The impact of introducing new vaccines on the health system: case studies from six low- and middle-income countries.

OBJECTIVE: We aimed to explore the impacts of new vaccine introductions on immunization programmes and health systems in low- and middle-income countries. METHODS: We conducted case studies of seven vaccine introductions in six countries (Cameroon, PCV;Ethiopia, PCV; Guatemala, rotavirus; Kenya, PCV; Mali, Meningitis A; Mali, PCV; Rwanda, HPV). Inter-views were conducted with 261 national, regional and district key informants and questionnaires were completed with staff from 196 health facilities. Routine data from districts and health facilities were gathered on vaccination and antenatal service use. Data collection and analysis were structured around the World Health Organisation health system building blocks. FINDINGS: The new vaccines were viewed positively and seemed to integrate well into existing health systems. The introductions were found to have had no impact on many elements within the building blocks framework. Despite many key informants and facility respondents perceiving that the new vaccine introductions had increased coverage of other vaccines, the routine data showed no change. Positive effects perceived included enhanced credibility of the immunisation programme and strengthened health workers' skills through training. Negative effects reported included an increase in workload and stock outs of the new vaccine, which created a perception in the community that all vaccines were out of stock in a facility. Most effects were found within the vaccination programmes; very few were reported on the broader health systems. Effects were primarily reported to be temporary, around the time of introduction only. CONCLUSION: Although the new vaccine introductions were viewed as intrinsically positive, on the whole there was no evidence that they had any major impact, positive or negative, on the broader health systems

New pneumococcal conjugate vaccine introductions in four sub-Saharan African countries: a cross-country analysis of health systems\u2019 impacts

Background: Pneumonia is a main cause of under-five mortality in low-income settings. The pneumococcal conjugate vaccine (PCV) has been introduced in many countries as a tool in the disease\u2019s prevention. Although PCV\u2019s effectiveness has been established, less is known about the effects of introducing additional injectable vaccines into routine immunisation programmes, particularly in the context of resource-constrained settings. Objectives: To explore the effects of PCV introduction on the immunisation programmes and health systems in four low-income countries. Methods: This study was carried out in Cameroon, Ethiopia, Kenya and Mali. Three to four regions and nine to 10 districts were selected within each country. Semi-structured interviews were carried out at national, regional and district levels (n=173). Researcher-administered questionnaires were completed with facility staff (n=124). Routine data on monthly vaccination activities were collected at district and facility levels. Results: PCV was generally well integrated into existing routine immunisation. Little or no impact was found in most areas of the health systems. Some minor effects were found on immunisation programmes, particularly in areas with either planning activities or investments e.g. staff skills were strengthened and there were limited improvements in surveillance. Although health sector workers perceived increases in the coverage of other vaccines following the introduction of PCV, routine service data did not confirm this claim. No substantial impacts were seen in health system management, service delivery or performance. Conclusions: The introduction of PCV had marginal impacts on the Expanded Programme for Immunisation and little to none on broader health systems

Effect of Baseline HIV Disease Parameters on CD4+ T Cell Recovery After Antiretroviral Therapy Initiation in Kenyan Women

Antiretroviral therapy (ART) for HIV infection reconstitutes the immune system and improves survival. However, the rate and extent of CD4+ T cell recovery varies widely. We assessed the impact of several factors on immune reconstitution in a large Kenyan cohort.HIV-infected female sex workers from a longitudinal cohort, with at least 1 year of pre-ART and 6 months of post-ART follow-up (n = 79), were enrolled in the current study. The median pre-ART follow-up was 4,040 days. CD4 counts were measured biannually and viral loads where available. The median CD4 count at ART initiation was 180 cells/ul, which increased to 339 cells/ul at the most recent study visit. The rate of CD4+ T cell increase on ART was 7.91 cells/month (mean = 13, range -25.92 to 169.4). LTNP status prior to ART initiation did not associate with the rate of CD4 recovery on ART. In univariate analyses, associations were observed for CD4 recovery rate and duration of pre-ART immunosuppression (r = -0.326, p = 0.004) and CD4 nadir (r = 0.284, p = 0.012). In multivariate analysis including age, CD4 nadir, duration of HIV infection, duration of pre-ART immunosuppression, and baseline viral load, only CD4 nadir (p = 0.007) and not duration of immunosuppression (p = 0.87) remained significantly associated with the rate of CD4 recovery.These data suggest that prior duration of immune suppression does not predict subsequent recovery once ART is initiated and confirm the previous observation that the degree of CD4 depletion prior to ART initiation is the most important determinant of subsequent immune reconstitution

