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

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.

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.

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

BACKGROUND: Utility 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. METHODS: In 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. RESULTS: The 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 cm(3) for right and by 5.79 cm(3) for left kidneys respectively; in the UM group by 9.31cm(3) for right and 8.87 cm(3) for left kidneys respectively. CONCLUSION: There 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.

Utilisation of malaria preventive measures during pregnancy and birth outcomes in Ibadan, Nigeria.

BACKGROUND: Malaria remains a major public health problem in sub Saharan Africa and the extent of utilisation of malaria preventive measures may impact on the burden of malaria in pregnancy. This study sought to determine the association between malaria preventive measures utilized during pregnancy and the birth outcomes of birth weight and preterm delivery. METHODS: This cross sectional survey involved 800 mothers who delivered at the University College Hospital, and Adeoyo Maternity Hospital, Ibadan. Data obtained included obstetric information, gestational age, birth weight and self reported use of malaria prevention strategies in index pregnancy. RESULTS: Most (95.6%) mothers used one or more malaria control measures. The most commonly used vector control measures were window net (84.0%), insecticide spray (71.5%) and insecticide treated bed nets (20.1%), while chemoprophylactic agents were pyrimethamine (23.5%), Intermittent Preventive Treatments with Sulphadoxine-Pyrimethamine (IPTsp) (18.5%) and intermittent chloroquine (9.5%) and 21.7% used herbal medications. The mean ± SD birthweight and gestational age of the babies were 3.02 kg ± 0.56 and 37.9 weeks ± 2.5 respectively. Preterm delivery rate was 19.4% and 9% had low birth weight. Comparing babies whose mothers had IPTsp with those who did not, mean birth weight was 3.13 kg ± 0.52 versus 3.0 kg ± 0.56 (p = 0.016) and mean gestational age was 38.5 weeks ± 2.1 versus 37.8 weeks ± 2.5 (p = 0.002). The non-use of IPTsp was associated with increased risk of having low birth weight babies (AOR: 2.27, 95% CI: 0.98; 5.28) and preterm birth (AOR: 1.93, 95% CI: 1.08, 3.44). The non use of herbal preparations (AOR: 0.55, 95% CI: 0.36, 0.85) was associated with reduced risk of preterm birth. The mean ± SD birth weight and gestational ages of babies born to mothers who slept under ITNs were not significantly different from those who did not (p = 0.07 and 0.09 respectively). CONCLUSIONS: There is a need for improved utilisation of IPTsp as well as discouraging the use of herbal medications in pregnancy in order to reduce pregnancy outcome measures of low birth weight and preterm deliveries in this environment.

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.

Edwardsiella ictaluri, an unusual cause of bacteraemia in a Nigerian child with acute bloody diarrhoea.

Enteric septicaemia of catfish was first detected in 1976 as an economically significant disease associated with commercial catfish production. Initially, Edwardsiella ictaluri was a host specific pathogen of catfish species but has also been reported from other hosts other than the catfish such as the zebrafish. E. ictaluri has not been isolated in humans hence it is not a zoonotic infection. There has been no previous report of isolation of this organism in humans. This was a case report of a 5 year old boy who presented with fever, vomiting, passage of bloody stool of 6 days and abdominal pain of a day duration. In the case of this 5 year old boy who presented with features of dysentery, blood culture using BACTEC™ grew E. ictaluri. E. ictaluri may be a pathogen which can infect humans just like another closely related species, Edwardsiella tarda. Although, E. ictaluri has not been reported in humans, could this be the first case? Non availability of diagnostic technique appropriate for its diagnosis may explain the rare incidence of the organism in humans, hence many cases would have been treated without isolating the organism.

Aflatoxin exposure in Nigerian children with severe acute malnutrition.

Aflatoxin exposure is an important public health concern in sub-Saharan Africa as well as parts of Latin America and Asia. In addition to hepatocellular carcinoma, chronic aflatoxin exposure is believed to play a role in childhood growth impairment. The most reliable biomarker of chronic aflatoxin exposure is the aflatoxin-albumin adduct, as measured by ELISA or isotope dilution mass spectrometry (IDMS). In this report, we have used high resolution LC-MS/MS with IDMS to quantitate AFB1-lysine in an extremely vulnerable population of Nigerian children suffering from severe acute malnutrition. To increase the sensitivity and reliability of the analyses, a labelled AFB1-13C615N2-lysine internal standard was synthesized. AFB1-lysine concentrations in this population ranged between 0.2 and 59.2 pg/mg albumin, with a median value of 2.6 pg/mg albumin. AFB1-lysine concentrations were significantly higher in stunted children (median = 4.6 pg/mg) compared to non-stunted (1.2 pg/mg), as well as in children with severe acute malnutrition (4.3 pg/mg) compared to controls (0.8 pg/mg). The median concentrations were also higher in children with kwashiorkor (6.3 pg/mg) compared to those suffering from marasmus (0.9 pg/mg). This is the first report of the use of high-resolution mass spectrometry to quantitate AFB1-lysine in humans.

Intestinal Bacterial Colonization in the First 2 Weeks of Life of Nigerian Neonates Using Standard Culture Methods.

