Olusegun O. Akinyinka

Esophageal, Tympanic, Rectal, and Skin Temperatures in Children Undergoing Surgery With General Anesthesia

The purpose of this study was to determine the degrees of agreement between various sites of temperature measurement and examine the trend of body temperature in children during surgery under general anaesthesia. Thirty-six consecutive children who underwent surgery with general anaesthesia, had temperatures measured at the oesophagus, skin, ear canal and rectum at baseline, every 15 minutes for the first hour and every 30 minutes thereafter. Spearman correlation and Bland-Altman analyses were used to compare data and trends of mean differences assessed by line graphs. The median age of the sample was 48 months. There were 575 temperature measurements taken. The inter-method correlation coefficients was highest for the oesophageal vs rectal (r = 0.96) temperature and lowest for rectal vs skin (r = -0.11) temperature. The lowest mean difference (95% CI) in temperature at commencement of surgery was between the oesophageal and rectal sites, -0.03°C (-0.08, -0.01) while the highest mean difference (95% CI) temperature was between oesophageal and skin sites, 3.24°C (2.65, 3.85). The trend in differential temperatures between sites remained throughout the duration of surgery. Bland-Altman plots showed that the least difference (bias) at baseline (0.3°C) was between the oesophageal and tympanic temperatures while at 1 hour (0.13°C ) was between the oesophageal and rectal temperatures. The oesophageal site was the closest to rectal for monitoring core temperature while the skin was the least reliable site in the study population. In the situation where oesophageal probe is not routine or functioning, rectal or tympanic temperatures may be used.

Nevirapine-Based Antiretroviral Therapy Impacts Artesunate and Dihydroartemisinin Disposition in HIV-Infected Nigerian Adults.

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 AUC0-96 (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 AUC0-96 = 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.

Drug Interactions in the Treatment and Chemoprophylaxis of Malaria in HIV Infected Individuals in Sub Saharan Africa

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.

Disposition of amodiaquine and desethylamodiaquine in HIV-infected Nigerian subjects on nevirapine-containing antiretroviral therapy

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 AUC₀₋₂₄ 145 versus 204 ng·h/mL, P = 0.02; DEAQ AUC₀₋₉₆ 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.

Metabolic derangements identified through untargeted metabolomics in a cross-sectional study of Nigerian children with severe acute malnutrition

IntroductionSevere acute malnutrition (SAM) is a major cause of child mortality worldwide, however the pathogenesis of SAM remains poorly understood. Recent studies have uncovered an altered gut microbiota composition in children with SAM, suggesting a role for microbes in the pathogenesis of malnutrition.ObjectivesTo elucidate the metabolic consequences of SAM and whether these changes are associated with changes in gut microbiota composition.MethodsWe applied an untargeted multi-platform metabolomics approach [gas chromatography–mass spectrometry (GC-MS) and liquid chromatography–mass spectrometry (LC-MS)] to stool and plasma samples from 47 Nigerian children with SAM and 11 control children. The composition of the stool microbiota was assessed by 16S rRNA gene sequencing.ResultsThe plasma metabolome discriminated children with SAM from controls, while no significant differences were observed in the microbial or small molecule composition of stool. The abundance of 585 features in plasma were significantly altered in malnourished children (Wilcoxon test, FDR corrected P < 0.1), representing approximately 15% of the metabolome. Consistent with previous studies, children with SAM exhibited a marked reduction in amino acids/dipeptides and phospholipids, and an increase in acylcarnitines. We also identified numerous metabolic perturbations which have not been reported previously, including increased disaccharides, truncated fibrinopeptides, angiotensin I, dihydroxybutyrate, lactate, and heme, and decreased bioactive lipids belonging to the eicosanoid and docosanoid family.ConclusionOur findings provide a deeper understanding of the metabolic consequences of malnutrition. Further research is required to determine if specific metabolites may guide improved management, and/or act as novel biomarkers for assessing response to treatment.

Artemether-Lumefantrine Exposure in HIV-Infected Nigerian Subjects on Nevirapine-Containing Antiretroviral Therapy

ABSTRACT Coadministration of nevirapine-based antiretroviral therapy (ART) and artemether-lumefantrine is reported to result in variable changes in lumefantrine exposure. We conducted an intensive pharmacokinetic study with 11 HIV-infected adults who were receiving artemether-lumefantrine plus nevirapine-based ART, and we compared the results with those for 16 HIV-negative adult historical controls. Exposure to artemether and lumefantrine was significantly lower and dihydroartemisinin exposure was unchanged in subjects receiving nevirapine-based ART, compared with controls. Nevirapine exposure was unchanged before and after artemether-lumefantrine administration.

Adolescent Girls’ Understanding of Tetanus Infection and Prevention: Implications for the Disease Control in Western Nigeria

Tetanus is a major cause of morbidity and mortality in developing countries. Nigeria is aiming to eliminate tetanus by maintaining coverage of routine vaccinations for infants and pregnant women, but little attention is given to the adolescents’ needs. This study assessed the understanding of adolescent girls about tetanus infection and prevention in order to provide information that may foster better policy. In this cross-sectional analytical study, 851 female adolescents were selected from eight secondary schools in Ibadan, south-west of Nigeria using a three-stage random sampling technique. A pre-tested structured questionnaire was used to obtain information on demographic and socio-economic characteristics, history of tetanus vaccination, and adolescents’ knowledge of tetanus infection. Mean age of respondents was 14.3 ± 1.9 years. Only 3.1% had received tetanus toxoid injection 1 year prior to the study, most frequently following a “wound or injury” (65.4%). Though 344 (40.4%) respondents claimed that they knew about tetanus as a “serious neurological disease,” only 46.5% correctly defined tetanus. Overall, the mean knowledge score was 4.8 ± 3.1 and 64.7% of the respondents had poor knowledge. Academic class was significantly associated with knowledge; higher mean score among the senior (5.3 ± 5.3) than junior classes (4.4 ± 3.2); p < 0.001. Over half (56.2%) of the adolescents disagreed with the statement that “tetanus immunization can be given to students in the school premises.” There is the need to improve immunization campaigns against tetanus among adolescent girls and consider the introduction of school-based immunization programs if the elimination of maternal and neonatal tetanus is to be achieved.

