Browsing by Author "Bosomprah S"

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Alcohol-focused and transdiagnostic treatments for unhealthy alcohol use among adults with HIV in Zambia: A 3-arm randomized controlled trial.
(2023-Apr) Vinikoor MJ; Sharma A; Murray LK; Figge CJ; Bosomprah S; Chitambi C; Paul R; Kanguya T; Sivile S; Nghiem V; Cropsey K; Kane JC
BACKGROUND: Clinical and quality of life outcomes in people living with human immunodeficiency virus (PLWH) are undermined by unhealthy alcohol use (UAU), which is highly prevalent in this population and is often complicated by mental health (MH) or other substance use (SU) comorbidity. In sub-Saharan Africa, evidence-based and implementable treatment options for people with HIV and UAU are needed. METHODS: We are conducting a hybrid clinical effectiveness-implementation trial at three public-sector HIV clinics in Lusaka, Zambia. Adults with HIV, who report UAU, and have suboptimal HIV clinical outcomes, will be randomized to one of three arms: an alcohol-focused brief intervention (BI), the BI with additional referral to a transdiagnostic cognitive behavioral therapy (Common Elements Treatment Approach [CETA]), or standard of care. The BI and CETA will be provided by HIV peer counselors, a common cadre of lay health worker in Zambia. Clinical outcomes will include HIV viral suppression, alcohol use, assessed by audio computer-assisted self-interview (ACASI) and direct alcohol biomarkers, Phophatidylethanol and Ethyl glucuronide, and comorbid MH and other SU. A range of implementation outcomes including cost effectiveness will also be analyzed. CONCLUSION: Hybrid and 3-arm trial design features facilitate the integrated evaluation of both brief, highly implementable, and more intensive, less implementable, treatment options for UAU among PLWH in sub-Saharan Africa. Use of ACASI and alcohol biomarkers will strengthen understanding of treatment effects.
Assessment of the influence of ABO blood groups on oral cholera vaccine immunogenicity in a cholera endemic area in Zambia.
(2023-Jan-23) Chisenga CC; Bosomprah S; Chilyabanyama ON; Alabi P; Simuyandi M; Mwaba J; Ng'ombe H; Laban NM; Luchen CC; Chilengi R
BACKGROUND: Histo-blood group antigens (HBGAs) which include the ABO and Lewis antigen systems have been known for determining predisposition to infections. For instance, blood group O individuals have a higher risk of severe illness due to V. cholerae compared to those with non-blood group O antigens. We set out to determine the influence that these HBGAs have on oral cholera vaccine immunogenicity and seroconversion in individuals residing within a cholera endemic area in Zambia. METHODOLOGY: We conducted a longitudinal study nested under a clinical trial in which samples from a cohort of 223 adults who were vaccinated with two doses of Shanchol™ and followed up over 4 years were used. We measured serum vibriocidal geometric mean titers (GMTs) at Baseline, Day 28, Months 6, 12, 24, 30, 36 and 48 in response to the vaccine. Saliva obtained at 1 year post vaccination was tested for HBGA phenotypes and secretor status using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Of the 133/223 participants included in the final analysis, the majority were above 34 years old (58%) and of these, 90% were males. Seroconversion rates to V. cholerae O1 Inaba with non-O (23%) and O (30%) blood types were comparable. The same pattern was observed against O1 Ogawa serotype between non-O (25%) and O (35%). This trend continued over the four-year follow-up period. Similarly, no significant differences were observed in seroconversion rates between the non-secretors (26%) and secretors (36%) against V. cholerae O1 Inaba. The same was observed for O1 Ogawa in non-secretors (22%) and the secretors (36%). CONCLUSION: Our results do not support the idea that ABO blood grouping influence vaccine uptake and responses against cholera.
Association of biomarkers of enteric dysfunction, systemic inflammation, and growth hormone resistance with seroconversion to oral rotavirus vaccine: A lasso for inference approach.
