Pretreatment and Acquired Drug Resistance in Children With Human Immunodeficiency Virus Type 1 in Jos, Nigeria.

We determined pretreatment and acquired human immunodeficiency virus (HIV) drug resistance among children with HIV type 1 (HIV-1) in Jos, Nigeria. The majority (71%) of those who failed first-line antiretroviral therapy were on a nevirapine-containing regimen. The prevalence of pretreatment (48%) and acquired (76%) HIV drug resistance mutations was high in our study. Wider access to HIV drug resistance testing after treatment failure is necessary to optimize second-line treatment options among children with HIV in Nigeria.

Antenatal jaundice instruction and acute bilirubin encephalopathy in Nigeria.

BACKGROUND: Acute Bilirubin Encephalopathy (ABE) is common in Nigeria. Parents' inability to recognize jaundice and delays in seeking care are significant barriers to its prevention. METHODS: We compared associations of (1) interactive antenatal maternal jaundice instruction with postnatal reinforcement, (2) standard postnatal instruction, and (3) no maternal instruction with the incidence of ABE among 647 jaundice admissions stratified for risk factors identified in initial descriptive analysis. RESULTS: Eighty-three (83/647;12.8%) admissions developed ABE including eleven jaundice-related deaths. ABE was present at admission in 20/22 (90.9%) if mothers received no jaundice instruction and no antenatal care, 42/182 (23.1%) if received antenatal care but no instruction, 16/95 (16.8%) if received postnatal instruction only, and 4/337 (1.2%) if mothers received both antenatal and postnatal instruction (p < .001). ABE was highly associated with out-of-hospital delivery, number of antenatal clinic visits, and birth attendant, but these risks were mitigated by antenatal/postnatal instruction. Admission rates with bilirubin levels below treatment guidelines (12 mg/dL) were higher following instruction (30.7%) than with no instruction (14.4%). Limiting subjects to those meeting admission criteria increased ABE rates in all groups without altering conclusions. CONCLUSION: Interactive antenatal instruction with postnatal reinforcement resulted in timely care seeking and a lower incidence of ABE. IMPACT: Empowering mothers to participate in neonatal jaundice management is critical in low-income countries where jaundice monitoring and follow up are unreliable. Instructing mothers about jaundice in antenatal clinics with postnatal reinforcement is more effective than standard postpartum instruction in facilitating jaundice detection, timely care seeking, and lowering the incidence of acute bilirubin encephalopathy (ABE). Antenatal training also mitigates risks for ABE associated with out-of-hospital deliveries, limited antenatal care, and unskilled birth attendants. IMPACT: Adding structured jaundice instruction in antenatal clinics could greatly reduce bilirubin induced brain injury in countries where ABE is common.

Quantitative assessment of umbilical cord care practices amongst mothers in Jos, Plateau State, Nigeria.

Introduction: A newly cut neonatal umbilical stump is a potential portal of pathogen entry leading to omphalitis. Neonatal sepsis can complicate omphalitis, but good cord care practices can reduce this risk. Objective: The objective of this study was to assess umbilical cord care practices in tertiary-, secondary- and primary-level healthcare facilities in Jos, Nigeria. Methods: A multi-centre, cross-sectional study of 284 mothers of infants aged 3-6 weeks old attending immunisation clinics in the three-level healthcare facilities using multistage sampling technique between April and September 2019. Data were analysed using SPSS version 23.0. Pearson's Chi-squared test was used to compare categorical variables. Adjusted odds ratios (AORs) and 95% confidence interval (CI) were used as point and interval estimates, respectively. P < 0.05 was adjudged to be statistically significant. Results: The mean age of the mothers and infants was 25 ± 6 years and 5 ± 1 week, respectively. Only 2.2% of mothers used chlorhexidine (CHX) gel for cord care. Mothers showed good knowledge but poor practice of cord care. A significant positive relationship was observed between quality of cord care practices and level of healthcare facility (χ2 = 15.213; df = 2; P < 0.001). Good cord care practices were predicted by mothers' age 30-46 (AOR = 3.6; CI: 1.4-9.1) and good knowledge of cord care (AOR = 4.7; 95% CI: 2.2-9.9). Conclusions: The study has highlighted the good knowledge but poor practices of cord care by mothers and the need to scale up the uptake of CHX gel in Jos. Mother's age and good knowledge of cord care are predictors of good cord care practices.

Design, Implementation, and Coordination of Malaria Therapeutic Efficacy Studies in Nigeria in 2018.

