Neonatal Jaundice: Knowledge and Practices of Healthcare Providers and Trainees in Southwest Nigeria.

Severe neonatal jaundice (SNNJ) is a leading cause of neonatal morbidity and mortality in low- and middle-income countries (LMICs). Risk mitigation and management modalities for SNNJ have led to marked reduction in complications in high-income countries but not in LMICs likely in part due to knowledge gaps among healthcare providers. This study, a cross-sectional study conducted in Ogbomosho, Nigeria, aimed to identify SNNJ knowledge and practices among Nigerian healthcare providers/trainees. Healthcare providers/trainees completed a structured questionnaire. Healthcare providers/trainees included are nurse midwives (33.4%), nurses (18.6%), nursing students (15.2%), traditional birth attendants (TBAs) (12.7%), physicians (10.2%), and medical students (9.9%). Most physicians were aware of the common causes of SNNJ; however, knowledge deficits in other groups were notable. Despite most providers endorsing that glucose-6-phosphate dehydrogenase deficiency can cause SNNJ (91% of physicians, 60% of nurses, 71% of midwives, 81% of medical students, 43% of nursing students, 7% of TBAs), very few providers recognized that it is common, ranging from 3% in nurses up to a high of 47% among medical students. Gaps in provider knowledge regarding preventative measures and sequela were also noted. These data identified significant knowledge gaps regarding the etiology of SNNJ among healthcare providers/trainees, which can lead to missed opportunities in effective prevention and treatment. These deficits must be addressed if we are to eliminate tragic and preventable complications from SNNJ in Nigeria and other LMICs.

Cluster-randomized controlled trial of intermittent preventive treatment in infancy using sulfadoxine-pyrimethamine (SP-IPTi): a pilot study in Nigeria.

BACKGROUND: Malaria kills a child in sub-Saharan Africa every 2 min despite widely available interventions including intermittent preventive treatment in infants (IPTi). Since 2010, when World Health Organization (WHO) recommended IPTi, no country has implemented it. To our knowledge, no IPTi study has been conducted in Nigeria. Considering severity of malaria in infancy and urgency to improve malaria prevention, we proposed a study to investigate the efficacy of this intervention in reducing malarial morbidity and mortality. OBJECTIVE(S): The aim of this was to determine the safety and efficacy of SP-IPTi in reducing the prevalence of asymptomatic malaria parasitemia and malarial-associated hospital admissions. METHODS: We performed a cluster-randomized controlled trial in 1379 infants. SP was administered alongside routine vaccinations in immunization centers randomized to intervention groups. Infants in control groups received only routine vaccines. Malarial 'morbidity and adverse events were monitored through passive case-detection and cross-sectional surveys'. RESULTS: SP-IPTi was safe. There was no statistically significant difference in terms of risks of asymptomatic parasitemia at 9 months, fever or hospitalization between our control and intervention groups. CONCLUSIONS: Our study demonstrated that SP-IPTi had no benefit but was well tolerated. WHO and some researchers have also reported declining efficacy of SP, due to increasing drug resistance.

Prevalence of hepatitis B virus infection among children attending the outpatient clinic of a tertiary health centre in Southwest Nigeria.

Introduction: hepatitis B virus (HBV) infection is a global health disease. One-third of the world´s population is reportedly infected with the virus. Infections in children are mostly perinatal and therefore acquired early in life, with a propensity to evolve into chronic diseases and their attendant life-threatening complications. Early diagnosis can, however, improve outcomes in this group of children. The study aimed to determine the prevalence of HBV among children attending the outpatient clinic of a tertiary hospital in Southwest Nigeria. Methods: we recruited a total of one hundred and ninety-eight children aged 6 months to 18 years from the children´s outpatient clinic of a tertiary health centre, using the systematic sampling technique. HBsAg was tested using the HBsAg test kit (PRO-med®, China), and the anti-HBs antibody was tested using the ELISA method. Data were analysed using SPSS version 26. Results: of the 198 children that were screened, 2 (1.0%) were positive. Of these, one (50.0%) had a Hepatitis B positive mother and was HBeAg positive. Two-thirds of the children had received the hepatitis B vaccine, as evidenced by caregivers´ recall, or sighting of the immunization record. There was no statistically significant relationship between the hepatitis B status of the children and the sociodemographic parameters. Conclusion: the study supports the fact that paediatric HBV infections are transmitted from mother to child. Though the prevalence of HBsAg in the study population was lower than the national average for the country, routine immunization program should be strengthened for further control of HBV. Age and gender were not significantly associated with HBV infection in this study.

