This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Live-attenuated, oral rotavirus vaccines have significantly reduced rotavirus-associated diarrhoe... more 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 rota...
Emerging and re-emerging mosquito-borne viral diseases are a threat to global health. This system... more Emerging and re-emerging mosquito-borne viral diseases are a threat to global health. This systematic review aimed to investigate the available evidence of mosquito-borne viral pathogens reported in Zambia. A search of literature was conducted in PubMed and Google Scholar for articles published from 1 January 1930 to 30 June 2020 using a combination of keywords. Eight mosquito-borne viruses belonging to three families, Togaviridae, Flaviviridae and Phenuiviridae were reported. Three viruses (Chikungunya virus, Mayaro virus, Mwinilunga virus) were reported among the togaviruses whilst four (dengue virus, West Nile virus, yellow fever virus, Zika virus) were among the flavivirus and only one virus, Rift Valley fever virus, was reported in the Phenuiviridae family. The majority of these mosquito-borne viruses were reported in Western and North-Western provinces. Aedes and Culex species were the main mosquito-borne viral vectors reported. Farming, fishing, movement of people and rain pa...
Background Shigella is a leading cause of bacterial diarrhea morbidity and mortality affecting ma... more Background Shigella is a leading cause of bacterial diarrhea morbidity and mortality affecting mainly children under five in the developing world. In Zambia, Shigella has a high prevalence of 34.7% in children with diarrhea and an attributable fraction of 6.7% in Zambian children with moderate to severe diarrhea. Zambian diarrhea management guidelines and the health ministry reporting tool Health Management Information System (HMIS) heavily rely on the WHO clinical classification of dysentery to potentially identify and estimate the burden of Shigella in children. This reliance on clinical dysentery as a proxy to shigellosis in under five children may be resulting in gross under-estimation of shigella disease burden in Zambia. Methods We used existing laboratory and clinical data to examine the sensitivity and predictive value of dysentery to correctly identify Shigella infection in under five children with PCR confirmed Shigella infection in Lusaka and Ndola districts, Zambia. Resu...
Oral rotavirus vaccines show diminished immunogenicity in low-resource settings where rotavirus b... more 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® (GlaxoSmithKline) vaccine administered at 9 months of age. A total of 214 infants aged 6 to 12 weeks were randomised to receive two doses of ROTARIX® as per standard schedule with other routine vaccinations or an additional third dose of ROTARIX® administered at 9 months old concomitantly with measles/rubella vaccination. Plasma collected pre-vaccination, 1 month after first- and second-dose vaccination, at 9 months old before receipt of third ROTARIX® dose and/or measles/rubella vaccination, and at 12 months old were assayed for rotavirus-specific IgA (RV-IgA). Geometric mean RV-IgA at 12 months of age and the incidence of clinical adverse events 1 month following administration of the third dose of ROTARIX® among infants in the intervention arm were compared between infants in t...
Background Histo-blood group antigens (HBGAs) which include the ABO and Lewis antigen systems hav... more 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 1...
Background Diarrhoeal disease remains a leading cause of death among children mostly in low and m... more 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 scor...
Stunting is a global public health issue. We sought to train and evaluate machine learning (ML) c... more Stunting is a global public health issue. We sought to train and evaluate machine learning (ML) classification algorithms on the Zambia Demographic Health Survey (ZDHS) dataset to predict stunting among children under the age of five in Zambia. We applied Logistic regression (LR), Random Forest (RF), SV classification (SVC), XG Boost (XgB) and Naïve Bayes (NB) algorithms to predict the probability of stunting among children under five years of age, on the 2018 ZDHS dataset. We calibrated predicted probabilities and plotted the calibration curves to compare model performance. We computed accuracy, recall, precision and F1 for each machine learning algorithm. About 2327 (34.2%) children were stunted. Thirteen of fifty-eight features were selected for inclusion in the model using random forest. Calibrating the predicted probabilities improved the performance of machine learning algorithms when evaluated using calibration curves. RF was the most accurate algorithm, with an accuracy scor...
