Circulating 25-hydroxycholecalciferol and calcium levels, and alkaline phosphatase activity among people living with and without human immunodeficiency virus and injecting drugs in kenya.

BACKGROUND: People who inject drugs (PWID) and living with the human immunodeficiency virus (PLHIV) are at higher risk of suffering marked derangements in micronutrient levels, leading to poor disease and treatment outcomes. Consequently, this can be monitored by measuring key biomarkers, such as total circulating (serum) 25-hydroxycholecalciferol (25(OH)D3), calcium, and alkaline phosphatase (ALP) for timely intervention. Therefore, circulating levels of 25(OH)D3 and calcium, and ALP activity were determined in PWID and are highly active anti-retroviral treatment (HAART)-experienced or -naive, along with those without HIV infection. METHODS: This cross-sectional study compared serum concentrations of 25(OH)D3, calcium, and ALP in Kenyan PLHIV and were HAART-naive (n = 30) or -experienced (n = 61), PWID and without HIV (n = 132). RESULTS: Circulating 25(OH)D3 levels were significantly different amongst the study groups (P < 0.001), and were significantly lower in the HAART-experienced (median, 17.3; IQR, 18.3 ng/ml; P < 0.001) and -naive participants (median, 21.7; IQR, 12.8 ng/ml; P = 0.015) relative to uninfected (median, 25.6; IQR, 6.8 ng/ml) PWID. In addition, the proportions of vitamin D deficiency (55.7%, 40.0%, and 17.4%) and insufficiency (31.1%, 53.3%, and 63.6%) compared to sufficiency (13.1%, 6.7%, and 18.9%; P < 0.001) were greater amongst HAART-experienced, -naive, and uninfected study groups, respectively. Likewise, serum total calcium concentrations were lower in the HAART-experienced relative to HIV-negative (P = 0.019) individuals. Serum ALP activity was also lower in the HAART-experienced in contrast to HIV-negative PWID (P = 0.048). Regression analysis indicated that predictors of circulating 25(OH)D3 were: age (ß = 0.287; R2 = 8.0%; P = 0.017) and serum ALP (ß = 0.283; R2 = 6.4%; P = 0.033) in the HAART-experienced PWID, and serum ALP (ß = 0.386; R2 = 14.5%; P < 0.001) in the HIV-negative PWID. CONCLUSION: This study suggests that HIV-1 infection and HAART, including injection substance use, decrease circulating 25(OH)D3, calcium and ALP activity. In addition, age and ALP activity are associated with low circulating vitamin D levels in HAART-experienced PWID. The results highlight the importance of incorporating vitamin D and calcium supplementation in treatment and rehabilitation protocols for PLHIV.

Assemblages and Subassemblages of Giardia duodenalis in Rural Western, Kenya: Association with Sources, Signs, and Symptoms.

Background: Giardia duodenalis causes sporadic or epidemic infections in humans. The parasite comprises assemblages A-H with A and B subdivided further into AI-IV and BI-IV subassemblages. Attempts aimed at linking these genotypes with sources and gastrointestinal manifestations of the infection are largely unexplored in rural communities. Methods: In this cross-sectional study, G. duodenalis infection was genotyped and associated with sources, and gastrointestinal signs and symptoms of the disease among residents of Busia County, a rural setting in western Kenya. Demographic and clinical information were captured using standardized forms. Stool specimens were obtained from the patients and used for genotyping at glutamate dehydrogenase and triose-phosphate isomerase loci using the polymerase chain reaction and restriction fragment length polymorphism. Results: Assemblage B (63.6%) was the most prevalent G. duodenalis infection, while A (20.5%) and mixed A/B (15.9%) were also detected. Among the subassemblages, AI (5.7%), AII (8.0%), AIII (3.4), BIII (30.7%), and BIV (17.0%) were diagnosed including the mixed AII/BIII (15.9%), BIII/BIV (15.9%), AI/AIII (2.3%), and AI/AII (1.1%) infections. Binary logistic regression indicated associations for assemblage A with stomach upset, history of nitroimidazole treatment, and residing in a homestead with cattle and B with age < 18 years, history of eating outdoors, vomiting, steatorrhea, and residing in a homestead with cattle, goats, and poultry (p < 0.05 for all). Among the subassemblages, associations were found for AI with residing in a homestead having cattle and history of nitroimidazole treatment, BIII with residing in a homestead having cattle and poultry, and BIV with steatorrhea (p < 0.05 for all). Altogether, this study illustrates that G. duodenalis assemblage B and subassemblage BIII are the most predominant and are linked to age < 18 years, gastrointestinal manifestations, and living in a homestead with domestic ruminants and poultry. Conclusion: Targeted mass prophylactic treatment of domestic animals and utilization of gastrointestinal presentations, age < 18 years, and a history of nitroimidazole use are useful in the diagnosis and prevention of giardiasis among residents of rural communities.

