The role of dissemination and implementation science in global breast cancer control programs: Frameworks, methods, and examples.

Global disparities in breast cancer outcomes are attributable to a sizable gap between evidence and practice in breast cancer control and management. Dissemination and implementation science (D&IS) seeks to understand how to promote the systematic uptake of evidence-based interventions and/or practices into real-world contexts. D&IS methods are useful for selecting strategies to implement evidence-based interventions, adapting their implementation to new settings, and evaluating the implementation process as well as its outcomes to determine success and failure, and adjust accordingly. Process models, explanatory theories, and evaluation frameworks are used in D&IS to develop implementation strategies, identify implementation outcomes, and design studies to evaluate these outcomes. In breast cancer control and management, research has been translated into evidence-based, resource-stratified guidelines by the Breast Health Global Initiative and others. D&IS should be leveraged to optimize the implementation of these guidelines, and other evidence-based interventions, into practice across the breast cancer care continuum, from optimizing public education to promoting early detection, increasing guideline-concordant clinical practice among providers, and analyzing and addressing barriers and facilitators in health care systems. Stakeholder engagement through processes such as co-creation is critical. In this article, the authors have provided a primer on the contribution of D&IS to phased implementation of global breast cancer control programs, provided 2 case examples of ongoing D&IS research projects in Tanzania, and concluded with recommendations for best practices for researchers undertaking this work.

Breast cancer treatment: A phased approach to implementation.

Optimal treatment outcomes for breast cancer are dependent on a timely diagnosis followed by an organized, multidisciplinary approach to care. However, in many low- and middle-income countries, effective care management pathways can be difficult to follow because of financial constraints, a lack of resources, an insufficiently trained workforce, and/or poor infrastructure. On the basis of prior work by the Breast Health Global Initiative, this article proposes a phased implementation strategy for developing sustainable approaches to enhancing patient care in limited-resource settings by creating roadmaps that are individualized and adapted to the baseline environment. This strategy proposes that, after a situational analysis, implementation phases begin with bolstering palliative care capacity, especially in settings where a late-stage diagnosis is common. This is followed by strengthening the patient pathway, with consideration given to a dynamic balance between centralization of services into centers of excellence to achieve better quality and decentralization of services to increase patient access. The use of resource checklists ensures that comprehensive therapy or palliative care can be delivered safely and effectively. Episodic or continuous monitoring with established process and quality metrics facilitates ongoing assessment, which should drive continual process improvements. A series of case studies provides a snapshot of country experiences with enhancing patient care, including the implementation of national cancer control plans in Kenya, palliative care in Romania, the introduction of a 1-stop clinic for diagnosis in Brazil, the surgical management of breast cancer in India, and the establishment of a women's cancer center in Ghana.

Factors Associated With Poor Linkage to Human Immunodeficiency Virus Care Among Index Clients and Sex Partners Receiving Human Immunodeficiency Virus Assisted Partner Services in Kenya.

INTRODUCTION: Human immunodeficiency virus (HIV) assisted partner services (aPS) has been recommended as a strategy to increase HIV case finding. We evaluated factors associated with poor linkage to HIV care among newly diagnosed HIV-positive individuals (index clients) and their partners after receiving aPS in Kenya. METHODS: In a cluster randomized trial conducted between 2013 and 2015, 9 facilities were randomized to immediate aPS (intervention). Linkage to care-defined as HIV clinic registration, and antiretroviral therapy (ART) initiation were self-reported. Antiretroviral therapy was only offered to those with CD4 less than 500 during this period. We estimated linkage to care and ART initiation separately for index clients and their partners using log-binomial generalized estimating equation models with exchangeable correlation structure and robust standard errors. RESULTS: Overall, 550 index clients and 621 sex partners enrolled, of whom 46% (284 of 621) were HIV-positive. Of the 284, 264 (93%) sex partners returned at 6 weeks: 120 newly diagnosed and 144 whom had known HIV-positive status. Among the 120 newly diagnosed, only 69% (83) linked to care at 6 weeks, whereas among the 18 known HIV-positive sex partners not already in care at baseline, 61% (11) linked. Newly diagnosed HIV-positive sex partners who were younger and single were less likely to link to care (P < 0.05 for all). CONCLUSION: Only two thirds of newly diagnosed, and known HIV-positive sex partners not in care linked to care after receiving aPS. The HIV aPS programs should optimize HIV care for newly diagnosed HIV-positive sex partners, especially those who are younger and single.

