Treating Hepatitis B Virus in Times of COVID-19: The Case for Clinical Pharmacogenomics Research in Tenofovir-Induced Kidney Toxicity.

The current pandemic has markedly shifted the focus of the global research and development ecosystem toward infectious agents such as SARS-CoV-2, the causative agent for COVID-19. A case in point is the chronic liver disease associated with hepatitis B virus (HBV) infection that continues to be a leading cause of severe liver disease and death globally. The burden of HBV infection is highest in the World Health Organization designated western Pacific and Africa regions. Tenofovir disoproxil fumarate (TDF) is a nucleoside analogue used in treatment of HBV infection but carries a potential for kidney toxicity. TDF is not metabolized by the cytochrome P450 enzymes and, therefore, its clearance in the proximal tubule of the renal nephron is controlled mostly by membrane transport proteins. Clinical pharmacogenomics of TDF with a focus on drug transporters, discussed in this perspective article, offers a timely example where resource-limited countries and regions of the world with high prevalence of HBV can strengthen the collective efforts to fight both COVID-19 and liver diseases impacting public health. We argue that precision/personalized medicine is invaluable to guide this line of research inquiry. In all, our experience in Ghana tells us that it is important not to forget the burden of chronic diseases while advancing research on infectious diseases such as COVID-19. For the long game with COVID-19, we need to address the public health burden of infectious agents and chronic diseases in tandem.

Anthropometric indices and cardiometabolic risk factors in a Ghanaian adolescent population.

OBJECTIVES: Adolescent overweight and obesity is a public health concern globally, especially in lower- and middle- income countries where there is an additional burden of undernutrition. The prevalence of adolescent overweight/2obesity has increased markedly over the past three decades. The transition in dietary habits coupled with reduced physical activity has been blamed for the increasing trend. Overweight/obesity in adolescence is complicated by cardiometabolic, respiratory, musculoskeletal and psychosocial disorders. Additionally, adolescent obesity is a predictor of future development of type 2 diabetes, cardiovascular diseases and metabolic disorders. The burden of cardiometabolic risk factors associated with adolescent overweight/obesity in Ghana is lacking, the project, therefore, was undertaken to add to the existing knowledge. METHODS: The study was undertaken in adolescent students of a tertiary institution in Ghana. Two hundred and one students consented to participate in the study. Questionnaires on sociodemographic characteristics, dietary and substance abuse habits were self-administered. Blood pressure, height, weight and waist circumference measures were performed and venous blood drawn for the determination of fasting serum total/LDL/HDL cholesterol and triglycerides. Body mass indices were determined as the weight per square of their heights. RESULTS: The prevalence of obesity was determined to be 15.81% generally, 27.71% in the females and 7.08% in the males. Diastolic blood pressure was the only cardiometabolic risk factor significantly associated with obesity in our study. CONCLUSION: Overweight/obesity is common in Ghanaian adolescents, with the prevalence highest in the female population.

A macro- and micronutrient-fortified complementary food supplement reduced acute infection, improved haemoglobin and showed a dose-response effect in improving linear growth: a 12-month cluster randomised trial.

Inadequate protein quality may be a risk factor for poor growth. To examine the effect of a macronutrient-micronutrient supplement KOKO Plus (KP), provided to infants from 6 to 18 months of age, on linear growth, a single-blind cluster-randomised study was implemented in Ghana. A total of thirty-eight communities were randomly allocated to receive KP (fourteen communities, n 322), a micronutrient powder (MN, thirteen communities, n 329) and nutrition education (NE, eleven communities, n 319). A comparison group was followed cross-sectionally (n 303). Supplement delivery and morbidity were measured weekly and anthropometry monthly. NE education was provided monthly. Baseline, midline and endline measurements at 6, 12 and 18 months included venous blood draws, diet, anthropometry, morbidity, food security and socio-economics. Length-for-age Z-score (LAZ) was the primary outcome. Analyses were intent-to-treat using mixed-effects regressions adjusted for clustering, sex, age and baseline. No differences existed in mean LAZ scores at endline (-1·219 (sd 0·06) KP, -1·211 (sd 0·03) MN, -1·266 (sd 0·03) NE). Acute infection prevalence was lower in the KP than NE group (P = 0·043). Mean serum Hb was higher in KP infants free from acute infection (114·02 (sd 1·87) g/l) than MN (107·8 (sd 2·5) g/l; P = 0·047) and NE (108·8 (sd 0·99) g/l; P = 0·051). Compliance was 84·9 % (KP) and 87·2 % (MN) but delivery 60 %. Adjusting for delivery and compliance, LAZ score at endline was significantly higher in the KP v. MN group (+0·2 LAZ; P = 0·026). A macro- and micronutrient-fortified supplement KP reduced acute infection, improved Hb and demonstrated a dose-response effect on LAZ adjusting consumption for delivery.

