A M J Oduola

Publications (30)71.34 Total impact

• Article: In vitro amodiaquine resistance and its association with mutations in pfcrt and pfmdr1 genes of Plasmodium falciparum isolates from Nigeria.

  O A Folarin, C Bustamante, G O Gbotosho, A Sowunmi, M G Zalis, A M J Oduola, C T Happi
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  ABSTRACT: Amodiaquine (AQ) is currently being used as a partner drug in combination with artesunate for treatment of uncomplicated malaria in most endemic countries of Africa. In the absence of molecular markers of artemisinin resistance, molecular markers of resistance to AQ may be useful for monitoring the development and spread of parasites resistance to Artesunate-Amodiaquine combination. This study was designed to assess the potential role of polymorphisms on pfcrt and pfmdr1 genes and parasite in vitro susceptibility for epidemiological surveillance of amodiaquine resistance in Plasmodium falciparum. The modified schizont inhibition assay was used to determine in vitro susceptibility profiles of 98 patients' isolates of P. falciparum to amodiaquine. Polymorphisms on parasites pfcrt and pfmdr1 genes were determined with nested PCR followed by sequencing. The geometric mean (GM) of AQ 50% inhibitory concentration (IC-50) in the 97 P. falciparum isolates was 20.48 nM (95% CI 16.53-25.36 nM). Based on the cut-off value for AQ in vitro susceptibility, 87% (84) of the P. falciparum isolates were sensitive to AQ (GM IC-50=16.32 nM; 95%CI 13.3-20.04 nM) while 13% were resistant to AQ in vitro (GM IC-50=88.73nM; 95%CI 69.67-113.0nM). Molecular analysis showed presence of mutant CVIET pfcrt haplotype, mutant pfmdr1Tyr86 allele and the double mutant CVIET pfcrt haplotype+pfmdr1Tyr86 in 72%, 49% and 35%, respectively. The GM IC-50 of isolates harboring the wild-type pfcrt CVMNK haplotype+pfmdr1Asn86 allele (3.93nM; 95%CI 1.82-8.46 nM) was significantly lower (p=0.001) than those isolates harboring the double mutant pfcrt CVIET haplotype+pfmdr1Tyr86 allele (50.40 nM; 95%CI 40.17-63.24 nM). Results from this study suggest that polymorphisms in pfcrt and pfmdr1 genes are important for AQ resistance and therefore may be useful for epidemiological surveillance of P. falciparum resistance to AQ.
  Acta tropica 09/2011; 120(3):224-30. · 2.22 Impact Factor
• Article: Comparison of the incision and aspiration methods for the diagnosis of placental malaria infection

  A. Sowunmi, A. E. J. Abohweyere, J. A. Akindele, A. O. Ilesanmi, C. O. Falade, A. M. J. Oduola
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  ABSTRACT: Summary A safe and efficient method for obtaining blood smears for the diagnosis of placental malaria infection is required in order to reduce the risks associated with direct blood contact. We describe a simple and safe method of needle aspiration of the placenta for the diagnosis of placental malaria infection. The method was compared with the conventional incision method in 60 consecutive placentae obtained at term. The quality of the blood smear prepared with the methods were similar. There was a significant correlation between parasite counts from samples prepared with both the incision and aspiration methods. Altman-Bland analysis of the counts revealed narrow limits of agreement with an insignificant bias. The method is useful for obtaining blood smears from the placenta for the diagnosis of placental malaria infection and reducing contact with potential pathogens in blood.
  07/2009; 16(5):316-320.
• Article: Placental falciparum infection and outcome of pregnancy in Nigerian mothers from an endemic area

