—  LONG COURSE #03  —

Diagnosing AIDS and Emerging Infections in Resource-Limited Settings:
The Role of the Pathologist in Patient Care and Disease Surveillance

Section 8 - Spectrum of Tissue Pathology in HIV/AIDS in India

Dhaneshwar N. Lanjewar


Since the start of the epidemic, issues related to HIV/AIDS have had a high profile in industrialized countries. However the burden of disease continues to fall most heavily, in developing countries, particularly in India and sub-Saharan Africa. India is considered to be a "next wave" country; that is, it stands at a critical point in its epidemic, with HIV poised to spread quickly. HIV has been detected in almost all states and union territories of India. In seven Indian states, the prevalence of HIV in women attending antenatal clinics exceeds 1 per cent, categorizing the epidemic as generalized. With an estimated 5.3 million individuals living with HIV in 2005, approximately 0.9 per cent of Indian adults are HIV positive. [1]Most HIV infection in India are due to sexual transmission (85%). In the North East, however, injection drug use is the main mode of transmission. Women account for 39% of India's estimated HIV/AIDS prevalence.

Next to sub-Saharan Africa, India has the second largest burden of HIV/AIDS related pathology. The first report of AIDS in India was published in 1986 [2] and the first autopsy on patient with AIDS was carried out in 1988. [3]Despite rapid growth of AIDS in India, very little is known about the spectrum of pathogenic infections in these patients. [4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31]

The Grant Medical College and Sir J. J. Hospital in Mumbai is a public hospital run by the state government that provides free services to patients and treats all patients with advanced HIV-associated diseases. The postmortem examination of fatal AIDS cases is recommended by our institute. During 1988 to August 2006, a total of 225 autopsies were performed on adult patients with HIV/AIDS in the Department of pathology, Grant Medical College, Mumbai.

The spectrum of pathologic lesions observed in this autopsy study demonstrated high frequency of secondary infections. [32] The spectrum of diseases identified were: tuberculosis (59%), bacterial pneumonia (15%), CMV infection (15%), toxoplasmosis (9%), cryptococcosis (7%), Pneumocystis carinii (Jeroveci) pneumonia (5%), candidiasis (4%), cryptosporidiosis (3%), aspergillosis (2%),Strongyloides stercoralis (2%). Extra pulmonary tuberculosis was identified in 48% cases. No pre-mortem or post-mortem cultures for tuberculosis were carried out and a diagnosis of tuberculosis was established on histology alone. In our geographical setting, tuberculosis is most likely caused by Mycobacterium tuberculosis species. High prevalence of tuberculosis is also observed in studies carried out in other centers in India. [15, 26, 27, 28, 30] Occasional cases of mycobacterial spindle cell pseudo tumor are identified in our patients. Recognition of this unusual manifestation of mycobacterial infection is important as it can be mistaken for a mesenchymal neoplasm. [33]

Pneumocystis carinii pneumonia remains the most common AIDS associated infection in developed countries, however Indian studies show 5%-14% prevalence of PCP. [28, 30] Although not reported in adult population from India in the pre-AIDS era, toxoplasmosis was the most frequently observed CNS opportunistic infection identified in 9%-20% of HIV infected patients. [6, 7, 27, 28]R are report of CNS toxoplasmosis co-existent with infection by acanthamoeba is described in patients with AIDS. [15] Occasional reports of cardiac toxoplasmosis are also described in Indian literature. [8, 22] The temporal trends observed in the prevalence of toxoplasmosis emphasize the importance of autopsy studies in not only documenting such a change, but also in increasing the awareness for such hitherto unsuspected lesions. Only two reports of PML are described in the Indian literature. [24, 25]

The spectrum of gastrointestinal lesions associated with AIDS in Indian patients showed cytomegalovirus, cryptosporidium, strongyloides stercoralis, hookworm, candidiasis, cryptococcosis and tuberculosis. [4, 5, 29] The prevalence of Isospora belli is identified in 13% of patients with AIDS presenting with chronic diarrhoea. [4] There are few reports of tuberculous abscesses in patients with AIDS. [12, 18, 19]

