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BACKGROUND: Despite being a preventable and treatable disease, tuberculosis (TB) is a leading cause of death among young people globally. Each year, an estimated 1.8 million adolescents and young adults (AYAs; 10–24 years old) develop TB. In 2019, an estimated 161,000 AYAs died of the disease. AYAs have unique developmental, psychosocial, and healthcare needs, but these needs have been neglected in both TB care and research agendas. In order to improve outcomes in this age group, the specific needs of AYAs must be considered and addressed. METHODS: Through a consensus process, an international panel of 34 clinicians, researchers, TB survivors, and advocates with expertise in child/adolescent TB and/or adolescent health proposed interventions for optimizing AYA engagement in TB care. The process consisted of reviewing the literature on TB in AYAs; identifying and discussing priority areas; and drafting and revising proposed interventions until consensus, defined a priori, was reached. RESULTS: The panel acknowledged the dearth of evidence on best practices for identifying and managing AYAs with TB. The final consensus statement, based on expert opinion, proposes nine interventions to reform current practices that may harm AYA health and well-being, and nine interventions to establish high-quality AYA-centered TB services. CONCLUSION: AYA-specific interventions for TB care and research are critical for improving outcomes in this age group. In the absence of evidence on best practices, this consensus statement from an international group of experts can help address the needs of AYA with TB or at risk for TB.

Objectives: This study aimed to examine the association between Family Adaptability, Partnership, Growth, Affec-tion and Resolve (Family APGAR) and HIV treatment outcomes.Design: A cross-sectional study using the Family APGAR questionnaireSetting: The study was conducted in Kumasi, Ghana, at the Komfo Anokye Teaching Hospital and the Kwame Nkru-mah University of Science and Technology HospitalParticipants: Consenting HIV-positive patients who had been on treatment for at least 12 months were recruited.Main outcome measures: The Family APGAR questionnaire was administered, and relevant data were extracted from hospital records and analysed using STATA® software. The relationship between Family APGAR and treatment outcomes was determined using Chi-squared tests or Fisher’s exact test.Results: Approximately 70.1% of 304 participants were females with a mean age of 41.8 years (±9.9). At treatment initiation, 47.4% of the patients presented at World Health Organisation (WHO) clinical stages I and II and had a CD4 count ≥ 200 cells/mm3. Females were less likely (Odds Ratio= 0.52; 95% CI=0.31 – 0.90, p = 0.018) to report late for treatment compared with the males. After 12 months of treatment, approximately 70% recorded undetectable viral load. Patients with functional families constituted 70.4%, which had a statistically significant relationship with viral load (p = 0.041).Conclusion: HIV care providers should incorporate family functionality evaluation into clinical practice and provide early essential support to enhance treatment outcomes.

BackgroundThe Global Point Prevalence Study (PPS) provides a platform for institutions to register and add clinical information on antimicrobial usage and determine variables related to proper antimicrobial stewardship.ObjectiveTo assess the trends in antimicrobial usage and quality indicators in antimicrobial prescriptions at our hospital.MethodWe retrospectively compared data collected at Komfo Anokye Teaching Hospital (KATH) during the Global PPS in 2015 and 2019. Both surveys took place on a day in September of the respective year. Medical records of all in-patients on admission at 0800 hours on a specific day were reviewed for antimicrobial use in the survey. Data on antibiotic use, including indications for use and the presence of quality indicators, were recorded.ResultsThe total number of patients on admission in 2015 and 2019 were 386 and 630, respectively. The proportion of patients on at least one antimicrobial was 64% (247/386) and 58.4% (368/630) in 2015 and 2019, respectively. Pneumonia was the most common medical condition for which antimicrobial was prescribed for 2015, 30(16.9%) and 2019, 44(23.0%), respectively. There was a decrease in Hospital-acquired infections from 2015, 6.2% (24/386) to 4.8% (30/630) in 2019. The use of biomarkers increased from 4.9% (12/247) to 7.6% (28/368).ConclusionOver 50% of hospitalised patients were on antimicrobials for both years. The inauguration of the antimicrobial stewardship committee at KATH will improve these quality indicators.

Background:Alcohol consumption accounts for major health related morbidity and mortality in the world with more than 3 million deaths and increasing global disease burden. The use of alcohol among the youth is very crucial due to prolonged complications established throughout the entire life of the individual. Objectives:This study aims to determine the factors that influence alcohol use among the youth in the Bosomtwe district of Ashanti Region, Ghana. Method:A cross- sectional study design was used for this study. The sample size estimated was 383 using the StatCalc tool on Epi Info 7, for the estimated population size with a 5% error margin. P-value of £0.05 was considered statistically significant at 95% confidence interval. Responses were collected from participants who consented to the study. The participant selection was dependent on the eligibility criteria for the study. The data was processed and analyzed with STATA 14. Chi- squared analysis was done to establish association between the independent and dependent variables. Results:51.7% of the participants from the Bosomtwe district had consumed alcoholic beverage before with 71.86% currently consuming alcoholic beverage. Majority (63.70%) of the participants knew alcohol had adverse effect on the various organs of the human body. 50.51% were introduced to alcohol use by their peers with 51.51% of them being influenced by their peers on the choice of alcoholic beverage. Most of the participants (45.45%) consumed alcoholic beverage due to the content displayed during advertisement with 66.16% being influenced to consume alcoholic beverage following bereaved family member or friend. Almost 70% of the participants consumed their first alcoholic drink between the age of 20-24years. Majority (64.14%) of the participants consumed alcohol just for fun. The significant factors influencing alcohol use in the study were educational status of the participants, gender, information gathered about alcoholic beverages and during bereavement. There were significant association between information regarding alcohol use, policies on alcohol consumption, bereavement of family members and current alcohol consumption with p-values of 0.008, 0.019 and 0.001 respectively. Conclusion:More than 70% of the participants in the Bosomtwe district were currently consuming alcoholic beverage with 53.55% of them engaging in binge drinking. Most of the participants had suffered some complications following alcohol use. There is the need for appropriate interventions in this area to reduce the morbidity and mortality related to alcohol use.

