Infectious Diseases: A Review

Sizable segments of the American population are at risk for acquiring a wide range of infectious diseases. Behaviors such as injection drug use (IDU), certain sexual practices, and sexual promiscuity are routes of transmission of human immunodeficiency virus (HIV), hepatitis B (HBV) and C (HCV), and numerous other sexually transmitted infections (STIs). Transplant recipients and patients receiving cancer chemotherapy and/or immunosuppressive therapy are also at higher risk for developing a variety of infectious diseases. Many Americans are not compliant in receiving recommended vaccinations. The risk of transmitting vaccine-preventable infections such as measles, mumps, and rubella is at one of the highest levels in the post-vaccination era. Finally, antimicrobial resistance has become one of the most significant public health treats of the new millennium. Some organisms have acquired such a high degree of resistance that resultant infections are not treatable. Therefore, dentists will be treating an increasing number of patients with infectious diseases.

Trends in Infectious Diseases Mortality: 1900–Present

Since the early 1900s, life expectancy and quality of life have steadily increased, due in large part to the ability to prevent and/or treat infectious diseases. Mortality from infectious diseases declined in the United States during the first 80 years of the 20th century, from 797 deaths among 100,000 infections in 1900 to just 36 deaths among the 100,000 infected in 1980.^1,2 Multiple factors are responsible for reducing infectious-disease mortality, including: the development of effective antimicrobial drugs—antibiotics, antivirals, antifungals, and antiparasitics; the development of safe and efficacious vaccines—MMR, smallpox, polio, diphtheria and tetanus, HBV, and influenza; and the implementation of other important prevention practices, such as improvements in sanitation, housing, and nutrition.^1,2

Morbidity and mortality from polio, measles, diphtheria, meningitis, tetanus, hepatitis A and B, influenza, and many other diseases have been significantly reduced, mostly as a result of compliance with recommended immunization schedules.³ However, for a variety of reasons, many people are declining to be vaccinated, and there is a very worrisome worldwide increase in vaccine-preventable diseases.⁴ One notable exception to the decline in infectious-disease mortality—and a dramatic example of the unpredictability of the emergence of infectious diseases and the lethality of the emergence of a novel influenza virus—was the 1918 to 1919 influenza pandemic. The pandemic resulted in a dramatic increase in the death rate during those years.^1,2 This flu killed at least 20 million people worldwide (estimates are as high as 50 million), including 500,000 Americans. These deaths all occurred in less than 1 year, far surpassing the death rate during such a short time of any war or famine in the world.^2,5 However, in 1980, a pandemic of a different sort emerged and the mortality rate increased.¹ First recognized in 1981,⁶ HIV/AIDS resulted in increased deaths between 1981 and the early 1990s in people 25 years and older.^1,2 Since the first report of HIV/AIDS in 1981, the infection has become an ever-growing pandemic;⁷ at the end of 2010, there were an estimated 34 million people in the world living with HIV, with 2.7 million new HIV infections diagnosed and 1.8 million deaths from AIDS-related illnesses that year alone. Since the beginning of the epidemic, nearly 30 million people have died from AIDS-related causes.⁷

Although the development of vaccines has been especially effective in preventing viral diseases,² the biology of HIV has been shown to be so complex that a safe and efficacious vaccine has yet to be developed. The same is true for HCV as well as other viral diseases of concern to the dental practitioner, such as herpes simplex virus (HSV). The second factor that has decreased the impact of infectious diseases has been the development of effective antibacterial, antiviral, and antifungal agents.² Since the discovery of penicillin and its introduction into clinical practice in the early 1940s, antibiotics have been used with great success to treat infections with streptococcal and staphylococcal infections, gonorrhea, syphilis, and numerous other bacterial infections, including those of odontogenic origin.² It is estimated that deaths in the United States declined by 220 per 100,000 with the introduction of sulfonamides and penicillin in the early antibiotic era, outweighing all of the gains achieved with any other medical advance in the past century.^1,2

Other antimicrobial drugs have been developed to treat viral, fungal, and parasitic diseases. The emergence of drug resistance in many organisms—including bacteria, viruses, fungi, and parasites—is threatening to reverse many of the therapeutic gains of the of the last 50 years. Antimicrobial resistance is emerging into one of the most significant public health threats of this century.

