Manage genital tuberculosis and the HIV-gynaecology interface

In one line

Genital tuberculosis is a paucibacillary, scarring disease of the upper genital tract — tubes first, then endometrium — that in South Africa presents as infertility rather than infection, is confirmed by endometrial sampling and a high-specificity but low-sensitivity GeneXpert, and is cured microbiologically by standard six-month therapy while leaving fertility largely unrecoverable; the HIV-gynaecology interface is the second half of the same epidemic, where immunosuppression accelerates cervical neoplasia, magnifies common infections, and turns every gynaecological encounter into an HIV care encounter governed by drug interactions and the rules of HIV gynaecology at registrar level.

Mechanism & pathophysiology

Mycobacterium tuberculosis almost never reaches the genital tract directly. The organism seeds the upper tract haematogenously or via lymphatics from a distant primary focus, usually a pulmonary or pleural one that may have healed and become radiologically silent years earlier; direct extension from intra-abdominal or peritoneal TB is the secondary route, and sexual acquisition from infected semen is described but rare. The blood-borne route explains the anatomical hierarchy that every consultant must hold, because it dictates where to sample and what to expect on imaging: the fallopian tubes are involved in about 90% of cases, the endometrium in roughly 70%, and the ovaries in about 25% — the tubes are the richly vascularised first landfall, the endometrium is seeded next, and the ovary, with its tougher capsule, is reached last.

The disease that follows is one of fibrosis, not suppuration. Tubal mucosa is destroyed and the tube fibroses into a rigid, beaded structure with cornual obstruction and, where the fimbrial end seals, a hydrosalpinx or pyosalpinx; the classic radiological signatures — the lead-pipe or beaded tube, the tobacco-pouch and golf-club deformities, mural calcification — are the imaging correlate of caseating granulomas healing by scar. In the endometrium, repeated granulomatous shedding and basal-layer destruction produce intrauterine synechiae and a shrunken, deformed cavity — an Asherman-like end-state reached by infection rather than instrumentation, which is why amenorrhoea or hypomenorrhoea is a presenting feature and why even a successful embryo transfer later fails to implant. The endometrial granulomas are also why the disease is paucibacillary: organism numbers are low, the inflammatory response is disproportionate to the bacterial load, and that single fact governs every diagnostic limitation downstream.

Two further mechanistic points separate the consultant from the registrar. First, the disease is overwhelmingly a reactivation phenomenon: a primary infection seeds the tubes during the bacillaemia of childhood or adolescence, then lies dormant within granulomas as latent genital TB until immune control falters, which is why presentation clusters in the reproductive years and why immunosuppression — HIV, but also the iatrogenic immunosuppression of assisted reproduction protocols and the relative tolerance of pregnancy — can tip latent disease into active. Second, the endometrial paradox explains the menstrual picture: because the functional endometrium is shed monthly, granulomas in the superficial layer are often expelled before they caseate, so a single curettage can miss disease that the basal layer harbours — and it is destruction of that basal layer and the underlying vasculature that produces the hypomenorrhoea, amenorrhoea and thin, refractory cavity, not a hormonal failure. The ovary is reached last and least, so ovarian reserve is frequently preserved even when the tubes and cavity are destroyed — a fact that matters enormously when counselling toward IVF, because the eggs are usually retrievable even when the natural pathway is gone.

HIV reshapes gynaecology by a different mechanism — progressive depletion of CD4 T cells removes the cell-mediated immunity that normally contains mucosal and intracellular pathogens, so the changes are patterned and predictable rather than random. The cervix is the organ where this matters most: HIV-positive women acquire HPV more readily, clear it less, and carry multiple high-risk types at once, so CIN incidence runs 2–4× higher and progresses faster to invasive disease, the relationship being bidirectional in that genital inflammation modestly raises HIV shedding. The same loss of containment makes candidiasis recurrent and refractory, herpes simplex lesions severe, atypical and aciclovir-resistant, syphilis more aggressive with a higher neurosyphilis risk, and pelvic inflammatory disease more likely to abscess. The STI–HIV interaction is explicitly bidirectional and is the mechanistic reason syndromic STI control is HIV-prevention work: ulcerative and inflammatory genital infections breach the mucosal barrier, recruit activated CD4 target cells to the genital mucosa and raise both HIV acquisition risk in the negative partner and HIV shedding in the positive one, while HIV in turn worsens the course of every co-infecting organism — a feed-forward loop that an effective treat-and-suppress strategy interrupts from both ends.

