Malaria parasite infection during pregnancy and at delivery in mother, placenta, and newborn: efficacy of chloroquine and mefloquine in rural Malawi.

Despite international recommendations to use malaria treatment and prevention in pregnant women in malaria-endemic areas, few studies have evaluated the efficacy of available antimalarial regimens. This issue is of particular concern in the face of spreading chloroquine (CQ)-resistance of Plasmodium falciparum in malarious areas of sub-Saharan Africa. In a prospective trial in rural Malawian pregnant women, we examined three regimens using CQ (including the existing national policy regimen) and one regimen using mefloquine (MQ). The efficacy of the regimens was determined by comparing rates of clearance of initial parasitemia; prevention of breakthrough infection; and parasitemia at delivery in maternal peripheral blood, placental blood, and in infant umbilical cord blood. Among 1,528 parasitemic women at enrollment, 281 (18.4%) had persistent infections; and among 1,852 initially aparasitemic women, 320 (17.3%) had breakthrough parasitemia on one or more follow-up visits. Compared with women on MQ, women on a CQ regimen were at significantly greater risk of persistent and breakthrough infection (odds ratios [OR] = 30.9 and 11.1, respectively, P < 10(-6)). Other significant risk factors for persistent and breakthrough infections in a multivariate model included first pregnancy; enrollment in the rainy or postrainy season; maternal age < or = 25 years; seropositivity to the human immunodeficiency virus (HIV) (persistent infections only); and no use of antimalarial prophylaxis before enrollment (breakthrough infections only). At delivery, compared with women on MQ, women on a CQ regimen were at significantly greater risk of peripheral, placental, or umbilical cord blood parasitemia (OR = 8.7, 7.4, and 4.1, respectively, P < 10(-6)). Additional risk factors for parasitemia at delivery in multivariate models included first pregnancy; delivery in the rainy or postrainy season; HIV-seropositivity; and maternal age < or = 25 years (risk for peripheral and placental blood parasitemia only). Maternal anemia (hematocrit < 30%) at enrollment or at delivery was not associated with persistent or breakthrough parasitemia or parasitemia at deliver in these multivariate models. While factors leading to increased malaria parasite exposure (high transmission seasons) and lowered or altered host immune response (low pregnancy number, young age, and HIV infection) are important risk factors for malaria in pregnant women, the use of an ineffective intervention (CQ in a setting with CQ-resistant parasites) was the most important determinant of P. falciparum parasitemia in these pregnant women. Strategies to reduce the impact of malaria in pregnant women must use efficacious interventions and may need to consider targeting the intervention to the most susceptible women during the seasons of high malaria exposure.

PIP: During September 1987 to June 1990, 3380 pregnant women with parasitemia attending 4 prenatal care clinics in rural Mangochi District, Malawi, were assigned to 1 of 4 regimens of antimalarial treatment and/or prophylaxis. The women were followed through delivery to determine the antimalarial drug efficacy on peripheral parasitemia during pregnancy and parasitemia at the time of delivery in peripheral, placental, and umbilical cord blood. The regimens were 3 regimens for chloroquine (CQ), 1 of which was the current standard of care in Malawi, and a mefloquine (MQ) regimen. Parasite clearance was not achieved in 18.4% of the 1528 women with parasitemia at enrollment. 17.3% of the 1852 women who were aparasitemic at enrollment had breakthrough infections. Women using a CQ regimen faced a significantly greater risk of persistent and breakthrough parasitemia (odds ratio [OR ] = 30.9 and 11.1, respectively; p 0.0000001). The multivariate analysis found other significant risk factors for malaria to be first pregnancy (OR = 3.6 for persistent malaria and 1.5 for breakthrough malaria), enrollment in the rainy or post-rainy season (OR = 2-3.4 for persistent parasitemia and 1.2-2.7 for breakthrough malaria), maternal age of at most 25 years (OR = 2.3 for persistent malaria and 1.6 for breakthrough malaria), and seropositivity to HIV (OR = 1.9 for persistent malaria). At delivery, women on a CQ regimen faced a significantly higher risk of peripheral, placental, or umbilical cord parasitemia than those using MQ (OR = 8.7, 7.4, and 4.1, respectively; p 0.000001). In the multivariate model, other significant risk factors for malaria at delivery were first pregnancy, enrollment in the rainy or post-rainy season, maternal age of at most 25 years, and seropositivity to HIV. The most important determinant of falciparum malaria in pregnant women was use of an ineffective intervention (i.e., CQ in an area with CQ-resistant parasites). Based on these findings, the researchers recommend that antimalarial programs focus on highly efficacious drugs and targeting pregnant women during the season of high malaria exposure.

