Project Title

Diagnosis of PCP using nasopharyngeal aspirates and venous blood samples in HIV-infected infants with severe pneumonia: an EMPIRICAL ancillary study

Project Objectives

Objectives PCP-PED primary aims are: Attempt to diagnose PCP infection in HIV-infected infants with severe pneumonia on empirical PCP treatment and enrolled in the EMPIRICAL trial at HCM and HDM with: nasopharyngeal aspirates using immunofluorescence. and real-time PCR; venous blood using β-D-glucan and KL-6 assays; Correlate confirmed PCP infection with clinical and radiological manifestations, specifically with hypoxemia; Evaluate the efficacy of cotrimoxazole preventive therapy by assessing pre-admission adherence in patients with study-confirmed PCP infection. This will include patients who were on cotrimoxazole as HIV-exposed infants who only had HIV infection confirmed at the time of hospitalization and children are already known to be HIV-infected at the time of admission. PCP-PED secondary aims are: To improve the knowledge of LRTIs in HIV-infected infants with severe pneumonia. To build and strengthen the capacity to establish a young researcher in sub-Saharan Africa. To strengthen the European-African research networks to approach poverty-related diseases.

Host Organisation

EDCTP Project Call

Career Development Fellowship (CDF)

Study Design

Methodology This is an EMPIRICAL ancillary study which will take place at Mozambican recruitment sites. These are currently Hospital Central de Maputo (HCM), Hospital Geral Jose Macamo (HGJM), and Hospital Distrital de Manhica (HDM), but if additional EMPIRICAL sites are added in the future, patients from these hospitals could also be recruited into PCP-PED. The primary endpoints related to the principal study objectives are: 1. Proportion of patients with positive PCP tests; 2. Sensitivity and specificity of hypoxemia for the diagnosis of PCP confirmed respiratory disease; 3. Proportion of patients with PCP among those previously initiated on PCP prophylaxis. Enrollment Enrollment will be done on the inpatient wards of Mozambique EMPIRICAL sites. An estimated 131 patients will be enrolled over the course of the EMPIRICAL trial, 65 from HCM, 36 from HGJM and 30 from HDM. The PCP-PED ancillary study will be conducted in recruited EMPIRICAL patients and no additional recruitment will be done for this ancillary study. Screening For EMPIRICAL enrollment, all infants 28 to 365 days of age with chest indrawing and severe pneumonia according to WHO guidelines will be screened for HIV-infection. If HIV status is unknown according to the site’s records, a confirmatory sample will be obtained for HIV-1 diagnosis (HIV-1 DNA/RNA test). Point of care HIV diagnosis will be available in all the sites. Study population HIV-infected infants from one month to 12 months of age who are admitted due to chest indrawing or severe pneumonia (following the WHO definition). Inclusion Criteria Age 28 days to 365 days of age Pneumonia as defined by fast breathing for age Need for parenteral treatment according to WHO severe pneumonia criteria Chest indrawing Unable to drink or breastfeed Vomiting everything ingested Having convulsions Being lethargic or unconscious Stridor while calm HIV-confirmed infection (with molecular methods) Informed consent obtained Exclusion criteria

Project Summary

EMPIRICAL is an EDCTP-funded multinational clinical trial that will evaluate the use of empirical valganciclovir and tuberculosis (TB) treatment in HIV-infected infants with severe pneumonia who receive antibiotics and treatment for pneumocystis jiroveci pneumonia (PCP) as standard of care treatment. The EMPIRICAL protocol includes testing for CMV and TB, but not for PCP. This proposal, PCP-PED, is for an EMPIRICAL ancillary study to be conducted at the 3 Mozambican study sites, Hospital Central de Maputo (HCM), Hospital Geral Jose Macamo (HGJM) and Hospital Distrital de Manhiça (HDM). The principal objectives are to 1) attempt to diagnose PCP infection in patients starting empirical PCP treatment using blood and nasopharyngeal aspirate samples, 2) correlate confirmed PCP infection with clinical and radiological manifestations, and 3) evaluate the efficacy of cotrimoxazole prophylactic therapy for prevention of PCP. As an EMPIRICAL ancillary study, PCP-PED will be very straightforward and feasible to implement. Patients who are enrolled in EMPIRICAL at Mozambique study sites will be included. No additional recruitment will be performed. EMPIRICAL patients will already have a nasopharyngeal aspirate collected for TB testing, and this specimen will be divided so that immunofluorescence and PCR testing for PCP can be performed. An additional blood sample will be collected near study enrollment for PCP biomarker testing, and in many cases, it will be possible to draw along with other EMPIRICAL labs without additional phlebotomy. PCP testing will be performed in the Universidade Eduardo Mondlane Microbiology laboratory, which already has experience in testing for PCP and other opportunistic fungal infections. Test results will be correlated with EMPIRICAL clinical data including oxygen saturation, history of cotrimoxazole adherence, and chest radiography. PCP-PED fits within EDCTP2 focus on Poverty Related Diseases and Child and Adolescent Health. The vast majority of new pediatric HIV infections occur in sub-Saharan Africa (SSA) and severe pneumonia continues to be one of the principal causes of morbidity and mortality in these infants. Both EMPIRICAL and PCP-PED endeavor to improve our understanding of the etiology and best treatment approaches for severe pneumonia in HIV-infected infants. PCP-PED also has the potential to expand access to PCP laboratory diagnosis to the areas most in need if it can demonstrate that diagnoses can be made with non-invasive specimens (blood and nasopharyngeal aspirates) as opposed to bronchoalveolar lavage, which is available in an extremely small percentage of pediatric hospitals in SSA.

Current Organisation

Eduardo Mondlane University

Current Job Title

Lecturer

Biography

Publications