COVID-19: HOW HAVE PUBLICATIONS (INCLUDING LAY PRESS) IMPROVED CLINICAL CARE AND PUBLIC HEALTH RESPONSE TO THE PANDEMIC(I).

Del Rio C and Malani P have spent many efforts to summarize the

flood of comunications about the most important aspects of the COVID-19-pandemic published in the last five months.

By doing that,they offer a platform for additional thoughts and discussions.I think that it is important to remember how the new coronavirus was „born“.

A doctor, Ai Fen, the chief of  the emergency unity at the Wuhan Central Hospital, had to deal with several patients with Pneumonia of unclear origin and had the idea and the opportunity to ask the laboratory of the hospital to test swabs from a patient  for SARS-Coronavirus (1).The laboratory had a real-time PCR-kit which could also identify the RNA of several viruses responsible for „atypical pneumonia“ including several betacoronaviruses and SARS-CoV-1 (2).

This was the basis for the sequencing work which was quickly performed by the chinese scientists(2).This would not have been routinely possible in many other hospitals in western countries.

As pointed out by Caterine Paules, Hilary Marston and Anthony Fauci(3) in their viewpoint,human Coronaviruses belonged to a family of  now seven components which have a large sequence similarity.With the exclusion of SARS-CoV-1 and MERS the other four HuCoV are responsible for 10-30% of atypical pneumonias every winter  around the world.These viruses use the same receptor(4) the new CoV  uses to colonize the human upper and lower airways.This means also that antibodies against those viruses are quite common in the sera of many persons(5) and we do not exactly know how COVID-19-specific the antibodies are which we are measuring in the sera of COVID-19 infected patients (6).

Serum level of neutralizing antibodies (7) will also decrease with time (8,9) and their presence does not mean that they will help to clear the virus and to prevent reinfection (10,11).

Under these conditions (6) and considering the not so positive past experience  performed with the influenza vaccine (12,13) the production of a COVID-19-vaccine represents a true challenge.

As we have recently learned that the pulmonary disease without thrombosis of the pulmonary vessels, is mainly responsible for the death of elderly COVID-19-patients with several comorbidities (14),while other organs supposed to be  invaded by the virus(15), seem not to be much damaged, efforts should focus on early supportive care and therapy to avoid development of severe respiratory insufficiency.Autopsy of the patients who died of the disease is still a priority especially in academic centers.

 

 

REFERENCES

1.Kuo L: Coronavirus:Whuan doctor speaks out against authorities.The Guardian 2020,March 11.

2.Zhu N,Zhang D, Wang W et al.A novel Coronavirus from patients

with pneumonia in China,2019 New Engl J Med2020;382:727-733.

3.Paules CI,Marston HD,Fauci AS.:Coronavirus Infection-More than just the common cold.JAMA2020;January 23:E1-E2.

4.Wu K,Li W,PenG G. Li F.:crystal structure on NL63 respiratory coronavirus receptor-binding domain complexed with ist human receptor.Proc Natl Acad Sci.2009;106(47):19970-19974.

5.Gorse GJ,Patel GB, Vitale JN,O`Connor Z.:Prevalence of antibodies to four human coronaviruses is lower in nasal secretions than in serum.Clin Vaccine Immunol 2010,17(2):1875-1880.

6.Eder S,Twohey M,Mandavill A.:Antibody test,seen as key to reopening country,does not yet deliver.The New York Times2020 April 10

7.Wölfel R, Corman VM, Guggemos W et.al.Virological assessment of hospitalized patients with COVID-2019.Nature 2020 April 1.

8.Du Z, Zhu F, Guo F et al.Detection of antibodies against SARS-CoV-2 in patients with COVID-19.J Med Virol 2020:1-4

9.Lin Q,Zhu L,Ni Z et al.:Duration of serum neutralizing antibodies for SARS-CoV-2:lessons from SARS-CoV infection.J Microbiol,

Immunol&Infect.2020.

10Chen D, Xu W Lei Z et al.:Recurrence of positive SARS-CoV-2-RNA in COVID-19:A case.Int J of Infec Dis 2020;93:297-299.

