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Buckle G.,University of Massachusetts Medical School | Maranda L.,University of Massachusetts Medical School | Skiles J.,Indiana University | Ong'echa J.M.,Center for Global Health ResearchKenya Medical Research InstituteKisumu Kenya | And 9 more authors.
International Journal of Cancer | Year: 2016

Discovering how to improve survival and establishing clinical reference points for children diagnosed with endemic Burkitt lymphoma (eBL) in resource-constrained settings has recaptured international attention. Using multivariate analyses, we evaluated 428 children with eBL in Kenya for age, gender, tumor stage, nutritional status, hemoglobin, lactate dehydrogenase (LDH), Epstein-Barr virus (EBV) and Plasmodium falciparum prior to induction of chemotherapy (cyclophosphamide, vincristine, methotrexate and doxorubicin) to identify predictive and prognostic biomarkers of survival. During this 10 year prospective study period, 22% died in-hospital and 78% completed six-courses of chemotherapy. Of those, 16% relapsed or died later; 31% achieved event-free-survival; and 31% were lost to follow-up; the overall one-year survival was 45%. After adjusting for covariates, low hemoglobin (<8 g/dL) and high LDH (>400 mU/ml) were associated with increased risk of death (adjusted Hazard Ratio (aHR)=1.57 [0.97-2.41]) and aHR=1.84, [0.91-3.69], respectively). Anemic children with malaria were 3.55 times more likely to die [1.10-11.44] compared to patients without anemia or malarial infection. EBV load did not differ by tumor stage nor was it associated with survival. System-level factors can also contribute to poor outcomes. Children were more likely to die when inadvertently overdosed by more than 115% of the correct dose of cyclophosphamide (aHR=1.43 [0.84-2.43]) or doxorubicin (aHR=1.25, [0.66-2.35]), compared with those receiving accurate doses of the respective agent in this setting. This study codifies risk factors associated with poor outcomes for eBL patients in Africa and provides a benchmark by which to assess improvements in survival for new chemotherapeutic approaches. © 2016 UICC. Source


Young M.R.,Emory University | Adera F.,Nyanza Reproductive Health Society | Mehta S.D.,University of Illinois at Chicago | Jaoko W.,University of Nairobi | And 6 more authors.
AIDS and Behavior | Year: 2016

Several countries scaling-up adult medical male circumcision (MMC) for HIV prevention intend to introduce early infant male circumcision (EIMC). To assess preference for EIMC in a community with a mature adult MMC program, we conducted a cross-sectional survey of a representative sample of mothers (n = 613) and fathers (n = 430) of baby boys (“index son”) at 16 health facilities in western Kenya. Most (59 %) were for EIMC, generally. Just 29 % were for circumcising the index son. Pain and protection from HIV were the most frequently cited barrier and facilitator to EIMC, respectively. In multivariable logistic regression, ever talking with the partner about EIMC and positive serostatus were associated with preference for EIMC for the index son. Attitudes towards EIMC are favorable. Willingness to circumcise an infant son is modest. To facilitate EIMC uptake, education about EIMC pain management and encouraging discussion between parents about EIMC during pregnancy should be integrated into programs. © 2016 Springer Science+Business Media New York Source


Buckle G.C.,University of Massachusetts Medical School | Collins J.P.,Case Western Reserve University | Sumba P.O.,Kenya Medical Research Institute | Nakalema B.,Uganda Cancer Institute | And 6 more authors.
Infectious Agents and Cancer | Year: 2013

Background: Survival rates for children diagnosed with Burkitt lymphoma (BL) in Africa are far below those achieved in developed countries. Late stage of presentation contributes to poor prognosis, therefore this study investigated factors leading to delays in BL diagnosis and treatment of children in Uganda and western Kenya. Methods. Guardians of children diagnosed with BL were interviewed at the Jaramogi Oginga Odinga Teaching and Referral Hospital (JTRH) and Uganda Cancer Institute (UCI) from Jan-Dec 2010. Information on sociodemographics, knowledge, attitudes, illness perceptions, health-seeking behaviors and prior health encounters was collected using a standardized, pre-tested questionnaire. Results: Eighty-two guardians were interviewed (20 JTRH, 62 UCI). Median «total delay» (1st symptoms to BL diagnosis) was 12.1 weeks [interquartile range (IQR) 4.9-19.9] in Kenya and 12.9 weeks (IQR 4.3-25.7) in Uganda. In Kenya, median «guardian delay» (1st symptoms to 1st health encounter) and «health system delay» (1st health encounter to BL diagnosis) were 9.0 weeks (IQR 3.6-15.7) and 2.0 weeks (IQR 1.6-5.8), respectively. Data on guardian and health system delay in Uganda were only available for those with < 4 prior health encounters (n = 26). Of these, median guardian delay was 4.3 weeks (range 0.7-149.9), health system delay 2.6 weeks (range 0.1-16.0), and total delay 10.7 weeks (range 1.7-154.3). Guardians in Uganda reported more health encounters than those in Kenya (median 5, range 3-16 vs. median 3, range 2-6). Among Kenyan guardians, source of income was the only independent predictor of delay, whereas in Uganda, guardian delay was influenced by guardians' beliefs on the curability of cancer, health system delay, by guardians' perceptions of cancer as a contagious disease, and total delay, by the number of children in the household and guardians' role as caretaker. Qualitative findings suggest financial costs, transportation, and other household responsibilities were major barriers to care. Conclusions: Delays from symptom onset to BL treatment were considerable given the rapid growth rate of this cancer, with guardian delay constituting the majority of total delay in both settings. Future interventions should aim to reduce structural barriers to care and increase awareness of BL in particular and cancer in general within the community, as well as among health professionals. © 2013 Buckle et al.; licensee BioMed Central Ltd. Source


