Pertussis

Pertussis, or whooping cough, is an acute infectious disease caused by the bacterium Bordetella pertussis. Pertussis is primarily a toxin-mediated disease. The bacteria attach to the cilia of the respiratory epithelial cells, produce toxins that paralyze the cilia, and cause infelammation of the respiratory tract, which interferes with the clearing of pulmonary secretions. Pertussis antigens appear to allow the organism to evade host defenses, in the lymphocytosis is promoted but chemotaxis is impaired. Until recently it was thought that B pertussis did not invade the tissues. However, recent studies have shown the bacteria to be present in alveolar macrophaes.

CLINICAL FEATURES
The incubation period of pertussis is commonly 7-10 days, with a range of 4-21 days, and rarely may be as long as 42 days. The clinical course of the illness is divided into three stages. The first stage, the catarrhal stage, is characterized by the insidious onset of coryza (runny nose), sneezing, low-grade fever, and a mild, occasional cough, similar to the common cold. The cough gradually becomes more severe, and after 1-2 weeks, the second, or paroxysmal stage, egins. Fever is generally minimal throughout the course of the illness.

It is during the paroxysmal stage that the diagnosis of pertussis is usually suspected. Characteristically, the patient has bursts, or paroxysms, of numerous, rapid coughs, apparently due to difficults expelling thick mucus from the tracheobroncial tree. At the end of the paroxysm, a long inspiratory effort in usually accompanied by a characteristic high-pitched whoop. During such an attack, the patient may become cyanotic (turn blue). children and young infants, especialy, appear very ill and distressed. Vomiting and exhaustion commonly follow the episode. The person does not appear to be ill between attacks.

Paroxysmal attacks occur more frequeintly at night, with an average of 15 attacks per 24 hours. During the first 1 or 2 weeks of this stage, the attacks increase in frequency, remain at the same level for 2 to 3 weeks, and then gradually decrease. The paroxysmal stage usually lasts 1 to 6 weeks but may persist for up to 10 weeks. Infants yourger than 6 months of age may not have the strength to have a whop, but they do have daroxysms of coughing.

In the convalescent stage, recovery is gradual. The cough becomes less paroxysmal and disappears in 2 to 3 weeks. However, paroxysms often recur with subsequent respiratory infections for many months after the onset of pertussis.

Adolescents and adults and children partially protected by the vaccine may become infected with B. pertussis but may have milder disease than infants and young children. Pertussis infection in these persons may be asymptomatic, or present as illness ranging from mild cough illness to classic pertussis with persistent cough (i.e., lasting more than 7 days). Inspiratory whoop is not common.

Even though the disease may be milder in older persons, those who are infected may transmit the disease to other susceptible persons, including unimmunized or incompletely immunized infants. Older persons are often found to have the first case in a household with multiple pertussis cases, and are often the source of infection for children.

LABORATORY DIAGNOSIS

Culture is considered the gold standard laboratory test and is the most specific of the laboratory tests for pertussis. However, fastidious growth requirements make B. pertussis difficult to culture. The yield of cuture can be affected by speciment collection, transportation, and isolation techniques. Specimens from the posterior nasopharynx, no the throat, should be obained using Dacron or calcium alginate (not cotton) swabs. Isolation rates are highest during the first 3 to 4 weeks of illness (catarrhal and early paroxysmal stages). Cultures are variable positive (30%-50%) and may take as long as 2 weeks, so results may be tooo late for clinical usefulness. cultures are less likely to be positive if performed later in the course of illness (more than 2 weeks after cough onset) or on speciments from persons who have received antibiotics or have been vaccinated. Since adolescents and adults have often been coughing for serveral weeks before they seek medical attention, it is often too late for culture to be useful.

Because of the increased sensitivity and faster reporting of results of PCR, many laboratories are now using this method exclusively. PCR should be used in addition to, and not as a replacement for culture. No PCR product has been approved by the Food and Drug Administration (FDA), and there are no standardized protocols, reagents, or reporting formats for pertussis PCR testing. Consequently, PCR assays vary widely among laboratories. Specificity can be poor, with high rates of false-positive results in some laboratories. Like culture, PCR is also affected by specimen collection. An inappropriately otained nasopharyngeal swab will likely be negative by both culture and PCR. PCR is less affected by prior antibiotic therapy, since the organism does not need to be viable to be positive by PCR. Continued use of culture is essential for confirmation of PCR results.

