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A correction to the article "Genome-wide association analyses identifies a susceptibility locus for tuberculosis on chromosome 18q11.2" that was published in the August 8, 2010 issue is presented.

Introduction: In South Africa, only children considered eligible for transplantation are offered dialysis as bridge to kidney transplantation. Maintenance peritoneal dialysis (PD) is preferred and has several advantages over hemodialysis (HD). While awaiting transplantation, PD may be discontinued due to permanent transfer to HD or death while on PD, of which the occurrence and burden is not known in our setting. We investigated the rate of discontinuation of maintenance PD, and associated factors among children awaiting a kidney transplant under challenging socio-economic circumstances in a low resource setting., Methods: Single center retrospective analysis of children receiving maintenance PD. Outcomes included the proportion of children who discontinued PD before transplantation, associated factors and timing of discontinuation, and the proportion transplanted. Time to discontinuation or transplantation was displayed using a Kaplan-Meier curve., Results: Sixty-seven children who received maintenance automated PD as initial dialysis modality were identified from the kidney transplant waiting list between January 2009 and December 2018. Complete data was available for 52 of the 67 children. Four children had prior failed kidney transplants. The median age was 11 years (interquartile range 6.0, 13.1). Overall, 17/52 (32.7%) children discontinued PD, with 13 (25%) transfers to HD and 4 deaths (7.7%), whereas 29/52 (55.8%) received a kidney transplant. Three of the deaths were PD related. Six children remained on maintenance PD at the end of the study period. Over a half of our patients discontinued PD by 12 months, and 80% by 30 months. Most PD discontinuations were associated with peritonitis., Conclusions: The proportion discontinuing PD was high, highlighting the need to optimize measures to improve retention rates, especially through prevention of peritonitis., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Over the last several decades, successful interventions in the health of newborns, infants, and children mean more children survive to become adolescents. There has been a global demand to improve health and care delivery for the adolescent population, guided by the United Nation's Sustainable Development Goals by 2030. However, with this deadline fast approaching and with a rising adolescent population, this demand is ever more critical. Adolescent health requires a similar rights-based approach to ensure equitable distribution of healthcare interventions and service delivery going forward. This scoping review aims to explore the existing landscape of adolescent-responsive healthcare and service delivery in Ghana. It was conducted using the Joanna Briggs Institute (JBI) guidelines and reported according to the PRISMA-Scr standards. We searched the PubMed database from inception through May 2022 using the following search criteria: "Ghana" + "Adolescent" + "Health". A total of 3172 studies were identified based on the search strategy outlined above, out of which 248 met the inclusion criteria. Both quantitative and qualitative analyses were conducted on all 248 studies to help synthesize findings. Overall, this review found that adolescent health care receives significant attention in Ghana, majority of which is focused on sexual and reproductive health (SRH). The studies available were a plethora of cross-sectional methods with large sample sizes, but their limited numbers of longitudinal studies and randomized control trials (RCTs) that could yield more robust evidence. This review is a call to action for a more comprehensive range of youth-driven, youth-responsive studies, interventions, and health programs that represent the whole range of challenges that confront adolescents in Ghana. This increased attention to adolescent needs will support a healthy cohort as they age into adulthood., Competing Interests: All authors declare no conflict of interest., (Copyright: Sheila Agyeiwaa Owusu et al.)

BACKGROUND: Whether HIV infection adversely affects exposure to first-line TB drugs in children is debatable. It is also not known whether HIV infection increases the risk of plasma underexposure or overexposure to TB drugs. This study sought to address these questions. DESIGN/METHODS: Children on TB treatment were enrolled. After 4 weeks on therapy, blood samples were collected at pre-dose, 1, 2, 4, 8, and 12 h post-dose for pharmacokinetic analysis. Plasma drug exposure below and above the lower and upper bounds of the 95% confidence intervals of the reference mean for children were considered underexposure and overexposure, respectively. The effect of HIV infection on drugs exposure and risk of underexposure were examined using multivariate analysis. RESULTS: Of 86 participants (median age: 4.9 years), 45 had HIV coinfection. HIV coinfection was associated with lower pyrazinamide (PZA) and ethambutol exposures in adjusted analysis. Patients with TB-HIV coinfection were three times more likely to have PZA underexposure than those with TB only. Underexposure of rifampin was common irrespective of HIV coinfection status. CONCLUSIONS: HIV coinfection was associated with a higher risk for PZA underexposure in children. This effect should be accounted for in models and simulations to determine optimal PZA dose for children.

Background: The World Health Organization recommended increased dosages of the first-line antituberculosis (anti-TB) drugs for children in 2010. We examined the frequency of and factors associated with low plasma maximum concentration (Cmax) of each drug in children treated with the revised dosages., Methods: Children on anti-TB therapy for at least 4 weeks underwent pharmacokinetic testing. Plasma Cmax below the lower limit of proposed reference range was considered low. Bivariate and multivariate analyses were used to examine the factors associated with low Cmax of each drug., Results: Of the 100 children, 58% were male, 50% HIV-infected and 49% younger than 5 years old. The median (interquartile range) Cmax was 5.9 (4.5-7.7) µg/mL for isoniazid, 6.5 (4.9-8.8) µg/mL for rifampin, 26.0 (21.2-33.4) µg/mL for pyrazinamide and 1.7 (0.9-2.7) µg/mL for ethambutol. There was a strong correlation between Cmax and AUC0-8h for all drugs. Low Cmax occurred in 9/100 (9.0%), 61/100 (61.0%), 17/97 (17.5%) and 60/97 (61.9%) for isoniazid, rifampin, pyrazinamide and ethambutol, respectively. In addition, 75/97 (77.3%) children had pyrazinamide Cmax < 35 µg/mL. Factors associated with low Cmax were NAT2 metabolizer phenotype status for isoniazid; height, dosage and HIV coinfection status for rifampin; height for pyrazinamide; and age, dosage and HIV coinfection status for ethambutol., Conclusions: The high frequency of low rifampin and ethambutol Cmax in our study is consistent with emerging pharmacokinetic data in children treated according to the new WHO recommendations. Higher dosages than currently recommended especially for rifampin may be necessary in children.

