Enhancing accreditation outcomes for medical laboratories on the Strengthening Laboratory Management Toward Accreditation programme in Kenya via a rapid results initiative.

Background: Since 2010, Kenya has used SLIPTA to prepare and improve quality management systems in medical laboratories to achieve ISO 15189 accreditation. However, less than 10% of enrolled laboratories had done so in the initial seven years of SLMTA implementation. Objective: We described Kenya's experience in accelerating medical laboratories on SLMTA to attain ISO 15189 accreditation. Methods: From March 2017 to July 2017, an aggressive top-down approach through high-level management stakeholder engagement for buy-in, needs-based expedited SLIPTA mentorship and on-site support as a rapid results initiative (RRI) was implemented in 39 laboratories whose quality improvement process had stagnated for 2-7 years. In July 2017, SLIPTA baseline and exit audit average scores on quality essential elements were compared to assess performance. Results: After RRI, laboratories achieving greater than a 2-star SLMTA rating increased significantly from 15 (38%) at baseline to 33 (85%) (p < 0.001). Overall, 34/39 (87%) laboratories received ISO 15189 accreditation within two years of RRI, leading to a 330% increase in the number of accredited laboratories in Kenya. The most improved of the 12 quality system essentials were Equipment Management (mean increase 95% CI: 5.31 ± 1.89) and Facilities and Biosafety (mean increase [95% CI: 4.05 ± 1.78]) (both: p < 0.0001). Information Management and Corrective Action Management remained the most challenging to improve, despite RRI interventions. Conclusion: High-level advocacy and targeted mentorship through RRI dramatically improved laboratory accreditation in Kenya. Similar approaches of strengthening SLIPTA implementation could improve SLMTA outcomes in other countries with similar challenges.

Clinical chemistry profiles in injection heroin users from Coastal Region, Kenya.

BACKGROUND: Although the co-burden of injection drug use and HIV is increasing in Africa, little is known about the laboratory markers of injection drug use and anti-retroviral treatment (ART) in Kenyan injection drug users. This study, therefore, aimed at determining the clinical chemistry profiles and identifying the key laboratory markers of HIV infection during ART in injection heroin users (IHUs). METHODS: Clinical chemistry measurements were performed on serum samples collected from HIV-1 infected ART-experienced (n = 22), naive (n = 16) and HIV-1 negative (n = 23) IHUs, and healthy controls (n = 15) from Mombasa, coastal Kenya. RESULTS: HIV uninfected IHUs had lower alanine aminotransferase (ALT) levels (P = 0.023) as ART-exposed IHUs exhibited lower albumin (P = 0.014) and higher AST to platelet index (APRI) (P < 0.0001). All IHUs presented with lower aspartate aminotransferase to ALT values (P = 0.001) and higher C-reactive protein (CRP) levels (P = 0.002). ART-naive IHUs had higher globulin levels (P = 0.013) while ART-experienced and naive IHUs had higher albumin to total protein (P < 0.0001) and albumin to globulin (P < 0.0001) values. In addition, CD4+ T cells correlated with ALT (ρ = -0.522, P = 0.011) and CRP (rho, ρ = 0.529, P = 0.011) in HIV negative and ART-experienced IHUs, respectively. HIV-1 viral load correlated with albumin to globulin index in ART-experienced (ρ = -0.468, P = 0.037) and naive (ρ = -0.554, P = 0.040) IHUs; and with albumin to total protein index (ρ = -0.554, P = 0.040) and globulin (ρ = 0.570, P = 0.033) in ART-naive IHUs. CONCLUSION: Absolute ALT, albumin, globulin, and CRP measurements in combination with APRI, AST to ALT, albumin to total protein and albumin to globulin indices may be useful laboratory markers for screening IHUs for initiating and monitoring treatment.

Using standard and institutional mentorship models to implement SLMTA in Kenya.

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.

HIV type 1 gag genetic diversity among antenatal clinic attendees in North Rift Valley, Kenya.

HIV genetic recombination and high mutation rate increase diversity allowing it to escape from host immune response or antiretroviral drugs. This diversity has enabled specific viral subtypes to be predominant in specific regions. To determine HIV-1 subtypes among seropositive antenatal clinic attendees in Kenya's North Rift Valley, a cross-sectional study was carried out on 116 HIV-1-positive blood samples. Proviral DNA was extracted from peripheral blood mononuclear cells by DNAzol lysis and ethanol precipitation. Polymerase chain reactions using specific primers for HIV-1 gag and population sequencing on resulting amplicons were carried out. Phylogenetic analysis revealed that 81 (70%) were subtype A1, 13 (11%) subtype D, 8 (7%) subtype C, 3 (3%) subtype A2, 1 (1%) subtype G, and 10 showed possible recombinants: 5 (4%) subtype A1D, 4 (3%) subtype A1C, and 1 (1%) subtype A2C. These data support the need to establish circulating subtypes for better evaluation of effective HIV diagnostic and treatment options in Kenya.

Genetic characterization of HIV type 1 among patients with suspected immune reconstitution inflammatory syndrome after initiation of antiretroviral therapy in Kenya.

