Journal Article > ResearchFull Text
Sci Rep. 2016 October 24; Volume 6; 35742.; DOI:10.1038/srep35742
Iyer AS, Ryan ET, Martin S, Legros D, Lessler J, et al.
Sci Rep. 2016 October 24; Volume 6; 35742.; DOI:10.1038/srep35742
Despite recent large-scale cholera outbreaks, little is known about the immunogenicity of oral cholera vaccines (OCV) in African populations, particularly among those at highest cholera risk. During a 2015 preemptive OCV campaign among internally displaced persons in South Sudan, a year after a large cholera outbreak, we enrolled 37 young children (1-5 years old), 67 older children (6-17 years old) and 101 adults (≥18 years old), who received two doses of OCV (Shanchol) spaced approximately 3 weeks apart. Cholera-specific antibody responses were determined at days 0, 21 and 35 post-immunization. High baseline vibriocidal titers (>80) were observed in 21% of the participants, suggesting recent cholera exposure or vaccination. Among those with titers ≤80, 90% young children, 73% older children and 72% adults seroconverted (≥4 fold titer rise) after the 1(st) OCV dose; with no additional seroconversion after the 2(nd) dose. Post-vaccination immunological endpoints did not differ across age groups. Our results indicate Shanchol was immunogenic in this vulnerable population and that a single dose alone may be sufficient to achieve similar short-term immunological responses to the currently licensed two-dose regimen. While we found no evidence of differential response by age, further immunologic and epidemiologic studies are needed.
Journal Article > ResearchFull Text
Lancet Planet Health. 2020 December 1; Volume 4; DOI:10.1016/S2542-5196(20)30255-2
Jones FK, Wamala JF, Rumunu J, Mawien PN, Kol MT, et al.
Lancet Planet Health. 2020 December 1; Volume 4; DOI:10.1016/S2542-5196(20)30255-2
Background
Between 2014 and 2017, successive cholera epidemics occurred in South Sudan within the context of civil war, population displacement, flooding, and drought. We aim to describe the spatiotemporal and molecular features of the three distinct epidemic waves and explore the role of vaccination campaigns, precipitation, and population movement in shaping cholera spread in this complex setting.
Methods
In this descriptive epidemiological study, we analysed cholera linelist data to describe the spatiotemporal progression of the epidemics. We placed whole-genome sequence data from pandemic Vibrio cholerae collected throughout these epidemics into the global phylogenetic context. Using whole-genome sequence data in combination with other molecular attributes, we characterise the relatedness of strains circulating in each wave and the region. We investigated the association of rainfall and the instantaneous basic reproduction number using distributed lag non-linear models, compared county-level attack rates between those with early and late reactive vaccination campaigns, and explored the consistency of the spatial patterns of displacement and suspected cholera case reports.
Findings
The 2014 (6389 cases) and 2015 (1818 cases) cholera epidemics in South Sudan remained spatially limited whereas the 2016–17 epidemic (20 438 cases) spread among settlements along the Nile river. Initial cases of each epidemic were reported in or around Juba soon after the start of the rainy season, but we found no evidence that rainfall modulated transmission during each epidemic. All isolates analysed had similar genotypic and phenotypic characteristics, closely related to sequences from Uganda and Democratic Republic of the Congo. Large-scale population movements between counties of South Sudan with cholera outbreaks were consistent with the spatial distribution of cases. 21 of 26 vaccination campaigns occurred during or after the county-level epidemic peak. Counties vaccinated on or after the peak incidence week had 2·2 times (95% CI 2·1–2·3) higher attack rates than those where vaccination occurred before the peak.
Interpretation
Pandemic V cholerae of the same clonal origin was isolated throughout the study period despite interepidemic periods of no reported cases. Although the complex emergency in South Sudan probably shaped some of the observed spatial and temporal patterns of cases, the full scope of transmission determinants remains unclear. Timely and well targeted use of vaccines can reduce the burden of cholera; however, rapid vaccine deployment in complex emergencies remains challenging.
Between 2014 and 2017, successive cholera epidemics occurred in South Sudan within the context of civil war, population displacement, flooding, and drought. We aim to describe the spatiotemporal and molecular features of the three distinct epidemic waves and explore the role of vaccination campaigns, precipitation, and population movement in shaping cholera spread in this complex setting.