Efficacy and safety of dual intravenous artesunate plus quinine compared to intravenous artesunate for cerebral malaria in a triple blinded parallel multisite randomized controlled trial in Nigerian children: DUAL PAQ TRIAL Protocol.

BACKGROUND: Evidence exists as to the criticality of the first 24 h in the management of cerebral malaria. The morbidity and the mortality rate (35%) with the current intravenous monotherapy for the initial treatment of cerebral malaria are unacceptably high. Combination therapy and a shorter course of effective medication have been shown to improve outcomes in human participants in the treatment of other diseases. This study outlines a protocol to conduct a triple blinded parallel randomized controlled trial on cerebral malaria using dual intravenous medications compared to the current standard of monotherapy. METHODS: This is a parallel multi-site randomized controlled superiority triple blinded trial consisting of intravenous artesunate plus quinine and a control arm of intravenous artesunate only. Eligible and assenting children aged 6 months to 17 years will be recruited from 4 tertiary hospitals by random selection from the list of tertiary hospitals in Nigeria. Participants will be randomized and assigned in parallel into two arms using random numbers generated from GraphPad Prism (version 9) by a clinical pharmacologist who has no link with the investigators, the patients, or the statistician. The primary measurable outcome is survival at 12, 24, and 48 h post-randomization. A composite secondary outcome consists of the number of children that regained consciousness, parasitaemia and defervescence at 12 and 24 h post-randomization and haematological and inflammatory markers at 24 and 48 h post-randomization. Adverse events both solicited and unsolicited are recorded all through the study post-randomization. The study is approved by the State Research Ethics Review Committee. Data analysis will be performed in GraphPad Prism version 9. DISCUSSION: The outcome of this analysis will give insight into the efficacy and safety of dual intravenous antimalaria in the treatment of cerebral malaria among Nigerian children compared with the standard of care. The safety profile of this intervention will also be highlighted. This may help inform physicians on the optimal treatment for cerebral malaria to improve outcomes and reduce recrudescence and treatment failure. TRIAL REGISTRATION: Pan Africa Clinical Trial Registry PACTR202102893629864 . 23/02/2021.

Determinants of Exclusive Breastfeeding Practices Among Mothers of Infants Less Than Six Months Attending an Immunization Clinic in Southwestern Nigeria.

Background Despite being a cost-effective means of improving the childhood health indices, exclusive breastfeeding (EBF) remains low in the low middle-income countries. Hence, we evaluated the determinants of EBF among mothers of infants less than six months in Southwestern Nigeria. Methods This was a cross-sectional descriptive study that involved 271 mothers of infants aged less than six months attending the immunization clinic of the Bowen University Teaching Hospital, Ogbomoso, Nigeria. Pretested semi-structured questionnaires were used to get relevant information from the mothers who were recruited using convenience sampling method. Descriptive statistics was carried out while chi square test and binary logistic regression were used for inferential statistics. Results The mean age (±SD) of the respondents was 30.4 ± 5.0 years. The EBF rate in this study was 46.1% (125/271); 40.6% of mothers breastfed their infants within an hour of birth, with most (91.1%) breastfeeding their babies on demand. Factors associated with EBF included mothers' age > 30 years (OR 2.080, 95% CI 1.274-3.395). After controlling for potential confounders, family size > 4, (adjusted OR 2.053, 95% CI 1.120-3.762) and having vaginal delivery (adjusted OR 2.769, 95% CI 1.585-4.829) were the significant determinants of EBF practices among the study participants. Conclusion EBF practice was average in the studied population. Family size >4 and vaginal delivery were the determinants of EBF. There is a need to sustain the promotion of appropriate breastfeeding practices.