11.Lan L,Xu D, Ye G et al. Positive RT-PCR test results in patients recovered from COVID-19.JAMA 2020;323(15):1502-1503

12Simonsen L, Reichert TA, Viboud C et al.:Inpact of influenza vaccination on seasonal mortality in the US elderly population.Arch Intern Med 2005;165:265-272.

13.Choe EJ Rolfes MA,O`Halloran A et al.Respiratory and non-respiratory Diagnoses associated with influenza in hospitalized Adults:JAMANetwork 2020March 20

14.Horowitz J.:Surviving Covid-19 May not feel like recovery for some.New York Times 2020 May 20

15.Schaller T, Hirschbühl K Burkhardt K et al.Postmortem examination of patients with COVID-19.JAMA 2020,May 21

A part of this article as been published in part as a comment to the vewpoint: Translating Science on COVID-19 to Improve Clinical Care and Support the Public Health Response, published online in the Journal of American Medical Association May 22 2020 by Carlos del Rio,and Preeti Malani

 

 

Intensive physical training and response to infection, comorbidities and ICU-admission, behavioural raccomendations for COVID 19 patients.

Looking at the number of deaths in northern Italy and listening to the continuous requests for

mechanical ventilation machines (1) and for extracorporal membrane oxigenation (ECMO) devices (2) now the time has come to realize that ICU-admission and intubation of all COVID-19-patients with acute respiratory problems very often is not saving lives. The use of prognostic scores (3) may be used to avoid ICU-admissions.  CT-scan of the chest and repetition of this procedure(4), however, is often not helpful and even dangerous as contrast medium is needed which may damage the kidney and augment blood volume. The report published by Arentz et al (5) clearly show that more than 50% of COVID-19 positive patients with severe comorbidities die shortly after ICU-admission, the other 50% continues to need mechanical ventilation.This severely reduces the ICU-capacity. A careful selection of ICU-admissions is necessary (6).

As suggested by Dr Bonazza (7), treatment of  patients with severe comorbidities should  better be treated with non invasive ventilation (NIV) (6).The questions asked by Dr Olgiati (8) are very appropriate. In fact many people believe that intensive physical exercise can only be healthy. This is not always the case (9), especially when„little“ viral Infections (e.g.common cold) are ongoing.

The answer to the third question is clearly affermative.This is even more approrpiate if we presume that many patients in home quarantene continue to smoke cigarettes.

 

REFERENCES

 1.Murthy S, Gomersll ChD, Fowler RA.:Care for critically ill patients with COVID-19.JAMA 2020  March 11

2.McLaren G,Fisher D,Brodie D.:Preparing for the most critically ill patients with COVID-19. The potential role of extracorporal Membrane oxygenation.JAMA 2020,February 19

3.Wujtewicz M et al.: COVID-19-what should anaesthesiologists and intensivists know about is. Anaestheiol Intensive Ther.2020;52:1-8

4.Wang D et al.:Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan,China.JAMA 2020 February 7

5.Arentz M et al.Characteristics and Outcomes of 21 critically ill patients with COVID-19 in Washington state.JAMA 2020 March 19

 

 

 

6.Sun Q,Qiu H,Yang Y.:Lower mortality of COVID-19 by early recognition and intervention:experience from Jiangsu Province. Ann Intensive Care 2020; 10:33

7.Bonazza P.:What about Non Invasive Ventilation in ICU/Sub-Intensive Units . Grasselli G,Pesenti A,Cecconi M :Critical Care Utilization for the COVID-19 Outbreak in Lombardy, ItalyEarly Experience and Forecast During an Emergency Response.JAMA 2020,March 11.

8.Olgiati S.:Behavioural factors; clinical COVID19

exacerbation,prevention and recommandations.Grasselli G,Pesenti A,Cecconi M.:Critical care utilization forthe covid-19..JAMA2020,March 11

9.Morici G et al.Endurance training:is it bad for you? Breathe 2016;12:140-147

 

 

 

 

ORGAN TROPISM OF HUMAN CORONAVIUSES: WHAT DO WE REALLY KNOW.

