Dengue fever

Dengue Fever is an acute febrile disease caused by the dengue virus. There are four strains (serotypes) of the virus that can circulate within a population concurrently.

Dengue Haemorrhagic Fever (“DHF”) is a potentially deadly complication of the fever brought about by repeated infection by different serotypes of the disease. DHF causes damage to the victim’s internal organs (as a result of internal bleeding). Bleeding in internal organs can lead to the onset of Dengue Shock Syndrome (“DSS”) if the patient does not receive adequate medical treatment. DHF is fatal in 10 – 20% of cases, with a higher mortality rate in children and those with compromised immune systems.

There is currently no approved therapeutic treatment; treatment consists of management of symptoms until the patient’s immune system defeats the virus.

That MAC/98alive™ offers a direct virucidal with the added benefit of boosting the recipient’s immune system makes it a compelling treatment candidate.

The estimated total economic cost of dengue in eight American and Asian countries was US$1.8 billion dollars. The government of Brazil recently announced a US$635 million vector control programme focused on reducing potential breeding habitats.

55% of the world’s population (approximately 3.4 billion people) is estimated to live in areas in which Dengue is endemic (including northern Australia). The virus is endemic in an estimated 124 countries causing between 70 and 500 million infections per year. An estimated 36 million cases of Dengue Fever and 2.1 million cases of DHF and DSS occur every year, with an estimated 21,000 deaths.

Over the past 10 years the level of Dengue infection has increased 30 fold.

Disease Control and Treatment Options

There are no antiviral cures or vaccines for the dengue virus currently available or licensed for sale. Treatment is effected via medication to lower the fever and decrease the pain of muscle aches and headaches. Blood transfusions may be necessary if severe haemorrhaging occurs.

Phase II Clinical Trial

A team including Professor Reynolds undertook a two centre single arm clinical study to ascertain the following:
  • The tolerability of MAC/98alive™ in dengue infected subjects at dosages between 300 and 900 mg per patient per day;
  • The effect of MAC/98alive™ on the viral load and NSI antigen concentration in the blood of dengue infected subjects;
  • The effect of MAC/98alive™ treatment on the severity of clinical dengue infection; and
  • Which dose is the most effective dose for curing dengue infection.

The study was evaluated and approved by the Testing Authority.

The cohort of 54 subjects meeting the inclusion criteria was split into five groups, four of which were to receive varying doses of MAC/98alive™ with the fifth being an untreated control group.

Distribution of Clinical Trial Subjects

Group Number of Subjects Daily Dosage Dengue Fever DHF Grade 1 DHF Grade 2 Serotype Number of Subjects
One 4 2 x 150mg 2 1 3 DV-1 10
Two 20 3x 150mg 12 5 5 DV-2 8
Three 20 2x 300mg 7 8 1 DV-3 10
Four 5 3x 300mg 3 1 1 DV-4 5
Five 5 None 3 1 1 Mixed 2
Total 54 27 16 11 54

Over the course of the nine-day treatment cycle, other than the control group and those receiving 300mg of MAC/98alive™ per day, all the subjects’ dengue viral loads were reduced to zero.

The natural course of Dengue infection, and that of the control group, is for an increasing incidence of viral loading with a peak between days three and five post infection (as the virus multiplies). The infected subject would normally be expected to be highly symptomatic during this period and would have the ability to pass on the infection to the vector.

In the treatment groups, the viral load decreased from day one (with no viral load peak). The control group’s viral load peaked on day three. The data are indicative of MAC/98alive™ having a high degree of potency when killing the virus, and its ability to act rapidly.

Group Average Viral Load Results
average viral load

The primary conclusions of the study included:

  • That MAC/98alive™ destroys all serotypes of the dengue virus, alleviating the symptoms of Dengue Fever;
  • That the speed of destruction was dose related;
  • That the [900] mg dose was most effective in treating dengue infection; and
  • That MAC/98alive™ was well tolerated in the test subjects.

Researchers also concluded that MAC/98alive™ decreased the plasma leakage process of infection with the dengue virus reducing the likelihood of Dengue Fever leading to the more life threatening condition of DHF and/or DSS.

The speed and comprehensive effect of MAC/98alive™ is likely to be a key factor in MAC/98alive™’s suitability to be used as both a prophylactic at the early stages of an epidemic as well as a fast acting therapeutic tool to control the spread of the virus.

No side effects (e.g. allergic reactions, gastrointestinal tract symptoms or hypertension) were observed from the treatment.

MAC/98aliveTM for Treatment of Dengue-PHASE III Clinical Trial

MAC/98alive™ commenced Phase III clinical trials at Airlangga University (Indonesia) in 2012, having successfully killed all four serotype infections in all the more than sixty study subjects to date.

On November 3rd 2013 at the infectious Disease Conference attended by over 600 scientists held at the Airlangga University Professor Nasronudin proudly announced to the world the successful Phase III clinical trial results.