Treatment outcomes of Nigerian patients with tuberculosis: A retrospective 25-year review in a regional medical center.

INTRODUCTION: Tuberculosis (TB) remains a global health challenge and leading infectious killer worldwide. The need for continuous evaluation of TB treatment outcomes becomes more imperative in the midst of a global economic meltdown substantially impacting resource-limited-settings. METHODS: This study retrospectively reviewed 25-years of treatment outcomes in 3,384 patients who were managed for TB at a tertiary hospital in Nigeria. Confirmed TB cases were given directly observed therapy of a short-course treatment regimen and monitored for clinical response. RESULTS: Out of 1,146,560 patients screened, there were 24,330 (2.1%) presumptive and 3,384 (13.9%) confirmed TB cases. The patients' mean age was 35.8 years (0.33-101 years). There were 1,902 (56.2%) male, 332(9.8%) pediatric, and 2,878 (85%) pulmonary TB cases. The annual mean measured treatment outcomes were as follows: adherence, 91.4(±5.8) %; successful outcome, 75.3(±8.8) % potentially unsatisfactory outcome, 14.8(±7.2) %; and mortality 10.0(±3.6) %. Female, extra-pulmonary TB (EPTB), newly diagnosed, and relapsed patients compliant with treatment had successful outcomes. Adulthood and HIV infection were mortality risk factors. CONCLUSION: The mean annual successful treatment outcome is 75.3(±8.8) %. Female, pediatric, EPTB, new, and relapsed patients were predisposed to successful treatment outcomes. Lessons learned will guide future program modifications.

Filtered sunlight versus intensive electric powered phototherapy in moderate-to-severe neonatal hyperbilirubinaemia: a randomised controlled non-inferiority trial.

BACKGROUND: Kernicterus resulting from severe neonatal hyperbilirubinaemia is a leading cause of preventable deaths and disabilities in low-income and middle-income countries, partly because high-quality intensive phototherapy is unavailable. Previously, we showed that filtered-sunlight phototherapy (FSPT) was efficacious and safe for treatment of mild-to-moderate neonatal hyperbilirubinaemia. We aimed to extend these studies to infants with moderate-to-severe hyperbilirubinaemia. METHODS: We did a prospective, randomised controlled non-inferiority trial in Ogbomoso, Nigeria-a simulated rural setting. Near-term or term infants aged 14 days or younger who were of 35 weeks or more gestational age and with total serum bilirubin concentrations at or above the recommended age-dependent treatment levels for high-risk neonates were randomly assigned (1:1) to either FSPT or intensive electric phototherapy (IEPT). Randomisation was computer-generated, and neither clinicians nor the parents or guardians of participants were masked to group allocation. FSPT was delivered in a transparent polycarbonate room lined with commercial tinting films that transmitted effective phototherapeutic light, blocked ultraviolet light, and reduced infrared radiation. The primary outcome was efficacy, which was based on assessable treatment days only (ie, those on which at least 4 h of phototherapy was delivered) and defined as a rate of increase in total serum bilirubin concentrations of less than 3·4 µmol/L/h in infants aged 72 h or younger, or a decrease in total serum bilirubin concentrations in those older than 72 h. Safety was defined as no sustained hypothermia, hyperthermia, dehydration, or sunburn and was based on all treatment days. Analysis was by intention to treat with a non-inferiority margin of 10%. FINDINGS: Between July 31, 2015, and April 30, 2017, 174 neonates were enrolled and randomly assigned: 87 to FSPT and 87 to IEPT. Neonates in the FSPT group received 215 days of phototherapy, 82 (38%) of which were not assessable. Neonates in the IEPT group received 219 treatment days of phototherapy, 67 (31%) of which were not assessable. Median irradiance was 37·3 µW/cm2/nm (IQR 21·4-56·4) in the FSPT group and 50·4 µW/cm2/nm (44·5-66·2) in the IEPT group. FSPT was efficacious on 116 (87·2%) of 133 treatment days; IEPT was efficacious on 135 (88·8%) of 152 treatment days (mean difference -1·6%, 95% CI -9·9 to 6·7; p=0·8165). Because the CI did not extend below -10%, we concluded that FSPT was not inferior to IEPT. Treatment was safe for all neonates. INTERPRETATION: FSPT is safe and no less efficacious than IEPT for treatment of moderate-to-severe neonatal hyperbilirubinaemia in near-term and term infants. FUNDING: Thrasher Research Fund and National Center for Advancing Translational Sciences.

