Antivirals for prevention of hepatitis B virus mother-to-child transmission in human immunodeficiency virus positive pregnant women co-infected with hepatitis B virus.

BACKGROUND: Hepatitis B virus (HBV)-human Immunodeficiency virus (HIV) co-infection promotes an aggressive disease course of HBV infection. In the only available non-Cochrane systematic review on antiviral therapy during pregnancy for prevention of mother-to-child transmission of HBV, none of the women studied had HBV-HIV co-infection but were either HBV- or HIV-seropositive. Treatment of HBV alone may develop HIV-strains that are resistant to non-nucleoside reverse transcriptase inhibitors. Accordingly, co-treatment of the HIV infection is recommended. OBJECTIVES: To evaluate the benefits and harms of tenofovir-based antiviral combination regimens versus placebo, tenofovir alone, or non-tenofovir-based antiviral regimen either alone or in combination with HBV for the prevention of mother-to-child transmission of HBV in HIV-positive pregnant women co-infected with HBV. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials, MEDLINE Ovid, Embase Ovid, LILACS (Bireme), Science Citation Index Expanded (Web of Science), and Conference Proceedings Citation Index-Science (Web of Science) on 30 January 2023. We manually searched the reference lists of included trials, searched on-line trial registries, and contacted experts in the field and pharmaceutical companies for any further potential trials. SELECTION CRITERIA: We aimed to include randomised clinical trials comparing tenofovir-based antiviral combination regimens (anti-HIV regimen with lopinavir-ritonavir therapy, or any other antiviral therapy, and two drugs with activity against HBV, specifically, tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF), plus lamivudine or emtricitabine) with placebo alone, or tenofovir alone, or non-tenofovir-based antiviral regimen (zidovudine, lamivudine, telbivudine, emtricitabine, entecavir, lopinavir-ritonavir, or any other antiviral therapy) either alone or in combination with at least two other antivirals. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Primary outcomes included all-cause infant mortality, proportion of infants with serious adverse events, proportion of infants with HBV mother-to-child transmission, all-cause maternal mortality, and proportion of mothers with serious adverse events. Secondary outcomes included proportion of infants with adverse events not considered serious, proportion of mothers with detectable HBV DNA (deoxyribonucleic acid) (before delivery), maternal hepatitis B e antigen (HBeAg) to HBe-antibody seroconversion (before delivery) and maternal adverse events not considered serious. We used RevMan Web to carry out analyses and presented results, where feasible, using a random-effects model and risk ratios (RR) with 95% confidence intervals (CIs). We performed sensitivity analysis. We assessed risk of bias using predefined domains, assessed the certainty of the evidence using GRADE, controlled risk of random errors with Trial Sequential Analysis, and presented outcome results in a summary of findings table. MAIN RESULTS: Five completed trials were included, of which four trials contributed data to one or more of the outcomes. They included a total of 533 participants randomised to tenofovir-based antiviral combination regimens (196 participants) versus control (337 participants). The control groups received non-tenofovir-based antiviral regimens either as zidovudine alone (three trials) or as a combination of zidovudine, lamivudine and lopinavir-ritonavir (five trials). None of the trials used placebo or tenofovir alone. All trials were at unclear risk of bias. Four trials used intention-to-treat analyses. In the remaining trial, two participants in the intervention group and two in the control group were lost to follow-up. However, the outcomes of these four participants were not described. Tenofovir-based antiviral combination regimen versus control We are very uncertain about the effect of a tenofovir-based antiviral combination regimen versus control on all-cause infant mortality (RR 2.24, 95% CI 0.72 to 6.96; participants = 132; trials = 1; very low-certainty evidence); proportion of infants with serious adverse events (RR 1.76, 95% CI 1.27 to 2.43; participants = 132; trials = 1; very low-certainty evidence), and proportion of mothers with serious adverse events (RR 0.90, 95% CI 0.62 to 1.32; participants = 262; trials = 2; very low-certainty evidence). No trial reported data on the proportion of infants with HBV mother-to-child transmission and all-cause maternal mortality. We are also very uncertain about the effect of tenofovir-based antiviral combination regimens versus control on the proportion of infants with adverse events not considered serious (RR 0.94, 95% CI 0.06 to 13.68; participants = 31; trials = 1; very low-certainty evidence), and proportion of mothers with detectable HBV DNA (before delivery) (RR 0.66, 95% CI 0.42 to 1.02; participants = 169; trials = 2; very low-certainty evidence). No trial reported data on maternal hepatitis B e antigen (HBeAg) to HBe-antibody seroconversion (before delivery) and maternal adverse events not considered serious. All trials received support from industry. AUTHORS' CONCLUSIONS: We do not know what the effects of tenofovir-based antiviral combination regimens are on all-cause infant mortality, proportion of infants with serious adverse events and proportion of mothers with serious adverse events, proportion of infants with adverse events not considered serious, and proportion of mothers with detectable HBV DNA before delivery because the certainty of evidence was very low. Only one or two trials, with insufficient power, contributed data for analyses. We lack randomised clinical trials at low risk of systematic and random errors, and fully reporting all-cause infant mortality, serious adverse events and reporting on clinical and laboratory outcomes, such as infants with HBV mother-to-child transmission, all-cause maternal mortality, maternal hepatitis B e antigen (HBeAg) to HBe-antibody seroconversion before delivery and maternal adverse events not considered serious.