Prior to 2018, malaria therapeutic efficacy studies (TESs) in Nigeria were implemented separately at different sites, as assigned by the National Malaria Elimination Program (NMEP). In 2018, however, the NMEP engaged the Nigerian Institute of Medical Research to coordinate the 2018 TESs in 3 of 14 sentinel sites with the objective of standardizing their conduct across all three sites: Enugu, Kano, and Plateau states in three of six geopolitical zones. Artemether-lumefantrine and artesunate-amodiaquine, the two first-line drugs for treatment of acute uncomplicated malaria in Nigeria, were tested in both Kano and Plateau states. In Enugu State, however, artemether-lumefantrine and dihydroartemisinin-piperaquine were the test drugs, with dihydroartemisinin-piperaquine being tested for potential inclusion in Nigerian treatment policy. The TES was conducted in 6-month to 8-year-old children and was funded by the Global Fund with additional support from the WHO. A multipartite core team comprised of the NMEP, the WHO, the U.S. Presidential Malaria Initiative, academia, and the Nigerian Institute of Medical Research was set up to oversee the execution of the 2018 TES. This communication reports best practices adopted to guide its coordination, and lessons learned during in the process, including applying developed standard operating procedures, powering the sample size adequately for each site to report independently, training the investigating team for fieldwork, facilitating stratification of decisions, determining efficiencies derived from monitoring and quality assessment, and optimizing logistics. The planning and coordination of the 2018 TES activities is a model of a consultative process for the sustainability of antimalarial resistance surveillance in Nigeria.

Facilitators and barriers to seasonal malaria chemoprevention (SMC) uptake in Nigeria: a qualitative approach.

BACKGROUND: SMC was adopted in Nigeria in 2014 and by 2021 was being implemented in 18 states, over four months between June and October by 143000 community drug distributors (CDDs) to a target population of 23million children. Further expansion of SMC is planned, extending to 21 states with four or five monthly cycles. In view of this massive scale-up, the National Malaria Elimination Programme undertook qualitative research in five states shortly after the 2021 campaign to understand community attitudes to SMC so that these perspectives inform future planning of SMC delivery in Nigeria. METHODS: In 20 wards representing urban and rural areas with low and high SMC coverage in five states, focus group discussions were held with caregivers, and in-depth interviews conducted with community leaders and community drug distributors. Interviews were also held with local government area and State malaria focal persons and at national level with the NMEP coordinator, and representatives of partners working on SMC in Nigeria. Interviews were recorded and transcribed, those in local languages translated into English, and transcripts analysed using NVivo software. RESULTS: In total, 84 focus groups and 106 interviews were completed. Malaria was seen as a major health concern, SMC was widely accepted as a key preventive measure, and community drug distributors (CDDs) were generally trusted. Caregivers preferred SMC delivered door-to-door to the fixed-point approach, because it allowed them to continue daily tasks, and allowed time for the CDD to answer questions. Barriers to SMC uptake included perceived side-effects of SMC drugs, a lack of understanding of the purpose of SMC, mistrust and suspicions that medicines provided free may be unsafe or ineffective, and local shortages of drugs. CONCLUSIONS: Recommendations from this study were shared with all community drug distributors and others involved in SMC campaigns during cascade training in 2022, including the need to strengthen communication about the safety and effectiveness of SMC, recruiting distributors from the local community, greater involvement of state and national level pharmacovigilance coordinators, and stricter adherence to the planned medicine allocations to avoid local shortages. The findings reinforce the importance of retaining door-to-door delivery of SMC.

Relationship between maternal and infant serum vitamin D levels in Jos, Plateau State, Nigeria: a cross-sectional study.

Introduction: there is growing interest in the link between maternal and infant vitamin D (VD) levels. Breast milk transmission and the fact that the mother and her child may share risk factors for VD, such as exposure to sunlight, diet, and sociocultural influences may impact VD status, the magnitude of which is largely unknown in our topical low-middle income setting. We assessed the connection between maternal and infant VD status including their correlates. Methods: this cross-sectional study investigated 95 maternal-infant pairs in Jos. Mothers were interviewed using a questionnaire. Blood sampling and analysis of serum total 25 hydroxy VD were performed using the chemiluminescent immunoassay method. Maternal and infant VD levels were classified as VD deficient (VDD), VD insufficient (VDI), and VD sufficient (VDS). The mean maternal and infant VD were compared, and the Spearman correlation between them was assessed, a stepwise linear regression was also performed with infant vitamin D as a dependent variable. For all statistical analysis, p<0.05 was considered significant. Results: the median maternal and infant VD was 29.68 ng/ml and 29.41 ng/ml, respectively. The mean infant VD (32.19 ± 10.61 ng/ml) was comparable to maternal VD (31.12 ± 12.94 ng/ml) (p=0.483), with a Spearman correlation coefficient of 0.3 (p=0.037). Maternal vitamin D (beta=0.539, duration of exclusive breastfeeding (beta=-3.490), and infant age (beta=1.655) were found to be significant independent predictors of infant vitamin. Conclusion: beyond neonatal age, a significant positive relationship between maternal and infants´ VD levels exists and suggests that family-focused vitamin D intervention might be an effective public health approach in the tropical city of Jos.

Health beliefs and (timely) use of facility-based care for under-five children: lessons from the qualitative component of Nigeria's 2019 VASA.

