Please select the eligibility criteria that correspond to the clinical trial below.
Title: Bronchopulmonary Function in Response to Azithromycin Treatment for Chronic Lung Disease in HIV-infected Children
Brief Summary: Chronic pulmonary disease (CLD) is the most common manifestation of HIV/AIDS among children, accounting for more than 50% of HIV-associated mortality. Recently, a novel form of CLD, affecting more than 30% of African HIV-infected older children was described by Ferrand et al in Zimbabwe, high-resolution CT scanning findings showed predominantly small airways disease consistent with constrictive obliterative bronchiolitis (OB). . Azithromycin has anti-inflammatory activity and treatment of CLD with this agent may lead to suppression of generalized immune activation.

This specific aims of this project are to:

1. Primary objective: To investigate whether adjuvant treatment with azithromycin results in improvement in lung function in HIV-infected children with chronic lung disease, who are stable on antiretroviral therapy.
2. Secondary objectives:

   1. To investigate the intervention effect on mortality, exacerbations of lung disease, quality of life, morbidity.
   2. To investigate adverse events related to azithromycin treatment

In total, 400 children aged 6-16 years, living with HIV and diagnosed with CLD will be enrolled at Harare Children´s Hospital in Harare (Zimbabwe) and Queen Elizabeth Central Hospital in Blantyre (Malawi). These will receive weekly treatment with azithromycin or placebo during 12 months. Another 100 children (50 per site) living with HIV but with no CLD will be enrolled as a comparison group for laboratory sub-studies.

Lung function will be assess using spirometry and the Forced expiratory volume in the first minute (FEV1) will be the primary outcome. The mean change in FEV1 z-score levels will be compared between trial arms after 12 months of initiation of azithromycin treatment.


Options:
A: Inclusion Criteria:

1. Diagnosis of chronic lung disease (defined as FEV1 and/or FVC \<80% predicted)
2. Age 6-19 years
3. Perinatally-acquired HIV infection the most likely source of transmission
4. On first or second-line ART for at least one year
5. HIV-1 viral load undetectable (as defined by each trial site)
6. A firm home address accessible for visiting and intending to remain there for 24 months
7. Willing to agree to participate in the study and to give samples of blood and sputum
8. HIV status disclosed to child for those aged older than 12 years

Exclusion Criteria:

1. Any condition (except HIV) that may prove fatal during the study period (e.g. malignancy, end-stage HIV disease or other conditions deemed likely fatal by the trial physician)
2. Diagnosis of active pulmonary TB
3. Infection with non-tuberculous mycobacteria (NTM)
4. Pregnant or breast-feeding
5. Condition likely to lead to lack of understanding of study procedures or to uncooperative behaviour e.g. neurocognitive disease, developmental delay or psychiatric illness
6. History of prolonged QTc syndrome or current or planned therapy with drugs likely to cause cardiac dysrhythmias
7. Abnormal ECG findings
8. Acute respiratory tract infection during enrolment (patients will be eligible once their acute infection is treated)
9. Creatinine clearance of \<30mls/minute
10. ALT more than 2 times the upper limit of normal
11. No defined guardian/stable caregiver
12. No consent/assent from guardian/child
B: Inclusion Criteria:

* Pregnant women (aged 18 to 45 years)
* in labour
* attending a health centre in western Gambia for delivery

Exclusion Criteria:

* Known HIV infection.
* Any chronic or acute conditions of the women that might interfere with the study as judged by the research clinician.
* Planned travelling out of the catchment area during the following 2 months (follow-up period)
* Planned caesarean section
* Known required referral
* Known multiple pregnancy
* Known severe congenital malformation
* Intrauterine death confirmed before randomization
* Known allergy to macrolides
* Consumption of antibiotic within the week before randomisation
C: Inclusion Criteria:

1. written informed consent provided by first or second degree relatives;
2. intubation and mechanical ventilation at least 48 hours prior to enrolment; c) age of patients equal to or more than 18 years;

d) diagnosis of Ventilator Associated Pneumonia; and e) signs of sepsis

Exclusion Criteria:

1. neutropenia, defined as less than 500 neutrophils/mm3;
2. HIV infection;
3. oral intake of corticosteroids at a dose equal to or higher than 1mg/kg equivalent prednisone for a period greater than one month;
4. administration of drotrecogin alpha the last five days prior to enrolment; and e) atrioventricular block of second or third degree.
D: Inclusion Criteria:

* Patients with culture-positive stool sample with Campylobacter concisus
* Diarrheic patients ≥ 18 years
* symptoms of diarrhea defined as three or more watery stools per day or
* two watery stools per day + at least one of the following symptoms: abdominal pain, nausea, vomiting or fever.
* Diarrheic symptoms for a minimum of 24 hours before enrollment.
* Diarrheic symptoms for a maximum of 21 days before enrollment.
* Informed oral and signed written consent, with documentation that all relevant information about the study is given to the patient.
* The patient must be willing and able to participate in the trial.

Exclusion Criteria:

* Hypersensitivity to azithromycin, erythromycin, macrolide or other ketolide-antibiotics
* Pregnancy or breastfeeding (if relevant).
* Culture positive stool sample with a Co-pathogen.
* Treatment with other antibiotics (in any stage 21 days before the first stool sample).
* Patients with severe liver disease.
* Patients with severe renal impairment (GFR \<10 ml / min).
* Patients with congenital or documented acquired QT prolongation.
* Patients treated with other active drugs that prolong the QT interval such as: antiarrhythmics of classes IA and III, cisapride and terfenadine.
* Patients with electrolyte disorders, particularly hypokalemia and hypomagnesemia.
* Patients with clinically relevant bradycardia, arrhythmia or severe heart failure.
* Inflammatory bowel diseases
* Chronic diarrhea of known cause.
* Dementia.
* Serious illness less than 21 days from the planned entry into the study.
* Patients treated with medications that have interactions with azithromycin e.g. alkaloids, ciclosporin or amiodarone.
* Patients involved in the planning or execution of the study.

Answer: A