David Mulama | Masinde Muliro University of Science and Technology (original) (raw)

Papers by David Mulama

Journal of Immunology, May 1, 2013

African Journal of Health Sciences, 2020

Cancer Research

Introduction The validation of patient derived cell lines and other biologics has gained importan... more Introduction The validation of patient derived cell lines and other biologics has gained importance due to more frequent laboratory collaborations. Polychromatic flow cytometry has been the gold standard for detection and analysis of biochemical, structural complexity and characterization of cellular particles in biological systems. Despite the tremendous advancement in flow cytometry from the earlier simple, slow version of 1960s to more recent complex, fast spectral analyzers with comprehensive structural and functional immune profiling capability, this development has not matched the ever-increasing need for high throughput output to phenotype cells. Mass cytometry (CyToF) uniquely combines time-of-flight mass spectrometry with metal-labeling technology which can theoretically but simultaneously analyze 50+ parameters on a single cell. Despite the functional similarities in utility, mass cytometers and flow cytometers have different operating platforms that may impact their funct...

African Health Sciences

Background: Despite upscaled control efforts, deaths and hospitalization due to malaria remained ... more Background: Despite upscaled control efforts, deaths and hospitalization due to malaria remained high in counties of western Kenya highlands. Objectives: This study assessed the knowledge of malaria in two rural communities, the control strategies they use, and their capacity to integrate the available control programs. Methods: A cross-sectional survey was carried out in two rural villages in November – December 2018. Focus group discussions and a questionnaire survey were carried out in 736 households. Frequencies and proportions were used for descriptive analysis while the Chi-square test was used to determine factors that were associated with knowledge of malaria at p ≤ 0.05 Results: Ninety-seven percent of the respondents had knowledge of malaria and this was associated with the level of education attained (χ2 = 30.108; p > 0.0001). Bed net ownership was at 86% and 92% correctly identified its use. Draining stagnant water (53.9%) was the most cited environmental management p...

Journal of Clinical Immunology and Research, 2020

African Health Sciences

Background: Insecticide treated bed nets and Indoor residual spraying remains the principal inter... more 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 l...

African Health Sciences

Introduction: Illicit substance use and HIV infection cause haematological derangements. Anaemia ... more Introduction: Illicit substance use and HIV infection cause haematological derangements. Anaemia characterized by a reduction in the quality and quantity erythrocytes is the most common disorder in both HIV-positive persons and illicit substance users. Objective: To describe anaemia burden, types, and its association with HIV in injectable substance users in Mombasa, Kenya. Methods: This descriptive case-control study evaluated red cell indices and morphology in 494 adults. The primary outcome was anaemia. The association of anaemia with HIV in injection substance users was determined using the chi-square test. Results: The participants included 275 injection substance users (ISU), (HIV-positive, n=62 and HIV-negative, n=213); and 219 non-injection substance users (nonISU), (HIV-positive, n=33 and HIV-negative, n=186). Overall, 49% were anaemic with anaemia burden significantly differing across the groups, Χ2(3, N=494) =12.1, p=0.0070. Anaemia burden was higher in HIV-positive ISU c...

The Pan African Medical Journal, 2021

Introduction high HIV-1 infection rates and genetic diversity especially in African population po... more Introduction high HIV-1 infection rates and genetic diversity especially in African population pose significant challenges in HIV-1 clinical management and drug design and development. HIV-1 is a major health challenge in Kenya and causes mortality and morbidity in the country as well as straining the healthcare system and the economy. This study sought to identify HIV-1 genetic subtypes circulating in Teso, Western Kenya which borders the Republic of Uganda. Methods a cross-sectional study was conducted in January 2019 to December 2019. Sequencing of the partial pol gene was carried out on 80 HIV positive individuals on antiretroviral therapy. Subtypes and recombinant forms were generated using the jumping profile hidden Markov model. Alignment of the sequences was done using ClustalW program and phylogenetic tree constructed using MEGA7 neighbor-joining method. Results sixty three samples were successful sequenced. In the analysis of these sequences, it was observed that HIV-1 sub...

