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2017 malaria outbreaks in Africa

août 20, 2017

The 2017 malaria avalanche

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April 2, 2017 – 19:29 — Pierre Lutgen
Bigpharma-WHO-Gates desperately try to ignore peer reviewed scientific papers documenting the spread of ACT resistance in at least 12 African countries (see “Artemisinin resistance In Africa” http://www.malariaworld.org).

Several medical teams in Africa have demonstrated in randomized, double blind clinical trials that Artemisia infusions are powerful in therapy and prophylaxis (see “Breaking news from clinical trials with Artemisia plants” http://www.malariaworld.org).

How long will the business and genocide with nets, pills and dubious vaccines last, before WHO authorizes the therapy with herbal Artemisia?

ZIMBABWE THE MALARIA CASES SURGE (Abigal Mwonde in The Herald, April 1. 2017).

The country has recorded a significant increase in malaria cases compared to the same period in the last two years according to the Ministry of Health. Dr Mberkunashe said 119 593 cases were recorded in the first 11 weeks of this year compared to 73 019 and 82 328 cases for the same periods in 2016 and 2015.

ALARMING RECRUDESCENCE IN NAMIBIA (Alvin Kapitako, New Era. Mar 29, 2017)

“Unfortunately, a resurgence occurred over the past three years with 24 682 cases reported in 2016, and 87 people succumbed to the disease,” said Haufiku. The minister added: “As evidenced by the outbreaks observed in 2014, 2016 and 2017, Namibia remains at risk for malaria epidemics and resurgence.” Ironically significant progress was made towards the goal of eradicating malaria with a 96 percent reduction in cases and deaths since 2001.

MALARIA IN 20 DISTRICTS, SPREADING AT ALARMING RATE (Deccan Chronicle. Apr 1, 2017),

While malaria was confined to Udupi and Dakshina Kannada in the past, it has now spread to eight districts of North Karnataka. Alarmed at the rate at which malaria is spreading in the state, the government is preparing to tackle it on a war footing. While malaria was confined to Udupi and Dakshina Kannada in the past, it has now spread to eight districts of North Karnataka and sporadic cases are being reported from another 12 districts, according to Secretary, Health and Family Welfare, Shalini Rajaneesh. “Malaria is now found in around 20 districts of the state and is spreading at an alarming rate,” she told reporters here.

BURUNDI MALARIA OUTBREAK KILLS OVER 4000 THIS YEAR (Rodney Muhumuza in Washington Post. March 29)

An outbreak of malaria has killed over 4,000 people in Burundi so far this year, the United Nations said Wednesday, a dramatic rise over the 700 victims the government announced just two weeks ago. There have been over 9 million cases of malaria in the East African nation since January 2016, according to the report by the U.N. humanitarian office. Burundi, one of the world’s poorest countries, has a population of about 11 million. The malaria cases are “well beyond the epidemic threshold,” the report said, citing World Health Organization investigators.

NIGERIA: 10 000 MALARIA, MENINGITIS PATIENTS IN 9 DAYS (Damilola Akinola, Nigerian Tribune April 2)

Sokoto State Government says it has treated no fewer than 10,000 meningitis and malaria patients since March 20 following the high alert in the state health sector. The state Commissioner for Health, Dr Balarabe Kakale, made this known to the News Agency of Nigeria (NAN) on Wednesday in Sokoto. They were treated of mixed cases of meningitis and malaria with some pockets of other minor ailments.

BOTSWANA: LEADERSHIP TACKELS MALARIA OUTBREAK (E Mmolai, Daily News Mar 27)

As a mitigating measure to the Malaria outbreak, North West leadership has agreed to embark on a massive indoor residual re-spraying exercise in the district. This comes after an announcement by health officials that the district was hard hit by the epidemic as currently it recorded 794 cases of Malaria and five deaths in the highly affected region.

PRETORIA: THE TRUTH ABOUT MALARIA OUTBREAK (Theto Mahlangu, The Citizen Mar 23)

The department recently distributed pamphlets, urging residents to, among other things, stay indoors between sunset and sunrise, or wear long pants, socks and shirts with long sleeves when they have to go outside. Other precautionary measures include to keep windows and doors closed before dark.

IN COLOMBIA; ECUADOR THE INCREASING TREND OF MALARIA CASES CONTNUED IN 2016,

Eight of the 21 endemic countries (the Bolivarian Republic of Venezuela, Colombia, the Dominican Republic, Ecuador, Guatemala, Honduras, Nicaragua, and Peru) reported an increase in cases compared to the previous year.According to a new Pan American Health Organization Epidemiological Alert this week, UN health officials are reporting an increase in malaria transmission in certain areas of this region in 2016, including an increase in the most serious strain of the mosquito borne parasite, Plasmodium falciparum.In summary a 16% increase compared to the cases reported in 2014

MALARIA RAISE IN RWANDA

According to 2016 WHO report « In November 2016 we registered nearly 700,000 cases countrywide. We also noticed the resistance to insecticide, » Aimable Mbiturumuremyi, an official at Rwanda’s Health Ministry stated

ANGOLA: MALARIA DEATHS RISING Reporting by Herculano Coroado;

« This new malaria outbreak has devastated the entire country, even in provinces that have low endemic prevalence we are seeing the spread and surge in cases, » the WHO’s Angola representative Hernando Agudelo Ospina said.

MALARIA EPIDEMIC OUTBREAKS IN RDCONGO Célestin N. Nsibu, Reference: MWJ2015, 6, 11 part I: cross-sectional survey in Mweka District A series of fever outbreaks has previously been reported in the DR Congo

MALAWI GOVERNEMENT IS FACING MALARIA CHALLENGE

Nyassa Times, Zawadi Chilunga, Mar 15 2017 Malawi government is facing challenges to fight malaria that kills many people every day, with the news about the acute shortage of anti-malarial drugs in the countr. Ministry of Health spokesperson Adrian Chikumbe confirmed that public health facilities have run out of the essential drugs such as Lumerfantrine Artemether commonly known as LA.Venezuela: cases of malaria surge 76%

TANZANIA: MALARIA SEEN ESCALATING

Dodoma — The government has released a statement to mark « Universal Malaria Day » that indicates that the current infection rate status in the country is worse compared to the situation that prevailed in the past five years.

According to a press release given out in Dodoma yesterday by the Minister for Health, Community Development, Gender, Elders and Children, Ms Ummy Mwalimu the infection rate this year has reached 14.8 per cent compared to 10 per cent in the year 2012.

MALARIA OUTBREAK IN MADAGASCAR

The surprise here was to observe one in a zone of high transmission where people are supposed to have developed immunity.

In COLOMBIA, ECUADOR, VENEZUELA the increasing trend of malaria cases continued in 2016.

