Jaramogi Oginga Odinga Teaching and Referral Hospital

Kisumu, Kenya

Jaramogi Oginga Odinga Teaching and Referral Hospital

Kisumu, Kenya
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Burmen B.,Kenya Medical Research Institute | Owuor N.,Kenya Medical Research Institute | Mitei P.,Jaramogi Oginga Odinga Teaching and Referral Hospital
Human Resources for Health | Year: 2017

Background: An optimal number of health workers, who are appropriately allocated across different occupations and geographical regions, are required to ensure population coverage of health interventions. Health worker shortages in HIV care provision are highest in areas that are worst hit by the HIV epidemic. Kenya is listed among countries that experience health worker shortages (<2.5 health workers per 1000 population) and have a high HIV burden (HIV prevalence 5.6 with 15.2% in Nyanza province). We set out to determine the optimum number of clinicians required to provide quality consultancy HIV care services at the Jaramogi Oginga Odinga Teaching and Referral Hospital, JOOTRH, HIV Clinic, the premier HIV clinic in Nyanza province with a cumulative client enrolment of PLHIV of over 20,000 persons. Case presentation: The World Health's Organization's Workload Indicators of Staffing Needs (WISN) was used to compute the staffing needs and sufficiency of staffing needs at the JOOTRH HIV clinic in Kisumu, Kenya, between January and December 2011. All people living with HIV (PLHIV) who received HIV care services at the HIV clinic at JOOTRH and all the clinicians attending to them were included in this analysis. The actual staffing was divided by the optimal staff requirement to give ratios of staffing excesses or shortages. A ratio of 1.0 indicated optimal staffing, less than 1.0 indicated suboptimal staffing, and more than 1 indicated supra optimal staffing. The HIV clinic is served by 56 staff of various cadres. Clinicians (doctors and clinical officers) comprise approximately one fifth of this population (n = 12). All clinicians (excluding the clinic manager, who is engaged in administrative duties and supervisory roles that consumes approximately one third of his time) provide full-time consultancy services. To operate at maximum efficiency, the clinic therefore requires 19 clinicians. The clinic therefore operates with only 60% of its staffing requirements. Conclusions: Our assessment revealed a severe shortage of clinicians providing consultation services at the HIV clinic. Human resources managers should oversee the rational planning, training, retention, and management of human resources for health using the WISN which is an objective and reliable means of estimating staffing needs. © 2017 The Author(s).

Oduor C.I.,Kenya Medical Research Institute | Oduor C.I.,Maseno University | Movassagh M.,University of Massachusetts Medical School | Kaymaz Y.,University of Massachusetts Medical School | And 5 more authors.
Frontiers in Microbiology | Year: 2017

Endemic Burkitt lymphoma (eBL) is an aggressive B cell lymphoma and is associated with Epstein-Barr virus (EBV) and Plasmodium falciparum malaria co-infections. Central to BL oncogenesis is the over-expression of the MYC proto-oncogene which is caused by a translocation of an Ig enhancer in approximation to the myc gene. While whole genome/transcriptome sequencing methods have been used to define driver mutations and transcriptional dysregulation, microRNA (miRNA) dysregulation and differential expression has yet to be fully characterized. We hypothesized that both human and EBV miRNAs contribute to eBL clinical presentation, disease progression, and poor outcomes. Using sensitive and precise deep sequencing, we identified miRNAs from 17 Kenyan eBL patient tumor samples and delineated the complement of both host and EBV miRNAs. One human miRNA, hsa-miR-10a-5p was found to be differentially expressed (DE), being down-regulated in jaw tumors relative to abdominal and in non-survivors compared to survivors. We also examined EBV miRNAs, which made up 2.7% of the miRNA composition in the eBL samples. However, we did not find any significant associations regarding initial patient outcome or anatomical presentation. Gene ontology analysis and pathway enrichment of previously validated targets of miR-10a-5p suggest that it can promote tumor cell survival as well as aid in evasion of apoptosis. To examine miR-10a-5p regulatory effect on gene expression in eBL, we performed a pairwise correlation coefficient analysis on the expression levels of all its validated targets. We found a significant enrichment of correlated target genes consistent with miR-10a-5p impacting expression. The functions of genes and their correlation fit with multiple target genes impacting tumor resilience. The observed downregulation of miR-10a and associated genes suggests a role for miRNA in eBL patient outcomes and has potential as a predictive biomarker that warrants further investigation. © 2017 Oduor, Movassagh, Kaymaz, Chelimo, Otieno, Ong'echa, Moormann and Bailey.

