Ohene Opare-Sem

Molecular and serological characterization of hepatitis B virus in deferred Ghanaian blood donors with and without elevated alanine aminotransferase.

Summary.  Candidate blood donors in Ghana are frequent carriers of hepatitis B virus (HBV). A comparative study of 117 donor samples including 46 with alanine aminotransferase (ALT) ≥ 60 IU/L and 71 with ≤40 IU/L level was undertaken. S and the basic core promoter‐precore regions (BCP/PC) sequencing was used to identify genotypes and variants relevant to HBV natural history, respectively. Age, viral load, HBe status were correlated with molecular data. HBV genotype E (87%) was dominant with little genotypes A (10%) and D (3%). Comparing individuals with or without liver disease, an association between liver disease and older age (P = 0.004) and higher viral load (P = 0.002) whether as a whole population or only genotype E was found. Compared with a commercial assay, BCP/PC sequencing had lower sensitivity to detect mixtures of wild‐type and variant viruses but detected BCP deletions. BCP 1762/1764 variants were positively correlated with older age (P < 0.0001) and elevated ALT levels (P = 0.01). PC 1896 stop codon was marginally correlated with viral load (P = 0.09). HBV genotype E infection natural history appears different from genotypes B and C prevalent in Asia. Donors with liver disease being older, with higher viral load and higher BCP variant proportion may be at higher risk of cirrhosis and hepatocellular carcinoma

Prevalence of persistent and latent viruses in untreated patients infected with HIV-1 from Ghana, West Africa.

Only limited epidemiological data, pertaining to the prevalence of common persistent viruses has been reported in Ghana. This study was conducted to determine the prevalence of persistent viruses in individuals with untreated HIV‐1 infection and uninfected blood donors. Paired plasma and cellular samples from HIV‐negative blood donors, asymptomatic HIV and symptomatic/AIDS cohorts were screened by multiplex PCR then qPCR for parvovirus B19 (B19V), hepatitis B virus (HBV), GB virus‐C (GBV‐C), cytomegalovirus (CMV), Epstein–Barr virus (EBV), human herpesvirus‐8 (HHV‐8) and varicella‐zoster virus (VZV). IgG antibodies specific to each target virus were tested to determine exposure rates. No evidence of viraemia was found for B19V and VZV in any group. Prevalence of GBV‐C plasma viraemia was significantly higher in asymptomatic and symptomatic HIV infection (16.7%) and (16.2%) than in blood donors (4%) P < 0.005. Occult HBV infection was significantly more frequent in symptomatic HIV infection (10.9%) compared to asymptomatic HIV (3.6%) and blood donors (1.6%) P < 0.005. Although there was a high background of EBV viraemia in cellular fractions of blood donors (8.3%), it was significantly higher in asymptomatic (44.6%) and symptomatic HIV (14.6%) P < 0.0001. For CMV, the significantly increased prevalence of viraemia was only observed in the plasma fraction of the symptomatic HIV‐1/AIDS patients (7.6%) compared to asymptomatic individuals (1.8%) and blood donors (0.8%) P ≤ 0.001. The background seroprevalence in blood donors was high for B19V (≥64%), HBV (≥70%), CMV and EBV (≥90%) and was significantly increased in HIV infections for HBV, CMV, VZV (symptomatic HIV), and HHV‐8 (asymptomatic and symptomatic HIV). J. Med. Virol. 81:1860–1868, 2009.

Multiplex real-time PCR for the detection and quantification of latent and persistent viral genomes in cellular or plasma blood fractions.

In common with latent viruses such as herpesviruses, parvovirus B19, HBV and GBV-C are contained successfully by the immune response and persist in the host. When immune control breaks down, reactivation of both latent and persistent viruses occurs. Two multiplex assays were developed (B19, HBV, HHV-8), (EBV, CMV, VZV) for blood screening, and tested on blood donor samples from Ghana to determine baseline prevalence of viraemia in immunocompetent persons. Single-virus real-time quantitative PCR (qPCR) assays were optimised for viral load determination of positive initial screening. The qPCR method utilised was absolute quantification with external standards. Multiplex and single-virus qPCR assays had similar sensitivity, except for the B19 assay in which sensitivity was 100-fold lower. Assays were optimised for reproducibility and repeatability, with R(2) of 0.9 being obtained for most assays. With the exception of B19 and CMV, assays had 100% detection limit ranging between 10(1) and 10(2) copies, IU or arbitrary units under single-virus and multiplex assay conditions. The prevalence of viraemia was 1.6% HBV (0.8% DNA+/HBsAg-, 0.8% DNA+/HBsAg+), 0.8% parvovirus B19, and 3.3% GBV-C viraemia in the plasma fraction. The prevalence of four herpesviruses was 1.0% HHV-8, 0.85% CMV, and 8.3% EBV, and no detectable VZV viraemia.

