William Worodria Mulago Hospital Kampala Uganda Outline The burden of Respiratory Illness The Diagnostic Approach to a patient with a respiratory presentation Community Acquired Pneumonia ID: 737131
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Slide1
The AIDS patient with a ‘respiratory’ presentation – diagnostic considerations
William WorodriaMulago Hospital, Kampala, Uganda Slide2
Outline
The burden of Respiratory IllnessThe Diagnostic Approach to a patient with a “respiratory” presentationCommunity Acquired PneumoniaTuberculosisPulmonary Kaposi SarcomaFungal infectionsOthers Slide3
Burden of Respiratory Illness in the AIDS patient
Pulmonary complications are the commonest presentation in AIDS patientsPresent 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 therapyRecurrent CAP is an AIDS-defining conditionSlide4
Important considerations
To obtaining the ideal sample for diagnosisTo use a test with the most suitable performance characteristicsSlide5
Samples for diagnosis of respiratory disease
Sputum – spontaneously expectorated or inducedSerumBody fluids – pleural, gastric, etcBronchoalveolar
lavage
Biopsy or aspirateSlide6
Community Acquired PneumoniaSlide7
Major cause of morbidity and mortality in HIVX 6 incidence in HIV+ vs HIV-
Mortality x 4 in subjects with pneumonia vs withoutCommonest pathogensS. pneumoniaS. aureusH. InfluenzaK. pneumonia (NEJM, 2005)Slide8
Diagnostic Considerations for CAP
Symptoms including cough, chest pain, difficulty in breathing and fever of recent onsetChest radiographSputum Gram stain & cultureOther tests (not routine):Blood cultures
Urinary Binax
Legionella Urinary Antigen
Pneumococcal PCR
Acute and convalescent sera for
Chlamydophila
pneumoniae
and
Mycoplasma
pneumoniaeSlide9
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
))
T
reatment is mostly empirical, based on known local epidemiological patterns
Non response to treatment for CAP prompts further evaluation for other pathogensSlide10
2488 adults with radiographic evidence of pneumonia enrolled from five hospitals
Cultures, serological testing, antigen detection, molecular diagnosticsPathogens were identified in 853 (38%)(NEJM 2015; 373: 415-27)Slide11
TuberculosisSlide12
Tuberculosis
A leading cause of death from a single infectious agent10.4 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 diagnosisSlide13
Diagnostic Considerations for Tuberculosis
Microscopy: Fluorescence microscopy is 15% more sensitive than Ziehl Neelsen stainsRapid 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
TBSlide14
(
PLoS ONE, 12(4): e0176186)Slide15
PCP/PKSSlide16
PCP/ PKSSlide17
PCP/PKSSlide18
Kaposi SarcomaSlide19
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
AfricaHuman Herpes Virus 8 is a necessary and essential factor in the development of KS
(
Nwabudike
SM
e
t al. Case Reports in Infectious Diseases 2016)Slide20
Of 6292 PLWH 215 (3.4%) had AIDS associated KS
Advanced KS and absence of chemotherapy was associated with mortalityThere should be early ART and chemotherapy in these students(Journal of the International AIDS Society 2010, 13:23)Slide21
Diagnosis of AIDS-Associated KS
HistologicalVisualization of typical violaceous endobronchial lesionsHHV 8 detected in BAL of 80% patients with pulmonary KSSlide22
Fungal PneumoniasSlide23
Burden of Fungal Infections in AIDS
Fungal Infections are a common cause of pulmonary disease in AIDS but are underdiagnosedIt may be difficult to differentiate colonization from infectionFungal infections in HIV present insidiously but may progress to severe disease if untreatedImportant differential diagnosis for smear negative disease in HIVSpecific diagnosis is crucial to ensure appropriate treatment
Require intensive
treatment followed by prolonged maintenance therapySlide24
Common Fungal Pathogens in AIDS patients
OpportunisticPneumocystis PneumoniaPulmonary CryptococcosisPulmonary CandidiasisPulmonary Aspergillosis
Endemic
Histoplasmosis
Emmonsiosis
(
Emergomyces
Africanus
)
Penicillosis
(Asia)Slide25
Microbiological Diagnosis
Direct microscopy and staining for fungal elements – cheap and useful Culture and identification – more sensitive than microscopyHistopathological diagnosis – visualization of fungal elements within tissuesImmunologic 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. 2011 December ; 32(6): 663–672)Slide26
132 smear negative patients underwent bronchoscopy and
bronchoalveolar lavageMedian CD4 count 23 cells/µL15(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): 269-274)Slide27
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 diagnosisSlide28
Summary
Respiratory disorders are a common manifestation of AIDSCommunity Acquired Pneumonia and Tuberculosis occur with increasing frequency in patients with AIDSOpportunistic Bacterial, Fungal Infections; and Malignancies occur in individuals with AIDS and are frequently underdiagnosedCurrent diagnostic tests are inadequate More novel and validated diagnostic are needed that target locally relevant pathogens causing lung diseaseSlide29
Thank you