represented 59.4% of the total resistant cases in 1981, but decreased to 37.5% in 1991 (0.02 > P > 0.01).