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.

Haemostatic profile of children with nephrotic syndrome attending University of Nigeria Teaching Hospital Ituku-Ozalla, Nigeria.

BACKGROUND: Haemostatic derangements are thought to be due to an imbalance between hepatic synthesis of pro-coagulants and urinary losses of anticoagulants. OBJECTIVES: This study evaluated the coagulation profile of Nigerian children with nephrotic syndrome and examined the relationship between coagulation variables, disease state and steroid responsiveness. METHODS: A cross- sectional hospital based study on evaluation of coagulation profile of children with nephrotic syndrome compared with their age- and gender- matched controls. RESULTS: The median fibrinogen level in subjects and controls was the same (2.9 g/L). Sixteen of 46 (35%) children with nephrotic syndrome had hyperfibrinogenaemia. The median fibrinogen level of children in remission was 2.3 g/L and differed significantly when compared with those of children in relapse (p = 0.001). The median APTT of children with nephrotic syndrome was 45.0 s and differed significantly compared with those of controls (42.0 s) (p value = 0.02). The median prothrombin time in children with and without nephrotic syndrome were 12.0 and 13.0 s respectively, (p = 0.004). About 90% of children with nephrotic syndrome had INR within reference range. Thrombocytosis was found in 15% of children with nephrotic syndrome. The median platelet count in children with new disease was 432 × 103cells/mm3 and differed significantly when compared with those of controls (p = 0.01). INR was significantly shorter in children with steroid resistant nephrotic syndrome (SRNS) (median 0.8 s; IQR 0.8 -0.9 s) compared with controls (median 1.0 s; IQR 1.0 -1.1 s) (p = 0.01). Steroid sensitivity was the strongest predictor of remission in children with nephrotic syndrome; steroid sensitive patients were 30 times more likely to be in remission than in relapse (OR 30.03; CI 2.01 - 448.04). CONCLUSION: This study shows that the haemostatic derangements in childhood nephrotic involve mostly fibrinogen, APTT, PT, INR and platelet counts. Antithrombin levels are largely unaffected. Variations in fibrinogen, APTT, PT and INR values may be due to the heterogeneous nature of the disease.

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.

The effectiveness of locally-prepared peritoneal dialysate in the management of children with acute kidney injury in a south-east Nigerian tertiary hospital.

Background: Peritoneal dialysis (PD) is the preferred mode of renal replacement therapy (RRT) in children with acute kidney injury (AKI). The gold standard remains the use of commercially-prepared PD fluid. In resource-poor nations, its availability and affordability remain a challenge. Aim: This study aims to report the effectiveness of locally-prepared PD fluid in the management of AKI in a south-east Nigerian tertiary hospital. Subjects and Methods: This was a retrospective study conducted at the paediatric ward of the University of Nigeria Teaching hospital, Enugu. The case records of 36 children seen over three years, diagnosed with AKI and requiring PD were reviewed. The retrieved information comprised biodata, aetiology of AKI, indications for PD, pre-and post-dialysis estimated glomerular filtration rate (eGFR) and patient outcomes. Results: The children (20 males and 16 females) were aged 3 to 36 months with a mean age of 9.92 ± 6.29 months. The common aetiologies of AKI were septicemia (30.6%), hemolytic uremic syndrome (19.4%), and toxic nephropathy (16.7%). The frequent indications for PD were uremic encephalopathy (58.3%) and severe metabolic acidosis (38.8%). The pre-and post-dialysis mean urine flow rate was 0.16 + 0.13 and 2.77 + 0.56 ml/kg/hour respectively. The eGFR before PD, at discontinuation, and a week later was 6.06 + 2.87, 24.44 + 15.71 and 59.07 + 22.22 mls/min/1.73m2 respectively. Conclusion: PD with locally-prepared dialysate is safe, effective and a life-saving alternative in the management of AKI in children.

Trends in the epidemiology of childhood nephrotic syndrome in Africa: A systematic review.