Malaria treatment and prevention in pregnancy: indications for use and adverse events associated with use of chloroquine or mefloquine.

In sub-Saharan Africa, women frequently report a variety of symptoms during pregnancy, some of which indicate possible illness. Given the adverse impact of malaria in pregnancy, these events may be important for at least two reasons: it may be possible to use reported fever illness as a determinant of which women need an antimalarial intervention, and, it is possible that adverse symptoms following the antimalarial intervention may be important determinants of continued adherence to the prevention regimen. In a cohort of pregnant women enrolled at first antenatal clinic visit in rural Malawi, we evaluated reported fever, determined parasitemia, and placed the women on antimalarial regimens containing chloroquine (CQ) or mefloquine (MQ). We then systematically evaluated reported symptoms following antimalarial drug use after initial therapeutic doses and subsequent prophylactic doses, and monitored women throughout their pregnancy and at delivery. Among 4,187 enrolled women, 1,048 (25%) reported at least one febrile episode during pregnancy before their first antenatal clinic visit. Factors associated with this reported fever included low parity, enrollment in the rainy season, human immunodeficiency virus seropositivity, use of antimalarial prophylaxis before enrollment, high socioeconomic status, normal (compared to low) maternal height and weight, and literacy. Fever before the first antenatal clinic visit was reported by 24.4% of parasitemic women and 25.4% of aparasitemic women; the sensitivity and specificity of fever to identify parasitemic women was 24% and 71%, respectively. In contrast, the sensitivity and specificity of first or second pregnancy to identify parasitemic women was 71% and 57%, respectively. Among women on a CQ or MQ regimen, approximately 60% reported side effects (e.g., itching, dizziness, and gastrointestinal disturbances) after a treatment dose and approximately 25% reported side effects after a prophylactic dose; rates and types of symptoms reported were similar in the CQ and MQ groups. Few serious side effects were observed and rates of fetal loss were low and similar in the groups. Reliance on fever illness will be wholly inadequate to identify parasitemic women; therefore, our findings support existing World Health Organization recommendations that presumptive treatment and prevention regimens should be offered to all pregnant women. When resources are inadequate to offer antimalarial prophylaxis to all pregnant women, women in their first or second pregnancy may be a more appropriate target group than pregnant women with reported fever. Education regarding expected minor side effects may reduce rates of poor compliance and improve the effectiveness of the prevention effort.