HIV/AIDS

While any infectious disease has the potential to influence the practice of dentistry, the emergence of HIV/AIDS has arguably had the most significant impact on the profession. Following the first reports of the disease in the early 1980s, HIV infection rates and AIDS deaths steadily increased, and mortality from this disease was thought to be in the vicinity of 100%.^6,8-12 With an ever-increasing number of cases being reported, a disproportionate fear of acquiring this new and mysterious infection generated an AIDS hysteria that steadily gained momentum. Because the routes of transmission and biology of HIV were poorly understood at the time, many became obsessively concerned about being exposed to and acquiring this infection, which was considered a virtual death sentence. This was certainly true for healthcare workers (HCWs), and was particularly true for dentists. At this time, infection control was of little concern to dental practitioners and most practiced without barriers (eg, gloves, masks, eye protection) despite the fact that most dental procedures exposed the practitioner to blood.

By 1991, the OSHA Bloodborne Path­ogens Standard required all HCWs in all disciplines to modify medical/dental practices to adapt Universal Precautions, which evolved into the Standard Precautions that are practiced today.¹³ Infection control—especially in dentistry—was thrust to the forefront, and as a direct result of the growing HIV/AIDS epidemic, clinical practice changed rapidly, almost overnight. Guidelines were published to ensure that the delivery of medical and dental care was modified to include acceptance of Universal/Standard Precautions and preventing the transmission of bloodborne pathogens and other infectious diseases in healthcare settings.^13-17 Today dentists, hygienists, and staff routinely encounter patients infected with HIV disease, and the use of Standard Precautions and adherence to the principles of sterilization—as delineated by the Centers for Disease Control and Prevention (CDC)—has been shown to prevent the transmission of HIV disease, as well as other bloodborne infections in healthcare delivery settings, including the dental office.

HIV Transmission

Since the first report of HIV in 1981, significant advances have been made in understanding the biology and pathogenesis of this infection. The routes of HIV transmission are well described; all involve contact with blood and/or bodily fluids that are infected with the virus.

There is a universal risk for unprotected sexual contact regardless of sexual preference; however, gay, bisexual, and other men who have sex with men of all races and ethnicities remain the population most severely affected by HIV.

The virus can be transmitted through the use of contaminated needles, such as those used for illicit injection drug use. Children can be infected both perinatally and while breastfeeding from an infected mother. The virus also can be contracted during blood/blood product transfusion or infusion; through organ transplantation; or occupational exposure, particularly in healthcare settings.^11,12,18-20

The CDC estimates that 1.2 million people in the United States are infected with HIV disease; however, 20% of those infected are unaware of their infection—ie, the HIV infection is undiagnosed.²⁰ More than 50,000 people in the United States become newly infected with HIV each year.²⁰ Over 1.1 million people have been diagnosed with AIDS, and more than 619,000 people with AIDS have died in the United States since the first cases were reported in 1981.20 Although the prognosis of HIV/AIDS was grim in the early years, antiretroviral therapy (ART) has been shown through controlled clinical trials to suppress the viral load, sustain this suppression, significantly improve immune function, and achieve a remarkable 60% to 80% reduction in new AIDS diagnoses, hospitalizations, and deaths.^11,12,18,19 This dramatic reversal of the prognosis of HIV disease is the direct result of inhibition of HIV replication and sustained reduction of viral load. HIV reproduces at a very high rate, and in the process of reproduction, HIV kills T-4 helper lymphocytes—also referred to as CD4 lymphocytes—leading to a dramatic decline of immune function. When the normal CD4 count of 1,000 falls to below 200, deterioration of immune function allows for the development of a myriad of opportunistic infections (OIs).^11,12,18,19 Today, more than 30 antiretroviral drugs—with several fixed-dose-combination preparations—in six different classes have been approved for use in the United States.^19,21 By inhibiting HIV reproduction at different points in its replication cycle, these drugs are combined to construct a number of highly effective regimens. ART significantly improves the prognosis of those infected with HIV, improves immune system function, reduces the incidence of opportunistic infections, and reduces the risk of HIV vertical transmission.^18,19,21 While highly efficacious, many of the drugs in the ART regimens cause significant adverse reactions such as nausea, vomiting, diarrhea, and other gastrointestinal and systemic symptoms that can often be severe and are sometimes fatal. Drug-to-drug interactions are common, and ART has been implicated in a number of significant metabolic side effects that include development of insulin-resistant diabetes, abnormal glucose tolerance tests, lipodystrophy (blood lipid changes, hypertryglyceridemia, hypercholesterolemia, and cardiovascular disease), and fat redistribution (increased abdominal girth, thin extremities, buffalo hump, enlarged breasts).^18,19,21 However, the benefits of ART outweigh the risks; ART regimens have been shown to significantly improve life expectancy to the extent that the life expectancy of a 20-year-old man or woman diagnosed with HIV today in North America is the early 70s, which is not much different from a non-HIV infected person.²²