Introduction: The Coronavirus disease 2019 (COVID-19) has become a cause of significant morbidity and mortality in the world. There are currently 4 COVID-19 vaccines have been developed for mass vaccination to combat the disease. Some people, however, have expressed safety and efficacy concerns with regards to the vaccines. In Ghana, junior doctors, being frontline doctors, are likely to first encounter patients presenting with COVID-19. They may also have the highest direct exposure to the virus even though their outcomes after infection may be good. The study sought to determine the potential acceptance rate of COVID-19 vaccine among junior doctors, the factors that will influence their acceptance and whether they will recommend the vaccine to their patients. Methods: The study was an ethically approved anonymous cross-sectional survey to determine the willingness to accept the SARS-CoV-2 vaccine among junior doctors in Ghana. The survey was designed using Google forms posted to the various junior doctor’s social media group pages such as WhatsApp and Facebook with the study participants responding to 15 items. Results: Out of a total of 305 participants, females were 155 (50.8%). Of the respondents, 171/305 (56.1%) had cared for Covid-19 patients before, 51/305 (16.7%) had had Covid-19 infection previously and 204/305 (66.9%) will be willing to take the vaccine when available. Females were more likely to take the vaccine and those who were willing to accept the vaccine were more likely to recommend same to their family and others. Conclusion: This study has showed a more than average willingness to accept the COVID-19 vaccine. Female gender, living with the extended family and history of SARS-Cov-2 infection were positively associated with willingness to accept the COVID-19 vaccine. Doctors who were willing to accept the vaccine were also more likely to recommend their patients and family members to also accept the COVID-19 vaccine.

Introduction:A pregnant woman’s knowledge of her human immune deficiency virus (HIV) serostatus and that of her sexual partner and the disclosure of her serostatus to the partner puts her in a better position to make informed choices about her pregnancy, adopt strategies to prevent mother to child transmission (PMTCT) of HIV and reduce sexual transmission of HIV. Some pregnant women however opt out of antenatal HIV testing while others have challenges with partner disclosure. This study sought to assess the pregnant women’s knowledge of their HIV serostatus and that of their partners, and disclosure to partners about their serostatus. Methods:An ethically approved cross-sectional descriptive study was conducted at the antenatal clinic (ANC) of the Kumasi South Hospital, Ghana from the period 8thMarch to 5thApril, 2016. A structured questionnaire was administered to 407 ANC attendants who were randomly selected to participate in the study. Data entry was in Microsoft Excel and analyzed using R Core Team (2014). Results:The study showed that 80.1% (n = 326/407) of the participants knew their HIV serostatus. Of these, 18.1% (n = 59/326) knew prior to the current pregnancy and 81.9% (n = 267/326) were told during the current pregnancy. Among those who knew their HIV serostatus, the majority [83.1%; (n = 271/326)] had disclosed to their partners. Most of the participants [70.76%; (n = 288/407)] had no knowledge of their partners’ status. Conclusion:Every pregnant woman should know their HIV status, disclose it to their sexual partners and know the status of their sexual partners as this will PMTCT, reduce HIV transmission and acquisition among sero- discordant couples.

Background Each year, approximately 15 million babies are born too early. Mortality associated with preterm birth is the highest contributor to under five mortality globally. At Komfo Anokye Teaching Hospital (KATH), preterm birth remains the leading cause of admission to the Mother and Baby Unit (MBU) and is the highest contributor to neonatal mortality. Objectives To determine the precipitating factors for preterm birth at KATH and to evaluate factors that influence the outcome of preterm babies admitted to the MBU. Methods A descriptive cross-sectional study was conducted on 80 babies delivered before 33 weeks gestation who were admitted to the MBU between January and March, 2021.Babies were selected prospectively by simple random sampling and their birth weight, gender, initial temperature, precipitating factors for delivery, admission and discharge/death dates were recorded on a case-record form and analysed using excel version 2016. Results Among the 80 cases studied, 56% were males, 54% were born vaginally and 42% were referred. Their gestational ages ranged from 25 to 32weeks (average 29 weeks). Their mean birth weight was 1.12kg (range 0.6kg to 1.9kg). Eighty-four percent of recruits had temperatures below 36.50C.Premature rupture of membranes (63%) was the leading precipitating factor and hypertensive disorders was associated with the highest mortality (55%). Conclusions The precipitating factors for preterm birth can be predominantly attributed to maternal infections therefore a comprehensive antenatal care with active screening and management of maternal infections can lead to a decline in preterm birth and its complications. Majority of babies were hypothermic on admission. The deleterious effect of hypothermia on the preterm infant has been widely studied. Robust interventions must be put in place especially during transfer of preterm infants to maintain their temperatures within the normal range. These can lead to improved outcomes which will contribute favourably to achieving the third sustainable development goal.