  A. Sowunmi, A. O. Ilesanmi, J. A. Akindele, A. E. J. Abohweyere, A. O. Fawole, C. O. Falade, A. M. J. Oduola
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  ABSTRACT: Summary Seventy-three placentae and 73 newborn babies were examined from 72 consecutive parturient Nigerian women at term. Ten of the placentae had ring forms of Plasmodium falciparum only, 17 placentae had ring forms and schizonts, and two placentae had only schizonts. Pigment granules alone was present in two placentae, and pigment granules in combination with ring forms and/or schizonts were seen in 10 placentae. There was seasonal variation in both maternal and placental parasite infection. There was also a positive correlation between peripheral and placental parasite density. First-born babies of primigravidae with infected placentae weighed less and had body lengths lower than those of first-born babies with non-infected placentae but the difference was not statistically significant. Their weights and lengths were also significantly less than those of babies of multigravidae with infected placentae. Peripheral parasitaemia was present in 16 of 73 (21 per cent) newborn babies. Parasite density in the newborn babies was low (8–159 asexual forms per (μ blood) and only one newborn baby was symptomatic within 24 hours of birth. Infected newborn babies weighed less than non-infected newborn babies but the difference was not statistically significant. Despite peripheral and/or placental parasitaemia in 25 of the parturient women, only 5 (20 per cent) had symptoms in the one week preceding presentation. Maternal weekly pyrimethamine prophylaxis appears not to confer protection against infection.
  07/2009; 16(4):211-216.
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  Article: Enhanced efficacy of amodiaquine and chlorpheniramine combination over amodiaquine alone in the treatment of acute uncomplicated Plasmodium falciparum malaria in children.

  C O Falade, S O Michael, A M J Oduola
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  ABSTRACT: To evaluate the comparative efficacy of amodiaquine (AMQ) alone and the combination of AMQ and chlorpheniramine (CP) in the treatment of acute uncomplicated malaria in children. Of the 110 children enrolled in the study, 103 with acute uncomplicated malaria, aged 6 months to 12 years, were evaluated using the 14-day modification of the WHO field test. The patients were randomized to 2 groups. Group 1 received supervised treatment with AMQ alone (10 mg AMQ base/kg daily for 3 days), while group 2 received supervised treatment with AMQ (same dose as group 1) plus CP (AMQCP) for 7 days. Both treatment regimens were well tolerated and no patient was withdrawn as a result of recurrent vomiting or drug-related adverse events. There was no significant difference in mean fever and parasite clearance times. The cure rates at day 7 were 90.2 versus 100% (rho = 0.027) for AMQ versus AMQCP, while the day 14 cure rates were 85.9 versus 98.1% for AMQ versus AMQCP, respectively (rho = 0.016). The combination of AMQ plus CP proved significantly more effective than AMQ alone in the treatment of acute uncomplicated falciparum malaria, most probably due to the enhancement of the antimalarial effect of AMQ by CP. The combination of AMQCP could be a better alternative to AMQ alone as a companion drug in artemisinin-based combination therapies.
  Medical Principles and Practice 02/2008; 17(3):197-201. · 0.89 Impact Factor
• Article: Comparative study of interactions between chloroquine and chlorpheniramine or promethazine in healthy volunteers: a potential combination-therapy phenomenon for resuscitating chloroquine for malaria treatment in Africa.

  G O Gbotosho, C T Happi, A Sijuade, O A T Ogundahunsi, A Sowunmi, A M J Oduola
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  ABSTRACT: Although, in in-vitro and limited in-vivo studies, chlorpheniramine (CP) and promethazine (PR) have each been shown to reverse chloroquine (CQ) resistance, the pharmacokinetic basis of this reversal has not been fully elucidated. In the present study, 15 healthy volunteers were randomly allotted to receive standard doses of CQ alone or in combination with CP or PR. Blood samples were collected from each volunteer at 21 time-points, from immediately before to 168 h after the initial dose. These samples were used to follow the changes in the plasma and erythrocytic concentrations of CQ. The ratio between the mean maximum CQ concentration in the erythrocytes and that in the plasma was 4.2 for the volunteers given CQ alone, 7.3 in those given CQ-CP, and 3.2 in those given CQ-PR. CP significantly enhanced the erythrocytic accumulation of CQ, increasing the maximum CQ concentration observed in the erythrocytes by 24% (P = 0.02). The bio-availability of CQ was also significantly increased in the presence of CP, with the mean value for the area under the curve, of erythrocytic concentration v. time, increasing from 99,921 to 214,516 ng/ml.h (P=0.001). The mean half-life of CQ in the erythrocytes also increased when CP was used, from 51 to 100 h, but this change was not statistically significant (P=0.83). In contrast to CP, PR had no statistically significant effect on the disposition of CQ. As CP clearly enhances disposition of CQ, a combination of CQ with CP may be useful in the management of CQ-resistant infections. Detailed toxicological studies are required to understand the full clinical implications of CP's elevation of erythrocytic CQ concentrations.
  Annals of Tropical Medicine and Parasitology 02/2008; 102(1):3-9. · 1.43 Impact Factor
• Article: Chloroquine Resistant Plasmodium falciparum in Nigeria: Relationship between pfcrt and pfmdr1 Polymorphisms, In-Vitro Resistance and Treatment Outcome.

