Epidemiology of HPV genotypes in Uganda and the role of the current preventive vaccines: A systematic review

<p>Abstract</p> <p>Background</p> <p>Limited data are available on the distribution of human papillomavirus (HPV) genotypes in the general population and in invasive cervical cancer (ICC) in Uganda. Yet, with the advent of preventive HPV vaccines that target HPV 16 and 18 responsible for causing about 70% of ICC cases in the world, such information is crucial to predict how vaccination and HPV-based screening will influence prevention of ICC.</p> <p>Methods</p> <p>To review the distribution of HPV infection and prevalent genotypes, electronic databases (e.g. PubMed/MEDLINE and HINARI) were searched for peer reviewed English articles on HPV infection up to November 30, 2010. Eligible studies were selected according to the following criteria: DNA-confirmed cervical or male genital HPV prevalence and genotypes, HPV incidence estimates and HPV seroprevalence among participants.</p> <p>Results</p> <p>Twenty studies were included in the review. Among HIV negative adult women, the prevalence of HR-HPV infections ranged from 10.2% -40.0% compared to 37.0% -100.0% among HIV positive women. Among HIV positive young women aged below 25 years, the prevalence of HR-HPV genotypes ranged from 41.6% -75.0% compared to 23.7% -67.1% among HIV negative women. Multiple infections with non vaccine HR-HPV genotypes were frequent in both HIV positive and HIV negative women. The main risk factors for prevalent HPV infections were age, lifetime number of sexual partners and HIV infection. Incident infections with HR-HPV genotypes were more frequent among adult HIV positive than HIV negative women estimated at 17.3 and 7.0 per 100 person-years, respectively. Similarly, incident HR-HPV among young women aged below 25 years were more frequent among HIV positive (40.0 per 100 person-years) than HIV negative women (20.3 per 100 person-years) women. The main risk factor for incident infection was HIV infection. HPV 16 and 18 were the most common genotypes in ICC with HPV 16/18 contributing up to 73.5% of cases with single infections.</p> <p>Among uncircumcised adult HIV positive males, HR-HPV prevalence ranged from 55.3% -76.6% compared to 38.6% -47.6% in HIV negative males. Incident and multiple HR-HPV infections were frequent in HIV positive males. Being uncircumcised was the main risk factor for both prevalent and incident HPV infection.</p> <p>Conclusion</p> <p>Infections with HR-HPV genotypes were very common particularly among HIV positive individuals and young women irrespective of HIV status. Given the high prevalence of HIV infection, HPV-associated conditions represent a major public health burden in Uganda. However, although the most common HPV genotypes in ICC cases in Uganda were those targeted by current preventive vaccines, there were a large number of individuals infected with other HR-HPV genotypes. Technology allowing, these other HR-HPV types should be considered in the development of the next generation of vaccines.</p

Pathogen Detection Using Metagenomic Next-Generation Sequencing of Plasma Samples from Patients with Sepsis in Uganda

Metagenomic sequencing is a promising new method for pathogen detection. We aimed to detect pathogens from archived plasma using metagenomic sequencing in a previously well-characterized cohort of 254 predominantly HIV-infected patients with sepsis in Uganda. We used Illumina sequencing and the Chan Zuckerberg ID metagenomics platform to sequence and identify pathogens. On average, each plasma sample yielded 3,404,737 ± 2,201,997 reads (mean ± standard deviation), of which 220,032 ± 416,691 (6.3% ± 8.6%) were identified as nonhuman reads. Using a background model filter, 414 genus-specific pathogen identifications were found in the 254 samples. Nineteen pathogens were previously detected positive by quantitative PCR (qPCR), compared to sequencing, which demonstrated 30.2% sensitivity and 99.5% specificity. Sensitivity was higher for viral pathogens than nonviral pathogens (37% versus 5%). For example, HIV viremia was detected in 69% of samples using qPCR, and sequencing revealed 70% sensitivity and 92% specificity. There were 75 genus-specific potential pathogens identified by sequencing in this cohort, including hepatitis B and Epstein-Barr virus (EBV), among several others. qPCR showed a prevalence of hepatitis B and EBV viremia of 17% and 45%, respectively. In-hospital mortality was associated with a lower qPCR threshold cycle value for EBV (adjusted odds ratio, 0.85; P < .001) but not for hepatitis B or HIV. In conclusion, a broad range of potential pathogens were identified by metagenomic sequencing in patients with sepsis in Uganda. Unexpectedly high rates of hepatitis B and EBV viremia were found. Whether these viral infections in HIV patients with sepsis are clinically important requires further study

The levels of anti-HPV16/18 and anti-HPV31/33/35/45/52/58 antibodies among AS04-adjuvanted HPV16/18 vaccinated and non-vaccinated Ugandan girls aged 10–16 years

