39 results on '"Sody Munsaka"'
Search Results
2. Prevalence and factors associated with moderate-to-severe anaemia among virally suppressed people with HIV at a tertiary hospital in Zambia
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Kingsley Kamvuma, Sepiso Masenga, Benson Hamooya, Warren Chanda, and Sody Munsaka
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Medicine ,Science - Published
- 2024
3. Malaria is the leading cause of acute kidney injury among a Zambian paediatric renal service cohort retrospectively evaluated for aetiologies, predictors of the need for dialysis, and outcomes.
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Chisambo Mwaba, Sody Munsaka, Bruce Bvulani, David Mwakazanga, Brian Chanda Chiluba, Kaiser Fitzwanga, and Evans Mpabalwani
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Medicine ,Science - Abstract
BackgroundWhilst malaria is a prominent aetiology associated with acute kidney injury (AKI) in many parts of Africa, a shift in the traditional AKI aetiologies has been witnessed in sections of the continent. Additionally, limited access to dialysis worsens patient outcomes in these low-resource settings. This retrospective cross-sectional study aimed to determine the associated aetiologies, predictors of need for dialysis and malaria-associated AKI (MAKI), and outcomes of AKI and dialysis among children evaluated by the renal service in Lusaka, Zambia.MethodsThe study sampled all children aged 16 years or below, diagnosed with AKI between 2017 and 2021, by the renal unit at the University Teaching Hospitals- Children's Hospital (UTH-CH), and retrospectively abstracted their records for exposures and outcomes. AKI was defined using the Kidney Disease Improving Global Outcomes (KDIGO) 2012 criteria. Frequency and percentage distributions were used to describe the occurrence of AKI aetiologies and treatment outcomes. Predictors of the need for dialysis, MAKI, and poor treatment outcome were identified by using multivariable logistic regression models.ResultsA total of 126 children diagnosed with AKI were included in this study. Malaria was the most frequent aetiology of AKI(61.1% (77/126, 95% Confidence Interval (CI): 52.0%-69.7%)). Of the 126 children with AKI, 74.6% (94) underwent dialysis. Predictors of the need for dialysis were oliguria (p = 0.0024; Odds ratio (OR) = 7.5, 95% CI: 2.1-27.7) and anuria (p = 0.0211; OR = 6.4, 95% CI = 1.3, 30.7). A fifth (18.3%, 23/126) of the children developed chronic kidney disease (CKD), 5.6% (7/126) died and, a year later, 77% (97/126) were lost to follow-up.ConclusionAt UTH-CH, malaria is the most frequent aetiology among children with AKI undergoing dialysis and children from low-medium malaria incidence areas are at risk; a considerable proportion of children with AKI need dialysis and Tenchoff catheter use in AKI is advocated.
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- 2023
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4. Maternal and Infant Histo-Blood Group Antigen (HBGA) Profiles and Their Influence on Oral Rotavirus Vaccine (RotarixTM) Immunogenicity among Infants in Zambia
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Adriace Chauwa, Samuel Bosomprah, Natasha Makabilo Laban, Bernard Phiri, Mwelwa Chibuye, Obvious Nchimunya Chilyabanyama, Sody Munsaka, Michelo Simuyandi, Innocent Mwape, Cynthia Mubanga, Masuzyo Chirwa Chobe, Caroline Chisenga, and Roma Chilengi
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rotavirus ,vaccines ,histo-blood groups ,immunogenicity ,Zambia ,Medicine - Abstract
Live-attenuated, oral rotavirus vaccines have significantly reduced rotavirus-associated diarrhoea morbidity and infant mortality. However, vaccine immunogenicity is diminished in low-income countries. We investigated whether maternal and infant intrinsic susceptibility to rotavirus infection via histo-blood group antigen (HBGA) profiles influenced rotavirus (ROTARIX®) vaccine-induced responses in Zambia. We studied 135 mother–infant pairs under a rotavirus vaccine clinical trial, with infants aged 6 to 12 weeks at pre-vaccination up to 12 months old. We determined maternal and infant ABO/H, Lewis, and secretor HBGA phenotypes, and infant FUT2 HBGA genotypes. Vaccine immunogenicity was measured as anti-rotavirus IgA antibody titres. Overall, 34 (31.3%) children were seroconverted at 14 weeks, and no statistically significant difference in seroconversion was observed across the various HBGA profiles in early infant life. We also observed a statistically significant difference in rotavirus-IgA titres across infant HBGA profiles at 12 months, though no statistically significant difference was observed between the study arms. There was no association between maternal HBGA profiles and infant vaccine immunogenicity. Overall, infant HBGAs were associated with RV vaccine immunogenicity at 12 months as opposed to in early infant life. Further investigation into the low efficacy of ROTARIX® and appropriate intervention is key to unlocking the full vaccine benefits for U5 children.
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- 2023
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5. Immune correlates of Mycobacterium Tuberculosis patients in Zambia stratified by HIV serostatus and level of immunity-a cross-sectional analytical laboratory based study.
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Patrick Lungu, Evarist Njelesani, Thomas Sukwa, Owen Ngalamika, Sody Munsaka, William Kilembe, Shabir Lakhi, and Peter Mwaba
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Medicine ,Science - Abstract
BackgroundPeople living with HIV (PLHIV) co-infected with tuberculosis (TB) have a distinct clinical presentation and poorer treatment outcomes compared to HIV-seronegative TB patients. Excluding low CD4 count, innate immune factors associated with TB are not fully elucidated. We, therefore, characterised and compared the expression of IL-6, TNF-α, IFN-γ, and IL-10 in whole blood of treatment naïve TB patients stimulated with heat-killed Mycobacterium tuberculosis stratified by HIV status and the level of CD4 count.ResultsWe recruited 39 HIV seropositive and 31 HIV seronegative TB patients. Median (IQR) age was 35(28-42) years and 31(25-36) years respectively, and a majority had pulmonary tuberculosis i.e. 38(95%) and 30(97%), respectively. The two groups were significantly different in the distribution of CD4 count, 563 [465-702.5 cells/mm3] vs 345 [157-483 cell/mm3] in HIV negative vs HIV positive respectively p = ConclusionsThis study suggests that HIV seronegative TB patients have a higher pro-inflammatory response to MTB than HIV seropositive TB patients. Further, it also shows that the level of CD4 influences immunomodulation. The findings suggest that the difference in cytokine expression may be responsible for the distinct patterns of TB presentation between HIV positive and HIV negative patient.
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- 2022
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6. Luna Virus and Helminths in Wild Mastomys natalensis in Two Contrasting Habitats in Zambia: Risk Factors and Evidence of Virus Dissemination in Semen
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Samuel Munalula Munjita, Given Moonga, Andrew Nalishuwa Mukubesa, Joseph Ndebe, Benjamin Mubemba, Manu Vanaerschot, Cristina Tato, John Tembo, Nathan Kapata, Simbarashe Chitanga, Katendi Changula, Mashiro Kajihara, Walter Muleya, Ayato Takada, Elisabeth Fichet-Calvet, Alimuddin Zumla, Hirofumi Sawa, Matthew Bates, Sody Munsaka, and Edgar Simulundu
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metagenomics ,semen ,foetus ,reads ,prevalence ,risk factors ,Medicine - Abstract
Transmission dynamics and the maintenance of mammarenaviruses in nature are poorly understood. Using metagenomic next-generation sequencing (mNGS) and RT-PCR, we investigated the presence of mammarenaviruses and co-infecting helminths in various tissues of 182 Mastomys natalensis rodents and 68 other small mammals in riverine and non-riverine habitats in Zambia. The Luna virus (LUAV) genome was the only mammarenavirus detected (7.7%; 14/182) from M. natalensis. Only one rodent from the non-riverine habitat was positive, while all six foetuses from one pregnant rodent carried LUAV. LUAV-specific mNGS reads were 24-fold higher in semen than in other tissues from males. Phylogenetically, the viruses were closely related to each other within the LUAV clade. Helminth infections were found in 11.5% (21/182) of M. natalensis. LUAV–helminth co-infections were observed in 50% (7/14) of virus-positive rodents. Juvenility (OR = 9.4; p = 0.018; 95% CI: 1.47–59.84), nematodes (OR = 15.5; p = 0.001; 95% CI: 3.11–76.70), cestodes (OR = 10.8; p = 0.025; 95% CI: 1.35–86.77), and being male (OR = 4.6; p = 0.036; 95% CI: 1.10–18.90) were associated with increased odds of LUAV RNA detection. The role of possible sexual and/or congenital transmission in the epidemiology of LUAV infections in rodents requires further study, along with the implications of possible helminth co-infection.
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- 2022
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7. Epstein–Barr Virus Detection in the Central Nervous System of HIV-Infected Patients
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Kalo Musukuma-Chifulo, Omar Khalik Siddiqi, Obvious Nchimunya Chilyabanyama, Matthew Bates, Caroline Cleopatra Chisenga, Michelo Simuyandi, Edford Sinkala, Xin Dang, Igor Jerome Koralnik, Roma Chilengi, and Sody Munsaka
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Epstein–Barr virus (EBV) ,central nervous system (CNS) ,human immunodeficiency virus (HIV) ,polymerase chain reaction (PCR) ,cerebrospinal fluid (CSF) ,Medicine - Abstract
Simply detecting Epstein–Barr virus deoxyribonucleic acid (EBV-DNA) is insufficient to diagnose EBV-associated diseases. The current literature around EBV-DNA detection from cerebrospinal fluid (CSF) in human immunodeficiency virus (HIV)-positive non-lymphoma patients was systematically reviewed and a meta-analysis reporting the estimated pooled prevalence in this population when PCR methods are employed, targeting different sequence segments within the EBV genome, was conducted. Using a combination of three key concepts—Epstein–Barr virus detection, central nervous system disease, and human cerebrospinal fluid—and their MeSH terms, the PubMed database was searched. A total of 273 papers reporting the detection of EBV in CNS were screened, of which 13 met the inclusion criteria. The meta-analysis revealed a pooled prevalence of EBV-DNA in CSF of 20% (CI: 12–31%). The highest pooled prevalence was from studies conducted on the African population at 39% (CI: 27–51%). The investigation of the presence of EBV-DNA in the CSF was also very varied, with several gene targets used. While most patients from the articles included in this review and meta-analysis were symptomatic of CNS disorders, the pathogenicity of EBV in non-lymphoma HIV patients when detected in CSF has still not been determined. The presence of EBV-DNA in the CNS remains a concern, and further research is warranted to understand its significance in causing CNS disorders.