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.

Kaymaz Y.,University of Massachusetts Medical School | Oduor C.I.,Kenya Medical Research Institute | Oduor C.I.,Maseno University | Yu H.,University of Massachusetts Medical School | And 4 more authors.
Molecular Cancer Research | Year: 2017

Endemic Burkitt lymphoma (eBL) is the most common pediatric cancer in malaria-endemic equatorial Africa and nearly always contains Epstein-Barrvirus (EBV), unlike sporadic Burkitt lymphoma (sBL) that occurs with a lower incidence in developed countries. Given these differences and the variable clinical presentation and outcomes, we sought to further understand pathogenesis by investigating transcriptomes using RNA sequencing (RNAseq) from multiple primary eBL tumors compared with sBL tumors. Within eBL tumors, minimal expression differences were found based on: anatomical presentation site, in-hospital survival rates, and EBV genome type, suggesting that eBL tumors are homogeneous without marked subtypes. The outstanding difference detected using surrogate variable analysis was the significantly decreased expression of key genes in the immunoproteasome complex (PSMB9/β1i, PSMB10/|32i, PSMB8/|β5i, and PSME2/PA28β) in eBL tumors carrying type 2 EBV compared with type 1 EBV. Second, in comparison with previously published pediatric sBL specimens, the majority of the expression and pathway differences was related to the PTEN/PI3K/mTOR signaling pathway and was correlated most strongly with EBV status rather than geographic designation. Third, common mutations were observed significantly less frequently in eBL tumors harboring EBV type 1, with mutation frequencies similar between tumors with EBV type 2 and without EBV. In addition to the previously reported genes, a set of new genes mutated in BL, including TFAP4, MSH6, PRRC2C, BCL7A, FOXO1, PLCG2, PRKDC, RAD50, and RPRD2, were identified. Overall, these data establish that EBV, particularly EBV type 1, supports BL oncogenesis, alleviating the need for certain driver mutations in the human genome. © 2017 American Association for Cancer Research.

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

Inzaule S.,Kenya Medical Research Institute | Inzaule S.,Makerere University | Otieno J.,Jaramogi Oginga Odinga Teaching and Referral Hospital | Kalyango J.,Makerere University | And 7 more authors.
PLoS ONE | Year: 2014

Background: Limited antiretroviral treatment regimens in resource-limited settings require long-term sustainability of patients on the few available options. We evaluated the incidence and predictors of combined antiretroviral treatment (cART) modifications, in an outpatient cohort of 955 patients who initiated cART between January 2009 and January 2011 in western Kenya. Methods: cART modification was defined as either first time single drug substitution or switch. Incidence rates were determined by Poisson regression and risk factor analysis assessed using multivariate Cox regression modeling. Results: Over a median follow-up period of 10.7 months, 178 (18.7%) patients modified regimens (incidence rate (IR); 18.6 per 100 person years [95% CI: 16.2-21.8]). Toxicity was the most common cited reason (66.3%). In adjusted multivariate Cox piecewise regression model, WHO disease stage III/IV (aHR; 1.82, 95%CI: 1.25-2.66), stavudine (d4T) use (aHR; 2.21 95%CI: 1.49-3.30) and increase in age (aHR; 1.02, 95%CI: 1.0-1.04) were associated with increased risk of treatment modification within the first year post-cART. Zidovudine (AZT) and tenofovir (TDF) use had a reduced risk for modification (aHR; 0.60 95%CI: 0.38-0.96 and aHR; 0.51 95%CI: 0.29-0.91 respectively). Beyond one year of treatment, d4T use (aHR; 2.75, 95% CI: 1.25-6.05), baseline CD4 counts ≤350 cells/mm3 (aHR; 2.45, 95%CI: 1.14-5.26), increase in age (aHR; 1.05 95%CI: 1.02-1.07) and high baseline weight >60kg aHR; 2.69 95% CI: 1.58-4.59) were associated with risk of cART modification. Conclusions: Early treatment initiation at higher CD4 counts and avoiding d4T use may reduce treatment modification and subsequently improve sustainability of patients on the available limited options. © 2014 Inzaule et al.