BackgroundWorld Health Organizations aims to eliminate mother to child transmission of HIV by 2030. Timely HIV infant diagnostics are required to save the lives of HIV-infected babies which fits into Sustainable development goal 3 (Good health and wellbeing). This study reviews early infant diagnosis (EID) practices at Komfo Anokye Teaching Hospital from January 2020 to August 2021 to assess how this aligns with national policy and its impact on infected infants.MethodsEarly Infant diagnosis tests done on KATH samples were extracted focusing on age, gender, dates sample was drawn/ PCR test was done, and results of tests. Dates were converted to days since birth. Descriptive and inferential statistics were used with statistical significance at p< 0.05 ResultsA total of 400 infants had samples within study period. Test results were available for 98% (392). Data on gender was available for 37% (148) only. Positive results were 8.9% (35/392). By the time infants were sampled for storage, 24.5% (96/392) were within 6 weeks and 8.7% (34/392) were 9 months. The rest, 66.8% (262/392) deviated from protocol. By the time PCR test was done on stored samples, 5.6% (22/392) were within 6 weeks and 3.1% (12/392) were 9 months. The rest, 91.3% (358/392) deviated from protocol. Positive PCR results for deviated protocol was 8.9% (32/358)The median duration from birth to getting samples taken for positive EID case was 97 days compared to 52 days for negative results, p< 0.002. The median duration from birth to getting test results for positive EID case was 186 days compared to 88 days for negative results, p< 0.0002. ConclusionProtocol deviations from EMTCT policy due to delay in reporting contributes to positive EID results. Delay in testing affects start in treatment and negatively impacts neurodevelopment. Positive EID should be fully audited to identify risks.

BackgroundAlthough there has been a decrease in mother to child transmission (MTCT) of HIV, new pediatric infections still occur especially during the postnatal period. Prevention of vertical transmission is a key strategy in reducing the incidence which is 15-30% during pregnancy and delivery and 5-20% during breastfeeding. Early infant diagnosis and prompt initiation of antiretroviral are among some of the interventions that help to reduce the risk of transmission.ObjectivesThe purpose of the study is to assess the prevalence of HIV infection and the socio-demographic characteristics of HIV exposed infants presenting to KATH infectious disease clinic. MethodsA retrospective review of folders of exposed infants presenting to the infectious disease clinic from September 2019 to September 2021 was done. Data was entered onto excel sheet and exported to SPSS version 20 for analysis. Descriptive statistics were used. ResultsA total of 245 HIV exposed infants were seen within study period of which 54.35 (133/245) were males. The mean (SD) of birth weight was 3.07 (0.50). The median (IQR) age in months were 2.3 (1.5-3.3) at first visit to the HIV exposed clinic. Mode of delivery was by spontaneous vaginal delivery for 50.6% (124/245) and by caesarian section for 36.3% (89/245). Exclusive breastfeeding was initiated in 72.7% (178/245), formula feeding in 6.1% (15/245), and mixed feeding in 4.1% (10/245). Antiretroviral were initiated at birth for 95.9% (235/245) of infants. Septrin prophylaxis was initiated at 6 weeks for 60% (147/245). A major limitation of this records review was high level of data missingness. Most of the early infant diagnosis results were missing. The very few recorded were negative making it impossible to evaluate the true status of the exposed infants.ConclusionEven though infants exposed to mothers with HIV are seen regularly at KATH, the quality of the data collections must improve to estimate accurately the prevalence and determinants of HIV infection in exposed infants.

Violence against women is a global challenge with negative health outcomes. Women living with HIV (WLHIV) in sero-discordant unions are at risk of violence after disclosure of their status. This st...

Poor adherence to antiretroviral therapy (ART) has significant consequences for adolescents. Conditional economic incentives (CEI) is an approach that may help address this challenge. This study evaluated the safety and preliminary efficacy of a group-based CEI program for ART adherence improvement among a sample of adolescents living in Ghana. A total of 35 adolescents (mean age: 14.7 years) on ART, though still with detectable viral load, were recruited from an HIV clinic and divided into 5 balanced groups to participate in peer-led group-based CEI activities during routine clinic visits. Four assessments were conducted across four visits at baseline and 3-, 6-, and 9-month follow-up, respectively. Main outcomes were ART adherence and viral load. Linear mixed models and thematic analysis were used for data analyses. The majority (91.4%) of the participants attended all four intervention activities. Participants reported missing an average of 1.06, 0.50, 0.91, 0.55 doses of ART in the past 7 days at baseline, 3-, 6-, and 9-month assessments, respectively. Most viral loads were ≥5,000 copies/ml at both baseline (68.6%) and 6-month assessments (54.3%). The incentive was divided between individual compensation for attending clinic and completing the assessment ($5 each, $20 in total) and a group-based compensation valued at $40 that was distributed during the 9-month assessment according to average group attendance (A≥90%, B≥75%, C≥60%, D