Prevalence of Non-Tuberculosis Mycobacterium Pulmonary Disease in HIV-1 Patients with Presumptive Pulmonary Tuberculosis in Western Kenya.

Background: Non-tuberculous mycobacteria (NTMs) are ubiquitous, free-living, environmental saprophytic microorganisms. NTMs belong to the genus Mycobacterium which includes Mycobacterium tuberculosis (MTB). NTMs have lately been a major cause of pulmonary disease (PD) in immuno-compromised individuals including HIV-1 patients. NTMs and MTB appear similar based on microscopy, radiology, and clinical symptoms; consequently, this may lead to misdiagnosis. This study sought to establish the prevalence of NTM pulmonary disease in HIV-1 patients presumed to have pulmonary tuberculosis. Methods: A cross-sectional analytical laboratory study design was used targeting 617 adult HIV-1 infected patients presenting with presumptive pulmonary TB at Bungoma County Hospital Comprehensive Care Clinic in Western Kenya between July 2021 to June 2022. Results: A total of 75 (12.2%, 4.6 -9.8 CI) of the participants presented with presumptive MTB and had TB-like symptoms while 542 (87.8%, 12.5 -30.7 CI) were negative. Additionally, 56 (9.1%) were infected with NTMs. HIV-positive participants had a significantly higher prevalence of NTMs 62 (11.8%, 5.6 -9.2 CI) compared to 2 (2.1%, 0.4 -1.8 CI). In HIV + study participants P<0.0001. M. avium was the most prevalent NTM, 25(33.3%), followed by M. fortuitum 20 (26.7%). A significant number of the isolates were M. tuberculosis 10 (13.3%) as well as M. kansasii 8 (10.7%). Conclusion: There seems to be a high prevalence of NTMPD in HIV-1 patients which is assumed to be pulmonary TB. Differential diagnosis of the mycobacterium species is necessary to help improve disease management and outcomes in this group of patients.

Resistance of Anopheles gambiae sensu lato to Pirimiphos-methyl Insecticide in Kakamega County, Highlands of Western Kenya.

Background: Insecticide treated bed nets and Indoor residual spraying remains the principal interventional malaria control strategies. To achieve malaria disease eradication, vector control programmes that monitor insecticide resistance profiles are necessary. Objective: The study evaluated pirimiphos-methyl susceptibility of Anopheles gambiae sensu lato in Kakamega County, western Kenya. Methods: Adult Anopheles gambiae sensu lato mosquitoes were assayed using World Health Organization tube bioassay against 0.25% pirimiphos-methyl. Susceptible and non-susceptible populations were characterized to species-level using Polymerase Chain Reaction. Susceptible and resistant mosquitoes were further subjected to G119S Acetylcholisterase (ace 1R) mutation detection. Results: Anopheles arabiensis was the predominant species in all study population Mumias east (62%), Malava (68%), Ikolomani (77%) and Lurambi (82%). Results showed phenotypic susceptibility to pirimiphos-methyl. Mortality was low in Mumias east (80.6%) and high in Lurambi (89.0%). G119S mutations ranged from 3.0% to 8.9% in Anopheles arabiensis whereas G119S mutations were relatively low ranging from 0.0% to 3.1% in Anopheles gambiae s.s populations. Study populations tested were consistent with Hardy-Weinberg equilibrium (P>0.05). Conclusion: We observed pirimiphos-methyl resistance in Anopheles arabiensis and Anopheles gambiae s.s. study populations. Results showed G119S mutation in resistance population. Resistance monitoring and management are urgently required.

rs1445776009 variants in the human ALB gene: Association with serum albumin and clinical outcomes in HIV-infected Kenyan injection substance users.