Methods
In this descriptive epidemiological study, we analysed cholera linelist data to describe the spatiotemporal progression of the epidemics. We placed whole-genome sequence data from pandemic Vibrio cholerae collected throughout these epidemics into the global phylogenetic context. Using whole-genome sequence data in combination with other molecular attributes, we characterise the relatedness of strains circulating in each wave and the region. We investigated the association of rainfall and the instantaneous basic reproduction number using distributed lag non-linear models, compared county-level attack rates between those with early and late reactive vaccination campaigns, and explored the consistency of the spatial patterns of displacement and suspected cholera case reports.
Findings
The 2014 (6389 cases) and 2015 (1818 cases) cholera epidemics in South Sudan remained spatially limited whereas the 2016–17 epidemic (20 438 cases) spread among settlements along the Nile river. Initial cases of each epidemic were reported in or around Juba soon after the start of the rainy season, but we found no evidence that rainfall modulated transmission during each epidemic. All isolates analysed had similar genotypic and phenotypic characteristics, closely related to sequences from Uganda and Democratic Republic of the Congo. Large-scale population movements between counties of South Sudan with cholera outbreaks were consistent with the spatial distribution of cases. 21 of 26 vaccination campaigns occurred during or after the county-level epidemic peak. Counties vaccinated on or after the peak incidence week had 2·2 times (95% CI 2·1–2·3) higher attack rates than those where vaccination occurred before the peak.
Interpretation
Pandemic V cholerae of the same clonal origin was isolated throughout the study period despite interepidemic periods of no reported cases. Although the complex emergency in South Sudan probably shaped some of the observed spatial and temporal patterns of cases, the full scope of transmission determinants remains unclear. Timely and well targeted use of vaccines can reduce the burden of cholera; however, rapid vaccine deployment in complex emergencies remains challenging.
Journal Article > ResearchFull Text
Int J Infect Dis. 2022 September 1; Volume 122; 215-221.; DOI:10.1016/j.ijid.2022.05.039
Zheng Q, Luquero FJ, Ciglenecki I, Wamala JF, Abubakar A, et al.
Int J Infect Dis. 2022 September 1; Volume 122; 215-221.; DOI:10.1016/j.ijid.2022.05.039
BACKGROUND
Cholera remains a public health threat but is inequitably distributed across sub-Saharan Africa. Lack of standardized reporting and inconsistent outbreak definitions limit our understanding of cholera outbreak epidemiology.
METHODS
From a database of cholera incidence and mortality, we extracted data from sub-Saharan Africa and reconstructed outbreaks of suspected cholera starting in January 2010 to December 2019 based on location-specific average weekly incidence rate thresholds. We then described the distribution of key outbreak metrics.
RESULTS
We identified 999 suspected cholera outbreaks in 744 regions across 25 sub-Saharan African countries. The outbreak periods accounted for 1.8 billion person-months (2% of the total during this period) from January 2010 to January 2020. Among 692 outbreaks reported from second-level administrative units (e.g., districts), the median attack rate was 0.8 per 1000 people (interquartile range (IQR), 0.3-2.4 per 1000), the median epidemic duration was 13 weeks (IQR, 8-19), and the median early outbreak reproductive number was 1.8 (range, 1.1-3.5). Larger attack rates were associated with longer times to outbreak peak, longer epidemic durations, and lower case fatality risks.
CONCLUSIONS
This study provides a baseline from which the progress toward cholera control and essential statistics to inform outbreak management in sub-Saharan Africa can be monitored.
Cholera remains a public health threat but is inequitably distributed across sub-Saharan Africa. Lack of standardized reporting and inconsistent outbreak definitions limit our understanding of cholera outbreak epidemiology.
METHODS
From a database of cholera incidence and mortality, we extracted data from sub-Saharan Africa and reconstructed outbreaks of suspected cholera starting in January 2010 to December 2019 based on location-specific average weekly incidence rate thresholds. We then described the distribution of key outbreak metrics.
