1. William Worodria Mulago Hospital, Kampala, Uganda
The AIDS patient with a ‘respiratory’ presentation – diagnostic considerations
William Worodria
Mulago Hospital,
Kampala, Uganda

2. Outline The burden of Respiratory Illness
The Diagnostic Approach to a patient with a “respiratory” presentation
Community Acquired Pneumonia
Tuberculosis
Pulmonary Kaposi Sarcoma
Fungal infections
Others

3. Burden of Respiratory Illness in the AIDS patient
Pulmonary complications are the commonest presentation in AIDS patients
Present as a variety of infectious and non infectious diseases
Community acquired pneumonia (CAP) is the commonest cause of respiratory disease
The high risk of CAP persists despite the use of Highly Active Antiretroviral therapy
Recurrent CAP is an AIDS-defining condition

4. Important considerations
To obtaining the ideal sample for diagnosis
To use a test with the most suitable performance characteristics

5. Samples for diagnosis of respiratory disease
Sputum – spontaneously expectorated or induced
Serum
Body fluids – pleural, gastric, etc
Bronchoalveolar lavage
Biopsy or aspirate

6. Community Acquired Pneumonia

7. Major cause of morbidity and mortality in HIV
X 6 incidence in HIV+ vs HIV-
Mortality x 4 in subjects with pneumonia vs without
Commonest pathogens
S. pneumonia
S. aureus
H. Influenza
K. pneumonia
(NEJM, 2005)

8. Diagnostic Considerations for CAP
Symptoms including cough, chest pain, difficulty in breathing and fever of recent onset
Chest radiograph
Sputum Gram stain & culture
Other tests (not routine):
Blood cultures
Urinary Binax
Legionella Urinary Antigen
Pneumococcal PCR
Acute and convalescent sera for Chlamydophila pneumoniae and Mycoplasma pneumoniae

9. Diagnosis of Community Acquired Pneumonia
The clinical signs and radiological features may be similar in HIV+ and HIV-ve persons
The management of CAP is compromised by the lack of bacteriological confirmation
(Pefura Yone, BMC Pulm Med 2012, 12(46))
Treatment is mostly empirical, based on known local epidemiological patterns
Non response to treatment for CAP prompts further evaluation for other pathogens

10. Pathogens were identified in 853 (38%)
2488 adults with radiographic evidence of pneumonia enrolled from five hospitals
Cultures, serological testing, antigen detection, molecular diagnostics
Pathogens were identified in 853 (38%)
(NEJM 2015; 373: )

11. Tuberculosis

12. Tuberculosis A leading cause of death from a single infectious agent
10.4 million people had TB disease in 2016 and 1,674,000 died from TB disease.
87% patients with TB occurred in Africa, Asia and the Western Pacific region. (Global TB Report, 2017)
Advanced HIV-related immune suppression may be associated with atypical clinical presentation and paucibacillary disease
Novel Diagnostics are needed to enhance diagnostic capacity of the traditional methods of TB diagnosis

13. Diagnostic Considerations for Tuberculosis
Microscopy: Fluorescence microscopy is 15% more sensitive than Ziehl Neelsen stains
Rapid Molecular test: Xpert MTB/RIF has been endorsed by World Health Organization as a first-line diagnostic test in all HIV patients
Urine LAM in CD4<50
Culture: Liquid or Solid culture remain the gold standard for TB diagnosis
Chest radiograph: mainly for triage and screening presumptive TB patients. It maybe diagnostic for miliary TB

14. Respiratory samples: sputum, bronchoalveolar lavage and gastric aspirates; Non respiratory samples: cavitary fluids, LNs, bone samples, CSF, pus, urine
(PLoS ONE, 12(4): e )

15. Homogenous opacities in both paracardiac areas and lower zones sparing the periphery. There are associated air bronchograms. The cardiac borders are obscured by the infiltrates.
Conclusion: Bilateral pneumonic conolidation (Rightmiddle lobe & lingula segment)
PCP/PKS

