Asymptomatic Bordetella pertussis infections in a longitudinal cohort of young African infants and their mothers

Gill, Christopher J.; Gunning, Christian E.; MacLeod, W. Bentley; Mwananyanda, Lawrence; Thea, Donald M; Pieciak, Rachel; Kwenda, Geoffrey; Mupila, Zachariah; Rohani, Pejman

doi:10.7554/elife.65663

Cited by 24 publications

(26 citation statements)

References 58 publications

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“…However, Ct is a continuous variable, and the selection of any Ct cut point is arbitrary and hence controversial. 19 We further note that most COVID-19 surveillance studies assess individuals who are acutely ill when viral loads, and hence PCR signals, are likely at peak intensity. By contrast, the population in this study were tested after they had died.…”

Section: Methodsmentioning

confidence: 90%

Sustained high prevalence of COVID-19 deaths from a systematic post-mortem study in Lusaka, Zambia: one year later

Gill

Mwananyanda

MacLeod

et al. 2022

Preprint

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BackgroundSparse data documenting the impact of COVID-19 in Africa has fostered the belief that COVID-19 ‘skipped Africa’. We previously published results from a systematic postmortem surveillance at a busy inner-city morgue in Lusaka, Zambia. Between June-October 2021, we detected COVID-19 in 15-19% of all deaths and concentrated in community settings where testing for COVID-19 was absent. Yet these conclusions rested on a small cohort of 70 COVID-19+ individuals. Subsequently, we conducted a longer and far larger follow-on survey using the same methodology.MethodsWe obtained a nasopharyngeal swab from each enrolled decedent and tested these using reverse transcriptase quantitative PCR (RT-qPCR). A subset of samples with a PCR cycle threshold <30 underwent genotyping to identify viral variants. We weighted our results to adjust for enrolment ratios and stratified them by setting (facility vs. community), time of year, age, and location.ResultsFrom 1,118 enrolled decedents, COVID-19 was detected among 32.0% (358/1,116). We observed three waves of transmission that peaked in July 2020, January 2021, and ∼June 2021 (end of surveillance). These were dominated by viral variants AE.1, Beta, and Delta, respectively. During peak transmission, COVID-19 was detected in ∼90% of all deaths. COVID-19 deaths clustered in Lusaka’s poorest city wards. Roughly four COVID-19 deaths occurred in the community for every facility death. Antemortem testing occurred for 52.6% (302/574) of facility deaths but only 1.8% (10/544) of community deaths; overall, only ∼10% of COVID-19+ deaths were identified in life.ConclusionsCOVID-19 had a devastating impact in Lusaka. COVID-19+ deaths occurred in all age groups and was the leading cause of death during peak transmission periods. Testing was rarely done for the vast majority of COVID-19 deaths that occurred in the community, yielding a substantial undercount. If typical, these findings contradict assertions that Africa was spared from the COVID-19 pandemic.What is already known on this topicData documenting the mortal impact of COVID-19 in Africa remain sparse.Previously, we reported that COVID-19 was present among 15-19% of all decedents passing through a busy city morgue in Lusaka.Several modeling groups have also argued that COVID-19’s impact in Africa has been underreported and hence underestimated.But this prior analysis was based on a relatively small cohort including only seventy COVID-19 positive deaths.What this study addsFrom data collected among a larger cohort over a longer period, we again document that COVID-19 has had a severe impact in Lusaka, Zambia.Most COVID-19 positive deceased adults presented with symptoms typical of COVID-19, arguing that COVID-19 caused their deaths and was not a co-incidental finding.Deaths occurred across the age spectrum, including among young children, indicating a different pattern of impact from what has been seen in high income country settings.We document three waves of transmission, attributable to the AE.1, Beta, and Delta variants, respectively.During peak transmission periods, ∼90% of all deceased individuals tested positive for COVID-19.Antemortem testing for COVID-19 captured only ∼10% of COVID-19 positive individuals indicating a substantial gap in surveillance.If these results are typical, the impact of COVID-19 in Africa has been vastly underestimated.