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- 2022
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8. Assessing required SARS-CoV-2 blanket testing rates for possible control of the outbreak in the epicentre Lusaka province of Zambia with consideration for asymptomatic individuals: A simple mathematical modelling study.
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Joseph Sichone, Musalula Sinkala, Sody Munsaka, Mervis Kikonko, and Martin Simuunza
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Medicine ,Science - Abstract
IntroductionThe novel Coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), in Africa is characterised by a more substantial proportion of asymptomatic (or mildly symptomatic) individuals thought to be playing a role in the spread of the infection. The exact proportion and degree of infectiousness of asymptomatic individuals remains unclear. Studies however indicate that their management is crucial for control of SARS-CoV-2 transmission.MethodologyWe developed a simplified deterministic susceptible-exposed-infectious-removed (SEIR) mathematical model to assess the effect of active isolation of SARS-CoV-2 infected but asymptomatic individuals through blanket testing for control of the outbreak in Lusaka Province of Zambia. Here we modelled two scenarios; (1) assuming asymptomatic individuals comprised 70% of all COVID-19 cases and (2) asymptomatic individuals comprised only 50% of the cases. For contrast, the model was assessed first under the assumption that asymptomatic individuals are equally as infectious as symptomatic individuals and then secondly, and more likely, assuming asymptomatic individuals are only half as infectious as symptomatic individuals.ResultsFor the model assuming 70% asymptomatic cases, a minimum sustained daily blanket testing rate of ≥ 7911 tests/100000 population was sufficient to control the outbreak if asymptomatic individuals are only half as infectious while if equal infectiousness was assumed then a testing rate of ≥ 10028 tests/ 100000 population would be required. For 50% asymptomatic, minimum blanket testing rates of ≥ 4540 tests/ 100000 population was sufficient to control the outbreak at both assumed levels of infectiousness for asymptomatic individuals relative to symptomatic individuals.Discussion and conclusionOur model predicts that active isolation of COVID-19 cases, including asymptomatic individuals, through blanket testing can be used as a possible measure for the control of the SARS-Cov-2 transmission in Lusaka, Zambia, but it would come at a high cost.
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- 2021
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9. High ELF4 expression in human cancers is associated with worse disease outcomes and increased resistance to anticancer drugs.
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Doris Kafita, Victor Daka, Panji Nkhoma, Mildred Zulu, Ephraim Zulu, Rabecca Tembo, Zifa Ngwira, Florence Mwaba, Musalula Sinkala, and Sody Munsaka
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Medicine ,Science - Abstract
The malignant phenotype of tumour cells is fuelled by changes in the expression of various transcription factors, including some of the well-studied proteins such as p53 and Myc. Despite significant progress made, little is known about several other transcription factors, including ELF4, and how they help shape the oncogenic processes in cancer cells. To this end, we performed a bioinformatics analysis to facilitate a detailed understanding of how the expression variations of ELF4 in human cancers are related to disease outcomes and the cancer cell drug responses. Here, using ELF4 mRNA expression data of 9,350 samples from the Cancer Genome Atlas pan-cancer project, we identify two groups of patient's tumours: those that expressed high ELF4 transcripts and those that expressed low ELF4 transcripts across 32 different human cancers. We uncover that patients segregated into these two groups are associated with different clinical outcomes. Further, we find that tumours that express high ELF4 mRNA levels tend to be of a higher-grade, afflict a significantly older patient population and have a significantly higher mutation burden. By analysing dose-response profiles to 397 anti-cancer drugs of 612 well-characterised human cancer cell lines, we discover that cell lines that expressed high ELF4 mRNA transcript are significantly less responsive to 129 anti-cancer drugs, and only significantly more response to three drugs: dasatinib, WH-4-023, and Ponatinib, all of which remarkably target the proto-oncogene tyrosine-protein kinase SRC and tyrosine-protein kinase ABL1. Collectively our analyses have shown that, across the 32 different human cancers, the patients afflicted with tumours that overexpress ELF4 tended to have a more aggressive disease that is also is more likely more refractory to most anti-cancer drugs, a finding upon which we could devise novel categorisation of patient tumours, treatment, and prognostic strategies.
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- 2021
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10. Rotavirus breakthrough infections responsible for gastroenteritis in vaccinated infants who presented with acute diarrhoea at University Teaching Hospitals, Children's Hospital in 2016, in Lusaka Zambia.
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Julia Simwaka, Mapaseka Seheri, Gina Mulundu, Patrick Kaonga, Jason M Mwenda, Roma Chilengi, Evans Mpabalwani, and Sody Munsaka
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Medicine ,Science - Abstract
BackgroundIn Zambia, before rotavirus vaccine introduction, the virus accounted for about 10 million episodes of diarrhoea, 63 000 hospitalisations and 15 000 deaths in 2015, making diarrhoea the third leading cause of death after pneumonia and malaria. In Zambia, despite the introduction of the vaccine acute diarrhoea due to rotaviruses has continued to affect children aged five years and below. This study aimed to characterise the rotavirus genotypes which were responsible for diarrhoeal infections in vaccinated infants aged 2 to 12 months and to determine the relationship between rotavirus strains and the severity of diarrhoea in 2016.MethodsStool samples from infants aged 2 to 12 months who presented to the hospital with acute diarrhoea of three or more episodes in 24 hours were tested for group A rotavirus. All positive specimens that had enough sample were genotyped using reverse transcriptase Polymerase Chain Reaction (RT-PCR). A 20-point Vesikari clinical score between 1-5 was considered as mild, 6-10 as moderate and greater or equal to 11 as severe.ResultsA total of 424 stool specimens were tested of which 153 (36%, 95% CI 31.5% to 40.9%) were positive for VP6 rotavirus antigen. The age-specific rotavirus infections decreased significantly (p = 0.041) from 2-4 months, 32.0% (49/118) followed by a 38.8% (70/181) infection rate in the 5-8 months' category and subsequently dropped in the infants aged 9-12 months with a positivity rate of 27.2%. 38.5% of infants who received a single dose, 34.5% of those who received a complete dose and 45.2% (19/42) of the unvaccinated tested positive for rotavirus. The predominant rotavirus genotypes included G2P[6] 36%, G1P[8] 32%, mixed infections 19%, G2P[4] 6%, G1P[6] 4% and G9P[6] 3%.Discussion and conclusionResults suggest breakthrough infection of heterotypic strains (G2P[6] (36%), homotypic, G1P[8] (32%) and mixed infections (19%) raises concerns about the effects of the vaccination on the rotavirus diversity, considering the selective pressure that rotavirus vaccines could exert on viral populations. This data indicates that the rotavirus vaccine has generally reduced the severity of diarrhoea despite the detection of the virus strains.
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- 2021
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11. Outcome markers of ART-treated HIV+ patients with early stage Kaposi's sarcoma.
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Owen Ngalamika, For Yue Tso, Salum Lidenge, Sody Munsaka, Danielle Shea, Charles Wood, and John West
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Medicine ,Science - Abstract
HIV-associated/epidemic Kaposi's sarcoma (EpKS) is an AIDS-defining angio-proliferative malignancy. It can be treated with antiretroviral therapy (ART) alone or with ART plus cytotoxic chemotherapy. ART-treated EpKS can either respond or worsen upon treatment. This study aimed at identifying immunological markers of ART-treatment response. We compared responders (those with clinical EpKS tumor regression) versus poor responders (those with progressive or non-responsive EpKS). We measured plasma cytokine and chemokine levels using cytometric bead assays. Kaposi's sarcoma herpesvirus (KSHV) neutralizing antibody (nAb) responses were also quantified to test associations with treatment outcome. Interleukin (IL)-5 levels were significantly elevated in responders versus poor-responders at baseline (0.76pg/ml vs. 0.37pg/ml; p
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- 2020
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12. In-vitro inhibitory effect of maternal breastmilk components on rotavirus vaccine replication and association with infant seroconversion to live oral rotavirus vaccine.
