ABSTRACT
CONTEXT: The benefit of malaria prophylaxis in pregnancy is threatened by emergence of Plasmodium falciparum resistance to antimalarial agents for chemoprophylaxis and treatment. AIM: This study aimed to compare the effectiveness of azithromycin (AZ) with sulphadoxine-pyrimethamine (SP) for malaria prevention. SETTINGS AND DESIGN: A prospective comparative study of antenatal clinic attendees at the University College Hospital, Ibadan, Nigeria. Participants were randomised to receive SP or AZ. SUBJECTS AND METHODS: The subjects were antenatal attendees and Samples for malaria parasitaemia were collected and repeated at follow-up visits; maternal peripheral blood film, placental and cord blood samples were collected at delivery. STATISTICAL ANALYSIS USED: Chi-square test and t-test in a per-protocol analysis. RESULTS: Of 200 participants (100 in each group), 166 (83.0%) completed the study: 86 (86.0%) of SP and 80 (80.0%) of AZ groups, respectively (P = 0.26). Four (4.7%) participants who had SP compared to five (6.2%) in AZ group developed malaria at mean gestational ages of 30.3 ± 1.56 and 33.0 ± 8.6, respectively (P = 0.56). Positive peripheral, placental and cord blood parasitaemia were found in ≤2% of the participants. Drug tolerability and foetal outcomes were comparable for both groups. CONCLUSION: AZ was comparable to SP for prevention of malaria in pregnancy and may be used in patients who do not tolerate SP.
Subject(s)
Azithromycin/therapeutic use , Malaria/prevention & control , Pregnancy Complications, Infectious/prevention & control , Pyrimethamine/therapeutic use , Sulfadoxine/therapeutic use , Adult , Drug Combinations , Female , Humans , Nigeria , Pregnancy , Prospective Studies , Young AdultABSTRACT
OBJECTIVES: Artesunate plus amodiaquine is used for malaria treatment in regions with overlapping HIV endemicity. Co-administration of artesunate/amodiaquine with antiretroviral therapy (ART) may result in drug-drug interactions, but minimal data exist. This study evaluated the impact of nevirapine-based ART, containing a backbone of zidovudine and lamivudine, on the disposition of amodiaquine and its active metabolite, desethylamodiaquine (DEAQ). METHODS: This was an open-label, parallel-group pharmacokinetic comparison between HIV-infected, adult subjects receiving steady-state nevirapine-based ART (n = 10) and ART-naive subjects (control group, n = 11). All subjects received a loose formulation of artesunate/amodiaquine (200/600 mg) daily for 3 days, with serial pharmacokinetic sampling over 96 h following the final dose of artesunate/amodiaquine. Amodiaquine and DEAQ were quantified using a validated HPLC method with UV detection. Pharmacokinetic parameters were determined using standard non-compartmental methods. RESULTS: Exposures to both amodiaquine and DEAQ were significantly lower in the nevirapine-based ART group compared with the control group (amodiaquine AUC0â24 145 versus 204 ng·h/mL, P = 0.02; DEAQ AUC0â96 14,571 versus 21,648 ng·h/mL, P < 0.01). The AUCDEAQ/AUC(amodiaquine) ratio was not different between groups (ART group 116 versus control group 102, P = 0.67). CONCLUSIONS: Subjects on nevirapine-based ART had lower exposure to both amodiaquine and DEAQ (28.9% and 32.7%, respectively). Consequently, this may negatively impact the effectiveness of artesunate/amodiaquine in HIV-infected individuals on this ART combination.