Most of the knowledge we aquired about the target organ(s) of human coronavirus originates from the clinical,radiological and,most importantly, autoptic studies (1-5) on patients who died during the SARS- and MERS- epidemics. Most of the actual informations about SARS-CoV-2(COVID 19) infection in hospitalized persons relys on clinical „surrogate“ findings and on CT-scans of the chest for both,those who were released from the hospital and those who unfortunately died of the disease (6-9). Infact no complete autoptic studies (with one single exception,10 ) have been performed in the more than 4.200 patients who died because of COVID 19.

By putting together the main clinical, radiological and histological data from the SARS-CoV 1 and MERS-epidemic we have a quite clear picture of the sequence of events occurring after the virus reaches first the bronchial and then the alveolar epithelium.

There is the invasion of the resident macrophages and of the epithelial cells by the virus and the recruitment of inflammatory

cells (granulocytes and macrophages) follows the release of pro-inflammatory cytokines and chemokines synthesized by the infected resident macrophages and epithelial cells(11,12) with some similarities to what happens in acute viral hepatitis( 13). The inflammatory  cells also cause release of fluid into the alveoli from   the capillaries which can be  damaged and trhombosised with reduction of functional tissue. The size of the area could be dependent on the viral load reaching the respiratory tract.

The degree of the functional reduction can be proportional to the size of the pulmonary area involved in the process and could be predicted by analysing the CT-scan.

Immunohistological, and electronmicroscopy studies have given indications for the presence and multiplication of virus particles in the inflamed areas of the lung. Similar findings have not been detected in other organs even if viral RNA has been detected in liver samples and in stool-samples in patients showing

mild elevation of serum transaminase levels at a later time after beginning of the disease, of the consequent hospitalisation (14) and transfer into ICU. No hepatic functional reduction  has been described in these patients. None of the retrospective clinical publications contained data indicating reduction of hepatic function,e.g. hyperbilirubinemia, or massive increase of transaminase serum level in patients dying from COVID 19.

Intriguing however is the low albumin serum level found not only in the ICU-care patients in two of the publications (6,8  ).Albumin serum level is an indicator for the synthetic capacity of the liver which is on the one hand dependent of sufficient nutritional delivery of proteins and or amino acids to the liver, and on the other hand, on the availability of enough healthy hepatocytes .This can happen in cases of acute hepatitis, when about a third of the hepatocytes dies and serum transminase levels and bilirubin are massively elevated.

No similar data have been found in COVID 19 patients (15).

The same is true for the kidney. No indication has been given for

viral replication in the kidney (2,3). A few autoptic data seem to support the assumption that  the kidney might be suffering from massive intravasal fluid reduction (2,16) which can cause tubular necrosis (2 ).This may be due to the intention to reduce cardiac work load in patients with hypoxia due to reduction of functional lung tissue and not by cardiac insufficiency. The complexity of the handling of such patients with additional comorbidities asks for doctors who can deal not only with respiratory insufficiency but also with the protection of other vital organs while the lung needs help to win the fight against the viral infection.

 

REFERENCES

1 Nicholls JM, Poon LLM,Lee KC,et al.:Lung pathology of fatal severe    acute respiratory syndrome.Lanct 2003;361:1773-1778

2 Chong PY,Chui P, Ling AE,et al.:Analysis of Death During the severe acute respiratory Syndrome (SARS) Epidemic in Singapore.Arch Pathol Lab Med 2004;128: 195-204

3 Gu J, Gong E,Zhang B,et al.:Multiple organ infection and the pathogenesis of SARS.J Exp Med 2005;202:415-424

4 Nicholls JM,Butany J Poon LM et al. Time course and cellular localisation of SARS-CoV nucleoprotein and RNA in Lungs from fatal cases of SARS.PloS Medicine 2006; 3(2):e27

5 Liu J,Zheng X, Tong Q,et al.: Overlapping and discete aspects oft he pathology and pathogenesis oft he emerging human pathogenic coronaviruses SARS-CoV,MERS-CoV, and 2019-nCoV.J Med Virol 2020 February 13:1-4

