Mulago Inpatient Noninvasive Diagnosis of Pneumocystis Pneumonia (MIND PCP) Study
Respiratory infections are the leading cause of death in HIV-infected patients in Africa, and difficulty identifying their etiology is the major obstacle to successful treatment. While tuberculosis (TB) and bacterial pneumonia are common, other processes may cause pneumonia in these patients, so bronchoscopy with bronchoalveolar lavage (BAL) is often indicated for definitive diagnosis, especially when empiric treatments fail. Recent studies employing BAL in Africa show that the leading cause of such presentations is pneumocystis pneumonia (PCP), affecting about 40%. Yet, limited resources mean that BAL is rarely performed in Africa, and without a diagnosis, these patients face certain death. The long-term goal of this research is to improve survival of HIV-infected people with PCP in Africa through reliable, non-invasive, and affordable diagnostic tests for respiratory infection. This study will evaluate the use of a polymerase chain reaction (PCR) assay on oropharyngeal wash (OPW) specimens to diagnose PCP. Patients gargle saline to produce an OPW, which is simpler and safer than BAL, which is expensive and invasive. In the U.S., PCR on OPW is nearly as accurate for PCP as BAL with conventional staining. While PCR is new to Africa, it has proven cost-effective for TB diagnosis in Kenya. PCR is routinely used to measure HIV viral loads at Makerere University's Mulago Hospital in Kampala, Uganda. This is a cross-sectional study to determine the accuracy of a PCR assay on OPW for PCP diagnosis in HIV-infected patients admitted to Kampala's Mulago Hospital with pneumonia. The study will collect clinical data, OPW, and BAL from all 200 participants. BAL samples will be conventionally stained to define who has PCP. OPW samples will be tested for pneumocystis by a PCR assay targeting the major surface glycoprotein gene. The study team will estimate the accuracy of OPW relative to the BAL gold-standard. Measuring the accuracy of OPW is critical to assessing its feasibility for clinical care in Africa and for future PCP studies. This fellowship will support the candidate's Master's Degree training and protect his time for this research. This proposal closely fits the agency's mission of "supporting research training and career development of new researchers to enable conduct of clinical research related to diagnosis of lung disease." Public Relevance: Pneumonia causes most deaths in patients with HIV in developing countries. Diagnosing pneumonia by standard methods is impossible because of limited resources. This study will test if DNA- fingerprinting of special mouthwashes can accurately diagnose HIV-related pneumonia, and save lives.