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Year : 2014 | Volume : 2 | Issue : 2 | Page : 69 - 71  


Editorial
Exploring the importance of incubation period in epidemiology of infectious diseases

Saurabh RamBihariLal Shrivastava1, Prateek Saurabh Shrivastava2, Jegadeesh Ramasamy3

1&2Assistant Professor, 3Professor & Head, Department of Community Medicine, Shri Sathya Sai Medical College & Research Institute, Kancheepuram, Tamil Nadu

 

Globally, in spite of the extensive progress and development in the prevention and control activities pertaining to the infectious diseases, they still remain a major public health concern.[1] This has been attributed to their universal distribution beyond geographical and regional boundaries, associated burden on the health care delivery system (both public and private health sector), negative impact on the well-being & quality of life of people, and associated disease specific death rates / case fatality rate.[1] The menace of infectious diseases is further compounded by the emergence and re-emergence of infectious diseases across the world in the last two-three decades mainly because of the rising trends of ant-microbial resistance to drugs.[2] On considering all the above mentioned parameters, the concept of incubation period deserves a crucial place in the epidemiology of communicable diseases, especially in the prevention and control of the disease.[3]

Incubation period is defined as the time-span between invasion by an infectious agent and appearance of the first clinical features of a specific disease.[3] However, in relation with the vector-borne diseases, terminologies like "intrinsic incubation period" and "extrinsic incubation period" have been employed.[3]

  1. Intrinsic incubation period: It is defined as the time span required for an organism to complete its development in the definitive host (where sexual phase of their life cycle is completed).[3] For instance, in malaria - intrinsic incubation period is 9-40 days (variable depending upon the species).[3]
  2. Extrinsic incubation period: It is defined as the time required by an organism to complete its development in intermediate host (where asexual phase of their life cycle is completed).[3] In other words, it is the time interval between the acquisition of an infectious agent by a vector and the ability of the vector to transmit the agent to other susceptible vertebrate hosts. For instance, in malaria - extrinsic incubation period is 10-20 days.[3-5]

Another important terminology pertaining to incubation period is the pre-patent period (as observed in lymphatic filariasis), which refers to the time interval between inoculation of infective larvae and the first appearance of detectable microfilariae in peripheral blood (or the period between the infection of the host by the infectious agent and the detection of the same agent in the tissues or secretions of the host).[3,6] From the patho-physiological point of view, during the span of the incubation period, the infectious agent undergoes multiplication in the host, and once sufficient density of the disease agent is achieved, the disease gets manifested.[7]

Incubation period is generally measured in terms of median incubation period (viz. the time in which almost fifty percent of the infected persons will develop clinical symptoms, following organism entry into the body).[6,8] A wide gamut of determinants have been identified that eventually determines the duration of incubation period, such as

  1. Generation time: It is the time interval between entry of an infectious agent and maximal infectivity of the host. Lesser the generation time of a specific pathogen means lesser the incubation period and vice versa.
  2. Infective dose: A directly proportional association has been observed between the infective dose and the incubation period (viz. smaller the inoculated dose, the longer is the incubation period and vice versa).
  3. Number of contacts with the infectious source: As the number of contacts with the source of infection increases, a reduction in the duration of incubation period is observed (owing to the repetitive inoculation of the infective pathogen in the host).
  4. Portal of entry: Generally the organisms which enter through the respiratory tract have a short incubation period (viz. influenza virus, para-influenza virus, etc.) in contrast to the organisms which enters through the skin/subcutaneous tissue (viz. Ancylostoma duodenale, etc.).
  5. Site of multiplication of the organism: Infections in which site of entry and site of lesion is same the incubation period is short (viz. respiratory infections, gastroenteritis – 1-3 days) as compared to the systemic diseases in which organism either enters through the respiratory or alimentary tract, nevertheless causes lesions in remote sites (viz. chicken-pox – 10-20 days). However, exceptions have been observed in cases of infections with arboviruses (like yellow fever or dengue fever) where the agent is directly introduced into the blood stream by the arthropod species.
  6. Rate of multiplication of the specific organism in the human host: The faster the rate of multiplication, lesser the duration of incubation period and vice versa (because of the short time interval in which organism acquires the ability to produce an infection).
  7. Speed with which the host defense mechanisms are mobilized: Longer incubation period has been observed for diseases in which host defense mechanism can be mobilized quickly and vice versa.
  8. Individual susceptibility: This is one of the key parameter which determines the duration of incubation period as any individual whose immune status has been compromised (because of infection with human immunodeficiency virus or exposure to immunosuppressant drugs like steroids, etc.) becomes susceptible to most of the opportunistic infections. In all these individuals a shorter duration of incubation period has been observed.[7,9-13]