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Katayi Mwila Kazimbaya, Caroline C Chisenga, Michelo Simuyandi, Cynthia Mubanga Phiri, Natasha Makabilo Laban, Samuel Bosomprah, Sallie R Permar, Sody Munsaka, and Roma Chilengi
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Medicine ,Science - Abstract
BackgroundDespite contributing to a significant reduction in rotavirus associated diarrhoea in highly burdened low- and middle-income countries, live attenuated, oral rotavirus vaccines have lower immunogenicity and efficacy in these settings in comparison to more developed countries. Breastmilk has been implicated among factors contributing to this lowered oral vaccine efficacy. We conducted in-vitro experiments to investigate the inhibitory effects of maternal antibody and other non-antibody components in breastmilk on rotavirus vaccine strain (Rotarix) multiplication in MA104 cell culture system and assessed associations with in-vivo vaccine seroconversion in vaccinated infants.MethodsBreastmilk samples were collected from mothers before routine rotavirus vaccination of their infant at 6 weeks of age. For each sample, whole breastmilk, purified IgA, purified IgG and IgG and IgA depleted breastmilk samples were prepared as exposure preparations. A 96 well microtitre plate was set up for each sample including a control in which only MA104 cells were grown as well as a virus control with MA104 cells and virus only. The outcome of interest was 50% inhibition dilution of each of the exposure preparations calculated as the titer at which 50% of virus dilution was achieved. Samples from 30 women were tested and correlated to vaccine seroconversion status of the infant. HIV status was also correlated to antiviral breastmilk proteins.ResultsThe mean 50% inhibitory dilution titer when whole breastmilk was added to virus infected MA104 cells was 14.3 (95% CI: 7.1, 22.7). Incubation with purified IgG resulted in a mean 50% inhibitory dilution of 5 (95%CI -1.6, 11.6). Incubating with purified IgA resulted in a mean 50% inhibitory dilution of 6.5 (95% CI -0.7, 13.7) and IgG and IgA depleted breastmilk did not yield any inhibition with a titer of 1.06 (95%CI 0.9, 1.2). Higher milk IgA levels contributed to a failure of infants to seroconvert. HIV was also not associated with any antiviral breastmilk proteins.Discussion and conclusionWhole breastmilk and breastmilk purified IgG and IgA fractions showed inhibitory activity against the rotavirus vaccine Rotarix™ whilst IgA and IgG depleted breastmilk with non-antibody breastmilk fraction failed to show any inhibition activity in-vitro. These findings suggest that IgA and IgG may have functional inhibitory properties and indicates a possible mechanism of how mothers in rotavirus endemic areas with high titres of IgA and IgG may inhibit viral multiplication in the infant gut and would potentially contribute to the failure of their infants to serocovert. There was not association of HIV with either lactoferrin, lactadherin or tenascin-C concentrations.
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- 2020
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13. Effect of innate antiviral glycoproteins in breast milk on seroconversion to rotavirus vaccine (Rotarix) in children in Lusaka, Zambia.
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Katayi Mwila-Kazimbaya, Miguel Pugliese Garcia, Samuel Bosomprah, Natasha Makabilo Laban, Caroline Cleopatra Chisenga, Sallie Robey Permar, Michelo Simuyandi, Sody Munsaka, and Roma Chilengi
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Medicine ,Science - Abstract
Rotavirus vaccines have been introduced into national immunization programmes to mitigate morbidity and mortality associated rotavirus diarrhoea. Lower vaccine effectiveness has however been noted in low-middle income countries, but little is known about the role of maternal components found in breast milk. This study assessed the effect of lactoferrin, lactadherin, and tenascin-c on rotavirus vaccine seroconversion.This was a retrospective cohort study of 128 infants who had been fully immunized with Rotarix™. Serum samples were collected from the infant at baseline and one month after second rotavirus vaccine dose. Breast milk samples were collected from mothers at baseline. Standard ELISA was used to determine titres of rotavirus-specific immunologlobulin G and A in breast milk and serum as well as concentrations of lactoferrin, lactadherin, and tenascin-c. Poisson regression model with robust standard error was used to estimate the effect of breast milk components on seroconversion. The components were modelled on log base 2 so that the effect would be interpreted as a doubling of the concentration.In a multivariable analysis adjusting for maternal age, maternal HIV status, seropositivity at baseline, sex, age of child at vaccination as well as breast milk IgA and IgG, we found evidence of independent effect of LA (Adjusted IRR = 0.95; 95% CI = 0.91-0.99; P = 0.019) on seroconversion while there was no evidence for TNC (Adjusted IRR = 1.00; 95% CI = 0.85-1.17; P = 0.967) and LF (Adjusted RR = 1.01; 95% CI = 0.96-1.05); P = 0.802). We explored the joint effects of the three components but we found no evidence (Adjusted RR = 0.95; 95% CI = 0.81; P = 0.535).High breast milk concentrations of lactadherin might play a role in infant's failure to seroconvert to rotavirus vaccines. Further research to understand this observed association is an important consideration.
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- 2017
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14. Kidney Disease for People Living with HIVin Sub-Saharan Africa; A Systematic Review
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Florence Mwaba, Panji Nkhoma, Brian Chiluba, PATRICK LOTI, and Sody Munsaka
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Sub saharan ,Adult patients ,business.industry ,030231 tropical medicine ,Human immunodeficiency virus (HIV) ,medicine.disease_cause ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Environmental health ,medicine ,Clinical significance ,030212 general & internal medicine ,business ,Kidney disease - Abstract
People living with HIV have been known to have a higher risk and threat of kidney disease. Globally, the prevalence of kidney disease for PLWH is postulated to be 6.4%. This prevalence is different for many different parts of the world, with 7.9% in Africa, 7.1% in North America, 5.7% in Asia and 3.7% in Europe. This systematic review set out to review and collect evidence from literature source and to provide a summary about factors influencing kidney disease for PLWH in Africa. We hypothesized that TDF containing ART is significantly associated with kidney disease. A systematic review and search of data was performed and all articles included were English articles from the following electronic databases: PubMed, Google Scholar and Embase. We carried out the selection of titles in three distinct phases: titles alone, abstracts, and then full text articles. 7 papers were included. While TDF was included in the ART regimens in all the studies, there was wide variation in ART combinations and concurrent medications and durations thereof.All studies except one included only adult patients of both men and women. Majority of the studies highlighted kidney disease and mostly these were hospital-based data. the findings establish a significant association between kidney disease and TDF use, but in terms of the clinical significance and weighting the risks against the benefits, we cannot discourage the continual use of the drug.
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- 2021
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15. Antiretroviral Therapy for HIV-Associated Cutaneous Kaposi's Sarcoma: Clinical, HIV-Related, and Sociodemographic Predictors of Outcome
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John T. West, Salum J. Lidenge, Owen Ngalamika, Charles E. Wood, and Sody Munsaka
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Immunology ,antiretroviral therapy ,Human immunodeficiency virus (HIV) ,HIV Infections ,medicine.disease_cause ,Malignancy ,outcomes ,Outcomes Research ,03 medical and health sciences ,0302 clinical medicine ,Virology ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Prospective Studies ,Kaposi's sarcoma ,Sarcoma, Kaposi ,business.industry ,food and beverages ,virus diseases ,HIV ,Viral Load ,medicine.disease ,Antiretroviral therapy ,CD4 Lymphocyte Count ,030104 developmental biology ,Infectious Diseases ,predictors ,Sarcoma ,business - Abstract
Kaposi's sarcoma (KS) is an AIDS-defining malignancy that can improve or worsen with antiretroviral therapy (ART). We aimed at identifying clinical, HIV-related, and sociodemographic factors associated with either progression or nonprogression (regression or stable disease) of ART-treated HIV-associated KS in patients with limited cutaneous disease. We conducted a prospective cohort study of ART-treated HIV-associated KS cases. Clinical, HIV-related, and sociodemographic variables were collected at baseline, and patients were followed up to determine treatment outcomes. Cox regression, linear mixed effects model, and Spearman's rank correlation were used for analysis. Half (50%) of the study participants had KS regression or stable disease, whereas the other half (50%) had disease progression during the treatment and follow-up period. Among the data analyzed, presence of KS nodules at baseline (hazard ratio = 5.47; 95% confidence interval = 1.32–22.65; p = .02) was an independent predictor of poor treatment outcome. Progressors and nonprogressors were indistinguishable in the changes they experienced in the HIV plasma viral load and CD4 counts as a result of ART. Even when cutaneous presentation is limited, the presence of nodular morphotype KS lesions should be considered an indicator for combined ART plus chemotherapy. Temporal trends in CD4 counts and HIV viral loads did not correlate with treatment outcome in ART-treated HIV-associated KS.
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- 2021
16. Spectrum of common Hodgkin lymphoma and non-Hodgkin lymphomas subtypes in Zambia: a 3-year records review
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Victor C. Mudenda, Sody Munsaka, Luwen Zhang, and Pascal Polepole
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Oncology ,medicine.medical_specialty ,RC620-627 ,Lymphoma ,Health, Toxicology and Mutagenesis ,Lymphocyte ,Population ,Zambia ,World Health Organization ,Hospitals, University ,immune system diseases ,Spectrum ,hemic and lymphatic diseases ,Internal medicine ,Epidemiology ,medicine ,Humans ,Nutritional diseases. Deficiency diseases ,education ,B cell ,Subtypes ,education.field_of_study ,business.industry ,Lymphoma, Non-Hodgkin ,Public Health, Environmental and Occupational Health ,medicine.disease ,Hodgkin Disease ,Exact test ,medicine.anatomical_structure ,Marginal zone B-cell lymphoma ,Public aspects of medicine ,RA1-1270 ,business ,Diffuse large B-cell lymphoma ,Research Article ,Food Science - Abstract
Background Lymphomas usually present with different occurrence patterns across different geographical locations, but their epidemiology in Zambia is yet to be extensively explored. Objectives To study the spectrum of lymphoma subtypes prevalent within the Zambian population. Methods Histopathological records with suspected lymphoma at the University Teaching Hospital (UTH) in Lusaka from the year 2014 to 2016, diagnosed based on the 2008 World Health Organization (WHO) criteria were reviewed. The analysis was done in terms of type, sex, age, and site of biopsy; and Fisher’s exact test was used for significance testing. Results During the study period (2014-2016), there were more B cell neoplasms {222 (92.5%)} than T cell neoplasms {18 (7.5%)}. Non-Hodgkin’s lymphoma (NHL) was seen in 191 (79.6%) whereas classic Hodgkin’s lymphoma (CHL) was seen in 39 (16.3%). Burkitt’s lymphoma (BL) and diffuse large B cell lymphoma (DLBCL) showed equal proportions {17.5% of all lymphoma cases (42/240) each}, as the most prevalent subtypes of NHL whereas marginal zone B cell lymphoma was the rarest subtype with 1.4% (4/240). For CHL, mixed cellularity and lymphocyte rich subtypes (4.6% of all lymphoma cases) were the most common subtypes. There was a statistically significant difference in the occurrences of lymphoma subtypes across different age categories (p = 0.002). Conclusion Zambia has a diverse lymphoma subtypes population, affecting a relatively young population. The data from this study will serve as a baseline for improved health care provision and more robust future studies.