Comparison of auditory brainstem response in HIV-1 exposed and unexposed newborns and correlation with the maternal viral load and CD4+ cell counts.

Objective:The effects of maternal HIV infection and antiretroviral therapy on hearing of HIV-exposed newborns in sub-Saharan Africa have not been investigated. We determined the prevalence of sensorineural hearing loss among HIV-exposed newborns and the association between the hearing threshold and maternal and newborn parameters. Design:A cohort audiometric study of newborns between October 2012 and April 2013. Settings:A secondary and tertiary hospital-based study. Participants:Consecutive 126 HIV-exposed and 121 HIV-unexposed newborns. Intervention:Hearing screening of the newborns was done with Auditory Brainstem Response and compared with maternal HAART, CD4+ cell counts, RNA viral loads and newborn CD4+ cell count percentage. Main outcome measure:Hearing threshold levels of both groups were measured and analysed. Results:Around 11.1% of HIV-exposed and 6.6% of unexposed newborns had hearing impairment (P = 0.2214). About 6.4% of HIV-exposed and 2.5% HIV-unexposed newborns had hearing threshold of more than 20 dBHL (P = 0.1578). There was no significant association between the hearing thresholds of HIV-exposed newborns and maternal CD4+ cell counts (P = 0.059) but there was with maternal viral load (P = 0.034). There was significant difference between the hearing thresholds of HIV-exposed newborns with CD4+% of 25 or less and more than 25. This study showed significant difference in the hearing of the 119 HAART-exposed newborns and seven unexposed newborns [P = 0.002; risk ratio, 0.13 (0.05–0.32)]. Conclusion:There was a trend towards more hearing loss in HIV-exposed newborns. However, hearing thresholds increase with increasing mothers’ viral load. The background information supports the need for further studies on the role of in-utero exposure to HIV and HAART in newborn hearing loss.

Static skinfold thickness in African newborns as an index of fetal nutritional assessment

Abstract Background: Fetal malnutrition (FM) has grave implications for the neonate and is reliably assessed by the CANSCORE which is time-consuming. Static skinfold thickness, a measure of adiposity, is a validated method of assessing malnutrition in older children. Aim: To establish if static skinfold measurements in neonates can serve as a reliable measure of FM. Objective: To compare static skinfold thickness measurements in neonates using the CANSCORE for the identification of FM. Method: 252 consecutive term neonates delivered at University College Hospital, Ibadan, Nigeria had their CANSCOREs and static skinfold thickness measured within 24 hours of delivery. Using correlation and linear regression analysis, static skinfold thickness cut-off points for FM were determined using a reference CANSCORE of <25. Results: Prevalence of FM was 20·2% and 26·2% using the CANSCORE and the sum of five skinfold thickness measurements, respectively. The mean (SD) skinfold thicknesses were triceps 3·91 mm (0·74), biceps 2·84 mm (0·55), subscapular 3·79 mm (0·91), supra-iliac 2·64 mm (0·62), quadriceps 4·43 mm (1) and the sum of all measurements 17·61 mm (3·16). All the skinfold thickness measurements correlated significantly with the CANSCORE, but the sum of the five had the best correlation. The quadriceps had the highest specificity of 85·6% and lowest sensitivity of 54·9%, while the sum of all had a sensitivity of 66·7% and specificity of 84·0%. Conclusion: The sum of all five skinfold measurements might be a useful screening tool for FM in view of its objectivity, convenience and simplicity, but it is not sufficiently sensitive or specific to replace the CANSCORE in the identification of FM in neonates.

Ultrasonographic renal sizes, cortical thickness and volume in Nigerian children with acute falciparum malaria

BackgroundUtility of sonographic assessments of renal changes during malaria illness are rarely reported in African children in spite of the high burden of malarial-related kidney damage.MethodsIn this case–control study, renal sizes, cortical thickness and volume of the kidneys of 131 healthy children and 170 with acute falciparum malaria comprising 85 uncomplicated malaria (UM) and 85 complicated malaria (CM) cases, measured within 24 hours of presenting in the hospital were compared.ResultsThe mean age of children with UM, CM and control groups was 49.7 ± 26.2 months, 50.7 ± 29.3 months and 73.4 ± 25.5 months, respectively (p < 0.001). The mean right kidney length of CM group was higher than control by 0.41cm (95% CI = 0.16, 0.65; p < 0.001) and UM by 0.32 cm (95% CI = 0.02, 0.62; p = 0.030). Similarly, mean left kidney length of CM was higher than control and UM by 0.34 cm (95% CI = 0.09, 0.60; p = 0.005) and 0.41cm (95% CI = 0.09, 0.72; p = 0.006), respectively. Estimated mean renal volume of the CM group was significantly higher than control group by 7.82 cm3 for right and by 5.79 cm3 for left kidneys respectively; in the UM group by 9.31cm3 for right and 8.87 cm3 for left kidneys respectively.ConclusionThere was a marginal increase in renal size of children with Plasmodium falciparum infection, which worsened with increasing severity of malaria morbidity. Ultrasonography provides important information for detecting renal changes in children with acute malaria.