Crucially for this objective, immunosuppression is itself a risk factor for TB reactivation, so in the South African setting the two halves of the chapter are not separate diseases but one converging epidemic: a CD4-depleted host both reactivates latent genital TB and tolerates its treatment less well. South Africa carries the highest TB/HIV co-infection burden in the world, with roughly two-thirds of incident TB occurring in HIV-positive people, so the pre-test probability of genital TB in an infertile woman, and the probability that she is also HIV-positive, are both materially higher than the international literature — written largely from the Indian subcontinent — would suggest.

Assessment

Genital TB is found, not suspected, because its symptoms are those of the conditions it mimics. The single most productive context to think of it is the infertility work-up, particularly tubal-factor infertility in a young woman from a high-prevalence community, often with primary infertility and a deceptively normal examination.

• Clinical clues that should raise it: primary or secondary infertility with menstrual disturbance (oligo-/hypomenorrhoea, amenorrhoea, occasionally menorrhagia early on), chronic pelvic pain, a personal or household history of TB, constitutional symptoms, an adnexal mass or ascites, or recurrent implantation failure after otherwise unexplained IVF. A normal pelvic examination does not exclude it.
• Endometrial sampling is the pivotal investigation — premenstrual endometrial aspirate or curettings sent in three parallel streams: histology (caseating granulomas, Langhans giant cells — specific but present in a minority because of the paucibacillary load), mycobacterial culture (the reference standard but slow and insensitive), and GeneXpert MTB/RIF, which simultaneously confirms the organism and reports rifampicin resistance.
• Interpreting GeneXpert is the consultant skill here. On endometrial samples its pooled sensitivity is only about 14% against a specificity near 100% — so a positive result effectively confirms the diagnosis and triggers treatment, while a negative result does not exclude it. The low sensitivity is intrinsic: paucibacillary tissue with few organisms and PCR inhibitors. The practical rule is that you treat on any one positive limb (histology, culture or Xpert) or on a composite clinical-plus-imaging picture, and you do not let a negative Xpert close the question.
• Imaging and endoscopy add the structural diagnosis. Hysterosalpingography shows the beaded or lead-pipe tube, cornual block, calcification and a shrunken or synechiae-deformed cavity; pelvic ultrasound may show a hydrosalpinx, a tubo-ovarian mass or ascites. Laparoscopy with hysteroscopy remains the highest-yield combined assessment — pelvic tubercles, caseous nodules, beaded tubes, peritubal and perihepatic ("violin-string") adhesions and a frozen pelvis are seen, and targeted biopsy and aspiration of peritoneal fluid raise the diagnostic yield — though tubercles regress on therapy while the adhesions and tubal destruction do not, which is the prognostic crux.
• Build a composite, not a single-test, diagnosis. Because no individual test is both sensitive and specific, the working standard is a composite reference: clinical context plus any positive among endometrial histology, culture or GeneXpert, supported by HSG and laparoscopic morphology. A raised CA-125 and ascites in a young infertile woman with a pelvic mass is the classic trap — it mimics ovarian malignancy, and abdominopelvic TB is the benign diagnosis that must be actively excluded before a young woman is committed to cancer surgery; peritoneal-fluid sampling and biopsy at laparoscopy resolve it. The differential also spans chronic PID, endometriosis and Asherman syndrome of instrumental origin, each of which the history and imaging help separate.
• Stage the host and the HIV interface in parallel. Every woman is HIV-tested; in a known-positive woman document the ART regimen and adherence, the current CD4 count and viral load, screen actively for active pulmonary TB (the source focus and a contraindication to immediate elective surgery), and confirm her cervical-screening status — because in South Africa the most likely serious gynaecological lesion in this population is not the TB but a cervical cancer missed through a screening lapse. A chest radiograph and sputum where indicated locate the primary focus and, occasionally, the only culturable source when the genital samples are negative.