Immune responses to P falciparum antibodies in symptomatic malaria patients with variant hemoglobin genotypes in Ghana.

BACKGROUND: Haemoglobin (Hb) variants such as sickle cell trait (SCT/HbAS) play a role in protecting against clinical malaria, but little is known about the development of immune responses against malaria parasite (Plasmodium falciparum surface protein 230 (Pfs230) and Plasmodium falciparum erythrocyte binding antigen 175 region-3 (PfEBA175-3R)) and vector (on the An. gambiae Salivary Gland Protein-6 peptide 1 (gSG6-P1)) antigens in individuals with variants Hb genotypes. This study assessed antibody (IgG) responses against malaria parasite, Pfs230 and PfEBA175-3R and vector, gSG6-P1 in febrile individuals with variant Hb genotypes. METHODS: The study was conducted on symptomatic malaria patients attending various healthcare facilities throughout Ghana. Microscopy and ELISA were used to determine the natural IgG antibody levels of gSG6-P1, PfEBA175-3R & Pfs230, and Capillarys 2 Flex Piercing was used for Hb variants determination. RESULTS: Of the 600 symptomatic malaria patients, 50.0% of the participants had malaria parasites by microscopy. The majority 79.0% (398/504) of the participants had Hb AA, followed by HbAS variant at 11.3% (57/504) and HbAC 6.7% (34/504). There were significantly (p < 0.0001) reduced levels of gSG6-P1 IgG in individuals with both HbAC and HbAS genotypes compared to the HbAA genotype. The levels of gSG6-P1 IgG were significantly (p < 0.0001) higher in HbAS compared to HbAC. Similarly, Pfs230 IgG and PfEBA-175-3R IgG distributions observed across the haemoglobin variants were significantly higher in HbAC relative to HbAS. CONCLUSION: The study has shown that haemoglobin variants significantly influence the pattern of anti-gSG6-P1, Pfs230, and PfEBA-175 IgG levels in malaria-endemic population. The HbAS genotype is suggested to confer protection against malaria infection. Reduced exposure to infection ultimately reduces the induction of antibodies targeted against P. falciparum antigens.

Hypertension and associated factors among patients attending HIV clinic at Korle-Bu Teaching Hospital.

Objectives: This study determined the prevalence of hypertension and its associated factors among patients attending the HIV clinic at the Korle-Bu Teaching Hospital (KBTH). Design: A hospital-based cross-sectional study was conducted at KBTH. The prevalence of hypertension was estimated among study participants, and socio-demographic, lifestyle, anthropometric, metabolic and HIV/ART-related factors associated with hypertension were determined by logistic regression modelling. Setting: Study participants were recruited from the HIV clinic at the KBTH. Participants: A total of 311 Persons Living with HIV were recruited as study participants. Interventions: Simple random sampling technique was used to recruit study participants. A questionnaire adapted from the WHO STEPwise approach to chronic disease risk-factor surveillance was used to collect study participants' data. Results: The prevalence of hypertension was 36.7%, and the factors associated with hypertension were increasing age, positive family history of hypertension, minimal exercising, current BMI ≥25.0 kg/m2, total cholesterol level ≥5.17 mmol/L, exposure to anti-retroviral therapy (ART) and increasing duration of ART exposure. Conclusions: This study shows a high prevalence of hypertension among patients attending the HIV clinic at KBTH, associated with exposure to ART and increasing duration of this exposure. Blood pressure monitoring should move from routine to a more purposeful screening of patients for hypertension. Patients with the identified risk factors should be encouraged to have regular blood pressure measurements at home and not only when they visit the HIV clinic. Funding: Office of Research, Innovation and Development (ORID) of the University of Ghana. The funding agency was not involved in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

Assessment of artemisinin tolerance in Plasmodium falciparum clinical isolates in children with uncomplicated malaria in Ghana.

