Multinational, Multicenter Evaluation of Prostate Cancer Tissue in Sub-Saharan Africa: Challenges and Opportunities.

PURPOSE: Prostate cancer disproportionately affects men of African descent, yet their representation in tissue-based studies is limited. This multinational, multicenter pilot study aims to establish the groundwork for collaborative research on prostate cancer in sub-Saharan Africa. METHODS: The Men of African Descent and Carcinoma of the Prostate network formed a pathologist working group representing eight institutions in five African countries. Formalin-fixed paraffin-embedded prostate tissue specimens were collected from Senegal, Nigeria, and Ghana. Histology slides were produced and digitally scanned. A central genitourinary pathologist (P.L.) and eight African general pathologists reviewed anonymized digital whole-slide images for International Society of Urological Pathology grade groups and other pathologic parameters. Discrepancies were re-evaluated, and consensus grading was assigned. A virtual training seminar on prostate cancer grading was followed by a second assessment on a subcohort of the same tissue set. RESULTS: Of 134 tissue blocks, 133 had evaluable tissue; 13 lacked cancer evidence, and four were of insufficient quality. Post-training, interobserver agreement for grade groups improved to 56%, with a median Cohen's quadratic weighted kappa of 0.83 (mean, 0.74), compared with an initial 46% agreement and a quadratic weighted kappa of 0.77. Interobserver agreement between African pathologist groups was 40%, with a quadratic weighted kappa of 0.66 (95% CI, 0.51 to 0.76). African pathologists tended to overgrade (36%) more frequently than undergrade (18%) compared with the reference genitourinary pathologist. Interobserver variability tended to worsen with a decrease in tissue quality. CONCLUSION: Tissue-based studies on prostate cancer in men of African descent are essential for a better understanding of this common disease. Standardized tissue handling protocols are crucial to ensure good tissue quality and data. The use of digital slide imaging can enhance collaboration among pathologists in multinational, multicenter studies.

Validation of a multi-ancestry polygenic risk score and age-specific risks of prostate cancer: A meta-analysis within diverse populations.

Background: We recently developed a multi-ancestry polygenic risk score (PRS) that effectively stratifies prostate cancer risk across populations. In this study, we validated the performance of the PRS in the multi-ancestry Million Veteran Program and additional independent studies. Methods: Within each ancestry population, the association of PRS with prostate cancer risk was evaluated separately in each case-control study and then combined in a fixed-effects inverse-variance-weighted meta-analysis. We further assessed the effect modification by age and estimated the age-specific absolute risk of prostate cancer for each ancestry population. Results: The PRS was evaluated in 31,925 cases and 490,507 controls, including men from European (22,049 cases, 414,249 controls), African (8794 cases, 55,657 controls), and Hispanic (1082 cases, 20,601 controls) populations. Comparing men in the top decile (90-100% of the PRS) to the average 40-60% PRS category, the prostate cancer odds ratio (OR) was 3.8-fold in European ancestry men (95% CI = 3.62-3.96), 2.8-fold in African ancestry men (95% CI = 2.59-3.03), and 3.2-fold in Hispanic men (95% CI = 2.64-3.92). The PRS did not discriminate risk of aggressive versus nonaggressive prostate cancer. However, the OR diminished with advancing age (European ancestry men in the top decile: ≤55 years, OR = 7.11; 55-60 years, OR = 4.26; >70 years, OR = 2.79). Men in the top PRS decile reached 5% absolute prostate cancer risk ~10 years younger than men in the 40-60% PRS category. Conclusions: Our findings validate the multi-ancestry PRS as an effective prostate cancer risk stratification tool across populations. A clinical study of PRS is warranted to determine whether the PRS could be used for risk-stratified screening and early detection. Funding: This work was supported by the National Cancer Institute at the National Institutes of Health (grant numbers U19 CA214253 to C.A.H., U01 CA257328 to C.A.H., U19 CA148537 to C.A.H., R01 CA165862 to C.A.H., K99 CA246063 to B.F.D, and T32CA229110 to F.C), the Prostate Cancer Foundation (grants 21YOUN11 to B.F.D. and 20CHAS03 to C.A.H.), the Achievement Rewards for College Scientists Foundation Los Angeles Founder Chapter to B.F.D, and the Million Veteran Program-MVP017. This research has been conducted using the UK Biobank Resource under application number 42195. This research is based on data from the Million Veteran Program, Office of Research and Development, and the Veterans Health Administration. This publication does not represent the views of the Department of Veteran Affairs or the United States Government.