Sero-prevalence of hepatitis B and C viral infections in Ghanaian HIV positive cohort: a consideration for their health care.

BACKGROUND: Antiretroviral therapy (ART) has significantly decreased HIV/AIDS-related morbidity and mortality. However, globally, many people living with HIV die from non-AIDS related illnesses including liver diseases which occur partly due to co-infection with HBV and or HCV. The aim of this study was to determine the seroprevalence of HBV and HCV among HIV infected individuals receiving care from three different hospitals in the Central Region of Ghana. METHODS: This research was a case-case study. The population consisted of ART naive persons (newly confirmed HIV cases) and those who had been on ART for more than 3 months (old cases). Each individual's sociodemographic characteristics and clinical data including their HBV and HCV status were collected. Those who knew their HBV and HCV status and those who did not know their status were tested for circulating HBsAg and anti-HCV using rapid diagnostic test cassettes. Descriptive analysis was done, and the data presented as median with interquartile range, frequency and percentage. Fisher's exact test and Pearson Chi-square (χ2) test were used to determine associations between categorical variables. RESULTS: Overall, 394 HIV individuals aged, 3 to 76 years old with a median age of 41 (IQR:34-49) participated in this study. Circulating HBsAg and anti-HCV were detected in 6.1% (24/394) and 0.5% (2/393) participants respectively with an overall seroprevalence of 6.6% (26/394). None of the participants was positive for both HBV and HCV infections. 92.1% (363/394) had no information on their HBV status while all the 394 participants did not know their HCV status during data collection. No significant association of HBV infection rate was found in all the socio-demographic data of the participants. But HBV infection rates were significantly higher in those at WHO clinical stages 2 and 3 (P = 0.004). CONCLUSION: HBV and HCV were detected among the HIV-infected participants. Majority of the participants had no information on their HBV status and none of the participants had information on his or her HCV status. This study recommends the need for policy makers to provide free HBV and HCV screening for all HIV infected individuals for their effective management.

Blood pressure control, glycemic control, and dyslipidemia among healthy adults in the Cape Coast metropolis, Ghana.

BACKGROUND: The World Health Organization recommends the implementation of interventions focused on the early detection of clinical risk factors for cardiovascular disease (CVD) as effective strategies for the control of CVD in low resource settings. However, due to health system resource constraints, surveillance capacity for the identification of high-risk populations for non-communicable diseases, including CVD have been inadequate. The purpose of this study was to describe the prevalence of CVD clinical risk factors among healthy adults residing in the Cape Coast metropolis of Ghana. The clinical risk factors assessed included glycemic control, insulin sensitivity, lipid control and blood pressure. METHODS: The study participants included 70 healthy adults without a previous diagnosis of CVD from Cape Coast metropolis. Blood samples, blood pressure and anthropometric measurement were obtained for each participant. Serum glycated hemoglobin (HbA1c), insulin, glucose, triglycerides, and cholesterol levels were measured. RESULTS: Approximately four out of ten participants were either overweight or obese. Almost three-quarters of the sample were considered prehypertensive or hypertensive. About three in ten were clinically prediabetic. About a third of the participants had high non-HDL cholesterol levels. Triglyceride concentration levels were found to be high in almost 10 percent of the study sample. Approximately six percent were identified as having metabolic syndrome. CONCLUSION: A significant proportion of the study participants were identified to be at risk for CVD. There is the need for adaptive and less resource-intensive CVD risk-factor screening interventions to allow for the timely detection and management of CVD risk factors in low-resource settings.

Renal dysfunction among adult HIV/AIDS patients on antiretroviral therapy at a tertiary facility in Ghana.

