Tuberculosis

Introduction

Tuberculosis or TB (short for tubercles bacillus) is a common and often deadly infectious disease caused by various strains of myco-bacteria. TB usually attacks the lungs but can also affect other parts of the body. It is spread through the air, when people who have the disease cough, sneeze, or spit. Most infections in humans result in an asymptomatic, latent infection and about one in ten latent infection events usually progresses to active disease, which, if left untreated, kills more than 50% of its victims.

Tuberculosis is a disease we see little of in Europe and the United States but it is unfortunately re-emerging as a global danger in the form of the Multi-Drug Resistant Tuberculosis (MDR TB).

Each year worldwide close to two million people die from TB. The increasing level of MDR TB in particular increases this figure because treatment is a long and protracted exercise and unfortunately the chances of recovery are still relatively low.

MDR TB accounts for approximately 4% of the total diagnosed global cases of TB.

Overall, approximately 9.4 million new cases are reported each year worldwide, of which China and India are prominently affected with 3.5 million new cases appearing between them each year, with 50% of all MDR TB cases being reported in these two countries.

South-east Asia including Indonesia, Thailand and Cambodia also have serious TB problems, which are often linked with AIDS patients.

Currently the cost of standard TB treatment is US$2,000 per patient, whilst MDR TB costs US$5,000 per patient.

MAC/98alive™ Application & Treatment

In 2004 the University of Western Australia completed tests which demonstrated MAC/ 98alive™ to have successfully challenged TB and other tests which indicated that a course of treatment with MAC/98alive™ need only last two months compared to existing six month products. MAC/98alive™ can be administered on a much more cost efficient basis.

Three years ago, MAC/98alive™ entered into a collaboration agreement with Griffith University in Queensland. Pursuant to that 98alive™ is presently completing a further collaboration agreement involving itself, Griffith University, the Chinese Academy of Medical Science (CAMS) and Peking Medical University College (PMUC).

In 2009 ten representatives from CAM and PMUC went to Brisbane and met with Professor Max Reynolds and Professor Cordia Chu of Griffith University. The purpose of this collaboration will be to focus on the applications listed below which have particular significance in China with the intention to carry out research in China regarding TB and selective cancers.

CHINESE ACADEMY OF MEDICAL SCIENCES (CAMS)

CAMS was formed in 1956 by the Chinese government and under the leadership of the Ministry of Health it is the most important medical institution in China. It was merged with the Peking Union Medical College (PUMC).

With eighteen research institutes located in five cities and six academic hospitals located in three cities, CAMS research priorities are mainly focusing on:

Basic Biomedical Research;
Major public health diseases;
Infectious diseases; and
Drugs and vaccines

PEKING MEDICAL UNIVERSITY COLLEGE (PMUC)

Peking Union Medical College Hospital is the clinical medical school of China Union Medical University, and the clinical medicine research centre of Chinese Academy of Medical Sciences (CAMS). It is a large-scale general hospital which integrates medical service, education and research. It owns a group of outstanding medical experts, medical educationists and medical research personnel. In addition, the hospital also owns numerous state-of-art facilities which meet international standards, a complete range of special departments, and abundant technology resources.

The hospital has 37 clinical research centres all of which have played positive roles in the development of education, research and medical service within the hospital. Every year, the hospital assumes around 240 research tasks for national, ministerial and provincial-level subjects.

Over the past fifteen years, the hospital was awarded 22 National Science and Technology Progress Prizes, and more than 100 provincial and ministerial level scientific research prizes. In the recent five years, the hospital also published more than 3,550 academic dissertations, both in China and abroad.

Griffith University has also introduced MAC/98alive™ and Professor Reynolds to the Centre for Disease Control (CDC) in the Zhejiang province in China so as to also test the efficacy of MAC/98alive in challenging TB and MDR TB.

Professor Reynolds met with the Chief Doctor, Deng Ganquiang, the Deputy Section Director, Wu Pinggu and the Director Professor Zhang Yanjun (all from the Centre of Disease Control, Zhejiang Province) on their recent visit to Australia and discussed the need for a more effective solution to TB and also MDR TB.

The CDC in Zhejiang has commenced initial trials with 98-Alive for two patients and from the successful preliminary results, will now trial 98alive with additional patients suffering from MDR TB.

First Case Results – Patient A

A 24 year old female contracted MDR TB when she was 16 and has been on treatment continuously for the past eight years. She is considered a terminal patient.

Patient A was treated with MAC/98alive™ inhalation and capsules for three days. The following clinical effects have been noted.

Increase of appetite

An increased sense of general well-being

A reduction in TB lesions (x-ray examination)

Second Case Results – Patient B

A 53 year old male was diagnosed with MDR TB, two years prior and could not tolerate second line drugs.

Patient B was treated with MAC/98alive™ inhalation and capsules for three days which his body has tolerated. The TB lesions have also been reduced (x-ray examination).

Considering the longevity of both patients infection, these results are remarkable as it was initially expected to see changes after one to three months of treatment with MAC/98alive™.

Professor Reynolds will be seeing these two patients in October 2010 when he visits China and it is expected that both should have made further advances in their health.

CDC wants to expand the trials and MAC/98alive™ has agreed to this. The Doctors at CDC are enthusiastic about the outcome so far as this is the first time they had any progress in dealing with this form of TB.

CDC would like to call a meeting with Professor Reynolds when he visits China in October 2010 to discuss the results and the possibility of working with MAC/98alive™ in the TB hospitals.

