Lecture Notes: INH Chemoprophylaxis

Chemoprophylaxis appears to reduce significantly the risk for progression from latent infection to active disease. In patients who have not received chemotherapy, a positive skin test result implies the presence of a few dormant but viable tubercle bacilli, which have the potential for reactivation. It has been demonstrated that the administration of INH daily for 6 to 12 months reduces the risk for reactivation by up to 80%. Because the risk for progressive disease is greatest soon after infection, recent converters to tuberculin reactivity are most likely to benefit from such therapy.

In 1999, the American Thoracic Society (ATS), the CDC, and the Infectious Disease Society of America revised the published guidelines for offering INH chemoprophylaxis of latent tuberculosis infection (LTBI). This revision was intended to sharpen the focus of tuberculin screening and chemoprophylaxis to those populations most likely to progress from latent infection to active pulmonary tuberculosis and to deemphasize the routine screening and chemoprophylaxis of persons at low risk of active TB. A person's candidacy for INH chemoprophylaxis should no longer depend on age, provided that other risk factors for progression to active disease are present. 

Candidates for INH chemoprophylaxis (with the respective criterion for skin test positivity noted in parentheses) include the following:

• Patients with known or suspected HIV infection (5 mm).
• Close (especially household) contacts of patients with known active pulmonary TB (5 mm). Children and adolescent contacts of a person with TB should be offered INH regardless of PPD status until a PPD test can be repeated at 12 weeks.
• Patients with fibronodular disease on chest radiography compatible with old, healed TB (5 mm).
• Patients who have received solid-organ transplantation or who are receiving treatment with immunosupressive drugs, particularly TNF inhibitors (5 mm).
• Recent immigrants (<5 countries="" endemic="" from="" is="" li="" mm="" tuberculosis="" where="" years="">
• Native-born patients from medically underserved low-income areas, especially if homeless (10 mm).
• Patients with documented PPD conversion within the preceding 2 years (10 mm).
• Injection-drug users uninfected with HIV (10 mm).
• Patients with medical conditions predisposing to active TB, such as silicosis, diabetes, chronic renal insufficiency, leukemia or lymphoma, or cancer of the head or neck; persons who have undergone gastrectomy or jejunoileal bypass or whose weight is 10% or more below their ideal body weight; and children less than 4 years of age.
• Patients residing or employees working in long-term care facilities such as nursing homes, correctional facilities, and mental institutions (10 mm).

Persons without risk factors for acquiring TB and without medical conditions predisposing to active TB should not be considered candidates for INH chemoprophylaxis.

Tuberculin Skin Test (Mantoux test / PPD)

The tuberculin skin test is the most useful test for the diagnosis of past or present tuberculous infection. The Mantoux test is more reliable than multiple-puncture tests, such as the tine test. PPD is available in three strengths:

• the first strength contains 1 tuberculin unit (TU), 
• the intermediate strength contains 5 TU, and 
• the second strength contains 250 TU. 

Only the 5-TU strength should be used for screening.

The tuberculin skin test result should be interpreted 48 to 72 hours after injection; the diameter of induration (not erythema) determines the interpretation. Until recently, a single standard was used to interpret the tuberculin skin test in all people:

• 0 to 4 mm was negative,
• 5 to 9 mm was doubtful, and 
• 10 mm or greater was positive. 

As noted earlier, authorities such as the Centers for Disease Control and Prevention (CDC) now recommend that different skin test criteria be applied to different population groups to provide a more accurate assessment of risk.

The current CDC criteria for skin test positivity include the following:

• Induration of 5 mm for patients who are: 
• HIV-positive, 
• have undergone solid-organ transplantation, 
• receiving immunosupressive therapy including TNF antagonists or the equivalent of 15 mg/d of prednisone for more than 1 month, 
• very likely to have TB, such as close contacts of documented cases and patients with chest x-ray films that strongly suggest TB.
• Induration of 10 mm for members of high-incidence populations, such as: 
• immigrants from countries where tuberculosis is endemic (particularly those who have immigrated within 5 years); 
• injection-drug users; 
• residents or employees of high-risk coagreggate settings (hospitals, nursing homes, homeless shelters, correctional facilities); 
• patients with medical conditions predisposing to active TB, such as silicosis, diabetes, chronic renal insufficiency, leukemia or lymphoma, or cancer of the head or neck; 
• persons who have undergone gastrectomy or jejunoileal bypass or whose weight is 10% or more below their ideal body weight; 
• and children younger than 4 years of age.
• Induration of 15 mm for persons with no identifiable risk factors.