BACKGROUND: Kidney diseases have emerged as significant cause of morbidity and mortality in HIV subject on antiretroviral therapy (ART). In Ghana, routine follow up of HIV positive clients is by estimation of serum creatinine and urea levels. Glomerular Filtration Rate (GFR) is not routinely calculated and proteinuria is not routinely checked. This study sought to investigate the kidney profiles of adult HIV/AIDS patients being managed on ART at the Cape Coast Teaching Hospital (CCTH), Ghana. METHODS: A hospital-based analytical cross sectional study with a retrospective component was conducted using systematic sampling method to recruit HIV/AIDS who visited the ART clinic. A total of 440 participants of both sexes aged 18 years and above, confirmed as HIV/AIDS positive and on ART were involved in this study. Blood and urine samples were collected from all subjects and the levels of serum creatinine and urea and proteinuria were estimated and eGFR calculated using the Modification of Diet in Renal Disease (MDRD) equations. Data analyses were performed using Stata version 13 software (Stata Corp, Texas USA). RESULTS: The mean age (years) of participants was 45.5 years (±11.6) with 288 (65.4%) being on Tenofovir based ART regimen. The mean eGFR was found to decrease from 112.4 ml/min/1.73 m at baseline, to 103.4 ml/min/1.73 m after 6 months on ART and to a mean of 99.4 ml/min/1.73 m at recruitment into this study. Factors which were found to be associated with having eGFR < 60 included age, gender and CD4 count though not statistically significant. Patients > 45 years had the highest odds with OR 2.0 (95% CI: 0.8-5.1), females had higher odds with OR 1.5 (95% CI: 0.5-5.2), and those with CD4 count > 350 had OR of 0.4 (95% CI 0.2-1.3). A total of 30.9% of the participants had proteinuria at recruitment. TDF based ART regimen had no statistically significant effect on serum creatinine and urea levels. CONCLUSION: Estimated GFR decreased after 6 months among patients on ART despite normal serum creatinine and urea levels. This finding suggests that clients in care at HIV/ART clinics in Ghana may benefit from routine estimation of GFR and proteinuria.

The effects of plasma chromium on lipid profile, glucose metabolism and cardiovascular risk in type 2 diabetes mellitus. A case - control study.

BACKGROUND: The study was aimed at determining the effect of plasma chromium concentration on the metabolism of glucose, and lipids and their subsequent cardiovascular risk in patients with type 2 diabetes in the Bolgatanga district of Ghana. MATERIAL AND METHODS: Fasting blood glucose and lipids profile were determined by enzymatic assay using the BT 5000® Random Access Chemistry Analyzer. Fasting serum insulin and High sensitive C-reactive protein were determined by ELISA, a solid phase direct sandwich immunoassay method. HOMA-IR, which is based on fasting blood sample for insulin and glucose concentrations measured in a single blood sample, was used to calculate insulin resistance. Plasma chromium was measured using an atomic Absorption Spectrometer. RESULTS: Patientswith diabeteshad significantly (p<0.0001) increased LDL, TC, TG, VLDL, insulin, CRP and HOMAIR and a significantly reduced plasma chromium (p<0.0001) (0.53± 0.02µg/l and 0.11±0.01µg/l control and case respectively). Low Cr (p ≤0.001) was associated with high blood pressure, obesity and lipid dysregulation. Plasma Cr significantly correlated negatively with blood pressure and LDL. CONCLUSION: Lower plasma Cr level was associated with hyperglycaemia, hyperinsulinemia, hypertension, insulin resistance and high inflammation marker HsCRP.

Knowledge Level and Determinants of Neonatal Jaundice: A Cross-Sectional Study in the Effutu Municipality of Ghana.

