Browsing by Author "Ndagire, Dorothy"

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Disproportionate Distribution of HBV Genotypes A and D and the Recombinant Genotype D/E in the High and Low HBV Endemic Regions of Uganda: A Wake-Up Call for Regional Specific HBV Management
(Hindawi, 2022-01-11) Mukasa Kafeero, Hussein; Ndagire, Dorothy; Ocama, Ponsiano; Kato, Charles Drago; Wampande, Eddie; Kajumbula, Henry; Kateete, David; Walusansa, Abdul; Kudamba, Ali; Kigozi, Edgar; Katabazi, Fred Ashaba; Namaganda, Maria Magdalene; Ssenku, Jamilu E.; Sendagire, Hakim
Background. Hepatitis B virus (HBV) is the leading cause of liver-related diseases. In Uganda, there is a regional disparity in the HBV burden. Our study was aimed at establishing the circulating genotypes in a low and a high endemic region to give plausible explanations for the differences in regional burden and guide the future management of the disease. Methods. A total of 200 HBsAg-seropositive subjects were recruited into the study by convenience sampling. The HBsAg Rapid Test Strip (Healgen Scientific Limited Liability Company, Houston, TX77047- USA) was used to screen for HBsAg while the Roche machine (Roche, Basel Switzerland/Abbot Technologies (USA)) was used to determine the viral load. The Chemistry Analyzer B120 (Mindray, China) was used for chemistry analysis. For HBV genotyping, total DNA was extracted from whole blood using the QIAamp® DNA extraction kit. Nested PCR amplification was performed using Platinum Taq DNA Polymerase (Invitrogen Corporation, USA) to amplify the 400 bp HBV polymerase gene. Purification of nested PCR products was performed using Purelink PCR product purification kit (Life Technologies, USA). Automated DNA sequencing was performed using BigDye Terminator v3.1 Cycle Sequencing Kit on 3130 Genetic Analyzer (Applied Biosystems, USA). The NCBI HBV genotyping tool (https://www.ncbi.nlm.nih.gov/projects/genotyping/formpage.cgi) was used for determination of genotype for each HBV sequence. Pearson’s chi-square, multinomial logistic regression, and Mann–Whitney U tests were used for the analysis. All the analyses were done using SPSS version 26.0 and MedCalc software version 19.1.3 at 95% CI. A p < 0:05 was considered statistically significant. Results. Majority of our study subjects were female (64.5%), youth (51.0%), and married (62.0%). Overall, genotype A was the most prevalent (46%). Genotype D and the recombinant genotype D/E were proportionately more distributed in the high endemic (38.2%) and low endemic (36.5%) regions, respectively. Genotype D was significantly more prevalent in the high endemic region and among the elderly (p < 0:05). Genotype D was significantly associated with elevated viral load and direct bilirubin (p < 0:05). The recombinant genotype D/E was significantly associated with elevated viral load (p < 0:05). Similarly, genotype A was significantly associated with elevated AST and GGT, lowered viral load, and normal direct bilirubin levels (p < 0:05). Conclusion. There is disproportionate distribution of genotypes A and D and the recombinant genotype D/E in the low and high endemic regions of Uganda. This probably could explain the differences in endemicity of HBV in our country signifying the need for regional specific HBV management and control strategies.
