Rodolfo Rossi

Epidemiology of HPV Genotypes among HIV Positive Women in Kenya: A Systematic Review and Meta-Analysis

Background There is a scarcity of data on the distribution of human papillomavirus (HPV) genotypes in the HIV positive population and in invasive cervical cancer (ICC) in Kenya. This may be different from genotypes found in abnormal cytology. Yet, with the advent of preventive HPV vaccines that target HPV 16 and 18, and the nonavalent vaccine targeting 90% of all ICC cases, such HPV genotype distribution data are indispensable for predicting the impact of vaccination and HPV screening on prevention. Even with a successful vaccination program, vaccinated women will still require screening to detect those who will develop ICC from other High risk (HR) HPV genotypes not prevented by current vaccines. The aim of this review is to report on the prevalence of pHR/HR HPV types and multiple pHR/HR HPV genotypes in Kenya among HIV positive women with normal, abnormal cytology and ICC. Methods PUBMED, EMBASE, SCOPUS, and PROQUEST were searched for articles on HPV infection up to August 2nd 2016. Search terms were HIV, HPV, Cervical Cancer, Incidence or Prevalence, and Kenya. Results The 13 studies included yielded a total of 2116 HIV-infected women, of which 89 had ICC. The overall prevalence of pHR/HR HPV genotypes among HIV-infected women was 64% (95%CI: 50%-77%). There was a borderline significant difference in the prevalence of pHR/HR HPV genotypes between Female Sex workers (FSW) compared to non-FSW in women with both normal and abnormal cytology. Multiple pHR/HR HPV genotypes were highly prominent in both normal cytology/HSIL and ICC. The most prevalent HR HPV genotypes in women with abnormal cytology were HPV 16 with 26%, (95%CI: 23.0%-30.0%) followed by HPV 35 and 52, with 21% (95%CI: 18%-25%) and 18% (95%CI: 15%-21%), respectively. In women with ICC, the most prevalent HPV genotypes were HPV 16 (37%; 95%CI: 28%-47%) and HPV 18 (24%; 95%CI: 16%-33%). Conclusion HPV 16/18 gains prominence as the severity of cervical disease increases, with HPV 16/18 accounting for 61% (95%CI: 50.0%-70.0%) of all ICC cases. A secondary prevention program will be necessary as this population harbors multiple pHR/HR HPV co-infections, which may not be covered by current vaccines. A triage based on FSW as an indicator may be warranted.

Convergence of a diabetes mellitus, protein energy malnutrition, and TB epidemic: the neglected elderly population

BackgroundOn a global scale, nearly two billion persons are infected with Mycobacterium tuberculosis. From this vast reservoir of latent tuberculosis (TB) infection, a substantial number will develop active TB during their lifetime, with some being able to transmit TB or Multi-drug- resistant (MDR) TB to others. There is clinical evidence pointing to a higher prevalence of infectious diseases including TB among individuals with Diabetes Mellitus (DM). Furthermore, ageing and diabetes mellitus may further aggravate protein-energy malnutrition (PEM), which in turn impairs T-lymphocyte mediated immunologic defenses, thereby increasing the risk of developing active TB and compromising TB treatment. This article aims to a) highlight synergistic mechanisms associated with immunosenescence, DM and PEM in relation to the development of active TB and b) identify nutritional, clinical and epidemiological research gaps.MethodsTo explore the synergistic relationship between ageing, DM, tuberculosis and PEM, a comprehensive review was undertaken. The MEDLINE and the Google Scholar databases were searched for articles published from 1990 to March 2015, using different MESH keywords in various combinations.ResultsAgeing and DM act synergistically to reduce levels of interferon gamma (IFN- γ), thereby increasing susceptibility to TB, for which cell mediated immunity (CMI) plays an instrumental role. These processes can set in motion a vicious nutritional cycle which can predispose to PEM, further impairing the CMI and consequently limiting host defenses. This ultimately transforms the latent TB infection into active disease. A clinical diagnostic algorithm and clinical guidelines need to be established for this population.ConclusionGiven the increase in ageing population with DM and PEM, especially in resource-poor settings, these synergistic tripartite interactions must be examined if a burgeoning TB epidemic is to be averted. Implementation of a comprehensive, all-encompassing approach to curb transmission is clearly indicated. To this end, clinical, nutritional and epidemiological research gaps must be addressed without a delay.

Human papilloma virus infection in HIV-infected women in Belgium: implications for prophylactic vaccines within this subpopulation.