Pediatric Trauma Care in Low Resource Settings: Challenges, Opportunities, and Solutions.

Trauma constitutes a significant cause of death and disability globally. The vast majority -about 95%, of the 5.8 million deaths each year, occur in low-and-middle-income countries (LMICs) 3-6. This includes almost 1 million children. The resource-adapted introduction of trauma care protocols, regionalized care and the growth specialized centers for trauma care within each LMIC are key to improved outcomes and the lowering of trauma-related morbidity and mortality globally. Resource limitations in LMICs make it necessary to develop injury prevention strategies and optimize the use of locally available resources when injury prevention measures fail. This will lead to the achievement of the best possible outcomes for critically ill and injured children. A commitment by the governments in LMICs working alone or in collaboration with international non-governmental organizations (NGOs) to provide adequate healthcare to their citizens is also crucial to improved survival after major trauma. The increase in global conflicts also has significantly deleterious effects on children, and governments and international organizations like the United Nations have a significant role to play in reducing these. This review details the evaluation and management of traumatic injuries in pediatric patients and gives some recommendations for improvements to trauma care in LMICs.

Case Presentation of Anti-NMDA Receptor Encephalitis in a 4-Year-Old Boy.

We report a case of a 4-year-old boy from Oyo, Nigeria, presenting with prolonged seizures and coma with the subsequent development of oro-lingual-facial dyskinesia with frequent tongue thrusting, dysconjugate gaze and choreoathetoid movements of the limbs because of autoimmune encephalitis consistent with anti-N-methyl-D-aspartate (anti-NMDAR) encephalitis.

A randomized two-way crossover bioequivalence study in healthy adult volunteers of paediatric zidovudine/lamivudine/nevirapine fast-disintegrating fixed-dose combination tablet.

OBJECTIVE: The bioequivalence study was conducted to compare the developed paediatric fixed-dose combination (FDC) zidovudine/lamivudine/nevirapine (60/30/50 mg) tablet - the test formulation - with the combined mixture of single-entity innovator products (reference product). METHODS: A single-dose open-label randomized two-way crossover study was conducted in healthy adult African volunteers after an informed consent was obtained. The 24 volunteers, divided into two groups, were administered the products after an overnight fast on two treatment days with 14 days of washout period. Blood samples were collected for 96 h and analysed using a validated RP-HPLC-UV assay method. Pharmacokinetic (PK) parameters (non-compartmental model) were assessed with WinNonlin® software. Analysis of variance (ANOVA) and FDA bioequivalence statistical criterion of 90% CI or 80% to 125% range (set at P < 0.05) of least square geometric means (LSGM) ratios of test: reference product for Cmax , AUC0-t , and AUC0-∞ were determined. RESULTS: ANOVA indicated that the period, sequence and formulation had no significant effect on the PK parameters (P > 0.05). The 90% CIs for all the drugs were within the 80% to 125% range. CONCLUSION: The developed FDC tablet is bioequivalent to the reference product.

