The patient was treated with intravenous clindamycin and gentamicin. She improved and was discharged home on the ninth hospital day to complete an oral course of antibiotics. Notably, her fiancé, who is also human immunodeficiency virus (HIV)-infected, was treated for gonorrhea while the patient was hospitalized.
Six to twenty-two percent of women in the United States who are diagnosed with PID also have HIV. Several retrospective studies have been conducted looking at the interaction between the two diseases; however, the lack of standard diagnostic criteria, clinical criteria, and microbiologic criteria clouded the interpretation of their results.
A prospective study by Irwin et al.  compared PID in 44 HIV-infected women and 163 non-HIV-infected women. Both groups presented with similar signs and symptoms, but HIV-infected women were more likely to have an adnexal mass on sonography (46% versus 27%). In the study, HIV-infected women had unusual features on endometrial histology, with a plasma cell endometritis, suggesting that HIV may impair the acute inflammatory response to bacterial endometritis. Microbiology in the two groups did not differ significantly. Sixteen percent of HIV-infected women versus 3.7% of non-infected women had invasive procedures to diagnose or treat PID.
Among populations of presumed HIV-seronegative women, clinical criteria alone had 46%–74% positive predictive value in diagnosing PID. A laparoscopic study in Kenya in women who presented with PID was recently published  . Of 133 women who had laparoscopically proven salpingitis, 39% were HIV positive. TOA were found in 30% of HIV-positive patients compared with 15% of HIV-negative patients. Fifty-five percent of HIV-infected women with a CD4 percentage <14 had a TOA compared with 28% of those with a CD4 percentage >14. A lower proportion of HIVinfected women with salpingitis had gonococcal or chlamydial infection and a higher proportion had anaerobic infections. Length of hospital stay was prolonged in HIV-infected women with a CD4 percentage <14. However, the response to antimicrobial therapy and drainage of TOA was similar regardless of HIV status.
Infectious perihepatitis, or the Fitz-Hugh-Curtis syndrome, is thought to occur in 1% to 10% of patients with PID. Some estimates are as high as 15%–30%. The syndrome was initially described in 1848 by a Danish surgeon, who called it “colica scrotorum.” The classic presentation is composed of two phases—acute and chronic. The acute phase is characterized by the sudden onset of excruciating, sharp pain at the right lower rib margin. The pain, which may be referred to the right shoulder or inner arm, is pleuritic, exacerbated by coughing, and may cause nausea or hiccoughs. Chills, fevers, and night sweats frequently accompany the other symptoms. At laparotomy, “violin string” adhesions may be observed between the anterior surface of the liver and the abdominal wall. Microscopic examination of the liver reveals inflammation of the capsule, but not the parenchyma. The chronic phase is characterized by either the persistence of right upper quadrant discomfort or the disappearance of all the symptoms. The initial view that this entity was only caused by the gonococcus and only occurred in women has been recently modified. It is now evident that C. trachomatis and anaerobic bacteria frequently play a role in this entity, and that Fitz-Hugh-Curtis syndrome also occurs in men  .
Irwin KL, et al. Influence of human immunodeficiency virus infection on pelvic inflammatory disease. Obstet Gynecol 2000;95:525–34. View Full Text | PubMed | CrossRef Cited Here... |
Cohen CR, et al. Effect of human immunodeficiency virus type 1 infection upon acute salpingitis: a laparoscopic study. J Infect Dis 1998;178:1352–8. View Full Text | PubMed | CrossRef Cited Here... |
Lopez-Zeno JA, et al. The Fitz-Hugh-Curtis syndrome revisited: changing perspectives after half a century. J Reprod Med 1985;30:567–82. PubMed Cited Here... |
ID Case 23: Rapidly Progressive Pneumonia in a Patient with an Unusual Occupation
History of present illness
A 39-year-old, previously healthy man was transferred for evaluation of pneumonia complicated by rapid respiratory failure. The patient worked as a biological weapons expert for the military. According to his wife, much of his work is classified, and she was not aware of the details of specific projects. The patient had recently been deployed on a mission to a northern European country. He developed a fever and a cough on the flight back to the United States. His symptoms progressed to include myalgias, arthralgias, a headache, and dyspnea over the next day. He was hospitalized and quickly developed respiratory failure requiring mechanical ventilation. Notably, the patient’s friend, who had been traveling with him, also had an acute febrile illness that began on the flight home. His friend had not reported to work. The patient was transferred to our hospital for further evaluation. Attempts to contact his supervisor overnight had failed.
