Simeon Mining

TP53 mutations, human papilloma virus DNA and inflammation markers in esophageal squamous cell carcinoma from the Rift Valley, a high-incidence area in Kenya

BackgroundSquamous Cell Carcinoma of Esophagus is one of the most common malignancies in both men and women in eastern and south-eastern Africa. In Kenya, clinical observations suggest that this cancer is frequent in the Rift Valley area. However, so far, there has been no report on the molecular characteristics of esophageal squamous cell carcinoma (ESCC) in this area.ResultsWe have analyzed TP53 mutations, the presence of human papilloma virus (HPV) DNA and expression of inflammation markers Cyclooxygenase 2 (Cox-2) and Nitrotyrosine (NTyR) in 28 cases (13 males and 15 females) of archived ESCC tissues collected at the Moi Teaching and Referral Hospital in Eldoret, Kenya. Eleven mutations were detected in TP53 exons 5 to 8 (39%). All ESCC samples were negative for HPV 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 70, 73 and 82. Immunohistochemical analysis of Cox-2 and NTyR showed a low proportion of positive cases (17.4% and 39.1%, respectively). No association between the above markers and suspected risk factors (alcohol or tobacco use, hot tea drinking, use of charcoal for cooking) was found.ConclusionOur findings suggest that mechanisms of esophageal carcinogenesis in eastern Africa might be different from other parts of the world. Low prevalence of TP53 mutation compared with other intermediate or high incidence areas of the world highlights this hypothesis. Our data did not support a possible ole of HPV in this series of cases. Further studies are needed to assess and compare the molecular patterns of ESCC from Kenya with those of high-incidence areas such as China or Central Asia.

Career choices and global health engagement: 24-year follow-up of U.S. participants in the Indiana University-Moi University elective

BACKGROUND Global health experiences evoke a profound awareness of cultural differences, inspire learners to prioritize professional values, and provide a lens for addressing global health care challenges. This study compares the long-term career and practice choices of participants in a 2-month Indiana University-Moi University, Kenya elective from 1989-2013 with those of a control group. METHODS Global health elective (GHE) participants and a random sample of alumni without GHE experience were surveyed on their clinical practice, public health and global health activities. RESULTS Responses from 176 former participants were compared with a control group of 177 alumni. GHE participants were more likely than similar controls to provide care to underserved U.S. populations (p=0.037), spend time in global health, public health, and public policy activities (p=0.005) and be involved in global health advocacy (p=0.001). Using multivariable analysis, GHE participants were more likely to be generalists (p<0.05), report that healthcare costs influenced medical decision-making (p<0.05), and provide healthcare outside the U.S. for ≥1 week/year (p<0.001). CONCLUSIONS Many years out of training, GHE participants were more likely to be generalists working with underserved populations, to be cost-conscious in their healthcare decision-making, and to be involved in global health, public health or public policy. IMPLICATIONS With the primary care provider shortage and need for greater awareness among providers of healthcare costs, our study shows that that global health experiences may yield broader benefits to the U.S. medical system.

High Prevalence of HIV Low Abundance Drug-Resistant Variants in a Treatment-Naive Population in North Rift Kenya.

The advent of antiretroviral treatment (ART) has resulted in a dramatic reduction in AIDS-related morbidity and mortality. However, the emergence and spread of antiretroviral drug resistance (DR) threaten to negatively impact treatment regimens and compromise efforts to control the epidemic. It is recommended that surveillance of drug resistance occur in conjunction with scale-up efforts to ensure that appropriate first-line therapy is offered relative to the resistance that exists. However, standard resistance testing methods used in Sub-Saharan Africa rely on techniques that do not include low abundance DR variants (LADRVs) that have been documented to contribute to treatment failure. The use of next generation sequencing (NGS) has been shown to be more sensitive to LADRVS. We have carried out a preliminary investigation using NGS to determine the prevalence of LDRVS among a drug-naive population in North Rift Kenya. Antiretroviral-naive patients attending a care clinic in North Rift Kenya were requested to provide and with consent provided blood samples for DR analysis. DNA was extracted and amplified and nested PCR was conducted on the pol RT region using primers tagged with multiplex identifiers (MID). Resulting PCR amplicons were purified, quantified, and pyrosequenced using a GS FLX Titanium PicoTiterPlate (Roche). Valid pyrosequencing reads were aligned with HXB-2 and the frequency and distribution of nucleotide and amino acid changes were determined using an in-house Perl script. DR mutations were identified using the IAS-USA HIV DR mutation database. Sixty samples were successfully sequenced of which 26 were subtype A, 9 were subtype D, 2 were subtype C, and the remaining were recombinants. Forty-six (76.6%) had at least one drug resistance mutation, with 25 (41.6%) indicated as major and the remaining 21 (35%) indicated as minor. The most prevalent mutation was NRTI position K219Q/R (11/46, 24%) followed by NRTI M184V (5/46, 11%) and NNRTI K103N (4/46, 9%). Our use of NGS technology revealed a high prevalence of LADRVs among drug-naive populations in Kenya, a region with predominantly non-B subtypes. The impact of these mutations on the clinical outcome of ART can be ascertained only through long-term follow-up.