  O A Folarin, G O Gbotosho, A Sowunmi, O O Olorunsogo, A M J Oduola, T C Happi
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  ABSTRACT: This study was designed to evaluate the association between polymorphisms in pfcrt and pfmdr1 genes and in-vitro chloroquine (CQ) sensitivity in fresh isolates of P. falciparum and patients' treatment outcome. The modified schizont inhibition assay was used to determine in-vitro sensitivity of P. falciparum. Polymorphisms in pfcrt and pfmdr1 genes were detected using nested PCR and RFLP techniques in 84 P. falciparum isolates obtained from patients with acute uncomplicated malaria.Eighty five percent (71/84) and 15% (13/84) of the parasites were resistant and sensitive in-vitro to CQ respectively. Molecular analysis showed presence of mutant pfcrtT76, pfmdr1Y86 and pfmdr1F184 alleles in 60%, 33% and 14% of the isolates respectively. There was a significant association between in-vitro and in-vivo CQ resistance (p=0.029) and also between the presence of mutant pfcrtT76+pfmdr1 Y86-Y184 haplotype and in-vitro (p=0.013) or in-vivo CQ resistance (p=0.024).Overall results from this study demonstrates that the presence of pfcrtT76+ pfmdr1 Y86-Y184 haplotype in Nigerian isolates of Plasmodium falciparum is predictive of in-vitro and in-vivo CQ resistance and therefore may be useful for monitoring resistance to this drug.
  The Open Tropical Medicine Journal 01/2008; 1:74-82.
• Article: Health-related biotechnologies for infectious disease control in Africa: Ethical, Legal and Social Implications (ELSI) of transfer and development.

  J Sommerfeld, A M J Oduola
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  ABSTRACT: The African continent is disproportionately affected by infectious diseases. Malaria, HIV/AIDS, tuberculosis, and more "neglected" diseases including African trypanosomiasis, Buruli ulcer, leishmaniasis, onchocerciasis and trachoma continue to dramatically impact social and economic development on the continent. Health biotechnologies provide potential to develop effective strategies for the fight against the vicious circle of poverty and infections by helping in the development and improvement of novel affordable drugs, diagnostics and vaccines against these diseases. As the prospects of this emerging biotechnology research and deployment of its products become a reality in Africa, there is a need to consider the ethical, legal and social implications of both the scientific and technological advances and their use in the communities. The article provides a short overview of the potential values of biotechnology, issues involved in its transfer and presents the rationale, design and recommendations of the international workshop/symposium held in April 2005 at the International Institute for Tropical Agriculture (IITA) in Ibadan, Nigeria.
  African journal of medicine and medical sciences 02/2007; 36 Suppl:1-5.
• Article: Linkage disequilibrium between two distinct loci in chromosomes 5 and 7 of Plasmodium falciparum and in vivo chloroquine resistance in Southwest Nigeria.