High Frequency of Active HCV Infection Among Seropositive Cases in West Africa and Evidence for Multiple Transmission Pathways

BACKGROUND Sub-Saharan Africa (SSA) has one of the highest global hepatitis C virus (HCV) prevalence estimates. However, reports that suggest high rates of serologic false positives and low levels of viremia have led to uncertainty regarding the burden of active infection in this region. Additionally, little is known about the predominant transmission risk factors in SSA. METHODS We prospectively recalled 363 past blood donors (180 who were rapid screen assay [RSA] positive and 183 who were RSA negative at time of donation) to identify the level of active infection and risk factors for infection at a teaching hospital in Kumasi, Ghana. Participants had repeat blood testing and were administered a questionnaire on risk factors. RESULTS The frequency of HCV active infection ranged from 74.4% to 88% depending on the criteria used to define serologically positive cases. Individuals with active disease had biochemical evidence of liver inflammation and median viral loads of 5.7 log copies/mL. Individuals from the northern and upper regions of Ghana had greater risks of infection compared with participants from other areas. Additional risk factors included traditional circumcision, home birth, tribal scarring, and hepatitis B virus coinfection. CONCLUSIONS Viremic infection was common among serologically confirmed cases. Attention to testing algorithms is needed in order to define the true HCV burden in SSA. These data also suggest that several transmission modes are likely contributing to the current HCV epidemic in Ghana and that the distribution of these practices may result in substantial regional variation in prevalence.

Hepatitis C in sub-saharan Africa: urgent need for attention.

The hepatitis C virus (HCV), which was not recognized as an infectious agent until the 1980s, is responsible for a worldwide epidemic. The World Health Organization estimates global prevalence at 2.8%, with 185 million persons infected. In contrast to hepatitis B, where successful vaccine campaigns have reduced the disease burden, much less progress has been made toward the control of HCV. Phylogenetic studies suggest that HCV originated in Africa and has been endemic in some regions for at least 500–600 years. However, little is known about the epidemiology, transmission, and clinical course of HCV in Africa. With the advent of highly effective anti-HCV agents, there exists great potential to at least curb the global epidemic. For regions such as sub-Saharan Africa, however, this will require a thorough understanding of the regional population-level epidemiology, risk factors, and transmission mechanisms. Only then can effective treatment and prevention strategies be introduced.

Recent patterns and predictors of neurological mortality among hospitalized patients in Central Ghana

BACKGROUND Although neurological disorders are projected to escalate globally in the coming decades, there is a paucity of enumerated data on the burden, spectrum and determinants of outcomes of adult neurological admissions in resource-limited settings, especially within sub-Saharan Africa. OBJECTIVE To evaluate the diversity, demography, and determinants of mortality among adult patients presenting with neurological disorders over a 6-year period in a tertiary medical referral institution in the Central belt of Ghana. METHODS A retrospective analysis of data on neurological admissions and in-patient outcomes between 2008 and 2013 was undertaken. Data collected for analyses included age, gender, neurological diagnosis, documented comorbidities, duration of admission and vital status at discharge. Predictors of in-patient mortality were evaluated using Kaplan-Meier survival curves and Cox Proportional Hazards regression models. RESULTS The 6494 admissions with neurological disorders represented 15.0% of all adult medical admissions over the study period. Male-to-female ratio of admissions was 1.6:1.0 with a mean±SD age of 52.9±20 years. The commonest neurological disorders were Cerebrovascular, Infectious, Seizures/epilepsy, Alcohol-use and Spinal cord disorders representing 54.0%, 26.7%, 10.3%, 4.0% and 2.3% of admissions respectively. Despite the low national HIV prevalence of 2.0%, the frequency of HIV infection among patients with infectious disorders of the nervous system was 40.9%. Overall crude mortality rate for neurologic admissions was 30.6% being 39.1% and 33.9% for Infectious affectations of the nervous system and stroke respectively and 7.4% for seizure disorders. Probability of death was higher for females than males aHR (95% CI) of 1.53 (1.40-1.68) and increasing age aHR (95% CI) of 1.11 (1.06-1.17) for each 20-year increase in age. CONCLUSION Almost one in three patients admitted with neurological disease to a tertiary care center in Ghana died in the hospital, and the majority of these deaths were due to non-communicable conditions. Enhanced multi-dimensional public health disease prevention strategies and neurological inpatient care processes are warranted.