BACKGROUND: Data on Human Papilloma virus (HPV) vaccine immune response in sub-Saharan Africa is still sparse yet such knowledge is critical for optimal implementation and monitoring of HPV vaccines. Our primary objective was to evaluate levels of anti-HPV-16/18 antibodies and six other ‘high risk’ HPV (hrHPV) types among the vaccinated and unvaccinated Ugandan girls. METHODS: We conducted a cross sectional study among AS04-adjuvanted HPV-16/18 vaccinated and unvaccinated school girls aged 10–16 years in Western Uganda using purposive sampling. The vaccinated girls were at 18 months post vaccination. After consenting and assenting, data was collected using interviewer administered questionnaires for demographics and sexual history. Blood was drawn from which serum samples were analysed by the multiplex HPV serology technology to determine anti-HPV antibody levels to HPV-16/18 and six other hrHPV types (31, 33, 35, 45, 52 and 58). The antibody levels were expressed as Median Fluorescent Intensity (MFI). A total of 207 vaccinated [mean age 13.1 years (SD 1.5); range 10-16 years] and 197 unvaccinated girls [mean age 13.6 years (SD 1.3); range 10-16 years] participated in the study. Sexual activity was self reported among 14/207 (6.8%) vaccinated and 5/197 (2.5%) unvaccinated girls. The MFI levels for HPV-16 and HPV-18 were 15 and 20 times higher respectively in the vaccinated girls than in the unvaccinated girls. HPV-16 mean MFI level was 4691(SD 1812; 95% CI: 4438-4958) among the vaccinated compared to 218 (SD 685; 95% CI: 190-252) among the unvaccinated girls. For HPV-18 the mean MFI level was 1615 (SD 1326; 95% CI: 1470-1776) among the vaccinated compared to MFI 103 (SD 506; 95% CI: 88 -121) among unvaccinated girls. In addition antibody levels to non vaccine hrHPV types (31, 33, 35, 45, 52 and 58) were all significantly higher in the vaccinated group than in the unvaccinated group (p<0.01). CONCLUSION: The AS04-Adjuvanted HPV-16/18 vaccinated girls showed a higher level of antibodies to HPV-16/18 and other non-vaccine hrHPV types compared to the unvaccinated girls. This may translate into protection against HPV-16/18 and other hrHPV types

High-Risk Cervical Human Papillomavirus Infections among Human Immunodeficiency Virus-Positive Women in the Bahamas

Background\ud \ud High-risk (HR) HPV genotypes other than 16 and 18 have been detected in a significant proportion of immunocompromised females. We aim to evaluate the frequency of HR HPV genotypes in a population of HIV-positive Caribbean women.\ud Methods\ud \ud One hundred sixty-seven consecutive, non-pregnant, HIV-positive females ≥18 years were recruited in this study. Each participant received a vaginal examination, PAP smear, and completed a questionnaire. DNA was extracted for HPV testing in 86 patients.\ud Results\ud \ud Mean age was 39.1 years for women positive for HR HPV and 43.1 years for women negative for HR HPV (P value = 0.040). 78% (130/167) of the women had HR HPV infections; the prevalence of abnormal cervical cytology was 38% among women who were HR HPV-positive compared to women who were HR HPV-negative (22%). Fifty-one percent of the 86 women with available genotype carried infections with HPV 16 and/or HPV 18; genotypes of unknown risk were also frequently observed. Women who had a CD4+ count of ≤200 had 7 times increased odds of carrying HR HPV infection in comparison to women with CD4+>200.\ud Conclusions\ud \ud HR HPV infections in HIV infected females may consist of more than just HPV 16 and 18, but also HPV 52 and 58. Further studies are needed to determine whether HPV 52 and 58 play a significant role in the development of cervical cytological abnormalities in HIV+ women

Investigaciones en ciencias humanas y sociales : del ABC disciplinar a la reflexión metodológica

Diversidad de objetos, variedad de enfoques, prácticas disciplinares y multidisciplinares, y ejemplos de ejecución de proyectos de investigación y desarrollo son los rasgos distintivos de los siete capítulos que integran esta obra. En ellos se recoge el material desplegado en los Seminarios-Talleres de Metodología de la Investigación en Humanidades que se realizaron en el marco de las V Jornadas de Investigación de la Facultad de Filosofía y Letras de la Universidad Nacional de Cuyo en setiembre de 2004: estudios sobre procesos sociales, cuestiones educativas, geográficas, históricas, lingüísticas y literarias. Algunos capítulos han mantenido el estilo y formato característicos del contexto de los seminarios-talleres, a veces con ligeras modificaciones; otros han sido enteramente reescritos para la convocatoria de esta publicación. Este libro refleja entonces abordajes disciplinares y pluridisciplinares diversos a problemáticas igualmente variadas. Por tratarse de propuestas orientadas a y/o basadas en seminarios-talleres, está claro que los autores involucrados no pueden abarcar todos los aspectos de los objetos de estudio respectivos. Sin embargo, la idea es al menos brindar algún punto de vista sobre el estadio de desarrollo de algunas de las investigaciones actualmente en ejecución en nuestra Facultad

Prevalence of anogenital HPV infection, related disease and risk factors among HIV-infected men in inner-city Johannesburg, South Africa: baseline findings from a cohort study.

