Promising developments in the management of Tuberculosis and Malaria

A few promising developments in the management of Tuberculosis and Malaria made the news recently.

Tuberculosis

Two new drug therapies have the potential to transform the way we manage Tuberculosis, especially drug resistant Tuberculosis.

Together, the new treatments, called BPaMZ and BPaL, could make treating TB much simpler and more effective.

BPaMZ

Bedaquiline + Pretomanid + Moxifloxacin + Pyrazinamide

“BPaMZ” is a promising TB treatment regimen in development that has the potential to be an improved treatment for the majority of TB patients.

The BPaMZ regimen consists of bedaquiline (B), pretomanid (also known as PA-824 or Pa), which are two of the newest and most promising drugs for tuberculosis (TB), and moxifloxacin (M) and pyrazinamide (Z), which are established drugs in the current treatment.

BPaMZ shows promise to reduce TB treatment to as little as three months. This is an oral regimen, removing the need for injectables as part of MDR-TB treatment and also projecting to be markedly less expensive than current MDR-TB therapy.

Trials carried out in 240 people across 10 countries in Africa suggest that it cures almost all cases of ordinary TB in four months, and most people with drug-resistant TB in about six months. In the majority of cases, the TB bacterium had disappeared from sputum within two months.

BPaL

Bedaquiline + Pretomanid + Linezolid

This drug combination represents the first TB regimen with no pre-existing resistance to reach testing in humans.

BPaL, a therapy that involves taking three drugs once a day, has so far cured 40 of 69 patients with “extremely-drug-resistant TB” – the most difficult form to treat. What’s more, it achieved this within six months. The 29 remaining participants in this trial are still to be assessed.

The TB Alliance says that BPaMZ has the potential to treat 99 per cent of people who catch TB each year, while BPaL could treat the remainder.

This regimen has the potential to shorten TB treatment to less than 4 months for patients sensitive to the therapies in the regimen, including some MDR-TB patients.

This is an oral regimen, removing the need for injectables as part of MDR-TB treatment and also projecting to be markedly less expensive than current MDR-TB therapy. This regimen also shows promise to be able to be administered alongside common ARV treatments, thereby improving treatment options for patients co-infected with TB and HIV.

Additionally, this regimen can be administered in a fixed dose for all patients, and will therefore be simpler for health systems to deliver and patients to use.

Malaria

A new vaccine for malaria is up to 100% effective when assessed at 10 weeks after last dose, according to the results of a clinical trial.

The vaccine called Sanaria PfSPZ vaccine incorporated fully viable — not weakened or otherwise inactivated — malaria pathogens together with the medication to combat them.

Note: PfSPZ vaccine stands for Plasmodium falciparum Sporozoite vaccine.

To quote the article published in Nature:

“we  assessed immunization by direct venous inoculation of aseptic, purified, cryopreserved, non-irradiated PfSPZ (‘PfSPZ Challenge’) to malaria-naive, healthy adult volunteers taking chloroquine for antimalarial chemoprophylaxis (vaccine approach denoted as PfSPZ-CVac).

Three doses of 5.12 × 104PfSPZ of PfSPZ Challenge at 28-day intervals were well tolerated and safe, and prevented infection in 9 out of 9 (100%) volunteers who underwent controlled human malaria infection ten weeks after the last dose (group III).

Protective efficacy was dependent on dose and regimen.

Immunization with 3.2 × 103 (group I) or 1.28 × 104 (group II) PfSPZ protected 3 out of 9 (33%) or 6 out of 9 (67%) volunteers, respectively.

Three doses of 5.12 × 104 PfSPZ at five-day intervals protected 5 out of 8 (63%) volunteers.

The frequency of Pf-specific polyfunctional CD4 memory T cells was associated with protection.”

It is obvious from the sample size that much more work needs to be done before the vaccine is approved for large-scale use. However, it does offer a glimpse into the possibilities in our fight against malaria.

Useful Links:

Link to a news article about the new TB options:

https://www.newscientist.com/article/2121354-two-new-drug-therapies-might-cure-every-form-of-tuberculosis/

Link to descriptions on the TB Alliance web site:

https://www.tballiance.org/portfolio/regimen/bpamz

https://www.tballiance.org/portfolio/regimen/bpal

Link to news article on the malaria vaccine:

http://www.thehindu.com/sci-tech/health/%E2%80%99New-malaria-vaccine-found-100-effective%E2%80%99/article17317160.ece

Link to the article in Nature (paid article, abstract is free):

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature21060.html

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