Browsing by Author "Newton, Robert"
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Item Application of sero- epidemiology data to inform interventions for HBV in Africa: should diagnosis and treatment replace catch-up vaccination?(Global Health, 2018) McNaughton, Anna L.; Lourenço, José; Armand Bester, Phillip; Mokaya, Jolynne; Lumley, Sheila F.; Forde, Donall; Maponga, Tongai G.; Katumba, Kenneth R.; Goedhals, Dominique; Gupta, Sunetra; Seeley, Janet; Newton, Robert; Ocama, Ponsiano; Matthews, Philippa C.International goals for hepatitis B virus (HBV) infection set ambitious targets for elimination by 2030. In populations with a high prevalence of infection, catch-up HBV vaccination of adults is sometimes deployed. An alternative approach of ‘test and treat’ could be applied as a population intervention for HBV. Methods: We used a systematic approach to determine the relationship between prevalence of HBV infection (HBsAg) and exposure (anti-HBc) in Africa. We applied a mathematical model to compare the impact of catch-up vaccination with a ‘test and treat’ strategy in a high prevalence setting. Findings: There is a strong relationship between the prevalence of HBsAg and anti- HBc (p<0·0001) across Africa, but the pattern differs between regions. Our data can be interactively visualised at https://hbv-geo.shinyapps.io/oxafricahbv/. In settings with high prevalence of infection, catch-up vaccination may have a transient effect. However, this intervention does not contribute to a sustained decline in prevalence, because a high proportion of adults are either already infected or immune as a result of prior exposure. In contrast, diagnosing and treating infection has a marked impact on reducing prevalence, equivalent to that of neonatal vaccination. Interpretation: We have developed a high-resolution picture of HBV epidemiology across Africa. In combination with robust neonatal vaccination programmes, testing and treating infection is likely to be of more benefit than catch-up vaccination. This alternative not only benefits the infected individual, but also has impact on transmission, thus contributing to sustained reductions in population prevalence.Item Association between malaria exposure and Kaposi’s sarcoma-associated herpes virus seropositivity in Uganda(Tropical medicine & international health, 2015) Nalwoga, Angela; Cose, Stephen; Wakeham, Katie; Miley, Wendell; Ndibazza, Juliet; Drakeley, Christopher; Elliott, Alison; Whitby, Denise; Newton, RobertUnlike other herpes viruses, Kaposi’s sarcoma-associated herpes virus (KSHV) is not ubiquitous worldwide and is most prevalent in sub-Saharan Africa. The reasons for this are unclear. As part of a wider investigation of factors that facilitate transmission in Uganda, a high prevalence country, we examined the association between antimalaria antibodies and seropositivity against KSHV. Antibodies against P. falciparum merozoite surface protein (PfMSP)-1, P. falciparumapical membrane antigen (PfAMA)-1 and KSHV antigens (ORF73 and K8.1) were measured in samples from 1164 mothers and 1227 children. results Kaposi’s sarcoma-associated herpes virus seroprevalence was 69% among mothers and 15% children. Among mothers, KSHV seroprevalence increased with malaria antibody titres: from 60% to 82% and from 54% to 77%, comparing those with the lowest and highest titres for PfMSP- 1 and PfAMA-1, respectively (P < 0.0001). Among children, only antibodies to PfAMA-1 were significantly associated with KSHV seropositivity, (P < 0.0001). In both mothers and children, anti- ORF73 antibodies were more strongly associated with malaria antibodies than anti-K8.1 antibodies. conclusion The association between malaria exposure and KSHV seropositivity suggests that malaria is a cofactor for KSHV infection or reactivation.Item Longitudinal evaluation of aflatoxin exposure in two cohorts in south-western Uganda(Food Additives & Contaminants: Part A, 2015) Kang, Min-Su; Nkurunziza, Peter; Muwanika, Richard; Qian, Guoqing; Tang, Lili; Songa, Xiao; Xue, Kathy; Nkwata, Allan; Ssempebwa, John; Lutalo, Tom; Asiki, Gershim; Serwadda, David; Seeley, Janet; Kaleebu, Pontiano; Nalugoda, Fred; Newton, Robert; William, Jonathan