BACKGROUND: Nigeria's under-five health outcomes have improved over the years, but the mortality rates remain unacceptably high. The qualitative component of Nigeria's 2019 verbal and social autopsy (VASA) showed that caregivers' health beliefs about causes of illnesses and efficacious treatment options contribute to non-use/delay in use of facility-based healthcare for under-five children. This study explored how these health beliefs vary across zones and how they shape how caregivers seek healthcare for their under-five children. METHODS: Data for this study come from the qualitative component of the 2019 Nigeria VASA, comprising 69 interviews with caregivers of under-five children who died in the five-year period preceding the 2018 Nigeria Demographic and Health Survey (NDHS); and 24 key informants and 48 focus group discussions (FGDs) in 12 states, two from each of the six geo-political zones. The transcripts were coded using predetermined themes on health beliefs from the 2019 VASA (qualitative component) using NVivo. RESULTS: The study documented zonal variation in belief in traditional medicine, biomedicine, spiritual causation of illnesses, syncretism, and fatalism, with greater prevalence of beliefs discouraging use of facility-based healthcare in the southern zones. Driven by these beliefs and factors such as availability, affordability, and access to and perceived quality of care in health facilities, caregivers often choose one or a combination of traditional medicines, care from medicine vendors, and faith healing. Most use facility-based care as the last option when other methods fail. CONCLUSION: Caregivers' health beliefs vary by zones, and these beliefs influence when and whether they will use facility-based healthcare services for their under-five children. In Nigeria's northern zones, health beliefs are less likely to deter caregivers from using facility-based healthcare services, but they face other barriers to accessing facility-based care. Interventions seeking to reduce under-five deaths in Nigeria need to consider subnational differences in caregivers' health beliefs and the healthcare options they choose based on those beliefs.

Assessment of the health related quality of life in children with asthma in a tertiary hospital in North Central, Nigeria.

Introduction: asthma is a chronic inflammatory disorder of the airways with over 339 million people affected worldwide. Asthma can impair the quality of life (QoL) in its various bio-psycho-social domains causing poor concentration, poor school performance and impaired daily activities. This study assessed the QoL in asthmatic children aged 7- 17 years. Methods: a descriptive cross-sectional study of 46 children with asthma. Relevant bio-data and medical history were documented and the QoL assessment was carried out using the paediatric asthma quality of life questionnaire. Asthma severity and asthma control were defined based on the global initiative for asthma protocol. The data was analysed with IBM SPSS version 22. Results: the mean age was 12.4 ± 3.3 years, with a male to female ratio of 1: 1.9. About 61% of the study population were moderately impaired in their QoL and 41.3% had uncontrolled asthma. The mean QoL score was 5.80 with the activity domain and the emotion domain having the lowest mean scores (5.78 ± 1.0 and 5.91 ± 1.2 respectively). There was a significant association between QoL and age, asthma severity, asthma control and social class (p< 0.05) but not Gender. The logistic regression did not identify any of these factors as being predictors of QoL in the children. Conclusion: the study participants had moderately impaired QoL with the 7-10 year-olds more severely affected. The activity and emotion domains are more impaired. Therefore in addition to providing medical intervention, the treatment of children with asthma should include psychological support and counselling.

Molecular profiling of the artemisinin resistance Kelch 13 gene in Plasmodium falciparum from Nigeria.

Accurate assessment and monitoring of the Plasmodium falciparum Kelch 13 (pfk13) gene associated with artemisinin resistance is critical to understand the emergence and spread of drug-resistant parasites in malaria-endemic regions. In this study, we evaluated the genomic profile of the pfk13 gene associated with artemisinin resistance in P. falciparum in Nigerian children by targeted sequencing of the pfk13 gene. Genomic DNA was extracted from 332 dried blood (DBS) spot filter paper samples from three Nigerian States. The pfk13 gene was amplified by nested polymerase chain reaction (PCR), and amplicons were sequenced to detect known and novel polymorphisms across the gene. Consensus sequences of samples were mapped to the reference gene sequence obtained from the National Center for Biotechnology Information (NCBI). Out of the 13 single nucleotide polymorphisms (SNPs) detected in the pfk13 gene, five (F451L, N664I, V487E, V692G and Q661H) have not been reported in other endemic countries to the best of our knowledge. Three of these SNPs (V692G, N664I and Q661H) and a non-novel SNP, C469C, were consistent with late parasitological failure (LPF) in two States (Enugu and Plateau States). There was no validated mutation associated with artemisinin resistance in this study. However, a correlation of our study with in vivo and in vitro phenotypes is needed to establish the functional role of detected mutations as markers of artemisinin resistance in Nigeria. This baseline information will be essential in tracking and monitoring P. falciparum resistance to artemisinin in Nigeria.

Genetic diversity and population structure of Plasmodium falciparum in Nigeria: insights from microsatellite loci analysis.