BackgroundDespite contributing to a significant reduction in rotavirus associated diarrhoea in hi... more 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 f...
Cellular immunity against rotavirus in children is incompletely understood. This review describes... more Cellular immunity against rotavirus in children is incompletely understood. This review describes the current understanding of T-cell immunity to rotavirus in children. A systematic literature search was conducted in Embase, MEDLINE, Web of Science, and Global Health databases using a combination of “t-cell”, “rotavirus” and “child” keywords to extract data from relevant articles published from January 1973 to March 2020. Only seventeen articles were identified. Rotavirus-specific T-cell immunity in children develops and broadens reactivity with increasing age. Whilst occurring in close association with antibody responses, T-cell responses are more transient but can occur in absence of detectable antibody responses. Rotavirus-induced T-cell immunity is largely of the gut homing phenotype and predominantly involves Th1 and cytotoxic subsets that may be influenced by IL-10 Tregs. However, rotavirus-specific T-cell responses in children are generally of low frequencies in peripheral bl...
Background Impaired growth among infants remains one of the leading nutrition problems globally. ... more Background Impaired growth among infants remains one of the leading nutrition problems globally. In this study, we aimed to compare the growth trajectory rate and evaluate growth trajectory characteristics among children, who are HIV exposed uninfected (HEU) and HIV unexposed uninfected (HUU), under two years in Zambia. Method Our study used data from the ROVAS II study (PACTR201804003096919), an open-label randomized control trial of two verses three doses of live, attenuated, oral RotarixTM administered 6 &10 weeks or at 6 &10 weeks plus an additional dose at 9 months of age, conducted at George clinic in Lusaka, Zambia. Anthropometric measurements (height and weight) were collected on all scheduled and unscheduled visits. We defined linear growth velocity as the rate of change in height and estimated linear growth velocity as the first derivative of the mixed effect model with fractional polynomial transformations and, thereafter, used the second derivative test to determine the ...
Introduction In cholera endemic areas, the periodicity of cholera outbreaks remains unpredictable... more 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%) a...
Background We set out to assess the impact of human immunodeficiency virus (HIV) and micronutrien... more 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...
Background:Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome corona... more Background:Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing global health crisis that has caused large scale morbidity and mortality. We aimed to determine the exposure to SARS-CoV-2 among young children and healthcare workers by measurement of anti-S1 antigen (spike protein) specific immunoglobulin G (IgG) using an in-house optimized indirect enzyme-linked immunosorbent assay (ELISA) method.Methods:Plasma samples were collected from cohorts of healthcare workers (n = 287) and young children aged from 6 weeks to 2 years old (n = 150) pre-COVID-19 pandemic between September 2018 and November 2019 and post-COVID-19 pandemic between August and December 2020 were simultaneously tested for anti-SARS-CoV-2 S1 specific IgG. The arithmetic mean of natural logarithm-transformed ELISA relative absorbance reading + (3 x standard deviation) of pre-pandemic plasma was used as the cut-off to determine SARS-CoV-2 IgG seroposit...
Introduction Shigellosis, is a leading cause of moderate-to-severe diarrhoea and related mortalit... more 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. fl...
Background: We aimed to document viral, bacterial, and protozoan enteric pathogens responsible fo... more Background: We aimed to document viral, bacterial, and protozoan enteric pathogens responsible for causing moderate-to-severe diarrhoea among children under five presenting at public health facilities in Zambia following the introduction of rotavirus vaccination. Methods: This was a cross-sectional study in which clinical data and stool samples were collected between July 2012 and October 2013 from children under five years presenting to outpatient clinics in Lusaka province with moderate-tosevere diarrhoea. The study was conducted during the early months post rotavirus vaccine introduction in Zambia. We used Luminex x-TAG® gastrointestinal pathogen panel to simultaneously detect enteric viruses, bacteria and protozoa from the stool samples. We applied the population attributable fraction to estimate pathogen-specific burden of moderate-to-severe diarrhoea. Results: We analysed 1,135 unique stool samples with clinical data, of which 56% had received one or full dose rotavirus vaccination. The median age was 14 months (IQR=8, 22). The prevalence of moderate-to-severe diarrhoea was estimated as 18.9% (95%CI=16.7, 21.2). The most attributable cases of moderate-to-severe diarrhoea were due to rotavirus {attributable fraction=24.5%; 95%CI=(5.4, 39.7)} followed by Shigella spp. {attributable fraction=6.7%; 95%CI=(0.1, 15.5)}. The top 5 enteric pathogens detected among children were rotavirus (67.6%), Adenovirus (41.5%), ETEC (40.7%), Salmonella (38.4%) and Giardia (37.0%). Conclusion: We found that about one-third of moderate-tosevere diarrhoea among children were attributable to rotavirus and Shigella spp.