Subject(s)
Amodiaquine/pharmacokinetics , Amodiaquine/therapeutic use , Anti-Retroviral Agents/therapeutic use , Antimalarials/pharmacokinetics , Antimalarials/therapeutic use , Drug Interactions , Nevirapine/therapeutic use , Adolescent , Adult , Antiretroviral Therapy, Highly Active/methods , Artemisinins/pharmacokinetics , Artemisinins/therapeutic use , Artesunate , Chromatography, High Pressure Liquid , Female , HIV Infections/complications , HIV Infections/drug therapy , Humans , Lamivudine/therapeutic use , Malaria/complications , Malaria/drug therapy , Male , Middle Aged , Nigeria , Plasma/chemistry , Young Adult , Zidovudine/therapeutic useSubject(s)
Acquired Immunodeficiency Syndrome , Malaria , Child , HIV Infections , Humans , Reverse Transcriptase Inhibitors , UgandaABSTRACT
BACKGROUND: Adverse drug reactions (ADRs) contribute to ill-health or life-threatening outcomes of therapy during management of infectious diseases. The exposure to anti-malarial and use of mobile phone technology to report ADRs following drug exposures were investigated in Sagamu--a peri-urban community in Southwest Nigeria. METHODS: Purchase of medicines was actively monitored for 28 days in three Community Pharmacies (CP) and four Patent and Proprietary Medicine Stores (PPMS) in the community. Information on experience of ADRs was obtained by telephone from 100 volunteers who purchased anti-malarials during the 28-day period. RESULTS AND DISCUSSION: A total of 12,093 purchases were recorded during the period. Antibiotics, analgesics, vitamins and anti-malarials were the most frequently purchased medicines. A total of 1,500 complete courses of anti-malarials were purchased (12.4% of total purchases); of this number, purchases of sulphadoxine-pyrimethamine (SP) and chloroquine (CQ) were highest (39.3 and 25.2% respectively). Other anti-malarials purchased were artesunate monotherapy (AS)--16.1%, artemether-lumefantrine (AL) 10.0%, amodiaquine (AQ)--6.6%, quinine (QNN)--1.9%, halofantrine (HF)--0.2% and proguanil (PR)--0.2%. CQ was the cheapest (USD 0.3) and halofantrine the most expensive (USD 7.7). AL was 15.6 times ($4.68) more expensive than CQ. The response to mobile phone monitoring of ADRs was 57% in the first 24 hours (day 1) after purchase and decreased to 33% by day 4. Participants in this monitoring exercise were mostly with low level of education (54%). CONCLUSION: The findings from this study indicate that ineffective anti-malaria medicines including monotherapies remain widely available and are frequently purchased in the study area. Cost may be a factor in the continued use of ineffective monotherapies. Availability of a toll-free telephone line may facilitate pharmacovigilance and follow up of response to medicines in a resource-poor setting.
Subject(s)
Adverse Drug Reaction Reporting Systems , Antimalarials/adverse effects , Antimalarials/therapeutic use , Cell Phone , Drug Utilization/statistics & numerical data , Humans , NigeriaABSTRACT
BACKGROUND AND PURPOSE: This study was based on the hypothesis that suboptimal immune response and low serum immunoglobulin G (IgG) may predispose to age-related hearing loss (ARHL), and the objective was to determine the serum levels of IgG and hearing thresholds of apparently healthy elderly subjects and assess their correlation. METHOD: This prospective study involved 126 participants ≥ 60 years old who were found to be free of any medical conditions. Pure-tone averages for both the speech (500-2,000 Hz) and high frequencies (3,000-8,000 Hz) and serum IgG levels were determined. Using 30 dB as cut-off for hearing loss, the correlation with serum IgG was assessed. RESULTS: There were 59 males and 67 females with a mean age ± SD of 67.0 ± 2.7 years. Speech frequency hearing loss was seen in 30.2%, while high-frequency hearing loss accounted for 74.6%. In the speech frequencies, the mean ± SD of serum IgG among subjects with normal hearing was 11.3 ± 3.9 g/l, while among those with hearing loss it was 8.3 ± 3.3 g/l (p = 0.01). In the high frequencies, the mean ± SD values of serum IgG among the subjects with normal hearing was 11.1 ± 2.3 g/l, while among those with hearing loss it was 8.7 ± 1.9 g/l (p = 0.01). CONCLUSION: Low serum IgG may be a contributory factor to the development of ARHL among the elderly. However, a longitudinal study involving intervention with immunoglobulin supplementation may further confirm this role.