OBJECTIVE: The pattern and timing of development of intestinal microflora in Nigerian infants have been scarcely researched. This study was carried out to investigate the bacteria flora in the rectum of healthy neonates in Ibadan, Nigeria. PATIENTS AND METHODS: In this hospital-based longitudinal study, rectal swabs of 70 neonates were taken within 6-12 h of birth (day 1) and subsequently on days 3, 9, and 14. Information collected included maternal sociodemographic characteristics, antibiotic use for the neonates, and type of feeding during the first 14 days of life. Identification and speciation of gram-negative isolates were done using the Analytical Profile Index 20E® and 20NE® as appropriate. Gram-positive bacteria were identified biochemically using the catalase and coagulase tests. Data were analyzed using descriptive statistics and Chi-square at p = 0.05. RESULTS: Majority (92.9%) of the neonates were delivered vaginally with a median gestational age of 38 weeks (range = 34-42). On the first day of life, Escherichia coli was isolated more frequently from the rectal swabs of preterm (50.0%) than term (23.1%) neonates (p = 0.031). On day 3 of life, coagulase-negative staphylococcus was the most frequently isolated bacteria from the rectal swabs of nonasphyxiated (64.4%) compared with asphyxiated (27.3%) neonates' rectal swabs (p = 0.042). Staphylococcus aureus was the most frequently isolated bacteria from the rectal swabs of nonexclusively breastfed (66.7%) than exclusively breastfed (21.3%) neonates on day 14 (p = 0.004). CONCLUSION: Staphylococcus aureus and Escherichia coli were the predominant isolates from the rectum of Nigerian neonates, and these isolates were influenced by breastfeeding and mild-moderate asphyxia. In all, bacterial diversity in the rectum increased as the neonates got older.

Prevalence and socio-demographic factors associated with non-protective immunity against tetanus among high school adolescents girls in Nigeria.

BACKGROUND: The low uptake of tetanus vaccine and its resultant high burden of tetanus in Nigeria suggest the need to improve routine and booster vaccination in children and adolescents. However, epidemiological evidence for vaccination in the adolescent age group needed for effective strategy and policy formulation is lacking. This study was carried out to determine the prevalence of protective immunity against tetanus and to identify risk factors for non-protective immunity among schooling adolescents. METHODS: Using a three-stage sampling technique, 851 female adolescents were randomly selected from secondary schools in Ibadan, Nigeria. A pre-tested questionnaire was used to obtain data on demographic and socio-economic characteristics and history of tetanus vaccination. An immuno-chromatographic rapid test kit, "Tetanos Quick Stick" was used to test specific anti-tetanus antibody protective level in venous blood samples. Descriptive statistics, Chi-square and logistic regression analyses were done with level of significance set at p = 0.05. RESULTS: Mean age of participants was 14.3 ± 1.9 years. Seroprevalence of protective immunity against tetanus was 38.1% and it significantly decreased with increasing age. More adolescents in public (65.4%) than private (44.7%) schools had non-protective level of immunity. A significantly increasing trend in the risk of non-protective immunity was observed with decreasing level of mothers' education. Also, the Odds of non-protective level of immunity was significantly higher in public than private schools (OR = 2.14; 95% CI =1.39, 3.20) but lower among adolescents who had history of recent tetanus toxoid injection than those who did not (OR = 0.11 95% CI = 0.09, 0.22). However, no significant association was found between protective immunity against tetanus and parents' marital status as well as family size. CONCLUSION: Protective immunity against tetanus among female adolescents was poor, more so in public schools and those who had not received vaccination a year prior to the study. Policy-makers need to consider the inclusion of immunization against tetanus in the school health programme.

Enhancement of health research capacity in Nigeria through north-south and in-country partnerships.

Research productivity in Sub-Saharan Africa has the potential to affect teaching, student quality, faculty career development, and translational country-relevant research as it has in developed countries. Nigeria is the most populous country in Africa, with an academic infrastructure that includes 129 universities and 45 medical schools; however, despite the size, the country has unacceptably poor health status indicators. To further develop the research infrastructure in Nigeria, faculty and research career development topics were identified within the six Nigerian universities of the nine institutions of the Medical Education Partnership Initiative in Nigeria (MEPIN) consortium. The consortium identified a training model that incorporated multi-institutional "train-the-trainers" programs at the University of Ibadan, followed by replication at the other MEPIN universities. More than 140 in-country trainers subsequently presented nine courses to more than 1,600 faculty, graduate students, and resident doctors throughout the consortium during the program's first three years (2011-2013). This model has fostered a new era of collaboration among the major Nigerian research universities, which now have increased capacity for collaborative research initiatives and improved research output. These changes, in turn, have the potential to improve the nation's health outcomes.

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

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.

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 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.

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.

Detection of fever in children emergency care: comparisons of tactile and rectal temperatures in Nigerian children.

BACKGROUND: Clinical thermometry is the objective method for temperature measurements but tactile assessment of fever at home is usually the basis for seeking medical attention especially where the cost and level of literacy preclude the use of thermometers. This study was carried out to determine the reliability of tactile perception of fever by caregivers, nurses and house physicians in comparison to rectal thermometry and also the use of commonly practiced surface of the hand in the care of ill children. All caregivers of children aged 6 to 59 months who presented to the emergency department were approached consecutively at the triage stage but 182 children participated. Each child had tactile assessment of fever using palmar and dorsal surfaces of the hand by the caregivers, House Physicians and Nursing Officers. Rectal temperature was also measured and read independently by nurses and house physicians. Comparisons were made between tactile assessments and thermometer readings using a cut-off for fever, 38.0 degrees C and above. FINDINGS: The caregivers' perception of fever had a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 95%, 23%, 66% and 73%, respectively compared with 93%, 26%, 67% and 69%, respectively for nursing officers. Irrespective of the groups studied, 77.1% of 336 assessors opined that the dorsal surface of the hand was more sensitive in tactile assessment of temperature and the frequently used site for assessment of fever were the head (35.6%) and neck (33.3%). Tactile assessment of temperature over-detected fever in >/= 24% of cases among the three groups of assessors. CONCLUSIONS: The present study suggests that tactile assessment of temperature may over estimate the prevalence of fever, it does not detect some cases and the need for objective measurement of temperature is emphasised in paediatric emergency care.