BACKGROUND: Malaria remains a public health burden especially in Nigeria. To develop new malaria control and elimination strategies or refine existing ones, understanding parasite population diversity and transmission patterns is crucial. METHODS: In this study, characterization of the parasite diversity and structure of Plasmodium falciparum isolates from 633 dried blood spot samples in Nigeria was carried out using 12 microsatellite loci of P. falciparum. These microsatellite loci were amplified via semi-nested polymerase chain reaction (PCR) and fragments were analysed using population genetic tools. RESULTS: Estimates of parasite genetic diversity, such as mean number of different alleles (13.52), effective alleles (7.13), allelic richness (11.15) and expected heterozygosity (0.804), were high. Overall linkage disequilibrium was weak (0.006, P < 0.001). Parasite population structure was low (Fst: 0.008-0.105, AMOVA: 0.039). CONCLUSION: The high level of parasite genetic diversity and low population structuring in this study suggests that parasite populations circulating in Nigeria are homogenous. However, higher resolution methods, such as the 24 SNP barcode and whole genome sequencing, may capture more specific parasite genetic signatures circulating in the country. The results obtained can be used as a baseline for parasite genetic diversity and structure, aiding in the formulation of appropriate therapeutic and control strategies in Nigeria.

Rifabutin pharmacokinetics and safety among TB/HIV-coinfected children receiving lopinavir/ritonavir-containing second-line ART.

BACKGROUND: Treatment options are limited for TB/HIV-coinfected children who require PI-based ART. Rifabutin is the preferred rifamycin for adults on PIs, but the one study evaluating rifabutin with PIs among children was stopped early due to severe neutropenia. METHODS: We evaluated rifabutin safety and plasma pharmacokinetics among coinfected children 3-15 years of age receiving rifabutin 2.5 mg/kg daily with standard doses of lopinavir/ritonavir. The AUC0-24 at 2, 4 and 8 weeks after rifabutin initiation was described using intensive sampling and non-compartmental analysis. Clinical and laboratory toxicities were intensively monitored at 12 visits throughout the study. RESULTS: Among 15 children with median (IQR) age 13.1 (10.9-14.0) years and weight 25.5 (22.3-30.5) kg, the median (IQR) rifabutin AUC0-24 was 5.21 (4.38-6.60) µg·h/mL. Four participants had AUC0-24 below 3.8 µg·h/mL (a target for the population average exposure) at week 2 and all had AUC0-24 higher than 3.8 µg·h/mL at the 4 and 8 week visits. Of 506 laboratory evaluations during rifabutin, grade 3 and grade 4 abnormalities occurred in 16 (3%) and 2 (0.4%) instances, respectively, involving 9 (60%) children. Specifically, grade 3 (n = 4) and grade 4 (n = 1) neutropenia resolved without treatment interruption or clinical sequelae in all patients. One child died at week 4 of HIV-related complications. CONCLUSIONS: In children, rifabutin 2.5 mg/kg daily achieved AUC0-24 comparable to adults and favourable HIV and TB treatment outcomes were observed. Severe neutropenia was relatively uncommon and improved with ongoing rifabutin therapy. These data support the use of rifabutin for TB/HIV-coinfected children who require lopinavir/ritonavir.

Prevalence of latent tuberculosis infection in HIV-1-infected children on antiretroviral therapy in Jos, Nigeria.

Background: There are few studies investigating the prevalence of latent tuberculosis infection (LTBI) in HIV-1-infected children on antiretroviral therapy (ART), but no data from Nigeria. This study determined the prevalence of LTBI in HIV-1-infected children on ART in our clinic. Knowing the prevalence and thus the burden of LTBI could help improve HIV care by enabling targeted isoniazid (INH) prophylaxis. Method: This observational study was carried out from September 2016 to August 2017 at the pediatric HIV clinic of the Jos University Teaching Hospital among HIV-1-infected children on ART, aged 6 months-15 years. LTBI was diagnosed using an interferon-gamma release assay, the ELISpot test, T-SPOT®.TB assay (Oxford Immunotec, Abingdon, UK) on freshly collected whole blood samples within 2 h. Children with a positive test were treated with INH after first excluding TB by chest X-ray and clinical evaluation. Results: Of the 90 children studied, 4 (4.4%) had LTBI diagnosed by ELISpot. Their median interquartile range (IQR) age was 10.4 years (7.9-12.5), the majority were male (54.4%) and most of them had originally received Bacille Calmette-Guérin (83/89, 93.3%). They had a median CD4 count of 694 cells/µL (472-1045). The median (IQR) CD4 count was higher in LTBI compared to non-LTBI children: 1286 cells/µL (953-1375) versus 683 cells/µL (465-1040), (P = 0.044). Conclusion: Although this study showed a very low prevalence of LTBI in our setting, it was still beneficial to the few children on ART identified with LTBI as it enabled treatment with INH. A larger study will be required to ascertain the actual burden of LTBI in such children in our setting.

Longitudinal evaluation of adherence, retention, and transition patterns of adolescents living with HIV in Nigeria.