Glucose-6-phosphate dehydrogenase deficiency in Nigerian children.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzymopathy and in Sub-Saharan Africa, is a significant cause of infection- and drug-induced hemolysis and neonatal jaundice. Our goals were to determine the prevalence of G6PD deficiency among Nigerian children of different ethnic backgrounds and to identify predictors of G6PD deficiency by analyzing vital signs and hematocrit and by asking screening questions about symptoms of hemolysis. We studied 1,122 children (561 males and 561 females) aged 1 month to 15 years. The mean age was 7.4 ± 3.2 years. Children of Yoruba ethnicity made up the largest group (77.5%) followed by those Igbo descent (10.6%) and those of Igede (10.2%) and Tiv (1.8%) ethnicity. G6PD status was determined using the fluorescent spot method. We found that the overall prevalence of G6PD deficiency was 15.3% (24.1% in males, 6.6% in females). Yoruba children had a higher prevalence (16.9%) than Igede (10.5%), Igbo (10.1%) and Tiv (5.0%) children. The odds of G6PD deficiency were 0.38 times as high in Igbo children compared to Yoruba children (p=0.0500). The odds for Igede and Tiv children were not significantly different from Yoruba children (p=0.7528 and 0.9789 respectively). Mean oxygen saturation, heart rate and hematocrit were not significantly different in G6PD deficient and G6PD sufficient children. The odds of being G6PD deficient were 2.1 times higher in children with scleral icterus than those without (p=0.0351). In conclusion, we determined the prevalence of G6PD deficiency in Nigerian sub-populations. The odds of G6PD deficiency were decreased in Igbo children compared to Yoruba children. There was no association between vital parameters or hematocrit and G6PD deficiency. We found that a history of scleral icterus may increase the odds of G6PD deficiency, but we did not exclude other common causes of icterus such as sickle cell disease or malarial infection.

A randomized pahse I bioequivalence clinincal trial of a paediatric fixed-dose combination antiretroviral reconstitutable suspension in healthy adult volunteers.

BACKGROUND: This study aimed to test the hypothesis that the paediatric fixed-dose combination granule for reconstitution (comprising lamivudine/zidovudine/nevirapine 30/60/50 mg per 5 ml) as a test product is bioequivalent to the coadministered single entities of the referenced products. Fixed-dose combination anti-retroviral therapy provides adequate suppression of HIV-1 replication, provides barrier to the development of resistance, simplifies dosage regimen and improves adherence. METHODS: An open label, randomized, two-way crossover study was conducted on 24 health adults under fasted conditions, with a washout period of 14 days between treatments. A total of 15 blood samples were collected before dosing and up to 96 h post dosing. The drugs were extracted from plasma and anlaysed using a validated high performance liquid chromatography- ultraviolet method. Non- compartmental pharmacokinetic (PK) analysis was performed to obtain the PK parameters, maximum plasma concentration (C max), area under the curve of plasma concentration-time curves from the time zero to last measurable concentration (AUC0-t) and the area under the curve extrapolated to infinity (AUC 0-∞) ANOVA test was performed to determine the effect of model factors on the PK parameters. The two one-sided t-tests were performed on the log-transformed data to determine the 90% CL for the ratio of test to reference PK parameters. RESULTS: The drugs were well tolerated and safe with minimal adverse events. The ANOVA test indicated the absence of any significant effects ( P>0.05) due to the model parameters. The 90% Cl for the geometric mean ratio of the test/reference for the Cmax, AUC0-t and the AUC0-∞ for lamivudine, zidovudine and nevirapine were within 80-125% bioequivalence limits. CONCLUSIONS: This single dose randomized study found that the test and reference products met the criteria for bioequivalence in the fasting healthy adult volunteers.

Cost comparison of microscopy vs. empiric treatment for malaria in Southwestern Nigeria: a prospective study.