Subject(s)
Auditory Threshold/physiology , Immunoglobulin G/blood , Presbycusis/immunology , Presbycusis/physiopathology , Aged , Audiometry, Pure-Tone , Biomarkers/blood , Female , Humans , Linear Models , Male , Presbycusis/diagnosis , Prospective StudiesABSTRACT
The study re-visited malaria burden and pre-hospital medication among malarious subjects in Maiduguri, Northeast Nigeria. A total of 1,657 febrile subjects were screened for malaria by microscopy at two health institutions. Giemsa-stained blood smears were examined for parasitaemia and gametocytaemia; and parasite density (PD), gametocyte density (GD) and gametocyte sex ratio (GSR) were determined. The mean age of the 1,657 subjects was 27.5 ± 12.2 years and 7.8% (130/1,657) of the subjects aged <5 years. Sex distribution showed 47.0% (778/1,657) males and 53.0% (879/1657) females. Parasitaemia was recorded in 22.6% (375/1,657) with geometric mean PD of 8,925 (320-275,000) parasites/µl blood. The prevalence of parasitaemia was highest among subjects <5 years (χ2 = 401.1; df = 5; p < 0.0001) and in August and September (χ2 = 406.9; df = 11; p < 0.0001). Prevalence of gametocytaemia was 12.8% (48/375) with geometric mean GD of 109 (8-464) gametocytes/µl blood. The prevalence was higher in dry (16.5%, 29/176) than wet (9.5%, 19/199) months (χ2 = 4.0; df = 1; p = 0.045). The weighted mean GSR was 0.4 ± 0.1 with highest value in March (0.7 ± 0.2). Pre-hospital medication was recorded in 74.1% (278/375) of the subjects with parasitaemia. Analgesics (51.7%; 194/375) accounted for the highest proportion of drug consumed while 9.3% (35/375) of the subjects took antimalarial drugs. Malaria persisted in Maiduguri especially among subjects <5 years during wet months and pre-hospital medication is a common practice. These findings could serve as guide for policy decision that could contribute to effective treatment and control of malaria in the region.
ABSTRACT
The activities of artemether-lumefantrine and amodiaquine-sulfalene-pyrimethamine against sexual-stage parasites were evaluated in 42 of 181 Nigerian children with uncomplicated Plasmodium falciparum malaria who had gametocytaemia before, during or after treatment with the two combination therapies. The children were randomized to the standard dose regimens. Clinical recovery from illness occurred in all children who carried gametocytes. Gametocytaemia was detected in 20 patients (11%) before treatment and in another 22 patients (12.2%) after treatment. Gametocyte carriage rates were similar in both combination treatment groups, but the area under the curve of gametocytaemia plotted against time was 8-fold higher in the amodiaquine-sulfalene-pyrimethamine-treated than in the artemether-lumefantrine-treated children. The pretreatment gametocyte sex ratio was female biased in both treatment groups. During follow-up, there was a short-lived but significant increase in the gametocyte sex ratio in children treated with amodiaquine-sulfalene-pyrimethamine but not in those treated with artemether-lumefantrine. These results indicate that both combination therapies had moderate effects on gametocyte carriage, but artemether-lumefantrine may be more potent at reducing transmissibility in P. falciparum malaria by exerting greater effects on post-treatment gametocyte density and gametocyte sex ratio.
