TREATING CHILDHOOD MALIGNANCIES IN SUB-SAHARAN AFRICA: MEDICAL HOBBYISM OR A SUSTAINABLE CONTRIBUTION TO CHILDREN’S HEALTH?

The new Rolls-Royce is a stunning example of modern technology: it not only features climate control for all four seats, but also massage chairs, umbrella’s hidden in the doors and a humidifier. The engine is state of the art and build with the finest materials and its safety is according to the manufacturer unsurpassed. It even has a malfunction detector that will automatically inform you as well as the garage that a certain part of the car is – or about to become – broken and should be replaced. So the question is: would we use this car to drive from Kinshasa to Harare? Probably not, unless you own a couple of them. The roads are not made for its suspension, the precious white leader seats too vulnerable for Africa’s black mud and if the car breaks down, spare parts cannot be found anywhere on the continent. Driving a Rolls-Royce through Africa is generally considered a laughable act of stupidity.

Pediatricians at the Academic Medical Center (AMC) in Amsterdam have initiated a pediatric oncology program in Malawi in collaboration with doctors from Stellenbosch University in South-Africa, who were already involved in treating childhood malignancies in Sub-Saharan Africa. Their main focus has been on Burkitt’s lymphoma, Wilms’ tumor and Karposi’s sarcoma. The first two are potentially curable diseases, while the latter is usually not. During a symposium at the AMC on 29 April, their latest result were shown to the public. It was all organized as a special celebration for Ms Trijn Israels’ PhD-thesis, which she successfully defended the day before. A subject of her research has been treating Wilms’ tumor in children in Malawi.

Treating Wilms’ tumor in the West is challenging: it requires a solid combination of chemotherapy, radiation and surgery to obtain favorable results and remission. After the first rounds of chemotherapy to downstage the tumor, patients should be optimally prepared for surgery. Duration of post-nefrectomy chemotherapy and radiation depends on the stage and grade of the tumor that can only be assessed after histopathological examination. During the whole course of treatment, healthcare staff should be fully concentrated on signs of toxicity, developing of fever or nausea and need for blood or platelets transfusion. To have a child with Wilms’ tumor on the ward is highly demanding for the medical as well as the non-medical staff.

In a pilot study in Malawi between 2006 and 2008, a total of 20 patients with Wilms’ tumor were included. Compared to European standards, children often presented at a late stage of the disease and 8 patients (40%) already had metastases. Of the 12 other patients who were able to undergo surgery after initial chemotherapy, 8 were still alive after the full treatment with a median follow up period of 8 months (survival rate 40%).

The picture with the treatment of Burkitt’s lymphoma (BL) is somewhat more encouraging. BL has a high prevalence in Sub-Saharan Africa that co-incites with the holo-endemic area for malaria. Increased exposure to the ubiquitous Epstein-Barr virus in combination with malnutrition is furthermore assumed to explain the existence of a ‘lymphoma belt’ that runs from Ivory Coast to Tanzania like a girdle around Africa’s waist.

BL is an aggressive tumor and Denis Burkitt already found out in Uganda in 1958 that a single dose of cyclophosphamide can make the tumor disappear like snow through sunshine. After Denis Burkitt first discovery, the world of pediatric oncology has moved forward like a high-speed train and European protocols exist for every stage of this disease. Overall cure rates are somewhere between 90% – 80% and most hazards derive from the treatment itself, like tumor lysis syndrome and septicaemia in a neutropenic patient. So when physicians of the Stellenbosch University and the AMC started to treat BL in Malawi using European protocols, it became a fair disappointment with many children dying from the toxic effects of the chemotherapy (survival rate just over 50%).

And so adjustments were made and instead of combining four cytotoxic agents to combat the malignant cells, cyclophosfamide monotherapy was developed as the standard treatment with the addition of intra-thecal methotrexate in stage 1 and 2 tumors. Additionally, the duration of treatment was decreased from 52 to 28 days. The yielded results were impressive: in stage 1 and 2 tumors, survival rates of 90% and 70% respectively were achieved. Patients with a stage 3 tumor have a 60% 1 year survival rate. The results in stage 4 tumors with CNS involvement continue to be dismal: only 10% of patients is still alive after 1 year. It needs to be emphasized that children with BL only have a 5% risk of relapse after the first year of remission.