Dr. Deng Ganquiang, Vice Director of Zhejiang Provincial Centre for Disease Control and Prevention, has requested Professor Reynolds to spend a day with him visiting hospitals, health centres and research facilities in view of a collaboration for the treatment of TB and MDR TB and other air and water-borne diseases (including Dengue Fever).

Any outbreaks are a major concern to the Centre for Disease Control

MAC/98alive™ & TUBERCULOSIS – Research

Toxicology

Toxicology work includes;

Acute dosing (single dose) – rats

30 day continuous dosing – rats and rabbits

90 day continuous dosing – rats

Fertility dosing – rats and rabbits

Dermal studies – guinea pigs

Micronucleus test

LD 50 studies

Full pharmacokinetic studies for drug distribution and exclusion from the body (50) volunteers have been completed as part of the Phase 1 work.

RESEARCH REPORTS

Our basic research work shows that MAC/98alive™ kills the tuberculosis mycobacterium, however the laboratory studies have to be expanded into animal models which is currently being discussed with the Chinese Academy of Medical Science in Beijing, who have one of the largest and best equipped animal laboratories available for this work.

In the meantime, work is continuing with the Chinese Centre for Disease Control (CDC) in treating humans with MDR TB in a hospital system using MAC inhalation techniques.

After the success with other lung diseases over the past three years, it is anticipated that MAC/98alive™ will be as effective against MDR TB.

REPORTS ON THE ANTI-TUBERCULOSIS ACTIVITY OF MEGABAC
by Professor Thomas Riley of the University of Western Australia
March 2005

These were the initial laboratory tests which established that MAC (formerly known as MegaBacTM) killed TB.

REPORT REGARDING THE EVALUATION OF THE SUSCEPTIBILITY OF MYCOBACTERIUM AVIUM SUBSPECIES PARA-TUBERCULOSIS TO THE ANTIMICROBIAL ACTIVITY TO MEGABAC by CSIRO

The experiments conducted by the CSIRO confirm that MAC (formerly known as MegaBacTM) is able to affect the bacterial metabolism of all three mycobacterial species tested at concentrations as low as 1% of the 10% solution supplied.

MURINE IMMUNE RESPONSE TO ‘ORAL MAC’ by Dr. Pauline Low, Ms. Amanda Clark and Professor Steve Ralph

This research shows the primary reasons why MAC/98alive™ assists the body to be better equipped in warding off the disease.

Multi Drug Resistant Tuberculosis (MDR TB)

MDR TB does not react to front line drugs that are used to treat normal TB. There have been a number of additional antibiotics recently introduced which can be fatal if taken for prolonged periods.

An MDR TBH patient may take two to eight years to be treated at an approximate cost of $50,000 per patient, with only a 50% success rate.

Possible side effects of these drugs can include weight loss, loss of appetite, fever, coughing and a constant sensation of feeling ill.

Potential Advantages of MAC/98alive™ in Tuberculosis Treatment

The current treatment is difficult and requires long courses of multiple antibiotics. Antibiotic resistance is a growing problem in (extensively) multi-drug-resistant tuberculosis. Tuberculosis prevention relies on screening programs and vaccinations.

MDR TBH does not react to front line drugs that are used to treat normal TB. Some recently introduced antibiotics can be fatal if taken for prolonged periods.

An MDR TBH patient may take two to eight years to be treated at an approximate cost of $50,000 per patient, with only a 50% success rate.

Possible side effects of these drugs can include weight loss, loss of appetite, fever, coughing and a constant sensation of feeling ill.

The potential advantages of MAC/98alive™ in the treatment of TB, MDR TB, and XMDR TB:

Table XIV

Property Impact of 98alive™
Bactericidal
  • 98alive™ kills bacteria rather than chemically inhibiting its  ability to replicate
  • 98alive™ exhibits anti-bacterial activity both in vitro and vivo
Universal application
  • 98alive™ has no restrictions on treatment candidates
MDR TB and XMDR TB
  • 98alive™ treatment is effective within two months other treatments last six months on average
Application
  • 98alive™ has been proven effective to kill MDR and XMDR strains of tuberculosis 
No resistance development risk
  •  98alive™ exterminates the bacteria itself rather than the virus being made less efficient in replication
  • Mutation will not impact 98alive™’s ability to exterminate all versions of the virus
Speed of action
  • 98alive™ demonstrates anti- bacterial activity within 10 minutes ( in vitro)
  • 98alive™ demonstrates rapid absorption into blood serum ( in vivo )
  • 98alive™ demonstrates swift bacterial destruction
Boost immune system
  • It is expected that 98alive™ accelerates the bacterial eradication as both 98alive™ and patient’s improved immune system attack it
Cost differential
  • 98alive™ is expected to cost significantly less than the current treatment

Conclusion

A shorter medication regime of no more than two months is required for the treatment of regular TB (the World Health Organization’s [WHO] stated goal) and new drugs for the treatment of MDR TB.

The work undertaken in China has focused on these two goals and it is believed that the first goal of lowering the treatment time can soon be achieved. MAC/98alive™ is currently working with the Chinese Academy of Science treating terminal patients with MDR TB and already there are some early signs of clinical improvements.

Each year there are 1.5 million new cases of TB in China with 5% representing as MDR TB. India has 2 million new cases with an unknown number of patients infected with MDR TB.