Background: Childhood nephrotic syndrome, if left untreated, leads to progressive kidney disease or death. We quantified the prevalence of steroid-sensitive nephrotic syndrome, steroid-resistant nephrotic syndrome, and histological types as the epidemiology of nephrotic syndrome in Africa remains unknown, yet impacts outcomes. Methods: We searched MEDLINE, Embase, African Journals Online, and WHO Global Health Library for articles in any language reporting on childhood nephrotic syndrome in Africa from January 1, 1946 to July 1, 2020. Primary outcomes included steroid response, biopsy defined minimal change disease, and focal segmental glomerulosclerosis (FSGS) by both pooled and individual proportions across regions and overall. Findings: There were 81 papers from 17 countries included. Majority of 8131 children were steroid-sensitive (64% [95% CI: 63-66%]) and the remaining were steroid-resistant (34% [95% CI: 33-35%]). Of children biopsied, pathological findings were 38% [95% CI: 36-40%] minimal change, 24% [95% CI: 22-25%] FSGS, and 38% [95% CI: 36-40%] secondary causes of nephrotic syndrome. Interpretation: Few African countries reported on the prevalence of childhood nephrotic syndrome. Steroid-sensitive disease is more common than steroid-resistant disease although prevalence of steroid-resistant nephrotic syndrome is higher than reported globally. Pathology findings suggest minimal change and secondary causes are common. Scarcity of data in Africa prevents appropriate healthcare resource allocation to diagnose and treat this treatable childhood kidney disease to prevent poor health outcomes. Funding: Funding was provided by the Canadian Institute for Health Research (CIHR) and the National Institute of Health (NIH) for the H3 Africa Kidney Disease Research Network. This research was undertaken, in part, from the Canada Research Chairs program.

The current status of kidney transplantation in Nigerian children: still awaiting light at the end of the tunnel.

BACKGROUND: Kidney transplantation (KT) is the gold standard treatment for children with chronic kidney disease stage 5 (CKD5). It is easily accessible in well-resourced countries, but not in low/middle-income countries (LMICs). We present, a multicentre experience of paediatric KT of children domiciled in Nigeria. We aim to highlight the challenges and ethical dilemmas that children, their parents or guardians and health care staff face on a daily basis. METHODS: A multicentre survey of Nigerian children who received KTs within or outside Nigeria from 1986 to 2019 was undertaken using a questionnaire emailed to all paediatric and adult consultants who are responsible for the care of children with kidney diseases in Nigeria. Demographic data, causes of CKD5, sources of funding, donor organs and graft and patient outcome were analysed. Using Kaplan-Meier survival analysis, we compared graft and patient survival. RESULTS: Twenty-two children, aged 4-18 years, received 23 KTs, of which 12 were performed in Nigeria. The male-to-female ratio was 3.4:1. Duration of pre-transplant haemodialysis was 4-48 months (median 7 months). Sixteen KTs were self-funded. State governments funded 3 philanthropists 4 KTs. Overall differences in graft and patient survival between the two groups, log rank test P = 0.68 and 0.40, respectively were not statistically significant. CONCLUSIONS: The transplant access rate for Nigerian children is dismal at < 0.2%. Poor funding is a major challenge. There is an urgent need for the federal government to fund health care and particularly KTs. Graphical Abstract.

Sickle Cell Nephropathy and Associated Factors among Asymptomatic Children with Sickle Cell Anaemia.

BACKGROUND: Sickle cell nephropathy (SCN) is a serious complication of sickle cell anaemia (SCA) with asymptomatic onset in childhood and possible progression to chronic kidney disease (CKD). In Southeast Nigeria, few studies have evaluated renal function in paediatric SCA patients for early detection of renal impairment and early intervention to reduce morbidity and mortality. Therefore, this study evaluated the renal function of paediatric SCA patients in a steady state based on glomerular filtration rate and urinalysis findings (proteinuria and haematuria). METHODS: A cross-sectional study of consecutively recruited sixty haemoglobin SS (HbSS) children in a steady state and sixty age- and sex-matched haemoglobin AA (HbAA) controls aged 2-18 years was done. Renal function of HbSS subjects was evaluated using estimated glomerular filtration rate (eGFR) which was compared with healthy HbAA subjects. The prevalence of significant proteinuria and haematuria, its association with eGFR, and the effect of past sickle cell crisis (in the preceding 24 months) on renal function were also evaluated. RESULTS: Mean eGFR was significantly higher in HbSS subjects than in the HbAA subjects (p = 0.001) and decreased with age. Significant proteinuria and haematuria were more prevalent in the HbSS group (3.4% and 6.7%, respectively) compared to the HbAA subjects (0% and 0%, respectively) (p = 0.496 and 0.119, respectively). No significant association was observed between eGFR and proteinuria (p = 1.000) or haematuria (p = 1.000). There was a positive correlation between eGFR and frequency of past painful crisis that required hospitalization (r = 0.138, p = 0.295) and between eGFR and frequency of blood transfusion (r = 0.679, p ≤ 0.001). CONCLUSIONS: Asymptomatic paediatric HbSS (SCA) patients had higher mean eGFR indicating an increased risk of nephropathy. There was no association between eGFR and proteinuria or haematuria. Frequent sickle cell crises especially one requiring transfusion were positively correlated with hyperfiltration.