RESULTS
We identified 999 suspected cholera outbreaks in 744 regions across 25 sub-Saharan African countries. The outbreak periods accounted for 1.8 billion person-months (2% of the total during this period) from January 2010 to January 2020. Among 692 outbreaks reported from second-level administrative units (e.g., districts), the median attack rate was 0.8 per 1000 people (interquartile range (IQR), 0.3-2.4 per 1000), the median epidemic duration was 13 weeks (IQR, 8-19), and the median early outbreak reproductive number was 1.8 (range, 1.1-3.5). Larger attack rates were associated with longer times to outbreak peak, longer epidemic durations, and lower case fatality risks.
CONCLUSIONS
This study provides a baseline from which the progress toward cholera control and essential statistics to inform outbreak management in sub-Saharan Africa can be monitored.
Journal Article > ResearchFull Text
Int J Infect Dis. 2022 May 19; Volume S1201-9712 (Issue 22); 00303-4.; DOI:10.1016/j.ijid.2022.05.039
Zheng Q, Luquero FJ, Ciglenecki I, Wamala JF, Abubakar A, et al.
Int J Infect Dis. 2022 May 19; Volume S1201-9712 (Issue 22); 00303-4.; DOI:10.1016/j.ijid.2022.05.039
BACKGROUND
Cholera remains a public health threat, but is inequitably distributed across sub-Saharan Africa. Lack of standardized reporting and inconsistent outbreak definitions limit our understanding of cholera outbreak epidemiology.
METHODS
From a database of cholera incidence and mortality, we extracted data from sub-Saharan Africa and reconstructed outbreaks of suspected cholera starting in January 2010 to December 2019 based on location-specific average weekly incidence rate thresholds. We then described the distribution of key outbreak metrics.
RESULTS
We identified 999 suspected cholera outbreaks in 744 regions across 25 sub-Saharan Africa countries, and outbreak periods accounted for 1.8 billion person-months (2% of the total during this period) from January 2010 through January 2020. Among 692 outbreaks reported from second-level administrative units (e.g., districts), the median attack rate was 0.8 per 1,000 people (IQR, 0.3-2.4 per 1,000), the median epidemic duration was 13 weeks (IQR, 8-19), and the median early outbreak reproductive number was 1.8 (range, 1.1-3.5). Larger attack rates were associated with longer times to outbreak peak, longer epidemic durations, and lower case fatality risks.
CONCLUSIONS
This work provides a baseline from which to monitor progress towards cholera control and essential statistics to inform outbreak management in sub-Saharan Africa.
Cholera remains a public health threat, but is inequitably distributed across sub-Saharan Africa. Lack of standardized reporting and inconsistent outbreak definitions limit our understanding of cholera outbreak epidemiology.
METHODS
From a database of cholera incidence and mortality, we extracted data from sub-Saharan Africa and reconstructed outbreaks of suspected cholera starting in January 2010 to December 2019 based on location-specific average weekly incidence rate thresholds. We then described the distribution of key outbreak metrics.
RESULTS
We identified 999 suspected cholera outbreaks in 744 regions across 25 sub-Saharan Africa countries, and outbreak periods accounted for 1.8 billion person-months (2% of the total during this period) from January 2010 through January 2020. Among 692 outbreaks reported from second-level administrative units (e.g., districts), the median attack rate was 0.8 per 1,000 people (IQR, 0.3-2.4 per 1,000), the median epidemic duration was 13 weeks (IQR, 8-19), and the median early outbreak reproductive number was 1.8 (range, 1.1-3.5). Larger attack rates were associated with longer times to outbreak peak, longer epidemic durations, and lower case fatality risks.
CONCLUSIONS
This work provides a baseline from which to monitor progress towards cholera control and essential statistics to inform outbreak management in sub-Saharan Africa.
Journal Article > ResearchFull Text
Lancet Global Health. 2016 November 1; Volume 4 (Issue 11); e856-e863.; DOI:10.1016/S2214-109X(16)30211-X
Azman AS, Parker LA, Rumunu J, Tadesse F, Grandesso F, et al.
