Category Archives: Drug Development

World No Tobacco Day – except to make malaria drugs

May 31st marks World No Tobacco Day. The Theme for 2017 is “Tobacco – a threat to development.” According to WHO, “Tobacco control has been enshrined in the Sustainable Development Agenda. It is seen as one of the most effective means to help achieve SDG target 3.4 of a one-third reduction globally, by 2030, of premature deaths from  noncommunicable diseases (NCDs).” Control is also associated with positive environmental and anti-poverty outcomes.

It is ironic then that the tobacco plant itself may be modified to produce life saving anti-malarial medicines. Nature reported that because Artemisia annua produces a precursor of the compound, artemisinic acid, only in low quantities, it is expensive to grow.  Consequently, “a team led by Ralph Bock at the Max Planck Institute of Molecular Plant Physiology in Potsdam-Golm, Germany, inserted genes for artemisinic acid synthesis into tobacco plants’ chloroplasts — abundant organelles that have their own DNA. By adding ‘accessory genes’ that make artemisinic acid production more efficient, they created a line that pumps out 120 milligrams of artemisinic acid per kilogram of biomass.”

Science magazine followed up to report that although “several years ago researchers transplanted the drugmaking genes into yeast, allowing them to collect the compound from a microbial brew, the fermentation process is still relatively expensive.” Tobacco, on the other hand, is an “inexpensive, high-volume crop.” Inserting the right genes into tobacco, they noted, would enable “harvesting artemisinic acid from a plot of land 200 square kilometers—less area than a city the size of Boston—would provide enough artemisinin to meet the entire worldwide demand.”

Malhotra et al. discovered another novel approach that found that, “Partially purified extracts from the leaves of transgenic tobacco plants inhibited in vitro growth progression of Plasmodium falciparum-infected red blood cells. Oral feeding of whole intact plant cells bioencapsulating the artemisinin reduced the parasitemia levels in challenged mice in comparison with commercial drug. Such novel synergistic approaches should facilitate low-cost production and delivery of artemisinin and other drugs through metabolic engineering of edible plants.”

Another approach looks at malaria vaccines. Beiss et al. note that malaria “transmission blocking vaccine (TBVs) need to be produced in large quantities at low cost.” They found a high level  transient expression in fresh leaves of Nicotiana benthamiana of an effective TBV candidate. Likewise Jones et al. demonstrated the potential of the new malaria vaccine candidate and also support feasibility of expressing Plasmodium antigens in Nicotiana benthamiana.

The American Cancer Society observed that most African Countries are in the early stages of the tobacco epidemic. This may be a good time to switch the production of tobacco on the continent from purveyor of cancer and NCDs to a ‘factory’ for producing malaria medicines. The sooner this can be done, the better since artemisinin  resistance is a growing threat.

Malaria, Onchocerciasis and Ivermectin – Possibility of Eliminating Two Diseases

Many tropical diseases are co-endemic in a given country and environment. Therefore, it only makes sense to learn whether there can be common strategies and synergies in disease control and elimination efforts. Onchocerciasis or River Blindness is carried by the black fly (simulium damnosum) that breeds along the banks of fast flowing rivers and malaria are examples.

Onchocerciasis was eliminated in many settings in the Sahel through the process or aerial spraying of these riverbanks to kill the black fly larvae. Though the insecticide used was often the same as used for malaria larviciding, the habitats differed and no synergies were achieved then.

?

Merck donates ivermectin to achieve control and elimination of onchocerciasis

Through subsequent programs using community directed treatment with ivermectin (Mectizan ®) interventions sponsored by the African Program for Onchocerciasis Control (APOC) it was learned that ivermectin also had beneficial effects on malaria transmission.

Ivermectin had been used in agriculture not only for internal parasites of animals. The agricultural community has long known that ivermectin kills both internal parasites (worms) but is also effective against some external parasites (lice and ticks).

Around 2010 scientists began to consider the anti-mosquito effects ivermectin might have when humans consumed it. It turns out that after a mass distribution in a community of ivermectin for onchocerciasis that mosquitoes feeding on people who had recently swallowed ivermectin would die. This was demonstrated when mosquitoes bit volunteers who took ivermectin of the first few days after consumption died there was no effect in the group not taking the drug.

buea3

Ivermectin distribution sessions in a Cameroonian village

Of particular interest was the fact that people who had consumed ivermectin would contribute to mosquito mortality even when they were outdoors. While the effect was not long lasting, the onchocerciasis control programs in the Americas have shown that it is safe to administer the drug two or four times a year.

Research that looks at the malaria parasite concluded that, “it is likely that ivermectin treatment is arresting parasite growth.” The researchers note that, “given the prior use of ivermectin and its safety record in humans and animals, it can be considered in combination therapy with other antimalarials.” The issue of dosage would need to be tested further.  Ivermectin at sub-lethal concentrations even inhibits the sporogony of P. falciparum in An. Gambiae.

Because of the need to find new and complementary tools to eliminate malaria the Malaria Policy Advisory Committee (MPAC) of the World Health Organization’s Global Malaria Program considered at its recent meeting the role of endectocides including ivermectin in the future of malaria control and elimination and the importance of further research.

The future of malaria elimination requires finding new tools to integrate with and the strengthening of existing tools. If these efforts also benefit the control and elimination of other diseases, the public’s health will benefit.

Preventing Malaria Drug Resistance in the African Setting …

and Dealing with it Should Resistance Occur

Professor Joseph Ana, Africa Centre for Clinical Governance Research & Patient Safety in Calabar, Nigeria shares his experiences and concerns in this blog.

Drug resistance is one of the biggest challenges facing health care systems in the world today. Around 25,000 people die each year from resistant viral and bacterial infections in Europe, but no new classes of antibiotics have come on the market for more than 25 years. The figures are difficult to obtain for Africa and other developing countries.