  C T Happi, G O Gbotosho, O A Folarin, A Sowunmi, O M Bolaji, B A Fateye, D E Kyle, W Milhous, D F Wirth, A M J Oduola
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  ABSTRACT: Chloroquine (CQ) resistance in Plasmodium falciparum is associated with polymorphisms in loci on pfcrt and pfmdr1 genes. In this study, we determined the association and linkage disequilibrium between in vivo CQ resistance and P. falciparum polymorphisms in pfcrt gene at codon 76 and pfmdr1 gene at codon 86 in isolates obtained from 111 children with acute uncomplicated falciparum malaria in Nigeria. Patients were treated with standard dosage of CQ and followed up for 28 days. Filter paper samples were collected at enrollment and during follow-up for parasites genotypes and identification of pfcrt and pfmdr1 mutations. Association and linkage disequilibrium between mutant pfcrtT76 and pfmdr1Y86 alleles in pretreatment isolates of P. falciparum was determined. Fifty-five out of the 111 patients (49.5%) failed treatment. Single mutant pfcrtT76 or pfmdr1Y86 alleles were found in 55 out of 111 P. falciparum isolates screened at enrollment. Of these 55 isolates, the mutant pfcrtT76 and pfmdr1Y86 alleles were found in 84%. Both mutant pfcrtT76 (p=0.0196) and pfmdr1Y86 (p=0.000042) alleles were associated with in vivo CQ resistance. In addition, the mutant pfcrtT76 (p=0.047) and pfmdr1Y86 (p=0.006) alleles were significantly selected by CQ in patients who failed treatment. Association analysis between paired single alleles at pfcrt and pfmdr1 loci showed a significant association (p=0.0349 and chi(2)=4.45) between the pfcrt T76 allele on chromosome 7 and the pfmdr1Y86 allele on chromosome 5 and that these two mutant alleles were in linkage disequilibrium (p=0.000, D'=0.64, and r(2)=0.28). Considering the high level of CQ resistance and drug use in the study area, the observed linkage disequilibrium between the mutant pfcrtT76 and pfmdr1Y86 alleles is maintained epistatically through directional CQ selective pressure.
  Parasitology Research 01/2007; 100(1):141-8. · 2.15 Impact Factor
• Article: The effects of alpha1-acid glycoprotein on the reversal of chloroquine resistance in Plasmodium falciparum.

  G O Gbotosho, O A Ogundahunsi, C T Happi, D E Kyle, L Gerena, W K Milhous, A Sowunmi, A M J Oduola, L A Salako
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  ABSTRACT: An in-vitro model based on the semi-automated microdilution technique has been developed for selecting compounds that might be used clinically for the reversal of chloroquine resistance. This was used initially to test the susceptibility of Plasmodium falciparum clone W2 to chloroquine (CQ). The model was then employed to investigate the effects of each of four resistance-reversing agents (verapamil, desipramine, chlorpheniramine and promethazine, at 1 microM) on this parasite's susceptibility to CQ, with and without alpha(1)-acid glycoprotein (AGP), at a patho-physiological concentration (1.25 g/litre), in the culture medium. In the absence of AGP, each of the resistance-reversing agents reduced the median inhibitory concentrations of CQ by 82%-97%, from a baseline value of about 94 ng/ml. In the presence of AGP, however, most of the resistance-reversing agents had much less effect. There appears to be competitive interaction between CQ, the resistance-reversing agents and AGP. The binding kinetics between CQ, resistance-reversing agents, AGP and other plasma proteins will clearly need to elucidated if clinically effective resistance-reversing agents are to be selected in vitro.
  Annals of Tropical Medicine and Parasitology 11/2006; 100(7):571-8. · 1.43 Impact Factor
• Article: How well equipped are healthcare facilities to manage childhood malaria? The situation in selected local government areas in South Western Nigeria.

  C O Falade, S O Oladoyinbo, T T Elemile, I O Ajayi, O I Fawole, O Oladepo, J D Adeniyi, A M J Oduola
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  ABSTRACT: Using a structured questionnaire, surveys were conducted in 55 of 123 primary and secondary healthcare facilities in 4 selected local government areas in Southwestern Nigeria. Heads of healthcare facilities (HCFs) surveyed include nurses (41.8%), medical officers (21.8%) and community extension workers (21.8%). Twenty five (45.5%) HCFs run special clinics for children. About one fifth (20.3%) of staff had received continuing education on management of malaria. Forty seven (85%) HCFs possessed and used national guidelines for management of malaria. Although 48.9% of HCFs had microscopes, fewer had microscope slides, lancets and Giemsa stain which are also required items for definitive diagnosis of malaria. Healthcare workers were not well informed on some aspects in the management of malaria. Selected healthcare workers from various categories attended a workshop where they were trained to correct inadequate knowledge, attitude and practice in the management of malaria. These workers were to train their colleagues on their return to their respective HCFs.
  African journal of medicine and medical sciences 10/2006; 35(3):329-35.
• Article: Association between mutations in Plasmodium falciparum chloroquine resistance transporter and P. falciparum multidrug resistance 1 genes and in vivo amodiaquine resistance in P. falciparum malaria-infected children in Nigeria.