Lancet Global Health. 2016 November 1; Volume 4 (Issue 11); e856-e863.; DOI:10.1016/S2214-109X(16)30211-X
BACKGROUND
Oral cholera vaccines represent a new effective tool to fight cholera and are licensed as two-dose regimens with 2-4 weeks between doses. Evidence from previous studies suggests that a single dose of oral cholera vaccine might provide substantial direct protection against cholera. During a cholera outbreak in May, 2015, in Juba, South Sudan, the Ministry of Health, Médecins Sans Frontières, and partners engaged in the first field deployment of a single dose of oral cholera vaccine to enhance the outbreak response. We did a vaccine effectiveness study in conjunction with this large public health intervention.
METHODS
We did a case-cohort study, combining information on the vaccination status and disease outcomes from a random cohort recruited from throughout the city of Juba with that from all the cases detected. Eligible cases were those aged 1 year or older on the first day of the vaccination campaign who sought care for diarrhoea at all three cholera treatment centres and seven rehydration posts throughout Juba. Confirmed cases were suspected cases who tested positive to PCR for Vibrio cholerae O1. We estimated the short-term protection (direct and indirect) conferred by one dose of cholera vaccine (Shanchol, Shantha Biotechnics, Hyderabad, India).
FINDINGS
Between Aug 9, 2015, and Sept 29, 2015, we enrolled 87 individuals with suspected cholera, and an 898-person cohort from throughout Juba. Of the 87 individuals with suspected cholera, 34 were classified as cholera positive, 52 as cholera negative, and one had indeterminate results. Of the 858 cohort members who completed a follow-up visit, none developed clinical cholera during follow-up. The unadjusted single-dose vaccine effectiveness was 80·2% (95% CI 61·5-100·0) and after adjusting for potential confounders was 87·3% (70·2-100·0).
INTERPRETATION
One dose of Shanchol was effective in preventing medically attended cholera in this study. These results support the use of a single-dose strategy in outbreaks in similar epidemiological settings.
Oral cholera vaccines represent a new effective tool to fight cholera and are licensed as two-dose regimens with 2-4 weeks between doses. Evidence from previous studies suggests that a single dose of oral cholera vaccine might provide substantial direct protection against cholera. During a cholera outbreak in May, 2015, in Juba, South Sudan, the Ministry of Health, Médecins Sans Frontières, and partners engaged in the first field deployment of a single dose of oral cholera vaccine to enhance the outbreak response. We did a vaccine effectiveness study in conjunction with this large public health intervention.
METHODS
We did a case-cohort study, combining information on the vaccination status and disease outcomes from a random cohort recruited from throughout the city of Juba with that from all the cases detected. Eligible cases were those aged 1 year or older on the first day of the vaccination campaign who sought care for diarrhoea at all three cholera treatment centres and seven rehydration posts throughout Juba. Confirmed cases were suspected cases who tested positive to PCR for Vibrio cholerae O1. We estimated the short-term protection (direct and indirect) conferred by one dose of cholera vaccine (Shanchol, Shantha Biotechnics, Hyderabad, India).
FINDINGS
Between Aug 9, 2015, and Sept 29, 2015, we enrolled 87 individuals with suspected cholera, and an 898-person cohort from throughout Juba. Of the 87 individuals with suspected cholera, 34 were classified as cholera positive, 52 as cholera negative, and one had indeterminate results. Of the 858 cohort members who completed a follow-up visit, none developed clinical cholera during follow-up. The unadjusted single-dose vaccine effectiveness was 80·2% (95% CI 61·5-100·0) and after adjusting for potential confounders was 87·3% (70·2-100·0).
INTERPRETATION
One dose of Shanchol was effective in preventing medically attended cholera in this study. These results support the use of a single-dose strategy in outbreaks in similar epidemiological settings.
Journal Article > CommentaryFull Text
Bull World Health Organ. 2018 June 1; Volume 96 (Issue 6); 428-435.; DOI:10.2471/BLT.17.207175
Mbangombe M, Pezzoli L, Reeder B, Kabuluzi S, Msyamboza K, et al.
Bull World Health Organ. 2018 June 1; Volume 96 (Issue 6); 428-435.; DOI:10.2471/BLT.17.207175
PROBLEM
With limited global supplies of oral cholera vaccine, countries need to identify priority areas for vaccination while longer-term solutions, such as water and sanitation infrastructure, are being developed.