The figures are from a recent study in which we investigated hemocytopenias, anaemia and immune s... more The figures are from a recent study in which we investigated hemocytopenias, anaemia and immune status in Kenyan injection and non-injection substance users. All HIV infected individuals were not under any active prophylaxis including antiretroviral treatment,

Strategic Journal of Business & Change Management, 2020

Endemic Burkitt’s lymphoma (eBL) is the most common cancer that affects children in Africa. Co-in... more Endemic Burkitt’s lymphoma (eBL) is the most common cancer that affects children in Africa. Co-infection of re-current Plasmodium falciparum (P.falciparum) Malaria with Epstein- Barr virus (EBV) is among risk factors of developing eBL. The study compared methods used to diagnose Plasmodium falciparum malaria, EBV, eBL and effect of socio-economic factors on occurrence and co-occurrence of Plasmodium falciparum malaria and eBL among children in Vihiga and Kisumu sub-Counties. From each sub-County, the study assessed thirty homesteads using a questionnaire to collect data on socio-economic factors and ten health centers for the case-control study. Results obtained showed that methods used to diagnose Plasmodium falciparum malaria, EBV and eBL in Vihiga and Kisumu East sub-Counties were inadequate. Rapid diagnostic test and microscopy were the main laboratory methods used to diagnose P. falciparum in the study regions but were not available in all health centers used. EBV and eBL were ...

The Pan African Medical Journal, 2021

Introduction mutations are important by ensuring that the HIV-1 agent remains fit in the environm... more Introduction mutations are important by ensuring that the HIV-1 agent remains fit in the environment and evades drugs that are developed purposely to kill them. In Kenya, mutations conferring resistance to available ARVs have been reported in previous studies. However, there is a paucity of information on whether these previous studies have reported all mutations conclusively that confer resistance to available drugs leading to virologic failure. Therefore, this study was sought to identify the current HIV-1 drug-resistant mutations attributable to virologic failure among adults on various ARV regimens. Methods the samples were collected March to June 2020. Analysis of viral loads and HIV-1 drug-resistant mutations through sequencing of the pol region of HIV-1 were done. Alignment of the cDNA sequences was done by Recall (beta version 3.05) software. HIV-1 resistant mutations were identified by Stanford University HIV drug resistance database. Results most of the participants had vi...

The Pan African Medical Journal, 2020

Introduction in Kenya, about 1.5 million people are living with the Human Immunodeficiency Virus ... more Introduction in Kenya, about 1.5 million people are living with the Human Immunodeficiency Virus (HIV). Antiretroviral therapy aids in viral suppression. However, drug-resistance threaten the gains of the HIV infection control program. To determine the prevalence of HIV-1 drug-resistant mutations among adults on ARV therapy attending Khunyangu sub-county hospital in Busia County, Kenya, 50 blood samples were analyzed. Methods the samples were collected from November 2019 to January 2020 and tested for HIV-1 viral load. HIV-1 drug-resistance was analyzed through the sequencing of the HIV-1 pol gene. Generated sequences were aligned using RECall (beta v3.05) software. HIV-1 drug-resistance was determined using the Stanford University HIV database. Results females were 34 and males 16. The general prevalence of HIV-1 drug-resistance was 68%. Out of 34 participants on first-line drugs, 59.9% had mutations against these drugs and 5.9% against the second-line drugs. Out of 16 participants...

Ethiopian Journal of Health Sciences, 2021

Background Management of malaria transmission relies heavily on vector control. Implementation an... more Background Management of malaria transmission relies heavily on vector control. Implementation and sustenance of effective control measures require regular monitoring of malaria vector occurrences, species abundance and distribution. The study assessed mosquito larval species composition, distribution and productivity in Kakamega County, western Kenya. Methods A cross-sectional survey of Anopheline larvae was conducted in various aquatic habitats and land use types in Kakamega County, highlands of western Kenya between the month of March and June 2019. Results One thousand, five hundred and seventy six aquatic habitats were sampled in various land use types. The mean densities of An. gambiae s.l (46.2), An. funestus (5.3), An. coustani (1.7), An. implexus (0.13) and An. squamosus (2.0) were observed in fish ponds, burrow pits, drainage ditches, and tire tracks, respectively. High mean densities of An. gambiae s.l was reported in farmland (20.4) while high mean abundance of An. funes...

Cancers

Children diagnosed with endemic Burkitt lymphoma (eBL) are deficient in interferon-γ (IFN-γ) resp... more Children diagnosed with endemic Burkitt lymphoma (eBL) are deficient in interferon-γ (IFN-γ) responses to Epstein–Barr Nuclear Antigen1 (EBNA1), the viral protein that defines the latency I pattern in this B cell tumor. However, the contributions of immune-regulatory cytokines and phenotypes of the EBNA1-specific T cells have not been characterized for eBL. Using a bespoke flow cytometry assay we measured intracellular IFN-γ, IL-10, IL-17A expression and phenotyped CD4+ and CD8+ T cell effector memory subsets specific to EBNA1 for eBL patients compared to two groups of healthy children with divergent malaria exposures. In response to EBNA1 and a malaria antigen (PfSEA-1A), the three study groups exhibited strikingly different cytokine expression and T cell memory profiles. EBNA1-specific IFN-γ-producing CD4+ T cell response rates were lowest in eBL (40%) compared to children with high malaria (84%) and low malaria (66%) exposures (p < 0.0001 and p = 0.0004, respectively). However...