HIV Testing

Although only about 20% of the HIV-infected in the United States are aware that they are infected, they are the source of almost half (49%) of the new transmissions.²³ Identification of people infected with HIV is of primary importance both to reduce the risk that they will unknowingly transmit HIV to others and to commence treatment for their infection as soon as possible. To help increase the number of people tested, the CDC has recommended routine voluntary HIV screening for all adults, adolescents, and pregnant women.²⁴ Rapid HIV tests have been developed with results being available during a single visit, usually within 40 to 60 minutes—in contrast to the standard HIV test, which requires a 1-week wait and a second visit to obtain results.^24-26 All approved tests are highly sensitive and specific; they have been proven to be as accurate as a standard enzyme-linked immunosorbent assay (ELISA).²⁶ A negative test result is interpreted to mean the person is not infected, unless he or she has engaged in high-risk behavior (unprotected sexual contact, needle sharing, etc.) during the 3 months previous to testing and could be in the very early stages of the disease before the HIV antibody would have been produced.²⁶ Most rapid tests use whole blood, plasma, or serum and require drawing of blood or a finger stick. However, the OraQuick Advance HIV-1/2® (OraSure Technologies, Inc, www..orasure.com) uses oral fluid. This unique test is simple to use and accurately produces a result in 20 to 30 minutes.

As dentists play a significant role in screening for hypertension and oral cancer, screening for HIV could easily be incorporated into a dental visit. However, there are steps that dentists must take before starting in-office rapid HIV testing. Among these are researching individual state laws regarding HIV testing and informed consent, Clinical Laboratory Improvement Amendment (CLIA) waivers, training, and securing follow-up and treatment for those who test positive.²⁷

Data collected for over 30 years clearly demonstrates that HIV-positive patients, as well as those infected with other bloodborne diseases, can be safely treated in the dental office when the recommended infection control guidelines are followed.⁴³

Hepatitis B

The hepatitis B virus (HBV) is readily transmitted through contact with the blood or other body fluids of an infected person.²⁸ The primary risk factors include intravenous drug use, unprotected sex with an infected partner, birth to an infected mother, unprotected sex with more than one partner, men having sex with other men, a history of other STDs, and exposure to infected blood (via transfusion, occupational/healthcare exposure).²⁸ The World Health Organization (WHO) estimates that about 2 billion people worldwide have been infected with the virus; 350 million live with chronic infection, and around 600,000 people die each year due to the acute or chronic consequences of HBV infection.²⁹ The CDC estimates that 800,000 to 1.4 million people living in the United States are chronically infected with HBV.³⁰ In most (90% to 95%), the infection resolves. However, 5% to 10% will develop chronic infection.²⁸ The risk for premature death from cirrhosis or hepatocellular carcinoma is 15% to 25% in those individuals.²⁸ Symptoms of HBV infection are highly variable; about half of those infected are asymptomatic.²⁸ HBV is the most infectious of the bloodborne pathogens and is thought to be 50 to 100 times more infectious than HIV.²⁹ Fortunately, a safe and effective vaccine is available and is required by OSHA to be offered to all employees who are exposed to blood and blood products.