Predictors of cervical cancer screening among Kenyan women: results of a nested case-control study in a nationally representative survey.

BACKGROUND: Cervical cancer is a major public health concern in Kenya. It is the leading cause of cancer morbidity and mortality among women. Although screening is an effective prevention method, uptake is low among eligible women. Little is known about predictors of cervical cancer screening uptake. This study explored relationship between uptake of cervical cancer screening, socio-demographic, behavioral and biological risk factors. METHODS: Nested case-control study within STEPS survey, a population-based cross-sectional household survey conducted between April and June 2015.Cases were women who had undergone cervical cancer screening and controls were unscreened women. Study participants were women eligible for cervical cancer screening (30-49 years). Variables included socio-demographic; behavioral risk factors such as physical activity, tobacco and alcohol use diet and biological factors like diabetes and hypertension. Outcome of interest was cervical cancer screening. Data analysis was done using STATA version 14. Logistic regression model was used to assess relationship between cervical cancer screening and socio-demographic, behavioral and biological risk factors. RESULTS: Of 1180 women interviewed, 16.4% (n = 194) had been screened for cervical cancer. Of unscreened women (n = 986), 67.9% were aware of cervical cancer screening. Higher screening rates were observed in more educated women (25.2%), highest income quintile (29.6%) and living in urban areas (23%) than in women with no formal education (3.2%), poorest (3.6%) and living in rural areas (13.8%). Younger women (35-39) and those with low High-density lipoprotein (HDL) were less likely to be screened [OR = 0.56; 95% CI = (0.34, 0.93); p-value = 0.025] and [OR = 0.51; 95% CI = (0.29, 0.91); p = value 0.023] respectively. Self-employed women, those in the fourth wealth quintile, binge drinkers, high sugar consumption and insufficient physical activity were more likely to be screened [OR 2.55 (1.12, 5.81) p value 0.026], [OR 3.56 (1.37, 9.28) p value 0.009], [OR 5.94 (1.52, 23.15) p value 0.010], [OR 2.99 (1.51, 5.89) p value 0.002] and [OR 2.79 (1.37, 5.68) p value 0.005] respectively. CONCLUSION: Uptake of cervical cancer screening is low despite high awareness. Strategies to improve cervical cancer screening in Kenya should be implemented with messages targeting persons with both risky and non-risky lifestyles especially younger women with no formal education living in rural areas.

Designing HIV Testing Algorithms Based on 2015 WHO Guidelines Using Data from Six Sites in Sub-Saharan Africa.

Our objective was to evaluate the performance of HIV testing algorithms based on WHO recommendations, using data from specimens collected at six HIV testing and counseling sites in sub-Saharan Africa (Conakry, Guinea; Kitgum and Arua, Uganda; Homa Bay, Kenya; Douala, Cameroon; Baraka, Democratic Republic of Congo). A total of 2,780 samples, including 1,306 HIV-positive samples, were included in the analysis. HIV testing algorithms were designed using Determine as a first test. Second and third rapid diagnostic tests (RDTs) were selected based on site-specific performance, adhering where possible to the WHO-recommended minimum requirements of ≥99% sensitivity and specificity. The threshold for specificity was reduced to 98% or 96% if necessary. We also simulated algorithms consisting of one RDT followed by a simple confirmatory assay. The positive predictive values (PPV) of the simulated algorithms ranged from 75.8% to 100% using strategies recommended for high-prevalence settings, 98.7% to 100% using strategies recommended for low-prevalence settings, and 98.1% to 100% using a rapid test followed by a simple confirmatory assay. Although we were able to design algorithms that met the recommended PPV of ≥99% in five of six sites using the applicable high-prevalence strategy, options were often very limited due to suboptimal performance of individual RDTs and to shared falsely reactive results. These results underscore the impact of the sequence of HIV tests and of shared false-reactivity data on algorithm performance. Where it is not possible to identify tests that meet WHO-recommended specifications, the low-prevalence strategy may be more suitable.

