Introduction: Tuberculosis is one of the leading infectious causes of death worldwide. The WHO estimates that 1.7 billion people close to one quarter of the humanity are infected with Mycobacterium Tuberculosis the bacteria that causes TB. Last year, 10.6 million fell ill from TB and 1.6 million died.¹

Moreover, multi resistance to the current anti-tuberculosis drugs is growing thus causing a serious challenge in controlling the spread of the disease worldwide.

Fortunately, as we demonstrated on previous studies that Artemisia Afra infusions given with the WHO approved drugs can shorten treatment duration and resistance from 9 months to 52 days maximum² and out of the 102 patients 95 were cured in 30 days and 7 in 52 days.

Most recently we also demonstrated that 25 patients of regular tuberculosis completely recovered after 30 days or less by combining Artemisia Afra infusions whereby the other 25 patients who took the WHO treatment ALONE either abandoned their treatment and if they continued it, they were still sick on day 30.³

The objective of this pilot study is to demonstrate that 25 patients with multi resistant tuberculosis when given Artemisia Afra infusions combined with second line anti tb drugs were able to recover in 35 days maximum instead of 90 days or more.

Methods: This case study involved 25 patients who were all multi resistant or recidivist to the tuberculosis and have failed the first line treatment. Moreover, they were confirmed by a GeneXpert test to be resistant to Rifampicin and or Isoniazid. All patients were hospitalized at Ijenda Hospital in Bujumbura rural Province, Burundi between February, and April 2024. They were given the second line treatment at the regular dose + Artemisia Afra infusion at 330 ml three times a day.

The patients were also fed with a protein rich meal and nurses made sure that medications were taken regularly according to DOT [Directly Observed Technique].

Results: All the 25 patients recovered in 35 days maximum (see details in the Tables below).

Conclusion: The combination therapy [Artemisia Afra infusions+ WHO protocol] has a lot of potential in curing tuberculosis but more studies on a larger cohort [300 patients] will be carried out and there will also be a third leg with multi resistant cases that failed first line treatment with many months of sickness.

Tuberculosis is a disease caused by bacteria that are spread from person to person through the air.

TB usually affects the lungs and cause the following symptoms for the most part: cough, chest pain, fever, weight loss, fatigue, and weakness. Moreover, globally, the estimated number of resistant cases (MDR/RR-TB) were 410.000 in 2022.¹

This poses a serious healthcare challenge that the international community faces. Fortunately, as we demonstrated in the previous studies it is possible to shorten the treatment duration of this disease by combining the current treatment with Artemisia Afra infusions but more studies in a larger cohort are encouraged.^2,3

The objective of this study is to demonstrate that even the resistant and recidivist tb cases can be cured by combining the second line treatment with the Artemisia Afra infusions given for 35 days maximum.

Study design

This study was conducted at the Ijenda District Hospital in Bujumbura rural province, Burundi. It was done on 25 patients between the ages of 12 to 70 recidivists or multi resistant who were on the second line of the WHO protocol with the following medications.

The Artemisia Afra infusion was prepared at the Ijenda Hospital, and it was given at 330 ml every 8 hours to the patients along with the WHO drugs by using the DOT technique.

Second line treatment common in drug resistant tuberculosis¹

1. Bedaquiline

Dose: Adults: 400 mg once daily for 2 weeks, followed by 200 mg once daily, thrice weekly for 22 weeks.

Side effects: Nausea, arthralgia (joint pain) and headache

2. Prothionamide

Dose: Adults: 15–20 mg/kg/day; upper daily dose is 1 g. Once-daily dosing is advised but clinicians can use 2 divided doses if tolerance is a problem, or until tolerance improves.

Many individuals require gradual ramping up of the dose and treatment due to gastrointestinal upset.

Side effects:

• Nausea
• Vomiting
• Metallic taste
• Anorexia
• Abdominal discomfort
• Diarrhea
• Weight loss.

3. Linezolid

Dose: 600 mg, once daily, upper daily dose is 1.2 g.

