NRU :: Browsing by Author "Sendagire, Hakim"

Browsing by Author "Sendagire, Hakim"

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The Challenge of HIV-1 Antiretroviral Resistance in Africa in the Era of HAART
(AIDS reviews, 2009) Sendagire, Hakim; Easterbrook, Philippa J.; Nankya, Immaculate; Arts, Eric; Thomas, David; Reynolds, Steven J.
Antiretroviral therapy programs in Africa are currently providing treatment for almost two million people. The long-term success of large scale antiretroviral therapy programs in sub-Saharan Africa remains uncertain because of the limited information currently available on rates of virologic failure and selection for drug-resistant variants in the different HIV subtypes. This article provides a comprehensive review of the published literature on the prevalence of primary and secondary HIV drug resistance with different subtypes and in various settings across sub-Saharan Africa.
Consolidating HIV testing in a public health laboratory for efficient and sustainable early infant diagnosis (EID) in Uganda
(Journal of Public Health Policy, 2015) Kiyaga, Charles; Sendagire, Hakim; Joseph, Eleanor; Grosz, Jeff; McConnell, Ian; Narayan, Vijay; Esiru, Godfrey; Elyanu, Peter; Akola, Zainab; Kirungi, Wilford; Musinguzi, Joshua; Opio, Alex
Uganda introduced an HIV Early Infant Diagnosis (EID) program in 2006, and then worked to improve the laboratory, transportation, and clinical elements. Reported here are the activities involved in setting up a prospective analysis in which theMinistry of Health, with its NGO partners, determined it would be more effective and efficient to consolidate the initial eight-laboratory system for EID testing of HIV dried blood samples offered by two nongovernmental partners operating research facilities into a single well-equipped and staffed laboratory within the Ministry. A retrospective analysis confirmed that redesign reduced overhead cost per PCR test of HIV dried blood samples from US$22.20 to an average of $5. Along with the revamped system of sample collection, transportation, and result communication, Uganda has been able to vastly increase the HIV diagnosis of babies and engagement of them and their mothers in clinical care, including antiretroviral therapy. Uganda reduced turnaround times for results reporting to clinicians from more than amonth in 2006 to just 2 weeks by 2014, even as samples tested increased dramatically. The next challenge is overcoming loss of babies and mothers to follow up.
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
(International journal of hepatology, 2022) Mukasa Kafeero, Hussein; Ndagire, Dorothy; Ocama, Ponsiano; Drago Kato, Charles; Wampande, Eddie; Kajumbula, Henry; Kateete, David; Walusansa, Abdul; Kudamba, Ali; Edgar, Kigozi; Ashaba Katabazi, Fred; Namaganda, Maria Magdalene; Ssenku, Jamilu E.; Sendagire, Hakim
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.
Host and Viral Factors Associated with Hepatitis B Clinical Outcomes in Chronic Infection
(International Journal of Pure Medical Research, 2019) Mukasa Kafeero, Hussein; Ocama, Ponsiano; Ndagire, Dorothy; Sendagire, Hakim
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􀃸uencing 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. Introduction Hepatitis B virus (HBV) is the causative agent for liver diseases, including chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (Matsuura, K., Tanaka, Y., Hige, S. et al., 2009). Hepatocellular carcinoma is one of the most common cancers globally with high incidents in Eastern Asia and Sub-Saharan Africa (Jemal, Bray, Center, Ferlay, & Ward, 2011). Most patients who get infected with hepatitis B virus go into an acute phase during when the virus is cleared. None the less, in some patients the virus persists resulting into chronic hepatitis B infection which may later progress to liver cancer. Immune responses and genetic factors of the host along with the viral characteristics remain pivotal in determining the course of the disease Hepatitis B genotypes and subtypes The HBV genome is composed of approximately 3,200 nucleotides (Matsuura et al., 2009). Arauz-Ruiz, Norder, Robertson, & Magnius, (2002) previously classi􀃶ed HBV into 8 genotype identi􀃶ed as A-H based on an intergroup divergence of 8% or more in complete nucleotide sequence whose geographical distributions was previously extensively studied by Sanchez-Tapias, Costa, Mas, Bruguera, & Rodes, (2002) who documented that genotype A is pandemic, B and C are predominant in Asia, D in southern Europe, E in Africa, F in United States of America, G in France while H in Central America. However recent studies by McMahon (2009), Cao (2009), Kurbanov, Tanaka, & Mizokami, (2010) have introduced two new genotypes designated as I and J giving a total of 10 genotypes together with several sub-genotypes. With the exception of the newly identi􀃶ed genotypes, the other genotypes and subgenotypes have well characterized ethnic and geographical distribution
