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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
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Observing functions (1) to (3), the following phenomena can be obtained: in the
case of no government compensation (=0), if the cost of treatment is high, not many people will have
enough ability to pay for the treatment, and people’s willingness to accept
treatment is very low, so the number of people cured within a unit of time is
also very small under the conditions of µ=0μ=0, α→∞, and γ→0. But when the cost of treatment is low, people have enough
ability to pay, so the willingness to be treated increases, and the number of
people cured per unit time increases if µ=0μ=0, α→0, and γ→1. The numerical simulation results based on equations
(4) to (6) are given in Figure 1.
As Figure 1 shows, at
high cost, even after 10 000 times of simulation, the number of infected people
is still as high as 0.5. But Figure 2 illustrates that at low-cost condition, the number of
infected people will drop to zero after about 1774 periods. The cost of
treatment has an important impact on the transmission of infectious diseases.
Figure 1 shows the
relationships between the 3 groups and the cost of treatment. When the cost of
treatment is high, the number of infections per stage increases (see Figure 1). Conversely, the
number of infections drops sharply after a limited period, indicating that the
infection is effectively and quickly controlled (see Figure 2). This conclusion is also in
concert with the reality. For example, although common cold is contagious, it
can be quickly controlled because of the low cost of treatment.
According to the assumption that the total population is constant, combined with
the conclusion of Figure
2, when the treatment cost is low, the number of healers quickly
reaches a maximum, and the number of infected persons is almost zero. This
indicates that the epidemic is effectively controlled. According to Figure 1, the total number
of social treatments and the total cost (the total number of infections
multiplied by the individual treatment costs) were further analyzed. The cost
for high-cost treatments was close to infinity; the number of low-cost
treatments was 1654.48, and the cost of treatment was 8272.40. Therefore, it is
explained in accordance with Figure 2. When treatment costs are low, the government does not have
Assume the number of population to be N in this group, including susceptibles, infected, and healers,
which are denoted as S, I, and R, respectively. The average effective contact (transferable) with
other people for a person in a unit time is β; the number of people who are cured within the unit time is
γ; the treatment cost is α; and the government compensation is µμ. In reality, the number of patients or the number of people
participating in the treatment depends on the treatment cost. To encourage infected
patients to take treatment promptly, the government should provide moderate
compensation. Furthermore, suppose γ=e−α+μ in this study and obviously γ∈(0,1]. As the cost of treatment increases, the number of people
participating in treatment decreases, but government financial compensation can
effectively promote the participation of infected patients in treatment. According
to the model proposed by Kermack et al in 1927, and based on China’s successful
experience in dealing with SARS, this article establishes the compensation model for
important infectious diseases as follows:
Functions (1) to (3) meet the constraint S(t)+I(t)+R(t)=N. Compared with the traditional infectious disease models, this
model analyzes treatment costs and the impact of government interventions on
infectious diseases. Different from the traditional infectious disease models, the
above model considers the impact of government intervention on infectious diseases.
According to function (3), we know that government intervention will significantly
increase the population of the cured individuals, thereby reducing the spread speed
among the infected population.
Exposure to airborne pathogens is a common denominator of all human life. With the improvement of research methods for studying airborne pathogens has come evidence indicating that microorganisms (e.g., viruses, bacteria, and fungal spores) from an infectious source may disperse over very great distances by air currents and ultimately be inhaled, ingested, or come into contact with individuals who have had no contact with the infectious source [2–5]. Airborne pathogens present a unique challenge in infectious disease and infection control, for a small percentage of infectious individuals appear to be responsible for disseminating the majority of infectious particles. This paper begins by reviewing the crucial elements of aerobiology and physics that allow infectious particles to be transmitted via airborne and droplet means. Building on the basics of aerobiology, we then explore the common origins of droplet and airborne infections, as these are factors critical to understanding the epidemiology of diverse airborne pathogens. We then discuss several environmental considerations that influence the airborne transmission of disease, for these greatly impact particular environments in which airborne pathogens are commonly believed to be problematic. Finally, we discuss airborne pathogens in the context of several specific examples: healthcare facilities, office buildings, and travel and leisure settings (e.g., commercial airplanes, cruise ships, and hotels).
Selected FFPE tissue sections were fixed on silanized slides with Poly-L-lysine 0,1% (Sigma-Aldrich, St. Louis, Missouri, USA), deparaffinized and hydrated in decreasing alcohol baths. Antigen retrieval (Supplemental Table 1) was done with citrate buffer (pH 6.0) using either the electric pressure cooker system (Electrolux Pressure Cooker PCC10, São Paulo, SP, Brazil) or proteinase K (Thermo Fisher Scientific, Waltham, MA, USA). Subsequently, there was blocking of endogenous peroxidase with distilled water and hydrogen peroxide (6%) for 25 min. All primary antibodies were diluted (Supplemental Table 1) and incubated in a humid chamber at 4 °C for 18–20 hours.
The SuperPicTure™ Polymer Detection kit (Invitrogen Corporation, Carlsbad, CA, USA) served as the secondary antibody and was incubated onto the FFPE sections in a humid chamber for 25 min at 25 °C. Binding between tissue antigens and antibodies was visualized by adding the chromogen 3,3′-diaminobenzidine (DAB, Invitrogen Life Technologies, Frederick, MD, USA) for 3 min. Finally, all slides were counter-stained with Harris haematoxylin and assembled with a commercial resin. Positive antigen controls consisted of FFPE tissue sections from previous studies13,18,38,63,64; negative controls consisted of the diluents of the primary antibodies which substituted each primary antibody. Positive and negative controls were included in each assay. Positive immunoreactivity for CDV, CPV-2, and CAdV-2 was considered when there was cytoplasmic immunolabelling within epithelial cells; positive immunoreactivity for CAdV-1 was considered when there was intranuclear/intracytoplasmic immunolabelling in hepatocytes and intracytoplasmic in other epithelial cells.