Background Viral suppression remains the most desired outcome in the management of patients with Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) and this can be achieved by an effective combined Antiretroviral Therapy (cART). However, some patients who achieve viral suppression may experience viral rebound with dire consequence. We evaluated viral suppression and rebound and their associated factors among adult patients on cART in Kumasi, Ghana. Methods This hospital-based retrospective study was conducted at the Komfo Anokye Teaching Hospital in Ghana. We reviewed the medical records of 720 HIV patients on cART. Statistical analyses were performed using SPSS Version 26.0 and GraphPad prism version 8.0. Pp<0.0001], having good adherence to ART [aOR=5.64, 95%CI (2.86-11.13), pp=0.0260] and increasing duration of treatment (pppppp=0.004) and Zidovudine/Lamivudine/Nevirapine (aOR=18.68, 95% CI: 1.58-220.90; p=0.02) were independently associated with higher odds of viral rebound. Conclusion Approximately 76% viral suppression rate among HIV patients on cART in Kumasi falls below the WHO 95% target by the year 2030. Choice of ART combination, drug adherence, WHO clinical staging and baseline viral load are factors associated with suppression or rebound. These clinical characteristics of HIV patients must be monitored concurrently with the viral load.

Neonatal sepsis is a life-threatening emergency, and empirical antimicrobial prescription is common. In this cross-sectional study of neonates admitted with suspected sepsis in a teaching hospital in Ghana from January–December 2021, we described antimicrobial prescription patterns, compliance with national standard treatment guidelines (STG), blood culture testing, antimicrobial resistance patterns and treatment outcomes. Of the 549 neonates admitted with suspected sepsis, 283 (52%) were males. Overall, 529 (96%) received empirical antimicrobials. Most neonates (n = 407, 76.9%) were treated empirically with cefuroxime + gentamicin, while cefotaxime was started as a modified treatment in the majority of neonates (46/68, 67.6%). Only one prescription complied with national STGs. Samples of 257 (47%) neonates underwent blood culture testing, of which 70 (27%) were positive. Isolates were predominantly Gram-positive bacteria, with coagulase-negative Staphylococcus and Staphylococcus aureus accounting for 79% of the isolates. Isolates showed high resistance to most penicillins, while resistance to aminoglycosides and quinolones was relatively low. The majority of neonates (n = 497, 90.5%) were discharged after successfully completing treatment, while 50 (9%) neonates died during treatment. Strengthening of antimicrobial stewardship programmes, periodic review of STGs and increased uptake of culture and sensitivity testing are needed to improve management of sepsis.

Objectives The current WHO weight-based dosing recommendations for efavirenz result in a wide variability of drug exposure in children. Our objectives are to characterize the effects of rifampicin- and isoniazid-containing anti-TB therapy and CYP2B6 activity on efavirenz concentrations in children, using non-linear mixed-effects modelling. Methods This is a pharmacokinetic (PK) substudy of a prospective study that examined the interactions between anti-TB therapy and efavirenz in HIV-infected children with and without TB. PK samples were obtained 4 weeks after starting efavirenz (PK1) and repeated 4 weeks after completing TB therapy (PK2) in TB/HIV coinfected patients. Drug concentrations were measured using LC-MS/MS. Composite CYP2B6 516/983/15582 genotype was determined. Population PK modelling was performed in Monolix. Simulations were performed to obtain the predicted mid-dose concentrations (C12). Results One hundred and five HIV-infected Ghanaian children (46 with TB/HIV) were included. The median age and weight were 7 years and 19 kg. The efavirenz concentrations over time were adequately described using a one-compartment model. Weight, composite CYP2B6 genotype and PK visit had a significant influence on the PK parameters, while TB therapy had no significant effect. Simulations showed adequate C12 for intermediate composite CYP2B6 metabolizers only. Conclusions Our model showed that rifampicin- and isoniazid-containing anti-TB therapy does not influence efavirenz PK parameters. On the other hand, it describes the effect of efavirenz autoinduction after completing TB treatment. In addition, dosing efavirenz in children based only on weight results in a large variability in drug exposure. We propose dose adjustments for slow and extensive composite CYP2B6 metabolizers.

Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor that is used in the treatment of human immunodeficiency virus (HIV) infection in children younger than 3 years old. Identifying genetic predictors of NVP pharmacokinetics (PK) in young children is important because inter-individual variability in NVP concentrations contributes to variable treatment response and the information may be used to individualize dosing decisions. We examined the relationship between genetic variations in relevant drug disposition genes and NVP PK parameters in Ghanaian children living with HIV eligible to initiate NVP-based antiretroviral therapy. Participants received NVP plus zidovudine and lamivudine or abacavir and lamivudine twice daily, and those with tuberculosis (TB) coinfection received concurrent anti-TB therapy with NVP. Pharmacokinetic sampling was performed after at least 4 weeks of antiretroviral therapy. Nevirapine minimum concentration (Cmin), area under the concentration-time curve from time 0 to 12 h (AUC0–12h), and apparent clearance (CL/F) were calculated using non-compartmental analysis using Phoenix v8.0 software. Genotyping for CYP2B6, CYP2A6, CYP3A5, ABCB1, NR1I2, and NR1I3 single nucleotide polymorphism (SNPs) was performed by TaqMan® allelic discrimination method. The median (range) NVP dose received was 10 (7–14) mg/kg. Of the 53 participants, the median (range) Cmin was 3.3 (0.0–14.0) mg/L and AUC0–12h was 56.0 (16.7–202.6) mg.hr/L. Using step-wise regression, CYP2B6 rs3745274 and NR1I2 rs6785049 SNPs were independent as well as joint predictors of NVP AUC0–12h, Cmin, and CL/F. We concluded that genotyping for CYP2B6 rs3745274, and the NR1I2 rs6785049 G > A SNP (which encodes the transcriptional factor, pregnane X receptor), could improve prediction of NVP PK for individualized therapy.