Subject(s)
Antimalarials/therapeutic use , Malaria, Falciparum/drug therapy , Malaria, Falciparum/parasitology , Plasmodium falciparum/drug effects , Plasmodium falciparum/growth & development , Amodiaquine/therapeutic use , Animals , Artemether , Artemisinins/therapeutic use , Child , Child, Preschool , Drug Therapy, Combination , Ethanolamines/therapeutic use , Female , Fluorenes/therapeutic use , Humans , Lumefantrine , Male , Pyrimethamine/therapeutic use , Sulfalene/therapeutic use , Survival Rate , Treatment OutcomeABSTRACT
The treatment efficacy and effects of artemether-lumefantrine (AL) and amodiaquine-sulfalene-pyrimethamine (ASP) on gametocyte carriage were evaluated in 181 children < or = 10 years of age with uncomplicated Plasmodium falciparum malaria randomized to receive either drug combination. All children recovered clinically. Fever clearance times were similar. The rate of P. falciparum reappearance (recrudescence or re-infection) between two and six weeks after the start of therapy was significantly higher in AL-treated children (P = 0.01). Parasite clearance was significantly faster in children treated with AL (mean +/- SD = 1.7 +/- 0.6 days, 95% confidence interval = 1.58 - 1.83, P = 0.0001) but the polymerase chain reaction-corrected cure rate (90 of 91 versus 84 of 90) and the rate of resolution of malaria-related anemia two weeks after treatment began (45 of 50 versus 33 of 46) were higher in children treated with ASP. Gametocyte carriage rates were similar. Both regimens were well tolerated. Artemether-lumefantrine clears parasitemia more rapidly than ASP but both combinations are effective in treatment of uncomplicated P. falciparum malaria in Nigerian children.
Subject(s)
Amodiaquine/therapeutic use , Antimalarials/therapeutic use , Artemisinins/therapeutic use , Ethanolamines/therapeutic use , Fluorenes/therapeutic use , Malaria, Falciparum/drug therapy , Plasmodium falciparum/growth & development , Pyrimethamine/therapeutic use , Sulfalene/therapeutic use , Animals , Artemether, Lumefantrine Drug Combination , Child , Child, Preschool , Drug Combinations , Drug Therapy, Combination , Female , Humans , Infant , Malaria, Falciparum/blood , Malaria, Falciparum/parasitology , Male , Nigeria , Parasitemia/drug therapy , Parasitemia/parasitologyABSTRACT
Background: Widespread dr ug-resistant Plasmodium falciparum strains have challenged the pivotal role played by 4-aminoquinolines, including chloroquine (CQ), which has been delisted for the treatment of malaria in most parts of the world. This study assessed the in vitro sensitivity of P. falciparum clinical isolates (PfCIs) to amodiaquine (AQ) and CQ in Northeast Nigeria. Materials and methods: PfCIs were collected from subjects with uncomplicated P. falciparum malaria in Azare, Bauchi State and Maiduguri, Borno State following an informed consent. The in vitro sensitivity was assessed by micro-test (MarkIII) method and the IC50 of AQ and CQ was determined using HN-NonLin Version VI.1 software. The reference standard cut-off values for in vitro AQ and CQ resistance of 80 and 160 nmol/l, respectively, were used. Isolates that were inhibited by lower AQ and CQ concentrations were referred to as sensitive. Results: Valid in vitro assay r esults were obtained for 88.9% (80/90) of the PfCIs; Azare had 93.3% (28/30) and Maiduguri had 86.7% (52/60) [χ2 = 0.35; df = 1; p = 0.486]. The geometric mean (GM) IC50 of AQ and CQ were 24.2 nmol/l (95% CI, 10.5 - 49.6 nmol/l) and 39.5 nmol/l (95% CI, 34.5 - 49.6 nmol/l), respectively. The AQ (p = 0.922) and CQ (p = 0.085) GM IC50 were similar between Azare and Maiduguri PfCIs. Only one isolate showed in vitro resistance to AQ giving a sensitivity of 98.8% (79/80) while 17 PfCIs showed in vitro resistance to CQ giving a sensitivity of 78.8% (63/80). The CQ sensitivity was similar between Azare (67.9%; 19/28) and Maiduguri (84.6%; 44/52) PfCIs (χ2 = 3.05; df = 1; p = 0.081). Conclusions: The findings may suggest that the AQ in vitro sensitivity remains high and the isolates in Northeast Nigeria may appear more sensitive to CQ than isolates from other parts. These findings may affect malaria treatment and control policy in Nigeria.