(2023) Mwila-Kazimbaya K; Bosomprah S; Chilyabanyama ON; Chisenga CC; Chibuye M; Laban NM; Simuyandi M; Huffer B; Iturriza-Gomara M; Choy RKM; Chilengi R
BACKGROUND: Rotavirus gastroenteritis remains a leading cause of morbidity and mortality despite the introduction of vaccines. Research shows there are several factors contributing to the reduced efficacy of rotavirus vaccines in low- and middle-income settings. Proposed factors include environmental enteric dysfunction (EED), malnutrition, and immune dysfunction. This study aimed to assess the effect of these factors on vaccine responses using a machine learning lasso approach. METHODS: Serum samples from two rotavirus clinical trials (CVIA 066 n = 99 and CVIA 061 n = 124) were assessed for 11 analytes using the novel Micronutrient and EED Assessment Tool (MEEDAT) multiplex ELISA. Immune responses to oral rotavirus vaccines (Rotarix, Rotavac, and Rotavac 5D) as well as a parenteral rotavirus vaccine (trivalent P2-VP8) were also measured and machine learning using the lasso approach was then applied to investigate any associations between immune responses and environmental enteric dysfunction, systemic inflammation, and growth hormone resistance biomarkers. RESULTS: Both oral and parenteral rotavirus vaccine responses were negatively associated with retinol binding protein 4 (RBP4), albeit only weakly for oral vaccines. The parenteral vaccine responses were positively associated with thyroglobulin (Tg) and histidine-rich protein 2 (HRP2) for all three serotypes (P8, P6 and P4), whilst intestinal fatty acid binding protein (I-FABP) was negatively associated with P6 and P4, but not P8, and soluble transferrin receptor (sTfR) was positively associated with P6 only. CONCLUSION: MEEDAT successfully measured biomarkers of growth, systemic inflammation, and EED in infants undergoing vaccination, with RBP4 being the only analyte associated with both oral and parenteral rotavirus vaccine responses. Tg and HRP2 were associated with responses to all three serotypes in the parenteral vaccine, while I-FABP and sTfR results indicated possible strain specific immune responses to parenteral immunization.
Associations of inter-annual rainfall decreases with subsequent HIV outcomes for persons with HIV on antiretroviral therapy in Southern Africa: a collaborative analysis of cohort studies.
(2023-Dec-19) Trickey A; Johnson LF; Fung F; Bonifacio R; Iwuji C; Biraro S; Bosomprah S; Chirimuta L; Euvrard J; Fatti G; Fox MP; Von Groote P; Gumulira J; Howard G; Jennings L; Kiragga A; Muula G; Tanser F; Wagener T; Low A; Vickerman P
BACKGROUND: Periods of droughts can lead to decreased food security, and altered behaviours, potentially affecting outcomes on antiretroviral therapy (ART) among persons with HIV (PWH). We investigated whether decreased rainfall is associated with adverse outcomes among PWH on ART in Southern Africa. METHODS: Data were combined from 11 clinical cohorts of PWH in Lesotho, Malawi, Mozambique, South Africa, Zambia, and Zimbabwe, participating in the International epidemiology Databases to Evaluate AIDS Southern Africa (IeDEA-SA) collaboration. Adult PWH who had started ART prior to 01/06/2016 and were in follow-up in the year prior to 01/06/2016 were included. Two-year rainfall from June 2014 to May 2016 at the location of each HIV centre was summed and ranked against historical 2-year rainfall amounts (1981-2016) to give an empirical relative percentile rainfall estimate. The IeDEA-SA and rainfall data were combined using each HIV centre's latitude/longitude. In individual-level analyses, multivariable Cox or generalized estimating equation regression models (GEEs) assessed associations between decreased rainfall versus historical levels and four separate outcomes (mortality, CD4 counts < 200 cells/mm RESULTS: Among 270,708 PWH across 386 HIV centres (67% female, median age 39 [IQR: 32-46]), lower rainfall than usual was associated with higher mortality (adjusted Hazard Ratio: 1.18 [95%CI: 1.07-1.32] per 10 percentile rainfall rank decrease) and unsuppressed viral loads (adjusted Odds Ratio: 1.05 [1.01-1.09]). Levels of rainfall were not strongly associated with CD4 counts < 200 cell/mm CONCLUSIONS: Decreased rainfall could negatively impact on HIV treatment behaviours and outcomes. Further research is needed to explore the reasons for these effects. Interventions to mitigate the health impact of severe weather events are required.
Burden of chronic kidney diseases and underlying causes in Zambia: evidence from the global burden of disease study 2019.
(2023-Feb-18) Bosomprah S; Bjonstad EC; Musuku J; Siyumbwa N; Ngandu M; Chisunka M; Banda P; Goma F; Mweemba A
INTRODUCTION: Chronic kidney disease (CKD) has been a global public health problem and a major source of suffering and poor quality of life for those afflicted. Using data from the global burden of disease (GBD) study 2019, we estimated the magnitude of the burden of CKD as well as the underlying causes of CKD in the Zambian population. METHOD: The data used for this study were extracted from the GBD 2019 study. The GBD 2019 provides estimates of several metrics of disease burden including the commonly used disability-adjusted life year (DALYs) for over 369 diseases and injuries, and 87 risk factors and combinations of these in 204 countries and territories from 1990 to 2019. We estimated the burden of CKD as the number and rates (per 100,000 population) of DALYs, disaggregated by year, sex, and age group. We examined the underlying causes of CKD by estimating the population attributable fraction as the percentage contributions of risk factors to CKD DALY. RESULTS: The number of DALYs for CKD was estimated as 76.03 million (95% UI: 61.01 to 93.36) in 2019 compared to 39.42 million (95% UI: 33.09 to 45.90) in 1990, representing 93% increase whereas the DALYs rate per 100,000 population was estimated as 416.89 (95% UI: 334.53 to 511.93) in 2019 compared to 496.38 (95% UI: 416.55 to 577.87) in 1990, representing 16% reduction. CKD due to hypertension accounted for 18.7% of CKD DALYs and CKD due to diabetes (types 1 and 2) accounted for 22.7%, while CKD from glomerulonephritis accounted for the most DALYs at 33%. The age group most impacted from CKD were adolescents and young adults. CONCLUSION: The burden of CKD remains high in the Zambian population with diabetes, high blood pressure, and glomerulonephritis as important causes. The results highlight the need to develop a comprehensive action plan to prevent and treat kidney disease. Increasing the awareness of CKD among the public as well as adaptation of guidelines for treating patients with end stage kidney disease are important considerations.
