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

Abstract

Recent pertussis resurgence in numerous countries may be driven by asymptomatic infections. Most pertussis surveillance studies are cross-sectional and cannot distinguish asymptomatic from pre-symptomatic infections. Longitudinal surveillance could overcome this barrier, providing more information about the true burden of pertussis at the population level. Here we analyze 17,442 nasopharyngeal samples from a longitudinal cohort of 1320 Zambian mother/infant pairs. Our analysis has two elements. First, we demonstrate that the full range of IS481 qPCR CT values provides insight into pertussis epidemiology, showing concordance of low and high CT results over time, within mother/infant pairs, and in relation to symptomatology. Second, we exploit these full-range qPCR data to demonstrate a high incidence of asymptomatic pertussis, including among infants. Our results demonstrate a wider burden of pertussis infection than we anticipated in this population, and expose key limitations of threshold-based interpretation of qPCR results in infectious disease surveillance.

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

“…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.…”

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

“…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.…”

“…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.…”

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

“…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.…”