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The CIDRZ Research Repository serves as an open-access archive for peer-reviewed publications, conference papers, and other scholarly outputs from CIDRZ researchers. Our goal is to promote the dissemination of knowledge and support evidence-based public health initiatives.

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Field performance of the Determine HBsAg point-of-care test for diagnosis of hepatitis B virus co-infection among HIV patients in Zambia.
(2018-Jan) Chisenga, Caroline C.; Musukuma, Kalo; Chilengi, Roma; Zürcher, Samuel; Munamunungu, Virginia; Siyunda, Alice; Ojok, David; Bauer, Sophie; Wandeler, Gilles; Vinikoor, Michael J.
BACKGROUND: We evaluated the field performance of a rapid point-of-care (POC) test for hepatitis B surface antigen (HBsAg) that could support decentralization and scale-up of hepatitis B virus (HBV) diagnosis in Africa. OBJECTIVE: To determine the field performance of the Determine HBsAg POC test for diagnosis of HBV co-infection among HIV patients in Zambia. STUDY DESIGN: Between 2013-2014, we screened HIV-infected adults for HBsAg at two urban clinics in Zambia. A subset were tested with the POC Determine HBsAg (Alere, USA) by finger prick in the clinic and HBsAg serology (Access2Analyzer, Beckman Coulter) at a reference laboratory. If either test was reactive, we determined HBV viral load (VL) and genotype. We described patient demographic and clinical characteristics (including liver fibrosis) and assessed the sensitivity, specificity, positive and negative predictive values (PPV and NPV) of the Determine test. In secondary analyses, we assessed sensitivity among patients with replicating HBV (i.e., VL>20 IU/ml) and with high HBV VL (i.e.,>20,000IU/ml). RESULTS: Among 412 participants with both HBsAg tests, median age was 34 years, 51% were women, and median CD4 was 208 cells/mm CONCLUSIONS: Determine HBsAg is a cheaper alternative HBV testing option compared to the gold standard ELISA and has high specificity and good sensitivity in the field among HIV-infected individuals.
Effect of innate antiviral glycoproteins in breast milk on seroconversion to rotavirus vaccine (Rotarix) in children in Lusaka, Zambia.
(2017) Mwila-Kazimbaya, Katayi; Garcia, Miguel P.; Bosomprah, Samuel; Laban, Natasha M.; Chisenga, Caroline C.; Permar, Sallie R.; Simuyandi, Michelo; Munsaka, Sody; Chilengi, Roma
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.
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(2025) Luchen, Charlie C.; Ngo'mbe, Harriet; Liswaniso, Fraser; Bosomprah, Samuel; Zhiteneva, Julia A.; Harris, Jason; Charles, Richelle C.; Ryan, Edward T.; Sack, David; Bernshtein, Biana; Chisenga, Caroline C.
BACKGROUND: Cholera is a public health threat in resource-limited settings and is responsible for causing over 3 million cases globally. Mucosal immune responses play an important role in protecting against METHODS: We conducted a cross-sectional antibody profiling study to analyse cholera-specific antibodies in saliva and plasma samples from 74 participants upon presenting to the cholera treatment centres. These were collected from four treatment centres in Lusaka during Zambia's most severe cholera outbreak in 2024 caused by RESULTS: Saliva and plasma antibody profiles were comparable, with elevated IgA1 and IgA2 responses to cholera toxin-B (CtxB), sialidase, HlyA, and TcpA in saliva. Broader systemic responses were seen in plasma, including high CtxB-specific IgM, IgA1, and total IgG levels. Notably, biomarkers such as HlyA, Ogawa O-specific polysaccharide (OSP), and sialidase exhibited significant positive correlations between plasma and saliva. Elevated biomarker levels of HlyA, Ogawa O-specific polysaccharide (OSP), and sialidase in people living with HIV/AIDS (PLWHA) suggested immunological differences that warrant further exploration. CONCLUSION: We demonstrate that saliva is a viable, non-invasive alternative for cholera antibody-based profiling, offering practical advantages in resource-constrained settings. Given its strong correlation with systemic antibody profiles, saliva may be a practical sample for sero-surveillance in resource-limited settings. Future studies should investigate the duration of these salivary responses to further substantiate their use in estimating disease burden and immunity.
Identification of cholera hotspots in Zambia: A spatiotemporal analysis of cholera data from 2008 to 2017.