Background: Family instability and partner conflicts are reportedly common in serodiscordant relationships. To date, the family adaptability, partnership, growth, affection and resolve (Family APGAR), a standardised tool for assessing family function, has not been used in any published literature involving this peculiar group. Aim: The aim of this study was to determine the predictors of family functionality and its association with human immunodeficiency virus (HIV) serodiscordance. Setting: The study was undertaken at the Kwame Nkrumah University of Science and Technology Hospital and Komfo Anokye Teaching Hospital in Kumasi, Ghana. Method: This was a cross-sectional study. A systematic sampling method was used to select HIV-positive clients whose partners were seropositive (concordant) or seronegative (discordant). A standardised format was used to extract relevant data. All data were analysed using STATA ® (version 14). Results were reported as odds ratios with 95% confidence intervals for study and outcome variables. Results: The study recruited 374 respondents, of which 52% (195) were in HIV-discordant relationships. Approximately 68% (254) of the respondents rated their families as functional, 15% (57) rated as moderately dysfunctional and 17% (63) rated as severely dysfunctional. A statistically significant relationship was found between family functionality and gender, as well as between family functionality and HIV status disclosure to the partner. No association was found between the Family APGAR and HIV serodiscordance. Conclusion: Amongst HIV couples, the strongest predictors of family functionality are gender and status disclosure. Healthcare providers should invest efforts into addressing gender-based challenges, utilise the Family APGAR and support disclosure of HIV status, especially amongst discordant couples.

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.

Background: Anorectal malformations (ARMs) are congenital defects affecting the distal gastrointestinal tract and anus with frequent fistulous connections to the genitourinary system. The spectrum of the disease is considerably wide, and thus, an individualised approach to its management is required. There are few recent publications about the burden of this malformation in Africa and the outcome of surgical intervention. We present our experiences with the management of ARM, peculiar challenges and the outcome at a tertiary hospital catering for the Northern and Central parts of Ghana. Materials and Methods: This was a retrospective folder review of children with ARM at the Paediatric Surgical Unit of Komfo Anokye Teaching Hospital, Kumasi, Ghana, from 2011 to 2015. The data extracted included diagnosis, associated features, initial and definitive surgical treatment and post-operative complications. Results: Of the 53 records that were conclusively retrieved, the sex ratio was 1:1. The median age of presentation was 4.5 days (neonates), 4.5 months (infants) and 1.6 years (older children). There were 12 (44%) rectoperineal and 18 (69%) rectovestibular fistulas, representing the most common types of ARM in boys and girls, respectively. Posterior sagittal anorectoplasty and abdominoperineal pull-through were the corrective procedures performed. The overall complication rate was

Background Paediatric sepsis remains a major public health problem with significant morbidity and mortality especially in developing countries. Clinical symptoms associated with sepsis are unreliable and laboratory parameters unspecific, making an early diagnosis of paediatric sepsis difficult. The lack of definitive biomarker(s) for early diagnosis of sepsis further leads to the misuse of antibiotics. Diagnosis based on a single biomarker does not provide adequate accuracy. Subsequently, combining multiple biomarkers into a single score will help clinicians make a better diagnostic judgment. Aims This study for the first time evaluated the individual and combined diagnostic accuracy of procalcitonin (PCT), presepsin (sCD14-ST) and high sensitive C-reactive protein (hs-CRP) using a Bioscore model. Materials and methods In a case control study conducted at the Paediatric Emergency Unit (PEU) and the Mother and Baby Unit (MBU) of Komfo Anokye Teaching Hospital (KATH), sixty (60) paediatric subjects aged zero to six (0–6) years, were diagnosed with sepsis using case-definition by the national neonatal bloodstream infection surveillance and Pediatric Sepsis Consensus Congress. Thirty (30) other paediatric subjects, aged and sex matched without sepsis or inflammatory conditions were used as controls. One-time blood sample was taken at the time of admission for blood culture and measurement of PCT, hs-CRP, and presepsin by ELISA. The Statistical Package for Social Sciences (SPSS release 20.0, Copyright ©SPSS Inc.) was used for analysis. Results Out of the sixty septic paediatric subjects, 14 patients (23.3%) had positive blood cultures (LCS) and 46 (76%) had negative for blood cultures (CS). Klebsiella spp. recorded the highest median levels of PCT, and hs-CRP while Pseudo. Aeruginasa recorded the highest of sCD14-ST levels. Significant elevations in PCT, sCD14-ST and hs-CRP levels were observed among septic cases in comparison to controls (p < 0.0001). Individually, PCT showed better accuracy (AUC = 78.7%) followed by hs-CRP (AUC = 78.4%) and sCD14-ST (AUC = 74.8%). Combination of PCT + hs-CRP had the highest accuracy (AUC = 80.1%) followed by hs-CRP + sCD14-ST (AUC = 77.2%), PCT + sCD14-ST + hs-CRP (AUC = 77.0%) and PCT + sCD14-ST (AUC = 75.9%). Conclusion: hs-CRP, PCT, and sCD14-ST are independent predictors of paediatric sepsis due to their high prognostic values. Moreover, Bioscore combination of these biomarkers was significantly associated with increased odds for sepsis. The incorporation of these biomarkers into routine diagnostic tests will aid in prompt diagnosis of paediatric sepsis., Musculoskeletal system; Renal system; Infectious disease; Immunology; Reproductive system; Paediatrics; Paediatric sepsis; Presepsin; Procalcitonin; High sensitive C-reactive protein; Bioscore model.