  C T Happi, G O Gbotosho, O A Folarin, O M Bolaji, A Sowunmi, D E Kyle, W Milhous, D F Wirth, A M J Oduola
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  ABSTRACT: This study investigated the association between Plasmodium falciparum chloroquine resistance transporter (pfcrt) T76 and P. falciparum multidrug resistance gene 1 (pfmdr1) Y86 alleles and in vivo amodiaquine (AQ) resistance, as well as the clearance of parasites harboring these two alleles in children treated with AQ in southwest Nigeria. One hundred one children with acute uncomplicated P. falciparum malaria infections were treated with the standard dosage of AQ and followed-up for 28 days. Blood samples were collected on filter paper samples at enrollment and during follow-up for identification of parasite genotypes and pfcrt and pfmdr1 mutations using polymerase chain reaction and restriction fragment length polymorphism approaches. Parasitologic assessment of response to treatment showed that 87% and 13% (RI) of patients were cured and failed treatment, respectively. Although infections in patients were polyclonal (as determined by merozoite surface protein 2 genotyping), the presence of both mutants pfcrtT76 and pfmdr1Y86 alleles in parasites is associated with in vivo AQ resistance (odds ratio = 7.58, 95% confidence interval = 1.58-36.25, P = 0.006) and is selected by the drug in children who failed AQ treatment. Treatment failure with the combination of mutant pfcrtT76 and pfmdr1Y86 alleles as well as the ability of patients to clear these resistant parasites is dependent on age, suggesting a critical role of host immunity in clearing AQ-resistant P. falciparum. The combination of mutant pfcrtT76 and pfmdr1Y86 alleles may be useful markers for monitoring the development and spread of AQ resistance, when combining this drug with other antimalarials for treatment of malaria in Africa.
  The American journal of tropical medicine and hygiene 08/2006; 75(1):155-61. · 2.59 Impact Factor
• Article: Predictors of the failure of treatment with pyrimethamine-sulfadoxine in children with uncomplicated falciparum malaria.

  A Sowunmi, B A Fateye, A A Adedeji, G O Gbotosho, T C Happi, A E Bamgboye, O M Bolaji, A M J Oduola
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  ABSTRACT: The prevalence of pyrimethamine-sulfadoxine (PS)-resistant Plasmodium falciparum malaria has been increasing in sub-Saharan Africa or other parts of the world in the last one or two decades. The factors that identify children at risk of treatment failure after being given PS were evaluated in 291 children with acute, symptomatic, uncomplicated, P. falciparum malaria. The children took part in four antimalarial drug trials between July 1996 and July 2004 in a hyperendemic area of southwestern Nigeria. Following treatment, 64 (22%) of 291 children failed treatment by day 7 or 14. In a multivariate analysis, an age < or = 1.5 years (AOR=2.9, 95% CI 1.3-6.4, P = 0.009) and presence of fever (AOR = 3.3, 95% CI 1.28-7.14, P = 0.01) were independent predictors of the failure of treatment with PS at presentation. Following treatment, delay in parasite clearance >3 days (AOR = 2.56, CI 1.19-5.56, P = 0.016) was an independent predictor of the failure of treatment with PS. In addition, compared with the children who had no fever then, children with fever three or more days after starting treatment were more likely to be treatment failures. These findings may have implications for malaria control efforts in some sub-Saharan African countries where treatment of malaria disease depends almost entirely on PS monotherapy, and for programmes employing PS or PS-based combination therapy.
  Acta Tropica 05/2006; 98(1):6-14. · 2.72 Impact Factor
• Article: Open randomized study of artesunate-amodiaquine vs. chloroquine-pyrimethamine-sulfadoxine for the treatment of uncomplicated Plasmodium falciparum malaria in Nigerian children.