OBJECTIVE: The coburden of human immunodeficiency virus (HIV) and injection substance use is high especially in coastal urban and peri-urban regions of sub-Saharan Africa. Although antiretroviral treatment (ART) has improved disease prognosis in HIV-1-infected patients, injection substance use is detrimental to these individuals. HIV-1 and injection substances use have been associated with a marked reduction in serum albumin levels. This is attributable to at least, in part, injection substance use, ARVs, HIV-1 infection, as well as host genetics. The albumin gene expression is modulated through several mechanisms including intronic consensus elements. Therefore, this study examined ALB gene rs1445776009 intronic polymorphism and its association with disease outcomes. METHODS: This cross-sectional study was conducted at Bomu Hospital, Mombasa County, Kenya. A total of 155 injection substance users (ISUs) were recruited comprising 93 ART experienced and 62 ART naive. Variant rs1445776009 was amplified through polymerase chain reaction and genotyped through restriction fragment length polymorphism. RESULTS: Carriers of the mutant and GG had significantly lower body mass index (P = 0.033), serum albumin (P = 0.002), CD4+ T cells (P = 0.031), and higher HIV-1 RNA copies (P = 0.018) relative to wild type, CC and heterozygous, CG; in ART-experienced ISUs. In addition, mutant GG carriers were at higher odds of presenting with hypoalbuminemia (OR, 1.933; 95% CI, 1.524-4.664; P = 0.033), underweight (OR, 2.412; 95% CI, 1.124-5.782; P = 0.026), immunosuppression (OR, 3.036; 95% CI, 1.957-9.633; P = 0.021), and high-density HIV viremia (OR, 1.836; 95% CI, 1.134-6.298; P = 0.016). CONCLUSION: This study's findings appear to suggest that loci rs1445776009 of the ALB gene could be modulating serum albumin levels and disease outcomes in HIV-1 ART-experienced ISUs.

Cytokine profiles in highly active antiretroviral treatment non-adherent, adherent and naive HIV-1 infected patients in Western Kenya.

Background: Cytokines play an important role in signaling the immune system to build an adequate immune response against HIV. HIV distorts the balance between pro and anti-inflammatory cytokines causing viral replication. Highly active antiretroviral treatment (HAART) acts by trying to restore pro and anti-inflammatory cytokine balance. It is not clear how HAART non-adherence influences circulating cytokine levels. This study therefore determined cytokine levels in HAART non-adherent individuals. Methods: This cross-sectional study recruited 163 participants (51 controls, 23 HIV-1+ HAART naive, 28 HAART-adherent 6 months, 19 HAART-adherent 12 months and 42 HAART non-adherent). Cytokines were analyzed by ELISA while CD4 T cells determined in 3.0 µl of whole blood using BD FACSCaliburTM and viral load in 0.2ml plasma sample using Abbott Molecular m2000sp sample preparation and m2000rt real-time amplification and detection systems (Abbott Molecular Inc., Illinois, USA) according to the manufacturer's methods. Results: IL-4, IL-6, IL-10, TNF-α and TGF-ß were significantly elevated in HIV-1 HAART non-adherent compared with HIV-1 HAART adherent and healthy controls P<0.01. IFN- γ was significantly decreased in HIV-1 HAART non-adherent compared with HIV-1 HAART adherent and healthy controls P<0.01. TNF-α and TGF-ß were significantly reduced in HIV-1 HAART adherent patients at 12 months compared to those at 6 months P<0.01. IL-4 and IL-10 correlated positively with viral load. IL-4, IL-6, IL-10, TNF-α and TGF- ß associated inversely with CD4 T cell counts and body mass index (BMI). Conclusion: This study established that HAART adherence is immunologically beneficial to the pro and anti-inflammatory cytokine balance milieu while non-adherence appears to cause alterations in pro and anti-inflammatory cytokines warping the balance in this dichotomy.

Anemia Burden, Types and Associated Risk Factors among Kenyan Human Immunodeficiency Virus-1 and Mycobacterium Tuberculosis Co-infected Injection Substance Users.

