Case reports involve a careful evaluation of a single case of disease, and may describe the transmission, natural clinical history, and/or response to treatment. Although case reports are based on an infection in a single patient, they may yield important new epidemiologic information regarding the disease. Examples of illustrative case reports follow.

Rabies Rabies is a zoonotic viral infection that is spread to humans by contact with body fluids (most commonly saliva) from an infected animal. Prior to rabies vaccination of domestic animals, most transmissions of this disease in the United States were associated with domestic animal bites.⁴ Rabies transmission was initially believed to require direct inoculation via a bite or other invasive contact with the infected animal. Infection is initially confined to the site of exposure without systemic viremia; hence the rabies vaccine can be given after exposure to prevent infection of the central nervous system (CNS). Such postexposure prophylaxis is usually successful. Moreover, it was universally believed that, in the absence of such treatment, rabies was fatal once the virus infected the CNS and signs and symptoms of CNS infection occurred. Early case reports of rabies overturned these long-held beliefs about the means of transmission of the virus and its natural history.

Aerosol transmission of rabies was described in a cave explorer, a spelunker, who developed rabies after exploring a cave inhabited by large numbers of bats in Frio, Texas.⁵ In this case, there was no history of a bite. This case was followed by a series of experiments in which animals were placed in the
cave and protected from bites and even insect transmission but were exposed to the air in the infected cave. After several animals developed rabies during this exposure, the classic concepts of rabies transmission were challenged.⁵ This hypothesis was confirmed in additional laboratory studies that showed rodents could be infected by aerosol inoculation.⁶, ⁷ This route of infection was further explored by a review of case reports of rabies in the United States between 1980 and 1996, which found that, in the majority of human cases, there was no clear documented evidence of a bite; however, the reports also suggested that an unreported or undetected bite remained the most plausible hypothesis regarding route of transmission.⁸ The control of rabies in domestic animals in the United States has resulted in fewer human cases, with a higher proportion of cases being attributed to wild animal exposures. These exposures are not as readily recognized as rabies risks, so preventive vaccination and postexposure prophylaxis may not be initiated. Reports of individual cases continue to provide information that contributes to our general understanding of the transmission of rabies.

The uniform fatality of rabies has also been challenged. In October 1970, a 6-year-old boy was bitten by a rabid bat. He was given 14 doses of duck embryo rabies vaccine but developed rabies 21 days later. He eventually recovered completely after treatment in an intensive care unit for nearly 2 months.⁹

A second report of survival from clinical rabies was reported in October 2004 in a previously healthy 15-year-old Wisconsin girl who was bitten on the left finger after handling a bat.¹⁰, ¹¹ Three weeks later she complained of fatigue, double vision, vomiting, and tingling in her left arm. Within 3 days she developed diploplia, and subsequently slurred speech and an unsteady gait. On the sixth day of her illness, the diagnosis of rabies was considered when the history of a bat bite was obtained. The patient was transferred to a tertiary care hospital and treated aggressively with a series of medications that included ketamine, midazolam, ribavirin, and amantadine. Ketamine had been shown in laboratory studies to inhibit rabies viral transcription.¹² The use of gamma-aminobutyric acid (GABA) receptor agonists with benzodiazepines and barbiturates was intended to reduce excitotoxicity, brain metabolism, and autonomic reactivity. Clinical reports of rabies cases had suggested that death resulted from the secondary complications of infections, primarily “neurotransmitter imbalance” and autonomic failure, rather than from direct cytolysis of the rabies virus. The patient survived and regained most of her cognitive function and has, so far, been able to live without major impairments.¹³ This was the first case of human rabies reported to have survived without the use of rabies vaccine or rabies immunoglobulin; since then, the same aggressive treatment protocol has been used on additional cases and is credited with saving the life of an 8-year-old
girl in Cali, Colombia. A third patient, a 15-yearold boy in Brazil, was also successfully administered this treatment protocol, after receiving postexposure prophylaxis.¹⁴

Although rabies still has among the highest case fatality rates, the successful treatment of these patients provides important insight into the pathophysiology of human rabies and offers promise for advances in treatment.

HIV/AIDS: Cure of HIV HIV is unique among infectious diseases in that clearance of disease was not believed to ever occur. Bryson and her colleagues from the University of California at Los Angeles reported the case of an infant who was born after 36 weeks’ gestation to an asymptomatic HIV-infected woman.¹⁵ The pregnancy was uncomplicated, and the mother had a CD4+ T-cell count of more than 1000 cells/mm³ at the time of delivery. At birth, the infant required hospitalization for 8 days because of mild respiratory distress syndrome. Laboratory studies on the newborn found a negative culture of cord blood for HIV. However, the infant’s blood culture was positive at 19 and 51 days of age, and the PCR was positive at 33 days of life. Subsequently, HIV antibodies disappeared by 12 months of age. Multiple cultures of peripheral blood lymphocytes and plasma for HIV were negative between 3 months and 5 years of age. The child was asymptomatic and had no laboratory evidence of HIV infection at 5 years of age. The authors believed that the infant was infected but cleared the HIV infection by immunologic or other mechanisms. This case report was followed up by a search for similar cases of spontaneous resolution of perinatal HIV infection in infants by other investigators; to date, no such cases have been reported.

More recently, physicians reported a case of an HIV-infected man who may have been cured with allogeneic stem-cell transplantation. The biological mechanism by which HIV binds to cells during infection has been well established: attachment occurs with a primary receptor (CD4) and with a co-receptor (either CCR5 or CXCR4). Epidemiologic studies played a critical role in identifying the importance of these co-receptors, whereby individuals with certain mutations (Δ32/Δ32 homozygosity) were at greatly reduced risk for HIV infection.¹⁶ In this case, an HIV-infected man who was undergoing allogeneic stem-cell transplantation to treat acute myeloid leukemia was specifically given cells from a matched donor who was also homogeneous for the Δ32/Δ32 mutation. The initial report in 2009 documented a lack of detectable virus through 20 weeks.¹⁷ A 2011 follow-up study documented continued absence of evidence of viral infection and recovery of the patient’s immune system through 3.5 years.¹⁸ The impact of these case reports has helped propel the search for a cure for HIV as a top research priority.

A second type of descriptive epidemiologic study is the case series. In this kind of study, data from a cluster or series of cases are reported. No comparison is made with controls; instead, the case series may be reported in sufficient epidemiologic detail that it is possible to infer the means of transmission and the risk factors for infection. A case series
of AIDS patients, which was reported early in the epidemic and prior to the identification of HIV, is described next.

AIDS Cluster A cluster of homosexual men with Kaposi’s sarcoma (KS) and/or Pneumocystis carinii pneumonia (PCP) was reported in 1984, prior to the identification of HIV.¹⁹ The investigators enumerated the sexual contacts of the first 19 homosexual male AIDS patients reported from Southern California. One man reported sexual contact with 12 of the AIDS patients within 5 years of the onset of their symptoms. Four of the patients from Southern California had contact with a non-California AIDS patient, who was also the sex partner of four AIDS patients from New York City. Ultimately, 40 AIDS patients in 10 cities were linked by sexual contact in this extensive sexual network (Figure 3-5). At the epicenter of this cluster was “patient zero,” who estimated that he had had approximately 250 different male sexual partners each year from 1979 through 1981 and was able to name 72 of his 750 partners during this 3-year period; 8 of these partners had developed AIDS. The sexual network linking these patients with the new disease (AIDS) was remarkably similar to the networks of patients with syphilis that were described four decades earlier. This remarkable study led the investigators to conclude that AIDS was caused by a sexually transmitted agent.