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- 2021
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17. Bacteriological profile and antimicrobial efficacy of alcohol-based hand rubs among health care workers and family caregivers at the children's university teaching hospital in Lusaka, Zambia
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Mukena Nawa, Sody Munsaka, Edgar Simulundu, Panji Nkhoma, Geoffrey Kwenda, Mulemba Tillika Samutela, and Annie Kalonda
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medicine.medical_specialty ,Multidisciplinary ,medicine.drug_class ,Family caregivers ,business.industry ,Transmission (medicine) ,Antibiotic resistance ,Antimicrobial efficacy ,Science ,Antibiotics ,Ciprofloxacin ,Family medicine ,Enterobacter agglomerans ,Health care ,medicine ,Healthcare workers ,University teaching ,Healthcare-associated infection ,business ,Alcohol-based hand rub ,Bacterial contamination ,Hand hygiene ,medicine.drug - Abstract
Background Hands of healthcare workers (HCWs) and family caregivers are a potential source of bacterial pathogens that may be transferred to susceptible individuals. However, there is a paucity of data regarding the effect of hand rubs used in Zambian hospitals. Therefore, we determined the effect of locally made alcohol-based hand rubs in three selected wards of the Children Hospital at the University Teaching Hospital in Zambia. Methods This was a cross-sectional study involving 31 participants (12 family caregivers, 5 doctors and 14 nurses). The samples were collected before and after the use of the alcohol-based hand rub by direct fingerprints. They were then cultured and identified using conventional microbiological methods. The Kirby-Bauer Disc Diffusion method was used for antimicrobial susceptibility testing. Results All samples collected from the participants yielded bacterial growth with a total of 7 species isolated. These included coagulase-negative staphylococcus (33.3%), Bacillus species (28.9%), Staphylococcus aureus (22.2%), Enterobacter agglomerans (6.7%), Corynebacterium species (4.4%), Escherichia coli (2.2%) and Burkholderia pseudomallei (2.2%). Notably, all study participants hands were not only contaminated but with drug-resistant organisms as most of the bacterial isolates were resistant to routine antibiotics used at the hospital including ciprofloxacin. S. aureus was also resistant to oxacillin thus suggesting the presence of Methicillin-Resistant S. aureus. The use of alcohol-based hand rubs reduced the bacterial load by 92.6% on doctors and nurses’ hands and by 84.5% on the hands of family caregivers. Conclusion This study confirms that the hands of HCWs and family caregivers may play a role in the transmission of drug-resistant bacteria and that alcohol-based hand rubs can be an effective way of reducing bacterial hand contamination among healthcare workers and family caregivers. Therefore, we recommend that measures be put in place by the hospital to ensure the availability of hand rubs to HCWs as well as caregivers.
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- 2021
18. Awareness and Acceptance of COVID-19 Vaccines among Pharmacy Students in Zambia: The Implications for Addressing Vaccine Hesitancy
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Christabel Nang’andu Hikaambo, Martin Kampamba, Johanna C Meyer, Moses Mukosha, Ruth Lindizyani Mfune, Brian Godman, Misheck Chileshe, Joseph O Fadare, Webrod Mufwambi, Roland Nnaemeka Okoro, Victor Daka, Sody Munsaka, Steward Mudenda, and Aubrey Chichonyi Kalungia
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Medical education ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Medicine ,Pharmacy ,business - Abstract
Background: Several vaccines have been developed and administered since coronavirus disease 2019 (COVID-19) was declared a pandemic in March 2020. In April 2021, the authorities in Zambia administered the first doses of the Oxford-AstraZeneca® COVID-19 vaccine. However, little is known about the awareness and acceptability of the vaccines among the Zambian population. This study was undertaken to address this starting with undergraduate pharmacy students in Zambia. Materials and methods: A descriptive cross-sectional survey was conducted among 326 undergraduate pharmacy students in Zambia using an online semi-structured questionnaire from 12th to 25th April 2021 and analysed using Stata version 16. Test of associations were undertaken using Pearson chi-square test or Fisher's exact test as appropriate. The multivariable logistic regression was used to investigate the determinants of awareness and acceptability. All statistical tests were performed at a 5% significance level and 95% confidence level. Results: Among 326 participants, 98.8% were aware of the COVID-19 vaccination programme but only 24.5% would accept the vaccine should it be made available to them. Awareness of the COVID-19 vaccine was influenced by religious beliefs (aOR=0.01, 95% CI: 0.01 to 0.20, p=0.004). Being male (aOR=1.78, 95% CI: 1.05 to 3.02, p=0.034) and single (aOR=2.61, 95% CI: 1.04 to 6.55, p=0.041) was associated with higher odds of accepting the vaccine. Being unemployed (aOR=0.31, 95% CI: 0.15 to 0.66, p=0.002) was associated with lower odds of vaccine acceptancy. Barriers to acceptance of the vaccine were possible side effects (78.5%) and scepticism about its effectiveness to prevent COVID-19 (10.2%). Conclusion: There was significant vaccine hesitancy towards COVID-19 vaccines among Zambian pharmacy students despite their awareness about the vaccines. Health authorities must work collaboratively with the Universities and other institutions to mitigate vaccine hesitancy, especially with pharmacy students a key part of the future healthcare workforce overseeing disease prevention strategies. These findings can help guide future interventions to address vaccine hesitancy to reduce future transmission rates of this virus.
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- 2021
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19. Correlates of Hypertension among Persons with HIV at Livingstone Central Hospital: CHAP study
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Leta Pilic, Douglas C. Heimburger, Annet Kirabo, Sody Munsaka, Benson M. Hamooya, Musalula Sinkala, John R. Koethe, and Sepiso K. Masenga
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medicine.medical_specialty ,business.industry ,Family medicine ,medicine ,Human immunodeficiency virus (HIV) ,business ,medicine.disease_cause - Abstract
Background: Persons with HIV (PWH) are more likely to develop hypertension and cardiovascular disease than the HIV-negative population. The new hypertension guidelines by the American Heart Association (AHA) and the American College of Cardiology (ACC) lowered the definition of hypertension from a systolic and diastolic blood pressure (BP) of ≥140/90mmHg to ≥130/80, respectively. This study was aimed at determining the prevalence and factors associated with hypertension in PWH using the new hypertension diagnostic criteria.Methods: This was a cross-sectional study. We recruited 226 antiretroviral treated PWH attending routine visits. Socio-demographic, health, and clinical data including BP readings were collected. Interviewer-structured questionnaires adapted from the World Health Organization Stepwise approach to Surveillance (WHO STEPs) and the international physical activity questionnaire (IPAQ) were used to collect data. Statistical evaluations were employed to elucidate relationships between hypertension and all response variables.Results: The prevalence of hypertension using the old and new guidelines was 16% and 42%, respectively. Factors significantly associated with increased and reduced odds for developing hypertension after adjustments in multivariate logistic regression were age, body mass index (BMI), employment status, fasting blood sugar (FBS) and table salt consumption, respectively (pConclusion: The major risk factors associated with hypertension in PWH were increasing age, BMI and FBS. We recommend inclusion of FBS in routine measurements in PWH. The AHA/ACC new guidelines should be re-enforced in low-cost settings to increase the treatment of hypertension among PWH.
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- 2021
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20. HIV-positive demonstrate more salt sensitivity and nocturnal non-dipping blood pressure than HIV-negative individuals
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Douglas C. Heimburger, John R. Koethe, Wilbroad Mutale, Benson M. Hamooya, Selestine Nzala, Leta Pilic, Sepiso K. Masenga, Sody Munsaka, Geoffrey Kwenda, and Annet Kirabo
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lcsh:Internal medicine ,medicine.medical_specialty ,Mean arterial pressure ,Ambulatory blood pressure ,Salt ,Population ,lcsh:Medicine ,Physiology ,030204 cardiovascular system & hematology ,Nocturnal ,03 medical and health sciences ,0302 clinical medicine ,Internal Medicine ,medicine ,030212 general & internal medicine ,Salt intake ,lcsh:RC31-1245 ,education ,Angiology ,education.field_of_study ,business.industry ,Research ,lcsh:R ,Nocturnal blood pressure dipping ,Blood pressure ,Salt sensitivity ,Hypertension ,Cohort ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background High dietary salt and a lack of reduced blood pressure (BP) at night (non-dipping) are risk factors for the development of hypertension which may result in end-organ damage and death. The effect of high dietary salt on BP in black people of sub-Saharan Africa living with HIV is not well established. The goal of this study was to explore the associations between salt sensitivity and nocturnal blood pressure dipping according to HIV and hypertension status in a cohort of adult Zambian population. Methods We conducted an interventional study among 43 HIV-positive and 42 HIV-negative adults matched for age and sex. Study participants were instructed to consume a low (4 g) dietary salt intake for a week followed by high (9 g) dietary salt intake for a week. Salt resistance and salt sensitivity were defined by a mean arterial pressure difference of ≤5 mmHg and ≥ 8 mmHg, respectively, between the last day of low and high dietary salt intervention. Nocturnal dipping was defined as a 10–15% decrease in night-time blood pressure measured with an ambulatory blood pressure monitor. Results The median age was 40 years for both the HIV-positive and the HIV-negative group with 1:1 male to female ratio. HIV positive individuals with hypertension exhibited a higher BP sensitivity to salt (95%) and non-dipping BP (86%) prevalence compared with the HIV negative hypertensive (71 and 67%), HIV positive (10 and 24%) and HIV-negative normotensive (29 and 52%) groups, respectively (p Conclusions The results of the present study suggest that high dietary salt intake raises blood pressure and worsens nocturnal BP dipping to a greater extent in hypertensive than normotensive individuals and that hypertensive individuals have higher dietary salt intake than their normotensive counterparts. Regarding HIV status, BP of HIV-positive hypertensive patients may be more sensitive to salt intake and demonstrate more non-dipping pattern compared to HIV-negative hypertensive group. However, further studies with a larger sample size are required to validate this.