 

 

 

6 Huang Ch,Wang Y,Li X et al.:Clinical features of patients infected with 2019 novel coronavirus in Wuhan,China.Lancet 2020;395 February 15

7 Shi H, Han X, Cao Y,et al.:Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan,China: a desciptive study.Lancet Infect Dis 2020;February 24

8 Zhou F, Du R, Fan G,et al.: Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan,China: aretrospective cohort study.Lancet 2020;March 9

9 Wang t, Du Z,Zhu F, et al.:Comorbidities and multi-organ injuries in the treatment of COVID-19.Lancet 2020;March 9

10 Zhe X, Wang Y, Zhang J,et al.: Pathological findings of COVID-19 associated with acute respiratory distress syndrome.Lancet Resp Med 2020,February 17.

11 Chien JY,HSUEH PR,Cheng WC et al.:Temporal changes in cytokine/chemokine profiles and pulmonary involvement in severe acute respiratory syndrome.Respirology 2006;11:715-722

12 Zhou J,Chu H,Li c et al.:Active replication of Middle east respiratory Syndrome Coronavirus and aberrant induction of inflammatory cytokines and chemokines in human macrophages:implications for pathogenesis.J Infec Dis 2014:209:1331-1342

13 Wietzke P, Schott P, Mihm S,et al.:Clearance of HCV RNA in a chronic hepatitis C virus-infected patient during acute hepatitis B virus superinfection.Liver 1999;19:348-353

14 Chau TN,Lee KC,Yao H, et al.:SARS-Associated Viral Hepatitis caused by a novel coronavirus:report of three cases.Hepatology 2004; 39:302-310.

15Zhang C, Shi L Wang FS.:Liver injury in COVID-19:management and challenges.Lancet Gastroenterol Hepatol 2020 March 4.

16 Ng DL, Al Hosani F, Keating K et al.:Clinicopathological,Immunohistochemical,and ultrastructural findings of a fatal case middle East Respiratory Syndrome coronavirus Infection in the United Arab Emirates,April 2014.Am J Pathol.2016;186:652-658.

A CRITICAL WORD ABOUT THE POSSIBLE CONSEQUENCES OF USING EXPERIMENTAL THERAPIES IN PATIENTS WITH COVID 19-POSITIVE PNEUMONIA

Thank the efforts and the generosity of chinese scientists

COVID 19 is now one of seven most common human coronaviruses(HuCoV:229E,NL 63,0C43,HKU1) including SARS and MERS. By using primers derived from the RNA-sequence published by chinese scientists it has become possible to identify the agent causing influenza-like symptoms and advanced pulmonary disease around the world.

The experience of the Diamond Princess cruise ship (1) tells us that 6 patients  of 705 infected persons have died.This amounts to less than 1 %.The cause of death, however, has not been determined by autoptic studies.

Furthermore it is not known which investigational drugs have been used in these patients.

In many cases use of investigational drugs, often together with corticosteroids, antibiotics and sedation drugs, not only may be responsible for clinical findings attributed to the virus.

Use of experimental drugs (2) may contribute however to increase the fear of the population and most importantly of the ICU medical and paramedical personnel that prognosis be bad, no matter what measure can be further taken.

This has also negative consequences  for psychology of the population and aggravates the fear especially in those areas wehre COVID-positive cases were found.

 

REFERENCES

1.Roköv J, Sjödin H, Wilder-Smith A, COVID-19 outbreak on the Diamond Princess cruise ship: estimating the epidemic potential and effectiveness of public health countermeasures Journal of Travel Medicine, taaa030, https://doi.org/10.1093/jtm/taaa030Published: 28 February 2020

2.Stebbing J,Phelan A,Griffin I, Tucker C, Oechsele O, Smith D Richardson P.:COVID-19:combining antiviral and anti-inflammatory tretments.Lancet,February 2020

MEDICAL OVERUSE:WHO SHOULD CONTROL AND STOP IT?