Community Development of Interprofessional Practice in Kenya

This chapter outlines the significance of the development of interprofessional education and practice in a community environment for Moi University in Kenya. This training of health professionals is for community work, while placing emphasis on health promotion and preventative care as described by Westberg (1999) and Godfrey et al. (2000). A community leadership approach was used along with evidence of leadership coming from the students. In both instances we are reminded of the servant-leadership model as described in practice by Neill et al. (2007). The concept of the servant-leader was developed by Robert K. Greenleaf, an American essayist, in 1970 in his book, The servant as leader.

Level of CD8 T Lymphocytes Activation in HIV-Infected Pregnant Women: In the Context of CD38 and HLA-DR Activation Markers

Background. To date the effect of pregnancy on the immune activation of CD8 T cells that may affect HIV disease progression has not been well studied and remains unclear. Objective. To determine the effect of pregnancy on CD8 T lymphocyte activation and its relationship with CD4 count in HIV infected pregnant women. Study Design. Case control. Study Site. AMPATH and MTRH in Eldoret, Kenya. Study Subjects. Newly diagnosed asymptomatic HIV positive pregnant and nonpregnant women with no prior receipt of antiretroviral medications. Study Methods. Blood samples were collected from the study participants and levels of activated CD8 T lymphocytes (CD38 and HLA-DR) were determined using flow cytometer and correlated with CD4 counts of the study participants. The descriptive data focusing on frequencies, correlation, and cross-tabulations was statistically determined. Significance of the results was set at P < 0.05. Results. HIV positive pregnant women had lower activated CD8 T lymphocyte counts than nonpregnant HIV positive women. Activated CD8 T lymphocyte counts were also noted to decrease in the second and third trimesters of pregnancy. Conclusion. Pregnancy has a significant suppression on CD8+ T lymphocyte immune activation during HIV infections. Follow-up studies with more control arms could confirm the present study results.

Drug Resistance Testing in HIV Infected Individuals on Treatment and Naive: Implications on Treatment Outcome

Background: The Government of Kenya started offering ART in the public sector since 2003. Despite the dramatic reduction in AIDS related morbidity and mortality, the emergence and spread of drug resistance (DR) threatens to negatively impact on treatment regimens and compromise efforts to control the epidemic. Therefore, there is a need for information on the situation of DR Mutations (DRMS) and their implications on treatment.

Abstract 3851: Molecular profiling of aggressive breast cancer in a unique patient population from Kenya

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Breast cancer rates of incidence and mortality vary significantly between different nations and racial groups. African nations have the highest breast cancer mortality rates in the world, even though the incidence rates are below those of many other nations. In Kenya, breast cancer tumors are often highly aggressive at presentation and occur at a significantly earlier age (as early as the teens and 20s), relative to North American women. In the United States, non-Hispanic white women have the highest incidence of breast cancer, but African-American women have the highest mortality. These striking racial disparities are due not only to inequities in screening and treatment but also to variations in the rates of aggressive breast cancer. Differences in disease progression suggest that aggressive breast cancer tumors may harbor components of a unique molecular signature that result in racial disparities. We aim to identify drivers of poor prognosis breast cancer growth by identifying molecular signatures with high prognostic value from tumor samples of patients with aggressive disease. We hypothesize that changes in the DNA, RNA, and post-translational protein regulation contribute to aggressive disease. To characterize the tumors from this patient population, we used samples from >100 Kenyan breast tumor tissue samples. We stained tissue microarray sections for clinical breast cancer markers including lymphocyte markers. Using DNA and RNA that we isolated from these patient-derived breast tumors, we are characterizing these tumors by analyzing them for gene expression, genome sequencing, proteomics, and pathology analysis coupled with bioinformatics to develop signatures of aggressive breast cancer growth and metastasis. Our data will be foundational in understanding how aggressive, lethal breast tumors of Kenyan breast cancer patients differ from less aggressive tumors and will enhance our ability to diagnose and eliminate outcome disparities in breast cancer patients. Citation Format: Rispah Torrorey, Maggie Kerper, Emilia Hartland, Zonggao Shi, Jenifer Prosperi, Sunil Badve, Sharon Stack, Simeon Mining, Laurie Littlepage. Molecular profiling of aggressive breast cancer in a unique patient population from Kenya. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3851. doi:10.1158/1538-7445.AM2014-3851