The financing, provision, and quality of healthcare systems; the availability of vaccines, antivirals, and antibiotics medicines, and appropriate compliance to treatment protocols are all important determinants of infectious disease transmission. Although the correlation between healthcare system financing and efficacy is not perfect, recent budget cuts to healthcare are an important consideration when anticipating infectious disease risk. In part related to the global economic crisis, it has been reported that many high-income governments have introduced policies to lower spending through cutting the prices of medical products and, for example, through budget restrictions and wage cuts in hospitals (54). There are many indirect and direct pathways through which budget cuts could affect disease transmission; to provide just one example, it has been estimated that 20–30% of healthcare-associated infections are preventable with intensive hygiene and control programmes2 – should investments in this area diminish, then healthcare-acquired infections could become an even more problematic issue. There are currently roughly 4.1 million healthcare-associated infections each year in the EU alone.3
A broader issue related to healthcare provision is population mobility for both healthcare professionals and patients who might increasingly seek work or healthcare in other countries – the provision of cross-border healthcare and the mitigation of cross-border health threats will necessitate collaboration across borders (55, 56) and solutions for the brain-drain of medical personnel from resource-poor countries (57). Also related to the healthcare provision and practice is the over-prescription or overuse of antibiotics. In combination with a lag in pharmaceutical innovation, rapid transmission, and poor infection control measures, this has driven resistance of organisms such as methicillin-resistant Staphylococcus aureus, or extended-spectrum beta-lactamases, and carbapenemase-producing gram-negatives such as Klebsiella pneumoniae carbapenemase (KPC) (58). Antimicrobial resistance is currently one of the major health risks facing society (59).
Food production systems remain a persistent source for human infectious diseases. Attempts are underway to estimate the global burden of food-borne disease (60), which is likely substantial. Many factors in food production affect human health. A vast range of familiar human pathogens can be acquired through the consumption of animal products and other disease drivers, such as global travel, further provoke this (61). In addition to farmed animals, the hunting and slaughtering of wild animals has led to the emergence of more exotic pathogens: SARS originated in wildlife markets and restaurants in southern China (62) and HIV and Ebola have both been linked to the hunting or slaughtering of primates and other wild animals (33, 63, 64). The density and health of livestock, meanwhile, have been linked to disease in humans (65, 66). Although inconclusive, there is some evidence to suggest that livestock production may lead to increased antibiotic resistance in human pathogens. There are certainly many pathways by which drug resistant pathogens could transmit from livestock to humans, including environmental contamination by excreted veterinary antibiotics (33, 67, 68).
Another major problem arising from genetic changes is the development of resistance to drugs. A typical example is seen in HIV. Besides drug-drug interactions and toxic side effects, drug resistance arising from drug pressure coupled with high rate of genomic variation (during viral replication) is a major obstacle in HIV antiretroviral therapy, leading to treatment failure and necessitating regimen switches [107, 108]. Current antiretroviral therapy therefore employs a combination of anti-HIV compounds from at least two classes or drug groups with different mechanisms of action against HIV replication. Combination ART is necessary to suppress plasma HIV viremia, restore immunologic function, and reduce likelihood of drug resistance development for favourable treatment outcomes. The problem of emergence of drug resistant microbes and resistance to antimicrobial agents very well characterizes many bacterial infectious agents such as Escherichia coli, Pneumococcus, Neisseria gonorrhoeae, and Staphylococcus aureus. Many well known antibiotics no longer clear bacterial infections due to microbial resistance. Evolution of drug resistant pathogens thus necessitates continued development of new antiviral and antimicrobial products. As such for HIV alone there are currently at least 25 anti-HIV compounds licensed for the treatment of AIDS.
Emerging infectious diseases under this category were subcategorized into 1a, 1b and 1c. Subcategory 1a covers known pathogens that occur in new ecological niches/geographical areas. A few past examples belonging to this subcategory are the introduction and spread of West Nile virus in North America; chikungunya virus of the Central/East Africa genotype in Reunion Island, the Indian subcontinent and South East Asia; and dengue virus of different serotypes in the Pacific Islands and Central and South America.18,19,20,21,22,23 Factors that contributed to the occurrence of emerging infectious diseases in this subcategory include population growth; urbanization; environmental and anthropogenic driven ecological changes; increased volume and speed of international travel and commerce with rapid, massive movement of people, animals and commodities; and deterioration of public health infrastructure. Subcategory 1b includes known and unknown infectious agents that occur in new host ‘niches'. Infectious microbes/agents placed under this subcategory are better known as ‘opportunistic' pathogens that normally do not cause disease in immunocompetent human hosts but that can lead to serious diseases in immunocompromised individuals. The increased susceptibility of human hosts to infectious agents is largely due to the HIV/acquired immune deficiency syndrome pandemic, and to a lesser extent, due to immunosuppression resulting from cancer chemotherapy, anti-rejection treatments in transplant recipients, and drugs and monoclonal antibodies that are used to treat autoimmune and immune-mediated disorders. A notable example is the increased incidence of progressive multifocal leukoencephalopathy, a demyelinating disease of the central nervous system that is caused by the polyomavirus ‘JC' following the increased use of immunomodulatory therapies for anti-rejection regimens and for the treatment of autoimmune diseases.24,25,26 Subcategory 1c includes known and unknown infectious agents causing infections associated with iatrogenic modalities. Some examples of emerging infections under this subcategory include therapeutic epidural injection of steroids that are contaminated with Exserhilum rostratum and infectious agents transmitted from donor to recipients through organ transplantation, such as rabies virus, West Nile virus, Dandenong virus or Acanthamoeba.27,28,29,30,31
If it is determined that an outbreak has taken place, preventive measures should be implemented. Depending on the type of the infectious disease and the timing of the outbreak, the prioritization and the specific details of the preventive measures will vary. In instances of single exposures, as in cases of food poisoning, the mode of transmission should be identified by preserving suspected foods or ensuring that the site of transmission remains intact. However, if the disease spreads through person-to-person transmission, prompt and active preventive measures need to be taken. For infectious diseases spread by person-to-person transmission, each patient is a source of infection, and it is therefore important to identify suspected cases as soon as possible and to treat them in isolation. Some diseases are transmitted during the incubation period, while other diseases are transmitted only after the onset of symptoms. The period of infectiousness as well as the natural history of a disease should be taken into consideration when implementing preventive measures. Infectious diseases such as the common cold and influenza are transmitted before the onset of symptoms, making it difficult and inefficient to identify and quarantine people who have been exposed. However, severe acute respiratory syndrome, and MERS are known to be infectious only after the onset of symptoms, not during the incubation period; therefore, actively identifying contacts to be monitored and close contacts to be quarantined can be an effective measure for preventing the spread of this disease. In order to carry out such measures, it is necessary to obtain information about the contact history of confirmed cases. It is also important to properly disinfect areas where confirmed cases have been present in order to eliminate the possibility of further infection.