Almost at the same time the Bertelsmann Foundation(05.11.2019) and JAMA(Journal of American Medical Association)Internal Medicine (published online september 9,2019) published data on overuse of the medical system including laboratory testing, radiological testing, medical (over)treatment ( antibiotics in urgent care clinics) and surgical (e.g. thyreoidectomy)interventions.
Both publications came m0re or less to the same conclusions „the findings suggest that many tests are overused,overtreatment is common,and unnecessary care can lead to patient harm“.
Therefore politicians should start a broad information campaign for all workers and employers who pay for health insurance and who sustain the health system.After that they should start to control the system more closely and to reduce expences. May be privatisation of the health care system and adoption of the „american“ DRG-system was not as successful as it was suggested it would be when both were introduced into the european systems more than 15 years ago.In fact now both sides of the atlantic independently from eachother come to the same conclusions:at least one third of the expenses can be avoided and even a better quality of the health care system with less patient harm could be the consequence.

Grote-Westrick,Marion,Münch Inga,Volbracht Eckhardt.Überversorgung schadet den Patienten.BertelsamnnStiftung05.11.2019
Morgan DJ,Dhruva SS, Coon ER,Wright SM, Korenstein D.:2019Update on medical overuse.A Review.JAMAInternal Medicinepublished onlin september 9;E1-7

ACADEMIC MEDICAL CENTERS (AMCs):How much is still academic?

This is a summary accompanied by some personal comments of a very recent Viewpoint report(Academic medical centers.Too large for their Own Health?) published in JAMA (june 17,2019,E1,E2) by S.Claiborne Johnstone (Dell academic medical school,university of texas,Austin)

1) fully accreditated medical schools(141) in the US not only educate medical students but they mainly „operate clinics and own hospitals“ defined as „Academic Medical Centers“ (AMCs)

It would be interesting to know how the accreditation procedure works.Who decides about the qualification of the teaching personnel and about the scientific quality of the publications? Deans of medical faculties are judged on the basis of the „quality“ of researchers they are able to hire The researchers are judged on the basis of their publications and of their funding.However there is no way to check the quality of the scientific production independent of the scientific journal lobby. More and more researchers within AMCs have not studied medicine.They can not even judge the real impact of their research on medical pathology.

2)56% of the AMCs have annual revenues greater than 500 million dollars.

The crucial question raised by the author is : „have some AMCs grown to large to survive a changing health care system,much less to lead the change required?“

In other words can the AMCs lead the necessary structural(dimension ) reduction by reducing the number of treatments to those really needed?

Or do the economical and occupational constraints dominate the scientific knowledge which seems to suggest that less is more for the comunity?

3)„AMCs generate an estimated 6.3 million jobs and contribute an estimated 562 billion dollars to gross domestic product“

  That is to say that each employee contributes with his medical insurance fee to the maintenance of the largest employers in many cities hosting AMCs.

4)„At the same time, academic medicine has contributed to the creation of a suboptimal health system.“

5)„The World Health Organisation ranks the US health care system 37th among countries worldwide,just above Cuba“

6)„and life expectancy has declined in the United States during the last 3 years“.

7)„health care costs in the united states are 25% greater than the second most expensive country and 14-fold greater than Cuba`s“.

That is to say that  „scientific progress“ contributes to increased expenses for the health care system but not to prolong life expectancy in a country with the most expensive health care system which, however, ranks  just above that of Cuba, still a comunist country. On the contrary,decreasing life expectansy  may be also because of an „aggressive“ DRG-based  health care system mainly working for profit  „.

8) „AMCs are major sources of health care in nearly every US metropolitan area,and costs of care at virtually all AMCs are particularly high“

9)„so there is no denying that they have contributed to the health care system that currentlx exsists“

This is a polite way to express the concept that AMCs,which are supposed to path the way for the rest of the health system by mainly contributing to the medical guidelines, instead of becoming more and more restrictive, are developing toward a growing business branch.This of course influences the consideration given (mostly by the CEOs) to less aggressive and chipper diagnostic and therapeutic procedure in comparison to more aggressive and more expensive tools with a disavantage for the patient. In fact,if the system can not be made responsible for the reduction of life expecatncy,it does not seem to be able to stop this trend.