Comparative analysis of cholera serum vibriocidal antibodies from Convalescent and vaccinated adults in Zambia.
(2024-Aug-13) Ng'ombe H; Bosomprah S; Phiri B; Muchimba M; Liswaniso F; Chibuye M; Luchen CC; Chibesa K; Musukuma-Chifulo K; Mwape K; Tigere S; Silwamba S; Sinkala A; Simuyandi M; Mbewe N; Kapaya F; Cunningham AF; Chilengi R; Sack D; Chisenga CC
Cholera is responsible for 1.3 to 4.0 million cholera cases globally and poses a significant threat, with Zambia reporting 17,169 cases as of 4th February 2024. Recognizing the crucial link between natural cholera infections and vaccine protection, this study aimed to assess immune responses post cholera infection and vaccination. This was a comparative study consisting of 50 participants enrolled during a cholera outbreak in Zambia's Eastern Province and an additional 56 participants who received oral cholera vaccinations in Zambia's Central Province. Vibriocidal antibodies were plotted as geometric mean titres in the naturally infected and vaccinated individuals. A significant difference (p < 0.047) emerged when comparing naturally infected to fully vaccinated individuals (2 doses) on day 28 against V. cholerae Ogawa. Those who received two doses of the oral cholera vaccine had higher antibody titres than those who were naturally infected. Notably, the lowest titres occurred between 0-9 days post onset, contrasting with peak responses at 10-19 days. This study addresses a critical knowledge gap in understanding cholera immunity dynamics, emphasizing the potential superiority of vaccination-induced immune responses. We recommend post infection vaccination after 40 days for sustained immunity and prolonged protection, especially in cholera hotspots.
Comparative effectiveness of in-person vs. remote delivery of the Common Elements Treatment Approach for addressing mental and behavioral health problems among adolescents and young adults in Zambia: protocol of a three-arm randomized controlled trial.
(2022-May-19) Figge CJ; Kane JC; Skavenski S; Haroz E; Mwenge M; Mulemba S; Aldridge LR; Vinikoor MJ; Sharma A; Inoue S; Paul R; Simenda F; Metz K; Bolton C; Kemp C; Bosomprah S; Sikazwe I; Murray LK
BACKGROUND: In low- and middle-income countries (LMIC), there is a substantial gap in the treatment of mental and behavioral health problems, which is particularly detrimental to adolescents and young adults (AYA). The Common Elements Treatment Approach (CETA) is an evidence-based, flexible, transdiagnostic intervention delivered by lay counselors to address comorbid mental and behavioral health conditions, though its effectiveness has not yet been tested among AYA. This paper describes the protocol for a randomized controlled trial that will test the effectiveness of traditional in-person delivered CETA and a telehealth-adapted version of CETA (T-CETA) in reducing mental and behavioral health problems among AYA in Zambia. Non-inferiority of T-CETA will also be assessed. METHODS: This study is a hybrid type 1 three-arm randomized trial to be conducted in Lusaka, Zambia. Following an apprenticeship model, experienced non-professional counselors in Zambia will be trained as CETA trainers using a remote, technology-delivered training method. The new CETA trainers will subsequently facilitate technology-delivered trainings for a new cohort of counselors recruited from community-based partner organizations throughout Lusaka. AYA with mental and behavioral health problems seeking services at these same organizations will then be identified and randomized to (1) in-person CETA delivery, (2) telehealth-delivered CETA (T-CETA), or (3) treatment as usual (TAU). In the superiority design, CETA and T-CETA will be compared to TAU, and using a non-inferiority design, T-CETA will be compared to CETA, which is already evidence-based in other populations. At baseline, post-treatment (approximately 3-4 months post-baseline), and 6 months post-treatment (approximately 9 months post-baseline), we will assess the primary outcomes such as client trauma symptoms, internalizing symptoms, and externalizing behaviors and secondary outcomes such as client substance use, aggression, violence, and health utility. CETA trainer and counselor competency and cost-effectiveness will also be measured as secondary outcomes. Mixed methods interviews will be conducted with trainers, counselors, and AYA participants to explore the feasibility, acceptability, and sustainability of technology-delivered training and T-CETA provision in the Zambian context. DISCUSSION: Adolescents and young adults in LMIC are a priority population for the treatment of mental and behavioral health problems. Technology-delivered approaches to training and intervention delivery can expand the reach of evidence-based interventions. If found effective, CETA and T-CETA would help address a major barrier to the scale-up and sustainability of mental and behavioral treatments among AYA in LMIC. TRIAL REGISTRATION: ClinicalTrials.gov NCT03458039 . Prospectively registered on May 10, 2021.