PIP: 4187 pregnant women with parasitemia attending 4 prenatal care clinics in rural Mangochi District, Malawi, were assigned to 1 of 4 regimens of antimalarial treatment and/or prophylaxis and followed through delivery. The aim was to examine maternal fever and to evaluate side effects and the frequency of adverse reproductive outcomes for their possible association with malaria or the antimalarial drug regimens. The regimens were 3 regimens for chloroquine (CQ), 1 of which was the current standard of care in Malawi, and a mefloquine (MQ) regimen. 25% of the pregnant women claimed to have had at least 1 febrile episode before their first prenatal care visit. Blood smear tests revealed the parasitemia prevalence rate at enrollment to be 44.4%. The sensitivity of fever to identify parasitemic pregnant women was 24%. Fever's specificity was 71%. Only high density parasitemia (10,000 parasites/sq m) was associated with fever (44.9% vs. 25.4% for no parasitemia; odds ratio [OR] = 2.54; p 0.000001). Other significant factors associated with high fever were low parity, enrollment in the rainy season, HIV seropositivity, use of antimalarial prophylaxis before enrollment, high socioeconomic status, normal maternal height and weight, and literacy. The sensitivity of first or second pregnancy to identify parasitemic women was 71%. Its specificity was 57%. About 60% of women from both CQ and MQ treatment groups had side effects after a treatment dose. About 25% had side effects after a prophylactic dose. The leading side effects were itching, dizziness, and gastrointestinal disturbances. There were few serious side effects. Among all women, the spontaneous abortion rate was 1.2% and the stillbirth rate was 3.9%. Women in the CQ and MQ treatment groups had similar abortion and stillbirth rates. Based on these findings, the researchers concluded that using fever as a means to identify parasitemic women is unreliable. They recommend antimalarial treatment and/or prophylaxis for all pregnant women, but when resources are limited it should be administered to women in their first or second pregnancy.

Malaria infection in infancy in rural Malawi.

Malaria infection is thought to be relatively infrequent in infants less than 90 days of age in sub-Saharan Africa. In a rural area of Malawi with intense malaria transmission, we examined the occurrence of malaria infection during infancy and risk factors for parasitemia in the first three months of life in the cohort of infants delivered to women in the Mangochi Malaria Research Project. Among 3,915 liveborn singleton infants, 3,432 (87.7%) were seen at least once during infancy (first 12 months of life); of these, malaria blood smear results were available on 2,649 (77.2%). Overall, in a cross-sectional analysis, 23.3% of infants at three months of age were infected with Plasmodium falciparum; this proportion increased to more than 30% during the high transmission season. By the age of 10 months, 60-80% of the infants were infected, depending on the season. Geometric mean parasite density increased each month after two months of age and plateaued at seven months of age. In a life-table analysis, the median time to acquisition of a positive smear was 199 days. Factors independently associated with smear positivity at < 4 months of age included visit during high transmission season (adjusted odds ratio [AOR] = 4.1), maternal smear positivity at the same visit (AOR = 3.5), history of infant fever in the previous two weeks (AOR = 2.8), birth during the rainy season (AOR = 1.7), low socioeconomic status (AOR = 1.6), and low maternal education (AOR = 1.5). The specificity of a recent fever history for malaria infection in early infancy was high (> 70%). Intervention strategies to reduce the risk of early infant infection need to be targeted toward mothers of infants at high risk.

Objectives and methodology in a study of malaria treatment and prevention in pregnancy in rural Malawi: The Mangochi Malaria Research Project.

Malaria infection due to Plasmodium falciparum has been widely recognized as associated with important adverse consequences in pregnant women, particularly in areas of high transmission. Although strategies using antimalarial drugs for prevention had been recommended, even by the late 1980s, few studies had been carried out to examine the efficacy of these prevention efforts. The objectives of the Mangochi Malaria Research Project investigation were to determine the comparative efficacy of regimens containing chloroquine (CQ) or mefloquine (MQ) antimalarial treatment and chemoprophylaxis in an area of CQ-resistant P. falciparum on the following outcomes: 1) the frequency of placental malaria infection; 2) the frequency of low birth weight; 3) the frequency of prematurity or intrauterine growth retardation; 4) the frequency of maternal fever illness and severe anemia; and 5) the likelihood of infant acquisition of malaria infection. Although the investigation was not designed to evaluate the role of antimalarial chemoprophylaxis and treatment on infant mortality reduction, because babies born to study women were scheduled to be followed for up to two years of life, the study allowed for an examination of mortality and morbidity in this population. The sample size was insufficient to provide more than descriptive analysis of mortality and morbidity in the fetal, perinatal, neonatal, postneonatal, and infant time intervals. The study design allowed for the evaluation of two additional aspects of maternal and infant health: other determinants of the above-listed outcomes in addition to malaria prevention (e.g., maternal age, gravidity, socioeconomic status, infection with human immunodeficiency virus or syphilis) and reported cause-specific mortality in the fetal-to-infant intervals. The study design included 22 months of enrollment of pregnant women at their first antenatal clinic visit from four clinic sites in Mangochi District, Malawi, with assignment to one of four antimalarial regimens and prospective follow-up through pregnancy, at delivery, and during infancy. All drug dosing was performed under supervision by the study team, making this an evaluation of intervention efficacy (excluding the role of patient compliance).

