Objective To classify the prevalence of multi-drug resistant tuberculosis (MDR-TB) in two different geographic settings in western Kenya using the Lot Quality Assurance Sampling (LQAS) methodology. Design The prevalence of drug resistance was classified among treatment-naïve smear positive TB patients in two settings, one rural and one urban. These regions were classified as having high or low prevalence of MDR-TB according to a static, two-way LQAS sampling plan selected to classify high resistance regions at greater than 5% resistance and low resistance regions at less than 1% resistance. Results This study classified both the urban and rural settings as having low levels of TB drug resistance. Out of the 105 patients screened in each setting, two patients were diagnosed with MDR-TB in the urban setting and one patient was diagnosed with MDR-TB in the rural setting. An additional 27 patients were diagnosed with a variety of mono- and poly- resistant strains. Conclusion Further drug resistance surveillance using LQAS may help identify the levels and geographical distribution of drug resistance in Kenya and may have applications in other countries in the African Region facing similar resource constraints.
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.
Abstract We deployed the Blended Genome Exome (BGE), a DNA library blending approach that generates low pass whole genome (1-4x mean depth) and deep whole exome (30-40x mean depth) data in a single sequencing run. This technology is cost-effective, empowers most genomic discoveries possible with deep whole genome sequencing, and provides an unbiased method to capture the diversity of common SNP variation across the globe. To evaluate this new technology at scale, we applied BGE to sequence >53,000 samples from the Populations Underrepresented in Mental Illness Associations Studies (PUMAS) Project, which included participants across African, African American, and Latin American populations. We evaluated the accuracy of BGE imputed genotypes against raw genotype calls from the Illumina Global Screening Array. All PUMAS cohorts had R 2 concordance ≥95% among SNPs with MAF≥1%, and never fell below ≥90% R 2 for SNPs with MAF<1%. Furthermore, concordance rates among local ancestries within two recently admixed cohorts were consistent among SNPs with MAF≥1%, with only minor deviations in SNPs with MAF<1%. We also benchmarked the discovery capacity of BGE to access protein-coding copy number variants (CNVs) against deep whole genome data, finding that deletions and duplications spanning at least 3 exons had a positive predicted value of ∼90%. Our results demonstrate BGE scalability and efficacy in capturing SNPs, indels, and CNVs in the human genome at 28% of the cost of deep whole-genome sequencing. BGE is poised to enhance access to genomic testing and empower genomic discoveries, particularly in underrepresented populations.
A cross-sectional study was conducted among prostitutes in Nairobi, Kenya, to determine the prevalence and correlates of cervical human immunodeficiency virus (HIV) DNA. Ninety-two HlV-seropositive prostitutes were evaluated during 137 clinic visits. Cervical HIV DNA was detected by polymerase chain reaction assay in 36 (39%) women at initial visits and in 40 (44%) women at any visit. There was a significant correlation between cervical HIV and microscopic evidence of cervical inflammation (odds ratio [OR], 7.2; 95% confidence interval [CI], 2.1–24.6). Using multivariate analysis to adjust for possible confounding, the adjusted OR for the association between cervical inflammation and cervical HIV DNA was 8.7 (95% CI, 2.0–37.2). Conditions associated with cervical inflammation are associated with the detection of HIV proviral DNA. Whether such conditions lead to increased infectivity remains to be proven.
Background Atrial fibrillation (AF) is a major contributor to the global cardiovascular disease burden. The clinical profile and outcomes of AF patients with valvular heart diseases in sub-Saharan Africa (SSA) have not been adequately described. We assessed clinical features and 12-month outcomes of patients with valvular AF (vAF) in comparison to AF patients without valvular heart disease (nvAF) in western Kenya. Methods We performed a cohort study with retrospective data gathering to characterize risk factors and prospective data collection to characterize their hospitalization, stroke and mortality rates. Results The AF patients included 77 with vAF and 69 with nvAF. The mean (SD) age of vAF and nvAF patients were 37.9(14.5) and 69.4(12.3) years, respectively. There were significant differences (p<0.001) between vAF and nvAF patients with respect to female sex (78% vs. 55%), rates of hypertension (29% vs. 73%) and heart failure (10% vs. 49%). vAF patients were more likely to be taking anticoagulation therapy compared to those with nvAF (97% vs. 76%; p<0.01). After 12-months of follow-up, the overall mortality, hospitalization and stroke rates for vAF patients were high, at 10%, 34% and 5% respectively, and were similar to the rates in the nvAF patients (15%, 36%, and 5%, respectively). Conclusion Despite younger age and few comorbid conditions, patients with vAF in this developing country setting are at high risk for nonfatal and fatal outcomes, and are in need of interventions to improve short and long-term outcomes.
