Biomedical subjects

A Sowunmi

Publications and source records attributed to A Sowunmi.

At least 37 records · Page 2Linked to original sources

PubMed2004

Molecular analysis of Plasmodium falciparum recrudescent malaria infections in children treated with chloroquine in Nigeria.

Parasite genotyping by a polymerase chain reaction was used to distinguish recrudescent from newly acquired Plasmodium falciparum infections in 50 of 160 Nigerian children taking part in a chloroquine efficacy study in Ibadan, Nigeria. A finger prick blood sample was taken from each child before and after treatment to identify recrudescent parasites. By investigating allelic variation in three polymorphic antigen loci, merozoite surface protein-1 (MSP-1), MSP-2, and glutamate-rich protein (GLURP), we determined parasite diversity in the population and in the infected host. DNA from pretreatment and post-treatment samples from 47 of the 50 patients who failed therapy was successfully amplified by the PCR. The MSP-1, MSP-2, and GLURP genotypes in all samples showed extensive diversity, indicating polyclonal infections. The average number of clones per infection in pre-treatment sample was 2.5 with MSP-1, 4.9 with MSP-2, and 2 with GLURP. The extent of multiplicity decreased significantly (P = 0.016) in posttreatment samples. Multiplicity of infection and initial parasite density were not age dependent. Comparison of the variant alleles in pretreatment and post-treatment samples of each patient indicates that 26 of the 47 children had genuinely recrudescent disease. Conversely, post-treatment samples from five children showed completely new genotypes, indicating either a previously sequestered population of parasites or a newly acquired infection. Overall, this study has shown the diversity and complexity of P. falciparum population in Ibadan, Nigeria. The study has also shown the dynamics of P. falciparum infections in this population before and after chloroquine treatment in an area of high malaria transmission.

Animals↗

PubMed2004

Malaria diagnosis: false negative parasight-F tests in falciparum malaria patients in Nigeria.

This study was designed to assess the relative reliability of microscopy, the dipstick technique based on the detection of Plasmodium falciparum-specific histidine rich protein II (HRPII) (Parasight-F) and PCR assays in diagnosing falciparum malaria infections in Nigerian children. The prevalence of P. falciparum infections in enrolled patients was 100% by microscopy. Parasite density ranged from 329 to 81,194 parasites/microL of blood, with a geometric mean parasite density of 5168 parasites/microL of blood. The sensitivity of the HRPII based dipstick, PCR and microscopy were 80%, 92% and 100% respectively. A false negative rate of 20% was observed with Parasight-F as compared with microscopy. The parasitemia in patients with false negative Parasight-F tests ranged from 319 to 54,680 parasites/microL of blood. Detailed PCR analysis of Isolates obtained from five out of the eight patients who exhibited a negative Parasight-F test, showed that the average numbers of P. falciparum clones in these five isolates were: 1.7 +/- 1.02 with MSPI, 3.2 +/- 1.3 with MSP2 and 1.4 +/- 1.72 with GLURP. Comparison of microscopy and HRPII results showed a significant (p=0.009) difference as opposed to microscopy and PCR (p=0.239). This study showed that caution should be exercised when excluding P. falciparum infections on the basis of HRPII based dipstick results alone. Microscopy or PCR diagnosis where possible, should be carried out in order to confirm negative P. falciparum HRPII-based dipstick tests.

Animals↗

PubMed2004

Plasmodium berghei: efficacy and safety of combinations of chloroquine and promethazine in chloroquine resistant infections in gravid mice.

Efficacy and safety of combinations ofChloroquine (CQ) and doses of Promethazine (PR) against CQ resistant Plasmodium berghei infections in gravid mice was evaluated. Parasites were cleared faster in mice treated with CQ combined with doses of PR ranging from 20mg/kg to 50mg/kg (3.4 +/- 0.5 to 2.7 +/- 0.7) compared with CQ alone (4.7 +/- 0.8) (P<0.5). Parturition resulting in live pups in animals treated with CQ and 20mg/ kg and 30mg/kg of PR (81%) was significantly higher than in animals treated with CQ alone (44%) or saline (13%). Mean birth weight of pups delivered by infected gravid animals treated with CQ and 30mg/kg or 40mg/kg of PR (1.51 +/- 0.16 or 1.56 +/- 0.16) was significantly higher than animals treated with CQ alone (1.33 +/- 0.13) (P=0.00004, 0.0014 respectively). No gross malformations were observed in pups delivered by infected or non-infected animals treated with the combinations of chloroquine and Promethazine.