Some haematological parameters in Malawian neonates.

Studies of haematological parameters were performed on 366 (177 male and 189 female) normal Malawian neonates with mean +/- s.d. birthweight of 2.99 +/- 0.37 (range 2.1-4.0) kg using a Nova Cell Track, Model Nova CT11. Cord anaemia (Cord Hb < 13.5g dl-1) was detected in 100 (27.3%) of the neonates. It was also shown that although the male babies had a significantly higher erythrocyte protoporphyrin level (p < 0.001) than the females, there were no significant differences (p > 0.05) in the red cell, white cell and platelet indices between the two sexes. When the haematological parameters of the 266 (72.7%) non-anaemic (Cord Hb > 13.5g dl-1) neonates were analysed, the mean +/- s.d. values which may serve as local reference standards were: Hb 16.0 +/- 1.7 (range 13.5-21.3) g dl-1, Hct 47.0 +/- 6.0 (range 36.5-67.5) percent, MCV 112.6 +/- 8.9 (range 72.2-131.0) fl, MCH 31.9 +/- 5.5 (range 24.4-48.5) pg, MCHC 33.5 +/- 2.8 (range 29.1-48.9) g dl-1 reticulocyte count 6.9 +/- 3.6 (range 1.2-25.0) percent, free erythrocyte protoporphyrin 3.3 +/- 0.9 (range 1.9-7.7) mgs ZPP gm-1 Hb, platelet count 269.9 +/- 57.7 (range 134.0-454.0) x 10(9) l-1 and total leucocyte count 12.3 +/- 4.8 (range 5.5-35.3) x 10(9) l-1. Further analysis of the differential wbc count disclosed normal levels of eosinophils and neutrophils similar to those given in standard haematology textbooks for Caucasian neonates; thus strengthening the belief that eosinophilia and relative neutropenia previously reported in adult Africans is not of genetic origin, but rather an acquired phenomena.

Cost-saving through microscopy-based versus presumptive diagnosis of malaria in adult outpatients in Malawi.

The cost implications of changing from a policy of presumptive diagnosis to one of microscopy-based diagnosis in the management of uncomplicated malaria in an urban hospital adult outpatient clinic in Malawi were studied. Costs were measured in three separate weeks during the rainy season. In weeks I and II all uncomplicated malaria cases were treated on the basis of a presumptive diagnosis. In week II, blood films were taken but the results were not made available and did not affect drug dispensing. In week III, antimalarial drugs were restricted to parasitaemic patients. In week I, a total of 7216 prescriptions were written and dispensed, of which 2883 (39.9%) were for antimalarial drugs. The proportion of antimalarial prescriptions fell to 1171/5556 (21.1%) in week II and 357/5377 (6.6%) in week III. We estimate annual savings from microscopy-directed treatment in this setting to be 52,000 Malawi kwacha (US$ 14,000). This represents 3% of the annual drugs budget for the hospital, and is large enough to justify a change in policy.

Antibodies to ring-infected erythrocyte surface antigen (Pf155/RESA) protect against P. falciparum parasitemia in highly exposed multigravidas women in Malawi.