In 2015, eight of the 21 endemic countries (the Bolivarian Republic of Venezuela, Colombia, the Dominican Republic, Ecuador, Guatemala, Honduras, Nicaragua, and Peru) reported an increase in cases compared to the previous year.According to a new Pan American Health Organization Epidemiological Alert this week, UN health officials are reporting an increase in malaria transmission in certain areas of this region in 2016, including an increase in the most serious strain of the mosquito borne parasite, Plasmodium falciparum.In summary a 16% increase compared to the cases reported in 2014.

IN LIMPOPO S.A. MALARIA CASES RISE 50%

Malaria remains a serious public health threat as it could easily rebound, the NICD’s deputy director, Lucille Blumberg, warned on 02 May 2017.

Recent papers indeed ring alarm bells

Plasmodium chabaudi malaria parasites through a step-wise increase in artesunate dose evolve extremely rapidly slow clearance rates. These slower clearance rates provide fitness advantages to the parasite through increased overall density, recrudescence after treatment and increased transmission potential. Removal of only the susceptible parasites by artesunate treatment led to substantial increases in the densities of resistant parasites.

LC Pollitt, S Huijben, A Read, Rapid response to selection and increased transmission potential in artesunate-selected Plasmodium parasites, PloS Pathogens 2014, 10,4, e1004019.

The same research team found that mixed infections also are frequent in the mosquito. Mixed strains are obtained after multiple infective bites and accumulate in the mosquito and increase malaria transmission to the vertebrate host, with implications for the evolution of the parasite virulence and the spread of drug resistant strains

LC Pollitt, A Read, Existing infection facilitates establishment and density of malaria parasites in the mosquito vector. PLOS Pathogens, 2015, e1005003

CAPE VERDE: ‘Sudden and unprecedented increase’ in malaria in 2017

SOUTH SUDAN : Over 4,000 people have died from Malaria in the past six months. (AFP)

The Malaria disease is spread in an “unprecedented” level in South Sudan, killing thousands in the past six months, revealed an official in the health ministry. Isaac Maber told Asharq Al-Awsat that at least 4,000 people have died from Malaria since February, with over 900,000 also being infected.

Publicités

Artemisia afra cures Buruli ulcer with high efficacy. Possible role of gallium.

juillet 15, 2017

Following up on same encouraging earlier trials, we launched with our African partners and the French association M4L larger scale clinical trials. The results obtained in these trials are extraordinary.
The trials were run in the Maniema province of RDC and were coordinated by Dr Jerome Munyangi who has alrready run the very successfull clinical trials with Artemisia plants against malaria, tuberculosis and bilharzia. The treatment consisted in the administration per os of an Artemisia afra decoction during 14 days and the application of a poultice containing an Artemisia afra extract during 28 days. These produces were from » Mother Nature » in Burundi. 21 patients completed the full treatment, some others were lost from sight. Those who took the complete treatment were totally cured, without any need
for surgical intervention. No remanent limitation in movements or other sequelae were noticed as it often happens after antibiotic treatment. Mycobacteria were counted under the microscope by the Ziehl-Neelsen method. No remaining mycobacteria could be detected after the treatment.

RTS vaccines: 20 years of false hopes

juin 14, 2017

The first results of the RTS,S vaccine already appeared in 1998 in a scientific paper. The conclusion was: Immune responses did not correlate with protection. Further optimization in vaccine composition will be required to induce longer-lasting protective immunity.
Stoute JA, Kester KE, Ballou Wr. Long-term efficacy and immune
responses following immunization with the RTS,S malaria vaccine.
J Infect Dis. 1998 178(4), 1139-44

Another randomised trial of the efficacy of RTS,S against natural P. falciparum infection in semi-immune adult men was run in The Gambia in 2001. Vaccine efficacy, adjusted for confounders, was 34%. Protection seemed to wane: estimated efficacy during the first 9 weeks of follow-up was 71% (46-85), but decreased to 0% (-52 to 34) in the last 6 weeks.
Bojang KA, Milligan PJ, RTS, S Malaria Vaccine Trial Team
Efficacy of RTS,S/AS02 malaria vaccine against Plasmodium
falciparum infection in semi-immune adult men in The Gambia: a
randomised trial. Lancet. 2001 Dec 8;358(9297):1927-34

In a trial of 2008, the rate of efficacy against the more clinically relevant end point of clinical malaria in children 1 to 4 years of age was 30%
Philip Bejon, John Lusingu, Ally Olotu., Efficacy of RTS,S/AS01E
Vaccine against Malaria in Children 5 to 17 Months of Age. NEJM
2008, 359, 2521-39

In 2009 vaccine efficacy over the 45-month surveillance period against a first or only episode of clinical malaria disease was 30.5% and the VE against all episodes was 25.6%
Sacarlal J, Alonso PL. Long-term safety and efficacy of the
RTS,S/AS02A malaria vaccine in Mozambican children. J Infect Dis.
2009 Aug 1;200(3):329-36. doi: 10.1086/600119.

In 2013 6,537 infants aged 6–12 wk and 8,923 children aged 5–17 mo were randomized to receive three doses of RTS,S/AS01. Vaccine efficiency against clinical malaria in infants was 27%, with no significant protection against severe malaria, malaria hospitalization, or all-cause hospitalization
Sanjeev Krishna, Academic Editor. Efficacy and Safety of the
RTS,S/AS01 Malaria Vaccine during 18 Months after Vaccination: A
Phase 3 Randomized, Controlled Trial in Children and Young
Infants at 11 African Sites. PLoS Med. 2014 Jul; 11(7):
e1001685.

To continuously raise false hopes by massive press releases is immoral. Who pays for all these guinea pigs: Bill Gates or GSK Wavre?