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- 2021
21. A Systems Approach Identifies Key Regulators of HPV-Positive Cervical Cancer
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Ephraim Zulu, Zifa Ngwira, Mildred Zulu, Doris Kafita, Musalula Sinkala, Victor Daka, Sody Munsaka, Panji Nkhoma, and Rabecca Tembo
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Homeobox protein NANOG ,Cervical cancer ,SOX2 ,Cancer stem cell ,Kinase ,Cancer cell ,Cancer research ,medicine ,Cell cycle ,Biology ,MAPK1 ,medicine.disease - Abstract
Cervical cancer has remained the most prevalent and lethal malignancy among women worldwide and accounted for over 250,000 deaths in 2019. Nearly ninety-five per cent of cervical cancer cases are associated with persistent infection with high-risk Human Papillomavirus (HPV), and seventy per cent of these are associated with viral integration in the host genome. HPV-infection imparts specific changes in the regulatory network of infected cancer cells that are of diagnostic, prognostic and importance. Here, we conducted a systems-level analysis of the regulatory network changes, and the associated regulatory proteins thereof, in HPV-positive cervical cancer. We applied functional pathway analysis to show that HPV-positive cancers are characterised by perturbations of numerous cellular processes, predominantly in those linked to the cell cycle, mitosis, cytokine and immune cell signalling. Using computational predictions, we revealed that HPV-positive cervical cancers are regulated by transcription factors including, SOX2, E2F, NANOG, OCT4, and MYC, which control various processes such as the renewal of cancer stem cells, and the proliferation and differentiation of tumour cells. Through the analysis of upstream regulatory kinases, we identified the mitogen-activated protein kinases; among others, MAPK1, MAPK3 and MAPK8, and the cyclin-dependent kinases; among others, CDK1, CDK2 and CDK4, as the key kinases that control the biological processes in HPV-positive cervical cancers. Taken together, we uncover a landscape of the key regulatory pathways and proteins in HPV-positive cervical cancers, all of which may provide attractive drug targets for future therapeutics.
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- 2021
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22. Immune activation and arterial stiffness in lean adults with HIV on antiretroviral therapy
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Douglas C. Heimburger, Chris Bambey Guure, John R. Koethe, Wilbroad Mutale, Sody Munsaka, Fastone Goma, Theresa Chikopela, and Longa Kaluba
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medicine.medical_specialty ,Population ,antiretroviral therapy ,030312 virology ,Overweight ,Gastroenterology ,endothelial dysfunction ,immune activation ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Medicine ,030212 general & internal medicine ,Endothelial dysfunction ,education ,Pulse wave velocity ,Original Research ,lean adults ,arterial stiffness ,0303 health sciences ,education.field_of_study ,business.industry ,lcsh:Public aspects of medicine ,lcsh:RA1-1270 ,medicine.disease ,Antiretroviral therapy ,Infectious Diseases ,Arterial stiffness ,medicine.symptom ,business ,CD8 ,Immune activation - Abstract
Background:Greater T-cell activation was associated with reduced vascular compliance amongst persons living with HIV (PLWH) especially among overweight and obese individuals. There is a paucity of data regarding immune activation and arterial stiffness amongst PLWH in sub-Saharan Africa (SSA). Objective:To determine the association between immune activation and arterial stiffness in lean PLWH in SSA. Method:Forty-eight human immunodeficiency virus positive (HIV+) adults on antiretroviral therapy (ART) >5 years and 26 HIV-negative adults, all with BMI < 25 kg/m2and no history of CVD, were enrolled. The relationship of vascular compliance with circulating CD4+ and CD8+ naïve, memory, activated and senescent T cells, and serum 8-isoprostane was assessed by HIV status. Results:Increased immune activation was observed in the CD4+ and CD8+ T cells of PLWH, 16.7% vs. 8.9% and 22.0% vs. 12.4% respectively;p< 0.001 (both). Furthermore, a higher proportion of senescent CD4+ T cells were associated with a lower carotid-femoral pulse wave velocity (cfPWV;p= 0.01), whilst a higher proportion of activated CD8+ T cells were associated with a lower carotid-radial pulse wave velocity (crPWV;p= 0.04), after adjustment for BMI and age. However, PLWH also had a higher median carotid-femoral augmentation index (cfAiX) (21.1% vs. 6.0%;p< 0.05) in comparison to their HIV controls. Conclusion:Our population of lean PLWH had increased immune activation and higher cfAiX, a marker of arterial stiffness, compared to HIV-negative persons. The negative association between immune activation and arterial stiffness as measured by crPWV in PLHW on long-term treatment needs further elucidation.
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- 2021
23. Anaemia Types and Severity in Patients aged 1 to 14 years at the Children’s Hospital of the University Teaching Hospitals in Zambia
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Doris Kafita, Florence Mwaba, Panji Nkhoma, Hamakwa Mantina, Sody Munsaka, Musalula Sinkala, Mwenechanya Oliver, and Patrick Loti
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medicine.medical_specialty ,Pediatrics ,Referral ,business.industry ,Public health ,Mortality rate ,medicine.disease ,Vitamin A deficiency ,medicine ,Smoking and pregnancy ,In patient ,University teaching ,business ,Severe anaemia - Abstract
Anaemia is a condition in which either the number of red blood cells or their oxygen-carrying capacity is insufficient to meet physiologic needs, which vary by age, sex, altitude, smoking and pregnancy status. The global estimate of childhood anaemia indicates that 293.1 million children are anaemic, and 28.5% of these children reside in sub-Sahara Africa. Also, anaemia is a significant public health problem with a high age-standardised death rate of 11.18 per 100,000 in Zambia.We conducted a cross-sectional study involving 392 anaemic children aged one year to 14 years. The study was conducted at the Children Hospital, University Teaching Hospitals, which is a third-level referral Hospital in Lusaka, Zambia. The aim was to determine the most common type of anaemia, it’s severity, and the most affected age groups among children aged 1–14 years.Out of 392 participants, 219 (56%) were female. Maximum haemoglobin recorded was 10.9g/dl, a minimum of 2.0 g/dl, a mean of 7.8g/dl and a standard deviation of 1.86g/dl. 200 (51%) participants had severe anaemia, and 192 (49%) had moderate anaemia with none having mild anaemia. Microcytic hypochromic anaemia was the commonest (60%), followed by normochromic normocytic anaemia (26%) and the least was macrocytic anaemia in 14% of the participants. An analysis of variance (ANOVA) showed that the difference in mean haemoglobin concentration between age groups was not significant, F (7.94) = 0.83, p > 0.57. A Chi-squared test was used to determine the relationship between anaemia types (microcytic, hypochromic) and age groups. The interaction was not significant (Chi-Square (1) = 1.28, p-value = 0.73. Microcytic hypochromic anaemia was the most prevalent and all age groups were equally affected. We recommend the country’s National Food and Nutrition Commission to revisit the Zambian National Strategy and Plan of Action for the Prevention and Control of Vitamin A Deficiency and Anaemia of 1999 to 2004 and implement the measures stated in the strategic plan.
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- 2020
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24. Assessing required SARS-CoV-2 blanket testing rates for possible control of the outbreak in the epicentre Lusaka province of Zambia with consideration for asymptomatic individuals: a simple mathematical modelling study
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Joseph Sichone, Mervis Kikonko, Martin Simuunza, Sody Munsaka, and Musalula Sinkala
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0301 basic medicine ,RNA viruses ,Viral Diseases ,Pediatrics ,Pulmonology ,Epidemiology ,Coronaviruses ,Disease ,Disease Outbreaks ,law.invention ,Geographical Locations ,0302 clinical medicine ,Medical Conditions ,law ,Medicine and Health Sciences ,030212 general & internal medicine ,Pathology and laboratory medicine ,Virus Testing ,education.field_of_study ,Multidisciplinary ,Transmission (medicine) ,Medical microbiology ,Infectious Diseases ,Transmission (mechanics) ,Viruses ,Medicine ,Severe acute respiratory syndrome coronavirus ,SARS CoV 2 ,Pathogens ,medicine.symptom ,Research Article ,medicine.medical_specialty ,SARS coronavirus ,Isolation (health care) ,Science ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Population ,Zambia ,Microbiology ,Models, Biological ,Asymptomatic ,Infectious Disease Epidemiology ,03 medical and health sciences ,Respiratory Disorders ,Diagnostic Medicine ,medicine ,Humans ,education ,Biology and life sciences ,SARS-CoV-2 ,business.industry ,Organisms ,Viral pathogens ,COVID-19 ,Outbreak ,Covid 19 ,Microbial pathogens ,030104 developmental biology ,Respiratory Infections ,People and Places ,Africa ,business - Abstract
IntroductionThe novel Coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus - 2 (SARS-CoV-2), in Africa is characterised by a more substantial proportion of asymptomatic (or mildly symptomatic) individuals thought to be playing a role in the spread of the infection. The exact proportion and degree of infectiousness of asymptomatic individuals remains unclear. Studies however indicate that their management is crucial for control of SARS-CoV-2 transmission.MethodologyWe developed a simplified deterministic susceptible-exposed-infectious-removed (SEIR) mathematical model to assess the effect of active isolation of SARS-CoV-2 infected but asymptomatic individuals through blanket testing for control of the outbreak in Lusaka Province of Zambia. Here we modelled two scenarios; (1) assuming asymptomatic individuals comprised 70% of all COVID-19 cases and (2) asymptomatic individuals comprised only 50% of the cases. For contrast, the model was assessed first under the assumption that asymptomatic individuals are equally as infectious as symptomatic individuals and then secondly, and more likely, assuming asymptomatic individuals are only half as infectious as symptomatic individuals.ResultsFor the model assuming 70% asymptomatic cases, a minimum sustained blanket testing rate of ≥ 7911 tests/100000 population was sufficient to control the outbreak if asymptomatic individuals are only half as infectious while if equal infectiousness was assumed then a testing rate of ≥ 10028 tests/ 100000 population would be required. For 50% asymptomatic, minimum blanket testing rates of ≥ 4540 tests/ 100000 population was sufficient to control the outbreak at both assumed levels of infectiousness for asymptomatic individuals relative to symptomatic individuals.Discussion and conclusionOur model predicts that the current testing rates of ≈ 150/100,000 population are inadequate to control transmission of SARS-Cov-2 in Lusaka. Active isolation of COVID-19 cases including asymptomatic individuals through blanket testing can be used as a possible measure for control of the SARS-Cov-2 transmission in Lusaka, Zambia.