INTRODUCTION: Adherence to antiretroviral therapy (ART) and retention in treatment programs are required for successful virologic suppression and treatment outcomes. As the number of adolescents living with HIV continues to increase globally, more information about adherence and retention patterns during and through transition from child- to adult-centered care is needed to ensure provision of a high level of care and inform development of targeted interventions to improve patient outcomes in this vulnerable population. In this analysis, we sought to describe long-term trends in adherence, retention, and virologic suppression in adolescents receiving ART at a pediatric HIV clinic in Nigeria through transition to the adult clinic. SETTING: The Jos University Teaching Hospital, United States President's Emergency Plan for AIDS Relief (PEPFAR)-funded HIV clinic in Jos, Plateau State, Nigeria. METHODS: We conducted a retrospective observational longitudinal evaluation of data that had been collected during the course of care in a large pediatric ART program in Nigeria. We used descriptive statistics to define our patient population and quantify retention from ART initiation through adolescence and transition to adult-centered care. Logistic regression was used to evaluate predictors of loss to follow-up. We used medication possession ratio (MPR) to quantify adherence for each year a patient was on ART. To evaluate adherence and virologic suppression, we measured the proportion of patients with ≥95% MPR and the proportion with virologic suppression (viral load ≤400 copies/mL) within each age cohort, and used bivariate analyses to examine any association between MPR and VL suppression for all person-years observed. RESULTS: A total of 476 patients received at least one dose of ART as an adolescent (ages 10-19 years). The proportions of patients lost to follow-up were: 11.9% (71/597) prior to adolescence, 19.1% (31/162) during adolescence, and 13.7% (10/73) during transition to adult-centered care. While over 80% of patients had ≥95% medication adherence in all age groups, their viral load suppression rates through adolescence and post-transition were only 55.6%-64.0%. For patients that successfully transitioned to adult-centered care, we observed 87.7% (50/57) retention at month 12 post-transition, but only 34.6% (9/26) viral load suppression. CONCLUSIONS: Our evaluation found considerable proportions of adolescents lost to follow-up throughout the ART program cascade. We also found discrepancies between the proportions of patients with ≥95% MPR and the proportions with VL suppression, suggesting that true medication adherence in this population may be poor. Significant attention and targeted interventions to improve retention and adherence focused on adolescents are needed in order for global programs to achieve 90-90-90 goals.

Prevalence of hepatitis B virus infection among pregnant women in Jos, Nigeria.

Objectives: The study sought to determine the prevalence and risk factors associated with Hepatitis B surface antigenemia (HBsAg) positivity among pregnant women in Jos, Nigeria. Methodology: This was a cross-sectional study carried out among the pregnant population in five healthcare facilities in Jos, between November 1, 2017 and April 30, 2018. Informed consent was obtained, and data on sociodemographic and risk factors for hepatitis B virus (HBV) infection were collected. Hepatitis B viral infection was assessed using the in vitro HBsAg diagnostic rapid kit (Acon Laboratories, USA). Descriptive statistics, Chi-square test, and logistic regression were performed to identify predictors of HBV infection in the study population. All statistical analyses were carried out on STATA version 15. Results: Of the 3,238 women enrolled, 7.4% (241/3238) (95% confidence interval [CI] = 6.6% to 8.4%) were HBsAg positive. The absence of HBV vaccination (adjusted odds ratio [AOR] = 2.49; 95% CI = 1.49-4.09; P < 0.001), co-infection with HIV (AOR = 1.90; 95% CI = 1.18-3.08; P = 0.009), and higher parity (AOR = 1.37; 95% CI = 1.04-1.79; P = 0.024) were independently associated with HBV infection in pregnancy. Conclusions: The prevalence of HBV infection among pregnant women was high, especially among those without prior vaccination for HBV, those with HIV co-infection and higher parity.

RésuméObjectifs: L'étude visait à déterminer la prévalence et les facteurs de risque associés à la positivité à l'antigénémie de surface de l'hépatite B (AgHBs) chez les femmes enceintes à Jos, Nigéria. Méthodologie: Il s'agit d'une étude transversale réalisée auprès de la population enceinte dans cinq dans les établissements de santé de Jos, entre le 1er novembre 2017 et le 30 avril 2018. Un consentement éclairé a été obtenu et des données sociodémographiques et des facteurs de risque d'infection par le virus de l'hépatite B (VHB) ont été collectés. L'infection virale de l'hépatite B a été évaluée à l'aide du diagnostic in vitro de l'HBsAg kit rapide (Acon Laboratories, USA). Des statistiques descriptives, un test du chi carré et une régression logistique ont été effectués pour identifier les prédicteurs de Infection par le VHB dans la population étudiée. Toutes les analyses statistiques ont été effectuées sur STATA version 15. Résultats: Sur les 3 238 femmes inscrites, 7,4% (241/3238) (intervalle de confiance à 95% [IC] = 6,6% à 8,4%) étaient positifs pour l'AgHBs. L'absence de vaccination contre le VHB (cotes ajustées rapport [AOR] = 2,49; IC à 95% = 1,49­4,09; P <0,001), co-infection par le VIH (AOR = 1,90; IC à 95% = 1,18­3,08; P = 0,009) et plus la parité (AOR = 1,37; IC à 95% = 1,04-1,79; P = 0,024) était indépendamment associée à l'infection par le VHB pendant la grossesse. Conclusions: le la prévalence de l'infection par le VHB était élevée chez les femmes enceintes, en particulier chez celles qui n'avaient pas été vaccinées contre le VHB, celles avec le VIH co-infection et parité plus élevée.