Effect of HIV infection on TB treatment outcomes and time to mortality in two urban hospitals in Ghana-a retrospective cohort study.

INTRODUCTION: Tuberculosis (TB) is currently causing more deaths than Human Immunodeficiency Virus (HIV) globally. Ghana as one of the 30 high burden TB/HIV countries has a high annual TB case-fatality rate of 10%. The study sought to assess the effect of HIV infection on TB treatment outcomes and assess the time to mortality after treatment onset. METHODS: We conducted a review of treatment files of TB patients who were treated from January 2013 to December 2015 in two urban hospitals in the Accra Metropolis. Modified Poisson regression analysis was used to measure the association between HIV infection and TB treatment outcomes. Kaplan-Meier survival estimates were used to plot survival curves. RESULTS: Seventy-seven percent (83/107) of HIV infected individuals had successful treatment, compared to 91.2% (382/419) treatment success among HIV non-infected individuals. The proportion of HIV-positive individuals who died was 21.5% (23/107) whilst that of HIV-negative individuals was 5.5% (23/419). Being HIV-positive increased the risk of adverse outcome relative to successful outcome by a factor of 2.89(95% CI 1.76-4.74). The total number of deaths recorded within the treatment period was 46; of which 29(63%) occurred within the first two months of TB treatment. The highest mortality rate observed was among HIV infected persons (38.6/1000 person months). Of the 107 TB/HIV co-infected patients, 4(3.7%) initiated ART during TB treatment. CONCLUSION: The uptake of ART in co-infected individuals in this study was very low. Measures should be put in place to improve ART coverage among persons with TB/HIV co-infection to help reduce mortality.

HER-2 Protein Overexpression in Patients with Gastric and Oesophageal Adenocarcinoma at a Tertiary Care Facility in Ghana.

The prognosis of gastric and oesophageal adenocarcinoma remains generally poor. However, mounting evidence suggests a positive role of human epidermal growth factor receptor-2 (HER-2) expression in the prognosis of patients with these cancers. In this work, the patterns of HER-2 protein expression were determined in patients with gastric or oesophageal adenocarcinoma. Retrospectively, we reviewed records of gastric and oesophageal biopsies received from 2008 to 2012 and their corresponding archived formalin-fixed paraffin-embedded tissue blocks selected for immunohistochemical analysis. The prevalence of gastric and oesophageal adenocarcinomas and their association with HER-2 protein overexpression were evaluated. Gastric adenocarcinoma made up 18.79% of the gastric biopsies reviewed, and majority of these cancers occurred in males. Regarding the tumour type, HER-2 overexpression was common in the intestinal subtype compared to the diffuse type. Although squamous cell carcinoma was observed to be the commonest (31%) tumour type in the oesophagus compared to adenocarcinoma (8.79%), HER-2 was overexpressed in 42.9% of oesophageal adenocarcinomas, like gastric adenocarcinoma (41.4%). There is a high prevalence of gastric and oesophageal adenocarcinoma, with significant overexpression of HER-2 in these tumours, a window of hope for the management of patients with these cancers.

Detection of Human Papillomavirus Genotypes and Epstein-Barr Virus in Nasopharyngeal Carcinomas at the Korle-Bu Teaching Hospital, Ghana.