Pre-Transition Readiness in Adolescents and Young Adults with Four Chronic Medical Conditions in South East Nigeria - An African Perspective to Adolescent Transition.

INTRODUCTION: When a child reaches a certain age, he or she moves over to the adult physician. For this to maximally benefit the child, there has to be a process of equipping the child with skills required for taking on more responsibilities. Transitioning involves a process in which the adolescent with chronic illness is prepared ahead of time to enable them to eventually transfer to adult care with good outcomes. In high-income countries with well-organized health financing, the transitioning process begins as early as 12 years. In Africa, this process is not as organized and most hospitals would write a referral letter once the child turns 18 and transfer to adult clinic. In four of our chronic disease clinics (asthma, HIV, sickle cell anaemia and chronic kidney diseases) patients up to 24 years old are still attending the paediatric clinics. Understanding transition readiness among African adolescents remains a gap. Our findings will form a basis for informed practices for adolescent clinics in African countries. METHODS: This was a descriptive cross-sectional study of pre-transition readiness in adolescents and young adults with chronic illnesses attending four outpatient specialist clinics in a tertiary hospital in Enugu Nigeria. This was done using the validated STARx Questionnaire. Total scores were computed and scores nearer the upper limit of 90 were acceptable, while mean subdomain scores of 4 and above were considered as optimal level of transition readiness. Demographic and clinical data were also collected. Acceptability to move on to adult-oriented care was documented using binary response (yes/no). Cross tabulations were done, and likelihood ratios obtained for predictors of acceptability of transition. Significant value was set at p-value of ≤0.05. RESULTS: A total of 142 adolescents and young adults aged 12 to 24 years were studied. There were 38.0% (54), 24.6% (35), 22.5% (32) and 14.8% (21) from HIV, sickle cell anaemia, asthma and nephrology clinics, respectively. Their mean age was 15.6 years ± 2.4, and 48.6% (69) were male. The mean total transition readiness score was 56±14 and this was not nearer the higher spectrum of total scores obtainable. Highest mean scores (3.7) occurred in the knowledge subdomain while least mean score (2) was noted in the use of medication reminders. The males had highest scores in the knowledge subdomain while the females were better informed about medication adherence and were more inquisitive about their chronic illness. Only about 37% (53) of the adolescents and young adults welcomed the idea of moving on to adult-care clinics. Children who had less frequent emergency hospital visits and better treatment outcome accepted the idea of transfer to adult care. Irrespective of the age all participants had suboptimal subdomain scores. High scores did not influence the participants' choice to embrace transfer to adult care. CONCLUSION: There is suboptimal transition readiness irrespective of the age. The older age groups were less willing to transfer to adult care. Better disease knowledge and better communication skills did not positively influence acceptability of transfer to adult care.

Relationship between renal dimensions using ultrasonography and body mass index in apparently healthy school children in Port Harcourt, Nigeria

Background: Renal size is an important parameter in evaluation and management of a child with kidney disease. Establishing the normal limits of renal sizes standardized against somatometric parameters will be a useful tool in detecting probable renal diseases in children.Aim: To determine renal sizes in relation to body mass index (BMI) in apparently healthy primary school children in Port Harcourt.Materials and Methods: This was a cross-sectional and multi-staged study involving 450 children aged 6-12 years. Renal ultrasonography was carried out using a portable DP 1100 PLUS real time ultrasound machine fitted with 3.5MHz probe. The length, width and anteroposterior diameter of the kidneys were measured, and renal volume calculated. The BMI percentile for age and sex were obtained. The renal sizes were correlated with somatometric parameters and regression equations derived.Results: The mean renal length and volume percentiles increased from 77.7 ± 5.6 and 49.2 ± 13.7 at 6years to 85.9 ± 5.9 and 60.4 ± 18.4 at 12years respectively. There were no significant differences in the length and volume between the right and left kidneys, and dimensions of the kidneys were not statistically different in males and females. There was a significant positive correlation between BMI and renal dimensions. The renal length and volume increased at a rate of 1.372mm and 1.951cm3 per year and at a rate of 0.067mm and 0.176cm3 per one percentile increase in BMI respectively. The regression model derived for predicting renal length in mm =65.731 + (1.372 Age X) + (0.067 BMI percentile X) while that for renal volume in cm3 =26.386 + (1.951 Age X) + (0.176 BMI percentile X), (Where X is the independent variables: age in years and BMI in percentile).Conclusion: BMI has a significant positive linear relationship with renal dimensions. This study has provided prediction models for deriving renal length and volume from subject's BMI and age