The length of the incubation period is characteristic of a specific disease and there is a minimum incubation period for every disease before which no illness can occur.[3,11-14] For many conditions, incubation periods are longer in adults than they are in children or infants. However, some of the infectious diseases are communicable during the later part of the incubation period (such as measles, chickenpox, etc.).[4,8] These individuals are often termed as incubatory carriers because of the shedding of the infectious agent during the incubation period of disease, and hence they are capable of infecting others before the onset of illness.[4,8,15]

Owing to the variability observed in different individuals, incubation period is generally expressed in a range (viz. mean and the 10th and 90th percentiles). In fact, the duration of the incubation period varies for different infectious diseases like few hours to 2-3 days – food poisoning, influenza, etc.; 10 days to 3 weeks – mumps, measles, etc.; and weeks to months or years – rabies, leprosy.[3,6,16-19]

Accurate estimates of an incubation period can be done by measuring the time taken for the onset of secondary cases following exposure to the index case, in family groups or in closed communities.[9] Moreover, even non-infectious diseases such as cancer, heart disease and mental illness also have incubation periods (also known as the latent period - the period from disease initiation to disease detection or the time interval between the first exposure to "suspected cause" and eventual development of disease), which may be in months or even years.[6,20] As the duration of incubation period (latent period) is very long it is difficult to link any specific etiological agent with the development of the disease.[3,6,20]

Owing to its significant role in the epidemiology of infectious diseases, incubation period has been found to be of extreme utility in conducting investigation of an outbreak / epidemic by aiding in

  1. tracing the probable source of infection and susceptible contacts – especially in diseases with a short incubation period ranging from a few hours to a few days (viz. in cases of food poisoning at times of some gathering, the probable cause of infection could be because of consumption of either contaminated food or water and the source of infection can be traced back to anyone who handled the food during the processing, manufacture, serving of the food);
  2. ascertaining the period of surveillance or quarantine - this period is usually equal to the maximum incubation period of the disease and thus interrupts the chain of transmission from potential source of infection to their susceptible contacts (this is more applicable to international airports and ship harbors);
  3. preventing onset of clinical illness by assisting in timely administration of vaccines / immunoglobulin / anti-sera (viz. in some of the diseases like tetanus, administration of immunoglobulins {passive immunization} has been employed as a strategy to prevent the onset of disease after exposure to the source of infection);
  4. reflecting infectivity of the agent – short incubation period means high infectivity and vice versa (viz. influenza has a short incubation period {in hours - days} and thus case fatality rate is high as compared to leprosy which has a very long incubation period {in months} and thus mortality attributed to the disease per se is very low);
  5. enabling identification of type of epidemic (viz. common source – single / continuous epidemic or propagated epidemics). In a common source epidemic, there will be a sudden rise in number of cases, all manifesting common signs & symptoms within a short span of time, as observed in cases of food poisoning or drinking water from a contaminated source.
  6. quantifying the prognosis of the disease (viz. in some of the diseases like rabies shorter the incubation period, poorer the prognosis of the disease); and
  7. in assisting epidemiologist to institute appropriate public health interventions (viz. depending on the duration of incubation period, the epidemiologists can implement adequate measures like isolation, administration of vaccine / immunoglobulin, disinfection, etc. to prevent the spread of the disease).[3,6,21,22]

For instance, three cases of chickenpox have been diagnosed in a hospital on 5 August, 15 August, and 21 September within the campus of a medical college among three medical undergraduate students. From an epidemiologist perspective, their aim is to investigate the outbreak and identify the potential source of infection and thus implement timely preventive & control measures to interrupt the chain of transmission. In such cases, the concept of incubation period becomes vital, especially when we have to identify the primary case or secondary case. As the incubation period of chicken pox varies from 10-21 days, we can tentatively presume that the second case has acquired infection after being exposed to the primary case (diagnosed on 5 August), provided exposure to any other source of infection (exposure to patients of chicken pox in hospital settings / outside) has been ruled out. However, the third diagnosed case (21 September) has been diagnosed almost after 36 days (viz. which is beyond the range of incubation period of chicken pox) and thus it is not related with the primary or the secondary case and thus other sources of infection should be explored. Also, an active search for chicken pox should be done among the other susceptible contacts for the maximal incubation period to detect cases at the earliest. Similarly, preventive & control measures should also be adopted to prevent the spread of the disease base on the communication period of the disease.

In-fact, from an epidemiological point of view, the concept of incubation period is utilized in calculating secondary attack rate (which refers to the number of exposed persons developing the disease within the range of the incubation period, following exposure to the primary case - the first case of a infectious disease introduced into the defined population).[6,23,24]

To conclude, amidst the emergence and re-emergence of infectious disease, ascertaining the incubation period of a specific disease can play a vital role in implementation of the timely preventive and control measures and thus aid in the strengthening of the existing public health system.