BACKGROUND: Presumptive treatment for malaria is common in resource-limited settings, yet controversial given the imprecision of clinical diagnosis. The researchers compared costs of diagnosis and drugs for two strategies: (1) empirical treatment of malaria via clinical diagnosis; and (2) empirical diagnosis followed by treatment only with Giemsa smear confirmation. METHODS: Patients with a diagnosis of clinical malaria were recruited from a mission/university teaching hospital in southwestern Nigeria. The patients underwent free Giemsa thick (diagnosis) and thin (differentiation) smears, but paid for all anti-malarial drugs. Clinical diagnosis was made on clinicians' judgments based on symptoms, including fever, diarrhoea, headache, and body aches. The paediatric regimen was artesunate (6-9 tablets of 3 mg/kg on day one and 1.5 mg/kg for the next four days) plus amodiaquine (10 mg/kg day 1-2 and 5 mg/kg on day three in suspension). Adults were given two treatment options: option one (four and one-half 50 mg artesunate tablets on day one and nine tablets for the next four days, plus three 500 mg sulphadoxine/25 mg pyrimethamine tablets) and option two (same artesunate regimen plus nine 200 mg tablets of amodiaquine at 10 mg/kg day 1-2 and 5 mg/kg on day three). The researchers calculated the costs of smears/drugs from standard hospital charges. RESULTS: Doctors diagnosed 304 patients (170 adults ages >16 years and 134 pediatric) with clinical malaria, prescribing antimalarial drugs to all. Giemsa thick smears were positive in 115/304 (38%). The typical patient cost for a Giemsa smear was 550 Naira (US$3.74 in 2009). For children, the cost of testing all, but treating only Giemsa positives was N888 ($6.04)/child; the cost of empiric treatment of all who were clinically diagnosed was lower, N660 ($4.49)/child. For adults, the cost of testing all, but treating only Giemsa positives was N711 ($4.84)/adult for treatment option one (artesunate and sulphadoxine/pyrimethamine) and N730 ($4.97)/adult for option two (artesunate and amodiaquine). This contrasts to lower costs of empiric treatment for both options one (N610 = $4.14/adult) and two (N680=$4.63/adult). CONCLUSIONS: Empiric treatment of all suspected cases of malaria was cheaper (at the end of the dry to the beginning of the rainy season) than only treating those who had microscopy-confirmed diagnoses of malaria, even though the majority of patients suspected to have malaria were negative via microscopy. One can acknowledge that giving many malaria-uninfected Nigerians anti-malarial drugs is undesirable for both their personal health and fears of drug resistance with overuse. Therefore, funding of rapid diagnostic tests whose performance exceeds the Giemsa smear is needed to achieve an ideal of diagnostic confirmation before treatment.

Etiologic agents and outcome determinants of community-acquired pneumonia in urban children: a hospital-based study.

Etiologic clues and prognostic indicators of community-acquired pneumonia (CAP) were sought in a 30-month study of under-5 admissions for acute lower respiratory infections (ALRIs). Investigative tools included blood culture, hemogram, immunofluorescence and serology. Associations of variables were tested using standard statistical tools. Of 419 ALRI, 323 (77%) had pneumonia, 234 (72.4%) bronchopneumonia, 66 (20.4%) lobar pneumonia and 23 (7.1%) both. More than 70% had poor parental socioeconomic parameters, 56.8% were overtly malnourished, 37.8% lived in overcrowded homes and 16.7% had been potentially exposed to wood smoke. Despite preconsultation antimicrobial use in 35.6%, 59 (28.8%) of 205 blood cultures proved positive; Staphylococcus aureus accounted for 22 (37.3%), Klebsiella species nine (15.3%) and Streptococcus pneumoniae three (5.1%). Ninety-two viruses were identified in 61 (50%) of 122 analyses. Respiratory syncytial virus (RSV) accounted for 28 (30.4%), parainfluenza virus type 3 (PIV-3) for 18 (19.5%) and influenza type-A (flu-A) 16 (17.3%). Twenty (16.4%) had > or = 2 viruses, while 40% of bacteremic cases with positive viral identification(s) had PIV-3. Pathogen detection was neither associated with hematologic parameters nor the final respiratory diagnosis. There were 35 (10.8%) deaths. Mortality was associated with maternal illiteracy (p = 0.045), wood smoke exposure (p = 0.006), preconsultation antimicrobial use (p = 0.04), malnutrition (p = 0.0003), bacteremia (p = 0.006) and polymorphonuclear leucocytosis (p = 0.023/0.013). RSV, PIV-3, flu-A, S. aureus and Klebsiella species constitute the major pathogens of pediatric CAP in urban Nigeria, while malnutrition, wood smoke exposure and bacteremia are strong risk factors of mortality. The poor prognostic import of antimicrobial abuse, vis-a-vis the apparent selection of necrotizing pathogens, are compelling indications for a reappraisal of current regional antimicrobial policies and exploring newer frontiers of disease control, including vaccine prevention.