Side effects:

• Nausea, vomiting and diarrhea.
• Myelosuppression
• Optic nerve toxicity
• Peripheral neuropathy

4. Moxifloxacin

Dose: 400 mg daily (oral or IV). High dose is 600–800 mg daily, depending on weight band.

Side effects:

• Diarrhea
• Nausea
• Bloating
• Arthralgia

The following extract from WHO guidelines show how complex it is to treat resistant and recidivist tuberculosis cases.

Treatment for people diagnosed with rifampicin-resistant TB (RR-TB), isoniazid-resistant TB and multidrug-resistant TB (MDR-TB, defined as resistance to isoniazid and rifampicin) requires regimens that include second-line drugs, such as bedaquiline and fluoroquinolones; these regimens are more expensive (≥US$ 1000 per person) and cause more side-effects than first-line treatments for drug-susceptible TB. Pre-extensively drug-resistant TB (pre-XDR-TB, defined as TB that is resistant to rifampicin and any fluoroquinolone) and XDR-TB (resistance to rifampicin, any fluoroquinolone and at least one of bedaquiline or linezolid) are even harder to treat.

Globally in 2020, 150 359 people were enrolled on treatment for MDR/RR-TB, down 15% from 177 100 in 2019. Most of those enrolled on treatment were adults. There was considerable country variation in treatment enrolment between 2009 and 2020.

The cumulative total number of people reported as enrolled on treatment for MDR/RR-TB from 2018 to 2020 was 482 683, only 32% of the 5-year target (2018-2022) of 1.5 million that was set at the UN high-level meeting on TB in 2018. For children specifically, the cumulative number was 12 219, only 11% of the 5-year target of 115 000.

Substantial improvements in treatment coverage at the global level require an intensification of efforts to diagnose and treat MDR/RR-TB. This requires one or more of the following to be increased:

• The proportion of people with TB who are detected and, of these, the proportion for whom TB is bacteriologically confirmed.
• The proportion of people with bacteriologically confirmed TB who are tested for drug resistance; and
• The proportion of people diagnosed with MDR/RR-TB who are enrolled in treatment.

Globally in 2018 (the latest patient cohort for which data are available), the treatment success rate for people treated for MDR/RR-TB with second-line regimens was 59%; this has improved steadily in recent years, from 50% in 2012.

Among WHO regions, the treatment success rate in 2018 ranged from 56% in the European Region to 69% in the African Region.

By the end of 2020, 109 countries were using bedaquiline as part of treatment for drug-resistant TB (DR-TB), 90 were using all-oral longer regimens for the treatment of MDR/RR-TB and 65 were using shorter regimens for the treatment of MDR/RR-TB. At least some people diagnosed with DR-TB were being monitored for adverse events in most countries. (WHO guidelines)

Resistant patients: 25

Drug-resistant tuberculosis (TB) continues to be a public health problem, taking a heavy toll on patients, communities, and health care systems.

Recent global estimates indicate that there were about half a million new cases of multidrug- or rifampicin-resistant TB (MDR/RR-TB) in 2018, with less than 40% of the estimated burden being notified and 32% reported to have started second-line treatment.¹

Current treatment regimens for MDR/RR-TB patients are far from satisfactory. Compared with treatments for drug-susceptible TB forms, these regimens require a longer course of treatment, a higher pill burden and the use of medicines with a higher toxicity profile; in addition, patients may develop significant adverse events and have poorer treatment outcomes.

Globally, although treatment success rates have increased, almost 15% of MDR/RR-TB patients die from the disease, and 26% of those deaths are in patients with extensively drug-resistant TB (XDR-TB).¹

Tuberculosis (TB) strains with drug resistance are more difficult to treat than drug-susceptible ones, and present a major challenge for patients, health care workers and health care services. In addition, the increase of drug-resistant TB threatens global progress towards the targets set by the End TB Strategy7 of the World Health Organization (WHO).

Thus, there is a critical need for the continual development of evidence-based policy recommendations on the treatment and care of patients with drug-resistant TB, based on the most recent and comprehensive evidence available.¹

We observed 25 patients who were multi resistant to the first line RHZE and we combined their treatment with Artemisia Afra infusions at a dose of 330 ml three times a day for 30 days or until the symptoms were resolved and tested negative to Gen expert.