Surveillance of HIV assisted partner services using routine health information systems in Kenya.

BACKGROUND: The utilization of routine health information systems (HIS) for surveillance of assisted partner services (aPS) for HIV in sub-Saharan is sub-optimal, in part due to poor data quality and limited use of information technology. Consequently, little is known about coverage, scope and quality of HIV aPS. Yet, affordable electronic data tools, software and data transmission infrastructure are now widely accessible in sub-Saharan Africa. METHODS: We designed and implemented a cased-based surveillance system using the HIV testing platform in 18 health facilities in Kenya. The components of this system included an electronic HIV Testing and Counseling (HTC) intake form, data transmission on the Global Systems for Mobile Communication (GSM), and data collection using the Open Data Kit (ODK) platform. We defined rates of new HIV diagnoses, and characterized HIV-infected cases. We also determined the proportion of clients who reported testing for HIV because a) they were notified by a sexual partner b) they were notified by a health provider, or c) they were informed of exposure by another other source. Data collection times were evaluated. RESULTS: Among 4351 clients, HIV prevalence was 14.2 %, ranging from 4.4-25.4 % across facilities. Regardless of other reasons for testing, only 107 (2.5 %) of all participants reported testing after being notified by a health provider or sexual partner. A similar proportion, 1.8 % (79 of 4351), reported partner notification as the only reason for seeking an HIV test. Among 79 clients who reported HIV partner services as the reason for testing, the majority (78.5 %), were notified by their sexual partners. The majority (52.8 %) of HIV-infected patients initiated their HIV testing, and 57.2 % tested in a Voluntary Counseling and Testing (VCT) site co-located in a health facility. Median time for data capture was 4 min (IQR: 3-15), with a longer duration for HIV-infected participants, and there was no reported data loss. CONCLUSION: aPS surveillance using new technologies is feasible, and could be readily expanded into HIV registries in Kenya and other sub-Saharan countries. Partner services are under-utilized in Kenya but further documentation of coverage and implementation gaps for HIV and aPS services is required.

Psychosocial functioning and depressive symptoms among HIV-positive persons receiving care and treatment in Kenya, Namibia, and Tanzania.

In sub-Saharan Africa, the prevalence of depressive symptoms among people living with HIV (PLHIV) is considerably greater than that among members of the general population. It is particularly important to treat depressive symptoms among PLHIV because they have been associated with poorer HIV care-related outcomes. This study describes overall psychosocial functioning and factors associated with depressive symptoms among PLHIV attending HIV care and treatment clinics in Kenya, Namibia, and Tanzania. Eighteen HIV care and treatment clinics (six per country) enrolled approximately 200 HIV-positive patients (for a total of 3,538 participants) and collected data on patients' physical and mental well-being, medical/health status, and psychosocial functioning. Although the majority of participants did not report clinically significant depressive symptoms (72 %), 28 % reported mild to severe depressive symptoms, with 12 % reporting severe depressive symptoms. Regression models indicated that greater levels of depressive symptoms were associated with: (1) being female, (2) younger age, (3) not being completely adherent to HIV medications, (4) likely dependence on alcohol, (5) disclosure to three or more people (versus one person), (6) experiences of recent violence, (7) less social support, and (8) poorer physical functioning. Participants from Kenya and Namibia reported greater depressive symptoms than those from Tanzania. Approximately 28 % of PLHIV reported clinically significant depressive symptoms. The scale-up of care and treatment services in sub-Saharan Africa provides an opportunity to address psychosocial and mental health needs for PLHIV as part of comprehensive care.

HIV misdiagnosis in sub-Saharan Africa: performance of diagnostic algorithms at six testing sites.