As with the other bloodborne pathogens, patients with HBV can be safely treated in the dental office when recommended infection control practices are followed.^13-17 However, any breaches in infection control procedures can transmit HBV. In a case that occurred in 2005, molecular epidemiologic techniques documented patient-to-patient transmission of HBV between two outpatient oral surgery patients treated on the same day.³¹ An investigation conclusively linked a 60-year-old woman with no traditional risk factors for HBV to a previously HBV-infected patient seen 161 minutes apart.³¹ The dental practice was following recommended infection control protocols, and the mechanism of transmission could not be determined, but some kind of cross-contamination was suspected because the chain of infection remained intact.³¹ In another dental setting, HBV was transmitted to five people (three patients and two volunteers) at a free dental clinic in West Virginia in November 2009.³² During this event, approximately 2,000 disadvantaged patients were treated by volunteer dentists and staff. The CDC investigation concluded that four people were likely infected by the same source but, once again, the origin of HBV transmission was not specifically determined. However, as in the previous case, cross-contamination was suspected, the chain of infection was left intact, and HBV was transmitted.³² A total of 31 outbreaks of viral hepatitis related to healthcare delivery were reported to the CDC during 2008 to 2011.³² Of these, 29 (94%) occurred in non-hospital settings. HBV was involved in a total of 19 outbreaks, 155 outbreak-associated cases, and 10,318 people notified for HBV screening.³²

Hepatitis C

The WHO estimates that about 130 to 170 million people are chronically infected with hepatitis C virus (HCV) and more than 350,000 people die from HCV-related liver diseases each year.³³ HCV infects about 2.7 to 3.9 million Americans, and each year about 17,000 Americans become newly infected with HCV.^30,34 In the United States, infection is most prevalent among those born between 1945 and 1965, who account for 75% of total cases.^30,34,35 Most of these infections occurred during the 1970s and 1980s, when rates were highest. Many of these resulted from infected blood transfusions before screening for HCV was instituted.^34,35 Deaths from HCV infection nearly doubled between 1999 and 2007 to more than 15,000.^30,34,35 In 2007, deaths from HCV surpassed deaths from HIV/AIDS.³⁵ Deaths from HCV are rising while deaths from HIV/AIDS are declining mainly because of the availability and success of ART; to date, HCV therapy lags far behind that of HIV/AIDS. HCV is the leading infectious cause of cirrhosis and liver cancer, and is the most common reason for liver transplants in the United States.^30,34,35

Routes of transmission are similar to HBV; intravenous drug use is especially efficient in transmitting HCV.^33,34 Inadequate infection control also causes a large number of HCV transmissions worldwide.³² In the United States, the CDC reports a total of 13 HCV outbreaks, with 102 outbreak-associated cases and 80,649 at-risk people notified for screening.³² While the great majority of those infected with HBV resolve the infection, the opposite is true for HCV. Approximately 80% to 85% of those infected with HCV become chronically infected and are unable to resolve the infection.^33,34 The great majority of HCV infections are asymptomatic or at most mildly symptomatic, thus, many of those infected with HCV are unaware of their infection.^33-35

Genetic analysis of HCV reveals the existence of six major genotypes—types 1 through 6—and numerous subtypes account for the high rate of chronicity. Genotype 1 is the most common in the United States, accounting for more than 75% of all HCV infections; genotypes 2 and 3 account for the majority of the remaining cases; and genotypes 4 through 6 are rarely seen in the United States.³⁶ HCV genotype does not appear to affect the rate of disease progression; however, genotype is a major predictor of response to therapy. Genotype 1 patients have overall response rates that are significantly lower (< 50%) than those infected with HCV genotypes 2 and 3, who have a much more favorable (> 80%) response to therapy.³⁶

Influenza

Seasonal influenza predictably occurs every year between November and March and causes, on average, 36,000 deaths in the United States each year.^37,38 The most vulnerable populations are people over age 65, infants/children under age 2, and pregnant women.^37,38 Influenza viruses are classified into three major types—influenza A, B, and C—based on their protein composition. Influenzas A and B are responsible for the majority of human infections; influenza C causes mild respiratory infections but usually does not cause widespread infection.^37-39 In addition to humans, influenza A can infect swine, equines, marine animals, and birds. Two phenomena known as antigenic drift and antigenic shift contribute to the development of new strains of influenza.^38,39