ABSTRACT
INTRODUCTION: Malaria remains a public health challenge, especially in sub-Saharan Africa where asymptomatic malaria is not uncommon. In the present study, the prevalence of asymptomatic falciparum malaria was investigated in almajirai, and the genetic polymorphisms of chloroquine (CQ) resistance biomarkers were assessed. METHODOLOGY: A total of 440 apparently healthy almajirai between 3 and 12 years of age were randomly enrolled in Maiduguri, northeast Nigeria, between July and December 2010. Parasitemia and gametocytemia were assessed by light microscopy, and polymorphisms of Pfcrt K76T and Pfmdr1 N86Y were detected by nested polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. RESULTS: The mean age of the subjects was 8.3 ± 4.5 years, with subjects ≤ 5 years accounting for 10.7% (47/440) of the population. Prevalence of asymptomatic falciparum parasitemia and gametocytemia were 12.7% (56/440) and 8.6% (38/440), respectively. Geometric mean parasite density (GMPD) was 240 (160-630) parasites/µL, while geometric mean gametocyte density (GMGD) was 53 (24-96) gametocytes/µL. The GMPD was higher among subjects ≤ 5 years of age (p = 0.027). Pfcrt 76T was detected in 5.4% (3/56) of the isolates, and no isolates harbored Pfmdr1 86Y mutant. CONCLUSIONS: The study reveals asymptomatic falciparum malaria in almajirai and low levels of Pfcrt 76T and Pfmdr1 86Y alleles. These findings could hinder malaria control measures, and hence almajirai should be incorporated into malaria control programs.
Subject(s)
Asymptomatic Diseases , Malaria, Falciparum/parasitology , Membrane Transport Proteins/genetics , Multidrug Resistance-Associated Proteins/genetics , Plasmodium falciparum/genetics , Polymorphism, Genetic , Protozoan Proteins/genetics , Child , Child, Preschool , Cross-Sectional Studies , Drug Resistance , Female , Genotype , Humans , Male , Mutation, Missense , Nigeria , Plasmodium falciparum/isolation & purification , Polymerase Chain Reaction , Polymorphism, Restriction Fragment LengthABSTRACT
Background. Nevirapine- (NVP-) based antiretroviral therapy (ART) and artesunate-amodiaquine are frequently coprescribed in areas of HIV and malaria endemicity. We explored the impact of this practice on artesunate and dihydroartemisinin pharmacokinetics. Methods. We conducted a parallel-group pharmacokinetic comparison between HIV-infected patients receiving NVP-based ART (n = 10) and ART-naive controls (n = 11). Artesunate-amodiaquine 200/600 mg was given daily for three days. Measurement of drug concentrations occurred between 0 and 96 hours after the final dose. Pharmacokinetic parameters were determined using noncompartmental analysis. Results. Comparing the NVP group to controls, clearance of artesunate was reduced 50% (1950 versus 2995 L/h; P = 0.03), resulting in a 45% increase in the AUC(0-96) (105 versus 69 ug(∗)hr/L; P = 0.02). The half-life of dihydroartemisinin was shorter in the NVP group (1.6 versuss 3.2 h; P = 0.004), but other dihydroartemisinin pharmacokinetic parameters were unchanged. A lower conversion of artesunate to dihydroartemisinin was observed in the NVP group (dihydroartemisinin: artesunate AUC(0-96) = 5.6 versuss 8.5 in NVP and control groups, respectively, P = 0.008). Conclusion. Although NVP-containing ART impacted some pharmacokinetic parameters of artesunate and dihydroartemisinin, overall exposure was similar or better in the NVP group.
