Please select the eligibility criteria that correspond to the clinical trial below.
Title: Impact of Systematic Early Tuberculosis Detection Using Xpert MTB/RIF Ultra in Children with Severe Pneumonia in High Tuberculosis Burden Countries
Brief Summary: Despite progress in reducing tuberculosis (TB) incidence and mortality in the past 20 years, TB is a top ten cause of death in children under 5 years worldwide. However, childhood TB remains massively underreported and undiagnosed, mostly because of the challenges in confirming its diagnosis due to the paucibacillary nature of the disease and the difficulty in obtaining expectorated sputum in children.

Pneumonia is the leading cause of death in children under the age of 5 years worldwide. There is growing evidence that, in high TB burden settings, TB is common in children with pneumonia, with up to 23% of those admitted to hospital with an initial diagnosis of pneumonia later being diagnosed as TB. However, the current World Health Organization (WHO) standard of care (SOC) for young children with pneumonia considers a diagnosis of TB only if the child has a history of prolonged symptoms or fails to respond to antibiotic treatments. Hence, TB is often under-diagnosed or diagnosed late in children presenting with pneumonia.

In this context, the investigators are proposing to assess the impact on mortality of adding the systematic early detection of TB using Xpert MTB/RIF Ultra, performed on NPAs and stool samples, to the WHO SOC for children with severe pneumonia, followed by immediate initiation of anti-TB treatment in children testing positive on any of the samples.

TB-Speed Pneumonia is a multicentric, stepped wedge diagnostic trial conducted in six countries with high TB incidence: Cote d'Ivoire, Cameroon, Uganda, Mozambique, Zambia and Cambodia.

The sub-study on Covid-19 will assess the prevalence and impact of the Covid-19 in young children hospitalized with severe pneumonia. The sub-study findings are expected to guide policy makers and clinicians on potential specific screening and management measures for these vulnerable groups of children. They are also key to analysing TB-Speed Pneumonia results on mortality in a context of the Covid-19 outbreak and to take into consideration SARS-CoV-2 infection status in the main study analysis.


Options:
A: Inclusion Criteria:

* children aged from 0 to 13 years
* confirmed HIV infection
* suspicion of tuberculosis
* informed consent signed by at least one parent or guardian
* on ARVs or not

Exclusion Criteria:

* history of anti TB treatment started in the past 2 years
* on going tuberculosis treatment
* Suspicion of exclusive extra-thoracic tuberculosis
B: Inclusion criteria:

1. Children aged 2 to 59 months
2. Newly hospitalized for severe pneumonia defined using WHO criteria as cough or difficulty in breathing with:

   1. Peripheral oxygen saturation \< 90% or central cyanosis, or
   2. Severe respiratory distress (e.g. grunting, nasal flaring, very severe chest indrawing), or
   3. Signs of pneumonia, defined as cough or difficulty in breathing with fast breathing (tachypnea) and/or chest indrawing, with any of the following danger signs:

      * Inability to breastfeed or drink,
      * Persistent vomiting
      * Lethargy or reduced level of consciousness
      * Convulsions,
      * Stridor in calm child
      * Severe malnutrition
3. Informed consent signed by parent/guardian

Exclusion criteria:

- Ongoing TB treatment or history of intake of anti-TB drugs in the last 6 months
C: Inclusion Criteria:

Facility-based screening arm

* Age 0-99 years
* Informed consent provided (or assent plus parent/guardian consent)
* Attending any of the study 28 study clinics in the facility-based screening arm

Contact tracing arm- Index Case

* Age 0-99 years
* Informed consent provided (or assent plus parent/guardian consent)
* Newly diagnosed (last 2 months) with TB at any of the 28 study clinics in the contact tracing arm

Contact tracing arm- Household Contact

* Age 0-99 years
* Informed consent provided (or assent plus parent/guardian consent)
* Living in the same household as an enrolled Index case (see above)

Contact tracing arm- Non-household Close Contact

* Age 0-99 years
* Informed consent provided (or assent plus parent/guardian consent)
* Referred to the study as a close contact of an enrolled Index case (see above)

Exclusion Criteria (all arms):

* Unable to provide informed consent.
D: Inclusion Criteria (HIV Negative patients):

* Has signed an informed consent
* Aged 18 to 65 years
* Has been diagnosed with active pulmonary TB:

  1. has a compatible clinical picture of TB according to South African guidelines with the intention to treat and 1 documented positive culture result or
  2. has a compatible clinical picture of TB according to South African Guidelines with the intention to treat and 1 documented positive GeneXpert analysis
* Is HIV negative confirmed by 2 two rapid tests
* Is willing and likely to comply with the trial procedures
* Is prepared to grant authorized persons access to their medical record

Inclusion Criteria (HIV Positive patients):

* Has signed an informed consent
* Aged 18-65 years
* Has been diagnosed with active pulmonary TB:

  1. has a compatible clinical picture of TB according to South African guidelines with the intention to treat and 1 documented positive culture result or
  2. has a compatible clinical picture of TB according to South African Guidelines with the intention to treat and 1 documented positive GeneXpert analysis
* Is HIV positive confirmed by:

  1. 2 positive rapid tests or
  2. 1 positive rapid tests and an additional confirmatory ELISA
* A CD4 count has been performed
* Is willing and likely to comply with the trial procedures
* Is prepared to grant authorized persons access to their medical records

Exclusion Criteria:

* Has been in treatment for TB for more than 2 weeks
* Has a known MDR/XDR-TB
* Has been vaccinated with a live vaccine within 6 weeks prior to the day of inclusion (e.g. MMR, yellow fever, oral typhoid vaccines) except BCG vaccine
* Has been tuberculin (TST) tested \< 12 months prior to the day of inclusion
* Is pregnant, breastfeeding or intending to get pregnant
* Is a female of child bearing potential not willing to use effective barrier (including spermicidal gel), hormonal or intrauterine contraceptive measures during the trial period
* Has an active disease affecting the lymphoid organs except for HIV (e.g., Hodgkin's disease, lymphoma, leukaemia, sarcoidosis)
* Has a current skin condition which interferes with the reading of the skin tests e.g. tattoos, severe scarring, burns/sunburns, rash, eczema, psoriasis, or any other skin disease at or near the injection sites
* Has a condition where blood drawings pose more than minimal risk for the patient, such as haemophilia, other coagulation disorders, or significantly impaired venous access
* Currently participating in another clinical trial with an investigational or non investigational drug or device, or has participated in another clinical trial within the 3 months prior to dosing
* Has participated in previous clinical trials investigating the ESAT-6 and/or CFP-10 antigens
* Has a condition which in the opinion of the investigator is not suitable for participation in the study

Answer: B