Animals↗

PubMed2004

Efficacy of herbal remedies used by herbalists in Oyo State Nigeria for treatment of Plasmodium falciparum infections--a survey and an observation.

In the course of evaluating the contribution of phytomedicine to possible drug discovery of antimalarial drugs, an ethnomedical survey of specialized children traditional clinics was done. In the observational multi center study, efficacy of eight different herbal remedies, each consisting of 3-8 ingredients and administered by herbalists were investigated in clients enrolled in the six traditional clinics in Oyo (urban center) and Otu (rural center) of Oyo State, Nigeria. The clients, aged between six months and fifteen years with clinical symptoms of malaria were enrolled in the clinics of the herbalists, as their usual practice. Oral informed consents were obtained from their parents or guardians. Microscopic diagnosis of malaria infection was used to evaluate parasitaemia and validate efficacy of herbal remedies. Results of the analysis showed that, of the 163 clients of the herbalists, only 62 (30 from Oyo, 32 from Otu) had microscopically confirmed P. falciparum infection. Only results from 54 clients (29/30 (Oyo) and 25/32 (Otu) with P. falciparum infection could be evaluated. Plasmodium falciparum infection in 88% (23/29) of clients from Oyo responded to treatment with the herbal remedies while cure rate in clients from Otu was 42% (13/25). Parasite densities ranged from 171 to 53,613 parasites/microl blood and 87 to 36,209 parasites/microl blood in patients from Oyo and Otu respectively. The herbalists administered the remedies and Gossypium arboreum, Anarcadium occidentalis, Citrus medica, Phyllanthus amarus and Lippia multiflora were the main ingredients in the efficacious remedies. The herbalists gave detailed descriptions of each of the 8 herbal remedies proffered. The results confirm the efficacy of two of the eight herbal remedies, thereby validating the role of ethnomedicine as a possible source for the discovery of new chemotherapeutic agents in the treatment of P. falciparum malaria.

Adolescent↗

PubMed2003

Plasmodium falciparum gametocytaemia in Nigerian children: before, during and after treatment with antimalarial drugs.

We evaluated gametocyte carriage and intensities of gametocytaemia in 710 children presenting with acute, symptomatic, uncomplicated Plasmodium falciparum malaria who were treated with various antimalarial drug regimens: chloroquine (CQ); chloroquine plus chlorpheniramine, a histamine H1 receptor antagonist that reverses CQ resistance in P. falciparum in vitro and in vivo (CQCP); chloroquine plus ketotifen, a histamine H1 receptor antagonist that reverses CQ resistance in P. falciparum in vitro but not in vivo in the present study (CQK); chloroquine plus pyrimethamine-sulphadoxine (CQPS); amodiaquine (AQ); amodiaquine plus pyrimethamine-sulphadoxine (AQPS); and pyrimethamine-sulphadoxine (PS). On presentation, gametocyte carriage was significantly higher in CQ-resistant (CQ-R) than in CQ-sensitive (CQ-S) infections. Following CQ treatment, gametocyte carriage was significantly higher at all times after treatment and gametocyte density significantly higher on day 7 of follow-up in children with CQ-R than CQ-S infections. CQ treatment of CQ-R infections resulted in significantly higher density of gametocytaemia on day 7 compared with pre-treatment (day 0), but similar treatment of CQ-S infections resulted in significantly lower density of gametocytaemia on day 14 compared with day 0. Among children with CQ-R infections, those with mild (RI) resistance carried gametocytes significantly more often than those with moderate (RII) resistance on days 5 and 7 of follow-up (P = 0.04 and 0.01, respectively). Disposition kinetics of gametocytaemia using a non-compartmental method showed that the half life of gametocytaemia was longer and the clearance slower in children with CQ-R than in those with CQ-S infections. PS treatment was associated with significantly higher gametocyte carriage at all times between days 1 and 14, and significantly higher gametocytaemias on days 7 and 14 than in the other treatment regimens. Combination of AQ with PS significantly decreased gametocyte carriage at all times between days 1 and 14 of follow-up. Continuing use of CQ in CQ-R infections may encourage transmission of CQ-R infections; SP monotherapy is associated with significant gametocyte carriage and gametocytaemia and may encourage transmission of SP resistant infections as resistance to the drug increases.