Although high-risk (HR) human papilloma virus (HPV) infection is the primary causative factor for cervical squamous intraepithelial lesions and invasive cervical cancer, the epidemiology of potentially HR (pHR) and low-risk HPV still remains to be elucidated in HIV-infected women. In addition, the synergistic potential of the multiplicity of HPV infections harboured renders it difficult to model the impact of vaccines. This cross-sectional analysis of HIV-infected women explores the epidemiology of abnormal cytology, thereby profiling and pairing pHR/HR HPV genotypes. This cross-sectional analysis reports the findings of 593 HIV-infected women, who underwent a cytological examination and HPV genotyping. A logistic regression model was fitted to adjust for age and coinfection with pHR/HR HPV genotypes. In the 143 women with abnormal cytology, a multiple pHR/HR HPV genotype prevalence of 64.1% [95% confidence interval (CI): 44.6–57.6%] was observed. A combined prevalence of HPV 16 and HPV 18 of 29.6% (95% CI: 22.2–37.8%) was found. HPV 6 and HPV 66 were found in two cases of low-grade squamous intraepithelial lesions as stand-alone genotypes and HPV 53 in a high-grade squamous intraepithelial lesion case. Pairing involving HPV 31 with HPV 16 and HPV 58 was found in high-grade squamous intraepithelial lesion cases. Significant associations were observed between abnormal cytology, multiple HPV, HPV 39 and HPV 53 [adjusted odds ratio (aOR): 2.02; P=0.01; 95% CI: 1.2–3.5; aOR: 3.8; P=0.01; 95% CI: 1.4–10.7; and aOR: 0.5; P=0.03; 95% CI: 0.2–0.9, respectively]. Coinfection with pHR/HR HPV genotypes HPV 39 and 53 was significantly associated with abnormal cytology. Research into the imputed role of HPV 31 in pairings, low-risk and pHR HPV genotypes in HIV-infected women is warranted.

Associations between highly active antiretroviral therapy and the presence of HPV, premalignant and malignant cervical lesions in sub-Saharan Africa, a systematic review: current evidence and directions for future research

Objectives In sub-Saharan Africa, substantial international funding along with evidence-based clinical practice have resulted in an unparalleled scale-up of access to antiretroviral treatment at a higher CD4 count. The role and timing of highly active antiretroviral therapy (HAART) in mediating cervical disease remains unclear. The aim of this article is to systematically review all evidence pertaining to Africa and identify research gaps regarding the epidemiological association between HAART use and the presence of premalignant/malignant cervical lesions. Method Five databases were searched until January 2017 to retrieve relevant literature from sub-Saharan Africa. Publications were included if they addressed prevalence, incidence or clearance of human papillomavirus (HPV) infection in women undergoing HAART as well as cytological or histological neoplastic abnormalities. Results 22 studies were included, of which seven were prospective studies. Women receiving HAART are less likely to develop squamous intraepithelial lesions (SILs). There is evidence that duration of HAART along with the CD4 count may reduce the prevalence of high-risk HPV (HR-HPV), suggesting that without HAART, severe immunosuppression increases the risk of becoming or remaining infected with HR-HPV. Furthermore, according to existent literature, the CD4 count, rather than HAART coverage or its duration, plays a central role in the prevalence of cervical intraepithelial neoplasia (CIN) 2 and CIN 3. Conclusion Our findings suggest a positive impact of HAART duration, in conjunction and interaction with CD4 count, on reducing the prevalence of HR-HPV. The greatest treatment effect might be seen among women starting at the lowest CD4 count, which may have a more instrumental role in cervical oncogenesis than either HAART use or the treatment duration on the prevalence of CIN 2 and CIN 3. There is still insufficient evidence to show a clear association between HAART coverage and the incidence of invasive cervical cancer. Enhanced surveillance on the impact of HAART treatment is crucial.

Associations between vaginal infections and potential high-risk and high-risk human papillomavirus genotypes in female sex workers in Western Kenya

