Browsing by Author "Munsaka S"

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Antimicrobial resistance and heterogeneity of Neisseria gonorrhoeae isolated from patients attending sexually transmitted infection clinics in Lusaka, Zambia.
(2024-Mar-18) Sarenje KL; van Zwetselaar M; Kumburu H; Sonda T; Mmbaga B; Ngalamika O; Maimbolwa MC; Siame A; Munsaka S; Kwenda G; Kilimanjaro Christian Medical University College, Moshi, Tanzania.; Department of Midwifery Child, and Women's Health, School of Nursing Sciences, University of Zambia, Lusaka, Zambia.; Department of Dermato-venereology, University Teaching Hospital, Lusaka, Zambia.; Kilimanjaro Christian Medical Centre, Moshi, Tanzania.; Kilimanjaro Clinical Research Institute, Moshi, Kilimanjaro, Tanzania.; Department of Dermato-venereology, University Teaching Hospital, Lusaka, Zambia. kelvinsarenje@gmail.com.; Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka, P.O. Box 50110, Zambia.; Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka, P.O. Box 50110, Zambia. kelvinsarenje@gmail.com.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Antimicrobial resistance (AMR) of Neisseria gonorrhoeae is a threat to public health as strains have developed resistance to antimicrobials available for the treatment of gonorrhea. Whole genome sequencing (WGS) can detect and predict antimicrobial resistance to enhance the control and prevention of gonorrhea. Data on the molecular epidemiology of N. gonorrhoeae is sparse in Zambia. This study aimed to determine the genetic diversity of N. gonorrhoeae isolated from patients attending sexually transmitted infection (STI) clinics in Lusaka, Zambia. METHODS: A cross-sectional study that sequenced 38 N. gonorrhoeae isolated from 122 patients with gonorrhea from 2019 to 2020 was conducted. The AMR profiles were determined by the E-test, and the DNA was extracted using the NucliSens easyMaG magnetic device. Whole genome sequencing was performed on the Illumina NextSeq550 platform. The Bacterial analysis pipeline (BAP) that is readily available at: https://cge.cbs.dtu.dk/services/CGEpipeline-1.1 was used for the identification of the species, assembling the genome, multi-locus sequence typing (MLST), detection of plasmids and AMR genes. Phylogeny by single nucleotide polymorphisms (SNPs) was determined with the CCphylo dataset. RESULTS: The most frequent STs with 18.4% of isolates each were ST CONCLUSION: This study revealed remarkable heterogeneity of N. gonorrhoeae with bla
Characterizing Epstein-Barr virus infection of the central nervous system in Zambian adults living with HIV.
(2023-Dec) Musukuma-Chifulo K; Ghebremichael M; Chilyabanyama ON; Bates M; Munsaka S; Simuyandi M; Chisenga C; Tembo J; Sinkala E; Koralnik IJ; Dang X; Chilengi R; Siddiqi OK; Harvard Medical School and Ragon Institute of Mass General, MIT and Harvard, Boston, MA, USA.; Department of Biomedical Sciences, School of Health Sciences, The University of Zambia, Lusaka, Zambia. kalomusukuma@gmail.com.; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.; Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia. kalomusukuma@gmail.com.; Center for Vaccines and Virology Research, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.; HerpeZ, University Teaching Hospital, Lusaka, Zambia.; Global Neurology Program, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA.; Department of Internal Medicine, University of Zambia School of Medicine, Lusaka, Zambia.; School of Life & Environmental Sciences, University of Lincoln, Lincoln, UK.; Department of Biomedical Sciences, School of Health Sciences, The University of Zambia, Lusaka, Zambia.; Zambia National Public Health Institute, Ministry of Health, 10101, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
The significance of Epstein-Barr virus (EBV) detection in the cerebrospinal spinal fluid (CSF) in people living with HIV (PLWH) is not entirely understood. The detection of EBV DNA may represent active central nervous system (CNS) infection, reactivation in the setting of another CNS pathogen or due to impaired immunity, or detection of quiescent virus. We screened 470 adult PLWH in Zambia with neurological symptoms for the presence of EBV DNA in the CSF. We performed quantitative EBV PCR on the CSF and blood. We then performed quantitative EBV DNA PCR on the blood of controls with documented HIV viral suppression without CNS symptoms. The prevalence of EBV DNA in the CSF of patients with CNS symptoms was 28.9% (136/470). EBV DNA positivity was associated with younger age, shorter duration of HIV diagnosis, lower CSF glucose levels, higher CSF protein and white blood cell levels, and a positive CSF Mycobacterium tuberculosis result. The median EBV DNA load was 8000 cps/mL in both the CSF and blood with a range of 2000-2,753,000 cps/mL in the CSF and 1000 to 1,871,000 cps/mL in the blood. Molecular screening of CSF for other possible causes of infection identified Mycobacterium tuberculosis in 30.1% and cytomegalovirus (CMV) in 10.5% of samples. EBV DNA load in the blood and CSF was not associated with mortality. Our results suggest that even though EBV DNA was commonly detected in the CSF of our population, it appears to have limited clinical significance regardless of EBV DNA load.
