BackgroundCholera surveillance relies on clinical diagnosis of acute watery diarrhea. Suspected c... more BackgroundCholera surveillance relies on clinical diagnosis of acute watery diarrhea. Suspected cholera case definitions have high sensitivity but low specificity, challenging our ability to characterize cholera burden and epidemiology. Our objective was to estimate the proportion of clinically suspected cholera that are true Vibrio cholerae infections and identify factors that explain variation in positivity.MethodsWe conducted a systematic review of studies from 2000-2021 that tested ≥10 suspected cholera cases for V. cholerae O1/O139 using culture, PCR and/or a rapid diagnostic test. We estimated diagnostic test sensitivity and specificity using a latent class meta-analysis. We estimated positivity using a random-effects meta-analysis, adjusting for test performance and study methodology.ResultsWe included 113 studies from 28 countries. V. cholerae positivity was lower in studies with representative sampling and lower minimum ages in suspected case definitions. After adjusting fo...
Background Moraxella catarrhalis is one of the bacterial pathogens associated with childhood pneu... more Background Moraxella catarrhalis is one of the bacterial pathogens associated with childhood pneumonia, but its clinical importance is not clearly defined. Objective This study aimed to investigate the microbiologic and virulence characteristics of M. catarrhalis isolates obtained from children with pneumonia in Lusaka, Zambia. Methods This retrospective, cross-sectional study analyzed 91 M. catarrhalis isolates from induced sputum samples of children less than 5 years of age with pneumonia enrolled in the Pneumonia Etiology Research for Child Health study in Lusaka, Zambia between 2011 and 2014. Bacteria identification and virulence genes detection were performed by PCR and DNA sequencing, while antimicrobial susceptibility testing was determined by the Kirby–Bauer method. Results All the M. catarrhalis isolates were obtained from good-quality sputum samples and were the predominant bacteria. These isolates harbored virulence genes copB (100%), ompE (69.2%), ompCD (71.4%), uspA1 (92.3%), and uspA2 (69.2%) and were all β-lactamase producers. They showed resistance to ampicillin (100%), amoxicillin (100%), trimethoprim-sulfamethoxazole (92.3%), ciprofloxacin (46.2%), chloramphenicol (45.1%), erythromycin (36.3%), tetracycline (25.3%), cefuroxime (11.0%), and amoxicillin-clavulanate (2.2%), with 71.4% displaying multi-drug resistant phenotype but all susceptible to imipenem (100%). Conclusion This study showed that M. catarrhalis isolates were the predominant or only bacterial isolates from the sputum samples analyzed. The findings provide supportive evidence for the pathogenic potential role of this bacterium in pediatric pneumonia. High multidrug resistance was also observed amongst the isolates, which can result in affected patients not responding to standard treatment, leading to prolonged illness, increased healthcare costs, and risk of death.
Background Cholera has been present and recurring in Zambia since 1977. However, there is a pauci... more Background Cholera has been present and recurring in Zambia since 1977. However, there is a paucity of data on genetic relatedness and diversity of the Vibrio cholerae isolates responsible for these outbreaks. Understanding whether the outbreaks are seeded from existing local isolates or if the outbreaks represent separate transmission events can inform public health decisions. Results Seventy-two V. cholerae isolates from outbreaks in 2009/2010, 2016, and 2017/2018 in Zambia were characterized using multilocus variable number tandem repeat analysis (MLVA) and whole genome sequencing (WGS). The isolates had eight distinct MLVA genotypes that clustered into three MLVA clonal complexes (CCs). Each CC contained isolates from only one outbreak. The results from WGS revealed both clustered and dispersed single nucleotide variants. The genetic relatedness of isolates based on WGS was consistent with the MLVA, each CC was a distinct genetic lineage and had nearest neighbors from other East...