Can the care for children with cancer be feasible in Africa? Patients often present at a very advanced stage of the disease, most come from rural areas which brings plenty of obstacles for the follow-up, many are malnourished and anemic even before initiation of treatment which further increases the risk of surgery and/or opportunistic infections, hospitals require a blood bank and well trained staff to observe and manage side-effects, supportive and palliative care including morphine should always be available and Western trained pediatricians with experience in oncology should be within arm’s reach to educate local staff.

It is highly respectable that pediatricians have taken up this challenge, are willing to face and deal with the hurdles that lay ahead and refuse to neglect the fate of children who suffer from a deathly disease that does not carry the name malaria, malnourishment, tuberculosis, diarrhea or HIV/AIDS. That they have chosen to do so by adjusting their own familiar Rolls-Royce treatment to the situation on the ground in Africa is a first step, but many more will have to be taken to make this initiative a success, particularly in regard to pushing back the number of patients that present at a advanced stage of disease.

HET DEFINITIEVE MORELE FAILLIET VAN ISRAEL

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Sinds haar oprichting in 1948 heeft Israël altijd geworsteld met haar legitimiteit. Voor Israël zelf, haar (Westerse) bondgenoten en ondergetekende staat haar bestaansrecht nog steeds buiten kijf, maar hoe anders is dat sinds mensenheugenis voor de omringende Arabische landen. Als ik niet zou schrijven maar zou tekenen dan zou ik deze Arabische staten voorstellen als een recalcitrante baby die in een kinderstoel zit. De kleine jongen wordt gevoed door een volwassene (Westerse bondgenoten) en de pap die hij krijgt toegestopt draagt de naam Israël. Met de lippen op elkaar schudt het kind telkens het hoofd als de lepel te dichtbij komt. De volwassene duwt de lepel tegen de lippen en knijpt in de wangen van de dwingeland om hem de pap door de strot te duwen. Maar stug blijft hij weigeren het toegediende (door) te slikken.

Deze opgelegde dwang cumuleert in 1967 in collectieve Arabische agressie jegens de Joodse staat. Israël voelt zich terecht bedreigd en slaat terug. Sterker nog, Israël deelt een ongenadig pak rammel uit en binnen 6 dagen is het pleit beslecht en heeft Israël niet alleen de eerste echte militaire overwinning in haar korte geschiedenis op zak, maar zijn ook de Sinaï woestijn, de Westelijke Jordaanoever en delen van Oost-Jeruzalem geannexeerd. Het geeft een enorme dosis zelfvertrouwen die echter al vrij snel ontwaart in ongekende hybris welke zich in de daaropvolgende jaren als onkruid nestelt in de politiek van Israël. Zo kan er een bibliotheek gevuld worden met alle VN resoluties die door Israël aan haar laars zijn gelapt, om maar één voorbeeld te noemen.

De afgelopen jaren hebben zo’n lange reeks aan misdaden gebracht dat die niet alleen meer disproportioneel is te noemen in relatie tot de dreiging van Hamas, maar ook dat het met alle mogelijke retoriek niet meer goed valt te praten en ook niet langer ongestraft kan blijven voortbestaan. Gebruik van clusterbommen in Libanon, een rücksichtslos bombardement in Gaza met 1300 burgerdoden, continuering van de bouw van illegale nederzettingen, het bouwen van een muur die dwars door Palestijnse boomgaarden loopt en de Palestijnse bevolking afscheidt van haar universiteiten, scholen en waterputten, mensonterende behandeling van Palestijnse vluchtelingen, weigering te praten over een kernwapenvrij Midden-Oosten en de totale blokkade van Gaza waarbij ook vrouwen en kinderen bijna letterlijk de keel wordt dichtgeknepen omdat Hamas er de – democratisch verkozen! – macht heeft.