Hepatitis B virus (HBV) serological patterns among the HBsAg negative hospital attendees screened for immunization
(Scientific Reports, 2022-05-06) Kafeero, Hussein Mukasa; Ndagire, Dorothy; Ocama, Ponsiano; Kato, Charles Drago; Wampande, Eddie; Walusansa, Abdul; Kajumbula, Henry; Kateete, David; Sendagire, Hakim
The Hepatitis B virus (HBV) is a highly infectious virus and is endemic in Uganda. It is one of the major etiological agents for liver diseases including liver cancer. In this work, we evaluated the prevalence of the HBV serological markers and the associated socio-demographic factors among hepatitis B surface antigen (HBsAg) seronegative persons screened during routine immunization against the virus in eastern Uganda. Data on the socio-demographic characteristics were collected using a structured questionnaire, while that on the serological markers were obtained from serum samples and evaluated by using the 5-panel HBV One Step Hepatitis B Virus Combo Test Device ( FastepR, HBV-P43M). The following markers were evaluated by the panel: HBsAg, HBsAb, HBcAb, and HBeAb. Data were analyzed using SPSS (version 26), and multinomial logistic regression was used to elicit the adjusted odds ratio. All the analysis were performed at a 95% confidence limit, and a P value ≤ 0.05 was considered significant. The 424 participants included in this study were mainly female (62.3%), married (55.4%) and aged 30 years and above (54.2%). The seropositivity of the HBsAb, HBeAb, HBcAb marker prevalence rates was 48(11.3%), 73(17.2%) and 45(10.6%) respectively. The majority of the participants (327, 77.1%) did not present with any marker. Married paricipants were significantly associated with reduced HBsAb seropositvity rate, whereas young people aged 18–29 years were associated the with increased odds of HBsAb seropositivity (p < 0.05). Male participants were significantly associated with the HBeAb and HBcAb seropositivity (p < 0.05). Similarly, contact with an HBV infected person was significantly associated with HBeAb and HBcAb seropositivity (p < 0.05). Further still, blood transfusion was significantly associated with the increased risk of HBcAb seropositivity (P < 0.05). This study has revealed a prevalence of HBV serological markers among the HBsAg seronegative persons in this community and an increased risk of transmission of the virus in the community. Our findings have key consequences pertaining the interventions that are pertinent in the control and prevention of the spread of the virus among apparently health persons. Hepatitis B virus (HBV) is the causative agent for liver inflammatory diseases, which, if not diagnosed in a timely manner and subsequently managed, are likely to progress to chronic liver diseases, liver fibrosis, liver cirrhosis, and liver cancer1. The virus has been implicated as one the most common oncogenic virus in humans2. It is a highly transmissible virus and is 50 to 100 times more infectious than Human Immune deficiency Virus (HIV). In addition, it has extreme resilience, allowing it to survive for several days on dry surfaces. This complicates its epidemiology and explains the increased chances of intra-familial horizontal transmissions3. Despite the presence of a safe and highly efficacious vaccine, HBV infection is still one of the major global health problems4. The Uganda Population-Based Impact Assessment (UPHIA) 2016–2017 survey reported a drastic decrease in the prevalence of HBV in Uganda5. According to this survey, the national prevalence of HBV dropped from 10% in the general population in 20156 to 4.3% in 2016 and 4.1% in 2017, with east-central posting a prevalence of 2.1%. However, HBV is a chronic infection and these data are suggestive of either massive death of the chronically infected persons or a higher level of sero-conversion to HBsAb between the sampling intervals. Nevertheless, the rapid sero-conversion indicated by a high prevalence of the HBsAb with normal levels of the correlates of liver damage over a short period of time seems to be unrealistic. Similarly, the drastic decrease in the risk of infection because of improved immunity or public health awareness appears idealistic. The relative importance of the socio-demographic factors to HBV infection varies from population to population7, and their contribution to community spread of HBV have been previously reported with concordance in some studies and contradictions in other studies8– 12. Understanding these sociodemographic factors related to infection and their relationship with markers of HBV exposure will provide plausible answers to the recent drastic decline in HBV in Uganda. To understand the sero-prevalence of hepatitis B virus, screening of a large number of people is needed. Serological markers for detection of HBV are diverse13 and include hepatitis B surface antibody (HBsAb), hepatitis B pre-core antibody (HBeAb), hepatitis B pre-core antigen (HBeAg), hepatitis B core antibody (HBcAb) and hepatitis B surface antigen (HBsAg). However, in resource limited settings, screening for hepatitis B virus infection is limited to only the HBsAg using the rapid diagnostic test. Unfortunately, the use of a single marker of exposure is associated with vast irregularities in the diagnosis of HBV. This inconclusive diagnosis is likely to mislead clinicians in their decisions when managing the HBV-infected persons as well as the decision to discard donated blood for transfusion by local and regional blood banks. HBV exposure markers have high sensitivity but low specificity, justifying the need to investigate them not in isolation for comprehensive case management and explicit assessment of blood for transfusion. The Anti-HBc is characteristic of a hidden HBV carrier state and/ or resolved disease14. Anti-HBs antibodies are associated with acquired immunity either due to previous exposure and natural response to the virus or due to vaccination15, whereas the Anti-HBe antibody is a marker of the minimally infective phase and disease remission or recovery from the infection16. Thus, as eluded from above, the relative significance of different sociodemographic risk factors for infection, the comparative expression of markers of liver damage and the relative prevalence of different markers of exposure to HBV at the community level can provide constructive clues on the trend of HBV prevalence and infectivity in a population. Consequently, we sought to understand the current state of the risk factors for HBV infection and the prevalence of the markers of immunity against HBV among HBsAg seronegative individuals to justify the drastic reduction in the burden of HBV in Uganda.