  A Sowunmi, F A Fehintola, A A Adedeji, G O Gbotosho, E Tambo, B A Fateye, T C Happi, A M J Oduola
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  ABSTRACT: Artemisinin-based combination antimalarials are currently considered effective alternatives for the treatment of malaria in Africa, but there are few studies of such combinations in Nigerian children. We assessed the safety, treatment efficacy and effects on gametocyte carriage of the combination of artesunate plus amodiaquine and chloroquine plus pyrimethamine-sulfadoxine in children. We evaluated 153 children who were aged 12 years or younger who had uncomplicated Plasmodium falciparum malaria. Patients were randomly assigned a combination of artesunate (4 mg/kg of body weight daily for 3 days) plus amodiaquine (30 mg/kg over 3 days), or chloroquine (25 mg/kg over 3 days) plus pyrimethamine-sulfadoxine (25 mg/kg of the sulfadoxine component at presentation). The primary endpoints were the proportions of children with adequate clinical and parasitological response, late parasitological failure, late clinical failure and early treatment failure. The parasitological cure rates on days 14-28 were also used as the primary endpoints. Both regimens were well tolerated; no child was withdrawn because of drug intolerance. All children treated with artesunate plus amodiaquine had adequate clinical and parasitological response (ACPR), while all but five children treated with chloroquine plus pyrimethamine-sulfadoxine had similar response. Fever clearance times were similar in the two treatment groups. However, the proportion of patients whose parasitaemia cleared by day 2 was significantly higher (100 vs. 50%, P = 0.00001) and parasite clearance was significantly faster (1.7 +/- 0.4 vs. 2.5 +/- 0.8 days, P = 0.0001) in children treated with artesunate plus amodiaquine. The cure rates on days 21 (100%vs. 94%, P = 0.03) and 28 (100%vs. 90%, P = 0.003) were also significantly higher in children treated with artesunate plus amodiaquine than in those treated with chloroquine plus pyrimethamine-sulfadoxine. Overall, a significantly higher proportion of children treated with chloroquine plus pyrimethamine-sulfadoxine carried gametocytes at least once during follow-up compared with those treated with artesunate plus amodiaquine [5 of 50 (10%) vs. 1 of 103 (0.97%), P = 0.01]. The combination of artesunate plus amodiaquine is therapeutically superior to a combination of chloroquine plus pyrimethamine-sulfadoxine, and significantly reduced gametocyte carriage following treatment.
  Tropical Medicine & International Health 12/2005; 10(11):1161-70. · 2.80 Impact Factor
• Article: Polymorphisms in Plasmodium falciparum dhfr and dhps genes and age related in vivo sulfadoxine-pyrimethamine resistance in malaria-infected patients from Nigeria.

  C T Happi, G O Gbotosho, O A Folarin, D O Akinboye, B O Yusuf, O O Ebong, A Sowunmi, D E Kyle, W Milhous, D F Wirth, A M J Oduola
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  ABSTRACT: Mutations in Plasmodium falciparum dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes have been used as means to predict treatment failure to sulfadoxine-pyrimethamine (SP) and for monitoring/surveillance of resistance to the drug in many areas where malaria is endemic. However, patients responses to treatment are significantly dependent on factors like host immunity profile of treated patients. In order to investigate the relationship between molecular markers of SP resistance, host immunity and clinical outcome, the association between pre-treatment dhfr and dhps genotypes, age and treatment outcomes was evaluated in 109 children treated with SP for acute uncomplicated malaria in Ibadan, Nigeria. Seventy-three percent of the children were cured with the drug, while 27% failed treatment after 28 days of follow-up. All children infected with parasites harboring less than two dhfr/dhps mutations were cured with SP. The dhfr triple (Asn-108/Ile-51/Arg-59) mutants or the dhps double mutants (Gly-437/Glu-540) were independently associated with SP treatment failure in children aged less than 5 years, but not in older children. The dhfr and dhps quintuple mutant (dhfr triple mutant+dhps double mutant) was the genotype most strongly associated with SP treatment failure (OR=24.72, 95%CI=8.24-74.15) in both younger and older children.
  Acta Tropica 10/2005; 95(3):183-93. · 2.72 Impact Factor
• Article: Predictors of the failure of treatment with chloroquine in children with acute, uncomplicated, Plasmodium falciparum malaria, in an area with high and increasing incidences of chloroquine resistance.