Background Rotavirus is the most common cause of fatal diarrhoeal disease among children under th... more Background Rotavirus is the most common cause of fatal diarrhoeal disease among children under the age of five globally and is responsible for millions of hospitalizations each year. Although nutritional status and environmental enteric dysfunction (EED) are recognized as important predictors of susceptibility to diarrhoeal disease, no research to date has examined the mechanisms by which undernutrition and EED may protect against prevalence of rotavirus infection.
Background: Environmental Enteropathy (EE) is a complex syndrome involving intestinal disorder wh... more Background: Environmental Enteropathy (EE) is a complex syndrome involving intestinal disorder which has been observed among children living in resource-poor settings. We investigated stored stool samples collected from children under-5 for relationships between specific enteric pathogens and levels of stool EE markers: Calprotectin (CALP), Alpha-1-Anti-Trypsin (AAT) and Myeloperoxidase (MPO). Methods: We used clinical data and stored stool samples collected prior to, and during the early months of widespread rotavirus vaccine implementation in Lusaka between July 2012 and October 2013 in Lusaka, Zambia. Children were considered eligible if they presented to the facility with symptoms of moderate-to-severe diarrhoea defined by having one or more of the following signs or symptoms: dehydration evidenced by sunken eyes, loss of normal skin turgor, or requiring intravenous resuscitation; dysentery (diarrhoea with blood in stool); or hospitalisation. We randomly selected 320 stool samples from the pool of 2,050 for analysis. We tested for 15 enteric pathogens using the Luminex XTag GPP panel and used commercial ELISA kits to assess the presence and levels of three known fecal markers of EE. We derived an EE score using a weighted sum of CALP, AAT, and MPO and applied a multivariable linear regression model to identify enteric pathogens independently associated with EE score. Results: After excluding insufficient samples (24) and those with missing clinical data (62), a total of the 234 were available for analysis. Of these, 114 (49%) were female, 103 (44%) were asymptomatic for diarrhoea, 181 (77%) had two or more enteric pathogens detected in stool. Fifty-six percent (131/234) children were positive for Rotavirus, 43.2% (101/234) Enterotoxigenic E. coli, 36% (86/234) Giardia, 35% (82/234) Adenovirus and 34.2% (80/234) had Shigella. The mean EE score was 5 (SD=2.25). The median concentration of MPO, CALP, and AAT were 2560.4 ng/ml (interquartile range (IQR)=806.1, 6522.9), 79.1 ng/ml (IQR=0, 362.5), and 48.6 mg/ml (IQR=12.1, 139.5) respectively. Shigella (coefficient=0.92; 95%CI=(0.14, 1.70); p=0.022) and Salmonella (coefficient=0.83; 95%CI=(0.08, 1.58); p=0.030) were independently associated with increase in mean EE score and together with E. coli accounted for 68.5% of the predicted variance in EE score. Conclusions: Salmonella and Shigella were found to be associated with EE and together with accounted for over two-thirds of variability in the EE score.