INTRODUCTION: We evaluated the diagnostic accuracy of HIV testing algorithms at six programmes in five sub-Saharan African countries. METHODS: In this prospective multisite diagnostic evaluation study (Conakry, Guinea; Kitgum, Uganda; Arua, Uganda; Homa Bay, Kenya; Doula, Cameroun and Baraka, Democratic Republic of Congo), samples from clients (greater than equal to five years of age) testing for HIV were collected and compared to a state-of-the-art algorithm from the AIDS reference laboratory at the Institute of Tropical Medicine, Belgium. The reference algorithm consisted of an enzyme-linked immuno-sorbent assay, a line-immunoassay, a single antigen-enzyme immunoassay and a DNA polymerase chain reaction test. RESULTS: Between August 2011 and January 2015, over 14,000 clients were tested for HIV at 6 HIV counselling and testing sites. Of those, 2786 (median age: 30; 38.1% males) were included in the study. Sensitivity of the testing algorithms ranged from 89.5% in Arua to 100% in Douala and Conakry, while specificity ranged from 98.3% in Doula to 100% in Conakry. Overall, 24 (0.9%) clients, and as many as 8 per site (1.7%), were misdiagnosed, with 16 false-positive and 8 false-negative results. Six false-negative specimens were retested with the on-site algorithm on the same sample and were found to be positive. Conversely, 13 false-positive specimens were retested: 8 remained false-positive with the on-site algorithm. CONCLUSIONS: The performance of algorithms at several sites failed to meet expectations and thresholds set by the World Health Organization, with unacceptably high rates of false results. Alongside the careful selection of rapid diagnostic tests and the validation of algorithms, strictly observing correct procedures can reduce the risk of false results. In the meantime, to identify false-positive diagnoses at initial testing, patients should be retested upon initiating antiretroviral therapy.

Towards more accurate HIV testing in sub-Saharan Africa: a multi-site evaluation of HIV RDTs and risk factors for false positives.

INTRODUCTION: Although individual HIV rapid diagnostic tests (RDTs) show good performance in evaluations conducted by WHO, reports from several African countries highlight potentially significant performance issues. Despite widespread use of RDTs for HIV diagnosis in resource-constrained settings, there has been no systematic, head-to-head evaluation of their accuracy with specimens from diverse settings across sub-Saharan Africa. We conducted a standardized, centralized evaluation of eight HIV RDTs and two simple confirmatory assays at a WHO collaborating centre for evaluation of HIV diagnostics using specimens from six sites in five sub-Saharan African countries. METHODS: Specimens were transported to the Institute of Tropical Medicine (ITM), Antwerp, Belgium for testing. The tests were evaluated by comparing their results to a state-of-the-art reference algorithm to estimate sensitivity, specificity and predictive values. RESULTS: 2785 samples collected from August 2011 to January 2015 were tested at ITM. All RDTs showed very high sensitivity, from 98.8% for First Response HIV Card Test 1-2.0 to 100% for Determine HIV 1/2, Genie Fast, SD Bioline HIV 1/2 3.0 and INSTI HIV-1/HIV-2 Antibody Test kit. Specificity ranged from 90.4% for First Response to 99.7% for HIV 1/2 STAT-PAK with wide variation based on the geographical origin of specimens. Multivariate analysis showed several factors were associated with false-positive results, including gender, provider-initiated testing and the geographical origin of specimens. For simple confirmatory assays, the total sensitivity and specificity was 100% and 98.8% for ImmunoComb II HIV 12 CombFirm (ImmunoComb) and 99.7% and 98.4% for Geenius HIV 1/2 with indeterminate rates of 8.9% and 9.4%. CONCLUSION: In this first systematic head-to-head evaluation of the most widely used RDTs, individual RDTs performed more poorly than in the WHO evaluations: only one test met the recommended thresholds for RDTs of ≥99% sensitivity and ≥98% specificity. By performing all tests in a centralized setting, we show that these differences in performance cannot be attributed to study procedure, end-user variation, storage conditions, or other methodological factors. These results highlight the existence of geographical and population differences in individual HIV RDT performance and underscore the challenges of designing locally validated algorithms that meet the latest WHO-recommended thresholds.

Understanding Barriers to Scaling Up HIV-Assisted Partner Services in Kenya.