Age Factors↗

PubMed2003

Changes in Plasmodium falciparum gametocytaemia in children with chloroquine-sensitive asexual infections.

A non-compartmental pharmacokinetic model was used to describe the changes in gametocytaemia in nine children with chloroquine-sensitive Plasmodium falciparum malaria in whom asexual parasitaemia cleared within 72 h of chloroquine treatment. Peak gametocytaemia was 74 +/- 19.9 (se), range 24-198, geometric mean 58 sf (sexual forms)/microliter. Time to peak gamelocytaemia was 43.2 +/- 14.4, range 0-120 h. Following peak gametocytaemia, gametocytes persisted in blood for a period of 168-504 h. The decline from peak gametocytaemia was exponential with a half-life of gametocytaemia of 43.2 +/- 20.4, range 13.1-206 h. The mean pre-treatment sex ratio was male-biased and remained so till complete elimination of gametocytaemia. Peak microgametocytaemia, area under the curve of microgametocytaemia versus time, and the half-life of microgametocytaemia were significantly higher than those of macrogametocytaemia. The volume of blood completely cleared of macrogametocytaemia per unit time was significantly higher than that of microgametocytaemia. Macrogometocytes are cleared from the circulation faster than microgametocytes but chloroquine treatment of chloroquine-sensitive infections has little or no significant effect on gametocyte sex ratios in this group of children.

Animals↗

PubMed2003

Gametocyte sex ratios in children with asymptomatic, recrudescent, pyrimethamine-sulfadoxine-resistant, Plasmodium falciparum malaria.

The clinical features of the primary Plasmodium falciparum infections in 25 children, and of the recrudescent infections that emerged after pyrimethamine-sulfadoxine (PS) treatment of the children had failed, were evaluated. In addition, the gametocyte sex ratios in these children and in age- and gender-matched controls who had PS-sensitive (PS-S) infections were also examined. Compared with the primary infections, the recrudescent infections were accompanied by significantly fewer symptoms and lower levels of parasitaemia but significantly higher gametocytaemia:parasitaemia ratios. Although the mean gametocyte sex ratio was female-biased pre-treatment, in both the PS-resistant (PS-R) and PS-S infections it became male-biased on days 7 and 14 post-treatment. The times taken to attain a sex ratio of 1 were similar in both groups. The predominance of macrogametocytes seen 'early' post-treatment (on day 3) was later replaced by a predominance of microgametocytes (on days 7 and 14). Analysis of the disposition of gametocytaemia, from the time to attain a sex ratio of 1, showed that the area under the curve of the plot of the level of microgametocytaemia upsilon. time and the mean half-life of the microgametocytaemia were significantly greater and microgametocytaemia clearance was significantly slower than the corresponding values for macrogametocytaemia. Although sex ratios in Plasmodium may naturally become more male-biased as the infection progresses, it is possible that PS treatment may have contributed to the male-biased sex ratios observed post-treatment.

Antimalarials↗

PubMed2003

A randomized comparison of chloroquine and chloroquine plus ketotifen in the treatment of acute, uncomplicated, Plasmodium falciparum malaria in children.