Prevalence and predictors of hepatitis B virus (HBV) infection in east Africa: evidence from a systematic review and meta-analysis of epidemiological studies published from 2005 to 2020
(Archives of Public Health, 2021) Mukasa Kafeero, Hussein; Ndagire, Dorothy; Ocama, Ponsiano; Kudamba, Ali; Walusansa, Abdul; Sendagire, Hakim
The epidemiology of hepatitis B virus (HBV) in the general population in east Africa is not well documented. In this meta-analysis, we examined 37 full published research articles to synthesise up-to-date data on the prevalence and predictors of the HBV burden for the effective prevention and management of the virus in our region. Methods: We examined 37 full published research articles found using PubMed, Scopus, African Journal Online (AJOL), and Google Scholar between May and October 2020. Dichotomous data on HBV prevalence and predictors of infection were extracted from the individual studies. The HBV prevalence, test of proportion, relative risk, and I2 statistics for heterogeneity were calculated using MedCalc software version 19.1.3. Begg’s tests was used to test for publication bias. Sources of heterogeneity were analysed through sensitivity analysis, meta-regression, and subgroup analysis at 95% CI. P < 0.05 was considered significant for all analyses. Results: The prevalence of HBV was generally high (6.025%), with publications from Kenya (8.54%), Uganda (8.454%) and those from between 2011 and 2015 (8.759%) reporting the highest prevalence (P < 0.05). Blood transfusion, scarification, promiscuity, HIV seropositivity, and being male were independent predictors significantly associated with HBV infection (P < 0.05), with the male sex being the most strongly associated predictor of HBV infection. Meta-regressions for the pooled HBV prevalence and sample size, as well as the year of publication, lacked statistical significance (P > 0.05). Omitting the study with the largest sample size slightly increased pooled HBV prevalence to 6.149%, suggesting that the studies are robust. Begg’s test showed no evidence of publication bias for overall meta-analysis (p > 0.05). Conclusion: The burden of HBV is still high, with the male sex, blood transfusion, body scarification, and HIV seropositivity being potential predictors of infection. Thus, it is important to scale up control and prevention measures targeting persons at high risk.
Rapid increase in resistance of Plasmodium falciparum to chloroquine-Fansidar in Uganda and the potential of amodiaquine-Fansidar as a better alternative
(Acta Tropica, 2005) Sendagire, Hakim; Kaddumukasa, Mark; Ndagire, Dorothy; Aguttu, Clare; Nassejje, Maureen; Pettersson, Madeleine; Swedberg, Gote; Kironde, Fred
Combinations of chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) [CQSP] as the first line agents in Uganda have replaced CQ monotherapy. The idea of the combination is to delay the development of malaria resistance to either drug when used alone. We compared the clinical, parasitological and molecular findings of two studies with treatment arms of CQSP, amodiaquine (AQ) plus SP (AQSP) both done in 2003 with a study done 1 year earlier (2002) using SP alone. There was a notable decrease in adequate clinical response (ACR) by day 14 from 92.7% with SP to 80% with the combination CQSP, a year later. AQSP combination was found to have the best effect (94.3% ACR). There were no early treatment failures in the AQSP group. However, treatment failures were recorded at 20% on day 14 and 43% on day 28 for CQSP treatment and 5.7% by day 14 and 28.8% by day 28 in the AQSP group. The number of mutations that are associated with SP resistance increased from 2002 to 2003 at all loci monitored, from 83.8 to 100% at codon 108, 58.7 to 76% at codon 59 in the DHFR gene, and from 58.8 to 86% at codon 437 and 33 to 43% at codon 540 in the DHPS gene. We conclude that there has been a rapid development of resistance since the introduction of the new policy guidelines. AQSP was found to be a superior drug combination compared to CQSP and could be used as a low cost alternative at the moment.