BACKGROUND: Artemisinin-based combination therapy (ACT) is the first-line treatment for uncomplicated malaria in Ghana. Artemisinin (ART) tolerance in Plasmodium falciparum has arisen in Southeast Asia and recently, in parts of East Africa. This is ascribed to the survival of ring-stage parasites post treatment. The present study sought to assess and characterize correlates of potential ART tolerance based on post-treatment parasite clearance, ex vivo and in vitro drug sensitivity, and molecular markers of drug resistance in P. falciparum isolates from children with uncomplicated malaria in Ghana. METHODS: Six months to fourteen years old children presenting with acute uncomplicated malaria (n = 115) were enrolled in two hospitals and a Health Centre in Ghana's Greater Accra region and treated with artemether-lumefantrine (AL) according to body weight. Pre- and post-treatment parasitaemia (day 0 and day 3) was confirmed by microscopy. The ex vivo ring-stage survival assay (RSA) was used to detect percent ring survival while the 72 h SYBR Green I assay was used to measure the 50% inhibition concentration (IC50s) of ART and its derivatives and partner drugs. Genetic markers of drug tolerance /resistance were evaluated using selective whole genome sequencing. RESULTS: Of the total of 115 participants, 85 were successfully followed up on day 3 post-treatment and 2/85 (2.4%) had parasitaemia. The IC50 values of ART, artesunate (AS), artemether (AM), dihydroartemisinin (DHA), amodiaquine (AQ), and lumefantrine (LUM) were not indicative of drug tolerance. However, 7/90 (7.8%) pre-treatment isolates had > 10% ring survival rates against DHA. Of the four isolates (2 RSA positive and 2 RSA negative) with high genomic coverage, P. falciparum (Pf) kelch 13 K188* and Pfcoronin V424I mutations were only present in the two RSA positive isolates with > 10% ring survival rates. CONCLUSIONS: The observed low proportion of participants with day-3 post-treatment parasitaemia is consistent with rapid ART clearance. However, the increased rates of survival observed in the ex vivo RSA against DHA, maybe a pointer of an early start of ART tolerance. Furthermore, the role of two novel mutations in PfK13 and Pfcoronin genes, harboured by the two RSA positive isolates that had high ring survival in the present study, remains to be elucidated.

Hypertension and associated factors among patients attending HIV clinic at KorleBu Teaching Hospita

Objectives: This study determined the prevalence of hypertension and its associated factors among patients attending the HIV clinic at the Korle-Bu Teaching Hospital (KBTH). Design: A hospital-based cross-sectional study was conducted at KBTH. The prevalence of hypertension was estimated among study participants, and socio-demographic, lifestyle, anthropometric, metabolic and HIV/ART-related factors associated with hypertension were determined by logistic regression modelling. Setting: Study participants were recruited from the HIV clinic at the KBTH. Participants: A total of 311 Persons Living with HIV were recruited as study participants Interventions: Simple random sampling technique was used to recruit study participants. A questionnaire adapted from the WHO STEPwise approach to chronic disease risk-factor surveillance was used to collect study participants' data. Results: The prevalence of hypertension was 36.7%, and the factors associated with hypertension were increasing age, positive family history of hypertension, minimal exercising, current BMI ≥25.0 kg/m2 , total cholesterol level ≥5.17 mmol/L, exposure to anti-retroviral therapy (ART) and increasing duration of ART exposure. Conclusions: This study shows a high prevalence of hypertension among patients attending the HIV clinic at KBTH,associated with exposure to ART and increasing duration of this exposure. Blood pressure monitoring should move from routine to a more purposeful screening of patients for hypertension. Patients with the identified risk factors should be encouraged to have regular blood pressure measurements at home and not only when they visit the HIV clinic.

Prevalence and key predictors of perinatal depression among postpartum women in Ghana.

OBJECTIVE: To determine the prevalence and key predictors of perinatal depression among women in Accra. METHOD: A two-step hospital-based cross-sectional study from May to July 2016. Patient Health Questionnaire version 9 was administered to postpartum mothers, and those aged 18 years or older with scores above 5 who delivered at LEKMA, Ridge, and Korle Bu Hospitals were recruited. A modified Edinburgh Postnatal Depression Scale was used to assess depression at 2 weeks postpartum. Associations between perinatal depression and sociodemographic/obstetric variables were assessed by χ2 and multivariate logistic regression. RESULTS: Among 1456 women screened, the prevalence of mental health disorders was 27.5% (400/1456). Of 350 women recruited, perinatal depression at 2 weeks postpartum was 8.6%, 31.6%, and 41.1% at LEKMA, Ridge, and Korle Bu, respectively. Mothers younger than 20 years and older than 35 years at Korle Bu had depression. Vaginal delivery increased the odds of perinatal depression at Ridge and Korle Bu. Blood transfusion was associated with depression at all three hospitals. CONCLUSION: Blood transfusion, but not other variables, was associated with perinatal depression at 2 weeks postpartum in Accra. Understanding the prevalence of perinatal depression and its associated risk factors in Ghana will aid policy decisions, planning, and clinical management.