The increasing resistance of Plasmodium falciparum to chloroquine (CQ) has created urgent needs for the evaluation of alternative antimalarial drugs that are effective, safe, readily available and affordable. Ketotifen, a histamine H(1)-receptor antagonist that reverses CQ resistance in P. falciparum in vitro, may potentially enhance the effects of CQ in vivo. The effects of oral treatment with CQ alone (30 mg/kg base given over 3 days) were compared with those of this CQ regimen combined with ketotifen fumarate (0.25 mg at presentation followed by 0.125 mg/kg every 8 h for 5 days). The subjects were 145 children aged 1-10 years who were suffering from acute, symptomatic, uncomplicated, P. falciparum malaria: 74 given CQ alone and 71 given CQ plus ketotifen (CQK). Although the mean fever-clearance time was significantly shorter following treatment with CQK than after treatment with CQ alone, all other therapeutic responses were similar in the two treatment groups. Among siblings in whom there was clustering of infections, the likelihood of cure was also similar in the two treatment groups. Retreatment of 17 CQ-treatment failures with CQK produced a cure in six children, and retreatment of 22 CQK-treatment failures with CQK produced a cure in eight children. Retreatment of all drug failures with a combination of amodiaquine plus pyrimethamine-sulfadoxine resulted in complete clearance of parasitaemia and symptoms within 2-3 days and a cure 'rate' of 100% on day 28. The prevalences and intensities of gametocytaemias on day 3 or days 3, 7 and/or 14 combined were similar in the two groups. Adverse drug reactions were always tolerable, and limited to pruritus, gastro-intestinal disturbances, drowsiness and weight gain; the latter two adverse effects were significantly more frequent in those treated with CQK than in those given CQ alone. Haematological and biochemical parameters were not adversely affected by either treatment regimen. The findings indicate that - at least at the dosing regimen used in the present study and among children with acute, uncomplicated, P. falciparum malaria from Ibadan - the addition of ketotifen to CQ produced little or no significant enhancement of the antimalarial effect of CQ.

Acute Disease↗

PubMed2003

Plasmodium falciparum gametocytaemia in Nigerian children: Peripheral immature gametocytaemia as an indicator of a poor response to chloroquine treatment, and its relationship to molecular determinants of chloroquine resistance.

A group of 161 children who presented with acute, symptomatic, uncomplicated, Plasmodium falciparum malaria in an endemic area of Nigeria was investigated. The aims of the study were to determine the clinical characteristics and responses to oral chloroquine (CQ) therapy of children who were gametocytaemic on presentation and those who were not [including those who were found to have developed peripheral immature gametocytaemias (PIG) when checked 72 h after commencing treatment], and to follow the development of PIG 72-336 h after the start of treatment. The 40 consecutive children who did have peripheral gametocytaemia on presentation and the 40 who did not were similar in their clinical characteristics and responses to oral CQ therapy. Nine of the 40 children who did not initially have gametocytaemias but who subsequently developed PIG (stages I-III) 72-336 h after commencing CQ treatment failed the treatment. In order to evaluate the presence of PIG as an indicator of response to CQ, the smears of blood from 81 children--66 classified as resistant to CQ (60, five and one considered RI, RII, RIII, respectively) and 15 who, though considered to have sensitive responses to CQ, cleared their peripheral parasitaemias > or =72 h after commencing CQ therapy--were examined for PIG. Most (42) of the 66 children with CQ-resistant (CQ-R) infections but none of the 15 with sensitive responses had PIG. Among the 66 children with CQ-R infections, the clinical features of those with PIG were generally similar to those without PIG, although those with PIG were more likely to have hepato-splenomegaly and less likely to have hepatomegaly alone. In the children with CQ-R infections, plasma concentrations of CQ on days 7 and 14 were generally above the level necessary to clear sensitive infections in the study area. The results of molecular analyses of isolates from children with both CQ-R infections and PIG revealed that all 14 checked for mutations in pfcrt had the T76 mutation associated with CQ resistance, and that four of the five also checked for mutations in pfmdr1 had the Y86 mutation associated with CQ resistance. The detection of PIG 72 h after the commencement of CQ treatment may be used as a microscopical indicator of a poor response to CQ in children from this endemic area.

ATP-Binding Cassette Transporters↗

PubMed2003

Asymptomatic, recrudescent, chloroquine-resistant Plasmodium falciparum infections in Nigerian children: clinical and parasitological characteristics and implications for the transmission of drug-resistant parasites.