PLOS ONE

There is an urgent need for reliable region-specific hematological reference values for clinical ... more There is an urgent need for reliable region-specific hematological reference values for clinical monitoring. Laboratory reference ranges are important for assessing study participant eligibility, toxicity grading and management of adverse events in clinical trials and clinical diagnosis. Most clinical laboratories in Kenya rely on hematological reference values provided by instrument manufacturers and/or textbooks, which are based on population from Europe or North America. The use of such values in medical practice could result in improper patient management, selection bias in selection of appropriate participants for clinical trials and flawed classification of the clinical adverse events when applied to African populations. The aim of this study was to establish local laboratory hematological reference values in infants aged 1 month to 17 months from Kombewa Sub-county that could be true representative of the existing rural population. The study participants in the current study ...

Vaccines, Apr 6, 2020

Primary infection with Epstein-Barr virus (EBV) is associated with acute infectious mononucleosis... more Primary infection with Epstein-Barr virus (EBV) is associated with acute infectious mononucleosis, whereas persistent infection is associated with chronic diseases such as autoimmune diseases and various types of cancer. Indeed, approximately 2% of all new cancer cases occurring annually worldwide are EBV-associated. Currently, there is no licensed EBV prophylactic vaccine. Selection of appropriate viral protein subunits is critical for development of an effective vaccine. Although the major EBV surface glycoprotein gp350/220 (gp350) has been proposed as an important prophylactic vaccine target, attempts to develop a potent vaccine based on gp350 alone have shown limited success in the clinic. We provide data showing that five EBV glycoproteins (gp350, gB, gp42, gH, and gL) involved in viral entry and infection can successfully be incorporated on the surface of EBV-like particles (EBV-LPs). These EBV-LPs, when administered together with aluminum hydroxide and monophosphoryl lipid A as adjuvants to New Zealand white rabbits, elicited EBV glycoprotein-specific antibodies capable of neutralizing viral infection in vitro in both B cells and epithelial cells, better than soluble gp350 ectodomain. Our findings suggest that a pentavalent EBV-LP formulation might be an ideal candidate for development as a safe and immunogenic EBV vaccine.

Journal of Immunology, May 1, 2013

African Journal of Health Sciences, 2020

Cancer Research

Introduction The validation of patient derived cell lines and other biologics has gained importan... more Introduction The validation of patient derived cell lines and other biologics has gained importance due to more frequent laboratory collaborations. Polychromatic flow cytometry has been the gold standard for detection and analysis of biochemical, structural complexity and characterization of cellular particles in biological systems. Despite the tremendous advancement in flow cytometry from the earlier simple, slow version of 1960s to more recent complex, fast spectral analyzers with comprehensive structural and functional immune profiling capability, this development has not matched the ever-increasing need for high throughput output to phenotype cells. Mass cytometry (CyToF) uniquely combines time-of-flight mass spectrometry with metal-labeling technology which can theoretically but simultaneously analyze 50+ parameters on a single cell. Despite the functional similarities in utility, mass cytometers and flow cytometers have different operating platforms that may impact their funct...

African Health Sciences

Background: Despite upscaled control efforts, deaths and hospitalization due to malaria remained ... more Background: Despite upscaled control efforts, deaths and hospitalization due to malaria remained high in counties of western Kenya highlands. Objectives: This study assessed the knowledge of malaria in two rural communities, the control strategies they use, and their capacity to integrate the available control programs. Methods: A cross-sectional survey was carried out in two rural villages in November – December 2018. Focus group discussions and a questionnaire survey were carried out in 736 households. Frequencies and proportions were used for descriptive analysis while the Chi-square test was used to determine factors that were associated with knowledge of malaria at p ≤ 0.05 Results: Ninety-seven percent of the respondents had knowledge of malaria and this was associated with the level of education attained (χ2 = 30.108; p > 0.0001). Bed net ownership was at 86% and 92% correctly identified its use. Draining stagnant water (53.9%) was the most cited environmental management p...

Journal of Clinical Immunology and Research, 2020

African Health Sciences

Background: Insecticide treated bed nets and Indoor residual spraying remains the principal inter... more 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 l...