Nasopharyngeal carcinomas (NPC) are endemic in Far East Asia and commonly harbour Epstein-Barr virus (EBV) which is known to serve as a key oncogenic promoter. Human papillomavirus (HPV) is known to contribute to the pathogenesis of NPC. However, in Ghana these two viruses have not been linked to NPC prevalence. This study was designed to determine the HPV genotypes and EBV involved in NPC tissue biopsies. A retrospective study design involving 72 formalin-fixed paraffin-embedded tissue (FFPET) samples of NPC from 2006 to 2012 were retrieved from the Department of Pathology, University of Ghana School of Biomedical and Allied Health Sciences. Sections were taken for histological analysis and for DNA lysate preparation. The DNA lysates were subjected to polymerase chain reaction (PCR) analysis to determine the presence of HPV genotypes and EBV. HPV specific primers were used to type for fourteen HPV genotypes (HPV-16, 18, 6/11, 31, 33, 35, 44, 42, 43, 45, 56, 52, 58, and 59). Out of the 72 NPC biopsies analyzed by PCR, EBV DNA was present in 18 (25%) cases and HPV DNA in 14 (19.23%). High risk HPV (HR-HPV) genotypes 18 and 31 were associated with the NPC. There were 3 (4.2%) cases of coinfection by both viruses. The EBV DNA present in the undifferentiated variant of the NPC and the histopathology of the NPC in Ghana is similar to the type described in endemic areas.

Giardia lamblia infections in children in Ghana.

INTRODUCTION: Though giardiasis is an important public health problem in Ghana, several aspects of its epidemiology, particularly the molecular epidemiology has not been investigated adequately. This could be a major hindrance to effective surveillance and control of giardiasis in the country. The study was carried out to determine the prevalence, risk factors and genotypes of Giardia lamblia infecting children at a paediatric hospital in Ghana. METHODS: A total of 485 patients including 365 diarrhoea and 120 non-diarrhoea children were enrolled into the study. Stool samples were collected and analysed for parasite presence using microscopy, ELISA and PCR. Positive samples were subsequently characterized into assemblages by PCR-RFLP, and further confirmed with sequencing of the glutamate dehydrogenase (gdh) gene. Epidemiological data on demographic, clinical and behavioral features of the study subjects were also collected. RESULTS: Prevalence of G. lamblia infections in diarrhoea and non-diarrhoea children were 5.8% and 5% respectively (P>0.5). Sequence data confirmed Giardia lamblia assemblage B as the predominant genotype in both diarrhoea and non-diarrhoea cases. There was no significant association of G. lamblia infection with any of the epidemiological variables investigated. CONCLUSION: Our findings suggest that assemblage B could be the predominant genotype causing giardiasis in children. Increased public health education focusing on good sanitary practices, particularly among mothers and children, could decrease the risk of G. lamblia infection.

Hepatitis B virus genotypes among chronic hepatitis B patients reporting at Korle-Bu teaching hospital, Accra, Ghana.

INTRODUCTION: Knowledge of hepatitis B virus (HBV) genotype is an important predictive variable which might have an impact in management and treatment of patients with chronic hepatitis B infection. In Ghana very little information is available on hepatitis B genotypes. This study was conducted to determine the distribution of HBV genotypes circulating among chronic hepatitis B patients reporting at the Korle-Bu Teaching Hospital (KBTH), Accra, Ghana. METHODS: Blood samples (10 ml) were collected from 250 consenting patients. DNA was extracted and amplified using polymerase chain reaction technique. Restriction fragment length polymorphism (RFLP) was used for the detection of genotypes. RESULTS: Out of the 250 chronic hepatitis B patients who were HBsAg positive, 91 (36.4%) were males aged 29.8 ± 9.1 and 159 (63.6%) females aged 33± 12.1 years. HBV DNA was detected in 111 (44.4%) but only 58 (52%) of these were typeable. These were classified as genotype A, 8 (7.2%); genotype D, 3 (2.7%) and genotype E, 47 (42.3%). Our results did not show any association between the infecting genotype and age (X2= 0.923; p-value=0.623) or gender (X2= 0.283, p= 0.579). CONCLUSION: Consistent with similar studies worldwide, the results suggest that genotypes A, D and E were the genotypes circulating among chronic hepatitis B patients who reported to the Korle-Bu Teaching Hospital with genotype E being the most predominant and therefore constitutes an important public health concern. We recommend further epidemiological studies to understand the implication of genotype E in terms of disease progression and treatment.