Peripheral neuropathy in patients with human immunodeficiency viral infection at a tertiary hospital in Ghana.

Peripheral neuropathy (PN) is the most frequent neurological complication in people living with HIV/AIDS. Neurological damage was identified to not only be caused by the viral infection itself but also through neurotoxic antiretroviral therapy (ART). PN is associated with a variety of risk factors; however, detailed knowledge is scarce for sub-Saharan African populations, bearing among the highest HIV/AIDS infection burden.In a cross-sectional study, we assessed the prevalence of PN in 525 adult outpatients suffering from HIV/AIDS and admitted to the largest tertiary hospital in Ghana. Through a detailed questionnaire and clinical examination including neurologic assessment and laboratory blood sample testing, this study investigated associations of PN with demographic and health determinants and identified risk factors associated with sensory neuropathy.The prevalence of PN in the Ghanaian cohort was 17.7% and increased odd ratios (OR) when patients were taller (> 1.57 m; OR = 3.84; 95% CI 1.38-10.66) or reached the age > 34 years (p = 0.124). Respondents with longer education duration had significantly less PN (≥ 9 years of education; OR = 0.49; 95% CI 0.26-0.92). The study also identified significant association of PN to both waist and hip girth and neutrophil counts. Curiously, higher adjusted odd ratios (aOR) of PN of patients under ART treatment were observed when CD4 lymphocytes were elevated (aOR = 0.81; 95% CI 0.36-1.83 and aOR = 2.17; 95% CI 0.93-5.05, for 300 and 600 counts, respectively). For patients on ART, an increase of 10 CD4 cell count units increased their chance of developing PN by 1% (aOR = 1.01; 95% CI 1.00 to 1.03).Despite current drug application regulations, prevalence of PN is still unacceptably high in sub-Saharan African populations. Reduction in chronic morbidity through a health system with routine monitoring, early diagnosis and prompt intervention, and effective case management can improve people living with HIV/AIDS' quality of life.

Association between eNOS Gene Polymorphism (T786C and VNTR) and Sickle Cell Disease Patients in Ghana.

Endothelial nitric oxide synthase (eNOS) variants have been found to be associated with several vascular disorders as well as the pathogenesis of sickle cell disease (SCD) complications such as vaso-occlusive crises (VOC). Studies on eNOS gene variants among SCD patients are rare in Ghana and several other African countries. The current study aimed to determine a possible association between variants of the eNOS gene (variable number of tandem repeats in intron 4 and T786C) in SCD complications among Ghanaian patients. This was a cross-sectional study involving 89 HbSS patients with complications and 46 HbSS patients without complications. Genomic DNA was extracted from leukocytes in the buffy coat and separated from collected whole blood samples of the study participants. PCR amplification, followed by restriction fragment length polymorphism (RFLP) was used to genotype T786C (rs2070744) variants. Variable number of tandem repeats (VNTR) in intron 4 was genotyped by PCR and direct electrophoresis. There was a significant difference in the genotype frequency of the T786C variant between HbSS patients with complications and those without complications (p = 0.0165). However, there was no significant difference in the VNTR intron 4 variant of the eNOS gene between patients with complications and those without complications (p > 0.05). The study shows an association between the eNOS gene variant (T786C) and complications in SCD.

Modern contraceptive use among women living with HIV/AIDS at the Korle Bu Teaching Hospital in Ghana.