African Health Sciences

Introduction: Illicit substance use and HIV infection cause haematological derangements. Anaemia ... more Introduction: Illicit substance use and HIV infection cause haematological derangements. Anaemia characterized by a reduction in the quality and quantity erythrocytes is the most common disorder in both HIV-positive persons and illicit substance users. Objective: To describe anaemia burden, types, and its association with HIV in injectable substance users in Mombasa, Kenya. Methods: This descriptive case-control study evaluated red cell indices and morphology in 494 adults. The primary outcome was anaemia. The association of anaemia with HIV in injection substance users was determined using the chi-square test. Results: The participants included 275 injection substance users (ISU), (HIV-positive, n=62 and HIV-negative, n=213); and 219 non-injection substance users (nonISU), (HIV-positive, n=33 and HIV-negative, n=186). Overall, 49% were anaemic with anaemia burden significantly differing across the groups, Χ2(3, N=494) =12.1, p=0.0070. Anaemia burden was higher in HIV-positive ISU c...

The Pan African Medical Journal, 2021

Introduction high HIV-1 infection rates and genetic diversity especially in African population po... more Introduction high HIV-1 infection rates and genetic diversity especially in African population pose significant challenges in HIV-1 clinical management and drug design and development. HIV-1 is a major health challenge in Kenya and causes mortality and morbidity in the country as well as straining the healthcare system and the economy. This study sought to identify HIV-1 genetic subtypes circulating in Teso, Western Kenya which borders the Republic of Uganda. Methods a cross-sectional study was conducted in January 2019 to December 2019. Sequencing of the partial pol gene was carried out on 80 HIV positive individuals on antiretroviral therapy. Subtypes and recombinant forms were generated using the jumping profile hidden Markov model. Alignment of the sequences was done using ClustalW program and phylogenetic tree constructed using MEGA7 neighbor-joining method. Results sixty three samples were successful sequenced. In the analysis of these sequences, it was observed that HIV-1 sub...

The figures are from a recent study in which we investigated hemocytopenias, anaemia and immune s... more The figures are from a recent study in which we investigated hemocytopenias, anaemia and immune status in Kenyan injection and non-injection substance users. All HIV infected individuals were not under any active prophylaxis including antiretroviral treatment,

Strategic Journal of Business & Change Management, 2020

Endemic Burkitt’s lymphoma (eBL) is the most common cancer that affects children in Africa. Co-in... more Endemic Burkitt’s lymphoma (eBL) is the most common cancer that affects children in Africa. Co-infection of re-current Plasmodium falciparum (P.falciparum) Malaria with Epstein- Barr virus (EBV) is among risk factors of developing eBL. The study compared methods used to diagnose Plasmodium falciparum malaria, EBV, eBL and effect of socio-economic factors on occurrence and co-occurrence of Plasmodium falciparum malaria and eBL among children in Vihiga and Kisumu sub-Counties. From each sub-County, the study assessed thirty homesteads using a questionnaire to collect data on socio-economic factors and ten health centers for the case-control study. Results obtained showed that methods used to diagnose Plasmodium falciparum malaria, EBV and eBL in Vihiga and Kisumu East sub-Counties were inadequate. Rapid diagnostic test and microscopy were the main laboratory methods used to diagnose P. falciparum in the study regions but were not available in all health centers used. EBV and eBL were ...

The Pan African Medical Journal, 2021

Introduction mutations are important by ensuring that the HIV-1 agent remains fit in the environm... more Introduction mutations are important by ensuring that the HIV-1 agent remains fit in the environment and evades drugs that are developed purposely to kill them. In Kenya, mutations conferring resistance to available ARVs have been reported in previous studies. However, there is a paucity of information on whether these previous studies have reported all mutations conclusively that confer resistance to available drugs leading to virologic failure. Therefore, this study was sought to identify the current HIV-1 drug-resistant mutations attributable to virologic failure among adults on various ARV regimens. Methods the samples were collected March to June 2020. Analysis of viral loads and HIV-1 drug-resistant mutations through sequencing of the pol region of HIV-1 were done. Alignment of the cDNA sequences was done by Recall (beta version 3.05) software. HIV-1 resistant mutations were identified by Stanford University HIV drug resistance database. Results most of the participants had vi...

The Pan African Medical Journal, 2020

Introduction in Kenya, about 1.5 million people are living with the Human Immunodeficiency Virus ... more Introduction in Kenya, about 1.5 million people are living with the Human Immunodeficiency Virus (HIV). Antiretroviral therapy aids in viral suppression. However, drug-resistance threaten the gains of the HIV infection control program. To determine the prevalence of HIV-1 drug-resistant mutations among adults on ARV therapy attending Khunyangu sub-county hospital in Busia County, Kenya, 50 blood samples were analyzed. Methods the samples were collected from November 2019 to January 2020 and tested for HIV-1 viral load. HIV-1 drug-resistance was analyzed through the sequencing of the HIV-1 pol gene. Generated sequences were aligned using RECall (beta v3.05) software. HIV-1 drug-resistance was determined using the Stanford University HIV database. Results females were 34 and males 16. The general prevalence of HIV-1 drug-resistance was 68%. Out of 34 participants on first-line drugs, 59.9% had mutations against these drugs and 5.9% against the second-line drugs. Out of 16 participants...