10)„the shiftng balance of the three major missions of AMCs-education,research, and clinical care-underlies the current challenge“

This is a crucial point. Education and research , existing within the same structure,can not be other than dominated by the economical constraints of clinical care,which forces to rewrite physiology , pathology,diagnostic and therapy toward profit oriented SOPs(standard oerating procedures) combined with ultra short permanence in the clinic.

Internal medicine has become much less important than surgery.

11)„however, the proportion of medical school funding derived from research has declined more recently,with federal grants making an average of 14% of medical schools revenues (Figure),with industry and foundation funding accounting for another 9%.“

12)“ from this perspective,funded research is actually a modest function of medical schools and their associated AMCs.Clinical revenue dearly is the dominating source of revenue at virtually every AMC.“

What we really would like to know is how many AMCs are in private hands,and how much private funding influences non private funding by lobbying work into the review system.How much is the educational system including scientififc society meetings,therapeutic tryials and scientific journals influenced by private interest groups? The continous advertising within the health care system does not make it different,if not even worse than other commercial branches with little possibility of defence for the „consumer“,in this special case, the sick patient.

13)„As greater and greater margins were realized from these faculty clinicians with revenue exceeding costs,more were hired and clinics and hospitals were constructed to support them“

14)“ These trends have accelerated during the last 20 years,with many faculty devoted nearly to clinical care“

At the same time the scientific world is asking itself why is the figure of the  physician scientist  within the AMCs disappearing ?

15)„Thus many of today`s AMCs are similar to huge tankers loaded with health care services,and research and education are merely passengers“.

The consequence of this developement is much worse.As mentioned above, the chief of administration are the true deus ex machina.They decide about who is going to be hired und who is „disturbing“ the business within the clinical teams. Honest medicine is in the middle of two enemies, the industry and the administrators of the clinical every day life.

15)„there is the  crux of the issue :any changes threatening the margins from clinical care will affect the intire mission of an AMC“.

This consideration does not take into account that  part of the revenues of the clnical care goes into the pocket of private investors at total disavantage of the fee-payers. This money influences the fate of  „honest“ medicine.

16)„Academic medical centers tend to do well in negotiating reimbursement rates from insurers,and they tend to admit patients who require more expensive and invasive interventions.“

This assumption goes back to the time where medical knowledge about tissue damage leading to organ dysfunction was poor and patients with acute or  with terminal organ insufficiency  made the bulk of the patient population. Conservative medicine has however made giant progresses and many invasive procedures (even oragan transplantation) are much less necessary than it was 20-30 years ago when patient presented with more advanced disease stages.

17) „Thus by necessity,the majority of AMCs are inclined to stay the course of the current health care system.“

18) “ A move to value-based care is more than just risky;it is counter to their best interests unless a clear line of sight to new payment models exists.

In fact so far using the DRG-system no attention  was paid to quality of medical treatment as it is not considered by the reimbursement system. For this reason number and quality of the persons involved in treatment was less important than costs.

 

19)„In the fee-for-service payment system, preventig illness and reducing wasteful diagnostics  or unnecessary treatment could reduce the income of AMCs (as well as other medical centers)“.

20)„Although many reports that have described the need to reallocate resources toward prevention,population health, and value-based care come from medical school faculty, the leaders of the AMC clinical enterprise will tend to resist change because it puts the entire institution at risk“.

21)„Faculty can discuss population health and value,but may be stymied from making important progress“.

22)„In this way,academic medicine is not fully aligned wih society´s interest in optimizing health outcomes or in reducing waste.“

23)„To better align with society´s interests,AMCs must reduce their reliance on fee-for -service medicine and the associated pressures to retain market share,raise prices,and increase consumption of health care.“

24)„Instead,they should leverage their expert leaders to develop and coordinate new models of care,focusing on solutions that enhance value„.

25)„If payers are reinbursing for value,the planning and coordination role naturally payed by AMCs could produce revenues that exceed costs.“

26)„Academic medicine could then lead in innovation and coordination of new models of care,being paid for value without necessarily owing all components of the system“.