APPROACH
In 2017, Malawi integrated oral cholera vaccine into its national cholera control plan. The process started with a desk review and analysis of previous surveillance and risk factor data. At a consultative meeting, researchers, national health and water officials and representatives from nongovernmental and international organizations reviewed the data and local epidemiological knowledge to determine priority districts for oral cholera vaccination. The final stage was preparation of an application to the global oral cholera vaccine stockpile for non-emergency use.
LOCAL SETTING
Malawi collects annual data on cholera and most districts have reported cases at least once since the 1970s.
RELEVANT CHANGES
The government’s application for 3.2 million doses of vaccine to be provided over 20 months in 12 districts was accepted in April 2017. By April 2018, over 1 million doses had been administered in five districts. Continuing surveillance in districts showed that cholera outbreaks were notably absent in vaccinated high-risk areas, despite a national outbreak in 2017–2018.
LESSONS LEARNT
Augmenting advanced mapping techniques with local information helped us extend priority areas beyond those identified as high-risk based on cholera incidence reported at the district level. Involvement of the water, sanitation and hygiene sectors is key to ensuring that short-term gains from cholera vaccine are backed by longer-term progress in reducing cholera transmission.
With limited global supplies of oral cholera vaccine, countries need to identify priority areas for vaccination while longer-term solutions, such as water and sanitation infrastructure, are being developed.
APPROACH
In 2017, Malawi integrated oral cholera vaccine into its national cholera control plan. The process started with a desk review and analysis of previous surveillance and risk factor data. At a consultative meeting, researchers, national health and water officials and representatives from nongovernmental and international organizations reviewed the data and local epidemiological knowledge to determine priority districts for oral cholera vaccination. The final stage was preparation of an application to the global oral cholera vaccine stockpile for non-emergency use.
LOCAL SETTING
Malawi collects annual data on cholera and most districts have reported cases at least once since the 1970s.
RELEVANT CHANGES
The government’s application for 3.2 million doses of vaccine to be provided over 20 months in 12 districts was accepted in April 2017. By April 2018, over 1 million doses had been administered in five districts. Continuing surveillance in districts showed that cholera outbreaks were notably absent in vaccinated high-risk areas, despite a national outbreak in 2017–2018.
LESSONS LEARNT
Augmenting advanced mapping techniques with local information helped us extend priority areas beyond those identified as high-risk based on cholera incidence reported at the district level. Involvement of the water, sanitation and hygiene sectors is key to ensuring that short-term gains from cholera vaccine are backed by longer-term progress in reducing cholera transmission.
Journal Article > CommentaryFull Text
Am J Trop Med Hyg. 2017 June 1; Volume 96 (Issue 6); 1270-1273.; DOI:10.4269/ajtmh.16-0427
Lessler J, Azman AS, McKay H, Moore SM
Am J Trop Med Hyg. 2017 June 1; Volume 96 (Issue 6); 1270-1273.; DOI:10.4269/ajtmh.16-0427
The importance of spatial clusters, or "hotspots," in infectious disease epidemiology has been increasingly recognized, and targeting hotspots is often seen as an important component of disease-control strategies. However, the precise meaning of "hotspot" varies widely in current research and policy documents. Hotspots have been variously described as areas of elevated incidence or prevalence, higher transmission efficiency or risk, or higher probability of disease emergence. This ambiguity has led to confusion and may result in mistaken inferences regarding the best way to target interventions. We surveyed the literature on epidemiologic hotspots, examining the multitude of ways in which the term is used; and highlight the difference in the geographic scale of hotspots and the properties they are supposed to have. In response to the diversity in the term's usage, we advocate the use of more precise terms, such as "burden hotspot," "transmission hotspot," and "emergence hotspot," as well as explicit specification of the spatiotemporal scale of interest. Increased precision in terminology is needed to ensure clear and effective policies for disease control.
Journal Article > ResearchFull Text
Lancet. 2018 May 1; Volume 391 (Issue 10133); DOI:10.1016/S0140-6736(17)33050-7
Lessler J, Moore SM, Luquero FJ, McKay H, Grais RF, et al.