La torture est légale aux Etats-Unis

mai 6, 2017

Extrait du livre de Tzvetan Tadorov. Les ennemis de la liberté, ed Robert Laffont 2012.
Abu Ghraib et Guantanamo ne sont pas des exceptions. Une publication officielle du gouvernement américain, datée d’avril 2009 sous Obama, a révélé la réglementation extrêmement tâtillonne de la torture, formulée dans les manuels de la CIA et reprise à leur compte par les responsables juridiques du gouvernement. Car telle est la nouveauté: la torture n’est plus présentée comme une infraction, regrettable, mais excusable. Elle est la norme même. On pouvait s’imaginer jusque-là que les pratiques de torture relevaient de ce qu’on appelée des bavures, dépassements involontaires des limites, provoqués par l’urgence du moment. On s’est aperçu au contraire qu’il s’agissait de procédures fixées dans les moindres détails, au centimètre et à la seconde près.
Ainsi les formes de tortures retenues sont-elles au nombre de dix, chiffre qui monte ensuite à treize. Elles sont reparties en trois catégories, dont chacune connaît plusieurs degrés d’intensité: préparatoires (nudité, alimentation manipulée, privation de sommeil), correctives (les coups) et coercitives (arrosage d’eau enfermement dans des boîtes, supplice de la baignoire). Pour les gifles, l’interrogateur doit frapper avec les doigts écartés, à égale distance entre l’extrémité du menton et le bas du lobe de l’oreille. L’arrosage d’eau du prisonnier nu peut durer vingt minutes si l’eau est à 5 degrés, quarante si elle est à 10 degrés et jusqu’à soixante si elle est à 15 degrés. Les privations de sommeil ne doivent pas dépasser quatre-vingts heures, mais après un repos de huit heures, elles peuvent recommencer. L’immersion dans la baignoire peut durer jusqu’à douze secondes, pas plus de deux heures par jour, pendant trente jours consécutifs. Un prisonnier particulièrement coriace a subi ce supplice à 183 reprises en mars 2003. L’enfermement dans une petite boîte ne doit pas dépasser deux heures, mais si la boîte permet au prisonnier de se tenir debout, on peut aller jusque huit heures de suite.
La contagion se répand bien au-delà du cercle limité des tortionnaires: plusieurs autres groupes de professionnels sont impliqués dans la pratique des supplices. Des conseillers juridiques du gouvernement sont là pour assurer l’impunité légale de leurs collègues et fournir une légitimation à leurs actes. Sont régulièrement présents des psychologies, des psychiatres, des médecins, des femmes (les tortionnaires sont des hommes, mais l’avilissement sous le regard des femmes aggrave l’humiliation). Pendant ce temps, des professeurs d’université produisent des justifications morales, légales et philosophiques de la torture. La torture marque de manière indélébile les torturés, mais elle corrompt aussi l’esprit des tortionnaires. De proche en proche la société entière se trouve atteinte par ce cancer. Un Etat qui légalise la torture n’est plus une démocratie.

Artemisias stronger than vaccines

mai 5, 2017

Tuesday, May 02, 2017 by: Tracey Watson

(Natural News) Though malaria is a virtually unknown disease to many in the U.S., it is a global menace that affects upwards of 212 million people annually, killing close to half a million in any given year. In the past, the medical approach to the treatment of malaria has been to prescribe a type of drug called Artemisinin Combination Therapies (ACTs). However, on the eve of World Malaria Day – which falls on the 25th of April each year – the World Health Organization (WHO) announced that it will be starting to test a new anti-malaria vaccine in the fields of Kenya, Ghana and Malawi, beginning in 2018. Though scientists involved with the development of the vaccine have called this “great news,” insisting it will “make a real difference,” is this vaccine really necessary, and will it live up to the hype? ………..
One wonders, therefore, why there is so much interest in developing an anti-malaria vaccine now, when the battle is clearly already being won. Very disturbing, too, is the fact that the Bill and Melinda Gates Foundation (BMGF) has been actively involved in the development of this vaccine, known as Mosquirix or RTS,S.
Granted, there has been a marked increase in the number of drug-resistant malaria cases worldwide, but that doesn’t mean a preventative vaccine is the best solution. Even if it doesn’t kill you – and who knows, when the BMGF is involved – vaccines have side effects and are not 100 percent effective. And there is a naturally available treatment that has been successfully used to treat malaria in traditional Amazonian, Chinese and African medicine for centuries, that doesn’t have side effects, can be grown anywhere and can even treat drug-resistant malaria: The Artemisia annua plant, commonly known as sweet wormwood or sweet annie.
The Health Ranger recently reported on a study published in the journal Phytomedicine, which describes how the Artemisia annua plant saved 18 patients in the Congo who were suffering from drug-resistant malaria that was totally unresponsive to any western medical treatment. When the patients failed to respond to ACTs, doctors tried the dried leaves of the Artemisia annua plant in a final bid to save their patients’ lives. After only five days of treatment, all 18 patients were 100 percent recovered, and blood tests revealed absolutely no remaining parasites in their blood.
If a naturally occurring, freely available plant medicine is available to treat drug-resistant strains of malaria, and other preventative measures have already turned the tide in the fight against this disease, any thinking person has to wonder why the BMGF, the WHO and others are suddenly pushing for the release of this new vaccine.

A new worldwide malaria outbreak

avril 17, 2017

A new worldwide malaria outbreak

Bigpharma-WHO-Gates desperately try to ignore peer reviewed scientific papers documenting the spread of ACT resistance in at least 12 African countries (see “Artemisinin resistance In Africa” http://www.malariaworld.org).
Several medical teams in Africa have demonstrated in randomized, double blind clinical trials that Artemisia infusions are powerful in therapy and prophylaxis (see “Breaking news from clinical trials with Artemisia plants” http://www.malariaworld.org)
How long will the business and genocide with nets, pills and dubious vaccines last, before WHO authorizes the therapy with herbal Artemisia?