BACKGROUND: Although injection substance users and individuals co-infected with Human Immunodeficiency Virus-1 and Mycobacterium tuberculosis suffer marked hematologic derangements, the rates, levels, morphologic types and associated risk factors of anemia among Human immunodeficiency virus and Mycobacterium tuberculosis coinfected injection substance users has not been reported in Kenya. METHODS: This cross-sectional study determined anemia rates, levels and morphologic types. Anemia was associated with clinical markers of disease- underweight, immunosuppression and viral load. Complete blood count, CD4 T-cell enumeration and viral load were determined via standard laboratory methods. RESULTS: All injection substance users had higher rates of anaemia (HIV+TB+ ISUs, 79.3%; HIV-TB+ISUs, 70.0%; HIV+TB- ISUs, 56.6% and HIV-TB- ISUs, 56.2%) relative to non-ISUs (16.6%; P<0.05). A significant proportion of HIV+TB+ISUs (47.8%) developed severe anemia than other clinical groups. The commonest morphologic type of anemia in HIV+TB+ISUs was microcytic hypochromic (43.5%) followed by normocytic hypochromic (17.4%) relative to the other clinical groups. HIV+TB+ ISUs with CD4 T-cells <200/uL (OR: 2.94, 95% CI: 1.41-6.13, P=0.004) and CD4 Tcells of 200-349/uL (OR: 3.24, 95% CI: 1.66-6.31, P=0.001) associated with higher odds of developing anemia. CONCLUSION: This study revealed that severe anemia and microcytic hypochromic anemia are the most common erythrocytic sequelae among Human Immunodeficiency Virus-1 and Mycobacterium tuberculosis co-infected ISUs. Those with CD4 T-cells < 350/uL are utmost expected to develop anemia.

Comparison of Microscopy and PCR for Detection of Giardia Lamblia and Entamoeba Histolytica in Human Stool Specimens in a Resource Limited Setting in Western Kenya.

BACKGROUND: Accurate diagnosis of Giardia lamblia and Entamoeba histolytica is important since these intestinal parasites account for a significant proportion of morbidity and mortality globally. Microscopy is the key diagnostic test used for diagnosis of the two parasites. Other tests including rapid diagnostic tests and polymerase chain reaction have been developed to improve the detection of these parasites. Most of these newer tests are not affordable in resource limited settings, hence the over reliance on microscopy. The objective of this study was to determine the reliability of microscopy in a resource limited setting in Western Kenya, a region endemic for the two intestinal parasites. METHODS: Polymerase chain reaction, the gold standard test, was performed on stool samples suspected for G. lamblia and E. histolytica. Microscopy was then performed on the same samples and the two tests compared. RESULTS: Microscopy was found to be 64.4% sensitive, 86.6% specific for the detection of G. lamblia. Additionally, this test was 64.2% sensitive and 83.6% specific for the diagnosis of E. histolytica. Cohen's kappa values of 0.51 and 0.47 were determined for microscopy for G. lamblia and E. histolytica respectively. McNemar's test revealed a significant difference between the two tests, P<0.001. CONCLUSION: This study found microscopy to be a reliable diagnostic test in this resource limited setting.

Epidemiological patterns and antimicrobial resistance of bacterial diarrhea among children in Nairobi City, Kenya.