Additional file 5 Supplemental Table 4: List of Clusters of Single Nucleotide Variants in Identif... more Additional file 5 Supplemental Table 4: List of Clusters of Single Nucleotide Variants in Identified Supplemental Table 3
Additional file 4 Supplemental Table 3: Single Nucleotide Variants Found in Each Isolate and the ... more Additional file 4 Supplemental Table 3: Single Nucleotide Variants Found in Each Isolate and the Gene in Which the Single Nucleotide Variants Occurred.
Additional file 1 Supplemental Figure 1: Unrooted Phylogram of the Genetic Relatedness of Isolate... more Additional file 1 Supplemental Figure 1: Unrooted Phylogram of the Genetic Relatedness of Isolates from Zambia, East Africa and Asia.
Additional file 3 Supplemental Table 2: Number of Single Nucleotide Variants Between Pairs of Iso... more Additional file 3 Supplemental Table 2: Number of Single Nucleotide Variants Between Pairs of Isolates.
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...
The global burden of cholera is increasing, with the majority (60%) of the cases occurring in sub... more 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,
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.
Two-dose killed oral cholera vaccines (OCV) are currently being used widely to control cholera. T... more 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).
In Bangladesh and West Bengal cholera is seasonal, transmission occurs consistently annually. By ... more In Bangladesh and West Bengal cholera is seasonal, transmission occurs consistently annually. By contrast, in most African countries, cholera has inconsistent seasonal patterns and long periods without obvious transmission. Transmission patterns in Africa occur during intermittent outbreaks followed by elimination of that genetic lineage. Later another outbreak may occur because of reintroduction of new or evolved lineages from adjacent areas, often by human travelers. These then subsequently undergo subsequent elimination. The frequent elimination and reintroduction has several implications when planning for cholera’s elimination including: a) reconsidering concepts of definition of elimination, b) stress on rapid detection and response to outbreaks, c) more effective use of oral cholera vaccine and WASH, d) need to readjust estimates of disease burden for Africa, e) re-examination of water as a reservoir for maintaining endemicity in Africa. This paper reviews major features of ch...
Background An improved understanding of childhood pneumonia etiology is required to inform preven... more Background An improved understanding of childhood pneumonia etiology is required to inform prevention and treatment strategies. Lung aspiration is the gold standard specimen for pneumonia diagnostics. We report findings from analyses of lung and pleural aspirates collected in the Pneumonia Etiology Research for Child Health (PERCH) study. Methods The PERCH study enrolled children aged 1–59 months hospitalized with World Health Organization–defined severe or very severe pneumonia in 7 countries in Africa and Asia. Percutaneous transthoracic lung aspiration (LA) and pleural fluid (PF) aspiration was performed on a sample of pneumonia cases with radiological consolidation and/or PF in 4 countries. Venous blood and nasopharyngeal/oropharyngeal swabs were collected from all cases. Multiplex quantitative polymerase chain reaction (PCR) and routine microbiologic culture were applied to clinical specimens. Results Of 44 LAs performed within 3 days of admission on 622 eligible cases, 13 (30%...
Introduction: in 2009 and 2010, more than 6,000 cholera cases were recorded during these outbreak... more Introduction: in 2009 and 2010, more than 6,000 cholera cases were recorded during these outbreaks with more than 80% of cases recorded in Lusaka province. After a five-year break, in 2016 an outbreak occurred in Lusaka, causing more than 1,000 cases of cholera. This study will strengthen the epidemiological information on the changing characteristics of the cholera outbreaks, for treatment, prevention and control of the disease. Methods: this was a laboratory-based descriptive cross-sectional study conducted at the University Teaching Hospital in Lusaka, Zambia. A total of 83 V. cholerae O1 isolates were characterised by biochemical testing, serotyping, antimicrobial susceptibility testing, and macrorestriction analysis using Pulsed-Field Gel Electrophoresis. Results: macrorestriction analysis of the isolates demonstrated high genetic diversity among the isolates with 16 different patterns. The largest pattern comprised 9 isolates while the smallest one had 1 isolate. 2009 and 2010 isolates were highly resistant to nalidixic acid and cotrimoxazole, but highly sensitive to azithromycin and ampicillin. Of the fifty-two isolates from the 2016 cholera outbreak, 90% (47) were sensitive to cotrimoxazole, 94% (49) to tetracycline, and 98% (51) to azithromycin, while 98% (51) were resistant to nalidixic acid and 31(60%) to ampicillin. Conclusion: macrorestriction analysis demonstrated high genetic diversity among the V. cholerae O1 strains, suggesting that these isolates were probably not from a similar source. This study also revealed the emergence of multidrug resistance among the 2016 V. cholerae outbreak isolates but were susceptible to cotrimoxazole, tetracycline, and azithromycin, which can be used for treatment of the cholera cases.
