Results of Research

The Ugandan Randomised Control Trial (RCT, Phase IIb)

Conducted by Makerere University's School of Health Sciences, Uganda (funded and supported by Moxafrica).

The study is completed, the data analysed and the results are now published in open source in the European Journal of Integrative Medicine.

You can download the report as a PDF file here:

 

This study comprises the first scientific investigation into whether this simple traditional therapy might help the challenge of reducing the persistent burden of TB in middle- and low-income countries.

 

Principle Investigator of the study was Professor Paul Waako (MBChB) MSc. Ph.D., Associate Professor and Head of Department Pharmacology and Therapeutics, College of Health Sciences, Makerere University Medical School, Kampala, Uganda. The study itself was supported both financially and technically by Moxafrica.

 

180 newly diagnosed TB patients were randomly assigned to two groups, one given standard first-line DOTS TB drug therapy, and the other first-line DOTS along with daily self-administered moxibustion. The two groups were carefully monitored for differences in recovery rates and serological and immunological markers were compared.

 

 

Please note:

The training manual used in the study can be examined by clicking: 

The research team discussing the findings: (from left to right) Frank Mubiru [biostatistician], Dr. Ibanda Hood [study doctor], Professor Paul Waako [principle investigator]

 

The principle positive findings were:

 

1.       Moxa patients converted to sputum negative faster when using moxa, particularly in the early stages of therapy.

2.       Moxa patients adhered to their drug therapy better.

3.       Moxa patients had increased levels of Hb

4.       Moxa patients had greater increases of Cd4 cells, although this data was not statistically significant.

5.       There were no adverse events.

6.       All of the first four findings were also seen in the HIV sub-group.

 

The paper concluded that more investigations should be developed to provide a broader understanding of both effect and potential benefit in treating human TB disease (both with and without co-infection with HIV). It furthermore recommended that these might include MDR-, XDR-, and programmatically-untreatable TB (including in palliative care scenarios) as well as in cases co-infected with HIV.

 

Study site

The study was carried out at Kiswa Health Centre, Kampala, Uganda.

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The Results of the Two Studies in North Korea
Two studies have been completed, and the data analysed and shared withMoxafrica by the North Korean Ministry of Public Health. They are reviewed in an 'opinion' article which forms part of the European Journal of Integrative Medicine's 'Special Collection on AMR (anti-microbial resistance)'. It can be downloaded as a pdf here:

 

The results of the first study

 

In this study, the DPRK Ministry of Public Health (MoPH) tested only MDR-TB cases (in sanatoria). There was a total of 64 cases – 30 on standard second-line drug therapy, and 34 on standard drug therapy plus moxa.

A higher dosage of moxa was used than in the Ugandan study, adding eight points on the lower back (Dr. Hara's 'loin points') in addition to the two-leg points (in accordance with what was recorded as being used in Japan in the pre-antibiotic era). This extra dosage was deliberately decided because of the clinical implications of drug resistance (given that the drugs used to treat it are weaker and therefore a stronger dose would be needed to see measurable results).

The following is the summary of their findings:

(* indicates p=<0.05 i.e. the data is of statistical significance)

  

   a)      The improvement rate of symptoms:  study group (89.96%*), control group (64.25%)

   b)      Mean period of improvement of symptoms (in days):  study group (49±12.89*), control group (82±37.84)

   c)       Improvement rate of Chest X-ray findings:  study group (12.5%),control group(6.67%)

   d)      Increase in body weight: moxa group (+2.72kg*), control group (-1.2kg)

   e)     Treatment outcome:  study group (85.3%*), control group (60.0%)

Importantly, overall the DPRK MoPH reported in a summary they supplied to us that they now have “positive opinions on the treatment effects of TB by moxa therapy”.

 

 

Discussion of these FIRST DPRK research study findings

 

The most exciting of these findings undoubtedly relate to the last graph (of positive treatment outcomes) bearing in mind that these cases were MDR-TB, its limitation being the small numbers studied. It’s worth considering that the current success rate for treating MDR-TB as reported in the most recent WHO Global TB Report is a lowly 56% (widely accepted as being too low to contain this disease) and in this study the Korean control group was reported as having a 60% success rate – i.e. similar to the global rate. The moxa group, however, reported an 85% success rate (a hike of 42%). We believe that it’s reasonable for us to suggest that (if this is confirmable by other studies) this difference is potentially game-changing.

To illustrate why we make this claim, we have extrapolated the proportional improvement in treatment outcome recorded in this study against the global success rate of 56% and can thus suggest that, if these data are corroborated by further studies, then the global success rate for treating MDR-TB could be lifted to 77% (for a meagre material cost of less than 30 dollars of moxa).

(It should be further noted that the current success rate for treating drug-susceptible TB is 82%, so this possible uplift by using moxa could potentially bring MDR success rates within shouting distance of more easily treated TB.)

What this needs, of course, is further testing on an urgent basis which so far we’ve so far been unable to either initiate or facilitate anywhere, although we have a top team lined up in Uganda willing to take on the challenge if funds can be raised.

 

With regards to symptom improvements it can also be seen that the improvements when using moxa weren’t just statistically significant: when they occurred they came through significantly faster as well. We are certainly cautious of reading too much into this, but (given that treatment for MDR-TB is generally lengthy – 9-24 months and with pernicious side-effects) any improvements in patients’ experiences could make adherence easier as well which could in turn also feed into improved outcomes and reduced mortality.