ZIMBABWE THE MALARIA CASES SURGE (Abigal Mwonde in The Herald, April 1. 2017).
The country has recorded a significant increase in malaria cases compared to the same period in the last two years according to the Ministry of Health. Dr Mberkunashe said 119 593 cases were recorded in the first 11 weeks of this year compared to 73 019 and 82 328 cases for the same periods in 2016 and 2015.
ALARMING RECRUDESCENCE IN NAMIBIA (Alvin Kapitako, New Era. Mar 29, 2017)
“Unfortunately, a resurgence occurred over the past three years with 24 682 cases reported in 2016, and 87 people succumbed to the disease,” said Haufiku. The minister added: “As evidenced by the outbreaks observed in 2014, 2016 and 2017, Namibia remains at risk for malaria epidemics and resurgence.” Ironically significant progress was made towards the goal of eradicating malaria with a 96 percent reduction in cases and deaths since 2001.
MALARIA IN 20 DISTRICTS, SPREADING AT ALARMING RATE (Deccan Chronicle. Apr 1, 2017),
While malaria was confined to Udupi and Dakshina Kannada in the past, it has now spread to eight districts of North Karnataka. Alarmed at the rate at which malaria is spreading in the state, the government is preparing to tackle it on a war footing. While malaria was confined to Udupi and Dakshina Kannada in the past, it has now spread to eight districts of North Karnataka and sporadic cases are being reported from another 12 districts, according to Secretary, Health and Family Welfare, Shalini Rajaneesh. “Malaria is now found in around 20 districts of the state and is spreading at an alarming rate,” she told reporters here.
BURUNDI MALARIA OUTBREAK KILLS OVER 4000 THIS YEAR (Rodney Muhumuza in Washington Post. March 29)
An outbreak of malaria has killed over 4,000 people in Burundi so far this year, the United Nations said Wednesday, a dramatic rise over the 700 victims the government announced just two weeks ago. There have been over 9 million cases of malaria in the East African nation since January 2016, according to the report by the U.N. humanitarian office. Burundi, one of the world’s poorest countries, has a population of about 11 million. The malaria cases are “well beyond the epidemic threshold,” the report said, citing World Health Organization investigators.
NIGERIA: 10 000 MALARIA, MENINGITIS PATIENTS IN 9 DAYS (Damilola Akinola, Nigerian Tribune April 2)
SOKOTO State Government says it has treated no fewer than 10,000 meningitis and malaria patients since March 20 following the high alert in the state health sector. The state Commissioner for Health, Dr Balarabe Kakale, made this known to the News Agency of Nigeria (NAN) on Wednesday in Sokoto. They were treated of mixed cases of meningitis and malaria with some pockets of other minor ailments.
BOTSWANA: LEADERSHIP TACKELS MALARIA OUTBREAK (E Mmolai, Daily News Mar 27)
As a mitigating measure to the Malaria outbreak, North West leadership has agreed to embark on a massive indoor residual re-spraying exercise in the district. This comes after an announcement by health officials that the district was hard hit by the epidemic as currently it recorded 794 cases of Malaria and five deaths in the highly affected region.
PRETORIA: THE TRUTH ABOUT MALARIA OUTBREAK (Theto Mahlangu, The Citizen Mar 23)
The department recently distributed pamphlets, urging residents to, among other things, stay indoors between sunset and sunrise, or wear long pants, socks and shirts with long sleeves when they have to go outside. Other precautionary measures include to keep windows and doors closed before dark being Okavango.
MALARIA ON THE RAISE IN RWANDA.
According to 2016 WHO report « In November 2016 we registered nearly 700,000 cases countrywide. We also noticed the resistance to insecticide, » Aimable Mbiturumuremyi, an official at Rwanda’s Health Ministry stated
ANGOLA: MALARIA DEATHS RISING (Reporting by Herculano Coroado)
« This new malaria outbreak has devastated the entire country, even in provinces that have low endemic prevalence we are seeing the spread and surge in cases, » the WHO’s Angola representative Hernando Agudelo Ospina said.
THE MALARIA CRISIS INDIA DOESN’T WANT TO AKNOWLEDGE (Ankita Rao & Vivekananda Nemana)
An investigation shows routine manipulation of data, shortages of supplies, understaffing and enduring dysfunction. The wide gulf between India’s official record of 1,018 deaths and The Lancet estimate of 46,800 is causing some to worry that bad data are keeping resources from reaching the people who need them most.
In COLOMBIA, ECUADOR, VENEZUELA the increasing trend of malaria cases continued in 2016.
In 2015, eight of the 21 endemic countries (the Bolivarian Republic of Venezuela, Colombia, the Dominican Republic, Ecuador, Guatemala, Honduras, Nicaragua, and Peru) reported an increase in cases compared to the previous year.According to a new Pan American Health Organization Epidemiological Alert this week, UN health officials are reporting an increase in malaria transmission in certain areas of this region in 2016, including an increase in the most serious strain of the mosquito borne parasite, Plasmodium falciparum.In summary a 16% increase compared to the cases reported in 2014.
MALARIA EPIDEMIC OUTBREAKS IN RDCONGO
Célestin N. Nsibu, Reference: MWJ2015, 6, 11 part I: cross-sectional survey in Mweka District
A series of fever outbreaks has previously been reported in the DR Congo
MALAWI GOVERNEMENT IS FACING MALARIA CHALLENGE (Nyassa Times, Zawadi Chilunga, Mar 15 2017)
Malawi government is facing challenges to fight malaria that kills many people every day, with the news about the acute shortage of anti-malarial drugs in the countr. Ministry of Health spokesperson Adrian Chikumbe confirmed that public health facilities have run out of the essential drugs such as Lumefantrine Artemether commonly known as LA.
MALARIA OUTBREAK IN KENYA
“We started seeing an increase of people admitted with malaria last month, but we may not really know what caused it,” said Dr Philip Muthoka of the department of disease surveillance and response.
Between March 6 and March 27, 112 cases have been reported from Turbo alone,” Dr Muthoka added.
“We started seeing an increase of people admitted with malaria last month, but we may not really know what caused it,” said Dr Philip Muthoka of the department of disease surveillance and response.
He said the increase in malaria cases has been reported only in Turbo sub-county. “Other counties are below the alert line, so there is no cause for alarm. Between March 6 and March 27, 112 cases have been reported from Turbo alone,” Dr Muthoka added.

Un second massacre au Burundi

février 7, 2017

ecrit par Emile Schmitz

Le coupable: non pas la race ou la religion, mais le dollar.

En dépit des cris de victoire de l’OMS proclamant chaque année une chute spectaculaire du paludisme certains pays sont hélas confrontés à une recrudescence catastrophique. Tel est le cas du Burundi.
Le pays a rapporté 4 716 152 cas en 2014 et 7 813 958 cas en 2016. Une mission d’urgence de l’OMS a confirmé cette flambée dans un rapport du 1er février. Le plus alarmant est qu’elle confesse un échec flagrant des techniques mises en oeuvre. Une distribution massive de moustiquaires (MILDA) en 2014 avait provoqué une baisse momentanée des cas. Cet effet fut de courte durée et comme dans d’autres pays africains cette distribution a souvent augmenté plutôt que diminué l’incidence. Cet effet est fort inquiétant et peut avoir plusieurs causes:
– de nombreuses études scientifiques ont montré que les moustiques deviennent de plus en plus résistants aux pyrethroides d’imprégnation. Et ces moustiques plus résistants sont plus virulents, plus efficaces pour la transmission.
– les pyrethroides comme d’autres insecticides affaiblissent le système immunitaire des enfants, premières victimes du paludisme.

La Ministre de la Santé du Burundi ne peut pas plaider l’innocence.
La mission de l’OMS ne manque pas de la critiquer vertement en constatant qu’elle a manqué de réaliser et de déclarer cette flambée, limitant ainsi les possibilités d’assistance internationale. Elle ne peut pas ignorer que dans les pays de la région un remède des plus efficaces est mis en œuvre contre le fléau: la tisane d’Artemisia. Et cela avec l’appui et l’encouragement des autorités sanitaires, des Ministères de la Santé et même de l’OMS-Afro. En Tanzanie, au Kenya, en Ouganda, en RDCongo, en Afrique du Sud et dans au moins six autres pays africains. Et la plante la plus efficace s’avère être une plante africaine, l’Artemisia afra, autant et plus que la variété chinoise Artemisia annua.