(2020-Apr) Mwaba, John; Debes, Amanda K.; Shea, Patrick; Mukonka, Victor; Chewe, Orbrie; Chisenga, Caroline C.; Simuyandi, Michelo; Kwenda, Geoffrey; Sack, David; Chilengi, Roma; Ali, Mohammad
The global burden of cholera is increasing, with the majority (60%) of the cases occurring in sub-Saharan Africa. In Zambia, widespread cholera outbreaks have occurred since 1977, predominantly in the capital city of Lusaka. During both the 2016 and 2018 outbreaks, the Ministry of Health implemented cholera vaccination in addition to other preventative and control measures, to stop the spread and control the outbreak. Given the limitations in vaccine availability and the logistical support required for vaccination, oral cholera vaccine (OCV) is now recommended for use in the high risk areas ("hotspots") for cholera. Hence, the aim of this study was to identify areas with an increased risk of cholera in Zambia. Retrospective cholera case data from 2008 to 2017 was obtained from the Ministry of Health, Department of Public Health and Disease Surveillance. The Zambian Central Statistical Office provided district-level population data, socioeconomic and water, sanitation and hygiene (WaSH) indicators. To identify districts at high risk, we performed a discrete Poisson-based space-time scan statistic to account for variations in cholera risk across both space and time over a 10-year study period. A zero-inflated negative binomial regression model was employed to identify the district level risk factors for cholera. The risk map was generated by classifying the relative risk of cholera in each district, as obtained from the space-scan test statistic. In total, 34,950 cases of cholera were reported in Zambia between 2008 and 2017. Cholera cases varied spatially by year. During the study period, Lusaka District had the highest burden of cholera, with 29,080 reported cases. The space-time scan statistic identified 16 districts to be at a significantly higher risk of having cholera. The relative risk of having cholera in these districts was significantly higher and ranged from 1.25 to 78.87 times higher when compared to elsewhere in the country. Proximity to waterbodies was the only factor associated with the increased risk for cholera (P<0.05). This study provides a basis for the cholera elimination program in Zambia. Outside Lusaka, the majority of high risk districts identified were near the border with the DRC, Tanzania, Mozambique, and Zimbabwe. This suggests that cholera in Zambia may be linked to movement of people from neighboring areas of cholera endemicity. A collaborative intervention program implemented in concert with neighboring countries could be an effective strategy for elimination of cholera in Zambia, while also reducing rates at a regional level.
Sero-prevalence of arthropod-borne viral infections among Lukanga swamp residents in Zambia.
(2020) Chisenga, Caroline C.; Bosomprah, Samuel; Musukuma, Kalo; Mubanga, Cynthia; Chilyabanyama, Obvious N.; Velu, Rachel M.; Kim, Young C.; Reyes-Sandoval, Arturo; Chilengi, Roma
INTRODUCTION: The re-emergence of vector borne diseases affecting millions of people in recent years has drawn attention to arboviruses globally. Here, we report on the sero-prevalence of chikungunya virus (CHIKV), dengue virus (DENV), mayaro virus (MAYV) and zika virus (ZIKV) in a swamp community in Zambia. METHODS: We collected blood and saliva samples from residents of Lukanga swamps in 2016 during a mass-cholera vaccination campaign. Over 10,000 residents were vaccinated with two doses of Shanchol™ during this period. The biological samples were collected prior to vaccination (baseline) and at specified time points after vaccination. We tested a total of 214 baseline stored serum samples for IgG antibodies against NS1 of DENV and ZIKV and E2 of CHIKV and MAYV on ELISA. We defined sero-prevalence as the proportion of participants with optical density (OD) values above a defined cut-off value, determined using a finite mixture model. RESULTS: Of the 214 participants, 79 (36.9%; 95% CI 30.5-43.8) were sero-positive for Chikungunya; 23 (10.8%; 95% CI 6.9-15.7) for Zika, 36 (16.8%; 95% CI 12.1-22.5) for Dengue and 42 (19.6%; 95% CI 14.5-25.6) for Mayaro. Older participants were more likely to have Zika virus whilst those involved with fishing activities were at greater risk of contracting Chikungunya virus. Among all the antigens tested, we also found that Chikungunya saliva antibody titres correlated with baseline serum titres (Spearman's correlation coefficient = 0.222; p = 0.03). CONCLUSION: Arbovirus transmission is occurring in Zambia. This requires proper screening tools as well as surveillance data to accurately report on disease burden in Zambia.
A pilot study on use of live attenuated rotavirus vaccine (Rotarix™) as an infection challenge model.