Background: Linear growth retardation is the most dominant nutritional problem globally. We aimed... more Background: Linear growth retardation is the most dominant nutritional problem globally. We aimed to describe linear growth trajectory among infants under 2 years of age using the WHO growth velocity standards. Method: This was a prospective cohort study of infants enrolled at 6 weeks of age and followed up for up to 24 months in Kamwala Urban Health Centre, Lusaka, Zambia. The study was conducted between April 2013 and March 2015. Infants were enrolled if they were 6-12 weeks of age and the mother was willing to participate voluntarily and provided informed consent. Anthropometric data were collected at scheduled clinic visits at 1 month, 2 months, 3 months, then quarterly until the infant was 24 months old. We defined linear growth velocity as the rate of change in height. We estimated linear growth velocity as the first derivative of the penalized cubic spline mixed effects model. Results: A total of 338 children were included in the analysis. Of these, 185 (54.7%) were female, 115 (34.1%) were born to HIV positive mothers and thus classified as HIV Exposed (HE). The mean age of children at enrollment was 1.6 months (SD = 0.15). On average, the growth velocity for 3-month length increments conditional on age were 0-3 months = 2.97 cm/3mo (95%CI = 2.69, 3.25); 3-6 months = 2.62 cm/3mo (95%CI = 2.38, 2.87); 6-9 months = 1.57 cm/ 3mo (95%CI = 1.43, 1.71); 9-12 months = 1.18 cm/3mo (95%CI = 1.08, 1.28); 12-15 month = 1.14 cm/3mo (95%CI = 1. 02, 1.27); 15-18 months = 0.87 cm/3mo (95%CI = 0.79, 0.96); 18-21 months = 0.80 cm/3mo (95%CI = 0.72, 0.89); and 21-24 months = 0.86 cm/3mo (95%CI = 0.77, 0.96). For both boys and girls, the growth velocity in our cohort were consistently below the 3rd percentile of the WHO linear growth velocity standard. The estimated mean height and the age at which growth begins to falter were 68.6 cm (95%CI = 68.0, 69.2) and 13.6 months (95%CI = 13.2, 14.1) respectively. Conclusion: We found slower rate of growth among otherwise healthy Zambian infants. The data suggests that growth retardation is universal and profound in this cohort and may have already been occurring in utero.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Live-attenuated, oral rotavirus vaccines have significantly reduced rotavirus-associated diarrhoe... more 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 rota...
Emerging and re-emerging mosquito-borne viral diseases are a threat to global health. This system... more Emerging and re-emerging mosquito-borne viral diseases are a threat to global health. This systematic review aimed to investigate the available evidence of mosquito-borne viral pathogens reported in Zambia. A search of literature was conducted in PubMed and Google Scholar for articles published from 1 January 1930 to 30 June 2020 using a combination of keywords. Eight mosquito-borne viruses belonging to three families, Togaviridae, Flaviviridae and Phenuiviridae were reported. Three viruses (Chikungunya virus, Mayaro virus, Mwinilunga virus) were reported among the togaviruses whilst four (dengue virus, West Nile virus, yellow fever virus, Zika virus) were among the flavivirus and only one virus, Rift Valley fever virus, was reported in the Phenuiviridae family. The majority of these mosquito-borne viruses were reported in Western and North-Western provinces. Aedes and Culex species were the main mosquito-borne viral vectors reported. Farming, fishing, movement of people and rain pa...
Background Shigella is a leading cause of bacterial diarrhea morbidity and mortality affecting ma... more Background Shigella is a leading cause of bacterial diarrhea morbidity and mortality affecting mainly children under five in the developing world. In Zambia, Shigella has a high prevalence of 34.7% in children with diarrhea and an attributable fraction of 6.7% in Zambian children with moderate to severe diarrhea. Zambian diarrhea management guidelines and the health ministry reporting tool Health Management Information System (HMIS) heavily rely on the WHO clinical classification of dysentery to potentially identify and estimate the burden of Shigella in children. This reliance on clinical dysentery as a proxy to shigellosis in under five children may be resulting in gross under-estimation of shigella disease burden in Zambia. Methods We used existing laboratory and clinical data to examine the sensitivity and predictive value of dysentery to correctly identify Shigella infection in under five children with PCR confirmed Shigella infection in Lusaka and Ndola districts, Zambia. Resu...