Their symptoms improved gradually as you can see in the graph below.

Fever, cough, and weight were monitored as outlined below.

The following assessment was made:

Day 0 upon admission

• Temperature was 39.5 degrees Celsius.
• Cough was very severe 100 % for all patients.
• The mean weight was 35 Kgs.

Day 5

• Temperature dropped to 38.6 degrees Celsius.
• Cough was persistent for 87% of the patients.
• The mean weight was 37.4 Kgs.

Day 10

• Temperature remained normal 37.3 degrees Celsius.
• Cough was present for 57% of the patients.
• The weight continued to increase to an average of 38 Kgs.

Day 15

• Temperature remained normal 37.3 degrees Celsius.
• Cough was persistent for 33% of the patients and many of them wanted to go back home to dig in their fields.
• The weight was soaring at 46.6Kgs.

Day 20

• Temperature remained the same 37 Celsius.
• Cough was still in 29% of cases.
• The average weight was 50.3 Kgs.

Day 25

• Temperature was stable, 37 Celsius.
• Cough was 25%.
• The average weight was 54.6 Kgs.

Day 30

• Temperature remained the same, 37 Celsius.
• Cough was almost completely cleared only 4 % (the patients were still coughing).
• The weight was 56.96 Kgs.

Day 35

• Temperature remained the same, 37 Celsius.
• Cough was completely cleared only 4 %.
• The mean weight was 62 Kgs.

For statistics of the people who were in the 3 groups, please look at the trend by comparing those in red [Artemisia plus WHO regular] and those in blue [WHO ALONE] and the artemisia plus WHO resistant in yellow.

Please look at the graphs which highlight the improvement in terms of temperature, cough and weight gain.

Cough in % of Severity

Cough

Figure 1 Cough in % of severity.

Temperature in Celsius

Temperature

Figure 2 Temperature in Celsius.

Weight in Kilograms

Figure 3 Weight in kilograms.

We are giving details for 2 cases WHO were outstanding:

First case: Esther:

Ester is a 16-year-old girl who was examined and tested positive on tuberculosis and was treated for 7 months but later developed multi resistant. She was therefore tested and her GeneXpert result was positive.

She started the following regimen along with Artemisia Afra infusions.

• Bedaquillin
• Linezolid
• Pretonamid
• Isoniazid
• Ethambutol
• Clofazimine
• Moxifloxacin

After 33 days of treatment, she got released after her Gen expert test turned negative.

Figure 4 16 years old girl who was examined before treatment and after treatment.

Second case: Jonathan: 24 years old, Male

He was on the following treatment:

• Bedaquillin
• Linezolid
• Pretonamid
• Moxifloxacin

After 27 days of the combined treatment, he got his Gen expert negative and was released to go home.

GeneXpert is a rapid test that can simultaneously identify the MTB and resistance to the first line treatment.

A negative GeneXpert rules out the presence of tuberculosis.

Figure 5 24 years old, male who was examined before treatment and after treatment.

The combined administration of Artemisia Afra infusions with second line conventional WHO treatment gave an unprecedent faster resolution of tuberculosis symptoms than conventional treatment alone, which may take up 24 months. Furthermore, as we mentioned before side effects of the WHO pills are unbelievably tough to patients that adherence is very difficult to reach in most cases.¹

As far as cost is concerned, according to a Californian study, the cost of hospitalization for a multi resistant case was USD 110,900 whereas the treatment for the combination of the WHO pills and Artemisia Afra infusion is barely USD 100.⁸

It is the author’s opinion that these remarkable results should constitute a wakeup call to different key opinion leaders to address this burden to the society in terms of cost, time wasted in hospital and suffering to the humanity with the unnecessary prolonged hospitalization. [9-24 months versus 35 days]

Thorax radiography protocol

Identity: patient number 28, Male, adult

1. Before treatment:

Right lung:

• Presence of reticular opacities
• Presence of hilar lymphadenopathy
• Scissuritis in the upper lu ng field. Left lung:
• Presence of reticular opacities in the lower field
• Presence of hilar lymphadenopathy.