The clinical features of their primary Plasmodium falciparum infections and of the recrudescent infections that emerged after chloroquine (CQ) treatment were evaluated in 48 children. Compared with the primary infections, the recrudescent infections were accompanied by significantly fewer symptoms and lower densities of parasitaemia but a much higher gametocytaemia:parasitaemia ratio (0.051 v. 0.00097; P = 0.0000000). There was a negative correlation between the recrudescent parasitaemia and the time elapsing between its detection and the subsequent onset of symptoms (r = -0.44; P = 0.006). The recrudescent parasitaemia was significantly lower [with geometric means and (ranges) of 117 (40-9756) v. 1112 (30-25,592) asexual forms/microl; P = 0.009] and the recrudescent gametocytaemia:parasitaemia ratio significantly higher (0.59 v. 0.024; P = 0.0000002) in those who were asymptomatic for at least 5 days after detection of the recrudescent parasitaemia than in those who were symptomatic at recrudescence. The disposition kinetics of the gametocytaemias in 18 primary infections--from nine children who failed CQ treatment and nine other children, matched for age and gender with the failures, who were CQ-treatment successes--were analysed. The results showed that the maximum gametocytaemia, time taken to reach the maximum gametocytaemia, the half-life of the gametocytaemia and the area inscribed by the plot of gametocytaemia against time were significantly higher, and the clearance of gametocytaemia significantly slower, in the children with primary infections that recrudesced. It therefore appears that continuing the use of CQ in areas where some parasites are resistant to the drug may confer survival and propagation advantages on the resistant parasites.

Animals↗

PubMed2003

Point mutations in the pfcrt and pfmdr-1 genes of Plasmodium falciparum and clinical response to chloroquine, among malaria patients from Nigeria.

Chloroquine (CQ) resistance in Plasmodium falciparum has been associated with specific point mutations in the pfcrt and pfmdr-1 genes. In the present study, 30 children aged 1-12 years, who were all suffering from acute, uncomplicated, P. falciparum malaria in Ibadan, Nigeria, were evaluated to assess the association between these mutations and clinical outcome following treatment with CQ. The parasites, in blood samples collected pre-treatment and, in those who failed treatment, on the day symptoms re-occurred post-treatment, were genotyped using the polymorphic MSP1, MSP2 and GLURP loci and PCR-RFLP. The results showed that, pre-treatment, all 30 patients had polyclonal infections, the mean numbers of P. falciparum clones detected per infection being 2.6 with MSP1, 4.2 with MSP2 and 2.8 with GLURP. The T76 allele of pfcrt and the Y86 allele of pfmdr-1 were found in 53% and 40%, respectively, of the pre-treatment samples from the 15 patients who failed CQ treatment, but the Y1246 mutation in pfmdr-1 was never detected. Although the parasites from the two patients with high-grade (RIII) resistance to CQ had both of these point mutations, the presence of the T76 allele of pfcrt or the Y86 allele of pfmdr-1 (considered individually) could not be used to predict treatment outcome. However, a high frequency of clonal multiplicity may confound attempts to associate the point mutations in pfcrt or pfmdr-1 with clinical response to CQ. It remains unclear whether the present results represent the characteristics of the predominant parasite populations in the study area. Further studies are needed before the strength of the association between the point mutations identified as markers of drug resistance and clinical outcome can be accurately evaluated, in this and other regions of intense transmission.

ATP-Binding Cassette Transporters↗

PubMed2002

Exposure to cyanide following a meal of cassava food.

Exposure to cyanide from gari, a popular cassava food in West Africa, is implicated in the causation of ataxic polyneuropathy and amblyopia, but this has been questioned because cyanide was not detected in gari in a study. This study was carried out to determine if gari is a source of exposure to cyanide. Gari (150 g) containing cyanohydrin, from which 128 micromol of cyanide ions could be released, was dissolved in 500 ml of cold water for each of the 12 healthy subjects to drink. Concentrations of cyanide in plasma and erythrocytes were determined at baseline and following the meal at 30 min, 1 h, hourly for 4 h and two hourly for 12 h. The mean concentrations of cyanide in the plasma were 6 micromol/l (95% CI 2-10) at baseline, 12 micromol/l (95% CI 6-17) at peak and 6 micromol/l (95% CI 2-10) on return to baseline. The mean amount of cyanide absorbed into the plasma was 13 micromol (S.D. 12), while the transit time of absorbed cyanide was 7.3 h (S.D. 2.1). This study shows that exposure to cyanide follows consumption of gari, but the amount of cyanide absorbed into the plasma from a single meal is small and unlikely to cause acute intoxication. The long transit time of absorbed cyanide in the plasma suggests that frequent intake of gari could cause cyanide to accumulate in the plasma.