To determine whether antibodies to defined B-cell epitopes of Plasmodium falciparum antigens were related to protection against parasitemic attacks in highly exposed pregnant women, two samples of 235 with no initial P. falciparum parasitemia (NP) and 89 multigravidas who presented initial P. falciparum parasitemia (IP) were enrolled in an antimalarial prophylaxis trial in the Mangochi District in Malawi. Sera were collected under effective prophylaxis and tested for antibody measurement using FAST-ELISA. Mean antibody titers to synthetic peptides reproducing the 3 major B-cell epitopes of the ring-infected erythrocyte surface antigen (Pf155/RESA), as (EENV)4, (EENVEHDA)4 and (DDEHVEEPTVA)3, were higher in the NP than in the IP multigravidas, and this remained consistent within the season of malaria transmission (all p < 0.05). All antibodies to Pf155/RESA were positively intercorrelated within each group. Mean antibody titers to peptide (PNAN)5 reproducing the major B-cell epitope of the circumsporozoite protein (CS protein) were similar between NP and IP multigravidas in both dry and rainy season. Antibodies to Pf155/RESA epitopes may contribute to immune protection against blood-stage parasite multiplication in these highly malaria-exposed pregnant women.

Antenatal chloroquine chemoprophylaxis in Malawi: chloroquine resistance, compliance, protective efficacy and cost.

The roles of Plasmodium falciparum resistance to chloroquine and compliance in the protective efficacy of the antenatal chloroquine prophylaxis programme in Malawi were evaluated by interviewing pregnant women attending antenatal clinics and examining them for P. falciparum parasites in thick smears and chloroquine metabolites in urine. 36% of 642 women had urine chloroquine metabolite levels compatible with regular compliance to the weekly chloroquine dosage schedule. Among a subgroup of 288 pregnant women who were provided weekly prophylaxis under supervision for 4 consecutive weeks, P. falciparum infection rates were 37%, representing the failure of chloroquine to eliminate P. falciparum in Malawi. Among pregnant women not taking prophylaxis, the P. falciparum infection rate was 48%. Based on the P. falciparum infection rates among these 2 groups of women, the protective efficacy of CQ chloroquine was estimated as 23%. If the 36% of pregnant women who had chloroquine in their urines accurately estimates the proportion of women who comply with the prophylaxis programme in Malawi, the actual protective efficacy of the programme would be 8%. The cost of preventing one P. falciparum infection among pregnant women in the Malawi programme is estimated at US$ 10.87. This is an unacceptably high cost in much of Africa, and research is required to define more cost-effective interventions, including more effective drugs, and health education programmes to improve compliance among pregnant women.

PIP: During February-June 1988 in Malawi, interviews with and blood samples from 802 pregnant women attending 4 prenatal clinics on the shore of Lake Malawi or in the highlands were conducted to examine the role of chloroquine resistance and compliance in the protective efficacy of the government's chloroquine prophylaxis program. Compliance rates were 20% for women on their first prenatal visit and 36% for those on a return visit (i.e., urine chloroquine levels 1 ppm). 37% of 228 women who completed 4 weeks of supervised chloroquine administration had Plasmodium falciparum parasites in their blood. The P. falciparum infection rate was 48% among the 160 women who had not received supervised chloroquine administration. Based on these two rates, the protective efficacy of chloroquine was 23%. If the 36% of women on a return visit had taken their chloroquine as prescribed yet had chloroquine in their urine samples, the protective efficacy of the government's chloroquine prophylaxis program would have been 8%. Assuming an attack rate of P. falciparum of 48% and a protective efficacy of 8%, the cost per malaria case prevented would have been US $10.87. This is too high of a cost in Africa. Research is needed to identify more cost-effective interventions, such as more effective drugs and health education programs to improve compliance among pregnant women.

Mefloquine therapy for Plasmodium falciparum malaria in children under 5 years of age in Malawi: in vivo/in vitro efficacy and correlation of drug concentration with parasitological outcome.