Repeated tuberculin skin tests can produce a booster effect, but only among patients already infected with TB. Among hospital employees or other populations who may undergo repeated skin testing, a booster effect can be mistaken for tuberculin conversion. Confusion can be avoided by repeated testing of persons with negative or doubtful skin test results 1 week later; any increase in the diameter of induration at 1 week can be attributed to the booster effect. In contrast, increased reactivity that occurs at 1 year, but not at 1 week, should be attributed to newly acquired infection. 

False-negative reactions (anergy) have been documented in up to 20% of patients with TB, particularly those who are: 

• immunocompromised by HIV infection, 
• overwhelming or advanced disease, 
• malnutrition, or 
• debility. 

In addition to immunologic incompetence of the host, other causes of false-negative skin test results are: 

• mishandling of the antigen and 
• faulty injection technique. 

Tuberculin should never be transferred from one container to another, and skin tests should be administered as soon as possible after the syringe is filled. Subcutaneous rather than intradermal injection may result in false-negative reactions. Because tuberculin sensitivity develops 2 to 10 weeks after initial infection, results of early skin tests may be negative in newly infected persons. 

Although tuberculin skin testing is highly specific, false-positive reactions may also occur, usually because of cross-reactivity with atypical mycobacterial antigens acquired environmentally. This may cause intermediate skin test reactions in people who have not been exposed to M. tuberculosis, hence the requirement for larger areas of induration when a low-risk population is screened.

Lecture Note: Antenatal Care: Tests & Procedures Week by Week

At each visit, weight, blood pressure, fundal height, fetal heart rate are measured, and a urine specimen is obtained and tested for protein and glucose. Review any concerns the patient may have about pregnancy, health, and nutrition.

6-12 Weeks

• Confirm uterine size and growth by pelvic examination.
• Document fetal heart tones (audible at 10–12 weeks of gestation by Doppler).
• First trimester screening and a discussion of choices of aneuploidy screening should be discussed at this time.
• Chorionic villus sampling is performed during this period (11–13 weeks).

16-20 Weeks

• The "quad screen" and amniocentesis are performed as indicated and requested by the patient during this time.
• Fetal ultrasound examination to determine pregnancy dating and evaluate fetal anatomy is also done.
• An earlier examination provides the most accurate dating, and a later examination demonstrates fetal anatomy in greatest detail. The best compromise is at 18–20 weeks of gestation.

20-24 Weeks

• Instruct patient about symptoms and signs of preterm labor and rupture of membranes. 
• Consider cervical length measurement by ultrasound after 18 weeks with history of prior preterm delivery (> 2.5 cm is normal).

24 Weeks to Delivery

• Ultrasound examination is performed as indicated. 
• Typically, fetal size and growth are evaluated when fundal height is 3 cm less than or more than expected for gestational age. 
• In multiple pregnancies, ultrasound should be performed every 4–6 weeks to evaluate for discordant growth.

24-28 Weeks

• Screening for gestational diabetes is performed using a 50-g glucose load (Glucola) and a 1-hour post-Glucola blood glucose determination. 
• Abnormal values ( 140 mg/dL) should be followed up with a 3-hour glucose tolerance test.

28 Weeks

• If initial antibody screen is negative, repeat antibody testing for Rh-negative patients is performed, but the result is not required before Rho(D) immune globulin is administered.

28-32 Weeks

• Repeat the complete blood count to evaluate for anemia of pregnancy. 
• Screening for syphilis and possibly HIV is also frequently performed at this time.

28 Weeks to Delivery

• Determine fetal position and presentation. 
• Question the patient at each visit for symptoms or signs of preterm labor or rupture of membranes. 
• Assess maternal perception of fetal movement at each visit. 
• Antepartum fetal testing is performed as medically indicated.

36 Weeks to Delivery

• Repeat syphilis and HIV testing, cervical cultures for N. gonorrhoeae and Chlamydia trachomatis should be performed in at-risk patients. 
• Discuss with the patient the indicators of onset of labor, admission to hospital, management of labor and delivery, and options for analgesia and anesthesia. 
• Weekly cervical examinations are not necessary unless indicated to assess a specific clinical situation. 
• Elective delivery (whether by induction or cesarean section) prior to 39 weeks of gestation requires confirmation of fetal lung maturity.

41 Weeks

• Examine the cervix to determine the probability of successful induction of labor. 
• Based on this, induction of labor is undertaken if the cervix is favorable (generally, cervix 2 cm dilated 50% effaced, vertex at –1 station, soft cervix, and midposition); if unfavorable, antepartum fetal testing is begun. 
• Induction is performed at 42 weeks gestation regardless of the cervical examination findings.

Source: Current Medical Diagnosis & Treatment 50th Edition