This article focuses on the process of epidemiologic investigations, and therefore does not describe preventive measures. The following items must be carried out during an epidemiologic investigation: 1) determining the period of infectiousness (for MERS, after the onset of symptoms); 2) tracing the movement of the cases during the period of infectiousness; 3) identifying contacts of the cases before quarantine; 4) if the confirmed cases visited any hospitals, blocking the spread of the infection in those hospitals by urging them to implement prompt preventive measures; 5) after identifying the major paths of cases, directly interviewing the cases if possible to verify their movements, supplementing their list of contacts, and, if necessary, obtaining consent for checking credit card details; 6) further confirming that the records of their movement are complete by checking credit card details; 7) checking whether contacts of the case show the symptoms of the disease and, if so, performing the same investigation that was performed for the first case; 8) when necessary, identifying any missing contacts by checking surveillance cameras; 9) when necessary, collecting environmental specimens and performing laboratory examinations; and 10) when necessary, inspecting hospital facilities to ensure that preventive measures are taken against the outbreak.
In the 1980s, hepatitis B surface antigen (HBsAg) positive rate was shown to be 6.6 to 8.6% in all populations12). However, since hepatitis B vaccine was first introduced in 1982, and then subsequently included in the immunization schedule table of the Korean Pediatric Society in 1991, and also in the national immunization program in 1995, HBsAg positive rate has significantly decreased9,13).
According to the 2008 National Health and Nutrition Survey in Korea, it has significantly decreased to 2.9% in populations aged 10 years or more (Fig. 4)14). Specifically, HBsAg positive rate in those aged 4 to 6 years was found to be 0.2%15) from a study with nationwide sampling in 2006. This data could be a basis for certification from the WHO that hepatitis B has been well-controlled in the ROK.
Canine morbillivirus (canine distemper virus, CDV) causes canine distemper (CD) in a wide range of mammalian hosts, and may produce systemic, respiratory, cutaneous, bone, and/or neurological manifestations in these animals1,2. CDV produces immunosuppression3 in susceptible hosts by targeting cells that express the signalling activation molecule (SLAM)4, which frequently results in opportunistic infectious diseases caused by agents such as Bordetella bronchiseptica5,6, Candida sp.7, Clostridium piliforme8, Toxoplasma gondii9–11, Dirofilaria immitis11, Mycoplasma cynos12, and Talaromyces marneffei13. Although the occurrence of CD is significantly reduced in domestic dog populations in developed countries due to the use of vaccination14, the disease is endemic and a major cause of canine mortality in urban populations of Brazil15,16, where an estimated 147.5–160.3 million USD is spent annually due to the therapy of the systemic effects of CDV15.
CDV has been diagnosed concomitantly with traditional viral infectious disease agents such as canine parvovirus-2 (CPV-2)17,18, canid alphaherpesvirus-118,19, canine adenovirus-1 and -2 (CAdV-1)20, and (CAdV-2)18,21 in dogs. Moreover, recently CDV has been identified in dogs simultaneously with emerging viral infectious agents including Canine kobuvirus22, Canine pneumovirus23, and Canine respiratory coronavirus6,23. Additionally, studies have detected canine infectious disease agents due to the amplification of nucleic acids in symptomatic6,23–25 and asymptomatic19 dogs by molecular assays. Alternatively studies have combined the pattern of organ disease observed by histopathology with electron microscopy20, immunohistochemistry (IHC)8,12,21,22,25,26 and/or the molecular identification8,10,12,18,22,27 of infectious disease agents of dogs.
Previous studies by our group8,10,18 and others12,21,26,27 have demonstrated the concomitant participation of several infectious disease agents in the development of diseases in dogs, principally puppies. It is proposed that puppies are probably more frequently coinfected by several infections disease agents than has been previously reported, particularly if there is the simultaneous involvement of CDV, and coinfections may result in the death of the affected dog due to multiple organ failure10. The objectives of this retrospective study were to evaluate the frequency of concomitant traditional infectious disease agents in the development of infectious diseases in puppies, correlate the presence of these pathogens with histopathologic patterns, and review specific aspects of the pathogenesis involving these infectious disease agents.
About 81,000 people received national support (120,000 won per person; about 100 USD) for immunoglobulin administration, antigen and antibody tests for hepatitis B to prevent vertical infection from infected mothers. The participation rate was 60% in 2002, 89% in 2003, 96% in 2004, 98% in 2005, and 98% in 2006.
Polio occurred in 1,000 to 2,500 patients between 1955 and 1963, 100 to 300 cases had been reported thereafter until 1973. Only several to dozens of cases were reported between 1974 and 1983, and since 5 cases were reported in 1983, wild poliovirus infections have not been reported, thus far (Fig. 3)5).
According to a study of polio cases between 1962 and 1964, those aged 1 year were most common and those aged 3 years or more accounted for 70%. Inactivated vaccines for injection were used in 1962, oral live attenuated vaccines were added in 1965, and improved inactivated vaccines for injection have been used from 20045,9,11).
It is now becoming accepted that disease eradication has a legitimate place in the armamentarium of responses to EIDs (6). Smallpox, a devastating reemerging disease for millennia, was eradicated in 1980, and the epizootic morbillivirus (measles-related) disease rinderpest was eradicated in 2011 (32, 33). With dracunculiasis and polio disease close to eradication, with measles on the path to eradication, and with significant strides in controlling such diseases as hepatitis B and even malaria and HIV infection being made, it is now possible to realistically consider eradication as an ultimate means of controlling certain EIDs.
Even though antibiotic resistance has accelerated alarmingly, new generations of antibiotics have kept pace (albeit, barely), and vaccines against some of the most important diseases have been developed or improved, such as those against Haemophilus influenzae type B, pneumococci, and cancer-causing human papillomavirus strains. The development of antivirals and antiviral combination therapies has led to a historic breakthrough in helping to control HIV/AIDS (12) and major strides in curing chronic hepatitis C virus infection. Future directions in research and drug development likely will include better antibacterial and antiviral combination therapies as well as the development and use of more narrow-spectrum drugs against infective agents, which are less likely to cause polymicrobial resistance.
In the 20 years since the IOM report on EIDs, remarkable progress has been made in understanding and controlling them. In 1992, HIV infection was considered a death sentence for most patients. In 2012, after the tragedy of more than 35 million AIDS deaths, persons treated early with combination antiretroviral therapy, although not “cured” of their viral infection, can expect to live normal life spans with only a low risk of transmitting infection to others. In 1992, at least a million children died annually of measles. In 2012, fewer than 100,000 are expected to die, and measles eradication based upon an already-available effective vaccine is a realistic near-term goal. In 1992, it was possible to enter villages in many developing countries to monitor poliovirus circulation by conducting childhood “lameness surveys.” In 2012, most lame individuals are adults whose children are largely free of the threat of polio and probably will live to see it eradicated (poliovirus type 2 has already been extinguished).