Lack of correlation between hepatitis B surface antigen and hepatitis B virus DNA levels in blood donors.

The shortage of human blood and organs has led to increased interest in animal substitutes. In both transplantation and transfusion, the greatest roadblock to the use of animal tissues is the expression of xenoantigens. A major xenoantigen in pigs is linear B (Gal α 1-3Gal β 14GlcNAc-R), a cross-reactive, B-like antigen expressed on red blood cells (RBCs) and other tissues that is recognized by naturally occurring antibodies present in human serum. 1,2

Fourteen-year experience of a tertiary hospital transfusion committee in West Africa.

Hospital transfusion committees (HTCs) have been established in the United States to link producers and users as well as to ensure appropriate use of blood. The HTC has been little reported in sub‐Saharan Africa (SSA), although it has been established in some hospitals.

High prevalence of multidrug-resistant tuberculosis among patients with rifampicin resistance using GeneXpert Mycobacterium tuberculosis/rifampicin in Ghana.

Objective/Background: Drug-resistant strains of tuberculosis (TB) represent a major threat to global TB control. In low- and middle-income countries, resource constraints make it difficult to identify and monitor cases of resistance using drug susceptibility testing and culture. Molecular assays such as the GeneXpert Mycobacterium tuberculosis/rifampicin may prove to be a cost-effective solution to this problem in these settings. The objective of this study is to evaluate the use of GeneXpert in the diagnosis of pulmonary TB since it was introduced into two tertiary hospitals in Ghana in 2013. Methods: A 2-year retrospective audit of clinical cases involving patients who presented with clinically suspected TB or documented TB not improving on standard therapy and had samples sent for GeneXpert testing. Results: GeneXpert identified 169 cases of TB, including 17 cases of rifampicin-resistant TB. Of the seven cases with final culture and drug susceptibility testing results, six demonstrated further drug resistance and five of these were multidrug-resistant TB. Conclusion: These findings call for a scale-up of TB control in Ghana and provide evidence that the expansion of GeneXpert may be an optimal means to improve case finding and guide treatment of drug-resistant TB in this setting.

Risk factors for stroke occurrence in a low HIV endemic West African country: A case-control study

BACKGROUND HIV infection is an emerging vascular risk factor associated with stroke occurrence. The weight of evidence from sub-Saharan Africa in support of this has accrued from countries with high HIV prevalence. Our objective was to assess the contribution of HIV sero-positivity to the occurrence and outcomes of stroke in a West African country with low HIV prevalence. METHODS A case-control study design conducted at a tertiary medical center in Ghana involved in the Stroke Investigative Research & Educational Networks (SIREN) epidemiological study. Stroke cases were adults (aged ≥18 years) with CT or MRI confirmed stroke and stroke-free controls were age-matched and recruited from communities in the catchment areas of cases. Standard instruments were used to assess vascular and lifestyle factors and serological screening for HIV antibodies was conducted for all study participants. Stroke patients were followed for in-patient mortality outcomes. Associations between HIV, demographic and vascular risk factors and stroke occurrence and outcomes were assessed using logistic regression analysis. RESULTS We enrolled 540 stroke cases and 540 control subjects with a mean (± SD) age of 60.8 ± 15.5 years (cases) and 60.0 ± 15.5 (controls). Among stroke cases, the frequency of HIV was 12/540 (2.2%, 95% CI: 1.3% - 3.6%) versus 15/540 (2.8%, 95% CI: 1.7% - 4.6%) among stroke-free controls, p = .70. However, the median (IQR) age of Persons Living with HIV (PLWH) with stroke was significantly lower at 46.5 (40-65.3) years versus 61.0 (50-74) years, p = .03 among HIV- stroke patients. Stroke among PLWHA was predominantly hemorrhagic in 7 out of 12 cases and ischemic in 5 of 12 with notable clustering of established factors such as hypertension, (100%), dyslipidemia, 83.3%, central obesity, 50.0%, diabetes mellitus, 33.3%, cardiac diseases, 8.3% in this group. None of the PLWH with stroke were receiving antiretroviral therapy. CONCLUSION We found no associations between HIV infection and stroke occurrence among Ghanaians. However a clustering of cardio-metabolic factors in the context of HIV may promote stroke occurrence in younger individuals.