Oral rotavirus vaccines show diminished immunogenicity in low-resource settings where rotavirus b... more 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® (GlaxoSmithKline) vaccine administered at 9 months of age. A total of 214 infants aged 6 to 12 weeks were randomised to receive two doses of ROTARIX® as per standard schedule with other routine vaccinations or an additional third dose of ROTARIX® administered at 9 months old concomitantly with measles/rubella vaccination. Plasma collected pre-vaccination, 1 month after first- and second-dose vaccination, at 9 months old before receipt of third ROTARIX® dose and/or measles/rubella vaccination, and at 12 months old were assayed for rotavirus-specific IgA (RV-IgA). Geometric mean RV-IgA at 12 months of age and the incidence of clinical adverse events 1 month following administration of the third dose of ROTARIX® among infants in the intervention arm were compared between infants in t...
Background Histo-blood group antigens (HBGAs) which include the ABO and Lewis antigen systems hav... more 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 1...
Background Diarrhoeal disease remains a leading cause of death among children mostly in low and m... more 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 scor...
Stunting is a global public health issue. We sought to train and evaluate machine learning (ML) c... more Stunting is a global public health issue. We sought to train and evaluate machine learning (ML) classification algorithms on the Zambia Demographic Health Survey (ZDHS) dataset to predict stunting among children under the age of five in Zambia. We applied Logistic regression (LR), Random Forest (RF), SV classification (SVC), XG Boost (XgB) and Naïve Bayes (NB) algorithms to predict the probability of stunting among children under five years of age, on the 2018 ZDHS dataset. We calibrated predicted probabilities and plotted the calibration curves to compare model performance. We computed accuracy, recall, precision and F1 for each machine learning algorithm. About 2327 (34.2%) children were stunted. Thirteen of fifty-eight features were selected for inclusion in the model using random forest. Calibrating the predicted probabilities improved the performance of machine learning algorithms when evaluated using calibration curves. RF was the most accurate algorithm, with an accuracy scor...
BackgroundDespite contributing to a significant reduction in rotavirus associated diarrhoea in hi... more 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 f...
Cellular immunity against rotavirus in children is incompletely understood. This review describes... more Cellular immunity against rotavirus in children is incompletely understood. This review describes the current understanding of T-cell immunity to rotavirus in children. A systematic literature search was conducted in Embase, MEDLINE, Web of Science, and Global Health databases using a combination of “t-cell”, “rotavirus” and “child” keywords to extract data from relevant articles published from January 1973 to March 2020. Only seventeen articles were identified. Rotavirus-specific T-cell immunity in children develops and broadens reactivity with increasing age. Whilst occurring in close association with antibody responses, T-cell responses are more transient but can occur in absence of detectable antibody responses. Rotavirus-induced T-cell immunity is largely of the gut homing phenotype and predominantly involves Th1 and cytotoxic subsets that may be influenced by IL-10 Tregs. However, rotavirus-specific T-cell responses in children are generally of low frequencies in peripheral bl...
Background Impaired growth among infants remains one of the leading nutrition problems globally. ... more Background Impaired growth among infants remains one of the leading nutrition problems globally. In this study, we aimed to compare the growth trajectory rate and evaluate growth trajectory characteristics among children, who are HIV exposed uninfected (HEU) and HIV unexposed uninfected (HUU), under two years in Zambia. Method Our study used data from the ROVAS II study (PACTR201804003096919), an open-label randomized control trial of two verses three doses of live, attenuated, oral RotarixTM administered 6 &10 weeks or at 6 &10 weeks plus an additional dose at 9 months of age, conducted at George clinic in Lusaka, Zambia. Anthropometric measurements (height and weight) were collected on all scheduled and unscheduled visits. We defined linear growth velocity as the rate of change in height and estimated linear growth velocity as the first derivative of the mixed effect model with fractional polynomial transformations and, thereafter, used the second derivative test to determine the ...
Introduction In cholera endemic areas, the periodicity of cholera outbreaks remains unpredictable... more 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%) a...