PURPOSE Infection with and persistence of high-risk human papillomavirus (HR HPV) are the strongest risk factors for cervical cancer. Little is known about the prevalence and role of concurrent sexually transmitted infections (STIs) found in HPV-infected female sex workers (FSW) in Africa. This study purports to test our a priori hypotheses that STIs are associated with genotypes pertaining to the α-group species 9. The objectives were to determine the prevalence of bacterial vaginosis (BV), Trichomonas vaginalis, and Candida spp in FSW, the association between these STIs and the prevalence of any potential HR and HR HPV genotypes in FSWs. METHODS A cross-sectional study design of 616 FSW from Western Kenya aged between 18 and 61 years during 2009-2015 using a peer recruitment sampling strategy. Inclusion criteria for the study entailed female sex and >18 years of age and having engaged in transactional sex in exchange for money, goods, services, or drugs in the last 3 months. Women were excluded if they were pregnant, <18 years of age, had a history of cervical dysplasia or cancer, had current abnormal bleeding, or had a hysterectomy. FINDINGS Of the FSW, 33.3% had HIV and 57.7% harbored a potential HR and HR HPV genotype. The 2 most prevalent potential HR and HR genotypes were HPV 16 (16.10%) and HPV 59 (12.20%). BV was the most common infection (48.3%), followed by Trichomonas vaginalis (31.4%) and Candida spp (19.9%). A multivariate regression revealed significant associations with both α-group 9 and 6; BV and HPV 58 (adjusted odds ratio [aOR] = 2.3; 95% CI, 1.0-5.2; P = 0.05), Trichomonas vaginalis and HPV 31 and HPV 35 (aOR = 2.0; 95% CI, 1.0-3.8; P = 0.04 and aOR = 1.8; 95% CI, 1.0-3.3, P = 0.05 respectively); and between Candida spp and HPV 53 (aOR = 2.0; 95% CI, 1.1-4.0; P = 0.03) and 16 (aOR = 1.9; 95% CI, 1.1-3.3; P = 0.03). IMPLICATIONS Snowball sampling may have inadvertently excluded FSW less likely to benefit from a social network. Significant associations between BV and HPV 58 and between Candida spp and HPV 16 and 53 suggest the need for sexually transmitted disease management within a cervical cancer prevention program. The probable synergistic effects of the vaginal microbiota should be elucidated, especially within this vulnerable population. Given the potential for FSW to transmit STIs, robust epidemiologic sampling methods are urgently required that account for the heterogeneity of the FSW population.

Do Maternal Living Arrangements Influence the Vaccination Status of Children Age 12–23 Months? A Data Analysis of Demographic Health Surveys 2010–11 from Zimbabwe

Introduction Although vaccination is an effective intervention to reduce childhood mortality and morbidity, reasons for incomplete vaccination, including maternal living arrangements, have been marginally explored. This study aims at assessing whether maternal living arrangements are associated with vaccination status of children aged 12–23 months in Zimbabwe. It also explores other variables that may be associated with having children not fully vaccinated. Materials and Methods A cross-sectional analysis was performed on the DHS-VI done in Zimbabwe in 2010–2011 (response rate 93%). Incomplete vaccination of children (outcome), was defined as not having received one dose of BCG and measles, 3 doses of polio and DPT/Pentavalent. Maternal living arrangements (main exposure), and other exposure variables were analysed. Survey logistic regression was used to calculate crude and adjusted OR for exposures against the outcome. Results The dataset included 1,031 children aged 12–23 months. 65.8% of children were fully vaccinated. 65.7% of the mothers were married and cohabitating with a partner, 20.3% were married/partnered but living separately and 14% were not married. Maternal living arrangements were not associated with the vaccination status of children both in crude and adjusted analysis. Factors associated with poorer vaccination status of the children included: no tetanus vaccination for mothers during pregnancy (adjusted OR = 2.1, 95%CI 1.5;3.0), child living away from mother (adjusted OR = 1.5, 95%CI 1.2;1.8), mother’s education (adjusted OR = 0.6, 95%CI 0.4;0.9), high number of children living in the household (adjusted OR = 1.5, 95%CI 1.1;2.2), child age (adjusted OR = 0.7, 95%CI 0.5;0.9). Discussion Maternal living arrangements were not associated with vaccination status of Zimbabwean children. Other factors, such as the mother’s health-seeking behaviour and education were major factors associated with the children’s vaccination status. Given the results of this study, it is strongly recommended that the vaccination coverage is increased by improving access to antenatal care and education for the parents.

Revisiting zoonotic human African trypanosomiasis control in Uganda

Objectives: Human migration and concomitant HIV infections are likely to bring about major changes in the epidemiology of zoonotic parasitic infections. Human African trypanosomiasis (HAT) control is particularly fraught with intricacies. The primarily zoonotic form, T.b. rhodesiense, and the non-zoonotic T.b. gambiense co-exist in Northern Uganda, leading to a potential geographic and genetic overlap of the two foci. This region also has the highest HIV prevalence in Uganda plus poor food security. We examine the bottlenecks facing the control program in a changed political and economic context. Method: We searched the literature in July 2015 using three databases: MEDLINE, Google Scholar, and Web of Science. Findings: Decentralized zoonotic HAT control for animal reservoirs and vectors compromise sustainability of the control programs. Human transmission potential may be underestimated in a region with other endemic diseases and where an HIV-HAT epidemic, could merge two strains. Conclusion: Our comprehensive literature review concludes that enhanced collaboration is imperative not only between human and animal health specialists, but also with political science. Multi-sectorial collaborations may need to be nurtured within existing operational national HIV prevention frameworks, with an integrated surveillance framework.