Effect of innate antiviral glycoproteins in breast milk on seroconversion to rotavirus vaccine (Rotarix) in children in Lusaka, Zambia.
(2017) Mwila-Kazimbaya K; Garcia MP; Bosomprah S; Laban NM; Chisenga CC; Permar SR; Simuyandi M; Munsaka S; Chilengi R; Department of Paediatrics, Human Vaccine Institute, Duke University, Durham, North Carolina.; University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, North Carolina, United States of America.; Department of biomedical sciences, School of Health sciences, University of Zambia, Lusaka, Zambia.; Department of Biostatistics, School of Public Health, University of Ghana, Legon, Accra, Ghana.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
Epstein-Barr Virus Detection in the Central Nervous System of HIV-Infected Patients.
(2022-Sep-22) Musukuma-Chifulo K; Siddiqi OK; Chilyabanyama ON; Bates M; Chisenga CC; Simuyandi M; Sinkala E; Dang X; Koralnik IJ; Chilengi R; Munsaka S; HerpeZ Infection Research and Training, University Teaching Hospital, Lusaka Private Bag RW1X Ridgeway, Lusaka P.O. Box 10101, Zambia.; Department of Biomedical Science, School of Health Sciences, University of Zambia, Lusaka P.O. Box 50110, Zambia.; Department of Research, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia.; Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.; School of Life & Environmental Sciences, University of Lincoln, Lincoln LN6 7TS, UK.; Department of Internal Medicine, School of Medicine, University of Zambia, Lusaka P.O. Box 50110, Zambia.; Department of Internal Medicine, Center for Virology and Vaccines Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.; Global Neurology Program, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
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.
In-vitro inhibitory effect of maternal breastmilk components on rotavirus vaccine replication and association with infant seroconversion to live oral rotavirus vaccine.
(2020) Kazimbaya KM; Chisenga CC; Simuyandi M; Phiri CM; Laban NM; Bosomprah S; Permar SR; Munsaka S; Chilengi R; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Pediatrics, Human Vaccine Institute, Duke University, Durham, North Carolina, United States of America.; Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka, Zambia.; Department of Biostatistics, School of Public Health, University of Ghana, Legon, Accra, Ghana.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Despite 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. METHODS: Breastmilk 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. RESULTS: The 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 CONCLUSION: Whole 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.
Maternal and Infant Histo-Blood Group Antigen (HBGA) Profiles and Their Influence on Oral Rotavirus Vaccine (Rotarix
(2023-Jul-31) Chauwa A; Bosomprah S; Laban NM; Phiri B; Chibuye M; Chilyabanyama ON; Munsaka S; Simuyandi M; Mwape I; Mubanga C; Chobe MC; Chisenga C; Chilengi R; Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.; Department of Global Health, Amsterdam Institute for Global Health and Development (AIGHD), Amsterdam University Medical Centers, University of Amsterdam, 1012 WP Amsterdam, The Netherlands.; Department of Biostatistics, School of Public Health, University of Ghana, Accra P.O. Box LG13, Ghana.; Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka P.O. Box 50110, Zambia.; Enteric Disease and Vaccine Research Unit, Centre for Infectious Disease Research in Zambia, Lusaka P.O. Box 34681, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
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
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.
(2021) Simwaka J; Seheri M; Mulundu G; Kaonga P; Mwenda JM; Chilengi R; Mpabalwani E; Munsaka S; Department of Virology, Diarrhoea Pathogens Research Unit and WHO AFRO Rotavirus Regional Reference Laboratory, South African Medical Research Council, Sefako Makgatho Health Sciences University, Pretoria, South Africa.; Center for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka, Zambia.; Department of Pathology and Microbiology, School of Medicine, University of Zambia, Lusaka, Zambia.; Department of Internal Medicine, University Teaching Hospital, Tropical Gastroenterology and Nutrition Group, Lusaka, Zambia.; Department of Paediatric and Child Health, School of Medicine, University of Zambia, Lusaka, Zambia.; Department of Epidemiology and Biostatistics, School of Public Health, University of Zambia, Lusaka, Zambia.; World Health Organization Regional Office for Africa (WHO/AFRO), Brazzaville, Congo.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: In 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. METHODS: Stool 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. RESULTS: A 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 CONCLUSION: Results 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.