Background We set out to assess the impact of human immunodeficiency virus (HIV) and micronutrien... more 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...
Background:Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome corona... more Background:Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing global health crisis that has caused large scale morbidity and mortality. We aimed to determine the exposure to SARS-CoV-2 among young children and healthcare workers by measurement of anti-S1 antigen (spike protein) specific immunoglobulin G (IgG) using an in-house optimized indirect enzyme-linked immunosorbent assay (ELISA) method.Methods:Plasma samples were collected from cohorts of healthcare workers (n = 287) and young children aged from 6 weeks to 2 years old (n = 150) pre-COVID-19 pandemic between September 2018 and November 2019 and post-COVID-19 pandemic between August and December 2020 were simultaneously tested for anti-SARS-CoV-2 S1 specific IgG. The arithmetic mean of natural logarithm-transformed ELISA relative absorbance reading + (3 x standard deviation) of pre-pandemic plasma was used as the cut-off to determine SARS-CoV-2 IgG seroposit...
Introduction Shigellosis, is a leading cause of moderate-to-severe diarrhoea and related mortalit... more 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. fl...
Background: We aimed to document viral, bacterial, and protozoan enteric pathogens responsible fo... more Background: We aimed to document viral, bacterial, and protozoan enteric pathogens responsible for causing moderate-to-severe diarrhoea among children under five presenting at public health facilities in Zambia following the introduction of rotavirus vaccination. Methods: This was a cross-sectional study in which clinical data and stool samples were collected between July 2012 and October 2013 from children under five years presenting to outpatient clinics in Lusaka province with moderate-tosevere diarrhoea. The study was conducted during the early months post rotavirus vaccine introduction in Zambia. We used Luminex x-TAG® gastrointestinal pathogen panel to simultaneously detect enteric viruses, bacteria and protozoa from the stool samples. We applied the population attributable fraction to estimate pathogen-specific burden of moderate-to-severe diarrhoea. Results: We analysed 1,135 unique stool samples with clinical data, of which 56% had received one or full dose rotavirus vaccination. The median age was 14 months (IQR=8, 22). The prevalence of moderate-to-severe diarrhoea was estimated as 18.9% (95%CI=16.7, 21.2). The most attributable cases of moderate-to-severe diarrhoea were due to rotavirus {attributable fraction=24.5%; 95%CI=(5.4, 39.7)} followed by Shigella spp. {attributable fraction=6.7%; 95%CI=(0.1, 15.5)}. The top 5 enteric pathogens detected among children were rotavirus (67.6%), Adenovirus (41.5%), ETEC (40.7%), Salmonella (38.4%) and Giardia (37.0%). Conclusion: We found that about one-third of moderate-tosevere diarrhoea among children were attributable to rotavirus and Shigella spp.
Background Rotavirus is the most common cause of fatal diarrhoeal disease among children under th... more Background Rotavirus is the most common cause of fatal diarrhoeal disease among children under the age of five globally and is responsible for millions of hospitalizations each year. Although nutritional status and environmental enteric dysfunction (EED) are recognized as important predictors of susceptibility to diarrhoeal disease, no research to date has examined the mechanisms by which undernutrition and EED may protect against prevalence of rotavirus infection.