Past medical history
No known allergies
Medications (on transfer)
The patient is married; there are no known sexual exposures outside of his marriage. There is no history of smoking or illicit drugs. The patient drinks alcohol occasionally.
Intubated male, sedated in respiratory and contact isolation. Temperature, 38.2°C; blood pressure, 108/51; pulse, 103 beats per minute; respiratory rate, 24/min.
Eyes: Anicteric, no injection, no evidence of conjunctivitis, pupils pinpoint
Nose: Mucous membranes were intact
Neck: No lymphadenopathy or rigidity, no jugular venous distention
Lungs: Course breath sounds, no dullness to percussion, no egophony, no wheezes, rhonchi
Heart: Tachycardic, without murmurs, rubs, or gallops
Abdomen: Soft, non-tender, non-distended without enlargement of the liver or spleen
Extremities: No clubbing, cyanosis, or edema
Skin: Erythematous, blanching rash on the neck. No petechiae, purpura, eschars, ulcers, vesicles, or ecchymoses
Genitourinary examination: Normal
Rectal: Brown stool, heme negative
Urinalysis: Hazy, 10–15 RBC, 2–3 WBC, + bilirubin
Chest roentgenogram: Diffuse bilateral infiltrates consistent with adult respiratory distress syndrome
Chest computed tomogram: Diffuse bilateral infiltrates consistent with pulmonary edema or adult respiratory distress syndrome
Pneumonic plague (Yersinia pestis)
Toxic shock syndrome secondary to group A streptococcus
Rocky Mountain spotted fever
This is a completely healthy man who developed a devastating febrile illness soon after a trip to Northern Europe. He had acute respiratory failure, anemia, thrombocytopenia, and an elevated bilirubin. There was neither renal involvement nor evidence of a hemolytic/microangiopathic process, thus excluding the hemolytic uremic syndrome or thrombotic thrombocytopenic purpura. The patient’s history of being a biological weapons expert and going on a recent “mission” raise the question of whether his illness could be a manifestation of a terrorist attack. Inhaled anthrax can lead to sepsis with adult respiratory distress syndrome and rapid death. However, the classic presentation is of hemorrhagic mediastinitis, with mediastinal widening on chest radiograph. The course of pulmonary anthrax is so rapid that the patient is typically moribund before pulmonary infiltrates develop. Pneumonic plague is another disease that has been manipulated for military use and should be considered in this patient. The absence of lymphadenopathy and hemoptysis make plague less likely, but do not rule it out. Many of the patient’s initial flu-like symptoms are typical of pneumonic tularemia. In this disease, there may be a progression to the respiratory distress syndrome, but typically the course is not as rapid as seen in this case. The possibility of exposure to any of the three agents of biological warfare is notably decreased by the lack of additional cases.
N. meningitidis should be considered and covered with appropriate therapy in any previously healthy individual with a rapidly progressing febrile illness. In this patient, there are no clinical signs of meningitis, purpura, or adrenal failure, which may be seen with overwhelming meningococcal sepsis. The pneumococcus is the most common cause of community acquired pneumonia and may cause severe illness. However, the pace of illness in this young man seems too rapid for S. pneumoniae. Legionella pneumophila can also cause acute respiratory failure and should be covered empirically in any patient being admitted to the intensive care unit with pneumonia. His age is strongly against the diagnosis. The blanching, erythematous rash on his neck is suggestive of a group A streptococcus infection and early toxic shock syndrome. S. aureus can also cause a rapidly progressive pneumonia, most classically after a bout of influenza. Lastly, influenza and hantavirus (Sin Nombre virus) should also be considered as potential etiologies, although the epidemiology was against both.
Diagnostic procedure/clinical course
Blood cultures yielded group A streptococcus. The patient was treated initially with cefepime and azithromycin in the intensive care unit. He rapidly improved over 5 days, was extubated, and sent to a regular hospital bed. After culture results, his antibiotic therapy was converted to penicillin.