Adult↗

PubMed2002

A randomized comparison of chloroquine, amodiaquine and their combination with pyrimethamine-sulfadoxine in the treatment of acute, uncomplicated, Plasmodium falciparum malaria in children.

The increasing resistance of Plasmodium falciparum to antimalarial monotherapy (MT) has created an urgent need for the evaluation of alternative effective, safe, cheap, readily available and affordable, combination treatments (CT) with antimalarial drugs. In the present study, the efficacies of chloroquine (CQ) or amodiaquine (AQ) in the oral treatment of acute, symptomatic, uncomplicated, Plasmodium falciparum malaria were compared with those of oral treatments with the combination of CQ or AQ with pyrimethamine-sulfadoxine (PS). The CQ and AQ were each given at a dose of 10 mg/kg.day for 3 days (days 0, 1 and 2), with or without PS given as a single dose (25 mg sulfadoxine/kg) at presentation (day 0). Overall, 303 children aged 0.5-10 years (74 given CQ, 82 AQ, 72 CQPS and 75 AQPS) were evaluated. The fever-clearance time (FCT) was significantly shorter in those treated with AQPS than in those treated with CQ or CQPS. The proportions of patients with complete clearance of their parasitaemias on days 1 and 2 were significantly larger and the parasite-clearance times (PCT) were all significantly shorter with the drug combinations than with their corresponding MT. For example, the mean (S.D.) PCT were 2.6 (0.8) days for CQ v. 2.1 (0.8) days for CQPS (P=0.0002), and 2.6 (0.7) days for AQ v. 2.1 (0.7) days for AQPS (P=0.00001). The cure 'rates' on days 14, 21 and 28 were also significantly higher with AQ, CQPS and AQPS than with CQ; those on day 28, for example, were 47.2%, 98.7%, 100% and 100% for CQ, AQ, CQPS and AQPS, respectively (P=0.000001). Gametocyte carriages on day 3 or on days 3, 7 and/or 14 combined were significantly lower in those treated with CQPS than in those given CQ; there was no gametocyte carriage in the CT groups on day 28. In the CQ group, eight of 13 children with gametocytaemia on day 3 had a response indicative of resistance. However, the five CQ-resistant infections that were re-treated with AQPS responded promptly, with a PCT significantly shorter than that during the initial treatment with CQ and with a cure 'rate' of 100% on day 28. Adverse reactions to treatment were similar on the first and subsequent days of treatment and were tolerable except for pruritus, which was significantly more common in children treated with CQ alone than in the other treatment groups. Haematological and biochemical parameters were not adversely affected by any treatment. The CQPS and AQPS combinations appear to be well tolerated and may be useful as alternatives to monotherapy with CQ or AQ as resistance to the single drugs develops.

Acute Disease↗

PubMed2002

The effects of chloroquine, amodiaquine and chloroquine plus chlorpheniramine on the disposition kinetics of the hepatomegaly associated with acute, uncomplicated, Plasmodium falciparum malaria in children.