Development and validation of a novel scale for antiretroviral therapy readiness among pregnant women in urban Zambia with newly diagnosed HIV infection.
(2023-Apr-06) Mubiana-Mbewe M; Bosomprah S; Saroj RK; Kadota J; Koyuncu A; Thankian K; Vinikoor MJ
BACKGROUND: Women who are newly diagnosed with HIV infection during pregnancy may not be ready to immediately initiate lifelong antiretroviral therapy (ART; called Option B +) as is recommended. Lack of "readiness" drives early disengagement from care and undermines prevention of HIV transmission to infants. Several studies have shown high early attrition of women initiating ART in pregnancy. Although poor ART uptake and adherence have been attributed to various factors including stigma, disclosure issues and structural issues, there is no standard way of determining which pregnant woman will face challenges and therefore need additional support. We developed and validated a novel ART readiness tool in Lusaka, Zambia. METHODS: The aim of this study was to develop and validate a tool that could be used to assess how ready a newly diagnosed pregnant woman living with HIV would be to initiate ART on the day of diagnosis. Using a mixed method design, we conducted this study in three public-setting health facilities in Lusaka, Zambia. Informed by qualitative research and literature review, we identified 27 candidate items. We assessed content validity using expert and target population judgment approaches. We administered the 27-item questionnaire to 454 newly diagnosed pregnant women living with HIV, who were enrolled into a randomized trial (trials number NCT02459678). We performed item reduction analysis and used Cronbach's alpha coefficient of 0.70 as threshold for reliability. RESULTS: A total of 454 pregnant women living with HIV enrolled in the study between March 2017 and December 2017; 452 had complete data for analysis. The correlation coefficient between the 27 items on the completed ART readiness scale ranged from 0.31 to 0.70 while item discrimination index ranged from -0.01 to 2.38. Sixteen items were selected for the final scale, representing three domains, which we classified as "internalized and anticipated HIV stigma", "partner support" and "anticipated structural barriers". CONCLUSION: We developed and validated a tool that could be used to assess readiness of newly diagnosed women living with HIV to initiate ART. This ART readiness tool could allow clinics to tailor limited resources to pregnant women living with HIV needing additional support to initiate and remain on ART.
Development of a diarrhoea severity scoring scale in a passive health facility-based surveillance system.
(2022) St Jean DT; Chilyabanyama ON; Bosomprah S; Asombang M; Velu RM; Chibuye M; Mureithi F; Sukwa N; Chirwa M; Mokha P; Chilengi R; Simuyandi M
BACKGROUND: Diarrhoeal disease remains a leading cause of death among children mostly in low and middle-income countries. Factors contributing to disease severity are complex and there is currently no consensus on a scoring tool for use in community-based studies. METHODS: Data were collected during a passive surveillance system in an outpatient health facility in Lusaka, Zambia from March 2019 to July 2019. Diarrhea episodes were assessed for severity using an in-house severity scoring tool (CIDRZ) and previously published scores (Vesikari, Clark, CODA, and DHAKA). The CIDRZ score was constructed using fieldworker-reported clinical signs and exploratory factor analysis. We used precision-recall curves measuring severe diarrhoea (i.e., requiring intravenous rehydration or referred for hospital admission) to determine the best performing scores. Then, we used Cronbach's alpha to assess the scale's internal consistency. Finally, we used Cohen's kappa to assess agreement between the scores. RESULTS: Of 110 diarrhea episodes, 3 (3%) required intravenous rehydration or were referred for hospital admission. The precision-recall area under the curve of each score as a predictor of severe diarrhoea requiring intravenous rehydration or hospital admission was 0.26 for Vesikari, 0.18 for CODA, 0.24 for Clark, 0.59 for DHAKA, and 0.59 for CIDRZ. The CIDRZ scale had substantial reliability and performed similarly to the DHAKA score. CONCLUSIONS: Diarrhoea severity scores focused on characteristics specific to dehydration status may better predict severe diarrhea among children in Lusaka. Aetiology-specific scoring tools may not be appropriate for use in community healthcare settings. Validation studies for the CIDRZ score in diverse settings and with larger sample sizes are warranted.