Conclusion: probable tuberculous pneumonia with signs of pulmonary fibrosis.

2. After treatment:

On the left and right: no opacity or sign of pneumonia in the two pulmonary fields, no visible after-effects.

The heart and other structures appear normal.

Conclusion: Good clinical remission.

Done in Goma on December 12, 2023.

Dr KAHATWA KIRINGA, Specialist in Internal Medicine.

Artemisia Afra Treatment Video

Original French version of the report above. [N°28]

The authors wish to declare that there is no conflict of interest in this study and recommend further studies on a larger cohort [300 people] to confirm what was observed in vitro by our colleagues Prof. Pamela Weathers⁴ and in vivo by Dr Jerome Munyangi on the Buruli Ulcer⁵ in dealing with Mycobacterium Species.

Finally, the authors acknowledge special support from different people who accompanied them financially, intellectually, and morally for the completion of this humble task and encourage others to pursue the fight against multi resistance of the mycobacterium tuberculosis⁶ thus reducing cost,⁸ suffering and burden to society.

As the WHO extract below rises an alarm on the recently discovered drugs because of their heavy toxicity it is our hope that this cheap, fast, and non-toxic solution⁷ will be considered for further research to address this burden that affects so many.

Drug-resistant tuberculosis remains a driving factor behind the worldwide tuberculosis epidemic, and shorter, safer, and more effective treatment regimens are needed.⁶

In 2020, a total of 157,903 cases of rifampin-resistant tuberculosis were reported, and 25,681 of these cases involved additional resistance to core drugs (i.e., levofloxacin or moxifloxacin, bedaquiline, and linezolid), although this case count is probably an underestimate.

Currently, treatment lasts between 9 and 24 months and involves multiple drugs that have serious side effects, including cardiac toxic effects, neuropathy, and liver dysfunction.

Within the past decade, the approval of several drugs for the treatment of drug resistant tuberculosis has heralded a new era in treatment. Bedaquiline, a diarylquinoline, inhibits mycobacterial ATP synthase and is licensed for use in the treatment of drug-resistant tuberculosis. Pretomanid is a nitroimidazooxazine with activity against replicating and dormant mycobacteria through inhibition of mycolic acid biosynthesis and nitric oxide release, respectively.

Linezolid is a repurposed oxazolidinone that inhibits mycobacterial protein synthesis, but its prolonged use is associated with peripheral neuropathy and myelosuppression, (WHO guidelines).¹

Additional information of detailed results is given in the tables 1-8 below:

None.

The authors declare that they have no conflicts of interest.

1. WHO guidelines.
2. Bagire PG, Ogwang PE, Lusi JKM, et al. Artemisia Afra infusions clinical benefits as a complementary treatment to “WHO” approved drugs against tuberculosis. Pharm Pharmacol Int J. 2022;10(5):157‒166.
3. Gisenya P, Ogwang PE, Katotola E, et al. Pilot study to compare the use of the national program drugs ALONE versus their combination with Artemisia Afra infusions for the treatment of pulmonary tuberculosis. Pharm Pharmacol Int J. 2023;11(4):118‒128.
4. Martini MC, Zhang T, Williams JT, et al. Artemisia annua and Artemisia Afra extracts exhibit strong bactericidal activity against Mycobacterium Tuberculosis. J Ethnopharmacol. 2020:262:113191.
5. Munyangi J, Lutgen P. Artemisia Afra cures Buruli ulcer with high efficacy. Malaria World. 2017.
6. Gygli SM, Borrell S, Trauner A, et al. Antimicrobial resistance in Mycobacterium tuberculosis: mechanistic and evolutionary perspectives. FEMS Microbiol Rev. 2017;41(3):354–373.
7. Mukinda JT, Syce JA. Acute and chronic toxicity of the aqueous extract of Artemisia Afra in rodents. J Ethnopharmacol. 2007;112(1):138–144.
8. Oh P, Pascopella L, Barry PM, et al. A systematic synthesis of direct costs to treat and manage tuberculosis disease applied to California, 2015. BMC Res Notes. 2017;10:434.