Predictors of Chemosensitivity in Triple Negative Breast Cancer: An Integrated Genomic Analysis

Background: Triple negative breast cancer (TNBC) is a highly heterogeneous and aggressive disease, and although no effective targeted therapies are available to date, about one-third of patients with TNBC achieve pathologic complete response (pCR) from standard-of-care anthracycline/taxane (ACT) chemotherapy. The heterogeneity of these tumors, however, has hindered the discovery of effective biomarkers to identify such patients. Methods and Findings: We performed whole exome sequencing on 29 TNBC cases from the MD Anderson Cancer Center (MDACC) selected because they had either pCR (n = 18) or extensive residual disease (n = 11) after neoadjuvant chemotherapy, with cases from The Cancer Genome Atlas (TCGA; n = 144) and METABRIC (n = 278) cohorts serving as validation cohorts. Our analysis revealed that mutations in the AR- and FOXA1-regulated networks, in which BRCA1 plays a key role, are associated with significantly higher sensitivity to ACT chemotherapy in the MDACC cohort (pCR rate of 94.1% compared to 16.6% in tumors without mutations in AR/FOXA1 pathway, adjusted p = 0.02) and significantly better survival outcome in the TCGA TNBC cohort (log-rank test, p = 0.05). Combined analysis of DNA sequencing, DNA methylation, and RNA sequencing identified tumors of a distinct BRCA-deficient (BRCA-D) TNBC subtype characterized by low levels of wild-type BRCA1/2 expression. Patients with functionally BRCA-D tumors had significantly better survival with standard-of-care chemotherapy than patients whose tumors were not BRCA-D (log-rank test, p = 0.021), and they had significantly higher mutation burden (p < 0.001) and presented clonal neoantigens that were associated with increased immune cell activity. A transcriptional signature of BRCA-D TNBC tumors was independently validated to be significantly associated with improved survival in the METABRIC dataset (log-rank test, p = 0.009). As a retrospective study, limitations include the small size and potential selection bias in the discovery cohort. Conclusions: The comprehensive molecular analysis presented in this study directly links BRCA deficiency with increased clonal mutation burden and significantly enhanced chemosensitivity in TNBC and suggests that functional RNA-based BRCA deficiency needs to be further examined in TNBC. © 2016 Jiang et al

In-depth analysis of patient-clinician cell phone communication during the WelTel Kenya1 antiretroviral adherence trial.

The WelTel Kenya1 trial demonstrated that text message support improved adherence to antiretroviral therapy (ART) and suppression of HIV-1 RNA load. The intervention involved sending weekly messages to patients inquiring how they were doing; participants were required to respond either that they were well or that there was a problem.1) Describe problems participants identified through mobile phone support and reasons why participants did not respond to the messages; 2) investigate factors associated with indicating a problem and not responding; and 3) examine participant perceptions of the intervention.Secondary analysis of WelTel Kenya1 trial data.Reasons participants indicated a problem or did not respond were extracted from the study log. Negative binomial regression was used to determine participant characteristics associated with indicating a problem and non-response. Data from follow-up questionnaires were used to describe participant perceptions of the intervention.Between 2007 and 2009, 271 participants generated 11,873 responses; 377 of which indicated a problem. Health issues were the primary reason for problem responses (72%). Rural residence (adjusted incidence rate ratio [IRR] 1.96; 95%CI 1.19-3.25; p=0.009 and age were associated with indicating a problem (adjusted IRR 0.63 per increase in age group category; 95%CI 0.50-0.80; p<0.001). Higher educational level was associated with a decreased rate of non-response (adjusted IRR 0.81; 95%CI 0.69-0.94; p=0.005). Of participants interviewed, 62% (n=129) stated there were no barriers to the intervention; cell phone issues were the most common barrier. Benefits included reminding patients to take medication and promoting a feeling that "someone cares".The WelTel intervention enabled frequent communication between clinicians and patients during the WelTel Kenya1 trial. Many patients valued the service for the support it provided, with health-related concerns comprising the majority of problems identified by participants. Few sociodemographic characteristics were associated with participant engagement in the intervention