Lancet. 2018 May 1; Volume 391 (Issue 10133); DOI:10.1016/S0140-6736(17)33050-7
Cholera remains a persistent health problem in sub-Saharan Africa and worldwide. Cholera can be controlled through appropriate water and sanitation, or by oral cholera vaccination, which provides transient (∼3 years) protection, although vaccine supplies remain scarce. We aimed to map cholera burden in sub-Saharan Africa and assess how geographical targeting could lead to more efficient interventions.
Journal Article > ResearchFull Text
Lancet Global Health. 2022 April 21; Volume S2214-109X (Issue 22); 00007-9.; DOI:10.1016/S2214-109X(22)00007-9
Perez-Saez J, Lessler J, Lee EC, Luquero FJ, Malembaka EB, et al.
Lancet Global Health. 2022 April 21; Volume S2214-109X (Issue 22); 00007-9.; DOI:10.1016/S2214-109X(22)00007-9
BACKGROUND
Cholera remains a major threat in sub-Saharan Africa (SSA), where some of the highest case-fatality rates are reported. Knowing in what months and where cholera tends to occur across the continent could aid in improving efforts to eliminate cholera as a public health concern. However, largely due to the absence of unified large-scale datasets, no continent-wide estimates exist. In this study, we aimed to estimate cholera seasonality across SSA and explore the correlation between hydroclimatic variables and cholera seasonality.
METHODS
Using the global cholera database of the Global Task Force on Cholera Control, we developed statistical models to synthesise data across spatial and temporal scales to infer the seasonality of excess (defined as incidence higher than the 2010-16 mean incidence rate) suspected cholera occurrence in SSA. We developed a Bayesian statistical model to infer the monthly risk of excess cholera at the first and second administrative levels. Seasonality patterns were then grouped into spatial clusters. Finally, we studied the association between seasonality estimates and hydroclimatic variables (mean monthly fraction of area flooded, mean monthly air temperature, and cumulative monthly precipitation).
FINDINGS
24 (71%) of the 34 countries studied had seasonal patterns of excess cholera risk, corresponding to approximately 86% of the SSA population. 12 (50%) of these 24 countries also had subnational differences in seasonality patterns, with strong differences in seasonality strength between regions. Seasonality patterns clustered into two macroregions (west Africa and the Sahel vs eastern and southern Africa), which were composed of subregional clusters with varying degrees of seasonality. Exploratory association analysis found most consistent and positive correlations between cholera seasonality and precipitation and, to a lesser extent, between cholera seasonality and temperature and flooding.
INTERPRETATION
Widespread cholera seasonality in SSA offers opportunities for intervention planning. Further studies are needed to study the association between cholera and climate.
Cholera remains a major threat in sub-Saharan Africa (SSA), where some of the highest case-fatality rates are reported. Knowing in what months and where cholera tends to occur across the continent could aid in improving efforts to eliminate cholera as a public health concern. However, largely due to the absence of unified large-scale datasets, no continent-wide estimates exist. In this study, we aimed to estimate cholera seasonality across SSA and explore the correlation between hydroclimatic variables and cholera seasonality.
METHODS
Using the global cholera database of the Global Task Force on Cholera Control, we developed statistical models to synthesise data across spatial and temporal scales to infer the seasonality of excess (defined as incidence higher than the 2010-16 mean incidence rate) suspected cholera occurrence in SSA. We developed a Bayesian statistical model to infer the monthly risk of excess cholera at the first and second administrative levels. Seasonality patterns were then grouped into spatial clusters. Finally, we studied the association between seasonality estimates and hydroclimatic variables (mean monthly fraction of area flooded, mean monthly air temperature, and cumulative monthly precipitation).
FINDINGS
24 (71%) of the 34 countries studied had seasonal patterns of excess cholera risk, corresponding to approximately 86% of the SSA population. 12 (50%) of these 24 countries also had subnational differences in seasonality patterns, with strong differences in seasonality strength between regions. Seasonality patterns clustered into two macroregions (west Africa and the Sahel vs eastern and southern Africa), which were composed of subregional clusters with varying degrees of seasonality. Exploratory association analysis found most consistent and positive correlations between cholera seasonality and precipitation and, to a lesser extent, between cholera seasonality and temperature and flooding.