All type-A influenza viruses are genetically labile and well adapted to elude host defenses. There are constant, permanent, and usually small changes in the antigenic composition of influenza A viruses. These mutations result in small changes in circulating strains of influenza, creating new antigenic variants. Influenza B undergoes a similar but much slower process known as antigenic drift. These changes, though subtle, require modification of the composition of the annual influenza vaccine. However, influenza A viruses—including subtypes from different species—can swap or “re-assort” genetic materials and merge. This is known as antigenic shift and results in a novel subtype different from both parent viruses. As these are completely new viruses never before seen in humans, no one has had previous exposure, so there is no natural immunity.^38,39

Antigenic shift has historically resulted in highly lethal pandemics, the most deadly of which occurred in 1918 to 1919.38,³⁹ In the more recent past, a reassorted virus, Influenza A H1N1 (swine flu) was first reported in Mexico in March 2009.^40,41 The first US case was diagnosed on April 15, 2009, as a probable influenza A, but the strain was unidentifiable at that time. A sample was sent for further analysis, where the virus was identified as an influenza A H1N1, which was a re-assortment of avian and swine viruses from North America, a swine flu strain usually seen in Asia, and a human influenza strain—a completely novel virus.

On April 26, 2009, the CDC declared H1N1 a public health emergency in the United States.^40,41 Because this was a new infection and no one had previous exposure or immunity, H1N1 very rapidly spread globally and the WHO declared H1N1 a pandemic on June 11, 2009.40,⁴¹ By June 2009, 18,000 cases were reported in the United States; a total of 74 countries eventually reported H1N1 cases.^40,41 By November 2009, 48 states had reported cases of H1N1, mostly in young people. The public health response to this flu was very vigorous, and a safe and efficacious vaccine was developed and put into production. However, the production of sufficient quantities of doses was delayed because of difficulty in growing sufficient quantities of virus to produce the vaccine. By November, more than 61 million doses were available, and an estimated 80 million Americans were vaccinated against H1N1.^40,41 This undoubtedly minimized the impact of the illness. However, despite development of a vaccine, the CDC estimated that 43 to 89 million cases of H1N1 occurred between April 2009 and April 2010; H1N1-related deaths were estimated to be between 8,870 and 18,300.⁴¹ On August 10, 2010, the WHO declared the H1N1 flu pandemic ended.^40,41

In November 2009, the CDC released Prevention of 2009 H1N1 Influenza Transmission in Dental Health Care Settings to help prevent the spread of H1N1 in the dental office.⁴² Essential to this prevention was the recommendation that all dental personnel receive the influenza vaccination.⁴² In support of the need to prevent the spread of influenza, on February 24, 2010, a panel of immunization experts voted to expand the recommendation for annual influenza vaccination to include all people aged 6 months and older to take effect in the 2010 to 2011 influenza season.⁴³

But the need for vaccination extends beyond influenza. In recent years, there has been a disturbing increase in the incidence of vaccine-preventable diseases such as measles, mumps, rubella, and pertussis.^3,4,44 Many people—for a variety of reasons, mostly misinformation—elect not to be vaccinated or have their children vaccinated.^3,4 This has left a segment of the population susceptible to these diseases and becomes a reservoir of infection in the community.^3,4 Most of the cases of vaccine-preventable diseases are acquired outside the United States and imported, infecting non-vaccinated contacts who are vulnerable to these infections.^3,4,44 All Americans, especially healthcare providers, should comply with vaccine schedules as recommended by the CDC.³ Annual influenza shots save lives and limit the spread of influenza; receiving the recommended vaccinations significantly lowers the morbidity and mortality of vaccine-preventable diseases. Dental practitioners have close daily contact with many patients and all should be current with their vaccinations. However, the decision to receive a vaccination should be determined by the current CDC recommended guidelines in conjunction with evaluation and/or consultation with a licensed physician.

