Vector-borne, Travel & Mycobacteria

Educational study digest pitched at a new ID fellow. The body distills board-review and case-conference teaching; the enrichment box is reviewer synthesis of additional evidence, each claim cited. Not medical advice, and not a substitute for the primary guidelines.

◆Which tick, which terrain — and how do you actually confirm it?

Ehrlichiosis and anaplasmosis are the near-twins a fellow has to pull apart, and the names carry the answer. Human monocytic ehrlichiosis (HME) is the monocyte disease, acquired in the range of the Lone Star tick (Amblyomma americanum), and it reaches into the South-Central and Southeastern states; human granulocytic anaplasmosis (HGA) is the granulocyte disease of the Northeast and upper Midwest and is rarely, if ever, acquired in the South-Central US. Both are diagnosed the same way at the bench: PCR of whole blood is high-yield for each — in deliberate contrast to the spotted-fever rickettsioses, where blood PCR is often negative and an eschar or skin sample is the better specimen — and a blood smear may reveal morulae, the mulberry-like intracytoplasmic inclusions, sitting in monocytes for ehrlichia and in granulocytes for anaplasma. Because the Ixodes tick that carries anaplasma also carries Borrelia burgdorferi and Babesia, actively look for co-infection rather than settling for a single diagnosis.

A returning fever with recurring febrile paroxysms and spirochetes visible on a routine blood smear is tick-borne relapsing fever. In the Western mountains of North America the agent is Borrelia hermsii, transmitted by the soft-bodied Ornithodoros tick, whose bite is brief and painless and usually goes unnoticed (the archetype is a night in a rustic mountain cabin). The incubation is 7–18 days — the detail that separates the tick-borne form from louse-borne relapsing fever (Borrelia recurrentis) and explains why B. hermsii, uniquely among the differential, is the one you actually expect to see as spirochetes on the smear.

The spotted-fever group turns on a single sign: the eschar. A patient from the mid- and South-Atlantic, South-Central, or Gulf states with an eschar at the bite site followed by fever and a maculopapular rash has Rickettsia parkeri rickettsiosis, and the eschar — often on the lower extremities — is exactly what distinguishes it from Rocky Mountain spotted fever, which produces no eschar. That the illness fails to respond to a cephalosporin (cephalexin) is a planted cue that a beta-lactam does not treat a rickettsiosis. Keep the geography honest as well: scrub typhus (Orientia tsutsugamushi) also makes an eschar, but it is a disease of Asia, not the United States.

The US vectors worth recognizing on sight map cleanly onto their diseases:

◆Fever in the traveler just back from an endemic region — what can’t you miss?

The workup of fever in a returning traveler is driven by geography visited, activities and exposures, the prophylaxis actually taken, and host factors — but the non-negotiable reflex is to always think malaria in anyone coming from a malaria-endemic region, and to think specifically of Plasmodium falciparum, the species that kills. Uncomplicated malaria is a nonspecific febrile illness — fevers, chills, headache, fatigue — with thrombocytopenia, mild anemia, and no leukocytosis, sometimes with hemolysis showing as a high bilirubin and LDH. The whole management fork is the next question: is this severe?

Severe falciparum malaria is defined by end-organ involvement or a high parasite burden, and any single criterion is enough. The distinction is not academic — it changes both the drug and the disposition.

Cerebral malaria is the feared CNS form. In adults it is anchored to a depressed level of consciousness (a GCS <11); in young children it is harder to score because age and development confound the exam, and imaging may show cerebral edema with papilledema and retinal hemorrhages.

Treatment follows the severity split. For uncomplicated disease in a chloroquine-resistant area (essentially everywhere falciparum is now transmitted), the oral options are artemether–lumefantrine (Coartem) for 3 days or atovaquone–proguanil (Malarone) for 3 days, with quinine for 3 days plus doxycycline for 7 days as the second-line combination, reserving chloroquine for the few areas where the parasite is still sensitive. For severe disease the answer — the point the whole malaria discussion drives at — is intravenous artesunate, with IV quinidine or quinine only as the fallback, and that fallback demands ICU monitoring for QT prolongation. One counterintuitive supportive rule earns its own emphasis: fluids should be conservative and restrictive. Restrictive management is safe and does not worsen renal function, whereas aggressive resuscitation risks worsening intracranial pressure.