H.; Wang, Jia-ShengAflatoxins (AF) are a group of mycotoxins. AF exposure causes acute and chronic adverse health effects such as aflatoxicosis and hepatocellular carcinoma in human populations, especially in the developing world. In this study, AF exposure was evaluated using archived serum samples from human immunodeficiency virus (HIV)-seronegative participants from two cohort studies in south-western Uganda. AFB1–lysine (AFB-Lys) adduct levels were determined via HPLC fluorescence in a total of 713 serum samples from the General Population Cohort (GPC), covering eight time periods between 1989 and 2010. Overall, 90% (642/713) of the samples were positive for AFB-Lys and the median level was 1.58 pg mg−1 albumin (range = 0.40–168 pg mg−1 albumin). AFB-Lys adduct levels were also measured in a total of 374 serum samples from the Rakai Community Cohort Study (RCCS), across four time periods between 1999 and 2003. The averaged detection rate was 92.5% (346/374) and the median level was 1.18 pg mg−1 albumin (range = 0.40–122.5 pg mg−1 albumin). In the GPC study there were no statistically significant differences between demographic parameters, such as age, sex and level of education, and levels of serum AFB-Lys adduct. In the RCCS study, longitudinal analysis using generalised estimating equations revealed significant differences between the adduct levels and residential areas (p = 0.05) and occupations (p = 0.02). This study indicates that AF exposure in people in two populations in south-western Uganda is persistent and has not significantly changed over time. Data from one study, but not the other, indicated that agriculture workers and rural area residents had more AF exposure than those non-agricultural workers and non-rural area residents. These results suggest the need for further study of AF-induced human adverse health effects, especially the predominant diseases in the region.Item Parasite infection is associated with Kaposi’s sarcoma associated herpesvirus (KSHV) in Ugandan women(Infectious Agents and Cancer, 2011) Wakeham, Katie; Webb, Emily L.; Sebina, Ismail; Muhangi, Lawrence; Miley, Wendell; Johnson, W. Thomas; Ndibazza, Juliet; Elliott, Alison M.; Whitby, Denise; Newton, RobertImmune modulation by parasites may influence susceptibility to bacteria and viruses. We examined the association between current parasite infections, HIV and syphilis (measured in blood or stool samples using standard methods) and antibodies against Kaposi’s sarcoma herpesvirus (KSHV), measured by ELISA, in 1915 stored plasma samples from pregnant women in Entebbe, Uganda. Seroprevalence of KSHV was higher in women with malaria parasitaemia (73% vs 60% p = 0.01), hookworm (67% vs 56% p = 0.001) and Mansonella perstans (69% vs 59% p = 0.05); seroprevalence increased with increasing intensity of hookworm infection (p < 0.001[trend]). No associations were found for HIV, five other parasites or active syphilis. These effects were not explained by socioeconomic status or education. Specific parasite infections are associated with presence of antibodies against KSHV, perhaps mediated via their effect on immune function.Item Risk Factors for Seropositivity to Kaposi Sarcoma–Associated Herpesvirus Among Children in Uganda(Journal of acquired immune deficiency syndromes, 2013) Wakeham, Katie; Webb, Emily L.; Sebina, Ismail; Nalwoga, Angela; Muhangi, Lawrence; Miley, Wendell; Johnston, W. Thomas; Ndibazza, Juliet; Whitby, Denise; Newton, Robert; Elliott, Alison M.Determinants of Kaposi sarcoma–associated herpesvirus (KSHV) seropositivity among children living in sub-Saharan African populations where infection is endemic are not well understood. Local environmental factors, including other infectious agents, may be key. Within the context of a well-characterized birth cohort, we examined associations between various factors and antibodies against KSHV, measured in stored plasma samples from 1823 mother–child pairs in Entebbe, Uganda.Item Traditional eye medicine use in microbial keratitis in Uganda: a mixed methods study [version 1; peer review: awaiting peer review](Wellcome open research, 2019) Arunga, Simon; Asiimwe, Allen; Apio