HIV-1 Coreceptor Tropism among Kenyans Under Highly Active Antiretroviral Therapy.

Despite the scale up of the use of combined highly active antiretroviral (ARV) therapy, many HIV-1 infected patients are still failing treatment in Kenya. In 2007, the Food Drug and Administration (FDA) approved the use of CCR5 antagonists in treatment experienced patients. CCR5 antagonists work by inhibiting the entry of HIV-1 that uses CCR5 as a coreceptor to gain entry into cells. CCR5 59029 A/G (promoter region—rs1799987) is a polymorphism that leads to the upregulation of the expression of the CCR5 protein thereby affecting the rate of HIV-1 infection. The use of these CCR5 antagonists in Kenya is limited partly because of minimal data on host genetics and coreceptor tropism among HIV-1 infected patients. In this study, we aimed at determining the prevalence of CCR5 tropic variants and CCR5 59029AG promoter polymorphism known to influence HIV-1 infection. We sequenced the V3 region of the env gene and inferred the HIV-1 tropism using clonal model of Geno2Pheno algorithm (FPR= 5%).   Also, we assessed the frequency of the CCR5 promoter polymorphisms among the patients by sequencing the polymorphic region of the CCR5 promoter. Majority of the patients (77.27%) had R5 tropic viruses whereas 22.73% of the study subjects had detectable CCR4 using viruses. The frequencies of the CCR5 59029 AA, AG, and GG genotypes were 14 (31.82%), 9 (20.45%) and 21(47.73%), respectively. Taken together, these results indicate that CCR5 antagonists could have potential therapeutic effects in the clinical management of HIV-1 among the infected patients in Kenya. Key words: CCR5 antagonists, CCR5 59029AG, HAART, HIV-1, Polymorphism, Tropis

Evaluation of the performance of a multiplex reverse transcription polymerase chain reaction kit as a potential diagnostic and surveillance kit for rotavirus in Kenya

Abstract Background Diarrhea is a serious concern worldwide, especially in developing countries. Rotavirus is implicated in approximately 400,000 infant deaths annually. It is highly contagious elevating the risk of outbreaks especially in enclosed settings such as daycare centers, hospitals, and boarding schools. Reliable testing methods are critical for early detection of infections, better clinical management, pathogen surveillance and evaluation of interventions such as vaccines. Enzyme immunoassays have proved to be reliable and practical in most settings; however, newer multiplex reverse transcription polymerase assays have been introduced in the Kenya market but have not been evaluated locally. Methods Stool samples collected from an ongoing Surveillance of Enteric Pathogens Causing diarrheal illness in Kenya (EPS) study were used to compare an established enzyme immunoassay, Premier™ Rotaclone® (Meridian Bioscience, Cincinnati, Ohio, U.S.A.), that can only detect group A rotavirus against a novel multiplex reverse transcription polymerase chain reaction kit, Seeplex® Diarrhea-V ACE Detection (Seegene, Seoul, Republic of Korea), that can detect rotavirus, astrovirus, adenovirus, and norovirus genogroups I and II. Detection frequency, sensitivity, specificity, turnaround time, and cost were compared to determine the suitability of each assay for clinical work in austere settings versus public health work in well-funded institutes in Kenya. Results The Premier™ Rotaclone® kit had a detection frequency of 11.2%, sensitivity of 77.8%, specificity of 100%, turnaround time of 93 min and an average cost per sample of 13.33 United States dollars (USD). The Seeplex® Diarrhea-V ACE Detection kit had a detection frequency of 16.0%, sensitivity of 100%, specificity of 98.1%, turnaround time of 359 min and an average cost per samples 32.74 United States dollars respectively. The detection frequency sensitivity and specificity of the Seeplex® Diarrhea-V ACE Detection kit mentioned above are for rotavirus only. Conclusions The higher sensitivity and multiplex nature of the Seeplex® Diarrhea-V ACE Detection kit make it suitable for surveillance of enteric viruses circulating in Kenya. However, its higher cost, longer turnaround time and complexity favor well-resourced clinical labs and research applications. The Premier™ Rotaclone®, on the other hand, had a higher specificity, shorter turnaround time, and lower cost making it more attractive for clinical work in low complexity labs in austere regions of the country. It is important to continuously evaluate assay platforms’ performance, operational cost, turnaround time, and usability in different settings so as to ensure quality results that are useful to the patients and public health practitioners.https://deepblue.lib.umich.edu/bitstream/2027.42/152177/1/40794_2019_Article_87.pd

Molecular clustering of patients with Mycobacterium tuberculosis strains cultured from the diabetic and non-diabetic newly diagnosed TB positive cases

Background: Social determinants of health, biological, and individual variants have been associated with Pulmonary TB (PTB) case clustering. None of the studies have focused on diabetes mellitus (DM) despite it being one of the co-morbidity affecting TB patients. Minimal data is available and it is not clear whether patients with DM and TB are more likely than TB patients without DM to be grouped into similar molecular clusters thus indicating a bias in transmission among TB/DM co-morbidity patients. Objective: To determine proportion of TB strains within TB and TB/DM cases that were clustered with their corresponding clinical outcomes and hence could be attributable to active TB transmission in the two urban counties of Nairobi, Kenya. Methods: We carried out a prospective cohort study of non-pregnant patients aged 15 years and above that tested positive for TB in two peri‑urban counties in Kenya between February 2014 and August 2015. Clinical and socio-demographic data were obtained from a questionnaire and medical records of the National TB program patient data base at two, three, five and six months. Spoligotyping data was then obtained and compared from previously identified strains in a data bank from the spolDB4. Results: We identified 7 different TB strains out of which East Asia Beijing, Euro America and Indo oceanic being the most dominant strain within the two counties accounting for 92.4% of the infections. DM was not a significant factor in increasing the likelihood of PTB patients to cluster according to the genotype of the infecting Mycobacterium tuberculosis bacillus. TB lineages, DM and County of the patient were found to be independent of the clinical outcomes that were observed in the study Conclusion: Diabetes mellitus is not a significant factor in increasing the molecular clustering among PTB patients. Keywords: Tuberculosis, Diabetes, Molecular clusterin

Antimicrobial properties and toxicity of Hagenia abyssinica (Bruce) J.F.Gmel, Fuerstia africana T.C.E. Fries, Asparagus racemosus (Willd.) and Ekebergia capensis Sparrm.

Background: The world health organization (WHO) estimates that 80% of population in Africa relies on traditional remedies for their healthcare. However, very few studies have been carried out to establish the therapeutic effects of these remedies. Objective: Four medicinal plants were investigated for antimicrobial activity and toxicity. Materials and Methods: Plants were collected from their natural habitat, dried, and extracted with organic and aqueous solvents. Antimicrobial activity was determined by the disc diffusion assay technique. In vitro cytotoxicity studies were carried out on extracts using MTT assay on Vero cell lines while acute toxicity in Swiss mice. Results: Extracts from H. abyssinica, F. africana and A. racemosus exhibited antibacterial activity with minimum inhibitory concentration of ≤ 6.25mg/ml against S. aureus, MRSA and P. aeruginosa. However, the plants studied had weak antifungal activity. H. abyssinica and F. africana extracts were found to be cytotoxic with CC50 of ˂ 90 µg/ml. These extracts were tested for acute toxicity and found to be safe at 5000 mg/kg body weight per day. Conclusion: The results of the study support the medicinal use of these plants and indicate that useful compounds from Hagenia abyssinica and Fuerstia africana can be isolated for further exploitation. Keywords: Medicinal plants, Antimicrobial activity, Cytotoxicity, Acute toxicit