Ecological Niche Modeling of
(2023-Sep-08) Velu RM; Kwenda G; Bosomprah S; Chisola MN; Simunyandi M; Chisenga CC; Bumbangi FN; Sande NC; Simubali L; Mburu MM; Tembo J; Bates M; Simuunza MC; Chilengi R; Orba Y; Sawa H; Simulundu E
The circulation of both West Nile Virus (WNV) and Chikungunya Virus (CHIKV) in humans and animals, coupled with a favorable tropical climate for mosquito proliferation in Zambia, call for the need for a better understanding of the ecological and epidemiological factors that govern their transmission dynamics in this region. This study aimed to examine the contribution of climatic variables to the distribution of
Effect of HIV status and retinol on immunogenicity to oral cholera vaccine in adult population living in an endemic area of Lukanga Swamps, Zambia.
(2021) Luchen CC; Mwaba J; Ng'ombe H; Alabi PIO; Simuyandi M; Chilyabanyama ON; Hatyoka LM; Mubanga C; Bosomprah S; Chilengi R; Chisenga CC
BACKGROUND: We set out to assess the impact of human immunodeficiency virus (HIV) and micronutrient deficiency as indicated by serum retinol levels on the immune responses to Oral Cholera Vaccine (Shanchol™) in a cohort of participants in Lukanga Swamps, Zambia. Cholera remains endemic in Zambia with vaccines being the only effective preventive measures. However, the effect of these vaccines on populations living with HIV has not been widely documented. METHODS: HIV testing and confirmation was done using the Alere Determine™ HIV-1/2 and Uni-Gold™ kits while vibriocidal antibody assay was applied for vaccine immunogenicity. Serum retinol analysis was assessed by Shimadzu Prominence HCT-2010 High Performance Liquid Chromatography (HPLC). The primary outcome was log transformed geometric mean titre. RESULTS: From 47 participants screened for HIV, 51% (24) tested positive. There was a statistically significant reduction in Ogawa geometric mean ratio (GMR) by 67% (GMR = 0.33; 95% CI: -0.15, 0.76; p-value = 0.009) attributable to HIV positivity with a non-significant reduction in Inaba GMR by about 50% due to HIV positivity. When doubling of retinol levels modelled, GMR reduction against Ogawa were non-significant but that against Inaba resulted in a significant reduction in geometric mean titer (GMT) (GMT-0.33, C.I 0.16-0.66, p-value 0.002). At 1000copies/ml viral load cut off and 350 cells/μl CD4 counts, Ogawa GMT was two times higher 11.16 (95%CI: 8.20-15.19) versus 6.06 (95%CI: 4.04-9.10) in low viremia participants, and three times higher in above threshold CD4 count participants; 24.81 (95%CI: 18.94-32.50) versus 7.07 (95%CI: 5.22-9.58). CONCLUSION: Our results show that while Shanchol™ is immunogenic in both HIV+/- individuals, HIV + participants responded poorly. Viral load and CD4 count affected vaccine immunogenicity. More research is required for detailed understanding of this in order to appropriately inform policy and practice. DOI: 10.1371/journal.pone.0260552
Evaluation of ROTARIX
(2023-Feb-03) Laban NM; Bosomprah S; Simuyandi M; Chibuye M; Chauwa A; Chirwa-Chobe M; Sukwa N; Chipeta C; Velu R; Njekwa K; Mubanga C; Mwape I; Goodier MR; Chilengi R
Oral rotavirus vaccines show diminished immunogenicity in low-resource settings where rotavirus burden is highest. This study assessed the safety and immune boosting effect of a third dose of oral ROTARIX
Hepatitis B viral replication markers and hepatic fibrosis in untreated chronic hepatitis B virus infection with and without HIV coinfection in Zambia.
(2023-Nov-01) Muula GK; Bosomprah S; Sinkala E; Nsokolo B; Musonda T; Hamusonde K; Bhattacharya D; Lauer G; Chung RT; Mulenga LB; Wandeler G; Vinikoor MJ
BACKGROUND: To inform novel therapies, a more nuanced understanding of HIV's impact on hepatitis B virus (HBV) natural history is needed, particularly in high burden countries. METHODS: In Lusaka, Zambia, we compared prospectively recruited adults (18+ years) with chronic HBV infection, with and without HIV. We excluded those with prior antiviral treatment experience or HBV diagnosis due to clinical suspicion (rather than routine testing). We assessed HBV DNA levels, hepatitis B e antigen (HBeAg), CD4 + (if HIV coinfection), and liver disease (transient elastography, serum alanine aminotransferase). In multivariable analyses, we evaluated the association of HIV overall and by level of CD4 + count on these markers. RESULTS: Among 713 adults analyzed, median age was 33 years, 63% were male, and 433 had HBV/HIV coinfection. Median CD4 + count was 200 cells/μl. HBV DNA was greater than 2000 IU/ml for 311 (51.0%) and 227 (32.5%) were HBeAg-positive. 15.5% had advanced fibrosis or cirrhosis. HIV coinfection was associated with five-fold increased HBV DNA levels [adjusted geometric mean ratio, 5.78; 95% confidence interval (CI), 2.29-14.62] and two times the odds of HBeAg-positivity (adjusted odds ratio, 2.54; 95% CI, 1.59-4.08). These associations were significant only at CD4 + counts 100-350 and <100 cells/μl. HIV was not associated with markers of fibrosis or ALT. DISCUSSION: HIV's impact on HBV natural history likely depends on the degree and duration of immune suppression. There is strong rationale to monitor HBV DNA in people with HBV/HIV coinfection and immune suppression. A better understanding is needed of mechanisms of increased liver-related mortality in people with HBV/HIV coinfection.
