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Using modelling to disentangle the relative contributions of zoonotic and anthroponotic transmission: the case of lassa fever.

Lo Iacono G, Cunningham AA, Fichet-Calvet E, Garry RF, Grant DS, Khan SH, Leach M, Moses LM, Schieffelin JS, Shaffer JG, Webb CT, Wood JL - PLoS Negl Trop Dis (2015)

Bottom Line: Zoonotic infections, which transmit from animals to humans, form the majority of new human pathogens.Indeed, large hospital-related outbreaks have been reported.However, we found much of this transmission is associated with a disproportionally large impact of a few individuals ('super-spreaders'), as we found only [Formula: see text] of human cases result in an effective reproduction number (i.e. the average number of secondary cases per infectious case) [Formula: see text], with a maximum value up to [Formula: see text].

View Article: PubMed Central - PubMed

Affiliation: Department of Veterinary Medicine, Disease Dynamics Unit, University of Cambridge, Cambridge, United Kingdom.

ABSTRACT

Background: Zoonotic infections, which transmit from animals to humans, form the majority of new human pathogens. Following zoonotic transmission, the pathogen may already have, or may acquire, the ability to transmit from human to human. With infections such as Lassa fever (LF), an often fatal, rodent-borne, hemorrhagic fever common in areas of West Africa, rodent-to-rodent, rodent-to-human, human-to-human and even human-to-rodent transmission patterns are possible. Indeed, large hospital-related outbreaks have been reported. Estimating the proportion of transmission due to human-to-human routes and related patterns (e.g. existence of super-spreaders), in these scenarios is challenging, but essential for planned interventions.

Methodology/principal findings: Here, we make use of an innovative modeling approach to analyze data from published outbreaks and the number of LF hospitalized patients to Kenema Government Hospital in Sierra Leone to estimate the likely contribution of human-to-human transmission. The analyses show that almost [Formula: see text] of the cases at KGH are secondary cases arising from human-to-human transmission. However, we found much of this transmission is associated with a disproportionally large impact of a few individuals ('super-spreaders'), as we found only [Formula: see text] of human cases result in an effective reproduction number (i.e. the average number of secondary cases per infectious case) [Formula: see text], with a maximum value up to [Formula: see text].

Conclusions/significance: This work explains the discrepancy between the sizes of reported LF outbreaks and a clinical perception that human-to-human transmission is low. Future assessment of risks of LF and infection control guidelines should take into account the potentially large impact of super-spreaders in human-to-human transmission. Our work highlights several neglected topics in LF research, the occurrence and nature of super-spreading events and aspects of social behavior in transmission and detection.

No MeSH data available.


Related in: MedlinePlus

Nosocomial outbreaks.A: Diagrammatic representation of LF cases admitted at Jos Hospital, Nigeria (total duration of the outbreak  days), showing period of illness and interrelation among patients [2]. The horizontal bars represent each patient. The x-axis is the time expressed in days from the start of the outbreak, when TS developed the illness (thus time  in the calculation corresponds to  December 1969). The grey portion of the bars are the period between the onset of the symptoms and admission to hospital; the black portion of the bars are the period between admission to hospital and discharge/death of the patients; the red thin lines are the period of exposure to the index case TS. The green bar represent the time when the patient was at the ward for unrelated illness. Note, the same diagram in [2] present an extra case, JT, which is not included here. This case refers to Dr. Jeanette M. Troup one of the first scientists working on Lassa Fever Virus, who contracted the disease from an autopsy accident incurred during examination of one of the fatal cases. B: Diagrammatic representation of LF cases admitted at Zorzor Hospital (total duration of the outbreak  days), Liberia, showing period of illness and interrelation among patients [3]. C: As in Fig. 1.A, but the periods of illness (symptoms plus time at hospital) are randomly permuted. The contact network is kept the same. D: An example of how the time  was calculated. In this particular case  if  and  otherwise, where  is the time when case  is no longer exposed to case .
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pntd-0003398-g001: Nosocomial outbreaks.A: Diagrammatic representation of LF cases admitted at Jos Hospital, Nigeria (total duration of the outbreak days), showing period of illness and interrelation among patients [2]. The horizontal bars represent each patient. The x-axis is the time expressed in days from the start of the outbreak, when TS developed the illness (thus time in the calculation corresponds to December 1969). The grey portion of the bars are the period between the onset of the symptoms and admission to hospital; the black portion of the bars are the period between admission to hospital and discharge/death of the patients; the red thin lines are the period of exposure to the index case TS. The green bar represent the time when the patient was at the ward for unrelated illness. Note, the same diagram in [2] present an extra case, JT, which is not included here. This case refers to Dr. Jeanette M. Troup one of the first scientists working on Lassa Fever Virus, who contracted the disease from an autopsy accident incurred during examination of one of the fatal cases. B: Diagrammatic representation of LF cases admitted at Zorzor Hospital (total duration of the outbreak days), Liberia, showing period of illness and interrelation among patients [3]. C: As in Fig. 1.A, but the periods of illness (symptoms plus time at hospital) are randomly permuted. The contact network is kept the same. D: An example of how the time was calculated. In this particular case if and otherwise, where is the time when case is no longer exposed to case .