Het is werkelijk onbegrijpelijk dat het Joodse volk, dat in haar bestaan zoveel ontberingen, leed en vervolging heeft moeten ondergaan, thans in staat is om zo meedogenloos met een ander volk om te gaan. Maar de climax van dit nietsontziende criminele beleid kwam deze week. Een konvooi van schepen met hulpgoederen (dekens, voedsel, tentzeil, kleding) werd in internationale wateren geënterd door Israëlische commando’s die het vuur openden en daarbij zeker 10 pro-Palestijnse activisten doodden. De overige opvarenden werden opgesloten. De hulp zou een poging zijn de legitimiteit van Israël te ondermijnen, maar dat heeft Israël met deze nieuwe grove schending van het internationale recht zelf gedaan. Wederom.

Het is zelfdestructief gedrag. Een land dat op een dergelijke neerbuigende manier omgaat met kritiek, mensenrechten en burgers (onder andere van Westerse bondgenoten) kan niet langer onvoorwaardelijk de hand boven het hoofd worden gehouden. Het is de hoogste tijd om deze kleine, eigenwijze en ongehoorzame snotneus los te laten en op eigen benen te laten staan en dan zullen we zien hoe snel volwassenheid bereikt wordt.

Nurse Jen

For quite some time now I have a serious weakness for nurses. My mother used to be one, but mockingly I have come to the conclusion that my admiration towards nurses has developed despite that and not because. I do remember though, how much I was impressed when my mother told me a story about a patient. My mother was 19 years old and the patient was a 27 year old convicted murderer. He had been admitted for appendicitis and his inflamed rudimentary organ had been surgically removed. There was a guard in front of his room 24/7. The dangerous patient, however, did not want to go back to his cell. He preferred the confined, near-sterile space of his hospital room and in order to avoid the harsh and dirty environment of jail, he smeared his own excrements into the fresh wound, deliberately prolonging his stay at the ward and herewith the close proximity of my mother, who happened to be his nurse.

At the end of my first year of medical school, I went to Santa Barbara in California to work as a nurse’s aide at the local hospital. This is a mandatory part of medical school to make the young and cocky doctors-to-be more familiar with the work done by the nurses. I was assigned to ward 6C (hematology and oncology) at the Santa Barbara Cottage Hospital and during one month my days consisted of giving sponge baths, cleaning sheets, folding sharp hospital corners, transport patients to radiology, disposing the contents of urinals, changing diapers, holding kidney trays in front of patients whose chemotherapy induced nausea had just pushed them towards vomiting, taking temperatures, checking i.v.’s, etcetera. But soon I learned that these elements just make up the skeleton of the work. The real soul of the job comes from the personality of the ones performing these duties.

There and then in 2001, I met nurse Jennifer Hubbard, 22 years old and fresh from nursing school at the University of South California. One day I was assigned to be her aide and it opened my eyes. Not only because of her beauty – she was stunning: a brunette with deer-like greenbrown eyes intensely radiating under long eyelashes, long and tainted fingers with manicured nails and perfect white teeth always exposed as she never stopped smiling – but mostly because she brought a personal touch to the work she did. Cheerful, tender, vivacious, compassionate and attentive; signaling deteriorations as well as improvements in patients’ conditions and acting accordingly. She seemed to naturally master every aspect of her job.


I was not the only one to notice. No matter how awfully sick they felt, patients would brighten up when she entered the room. She was genuinely interested and had a second nature for making people feel at ease. That included me, even though I remember how she once put a hand on my shoulder and I felt like sparkling water was running through my veins towards my brain and abdomen. Many times afterwards, it took much less from nurses for me to fall in love with them, but Jennifer was the first one. We kept in touch occasionally, and I have been contemplating on that small possibility our paths would cross again. To catch up, so to speak.

Today I found out that she had a car accident. On an early Saturday morning she was on her way to ward 6C. She swerved of the road and crashed on the shoulder. Her car flipped over. When the paramedics came her heart was no longer beating and her lungs had given up all attempts to breath. She died at the scene.


JENNIFER SHAY HUBBARD 8 SEPTEMBER 1977 - 15 MAY 2010

NO MORE GOOGLE IN CHINA ;(

It will not be long before people will start to ask each other the question which of the two superpowers they prefer: China or the United States. It will be a personal one and most likely not to be answered by a shrug of the shoulders: the differences between the two are just too striking.