Enterotoxigenic Escherichia Coli (ETEC) is an important cause for diarrheal disease in children a... more Enterotoxigenic Escherichia Coli (ETEC) is an important cause for diarrheal disease in children and travelers globally. Epidemiological data on the distribution of strains of ETEC and associated colonization factors (CFs) is important for evaluation of candidate vaccines. We used conventional PCR and quantitative PCR to screen for toxins and CFs using DNA extracted from stool samples which tested positive for ETEC using the Luminex GPP panel collected from children presenting with moderate to severe diarrhea at selected health facilities in Lusaka. 49/106 (46.2%) were positive for at least one toxin (i.e. LT/STh/STp), ST was 18 (17%) [STh 16(15%) and STp 2 (~2%)], and LT 16(15%). The most frequent CF detected was CS6 with 6/49 (12.2%), followed by CS2, CS3 and CS7 with 2/49 (4.1%) each. CS6 was common across all toxin combinations (LT only, STh only and a combination of
Tropical Medicine & International Health, 2018
objective To assess the performance of the SD Bioline Cholera Ag O1/O139 rapid diagnostic test (R... more objective To assess the performance of the SD Bioline Cholera Ag O1/O139 rapid diagnostic test (RDT) compared to a reference standard combining culture and PCR for the diagnosis of cholera cases during an outbreak. methods RDT and bacterial culture were performed on site using fresh stools collected from cholera suspected cases, and from stools enriched in alkaline peptone water. Dried stool samples on filter paper were tested for V. cholerae by PCR in Lusaka (as part of a laboratory technology transfer project) and at a reference laboratory in Paris, France. A sample was considered positive for cholera by the reference standard if any of the culture or PCR tests was positive for V. cholerae O1 or O139. results Among the 170 samples tested with SD Bioline and compared to the reference standard, the RDT showed a sensitivity of 90.9% (95% CI: 81.3-96.6) and specificity of 95.2% (95% CI: 89.1-98.4). After enrichment, the sensitivity was 95.5% (95% CI: 87.3-99.1) and specificity 100% (95% CI: 96.5-100). conclusion The observed sensitivity and specificity were within recommendations set by the Global Task Force for Cholera Control on the use of cholera RDT (sensitivity = 90%; specificity = 85%). Although the sample size was small, our findings suggest that the SD Bioline RDT could be used in the field to rapidly alert public health officials to the likely presence of cholera cases when an outbreak is suspected. keywords cholera, rapid diagnostic test, diagnostic accuracy, outbreak
Deployment of rotavirus vaccines has contributed to significant declines in diarrheal morbidity a... more Deployment of rotavirus vaccines has contributed to significant declines in diarrheal morbidity and mortality globally. Unfortunately, vaccine performance in low-middle income countries (LMICs) is generally lower than in developed countries. The cause for this has been associated with several host and maternal factors including poor water sanitation and hygiene (WASH) status, which are predominant in LMICs. More recently, environmental enteric dysfunction (EED) has specifically been hypothesized to contribute to poor vaccine uptake and response. The aim of this study was to examine the association between serological biomarkers of EED and seroconversion to rotavirus vaccine in Zambian infants. This was a retrospective cohort study of 142 infants who had been fully immunized with Rotarix™, and had known seroconversion status. Seroconversion was defined as 4-fold or more increase in rotavirus-specific IgA titres between pre-vaccination and one month post-dose two vaccination. We perfo...