Despite extraordinary progress during the past 2 decades, infectious diseases still kill 15 million people each year (6), and new and deadly diseases continue to emerge and reemerge. The perpetual nature of the emergence of infectious diseases poses a continuing challenge, which is volatile and ever-changing. This challenge includes a need for constant surveillance and prompt, efficient diagnosis; a need to develop and deploy new vaccines and drugs to combat new diseases; and a need for ongoing research not only in developing countermeasures but also in understanding the basic biology of new organisms and our susceptibilities to them. The future is ever uncertain, because unimagined new diseases surely lie in wait, ready to emerge unexpectedly; however, our ability to detect and identify them, our armamentarium of treatment and prevention options, our capacity to undertake and maintain basic and applied research, and our commitment to eradicating certain EIDs have never been greater. We have made far-reaching advances in the past 20 years since the original IOM report, and scientists are guardedly optimistic that further breakthroughs lie ahead.
The goal for managing influenza is decreasing morbidity and mortality rate to achieve reduced disease burden. The vaccination program selected the high risk groups for vaccination with priority. The influenza surveillance system operated and monitored daily and weekly surveillance for influenza and influenza like illness altogether with laboratory surveillance.
Unlike Ebola, HBV is both treatable and preventable. Although the preventive vaccine is highly effective, 5% of individuals do not respond, and genetic predictors of vaccine non-response are being identified. Screening for such genetic markers could exempt non-responders from vaccination that would otherwise be mandatory, for instance among healthcare workers. Such screening could also influence decisions about access to therapy, especially in settings with limited resources. Treatment for hepatitis B, although very effective, is not curative. If an immunotherapy-based cure is found, treatment might be provided preferentially to individuals with genotypes associated with more rapid disease progression if resources for such therapies are scarce. Also, individuals with genotypes associated with better response to immunotherapy may receive priority for treatment. Alternatively, those most likely to die from these infections might be given priority if vaccines are scarce.
Aerobiology is the study of the processes involved in the movement of microorganisms in the atmosphere from one geographical location to another, including the aerosolized transmission of disease. The aerosolized transmission of disease occurs through both “droplet” and “airborne” means. Droplet transmission is defined as the transmission of diseases by expelled particles that are likely to settle to a surface quickly, typically within three feet of the source [8–10]. Thus, for example, in order for an infection to be caused by droplet transmission, a susceptible individual must be close enough to the source of the infection (e.g., an infected individual) in order for the droplet (containing the infectious microorganism) to make contact with the susceptible individual's respiratory tract, eyes, mouth, nasal passages, and so forth. In contrast, airborne transmission is defined as the transmission of infection by expelled particles that are comparatively smaller in size and thus can remain suspended in air for long periods of time. Airborne particles are particularly worrisome simply because they can remain suspended in the air for extended periods of time. Seminal studies from the 1930s and 1940s [8, 12, 13] demonstrated that airborne particles can remain airborne for as long as one week after initial aerosolization, and suggested further that these particles likely remained airborne for much longer. They thus potentially expose a much higher number of susceptible individuals at a much greater distance from the source of infection [10, 11, 14, 15]. Depending on environmental factors (e.g., meteorological conditions outdoors and fluid dynamic effects and pressure differentials indoors), airborne particles are easily measured 20 m from their source. These factors would be of no concern but for the fact that airborne bacterial, viral, and fungal particles are often infectious.
A complicating factor is the heterogeneous nature of droplet and airborne releases, which generally consist of mixtures of both single and multiple cells, spores, and viruses carried by both respiratory secretions and inert particles (e.g., dust). The origins of droplet or airborne infectious microorganisms are also heterogeneous: infectious particles may be generated from, for example, infectious persons, heating, ventilation, and air conditioning (HVAC) systems, and cooling tower water in hospitals. All of these sources can produce airborne infectious particles. Furthermore, Aspergillus fumigatus spores are common in dusts during outdoor and indoor construction, in air conditioners, ceiling tile, carpet, and other infectious aerosol carriers generated from dry sources; they may absorb water in the airborne state but still measure in the infectious particle size range. Also, droplet and airborne transmission are not mutually exclusive. That is, independent of origin, particles carrying infectious microorganisms do not exclusively disperse by airborne or droplet transmission, but by both methods simultaneously.
Transmission of infectious disease by the airborne route is dependent on the interplay of several critical factors, primarily particle size (i.e., the diameter of the particle) and the extent of desiccation. The literature suggests that a particle's size is of central importance in determining whether it becomes and remains airborne and infectious [18–23]. Simply illustrated, large particles fall out of the air and small particles remain airborne. The World Health Organization uses a particle diameter of 5 μm to delineate between airborne (≤5 μm) and droplet (>5 μm) transmission [17, 24, 25]. How particle size affects spatial distribution in the human respiratory tract has been studied extensively. Some studies suggest that particles over 6 μm tend to mainly deposit in the upper airway, while particles under 2 μm deposit mainly in the alveolar region. Other studies conclude that particles under 10 μm can penetrate deeper into the respiratory tract, and particles over 10 μm are more likely to deposit on the surfaces of the upper airways and are less likely to penetrate into the lower pulmonary region [27–35].
One of the challenges facing practitioners, particularly in an enclosed building, is that even large-sized droplets can remain suspended in air for long periods. The reason is that droplets settle out of air onto a surface at a velocity dictated by their mass. If the upward velocity of the air in which they circulate exceeds this velocity, they remain airborne. Hence, droplet aerosols up to 100 μm diameter have been shown to remain suspended in air for prolonged periods when the velocity of air moving throughout a room exceeds the terminal settling velocity of the particle.
Another critical variable is the rate at which particles desiccate. Even large, moisture laden droplet particles desiccate rapidly. In his seminal paper, Wells showed that particles begin desiccating immediately upon expulsion into the air and do so rapidly: particles up to 50 μm can desiccate completely within 0.5 seconds. Rapid desiccation is a concern since the smaller and lighter the infectious particle, the longer it will remain airborne. Hence, even when infectious agents are expelled from the respiratory tract in a matrix of mucus and other secretions, causing large, heavy particles, rapid desiccation can lengthen the time they remain airborne (the dried residuals of these large aerosols, termed droplet nuclei, are typically 0.5–12 μm in diameter). Of further concern, very large aerosol particles may initially fall out of the air only to become airborne again once they have desiccated.