After admission, additional background information about the patient became available. He is a biological weapons expert who works in a military lab. He manages polymerase chain reaction studies on plates collected from machines called portal shields. These devices are large air samplers that detect pathogens that may be used as biological weapons. They are deployed in areas where troops are located. The patient’s lab screens these samples and attempts to quickly identify potential pathogens or toxins and relay the information back to the field commander. The patient’s supervisors did not believe that he had been exposed to biological weapons. His recent trip to Northern Europe was for a conference on biological weapons. He has been immunized against anthrax, meningococcus, and hepatitis A and B. His friend, who also became ill on the trip home, had a mild febrile illness, which was treated with amoxicillin/clavulanate, with an uneventful recovery.
This patient was ultimately determined to have a severe community-acquired pneumonia caused by group A streptococcus, with elements of the toxic shock syndrome. The drama of his patient’s presentation was augmented considerably by his occupation, and concern that his illness was caused by an agent of biological warfare. The scant historical information that was available in the first 12 hours of his illness compounded anxieties. In this section, I will review concerns that have been raised in the past few years about biological weapons and terrorism.
There are several infectious agents that may be suitable as biological weapons. Ideal pathogens or toxins should be easy to grow and manufacture, survive aerosolization, have a high case fatality rate, and have the potential for secondary spread. The organisms or toxins that have been considered for military or terrorist purposes include Bacillus anthracis, variola, Yersinia pestis, botulinum toxin, Francisella tularensis, and a number of agents that cause viral hemorrhagic fever [1–4] . In recent years, we have become aware of the extensive biological weapons’ program of the former Soviet Union and the accidental release of anthrax at Sverdlovsk. Additionally, 8000 L of anthrax spore suspension and botulinum toxin were loaded onto SCUD missiles by Iraq during the Iraq-Iran war. The religious cult that was responsible for the sarin nerve gas attack in Japan in 1995 had tried and failed to release anthrax and botulinum toxin eight times previously. Given the escalation of conflict throughout the world over the past few months, it is worth briefly reviewing the two most dreaded potential biological weapons: anthrax and smallpox.
B. anthracis is an aerobic, gram-positive, spore-forming, nonmotile rod. The spores can easily be aerosolized and will germinate in a suitable host. The three clinical manifestations of naturally acquired anthrax are gastrointestinal, cutaneous, and inhalational. Wool sorters and individuals who work with animal hides are at particular risk for anthrax. In the gut, the spores germinate in the upper or lower gastrointestinal track and cause ulceration, regional lymphadenopathy, edema, and sepsis. When the cecum and terminal ileum are involved, patients develop vomiting, malaise, and bloody diarrhea that progresses to an acute abdomen and shock. Cutaneous anthrax occurs after inoculation of the spores into the skin. Symptoms may occur as late as 12 days after infection. The skin lesion begins as a pruritic papule that enlarges within 1–2 days into a round, regular ulcer surrounded by vesicles. Subsequently, a black, necrotic central eschar develops with associated edema. After 1–2 weeks, the lesion dries and falls off. Antibiotics do not affect the development of the eschar but decrease mortality from secondary sepsis substantially.
Inhalational anthrax is the most feared form of disease: the case fatality rate is 80% to 100%. Only 2500–55,000 spores are needed to kill 50% of persons exposed. As an aerosol, anthrax spores are odorless and colorless. Disease can occur as late as 60 days after exposure. The spores are inhaled, ingested by pulmonary macrophages, and are transported to the mediastinal lymph nodes. Once the spores germinate, they cause disease rapidly. In the first phase of the illness, only nonspecific signs are present: fever, dyspnea, cough, headache, vomiting, chills, weakness, abdominal pain, and chest pain. After a few hours or days there is an abrupt development of high fever, dyspnea, diaphoresis, shock, massive lymphadenopathy, and expansion of the mediastinum, which produces a characteristic appearance on chest roentgenogram. Up to half of patients develop hemorrhagic meningitis. Death occurs within hours. The lung pathology does not show a pneumonia, but hemorrhagic thoracic lymphadenitis and hemorrhagic mediastinitis. Focal necrotizing hemorrhagic lesions can be seen in the lungs. B. anthracis grows well in cultures from blood or skin lesions, but can also be visualized in biopsy specimens and peripheral blood smears. A problem with the unsuspected case is the tendency of most labs to discard blood cultures as “Bacillus sp.—probable contaminant” without speciation. The simultaneous appearance of multiple cases of a severe flu-like illness, characterized by a fulminant course, a widened mediastinum on chest roentgenogram, or gram-positive rods in a blood smear or culture, is suggestive of a military attack with anthrax.