BACKGROUND: Neonatal jaundice (NNJ) is a major cause of hospital admission during the neonatal period and is associated with significant mortality. This case-control study with cross-sectional design sought to identify the possible factors associated with neonatal jaundice and assess maternal knowledge level of this condition. METHODS: One hundred and fifty (150) neonates comprising 100 with clinically evident jaundice and 50 without jaundice were conveniently recruited from the Trauma and Specialist Hospital in the Effutu Municipality. Blood samples were collected for the determination of serum bilirubin, glucose-6-phosphate dehydrogenase (G6PD), status and blood group (ABO and Rhesus). Well-structured questionnaire was used to collect maternal and neonate sociodemographic and clinical history. RESULTS: Majority (54%) of neonates developed jaundice within 1-3 days after birth with 10% having it at birth. Duration of labour and neonatal birth weight were associated with neonatal jaundice (P < 0.05). G6PD abnormality was found in 11 (12%) of the neonates with jaundice and ABO incompatibility was present in 18%. Neonates delivered by mothers with formal occupation and those who had prolonged duration of labour were significantly more likely to have neonatal jaundice (OR = 4.174, P = 0.003; OR = 2.389, P = 0.025, resp.). Neonates with low birth weight were also more likely to develop neonatal jaundice (OR = 2.347, P = 0.044). Only 17.3% of mothers had heard of neonatal jaundice. School was the major source of information on neonatal jaundice (34.6%). Majority of participants (mothers) did not know that NNJ can cause damage to other organs in the body (90%). CONCLUSION: Low neonatal birth weight and prolonged duration of labour are associated with neonatal jaundice. Mothers had inadequate knowledge of neonatal jaundice and its causes.

Sero-prevalence and risk factors for hepatitis E virus infection among pregnant women in the Cape Coast Metropolis, Ghana.

BACKGROUND: Hepatitis E virus is an emerging infection in Africa with poor maternal and foetal outcomes. There is scanty data on the sero-prevalence of HEV infection among pregnant women in Ghana. This study highlighted the prevalence and risk factors associated with HEV infection among pregnant women in Cape Coast Metropolis, Central Region of Ghana. METHODS: A multicenter (3 selected sites) analytical cross sectional study involving 398 pregnant women in the Cape Coast metropolis was conducted. HEV (Anti-HEV IgG and Anti-HEV IgM) ELISA was performed. Sero-positive women had liver chemistries done and data collected on maternal and neonatal outcomes. Data analyses were performed using Stata version 13 software (STATA Corp, Texas USA). RESULTS: Mean age was 28.01 (± 5.93) years. HEV sero-prevalence was 12.2% (n = 48) for IgG and 0.2% (n = 1) for IgM with overall of 12.3%. The odds of being HEV sero-positive for women aged 26-35 years was 3.1 (95% CI: 1.1-8.1), p = 0.02 and ≥36 years it was 10.7 (95% CI; 3.4-33.5), p = 0.0001. Living in urban settlement was associated with lowest odds of HEV infection {OR 0.4 (95% CI; 0.2-0.8), p = 0.01}. Factors with no statistical evidence of association include main source of drinking water and history of blood transfusion. The sero-prevalence of HEV IgG increased progressively across trimesters with the highest among women in their third trimester (55.3%). None of the 49 HEV sero-positive women had elevated ALT level. Ten (N = 41) of the neonates born to sero-positive women developed jaundice in the neonatal period. The mean birth weight was 3.1kg (SD 0.4). CONCLUSION: HEV sero-prevalence among pregnant women in the Cape Coast Metropolis is high enough to deserve more attention than it has received so far. It is therefore important to conduct further research on the potential impact on maternal and neonatal mortality and morbidity in Ghana.

Impact of universal childhood vaccination against hepatitis B in Ghana: A pilot study.

Hepatitis B virus (HBV) infection is of public health importance worldwide. Vaccination against the infection, especially in early childhood has significantly reduced the public health impact. This pilot study was undertaken in Cape Coast Metropolitan area to assess the impact of the introduction of HBV vaccination in children. A cross-sectional multi-stage cluster sampling of 501 pupils from 30 public and private primary and junior high schools within the Cape Coast metropolis. A questionnaire covering basic demographic details and immunisation history were administered to the participants after consent and assent had been sought. Hepatitis B serological test for HBsAg, HBcAb, HBsAb, HBeAg and HbeAb was undertaken using Hepatitis B test kit and capillary blood from the participants. The general prevalence of HBcAb, HBsAg and HBsAb was found to be 3.6, 2.6 and 19.8% respectively. The prevalence of HBcAb was 2.6 and 6.1% among pupils delivered after and before the vaccine programme introduction respectively. Introduction of the vaccination programme in Ghana has had a positive impact on the HBV infection in Ghana.