When George W. Bush met Hu Jintao – the president of China – in Washington in 2003, the two of them exchanged personal thoughts and views in an open and mutually friendly atmosphere . That is according to the statement made by The White House afterwards. The conversation between both leaders was later revealed in more detail.

“The upmost important within a society”, stated Bush confidently after taking a sip of his tea, “is liberty and the freedom of speech.” He knew what he was talking about since he himself had delivered liberty and freedom to the people of Iraq.

Hu Jintao replied in his humble voice after a moment of silence. His modesty could not, however, camouflage his firm inclination.
“I do not agree. The most important is harmony between the people that make up the society.”

For him and the majority of Chinese people in China, that is the end of the discussion. Contrarily, for many outside of China, that marks just the beginning of one: primarily through websites that cannot go beyond the Great Firewall of China.

HUMANITARIANISM AT STAKE

James Orbinski's "An Imperfect Offering" Reviewed

Since 1945 the art of warfare has changed dramatically: of the 80 wars fought after World War 2 only 28 were traditional battles between regular armies of two or more nations. There has been a steep increase in civil wars and guerrilla war tactics in the second half of the 20 century and the majority of all these wars took place in developing countries (65 out of 80). James Orbinski, a Canadian physician and former general director of Médecine Sans Frontiers (MSF), takes us in his autobiographical page-turner to the frontlines of these battlefields where total anarchy is the only rule and where not only his own life was in jeopardy regularly but the act of humanitarianism as well.

We meet the protagonist when he is 27 years old, fresh out of medical school and heading for Rwanda to do research on paediatric AIDS. Before that he had told us already about his childhood, his Irish background and the first encounter with humankind’s cruelty when he links the tattooed number on the arm of the Jewish cobbler down the street to the images shown on a program on TV about the holocaust. He is then 13 years old and very upset.

In Rwanda he eagerly commences his research about the relationship between craniofacial dysmorphy and HIV infection during pregnancy. Oblivious to the country’s horrible colonial past where German and Belgium doctors and anthropologists draw racial conclusions based on facial features, the young graduate measures meticulously the characteristics of the faces of Rwandan HIV infected children, looking for differences.

A few years later in Somalia, on his first mission for MSF, Orbinski swiftly loses his naivety: for the first time he is confronted with the destructive effects of violence and anarchy. He is exposed continuously to people in sheer agony and at the same time gets involved in world politics when George Bush senior decides to dispatch troops to provide security for famine-relief operations, like the one Orbinski is working for.

When back in Canada he feels a stranger in his own country, and when he is offered the posting of head of mission in Rwanda in 1994, he has no shred of doubt. It is there and then that the devastating effects of the genocide and the endless frustration from the idle of the West and the Security Council presented to him is multiplied beyond description and it makes his work the more admirable yet incredibly daunting. His innocence is lost, just as is so many other’s.

After a final mission in war-torn Goma in the Democratic Republic of Congo, he retreats from the actual medical frontline when he is elected general director of MSF. He becomes a frequent flyer and commutes between failed states, Geneva, Brussels and the UN headquarters in New York, where he occasionally addresses the Security Council. Orbinski is a widely recognized good public speaker, solid words spoken with a soft voice, and the written sentences in his book add to his determination to improve the situation for the world’s less privileged.

Orbinski does not mince words. His first fight was against the prices of anti-retroviral treatment (ART), deliberately maintained high by the pharmaceutical industry, and it was a good one from the beginning. In that fight world politics, national interests, pharmaceutical companies, NGO’s, the UN, judges, journalists and patients all came together and with clever diplomacy, science, international trade laws and persistence from a carefully chosen coalition, Goliath was eventually defeated by David but the battle is far from over.

The latest threat to humanitarianism comes – again – from the West. In the last decade invading coalition forces have been initiating humanitarian actions as well to win “hearts and minds”. As a result the clear distinction between aggression and aid has become blurry. Where in Africa MSF was still able to work in the midst of rival armies, bullets where seldom aimed at them. But in Iraq and Afghanistan MSF had to suspend its operations after intentional attacks and kidnapping of its employees.