Coping strategies of HIV-affected households in Ghana.

BACKGROUND: HIV and negative coping mechanisms have a cyclical relationship. HIV infections may lead to the adoption of coping strategies, which may have undesired, negative consequences. We present data on the various coping mechanisms that HIV-affected households in Ghana resort to. METHODS: We collected data on coping strategies, livelihood activities, food consumption, and asset wealth from a nationally representative sample of 1,745 Ghanaian HIV-affected households. We computed coping strategies index (CSI), effective dependency rate, and asset wealth using previously validated methodologies. RESULTS: Various dehumanizing coping strategies instituted by the HIV-affected households included skipping an entire day's meal (13%), reducing portion sizes (61.3%), harvesting immature crops (7.6%), and begging (5.6%). Two-thirds of the households were asset poor. Asset-poor households had higher CSI than asset-rich households (p <0.001). CSI were also higher among female-headed households and lower where the education level of the household head is higher. Households caring for chronically ill members recorded higher CSI in comparison with their counterparts without the chronically ill (p < 0.05). CONCLUSIONS: Institution of degrading measures by HIV-affected households in reaction to threat of food insecurity was prevalent. The three most important coping strategies used by households were limiting portion size (61.3%), reducing number of meals per day (59.5%) and relying on less expensive foods (56.2%). The least employed strategies included household member going begging (5.6%), eating elsewhere (8.7%) and harvesting immature crop (7.6%). Given that household assets, and caring for the chronically ill were associated with high CSI, a policy focusing on helping HIV-affected households gradually build up their asset base, or targeting households caring for chronically ill member(s) with conditional household-level support may be reasonable.

Bacterial contamination of blood and blood components in three major blood transfusion centers, Accra, Ghana.

Reports from studies conducted in several countries indicate a high incidence of bacterial contamination of donor blood. The prevalence of bacterial contamination of blood and its products in Ghana is not known. This study was conducted to determine the prevalence of bacterial contamination of blood and its products at the three major blood transfusion centers in the Greater Accra Region of Ghana. Stored whole blood and its products were cultured on different media, and isolates were identified using standard biochemical and bacteriological methods. The susceptibility of the isolates to selected antimicrobial agents was also determined by the disc diffusion method. The overall prevalence rate was 9% (28/303; whole blood, 13% [24/192]; plasma, 3% [2/79]; platelet, 9% [2/22]). The Gram-positive bacteria isolated were coagulase-negative Staphylococcus, S. aureus, and Bacillus spp., and the Gram-negative organisms were Yersinia enterocolitica, Citrobacter freundii, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. The Gram-positive bacteria were sensitive to cloxacillin, erythromycin, tetracycline, and gentamicin but resistant to penicillin, ampicillin, cefuroxime, and cotrimoxazole, while the Gram-negative bacteria were sensitive to amikacin and gentamicin but resistant to chloramphenicol, tetracycline, ampicillin, cefuroxime, cefotaxime (except Y. enterocolitica), and cotrimoxazole. Our results suggest that bacterial contamination of blood and its products is prevalent in Ghana.

Cytokines and adhesion molecules expression in the brain in human cerebral malaria.

Although the role of systemic proinflammatory cytokines, IL-1beta and TNF-alpha, and their up-regulation of adhesion molecules, ICAM-1, VCAM-1 and E-Selectin, in the pathogenesis of cerebral malaria (CM) is well established, the role of local cytokine release remain unclear. Immunohistochemistry (IHC) was used to compare the expression of ICAM-1, VCAM-1, E-Selectin, IL-1beta, TNF-a and TGF-beta at light microscopic level in cerebral, cerebellar and brainstem postmortem cryostat sections from 10 CM, 5 severe malarial anemia (SMA), 1 purulent bacterial meningitis (PBM), 2 non-central nervous system infections (NCNSI) and 3 non-infections (NI) deaths in Ghanaian children. Fatal malaria and Salmonella sepsis showed significantly higher vascular expression of all 3 adhesion molecules, with highly significant co-localization with sequestration in the malaria cases. However, there was negligible difference between CM and SMA. TGF-beta showed intravascular and perivascular distribution in all cases, but expression was most intense in the PBM case and CM group. TNF-alpha and IL-1beta showed prominent brain parenchymal staining, in addition to intravascular and perivascular staining, in only the PBM case and CM group. The maximal expression of all 6 antigens studied was in the cerebellar sections of the malaria cases. Endothelial activation is a feature of fatal malaria and Salmonella sepsis, with adhesion molecule expression being highly correlated with sequestration. IL-1beta and TNF-alpha are upregulated in only cases with neurodegenerative lesions, whilst TGF-beta is present in all cases. Both cytokines and adhesion molecules were maximally upregulated in the cerebellar sections of the malaria cases.