Le Ministère de la Santé du Burundi semble tout faire pour que cette thérapie ne soit pas connue. En 2014 une équipe d’experts universitaires internationaux qui venaient au Burundi pour en parler ont vu leur conférence interdite par ce même Ministère. Et pourtant des plantations de Artemisia annua et afra existent au Burundi depuis dix ans grâce à Hannelore Klabes. On sait aujourd’hui que c’est sur injonction de Bigpharma, de l’OMS, de MSF et de l’Institut des Maladies Tropicales et Coloniales d’Anvers que la conférence était interdite. On sait aussi que certaines de ces organisations gagnent jusque 6% sur chaque pilule ACT vendue en Afrique.
Il y a aussi l’énorme lobby des moustiquaires ou UNCEF, Bill & Melinda, USAID et Global Fund sont les distributeurs/vendeurs attitrés. Le marché du paludisme en Afrique et les bénéfices qui en découlent sont colossaux. De l’argent sale entaché de sang.
Le Burundi a reçu cette année $32 195 135 pour l’achat de MILDA et d’ACT.
En absence de toute autre approche approuvée par les financiers du Nord, la mission de l’OMS recommande d’augmenter la distribution de moustiquaires (sic) avec un nouveau subside de $36 000 000. Les ACT ont presque disparu du marché à l’exception des falsifications. Les ACT ont donné des résistances non seulement au Cambodge mais également dans une dizaine de pays africains, selon des études scientifiques publiées. Un génocide programmé.
Et pourtant des essais cliniques récents sur un millier de patients impaludés au Maniema voisin ont montré que l’infusion d’Artemisia est beaucoup plus efficace que les pilules ACT-ASAQ, et sans effets secondaires, sans recrudescence. En effet au 28e jour il n’y a plus de parasites ni même de gamétocytes dans le sang. Cette absence de gamétocytes a été confirmée dans un essai de prophylaxie récent avec 200 enfants dans deux écoles de la même province congolaise. Après un mois de traitement de trois tasses d’infusion par semaine une absence totale de paludisme a été observée chez ces enfants. On peut donc, non seulement guérir ou prévenir le paludisme avec cette plante, mais également enrayer la transmission au moustique. Oui, éradiquer ce fléau.
L’Artemisia afra est une plante pérenne ne contenant pas d’artemisine et utilisée depuis des générations contre la malaria et d’autres maladies, donc selon les règles mêmes de l’OMS et la FAO automatiquement qualifiée comme plante médicinale et complément alimentaire dans ces pays africains.
Ce sont de courageux médecins de plusieurs pays africains qui ont développé et démontré cette approche révolutionnaire.
Comme Kenyatta, Nkrumah, Lumumba, Mandela, ont conquis l’indépendance politique, eux
entreront dans l’histoire comme vainqueurs du néocolonialisme de BigpharmaOMS et de ses laquais basanés.

Émile Schmitz Athus

Artemisia afra clinical trials: malaria, tuberculosis, bilharzia

novembre 13, 2016

Jérôme Munyangi, Maniema, RDCongo, Lucile Cornet-Vernet, M4L France, Pierre Lutgen, IFBV-BELHERB, Luxembourg,
Contact: lutgenp@gms.lu
Since 9 years the association IFBV-BELHERB from Luxembourg has established a working relationship with African and South American universities, in close cooperation with other European research institutions. Several of these partners have run clinical trials with Artemisia annua tea. In all these trials a therapeutical effect of 95 % or higher was confirmed by the use over 7 days of whole leaf infusion [1], [2], [3], [4] capsules or tablets. One of the surprising effects noticed in these trials was that that the artemisinin content had very little impact on the results. This lead us to make an analysis as complete as possible of all the constituents, organic and inorganic, in a large series of Artemisia annua samples from different origins [5]. The effect of polysaccharides, amino acids, polyunsaturated fatty acids, pentacyclic triterpenes, cumarins, phytosterols and saponins has been neglected in the past [6]. Several papers have shown that A. annua ingested as powdered leaves or in conjunction with fatty food significantly increases the artemisinin concentration in the blood and even overcomes resistance to artemisinin [7]. It is well documented in the literature that A. afra or sieberi which contain little or no artemisinin are extensively used as antimalarials. They contain at least 5 molecules of the same antimalarial efficacy as artemisinin. Recent research from the Al Quds University has shown that aqueous infusions of several Artemisia species strongly inhibit beta-hematin, like chloroquine did [8]. But the most important finding in several of the clinical trials, especially in Kenya and Uganda, was that people who drink one or two cups of Artemisia annua tea per week become immune against malaria [9]. At Lubumbashi, RDCongo Dr C Kansango Tchandema has shown in 2014 that Artemisia annua and Artemisia afra raised CD4+[see2]. Anti-HIV properties of Artemisia afra have been documented by a team at the University of Leiden [10]. Strong prophylactic results have been obtained with ARTAVOL, a mixture of herbs developed Dr Patrick Ogwang at the Ministry of Health . The produce does not contains Artemisia without artemisinin. In fact the antimalarial properties of Artemisia plants other than Artemisia annua are no surprise. The Chinese favoured Artemisia apiacea and the French in Algeria during 100 years protected their soldiers against malaria with Artemisia absinthium.
In 2015 [11] a team of medical doctors in RDCongo, Jerome Munyangi and Michel Idumbo, have run randomized clinical trials on a large scale in the Maniema province with the participation of some 1000 malaria infected patients. The trials were run in conformity with the WHO procedures and compared Artemisia annua and Artemisia afra with ACTs (Coartem and ASAQ). For all the parameters tested herbal treatment was significantly better than ACTs: faster clearance for fever and parasitemia, absence of parasites and gametocytes as confirmed by PCR on day 28 for 99.5% of the Artemisia treatments and 79.5% only for the ACT treatments. A total absence of side effects was evident for the treatments with the plants, but for the 498 patients treated with ACTs, 210 suffered from diarrhea, and/or nausea, pruritus, hypoglycemia etc. The efficiency was equivalent for Artemisia annua and Artemisia afra [see2]. More important even is the observation for the total absence of gametocytes after 7 days treatment with the herb. A tremendous hope for malaria eradication. The results have been communicated to the local health authorities, and to the Ministries of Health and Research in the RDCongo who were supportive of these trials. The draft of a paper is almost ready and will be submitted to a peer reviewed scientific journal.
In parallel with the clinical trials against malaria, (see Breaking News Jan. 5 on http://www.malariaworld.org) the same team has completed another large scale randomized, double blind trial against schistosomiasis, Artemisia vs Praziquantel. The results confirm previous anecdotic results from several countries in Africa. Both arms in this trial had 400 infected patients. The treatment efficiency was 97 % in the Artemisia arm and 71% in the Praziquantel arm. No side effects were noticed in the Artemisia treatment. Praziquantel caused vomiting in 26.5% of the patients, abdominal pain in 18.5%, cephalalgy in 15.5%. Very impressive is the fact that the Artemisia treatment led to an unexpected almost complete absence of eggs in feces after 2 months. Schistosomiasis kills 150 000 Africans per year and more than 70 000 000 are infected. A neglected disease in neglected, poor populations where the only existing drug, Praziquantel, loses efficiency year after year.
In 2016 clinical trials have been run against Tuberculosis and Buruli ulcer with Artemisia annua and Artemisia afra. Screening trials in 2015 had been promising and these recent large scale, randomized, double blind have resulted in an obvious therapeutic effect of these plants against Mycobacteria, not only tuberculosis but also Buruli ulcer. After three weeks of treatment the Ziehl stain assay is negative for alcohol-resistant bacteria. They will be published in the scientific literature. Most of us ignore that on Nov 3, 2015 a Convention was signed in Bali declaring the fight against the looming TB-Diabetes co-epidemic, one of the greatest global health challenges. An estimated two billion people, or one third of all people worldwide, live with a tuberculosis (TB) infection, of whom 9.6 million people develop active TB disease annually. TB is the leading cause of death worldwide due to a single infectious pathogen, responsible for 1.5 million human deaths in 2014, and 95 percent of human TB deaths occur in low- and middle-income countries. Diabetes mellitus is escalating worldwide. Clinical assays are planned to be run in the Katanga province of RDCongo with Artemisia plants against diabetes.
All these trials are run in compliance with the WHO protocol, full approval of the health authorities of the country and the province and encouragements of WHO-Afro.
References:
1.Chougouo Kengne RD, Kouamouo J, Moyou Somo R, Penge On Okoko, (2009). Comparative Study of the Quality and Efficiency of Artemisinin Drug Based and Artemisia annua grown in Cameroun, MIM conference, Nairobi, Kenya, 2 Nov 2009, MIM 15225512
2. Kansango Tchandema C, Lutgen P. (2016) In Vivo Trial on the Therapeutic Effects of Encapsulated Artemisia annua and Artemisia afra. Global Journal for Research Analysis, 5(6), 228-234
3.Gebeyaw T, Vigzaw 1,, Tegbar V. (2010), Use of the Plant Artemisia annua as Natural Anti-Malarial Herb in Arbaminch Town, Ethiop J Health Biomed Sc 2(2), 75-81
4. Zime-Diawara H, Ganfon H, Gbaguidi F, Yemoa A (2015), The antimalarial action of aqueous and hydro alcoholic extracts of Artemisia annua L. cultivated in Benin, Journal of Chemical and Pharmaceutical Research, 7(8): 817-823
5.Chougouo Kengne RD (2010) Rapport de Stage. Mise au Point et Validation des Procédures analytiques pour la Détermination de certains Composés de la Plante Artemisia annua, Université des Montagnes, Cameroon, Laboratoire National de la Santé, Luxembourg
6.Onimus M, Carteron S, Lutgen P (2013) The Surprising Efficiency of Artemisia annua Powder Capsules. Med Aromat Plants 2: 125. doi:10.4172/2167-0412.1000125
7. Elfawal M, Towler M, Reich NG, Weathers P and Rich S (2014) Dried whole-plant Artemisia annua slows evolution of malaria drug resistance and overcomes resistance to artemisinin. http://www.pnas.org/cgi/doi/10.1073/pnas.1413127112
8. Akkawi M, Suhair J, Ogwang PE, Lutgen P (2014), Investigations of Artemisia annua and Artemisia sieberi water extracts, Medicinal & Aromatic Plants 3:1, ISSN: 2167-0412
9. Ogwang PE, Ogwal JO. Kasasa S. Deogratius O, Obua C (2012) Artemisia annua L. Infusion consumed once a Week reduces Risk of multiple Episodes of Malaria: A randomised tTrial in an Ugandan Community, Trop J Pharm res 13(3) 445-453
10.Van der Kooy F. Artemisia annua and its Anti-HIV Activity (2014) T. Aftab et al. (eds.), Artemisia annua – Pharmacology and Biotechnology, DOI: 10.1007/978-3-642-41027-7_14, Springer-Verlag Berlin Heidelberg
11 This document is an abstract intended for fast disclosure. It is based on personal communications. Figures, graphs and references of the clinical trials will be included in the peer reviewed scientific papers to be published in the coming months..