ABSTRACT
CONCLUSION: Low plasma melatonin is significant in the development of high frequency hearing loss (HL) among the elderly. OBJECTIVE: To determine the correlation between hearing threshold and the plasma melatonin and ascorbic acid (vitamin C). METHODS: This was a cross-sectional study involving 126 apparently healthy elderly subjects, 59 males and 67 females, aged >60 years. Subjects underwent pure tone audiometry and plasma melatonin and vitamin C were assayed using high-performance liquid chromatography. RESULTS: The mean ± SD of plasma melatonin among the subjects with normal hearing (NH) (0-30 dB) and those with HL in the speech frequencies was 18.3 ± 3.6 µg/L and 16.4 ± 4.7 µg/L, respectively. In the high frequencies the values were 17.7 ± 6.2 µg/L and 13.1 ± 6.4 µg/L for NH and HL, respectively. For vitamin C, the mean ± SD among subjects with NH and those with HL in the speech frequencies were 1.2 ± 0.2 µg/L and 1.0 ± 0.1 µg/L, respectively. In the high frequencies, the values were 1.0 ± 0.2 µg/L and 0.9 ± 0.3 µg/L for NH and HL, respectively. Among subjects with high frequency HL, Spearman's correlation revealed significant correlation between increasing hearing threshold and melatonin (correlation coefficient = -0.30, p = 0.01), but not for vitamin C (correlation coefficient = -0.12, p = 0.22). Linear regression, adjusting for age, still revealed significant correlation between the melatonin (correlation coefficient = -0.03, p = 0.00) and hearing threshold in the high frequencies.
Subject(s)
Aging/blood , Ascorbic Acid/blood , Hearing Loss, High-Frequency/blood , Melatonin/blood , Presbycusis/blood , Aged , Aged, 80 and over , Auditory Threshold , Cross-Sectional Studies , Female , Free Radical Scavengers/blood , Humans , Male , Middle AgedABSTRACT
Malaria and HIV/AIDS remain diseases of public health importance in sub-Saharan Africa as both infections are responsible for high morbidity and mortality rates. Malaria disproportionately affects young children and pregnant women and HIV/AIDS affects mostly adolescents and young adults. The widespread nature of both infections has led to co-infection in many residents of sub-Saharan African countries. HIV-infected individuals are more susceptible to frequent attacks of malaria thus requiring combination antiretroviral therapy and antimalarial drugs. There is, in general, lack of information on the influence of the chronic use of antiretroviral medicines on the outcome of repeated treatment of malaria. Pharmacokinetic drug interactions with HIV medications that lead to sub-therapeutic concentrations of antimalarial drugs will promote drug resistance in patients with malaria. The objective of this review is to summarize the available information on the adverse drug reactions and drug interactions of commonly used antimalarial drugs in the context of combination antiretroviral therapy and propose a clinical pharmacology research plan to develop dosing recommendations for patients with malaria and HIV co-infection.
Subject(s)
Anti-Retroviral Agents/therapeutic use , Antimalarials/therapeutic use , HIV Infections/complications , Malaria/drug therapy , Malaria/prevention & control , Africa South of the Sahara , Anti-Retroviral Agents/adverse effects , Anti-Retroviral Agents/pharmacokinetics , Antimalarials/adverse effects , Antimalarials/pharmacokinetics , Antiretroviral Therapy, Highly Active/adverse effects , Biomedical Research/trends , Biotransformation , Drug Interactions , Drug Resistance , Humans , Malaria/complicationsABSTRACT
OBJECTIVE: Determine the correlation between the hearing threshold and the serum levels of vitamin B12 (cobalamin) and folic acid among elderly subjects (> 60 years) with age-related hearing loss (ARHL). STUDY DESIGN: Cross-sectional. SETTING: Community. SUBJECTS AND METHODS: Subjects included elderly who were found apparently healthy following repeated examination by physicians. The pure tone average (PTA) for the speech and high frequencies, and the serum folate and cobalamin were determined and the correlation found. RESULTS: The mean ± SD values of serum folate among the subjects with normal PTA in the speech frequencies (0-30 dB) was 412.3 nmol/L ± 17.6 nmol/L, while among those with hearing loss (HL), it was 279.1 nmol/L ± 17.2 nmol/L (P = 0.01). In the high frequencies, the mean ± SD values among the subjects with normal PTA was 426.3 nmol/L ± 17.6 nmol/L, while among those with HL, it was 279.14 nmol/L ± 171.2 nmol/L. The serum cobalamin among the subjects with normal PTA within the speech frequencies was 49.7 pmol/L ± 9.4 pmol/L, while among those with speech-frequency HL, it was 42.6 pmol/L ± 10.2 pmol/L. However, for high frequencies, the mean ± SD values among the subjects with normal PTA was 47.4 pmol/L ± 7.3 pmol/L, while among those with HL, it was 41.3 pmol/L ± 9.2 pmol/L. Spearman's correlation revealed that low folate (correlation coefficient = -0.27, P = 0.01) and cyanocobalamin (correlation coefficient = -0.35, P = 0.02) were significantly associated with increasing hearing threshold in the high frequencies. After adjusting for age, serum folate (correlation coefficient = -0.01, P = 0.01) was significant, while vitamin B12 (correlation coefficient = -0.01, P = 0.74) was not. CONCLUSION: Serum folate was significantly lower among elderly with ARHL. Trials on nutritional supplementation may substantiate the role of serum folate in ARHL.
