I thought I had finished my take on lab tests, but came up with a number of curiosities that have always interested me, & might be worth posting. They may seem obscure, but do involve some common conditions.
PERTUSSIS
“Whooping cough” is always in the news, reemerging as an important pathogen among teens & adults, since childhood vaccination isn’t long-lasting. Now we have acellular pertussis vaccine (“TdaP”), although nobody really knows the durability of its immunity, nor how often to recommend booster shots.
It’s very hard to test for this bacteria. Nasopharyngeal culture has poor sensitivity; its false-negative rate may approach 80%. Nucleic acid amplification (e.g. PCR) is much better, but 1) it’s expensive, and even worse, 2) has poor specificity. The test cannot distinguish Bordetella pertussis from a related species B holmesii; the latter is also pathogenic but less virulent, & doesn’t respond as well to macrolides (see recent Lancet review; link is to a brief abstract, though the actual article is purchase-only).
So what do we do about Pertussis? Azithromycin shortens symptom duration & decreases transmission if given within 2 weeks (maybe 3 weeks; but note that CDC case definition doesn’t apply until cough has persisted 2 weeks). I consider treating patients with severe coughing paroxysms, especially if they provoke post-tussive emesis. Warning — if we’re lax on our criteria, we’ll wind up fooling ourselves and overusing antibiotics on lots of patients.
Actually, my main reason for treating presumed pertussis is if the patient has contact with a neonate, or other unvaccinated infant. Those are the ones who die. And since exposure would already have occurred, I write a note for parents to show pediatrics if the baby develops new rhinitis (the pertussis prodrome) or a cough.
CHLAMYDIA
A colleague’s patient recently presented with his third rectal infection in 3 months. Of course we always treated the partner along with the patient, but theirs was an open relationship, each (but especially the partner) having sex with other men (MSM), too. A definite problem.
The patient’s first episode was quite uncomfortable. The next, six weeks later, was mild. And the third, at another 6 weeks, was simply an asymptomatic test-of-cure. Since testing was done by highly-sensitive PCR, could this last “positive” result merely have identified dead organisms?
Standard recommendation is to wait 3 weeks after treatment before repeating the test. However, a recent CDC review notes that this interval comes from old studies (1990’s) involving older tests, and expresses a need for newer studies.
So what should we do? Maybe wait longer before testing for cure (4 wks? 6 wks?)? Another option (possibly heretical?) would be to skip screening asymptomatic MSM altogether. After all, whereas women with asymptomatic genital chlamydia can develop tubal scars that lead to infertility, men do not suffer any occult sequelae, reproductive or otherwise. Asymptomatic gonorrhea, especially in the pharynx, can acquire resistance from other nearby bacteria even in the absence of antibiotic pressure, but this doesn’t happen to chlamydia.
So maybe chlamydia isn’t serious or important enough for MSM to warrant widespread screening, especially since effective treatment is readily available at the first onset of symptoms. Of course, public health advocates will argue that screening helps prevent spread. But since there are so many sexually-active young men out there, who are otherwise-healthy & thus rarely seek care, it’d be worth a study to see if screening the few who are our regular patients has much (or any) impact on the community at large.
HEPATITIS B
Lab tests here have always been a little confusing. We’ve covered this before (see posts Acute Hepatitis and Chronic Hepatitis), but we’ll review Chronic Hep B again. Here’s a summary of the Hep B lab tests, before we get more confusing.
Most important, distinguish “Antigens” from “Antibody”. Antigens are viral particles; if we find them, there’s definite evidence of infection. The different Antibodies, indicating past infection, may confer lifelong immunity, or may remain positive in the face of chronic infection.
Hep B surface Antigen (HBsAg) is positive during acute infection, then disappears. If HBsAg remains positive 6 months later, by definition the patient has a form of Chronic Hep B Infection.
Hep B “e” Antigen (HBeAg) is present in the most common form of Chronic Infection (we only test for it once we’ve documented ongoing presence of “surface antigen” HBsAg). However, there’s a less-common, more-virulent form of Chronic Hep B involving a mutation (called “pre-core mutant) that’s “e-antigen negative.”