  A Sowunmi, B A Fateye, A A Adedeji, F A Fehintola, G O Gbotosho, T C Happi, E Tambo, A M J Oduola
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  ABSTRACT: Resistance to chloroquine (CQ) in Plasmodium falciparum has reached unacceptably high levels in many endemic countries. The pre-treatment factors that identify the children who are at risk of treatment failure after being given CQ were evaluated in 385 children with acute, uncomplicated, Plasmodium falciparum malaria. These children each took part in one of six antimalarial drug trials conducted, between July 1996 and July 2004, in a hyper-endemic area of south-western Nigeria. Following treatment with CQ, 149 (39%) of the children failed treatment by day 7 or 14. In a multivariate analysis, an age of < or =7 years [giving an adjusted odds ratio (AOR) of 2.17, with a 95% confidence interval (CI) of 1.19-3.85; P = 0.01], an asexual parasitaemia of > or =100,000/microl (AOR = 2.17; CI = 1.08-4.35; P = 0.03), the presence of gametocytaemia (AOR = 2.08; CI = 1.14-3.85; P = 0.02) and enrolment >4 years after commencement of the study (i.e. after 2000; AOR = 2.13; CI = 1.3-4.0; P = 0.003) were found to be independent predictors at presentation of the subsequent failure of treatment with CQ. Compared with the other children, those who failed to clear their parasitaemias within 3 days and those who still had fever 1-2 days after commencing treatment were more likely to be treatment failures. Together, these findings may have implications for malaria-control efforts in all areas of sub-Saharan Africa where treatment of malaria depends almost entirely on antimalarial monotherapy.
  Annals of Tropical Medicine and Parasitology 10/2005; 99(6):535-44. · 1.43 Impact Factor
• Article: Predictors of the failure of treatment with chloroquine plus chlorpheniramine, in children with acute, uncomplicated, Plasmodium falciparum malaria.

  A Sowunmi, B A Fateye, A A Adedeji, F A Fehintola, G O Gbotosho, T C Happi, A M J Oduola
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  ABSTRACT: Resistance to chloroquine in Plasmodium falciparum can be reversed, both in vitro and in vivo, by chlorpheniramine, a histamine H(1) receptor antagonist. This reversal raises the possibility of using chlorpheniramine to prolong the clinical usefulness of chloroquine in resource-poor communities. The factors that identify children at risk of treatment failure after being given chloroquine plus chlorpheniramine have now been evaluated in 281 children with uncomplicated, P. falciparum malaria. The children, who had taken part in six trials of antimalarial drugs between February 1996 and September 1999, in a hyper-endemic area of south-western Nigeria, were enrolled prospectively for the present study. Following treatment with chloroquine plus chlorpheniramine, 13 (5%) of the children failed treatment by day 7 or 14. In a multivariate analysis, an age of < or =3 years (adjusted odds ratio = 11.1; 95% confidence interval = 2.2-55.3; P = 0.003) and a parasitaemia that took >3 days to clear (adjusted odds ratio=7.9; 95% confidence interval = 1.3-49.4; P = 0.027) were found to be independent predictors of treatment failure. In addition, compared with the children who had a lower axillary temperature then, the children who had an axillary temperature of > or =38 degrees C 2 days after commencing treatment were significantly more likely to be treatment failures. In resource-poor communities using chloroquine plus chlorpheniramine, the easily identifiable predictors of treatment failure might be used to identify children requiring alternative antimalarial drugs.
  Annals of Tropical Medicine and Parasitology 06/2005; 99(4):331-8. · 1.43 Impact Factor
• Article: Efficacy of herbal remedies used by herbalists in Oyo State Nigeria for treatment of Plasmodium falciparum infections--a survey and an observation.

  E O Ajaiyeoba, C O Falade, O I Fawole, D O Akinboye, G O Gbotosho, O M Bolaji, J S Ashidi, O O Abiodun, O S Osowole, O A Itiola, O Oladepo, A Sowunmi, A M J Oduola
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  ABSTRACT: 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.
  African journal of medicine and medical sciences 07/2004; 33(2):115-9.
• Article: Comparison of chlorproguanil-dapsone with sulfadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria in young African children: double-blind randomised controlled trial.