OBJECTIVE: To examine factors influencing contraceptive use among women living with HIV/AIDS. METHODS: The present cross-sectional study included a randomly selected sample of sexually active females aged 15-60 years who were living with HIV/AIDS and receiving care at the HIV Clinic, Korle Bu Teaching Hospital, Accra, Ghana, between September 1 and November 31, 2016. Data were collected via a structured interviewer-administered questionnaire. RESULTS: Among 202 women who completed the survey, 50 (24.7%) were using contraceptives. Of the women using contraception, 39 (78%) were married and 6 (12%) were cohabiting. Twenty-eight (56%) reported that their primary sexual partners were HIV-positive, 14 (28%) had HIV-negative partners, and 8 (16%) did not know their partner's HIV status. Condoms were used by 42 (84%) women and the majority (41 [82%]) wanted to have more children; almost all (47 [94%]) had received counseling on contraceptive use. Overall, 133 (65.8%) and 45 (22.3%) women reported that they would prefer to share their family planning concerns with a doctor and nurse, respectively, at the HIV clinic. CONCLUSION: Women living with HIV/AIDS desired more children but preferred to share their family planning concerns with their clinician at the HIV clinic. Integrating HIV care and reproductive health services could help these women achieve childbearing goals safely.

Genetic polymorphisms of patients on stable warfarin maintenance therapy in a Ghanaian population.

BACKGROUND: Warfarin is a widely prescribed anticoagulant with narrow therapeutic window for thromboembolic events. Warfarin displays large individual variability in dose requirements. The purpose of this study is to assess the contribution of patient-specific and genetic risk factors to dose requirements of patients on either high or low warfarin maintenance dose in Ghana. Blood samples were collected from 141 (62 males, 79 females) Ghanaian patients on stable warfarin dose to determine their INR. Influence of patient specific factors and gene variations within VKORC1, CYP2C9 and CYP4F2 were determined in patients on either high or low warfarin maintenance dose. RESULTS: One hundred and forty-one patients took part in the study with 79 (56%) participants being Female. The median age of the study participants was 48 years [IQR: 34-58]. The median duration for patients to be on warfarin therapy was 24 months [IQR: 10-72]. Majority of the study participants (80.9%, n = 114) did not have any side effects to warfarin. CYP2C9*2 and CYP2C9*3 variant alleles were not detected. VKORC1 variant allele was observed at 6% and CYP4F2 variant allele was observed at 41%. Duration of patients on warfarin therapy was marginally associated with high warfarin dose (adjusted OR = 1.01 [95% CI 1.00-1.02], p = 0.033) while the odds of heterozygous individuals (G/A) for VKORC1 gene to have high warfarin dose compared to persons with homozygous (G/G) (adjusted OR = 0.06 [95% CI 0.01-0.63], p = 0.019). Age, gender, diagnosis, presence of side effects and other medications were not associated with warfarin dose (p = 0.05). CONCLUSION: This study provides data on VKORC1 and CYP4F2 variants among an indigenous African population. Duration of patients on warfarin therapy was marginally associated with high warfarin dose. CYP2C9*2 and *3 variants were not detected and may not be the most important genetic factor for warfarin maintenance dose among Ghanaians.

Profile of adverse events in patients receiving treatment for malaria in urban Ghana: a cohort-event monitoring study.

BACKGROUND: Antimalarial treatment strategies have changed much in the last 15 years, resulting in an increased variety of medicines available. Active pharmacovigilance methods are important for continued safety surveillance of these medicines, particularly in environments in which there is variability in treatments prescribed and limited confirmatory diagnostic capacity as well as limited ability of spontaneous reporting pharmacovigilance systems to generate much needed safety information quickly and efficiently. OBJECTIVE: Our objective was to use the cohort-event monitoring (CEM) technique to gather drug utilization and adverse event data for patients prescribed antimalarial medicines in an outpatient setting. METHODS: The characteristics of a large urban African cohort of outpatients (n = 2,831) receiving antimalarial medications are described. The cohort was actively surveyed over the subsequent week to record adverse events, using follow-up phone calls, paper reports, and/or voluntary return clinic visits. Adverse events reported in the cohort were analysed overall and by clinically relevant age and medication groupings. RESULTS: At least one event was reported in 29.4 % of patients. Adverse events were more likely to be reported in subjects older than 12 years of age, and by patients prescribed an artesunate-amodiaquine combination. A range of adverse events were reported, the most frequent higher level terms being asthenic conditions (10.1 % of total cohort), neurological signs and symptoms (4.5 %), headaches (3.1 %), appetite disorders (2.1 %), and disturbances in consciousness (1.6 %). There were three reports of possible extrapyramidal events (two cases of tremor "hand and back shaking all over" and one case of tongue protrusion), which may appear to be related to combinations including amodiaquine and an artemisinin. CONCLUSION: The CEM methodology is a useful tool for monitoring the safety of widely available and utilized medicines, particularly in an urban environment where spontaneous reporting yields poor results and where the availability of various regimens and high levels of medicine usage can give valuable 'real-life' safety data. The types and frequencies of events reported reflected the types of events expected in patients prescribed antimalarials and nearly all events reported are listed in the summary of product characteristics of the medicines involved.