The in vivo and in vitro response of Plasmodium falciparum to a single oral dose of mefloquine (25 mg/kg body weight (M25) or 15 mg/kg (M15] was studied in children under 5 years of age in Malawi. Of the children who received mefloquine, 35% vomited at least once, and 10% did not tolerate the drug because of vomiting. The therapy failure rates for the M25 group on day 7, 14, and 28 were 15%, 18%, and 42%, respectively, and these did not differ significantly from those for the M15 group (4%, 18%, and 59%). In contrast, 34 in vitro microtests (17 per group) showed schizont inhibition at less than or equal to 32 pmol mefloquine per test well. On day 7, the concentration of mefloquine in samples of blood was significantly lower in both the M25 and M15 groups for children who were parasitaemic on day 7 than in samples from those who were aparasitaemic. A positive blood smear on day 7 was strongly associated with a mefloquine concentration of less than 500 ng/ml blood on day 2 or day 7 (P less than 0.0003). Vomiting was associated with a low mefloquine concentration on day 2 but not day 7. These results suggest that mefloquine is effective against P. falciparum in Malawi but that for young children the therapy appears to be complicated by frequent vomiting.

Mefloquine therapy for Plasmodium falciparum malaria in children under 5 years of age in Malawi: in vivo/in vitro efficacy and correlation of drug concentration with parasitological outcome

The in vivo and in vitro response of Plasmodium falciparum to a singleel oral dose of mefloquine (25 mg/kg body weight (M25) or 15 mg/kg (M15) was studied in children under 5 years of age in Malawi. Of the children who received mefloquine, 35 per cent vomited at least once, and 10 per cent did not tolerate the drug because of vomiting. The therapy failure rates for the M25 group on day 7, 14 and 28 were 15 per cent, 18 per cent, and 42 per cent, respectively, and these did not differ significantly from those for the M15 group (4 per cent, 18 per cent, and 59 per cent). In contrast, 34 in vitro microtests (17 per group) showed schizont inhibition at /= 32 pmol mefloquine per test well. On day 7, the concentration of mefloquine in samples of blood was significantly lower in both the M25 and M15 groups for children who were parasitaemic on day 7 than in samples from those who were aparasitaemic. A positive blood smear on day 7 was strongly associated with a low mefloquine concentration of 500 ng/ml blood on day 2 or day 7 (P0.0003). Vomiting was associated with a low mefloquine concentration on day 2 but not day 7. These results suggest that mefloquine is effective against P. falciparum in Malawi but that for your children the therapy appears to be complicated by frequent vomiting(AU)

Mefloquine therapy for Plasmodium falciparum malaria in children under 5 years of age in Malawi: in vivo/in vitro efficacy and correlation of drug concentration with parasitological outcome

The in vivo and in vitro response of Plasmodium falciparum to a single oral dose of mefloquine (25 mg/kg body weight (M25) or 15 mg/kg (M15] was studied in children under 5 years of age in Malawi. Of the children who received mefloquine, 35% vomited at least once, and 10% did not tolerate the drug because of vomiting. The therapy failure rates for the M25 group on day 7, 14, and 28 were 15%, 18%, and 42%, respectively, and these did not differ significantly from those for the M15 group (4%, 18%, and 59%). In contrast, 34 in vitro microtests (17 per group) showed schizont inhibition at less than or equal to 32 pmol mefloquine per test well. On day 7, the concentration of mefloquine in samples of blood was significantly lower in both the M25 and M15 groups for children who were parasitaemic on day 7 than in samples from those who were aparasitaemic. A positive blood smear on day 7 was strongly associated with a mefloquine concentration of less than 500 ng/ml blood on day 2 or day 7 (P less than 0.0003). Vomiting was associated with a low mefloquine concentration on day 2 but not day 7. These results suggest that mefloquine is effective against P. falciparum in Malawi but that for young children the therapy appears to be complicated by frequent vomiting

Clinical trials with halofantrine hydrochloride in Malawi

Two clinical trials of the phenanthrene treatment of Plasmodium falciparum were conducted in Malawi; in areas where the parasite was known to be chloroquine resistant. Of 49 children followed up for 14 days; 47 became aparasitaemic -ie; the cure rate was 96 percent. In both trials the drug was very well tolerated. Halofantrine hydrochloride seems to be effective against P. falciparum chloroquine sensitive and resistant strains in Africa

Comparative efficacy of alternative primary therapies for Plasmodium falciparum infections in Malawi.