One reason why particle size is such an important variable in airborne and droplet disease transmission is that the ability of an infectious disease to cause an infection depends on the concentration of the microorganism, the human infectious dose, and the virulence of the organism. Humans can acquire devastating infectious diseases through exposure to very low levels of infectious particles. For example, Influenza A is believed to transmit via airborne and droplet means, and the infectious dose of Influenza A for humans is very low. Additionally, the infectious dose for Francisella tularensis is reported to be a single organism. Only a few cells of Mycobacterium tuberculosis are required to overcome normal lung clearance and inactivation mechanisms in a susceptible host.
For a long time, children’s infectious diseases have been the number one disease type to harm children’s health and threaten children’s lives. With the continuous development of medical undertakings, although human beings have made brilliant achievements in controlling and defeating children’s infectious diseases, the harm and threat of children’s infectious diseases are still very serious today. Children’s infectious diseases are prone to various complications threatening children’s lives; therefore, understanding the occurrence and changes of children’s infectious diseases is of great significance to the prevention and treatment of infectious diseases and the promotion of children’s health.
Infection surveillance is important in infectious disease management and prevention. The surveillance of notifiable diseases in China was first initiated in the 1950s. Accurate and timely surveillance of infectious diseases laid the foundation for effective disease control and prevention in China. After the severe acute respiratory syndrome (SARS) crisis in 2003, the Chinese government strengthened the construction of the public health information system. China officially initiated the China Information System for Disease Control and Prevention (CISDCP) in January 2004. This system is the most comprehensive and macroscopic notifiable disease surveillance system in China. Timely analysis of notifiable disease surveillance data to understand epidemic trends and their main characteristics is the basis for the prevention and control of infectious diseases.
Zhejiang province, located in the southeastern coast of China, has moist air, a mild climate, a developed economy, and large population mobility. It covers an area of 101,800 km2 and is one of the most densely populated provinces in China. By 2017, the population has reached up to 56 million, and the population aged 0–14 years is about 7.5 million.
In this paper, we described epidemiological characteristics of notifiable diseases in children aged 0–14 years reported in Zhejiang Province in 2008–2017, for the purpose of providing a reference for the prevention and control of infectious diseases in children in Zhejiang Province. The results are reported as follows.
In 2008–2017, morbidity of Class B infectious diseases showed a significant downward trend, from 185.34/100,000 in 2008 to 54.36/100,000 in 2017 (χ2trend = 11,093.22, p < 0.05), with an annual morbidity of 90.39/100,000; morbidity of Class C infectious diseases showed a fluctuating upward trend, from 1352.97/100,000 in 2008 to 2549.03/100,000 in 2017 (χ2trend = 97,595.69, p < 0.05), with an average annual morbidity rate of 2412.47/100,000 (Table 1).
The top 5 reported Class B infectious diseases were dysentery, scarlet fever, measles, Influenza A (H1N1) and syphilis. The morbidity of measles, dysentery and syphilis showed a decline (measles: χ2trend = 10,156.59, p < 0.05; dysentery: χ2trend = 6301.75, p < 0.05; syphilis: χ2trend = 3376.99, p < 0.05); and that of scarlet fever was on the rise in recent years (χ2trend = 4185.20, p < 0.05). Influenza A (H1N1) was classified as a Class B infectious disease in 2009; 5805 cases of influenza A (H1N1) were reported in 2009, ranking first among Class B infectious diseases reported in the same year. This disease showed a decline in 2010 (χ2 = 5126.04, p < 0.05), and the number of cases reported was between 3 and 259 in 2010–2013. Since 1 January 2014, it was removed from Class B to Class C under the management of existing influenza (Figure 1).
The top 5 reported Class C infectious diseases were hand-foot-and-mouth disease (HFMD), other infectious diarrheal diseases, mumps, influenza and acute hemorrhagic conjunctivitis, among which the morbidity of HFMD, other infectious diarrheal diseases, and influenza were on the rise, while the morbidity of acute hemorrhagic conjunctivitis and mumps were decreasing year by year. In 2010, 11,789 cases of acute hemorrhagic conjunctivitis were reported, and thereafter the number of cases reported decreased rapidly (Figure 2).
Infectious diseases have affected humans since the first recorded history of man. Infectious diseases remain the second leading cause of death worldwide despite the recent rapid developments and advancements in modern medicine, science and biotechnology. Greater than 15 million (>25%) of an estimated 57 million deaths that occur throughout the world annually are directly caused by infectious diseases. Millions more deaths are due to the secondary effects of infections. Moreover, infectious diseases cause increased morbidity and a loss of work productivity as a result of compromised health and disability, accounting for approximately 30% of all disability-adjusted life years globally.1,2
Compounding the existing infectious disease burden, the world has experienced an increased incidence and transboundary spread of emerging infectious diseases due to population growth, urbanization and globalization over the past four decades.3,4,5,6,7,8 Most of these newly emerging and re-emerging pathogens are viruses, although fewer than 200 of the approximately 1400 pathogen species recognized to infect humans are viruses. On average, however, more than two new species of viruses infecting humans are reported worldwide every year,9 most of which are likely to be RNA viruses.6
Emerging novel viruses are a major public health concern with the potential of causing high health and socioeconomic impacts, as has occurred with progressive pandemic infectious diseases such as human immunodeficiency viruses (HIV), the recent pandemic caused by the novel quadruple re-assortment strain of influenza A virus (H1N1), and more transient events such as the outbreaks of Nipah virus in 1998/1999 and severe acute respiratory syndrome (SARS) coronavirus in 2003.10,11,12,13,14 In addition, other emerging infections of regional or global interest include highly pathogenic avian influenza H5N1, henipavirus, Ebola virus, expanded multidrug-resistant Mycobacterium tuberculosis and antimicrobial resistant microorganisms, as well as acute hemorrhagic diseases caused by hantaviruses, arenaviruses and dengue viruses.
To minimize the health and socioeconomic impacts of emerging epidemic infectious diseases, major challenges must be overcome in the national and international capacity for early detection, rapid and accurate etiological identification (especially those caused by novel pathogens), rapid response and effective control (Figure 1). The diagnostic laboratory plays a central role in identifying the etiological agent causing an outbreak and provides timely, accurate information required to guide control measures. This is exemplified by the epidemic of Nipah virus in Malaysia in 1998/1999, which took more than six months to effectively control as a consequence of the misdiagnosis of the etiologic agent and the resulting implementation of incorrect control measures.15,16 However, there are occasions when control measures must be based on the epidemiological features of the outbreak and pattern of disease transmission, as not all pathogens are easily identifiable in the early stage of the outbreak (Figure 1). Establishing laboratory and epidemiological capacity at the country and regional levels, therefore, is critical to minimize the impact of future emerging infectious disease epidemics. Developing such public health capacity requires commitment on the part of all countries in the region. However, to develop and establish such an effective national public health capacity, especially the laboratory component to support infectious disease surveillance, outbreak investigation and early response, a good understanding of the concepts of emerging infectious diseases and an integrated country and regional public health laboratory system in accordance with the nature and type of emerging pathogens, especially novel ones, are highly recommended.