Antiretroviral therapy (ART) has improved the survival of HIV patients but is also associated with unique manifestations of disease in some subjects during the initial months of therapy. Immune reconstitution inflammatory syndrome (IRIS) is a disorder among individuals starting ART, with no evidence-based treatment and management guidelines. We characterized HIV-1 and determined drug resistance among 14 Kenyan patients with suspected IRIS after ART initiation in 2005. Polymerase chain reaction, sequencing, and phylogenetic analysis of viral pol and env showed the following HIV-1 subtypes: A1/A1/A1 (pol-RT/gp41/C2V3), 5; A1/C/A1, 1; A1/D/A1, 2; D/A1/A1, 1; D/C/A1, 1; D/D/A1, 2; D/D/D, 1; and D/A1/A2, 1. Three patients had viruses with major drug resistance-associated mutations. These included nucleoside reverse transcriptase inhibitor (RTI) mutations: M41L, K65R, D67N, K70R, M184V, and K219Q, and nonnucleoside RTI mutations: K101P, L100I, K103N, and Y181C. Twelve patients harbored viruses that are predicted to use chemokine coreceptor 5 (CCR5) whereas two had variant viruses predicted to use the CXCR4 coreceptor. Drug resistance may not be the only cause of ART adverse events. HIV-1 characterization would be important before and during HIV therapy to avoid treatment failure.

HIV-1 subtype and viral tropism determination for evaluating antiretroviral therapy options: an analysis of archived Kenyan blood samples.

BACKGROUND: Infection with HIV-1 is characterized by genetic diversity such that specific viral subtypes are predominant in specific geographical areas. The genetic variation in HIV-1 pol and env genes is responsible for rapid development of resistance to current drugs. This variation has influenced disease progression among the infected and necessitated the search for alternative drugs with novel targets. Though successfully used in developed countries, these novel drugs are still limited in resource-poor countries. The aim of this study was to determine HIV-1 subtypes, recombination, dual infections and viral tropism of HIV-1 among Kenyan patients prior to widespread use of antiretroviral drugs. METHODS: Remnant blood samples from consenting sexually transmitted infection (STI) patients in Nairobi were collected between February and May 2001 and stored. Polymerase chain reaction and cloning of portions of HIV-1 gag, pol and env genes was carried out followed by automated DNA sequencing. RESULTS: Twenty HIV-1 positive samples (from 11 females and 9 males) were analyzed. The average age of males (32.5 years) and females (26.5 years) was significantly different (p value < 0.0001). Phylogenetic analysis revealed that 90% (18/20) were concordant HIV-1 subtypes: 12 were subtype A1; 2, A2; 3, D and 1, C. Two samples (10%) were discordant showing different subtypes in the three regions. Of 19 samples checked for co-receptor usage, 14 (73.7%) were chemokine co-receptor 5 (CCR5) variants while three (15.8%) were CXCR4 variants. Two had dual/mixed co-receptor use with X4 variants being minor population. CONCLUSION: HIV-1 subtype A accounted for majority of the infections. Though perceived to be a high risk population, the prevalence of recombination in this sample was low with no dual infections detected. Genotypic co-receptor analysis showed that most patients harbored viruses that are predicted to use CCR5.

HIV type 1 subtype diversity and drug resistance among HIV type 1-infected Kenyan patients initiating antiretroviral therapy.

The treatment of HIV-1 infection with antiretroviral drugs has greatly improved the survival of those who are infected. However, HIV-1 diversity and drug resistance are major challenges in patient management, especially in resource-poor countries. To evaluate HIV-1 genetic diversity and drug resistance-associated mutations among drug-naive patients in Kenya prior to antiretroviral therapy (ART), a genetic analysis of HIV-1 pol-RT and env-gp41 was performed on samples collected from 53 (18 males and 35 females) consenting patients between April and June 2005. The average age, baseline CD4(+) T cell counts, and viral loads were 38 (range, 24-62) years, 475 (range, 203-799) cells/mm(3), and 4.7 (range, 3.4-5.9) log(10) copies/ml, respectively. Phylogenetic analysis revealed that 40 samples (75.5%) were concordant subtypes for the two genes and 13 (24.5%) were discordant, suggesting possible recombination and/or dual infections. Prevalent subtypes included A1/A1(pol-RT/env-gp41), 31 (58.5%); D/D, 9 (16.9%); A1/C, 2 (3.8%); A1/D, 4 (7.5%); G/A1, 2 (3.8%); A1/A2, 1 (1.9%); C/A1, 2 (3.8%); D/A1, 1(1.9%); and D/A2, 1 (1.9%). Major reverse transcriptase inhibitor (RTI) resistance-associated mutations were found in four patients (7.5%). Of these patients, three had nucleoside RTI resistance mutations, such as M184V, K65R, D67N, K70R, and K219Q. Nonnucleoside RTI resistance-associated mutations K103N and Y181C were detected in three patients and one patient, respectively. Multiple drug resistance mutations were observed in this drug-naive population. With increasing numbers of patients that require treatment and the rapid upscaling of ART in Kenya, HIV-1 drug resistance testing is recommended before starting treatment in order to achieve better clinical outcomes.

HIV type 1 subtypes among STI patients in Nairobi: a genotypic study based on partial pol gene sequencing.

Circulating strains of human immunodeficiency virus (HIV) exhibit an extraordinary degree of genetic diversity and have been classified on the basis of relationships into distinct lineages called groups, types, subtypes, and subsubtypes. Sexually transmitted infections (STIs) are known to be a risk factor for HIV infection. To establish HIV-1 subtype diversity among STI patients in Nairobi, 140 samples were collected and partial pol gene sequencing done. From the analysis it was established that subtype A1 was the major subtype (64%) followed by D (17%), C (9%), G (1%), and recombinants AD (4%), AC (3%), CRF02()AG (1%), and CRF16()A2D (1%). These results suggest that the HIV-1 epidemic may be evolving toward more virulent and complex subtypes through transmission of complex recombinants due to viral mixing. Any use of ARVs may therefore require initial testing for de novo resistance before commencement of treatment and/or management.