Subject(s)
Folic Acid Deficiency/complications , Folic Acid/blood , Hearing Loss/blood , Vitamin B 12 Deficiency/complications , Vitamin B 12/blood , Age Factors , Aged , Aged, 80 and over , Audiometry, Pure-Tone , Cross-Sectional Studies , Female , Folic Acid Deficiency/blood , Hearing Loss/complications , Hearing Loss/diagnosis , Humans , Male , Middle Aged , Vitamin B 12 Deficiency/bloodABSTRACT
The activities of artesunate-cotrimoxazole and artesunate-amodiaquine combinations against asexual-and sexual-stage parasites were evaluated in 182 Nigerian children with uncomplicated Plasmodium falciparum malaria. One hundred and twenty-one children received artesunate-cotrimoxazole and 61 received artesunate-amodiaquine and all were followed up for 28 days. Clinical recovery from illness occurred in all children. There was no significant difference in fever clearance time (P = 0.35). Both treatment groups achieved a parasite clearance time of less than 2 days (1.84 +/- 0.66 days and 1.31 +/- 0.48 days); gametocyte carriage rates were comparable in the two treatment groups prior to and following treatment; both treatments appeared to reduce gametocyte carriage. The pretreatment gametocyte sex ratio, which was female-biased, was maintained throughout the period of follow up in both treatment groups. Reduction of gametocyte carriage by these two treatment regimens may reduce transmissibility in P. falciparum malaria, and this reduction is presumed to be related to the accelerated clearance of the asexual forms of the parasite.
Subject(s)
Amodiaquine/therapeutic use , Antimalarials/therapeutic use , Artemisinins/therapeutic use , Malaria, Falciparum/drug therapy , Plasmodium falciparum/drug effects , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use , Animals , Artesunate , Child , Child, Preschool , Drug Combinations , Drug Therapy, Combination , Female , Humans , Infant , Life Cycle Stages/drug effects , Male , Nigeria , Plasmodium falciparum/growth & development , Treatment OutcomeABSTRACT
The activities of amodiaquine, artesunate, and artesunate-amodiaquine against asexual- and sexual-stage parasites were evaluated in 360 Nigerian children with uncomplicated Plasmodium falciparum malaria randomized to the standard dose regimens of the three drugs/combination. Clinical recovery from illness occurred in all children. There were no significant differences in fever clearance times. Patients treated with artesunate or artesunate-amodiaquine had significantly shorter parasite clearance times (1.4 +/- 0.5 days or 1.4 +/- 0.6 days versus 3.2 +/- 2.3 days, P = 0.0001) and lower gametocyte carriage rates (3.3 or 1.7% versus 11.7%, P = 0.001) than those treated with amodiaquine alone. Gametocytemia was detected in 62 patients (11.7% before treatment and 5.6% after treatment). The pretreatment gametocyte sex ratio, which was female biased, increased significantly during the course of treatment with amodiaquine but not with artesunate and artesunate-amodiaquine. These results suggest that artesunate and artesunate-amodiaquine reduce gametocyte carriage and may reduce transmissibility in P. falciparum malaria by accelerating asexual clearance and influencing gametocyte sex ratio.