IFN-γ release assays (IGRAs) often present false-negative or indeterminate results in children with tuberculosis. HIV co-infection may contribute to decreased sensitivity of IGRAs by impairing T-cell IFN-γ expression. Measurement of alternative cytokines in QuantiFERON ® (QFT) supernatants can circumvent the IFN-γ-dependency and may improve QFT sensitivity. We aimed to identify additional cytokines from QFT supernatants for detection of Mycobacterium tuberculosis infection in children with tuberculosis and HIV co-infection from Ghana. Concentrations of 18 cytokines in QFT supernatants from children (0-16 years) with tuberculosis concomitantly infected with HIV (n = 25) or without HIV (n = 24) from Ghana were measured using cytometric bead array (CBA). 29% of the children showed positive IFN-γ test results, and five cytokines, i.e., IL-6, IL-21, TNF-α, IL-1α and IP-10, detected M. tuberculosis infection with comparable or, for IL-6, with significantly higher sensitivity (59%). Increased age and HIV co-infection were associated with decreased cytokine induction, and especially IL-21 and IP-10 were less prevalent in HIV co-infected children with tuberculosis. Combined cytokine analyses increased proportions of positive tests, and a four-cytokine subset (i.e., IL-6, IL-21, IFN-γ, IL-1α) predicted 78% of the children with tuberculosis correctly. Combined evaluation of IFN-γ and alternative cytokines improved IGRA-sensitivity in children with tuberculosis.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against Plasmodium falciparum malaria, but the precise nature of the protective effecthas proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outcome of P. falciparum infection. Here we report an analysis of multiple allelic forms of G6PD deficiency in a large multi-centre case-control study of severe malaria, using the WHO classification of G6PD mutations to estimate each individual's level of enzyme activity from their genotype. Aggregated across all genotypes, we find that increasing levels of G6PD deficiency are associated with decreasing risk of cerebral malaria, but with increased risk of severe malarial anaemia. Models of balancing selection based on these findings indicate that an evolutionary trade-off between different clinical outcomes of P. falciparum infection could have been a major cause of the high levels of G6PD polymorphism seen in human populations., Competing Interests: JF: Director of the Wellcome Trust, one of the three founding funders of eLife. The other authors declare that no competing interests exist.

Objective: To evaluate hearing loss in children as a complication of sickle-cell disease., Methods: In Kumasi, Ghana, 35 children with SCD aged 6 months to 10 years underwent transient-evoked otoacoustic emissions testing (TEOAE) to investigate the function of the inner ear. Healthy Ghanaian children recruited in school and kindergarten served as controls., Results: One of 35 children with SCD and 13 of 115 control children failed the otoacoustic emissions testing. This difference between the control group and the children with SCD was not statistically significant., Conclusion: Early hearing impairment does not regularly occur in sickle-cell disease, and in children, it is not a likely cause of delayed or impaired language development., (© 2015 John Wiley & Sons Ltd.)

Background: Malnutrition and HIV infection in children interact adversely and may have a combined effect on clinical outcomes, including response to antiretroviral treatment (ART). Evidence of the role of malnutrition at the point of registration at HIV clinics is limited. This study sought to determine the role of nutritional status and other clinical factors on loss to follow-up (LTFU) among children at Komfo Anokye Teaching Hospital Pediatric HIV clinic in Kumasi, Ghana., Study Design: A total of 324 HIV-positive children aged 1.5 to 10 years old who were registered at the clinic from January 1, 2007 to June 30, 2011 were included in this retrospective study. Weight-for-age z-score (WAZ) was used to classify nutritional status. Characteristics of children who were LTFU and those who remained in care were compared using bivariate analysis and logistic regression., Results: At registration, 116 (35.8%) children were severely underweight (WAZ < -3) and 72 (22.2%) were underweight (WAZ < -2). A total of 163 (50.3%) children were LTFU during the course of one year. Malnourished children compared to normal weight children (WAZ > -2) were more likely to be LTFU (P = 0.003). Initiation of antiretroviral therapy was associated with a lower risk of LTFU. In the multivariate analysis, hospital admission (OR 4.38; 95% CI 2.30, 8.34) and initiation of ART (OR 0.33; CI 0.19, 0.56) were independently associated with LTFU., Conclusion: Malnutrition was common among Ghanaian HIV-infected children and appeared to be associated with a higher risk of hospitalization and LTFU. Irrespective of nutritional status, the initiation of ART was associated with better retention in care.

We combined two tuberculosis genome-wide association studies from Ghana and The Gambia with subsequent replication in a combined 11,425 individuals. rs4331426, located in a gene-poor region on chromosome 18q11.2, was associated with disease (combined P = 6.8 x 10(-9), odds ratio = 1.19, 95% CI = 1.13-1.27). Our study demonstrates that genome-wide association studies can identify new susceptibility loci for infectious diseases, even in African populations, in which levels of linkage disequilibrium are particularly low.