Geographical associations of HIV prevalence in female sex workers from Nairobi, Kenya (2014-2017)

Background: Kenya’s HIV epidemic is heterogeneously distributed. Although HIV incidence in Kenya has shown signs of recent decline, focused interventions are still needed for female sex workers (FSWs). Geo-spatially-informed approaches have been advocated for targeted HIV prevention. We quantified heterogeneity in HIV burden in Nairobi-based FSWs by place of origin within Kenya, and hotspots and residence within Nairobi. Methods: Data were collected as part of enrolment in the Sex Workers Outreach Program (SWOP) in Nairobibetween 2014 to 2017. Prevalence ratios (PRs) were used to quantify the risk of HIV by high prevalence counties (HPC) using modified Poisson regression analyses. Crude and fully adjusted models were fitted to the data. In heterogeneity analyses, hotspots and residences were aggregated to the Nairobiconstituency level (n=17). Inequality in the geographic distribution of HIV prevalence was measured using the Gini coefficient. Results: A total of 11,899 FSWs were included. Overall HIV prevalence was 16%. FSWs originating from HPC were at 2-fold increased risk of living with HIV in adjusted analysis (PR 1.95, 95% CI: 1.76-2.17). HIVprevalence was also highly heterogeneous by hotspot, ranging from 7% to 52% by hotspot (Gini coefficient: 0.37; 95% CI: 0.23-0.50). In contrast, constituency of residence had a Gini coefficient of 0.08 (95% CI: 0.06-0.10), suggesting minimal heterogeneity by residence. Conclusion: HIV prevalence in FSW is heterogeneous by place of work within Nairobi, and by county of birth within Kenya. As HIV incidence declines and financial commitments flatline, tailoring interventions to FSWs at highest HIV risk becomes increasingly important

"How I Wish This Thing Was Initiated 100 Years Ago!" Willingness to Take Daily Oral Pre-Exposure Prophylaxis among Men Who Have Sex with Men in Kenya.

BACKGROUND:The MSM population in Kenya contributes to 15% of HIV incidence. This calls for innovative HIV prevention interventions. Pre-exposure prophylaxis (PrEP) has been efficacious in preventing HIV among MSM in trials. There is limited data on the willingness to take daily oral PrEP in sub-Sahara Africa. PrEP has not been approved for routine use in most countries globally. This study aimed to document the willingness to take PrEP and barriers to uptake and adherence to PrEP in Kenya. The findings will inform the design of a PrEP delivery program as part of the routine HIV combination prevention. METHODS:Eighty MSM were recruited in 2 Counties in December 2013. Quantitative data on sexual behaviour and willingness to take PrEP were collected using semi-structured interviews and analysed using SPSS. Qualitative data on knowledge of PrEP, motivators and barriers to uptake and adherence to PrEP were collected using in-depth interviews and FGDs and analysed using Nvivo. Analysis of data in willingness to take PrEP was conducted on the HIV negative participants (n = 55). RESULTS:83% of MSM were willing to take daily oral HIV PrEP. Willingness to take PrEP was higher among the bi-sexual and younger men. Motivators for taking PrEP were the need to stay HIV negative and to protect their partners. History of poor medication adherence, fear of side effects and HIV stigma were identified as potential barriers to adherence. Participants were willing to buy PrEP at a subsidized price. CONCLUSIONS:There is willingness to take PrEP among MSM in Kenya and there is need to invest in targeted education and messaging on PrEP to enhance adherence, proper use and reduce stigma in the general population and among policy makers