HOST AND VIRAL FACTORS ASSOCIATED WITH HEPATITIS B CLINICAL OUTCOMES IN CHRONIC INFECTION -REVIEW ARTICLE
(International Journal of Pure Medical Research, 2019) Kafeero, Mukasa Hussein; Sendagire, Hakim; Ocama, Ponsiano; Ndagire, Dorothy
Viral and host factors have been implicated in persistence of HBV infection to chronicity and perhaps to liver cancer. Fortunately 90- 95% of those who get infected in adult hood clear the virus and remain with antibodies suggesting previous exposure to HBV. The underlying reasons as to why majority of the patients with acute infection clear the virus while a small proportion progress to chronic infection lies in the difference in host immunological and genetic factors. The immune determinants of complete clearance are not fully understood but both innate and adaptive are paramount in this response. Similarly, the role of the host genes in the pathogenesis of the virus are not fully elucidated but polymorphisms in genes encoding for the HLA, cytokine and vitamin D receptor (VDR) have been highlighted in in influencing both disease clearance and progression to chronicity. In this review, the host and viral factors responsible for differential clinical presentation of hepatitis B are discussed.
Sero‑prevalence of human immunodeficiency virus–hepatitis B virus (HIV– HBV) co‑infection among pregnant women attending antenatal care (ANC) in sub‑Saharan Africa (SSA) and the associated risk factors: a systematic review and meta‑analysis
(BMC, 2020-10-27) kafeero, Hussein; Ndagire, Dorothy; Ocama, Ponsiano; Walusansa, Abdul; Sendagire, Hakim
Background: There is plenitude of information on HIV infection among pregnant mothers attending antenatal care (ANC) in sub-Saharan Africa. However, the epidemiology of HBV–HIV co-infections in the same cohort is not clear despite the common route of transmission of both viruses. The aim of our study was to synthesize data on the prevalence of HBV–HIV co-infection among pregnant women attending ANC in Sub-Saharan Africa to assist in the design of public health interventions to mitigate the challenge. Methods: The study was done in tandem with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) standards and the Cochran’s Q test, I2 statistics for heterogeneity and the prevalence were calculated using commercially available software called MedCalcs (https ://www.medca lc.org). A random effect model was used to pool the prevalence since all the heterogeneities were high (≥ 78%) and Phet< 0.05 indicated significant heterogeneities. The risk factors and risk differences for HBV–HIV co-infection were analyzed. Any likely sources of heterogeneity were analyzed through sensitivity analysis, meta-regression and sub-group analysis. All analyses were done at 95% level of significance and a P < 0.05 was considered significant. Results: The overall pooled prevalence of HBV–HIV co-infection among pregnant mothers in sub-Saharan Africa was low 3.302% (95%CI = 2.285 to 4.4498%) with heterogeneities ( I2) of 97.59% (P > 0.0001). Within regional sub group meta-analyses, West Africa had significantly higher prevalence of 5.155% (95% = 2.671 to 8.392%) with heterogeneity (I2) of 92.25% (P < 0.0001) than any other region (P < 0.001). Articles published from 2004–2010 had significantly higher prevalence of 6.356% (95% = 3.611 to 9.811%) with heterogeneity (I2) 91.15% (P < 0.0001) compared to those published from 2011 to 2019 (P < 0.001). The HIV positive cohort had significantly higher prevalence of HBV–HIV co-infection of 8.312% (95% CI = 5.806 to 11.22%) with heterogeneity (I2)94.90% (P < 0.0001) than the mothers sampled from the general population with a prevalence of 2.152% (95% CI = 1.358 to 3.125%) (P < 0.001). The overall and sub group analyses had high heterogeneities ( I2 > 89%, P < 0.0001) but was reduced for South Africa (I2) = 78.4% (P = 0.0314). Age, marital status and employment were independent factors significantly associated with risk of HBV–HIV co-infection (P < 0.001) but not extent of gravidity and education level (P > 0.05). After meta-regression for year of publication and sample size for HBsAg positivity, the results were not significantly associated with HBV pooled prevalence for sample size (P = 0.146) and year of publication (P = 0.560). Following sensitivity analysis, the HBsAg pooled prevalence slightly increased to 3.429% (95% CI = 2.459 to 4.554%) with heterogeneity I2 = 96.59% (95% CI = 95.93 to 97.14%), P < 0.0001 Conclusion: There is an urgent need for routine HBV screening among HIV positive pregnant mothers attending antenatal care in sub-Saharan Africa to establish the extent of HBV–HIV co-infection in this cohort. Future studies need to investigate the putative risk factors for HBV–HIV co-infection and prioritize plausible control strategies.
