It’s been three months since a global tuberculosis (TB) drug shortage was first reported. Motherwell Community Health Centre in Gqeberha, Eastern Cape is only left with five boxes of Rifinah, a fixed-dose combination of two anti-TB drugs rifampicin and isoniazid. 

A health worker at the clinic tells Health-e News that they see about 20 TB patients a day and are worried that the pills they have in stock won’t last a month. As a result, she says, they are being forced to ration the medicine and give patients just seven days’ worth of pills instead of the usual four months’ supply. 

The standard treatment for pulmonary TB is six months. In the first two months, patients are given a combination of isoniazid, rifampicin, pyrazinamide, and ethambutol. In the last four months of treatment, patients take treatment of isoniazid and rifampicin – this is usually given in the form of rifinah.

South Africa is one of 30 countries in the world with a high TB burden. In 2023, 270,000 people were newly diagnosed with the disease, and over 240,000 people were receiving treatment. 

The World Health Organisation (WHO) confirms the global shortage. “The drugs concerned are the rifamycins in particular rifampicin which is the most commonly used and most potent first-line anti-TB drug.” 

National health spokesperson Foster Mohale says most provinces have been affected by the stockout. Limpopo Health spokesperson Neil Shikwambane says limited quantities are still available. Meanwhile, North West health spokesperson Lucas Mothibedi says the province has over 83% of TB medicine available. 

Mohale explains that a shortage of fixed-dose combination TB medicine does not mean provinces are completely out of stock. Some stocks are still available for use. Health facilities have been advised to redistribute stock between facilities and provinces. 

Dangers of treatment interruption

The health worker Health-e News spoke with says she is concerned that the shortage could lead to patients defaulting on their treatment.  “Even the medication for the first two months of TB treatment is not enough,” she warns. “This could lead to the development of drug-resistant TB.” 

Professor Susan Purchase a research clinician at Stellenbosch University’s Desmond Tutu TB Centre says interrupting treatment lowers the likelihood of a person being cured of the disease.  Research shows that a 10% rise in TB drug stockouts lowered the cure rate by 2.1% –  the percentage of sputum-positive TB patients who become smear-negative;   and the success rate by 1.4% – the percentage of all TB patients started in treatment who were cured or who completed treatment.

“Patients who miss doses or stop treatment may once again develop symptoms of TB. Those who relapse may develop more severe forms of TB and would need to restart TB treatment,” Purchase says.

She explains that when a patient interrupts treatment, the TB bacterium may not be completely eradicated and may begin to multiply.  

“Patients with actively multiplying TB germs in their lungs are infectious and can pass TB to other people. This means a patient remains infectious for a much longer period of time.” 

Purchase says TB patients who miss less than two months of their treatment can have the missed doses added to the end of their treatment regimen. Patients who miss more than two months of their treatment would need to restart their treatment regimen. 

Impact of drug shortage 

According to the WHO, two factors have led to the shortage. 

The first is the unreliability of the supply of the active pharmaceutical ingredients (API)  prequalified by the WHO because of the sudden closure of a supplier. The second factor is the shift in 2024 by several high-TB-burden countries from using TB medicine from non-WHO prequalified suppliers to prequalified suppliers. This has added pressure to the global market.

However, the WHO says this has not impacted treatment adherence. 

“The supply shortage issue is currently being addressed by increasing the number of WHO prequalified API suppliers and by discussing supply orders with the largest high TB burden countries to control sudden requests of WHO prequalified medicine that could affect supply availability for other countries.”

In South Africa, a health department circular issued earlier this month gives guidance on alternative treatment. 

“To ensure continuity of care, while the supply of RH (rifinah) remains unstable, rifapentine in combination with isoniazid may be used in the continuation phase as an alternative. Provinces are encouraged to obtain limited quantities of rifapentine single-drug formulation from the donated stock available at Cape Medical Depot.”

The shortage is expected to be resolved by May 2025. – Health-e News