Responses of multidrug-resistant Plasmodium falciparum parasites to mefloquine in Nigerian children.

Thirty-three children aged 6 months to 7 years from an area with multidrug-resistant Plasmodium falciparum strains were treated with 25 mg/kg body weight of mefloquine base as a single oral dose. They were followed-up using the modified 28-day WHO extended field test. The parasite isolates from these patients were cultured in vitro with different concentrations of mefloquine. All children were parasite-negative by day 4, and 31 remained so throughout the period of observation. Two patients who were parasitaemic on days 16 and 28 were successfully treated with a sulphadoxine/pyrimethamine combination. Parasitological and clinical responses were well correlated. The mean parasite clearance time was 65 +/- 10.2 hours. A mefloquine concentration of 64 pmol/well inhibited schizont growth and the EC50 and EC99 were 5.5 and 5.4 pmol/well (1.1 and 10.8 mumol/l blood) respectively. This indicates reduced parasite susceptibility to the drug in vitro.

Malaria in pregnancy: efficacy of a low dose of mefloquine in an area holoendemic for multi-drug resistant Plasmodium falciparum.

Thirty-three pregnant women with pure P. falciparum parasitaemias (> or = 10(3) parasites/microliters blood), were each treated with a single, oral dose (12.5 mg/kg body weight) of mefloquine base (MQ), at Ahmadu Bello University Teaching Hospital, Zaria urban area, Nigeria. All 33 women were aparasitaemic by day 6 post-treatment and none became parasitaemic during the remaining 21 days of observation. Minimal side-effects were reported by the patients. The mean (S.D.) fever- and parasite-clearance times were 48 (17) and 50 (26) h, respectively. In standard microtests in vitro, schizont maturation was inhibited with MQ at 16 pmol/well (3.2 pmol/microliters). These findings indicate that, at least in the study area, semi-immune, pregnant women have high tolerability to relatively low doses of MQ and that such doses are fully effective against the local P. falciparum isolates.

Sensitivity of Plasmodium falciparum to reduced dose of mefloquine in pregnant women in Nigeria.

Mefloquine base, (12.5 mg/kg body weight), was administered as a single oral dose to 34 pregnant women with Plasmodium falciparum parasitaemia. They were followed up in vivo using the modified 28-day WHO extended field test. The sensitivity of P. falciparum isolates obtained from these women to mefloquine (MQ) was evaluated in vitro. All women were parasite negative by day 4 and remained aparasitaemic throughout the 28-day period of observation. Parasitological and clinical responses were well correlated in all the patients. Minimal side effects, after drug intake, were reported by these women, but they all resolved spontaneously. The determined Mean Parasite Clearance Time (MPCT) was 57.7 +/- 14 hours. Seventeen parasite isolates were cultured in vitro; 9 (53%) grew satisfactorily. Schizont growth inhibitions was obtained at mefloquine concentration of 32 pmol/well (6.4 pmol/mu L). The effective drug concentration that gave 99% parasite growth inhibition (EC99) was 25.6 pmol/well (5.1 pmol/mu L); which indicates high parasite susceptibility to the drug in vitro. However, low dose of MQ may be ineffective in clearing parasitaemia in areas with mefloquine resistant parasite strains.

Efficacy of a 3-day oral regimen of quinine in an area of northern Nigeria with low-grade resistance of Plasmodium falciparum to chloroquine and sulphadoxine-pyrimethamine.

The efficacy in vivo of a 3-day oral regimen of quinine (30 mg/kg/day) was assessed in 34 children with falciparum malaria in an area of northern Nigeria with previously documented low-grade parasite resistance to chloroquine and sulphadoxine-pyrimethamine (SDX/PYR). By day 4, all 34 children were free of parasites. Mean parasite clearance time and fever clearance time were 2.7 and 1.7 days, respectively. However, on day 14, 5 (14.7%) children were again parasitaemic and 4 of them were clinically ill. They were again treated successfully with a standard course of oral chloroquine. No adverse drug effects were recorded. Of the 34 children, 9 parasite isolates were successfully cultured in vitro. EC50 and EC99 were 14.0 and 126.0 pmol per well respectively, indicating decreased parasite sensitivity but no resistance in vitro. In conclusion, the 3-day course of quinine was found to be an effective alternative to standard chloroquine treatment in the study area.

Sensitivity of Plasmodium falciparum to pyrimethamine in vivo and to sulphadoxine/pyrimethamine combination in vitro in pregnant women of northern Nigeria.