PubMed | Kenya Medical Research Institute, Jaramogi Oginga Odinga Teaching and Referral Hospital and Centers for Disease Control and Prevention
Type: Journal Article | Journal: Tropical medicine & international health : TM & IH | Year: 2016

The prevalence of anaemia during pregnancy is estimated to be 35-75% in sub-Saharan Africa and is associated with an increased risk of maternal mortality. We evaluated the frequency and factors associated with anaemia in HIV-infected women undergoing antiretroviral (ARV) therapy for prevention of mother-to-child transmission (PMTCT) enrolled in The Kisumu Breastfeeding Study 2003-2009.Maternal haematological parameters were monitored from 32 to 34 weeks of gestation to 2 years post-delivery among 522 enrolled women. Clinical and laboratory assessments for causes of anaemia were performed, and appropriate management was initiated. Anaemia was graded using the National Institutes of Health Division of AIDS 1994 Adult Toxicity Tables. Data were analysed using SAS software, v 9.2. The Wilcoxon two-sample rank test was used to compare groups. A logistic regression model was fitted to describe the trend in anaemia over time.At enrolment, the prevalence of any grade anaemia (Hb < 9.4 g/dl) was 61.8%, but fell during ARV therapy, reaching a nadir (7.4%) by 6 months post-partum. A total of 41 women (8%) developed severe anaemia (Hb < 7 g/dl) during follow-up; 2 (4.9%) were hospitalised for blood transfusion, whereas 3 (7.3%) were transfused while hospitalised (for delivery). The greatest proportion of severe anaemia events occurred around delivery (48.8%; n = 20). Anaemia (Hb 7 and < 9.4 g/dl) at enrolment was associated with severe anaemia at delivery (OR 5.87; 95% CI: 4.48, 7.68, P < 0.01). Few cases of severe anaemia coincided with clinical malaria (24.4%; n = 10) and helminth (7.3%; n = 3) infections.Resolution of anaemia among most participants during study follow-up was likely related to receipt of ARV therapy. Efforts should be geared towards addressing common causes of anaemia in HIV-infected pregnant women, prioritising initiation of ARV therapy and management of peripartum blood loss.

PubMed | University of Amsterdam, Centers for Disease Control and Prevention, National Center for HIV, Jaramogi Oginga Odinga Teaching and Referral Hospital and 2 more.
Type: Clinical Trial | Journal: PloS one | Year: 2015