Olet, Eunice; Kagoro-Rugunda, Grace; Ayebazibwe, Bosco; Onyango, John; Newton, Robert; Leck, Astrid; Macleod, David; Hu, Victor H.; Seeley, Janet; Burton, Matthew J.Traditional eye medicine (TEM) is frequently used to treat microbial keratitis (MK) in many parts of Africa. Few reports have suggested that this is associated with a worse outcome. We undertook this large prospective study to determine how TEM use impacts presentation and outcome of MK and to explore reasons why people use TEM for treatment in Uganda. Methods: In a mixed method prospective cohort study, we enrolled patients presenting with MK at the two main eye units in Southern Uganda between December 2016 and March 2018 and collected information on history, TEM use, microbiology and 3-month outcomes. We conducted qualitative interviews with patients, carers traditional healers on reasons why people use TEM. Outcome measures included presenting vision and at 3-months, comparing TEM Users versus Non-Users. A thematic coding framework was deployed to explore reasons for use of TEM. Results: 188 out of 313 participants reported TEM use. TEM Users had a delayed presentation; median presenting time 18 days versus 14 days, p= 0.005; had larger ulcers 5.6 mm versus 4.3 mm p=0.0005; a worse presenting visual acuity median logarithm of the minimum angle of resolution (Log MAR) 1.5 versus 0.6, p=0.005; and, a worse visual acuity at 3 months median Log MAR 0.6 versus 0.2, p=0.010. In a multivariable logistic regression model, distance from the eye hospital and delayed presentation were associated with TEM use. Reasons for TEM use included lack of confidence in conventional medicine, health system breakdown, poverty, fear of the eye hospital, cultural belief in TEM, influence from traditional healers, personal circumstances and ignorance. : TEM users h Conclusion ad poorer clinical presentation and outcomes. Capacity building of the primary health centres to improve access to eye care and community behavioural change initiatives against TEM use should be encouraged.Item Visual inspection with acetic acid (VIA) positivity among female sex workers: a cross-sectional study highlighting one-year experiences in early detection of precancerous and cancerous cervical lesions in Kampala, Uganda(Infectious Agents and Cancer, 2021) Namale, Gertrude; Mayanja, Yunia; Kamacooko, Onesmus; Bagiire, Daniel; Ssali, Agnes; Seeley, Janet; Newton, Robert; Kamali, AnatoliAlthough cervical cancer is preventable, most women in sub-Saharan Africa (SSA) do not receive routine screening and few treatment options exist. Female Sex Workers (FSWs) are among the Ugandan female population at highest risk of acquiring sexually transmitted infections (STIs) including HIV and human papilloma viruses (HPV), the cause of cervical cancer. We report one-year experiences of visual inspection with acetic acid (VIA) positivity among FSWs in the early detection of pre-cancerous and cancerous cervical lesions in Kampala, Uganda. Methods: Between June 2014 and July 2015, we enrolled FSWs into a cross-sectional study at a research clinic. The women were screened using the VIA method (application of 3–5 % acetic acid to the cervix). All VIA positive women were referred to a tertiary hospital for colposcopy, biopsy, and immediate treatment (if indicated) at the same visit according to national guidelines. Data on socio-demographic, sexual behaviour, sexual reproductive health and clinical characteristics were collected. We used logistic regression to identify factors associated with VIA positivity. Results: Of 842 women assessed for eligibility, 719 (85 %) of median age 30 (IQR 26, 35) were screened, and 40 (6 %) women were VIA positive. Of the 24 histology specimens analysed, 6 showed inflammation, only 1 showed cervical intraepithelial neoplasia (CIN) 1, 13 women showed CIN2/3, while 4 women already had invasive cervical cancer. The overall prevalence of HIV was 43 %, of whom only 35 % were receiving ART. In the age-adjusted analysis, VIA positivity was more likely among women who reported having > 100 life-time partners (aOR = 3.34, 95 %CI: 1.38–8.12), and HIV positive women (aOR = 4.55; 95 %CI: 2.12–9.84).