Background: Children with chronic constipation dating to infancy frequently undergo rectal biopsy in order to rule out Hirschsprung's disease (HD) which is a common cause of this sort of presentation. Few publications have however focused on the documentation of the proportion of such patients who truly had histopathological findings confirming the disease. In this preliminary work, we aim to present the histopathological findings of children who had rectal biopsies in our centre from 2009 to 2014. Patients and Methods: A retrospective study was undertaken to review the histopathology reports of all rectal biopsies submitted to the Department of Pathology of the Komfo Anokye Teaching Hospital, Kumasi, from 2009 to 2014 on account of refractory constipation and suspected HD. Patient's biodata, clinical signs and symptoms were extracted from the request form. Results: Eighty-eight cases were seen during the study period with male to female ratio 2.8:1 and age range 6 months to 10 years. The modal age range is 24–36 months. Seventy-six of the specimens were adequate for histopathological assessment with 64 cases confirmed as HD while 12 cases were normal. Out of the confirmed cases, 3 cases showed absence of ganglion cells but no hypertrophy of nerve fibres. Conclusion: This preliminary work reveals that HD is rarely confirmed by biopsy in early infancy in our setting due to late presentation although the epidemiology of the disease is similar to that reported elsewhere.

Nevirapine-based antiretroviral therapy (ART) is one of the limited options in HIV-infected children younger than 3 years old (young children) with tuberculosis (TB) coinfection. To date, there are insufficient data to recommend nevirapine-based therapy during first-line antituberculosis (anti-TB) therapy in young children. We compared nevirapine pharmacokinetics (PK) in HIV-infected young children with and without TB coinfection. In the coinfected group, nevirapine PK was evaluated while on anti-TB therapy and after completing an anti-TB therapy regimen. Of 53 participants, 23 (43%) had TB-HIV coinfection. While the mean difference in nevirapine PK parameters between the two groups was not significant (P > 0.05), 14/23 (61%) of the children with TB-HIV coinfection and 9/30 (30%) with HIV infection had a nevirapine minimum concentration (C(min)) below the proposed target of 3.0 mg/liter (P = 0.03). In multivariate analysis, anti-TB therapy and the CYP2B6 516G>T genotype were joint predictors of nevirapine PK parameters. Differences in nevirapine PK parameters between the two groups were significant in children with CYP2B6 516GG but not the GT or TT genotype. Among 14 TB-HIV-coinfected participants with paired data, the geometric mean C(min) and area under the drug concentration-time curve from time zero to 12 h (AUC(0–12)) were about 34% lower when patients were taking anti-TB therapy, while the nevirapine apparent oral clearance (CL/F) was about 45% higher. While the induction effect of anti-TB therapy on nevirapine PK in our study was modest, the CYP2B6 genotype-dependent variability in the TB drug regimen effect would complicate any dose adjustment strategy in young children with TB-HIV coinfection. Alternate ART regimens that are more compatible with TB treatment in this age group are needed. (This study has been registered at ClinicalTrials.gov under identifier NCT01699633.)

We conducted a genome-wide association study of host resistance to severePlasmodium falciparummalaria in over 17,000 individuals from 11 malaria-endemic countries, undertaking a wide ranging analysis which identifies five replicable associations with genome-wide levels of evidence. Our findings include a newly implicated variant on chromosome 6 associated with risk of cerebral malaria, and the discovery of an erythroid-specific transcription start site underlying the association inATP2B4. Previously reported HLA associations cannot be replicated in this dataset. We estimate substantial heritability of severe malaria (h2~ 23%), of which around 10% is explained by the currently identified associations. Our dataset will provide a major building block for future research on the genetic determinants of disease in these diverse human populations.