Buckle G.,University of Massachusetts Medical School | Maranda L.,University of Massachusetts Medical School | Skiles J.,Indiana University | Ong'echa J.M.,Kenya Medical Research Institute | And 11 more authors.
International Journal of Cancer | Year: 2016

Discovering how to improve survival and establishing clinical reference points for children diagnosed with endemic Burkitt lymphoma (eBL) in resource-constrained settings has recaptured international attention. Using multivariate analyses, we evaluated 428 children with eBL in Kenya for age, gender, tumor stage, nutritional status, hemoglobin, lactate dehydrogenase (LDH), Epstein-Barr virus (EBV) and Plasmodium falciparum prior to induction of chemotherapy (cyclophosphamide, vincristine, methotrexate and doxorubicin) to identify predictive and prognostic biomarkers of survival. During this 10 year prospective study period, 22% died in-hospital and 78% completed six-courses of chemotherapy. Of those, 16% relapsed or died later; 31% achieved event-free-survival; and 31% were lost to follow-up; the overall one-year survival was 45%. After adjusting for covariates, low hemoglobin (<8 g/dL) and high LDH (>400 mU/ml) were associated with increased risk of death (adjusted Hazard Ratio (aHR) = 1.57 [0.97–2.41]) and aHR = 1.84, [0.91–3.69], respectively). Anemic children with malaria were 3.55 times more likely to die [1.10–11.44] compared to patients without anemia or malarial infection. EBV load did not differ by tumor stage nor was it associated with survival. System-level factors can also contribute to poor outcomes. Children were more likely to die when inadvertently overdosed by more than 115% of the correct dose of cyclophosphamide (aHR = 1.43 [0.84–2.43]) or doxorubicin (aHR = 1.25, [0.66–2.35]), compared with those receiving accurate doses of the respective agent in this setting. This study codifies risk factors associated with poor outcomes for eBL patients in Africa and provides a benchmark by which to assess improvements in survival for new chemotherapeutic approaches. © 2016 UICC Source


Mulama D.H.,Kenya Medical Research Institute | Mulama D.H.,Maseno University | Bailey J.A.,University of Massachusetts Medical School | Foley J.,University of Massachusetts Medical School | And 7 more authors.
International Journal of Cancer | Year: 2013

Endemic Burkitt lymphoma (eBL) is associated with Epstein-Barr virus (EBV) and Plasmodium falciparum coinfections. Malaria appears to dysregulate immunity that would otherwise control EBV, thereby contributing to eBL etiology. Juxtaposed to human genetic variants associated with protection from malaria, it has been hypothesized that such variants could decrease eBL susceptibility, historically referred to as "the protective hypothesis." Past studies attempting to link sickle cell trait (HbAS), which is known to be protective against malaria, with protection from eBL were contradictory and underpowered. Therefore, using a case-control study design, we examined HbAS frequency in 306 Kenyan children diagnosed with eBL compared to 537 geographically defined and ethnically matched controls. We found 23.8% HbAS for eBL patients, which was not significantly different compared to 27.0% HbAS for controls [odds ratio (OR) = 0.85; 95% confidence interval (CI) 0.61-1.17; p-value = 0.33]. Even though cellular EBV titers, indicative of the number of latently infected B cells, were significantly higher (p-value < 0.0003) in children residing in malaria holoendemic compared to hypoendemic areas, levels were not associated with HbAS genotype. Combined, this suggests that although HbAS protects against severe malaria and hyperparasitemia, it is not associated with viral control or eBL protection. However, based on receiver operating characteristic curves factors that enable the establishment of EBV persistence, in contrast to those involved in EBV lytic reactivation, may have utility as an eBL precursor biomarker. This has implications for future human genetic association studies to consider variants influencing control over EBV in addition to malaria as risk factors for eBL. © 2013 UICC. Source

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