Hep B viral DNA (HBV DNA) helps determine how bad Chronic Hep B is, & the need for treatment. This is also called the “Hep B viral load.” In contrast to HIV viral load, which is considered “very high” if >100,000 copies, or Hep C where “very high” is >1,000,000 copies, I’ve seen a Hep B viral load that was >2.5 billion copies (how many virions can fit on the head of a needle?).
Note that HBV DNA can be measured in either “copies” or “units” (IU’s). As a ballpark approximation, 5 copies = 1 IU.
In Chronic Hep B (defined by HBsAg Pos twice 6 mo apart), we treat if:
- HBeAg Pos & HBV DNA >100,000 copies (20,000 IU)
- HBeAg Neg and HBV DNA >10,000 copies (2,000 IU) [lower threshold here, since “e-antigen negative” Hep B is more virulent]
- NO Treatment if ALT & AST persistently normal
- Certainly treat if patient is getting highly immunosuppressive chemotherapy or a transplant
Now, on to the Antibodies:
Hep B surface Antibody (anti-HBsAb) confers lifelong immunity. It develops naturally in the 90% of people who get acute Hep B & clear the virus on their own, and also in around 98% of persons vaccinated. To see if vaccine works (“takes”), obtain this antibody test 1-2 months after their last dose. For reasons of cost, we only usually do this for the immunocompromised, who have a higher chance of “non-take.” We certainly don’t test all every infant vaccinated at birth. And we certainly do test us healthcare workers.
Hep B “e” Antibody converts if the body clears HBeAg. For patients with Chronic Hep B, we might test along with HBeAg, but get little actionable information. Those who convert the “e” Antibody tend to lose “e” antigen. & don’t tend to get sequelae from chronic active hepatitis. But the bottom line in treatment still depends on HBV DNA levels according to status of “e” antigen, as above.
Hep B core Antibody (anti-HBcAb). The IgM fraction is diagnostic of either acute Hep B, or a flare of chronic active Hep B. The IgG fraction of core Antibody is a marker for having had Hep B.
Those who clear the virus and convert protective surface Ab still remain positive for core Ab. Those who remain chronically infected (always HBsAg positive), & never make surface Ab, are also positive for core Ab. As such, core Ab is rarely useful. If we want to see if there’s immunity, we test for surface Ab.
However, there’s the phenomenon of “Occult Hepatitis B“. These patients are:
- HBsAg negative (no antigen, so apparently not infected);
- Anti-HBsAb negative (no surface antibody, so not protected);
- BUT… Anti-HBcAb positive (a marker for having been infected)!!!
So, what does that mean?
Well, they could be in the brief window period of recovering from acute Hep B, when surface Ag has been cleared but surface Ab not yet detectable. In such cases, if we fractionated the antibody, we’d find IgM (the standard, cheaper test for Anti-HBcoreAb only tests total antibody). This would be unlikely if the patient is asymptomatic, with normal LFTs.
More likely, the patient had gotten Hep B at some point in their life, and never became immune. They probably have tiny undetectable levels of HBsAg floating around, but not enough to be significant. Usually.
However, if such people become profoundly immunosuppressed, like for organ transplant, or heavy chemotherapy, Hep B could flare & damage the liver. Therefore, in such situations, patients get tested for HBV DNA. If that’s detectable, they get treated, at least during the period of immunosuppression. Some specialists may simply treat without even checking for DNA.
Interestingly, among all patients with “Occult Hep B,” i.e. core-antibody positive & no other antigens or antibodies, a certain percent have detectable HBV DNA. But so do a certain low percentage of people with positive surface-Antibody (that’s not supposed to happen — they’re clear & immune!!!). And so do some people who are negative for all Hep B markers (who’d seemingly never even been infected!!!!!!).
So what does it all mean? Who knows. Basically:
- HBsAg Pos = infected. Test for HBeAg & for viral load (DNA). Treat as per parameters above.
- anti-HBsAb Pos = immune
- anti-HBcAb Pos, and both of above Neg = only worry if severely immunocompromised
Next time, Herpes Simplex Virus.
DiagnosisDude 