The in-vivo response of Plasmodium falciparum to a single dose of 25 mg pyrimethamine was evaluated in pregnant women in a semi-rural area of Zaria, northern Nigeria. Forty-four women were enrolled in the study and followed up for 14 days. Thirty-one (70%) of the women had cleared their parasitaemia by Day 7 and they remained parasite negative throughout the 14-day period of observation. The MPCT was 2.48 +/- 0.76 days. Thirteen (30%) of the 44 women were parasite positive either on Day 7 (7.16%) or Day 14 (6.14%) and re-treatment with a curative dose of chloroquine (25 mg kg-1 over 3 days) resulted in complete parasite clearance. Of the eight P. falciparum isolates successfully cultured from these women, seven (87.5%) were highly sensitive and one was resistant in vitro to the SDX/PYR combination.

Sensitivity of Plasmodium falciparum to chloroquine in pregnant women in Zaria, northern Nigeria.

Thirty-five pregnant women with Plasmodium falciparum parasitaemia were treated with chloroquine 25 mg/kg body weight over 3 days. They were followed up in vivo by use of a modified 14-day WHO extended field test. In vitro sensitivity of the parasite isolates to chloroquine was assessed by using the WHO microtest method. All pregnant women were aparasitaemic by day 7 and there was no parasite reappearance throughout the 14-day observation period. The mean parasite clearance time (MPCT) was 3.2 +/- 1.4 days. Eleven parasite isolates obtained from the women were highly susceptible to chloroquine in vitro. The effective drug concentration that gave 99% parasite growth inhibition (EC 99) was 0.36 mumol/l.

Chloroquine-resistant Plasmodium falciparum with reduced sensitivity in vitro to mefloquine and quinine in Zaria, northern Nigeria.

Thirty-six P. falciparum isolates collected from children with malaria were tested for their susceptibility to chloroquine, mefloquine and quinine in vitro using the WHO microtest system. 37% of the isolates grew in the presence of 1.6 mumol chloroquine 1(-1) blood, indicating resistance. The sensitivity to both mefloquine and quinine was markedly reduced. The inhibitory endpoints for quinine correlated with those for chloroquine and mefloquine, but no such correlation was found between chloroquine and mefloquine.

The effect of short-term malaria chemoprophylaxis on the immune response of semi-immune adult volunteers.

In 17 semi-immune adult volunteers, chemoprophylaxis with 300 mg chloroquine base weekly for six months was found to be effective in suppressing malaria. However, following 3 months of chemoprophylaxis, a significant reduction of IFA titres was seen lasting up to 2 months after chloroquine withdrawal. There was resurgence of malaria in the post-intervention phase. 2 months after drug withdrawal, serum concentrations of IgG and factor B were significantly reduced. 3 months after initiation of chloroquine prophylaxis, a temporary but significant decrease of IgG and IgM serum concentrations was found with a corresponding decline in the number of B-lymphocytes and regulatory T-cells. These returned to normal at 6 months of chemoprophylaxis. Our findings suggest that short-term malaria chemoprophylaxis may significantly interfere with humoral and cell-mediated immunity in areas of intensive P. falciparum transmission.

Resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine combination in semi-immune children in Zaria, northern Nigeria.

The World Health Organization (WHO) extended field test was employed to assess the in vivo sensitivity of Plasmodium falciparum to sulfadoxine-pyrimethamine combination in 44 children in Zaria urban area. 36 children (82%) were fully sensitive to the drug and 8 (18%) were resistant at the RI level. 8 parasite isolates were obtained from the children and successfully cultured in vitro using the WHO microtest (mark II) system. The 8 isolates underwent schizogony at concentrations of 10,000 pmol sulfadoxine/125 pmol pyrimethamine per well, indicating in vitro resistance.

Chloroquine resistance of Plasmodium falciparum in semi-immune children in Zaria, northern Nigeria.

Fifty-nine children with Plasmodium falciparum malaria were subjected to the World Health Organization (WHO) extended field test to assess the in vivo sensitivity of the parasite to chloroquine in Zaria urban area, Nigeria. The parasites in 53 children (90%) were positive but those in 6 (10%) were resistant at the RI-RII level. 36 isolates from the patients were successfully cultured in vitro for the WHO standard microtest. 13 (37%) of the isolates underwent schizogony at chloroquine concentrations of 1.6 microM/litre and above. Probit analysis showed that the chloroquine concentrations producing 50% (EC50), 90% (EC90) and 99% (EC99) schizont inhibition were 0.4, 1.6 and 4.9 microM/litre, respectively. The results indicate a rapid decline in the sensitivity of P. falciparum to chloroquine in the study area during the past 3 years.

In-vivo sensitivity of Plasmodium falciparum to chloroquine in Zaria, Nigeria.

In 33 children with confirmed Plasmodium falciparum malaria, the WHO Extended Field Test was employed to test the sensitivity of the parasite to chloroquine in Zaria urban area. No evidence of resistance to the drug was found. In 82% of the patients parasitaemia had disappeared within 3 days, while the remaining 18% were parasite negative on day 4 or 5. The mean parasite clearance time was calculated as 3.45 +/- 1.23 days. The results suggest that chloroquine sensitivity of P. falciparum may be decreased in this part of Nigeria.