◆Why won’t tuberculosis take a Gram stain — and what follows from that?

Mycobacterium tuberculosis is invisible to the Gram stain because its cell wall is built on a thick layer of mycolic acids — long-chain fatty acids and glycolipids that make the wall waxy and impermeable to the Gram reagents. That same high-lipid wall is why the organism is acid-fast and why it grows slowly. And because it is an intracellular, lipid-armored pathogen, the host’s decisive defense is not antibody but cell-mediated (T-cell) immunity — the arm of adaptive immunity most critical to controlling TB, which is precisely why conditions that deplete T cells reactivate it.

The interferon-gamma release assay (IGRA) operationalizes that T-cell response across four tubes, and naming each is fair game: a Nil tube (negative control, to subtract background IFN-γ), TB1 (long TB peptides that stimulate CD4 cells), TB2 (short and long peptides that also engage CD8 cells), and a Mitogen tube (positive control that should react in anyone with functioning T cells — if it fails to, the result is indeterminate rather than negative).

Diagnosing pulmonary TB is a defined sequence. The chest radiograph is the screen — a normal film usually means no pulmonary TB, unless the patient is immunocompromised. Confirmation then rests on three sputum specimens collected at least 8 hours apart, at least one of them a morning sample, each sent for smear and culture, with at least two nucleic-acid amplification tests (NAAT). The cardinal rule when suspicion is high: a negative smear does not clear the patient — await the culture, because culture remains the standard the diagnosis ultimately turns on. Treatment was framed as the closing pair of questions — latent TB infection versus active disease: latent infection (a positive IGRA or TST without active disease) is treated to prevent progression, while active pulmonary TB requires a longer multidrug regimen. The specific regimens, along with whom to test for latent TB and how to approach extrapulmonary and drug-resistant disease, were flagged as important but beyond the session.

◆Nontuberculous mycobacteria — how do you split them, and why do three light up an IGRA?

The first cut across the nontuberculous mycobacteria (NTM) is growth rate: slow growers take >7 days to appear on solid media, rapid growers <7 days. The slow growers carry the familiar clinical names — M. kansasii, M. marinum, M. gordonae, M. scrofulaceum, the M. avium complex, and the M. terrae complex — while the rapid growers are the trio M. fortuitum, M. chelonae, and M. abscessus. The older Runyon classification subdivides them by pigment: I — photochromogens pigment only when exposed to light (M. kansasii, M. marinum, M. simiae); II — scotochromogens pigment in light or dark (M. gordonae, M. scrofulaceum, M. szulgai); III — nonphotochromogens make no pigment regardless of light (M. avium, M. xenopi, M. malmoense); and IV — rapid growers, which turn over in roughly 5–10 days.

Here the NTM story loops back to the IGRA. The assay’s selling point is that it reads antigens specific to M. tuberculosis and so is not fooled by prior BCG or by most environmental mycobacteria — but there are three exceptions that share those antigens and can produce a false-positive IGRA: M. kansasii, M. marinum, and M. szulgai. Commit those three; they are the clang-association answer whenever an IGRA is positive and the clinical story does not fit tuberculosis.

Sources: Consolidated ID board-review and case-conference teaching — tick-borne illness (ehrlichiosis / anaplasmosis, tick-borne relapsing fever, Rickettsia parkeri vs Rocky Mountain spotted fever, US tick vectors); malaria in the returning traveler; tuberculosis (microbiology, cell-mediated immunity, IGRA mechanics, pulmonary diagnosis); and nontuberculous mycobacteria (2025–2026). Enrichment: Meintjes G, Maartens G. HIV-Associated Tuberculosis. N Engl J Med 2024;391(4):343–355 (doi:10.1056/NEJMra2308181; PMID 39047241).