Orbinski’s life story is impressive and adventurous, but what begins as an exciting boys’ book soon evolves into dramatic non-fiction. He gives us details we would rather not hear but we cannot look away: his style is too accessible for that, his story too gripping. Yet after all the tragedies and massacres witnessed, he is still able to hold on to his optimism and the epilogue exhales hope: no one can do everything, but everyone can do something.

Precies goed!

De minst stressbestendige verpleegkundige komt nerveus naar me toe om te melden dat er een 6 jarig jongetje met topletsel is binnengekomen. Het huilen in de gang zwelt aan en ik zie een bebloede gele theedoek die om een linker hand is gewikkeld met daarachter het van pijn verwrongen gezicht van – naar ik later zal vernemen – Timon. Zijn ouders lijken nog meer ontdaan. Als hij in een kamertje zit en de deur is gesloten, komt ook de rust weer terug.

Er zijn weinig collega’s die enthousiast worden van een topletsel, of beter gezegd een afgescheurd, gesneden of getrokken topje van een vinger en zeker niet als daar een theedoek omheen zit. Bij het afwikkelen ervan weet je nooit wat je tegen zult komen. Vaak zijn het kinderen die nog even snel hun vinger tussen de auto- of voordeur steken voordat papa hem dichtsmijt.

Voordat ik de kamer binnenloop trek ik alvast verdoving op en stop het weg in de zak van mijn jas. Als ik de deur opendoe is het huilen inmiddels gereduceerd tot een snikken. Ik geef de ouders een hand en begroet de jongen. “Waarom ben jij hier?”

“Nou”, begint het rustig, “Damon woont op nummer 12 maar hij kan er niets aan doen”. Damon is dus de oorzaak van het consult, zover is het nu duidelijk. “Ik was daar aan het spelen. Ik woon zelf op nummer 7, vlakbij het voetbalveldje”. Maar hij is nog niet uitgesproken, dit was slechts een introductie. “Ik was bij Damon aan het spelen, maar hij kan er echt niets aan doen”. Iedereen in de kamer hangt aan zijn lippen. En toen? “Nou, we wilden naar het veldje maar toen heeft hij de deur dicht gegooid. Maar hij zag niet dat ik achter hem liep”.

Ik wil het wel zien, zijn ouders liever niet. Timon is ook nieuwsgierig als ik de theedoek verwijder. Het snikken blijft uit, hij is voor het eerst stil. Het topje van de linker wijsvinger ligt er bijna in zijn geheel af. Er staat nog een klein stukje huid dat als een bruggetje van nog geen vijf millimeter het topje incluis nagel met de rest van de vinger verbindt.

“Maar wat ga je nu dan doen want ik moet straks nog naar voetbaltraining?” zegt hij. Ik vertel dat de vinger weer helemaal mooi zal worden maar dat ik hem eerst moet verdoven. Zodra hij hoort dat daar een naald voor nodig is begint het snotteren. Als een paar seconden later de basis van de vinger wordt verdoofd is het snotteren aangezwollen tot gebrul. Daar is gelukkig het woord “klaar” voor uitgevonden.

Als ik de eerste hechting zet, is de spraakwaterval alweer in volle gang. Hij verhaalt over het voetbalveldje waar toch een groot deel van zijn leven moet afspelen en van zijn nieuwe keeperhandschoenen gaat het naar Finding Nemo om vervolgens de verwarming aan te halen waar hij vorig jaar nog op was gevallen. Ik kijk met een schuin oog zijn moeder aan. “Als hij eenmaal begonnen is houdt hij niet meer op”, beantwoordt ze mijn blik.

Ondertussen houdt hij aandachtig mijn handelingen in de gaten. Hij heeft gezien hoe de eerste hechting is gezet en geeft mij nu aanwijzingen voor de tweede. “Ja, en nu moet je een knoopje maken”, is zijn advies. Ik volg het op en geef hem de schaar in zijn rechterhand. Direct wil hij de draadjes doorknippen, maar ik kan hem net op tijd tegenhouden. Ik kijk hem aan. “Ik werk hier al meer dan 20 jaar”, zeg ik, “en niemand heeft ooit voor mij de draad doorgeknipt”. Zijn mond beweegt niet meer en ik heb zijn aandacht. “Dat komt omdat ik ze niet te lang wil hebben en ook niet te kort. Het moet precies goed. Knip maar!”.