Bali, tuberculosis, diabetes and Artemisia

août 18, 2016

Most of us ignore that on Nov 3, 2015 a Convention was signed in Bali declaring the fight against the looming TB-Diabetes co-epidemic, one of the greatest global health challenges.
An estimated two billion people, or one third of all people worldwide, live with a tuberculosis (TB) infection, of whom 9.6 million people develop active TB disease annually. TB is the leading cause of death worldwide due to a single infectious pathogen, responsible for 1.5 million human deaths in 2014, and 95 percent of human TB deaths occur in low- and middle-income countries.
Diabetes mellitus is escalating worldwide. More than half of people with diabetes are unaware of their condition as they have never been tested, and 84% of all undiagnosed cases live in low and middle income countries,
People with diabetes are two-to-three times more likely to develop TB when compared to people without diabetes. The excess vulnerability to TB disease in people with diabetes is mainly related to altered immune response to TB infection as a consequence of high blood sugar due to undiagnosed or poorly controlled diabetes.
A Lancet study in 2009 had confirmed the convergence of the two epidemics (KE Dooley et al. Lancet Infect Dis. 2009. 91, 737-746). In 1934 already this link had been discovered in Boston MA (H Root, N Eng J Med 1934, 210,78). In a study in Egypt, which compared 119 patients with treatment failure to 119 controls, diabetes conferred a 3 times increased risk of treatment failure (AM Morsy et al., East Meditter Health J. 2003, 9, 689-701). Two retrospective cohort studies of patients with pulmonary tuberculosis in Maryland, USA, have shown a 6.5 times increased risk of death in diabetes patients (KK Oursler et al., Clin Infect Dis 2002, 34, 752-59). It appears also that tuberculosis may lead to diabetes in those not previously known to be diabetic (GP Nichols, Am Rev Tuberc 1957 76, 1016-30).
Our associations IFBV-BELHERB from Luxembourg and M4L from Paris are involved in clinical trials with African partners to study the in vivo effect of Artemisia annua and Artemisia afra on these diseases. Screening trials in 2015 had been promising and recent large scale, randomized, double blind have resulted in an obvious therapeutic effect of these plants against Mycobacteria, not only tuberculosis but also Buruli ulcer. After three weeks of treatment the Ziehl stain assay is negative for alcohol-resistant bacteria.
These trials were run in the province of Maniema, RDC Congo, in accordance with the WHO protocol and ethical approval of the local health authorities. They will be published in the scientific literature.