Assisted partner services (APS) are more effective than passive referral in identifying new cases of HIV in many settings. Understanding the barriers to the uptake of APS in sub-Saharan Africa is important before its scale up. In this qualitative study, we explored client, community, and healthcare worker barriers to APS within a cluster randomized trial of APS in Kenya. We conducted 20 in-depth interviews with clients who declined enrollment in the APS study and 9 focus group discussions with health advisors, HIV testing and counseling (HTC) counselors, and the general HTC client population. Two analysts coded the data using an open coding approach and identified major themes and subthemes. Many participants reported needing more time to process an HIV-positive result before providing partner information. Lack of trust in the HTC counselor led many to fear a breach of confidentiality, which exacerbated the fears of stigma in the community and relationship conflicts. The type of relationship affected the decision to provide partner information, and the lack of understanding of APS at the community level contributed to the discomfort in enrolling in the study. Establishing trust between the client and HTC counselor may increase uptake of APS in Kenya. A client's decision to provide partner information may depend on the type of relationship he or she is in, and alternative methods of disclosure may need to be offered to accommodate different contexts. Spreading awareness about APS in the community may make clients more comfortable providing partner information.

Assisted partner notification services to augment HIV testing and linkage to care in Kenya: study protocol for a cluster randomized trial.

BACKGROUND: HIV case-finding and linkage to care are critical for control of HIV transmission. In Kenya, >50% of seropositive individuals are unaware of their status. Assisted partner notification is a public health strategy that provides HIV testing to individuals with sexual exposure to HIV and are at risk of infection and disease. This parallel, cluster-randomized controlled trial will evaluate the effectiveness, cost-effectiveness, and feasibility of implementing HIV assisted partner notification services at HIV testing sites (clusters) in Kenya. METHODS/DESIGN: Eighteen sites were selected among health facilities in Kenya with well-established, high-volume HIV testing programs, to reflect diverse communities and health-care settings. Restricted randomization was used to balance site characteristics between study arms (n = 9 per arm). Sixty individuals testing HIV positive ('index partners') will be enrolled per site (inclusion criteria: ≥18 years, positive HIV test at a study site, willing to disclose sexual partners, and never enrolled for HIV care; exclusion criteria: pregnancy or high risk of intimate partner violence). Index partners provide names and contact information for all sexual partners in the past 3 years. At intervention sites, study staff immediately contact sexual partners to notify them of exposure, offer HIV testing, and link to care if HIV seropositive. At control sites, passive partner referral is performed according to national guidelines, and assisted partner notification is delayed by 6 weeks. Primary outcomes, assessed 6 weeks after index partner enrollment and analyzed at the cluster level, are the number of partners accepting HIV testing and number of HIV infections diagnosed and linked to care per index partner. Secondary outcomes are the incremental cost-effectiveness of partner notification and the costs of identifying >1 partner per index case. Participants are closely monitored for adverse outcomes, particularly intimate partner violence. The study is unblinded due to practical limitations. DISCUSSION: This rigorously designed trial will inform policy decisions regarding implementation of HIV partner notification services in Kenya, with possible application to other parts of sub-Saharan Africa. Examination of effectiveness and cost-effectiveness in diverse settings will enable targeted application and define best practices. TRIAL REGISTRATION: ClinicalTrials.gov NCT01616420 .

The status of HIV testing and counseling in Kenya: results from a nationally representative population-based survey.

BACKGROUND: HIV testing and counseling (HTC) is essential for successful HIV prevention and treatment programs. The national target for HTC is 80% of the adult population in Kenya. Population-based data to measure progress towards this HTC target are needed to assess the country's changing needs for HIV prevention and treatment. METHODS: In 2012-2013, we conducted a national HIV survey among Kenyans aged 18 months to 64 years. Respondents aged 15-64 years were administered a questionnaire that collected information on demographics, HIV testing behavior, and self-reported HIV status. Blood samples were collected for HIV testing in a central laboratory. Participants were offered home-based testing and counseling to learn their HIV status in the home and point-of-care CD4 testing if they tested HIV-positive. RESULTS: Of 13,720 adults who were interviewed, 71.6% [95% confidence interval (CI): 70.2 to 73.1] had been tested for HIV. Among those, 56.1% (95% CI: 52.8 to 59.4) had been tested in the past year, 69.4% (95% CI: 68.0 to 70.8) had been tested more than once, and 37.2% (95% CI: 35.7 to 38.8) had been tested with a partner. Fifty-three percent (95% CI: 47.6 to 58.7) of HIV-infected persons were unaware of their infection. Overall 9874 (72.0%) of participants accepted home-based HIV testing and counseling; 4.1% (95% CI: 3.3 to 4.9) tested HIV-positive, and of those, 42.5% (95% CI 31.4 to 53.6) were in need of immediate treatment for their HIV infection but not receiving it. CONCLUSIONS: HIV testing rates have nearly reached the national target for HTC in Kenya. However, knowledge of HIV status among HIV-infected persons remains low. HTC needs to be expanded to reach more men and couples, and strategies are needed to increase repeat testing for persons at risk for HIV infection.