Human cytomegalovirus seropositivity and its influence on oral rotavirus vaccine immunogenicity: a specific concern for HIV-exposed-uninfected infants.
(2024-Jun-20) Laban N; Bosomprah S; Chilengi R; Simuyandi M; Chisenga C; Ng'ombe H; Musukuma-Chifulo K; Goodier M
Oral rotavirus vaccines demonstrate diminished immunogenicity in low-income settings where human cytomegalovirus infection is acquired early in childhood and modulates immunity. We hypothesized that human cytomegalovirus infection around the time of vaccination may influence immunogenicity. We measured plasma human cytomegalovirus-specific immunoglobulin M antibodies in rotavirus vaccinated infants from 6 weeks to 12 months old and compared rotavirus immunoglobulin A antibody titers between human cytomegalovirus seropositive and seronegative infants. There was no evidence of an association between human cytomegalovirus serostatus at 9 months and rotavirus-specific antibody titers at 12 months (geometric mean ratio 1.01, 95% CI: 0.70, 1.45; P = 0.976) or fold-increase in RV-IgA titer between 9 and 12 months (risk ratio 0.999, 95%CI: 0.66, 1.52; P = 0.995) overall. However, HIV-exposed-uninfected infants who were seropositive for human cytomegalovirus at 9 months old had a 63% reduction in rotavirus antibody geometric mean titers at 12 months compared to HIV-exposed-uninfected infants who were seronegative for human cytomegalovirus (geometric mean ratio 0.37, 95% CI: 0.17, 0.77; P = 0.008). While the broader implications of human cytomegalovirus infections on oral rotavirus vaccine response might be limited in the general infant population, the potential impact in the HIV-exposed-uninfected infants cannot be overlooked. This study highlights the complexity of immunological responses and the need for targeted interventions to ensure oral rotavirus vaccine efficacy, especially in vulnerable subpopulations.
Immunogenicity and waning immunity from the oral cholera vaccine (Shanchol™) in adults residing in Lukanga Swamps of Zambia.
(2022) Ng Ombe H; Simuyandi M; Mwaba J; Luchen CC; Alabi P; Chilyabanyama ON; Mubanga C; Hatyoka LM; Muchimba M; Bosomprah S; Chilengi R; Kwenda G; Chisenga CC
INTRODUCTION: In cholera endemic areas, the periodicity of cholera outbreaks remains unpredictable, making it difficult to organize preventive efforts. Lack of data on duration of protection conferred by oral cholera vaccines further makes it difficult to determine when to deploy preemptive vaccination. We report on the immunogenicity and waning of immunity to Shanchol™ in Lukanga Swamps. METHODS: We enrolled a cohort of 223 participants aged between 18 and 65 years old from whom serum samples were collected at baseline, day 28 before administration of the second dose, and consecutively at 6, 12, 24, 30, 36, and 48 months. Vibriocidal antibody titres were measured and expressed as geometric mean titres. Box plots and 95% CI were computed at each visit for both Inaba and Ogawa. Seroconversion was defined as a four fold or greater increase in antibody titres compared to baseline titres. RESULTS: Overall, seroconversion against V. cholerae Inaba and Ogawa after 1st dose was 35/134 (26%) and 34/134 (25%) respectively. We observed a statistical difference in seroconversion between the two subgroups of baseline titres (low <80 and high ≥80) for both Inaba (p = 0.02) and Ogawa (p<0.0001). From a baseline of 13.58, anti-Ogawa GMT increased to 21.95 after the first dose, but rapidly waned to 14.52, 13.13, and 12.78 at months 6, 12 and 24 respectively, and then increased to 13.21, 18.67 and 23.65 at months 30, 36 and 48 respectively. A similar trend was observed for anti-Inaba GMT across the same time points. CONCLUSION: We found that Shanchol™ was immunogenic in our study population and that vibriocidal antibodies may not be a good marker for long-term immunity. The observed rise in titres after 36 months suggests natural exposure, and this may be a critical time window opening for natural transmission in an endemic areas. We recommend re-vaccination at this time point in high risk areas.