The anthrax vaccine requires six doses to complete the series; however, adequate protection is thought to occur after two doses. The availability of this vaccine is limited to military personnel. In the setting of a contained casualty setting, intravenous ciprofloxacin is recommended by the Working Group of Civilian Biodefense. Therapy may be converted to an oral preparation when the patient has stabilized, but must be continued for 60 days because of the danger of delayed spore germination. Ciprofloxacin is recommended for children and pregnant women in this setting, because the risk of death from inhalational anthrax far exceeds the risk of toxicity of the drugs. Penicillin and doxycycline are alternatives but should only be used when the susceptibilities are known. If intravenous therapy is not feasible because of a large-scale attack, then oral ciprofloxacin, doxycycline, or amoxicillin may be used. Respiratory isolation is not required, and the risk of secondary spread is negligible.
Smallpox is caused by a DNA virus of the genus Orthopoxvirus. There have been no human cases since 1978. There are two strains, variola minor and major. Vaccination in the United States was stopped in 1972, and currently no more than 20% of the population is immune. Variola major causes an illness with a mortality rate of 30%. There is no treatment, and in an aerosol form, the virus can survive for 24 hours or more and is highly infectious: a few virions may be sufficient to cause infection. Unlike anthrax, secondary spread is of paramount concern with smallpox. For every case of smallpox, it is estimated that at least 10 secondary cases will result.
Infection is caused by virus implantation in the upper airways. After migration to lymph nodes, patients become viremic on day 3 or 4. A secondary viremia develops at around day 8, but the incubation may range from 7 to 17 days. Symptoms include high fever, malaise, prostration, headache, backache, and toxemia. A maculopapular rash appears initially on the mucosa of the mouth, pharynx, face, and forearms, and subsequently spreads to the trunk and legs. It then becomes vesicular, and eventually forms tense pustules. All of the cutaneous lesions are in the same phase of development, unlike chickenpox in which lesions are in different phases of development at presentation. The rash begins to resolve on the eighth or ninth day. The patient is contagious via droplet nuclei or fomites when the rash is present. There are two other forms of the disease worth mentioning. In the hemorrhagic form, severe toxemia and a dusky erythematous rash develop and evolve into petechiae and frank hemorrhage into the skin and mucous membranes. Death ensues in about 30%, usually on the fifth or sixth day after the onset of rash. In the malignant form, toxemia is followed by soft, flat, velvety, and confluent lesions, which never become pustules. If the patient survives, large amounts of dermis may slough, leaving the tell-tale pitted scars.
There is no treatment for smallpox except supportive care, but the administration of vaccine in the first 4 days of exposure may prevent or significantly ameliorate subsequent illness. This is thought to be particularly effective in those with prior vaccinations due to amnestic responses. However, vaccine supplies are limited and in the advent of an attack, it may not be possible to vaccinate all exposed. Vaccinia immune globulin is also available in extremely limited supply and is recommend in those who experience vaccine reactions or for the immunocompromised. All suspected infected individuals should be put into very strict respiratory and contact isolation.
1. Inglesby T, Grossman R, O’Toole T. A plague on your city: observations from topoff. Clin Infect Dis 2001; 32:436–45.
2. O’Toole T, Inglesby TV. Facing the biological weapons threat. Lancet 2000; 356:1128–9.
3. Henderson DA, Inglesby TV, Bartlett JG, Ascher MS, Eitzen E, Jahrling PB, Hauer J, Layton M, McDade J, Osterholm MT, O’Toole T, Parker G, Perl T, Russell PK, Tonat K. Smallpox as a biological weapon: medical and public health management. Working Group on Civilian Biodefense. JAMA 1999; 281:2127–37.
© 2001 Lippincott Williams & Wilkins, Inc.
4. Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Friedlander AM, Hauer J, McDade J, Osterholm MT, O’Toole T, Parker G, Perl TM, Russell PK, Tonat K. Anthrax as a biological weapon: medical and public health management. Working Group on Civilian Biodefense. JAMA 1999; 281:1735–45.