Safety, reactogenicity, and immunogenicity of a chimpanzee adenovirus vectored Ebola vaccine in adults in Africa: a randomised, observer-blind, placebo-controlled, phase 2 trial.

BACKGROUND: The 2014 Zaire Ebola virus disease epidemic accelerated vaccine development for the virus. We aimed to assess the safety, reactogenicity, and immunogenicity of one dose of monovalent, recombinant, chimpanzee adenovirus type-3 vectored Zaire Ebola glycoprotein vaccine (ChAd3-EBO-Z) in adults. METHODS: This phase 2, randomised, observer-blind, controlled trial was done in study centres in Cameroon, Mali, Nigeria, and Senegal. Healthy adults (≥18 years) were randomly assigned with a web-based system (1:1; minimisation procedure accounting for age, gender, centre) to receive ChAd3-EBO-Z (day 0), or saline placebo (day 0) and ChAd3-EBO-Z (month 6). The study was observer-blind until planned interim day 30 analysis, single-blind until month 6, and open-label after month 6 vaccination. Primary outcomes assessed in the total vaccinated cohort, which comprised all participants with at least one study dose administration documented, were serious adverse events (up to study end, month 12); and for a subcohort were solicited local or general adverse events (7 days post-vaccination), unsolicited adverse events (30 days post-vaccination), haematological or biochemical abnormalities, and clinical symptoms of thrombocytopenia (day 0-6). Secondary endpoints (subcohort; per-protocol cohort) evaluated anti-glycoprotein Ebola virus antibody titres (ELISA) pre-vaccination and 30 days post-vaccination. This study is registered with ClinicalTrials.gov, NCT02485301. FINDINGS: Between July 22, 2015, and Dec 10, 2015, 3030 adults were randomly assigned; 3013 were included in the total vaccinated cohort (1509 [50·1%] in the ChAd3-EBO-Z group and 1504 [49·9%] in the placebo/ChAd3-EBO-Z group), 17 were excluded because no vaccine was administered. The most common solicited injection site symptom was pain (356 [48%] of 748 in the ChAd3-EBO-Z group vs 57 [8%] of 751 in the placebo/ChAd3-EBO-Z group); the most common solicited general adverse event was headache (345 [46%] in the ChAd3-EBO-Z group vs 136 [18%] in the placebo/ChAd3-EBO-Z group). Unsolicited adverse events were reported by 123 (16%) of 749 in the ChAd3-EBO-Z group and 119 (16%) of 751 in the placebo/ChAd3-EBO-Z group. Serious adverse events were reported for 11 (1%) of 1509 adults in the ChAd3-EBO-Z group, and 18 (1%) of 1504 in the placebo/ChAd3-EBO-Z group; none were considered vaccination-related. No clinically meaningful thrombocytopenia was reported. At day 30, anti-glycoprotein Ebola virus antibody geometric mean concentration was 900 (95% CI 824-983) in the ChAd3-EBO-Z group. There were no treatment-related deaths. INTERPRETATION: ChAd3-EBO-Z was immunogenic and well tolerated in adults. Our findings provide a strong basis for future development steps, which should concentrate on multivalent approaches (including Sudan and Marburg strains). Additionally, prime-boost approaches should be a focus with a ChAd3-based vaccine for priming and boosted by a modified vaccinia Ankara-based vaccine. FUNDING: EU's Horizon 2020 research and innovation programme and GlaxoSmithKline Biologicals SA.

Safety, reactogenicity, and immunogenicity of a chimpanzee adenovirus vectored Ebola vaccine in children in Africa: a randomised, observer-blind, placebo-controlled, phase 2 trial.