27)„Academic medical centers should be optimized to enable rapid innovation in health that aligns with society´s interests.“

28)„Getting this alignement right will not be easy,particularly in an industry that has rewarded the traditional fee-for-service model with fairly reliable margins“

29)„Similar to a nimble schooner,an AMC that can alter course quickly and test new waters may be more valuable to society than megatanker,particularly given the narrow straits ahead“.

This would however mean reduction of the number of beds and of the number of employees,which is politically very inconvenient.

 

Republik Kongo (DRC) bedroht die Ausrottungsanstrengungen. Polio-Ausbruch in der Demokratischen Das Virus aus dem Polio-Impfstoff breitet sich aus trotz der Notmaßnahmen.

Während des Ebolaausbruchs in der DRC ist der Polio-Ausbruch in den Hintergrund geraten. Trotz der seit Monaten andauernden Anstrengungen breitet sich die Infektion aus. Mittlerweile sind 29 Kinder an der Lähmung erkrankt. Starke Besorgnisse hat der Fall ausgelößt, der am 21 Juni an der Grenze zu Uganda gemeldet wurde. In der Tat hat sich der Fall weit von der ursprünglichen Ausbruchsgegend entfernt ereignet.

Dieser Ausbruch wurde nicht vom Virus-Wildtyp bestimmt, wie es noch in Afganistan, Pakistan und vielleicht Nigeria der Fall ist, sondern von einer seltenen Mutante des Serotyps 2 aus der früheren oralen trivalenten Polio-Vakzine (OPV)

In der Tat, während die OPV-Impfkampagnen fast zu totaler Ausrottung des Wildtyps geführt haben, ist die Zirkulation des aus der Vakzine-entstandenen Viruses (cVDPVs) eine erneute Gefahr für die Länder geworden,die bislang frei von Polio waren und kann das ganze Projekt gefährden. Mittlerweile ist die Beseitigung dieses Ausbruches durch den Serotyp 2 fast wichtiger geworden als die Ausrottung des Wildtyps  . In armen Ländern, wie DRC kann es passieren, dass attenuierte Viren aus der alten trivalenten Vakzine an die vielen Kinder weitergegeben werden, die nicht geimpft worden waren. Dadurch konnte das Virus jahrelang im Umlauf bleiben. In dieser Zeit konnte das Virus derart mutieren, dass es gefährlich werden konnte. Die große Mehrzahl dieser Viren (cVDPVs) gehört zum Serotyp 2 der ursprünglich (bis 2016) zu den drei Varianten des OPV- Impfstoffes (1,2,3) gehörten. Diese Variante wurde dann entfernt, weil der Serotyp 2 in der Weltbevölkerung als ausgerottet galt aber als Ursache für die seltenen Lähmungen als Impfkomplikation (1:1 Million) nach Impfung mit dem trivalenten Impfstoff bei geimpften Kindern festgestellt wurde. Im April 2016 wurde die trivalente Vakzine in 155 Ländern der Welt durch die bivalente (ohne Serotyp 2) ersetzt. Obwohl niemand richtig wusste, wie es ausgehen würde, hatte man weiterhin mit seltenen Fällen von Lähmungen durch Serotyp 2 gerechnet. Zur Verhinderung der Entstehung von größeren Ausbrüchen wurde eine Serotyp 2 -„Einzelvakzine“  (monovalente),mOPV2,hergestellt.Die Entscheidung , diese Vakzine einzusetzen wird von dem WHO-Generaldirektor getroffen.

Seit 2016 ist diese Vakzine in 10 Ländern angeordnet worden.

Obwohl diese Strategie zu funktionieren scheint, hat Serotyp 2 im letzten Jahr in Syrien 74 Fälle von Kinderlähmungen verursacht, bevor der Ausbruch für beendet erklärt werden konnte.