Declining responsiveness of childhood Plasmodium falciparum infections to artemisinin-based combination treatments ten years following deployment as first-line antimalarials in Nigeria.

BACKGROUND: The development and spread of artemisinin-resistant Plasmodium falciparum malaria in Greater Mekong Subregion has created impetus for continuing global monitoring of efficacy of artemisinin-based combination therapies (ACTs). This post analyses is aimed to evaluate changes in early treatment response markers 10 years after the adoption of ACTs as first-line treatments of uncomplicated falciparum malaria in Nigeria. METHODS: At 14 sentinel sites in six geographical areas of Nigeria, we evaluated treatment responses in 1341 children under 5 years and in additional 360 children under 16 years with uncomplicated malaria enrolled in randomized trials of artemether-lumefantrine versus artesunate-amodiaquine at 5-year interval in 2009-2010 and 2014-2015 and at 2-year interval in 2009-2010 and 2012-2015, respectively after deployment in 2005. RESULTS: Asexual parasite positivity 1 day after treatment initiation (APPD1) rose from 54 to 62% and 2 days after treatment initiation from 5 to 26% in 2009-2010 to 2014-2015 (P = 0.002 and P <  0.0001, respectively). Parasite clearance time increased significantly from 1.6 days (95% confidence interval [CI]: 1.55-1.64) to 1.9 days (95% CI, 1.9-2.0) and geometric mean parasite reduction ratio 2 days after treatment initiation decreased significantly from 11 000 to 4700 within the same time period (P <  0.0001 for each). Enrolment parasitaemia > 75 000 µl- 1, haematocrit > 27% 1 day post-treatment initiation, treatment with artemether-lumefantrine and enrolment in 2014-2015 independently predicted APPD1. In parallel, Kaplan-Meier estimated risk of recurrent infections by day 28 rose from 8 to 14% (P = 0.005) and from 9 to 15% (P = 0.02) with artemether-lumefantrine and artesunate-amodiaquine, respectively. Mean asexual parasitaemia half-life increased significantly from 1.1 h to 1.3 h within 2 years (P <  0.0001). CONCLUSIONS: These data indicate declining parasitological responses through time to the two ACTs may be due to emergence of parasites with reduced susceptibility or decrease in immunity to the infections in these children. TRIAL REGISTRATION: Pan African Clinical Trial Registration PACTR201508001188143 , 3 July 2015; PACTR201508001191898 , 7 July 2015 and PACTR201508001193368 , 8 July 2015 PACTR201510001189370 , 3 July 2015; PACTR201709002064150 , 1 March 2017; https://www.pactr.samrca.ac.za.

Characterization of Plasmodium falciparum structure in Nigeria with malaria SNPs barcode.

BACKGROUND: Plasmodium falciparum malaria remains a major health challenge in Nigeria despite the global decline of its incidence and mortality rates. Although significant progress has been made in preventing the transmission of P. falciparum and controlling the spread of the infection, there is much to be done in the area of proper monitoring, surveillance of the parasite, investigating the population dynamics and drug resistance profiling of the parasite as these are important to its eventual eradication. Polymorphic loci of msp1, msp2 and/or glurp genes or microsatellites have been traditionally used to characterize P. falciparum population structure in various parts of Nigeria. The lack of standardization in the interpretation of results, as well as the inability of these methods to distinguish closely related parasites, remains a limitation of these techniques. Conversely, the recently developed 24 single nucleotide polymorphism (SNP)-based molecular barcode assay has the possibility of differentiating between closely related parasites and offer additional information in determining the population diversity of P. falciparum within and between parasite populations. This study is therefore aimed at defining the population diversity of P. falciparum in and between two localities in Nigeria using the SNPs barcode technique. METHODS: The 24-SNP high-resolution melt (HRM) barcode assay and msp2 genotyping was used to investigate both intra and inter population diversity of the parasite population in two urban cities of Nigeria. RESULTS: Based on SNP barcode analysis, polygenomic malaria infections were observed in 17.9% and 13.5% of population from Enugu and Ibadan, respectively, while msp2 analyses showed 21% and 19.4% polygenomic infections in Enugu and Ibadan, respectively. Low levels of genetic diversity (π) of 0.328 and 0.318 were observed in Enugu and Ibadan parasite populations, respectively, while the FST value of 0.02 (p = 0.055) was obtained when the genetic divergence of both populations was considered. CONCLUSIONS: The 24-SNP barcode assay was effective in analysing P. falciparum population diversity. This study also showed that P. falciparum populations in Enugu and Ibadan had a degree of intra-population diversity, but very low divergence between the population. A low degree of polygenomic infections were also observed in the two parasite populations unlike previous years. This maybe as a result of the effect of artemisinin-based combination therapy (ACT), long-lasting insecticide-treated nets (LLITNs) and intermittent preventive treatments in the study populations.