THE RESULTS OF THIS TWO YEAR PHASE III HUMAN CLINICAL TRIAL BY AIRLANGGA UNIVERSITY INTO 98 ALIVE™’S EFFICACY IN TREATING DENGUE FEVER HAVE BEEN SO POSITIVE THAT EXPERTS ARE NOW SUGGESTING THAT THE DRUG BE ADOPTED AS THE STANDARD TREATMENT FOR THE DEADLY VIRUS IN INDONESIA.

Conducted by 12 leading scientists in Indonesia’s Airlangga University, the trial found the active ingredient in 98alive™ decreased the viral load of all four strains of dengue fever at an average rate of 96.67%.

The trial’s principal investigator Professor Nasronudin stated that 98alive™ has achieved what many international health organisations have been trying for decades to do.

“This finding is an innovation in treating dengue fever which up until now has had no vaccine or treatment therapy available.” Professor Nasronudin said. “Not only did it show 98alive™ has antiviral activity against the Dengue Virus, but results also indicated that it strengthens the immune system. Patients treated in the viral load group showed CD 4 cells increasing by 41% and CD8 cells increasing by 24%.”

Privately funded by the product’s developer Australian based 98 Alive Pty Ltd, the double blind, randomized and placebo controlled trial involved 530 patients in whom dengue fever infection was shown by Ns-1, 1gG and 1gM positive detection.

Professor Nasronudin states the results of the trial which was approved by the Medical Research Ethical Committee of Soetomo Hospital in Surabaya and supported by five hospitals and 10 primary centres, prove it to be a viable treatment for dengue.

“We are strongly suggesting to the Indonesian Government that 98alive™ be adopted as the standard treatment for all four strains of the dengue virus nationally” he explained. “No other product has produced the same results that we have with 98alive™ having no side effects; we can’t see any reason why it can’t be the primary treatment against that dengue fever in Indonesia.”

The Directors believe that the Phase III Airlangga University Clinical Trial’s successful outcome will facilitate gaining rapid regulatory approval both within the territories covered by the Initial Distribution Agreements and beyond as the only clinically proven, effective therapeutic treatment for Dengue Fever.

Potential Advantages of MAC/98alive™ for Treatment of Dengue

MAC/98aliveTM has a number of advantages over the proposed vaccine regimes under development.

These advantages will create significant competitive advantages over vaccines if they are ever developed successfully for commercialisation, and help establish MAC/98aliveTM as the primary treatment for dengue virus infection as well as an adjunct to vaccination in controlling infection during an epidemic as well as a treatment greatly alleviating suffering for those infected.

Competitive Advantages of MAC/98aliveTM for Treating Dengue Fever

Property Competitive Advantage
No competing product No commercially therapeutic treatment is currently available for Dengue Fever.
Therapeutic efficacy Proven virucidal properties against all serotypes of the virus.High-speed bioavailability means 98alive™ acts quickly against viral infection from first administration.
Speed of action Demonstrated virucidal activity within 10 minutes (in vitro).Demonstrated rapid absorption into blood serum (in vivo).

Demonstrated swift virus reduction and destruction.

No viral resistance risk Vaccines are always susceptible to viral mutation making them ineffective.  With no known report of viral resistance it offers the prospects of being a long-term therapeutic for dengue infection.
Infection Control By killing the virus so quickly, MAC/98aliveTM can minimise the number of humans capable of  passing on the virus to an uninfected vector both in terms of absolute numbers and also in terms of shortening the time frame during which they are capable to passing on infection.Travellers/visitors to an affected area can take MAC/98aliveTM as a prophylactic to reduce risk of carrying virus into previously unaffected areas or home.
Cost Treatment with MAC/98alive™ will prove less costly and more certain of outcome than vector control programmes.
Boost immune system Accelerates virus eradication by boosting the recipient’s immune system and therefore the recipient’s ability to fight the viral infection.Helps those most at risk by boosting impaired immune systems.

Principal Conclusions from Research to date:

  • MAC/98alive™ has proven rapid virucidal effects against four serotypes of Dengue virus
  • MAC/98alive™ caused no reported adverse effects
  • There has been no reported evidence of viral resistance developing inMAC/ 98alive™
  • MAC/98alive™ at the proposed dosage of 600mg per day is safe for human consumption
  • MAC/98alive™ at the clinical trial dosage of four capsules a day was well tolerated by human recipients.

Current Status
Clinical trials

MAC/98alive™ has completed a 500 plus person Phase III clinical trial at Airlangga University in Jakarta under Indonesian Government supervision.

Dengue Fever

Recommended Treatment
Table VIII

Treatment Recommended dosage for patients ages 7 and above (98alive™ capsule) Children from 2 to 7

 (98alive™ syrup)

General Dengue prevention 1 x 150 mg/day, for 16 days prior to exposure to infected patients 3 ml/day, for 16 days prior to exposure to infected patients
Dengue Fever 4 x 150 mg/day, for 3 days 3 ml/day, for 3 days
Dengue Haemorrhagic Fever and/or Dengue Shock Syndrome 4 x 150 mg/day, for 3 days 3 ml/day, for 3 days

Regulatory Approvals

Regulatory approvals are currently underway in countries where Dengue fever is widespread.