Jerome Munyangi, Lucile Cornet-Vernet, Pierre Lutgen

Why are Artemisia infusions prophylactic? the herbicidal hypothesis

juin 3, 2016

Ἓν οἶδα ὅτι οὐδὲν οἶδα
Σωκράτης
Our association IFBV-BELHERB has received numerous anecdotic reports on the prophylactic effects of Artemisia plants. This effect has been documented in scientific papers. Patrick Ogwang from Uganda (Ogwang PE, et al. Trop J Pharm Res. 2012;11:445–53) showed that an infusion of Artemisia annua consumed once weekly reduced the risk of Plasmodium falciparum episodes due to a yet unidentified constituent. All this is an important lead as classical antimalarial drugs like quinine (D.Shanks, Am Soc Trop Med Hyg, 2016, May), chloroquine (T Sahu et al., Frontiers in Microbiology, 2015, 1, 283), artemisinin are not prophylactic. They only act on the erythrocytic stage but have no impact on the liver stage invasion. They are just designed to kill the parasites in the erythrocytes, but they leave a bloody battlefield and a depressed immune system. Some even enhance the gametocytogenesis.
Many medicinal plants used against malaria in endemic areas are aimed to treat the acute symptoms of the disease such as fevers and their action is limited to these symptoms. In some endemic areas of the Brazilian Amazon region one medicinal plant seems to be an exception: Ampelozyziphus amazonicus, localla named “Indian beer” used to prevent the disease when taken daily as a cold suspension of powdered dried roots (VF Andrade-Neto et al., Int J Parasitology, 2008, 38, 1505-11). In infections induced by sporozoites, chickens treated with extracts of this plant were partially protected against Plasmodium gallinaceum. Some animals did not become infected, whereas others had a delayed prepatent period, lower parasitemia and a reduction in mortality. A delay in the time until parasites establish blood stage infection is not a minor effect. It reduces the risk of severe and cerebral malaria.
In a previous document published on http://www.malariaworld.org “Pentacyclic triterpenes in antimalarial plants, a new paradigm” we alerted to the important role these acids play in malaria control. And indeed Ampelozyziphus amazonicus is very rich in pentacyclic triterpenes, mainly betulinic acid (D do Carmo et al., Pharmacognosy Magazine, 2015, 11, 244-250). Betulinic acid, maslinic acid, oleanolic acid, ursolic acid and others seem thus to be responsible for the prophylactic activity of these plants. But that does not explain why.
Another good example for the antimalarial and prophylactic effect is Phyllantus amarus. This plant is well known for these properties in Ghana (R Appiah-Opong et al., Ghana Medical Journal, 2011, 45, 143-146), in Burkina Faso (M Traore et al., Phytother Res. 2008. 22, 550-1, in Nigeria, RDCongo (L Tona aet al., J Ethnopharmacol. 2004, 93, 27-32), but also in China, India, Brazil. The aqueous extract shows suppressive and curative properties similar to standard antimalarials like chloroquine, or artesunate, but it also shows prophylactic properties by delaying the onset of infection (T Ajala et al., Asian Pacific J Trop Med 2011). The plant is very rich in pentacyclic triterpenes.
DO PENTACYCLIC TRITERPENES ACT AS HERBICIDES AGAINST THE PLASMODIUM APICOPLAST
The apicoplast is a plastid organelle, homologous to chloroplasts of plants or algae, that is found in apicomplexan parasites like Plasmodium or Toxoplasma. In hindsight it seems incredible that such an organelle with a nonmammalian metabolism could so long have concealed its identity in parasites that have received as much scientific attention as Plasmodium (RF Waller et al., Curr Issues Mol Biol 7, 2005, 57-80). It is now recognized that this large group of parasites had a photosynthetic ancestry and were converted into parasitism early in the evalution of animals. Apicoplast function is necessary for both intraerythrocytic and intrahepatic development. Recently it was found that the apicoplast is also present in the gametocytogenesis, in the sexual stage of Plasmodium falciparum. But only the female macrogametes have an apicoplast, the male microgametes don’t (N Okamoto et al., Eukaryot Cell 8(1) 2009, 128-132).
Attempts have been made to find antimalarials which selectively attack the apicoplast. Several antibiotics are known to interfer with this organelle. They do not kill parasites in the first generation, but the progeny of drug-treated parasites suffer a delayed death, probably because they lose their apicoplast and the second generation of merozoites is unable to penetrate erythrocytes. Antibiotic treatment specifically inhibits the biogenesis and inheritance of the apicoplast in Plasmodium falciparum liverstage, resulting in continuous liver stage maturation but subsequent failure to establish blood-stage infection. This process of maturation of numerous merozoites in the liver induces potent immune protection for subsequent infections. This prophylactic protection obtained by several antibiotics was demonstrated to be exceptionally robust (J Friesen et al., http://www.ScienceTranslationalMedicine.org, 2010, 2).
Many herbicides also have an activity against the malaria protozoan (S O Duke, Weed Science, 58, 2010, 334-339). Herbicides interfer with plant cells by interrupting mitosis and the formation of multinucleated cells. A good example is the action of herbicides from the nitroanilin family (trifluralin, oryzalin). They have a strong action on Plasmodium falciparum. The herbicide amiprophosmethyl also has antimalarial activity and a significant action on schizogony, i.e. the formation of multinucleated parasites. A more surprising example is the effect of the well known glyphosate on several apicomplexa like Plasmodium falciparum, Toxoplasma gondii (F Roberts et al., Nature 393, 801-805, 1998).
Several herbicides including those of the cyclohexanedione family act by perturbing the apicoplast fatty acid biosynthesis (C Goodman et al., Int J Parasitol. 2014, 44, 285-289). This synthesis is dispensable in blood stages of human and rodent malaria, but vital for for the liver stage.
Artemisia annua has strong allelopathic properties as was documented by Mediplant in Switzerland. In other words the plant becomes invasive and inhibits the growth of other plants or cash crop on fields where Artemisia has been planted for the extraction of artemisinin. A recent paper from Iran (MH Bijeh Keshhavarzi et al, J Biol & Envir Sci. Nov 2014) describes the allelopathic effects of Artemisia annua on lettuce Lactuca sativa. The aqueous extract on an outside plot significantly reduced germination percentage and rate, fresh and dry weight. Another paper (Seyed Mohsen et al., Annals of Biological Research, 2011, 2-6, 687-69) describes the allelopathic effect of Artemisia annua aqueous extracts on vegetables and plants like Portulaca olearcea (pursley), Chenopodium album (goose-foot), Avena ludoviciana (oat), Plantago ovata (plantain). For the latter the effects are noticeable on germination percentage, germination rate, plumule length, radicle length, wet weight, dry weight. A Chinese paper (Shen He et al., Ying Yong Sheng Tai Xue Bao. 2005 Apr;16(4):740-3) had previously studied the allelopathy of different plants. Artemisia annua affected the seedling height and fresh weight of radish, cucumber, wheat and maize around 50%.
But the allelopathy of Artemisia remains a controversial issue. Although in vitro trials on seed germination of various plants show an impact of artemisinin and flavonoids, this remains far from field effects noticed and may only offer a partial explanation, Artemisinin and flavonoids are hardly soluble in water and rapidly degraded in the soil.
A recent paper offers an explanation which is very attractive proposing the role of pentacyclic triterpenoids in the allelopathic effects of Alstonia scholaris. (Wang CM1, J Chem Ecol. 2014 Jan;40(1):90-8). Alstonia scholaris is a tropical evergreen tree native to South and Southeast Asia. Alstonia forests frequently lack understory species. However, potential mechanisms, particularly the allelochemicals involved remain unclear. They identified allelochemicals of A. scholaris, and clarified the role of allelopathic substances from A. scholaris in interactions with neighboring plants and showed that the allelochemicals from leaves, litter, and soil from A. scholaris were identified as pentacyclic triterpenoids, including betulinic acid, oleanolic acid, and ursolic acid. In the field, ursolic acid accumulated abundantly in the soil in A. scholaris forests, and suppressed weed growth during summer and winter. A. scholaris pentacyclic triterpenoids influence the growth of neighboring weeds by inhibiting seed germination, radicle growth, and functioning of the photosystem.