Profile of chronic kidney disease modifiable risk factors in a rural community of south east Nigeria.

BACKGROUND: Chronic kidney disease (CKD) is on the increase globally. Prevention of this condition is ideal, however early detection of the disease becomes desirable where the disease process has begun as there are known interventions which can slow the progress to end stage renal disease (ESRD). This study aimed at detecting the profile of some modifiable risk factors for CKD in a cohort of household heads in a rural community with limited resources for managing chronic kidney diseases. METHODS: The study was conducted in a rural community in southeast Nigeria. One hundred and forty five household heads from randomly selected households were interviewed. Their blood pressures were taken and their urine tested. The data was analyzed using SPSS version 21. Simple frequencies and means were calculated. RESULTS: A total of 145 house hold heads were enrolled. Their mean age was 45.08 (19.65) years. Forty-seven percent had no prior knowledge of their blood pressure and 31.5% were found to be hypertensive. Only one study participant (1%) had ever had a urinalysis test and proteinuria and glycosuria were found in 50.4 and 27.9% respectively. Most (75%) patronized patent medicine vendors for their primary healthcare while 31.8% had taken herbal mixtures in the past. CONCLUSION: There are presently many modifiable risk factors for the development of chronic kidney disease in rural communities in south-east Nigeria. Urgent targeted intervention is required to forestall an epidemic of CKD in the near future.

Provider and patient perceptions of malaria rapid diagnostic test use in Nigeria: a cross-sectional evaluation.

BACKGROUND: Nigeria commenced a phased programmatic deployment of rapid diagnostic tests (RDT) at the primary health care (PHC) facility levels since 2011. Despite various efforts, the national testing rate for malaria is still very low. The uptake of RDT has been variable. This study was undertaken to determine the provider and patient perceptions to RDT use at the PHC level in Nigeria with their implications for improving uptake and compliance. METHODS: A cross-sectional survey was conducted in 120 randomly selected PHCs across six states, across the six-geopolitical zones of Nigeria in January 2013. Health facility staff interviews were conducted to assess health workers (HW) perception, prescription practices and determinants of RDT use. Patient exit interviews were conducted to assess patient perception of RDT from ten patients/caregivers who met the eligibility criterion and were consecutively selected in each PHC, and to determine HW's compliance with RDT test results indirectly. Community members, each selected by their ward development committees in each Local Government Area were recruited for focus group discussion on their perceptions to RDT use. RESULTS: Health workers would use RDT results because of confidence in RDT results (95.4%) and its reduction in irrational use of artemisinin-based combination therapy (ACT) (87.2%). However, in Enugu state, RDT was not used by health workers because of the pervasive notion RDT that results were inaccurate. Among the 1207 exit interviews conducted, 549 (45.5%) had received RDT test. Compliance rate (administering ACT to positive patients and withholding ACT from negative patients) from patient exit interviews was 90.2%. Among caregivers/patients who had RDT done, over 95% knew that RDT tested for malaria, felt it was necessary and liked the test. Age of patients less than 5 years (p = 0.04) and "high" educational status (p = 0.0006) were factors influencing HW's prescription of ACT to RDT negative patients. CONCLUSION: The study demonstrated positive perception to RDT use by HW and among community members with good compliance rate among health workers at the PHC level. This positive perception should be explored in improving the current low level of malaria testing in Nigeria while addressing the influence of age on HW administration of ACT to RDT negative cases.

National survey found that managing childhood nephrotic syndrome in Nigeria varied widely and did not comply with the best evidence.