We compared efavirenz pharmacokinetic (PK) parameters in children with tuberculosis (TB)/human immunodeficiency virus (HIV) coinfection on and off first-line antituberculosis therapy to that in HIV-infected children. Children 3 to 14 years old with HIV infection, with and without TB, were treated with standard efavirenz-based antiretroviral therapy without any efavirenz dose adjustments., We compared efavirenz pharmacokinetic (PK) parameters in children with tuberculosis (TB)/human immunodeficiency virus (HIV) coinfection on and off first-line antituberculosis therapy to that in HIV-infected children. Children 3 to 14 years old with HIV infection, with and without TB, were treated with standard efavirenz-based antiretroviral therapy without any efavirenz dose adjustments. The new World Health Organization-recommended antituberculosis drug dosages were used in the coinfected participants. Steady-state efavirenz concentrations after 4 weeks of antiretroviral therapy were measured using validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) assays. Pharmacokinetic parameters were calculated using noncompartmental analysis. Between groups, PK parameters were compared by Wilcoxon rank-sum test and within group by signed-rank test. Of the 105 participants, 43 (41.0%) had TB coinfection. Children with TB/HIV coinfection compared to those with HIV infection were younger, had lower median weight-for-age Z score, and received a higher median efavirenz weight-adjusted dose. Geometric mean (GM) efavirenz peak concentration (Cmax), concentration at 12 h (C12h), Cmin, and total area under the curve from time 0 to 24 h (AUC0–24h) values were similar in children with HIV infection and those with TB/HIV coinfection during anti-TB therapy. Geometric mean efavirenz C12h, Cmin, and AUC0–24h values were lower in TB/HIV-coinfected patients off anti-TB therapy than in the children with HIV infection or TB/HIV coinfection on anti-TB therapy. Efavirenz clearance was lower and AUC0–24h was higher on than in patients off anti-TB therapy. Reduced efavirenz clearance by first-line anti-TB therapy at the population level led to similar PK parameters in HIV-infected children with and without TB coinfection. Our findings do not support modification of efavirenz weight-band dosing guidelines based on TB coinfection status in children. (The study was registered with ClinicalTrials.gov under registration number NCT01704144.)

Purpose Acute Respiratory Infection (ARI) is one of the topmost childhood killers ahead of diarrhoea and malnutrition in children. This exploratory qualitative study sought to examine the influence of maternal social constructs on the recognition and care seeking for fast breathing in children to inform the development of an intervention aimed at addressing fast breathing and acute respiratory infection related illness among children in Ghana. Method Focus group discussions with 23 mothers with children aged 6 weeks – 12 weeks old was conducted. The study used an abbreviated grounded theory and thus the full iterative cycle was not performed during the interview and data analysis. Results Fast breathing is locally called ‘oteeso’(difficulty in breathing), and ‘mframa-ko-ne-mu’(air has entered the child). Evil spirit, heredity, and exposure to windy weather were mentioned as the causes. Herbs and herbal preparations are perceived to be more effective in managing fast breathing. Mothers have varying construction of causes, presentation and treatment options for fast breathing, and these have implications in control and prevention. Conclusion Understanding the local construction of illness beliefs is key to designing interventions aimed at empowering mothers to seek early care for their children on respiratory related illness.

Increased accessibility to Antiretroviral Therapy (ART) has resulted in the decline of deaths among children with Perinatally Infected Human Immunodeficiency Virus (PIHIV). Their adherence to Highly Active ART (HAART) is vital for their survival and quality of life. This study aimed at determining HAART medication adherence among adolescents with PIHIV. The study was cross-sectional conducted from September 2015 to January 2016 at a teaching hospital in Ghana. It involved 106 adolescents aged 10-20 years. Morisky's eight-item medication adherence scale was adapted and used to determine the adherence level. Factors influencing adherence were also determined by interviewing the adolescents. EpiData 3.1 and Stata version 12 were used for data entry and analysis respectively. There was low adherence in 76.4% of the adolescents, and the HAART regimen associated with high medication adherence was tenofovir, lamivudine and efavirenz combinations (p = .011). Forgetfulness (p = .001) and inability to come for refill (p = .013) were the main factors associated with low adherence. However adherence was not significantly associated with a lack of medication supply or stigmatization. Addressing the modifiable factors found in this study to be associated with low adherence are essential interventions for their long-term quality of life.

Background: The Expanded Programme on Immunization (EPI), since its inception in 1974, has helped avert about 2-3 million deaths annually. In Ghana, there is inadequate information on the transition from knowledge acquired in the classroom to practice among vaccinators. This study seeks to provide evidence on the level of knowledge and competencies of vaccinators in Ghana. Method: A prospective cross-sectional study with consecutive sampling technique was employed to select 110 eligible subjects from health facilities in two districts in the Ashanti region of Ghana. Data were collected in real time using standardised tools, uploaded on the Open Data Kit (ODK), and subsequently exported to STATA 13.0 for statistical analysis. Results: Seventy two percent (72.73%) of respondents were from urban health facilities. Community Health Nurses constituted majority of respondents 83.09%. Sixty-five percent (65.46%) of participants had less than five years’ experience in vaccination. BCG was correctly identified by 91.82% of respondents as a single dose vaccine and yellow fever by 89.09%. Pentavalent, rotavirus and pneumococcal vaccine were correctly identified by 91.82%, 82.73% and 82.73% respectively as multiple dose vaccines. Ninety seven percent (97.27%) of respondents correctly mentioned pentavalent as having its first dose administered at 6 weeks. 98.18% correctly indicated pentavalent and pneumococcal as given intramuscularly whereas 92.27% identified OPV and rotavirus as given orally. Eighty-eight percent (88.18%) of respondents knew vaccine temperature charting is required twice a day. Conclusion: The study revealed gaps in the principles of vaccine handling and administration. A critical need for routine assessment and refresher training for population where vaccination is conducted by different level of training.