Ethiopian Journal of Health Sciences, 2021

Background Management of malaria transmission relies heavily on vector control. Implementation an... more Background Management of malaria transmission relies heavily on vector control. Implementation and sustenance of effective control measures require regular monitoring of malaria vector occurrences, species abundance and distribution. The study assessed mosquito larval species composition, distribution and productivity in Kakamega County, western Kenya. Methods A cross-sectional survey of Anopheline larvae was conducted in various aquatic habitats and land use types in Kakamega County, highlands of western Kenya between the month of March and June 2019. Results One thousand, five hundred and seventy six aquatic habitats were sampled in various land use types. The mean densities of An. gambiae s.l (46.2), An. funestus (5.3), An. coustani (1.7), An. implexus (0.13) and An. squamosus (2.0) were observed in fish ponds, burrow pits, drainage ditches, and tire tracks, respectively. High mean densities of An. gambiae s.l was reported in farmland (20.4) while high mean abundance of An. funes...

Cancers

Children diagnosed with endemic Burkitt lymphoma (eBL) are deficient in interferon-γ (IFN-γ) resp... more Children diagnosed with endemic Burkitt lymphoma (eBL) are deficient in interferon-γ (IFN-γ) responses to Epstein–Barr Nuclear Antigen1 (EBNA1), the viral protein that defines the latency I pattern in this B cell tumor. However, the contributions of immune-regulatory cytokines and phenotypes of the EBNA1-specific T cells have not been characterized for eBL. Using a bespoke flow cytometry assay we measured intracellular IFN-γ, IL-10, IL-17A expression and phenotyped CD4+ and CD8+ T cell effector memory subsets specific to EBNA1 for eBL patients compared to two groups of healthy children with divergent malaria exposures. In response to EBNA1 and a malaria antigen (PfSEA-1A), the three study groups exhibited strikingly different cytokine expression and T cell memory profiles. EBNA1-specific IFN-γ-producing CD4+ T cell response rates were lowest in eBL (40%) compared to children with high malaria (84%) and low malaria (66%) exposures (p < 0.0001 and p = 0.0004, respectively). However...

PLOS ONE

There is an urgent need for reliable region-specific hematological reference values for clinical ... more There is an urgent need for reliable region-specific hematological reference values for clinical monitoring. Laboratory reference ranges are important for assessing study participant eligibility, toxicity grading and management of adverse events in clinical trials and clinical diagnosis. Most clinical laboratories in Kenya rely on hematological reference values provided by instrument manufacturers and/or textbooks, which are based on population from Europe or North America. The use of such values in medical practice could result in improper patient management, selection bias in selection of appropriate participants for clinical trials and flawed classification of the clinical adverse events when applied to African populations. The aim of this study was to establish local laboratory hematological reference values in infants aged 1 month to 17 months from Kombewa Sub-county that could be true representative of the existing rural population. The study participants in the current study ...

Vaccines, Apr 6, 2020

Primary infection with Epstein-Barr virus (EBV) is associated with acute infectious mononucleosis... more Primary infection with Epstein-Barr virus (EBV) is associated with acute infectious mononucleosis, whereas persistent infection is associated with chronic diseases such as autoimmune diseases and various types of cancer. Indeed, approximately 2% of all new cancer cases occurring annually worldwide are EBV-associated. Currently, there is no licensed EBV prophylactic vaccine. Selection of appropriate viral protein subunits is critical for development of an effective vaccine. Although the major EBV surface glycoprotein gp350/220 (gp350) has been proposed as an important prophylactic vaccine target, attempts to develop a potent vaccine based on gp350 alone have shown limited success in the clinic. We provide data showing that five EBV glycoproteins (gp350, gB, gp42, gH, and gL) involved in viral entry and infection can successfully be incorporated on the surface of EBV-like particles (EBV-LPs). These EBV-LPs, when administered together with aluminum hydroxide and monophosphoryl lipid A as adjuvants to New Zealand white rabbits, elicited EBV glycoprotein-specific antibodies capable of neutralizing viral infection in vitro in both B cells and epithelial cells, better than soluble gp350 ectodomain. Our findings suggest that a pentavalent EBV-LP formulation might be an ideal candidate for development as a safe and immunogenic EBV vaccine.