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- 2020
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25. ELF4 Expression is Associated with Worse Disease Outcomes and Increased Resistance to Anticancer Agents in Human Cancers
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Panji Nkhoma, Victor Daka, Sody Munsaka, Ephraim Zulu, Rabecca Tembo, Zifa Ngwira, Mildred Zulu, Musalula Sinkala, Doris Kafita, and Florence Mwaba
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Drug ,Messenger RNA ,Disease outcome ,business.industry ,media_common.quotation_subject ,Genomics ,Cell culture ,Transcription (biology) ,Cancer cell ,Cancer research ,Medicine ,business ,Transcription factor ,media_common - Abstract
The malignant phenotype of tumour cells is fuelled by changes in the expression of various transcription factors, which include some of the well-studied proteins such as p53 and Myc. Despite significant progress made, little is known about several other transcription factors, including ELF4, and how they help shape the oncogenic processes that occur in cancer cells. To this end, we performed a bioinformatics analysis to facilitate a detailed understanding of how the transcriptional variations of ELF4 in human cancers are related to disease outcomes and the cancer cell drug responses. Here, using mRNA transcription data of ELF4 from the Cancer Genome Atlas pan-cancer project of 9,350 samples, we identify two groups of patient's tumours: those that expressed high ELF4 transcripts and those that expressed low ELF4 transcripts across 32 different human cancers. We uncover that patients segregated into these two groups are associated with different clinical outcomes. Further, we found that, besides being associated with comparatively worse disease outcomes, tumours that express high ELF4 mRNA transcript tend to be of a higher-grade, afflict a significantly older patient population and have a significantly higher mutation burden. By analysing dose-response profiles to 397 anti-cancer drugs of 612 well-characterised human cancer cell lines from the Genomics of Drug Sensitivity in Cancer, we discover that cell lines that express high ELF4 mRNA transcript are significantly less responsive to 129 anti-cancer drugs. Collectively our analyses have shown that, across the 32 different human cancers, the patients afflicted with tumours that overexpress ELF4 tended to have a more aggressive disease that is also is more likely more refractory to most anti-cancer drugs, a finding upon which we could devise novel categorisation of patient tumours, treatment and prognostic strategies.
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- 2020
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26. Immunity, parasites, genetics and sex hormones: contributors to mild inflammatory responses in COVID-19?
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Sody Munsaka, Mulemba Tillika Samutela, Samuel Munalula Munjita, and Kunda Ndashe
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2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,Essay ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,030231 tropical medicine ,Rodentia ,Inflammation ,parasites ,Severity of Illness Index ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Immunity ,Pandemic ,Parasitic Diseases ,Animals ,Humans ,Medicine ,genetics ,030212 general & internal medicine ,Gonadal Steroid Hormones ,hormones ,business.industry ,COVID-19 ,General Medicine ,cytokines ,mild symptoms ,Immunology ,medicine.symptom ,business ,Hormone - Abstract
The Coronavirus disease 2019 (COVID-19) pandemic has killed over two hundred thousand people by end of April, 2020. America and Europe top in deaths from COVID-19 whereas the numbers are lower in Africa for unclear reasons. Emerging evidence suggests the role of hyperactive immune responses characterised by high pro-inflammatory cytokines in severe cases of COVID-19 and deaths. In this perspective, we explore the possible factors that may contribute to mild inflammatory responses in some cases of COVID-19 by focusing on immune education, parasites, sex hormones and chronic diseases, as well as genetic tolerance. To build our perspective, evidence is also extracted from wild rodents due to their multi-tasking immune responses as a result of constant exposure to pathogens.
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- 2020
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27. Effects of Blood Sugar Levels, Kidney Disease and Medication on Anaemia Status of Type 2 Diabetes Mellitus Patients
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Pauline Okuku, Malala Mulavu, Panji Nkhoma, Mildred Zulu, Sody Munsaka, and Musalula Sinkala
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medicine.medical_specialty ,business.industry ,Insulin ,medicine.medical_treatment ,Blood sugar ,Renal function ,Type 2 Diabetes Mellitus ,Disease ,medicine.disease ,Metformin ,Internal medicine ,Diabetes mellitus ,medicine ,business ,medicine.drug ,Kidney disease - Abstract
IntroductionLifestyle-related diseases like type 2 diabetes mellitus, have emerged as a significant public health problem due to rapid urbanization and industrialization. In 2018, the prevalence of type 2 diabetes mellitus was estimated to be 500 million cases worldwide and was comparable between high- and low-income countries. Diabetes leads to multiple complications, including end-stage renal disease, cardiovascular disease, infection, and death. Anaemia in diabetic individuals has severe adverse effects on the quality of life and is associated with disease progression. A cross-sectional study was conducted that included 101 participants. The study aimed to determine the prevalence of anaemia and kidney disease and their interplay with medication and/or blood glucose levels in T2D patients.Resultsseventy-one per cent of participants were females. Majority of patients 62% were on Insulin, 30% on metformin, 7% on a combination of metformin and glimepiride and 1% on glimepiride. Ninety-five (94%) of the participants were HIV negative. The prevalence of anaemia among the participants was 23% out of which 56% had moderate anaemia, and 44% had mild anaemia. Twenty-one per cent (21%) of the participants had high creatinine levels signifying impaired kidney function or kidney disease. Anaemia was significantly associated with kidney function, fasting blood glucose and use of metformin; p = 0.042 beta = 2.5, p = 0.025 beta = 2.7 and p = 0.040 beta = −2.5 respectively.ConclusionThe study found the prevalence of anaemia of 23%, which was of moderate public health concern. Also, the prevalence of kidney disease was high in patients with Type 2 Diabetes Mellitus. It also found that kidney disease and high blood glucose levels increase the chances of developing anaemia. However, we found that metformin had a protective role against the development of anaemia in Type 2 Diabetes Mellitus patients.
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- 2020
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28. In-vitro inhibitory effect of maternal breastmilk components on rotavirus vaccine replication and association with infant seroconversion to live oral rotavirus vaccine
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Cynthia Mubanga Phiri, Sody Munsaka, Sallie R. Permar, Caroline C. Chisenga, Michelo Simuyandi, Samuel Bosomprah, Roma Chilengi, Katayi Mwila Kazimbaya, and Natasha Makabilo Laban
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Rotavirus ,RNA viruses ,Viral Diseases ,Administration, Oral ,medicine.disease_cause ,Virus Replication ,Pathology and Laboratory Medicine ,Families ,Immunodeficiency Viruses ,Reoviruses ,Medicine ,Public and Occupational Health ,Children ,Vaccines ,Multidisciplinary ,biology ,Lactoferrin ,Viral Vaccine ,Rotavirus vaccine ,Vaccination and Immunization ,Titer ,Seroconversion ,Medical Microbiology ,Viral Pathogens ,Viruses ,Infectious diseases ,Female ,Pathogens ,Infants ,Research Article ,Medical conditions ,Science ,Immunology ,In Vitro Techniques ,Vaccines, Attenuated ,Microbiology ,Virus ,Cell Line ,Virology ,Infectious disease control ,Vaccine Development ,Retroviruses ,Humans ,Microbial Pathogens ,Rotavirus Infection ,Medicine and health sciences ,Milk, Human ,Biology and life sciences ,business.industry ,Viral vaccines ,Lentivirus ,Rotavirus Vaccines ,HIV vaccines ,Organisms ,Infant ,HIV ,Vaccine efficacy ,Viral Replication ,Immunoglobulin A ,Age Groups ,Immunoglobulin G ,People and Places ,biology.protein ,Population Groupings ,Preventive Medicine ,business - Abstract
BackgroundDespite contributing to a significant reduction in rotavirus associated diarrhoea in highly burdened low- and middle-income countries, live attenuated, oral rotavirus vaccines have lower immunogenicity and efficacy in these settings in comparison to more developed countries. Breastmilk has been implicated among factors contributing to this lowered oral vaccine efficacy. We conductedin-vitroexperiments to investigate the inhibitory effects of maternal antibody and other non-antibody components in breastmilk on rotavirus vaccine strain (Rotarix) multiplication in MA104 cell culture system and assessed associations within-vivovaccine seroconversion in vaccinated infants.MethodsBreastmilk samples were collected from mothers before routine rotavirus vaccination of their infant at 6 weeks of age. For each sample, whole breastmilk, purified IgA, purified IgG and IgG and IgA depleted breastmilk samples were prepared as exposure preparations. A 96 well microtitre plate was set up for each sample including a control in which only MA104 cells were grown as well as a virus control with MA104 cells and virus only. The outcome of interest was 50% inhibition dilution of each of the exposure preparations calculated as the titer at which 50% of virus dilution was achieved. Samples from 30 women were tested and correlated to vaccine seroconversion status of the infant. HIV status was also correlated to antiviral breastmilk proteins.ResultsThe mean 50% inhibitory dilution titer when whole breastmilk was added to virus infected MA104 cells was 14.3 (95% CI: 7.1, 22.7). Incubation with purified IgG resulted in a mean 50% inhibitory dilution of 5 (95%CI -1.6, 11.6). Incubating with purified IgA resulted in a mean 50% inhibitory dilution of 6.5 (95% CI -0.7, 13.7) and IgG and IgA depleted breastmilk did not yield any inhibition with a titer of 1.06 (95%CI 0.9, 1.2). Higher milk IgA levels contributed to a failure of infants to seroconvert. HIV was also not associated with any antiviral breastmilk proteins.Discussion and conclusionWhole breastmilk and breastmilk purified IgG and IgA fractions showed inhibitory activity against the rotavirus vaccine Rotarix™ whilst IgA and IgG depleted breastmilk with non-antibody breastmilk fraction failed to show any inhibition activityin-vitro. These findings suggest that IgA and IgG may have functional inhibitory properties and indicates a possible mechanism of how mothers in rotavirus endemic areas with high titres of IgA and IgG may inhibit viral multiplication in the infant gut and would potentially contribute to the failure of their infants to serocovert. There was not association of HIV with either lactoferrin, lactadherin or tenascin-C concentrations.