Healthcare-Associated Infection and Antimicrobial Resistance

The CDC estimates that 1.7 million healthcare-associated infections (HAI) occur each year.^45,46 These infections contribute to the death of 99,000 patients annually, which makes HAI the fourth leading cause of death in the United States; they kill more people every year than AIDS, breast cancer, and automobile accidents combined.^45,46 The annual medical costs of HAI in US hospitals is estimated to be between $28 and $45 billion, adjusted to 2007 dollars.^45,46 HAI is a threat to patient safety and collectively are the most common adverse events resulting from hospitalization.⁴⁷ Approximately 5% to 10% of hospitalized patients in the developed world acquire such infections.⁴⁸ In developing countries, the acquisition of HAI is much higher.⁴⁸

Proper use of hand hygiene is critical to the prevention of these infections. However, compliance among HCWs is poor, usually below 40%.^47,48 Most HAIs are caused by resistant organisms, and multiple-drug-resistant organisms are now more and more frequently encountered in both hospital and community settings.^45-51 Resistant infections are more difficult to treat and result in much higher morbidity and mortality.^47,48 The development of antimicrobial resistance is complex, multifactorial, and is rapidly becoming a major public health threat. The four significant factors that contribute to the emergence and proliferation of resistant microorganisms include: adaptability of the organisms and natural biological changes (mutation and gene transfer); indiscriminate/inappropriate use of antibiotic/antimicrobial agents in all healthcare settings; overuse and/or misuse of antibiotics in farming/animal husbandry; and noncompliance with infection control practices.^49-51

In a natural evolutionary biological process, microorganisms are very adaptable and are constantly changing to survive in unfavorable environments. Development of antimicrobial resistance (AMR) is an inevitable part of this process. When an organism is exposed to an antimicrobial agent, the organism is either killed or it is not. The surviving organisms are resistant, and by selective pressure and natural selection, these organisms thrive and are able to pass on resistance to their progeny. Therefore, one of the most significant factors in the development of AMR has been the indiscriminate and inappropriate use of antibiotics, which has occurred over many decades and is still occurring in almost every healthcare setting.^49-51 According to the WHO, up to 50% of antimicrobial use is inappropriate.⁴⁹ They are given when they are not needed; they are continued when they are no longer necessary; they are given at the wrong dose; broad-spectrum agents are used to treat very susceptible, non-resistant bacteria; and the wrong antibiotic is given to treat an infection.

Additionally, new patterns and pathways of resistance that facilitate the development and spread of resistant organisms are constantly emerging.^49-51 Poor infection prevention/infection control amplifies and perpetuates AMR.^47-49 HCWs, who are notoriously noncompliant with hand hygiene and recommended infection control practices, are among those spreading drug-resistant infections.^47-49 Infected patients become carriers of resistant microorganisms, reservoirs of infection, and sources of community-acquired resistant infections.^47-49 Clearly, improvement in compliance with Standard Precautions, safe injection practices, and the principles of infection control must be implemented and vigorously enforced in all disciplines of healthcare, including dentistry.^13-17 Antibiotics are a shared resource and are rapidly becoming a scarce resource and should be used only when indicated.^49-51 The American Dental Association Council on Scientific Affairs recommends that dentists use the following guidelines when prescribing antibacterial drugs:⁵²

• Make an accurate diagnosis.
• Use appropriate antibiotics and dosing schedules.
• Consider using narrow-spectrum antibacterial drugs in simple infections to minimize disturbance of the normal microflora, and reserve the use of broad-spectrum drugs for more complex infections.
• Avoid unnecessary use of antibacterial drugs in treating viral infections.
• If treating empirically, revise the treatment regimen based on patient progress or test results.
• Obtain a thorough knowledge of the side effects and drug interactions of an antibacterial drug before prescribing it.
• Educate the patient regarding proper use of the drug and stress the importance of completing the full course of therapy, taking all doses for the prescribed treatment time.

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About the Author

Louis G. DePaola, DDS, MS
Professor
Department of Oncology and Diagnostic Sciences
School of Dentistry
University of Maryland Baltimore
Baltimore, Maryland