Traditionally, emerging infectious diseases are broadly defined as infections that: (i) have newly appeared in a population; (ii) are increasing in incidence or geographic range; or (iii) whose incidence threatens to increase in the near future.6,17 Six major factors, and combinations of these factors, have been reported to contribute to disease emergence and re-emergence: (i) changes in human demographics and behavior; (ii) advances in technology and changes in industry practices; (iii) economic development and changes in land use patterns; (iv) dramatic increases in volume and speed of international travel and commerce; (v) microbial mutation and adaptation; and (vi) inadequate public health capacity.6,17
From the perspective of public health planning and preparedness for effective emerging infectious disease surveillance, outbreak investigation and early response, the above working definition of emerging infectious disease and its associated factors that contribute to infectious disease emergence are too broad and generic for more specific application and for the development of a national public health system, especially in the context of a public health laboratory system in a country. Thus, in this article, emerging infectious diseases are divided into four categories based on the nature and characteristics of pathogens or infectious agents causing the emerging infections; these categories are summarized in Table 1. The categorization is based on the patterns of infectious disease emergence and modes leading to the discovery of the causative novel pathogens. The factors or combinations of factors contributing to the emergence of these pathogens also vary within each category. Likewise, the strategic approaches and types of public health preparedness that need to be adopted, in particular with respect to the types of public health laboratories that need to be developed for optimal system performance, will also vary greatly with respect to each category of emerging infectious diseases. These four categories of emerging infectious diseases and the factors that contribute to the emergence of infectious diseases in each category are briefly described below.
Network analysis tools for exploring the infectious contact network provides a key opportunity to uncover the topologies of the contact networks of individuals in the transmission of MERS. However, the epidemiological topology of the contact network of infectious individuals and healthcare facilities has not, until now, been systematically investigated in relation to MERS. This underscores the necessity of understanding the structural properties in contact networks, particularly as infection transmission correlates to the super-spreading characteristic of epidemics and the prevalence of nosocomial infection in healthcare facilities.
The results show that a small number of healthcare facilities where hub infectious hosts tended to visit for a limited time for MERS diagnosis and treatment had an excessively certain influence on the early spread of MERS throughout the population. The MERS epidemic was more likely to be associated with the increased probability of contact events among individual hosts, and nosocomial infections rapidly increased the proportions of epidemic. Additionally, personal contacts initiated by super-spreaders were considered as potential risk factors for the persistence of the MERS infection on networks and contributed to the epidemic onset with high transmissibility in healthcare settings. In other words, both nosocomial and personal contacts might have played a dominant role in enhancing the risk of the transmission of MERS and subsequent infection in healthcare facilities in a relatively short period of time. This implies that infection prevention and control policies to limit the spread of diseases should aim at targeted surveillance programs and control strategies by investigating and monitoring the introduction and spread of infectious diseases through contact networks.
Our findings contribute to previous studies in several ways. It highlights the role of network analysis tools in analysing the epidemiological topologies of infectious diseases through comprehensive analytical methods. It also underscores the need for further research to develop different epidemiological models for a broader understanding of the structural properties of epidemic transmission. In addition, we reveal that the small-world network with scale-free dynamics is highly relevant to the emergence of complexification of the disease-spreading dynamics, and tends to minimise the average path distance over all the pairs of infectious and susceptible individuals. Finally, notwithstanding the relatively high prevalence and probability of person-to-person disease transmission based on the movement and relationships of individuals, our results confirmed that MERS was often a nosocomial infection.
Based on results, we suggest clear implications on strategy-driven interventions to prevent disease transmission. First, prevention and control efforts should target individuals with the highest likelihood of transmitting the disease. Our results justify the interventions directed towards investigating and monitoring the introduction and subsequent spread of diseases by highly infectious super-spreaders. To mitigate the super-spreading of the MERS among people in homes and in communities, home care for patients with mild symptoms should be provided under close medical observation, after patients and family caregivers must have received appropriate training on personal hygiene, basic infection prevention, and control measures. However, patients with worsening conditions should seek prompt medical attention following a monitor of their health status for 14 days after the exposure event41,42. Secondly, our analysis reveals that relatively large tertiary hospitals have higher rates of MERS transmission than small community hospitals, because, in addition to poor disease control facilities, they typically have large numbers of patients and visitors who are engaged in doctor shopping43,44. Therefore, it is necessary to put effective quarantine and adequate facility ventilation on the agenda. Furthermore, to improve the response activities of hospital staff in infection prevention and control, timely education and training must be provided43. It is also necessary that, regardless of the diagnosis, healthcare facilities should always share essential information in a timely manner with other facilities at the early stage of the outbreak. Finally, until more is understood about MERS, the government should provide reliable and timely information to the public, and establish an efficient disease-control system as preventive measures against the initial spread of MERS.
Despite the comprehensive findings, this study has several limitations. First, it is difficult to control any confounding factors that could influence the study results. Information, such as the determinants of the patient’s choice of healthcare facilities, are frequently not available, which can result in bias in the contact network analysis. Second, this study is based on contact network relationships as traced among individual hosts infected by the MERS. Therefore, it is necessary for future research to identify and analyse the patients in relation to the different patterns associated with both modes of transmission, person-to-person contact transmission and nosocomial infection, to provide a more profound insight into how they differ. Furthermore, the study is limited to the MERS-infected population in Korea. Therefore, the generalisability of findings may be limited. We believe that the limitations of this study can be overcome by comparing various epidemiology models that demonstrate the spread of infections with sufficiently large evidence-based datasets.
The progress made over the past century in combating emerging infectious diseases came about as a result of engagement of several disciplines, namely, environmental studies, epidemiology, immunology, public health, social and cultural studies, pharmacology, medicine, molecular biology, chemistry, veterinary science, sociology, and anthropology among others [85–87]. Advances in basic science research and development of molecular technology and diagnostics have enhanced understanding of disease aetiology, pathogenesis, and molecular epidemiology, which provide basis for appropriate detection, prevention, and control measures as well as rational design of vaccine, by which some diseases have been successfully eliminated.