The effects of chloroquine (CQ), amodiaquine (AQ) and CQ plus chlorpheniramine (a histamine H(1) antagonist that reverses CQ resistance in vitro and in vivo) on the disposition of the enlarged liver associated with acute, symptomatic, uncomplicated, Plasmodium falciparum malaria were evaluated. The subjects, 131 children aged 0.6-12 years who lived in an endemic area of Nigeria, were randomly allotted to the three treatment groups. The cumulative proportions of the children with complete resolution of their enlarged livers at 48, 96, 168 or 336 and 504 h after commencement of treatment were significantly higher in those treated with CQ plus chlorpheniramine (CQCP) than in the other two treatment groups (with P-values of 0.02, 0.001, 0.00000 and 0.00002, respectively). Among those with complete resolution, however, the times to resolution of 50% (HR50) or 90% (HR90) of the liver enlargement were similar in all the treatment groups. Complete resolution of the enlarged liver within 168 h was associated with a sensitive response to each treatment. Overall, in children with complete or partial resolution of their enlarged livers, the area produced by plotting liver size against time (i.e. the area under the curve of hepatomegaly v. time, or AUC(hp)) and the half-life of the hepatomegaly (t(1/2hp)) were significantly lower in the CQCP group than in the other two groups. The volume of blood completely cleared of the 'hepatic pathological processes' which led to the hepatomegaly (CL(Bhp)) and the fractional reduction of AUC(hp) at 48 and 96 h (i.e. AUC(hpFr148) and AUC(hpFr96)) were significantly higher in the CQCP group than in the other treatment groups. When the children with complete resolution of their liver enlargement were considered separately, t(1/2hp) (P=0.0008) but not AUC(hp) was found to be significantly lower, and AUC(hpFr196) (P=0.01) and CL(Bhl) (P=0.002) were found to be significantly higher in the CQCP group than in the other groups. Among the children with only partial resolution of their enlarged livers, the indices of resolution and the kinetic parameters of disposition were similar in all three groups. The data indicate that the addition of chlorpheniramine to chloroquine had a beneficial effect on both the early and late stages of the resolution of the liver enlargement associated with acute, symptomatic, uncomplicated, P. falciparum malaria.

Acute Disease↗

PubMed2001

Clinical characteristics and disposition kinetics of the hepatomegaly associated with acute, uncomplicated, Plasmodium falciparum malaria in children.

The clinical characteristics and the kinetics of the disposition of the hepatomegaly associated with acute, uncomplicated Plasmodium falciparum malaria were investigated in 162 children in an endemic area of Nigeria. Hepatomegaly was significantly more common in the younger than in the older children. Complete resolution occurred in 48% following antimalarial chemotherapy. In the children in whom hepatomegaly did not resolve, a reduction in liver size of < 17% by the time parasitaemia was cleared (usually on day 3) was associated with non-resolution of hepatomegaly by days 7 or 14 of follow-up. An increase in liver size to at least 125% of the baseline value by day 4 or 5 was associated with a lack of therapeutic response, providing the child involved was aged < 5 years. In the children who had complete clearance of parasitaemia and resolution of hepatomegaly, there was no significant relationship between the parasitaemia-derived conventional indices of therapeutic response [i.e. time to clearance of 50% (PC50) or 90% (PC90) of the parasitaemia, and the parasite-clearance time (PCT)] and the corresponding parameters derived from measurement of liver size [i.e. time for resolution of 50% (HR50) or 90% (HR90) of the hepatomegaly and the hepatomegaly-resolution time (HRT)] in the same patients. However, as the HR50:PC50, HR90:PC90 and HRT:PCT ratios were similar (range = 1.6-2.1), the liver parameters may have therapeutic application. In the children with drug-sensitive P. falciparum infections and in whom hepatomegaly completely resolved, the area produced by plotting liver size against time (i.e. the area under the curve of hepatomegaly v. time, or AUChp) increased in proportion to the liver size below the costal margin (P = 0.02, from analysis of variance), but there was no significant difference in the half-lives of hepatomegaly (t1/2hp) or in the ratios of liver size to AUChp, indicating that the kinetics of the resolution of hepatomegaly were linear in the range examined. Comparison of the kinetic indices of hepatomegaly and parasitaemia showed that, although the half-lives of parasitaemia and hepatomegaly and the corresponding clearance values were similar, there was no correlation between these parameters among those in whom hepatomegaly completely resolved and parasitaemia completely cleared. These results indicate that routine clinical measurement of the liver size in children with hepatomegaly during acute, uncomplicated, P. falciparum malaria may have some use in evaluating and monitoring the therapeutic responses of infections. The resolution of hepatomegaly, a reflection of pathological changes, lags behind clearance of parasitaemia in children with P. falciparum malaria, and supports the use of the liver 'rate' as a malariometric index for assessing the intensity of transmission in endemic areas.