AIM: This study explored any variations in managing childhood nephrotic syndrome between specialist centres in Nigeria and how closely the care reflected the best available evidence. METHODS: In 2016, the heads of Nigerian paediatric nephrology units were asked to complete a study questionnaire that focused on managing nephrotic syndrome. RESULTS: Of the 31 clinicians we approached, 81% returned the completed questionnaire. The majority (64%) had received paediatric nephrology training and 40% had practised for at least 10 years. We found that 60% prescribed an initial daily prednisolone for four weeks before reducing the dose and 32% prescribed it for six weeks. However, more marked variations were observed with the total steroid duration for new-onset nephrotic syndrome, with 16%, 44% and 40% prescribing prednisolone for 8, 12 and at least 16 weeks, respectively. Similarly, 56% prescribed prednisolone for less than eight weeks before diagnosing steroid-resistant nephrotic syndrome (SRNS) and 12% rarely requested a kidney biopsy for SRNS. In addition, 32% of the respondents preferred cyclophosphamide to calcineurin inhibitors for SRNS. CONCLUSION: There were significant variations in the management of childhood nephrotic syndrome in Nigeria and the diagnosis and treatment of SRNS differed substantially from the best available evidence.

Anaemia following Artemisinin-Based Combination Treatments of Uncomplicated Plasmodium falciparum Malaria in Children: Temporal Patterns of Haematocrit and the Use of Uncomplicated Hyperparasitaemia as a Model for Evaluating Late-Appearing Anaemia.

BACKGROUND: In severe malaria, intravenous artesunate may cause delayed haemolytic anaemia but there has been little evaluation of the propensity of oral artemisinin-based combination treatments (ACTs) to cause late-appearing anaemia. METHODS: The frequency of anaemia (haematocrit <30%), and temporal changes in haematocrit were evaluated in 1,191 malarious children following ACTs. "Haematocrit conservation" was evaluated by using the fall in haematocrit/1,000 asexual parasites cleared from the peripheral blood (FIH/1,000 asexual parasites cpb), and the ratio of the average haematocrit (on the first 3 days of starting treatment):total parasitaemia cleared. RESULTS: The frequency of anaemia decreased significantly following treatment. FIH/1,000 asexual parasites cpb, average haematocrit:total parasitaemia cleared, and mean haematocrit 5 weeks after treatment began were significantly lower in hyperparasitaemic children than in children without hyperparasitaemia, suggesting haematocrit conservation during treatment followed later by a loss of haematocrit. Asymptomatic late-appearing anaemia occurred in 6% of the children. CONCLUSION: Artesunate-amodiaquine and artemether-lumefantrine contribute to haematocrit conservation at high parasitaemias but may cause late-appearing anaemia.

Therapeutic efficacy and effects of artemisinin-based combination treatments on uncomplicated Plasmodium falciparum malaria -associated anaemia in Nigerian children during seven years of adoption as first-line treatments.

BACKGROUND: Artemisinin-based combination treatments (ACTs) are the first-line treatments of uncomplicated Plasmodium falciparum malaria in many endemic areas but there are few evaluation of their efficacy in anaemic malarious children. METHODS: Therapeutic efficacy of 3-day regimens of artesunate-amodiaquine and artemether-lumefantrine was evaluated in 437 anaemic and 909 non-anaemic malarious children following treatment during a seven-year period (2008-2014). Patterns of temporal changes in haematocrit were classified based on haematocrit values <30% and ≥30%. Kinetics of the disposition of the deficit in haematocrit from 30% following treatment were evaluated using a non-compartment model. RESULTS: PCR-corrected parasitological efficacy 28 days after start of treatment was significantly higher in artesunate-amodiaquine- compared to artemether-lumefantrine-treated children [97% (95%CI: 92.8-100) versus 96.4% (95%CI: 91.3-99.4), P = 0.02], but it was similar in non-anaemic and anaemic children. Fall in haematocrit/1 000 asexual parasites cleared from peripheral blood was significantly greater at lower compared to higher parasitaemias (P < 0.0001), and in non-anaemic compared to anaemic children (P = 0.007). In anaemic children at presentation, mean anaemia recovery time (AnRT) was 15.4 days (95%CI: 13.3-17.4) and it did not change over the years. Declines in haematocrit deficits from 30% were monoexponential with mean estimated half-time of 1.4 days (95%CI: 1.2-1.6). Anaemia half-time (t½anaemia) correlated positively with AnRT in the same patients (r = 0.69, P < 0.0001). Bland-Altman analysis of 10 multiples of t½anaemia and AnRT showed narrow limit of agreement with insignificant bias (P = 0.07) suggesting both can be used interchangeably in the same patients. CONCLUSIONS: Artesunate-amodiaquine and artemether-lumefantrine remain efficacious treatments of uncomplicated P. falciparum infections in non-anaemic and anaemic Nigerian children in the last 7 years of adoption as first-line treatments. These ACTs may also conserve haematocrit at high parasitaemias and in anaemic children. TRIALS REGISTRATION: Pan African Clinical Trial Registry PACTR201508001188143 , 3 July 2015; PACTR201510001189370 , 3 July 2015; PACTR201508001191898 , 7 July 2015 and PACTR201508001193368 , 8 July 2015.