Antioxidant and gastric cytoprotective prostaglandins properties of Cassia sieberiana roots bark extract as an anti-ulcerogenic agent.

BACKGROUND: Cassia sieberiana is a savannah tree with a wide phytotherapeutic application including the use of its roots in the management of various stomach disorders including gastric ulcer, stomach pains and indigestion. The aim of the study is to evaluate the antioxidant, gastric cytoprotective prostaglandins, secretory phospholipase A2, phytochemical and acute toxicity properties of Cassia sieberiana roots bark extract in a bid to justify its phytotherapeutic applications in gastric ulcer. METHODS: Antioxidant and radical scavenging activities of the roots bark extract of Cassia sieberiana were assayed. Serum secretory phospholipase A2 (sPLA2) concentration and activity and the formation of gastric mucosal prostaglandins E2 (PGE2) and I2 (PGI2) were also assessed. Comparisons between means were performed using analysis of variance (ANOVA) followed by Students Standard Newman-Keuls post hoc analysis to determine statistical significance. P < 0.05 was considered significant. RESULTS: The extract was found to possess significant ferric reducing antioxidant power and can scavenge hydroxyl radicals. The extract also possesses DPPH scavenging activity, can chelate ferrous ion and a dose-dependent protective effect against lipid peroxidation and free radical generation. Prostaglandin studies showed that the roots bark extract dose dependently increased gastric mucosal PGE2 and PGI2 levels and also decreased serum sPLA2 activity. Phytochemical analyses suggest that the roots extract contains polyhydroxyl/phenolic substances. Acute toxicity test showed no sign of toxicity up to a dose level of 2000 mg/kg body weight p.o. CONCLUSIONS: C. sieberiana roots extract possesses significant antioxidant and gastric cytoprotective prostaglandin properties as well as serum secretory phospholipase A2 inhibitory activity which could be due to its content of polyhydroxy and/or phenolic substances. This may justify its use as an anti-ulcerogenic agent in traditional medicine in West Africa.

Pharmacogenetics and rational drug use around the world.

The WHO embraces evidence-based medicine to formulate an essential medicines list (EML) considering disease prevalence, drug efficacy, drug safety and cost-effectiveness. The EML is used by developing countries to build a national formulary. As pharmacogenetics in developed countries evolves, the Pharmacogenetics for Every Nation Initiative (PGENI) convened with representatives from China, Mexico, Ghana and South Africa in August 2009 to evaluate the use of human pharmacogenetics to enhance global drug use policy. The diseases causing mortality, the lack of integration of pharmacovigilance at the national formulary level, the pharmacogenetics research agenda and pharmacogenetics clinician education did not differ greatly among the countries. While there are many unanswered questions, systematically incorporating pharmacogenetics at the national formulary level promises to improve global drug use.

Genetic polymorphisms in MDR1, CYP3A4 and CYP3A5 genes in a Ghanaian population: a plausible explanation for altered metabolism of ivermectin in humans?