Adolescent↗

PubMed2001

Randomized comparison of chloroquine and amodiaquine in the treatment of acute, uncomplicated, Plasmodium falciparum malaria in children.

The increasing resistance of Plasmodium falciparum to chloroquine (CQ) has created an urgent need for the evaluation of alternative, effective, safe, cheap, readily available and affordable antimalarial treatments. In the present study, the efficacy of amodiaquine (AQ) in the treatment of acute, symptomatic, uncomplicated, P. falciparum malaria was compared with that of CQ, each drug being given at 10 mg/kg per day for 3 days (days 0, 1 and 2). The 210 subjects (104 given AQ and 106 CQ) were Nigerian children aged 5 months-12 years. Fever-clearance times (FCT), parasite densities on days 1-4 and parasite-clearance times (PCT) were all significantly lower with AQ than with CQ. Mean (S.D.) PCT, for example, were 2.6 (0.8) days with AQ and 3.0 (1.0) days with CQ (P = 0.001). The cure rates obtained on days 14, 21 and 28 - 98.1% v. 79.3% (P =0.000), 97.1% v. 64.2% (P = 0.00001) and 95.2% v. 58.5% (P = 0.0000000) with AQ and CQ, respectively - were all also significantly higher with AQ. All but two of the 20 subjects who were considered CQ-treatment failures by day 14 (i.e. two RIII, two RII and 16 RI) responded to subsequent treatment with AQ, with PCT (but not FCT) significantly shorter than during their initial treatment with CQ. In siblings in whom there was clustering of infections, the cure rates were 100% with AQ (N =12) and 63.6% with CQ (N = 11; P = 0.03). Adverse reactions to CQ and AQ were similar and tolerable: pruritus in 10 and 11 children in the AQ and CQ groups, respectively, and gastro-intestinal disturbances which occurred in three children from each group. Haematological parameters were not adversely affected by either drug. At least in the setting of the present study, AQ appears more effective than CQ, effective against CQ-resistant infections, and well tolerated by children with acute, uncomplicated, P. falciparum malaria. It may therefore be useful as an alternative to CQ in areas of CQ resistance.

Age Factors↗

PubMed2001

Comparative clinical characteristics and responses to oral 4-aminoquinoline therapy of malarious children who did and did not develop 4-aminoquinoline-induced pruritus.

The clinical characteristics and the responses to oral 4-aminoquinoline therapy of 150 malarious children presenting consecutively were investigated in an endemic area. At presentation, the 75 children who subsequently developed pruritus were significantly older and had significantly higher body temperatures than the 75 children who did not develop pruritus. There were no other significant differences in clinical presentation between the two groups. In children with pruritus, there was no correlation between age, weight, presenting body temperature, duration of illness or presenting peripheral parasite density and duration of pruritus. Responses to oral antimalarial drugs were similar in both groups. There was no correlation between indices of therapeutic response and the duration of pruritus. Analysis of the disposition kinetics of parasitaemia and of the hepatomegaly associated with malaria, using a non-compartmental model similar to that used in characterizing drug disposition, showed that the two groups had similar half-lives of parasitaemia (t(1/2 pd)), volumes of blood completely cleared of parasites per unit time (CL(Bpd)) and ratios of parasite-clearance time to t(1/2 pd), and similar values for the corresponding parameters derived from hepatomegaly resolution. There was no apparent relationship between the indices of parasite- or hepatomegaly-disposition kinetics and the duration of pruritus.

Acute Disease↗

PubMed2000

Gastrointestinal manifestations of acute falciparum malaria in children.

The gastrointestinal manifestations of acute symptomatic uncomplicated falciparum malaria were studied in 184 consecutive children aged from 6 months to 15 years. Vomiting was the most common and epigastralgia the least common presenting symptom. Peripheral parasite density was higher in children who were vomiting than in those who were not. There was no relationship between the density of peripheral parasitaemia and the duration of gastrointestinal symptoms at presentation. All gastrointestinal symptoms cleared within 3 days after instituting antimalarial therapy.

Acute Disease↗