Subject(s)
Amodiaquine/therapeutic use , Antimalarials/therapeutic use , Artemisinins/therapeutic use , Malaria, Falciparum/drug therapy , Sesquiterpenes/therapeutic use , Adolescent , Amodiaquine/administration & dosage , Animals , Artemisinins/administration & dosage , Artesunate , Child , Child, Preschool , Drug Therapy, Combination , Female , Humans , Malaria, Falciparum/parasitology , Male , Plasmodium falciparum/drug effects , Sesquiterpenes/administration & dosage , Sex RatioABSTRACT
The impacts of acute falciparum malaria on body weight and the host and parasite factors predictive of change in body weight were characterized in 465 prospectively studied children in an endemic area of southwest Nigeria. Pre-treatment weights were significantly lower than the 14 to 28-day post-treatment weights (P = 0.0001). In 187 children, fractional fall in body weight (FFBW) exceeded 4.9%. FFBW correlated negatively with age and body weight (P = 0.014 and 0.0001, respectively), but not with enrollment parasitaemia. In a multiple regression model, an age < or =5 years (AOR = 2.03, 95% CI 1.2-3.2, P = 0.003), a hematocrit < or =29% (AOR = 1.6, 95% CI 1.0-2.3, P = 0.037), and a body weight < or =9.6 kg (AOR = 5.4, 95% CI 1.7-20, P = 0.003) were independent predictors of FFBW > or =5% at presentation. Children who, after initial clearance, had recurrence of their parasitaemia within 28 days had a significantly higher propensity not to gain weight than children who were aparasitaemic after treatment (log-rank statistic 6.76, df = 1, P = 0.009). These results indicate that acute malaria contribute to sub-optimal growth in young children and may have implications for malaria control efforts in sub-Saharan Africa.
Subject(s)
Body Weight , Malaria, Falciparum/physiopathology , Adolescent , Age Factors , Child , Child, Preschool , Endemic Diseases , Female , Hematocrit , Humans , Infant , Malaria, Falciparum/epidemiology , Male , Nigeria , Parasitemia , Prospective Studies , Regression AnalysisABSTRACT
Resistance in Plasmodium falciparum to amodiaquine (AQ) can be reversed in vitro with with antihistaminic and tricyclic antidepressant compounds, but its significance in vivo is unclear. The present report presents the enhancement of the antimalarial efficacy of AQ by chlorpheniramine, an H1 receptor antagonist that reverses chloroquine (CQ) resistance in vitro and enhances its efficacy in vivo, in five children who failed CQ and/or AQ treatment, and who were subsequently retreated and cured with a combination of AQ plus CP, despite the fact that parasites infecting the children harboured mutant pfcrtT76 and pfmdr1Y86 alleles associated with AQ resistance. This suggests a potential clinical application of the reversal phenomenon.
Subject(s)
Amodiaquine/administration & dosage , Antimalarials/administration & dosage , Chloroquine/administration & dosage , Chlorpheniramine/administration & dosage , Histamine H1 Antagonists/administration & dosage , Malaria, Falciparum/drug therapy , Adolescent , Animals , Child , Child, Preschool , Drug Synergism , Drug Therapy, Combination , Humans , Infant , Malaria, Falciparum/parasitology , Membrane Transport Proteins/genetics , Plasmodium falciparum/drug effects , Plasmodium falciparum/genetics , Protozoan Proteins/geneticsABSTRACT
Resistance in Plasmodium falciparum to amodiaquine (AQ) can be reversed in vitro with with antihistaminic and tricyclic antidepressant compounds, but its significance in vivo is unclear. The present report presents the enhancement of the antimalarial efficacy of AQ by chlorpheniramine, an H1 receptor antagonist that reverses chloroquine (CQ) resistance in vitro and enhances its efficacy in vivo, in five children who failed CQ and/or AQ treatment, and who were subsequently retreated and cured with a combination of AQ plus CP, despite the fact that parasites infecting the children harboured mutant pfcrtT76 and pfmdr1Y86 alleles associated with AQ resistance. This suggests a potential clinical appliation of the reversal phenomenon.