BACKGROUND: Ivermectin, a substrate of multidrug resistance (MDR1) gene and cytochrome P450 (CYP) 3A4, has been used successfully in the treatment of onchocerciasis in Ghana. However, there have been reports of suboptimal response in some patients after repeated treatment. Polymorphisms in host MDR1 and CYP3A genes may explain the observed suboptimal response to ivermectin. We genotyped relevant functional polymorphisms of MDR1 and CYP3A in a random sample of healthy Ghanaians and compared the data with that of ivermectin-treated patients with a view to exploring the relationship between suboptimal response to ivermectin and MDR1 and CYP3A allelic frequencies. METHODS: Using PCR-RFLP, relevant polymorphic alleles of MDR1 and CYP3A4 genes were analysed in 204 randomly selected individuals and in 42 ivermectin treated patients. RESULTS: We recorded significantly higher MDR1 (3435T) variant allele frequency in suboptimal responders (21%) than in patients who responded to treatment (12%) or the random population sample (11%). CYP3A4*1B, CYP3A5*3 and CYP3A5*6 alleles were detected at varied frequencies for the sampled Ghanaian population, responders and suboptimal responders to ivermectin. CYP3A5*1/CYP3A5*1 and CYP3A5*1/CYP3A5*3 genotypes were also found to be significantly different for responders and suboptimal responders. Haplotype (*1/*1/*3/*1) was determined to be significantly different between responders and suboptimal responders indicating a possible role of these haplotypes in treatment response with ivermectin. CONCLUSION: A profile of pharmacogenetically relevant variants for MDR1, CYP3A4 and CYP3A5 genes has been generated for a random population of 204 Ghanaians to address the scarcity of data within indigenous African populations. In 42 patients treated with ivermectin, difference in MDR1 variant allele frequency was observed between suboptimal responders and responders.

Characterisation of CYP2C8, CYP2C9 and CYP2C19 polymorphisms in a Ghanaian population.

BACKGROUND: Genetic influences on drug efficacy and tolerability are now widely known. Pharmacogenetics has thus become an expanding field with great potential for improving drug efficacy and reducing toxicity. Many pharmacologically-relevant polymorphisms do show variability among different populations. Knowledge of allelic frequency distribution within specified populations can be useful in explaining therapeutic failures, identifying potential risk groups for adverse drug reactions (ADRs) and optimising doses for therapeutic efficacy. We sought to determine the prevalence of clinically relevant Cytochrome P450 (CYP) 2C8, CYP2C9, and CYP2C19 variants in Ghanaians. We compared the data with other ethnic groups and further investigated intra country differences within the Ghanaian population to determine its value to pharmacogenetics studies. METHODS: RFLP assays were used to genotype CYP2C8 (*2, *3, *4) variant alleles in 204 unrelated Ghanaians. CYP2C9*2 and CYP2C19 (*2 and *3) variants were determined by single-tube tetra-primer assays while CYP2C9 (*3, *4, *5 and *11) variants were assessed by direct sequencing. RESULTS: Allelic frequencies were obtained for CYP2C8*2 (17%), CYP2C8*3 (0%), CYP2C8*4 (0%), CYP2C9*2 (0%), CYP2C9*3 (0%), CYP2C9*4 (0%), CYP2C9*5 (0%), CYP2C9*11 (2%), CYP2C19*2 (6%) and CYP2C19*3 (0%). CONCLUSION: Allele frequency distributions for CYP2C8, CYP2C9 and CYP2C19 among the Ghanaian population are comparable to other African ethnic groups but significantly differ from Caucasian and Asian populations. Variant allele frequencies for CYP2C9 and CYP2C19 are reported for the first time among indigenous Ghanaian population.

Prevalence of antibodies to syphilis among blood donors in Accra, Ghana.

Several infectious diseases have been found to be associated with transfusion of blood and blood components. Reports from studies conducted in many African countries indicate a high incidence of blood-borne pathogens such as syphilis infections among healthy blood donors. The prevalence of syphilis antibodies in blood donors in Ghana is not known. This study was therefore conducted in order to determine the prevalence of antibodies to syphilis among blood donors seen between the months of January and March 2003 at the National Blood Transfusion Service, Accra area (Blood Bank) at the Korle-Bu Teaching Hospital, Accra, Ghana. The presence of antibodies specific for syphilis was tested using Venereal Disease Research Laboratory and particle agglutination test kit. A sero-prevalence rate of 7.5% was found. Our sample of blood donors was largely comprised of male subjects (500 out of 536 donors, and only 1 out of the 36 screened female donors was positive), making sex comparisons statistically undesirable. In both sexes, the age distribution of subjects positive for syphilis antibodies was from 19 - 54 (median age, 32) years. In conclusion, our results indicate that syphilis is prevalent among healthy blood donors in Ghana, and that there is a need to introduce the screening of donated blood for syphilis in Ghana.