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- 2020
29. Elevated Eosinophils as a Feature of Inflammation Associated With Hypertension in Virally Suppressed People Living With HIV
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Douglas C. Heimburger, Fernando Elijovich, Wilbroad Mutale, Geoffrey Kwenda, Benson M. Hamooya, Sody Munsaka, Shilin Zhao, John R. Koethe, Selestine Nzala, Annet Kirabo, and Sepiso K. Masenga
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2. Zero hunger ,0303 health sciences ,business.industry ,Inflammation ,Disease ,030204 cardiovascular system & hematology ,Eosinophil ,3. Good health ,Proinflammatory cytokine ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,medicine.anatomical_structure ,Immunology ,medicine ,Eosinophilia ,Tumor necrosis factor alpha ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Body mass index ,030304 developmental biology - Abstract
Background People living with HIV ( PLWH ) are at increased risk of cardiovascular disease, including hypertension, which persists despite effective plasma viral suppression on antiretroviral therapy. HIV infection is characterized by long‐term alterations in immune function, but the contribution of immune factors to hypertension in PLWH is not fully understood. Prior studies have found that both innate and adaptive immune cell activation contributes to hypertension. Methods and Results We hypothesized that chronic inflammation may contribute to hypertension in PLWH . To test this hypothesis, we enrolled a cohort of 70 PLWH (44% hypertensive) on a long‐term single antiretroviral therapy regimen for broad phenotyping of inflammation biomarkers. We found that hypertensive PLWH had higher levels of inflammatory cytokines, including tumor necrosis factor‐α receptor 1, interleukin‐6, interleukin‐17, interleukin‐5, intercellular adhesion molecule 1 and macrophage inflammatory protein‐1α. After adjustment for age, sex, and fat mass index, the circulating eosinophils remained significantly associated with hypertension. On the basis of these results, we assessed the relationship of eosinophils and hypertension in 2 cohorts of 50 and 81 039 similar HIV ‐negative people; although eosinophil count was associated with prevalent hypertension, this relationship was abrogated by body mass index. Conclusions These findings may represent a unique linkage between immune status and cardiovascular physiological characteristics in HIV infection, which should be evaluated further.
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- 2020
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30. Cells of the Innate and Adaptive Immune Systems in Kaposi’s Sarcoma
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Owen Ngalamika and Sody Munsaka
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Cell type ,Immunology ,Cell ,Review Article ,Adaptive Immunity ,Malignancy ,Immunomodulation ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Tumor Microenvironment ,medicine ,Animals ,Humans ,Immunology and Allergy ,Molecular Targeted Therapy ,Sarcoma, Kaposi ,Kaposi's sarcoma ,030304 developmental biology ,0303 health sciences ,business.industry ,virus diseases ,Herpesviridae Infections ,General Medicine ,biochemical phenomena, metabolism, and nutrition ,RC581-607 ,Cell Transformation, Viral ,medicine.disease ,Combined Modality Therapy ,Immunity, Innate ,medicine.anatomical_structure ,Immune System ,030220 oncology & carcinogenesis ,Herpesvirus 8, Human ,Narrative review ,Disease Susceptibility ,Sarcoma ,Immunologic diseases. Allergy ,business - Abstract
Kaposi’s sarcoma (KS) is an angioproliferative malignancy whose associated etiologic agent is the Kaposi’s sarcoma-associated herpesvirus (KSHV). KS is the most prevalent malignancy among HIV-infected individuals globally and is considered an AIDS-defining malignancy. The different forms of KS including HIV-associated KS, iatrogenic (immunosuppression-related) KS, and classical KS in elderly males suggest that immune cell dysregulation is among the key components in promoting KS development in KSHV-infected individuals. It is therefore expected that different cell types of the immune system likely play distinct roles in promoting or inhibiting KS development. This narrative review is focused on discussing cells of the innate and adaptive immune systems in KSHV infection and KS pathogenesis, including how these cells can be useful in the control of KSHV infection and treatment of KS.
- Published
- 2020
31. Patho-immune Mechanisms of Hypertension in HIV: a Systematic and Thematic Review
- Author
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John R. Koethe, Benson M. Hamooya, Douglas C. Heimburger, Selestine Nzala, Annet Kirabo, Sepiso K. Masenga, Wilbroad Mutale, Geoffrey Kwenda, and Sody Munsaka
- Subjects
Nephrology ,medicine.medical_specialty ,T cell ,Human immunodeficiency virus (HIV) ,Inflammation ,HIV Infections ,Disease ,030204 cardiovascular system & hematology ,medicine.disease_cause ,Pathogenesis ,Inflammation and Cardiovascular Diseases (A Kirabo, Section Editor) ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Internal Medicine ,medicine ,Prevalence ,Humans ,030212 general & internal medicine ,Patho-immune mechanisms ,Immunity, Cellular ,business.industry ,Interleukin ,HIV ,3. Good health ,Immunity, Humoral ,Systematic review ,medicine.anatomical_structure ,Cardiovascular Diseases ,Hypertension ,medicine.symptom ,business - Abstract
Purpose of Review To systematically review recent findings on the role of immune cell activation in the pathogenesis of hypertension in people living with HIV (PLWH) and compare studies from Sub-Saharan Africa with what is reported in the USA and European literature according to guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Recent Findings PLWH have an increased risk for development of hypertension and cardiovascular disease. Chronic immune activation contributes to hypertension but the inflammatory milieu that predisposes PLWH to hypertension is poorly understood. We identified 45 relevant studies from 13 unique African countries. The prevalence of hypertension in PLWH on antiretroviral therapy (ART) and the ART-naive PLWH ranged from 6 to 50% and 2 to 41%, respectively. Interleukin (IL)-17A, interferon (IFN)-γ, and higher CD4+ T cell counts were associated with hypertension in ART-treated participants. Summary Targeting adaptive immune activation could provide improved care for hypertensive PLWH. Further research is needed to characterize the inflammatory milieu contributing to hypertension in PLWH especially in African populations where the global burden of HIV is the highest.
- Published
- 2019
32. HIV, immune activation and salt-sensitive hypertension (HISH): a research proposal
- Author
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Annet Kirabo, John R. Koethe, Douglas C. Heimburger, Benson M. Hamooya, Sody Munsaka, Sepiso K. Masenga, Wilbroad Mutale, Selestine Nzala, and Geoffrey Kwenda
- Subjects
0301 basic medicine ,Adult ,Male ,Salt-sensitivity ,Human immunodeficiency virus (HIV) ,lcsh:Medicine ,Zambia ,Inflammation ,Blood Pressure ,HIV Infections ,medicine.disease_cause ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Immune Cell Activation ,Medicine ,Humans ,030212 general & internal medicine ,Prospective Studies ,Sodium Chloride, Dietary ,lcsh:Science (General) ,lcsh:QH301-705.5 ,Immune activation ,business.industry ,lcsh:R ,virus diseases ,HIV ,General Medicine ,3. Good health ,Research Note ,030104 developmental biology ,Blood pressure ,lcsh:Biology (General) ,Anti-Retroviral Agents ,Research Design ,Salt sensitivity ,Immune System ,Immunology ,Hypertension ,Female ,Animal studies ,medicine.symptom ,business ,Dietary salt ,lcsh:Q1-390 - Abstract
Objective The objective of this study is to quantify and compare the effect of excess dietary salt on immune cell activation and blood pressure in HIV versus HIV negative individuals. Results Salt-sensitivity is associated with increased immune cell activation in animal studies. This concept has not been tested in people living with HIV. This study will therefore add more information in elucidating the interaction between HIV infection and/or anti-retroviral therapy (ART), immune-activation/inflammation and hypertension. Electronic supplementary material The online version of this article (10.1186/s13104-019-4470-2) contains supplementary material, which is available to authorized users.
- Published
- 2019
33. Nature and role of traditional forms of counselling in Zambia: a case of Lusaka province
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Hector Chiboola and Sody Munsaka
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Medical education ,Data collection ,business.industry ,05 social sciences ,Gender studies ,Sample (statistics) ,Focus group ,Unit of analysis ,Nonprobability sampling ,050106 general psychology & cognitive sciences ,Snowball sampling ,0502 economics and business ,Medicine ,0501 psychology and cognitive sciences ,business ,050203 business & management ,Applied Psychology ,Social influence ,Qualitative research - Abstract
The aim of this study was to determine the nature and role of traditional forms of counselling and the scope of common problems presented to traditional counsellors in Lusaka province. It used a qualitative research methodology and deployed a holistic single-case study design with multiple embedded units of analysis. The sample consisted of 80 adult participants and one focus group interview with 8 discussants; and it was selected based on the purposive sampling method and snowball technique. Data collection was elicited through structured individual interviews and semi-structured group interview. The study revealed that traditional forms of counselling are rooted in traditional systems of knowledge and sociocultural values, customs, and practices; and they are essentially community-based and multicultural in nature.
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- 2016
- Full Text
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34. Zika Virus: Why Should We Care? What Do We Do About It?