Background: Environmental Enteropathy (EE) is a complex syndrome involving intestinal disorder wh... more Background: Environmental Enteropathy (EE) is a complex syndrome involving intestinal disorder which has been observed among children living in resource-poor settings. We investigated stored stool samples collected from children under-5 for relationships between specific enteric pathogens and levels of stool EE markers: Calprotectin (CALP), Alpha-1-Anti-Trypsin (AAT) and Myeloperoxidase (MPO). Methods: We used clinical data and stored stool samples collected prior to, and during the early months of widespread rotavirus vaccine implementation in Lusaka between July 2012 and October 2013 in Lusaka, Zambia. Children were considered eligible if they presented to the facility with symptoms of moderate-to-severe diarrhoea defined by having one or more of the following signs or symptoms: dehydration evidenced by sunken eyes, loss of normal skin turgor, or requiring intravenous resuscitation; dysentery (diarrhoea with blood in stool); or hospitalisation. We randomly selected 320 stool samples from the pool of 2,050 for analysis. We tested for 15 enteric pathogens using the Luminex XTag GPP panel and used commercial ELISA kits to assess the presence and levels of three known fecal markers of EE. We derived an EE score using a weighted sum of CALP, AAT, and MPO and applied a multivariable linear regression model to identify enteric pathogens independently associated with EE score. Results: After excluding insufficient samples (24) and those with missing clinical data (62), a total of the 234 were available for analysis. Of these, 114 (49%) were female, 103 (44%) were asymptomatic for diarrhoea, 181 (77%) had two or more enteric pathogens detected in stool. Fifty-six percent (131/234) children were positive for Rotavirus, 43.2% (101/234) Enterotoxigenic E. coli, 36% (86/234) Giardia, 35% (82/234) Adenovirus and 34.2% (80/234) had Shigella. The mean EE score was 5 (SD=2.25). The median concentration of MPO, CALP, and AAT were 2560.4 ng/ml (interquartile range (IQR)=806.1, 6522.9), 79.1 ng/ml (IQR=0, 362.5), and 48.6 mg/ml (IQR=12.1, 139.5) respectively. Shigella (coefficient=0.92; 95%CI=(0.14, 1.70); p=0.022) and Salmonella (coefficient=0.83; 95%CI=(0.08, 1.58); p=0.030) were independently associated with increase in mean EE score and together with E. coli accounted for 68.5% of the predicted variance in EE score. Conclusions: Salmonella and Shigella were found to be associated with EE and together with accounted for over two-thirds of variability in the EE score.
Background: Linear growth retardation is the most dominant nutritional problem globally. We aimed... more Background: Linear growth retardation is the most dominant nutritional problem globally. We aimed to describe linear growth trajectory among infants under 2 years of age using the WHO growth velocity standards. Method: This was a prospective cohort study of infants enrolled at 6 weeks of age and followed up for up to 24 months in Kamwala Urban Health Centre, Lusaka, Zambia. The study was conducted between April 2013 and March 2015. Infants were enrolled if they were 6-12 weeks of age and the mother was willing to participate voluntarily and provided informed consent. Anthropometric data were collected at scheduled clinic visits at 1 month, 2 months, 3 months, then quarterly until the infant was 24 months old. We defined linear growth velocity as the rate of change in height. We estimated linear growth velocity as the first derivative of the penalized cubic spline mixed effects model. Results: A total of 338 children were included in the analysis. Of these, 185 (54.7%) were female, 115 (34.1%) were born to HIV positive mothers and thus classified as HIV Exposed (HE). The mean age of children at enrollment was 1.6 months (SD = 0.15). On average, the growth velocity for 3-month length increments conditional on age were 0-3 months = 2.97 cm/3mo (95%CI = 2.69, 3.25); 3-6 months = 2.62 cm/3mo (95%CI = 2.38, 2.87); 6-9 months = 1.57 cm/ 3mo (95%CI = 1.43, 1.71); 9-12 months = 1.18 cm/3mo (95%CI = 1.08, 1.28); 12-15 month = 1.14 cm/3mo (95%CI = 1. 02, 1.27); 15-18 months = 0.87 cm/3mo (95%CI = 0.79, 0.96); 18-21 months = 0.80 cm/3mo (95%CI = 0.72, 0.89); and 21-24 months = 0.86 cm/3mo (95%CI = 0.77, 0.96). For both boys and girls, the growth velocity in our cohort were consistently below the 3rd percentile of the WHO linear growth velocity standard. The estimated mean height and the age at which growth begins to falter were 68.6 cm (95%CI = 68.0, 69.2) and 13.6 months (95%CI = 13.2, 14.1) respectively. Conclusion: We found slower rate of growth among otherwise healthy Zambian infants. The data suggests that growth retardation is universal and profound in this cohort and may have already been occurring in utero.
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Papers by Samuel Bosomprah