Background: Kenya is home to several high-performing internationally-accredited research laboratories, whilst most public sector laboratories have historically lacked functioning quality management systems. In 2010, Kenya enrolled an initial eight regional and four national laboratories into the Strengthening Laboratory Management Toward Accreditation (SLMTA) programme. To address the challenge of a lack of mentors for the regional laboratories, three were paired, or ‘twinned’, with nearby accredited research laboratories to provide institutional mentorship, whilst the other five received standard mentorship.Objectives: This study examines results from the eight regional laboratories in the initial SLMTA group, with a focus on mentorship models.Methods: Three SLMTA workshops were interspersed with three-month periods of improvement project implementation and mentorship. Progress was evaluated at baseline, mid-term, and exit using the Stepwise Laboratory Quality Improvement Process Towards Accreditation (SLIPTA) audit checklist and scores were converted into a zero- to five-star scale.Results: At baseline, the mean score for the eight laboratories was 32%; all laboratories were below the one-star level. At mid-term, all laboratories had measured improvements. However, the three twinned laboratories had increased an average of 32 percentage points and reached one to three stars; whilst the five non-twinned laboratories increased an average of 10 percentage points and remained at zero stars. At exit, twinned laboratories had increased an average 12 additional percentage points (44 total), reaching two to four stars; non-twinned laboratories increased an average of 28 additional percentage points (38 total), reaching one to three stars.Conclusion: The partnership used by the twinning model holds promise for future collaborations between ministries of health and state-of-the-art research laboratories in their regions for laboratory quality improvement. Where they exist, such laboratories may be valuable resources to be used judiciously so as to accelerate sustainable quality improvement initiated through SLMTA.
Antiretroviral treatment interruptions (TIs) cause suboptimal clinical outcomes. Data on TIs during social disruption are limited. We determined effects of unplanned TIs after the 2007-2008 Kenyan postelection violence on virological failure, comparing viral load (VL) outcomes in HIV-infected adults with and without conflict-induced TI. Two hundred and one patients were enrolled, median 2.2 years after conflict and 4.3 years on treatment. Eighty-eight patients experienced conflict-related TIs and 113 received continuous treatment. After adjusting for preconflict CD4, patients with TIs were more likely to have detectable VL, VL >5,000 and VL >10,000. Unplanned conflict-related TIs are associated with increased likelihood of virological failure.
The main objective of the study was to compare morphological and flow cytometric diagnosis in patients previously diagnosed with leukemia. The retrospective study was carried out at Moi Teaching and Referral Hospital and patient’s data for the period of July 2013 and June 2014 was used. After Institutional Research Ethics approval was granted. Consecutive sampling was done and information was extracted from patient’s files. Data for all who were previously diagnosed with leukemia through both morphology and immunophenotyping was recorded. The data was collected using a data collection form where socio-demographic data, morphological and flow cytometry results were recorded. The findings were based on 33 patients who underwent both flow cytometry and bone marrow morphology tests for diagnosis of leukemia between July 2013 and June 2014. The ages of the patients ranged from 3 to 76 years. The ratio of male to female was 1:1.1. Using the Bone marrow morphology, 17 patients had AML and 15 had ALL, one case was inconclusive There were five categories for the flow cytometry. They comprised of B-ALL-6 cases, T-ALL-13 cases, AML-10 cases, Biphynotypic-1 case and inconclusive-1case. There was concordance between the morphological and flow cytometry on 25 out of the 33 cases. As a conclusion we can say that at MTRH , Flow cytometry had a role to play to confirm a definite and a probable diagnosis of patients with acute leukemia.
Journal Article Human Immunodeficiency Virus Infection among High-Risk Seronegative Prostitutes in Nairobi Get access Dennis M. Willerford, Dennis M. Willerford Reprints or correspondence (present address): Dr. Dennis M. Willerford, Hematology-Oncology Unit, Massachusetts General Hospital, Boston, MA 02114. Search for other works by this author on: Oxford Academic PubMed Google Scholar Job J. Bwayo, Job J. Bwayo Search for other works by this author on: Oxford Academic PubMed Google Scholar Michelle Hensel, Michelle Hensel Search for other works by this author on: Oxford Academic PubMed Google Scholar Wilfred Emonyi, Wilfred Emonyi Search for other works by this author on: Oxford Academic PubMed Google Scholar Francis A. Plummer, Francis A. Plummer Search for other works by this author on: Oxford Academic PubMed Google Scholar Elizabeth N. Ngugi, Elizabeth N. Ngugi Search for other works by this author on: Oxford Academic PubMed Google Scholar Nico Nagelkerke, Nico Nagelkerke Search for other works by this author on: Oxford Academic PubMed Google Scholar W. Michael Gallatin, W. Michael Gallatin Search for other works by this author on: Oxford Academic PubMed Google Scholar Joan Kreiss Joan Kreiss Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 167, Issue 6, June 1993, Pages 1414–1417, https://doi.org/10.1093/infdis/167.6.1414 Published: 01 June 1993 Article history Received: 08 October 1992 Revision received: 13 January 1993 Published: 01 June 1993
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