PU535 Unit 4 Host Response Brief Example

Two Hundred Forty Exposed, Ninety-Six Infected, Seven Ill: A Host Response Brief Explaining the Tuberculosis Contact Funnel by Cell-Mediated Containment, Naming What Breaks It, and Ranking Which Contacts a District Program Should Examine First

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Purdue University Global

PU535: Public Health Biology - A Global Perspective

Unit 4 Host Response Brief

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[Date]

The district, its 240 contacts and its case counts are composite; the proportions, the risk factors and the research cited are real.

Bottom Line

Infection is common among household contacts in this district and disease is not. Four of every ten contacts screened show evidence of infection, while three in a hundred have active tuberculosis. The difference is not mainly a matter of how much each person was exposed to. It is a matter of host immunity, and of the specific conditions that weaken it. The program should stop treating all contacts as one queue and examine first the contacts whose immune containment is least likely to hold.

The Funnel in Three Counts

1. Contacts screened around 48 confirmed cases: 240.

2. Contacts with evidence of infection on testing: 96, or 40 percent.

3. Contacts found to have active disease: 7, or 2.9 percent.

These proportions are close to what contact investigations report elsewhere: pooled across studies in low and middle income countries, about half of household contacts show infection and roughly 3 percent have active disease at the time of screening (Fox et al., 2013). The district's figures are therefore ordinary, which is the first thing worth saying to a manager who suspects a local failure.

A Wall Built of Cells, Not Antibodies

Inhaled bacilli are taken up by the lung's resident macrophages, which cannot clear them unaided. Over several weeks T cells recognize the infection and direct those macrophages, and the two cell types together build the granuloma, a walled collection of cells that holds the organism in a state where it neither multiplies freely nor is eliminated. In most people that wall holds for life, and the only evidence of it is a positive skin or blood test. Antibody responses occur and matter little here, because the organism lives inside cells where antibody cannot reach it. This single mechanism accounts for the whole funnel: the 96 infected contacts built a wall, and the 7 ill contacts did not, or built one that later failed. A positive test in this district is evidence that containment worked, not evidence that treatment failed.

Four Ways Containment Fails

Each factor below is grouped by what it does to the wall rather than listed alphabetically, because the grouping is what turns biology into screening priorities.

1. HIV infection depletes the T cells that direct the response. Risk of active disease rises from a lifetime figure of roughly 5 to 10 percent to several percent each year; the cohort that first measured this found tuberculosis developing at about 8 percent per year in people with untreated HIV infection and a positive tuberculin test (Selwyn et al., 1989).

2. Early childhood means an immune system that has not finished learning. Risk is highest in the first years after infection and highest of all in infants, which is why a positive test in a young child is treated as a recent event and acted on quickly (Comstock et al., 1974).

3. Undernutrition weakens cellular immunity in general. Across populations, tuberculosis incidence rises steadily as average body mass index falls, with no threshold below which the relationship stops (Lonnroth et al., 2010).

4. Diabetes and immune-suppressing drugs, including corticosteroids and the newer anti-inflammatory biologics, each interfere with the macrophage and T cell partnership the granuloma depends on.

What the Childhood Vaccine Does and Does Not Cover

Several of the district's contacts are children who received BCG at birth, and the program should not read that as protection against infection. The vaccine's measured benefit is against the severe disseminated forms in young children, meningitis and miliary disease, where it prevents a substantial majority of cases; its protection against pulmonary tuberculosis in older children and adults is inconsistent (Trunz et al., 2006). A vaccinated child who has been exposed still needs testing and, if infected, still needs preventive treatment.

Who to Examine First

1. Contacts with HIV infection, of any age, because their annual risk is the highest in the district and preventive treatment benefits them most.

2. Children under five, because risk concentrates in the first two years after infection and the severe forms appear in this group.

3. Contacts who are visibly underweight or report weight loss, as low body mass raises risk across the whole range.

4. Contacts with diabetes or on immune-suppressing drugs.

5. All remaining adult contacts, screened on the program's standard schedule.

Ranking contacts this way does not require more staff. It requires the register to record HIV status, age and weight at the first visit, which are three fields the district already collects at the clinic but not in the contact list. The seven active cases found in this round were spread across the first four groups above, and a program that examines those groups in the first week will find most of its cases earlier than one that works through 240 names in the order they were written down.

References

Comstock, G. W., Livesay, V. T., & Woolpert, S. F. (1974). The prognosis of a positive tuberculin reaction in childhood and adolescence. American Journal of Epidemiology, 99(2), 131-138. https://doi.org/10.1093/oxfordjournals.aje.a121593

Fox, G. J., Barry, S. E., Britton, W. J., & Marks, G. B. (2013). Contact investigation for tuberculosis: A systematic review and meta-analysis. European Respiratory Journal, 41(1), 140-156. https://doi.org/10.1183/09031936.00070812

Lonnroth, K., Williams, B. G., Cegielski, P., & Dye, C. (2010). A consistent log-linear relationship between tuberculosis incidence and body mass index. International Journal of Epidemiology, 39(1), 149-155. https://doi.org/10.1093/ije/dyp308

Selwyn, P. A., Hartel, D., Lewis, V. A., Schoenbaum, E. E., Vermund, S. H., Klein, R. S., Walker, A. T., & Friedland, G. H. (1989). A prospective study of the risk of tuberculosis among intravenous drug users with human immunodeficiency virus infection. The New England Journal of Medicine, 320(9), 545-550. https://doi.org/10.1056/NEJM198903023200901

Trunz, B. B., Fine, P. E. M., & Dye, C. (2006). Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: A meta-analysis and assessment of cost-effectiveness. The Lancet, 367(9517), 1173-1180. https://doi.org/10.1016/S0140-6736(06)68507-3