BACKGROUND: Persistent high-risk human papillomavirus (HR-HPV) infection is associated with the development of anogenital cancers, particularly in men living with HIV (MLWH). We describe the prevalence of anogenital HPV infection, abnormal anal cytology and anogenital warts (AGWs) in MLWH in Johannesburg, and explore whether HPV infection and receipt of antiretroviral treatment is associated with detection of abnormal anal cytology and AGWs. METHODS: We enrolled a cohort of 304 sexually-active MLWH ≥18 years, who completed a questionnaire and physical examination. Genital swabs were collected from all men and intra-anal swabs from 250 (82%). Swabs were tested for HPV DNA and genotypes, and anal smears graded using the Bethesda classification. Factors associated with anogenital disease were assessed by logistic regression models. RESULTS: Two thirds were receiving antiretroviral treatment, for a median 33 months (IQR = 15-58) and 54% were HIV-virologically suppressed. Only 5% reported ever having sex with men. Among 283 genital swabs with valid results, 79% had any HPV, 52% had HR-HPV and 27% had >1 HR-HPV infection. By comparison, 39% of the 227 valid intra-anal swabs had detectable HPV, 25% had any HR-HPV and 7% >1 HR infection. While most anal smears were normal (51%), 20% had ASCUS and 29% were LSIL. No cases had HSIL or cancer. Infection with >1 HR type (adjusted OR [aOR] = 2.39; 95%CI = 1.02-5.58) and alpha-9 types (aOR = 3.98; 95%CI = 1.42-11.16) were associated with having abnormal cytology. Prevalence of AGWs was 12%. Infection with any LR type (aOR = 41.28; 95%CI = 13.57-125.62), >1 LR type (aOR = 4.14; 95%CI = 1.60-10.69), being <6 months on antiretroviral treatment (aOR = 6.90; 95%CI = 1.63-29.20) and having a CD4+ count <200 cells/μL (aOR = 5.48; 95%CI: 1.60-18.78) were associated with having AGWs. CONCLUSIONS: In this population, anogenital HR-HPV infection and associated low-grade disease is common, but severe anal dysplasia was not detected. Findings reinforce the need for HPV vaccination in men for preventing both AGWs and HR-HPV infection. Given the absence of anal HSILs, however, the findings do not support the use of anal screening programmes in this population

Agreement between physicians and non-physician clinicians in starting antiretroviral therapy in rural Uganda

<p>Abstract</p> <p>Background</p> <p>The scarcity of physicians in sub-Saharan Africa – particularly in rural clinics staffed only by non-physician health workers – is constraining access to HIV treatment, as only they are legally allowed to start antiretroviral therapy in the HIV-positive patient. Here we present a pilot study from Uganda assessing agreement between non-physician clinicians (nurses and clinical officers) and physicians in their decisions as to whether to start therapy.</p> <p>Methods</p> <p>We conducted the study at 12 government antiretroviral therapy sites in three regions of Uganda, all of which had staff trained in delivery of antiretroviral therapy using the WHO Integrated Management of Adult and Adolescent Illness guidelines for chronic HIV care. We collected seven key variables to measure patient assessment and the decision as to whether to start antiretroviral therapy, the primary variable of interest being the Final Antiretroviral Therapy Recommendation. Patients saw either a clinical officer or nurse first, and then were screened identically by a blinded physician during the same clinic visit. We measured inter-rater agreement between the decisions of the non-physician health workers and physicians in the antiretroviral therapy assessment variables using simple and weighted Kappa analysis.</p> <p>Results</p> <p>Two hundred fifty-four patients were seen by a nurse and physician, while 267 were seen by a clinical officer and physician. The majority (> 50%) in each arm of the study were in World Health Organization Clinical Stages I and II and therefore not currently eligible for antiretroviral therapy according to national antiretroviral therapy guidelines. Nurses and clinical officers both showed moderate to almost perfect agreement with physicians in their Final Antiretroviral Therapy Recommendation (unweighted κ = 0.59 and κ = 0.91, respectively). Agreement was also substantial for nurses versus physicians for assigning World Health Organization Clinical Stage (weighted κ = 0.65), but moderate for clinical officers versus physicians (κ = 0.44).</p> <p>Conclusion</p> <p>Both nurses and clinical officers demonstrated strong agreement with physicians in deciding whether to initiate antiretroviral therapy in the HIV patient. This could lead to immediate benefits with respect to antiretroviral therapy scale-up and decentralization to rural areas in Uganda, as non-physician clinicians – particularly clinical officers – demonstrated the capacity to make correct clinical decisions to start antiretroviral therapy. These preliminary data warrant more detailed and multicountry investigation into decision-making of non-physician clinicians in the management of HIV disease with antiretroviral therapy, and should lead policy-makers to more carefully explore task-shifting as a shorter-term response to addressing the human resource crisis in HIV care and treatment.</p