These molecules are stable in powder form and in water for months (P Puttarak et al., Natural Product Sciences, 2016, 22, 1-20)
If the pentacyclic triterpenes have an allelopathic, herbicidal effect, this offers a completely new hypothesis and opportunity for destroying the malaria parasite in all its forms, from hepatocytes to gametocytes.
THE SKIN AS BARRIER
As the primary interface between the body and the outside environment, the skin protects the host against invading organisms.
It has always been assumed that sporozoites rapidly exit the injection site and enter the blood circulation. But it was demonstrated by PCR that the majority of the infective sporozoites remain in the skin for hours (L M Yamauchi et al., Cellular Microbiology, 2007, 9, 1215-22). The same authors had shown in preliminary studies no decrease in the sporozoite loads in the skin up to 3h. These findings imply that there is ample time for host and parasite to interact at the inoculation site and that tailored treatments of the skin might inhibit the survival of the sporozoites before they enter the bloodstream. At 37°C the time required for sporozoite penetration in hepatoma cells is 3 hours (VF Andrade-Neto op.cit.). Malaria-specific CD8⁺ T cells are primed in the skin draining lymphs (S Chakravarty et al., Nat Med 2007, 13, 1035-1041). A significant reduction in anti-sporozoite CD8⁺T cell response was observed in animals that had their draining lymph nodes removed prior to sporozoite infection. Pentacyclic triterpenes could play a role. Topical application of ursolic and maslinic acid for example significantly reduces epidermal inflammation, NF-κB, Cox-2 and skin tumor proliferation (Jiyoon Cho et al., Oncotarget, 6-36, 39292-305).
The high concentration of pentacyclic triterpenes in the skin of fruits or barks of trees evidently has the function to repel parasites and molds and to prevent their entry into the fruit or plant. Betulinic acid acts as an antifeedant (SG Jagadesh et al., J Agric Food Chem. 1998, 46, 2297-99). It affects the growth of larvae and pupae (V Lingampally et al., Asian J Plant Sc and Res. 2012, 2, 198-206).
HEPATOCYTES
Unlike many other microbial organisms that utilize the phagocytic properties of their host for invasion, sporozoites actively invade hepatocytes. They even pass through several hepatocytes prior to the final hepatocyte in which they develop. The reason for this process is not well understood; it is likely that the sporozoites choose the best environment for their differentiation into merozoites. Sporozoites have specialized secreting organelles in the apical region which play a central role in host cell invasion. The migration through several hepatocytes increases sporozoite competency for the formation of these apical organelles.
To survive and develop in the parasitophorous vacuole inside the hepatocyte the parasite has developed several strategies including depletion of CD-8 lymphocytes and suppression of NF-κB to prevent cell death. The circumsporozoite protein (CSP) plays a key role in this inhibition of NF-κB.
Memory CD8⁺T cell populations residing in the liver provide the first line of defence against naïve infections, but more even in subsequent infections and are the key players of the recall response. Any immune strengthening approach, including vaccines, requires the generation of a robust, stable memory population. In particular, CD4⁺cell help was shown to be required for CD8⁺memory cell responses against malaria (She-Wak Tse et al., Mem Inst Oswaldo Cruz 2011, 106, 172-178). CD4⁺helper T cells are critical orchestrators of immune responses. CD4⁺T cells decrease the threshold required for protective immunity and this immunity may last for months (NW Schmidt et al., PNAS, 2008, 105, 14017-22).
It was shown that oleanolic acid upregulates the CD4⁺and CD8⁺populations (J Wang et al., International Immunopharmacology 2012, 14-4). It was also found that betulinic acid increased the total number of thimocytes, splenocytes, lymphocytes. It is a potential biological response modifier and may strengthen the immune response of its host (Y Jine Polish J Veterinary Sc. 2012, 15, 305-13). This is in line with our findings in Katanga where we confirmed that administration of capsules containing Artemisia leaf powder raised the CD4⁺ (Constant Kansongo Tchandema, personal communication). This strengthening of the immune system by Artemisia plants may also be related to the pentacyclic triterpenes they contain.
Delayed apoptosis of infected hepacytes is another strategy of defence of the sporozoites. Blocking apoptosis allows the parasite to complete its full cycle and the merozoite burden is strongly enhanced. It fully exploits host cell resources and ultimately produces tens of thousands of merozoites which are released from the hepatocyte. Sensitizing the infected hepatocyte to apoptosis may substantially reduce parasite burden. Recent evidence suggests that Plasmodium infected hepatocytes are similar to cancer cells. The authors demonstrate that the anticancer drug obatoclax reduced the number of infected hepatocytes by > 70%, but had limited effect on uninfected cells (A Kaushansky et al., Cell Death and Disease, 4. E762). Many pentacyclic triterpenes, like betulinic acid, are used in cancer treatment. It seems worthwile to study their effect in malaria infection.
Several antibiotics also have an effect during the hepatocytic stage. Others, including tetracyclines and clindamycin used for the treatment of malaria, have little action on the pre-erythrocytic stages.
An extensive study has been made on the antibiotic thiostrepton and the effects of this drug on life-cycle stages of the malaria parasite in vivo. Preincubation of mature infective sporozoites with thiostrepton has no observable effect on their infectivity. Sporozoite infection both by mosquito bite and sporozoite injection was prevented by pretreatment of mice with thiostrepton. Thiostrepton eliminates infection with erythrocytic forms of Plasmodium berghei in mice. (M Sullivan et al., Mol Biochem Parasit 2000 109, 17-23).
After its release from the hepatocyte the merozoites penetrate the erythrocytes very rapidly. Parasite entry into erythrocytes is a complex, dynamic process. The invading merozoite orients its apical end toward the junction of invasion. Invagination of the erythrocyte bilayer then results in engulfment of the parasite. Merozoites without their apicoplast are unable to penetrate red blood cells.
GAMETOCYTES
A study of the Walter Reed Army Institute already in 1992 found that the herbicide Trifluralin showed strong anti-malarial effects not only on Plasmodium falciparum in cultures, but also transmission blocking by inhibiting gametocyte maturation and viability (J Nath et al., 19th Army Science Conference, 1994).
Thiostrepton (op.cit) treatment of infected mice reduces transmission of parasites by more than ten-fold, indicating that the plastid has a role in sexual development of the parasite. These results also indicate that the plastid function is accessible to drug action in vivo and important to the development of both sexual and asexual forms of the parasite.
Supply of the isoprenoid building blocks isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) is the essential metabolic function of the apicoplast for isoprenoid biosynthesis, particularly during gametocytogenesis. When IPP supplementation was removed early in gametocytogenesis, developmental defects were observed, supporting the essential role of isoprenoids for normal gametocytogenesis. Furthermore, mosquitoes infected with gametocytes lacking the apicoplast developed fewer and smaller oocysts that failed to produce sporozoites. This finding further supports the essential role of the apicoplast in establishing a successful infection in the mosquito vector (J Wiley et al., Eukaryotic Cell 2015, 14, 128-133)