Decentralized control of human visceral leishmaniasis in endemic urban areas of Brazil: a literature review

ObjectivesHuman migration and concomitant HIV infections are likely to bring about major changes in the epidemiology of some parasitic infections in Brazil. Human visceral leishmaniasis (HVL) control is particularly fraught with intricacies. It is against a backdrop of decentralized health care that the complex HVL control initiatives are brought to bear. This comprehensive review aims to explore the obstacles facing decentralized HVL control in urban endemic areas in Brazil.MethodA literature search was carried out in December 2015 by means of three databases: MEDLINE, Google Scholar, and Web of Science.ResultsAlthough there have been many strides that have been made in elucidating the eco-epidemiology of Leishmania infantum, which forms the underpinnings of the national control program, transmission risk factors for HVL are still insufficiently elucidated in urban settings. Decentralized HVL epidemiological surveillance and control for animal reservoirs and vectors may compromise sustainability. In addition, it may hamper timely human HVL case management. With the burgeoning of the HIV-HVL co-infection, the potential human transmission may be underestimated.ConclusionHVL is a disease with focal transmission at a critical juncture, which warrants that the bottlenecks facing the control program within contexts of decentralized healthcare systems be taken into account. In addition, HIV-driven HVL epidemics may substantially increase the transmission potential of the human reservoir. Calculating the basic reproductive number to fine-tune interventions will have to take into consideration the specific socio-economic development context.

Human papilloma virus correlates of high grade cervical dysplasia in HIV-infected women in Mombasa, Kenya: a cross-sectional analysis

BackgroundWomen living with HIV are at increased risk to be co-infected with HPV, persistent high-risk (HR) human papillomavirus (HPV) infection and increased HR HPV viral load, which make them more at risk for cervical cancer. Despite their inherent vulnerability, there is a scarcity of data on potential high risk (pHR) and HR HPV genotypes in HIV- infected women with cervical dysplasia and HPV-type specific viral load in this population in Sub Saharan Africa.The aim of this analysis of HIV-infected women was to explore the virological correlates of high-grade cervical dysplasia (CIN 2+) in HIV-infected women, thereby profiling HPV genotypes.MethodThis analysis assesses baseline data obtained from a cohort study of 74 HIV-infected women with abnormal cytology attending a Comprehensive Care Centre for patients with HIV infection in Mombasa, Kenya. Quantitative real-time PCR was used for HPV typing and viral load.ResultsCIN 2 was observed in 16% (12/74) of women, CIN 3 in 23% (17/74), and, invasive cervical carcinoma (ICC) in 1% (1/74) of women. In women with CIN 3+, HPV 16 (44%), HPV 56 (33%), HPV 33 and 53 (HPV 53 (28%) were the most prevalent genotypes. HPV 53 was observed as a stand-alone HPV in one woman with ICC.A multivariate logistic regression adjusting for age, CD4 count and HPV co-infections suggested the presence of HPV 31 as a predictor of CIN 2+ (adjusted odds ratio [aOR]:4.9; p = 0.05; 95% (Confidence Interval) [CI]:1.03–22.5). Women with CIN2+ had a significantly higher viral log mean of HPV 16, (11.2 copies/ 10,000 cells; 95% CI: 9.0–13.4) than with CIN 1.ConclusionThe high prevalence of HPV 53 in CIN 3 and as a stand-alone genotype in the patient with invasive cervical cancer warrants that its clinical significance be further revisited among HIV-infected women. HPV 31, along with elevated means of HPV 16 viral load were predictors of CIN 2 + .

Public health approach to prevent cervical cancer in HIV-infected women in Kenya : issues to consider in the design of prevention programs

Women living with HIV in Africa are at increased risk to be co-infected with Human Papilloma Virus (HPV), persistent high risk (HR) HPV infection and bacterial vaginosis (BV), which compounds HPV persistence, thereby increasing the risk for cervical dysplasia. New guidance from WHO in 2014 advocating for a “screen and treat” approach in resource poor settings is becoming a more widely recommended screening tool for cervical cancer prevention programs in such contexts. This review article summarizes the risk factors to be considered when designing a primary and secondary cervical prevention program in a post-vaccination era for HIV-infected women in Kenya. This review article is based on our prior research on the epidemiology of pHR/HR-HPV genotypes in HIV-infected women and CIN 2 + in Kenya and other sub-Saharan contexts. In order to contextualize the findings, a literature search was carried out in March 2017 by means of four electronic databases: PUBMED, EMBASE, SCOPUS, and PROQUEST. Risk factors for potential (pHR)/HR HPV acquisition, including CD4 count, HAART initiation, Female Sex Worker status (FSW) and BV need to be considered. Furthermore, there may be risk factors for abnormal cytology, including FSW status, multiple potential (p)HR/HR HPV genotypes, which may require that HIV-infected women be subjected to screening at more frequent intervals than the three year recommended by the WHO. The quadruple synergistic interaction between HIV, HPV and BV and its related cervicitis may need to be reflected within a larger prevention framework at the community level. The opportunities brought forth by the roll out of HAART could lead to task shifting of HIV-HPV-BV care to nurses, which may increase access in poorly-served areas.