Impact of antibiotics on gut microbiome composition and resistome in the first years of life in low- to middle-income countries: A systematic review.
(2023-Jun) Luchen CC; Chibuye M; Spijker R; Simuyandi M; Chisenga C; Bosomprah S; Chilengi R; Schultsz C; Mende DR; Harris VC
BACKGROUND: Inappropriate antimicrobial usage is a key driver of antimicrobial resistance (AMR). Low- and middle-income countries (LMICs) are disproportionately burdened by AMR and young children are especially vulnerable to infections with AMR-bearing pathogens. The impact of antibiotics on the microbiome, selection, persistence, and horizontal spread of AMR genes is insufficiently characterized and understood in children in LMICs. This systematic review aims to collate and evaluate the available literature describing the impact of antibiotics on the infant gut microbiome and resistome in LMICs. METHODS AND FINDINGS: In this systematic review, we searched the online databases MEDLINE (1946 to 28 January 2023), EMBASE (1947 to 28 January 2023), SCOPUS (1945 to 29 January 2023), WHO Global Index Medicus (searched up to 29 January 2023), and SciELO (searched up to 29 January 2023). A total of 4,369 articles were retrieved across the databases. Duplicates were removed resulting in 2,748 unique articles. Screening by title and abstract excluded 2,666 articles, 92 articles were assessed based on the full text, and 10 studies met the eligibility criteria that included human studies conducted in LMICs among children below the age of 2 that reported gut microbiome composition and/or resistome composition (AMR genes) following antibiotic usage. The included studies were all randomized control trials (RCTs) and were assessed for risk of bias using the Cochrane risk-of-bias for randomized studies tool. Overall, antibiotics reduced gut microbiome diversity and increased antibiotic-specific resistance gene abundance in antibiotic treatment groups as compared to the placebo. The most widely tested antibiotic was azithromycin that decreased the diversity of the gut microbiome and significantly increased macrolide resistance as early as 5 days posttreatment. A major limitation of this study was paucity of available studies that cover this subject area. Specifically, the range of antibiotics assessed did not include the most commonly used antibiotics in LMIC populations. CONCLUSION: In this study, we observed that antibiotics significantly reduce the diversity and alter the composition of the infant gut microbiome in LMICs, while concomitantly selecting for resistance genes whose persistence can last for months following treatment. Considerable heterogeneity in study methodology, timing and duration of sampling, and sequencing methodology in currently available research limit insights into antibiotic impacts on the microbiome and resistome in children in LMICs. More research is urgently needed to fill this gap in order to better understand whether antibiotic-driven reductions in microbiome diversity and selection of AMR genes place LMIC children at risk for adverse health outcomes, including infections with AMR-bearing pathogens.
Integrating isoniazid preventive therapy into the fast-track HIV treatment model in urban Zambia: A proof-of -concept pilot project.
(2023) Mukumbwa-Mwenechanya M; Mubiana M; Somwe P; Zyambo K; Simwenda M; Zongwe N; Kalunkumya E; Mwango LK; Rabkin M; Mpesela F; Chungu F; Mwanza F; Preko P; Bolton-Moore C; Bosomprah S; Sharma A; Morton K; Kasonde P; Mulenga L; Lingu P; Mulenga PL
Most people living with HIV (PLHIV) established on treatment in Zambia receive multi-month prescribing and dispensing (MMSD) antiretroviral therapy (ART) and are enrolled in less-intensive differentiated service delivery (DSD) models such as Fast Track (FT), where clients collect ART every 3-6 months and make clinical visits every 6 months. In 2019, Zambia introduced Isoniazid Preventive Therapy (IPT) with scheduled visits at 2 weeks and 1, 3, and 6 months. Asynchronous IPT and HIV appointment schedules were inconvenient and not client centered. In response, we piloted integrated MMSD/IPT in FT HIV treatment model. We implemented and evaluated a proof-of-concept project at one purposively selected high-volume facility in Lusaka, Zambia between July 2019 and May 2020. We sensitized stakeholders, adapted training materials, standard operating procedures, and screened adults in FT for TB as per national guidelines. Participants received structured TB/IPT education, 6-month supply of isoniazid and ART, aligned 6th month IPT/MMSD clinic appointment, and phone appointments at 2 weeks and months 1-5 following IPT initiation. We used descriptive statistics to characterize IPT completion rates, phone appointment keeping, side effect frequency and Fisher's exact test to determine variation by participant characteristics. Key lessons learned were synthesized from monthly meeting notes. 1,167 clients were screened with 818 (70.1%) enrolled, two thirds (66%) were female and median age 42 years. 738 (90.2%) completed 6-month IPT course and 66 (8.1%) reported IPT-related side effects. 539 clients (65.9%) attended all 7 telephone appointments. There were insignificant differences of outcomes by age or sex. Lessons learnt included promoting project ownership, client empowerment, securing supply chain, adapting existing processes, and cultivating collaborative structured learning. Integrating multi-month dispensing and telephone follow up of IPT into the FT HIV treatment model is a promising approach to scaling-up TB preventive treatment among PLHIV, although limited by barriers to consistent phone access.