  A Alloueche, W Bailey, S Barton, J Bwika, P Chimpeni, C O Falade, F A Fehintola, J Horton, S Jaffar, T Kanyok, [......], J G Kublin, T Lang, M A Missinou, C Mkandala, A M J Oduola, Z Premji, L Robertson, A Sowunmi, S A Ward, P A Winstanley
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  ABSTRACT: Increasing resistance to sulfadoxine-pyrimethamine is leading to a decline in its effectiveness. We aimed to assess the safety profile of chlorproguanil-dapsone (CD), and to compare the safety and efficacy of this drug with that of sulfadoxine-pyrimethamine (SP) as treatment for uncomplicated falciparum malaria. We undertook a double-blind, randomised trial in 1850 consecutively recruited children with uncomplicated falciparum malaria, pooling data from five African countries. Analyses were based on all randomised patients with available data. CD was significantly more efficacious than SP (odds ratio 3.1 [95% CI 2.0-4.8]); 1313 patients (96%) given CD and 306 (89%) given SP achieved acceptable clinical and parasitological response by day 14. Adverse events were reported in 46% and 50% of patients randomised to CD and SP, respectively (treatment difference -4.4%, [95% CI -10.1 to 1.3]). Haemoglobin in the CD group was significantly lower than in the SP group at day 7, a difference of -4 g/L (95% CI -6 to -2). Mean day 14 haemoglobin (measured only for the small number of patients whose day 7 data caused concern) was 94 g/L (92-96) and 97 g/L (92-102) after CD and SP, respectively. Glucose-6-phosphate dehydrogenase deficient patients on CD had greater odds than those on SP of having a fall of 20 g/dL or more in haemoglobin when baseline temperature was high. Methaemoglobinaemia was seen in the CD group (n=320, mean 0.4% [95% CI 0.4-0.4]) before treatment, 4.2% (95% CI 3.8-4.6) (n=301) at day 3, and 0.6% (0.6-0.7) (n=300) at day 7). CD had greater efficacy than SP in Africa and was well tolerated. Haematological adverse effects were more common with CD than with SP and were reversible. CD is a useful alternative where SP is failing due to resistance.
  The Lancet 07/2004; 363(9424):1843-8. · 38.28 Impact Factor
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  Available from: Babasola Fateye

  Article: Open randomized study of pyrimethamine-sulphadoxine vs. pyrimethamine-sulphadoxine plus probenecid for the treatment of uncomplicated Plasmodium falciparum malaria in children.

  A Sowunmi, F A Fehintola, A A Adedeji, G O Gbotosho, C O Falade, E Tambo, B A Fateye, T C Happi, A M J Oduola
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  ABSTRACT: Increasing drug resistance in Plasmodium falciparum has necessitated renewed search for cheap, effective alternatives to commonly available antimalarials, chloroquine and pyrimethamine-sulphadoxine, for the treatment of malaria in Africa. Probenecid, an inhibitor of organic anion transporters and multiresistance-associated proteins, can chemosensitize P. falciparum to pyrimethamine and sulphadoxine in vitro, but the clinical significance is unclear. We assessed the safety, treatment efficacy, and effects on gametocyte carriage of adding probenecid to pyrimethamine-sulphadoxine. We evaluated 151 children aged 12 years or younger who had uncomplicated P. falciparum malaria. Patients were randomly assigned pyrimethamine-sulphadoxine (25 mg/kg of the sulphadoxine component) or pyrimethamine-sulphadoxine as above plus probenecid 20-25 mg/kg of bodyweight in two divided doses daily for 3 days. The primary endpoints were parasitological cure rates on days 14 and 28. Both regimens were well tolerated; no child was withdrawn because of drug intolerance. Fever (1.9 +/- 1.1 vs. 2.4 +/- 1.2 days, P = 0.02) and parasite clearance (2.3 +/- 0.9 vs. 2.7 +/- 1.1 days, P = 0.04) were significantly shorter, and the parasitological cure rate on day 14 (96.2%vs. 83.5%, P = 0.02) but not day 28 (79.4%vs. 72.6%, P = 0.4), was significantly higher in children treated with pyrimethamine-sulphadoxine-probenecid than in those treated with pyrimethamine-sulphadoxine. Gametocyte carriage was similar with both treatment regimens. The combination of pyrimethamine-sulphadoxine, and probenecid, at a relatively moderate dose, improved treatment efficacy but had no effect on gametocyte carriage. The pyrimethamine-sulphadoxine-probenecid combination merits further evaluation as a potential treatment for use in Nigeria.
  Tropical Medicine & International Health 06/2004; 9(5):606-14. · 2.80 Impact Factor
• Article: Plasmodium berghei: efficacy and safety of combinations of chloroquine and promethazine in chloroquine resistant infections in gravid mice.

  O O Oduola, T C Happi, G O Gbotosho, O A T Ogundahunsi, C O Falade, D O Akinboye, A Sowunmi, A M J Oduola
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  ABSTRACT: 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.
  African journal of medicine and medical sciences 04/2004; 33(1):77-81.