16. Bilateral cotton – wool fluffy infiltrates sparing only the left apical region.
Conclusion: widespread pneumonia with alveolar pattern. ? Fungal, ?Bacterial infection.
PCP/ PKS

17. Bilateral heterogenous infiltrates in both lower lung fields, sparing the periphery.
Conclusion: bilateral pneumonia PTB and PCP likely.
PCP/PKS

18. Kaposi Sarcoma

19. Pulmonary Kaposi’s Sarcoma
Kaposi's sarcoma (KS) is a vascular tumor of blood vessels and lymph nodes
KS is the most common and life threatening cancer in Sub-Saharan Africa
Human Herpes Virus 8 is a necessary and essential factor in the development of KS
(Nwabudike SM et al. Case Reports in Infectious Diseases 2016)

20. Of 6292 PLWH 215 (3.4%) had AIDS associated KS
Advanced KS and absence of chemotherapy was associated with mortality
There should be early ART and chemotherapy in these students
(Journal of the International AIDS Society 2010, 13:23)

21. Diagnosis of AIDS-Associated KS
Histological
Visualization of typical violaceous endobronchial lesions
HHV 8 detected in BAL of 80% patients with pulmonary KS

22. Fungal Pneumonias

23. Burden of Fungal Infections in AIDS
Fungal Infections are a common cause of pulmonary disease in AIDS but are underdiagnosed
It may be difficult to differentiate colonization from infection
Fungal infections in HIV present insidiously but may progress to severe disease if untreated
Important differential diagnosis for smear negative disease in HIV
Specific diagnosis is crucial to ensure appropriate treatment
Require intensive treatment followed by prolonged maintenance therapy

24. Common Fungal Pathogens in AIDS patients
Opportunistic
Pneumocystis Pneumonia
Pulmonary Cryptococcosis
Pulmonary Candidiasis
Pulmonary Aspergillosis
Endemic
Histoplasmosis
Emmonsiosis (Emergomyces Africanus)
Penicillosis (Asia)

25. Microbiological Diagnosis
Direct microscopy and staining for fungal elements – cheap and useful
Culture and identification – more sensitive than microscopy
Histopathological diagnosis – visualization of fungal elements within tissues
Immunologic and Biochemical – complement fixing antibodies; fungal antigen detection in blood (Histoplasmosis, Cryptococcosis)
Aspergillus Galactomannan Antigen Test
Molecular Diagnostics – PCR-based assays (Candida, Aspergillus, P.jiroveci)
(Semin Respir Crit Care Med December ; 32(6): 663–672)

26. Median CD4 count 23 cells/µL
132 smear negative patients underwent bronchoscopy and bronchoalveolar lavage
Median CD4 count 23 cells/µL
15(11%) grew Cryptococcus neoformans (none were suspected to have pulmonary cryptococcosis at enrollment)
9(60%) were alive at 6 months, 4 died and 2 were lost to follow up
(J Acquir Immune Def, 2011; 54(3): )

27. An estimate of the prevalence of pulmonary aspergillosis in HIV-positive Ugandan in patients diagnosed as smear-negative pulmonary tuberculosis. Page ID, Worodria W, Andama A, Ayakaka I, Kwizera R, Davis L, Huang L, Richardson M, Denning WR
39 HIV+ with abnormal CXR; Mean 35 years
Median CD4 109 cells/µL
Aspergillus specific IgG was positive in 26% (vs 2% in controls)
40% with a positive result died within two months of diagnosis

28. Summary Respiratory disorders are a common manifestation of AIDS
Community Acquired Pneumonia and Tuberculosis occur with increasing frequency in patients with AIDS
Opportunistic Bacterial, Fungal Infections; and Malignancies occur in individuals with AIDS and are frequently underdiagnosed
Current diagnostic tests are inadequate
More novel and validated diagnostic are needed that target locally relevant pathogens causing lung disease

29. Thank you