(2020-Oct-27) Chilengi, Roma; Simuyandi, Michelo; Chibuye, Mwelwa; Chirwa, Masuzyo; Sukwa, Nsofwa; Laban, Natasha; Chisenga, Caroline C.; Silwamba, Suwilanji; Grassly, Nicholas; Bosomprah, Samuel
BACKGROUND: Rotavirus remains the commonest cause of dehydrating diarrhoea, particularly in developing countries. Human infection challenge studies in children in these countries offers an opportunity to rapidly evaluate new vaccine candidates that may have improved efficacy. We evaluated use of Rotarix™ as a live-attenuated challenge agent. METHODS: We undertook an open label, exploratory study in infants receiving two standard doses of Rotarix™ at 6 and 10 weeks of age in a cohort of 22 Zambian infants. The first vaccine dose was considered as primary vaccination, and the second at day 28 as a live-attenuated virus challenge. Saliva, stool and serum samples were collected on days 0, 3, 5, 7, 14, and 28 following each dose. The primary outcome was stool shedding of rotavirus, determined by NSP2 qPCR. We calculated mean shedding index as average of natural logarithm of viral copies per gram of stool. FINDINGS: After the first dose, viral shedding was high at day 3, peaked by day 5. After the second dose, viral shedding at day 3 was low and reduced gradually in most infants until day 14. Mean shedding index was significantly lower post dose 2 across all infants and timepoints (5.0 virus copies/g of stool [95%CI: 0.3-9.7] vs 10.4 virus copies/g of stool [95%CI: 6.2-14.6]; p-value < 0.0001; rho = 0.20, SD = 4.97. Seroconversion at day 28 was associated with a mean reduction of -1.03 (95%CI = -8.07, 6.01) in viral shedding after challenge dose but this was not statistically significant (p = 0.774). A borderline positive correlation between fold-change in IgA titre at day 28 from day 0 in saliva and serum was observed; Spearman's correlation coefficient, r = 0.69; p = 0.086. INTERPRETATION: Shedding after the 'challenge' dose was reduced compared with the first dose, consistent with the induction of mucosal immunity by the first dose. This supports the use of Rotarix vaccine as a live-attenuated infection challenge. FUNDING: Medical Research Council (UK) through the HIC-Vac Network.
In-vitro inhibitory effect of maternal breastmilk components on rotavirus vaccine replication and association with infant seroconversion to live oral rotavirus vaccine.
(2020) Kazimbaya, Katayi M.; Chisenga, Caroline C.; Simuyandi, Michelo; Phiri, Cynthia M.; Laban, Natasha M.; Bosomprah, Samuel; Permar, Sallie R.; Munsaka, Sody; Chilengi, Roma
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.
Shigella-specific antibodies in the first year of life among Zambian infants: A longitudinal cohort study.
(2021) Chisenga, Caroline C.; Bosomprah, Samuel; Simuyandi, Michelo; Mwila-Kazimbaya, Katayi; Chilyabanyama, Obvious N.; Laban, Natasha M.; Bialik, Anya; Asato, Valeria; Meron-Sudai, Shiri; Frankel, Gad; Cohen, Daniel; Chilengi, Roma
INTRODUCTION: Shigellosis, is a leading cause of moderate-to-severe diarrhoea and related mortality in young children in low and middle income countries (LMICs). Knowledge on naturally acquired immunity can support the development of Shigella candidate vaccines mostly needed in LMICs. We aimed to quantify Shigella-specific antibodies of maternal origin and those naturally acquired in Zambian infants. METHODS: Plasma samples collected from infants at age 6, 14 and 52-weeks were tested for Shigella (S. sonnei and S. flexneri 2a) lipopolysaccharide (LPS) antigen specific immunoglobulin G (IgG) and A (IgA) by enzyme-linked immunosorbent assay. RESULTS: At 6 weeks infant age, the IgG geometric mean titres (GMT) against S. sonnei (N = 159) and S. flexneri 2a (N = 135) LPS were 311 (95% CI 259-372) and 446 (95% CI 343-580) respectively. By 14 weeks, a decline in IgG GMT was observed for both S. sonnei to 104 (95% CI 88-124), and S. flexneri 2a to 183 (95% CI 147-230). Both S. sonnei and S. flexneri 2a specific IgG GMT continued to decrease by 52 weeks infant age when compared to 6 weeks. In 27% and 8% of infants a significant rise in titre (4 fold and greater) against S. flexneri 2a and S. sonnei LPS, respectively, was detected between the ages of 14 and 52 weeks. IgA levels against both species LPS were very low at 6 and 14 weeks and raised significantly against S. flexneri 2a and S. sonnei LPS in 29% and 10% of the infants, respectively. CONCLUSION: In our setting, transplacental IgG anti-Shigella LPS is present at high levels in early infancy, and begins to decrease by age 14 weeks. Our results are consistent with early exposure to Shigella and indicate naturally acquired IgG and IgA antibodies to S. flexneri 2a and S. sonnei LPS in part of infants between 14 and 52 weeks of age. These results suggest that a potential timing of vaccination would be after 14 and before 52 weeks of age to ensure early infant protection against shigellosis.