Tuberculosis (TB) is a major cause of human mortality particularly in association with the human immunodeficiency virus (HIV). Nocardia spp. has emerged as an opportunistic infection especially in HIV patients. The high prevalence of TB and HIV coupled with the lack of a definitive laboratory diagnosis for Nocardia spp. could lead to misdiagnosed pulmonary TB. This study determined the prevalence of pulmonary infections due to Nocardia spp. and Mycobacterium tuberculosis in sputum of HIV and non-HIV patients with suspected pulmonary tuberculosis at KATH. A total of sixty sputum samples were obtained from HIV and non-HIV patients with suspected pulmonary tuberculosis. Samples were examined by fluorescence based Ziehl–Neelsen staining, culture, and PCR methods. The prevalence of Nocardia spp. and Mycobacterium tuberculosis was 18.3% and 20%, respectively, with the latter having the highest rate among patients aged 21–40 years (P=0.075). The prevalence of Nocardia spp. among HIV patients was 90.9% whilst 16.7% of the patients had HIV/Nocardia spp. coinfection. Detection of Mycobacterium tuberculosis by fluorescence-based Ziehl–Neelsen staining, culture, and PCR yielded 9 (15%), 11 (18.3%), and 12 (20%), respectively. There is a high prevalence of nocardiosis especially in HIV patients. PCR is a better diagnostic method that detects both Nocardia spp. and Mycobacterium tuberculosis and should be incorporated into routine diagnosis for pulmonary infections.

Adolescents with perinatally acquired HIV seem to be most stigmatized. There is a need to put together policies to enable them cope with the burden and live fruitful lives. In Ghana, a group of activities and rewards are being put in place to aid in helping these teens cope with the stigma.

Objective. This study sought to describe the trend of sputum organism density and the rate of bacteriological conversion among smear positive TB patients assessing care at the Komfo Anokye Teaching Hospital (KATH), Kumasi, Ghana. Methods. We conducted a retrospective patient folder review from January 2013 to March 2016 at the KATH, a tertiary hospital in Ghana. The data was entered into Microsoft Access database and exported into STATA for analysis. We applied basic descriptive statistics to study variables. Sputum conversion rate (SCR) was estimated using the number of negative tests recorded over a period (numerator) and the number of patients reported in the same period (denominator) and expressed as a percentage. Results. A total of 278 patient records with sputum smear positive at onset were studied. Before treatment sputum density detected in smear microscopy was as follows: 1 acid-fast bacillus (+) (n=114), scanty (n=19), ++ (n=67), and +++ (n=78). We recorded sputum conversion rate of 80.90%, 94.56%, and 98.31% in the intensive, continuation, and completion phases, respectively. Conclusion. This study has shown an increasing trend in sputum conversion of smear positive pulmonary tuberculosis and an increasing trend in loss to follow-ups among tuberculosis patients on treatment.

Although human immunodeficiency virus (HIV) coinfection is the most important risk factor for a poor antituberculosis (anti-TB) treatment response, its effect on the pharmacokinetics of the first-line drugs in children is understudied. This study examined the pharmacokinetics of the four first-line anti-TB drugs in children with TB with and without HIV coinfection. Ghanaian children with TB on isoniazid, rifampin, pyrazinamide, and ethambutol for at least 4 weeks had blood samples collected predose and at 1, 2, 4, and 8 hours postdose. Drug concentrations were determined by validated liquid chromatography-mass spectrometry methods and pharmacokinetic parameters calculated using noncompartmental analysis. The area under the concentration-time curve from 0 to 8 h (AUC 0–8 ), maximum concentration ( C max ), and apparent oral clearance divided by bioavailability (CL/F) for each drug were compared between children with and without HIV coinfection. Of 113 participants, 59 (52.2%) had HIV coinfection. The baseline characteristics were similar except that the coinfected patients were more likely to have lower weight-for-age and height-for-age Z scores ( P < 0.05). Rifampin, pyrazinamide, and ethambutol median body weight-normalized CL/F values were significantly higher, whereas the plasma AUC 0–8 values were lower, in the coinfected children than in those with TB alone. In the multivariate analysis, drug dose and HIV coinfection jointly influenced the apparent oral clearance and AUC 0–8 for rifampin, pyrazinamide, and ethambutol. Isoniazid pharmacokinetics were not different by HIV coinfection status. HIV coinfection was associated with lower plasma exposure of three of the four first-line anti-TB drugs in children. Whether TB/HIV-coinfected children need higher dosages of rifampin, pyrazinamide, and ethambutol requires further investigation. (This study has been registered at ClinicalTrials.gov under identifier NCT01687504.)

Many human genetic associations with resistance to malaria have been reported, but few have been reliably replicated. We collected data on 11,890 cases of severe malaria due to Plasmodium falciparum and 17,441 controls from 12 locations in Africa, Asia and Oceania. We tested 55 SNPs in 27 loci previously reported to associate with severe malaria. There was evidence of association at P < 1 × 10(-4) with the HBB, ABO, ATP2B4, G6PD and CD40LG loci, but previously reported associations at 22 other loci did not replicate in the multicenter analysis. The large sample size made it possible to identify authentic genetic effects that are heterogeneous across populations or phenotypes, with a striking example being the main African form of G6PD deficiency, which reduced the risk of cerebral malaria but increased the risk of severe malarial anemia. The finding that G6PD deficiency has opposing effects on different fatal complications of P. falciparum infection indicates that the evolutionary origins of this common human genetic disorder are more complex than previously supposed.

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.