References

  1. Jones KE, Patel NG, Levy MA, Storeygard A, Balk D, Gittleman JL, et al. Global trends in emerging infectious diseases. Nature 2008;451:990-3.
  2. Shrivastava SR, Shrivastava PS, Ramasamy J. Emerging and re-emerging infectious diseases - Public health perspective. Int J Prev Med 2013;4:736-7.
  3. Park K. Principles of epidemiology and epidemiologic methods. In: Park K, editor. Textbook of Preventive and Social Medicine. 20th ed. Jabalpur: Banarsidas Bhanot; 2009. p. 94-6.
  4. Tjaden NB, Thomas SM, Fischer D, Beierkuhnlein C. Extrinsic incubation period of dengue: Knowledge, backlog, and applications of temperature dependence. PLoS Negl Trop Dis 2013;7:e2207.
  5. Limongi JE, Costa DC, Carvalho LH, Lopes IS, Silva AA, Ferreira MS. Plasmodium ovale malaria in Brazil: report of an imported case with a prolonged incubation period. J Infect Dev Ctries 2014;8:554-7.
  6. Gupta MC, Mahajan BK. Epidemiological approach in preventive and social medicine. In: Roy RN, Saha I, editors. Textbook of Preventive and Social Medicine. 4th ed. New Delhi: Jaypee publishers; 2013. p. 17-22.
  7. Zeng G, Xie SY, Li Q, Ou JM. Infectivity of severe acute respiratory syndrome during its incubation period. Biomed Environ Sci 2009;22:502-10.
  8. Fitzgerald TL, Durrheim DN, Merritt TD, Birch C, Tran T. Measles with a possible 23 day incubation period. Commun Dis Intell Q Rep 2012;36:e277-80.
  9. Reich NG, Lessler J, Cummings DA, Brookmeyer R. Estimating incubation period distributions with coarse data. Stat Med 2009;28:2769-84.
  10. Tam WW, Wong TW. Estimating incubation period with multiple contact days. Scand J Infect Dis 2007;39:609-11.
  11. Cai QC, Xu QF, Xu JM, Guo Q, Cheng X, Zhao GM, et al. Refined estimate of the incubation period of severe acute respiratory syndrome and related influencing factors. Am J Epidemiol 2006;163:211-6.
  12. Leclerc M, Dore T, Gilligan CA, Lucas P, Filipe JA. Estimating the delay between host infection and disease (incubation period) and assessing its significance to the epidemiology of plant diseases. PLoS One 2014;9:e86568.
  13. Lover AA, Coker RJ. Re-assessing the relationship between sporozoite dose and incubation period in Plasmodium vivax malaria: a systematic re-analysis. Parasitology 2014;141:859-68
  14. Vargas-De-Leon C. Global analysis of a delayed vector-bias model for malaria transmission with incubation period in mosquitoes. Math Biosci Eng 2012;9:165-74
  15. Azman AS, Rudolph KE, Cummings DA, Lessler J. The incubation period of cholera: a systematic review. J Infect 2013;66:432-8
  16. Naderi H, Sheybani F, Bojdi A, Khosravi N, Mostafavi I. Fatal nosocomial spread of Crimean-Congo hemorrhagic fever with very short incubation period. Am J Trop Med Hyg 2013;88:469-71
  17. Lee DW, Gwack J, Youn SK. Enteropathogenic Escherichia coli outbreak and its incubation period: Is it short or long? Osong Public Health Res Perspect 2012;3:43-7.
  18. Huai Y, Xiang N, Zhou L, Feng L, Peng Z, Chapman RS, et al. Incubation period for human cases of avian influenza A (H5N1) infection, China. Emerg Infect Dis 2008;14:1819-21.
  19. Boelle PY, Valleron AJ. Incubation period of human prion disease. Lancet 2006;368:914-5.
  20. Rose G. Incubation period of coronary heart disease, 1982. Int J Epidemiol 2005;34:242-4.
  21. Horn BJ, Lake RJ. Incubation period for campylobacteriosis and its importance in the estimation of incidence related to travel. Euro Surveill 2013;18:20602.
  22. Klinkenberg D, Nishiura H. The correlation between infectivity and incubation period of measles, estimated from households with two cases. J Theor Biol 2011;284:52-60.
  23. Ceyhan M, Tezer H, Yildirim I. Secondary attack rate of hepatitis A, varicella and mumps in household settings and reliability of family history to detect seronegative children for necessity of vaccination. Scand J Infect Dis 2009;41:501-6.
  24. Whalen CC, Zalwango S, Chiunda A, Malone L, Eisenach K, Joloba M, et al. Secondary attack rate of tuberculosis in urban households in Kampala, Uganda. PLoS One 2011;6:e16137

 





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