Cryptosporidium Spp., a frequent cause of diarrhea among children at the Korle-Bu Teaching Hospital, Accra, Ghana.

This report presents the results of a study conducted at the Child Health Department, Korle-Bu Teaching Hospital, Accra, Ghana, between the months of October 2001 and June 2002. Stool samples from 227 children with diarrhea and 77 children without diarrhea, aged less than 5 years, were tested for Cryptosporidium spp. Prevalence rates were 27.8 and 15.6% in children with and without diarrhea, respectively. Cryptosporidium infection was found to be high in children between the ages of 6 and 24 months. Cryptosporidium spp. was more common in malnourished children, but was not isolated in children under 6 months of age who were exclusively breastfed. Neither the presence of domestic animals, abdominal pain, blood in stool, nausea, vomiting, nor the consumption of untreated water was associated with Cryptosporidium spp. infection. Shigella, Salmonella, and yeast-like organisms were the most frequently identified enteropathogenic bacteria. In summary, this study demonstrates the prevalence of Cryptosporidium spp. among Ghanaian children.

Evaluation of a rapid serological chromatographic immunoassay for the diagnosis of pulmonary tuberculosis in Accra, Ghana.

Advances in serologic assays for tuberculosis (TB) have made serology an attractive surveillance tool. The sensitivity, specificity, and predictive value of these new assays have been well established. We employed an immunochromatographic serodiagnostic test for detecting antibodies (immunoglobulin [Ig] G, IgA, and IgM) specific for mycobacteria-specific antigen 60 (A60) in the serum of suspected TB patients (n=310) attending the Chest Clinic of the Korle-Bu Teaching Hospital, Accra, Ghana. Compared to the gold standard, sputum culture, the performance indexes of the test kit indicated a sensitivity of 80% and a specificity of 98.2%, respectively. The positive predictive value and the likelihood ratios for positive and negative results were 96.6, 44.4, and 0.2%, respectively, when compared to sputum culture. Our results suggest that the serodiagnostic test kit may be a valuable tool for the diagnosis of TB, and can provide simple and satisfactory results, particularly in cases in which TB is clinically difficult to diagnose by the usual clinical and laboratory tests.

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.

Human T-lymphotropic type-1 virus specific antibody detected in sera of HIV/AIDS patients in Ghana.

Serum samples from 124 acquired immunodeficiency syndrome (AIDS) hospitalized patients at the Fevers Unit, Korle-Bu Teaching Hospital, Accra, Ghana, were examined by the particle agglutination test for antibodies to human T-lymphotropic virus type 1 (HTLV-1) core proteins. The subjects included 84 males and 40 females, aged 16 to 54 years. Specific antibodies were detected in only 14 out of the 124 sera samples, giving an overall prevalence rate of 11.29%. The incidence was lower in males (5.95%; 5/84) than in females (22.50%; 9/40) (P<0.05). In both sexes, the age distribution of subjects positive for HTLV-1 antibodies ranged from 35 to 54 years. The prevalence rate reported herein is too low to suggest an association of HTLV-1 with AIDS, though it may indicate an opportunistic infection of AIDS patients by HTLV-1. Whether HTLV-1 is an underlying disease association or whether HTLV-1 plays some auxiliary role in the acquisition and progression of AIDS remains to be determined.