TREAT-B Algorithm for Treatment Eligibility Among Chronically Infected Hepatitis B Virus Persons in a Low and a High Endemic Region: A Potential Strategy Towards Virus Elimination by 2030
(Frontiers in Virology, 2022-04-11) Kafeero, Hussein Mukasa; Ndagire, Dorothy; Ocama, Ponsiano; Drago, Charles; Wampande, Eddie; Kajumbula, Henry; Kateete, David Patrick; Walusansa, Abdul; Kudamba, Ali; Ssenku, Jamilu E.; Sendagire, Hakim
Background: Little is known about treatment eligibility in Africa for the hepatitis B virus (TREAT-B) algorithm. We investigated the treatment eligibility among the HBV chronically infected patients in a low and a high endemic region using the TREAT-B algorithm. Methods: We recruited 227 treatment-naïve HBV-infected hospital attendees from the low and high HBV endemic regions. We assessed the treatment eligibility by testing for HBeAg serostatus and ALT levels. Socio-demographic data were collected with a structured questionnaire. The accessory correlates of treatment eligibility (AST, ALP, ALB, GGT, and TBIL) and the socio-demographic factors were analyzed by both univariate and multinomial logistic regression using the SPSS and Medcalc. The analysis was done at 95% CI and a p < 0.05 was considered statistically significant. Results: Overall, 56.8% of the participants qualified for treatment at TREAT-B cutoffs of ≥2, with those from the low endemic region (90, 69.8%) having significantly higher treatment eligibility indication than those from the high endemic region (p < 0.05). Alcohol use and household contact with an HBV-infected person were independent socio-demographic factors significantly associated with treatment eligibility for both low and high endemic regions (p < 0.05). However, birth place was only indicated for treatment eligibility among the high endemic participants (p < 0.05). AST, GGT, and total bilirubin were the liver-related parameters significantly associated with treatment eligibility (p < 0.05), with GGT and AST being significantly elevated among the eligible low endemic dwellers compared to high endemic dwellers (p < 0.05). Conclusion: Using TREAT-B algorithm can be a plausible alternative to the orthodox methods to specify treatment eligibility with the potential to scale up interventions targeting HBV management and elimination.
Tumor Necrosis Factor-α-863C/A and 1031 T/C Single nucleotide polymorphic sites (SNPs) may be putative markers of HBV disease prognosis among Caucasoids: Evidence from a systematic review with meta-analysis
(Elsevier, 2022-01-19) Mukasa Kafeero, Hussein; Ndagire, Dorothy; Ocama, Ponsiano; Walusansa, Abdul; Sendagire, Hakim
Background: The pathogenesis and prognosis of hepatitis B virus (HBV) infection have been correlated with genetic polymorphisms in the gene loci within the promoter region of the immune system modulator molecules such as the cytokines including the tumor necrosis factor (TNF)-alpha. Besides, these polymorphisms vary at population levels but it is not conclusive whether races are involved or not. We aimed at testing the hypothesis that the SNPs in the promoter region of the TNF-alpha gene may have different effects in the Caucasoid populations by pooling the odds of association with the clearance/increased risk of the HBV infection from a large sample size obtained from many primary studies. We searched Scopus, PubMed, EMBASE, Cochrane, Willy and Google scholar databases for the published studies between January 1998 to December 2020. Studies that investigated the association between the TNF-α-238G/A, -308G/A, -857C/T, -863C/A and -1031 T/C gene promoter polymorphisms with the resolution/increased risk of HBV infection published in English and in peer reviewed journals were included. The odds ratios were used to evaluate the association of the TNF-α-gene SNPs with the risk/resolution of the disease. This study is registered on PROSPERO, number CRD42021266944. Results: A significant association was observed between the TNF-α-857 homozygous mutation TT and its allele T with reduced risk of infection or resolution of the disease among both the Caucasoids and the Mongoloids (p < 0.05, OR < 1.0). In contrast, the TNF-α-1031 wild type genotypes TT; p = 0.001, OR = 0.634, 95%CI = [0.489 to 0.822%] and its allele T; p = 0.001, OR = 0.701, 95%CI = [0.571 to 0.860%] were significantly associated with reduced risk of infection or increased chances of resolution of the disease among the Caucasoids only. However, the TNF-α-863 homozygous mutation AA or its allele A and the TNF-α-1031 heterozygous mutation CT or the allele C were significantly associated with unresolved HBV infection among the Caucasoids (p < 0.05, OR > 1.0) but not among the Mongoloids. Conclusion: Tumor Necrosis Factor-α-863C/A and 1031 T/C polymorphic sites may be putative markers of HBV disease prognosis and pathogenesis among the Caucasoid populations but not among the Mongoloid populations. Future research therefore should focus on the role of these presumed TNF-α-polymorphisms in the clinical profile of the HBV infections targeting an African or Negroid population.