BACKGROUND: During the large 2013-16 Ebola virus outbreak caused by the Zaire Ebola virus, about 20% of cases were reported in children. This study is the first, to our knowledge, to evaluate an Ebola vaccine in children younger than 6 years. We aimed to evaluate the safety, reactogenicity, and immunogenicity of a monovalent, recombinant, chimpanzee adenovirus type-3 vectored Zaire Ebola glycoprotein vaccine (ChAd3-EBO-Z) in a paediatric population. METHODS: This phase 2, randomised, observer-blind, controlled trial was done in a vaccine centre in Mali and a university hospital centre in Senegal. Healthy children were randomly assigned through a web-based system (1:1; stratified by age group, gender, and centre) to receive ChAd3-EBO-Z (day 0) and meningococcal serogroups A,C,W-135,Y tetanus toxoid conjugate vaccine (MenACWY-TT; month 6), or MenACWY-TT (day 0) and ChAd3-EBO-Z (month 6). The study was observer-blind from study start until interim day 30 analysis and became single-blind as of interim analysis. Primary outcomes assessed were serious adverse events (up to study end, month 12), solicited local or general adverse events (7 days post-vaccination), unsolicited adverse events (30 days post-vaccination), haematological or biochemical abnormalities, and clinical symptoms of thrombocytopenia (day 0-6). As secondary endpoints, we evaluated anti-glycoprotein Zaire Ebola virus antibody titres (ELISA) pre-vaccination and 30 days post-vaccination. This study is registered with ClinicalTrials.gov, NCT02548078. FINDINGS: From Nov 11, 2015, to May 9, 2016, of 776 children screened for eligibility, 600 were randomly assigned (200 [33%] in each age strata: 1-5, 6-12, 13-17 years), 300 (50%) to the ChAd3-EBO-Z/MenACWY-TT group and 300 (50%) to the MenACWY-TT/ChAd3-EBO-Z group; all were included in the total vaccinated cohort. Post-day 0 vaccination, the most common solicited injection site symptom was pain (127 [42%] of 300 in the ChAd3-EBO-Z/MenACWY-TT group vs 60 [20%] of 300 in the MenACWY-TT/ChAd3-EBO-Z group); the most common solicited general adverse event was fever (95 [32%] of 300 in the ChAd3-EBO-Z/MenACWY-TT group vs 28 [9%] of 300 in the MenACWY-TT/ChAd3-EBO-Z group). Unsolicited adverse events post-day 0 vaccination were reported by 41 (14%) of 300 participants in the ChAd3-EBO-Z/MenACWY-TT group and 24 (8%) of 300 MenACWY-TT/ChAd3-EBO-Z recipients. Serious adverse events were reported for two (1%) of 300 children in each group; none were considered vaccination related. No clinical symptoms of thrombocytopenia were reported. At day 30, anti-glycoprotein Ebola virus antibody geometric mean concentrations (GMC) in the ChAd3-EBO-Z/MenACWY-TT group were 1564 (95% CI 1340-1826) for those aged 13-17 years, 1395 (1175-1655) for 6-12 years, and 2406 (1942-2979) for 1-5 years. Anti-glycoprotein Ebola virus IgG antibody responses persisted up to 12 months post-vaccination, with a GMC of 716 (95% CI 619-828) for those aged 13-17 years, 752 (645-876) for 6-12 years, and 1424 (1119-1814) for 1-5 years. INTERPRETATION: ChAd3-EBO-Z was immunogenic and well tolerated in children aged 1-17 years. This study provides the first ChAd3-EBO-Z data in a paediatric population. Further development should focus on multivalent approaches including Sudan and Marburg strains, and heterologous prime-boost strategies, for instance using modified vaccinia Ankara-based vaccine to boost the immune response. FUNDING: EU's Horizon 2020 research and innovation programme and GlaxoSmithKline Biologicals SA.

Maternal Instruction About Jaundice and the Incidence of Acute Bilirubin Encephalopathy in Nigeria.

OBJECTIVE: To evaluate whether teaching mothers about neonatal jaundice will decrease the incidence of acute bilirubin encephalopathy among infants admitted for jaundice. STUDY DESIGN: This was a multicenter, before-after and cross-sectional study. Baseline incidences of encephalopathy were obtained at 4 collaborating medical centers between January 2014 and May 2015 (Phase 1). Structured jaundice instruction was then offered (May to November 2015; Phase 2) in antenatal clinics and postpartum. Descriptive statistics and logistic regression models compared 3 groups: 843 Phase 1 controls, 338 Phase 2 infants whose mothers received both antenatal and postnatal instruction (group A), and 215 Phase 2 infants whose mothers received no instruction (group B) either because the program was not offered to them or by choice. RESULTS: Acute bilirubin encephalopathy occurred in 147 of 843 (17%) Phase 1 and 85 of 659 (13%) Phase 2 admissions, which included 63 of 215 (29%) group B and 5 of 338 (1.5%) group A infants. OR for having acute bilirubin encephalopathy, comparing group A and group B infants adjusted for confounding risk factors, was 0.12 (95% CI 0.03-0.60). Delayed care-seeking (defined as an admission total bilirubin ≥18 mg/dL at age ≥48 hours) was the strongest single predictor of acute bilirubin encephalopathy (OR 11.4; 6.6-19.5). Instruction decreased delay from 49% to 17%. Other major risk factors were home births (OR 2.67; 1.69-4.22) and hemolytic disease (hematocrit ≤35% plus bilirubin ≥20 mg/dL) (OR 3.03; 1.77-5.18). The greater rate of acute bilirubin encephalopathy with home vs hospital birth disappeared if mothers received jaundice instruction. CONCLUSIONS: Providing information about jaundice to mothers was associated with a reduction in the incidence of bilirubin encephalopathy per hospital admission.

Improving the diagnosis of pulmonary tuberculosis using line probe assay and determining the factors associated with the disease in children in Jos, Nigeria.

