Abstract
Four cases of concomitant tuberculosis and cryptococcosis infection in HIV-positive patients are described. As the HIV pandemic progresses and the proportion of patients with end-stage disease increases, a high suspicion of incidence and unusual forms of infections must always be kept in mind.
Introduction
Tuberculosis (TB) and cryptococcosis are important causes of morbidity and mortality among those infected with HIV. There have been infrequent reports of this dual pathology from India. 1–8 The most common clinical presentation is chronic meningitis with or without symptoms of pulmonary TB, 1,5,8,9 concomitant pulmonary 2,3 and, rarely, extra pulmonary forms. 4,6,7
We present four case studies and a brief review of the published literature on the concomitant infection of TB with cryptococcosis in HIV-infected patients in this region.
Case histories
Case 1
A 40-year-old man was admitted to Safdarjung Hospital, New Delhi, India, complaining of headache, vomiting and altered sensorium of two-days' duration. He was HIV seropositive and a known case of pulmonary TB on antitubercular treatment (ATT). His wife had died of disseminated TB. On examination, he was disoriented, irritable and incoherent, with signs of meningeal reaction. The India ink preparation and Gram staining of cerebrospinal fluid (CSF) and urine showed the presence of capsulated budding yeast cells and the latex agglutination test (LAT) for cryptococcal antigen (Pastorex, CRYPTO Plus, Biorad, France) gave a positive result. Cryptococcus neoformans was isolated which was identified by melanin production on Niger seed agar, hydrolysis of urea and cyclohexamide (0.06 μg/mL) sensitivity. Ziehl-Nielsen's staining of CSF for acid-fast bacilli (AFB) was negative, as was the culture. However, the patient's sputum smear was positive for AFB and culture grew Mycobacterium tuberculosis. Amphotericin B and oral fluconazole was added to ATT. The patient recovered gradually. A subsequent lumbar puncture showed no growth of C. neoformans and a fall in titre by the LA test was observed. The patient was discharged on ATT with fluconazole and referred to a National AIDS Control Organization Centre for antiretroviral therapy.
Case 2
The second case was a 45-year-old man with recurrent headache, vomiting and altered sensorium of two-days' duration. He was a HIV seropositive case of TB and had been on ATT for a year. On examination, he was disoriented with signs of meningeal irritation. Chest examination revealed bilateral crepitations and an abdominal examination showed mild hepatosplenomegaly. Disseminated cryptococcosis was diagnosed on microscopy, LAT and culture from CSF and a respiratory specimen. CSF also grew M. tuberculosis. He was put on ATT, injection amphotericin B and oral fluconazole and recovered gradually.
Case 3
The third patient was a 34-year-old man admitted with history of breathlessness, fever, cough with expectoration for seven days and altered sensorium for two days. He was an HIV seropositive case of pulmonary TB and had been on ATT for six months. He showed signs of meningeal irritation and bilateral crepitations. Cryptococcal meningitis was diagnosed on microscopy, LAT and culture and CSF grew M. tuberculosis. ATT, injections of amphotericin and oral fluconazole were started but the patient died on the 4th day.
Case 4
The last case was a 45-year-old man admitted with complaints of headache for one month, fever with cough for a week and altered sensorium for two days. He gave a history of a single episode of seizure. He was an HIV seropositive case of pulmonary TB on irregular ATT. Cryptococcus was detected confirmed by various tests and sputum grew M. tuberculosis. He was on ATT, injections of amphotericin B and oral fluconazole. The patient improved and was discharged.
Discussion
HIV makes patients susceptible to a plethora of opportunistic infections. TB and cryptococcosis are prevalent infections in HIV patients: TB occurs when CD4 is <200 cells/μL and cryptococcosis when it is <100 cells/μL. The dual pathology is known to increase mortality in patients with HIV. 9 The co-existence of TB with cryptococcosis has been reported since the mid-1960s. 1–8 In India there have been few such reports: Shome et al. 2 documented the first case in 1969. This may be due to the non-availability of diagnostic tools and the possibility that the patient may die prior to diagnosis.
In all the four cases the patients were HIV seropositive and were on treatment for pulmonary TB when cryptococcosis was diagnosed. There are various similarities in the evolution of TB and cryptococcosis. In both, infection occurs via inhalation and the primary infection is localized to the lung from where the organisms can disseminate to other organs. Both manifest clinically by the reactivation of primary infection. Possibly this ‘primary cryptococcal complex’ is being misinterpreted as TB, both clinically and radiologically, due to endemicity. Shome et al. 2,3 found repeated isolation of C. neoformans in their cases indicated a pulmonary focus discharging the yeast into the bronchi and CSF facilitated infection, as it lacked complement, immunoglobulin and acted as a good culture medium. Cryptococcal meningitis, particularly in HIV-infected patients, often results in minor CSF changes. Silber et al. 1 1998 observed that this was true in patients with cryptococcal meningitis, but that patients with co-infection had raised protein and cell counts. This indicates that immunocompromised patients with high levels of CSF protein and lymphocytosis should be investigated for more than single pathology. 4,6,7
In communities with high rates of the prevalence of HIV, concurrent multiple opportunistic infections should always be considered. As clinically and radiologically cryptococcosis mimics TB, a strong suspicion for both is needed and investigations should be carried out accordingly. The possibility of unusual forms of dual presentation of these diseases should also be borne in mind.