AIM: Determine the prevalence of enteric bacterial pathogens and their antimicrobial resistance among diarrheic children in Nairobi City, Kenya. BACKGROUND: Regardless of enteric bacterial pathogens being a major cause of gastroenteritis in children, their occurrence and antimicrobial resistance patterns reveals regional spatial and temporal variation. METHODS: In a cross-sectional study, a total of 374 children below five years presenting with diarrhea at Mbagathi County Hospital were recruited. Stool microbiology test was used to detect enteric bacterial infection. Antimicrobial resistance was determined using the disk diffusion method. RESULTS: Diarrheagenic E. coli (36.4%) was the leading species followed by Shigella (3.2%), Salmonella (2.4%), Campylobacter (1.6%), Yersinia (1.3%) and Aeromonas (1.1%) species. Escherichia coli pathotyping revealed that 20.9%, 4.0%, 10.2% and 0.5% of the study participants were infected with enteroaggregative E. coli (EAEC), enteropathogenic E. coli (EPEC), enterotoxigenic E. coli (ETEC) and enteroinvasive E. coli (EIEC) pure isolates while the prevalence of mixed pathotype infections was 0.3% for EAEC/EPEC/ETEC and 0.5% for EAEC/ETEC. Shigella sero-grouping revealed that 0.5%, 0.3%, 1.9%, and 0.5% were infected with Shigella boydii, Shigella dysentriae, Shigella flexneri and Shigella sonnei pure isolates. Shigella species and E. coli co-infection was detected in 2.4% of the children, specifically, 1.1% for EAEC/Shigella boydii, 0.5% for EAEC/Shigella dysentriae and 0.3% in each case of EAEC/Shigella sonnei, EPEC/Shigella flexneri and ETEC/Shigella flexneri co-infections. Most of the isolates were resistant to commonly prescribed antibiotics. CONCLUSION: There was a high prevalence of enteric bacterial pathogens and co-infection alters epidemiological dynamics of bacterial diarrhea in children. Continuous antibiotic resistance surveillance is justified because the pathogens were highly resistant to commonly prescribed antimicrobials.

Selected genes of Human herpesvirus-8 associated Kaposi's sarcoma among patients with Human Immunodeficiency Virus-1 and Acquired Immunodeficiency Disease Syndrome.

INTRODUCTION: Kaposi's sarcoma (KS) is a kind of cancer that causes flat or raised lesions containing Human herpes virus 8 (HHV8). The KS lesions are common among immunosuppressed HIV patients. Highly Active Antiretroviral (HHART) treats and prevents the development of KS. The objective of this study was to determine the presence of K1 and K15 (predominant alleles) genes in Kaposi's sarcoma-associated herpes virus (KSHV) among immunosuppressed patients due to HIV-1. METHODS: This was a cross-sectional descriptive study where consecutive sampling technique was adopted to pick archived tissue blocks from the Thematic Unit of Anatomic Pathology, Department of Human Pathology, College of Health Sciences, University of Nairobi and Department of Laboratory Medicine, Histology Section, Kenyatta National Hospital. RESULTS: Upon staining 81 tissue blocks with H & E, 84% (68/81) were diagnosed as KS and 16% (13/81) as KS-like. The K1 and K15 (P) genes were both detected at 88.9% (72/81) in the tissue blocks, with 95.8% (69/72) detection from KS and 4.2% (3/72) from the KS-like. CONCLUSION: The K1 and K15 (P) genes of KSHV were present among the immunosuppressed patients with Human Immunodeficiency Virus (HIV)-1. It is important to carry out K1 and K15 (P) genes detection on tissues that are diagnosed as KS or KS-like by histology technique.

Circulating Interferon-Gamma Levels Are Associated with Low Body Weight in Newly Diagnosed Kenyan Non-Substance Using Tuberculosis Individuals.

Although interferon-gamma, interleukin-10, and adiponectin are key immunopathogenesis mediators of tuberculosis, their association with clinical manifestations of early stage disease is inconclusive. We determined interferon-gamma, interleukin-10, and adiponectin levels in clinically and phenotypically well-characterised non-substance using new pulmonary tuberculosis patients (n = 13) and controls (n = 14) from Kenya. Interferon-gamma levels (P < 0.0001) and interferon-gamma to interleukin-10 (P < 0.001) and interferon-gamma to adiponectin (P = 0.027) ratios were elevated in tuberculosis cases. Correlation analyses in tuberculosis cases showed associations of interferon-gamma levels with body weight (ρ = -0.849; P < 0.0001), body mass index (ρ = 0.664; P = 0.013), hip girth (ρ = -0.579; P = 0.038), and plateletcrit (ρ = 0.605; P = 0.028); interferon-gamma to interleukin-10 ratio with diastolic pressure (ρ = -0.729; P = 0.005); and interferon-gamma to adiponectin ratio with body weight (ρ = -0.560; P = 0.047), body mass index (ρ = -0.604; P = 0.029), and plateletcrit (ρ = 0.793; P = 0.001). Taken together, our results suggest mild-inflammation in early stage infection characterised by upregulation of circulating interferon-gamma production in newly infected TB patients.