Meanwhile, the most basic data of all – that the moxa patients’ weight improved during therapy, while the control group lost weight – not only supports the rest of the data, it suggests that moxa was helping patients to constitutionally recover as well.

*

In the meantime geopolitics sadly inflicted its own pernicious impact on the North Korean TB epidemic and its vulnerable population. The Global Fund (which had until then been supplying drugs and diagnostics for the treatment of both TB and malaria in the country) cut off all its support early in 2018 (at the same time as the results of this first study were shared). No convincing explanations were available as to why this decision was made - and to make things worse this coincided with support from the WHO being sadly lacking as well. This left TB patients in the country at enormous risk, threw the national program into disarray, threatening an epidemiologically inevitable hike in existing numbers of MDR-TB cases.

Moxafrica committed to doing all it could to offer help in what was an emerging and continuing humanitarian crisis.

 

The Results of the Second DPRK Study

 

 

The second study looked at the possible preventative efficacy of low-dose daily moxa in reducing the incidence of active tuberculosis occurring in a vulnerable group.

This time they looked at disease activation rates of latent TB cases who were known to be in close contact with ‘smear-positive’ infectious pulmonary TB cases, and they have since then shared their results with us.

They studied a total of 294 close contacts of infectious cases, 152 of whom used a daily prophylactic dose of small cone moxa at St36 for a 3 month period, the other 142 using the standard WHO-approved isoniazid  (INH) medication (10㎎/㎏ per day) for a period of 6 months.

The results in terms of incidence of TB disease were compared in each case studied at the end of a 12 month period.

 

(Why did they only use a 3 month treatment regimen for the moxa patients, compared with a 6 month one for the INH group? Unfortunately, we don’t know because we weren’t party to the final study design, but we believe that it may have been down to a misunderstanding because we’re sure it should have been for at least 6 months, and wonder whether the results in the moxa group might have been better had this been the case).

 

The results revealed no difference in numbers of new disease between the two groups (with 2 new active cases emerging in each group making for a 1.31% and 1.41% incidence rate in each group respectively). In other words, moxa appeared to be neither worse nor better in preventing activation of disease from latency than isoniazid – and isoniazid is the current approved treatment for latent infectious TB.

 

This may not seem of any significance, but it is actually a very significant finding indeed for reasons we will explain further below.

But before doing so, it is noteworthy that they also found a 'trend' of raised WBC and lymphocyte count in the moxa group. This suggests (yet again) that moxa provokes a host immune response that is beneficial in TB infection – but we now have evidence that it may do so at an earlier sub-clinical stage of the disease as well as after reactivation.

This table shows the difference in WBC and lymphocyte counts befaore and after treatment.

The problem with this data is once again the low numbers, along with the fact that we have been given no comparative hematological data for the control INH group (which we are asking for).

 

The reason for the low number is simple, unfortunate: the  DPRK has been so starved of international support for the last year-and-a-half that they only had enough reagent spare to test 20 of those studied so this finding is sadly nowhere near as robust as we'd like as a result.

Nevertheless, the MoPH has reported these findings with some confidence, stating that their “laboratory studies were particularly trending elevated lymphocytes”, and on this basis they’ve stated their intention of rolling out the use of moxa as a preventative therapy.

Discussion of this second set of DPRK results

The underlying significance of the general finding (that moxa may be basically comparable with isoniazid in terms of preventing outcome of new disease) is not obvious, but we think it is potentially huge. This is because all of the cases studied were confirmed as having existing latent infection with TB - and these data have special significance for when such latent infections are drug-resistant.

 

It's currently estimated that 1.7 billion people worldwide are latently infected with 'all' types of TB so are all living with an ongoing risk of active disease (a staggering 23% of mankind) - but exactly how many of these may be already latently infected with MDR-TB strains remains very uncertain (in fact it's still subject to speculative estimates based on mathematical modelling which is itself based on many uncertainties).

This drug-resistant aspect of latency is massively important because of the fact that isoniazid (INH), the drug which is used to treat latent infection in most cases, is also one of the two drugs that are used to define multi-drug resistant tuberculosis (the other one being rifampicin). In other words, if a latent infection is MDR, then it is de facto INH-resistant which in turn means that the standard treatment for latent infection is unlikely to be effective (so the standard 6-12 months of preventative therapy won't do them any good at all).

Behind this problem lie two very uncomfortable truths: one is that currently it's impossible to determine whether or not a latent infection is drug-resistant; the other is that there is currently no default WHO-approved therapy for drug-resistant latent TB (and if any is developed and approved it will without question incorporate a recently patented drug like Delaminid and therefore be very expensive). 

Meanwhile, there is a massive target that's been set for ramping up treatment of latent TB in higher-risk patients by 2022 (30 million), but this ambitious target contains within it a huge clinical flaw (above and beyond the challenge of its implication) - it won't just fail with any cases that are DR - it may even exacerbate health and stoke resistance.

So we wonder whether these findings suggest that moxa can help reduce this risk (at a material cost of less than US$10 per latent infection…).

This is not in any way a trivial suggestion. A British paper published in 2016 reckoned that 10.9% of those 1.7 billion people who currently have latent TB carry an INH-resistant strain of disease.  This would makes for more than 180 million people who need preventative therapy but can't be helped by the current approved treatment for latent TB using INH.

If the North Korean data can be verified (here we go again!!) we may truly be on to something else of real significance - that's cheap, and low-tech and appropriate where needed.

So once again, we stress that this second study needs urgent further testing.

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