Liver abscesses due to tubercle bacilli are an unusual manifestation of the natural history of tuberculosis. Inflammatory diseases of skin are described in 38%-53% in our patients. [11, 13, 20] The prevalence of Penicillium marneffei infection has increased in eastern India where the disease was not known before. The first report of four autochthonous cases of indigenous disseminated Penicillium marneffei infection in HIV-infected patients came from the State of Manipur, in 1999. [21] To date 46 cases of Penicillium marneffei infection are reported from Manipur-a northeastern State of India. [32]

In our study AIDS associated tumors were identified in only 4 cases which comprised of lymphoma (2%) and Kaposi's sarcoma (1%). Only three reports of Kaposi's sarcoma are described in Indian literature. [13, 17, 23] Squamous cell carcinoma of penis was identified in 5% of young patients with HIV infection. Government of India announced its intention to provide HAART at government hospitals to people living with HIV/AIDS and the programme was started since April 2004. The Non Government Organisations working in the field of HIV/AIDS are also treating patients with HAART. Report of immune reconstitution inflammatory syndrome (IRIS) in patients on HAART are also described in Indian literature. [34]

During January 1997 to June 2006, biopsies from 721 patients with HIV/AIDS were received for microscopic evaluation in our surgical pathology division. The most frequent sites of AIDS diagnostic diseases were: skin (426), bone marrow (133), lymph nodes (62), liver (27), Gynecology specimens (24), GIT (21), lung (19), kidney (3), and other sites (6). infectious diseases were identified in 60/721(8%) cases. Tuberculosis was the most frequent infection noted in 7% cases. 35/721(5%) cases showed neoplasm which comprised of lymphoma in 16 cases and squamous cell carcinoma in another 16 cases.

During January 2004 to July 2006, FNACs from 374 patients with HIV/AIDS were received for cytological evaluation. Lymph nodes were the most frequent sites of FNAC (332 cases, 89%). Tuberculosis was diagnosed in 238/374 (64%) cases. In only 6 cases (2%) Non Hodgkin's lymphoma was identified.

Pathologists and microbiologists of our country are playing significant role in diagnosing AIDS-associated infections; however the data is not well published. Hence a structured questionnaire was designed to a) know available techniques/infrastructure/practices in pathology and microbiology for laboratory diagnosis of AIDS associated infections and b) to know frequency and type of various AIDS associated infections prevalent nation wide. The questionnaire was sent through posts to pathologists/microbiologists working in various medical institutes Some of the participants have responded to the questionnaire and the preliminary observations showed that tuberculosis is the most frequently identified infection (60%) in patients with HIV/AIDS. The prevalence of other infectious agents is similar to those observed in our autopsy reports.

The current practices in pathology and microbiology can help in diagnosis of commonly identified infections such as tuberculosis. However there is need of molecular diagnosis and species identification of Mycobacterium species. The techniques available for tissue diagnosis of CMV, Papova, and Toxoplasma gondii by immunohistochemistry are not available in more than 99% institutes. Similarly a facility for diagnosis of pneumocystis carinii by direct fluorescent antibody technique is also not available in many centers. Diagnosis of microsporidia is also not possible due to deficiencies in laboratory techniques.

Hence for India and other developing countries, there is a need to develop standards of practice for pathologists, microbiologists and technicians. Training of committed pathologists and microbiologists to acquire skills in diagnosis of AIDS associated infections is essential. All developing countries need assistance to establish a state of art pathology and microbiology laboratory where all facilities/technologies for diagnosis of AIDS associated infections is available.

Since significant data of HIV/AIDS associated infections in India remains unpublished, there is a need for establishment of AIDS registry. The registry will facilitate recording of AIDS associated infections and cancers through which national data may emerge. The information on opportunistic infections generated through such registry will be useful for development of strategies for laboratory diagnosis of AIDS associated infections and for better management of HIV infected patients.

References

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