Intersection of alcohol use, HIV infection, and the HIV care continuum in Zambia: nationally representative survey.
(2023-Oct) Vinikoor MJ; Sikazwe I; Sharma A; Kanguya T; Chipungu J; Murray LK; Chander G; Cropsey K; Bosomprah S; Mulenga LB; Paul R; Kane J
Through a nationally-representative household survey, we measured the prevalence and correlates of unhealthy alcohol use (UAU) in Zambia and its association with the HIV care continuum. Adolescent and adult (ages 15-59 years) data, including the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), from the 2016 Zambia Population-based HIV Impact Assessment, were analyzed. UAU was defined as AUDIT-C of 3 + points for women and 4 + for men. Among 20,923 participants, 15.3% had UAU; this was 21.6% among people living with HIV (PLWH). Male sex, increasing age, being employed, urban residence, and having HIV were independent correlates of UAU (all
Liver steatosis and metabolic dysfunction-associated fatty liver disease among HIV-positive and negative adults in urban Zambia.
(2022-Jul) Chihota BV; Riebensahm C; Muula G; Sinkala E; Chilengi R; Mulenga L; Bosomprah S; Vinikoor MJ; Bolton-Moore C; Egger M; Rauch A; Berzigotti A; Wandeler G
INTRODUCTION: The growing importance of non-communicable diseases (NCDs) and high HIV prevalence in urban African settings may increase the burden of metabolic dysfunction-associated fatty liver disease (MAFLD). We assessed liver steatosis among HIV-positive and negative adults in urban Zambia. METHODS: Adults 30 years and older who were newly diagnosed with HIV, or tested HIV-negative at two primary care clinics in Lusaka, Zambia, were assessed for liver steatosis. Cardiometabolic data were collected through comprehensive clinical and laboratory assessments. Transient elastography was performed to measure controlled-attenuation parameter (≥248 dB/m). We used multivariable logistic regression models to determine the factors associated with the presence of steatosis. RESULTS: We enrolled 381 patients, including 154 (40%) antiretroviral therapy-naïve people living with HIV (PLWH) with a median CD4+ count of 247 cells/mm CONCLUSIONS: The prevalence of liver steatosis in this urban cohort of HIV-positive and negative adults in Zambia was low, despite a large proportion of patients with high BMI and central obesity. Our study is among the first to report data on MAFLD among adults in Africa, demonstrating that metabolic risk factors are key drivers of liver steatosis and supporting the adoption of the criteria for MAFLD in African populations.
Long-term Hepatitis B and Liver Outcomes Among Adults Taking Tenofovir-Containing Antiretroviral Therapy for HBV/HIV Coinfection in Zambia.
(2024-Jun-14) Vinikoor MJ; Hamusonde K; Muula G; Asombang M; Riebensahm C; Chitundu H; Sunkuntu-Sichizya V; Bhattacharya D; Sinkala E; Lauer G; Chung R; Mbewe W; Egger M; Bosomprah S; Wandeler G
BACKGROUND: Long-term outcomes of tenofovir-containing antiretroviral therapy (ART) for hepatitis B virus (HBV)/human immunodeficiency virus (HIV) coinfection were evaluated in Zambia. METHODS: A prospective cohort of adults with HIV and hepatitis B surface antigen (HBsAg)-positivity was enrolled at ART initiation. On tenofovir-containing ART, we ascertained HBV viral load (VL) non-suppression, alanine aminotransferase (ALT) elevation, serologic end-points, progression of liver fibrosis based on elastography, and hepatocellular carcinoma (HCC) incidence. We also described a subgroup (low HBV VL and no/minimal fibrosis at baseline) that, under current international guidelines, would not have been treated in the absence of their HIV infection. RESULTS: Among 289 participants at ART start, median age was 34 years, 40.1% were women, median CD4 count was 191 cells/mm3, 44.2% were hepatitis B e antigen-positive, and 28.4% had liver fibrosis/cirrhosis. Over median 5.91 years of ART, 13.6% developed HBV viral non-suppression, which was associated with advanced HIV disease. ALT elevation on ART was linked with HBV VL non-suppression. Regression of fibrosis and cirrhosis were common, progression to cirrhosis was absent, and no cases of HCC were ascertained. HBsAg seroclearance was 9.4% at 2 and 15.4% at 5 years, with higher rates among patients with low baseline HBV replication markers. CONCLUSIONS: Reassuring long-term liver outcomes were ascertained during tenofovir-based ART for HBV/HIV coinfection in Zambia. Higher than expected HBsAg seroclearance during ART underscores the need to include people with HIV in HBV cure research.