The development of the nucleic acid detection and genome sequencing technology in the nineteenth century has tremendously revolutionized infectious disease research, especially pathogenesis, diagnosis, and treatment and hence optimum patient care and management. A number of molecular assays have been developed for the detection, characterization, and quantitation of the ever-increasing number of infectious pathogens at a faster rate and with higher sensitivity and specificity as compared to traditional methods [2, 88]. From the initial stages of single pathogen detection, nucleic acid amplification methods today have been developed with a high-throughput capacity to generate a wealth of data on various types of pathogens (e.g., bacteria, parasites, and viruses) with specific disease markers (e.g., virulence, antibiotic resistance, and susceptibility factors) present in various types of specimen including blood, stool, swabs, urine, cerebrospinal fluid (CSF) samples, and respiratory secretions. Further, automation of nucleic acid detection technology provides “cutting-edge” platforms, the output of which ultimately greatly impacts patient management [89, 90] and also affords more efficient epidemiological and public health interventions.
Advances in molecular diagnostics and sequencing technology have played pivotal role in the control of many infectious diseases. In HIV disease treatment, for example, measurement of plasma HIV-1 viral load is an important technique for monitoring treatment efficacy; while viral gene sequencing is a crucial method by means of which drug resistance development is monitored in HIV-infected persons on antiretroviral therapy (ART). These techniques have been tremendously instrumental in the current ART success story.
The acquisition of genomic and protein data has contributed to successful vaccine design and drug development against most of the infectious disease pathogens. A better understanding of known pathogens and discovery of new or previously unknown infectious diseases has been facilitated through genomic and proteomic studies. Elucidation of the pathogenesis of the malaria parasite Plasmodium falciparum and individual's susceptibility or resistance to malaria contributed to the development of malaria vaccine (Mosquirix, the first against a parasitic infection in humans). Other achievements include the discovery of polio vaccine, anti-HIV drugs, and antimicrobials for various infectious agents like cancer-causing human papilloma virus, meningitis-causing pneumococci, and Haemophilus influenza type B; the recent Ebola vaccine represents landmark breakthroughs [12, 94].
Not only has advance in acquisition of genomic data contributed substantially to the development of vaccines and antimicrobials, but also it has important application in deciding and guiding successful treatment. Typical examples can be found in HIV antiretroviral therapy. Assay for the type of coreceptor usage by a patient's predominant virus population, whether CCR5- or CXCR4-tropic virus, is necessary before using the antiretroviral drug Maraviroc, which is a CCR5 coreceptor antagonist; the nucleoside reverse transcriptase inhibitor d, Abacavir (ABC), is associated with drug hypersensitivity reactions. This drug may lead to high rates of myocardial infarction in patients who are positive for human leukocyte antigen (HLA) type B∗5701 allele. Safe use of Abacavir therefore requires testing patients genetic data for HLA B∗5701 allele.
Besides pathogen and human factors, notable milestones have been achieved in the global sociopolitical front in addressing infectious disease problems. Since the dawn of this century concerted efforts have been made globally by global organizations, governments, foundations, and partner bodies towards infectious disease control. The United Nation's decision to “combat HIV/AIDS, malaria, and other related diseases” as part, sixth goal, of the eight MDGs has led to transforming HIV from deadly to chronic, manageable disease. Other global initiatives in the fight against HIV include the United Nations–supported Global Fund to Fight AIDS, Tuberculosis, and Malaria (GFATM), the World Health Organization (WHO) “3 by 5” initiative, and the US President's Emergency Program for AIDS Relief (PEPFAR) [97, 98]. NTDs have also received impressive and unprecedented global attention, with heavy financial and research commitments by major institutions and organizations (see section on public health response) [76, 99].
In real terms, the outcome of advances in response to infectious disease threats reflects in marked progress in infectious disease control and human health protection. The discovery of vaccine about two hundred years ago by Edward Jenner (the English physician) has made it possible to prevent approximately 9 million deaths each year globally through routine immunization [100, 101]. Some vaccine-preventable diseases that are at various levels towards eradication include polio, diphtheria, whooping cough, measles, neonatal tetanus, hepatitis B, and tuberculosis. Others are Rubella, Dracunculiasis (Guinea worm), Lymphatic filariasis (elephantiasis), onchocerciasis (river blindness), and Mumps [37, 51, 102].
WHO has planned to eliminate measles by the year 2020. Polio is currently seen in three countries, Afghanistan, Nigeria, and Pakistan, but efforts are underway for its complete eradication and, down from nearly 3.5 million cases in 1986, today there are just 126 cases of Guinea worm recorded globally; Guinea worm disease could be the second human disease after smallpox to be eradicated.
The incidence of various emerging and reemerging infectious diseases continues to pose a substantial threat to the human health throughout the world. During the past two decades newly emerging ones, for example, severe acute respiratory syndrome (SARS), reemerging ones, for example, West Nile virus, and even deliberately disseminated infectious diseases, for example, anthrax from bioterrorism, threaten the health of the hundreds and millions of the people globally. During early nineties, there was a consensus that it was the time to close the book as the battle against infectious disease had been won. But reemergence of cholera to the Americas in 1991, the plague outbreak in India in 1994, and the emergence of SARS outbreak in 2002-2003, Swine flu (H1N1) pandemic in 2009, and most recently Zika outbreak in Brazil in 2015 eventually prove that thought wrong. Ebola virus disease (EVD) is one of the notorious emerging infectious diseases that endanger the human lives from time to time since its appearance in 1976 in Zaire (later renamed the Democratic Republic of the Congo) and Sudan in Africa continent. The recent epidemic of EVD started in Guinea in December 2013. Within a short period of time, it has spread across land borders to Sierra Leone and Liberia, by air to Nigeria and USA, and by land to Mali and Senegal. On August 8, 2014, the World Health Organization (WHO) declared the EVD outbreak in West Africa a Public Health Emergency of International Concern (PHEIC) under the International Health Regulations (2005). On March 29, 2016, PHEIC related to EVD was lifted from West Africa and on June 9, 2016, WHO declared the end of the most recent outbreak of EVD. By the end of the epidemic, total 15227 confirmed EVD cases have been reported with 11310 deaths in Guinea, Liberia, and Sierra Leone. Till date no indigenous EVD case has been reported in India. But no country is free from the threat of EVD outbreak. A precise prediction about transmission and consequences after an EVD outbreak in India will be effective for proper planning and management to combat with the situation.