BackgroundCholera surveillance relies on clinical diagnosis of acute watery diarrhea. Suspected c... more BackgroundCholera surveillance relies on clinical diagnosis of acute watery diarrhea. Suspected cholera case definitions have high sensitivity but low specificity, challenging our ability to characterize cholera burden and epidemiology. Our objective was to estimate the proportion of clinically suspected cholera that are true Vibrio cholerae infections and identify factors that explain variation in positivity.MethodsWe conducted a systematic review of studies from 2000-2021 that tested ≥10 suspected cholera cases for V. cholerae O1/O139 using culture, PCR and/or a rapid diagnostic test. We estimated diagnostic test sensitivity and specificity using a latent class meta-analysis. We estimated positivity using a random-effects meta-analysis, adjusting for test performance and study methodology.ResultsWe included 113 studies from 28 countries. V. cholerae positivity was lower in studies with representative sampling and lower minimum ages in suspected case definitions. After adjusting fo...
Background Moraxella catarrhalis is one of the bacterial pathogens associated with childhood pneu... more Background Moraxella catarrhalis is one of the bacterial pathogens associated with childhood pneumonia, but its clinical importance is not clearly defined. Objective This study aimed to investigate the microbiologic and virulence characteristics of M. catarrhalis isolates obtained from children with pneumonia in Lusaka, Zambia. Methods This retrospective, cross-sectional study analyzed 91 M. catarrhalis isolates from induced sputum samples of children less than 5 years of age with pneumonia enrolled in the Pneumonia Etiology Research for Child Health study in Lusaka, Zambia between 2011 and 2014. Bacteria identification and virulence genes detection were performed by PCR and DNA sequencing, while antimicrobial susceptibility testing was determined by the Kirby–Bauer method. Results All the M. catarrhalis isolates were obtained from good-quality sputum samples and were the predominant bacteria. These isolates harbored virulence genes copB (100%), ompE (69.2%), ompCD (71.4%), uspA1 (92.3%), and uspA2 (69.2%) and were all β-lactamase producers. They showed resistance to ampicillin (100%), amoxicillin (100%), trimethoprim-sulfamethoxazole (92.3%), ciprofloxacin (46.2%), chloramphenicol (45.1%), erythromycin (36.3%), tetracycline (25.3%), cefuroxime (11.0%), and amoxicillin-clavulanate (2.2%), with 71.4% displaying multi-drug resistant phenotype but all susceptible to imipenem (100%). Conclusion This study showed that M. catarrhalis isolates were the predominant or only bacterial isolates from the sputum samples analyzed. The findings provide supportive evidence for the pathogenic potential role of this bacterium in pediatric pneumonia. High multidrug resistance was also observed amongst the isolates, which can result in affected patients not responding to standard treatment, leading to prolonged illness, increased healthcare costs, and risk of death.
Background Cholera has been present and recurring in Zambia since 1977. However, there is a pauci... more Background Cholera has been present and recurring in Zambia since 1977. However, there is a paucity of data on genetic relatedness and diversity of the Vibrio cholerae isolates responsible for these outbreaks. Understanding whether the outbreaks are seeded from existing local isolates or if the outbreaks represent separate transmission events can inform public health decisions. Results Seventy-two V. cholerae isolates from outbreaks in 2009/2010, 2016, and 2017/2018 in Zambia were characterized using multilocus variable number tandem repeat analysis (MLVA) and whole genome sequencing (WGS). The isolates had eight distinct MLVA genotypes that clustered into three MLVA clonal complexes (CCs). Each CC contained isolates from only one outbreak. The results from WGS revealed both clustered and dispersed single nucleotide variants. The genetic relatedness of isolates based on WGS was consistent with the MLVA, each CC was a distinct genetic lineage and had nearest neighbors from other East...
Additional file 5 Supplemental Table 4: List of Clusters of Single Nucleotide Variants in Identif... more Additional file 5 Supplemental Table 4: List of Clusters of Single Nucleotide Variants in Identified Supplemental Table 3
Additional file 4 Supplemental Table 3: Single Nucleotide Variants Found in Each Isolate and the ... more Additional file 4 Supplemental Table 3: Single Nucleotide Variants Found in Each Isolate and the Gene in Which the Single Nucleotide Variants Occurred.