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 public health, 2006) Mukasa Kafeero, Hussein; Ndagire, Dorothy; Ocama, Ponsiano; Walusansa, Abdul; Sendagire, Hakim
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.
Uganda’s New National Laboratory Sample Transport System: A Successful Model for Improving Access to Diagnostic Services for Early Infant HIV Diagnosis and Other Programs
(PLoS ONE, 2013) Kiyaga, Charles; Sendagire, Hakim; Joseph, Eleanor; McConnell, Ian; Grosz, Jeff; Narayan, Vijay; Esiru, Godfrey; Elyanu, Peter; Akol, Zainab; Kirungi, Wilford; Musinguzi, Joshua; Opio, Alex
Uganda scaled-up Early HIV Infant Diagnosis (EID) when simplified methods for testing of infants using dried blood spots (DBS) were adopted in 2006 and sample transport and management was therefore made feasible in rural settings. Before this time only 35% of the facilities that were providing EID services were reached through the national postal courier system, Posta Uganda. The transportation of samples during this scale-up, therefore, quickly became a challenge and varied from facility to facility as different methods were used to transport the samples. This study evaluates a novel specimen transport network system for EID testing. Methods: A retrospective study was done in mid-2012 on 19 pilot hubs serving 616 health facilities in Uganda. The effect on sample-result turnaround time (TAT) and the cost of DBS sample transport on 876 sample-results was analyzed. Results: The HUB network system provided increased access to EID services ranging from 36% to 51%, drastically reduced transportation costs by 62%, reduced turn-around times by 46.9% and by a further 46.2% through introduction of SMS printers. Conclusions: The HUB model provides a functional, reliable and efficient national referral network against which other health system strengthening initiatives can be built to increase access to critical diagnostic and treatment monitoring services, improve the quality of laboratory and diagnostic services, with reduced turn-around times and improved quality of prevention and treatment programs thereby reducing long-term costs.
Virologic versus immunologic monitoring and the rate of accumulated genotypic resistance to first-line antiretroviral drugs in Uganda
(BMC infectious diseases, 2012) Reynolds, Steven J; Sendagire, Hakim; Newell, Kevin; Castelnuovo, Barbara; Nankya, Immaculate; Kamya, Moses; Quinn, Thomas C.; Manabe, Yukari C.; Kambugu, Andrew
Viral load monitoring (VLM) to identify individuals failing antiretroviral therapy (ART) is not widely available in resource-limited settings. We compared the genotypic resistance patterns between clients with VLM versus immunological monitoring (IM).Between 2004–2008, 559 ART naïve clients were enrolled in a prospective cohort, initiated on ART, and monitored with viral load (VL) and CD4+ cell counts every 6 months (VLM group). From February 2008 through June 2009, 998 clients on ART for 36–40 months (corresponding to the follow-up time of the VLM group) at the same clinic and monitored with CD4+ cell counts every 6 months were recruited into a cross sectional study (IM group). Samples from VLM clients at 12, 24 and 36 months and IM clients at 36–40 months with VL > 2000 copies/ml underwent genotypic drug resistance testing.Baseline characteristics were similar. Virologic failure (VL > 400 copies/ml) at 12, 24 and 36 months in the VLM group were 12%, 6% and 8% respectively, and in the IM group 10% at 36–40 months. Samples from 39 VLM and 70 IM clients were genotyped. 23/39 (59%) clients in the VLM group (at 12, 24 or 36 months) compared to 63/70 (90%) in the IM group, (P < 0.0001) had at least 1 non-nucleoside reverse transcriptase mutation. 19/39 (49%) of VLM clients had an M184V mutation compared to 61/70 (87%) in the IM group (P < 0.0001). Only 2/39 (5%) of VLM clients developed thymidine analogue mutations compared to 34/70 (49%) of IM clients (P < 0.0001).Routine VL monitoring reduced the rate of accumulated genotypic resistance to commonly used ART in Uganda.

Browsing by Author "Sendagire, Hakim"

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