Mentions: This narrative concerning the relative importance of human-to-human transmission for LASV, however, requires re-evaluation as there are important indications of human-to-human transmission. More precisely, one of the early nosocomial outbreaks, in Jos, Nigeria (see [2], Fig. 1 and also the Supporting Information, S2 Text) was triggered by an index case that transmitted to possibly others in the hospital, with no indication of iatrogenic transfer. Further cases of extra-hospital transmission within a single family (five from the same family, , , , , and who likely initiated the chain) were reported, here and throughout we refer to this chain as an ‘extra-nosocomial’ chain. Haas et al.[14] investigated secondary transmission after an imported case of LF into Europe and found that one of contacts that were tested serologically, a physician who examined the patient on day of illness, had become infected. The authors concluded that, during the initial phase of symptomatic LF the risk of transmission is low, but it may increase with progression of disease and increasing viral excretion. Emond et al.[15] described a case of LF in the UK in which the virus was isolated from urine days after the acute phase had ended, despite not being detected earlier. The virus may also be found in pharyngeal secretions for weeks after the onset of clinical signs [16]. In an experimental model, Stephenson et al.[17] showed the ability to infect guinea pigs and cynomolgus monkeys with LASV via the respiratory route and Peters et al.[18] demonstrated fatal LASV transmission to monkeys through being held in the same room for days with inoculated rodents. Sagripanti et al.[19], in a dark room at ambient laboratory temperatures controlled between and and relative humidity, showed that the time required for a reduction in viral load of LASV in glass containers was hours and was days for a relative humidity. Also, Kernéis et al.[20] identified that risk factors for positive seroconversion to LASV included either having received a medical injection, or having lived with someone displaying a haemorrhage, in the previous twelve months. No factors related to contact with rodents were identified. Similarly, McCormick et al.[21] reported a lack of correlation between human LASV-specific IgG prevalence and either the level of domestic infestation by Mastomys, or the presence of LASV infection in Mastomys. These observations, taken together, suggest that a significant (if perhaps variable) proportion of the burden of LF might be associated with human-to-human transmission.


Using modelling to disentangle the relative contributions of zoonotic and anthroponotic transmission: the case of lassa fever.

Lo Iacono G, Cunningham AA, Fichet-Calvet E, Garry RF, Grant DS, Khan SH, Leach M, Moses LM, Schieffelin JS, Shaffer JG, Webb CT, Wood JL - PLoS Negl Trop Dis (2015)

Nosocomial outbreaks.A: Diagrammatic representation of LF cases admitted at Jos Hospital, Nigeria (total duration of the outbreak  days), showing period of illness and interrelation among patients [2]. The horizontal bars represent each patient. The x-axis is the time expressed in days from the start of the outbreak, when TS developed the illness (thus time  in the calculation corresponds to  December 1969). The grey portion of the bars are the period between the onset of the symptoms and admission to hospital; the black portion of the bars are the period between admission to hospital and discharge/death of the patients; the red thin lines are the period of exposure to the index case TS. The green bar represent the time when the patient was at the ward for unrelated illness. Note, the same diagram in [2] present an extra case, JT, which is not included here. This case refers to Dr. Jeanette M. Troup one of the first scientists working on Lassa Fever Virus, who contracted the disease from an autopsy accident incurred during examination of one of the fatal cases. B: Diagrammatic representation of LF cases admitted at Zorzor Hospital (total duration of the outbreak  days), Liberia, showing period of illness and interrelation among patients [3]. C: As in Fig. 1.A, but the periods of illness (symptoms plus time at hospital) are randomly permuted. The contact network is kept the same. D: An example of how the time  was calculated. In this particular case  if  and  otherwise, where  is the time when case  is no longer exposed to case .
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4288732&req=5