Serologic testing could be useful for adults and adolescents who present late in the course of their illness, when both culture and PCR are likely to be negative. However, there is no FDA-approved diagnostic test. The currently available serologic tests measure antibodies that could result from either infection or vacination, so a positive serologic response simple means that the person has been exposed to pertussis by either recent or remote infection or by recent or remote vaccination. Since vaccination can indue both IgM and IgA antibodies (in addition to IgG antibidies), use of such serlogic assays cannot differentiate infection from vaccine response. At this time, serologic test results should not be relied upon for case confirmation of pertussis infection.

An elevated white blood cell count with a lymphacytosis is usually present in classical disease of infants. the absolute lymphocyte count often reaches 20,000 or greater. However, there may be no lymphocytosis in some infants and children or in persons with mild or modified cases of pertussis. More information on the laboratory diagnosis of pertussis is available at: http://www.cdc.gov/vaccines/pubs/surv-manual/default.pdf

Brucellosis

Photo source CDC.gov

OVERVIEW: 

The Brucellae are a group of gram-negative cocco-baccillary organisms, of which four species are pathogenic in humans.  Abattoir and laboratory workers infections suggest that Brucella spp. are highly infectious via the aerosol route.  It is estimated that inhalation of only 10 to 100 bacteria is sufficient to cause disease in man.  The relatively long and variable incubation period (5-60 days) and the fact that many infections are asymptomatic under natural conditions has made it a less desirable agent for weaponization, although large aerosol doses may shorten the incubation period and increase the clinical attack rate.  Brucellosis infection has a low mortality rate (5% of untreated cases) with most deaths caused by endocarditis or meningitis.  It is an incapacitating and disabling disease in its natural form.

HISTORY AND SIGNIFICANCE:  Marston described disease caused by B. melitensis among British soldiers on Malta during the Crimean War as “Mediterranean gastric remittent fever”.  Work by the Mediterranean Fever Commission identified goats as the source of human brucella infection on Malta, and restriction of the ingestion of unpasteurized goats milk and cheese soon decreased the number of cases of brucellosis among military personnel.

In 1997, most cases were associated with ingestion of unpasteurized dairy products and abattoir and veterinary work.  In the United States most cases are reported from Florida, California, Virginia, and Texas.  It is a rare disease in the United States with an incidence of 0.5 per 100,000 population.

In 1954,Brucella suis became the first agent weaponized by the U.S. in the days of its offensive BW program at the newly constructed Pine Bluff Arsenal.  Despite this, B melitensis actually produces more severe human disease.

CLINICAL FEATURES:  Brucellosis may present as a nonspecific febrile illness which resembles influenza.  Fever, headache, myalgia, arthralgia, back pain, sweats, chills, and generalized weakness and malaise are common complaints.  Cough and pleuritic chest pain may occur in up to twenty percent of cases, but these are usually not associated with acute pneumonitis.  Pulmonary symptoms may not correlate with radiographic findings.  The chest x-ray may be normal, or show lung abscesses, single or miliary nodules, bronchopneumonia, enlarged hilar lymph nodes, and pleural effusions.  Gastrointestinal symptoms occur in up to 70 percent of adult cases, and less frequently in children.  These include anorexia, nausea, vomiting, diarrhea and constipation, ileitis, colitis and granulomatous or a mononuclear infiltrative hepatitis may occur.  Lumbar pain and tenderness can occur in up to 60% of cases is due to various osteoarticular infections of the axial skeletal system.  Paravertebral abscesses may occur and can be imaged by CT scan or MRI.  CT scans often show vertebral sclerosis.  Vertebral and disc space destruction may occur in chronic cases.  One or, less frequently, both sacroiliac joints may be infected causing low back, and buttock pain that is intensified by stressing the sacroiliac joints on physical exam.  Hepatomegaly and splenomegaly can occur in up to 45-63 percent of cases.  Peripheral joint involvement may vary from pain on range of motion testing to joint immobility and effusion.  Peripheral joint effusions usually show a mononuclear cell predominance and organisms can be isolated in up to 50% of cases.  The hip joints are the most commonly involved peripheral joints, but ankle, knee, and sternoclavicular joint infection may occur.  Plain radiographs of involved sacroiliac joints usually show blurring of articular margins and widening of the joint space.  Technetium or Gallium-67 bone scans are 90% sensitive for detecting sacroileitis and will also detect other sites of bone and joint involvement; they are also useful for differentiating sacroiliac from hip joint involvement.