Anemia results in increased morbidity and mortality, underscoring the need to better understand its pathophysiology amongst HIV-exposed and infected children in sub-Saharan Africa, the region where most infant HIV exposure and infections occur.This analysis used samples obtained from children in the Kisumu Breastfeeding Study (KiBS). KiBS was a longitudinal phase IIB, open-label, one-arm clinical trial, designed to investigate the safety, tolerability and effectiveness of a maternal triple-antiretroviral (ARV) regimen for prevention of mother-to-child transmission (PMTCT) of HIV, during late pregnancy and early infancy while breastfeeding. Blood samples from 482 children were obtained at birth, 2, 6, 10 and 14 weeks and 6, 9, 12, 18 and 24 months. Severity of anemia was graded using the NIH Division of AIDS (DAIDS) toxicity tables. We describe the proportion of children with anemia and anomalies in red blood cell parameters at various time points over 24 months and compare rates of anemia between HIV-infected and HIV-uninfected children and by mothers ARV regimen and infant malaria infection.The proportion of children with anemia significantly increased after the breastfeeding period in both HIV-infected and HIV-uninfected children with higher proportion among HIV-infected children compared to HIV-uninfected children (RR: 1.72; CI: 1.22-2.44, p = 0.002). Maternal triple-antiretroviral regimen was not associated with infant anemia (p = 0.11). There was no significant difference in mean hemoglobin between HIV-uninfected children with and without malaria at each time point except at 24 months.A relatively lower proportion of children with severe anemia during the breastfeeding period suggest that exposure to mothers triple antiretroviral combinations through breast milk, posed minimal risk of hematologic toxicity.

PubMed | Jaramogi Oginga Odinga Teaching and Referral Hospital, Indiana University, Kenya Medical Research Institute, Direct Relief and 2 more.
Type: Journal Article | Journal: 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 (a HR=1.43 [0.84-2.43]) or doxorubicin (a HR=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.

PubMed | Jaramogi Oginga Odinga Teaching and Referral Hospital, University of Zürich, Rhode Island Hospital, Uniformed Services University of the Health Sciences and 2 more.
Type: Journal Article | Journal: PloS one | Year: 2016

Deficiencies in Epstein-Barr virus (EBV)-specific T cell immunosurveillance appear to precede the development of endemic Burkitt lymphoma (eBL), a malaria-associated pediatric cancer common in sub-Saharan Africa. However, T cell contributions to eBL disease progression and survival have not been characterized. Our objective was to investigate regulatory and inflammatory T cell responses in eBL patients associated with clinical outcomes. By multi-parameter flow cytometry, we examined peripheral blood mononuclear cells from 38 eBL patients enrolled in a prospective cohort study in Kisumu, Kenya from 2008-2010, and 14 healthy age-matched Kenyan controls. Children diagnosed with eBL were prospectively followed and outcomes categorized as 2-year event-free survivors, cases of relapses, or those who died. At the time of diagnosis, eBL children with higher CD25+Foxp3+ regulatory T (Treg) cell frequencies were less likely to survive than patients with lower Treg frequencies (p = 00194). Non-survivors also had higher absolute counts of CD45RA+Foxp3lo nave and CD45RA-Foxp3hi effector Treg subsets compared to survivors and healthy controls. Once patients went into clinical remission, Treg frequencies remained low in event-free survivors. Patients who relapsed, however, showed elevated Treg frequencies months prior to their adverse event. Neither concurrent peripheral blood EBV load nor malaria infection could explain higher Treg cell frequencies. CD8+ T cell PD-1 expression was elevated in all eBL patients at time of diagnosis, but relapse patients tended to have persistently high PD-1 expression compared to long-term survivors. Non-survivors produced more CD4+ T-cell IL-10 in response to both Epstein-Barr Nuclear Antigen-1 (EBNA-1) (p = 0026) and the malaria antigen Plasmodium falciparum Schizont Egress Antigen-1 (p = 00158) compared to survivors, and were concurrently deficient in (EBNA-1)-specific CD8+ T-cell derived IFN- production (p = 0002). In addition, we identified the presence of Foxp3-IL10+ regulatory Type 1 cells responding to EBNA-1 in contrast to the malaria antigen tested. These novel findings suggest that poor outcomes in eBL patients are associated with a predominantly immuno-regulatory environment. Therefore, Treg frequencies could be a predictive biomarker of disease progression and manipulation of Treg activity has potential as a therapeutic target to improve eBL survival.

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