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Sody Munsaka
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biology ,business.industry ,Medicine ,biology.organism_classification ,business ,Virology ,Zika virus - Published
- 2016
- Full Text
- View/download PDF
35. Efficacy and Effectiveness of Rotavirus Vaccine on Incidence of Diarrhoea among Children: A Meta-analysis
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Michelo Simuy, Samue Bosomprah, Sody Munsaka, Katayi Mwila-Kazimbaya, Caroline C. Chisenga, and Roma Chilengi
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medicine.medical_specialty ,business.industry ,Incidence (epidemiology) ,Booster dose ,Vaccine efficacy ,medicine.disease_cause ,Rotavirus vaccine ,Confidence interval ,Internal medicine ,Meta-analysis ,Relative risk ,Rotavirus ,medicine ,business - Abstract
Background: Introduction of rotavirus vaccines has resulted in a decrease in rotavirus related mortality and morbidity. We sought to conduct a meta-analysis to estimate the effect of rotavirus vaccine on incidence of diarrhoea. Methods: The MEDLINE database was searched through PubMed interface using both textword and subject headings (MeSH). The search strategies were [“rotavirus vaccine effectiveness” or “rotavirus vaccine efficacy” or “rotavirus vaccine eff*”]. The reference lists of the most recent studies identified by the search were checked for additional studies (if not already retrieved). We included both randomised trials and observational studies, which investigated the effect of rotavirus vaccine on incidence of diarrhoea. Results: There was strong evidence of vaccine efficacy (70%) on incidence of diarrhoea (Pooled risk ratio (pRR)=0.30; 95% confidence interval (CI)=(0.24,0.38); p
- Published
- 2018
- Full Text
- View/download PDF
36. Independent and Co-morbid HIV Infection and Meth Use Disorders on Oxidative Stress Markers in the Cerebrospinal Fluid and Depressive Symptoms
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Marla J. Berry, Sody Munsaka, Xiaosha Pang, Linda Chang, and Jun Panee
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Male ,Aging ,medicine.medical_specialty ,Amphetamine-Related Disorders ,Immunology ,Neuroscience (miscellaneous) ,HIV Infections ,medicine.disease_cause ,Article ,Methamphetamine ,chemistry.chemical_compound ,Cerebrospinal fluid ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Depression (differential diagnoses) ,Psychiatric Status Rating Scales ,Pharmacology ,chemistry.chemical_classification ,Depression ,business.industry ,Glutathione peroxidase ,Meth ,Glutathione ,Middle Aged ,Oxidative Stress ,Endocrinology ,chemistry ,Dementia ,Female ,business ,Biomarkers ,Oxidative stress ,medicine.drug - Abstract
Both HIV infection and Methamphetamine (Meth) use disorders are associated with greater depressive symptoms and oxidative stress; whether the two conditions would show additive or interactive effects on the severity of depressive symptoms, and whether this is related to the level of oxidative stress in the CNS is unknown. 123 participants were evaluated, which included 41 HIV-seronegative subjects without substance use disorders (Control), 25 with recent (
- Published
- 2015
- Full Text
- View/download PDF
37. Magnetic Resonance Spectroscopy to Assess NeuroInflammation and Neuropathic Pain
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Thomas Ernst, Stephanie D. Kraft-Terry, Linda Chang, and Sody Munsaka
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Pathology ,medicine.medical_specialty ,Magnetic Resonance Spectroscopy ,Immunology ,Neuroscience (miscellaneous) ,Article ,chemistry.chemical_compound ,medicine ,Immunology and Allergy ,Choline ,Animals ,Humans ,Neuroinflammation ,Pharmacology ,Inflammation ,Neurons ,Microglia ,business.industry ,Multiple sclerosis ,Chronic pain ,Glutamate receptor ,Methamphetamine ,medicine.disease ,medicine.anatomical_structure ,chemistry ,nervous system ,Neuropathic pain ,Neuralgia ,business ,Neuroscience ,medicine.drug - Abstract
Proton magnetic resonance spectroscopy ((1)H MRS) has been applied to numerous clinical studies, especially for neurological disorders. This technique can non-invasively evaluate brain metabolites and neurochemicals in selected brain regions and is particularly useful for assessing neuroinflammatory disorders. Neurometabolites assessed with MRS include the neuronal markers N-acetylaspartate (NAA) and glutamate (Glu), as well as the glial marker myo-inositol (MI). Therefore, the concentrations of these metabolites typically correspond to disease severity and often correlate well with clinical variables in the various brain disorders. Neuroinflammation with activated astrocytes and microglia in brain disorders are often associated with elevated MI, and to a lesser extent elevated total creatine (tCr) and choline containing compounds (Cho), which are found in higher concentrations in glia than neurons, while neuronal injury is indicated by lower than normal levels of NAA and Glu. This review summarizes the neurometabolite abnormalities found in MRS studies performed in patients with neuroinflammatory disorders or neuropathic pain, which also may be associated with neuroinflammation. These brain disorders include multiple sclerosis, neuroviral infections (including Human Immunodeficiency virus and Hepatitis C), degenerative brain disorders (including Alzheimer's disease and Parkinson's disease), stimulant abuse (including methamphetamine and cocaine) as well as several chronic pain syndromes.
- Published
- 2013
38. APOE ε 4 allele and CSF APOE on cognition in HIV-infected subjects
- Author
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Avindra Nath, Caroline S. Jiang, Ute Feger, Linda Chang, Sody Munsaka, and Marilou A. Andres
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Apolipoprotein E ,Male ,medicine.medical_specialty ,Pathology ,AIDS Dementia Complex ,Genotype ,Immunology ,Apolipoprotein E4 ,Neuroscience (miscellaneous) ,Enzyme-Linked Immunosorbent Assay ,Neuropsychological Tests ,Article ,Apolipoproteins E ,Cerebrospinal fluid ,Cognition ,Internal medicine ,medicine ,Immunology and Allergy ,Dementia ,Humans ,Protein Isoforms ,Genetic Predisposition to Disease ,Neuropsychological assessment ,Effects of sleep deprivation on cognitive performance ,Allele ,Alleles ,Pharmacology ,medicine.diagnostic_test ,Middle Aged ,medicine.disease ,Endocrinology ,lipids (amino acids, peptides, and proteins) ,Female ,Psychology - Abstract
The significance of the cerebrospinal fluid (CSF) Apolipoprotein E (APOE) level and whether it might have differential effects on brain function due to the presence of APOE e 4 allele(s) in HIV-infected patients are unknown. However, APOE e 4 allele has been associated with greater incidence of HIV-associated dementia and accelerated progression of HIV infection. Here, we show further evidence for the role of APOE e 4 in promoting cognitive impairment. We measured the APOE levels in the CSF of HIV-infected individuals. HIV+ subjects showed lower CSF APOE proteins than SN controls (-19%, p= 0.03). While SN subjects with or without e 4 allele showed no difference in CSF APOE levels, e 4+ HIV+ subjects had similar levels to the SN subjects but higher levels than e 4- HIV+ subjects (+34%, p= 0.01). Furthermore, while HIV+ subjects with e 2 or e 3 allele(s) showed a positive relationship between their CSF APOE levels and cognitive performance on the speed of processing domain (r= +0.35, p= 0.05), e 4+ HIV+ subjects, in contrast, exhibited a negative relationship such that those with higher levels of CSF APOE(4) performed worse on the HIV Dementia Scale (r= -0.61, p= 0.02), had lower Global Cognitive Scores (r= -0.57, p= 0.03), and had poorer performance on tests involving learning (e 4 allele x [APOE] interaction, p = 0.01). Our findings also suggest that the relatively higher levels of CSF APOE in e 4+ HIV+ (having primarily APOE4 isoforms) may negatively impact the brain and lead to poorer cognitive outcomes, while those individuals without the e 4 allele (with primarily APOE2 or APOE3 isoforms) may show compensatory responses that lead to better cognitive performance.
- Published
- 2010
39. Characteristics of Activated Monocyte Phenotype Support R5-Tropic Human Immunodeficiency Virus
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Sody Munsaka, Ningjie Hu, Melissa Agsalda, David Troelstrup, Qigui Yu, and Bruce Shiramizu
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medicine.diagnostic_test ,Lipopolysaccharide ,business.industry ,CD14 ,Monocyte ,Immunology ,virus diseases ,CD16 ,Bioinformatics ,Virus ,Article ,Flow cytometry ,Pathogenesis ,chemistry.chemical_compound ,medicine.anatomical_structure ,chemistry ,medicine ,Immunology and Allergy ,Tumor necrosis factor alpha ,business - Abstract
Background: Microbial translocation has been recognized as an important factor in monocyte activation and contributing to AIDS pathogenesis with elevated plasma lipopolysaccharide (LPS) levels, as a marker for microbial translocation, seen in advanced HIV disease. Therefore, the current study was undertaken to assess monocyte activation in vitro by LPS and to determine its impact on monocyte phenotype. Methods: Monocytes from non-HIV-infected donors were analyzed for CD14, CD16, CD69, TNFα, and CCR5 by flow cytometry pre- and post-stimulation with LPS. In-vitro cultures were then set up to expose non-activated and activated monocytes to R5-, X4-, and dual (R5/X4)-tropic viruses; and the amount of HIV present on the cells was assayed. Results: Non-HIV-infected monocytes, after LPS stimulation, were confirmed to have an activated phenotype with increase in CD16 and CD69 surface expressions (p 0.05). The activation phenotype was supported by increase in TNFα production, p 0.05. The activated monocytes had increased surface CCR5 (from 21% to 98%; p = 0.05); and were found to have more R5-tropic virus than non-activated monocytes (p 0.05). Conclusions: Following activation by LPS, non-HIV-infected monocytes were found to have increase in surface CCR5. These activated monocytes, when exposed to R5-tropic virus, were found to have more virus compared to non-activated monocytes. The significance of the findings could lie in explaining how microbial translocation plays a role in HIV progression; and possibly promoting CCR5-directed strategies in treating HIV.
- Published
- 2009
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