Additional file 1 Supplemental Figure 1: Unrooted Phylogram of the Genetic Relatedness of Isolate... more Additional file 1 Supplemental Figure 1: Unrooted Phylogram of the Genetic Relatedness of Isolates from Zambia, East Africa and Asia.
Additional file 3 Supplemental Table 2: Number of Single Nucleotide Variants Between Pairs of Iso... more Additional file 3 Supplemental Table 2: Number of Single Nucleotide Variants Between Pairs of Isolates.
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...
The global burden of cholera is increasing, with the majority (60%) of the cases occurring in sub... more 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,
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.
Two-dose killed oral cholera vaccines (OCV) are currently being used widely to control cholera. T... more 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).
In Bangladesh and West Bengal cholera is seasonal, transmission occurs consistently annually. By ... more In Bangladesh and West Bengal cholera is seasonal, transmission occurs consistently annually. By contrast, in most African countries, cholera has inconsistent seasonal patterns and long periods without obvious transmission. Transmission patterns in Africa occur during intermittent outbreaks followed by elimination of that genetic lineage. Later another outbreak may occur because of reintroduction of new or evolved lineages from adjacent areas, often by human travelers. These then subsequently undergo subsequent elimination. The frequent elimination and reintroduction has several implications when planning for cholera’s elimination including: a) reconsidering concepts of definition of elimination, b) stress on rapid detection and response to outbreaks, c) more effective use of oral cholera vaccine and WASH, d) need to readjust estimates of disease burden for Africa, e) re-examination of water as a reservoir for maintaining endemicity in Africa. This paper reviews major features of ch...
Background An improved understanding of childhood pneumonia etiology is required to inform preven... more Background An improved understanding of childhood pneumonia etiology is required to inform prevention and treatment strategies. Lung aspiration is the gold standard specimen for pneumonia diagnostics. We report findings from analyses of lung and pleural aspirates collected in the Pneumonia Etiology Research for Child Health (PERCH) study. Methods The PERCH study enrolled children aged 1–59 months hospitalized with World Health Organization–defined severe or very severe pneumonia in 7 countries in Africa and Asia. Percutaneous transthoracic lung aspiration (LA) and pleural fluid (PF) aspiration was performed on a sample of pneumonia cases with radiological consolidation and/or PF in 4 countries. Venous blood and nasopharyngeal/oropharyngeal swabs were collected from all cases. Multiplex quantitative polymerase chain reaction (PCR) and routine microbiologic culture were applied to clinical specimens. Results Of 44 LAs performed within 3 days of admission on 622 eligible cases, 13 (30%...
Introduction: in 2009 and 2010, more than 6,000 cholera cases were recorded during these outbreak... more Introduction: in 2009 and 2010, more than 6,000 cholera cases were recorded during these outbreaks with more than 80% of cases recorded in Lusaka province. After a five-year break, in 2016 an outbreak occurred in Lusaka, causing more than 1,000 cases of cholera. This study will strengthen the epidemiological information on the changing characteristics of the cholera outbreaks, for treatment, prevention and control of the disease. Methods: this was a laboratory-based descriptive cross-sectional study conducted at the University Teaching Hospital in Lusaka, Zambia. A total of 83 V. cholerae O1 isolates were characterised by biochemical testing, serotyping, antimicrobial susceptibility testing, and macrorestriction analysis using Pulsed-Field Gel Electrophoresis. Results: macrorestriction analysis of the isolates demonstrated high genetic diversity among the isolates with 16 different patterns. The largest pattern comprised 9 isolates while the smallest one had 1 isolate. 2009 and 2010 isolates were highly resistant to nalidixic acid and cotrimoxazole, but highly sensitive to azithromycin and ampicillin. Of the fifty-two isolates from the 2016 cholera outbreak, 90% (47) were sensitive to cotrimoxazole, 94% (49) to tetracycline, and 98% (51) to azithromycin, while 98% (51) were resistant to nalidixic acid and 31(60%) to ampicillin. Conclusion: macrorestriction analysis demonstrated high genetic diversity among the V. cholerae O1 strains, suggesting that these isolates were probably not from a similar source. This study also revealed the emergence of multidrug resistance among the 2016 V. cholerae outbreak isolates but were susceptible to cotrimoxazole, tetracycline, and azithromycin, which can be used for treatment of the cholera cases.