Status of the use and compliance with malaria rapid diagnostic tests in formal private health facilities in Nigeria.

BACKGROUND: Nigeria has the largest number of malaria-related deaths, accounting for a third of global malaria deaths. It is important that the country attains universal coverage of key malaria interventions, one of which is the policy of universal testing before treatment, which the country has recently adopted. However, there is a dearth of data on its implementation in formal private health facilities, where close to a third of the population seek health care. This study identified the level of use of malaria rapid diagnostic testing (RDT), compliance with test results and associated challenges in the formal private health facilities in Nigeria. METHODS: A cross-sectional study that involved a multi-stage, random sampling of 240 formal private health facilities from the country's six geo-political zones was conducted from July to August 2014. Data were collected using health facility records, healthcare workers' interviews and an exit survey of febrile patients seen at the facilities, in order to determine fever prevalence, level of testing of febrile patience, compliance with test results, and health workers' perceptions to RDT use. RESULTS: Data from the 201 health facilities analysed indicated a fever prevalence of 38.5% (112,521/292,430). Of the 2077 exit interviews for febrile patients, malaria testing was ordered in 73.8% (95% CI 71.7-75.7%). Among the 1270 tested, 61.8% (719/1270) were tested with microscopy and 38.2% (445/1270) with RDT. Compliance to malaria test result [administering arteminisin-based combination therapy (ACT) to positive patients and withholding ACT from negative patients] was 80.9% (95% CI 78.7-83%). Compliance was not influenced by the age of patients or type of malaria test. The health facilities have various cadres of the health workers knowledgeable on RDT with 70% knowing the meaning, while 84.5% knew what it assesses. However, there was clearly a preference for microscopy as only 20% reported performing only RDT. CONCLUSION: In formal private health facilities in Nigeria there is a high rate of malaria testing for febrile patients, high level of compliance with test results but relatively low level of RDT utilization. This calls for improved engagement of the formal private health sector with a view to achieving universal coverage targets on malaria testing.

Chronic kidney disease in children and the role of epigenetics: Future therapeutic trajectories.

Global differences in the observed causes of chronic kidney disease (CKD) in children are well documented and are attributed to dissimilarities in clime, race, hereditary, and ancestry. Thus, familial clustering and disparities in CKD prevalence rates across ethnic and racial groups indicate that the progression of renal disease has a strong genetic component. Mammalian studies have demonstrated a feasible nexus between nutrition and non-genetic exposure (around the time of conception and in epigenetic changes) in the expression of major genes identified in renal organogenesis. The major consequence is a reduction in the number of nephrons, with subsequent predisposition to hypertension and CKD. Identifying these epigenetic changes is crucial (due to their potentially reversible nature), as they may serve as future therapeutic targets to prevent kidney fibrosis and CKD. Despite progress in the field of epigenetics in oncology, research in other subspecialties of medicine is largely experimental with few existing studies regarding the clinical implication of epigenetics in renal disease. Therapeutic trajectories for CKD in children based on the influence of epigenetics may eventually revolutionize the management of this disease. The aim of the current narrative review is to appraise the role of epigenetics in CKD, and highlight the potential future therapeutic pathways.

Urinary screening for asymptomatic renal disorders in pre-school children in Enugu metropolis, South-east Nigeria: Useful or useless.

To evaluate the usefulness of simple screening tests such as urinalysis and blood pressure measurement in the early detection of renal disorders in pre-School children, we used a multi-staged random sampling method to select subjects from registered nursery schools within Enugu metropolis in south-east Nigeria. We selected 630 children for this cohort study. There was a prevalence of 2.7%, 0% and 1.9% for asymptomatic proteinuria, hematuria and hypertension, respectively. There was no age, gender or social class preponderance (P = 0.44). Hypertension seemed to be limited to children close to the age group of five years (P <0.001). No correlations could be documented between asymptomatic proteinuria, hematuria or hypertension. The prevalence of persistent proteinuria was found to be 1.6% and the mean urinary protein excretion estimation (spot urine protein/creatinine) was 1.88 g/mg ± 0.53, with a mean glomerular filtration rate of 78.7 ± 12.6 mL/min/1.73 m³ . Renal ultrasonography revealed abnormal findings in 30% of the children with persistent proteinuria. Asymptomatic persistent proteinuria with or without hematuria and hypertension could be a presumptive evidence of an underlying renal parenchymal disease and should be properly investigated and followed-up.