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

Identifying factors associated with the uptake of prevention of mother to child HIV transmission programme in Tigray region, Ethiopia: a multilevel modeling approach

Background: Prevention of mother to child HIV transmission (PMTCT) remains a challenge in low and middle-income countries. Determinants of utilization occur – and often interact - at both individual and community levels, but most studies do not address how determinants interact across levels. Multilevel models allow for the importance of both groups and individuals in understanding health outcomes and provide one way to link the traditionally distinct ecological- and individual-level studies. This study examined individual and community level determinants of mother and child receiving PMTCT services in Tigray region, Ethiopia. Methods: A multistage probability sampling method was used for this 2011 cross-sectional study of 220 HIV positive post-partum women attending child immunization services at 50 health facilities in 46 districts. In view of the nested nature of the data, we used multilevel modeling methods and assessed macro level random effects. Results: Seventy nine percent of mothers and 55.7% of their children had received PMTCT services. Multivariate multilevel modeling found that mothers who delivered at a health facility were 18 times (AOR = 18.21; 95% CI 4.37,75.91) and children born at a health facility were 5 times (AOR = 4.77; 95% CI 1.21,18.83) more likely to receive PMTCT services, compared to mothers delivering at home. For every addition of one nurse per 1500 people, the likelihood of getting PMTCT services for a mother increases by 7.22 fold (AOR = 7.22; 95% CI 1.02,51.26), when other individual and community level factors were controlled simultaneously. In addition, district-level variation was low for mothers receiving PMTCT services (0.6% between districts) but higher for children (27.2% variation between districts). Conclusions: This study, using a multilevel modeling approach, was able to identify factors operating at both individual and community levels that affect mothers and children getting PMTCT services. This may allow differentiating and accentuating approaches for different settings in Ethiopia. Increasing health facility delivery and HCT coverage could increase mother-child pairs who are getting PMTCT. Reducing the distance to health facility and increasing the number of nurses and laboratory technicians are also important variables to be considered by the government

Prediction of hospital bed capacity during the COVID-19 pandemic

Background: Prediction of the necessary capacity of beds by ward type (e.g. ICU) is essential for planning purposes during epidemics, such as the COVID− 19 pandemic. The COVID− 19 taskforce within the Ghent University hospital made use of ten-day forecasts on the required number of beds for COVID− 19 patients across different wards. Methods: The planning tool combined a Poisson model for the number of newly admitted patients on each day with a multistate model for the transitions of admitted patients to the different wards, discharge or death. These models were used to simulate the required capacity of beds by ward type over the next 10 days, along with worst-case and best-case bounds. Results: Overall, the models resulted in good predictions of the required number of beds across different hospital wards. Short-term predictions were especially accurate as these are less sensitive to sudden changes in number of beds on a given ward (e.g. due to referrals). Code snippets and details on the set-up are provided to guide the reader to apply the planning tool on one’s own hospital data. Conclusions: We were able to achieve a fast setup of a planning tool useful within the COVID− 19 pandemic, with a fair prediction on the needed capacity by ward type. This methodology can also be applied for other epidemics

Designing cross-sector collaboration to foster technological innovation::Empirical insights from eHealth partnerships in five countries

This article examines the impact of partnership design on technological innovation in public-private innovation partnerships. It develops two competing hypotheses on how specific partnership characteristics lead to innovation in health care services. The study compares 19 eHealth partnerships across five European countries and uses fuzzy-set qualitative comparative analysis to test the hypotheses. The findings show that small, centralized, and homogeneous partnerships are most successful at achieving technological innovation. The study highlights the importance of partnership design in spurring innovation and calls for a reconsideration of some of the underlying assumptions of collaborative innovation theory

Antibiotic use and risk of colorectal cancer : a systematic review and dose-response meta-analysis

Background It is understudied whether the posed association of oral antibiotics with colorectal cancer (CRC) varies between antibiotic spectrums, colorectal continuum, and if a non-linear dose-dependent relationship is present. Design Three electronic databases and a trial platform were searched for all relevant studies, from inception until February 2020, without restrictions. Random-effects meta-analyses provided pooled effect-sizes (ES) with 95% confidence intervals (CI). Dose-response analyses modelling the relationship between number of days exposed to antibiotics and CRC risk were extended to non-linear multivariable random-effects models. Results Of 6483 identified publications ten were eligible, including 4.1 million individuals and over 73,550 CRC cases. The pooled CRC risk was increased among individuals who ever-used antibiotics (ES = 1.17, 95%CI 1.05-1.30), particularly for broad-spectrum antibiotics (ES = 1.70, 95%CI 1.26-2.30), but not for narrow-spectrum antibiotic (ES = 1.11, 95% 0.93-1.32). The dose-response analysis did not provide strong evidence of any particular dose-response association, and the risk patterns were rather similar for colon and rectal cancer. Discussion The antibiotic use associated CRC risk seemingly differs between broad- and narrow-spectrum antibiotics, and possibly within the colorectal continuum. It remains unclear whether this association is causal, requiring more mechanistic studies and further clarification of drug-microbiome interactions

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

Background: Women 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. Method: This 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. Results: CIN 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. Conclusion: The 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 + 

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

Health and budget impact of combined HIV prevention : first results of the BELHIVPREV model

Objectives: We developed a pragmatic modelling approach to estimate the impact of treatment as prevention (TasP); outreach testing strategies; and pre-exposure prophylaxis (PrEP) on the epidemiology of HIV and its associated pharmaceutical expenses. Methods: Our model estimates the incremental health (in terms of new HIV diagnoses) and budget impact of two prevention scenarios (outreach+TasP and outreach+TasP+PrEP) against a 'no additional prevention' scenario. Model parameters were estimated from reported Belgian epidemiology and literature data. The analysis was performed from a healthcare payer perspective with a 15-year-time horizon. It considers subpopulation differences, HIV infections diagnosed in Belgium having occurred prior to migration, and the effects of an ageing HIV population. Results: Without additional prevention measures, the annual number of new HIV diagnoses rises to over 1350 new diagnoses in 2030 as compared to baseline, resulting in a budget expenditure of (sic)260.5 million. Implementation of outreach+TasP and outreach+TasP+PrEP results in a decrease in the number of new HIV diagnoses to 865 and 663 per year, respectively. Respective budget impacts decrease by (sic)20.6 million and (sic)33.7 million. Conclusion: Foregoing additional investments in prevention is not an option. An approach combining TasP, outreach and PrEP is most effective in reducing the number of new HIV diagnoses and the HIV treatment budget. Our model is the first pragmatic HIV model in Belgium estimating the consequences of a combined preventive approach on the HIV epidemiology and its economic burden assuming other prevention efforts such as condom use and harm reduction strategies remain the same