INTRODUCTION: Diagnosing tuberculosis (TB), including pulmonary tuberculosis (PTB), in children remains a challenge, partly due to its paucibacillary nature in young children. Data on the use of line probe assay (LPA), on gastric and sputum samples, for diagnosing PTB in children are scarce. We determined the proportion of samples positive for Mycobacterium tuberculosis (MTB) by smear microscopy (SM) and LPA in presumptive PTB cases as well as the factors associated with PTB confirmed by LPA, in children in Jos, Nigeria. METHODS: An observational study in children aged 6 months-16 years. Gastric and sputum samples were examined by SM and by LPA for MTB using GenoType MTBDRplus Ver 2.0 (Hain Lifescience). Multivariate logistic regression was performed to determine the factors associated with PTB. RESULTS: Out of 103 children with presumptive PTB, 47 had confirmed PTB, 26 unconfirmed PTB and 30 unlikely PTB by LPA. In 67 gastric samples, MTB was identified by SM in 2 (3.0%) compared to 28 (41.8%) by LPA while in 31 sputum samples, MTB was identified by SM in 5 (16.1%) compared to 18 (58.1%) by LPA. The factors associated with pulmonary tuberculosis were an abnormal chest X-ray (adjusted odds ratio (AOR))=12.39 [3.75-40.90], p<0.001), sleeping in the same room with more than three persons (AOR=3.30 [1.23-8.85], p=0.018) and sleeping in a room with none or one window (AOR=2.86 [1.03-7.95], p=0.044). CONCLUSIONS: Line probe assay improves the diagnosis of pulmonary TB in children, especially with gastric samples, while an abnormal chest X-ray is a useful adjunct in PTB diagnosis. Avoiding overcrowding and having windows in sleeping rooms are a necessary part of TB prevention.

Effectiveness and Safety of Hydroxyurea in the Treatment of Sickle Cell Anaemia Children in Jos, North Central Nigeria.

BACKGROUND: Hydroxyurea has been shown to positively modify sickle cell disease pathogenesis, but its use is low among Nigerian sickle cell anaemia (SCA) patients because of effectiveness and safety concerns. METHODS: We conducted a quasi-experimental study to evaluate the effectiveness and safety of hydroxyurea in 54 SCA children aged 4-17 years. Clinical and haematological parameters were compared at baseline and 12 months after hydroxyurea therapy. The participants were monitored for adverse events. The parameters were compared using relative risk and Wilcoxon Signed-Rank Test. RESULTS: The number of subjects who had more than two episodes of painful crises reduced from 27 (50%) to 2 (2.7%) (p < 0.001), while those who had acute chest syndrome reduced from 6 (11.1%) to 0 (0.0%; p < 0.001). The risk of being transfused more than once was 0.11 times the risk in the 12 months period preceding therapy (95% CI = 0.02-0.85; p = 0.016). Similarly, the risk of hospital stay >7 days was 0.08 times the risk at the baseline (95% CI = 0.02-0.24; p < 0.0001). The median haematocrit and percentage foetal haemoglobin increased from 26 to 28% and 7.8 to 14%, respectively (p < 0.0001). A dose-dependent but reversible leucopenia was observed among six children (11.1%), otherwise, hydroxyurea was safe in the study population. CONCLUSION: Hydroxyurea is effective and safe in SCA children in Jos, Nigeria. The findings could strengthen educational programme aimed at improving the utilization of hydroxyurea among SCA children.

Clinical illness and outcomes in Nigerian children with persistent early-appearing anaemia following initiation of artemisinin-based combination treatments of uncomplicated falciparum malaria.

In non-anaemic children with malaria, early-appearing anaemia (EAA) is common following artemisinin-based combination treatments (ACTs) and it may become persistent (PEAA). The factors contributing to and kinetics of resolution of the deficit in haematocrit from baseline (DIHFB) characteristic of ACTs-related PEAA were evaluated in 540 consecutive children with malaria treated with artemether-lumefantrine, artesunate-amodiaquine or dihydroartemisinin-piperaquine. Asymptomatic PEAA occurred in 62 children. In a multiple logistic regression model, a duration of illness ≤3 days before presentation, haematocrit <35% before and <25% one day after treatment initiation, drug attributable fall in haematocrit ≥6%, and treatment with dihydroartemisinin-piperaquine independently predicted PEAA. Overall, mean DIHFB was 5.7% (95% CI 4.8-6.6) 7 days after treatment initiation and was similar for all treatments. Time to 90% reduction in DIHFB was significantly longer in artemether-lumefantrine-treated children compared with other treatments. In a one compartment model, declines in DIHFB were monoexponential with overall mean estimated half-time of 3.9 days (95% CI 2.6-5.1), Cmax of 7.6% (95% CI 6.7-8.4), and Vd of 0.17 L/kg (95% CI 0.04-0.95). In Bland-Altman analyses, overall mean anaemia recovery time (AnRT) of 17.4 days (95% CI 15.5-19.4) showed insignificant bias with 4, 5 or 6 multiples of half-time of DIHFB. Ten children after recovery from PEAA progressed to late-appearing anaemia (LAA). Progression was associated with female gender and artesunate-amodiaquine treatment. Asymptomatic PEAA is common following ACTs. PEAA or its progression to LAA may have implications for case and community management of anaemia and for anaemia control efforts in sub-Saharan Africa where ACTs have become first-line antimalarials. Trial registration: Pan Africa Clinical Trial Registration PACTR201709002064150, 1 March 2017 http://www.pactr.org.