INTERPRETATION
Widespread cholera seasonality in SSA offers opportunities for intervention planning. Further studies are needed to study the association between cholera and climate.
Journal Article > ReviewFull Text
Clin Infect Dis. 2019 August 19; Volume 71 (Issue 1); 89-97.; DOI:10.1093/cid/ciz808
Truelove SA, Keegan LT, Moss WJ, Chaisson LH, Macher E, et al.
Clin Infect Dis. 2019 August 19; Volume 71 (Issue 1); 89-97.; DOI:10.1093/cid/ciz808
BACKGROUND
Diphtheria, once a major cause of childhood morbidity and mortality, all but disappeared following introduction of diphtheria vaccine. Recent outbreaks highlight the risk diphtheria poses when civil unrest interrupts vaccination and healthcare access. Lack of interest over the last century resulted in knowledge gaps about diphtheria’s epidemiology, transmission, and control.
METHODS
We conducted 9 distinct systematic reviews on PubMed and Scopus (March–May 2018). We pooled and analyzed extracted data to fill in these key knowledge gaps.
RESULTS
We identified 6934 articles, reviewed 781 full texts, and included 266. From this, we estimate that the median incubation period is 1.4 days. On average, untreated cases are colonized for 18.5 days (95% credible interval [CrI], 17.7–19.4 days), and 95% clear Corynebacterium diphtheriae within 48 days (95% CrI, 46–51 days). Asymptomatic carriers cause 76% (95% confidence interval, 59%–87%) fewer cases over the course of infection than symptomatic cases. The basic reproductive number is 1.7–4.3. Receipt of 3 doses of diphtheria toxoid vaccine is 87% (95% CrI, 68%–97%) effective against symptomatic disease and reduces transmission by 60% (95% CrI, 51%–68%). Vaccinated individuals can become colonized and transmit; consequently, vaccination alone can only interrupt transmission in 28% of outbreak settings, making isolation and antibiotics essential. While antibiotics reduce the duration of infection, they must be paired with diphtheria antitoxin to limit morbidity.
CONCLUSIONS
Appropriate tools to confront diphtheria exist; however, accurate understanding of the unique characteristics is crucial and lifesaving treatments must be made widely available. This comprehensive update provides clinical and public health guidance for diphtheria-specific preparedness and response.
Diphtheria, once a major cause of childhood morbidity and mortality, all but disappeared following introduction of diphtheria vaccine. Recent outbreaks highlight the risk diphtheria poses when civil unrest interrupts vaccination and healthcare access. Lack of interest over the last century resulted in knowledge gaps about diphtheria’s epidemiology, transmission, and control.
METHODS
We conducted 9 distinct systematic reviews on PubMed and Scopus (March–May 2018). We pooled and analyzed extracted data to fill in these key knowledge gaps.
RESULTS
We identified 6934 articles, reviewed 781 full texts, and included 266. From this, we estimate that the median incubation period is 1.4 days. On average, untreated cases are colonized for 18.5 days (95% credible interval [CrI], 17.7–19.4 days), and 95% clear Corynebacterium diphtheriae within 48 days (95% CrI, 46–51 days). Asymptomatic carriers cause 76% (95% confidence interval, 59%–87%) fewer cases over the course of infection than symptomatic cases. The basic reproductive number is 1.7–4.3. Receipt of 3 doses of diphtheria toxoid vaccine is 87% (95% CrI, 68%–97%) effective against symptomatic disease and reduces transmission by 60% (95% CrI, 51%–68%). Vaccinated individuals can become colonized and transmit; consequently, vaccination alone can only interrupt transmission in 28% of outbreak settings, making isolation and antibiotics essential. While antibiotics reduce the duration of infection, they must be paired with diphtheria antitoxin to limit morbidity.
CONCLUSIONS
Appropriate tools to confront diphtheria exist; however, accurate understanding of the unique characteristics is crucial and lifesaving treatments must be made widely available. This comprehensive update provides clinical and public health guidance for diphtheria-specific preparedness and response.