In Malawi, where high levels of chloroquine resistance were shown using a modified 7-day in vivo test, amodiaquine and pyrimethamine-sulfadoxine were evaluated as alternative initial therapies for Plasmodium falciparum infections in children under 5 years old. Therapy success rates, judged by parasite clearance by day 7 after initiation of therapy, were significantly greater among 39 children treated with amodiaquine at 10 mg/kg (90%), 37 receiving amodiaquine at 25 mg/kg (97%), and 34 receiving pyrimethamine-sulfadoxine (100%) at a dose of 25 mg sulfadoxine/kg, than among those treated with chloroquine at a dose of 25 mg/kg (59%) (P = 0.01). Extension of the follow-up period of those receiving amodiaquine (25 mg/kg) and pyrimethamine-sulfadoxine to 21 d revealed a progressively increasing rate of parasite recrudescence in the amodiaquine group (34%), but no recrudescence in the pyrimethamine-sulfadoxine group. These results suggest that, in Malawi, amodiaquine and pyrimethamine-sulfadoxine are superior to chloroquine in producing prompt clearance of P. falciparum parasites among young children, and that pyrimethamine-sulfadoxine alone is superior to the 4-aminoquinolines in sustaining P. falciparum clearance.

In vivo efficacy of chloroquine treatment for Plasmodium falciparum in Malawian children under five years of age.

In 1984 the government of Malawi instituted a program to reduce malaria mortality and morbidity in children less than 5 years of age as a part of the Combatting Childhood Communicable Diseases (CCCD) program. To define the appropriate malaria therapy regimen, investigators used a quality assurance design in a simplified 7-day in vivo drug response study with follow-up observations on day 2 (D2), D3, and D7 after the initial day of the study (D0). The efficacy of oral chloroquine was assessed in 224 children who were enrolled at 6 sites, 2 in each of the 3 administrative regions of Malawi. Parasitological failure, defined as failure of parasitemia to decrease by 75% of the value by D3 or presence of any detectable parasitemia on D7, ranged from 41%-65% following administration of chloroquine 25 mg (base)/kg. However, only 8% of children who were parasitemic on D7 were febrile or judged to be ill. Considering these therapeutic results and the higher cost and limited availability of alternative therapies, chloroquine 25 mg/kg therapy was adopted as the primary therapy for malaria.

In vivo efficacy of chloroquine treatment for Plasmodium falciparum in Malawian children under five years of age

In 1984 the government of Malawi instituted a program to reduce malaria mortality and morbidity in children less than 5 years of age as a part of the Combatting Childhood Communicable Diseases (CCCD) program. To define the appropriate malaria therapy regimen; investigators used a quality assurance design in a simplified 7-day in vivo drug response study with follow-up observations on day 2 (D2) ; D3; and D7 after the initial day of the study (D0). The efficacy of oral chloroquine was assessed in 224 children who were enrolled at 6 sites; 2 in each of the 3 administrative regions of Malawi. Parasitological failure; defined as failure of parasitemia to decrease by 75 percent of the value by D3 or presence of any detectable parasitemia on D7; ranged from 41 percent -65 percent following administration of chloroquine 25 mg (base)/kg. However; only 8 percent of children who were parasitemic on D7 were febrile or judged to be ill. Considering these therapeutic results and the higher cost and limited availability of alternative therapies; chloroquine 25 mg/kg therapy was adopted as the primary therapy for malaria