Medicine shops may sell inappropriate malaria medicines, thus contributing to resistance

Medicine shops may sell inappropriate malaria medicines, thus contributing to resistance

Drug resistance is considered important in the failure of control and treatment of diseases its consequences, and it is considered to be one of the causes of emergence of new strains of infective organisms and re-emergence of once-controlled diseases. The occurrence and impact of the phenomenon is worse in Africa and parts of Asia for malaria according to WHO and the US CDC. Viral and bacterial diseases are also affected in this region.

Therefore, there is urgent need for global sustained action to prevent drug resistance from happening, and to control it, if it happens. The causes of Drug resistance are varied including lack of or poor implementation of the control of access to drugs, population migration and movement, misdiagnosis, under-treatment and irrational drug prescription and use.

Global Report malaria drug resistanceTo prevent drug resistance, countries need to legislate and implement adequate control of access to drugs, sustain public education on the dangers of drug resistance, educate health workers on and enforce rational drug prescribing and use. Effective monitoring of treatment outcomes is also important to know when drug resistance is occurring. With the global and country by country best efforts drug resistance may still occur because of mutation and adaptation of infective organisms.

For diseases like Malaria for which resistance to the most effective drug today, artemisinin-combination drugs, is being reported from Southeast Asia, the development of new drugs alongside vector control is essential by all countries, particularly in Africa.


Professor Joseph Ana – BM.BCh (UNN), FRCSEd, FRSPH, JtCertRCGP-UK, DFFP (RCOG)-UK, DipUrology-UK, Cert.ClinGov.UK; Lead Consultant Trainer / CEO; joseph ana <jneana@yahoo.co.uk>; Contact: Africa Centre for Clinical Governance Research & Patient Safety; @Health Resources International (HRI WA); Consultants in Clinical Governance & Patient Safety (MDCN Accredited CPD Provider); 8 Amaku Street State Housing  (& 20 Eta Agbor Road UNICAL Road),  Calabar, Nigeria.

Visit Website: www.hriwestafrica.com; email: hriwestafrica@gmail.com    Tel: +2348063600642

Pneumonia and Malaria – similar challenges and pathways to success

ConcentrationOfPneumoniaDeathsWorld Pneumonia Day (WPD) helps us focus on the major killers of children globally. While Pneumonia is responsible for more child mortality across the world, in tropical malaria endemic areas both create nearly equal damage (see WPD graphic showing Nigeria and DRC which are both have the highest burden for pneumonia, but also malaria). Of particular concern is case management at the clinic and community level where there is great need to differentiate between these two forms of febrile illness so that the right care is given and lives are saved.

WPD_2014_logo_portraitDiagnostics are a particular challenge. While we now have malaria rapid diagnostic test kits that can be used at the community level, we must rely on breath counting for malaria. The Pneumonia Diagnostics Project (see video) “is working to identify the most accurate and acceptable devices for use by frontline health workers in remote settings in Cambodia, Ethiopia, South Sudan and Uganda.”

Ease of use at low cost must be achieved. One approach to solve the pneumonia diagnostics challenge at community and front line clinic level is to find “mobile phone applications or alternative energy for pulse oximetry,” to test low oxygen levels.

PneumoniaCareVaccine development for both diseases is underway. The challenge for malaria results from the different stages of the parasites life-cycle. Lack of affordable vaccines for pneumonia limits at present widespread preventive action, though public-private partnerships offer hope.

Dispersable and correct dose for age prepackaged malaria drugs are already available. Now more child-friendly medicines for pneumonia are being developed. In low resource settings, “amoxicillin dispersible tablets are a better option, particularly for children who can’t swallow pills. They have a longer shelf-life, are cost-effective, don’t need refrigeration, and are easy to administer.”

Similarities in the problems and solutions to control these two diseases require that interventions must continue to be developed and implemented jointly in order to benefit children the most. As can be seen again from the WPD graphics (right), many children do not get needed treatment. Integrated case management at all levels is the answer.

Open Source for Malaria Drug Development

Malaria Journal has launched a new series on malaria elimination in which the Journal’s editorial notes that, “The challenges remain formidable, but efforts must focus at all levels from developing better tools to how existing and future tools can be strategically combined for maximum synergistic effectiveness when integrated into different health and social systems prevailing in endemic areas.”

dscn7285sm.JPGGlaxoSmithKline (GSK)yesterday annnounced one way to help develop better malaria control tools. At the Council on Foreign Relations Andrew Witty announced the ‘open innovation’ strategy focusing on neglected diseases and malaria and explained that …

we have spent the last 12 months screening two million molecules in our compound library for reactions to the malaria parasite P. falciparum, the deadliest form of malaria found primarily in sub-Saharan Africa. This exercise has yielded more than 13,500 ‘hits’ that inhibited the parasite.

Apparently GSK itself has 5 or 6 in advanced phases of development. With this open sourcing, researchers, NGOs, governments and manufacturers in endemic countries can continue the work of drug development on the many other open source chemicals.  For HIV drugs GSK already has local manufacturers producing its products without charging royalties.

These activities build on GSK’s commitment, announced in February 2009, “to searching for new treatments for many of the diseases that affect millions of people in some of the world’s least well off nations. We have a heritage and expertise in researching and developing new medicines and vaccines, and we are directing our scientific resources into this important area.”

Hopefully such openness will spur local and appropriate solutions to disease control. Andrew Witty also encouraged other pharmaceutical companies to join in this process. With the early signs of artemisinin resistance on the horizon, new malaria drug research and development will always be needed until eradication is finally certified in the future.

PS – GSK contributes Albendazole for free to compliment donations of Mectizan by Merck for the lymphatic filariasis elimination program.