Serum vibriocidal responses when second doses of oral cholera vaccine are delayed 6 months in Zambia.
(2021-Jul-22) Mwaba, John; Chisenga, Caroline C.; Xiao, Shaoming; Ng'ombe, Harriet; Banda, Elena; Shea, Patrick; Mabula-Bwalya, Chileshe; Mwila-Kazimbaya, Katayi; Laban, Natasha M.; Alabi, Peter; Chirwa-Chobe, Masuzyo; Simuyandi, Michelo; Harris, Jason; Iyer, Anita S.; Bosomprah, Samuel; Scalzo, Paul; Murt, Kelsey N.; Ram, Malathi ; Kwenda, Geoffrey; Ali, Mohammad; Sack, David A.; Chilengi, Roma; Debes, Amanda K.
Two-dose killed oral cholera vaccines (OCV) are currently being used widely to control cholera. The standard dose-interval for OCV is 2 weeks; however, during emergency use of the vaccine, it may be more appropriate to use the available doses to quickly give a single dose to more people and give a delayed second dose when more vaccine becomes available. This study is an open label, randomized, phase 2 clinical trial of the vibriocidal response induced by OCV, comparing the responses when the second dose was given either 2 weeks (standard dose interval) or 6 months (extended dose interval) after the first dose. Vaccine was administered to healthy participants > 1 year of age living in the Lukanga Swamps area of Zambia. Three age cohorts (<5 years, 5-14 years, and ≥ 15 years) were randomized to the either dose-interval. The primary outcome was the vibriocidal GMT 14 days after the second dose. 156 of 172 subjects enrolled in the study were included in this analysis. The Inaba vibriocidal titers were not significantly different 14 days post dose two for a standard dose-interval GMT: 45.6 (32-64.9), as compared to the GMT 47.6 (32.6-69.3), for the extended dose-interval, (p = 0.87). However, the Ogawa vibriocidal GMTs were significantly higher 14 days post dose two for the extended-dose interval at 87.6 (58.9-130.4) compared to the standard dose-interval group at 49.7 (34.1-72.3), p = 0.04. Vibriocidal seroconversion rates (a > 4-fold rise in vibriocidal titer) were not significantly different between dose-interval groups. This study demonstrated that vibriocidal titers 14 days after a second dose when given at an extended\ dose interval were similar to the standard dose-interval. The findings suggest that a flexible dosing schedule may be considered when epidemiologically appropriate. The trial was registered at Clinical Trials.gov (NCT03373669).
Field evaluation of a novel, rapid diagnostic assay, and molecular epidemiology of enterotoxigenic E. coli among Zambian children presenting with diarrhea.
(2022-Aug) Silwamba, Suwilanji; Chilyabanyama, Obvious N.; Liswaniso, Fraser; Chisenga, Caroline C.; Chilengi, Roma; Dougan, Gordon; Kwenda, Geoffrey; Chakraborty, Subhra; Simuyandi, Michelo
BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) is one of the top aetiologic agents of diarrhea in children under the age of 5 in low-middle income countries (LMICs). The lack of point of care diagnostic tools for routine ETEC diagnosis results in limited data regarding the actual burden and epidemiology in the endemic areas. We evaluated performance of the novel Rapid LAMP based Diagnostic Test (RLDT) for detection of ETEC in stool as a point of care diagnostic assay in a resource-limited setting. METHODS: We conducted a cross-sectional study of 324 randomly selected stool samples from children under 5 presenting with moderate to severe diarrhea (MSD). The samples were collected between November 2012 to September 2013 at selected health facilities in Zambia. The RLDT was evaluated by targeting three ETEC toxin genes [heat labile toxin (LT) and heat stable toxins (STh and STp)]. Quantitative PCR was used as the "gold standard" to evaluate the diagnostic sensitivity and specificity of RLDT for detection of ETEC. We additionally described the prevalence and seasonality of ETEC. RESULTS: The study included 324 participants, 50.6% of which were female. The overall prevalence of ETEC was 19.8% by qPCR and 19.4% by RLDT. The children between 12 to 59 months had the highest prevalence of 22%. The study determined ETEC toxin distribution was LT 28/321(9%), ST 18/321(6%) and LT/ST 16/321(5%). The sensitivity and specificity of the RLDT compared to qPCR using a Ct 35 as the cut-off, were 90.7% and 97.5% for LT, 85.2% and 99.3% for STh and 100% and 99.7% for STp, respectively. CONCLUSION: The results of this study suggest that RLDT is sufficiently sensitive and specific and easy to implement in the endemic countries. Being rapid and simple, the RLDT also presents as an attractive tool for point-of-care testing at the health facilities and laboratories in the resource-limited settings.

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