Na de schaarbeweging blijven er twee draadjes over die als blauwe haren van bijna vier centimeter uit de vingertop steken. “Precies goed!”, zeg ik waarna hij zich niet meer stil kan houden. Hij kijkt zijn ouders aan als hij vertelt hoe belangrijk het is om de draadjes op de juiste lengte af te knippen. Samen naaien we de vingertop er weer aan. Hij heeft een talent voor knippen, ieder draadje is precies goed!

Als de vinger is verbonden loopt mij naar de radiologie afdeling voor een foto. Bij terugkomst weet hij mij al te vermelden dat het niet is gebroken. Want anders hadden we volgens hem de vinger in moeten gipsen. “En ook dat moet altijd precies goed!”.

THE AMBIGUITY OF THE NEW MALARIA VACCINE CANDIDATE

In the quest for a new, reliable malaria vaccine, GlaxoSmithKline (GSK) is way ahead. Their product, known under the code name RTS,S/AS02D, is the most promising candidate to become officially registrated as a vaccine against malaria. After encouraging results in children in Mozambique in 2004, a pivotal fase III randomized controlled clinical trial has recently been initiated in Mozambique, Tanzania, Gabon, Ghana and Kenya and the stakes are high. So will these achievements eventually bring a world where malaria can be contained closer or are they just part of a vulgar pharmaceutical rat race?

In Verona last September at the 6th European Congress on Tropical Medicine and International Health, there was a pleasant mixture of lectures, workshops and round-table discussions. A wide range of tropical diseases was covered with a special emphasis on malaria. And so the stage was set at one point for GlaxoSmithKline to deliver a lecture on the development of their vaccine and the latest results. The message was clear and encouraging: what started in 1987 with the first steps has now resulted in a safe, reliable and effective vaccine against malaria in infants and young children. Colourful graphs and fancy tables were shown to the public: after a 3 dose regimen 1442 children were followed for 18 months for episodes of malaria and side effects. RTS,S reduced clinical malaria episodes by 35 percent and severe malaria episodes by 49 percent. No serious side effects were reported. Overall it turned out that children vaccinated with RTS,S were 29 percent less likely to develop malaria after the full follow up period. The fase III trial will bring the definite answer to the question of reliability, safety and effectiveness of RTS,S.


And so after these hopeful sounds there was room for a couple of questions from the audience. A gentleman from England introduced himself: he was a microbiologist. He wondered whether a vaccine that is effective in only half of the population will increase the virulence of the parasite in the other half. Should we be aware of an increase in cases of severe malaria after final introduction of the vaccine? The answer was all but straightforward: that could not be predicted yet. The trial lacked data on the severity of malaria episodes witnessed in the control group. Time should tell us. Next question please. A woman from Kenya raised her finger. First of all she praised all the work done by GSK and was hoping for a quick introduction of the vaccine after the fase III trial. In her opinion, the vaccine had already proven its use. Her question was whether GSK was willing to sell the vaccine for its actual value. Or else, was the company willing to produce the vaccine in cooperation with other (local?) pharmaceutical companies so that it could be spread among the population at the lowest possible cost? The representative of GSK had been expecting this question. He swiftly replied. “We have developed this vaccine for over 20 years and we have put a vast amount of our resources into producing it. We cannot afford to have other companies profit from all the effort we have put in."

Hence, after a one hour session one item remains unanswered while on one item the company’s position is crystal clear. For the future it remains doubtful whether the effectiveness in about half the children will have serious consequences on the severity of malaria episodes experienced in the other half that actually gets infected despite vaccination. However, when the malaria vaccine by GSK will be approved after the fase III trial and its distribution in the developing countries can commence, it will not be for the lowest possible amount of money. For that, GSK already had to make to many financial sacrifices.