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Section: Methodsmentioning

confidence: 90%

Sustained high prevalence of COVID-19 deaths from a systematic post-mortem study in Lusaka, Zambia: one year later

Gill

Mwananyanda

MacLeod

et al. 2022

Preprint

Self Cite

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“…Postmortem descriptions of lung pathology in 8 human infants who died from infantile pertussis revealed marked leukocytosis and pulmonary hypertension (37), features replicated in mouse and baboon pneumonic models (36,38,39), suggesting that these conventional pneumonic infection models reasonably replicate the most extreme form of human disease. However, these cases are extreme; pertussis generally is described as a disease of the upper respiratory tract that induces relatively little inflammation and histopathology (40,41) and often could occur with minimal symptoms and go undiagnosed (25). B. pertussis is highly infectious to humans, indicating that small numbers of bacteria landing in the upper respiratory tract can efficiently colonize, grow, and spread.…”

Section: Discussionmentioning

confidence: 99%

“…Of note, these aspects of early infection are most relevant to the current challenge of the ongoing circulation of B. pertussis. Indeed, recent work has revealed that a large proportion of human infections are asymptomatic and undiagnosed (25). Assays that specifically measure how colonization, early growth, and immunomodulation contribute to shedding and transmission during the catarrhal stage of infection, before and perhaps independent of lower respiratory tract infection, are critical for development of vaccines that can prevent transmission.…”

Section: Modeling Immune Evasion and Vaccine Limitations By Targeted Nasopharyngeal Bordetella Pertussis Inoculation In Micementioning

confidence: 99%

Modeling Immune Evasion and Vaccine Limitations by Targeted Nasopharyngeal Bordetella pertussis Inoculation in Mice

Soumana¹,

Linz²,

Dewan³

et al. 2021

Emerg. Infect. Dis.

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“…Among all these reasons, the inefficient protection afforded by current aP vaccines may be the major issue for the insufficient prevention and control of whooping cough. Several studies have suggested that current aP vaccines cannot prevent B. pertussi s infection and transmission because they induce only humoral immune responses but not efficient cellular and mucosal immune responses ( 8 – 10 ). The current intramuscular acellular pertussis (aP) vaccines elicit strong antibody and Th2-biased responses but not necessary cellular and mucosal immunity.…”

Section: Introductionmentioning

confidence: 99%

Intranasal Immunization With a c-di-GMP-Adjuvanted Acellular Pertussis Vaccine Provides Superior Immunity Against Bordetella pertussis in a Mouse Model

Jiang

Wang

et al. 2022

Front. Immunol.

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Pertussis, caused by the gram-negative bacterium Bordetella pertussis, is a highly contagious respiratory disease. Intranasal vaccination is an ideal strategy to prevent pertussis, as the nasal mucosa represents the first-line barrier to B. pertussis infection. The current intramuscular acellular pertussis (aP) vaccines elicit strong antibody and Th2-biased responses but not necessary cellular and mucosal immunity. Here, we formulated two cyclic dinucleotide (CDN)-adjuvanted aP subunit vaccines, a mammalian 2’,3’-cGAMP-adjuvanted aP vaccine and a bacterial-derived c-di-GMP-adjuvanted aP vaccine, and evaluated their immunogenicity in a mouse model. We found that the aP vaccine alone delivered intranasally (IN) induced moderate systemic and mucosal humoral immunity but weak cellular immunity, whereas the alum-adjuvanted aP vaccine administered intraperitoneally elicited higher Th2 and systemic humoral immune responses but weaker Th1 and Th17 and mucosal immune responses. In contrast, both CDN-adjuvanted aP vaccines administered via the IN route induced robust humoral and cellular immunity systemically and mucosally. Furthermore, the c-di-GMP-adjuvanted aP vaccine generated better antibody production and stronger Th1 and Th17 responses than the 2′,3′-cGAMP-adjuvanted aP vaccine. In addition, following B. pertussis challenge, the group of mice that received IN immunization with the c-di-GMP-adjuvanted aP vaccine showed better protection than all other groups of vaccinated mice, with decreased inflammatory cell infiltration in the lung and reduced bacterial burden in both the upper and lower respiratory tracts. In summary, the c-di-GMP-adjuvanted aP vaccine can elicit a multifaceted potent immune response resulting in robust bacterial clearance in the respiratory tract, which indicates that c-di-GMP can serve as a potential mucosal adjuvant for the pertussis vaccine.

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Asymptomatic Bordetella pertussis infections in a longitudinal cohort of young African infants and their mothers

Cited by 24 publications

References 58 publications

Sustained high prevalence of COVID-19 deaths from a systematic post-mortem study in Lusaka, Zambia: one year later

Sustained high prevalence of COVID-19 deaths from a systematic post-mortem study in Lusaka, Zambia: one year later

Modeling Immune Evasion and Vaccine Limitations by Targeted Nasopharyngeal Bordetella pertussis Inoculation in Mice

Intranasal Immunization With a c-di-GMP-Adjuvanted Acellular Pertussis Vaccine Provides Superior Immunity Against Bordetella pertussis in a Mouse Model

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