pntd-0003398-g001: Nosocomial outbreaks.A: Diagrammatic representation of LF cases admitted at Jos Hospital, Nigeria (total duration of the outbreak days), showing period of illness and interrelation among patients [2]. The horizontal bars represent each patient. The x-axis is the time expressed in days from the start of the outbreak, when TS developed the illness (thus time in the calculation corresponds to December 1969). The grey portion of the bars are the period between the onset of the symptoms and admission to hospital; the black portion of the bars are the period between admission to hospital and discharge/death of the patients; the red thin lines are the period of exposure to the index case TS. The green bar represent the time when the patient was at the ward for unrelated illness. Note, the same diagram in [2] present an extra case, JT, which is not included here. This case refers to Dr. Jeanette M. Troup one of the first scientists working on Lassa Fever Virus, who contracted the disease from an autopsy accident incurred during examination of one of the fatal cases. B: Diagrammatic representation of LF cases admitted at Zorzor Hospital (total duration of the outbreak days), Liberia, showing period of illness and interrelation among patients [3]. C: As in Fig. 1.A, but the periods of illness (symptoms plus time at hospital) are randomly permuted. The contact network is kept the same. D: An example of how the time was calculated. In this particular case if and otherwise, where is the time when case is no longer exposed to case .
Mentions: This narrative concerning the relative importance of human-to-human transmission for LASV, however, requires re-evaluation as there are important indications of human-to-human transmission. More precisely, one of the early nosocomial outbreaks, in Jos, Nigeria (see [2], Fig. 1 and also the Supporting Information, S2 Text) was triggered by an index case that transmitted to possibly others in the hospital, with no indication of iatrogenic transfer. Further cases of extra-hospital transmission within a single family (five from the same family, , , , , and who likely initiated the chain) were reported, here and throughout we refer to this chain as an ‘extra-nosocomial’ chain. Haas et al.[14] investigated secondary transmission after an imported case of LF into Europe and found that one of contacts that were tested serologically, a physician who examined the patient on day of illness, had become infected. The authors concluded that, during the initial phase of symptomatic LF the risk of transmission is low, but it may increase with progression of disease and increasing viral excretion. Emond et al.[15] described a case of LF in the UK in which the virus was isolated from urine days after the acute phase had ended, despite not being detected earlier. The virus may also be found in pharyngeal secretions for weeks after the onset of clinical signs [16]. In an experimental model, Stephenson et al.[17] showed the ability to infect guinea pigs and cynomolgus monkeys with LASV via the respiratory route and Peters et al.[18] demonstrated fatal LASV transmission to monkeys through being held in the same room for days with inoculated rodents. Sagripanti et al.[19], in a dark room at ambient laboratory temperatures controlled between and and relative humidity, showed that the time required for a reduction in viral load of LASV in glass containers was hours and was days for a relative humidity. Also, Kernéis et al.[20] identified that risk factors for positive seroconversion to LASV included either having received a medical injection, or having lived with someone displaying a haemorrhage, in the previous twelve months. No factors related to contact with rodents were identified. Similarly, McCormick et al.[21] reported a lack of correlation between human LASV-specific IgG prevalence and either the level of domestic infestation by Mastomys, or the presence of LASV infection in Mastomys. These observations, taken together, suggest that a significant (if perhaps variable) proportion of the burden of LF might be associated with human-to-human transmission.

Bottom Line: Zoonotic infections, which transmit from animals to humans, form the majority of new human pathogens.Indeed, large hospital-related outbreaks have been reported.However, we found much of this transmission is associated with a disproportionally large impact of a few individuals ('super-spreaders'), as we found only [Formula: see text] of human cases result in an effective reproduction number (i.e. the average number of secondary cases per infectious case) [Formula: see text], with a maximum value up to [Formula: see text].

View Article: PubMed Central - PubMed

Affiliation: Department of Veterinary Medicine, Disease Dynamics Unit, University of Cambridge, Cambridge, United Kingdom.

ABSTRACT

Background: Zoonotic infections, which transmit from animals to humans, form the majority of new human pathogens. Following zoonotic transmission, the pathogen may already have, or may acquire, the ability to transmit from human to human. With infections such as Lassa fever (LF), an often fatal, rodent-borne, hemorrhagic fever common in areas of West Africa, rodent-to-rodent, rodent-to-human, human-to-human and even human-to-rodent transmission patterns are possible. Indeed, large hospital-related outbreaks have been reported. Estimating the proportion of transmission due to human-to-human routes and related patterns (e.g. existence of super-spreaders), in these scenarios is challenging, but essential for planned interventions.

Methodology/principal findings: Here, we make use of an innovative modeling approach to analyze data from published outbreaks and the number of LF hospitalized patients to Kenema Government Hospital in Sierra Leone to estimate the likely contribution of human-to-human transmission. The analyses show that almost [Formula: see text] of the cases at KGH are secondary cases arising from human-to-human transmission. However, we found much of this transmission is associated with a disproportionally large impact of a few individuals ('super-spreaders'), as we found only [Formula: see text] of human cases result in an effective reproduction number (i.e. the average number of secondary cases per infectious case) [Formula: see text], with a maximum value up to [Formula: see text].

Conclusions/significance: This work explains the discrepancy between the sizes of reported LF outbreaks and a clinical perception that human-to-human transmission is low. Future assessment of risks of LF and infection control guidelines should take into account the potentially large impact of super-spreaders in human-to-human transmission. Our work highlights several neglected topics in LF research, the occurrence and nature of super-spreading events and aspects of social behavior in transmission and detection.

No MeSH data available.


Related in: MedlinePlus