Enterotoxigenic Escherichia Coli (ETEC) is an important cause for diarrheal disease in children a... more Enterotoxigenic Escherichia Coli (ETEC) is an important cause for diarrheal disease in children and travelers globally. Epidemiological data on the distribution of strains of ETEC and associated colonization factors (CFs) is important for evaluation of candidate vaccines. We used conventional PCR and quantitative PCR to screen for toxins and CFs using DNA extracted from stool samples which tested positive for ETEC using the Luminex GPP panel collected from children presenting with moderate to severe diarrhea at selected health facilities in Lusaka. 49/106 (46.2%) were positive for at least one toxin (i.e. LT/STh/STp), ST was 18 (17%) [STh 16(15%) and STp 2 (~2%)], and LT 16(15%). The most frequent CF detected was CS6 with 6/49 (12.2%), followed by CS2, CS3 and CS7 with 2/49 (4.1%) each. CS6 was common across all toxin combinations (LT only, STh only and a combination of
Tropical Medicine & International Health, 2018
objective To assess the performance of the SD Bioline Cholera Ag O1/O139 rapid diagnostic test (R... more objective To assess the performance of the SD Bioline Cholera Ag O1/O139 rapid diagnostic test (RDT) compared to a reference standard combining culture and PCR for the diagnosis of cholera cases during an outbreak. methods RDT and bacterial culture were performed on site using fresh stools collected from cholera suspected cases, and from stools enriched in alkaline peptone water. Dried stool samples on filter paper were tested for V. cholerae by PCR in Lusaka (as part of a laboratory technology transfer project) and at a reference laboratory in Paris, France. A sample was considered positive for cholera by the reference standard if any of the culture or PCR tests was positive for V. cholerae O1 or O139. results Among the 170 samples tested with SD Bioline and compared to the reference standard, the RDT showed a sensitivity of 90.9% (95% CI: 81.3-96.6) and specificity of 95.2% (95% CI: 89.1-98.4). After enrichment, the sensitivity was 95.5% (95% CI: 87.3-99.1) and specificity 100% (95% CI: 96.5-100). conclusion The observed sensitivity and specificity were within recommendations set by the Global Task Force for Cholera Control on the use of cholera RDT (sensitivity = 90%; specificity = 85%). Although the sample size was small, our findings suggest that the SD Bioline RDT could be used in the field to rapidly alert public health officials to the likely presence of cholera cases when an outbreak is suspected. keywords cholera, rapid diagnostic test, diagnostic accuracy, outbreak
Deployment of rotavirus vaccines has contributed to significant declines in diarrheal morbidity a... more Deployment of rotavirus vaccines has contributed to significant declines in diarrheal morbidity and mortality globally. Unfortunately, vaccine performance in low-middle income countries (LMICs) is generally lower than in developed countries. The cause for this has been associated with several host and maternal factors including poor water sanitation and hygiene (WASH) status, which are predominant in LMICs. More recently, environmental enteric dysfunction (EED) has specifically been hypothesized to contribute to poor vaccine uptake and response. The aim of this study was to examine the association between serological biomarkers of EED and seroconversion to rotavirus vaccine in Zambian infants. This was a retrospective cohort study of 142 infants who had been fully immunized with Rotarix™, and had known seroconversion status. Seroconversion was defined as 4-fold or more increase in rotavirus-specific IgA titres between pre-vaccination and one month post-dose two vaccination. We perfo...
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Papers by john mwaba