Meningitis occurs in less than 5% of cases and may be an acute presenting illness of a chronic syndrome occurring late in the course of a persistent infection.  The cerebrospinal fluid contains an increased number of lymphocytes and a low to normal glucose.  Culture of the CSF has sensitivity of 50%, and specific brucella antibodies can be detected in the fluid in a higher percentage of cases.  Encephalitis, peripheral neuropathy, radiculoneuropathy and meningovascular syndromes have also been observed in rare cases.  Behavioral disturbances in children and psychoses may occur as the most frequent genitourinary form of burcellosis.  Rases occur in less than 5% if cases and include macules, papules, ulcers, purpura, petechiae, and erythema nodosum.

DIAGNOSIS:  The leukocyte count is usually normal but may be low.  Anemia and thrombocytopenia may occur.  Blood and bone marrow culture during the acute febrile phase of the illness will yield a positivity rate of 15-70% and 92% respectively.  A biphasic culture method for blood (Castaneda bottle) may increase the number of isolates.  The serum agglutination test (SAT) will detect both IgM and IgG antibioties.  A titer of 1:160 or greater is indicative of active disease.  The IgM titer can be measured by adding a reduced agent such as 2-mercaptoethanol to the serum.  This will destroy the agglutinability of IgM allowing the IgM titer to be measured by subtracting the now lower titer from the total serum agglutinin titer.  A dot-ELISA using an autoclaved extract of B. abortus has been found to be a sensitive and specific screening test for detection of Brucella antibodies under field conditions.  ELISA tests for antibody detection require standardization using a specific antigen before they will be widely available.  Antigen detection on DNA extracted from blood mononuclear cells has been accomplished using PCR analysis of a target sequence on the 31-kilodalton B. abortus protein BCSP 31.  This test has been proven to be rapid and specific and may replace blood culture in the future, since the latter may require incubation for up to 6 weeks.  PCR for Brucella species is not available at this time except in research laboratories, but shows promise for future use.

MEDICAL MANAGEMENT:  Isolation is not required other than contact isolation for draining lesions.  Person to person transmission is possible via contact with such lesions.  Biosafety level 3 practices should be used for suspected brucella cultures in the laboratory because of the danger of inhalation infection.  Antibiotic therapy is recommended as the sole therapy unless there are surgical indications for the treatment of localized diseases (e.g., valve replacement for endocarditis).

The treatment recommended by the World Health Organization for acute brucellosis is adults is doxycycline 200 mg/day p.o. plus rifampin 600-900 mg/day for a minimum of six weeks.  The previously established regimen of intramuscular streptomycin along with an oral tetracycline may give fewer relapses but is no longer the primary recommendation.   Ofloxacin 400 mg/day and rifampin 600mg/day p.o. is also an effective combination.  Combination therapy with rifampin, a tetracycline, and an aminoglycoside is indicated for infections with complications such as meningoencephalitis or endocarditis.  Doxycycline clearance is increased in the presence of rifampin and plasma levels are lower than when streptomycin is used instead of rifampin.

PROPHYLAXIS:  Live animal vaccines are used widely.  Consumption of unpasteurized milk and cheese should be avoided.  No approved human brucella vaccine is available.  An experimental human burcellosis vaccine has been tested on 271 subjects with a 25% rate of unpleasant acute side effects, but no long term adverse side effects.

Reference: Biological Warfare and Terrorism, The Military and Public Health Response, Satellite Broadcast, Sept. 1999.