The Kenya AIDS Indicator Survey 2012: rationale, methods, description of participants, and response rates.

BACKGROUND: Cross-sectional population-based surveys are essential surveillance tools for tracking changes in HIV epidemics. In 2007, Kenya implemented the first AIDS Indicator Survey [Kenya AIDS Indicator Survey (KAIS) 2007)], a nationally representative, population-based survey that collected demographic and behavioral data and blood specimens from individuals aged 15-64 years. Kenya's second AIDS Indicator Survey (KAIS 2012) was conducted to monitor changes in the epidemic, evaluate HIV prevention, care, and treatment initiatives, and plan for an efficient and effective response to the HIV epidemic. METHODS: KAIS 2012 was a cross-sectional 2-stage cluster sampling design, household-based HIV serologic survey that collected information on households as well as demographic and behavioral data from Kenyans aged 18 months to 64 years. Participants also provided blood samples for HIV serology and other related tests at the National HIV Reference Laboratory. RESULTS: Among 9300 households sampled, 9189 (98.8%) were eligible for the survey. Of the eligible households, 8035 (87.4%) completed household-level questionnaires. Of 16,383 eligible individuals aged 15-64 years and emancipated minors aged less than 15 years in these households, 13,720 (83.7%) completed interviews; 11,626 (84.7%) of the interviewees provided a blood specimen. Of 6302 eligible children aged 18 months to 14 years, 4340 (68.9%) provided a blood specimen. Of the 2094 eligible children aged 10-14 years, 1661 (79.3%) completed interviews. CONCLUSIONS: KAIS 2012 provided representative data to inform a strategic response to the HIV epidemic in the country.

Prevalence and incidence of HIV infection, trends, and risk factors among persons aged 15-64 years in Kenya: results from a nationally representative study.

BACKGROUND: Enhanced HIV surveillance using demographic, behavioral, and biologic data from national surveys can provide information to evaluate and respond to HIV epidemics efficiently. METHODS: From October 2012 to February 2013, we conducted a 2-stage cluster sampling survey of persons aged 18 months to 64 years in 9 geographic regions in Kenya. Participants answered questionnaires and provided blood for HIV testing. We estimated HIV prevalence, HIV incidence, described trends in HIV prevalence over the past 5 years, and identified factors associated with HIV infection. This analysis was restricted to persons aged 15-64 years. RESULTS: HIV prevalence was 5.6% [95% confidence interval (CI): 4.9 to 6.3] in 2012, a significant decrease from 2007, when HIV prevalence, excluding the North Eastern region, was 7.2% (95% CI: 6.6 to 7.9). HIV incidence was 0.5% (95% CI: 0.2 to 0.9) in 2012. Among women, factors associated with undiagnosed HIV infection included being aged 35-39 years, divorced or separated, from urban residences and Nyanza region, self-perceiving a moderate risk of HIV infection, condom use with the last partner in the previous 12 months, and reporting 4 or more lifetime number of partners. Among men, widowhood, condom use with the last partner in the previous 12 months, and lack of circumcision were associated with undiagnosed HIV infection. CONCLUSIONS: HIV prevalence has declined in Kenya since 2007. With improved access to treatment, HIV prevalence has become more challenging to interpret without data on new infections and mortality. Correlates of undiagnosed HIV infection provide important information on where to prioritize prevention interventions to reduce transmission of HIV in the broader population.