Precision public health is a state-of-the-art concept in the new era of public health research and its application in health care. The concept of precision public health evolved within the last two to three years. The precision public health can be simply described as improving the ability to prevent disease, promote health, and reduce health disparities in populations by applying emerging methods and technologies for measuring disease, pathogens, exposures, behaviours, and susceptibility in populations and developing interventional policies for targeted public health programs to improve health. The emergent areas of precession public health are improving methodologies for early detection of pathogens and infectious disease outbreaks, modernizing public health surveillance, epidemiology, and information systems, and targeting health interventions to improve health and prevent diseases. Application of information technology and data science, like real time data acquisition, geospatial epidemiological modelling, big data analytics, and machine learning technology, in field of epidemiology paves the way to its transformation to digital epidemiology, which is conceptually more accurate and precise in nature [8, 9].
Geospatial epidemiological modelling, an application of geographic information system (GIS), is an important tool of precision public health to study the dynamics of disease transmission more accurately. This tool can be applied to predict the spread of an outbreak. Various interventional measures and subsequent outcome can also be studied, which will help to develop efficient and effective disease specific outbreak prevention and management strategies.
Keeping the concept of precision public health and geospatial epidemiological modelling in mind, a computer simulation based study, related to hypothetical EVD outbreak in India, was undertaken with following objectives: To simulate the spread of Ebola virus disease after a hypothetical outbreak in India on 01.01.2017 at New Delhi and to predict the number of exposed and infectious persons and deaths due to that EVD outbreak within a span of 2 years.
From 2008 to 2017, China achieved impressive reductions in the burden from infectious diseases in children and adolescents aged 6 to 22 years. This complements the reduction in mortality from infectious diseases in under 5s—a longstanding focus of the Millennium Development Goals, and will contribute to reductions in the overall burden from infectious diseases in China.16
60 However, China’s rapid success poses challenges for policy makers as priorities for infectious disease control continue to evolve. Beyond maintaining the gains, the priorities for the coming decade include reducing regional inequalities; scaling-up vaccination for mumps, seasonal influenza, and hepatitis B; preventing further escalation of HIV/AIDS and other sexually transmitted diseases; and redoubling efforts around persisting diseases, including tuberculosis, rabies, and scarlet fever. Different responses will be needed by region and by age across childhood and adolescence, while the newer emerging disease epidemics will require rapid and targeted responses. Seasonal variation in respiratory infections and in gastrointestinal and enterovirus diseases reflect the high vulnerability of children and adolescents. A comprehensive national surveillance system remains an integral part of infectious disease control in these age groups to maintain the gains of recent decades and respond effectively to new epidemics.
Emerging infectious diseases have been defined as, “infections that have newly appeared in a population or have existed previously but are rapidly increasing in incidence or geographic range.” Several features may make them particularly threatening. First, recognizing the disease can be difficult when the first cases appear, especially when the symptoms are non-specific. Second, no vaccine or specific treatment may be known initially. Moreover, heterogeneities in disease transmission may create high-risk groups, such as healthcare workers– and high-risk geographical areas, thereby dramatically enhancing the impact of the outbreak.
The 2003 severe acute respiratory syndrome (SARS) outbreak in Hong Kong is remarkably illustrative of the above issues: symptoms were similar to pneumonia; the incubation period was long enough for local and international transmission to occur; no vaccine or treatment was available; as much as 21% of cases worldwide were healthcare workers. The outbreak also demonstrated the possible existence of super-spreading events (SSEs), during which a few infectious individuals contaminated a high number of secondary cases. Hong Kong had two SSEs: the first occurred in Hospital X around March 3 and led to about 125 cases; the second occurred in Housing Estate Y on March 19, and led to over 300 cases,. Despite its particularly threatening features, the outbreak was brought under control.
In this context, once the epidemic is detected, spontaneous changes in behavior will occur, and non-pharmacological measures are usually initiated to control the outbreak. The resulting effects of these two phenomena on disease transmission is not easily quantified.
The effective contact rate, which reflects the combined influences of social proximity (the number of contacts per time unit) and the probability of infection through each contact, is an essential determinant of disease spread. Our aim was to estimate the temporal variation of this parameter in the community and hospitals, over the course of the outbreak.
Previously published mathematical models of parameter estimation addressed the issues of temporal variability, or social heterogeneity,. Here we present an approach that deals with both issues, together with the occurrence of SSEs. Then the method is applied to the 2003 SARS epidemic in Hong Kong (SARSID database).
The use of chemoprophylaxis and treatment against infections in the military continues to be an extensive field with opportunities for further exploration. During the American Civil War from 1861 to 1865, three studies on antiseptics (bromide, turpentine and nitric acid) showed reductions in mortality from hospital gangrene. Almost 80 years later during the Second World War, the critical discovery of penicillin’s antibiotic effects propelled it to become second highest priority (behind the atomic bomb) by the U.S. War Production Board. Its use has often been cited as pivotal to success of the Allied Forces.
Apart from antibiotics, military medicine has also helmed developments and innovations in the use of anti-parasitic and anti-viral chemoprophylaxis. The anti-malarial drug mefloquine was developed by the Walter Reed Army Institute in the 1960s, in collaboration with the World Health Organisation and Hoffman-LaRoche. Further studies also showed synergism between atovaquone and proguanil, with subsequent co-administration trials conducted at various sites by military-associated laboratories in Kenya, Brazil and Indonesia. The Influenza A(H1N1)pdm09 pandemic also saw the effective use of oseltamivir ring prophylaxis in the Singapore Military in localised outbreaks to bring about significant reductions in the reproductive number (the number of new cases attributable to the index case) from 1.91 to 0.11, with significantly reduced rates of infection.
Other drugs have been, or are being evaluated for possible benefits of chemoprophylaxis in the military setting. These include the successful use of rifaximin for the prevention of travellers’ diarrhoea among travellers and deployed military personnel, and dilute Dakin solution for angioinvasive fungal infection in the combat wounded.
Militaries around the world have also implemented chemoprophylaxis programs against specific threats. The U.S. military has guidelines for different infectious diseases including pre-exposure prophylaxis for malaria during deployments to affected areas and post-exposure prophylaxis for anthrax and meningococcus exposure. The Republic of Korea Army instituted a malaria prophylaxis program in 1997, and no malaria deaths have been reported since. In Singapore, malaria prophylaxis is routinely used for travel to malarious locations globally. At the same time, on Singapore’s Tekong Island which houses a military training facility, an integrated combination malaria eradication strategy since 2006 has negated the need for malaria prophylaxis.