Der Ausbruch in DRC wurde im Juni 2017 in der Provinz Maniema in der Mitte des Landes erstmals entdeckt. Nach wenigen Tagen wurde der zweite Fall 900 Km entfernt im Südosten des Landes (Provinz Haut-Lomani) erfasst. Eine genetische Analyse beider Viren zeigte, dass es sich um zwei unterschiedliche Stämme des cVDPV2 handelte und dass die

Viren in den letzten 2 Jahren unbemerkt zirkuliert hatten. Es wurde mit der mOPV2-Vakzinierung in 8 Distrikten begonnen,

die als am meisten gefährdet angesehen wurden. Da man nicht alle entfernten Dörfer erreichen konnte, konnte sich das Haut-Lomami-virus  nach Süden nach Tanganyka und dann auch nach Haut-Katanga ausbreiten. Anfang Juni 2018 wurde ein weiterer Fall auf der anderen Seite des Landes bestätigt. Dort war auch Ebola ausgebrochen. Auch in diesem Fall handelte es sich um einen von den anderen unabhängigen Stamm als Hinweis für die schwache Überwachung in DRC. Noch alarmierender ist der Fall, der zwei Wochen später im Nordosten des Lander in der Nähe der Grenze zu Uganda gemeldet wurde. Das Haut-Lomani-Virus hatte einen Sprung in den Norden getan, in eine Gegend, wo keine mOPV2-Impfung zur Eindämmung der Ausbreitung diesen Stammes stattgefunden hatte. Sollte es zu einer größeren Ausbreitung innerhalb Afrikas kommen, müsste die trivalente Vakzine wieder eingeführt werden. Dadurch könnte die definitive Ausrottung der Poliolähmung, mit den jährlichen Kosten von einer Billion Dollar/Jahr, in weitere Ferne rücken.

Erläuterung:

OPV= orale Polio Vakzine (Serotyp 1,2,3),die ursprüngliche   Vakzine,

cVDPVs= zirkulierende aus der OPV-Vakzine hervorgegangene Viren (meistens Serotyp 2)

mOPV2= monovalente Serotyp 2-Vakzine

Zusammenfassung und Übersetzung aus dem Artikel von Leslie Roberts veröffentlicht am 06.07.2018 in Science Vol. 361 Heft 6397:10-11

G.Ramadori

Hierarchy and „flat“ organisation:the american example of the FBI director

James Comey; A HIGHER LOYALTY 2018:156

No matter how „flat“ an organisation, there is a hierarchy, and everyone knows  what it is.Even if everyone in the room is wearing a hooded sweatshirt,ripped jeans,and flip-flops.Even if we are all sitting on beanbags eating trail mix and spitballing ideas on a whiteboard,if anyone in the room is  a boss or owner,everyone knows it.Someone in the room is“above“ the others,whether that rank is expilicit or not.

 

THE POLIO ENDGAME: SECURING A WORLD FREE OF ALL POLIOVIRUSES

1-Seit 1988 Verringerung der Zahl der Krankheitsfälle durch wildes Poliovirus von 350.000 in 125 endemischen Ländern auf 20 in 2 Ländern (2017,99%-Reduktion).

Dies bedeutet, dass etwa 16 Millionen Menschen unter den Folgen der Polio-induzierten Lähmung zu leiden gehabt hätten, wenn der Impfstoff nicht eingeführt worden wäre.

2-Heute lebt 80% der Weltbevölkerung in Ländern, die von der WHO als Polio-frei erklärt worden sind.

3-In Nigeria, Pakistan und Afganistan ist wild Polio heute noch endemisch. In Pakistan sind leider in den Jahren 2013/2014 mehr als 50 Mitarbeiter der Impforganisation und am 20 April 2016 7 Polizisten, die die Impfenden schützen sollten ermordet worden (1). Pakistan hat eine lange Grenze zu Afganistan und eine große Zahl von afganischen Bürgern ist nach Pakistan geflüchtet. Das pakistanische Institut für Migrationspolitik schätzt, dass es an der afganischen Grenze ca. 1.400.000 nicht registrierte Flüchtlinge während 1.543,536 registriert wurden (Stand 25 Februar 2016)(2)

4-Von den 3 Polio-Stämmen (1,2,3) wird heute nur noch wild Polio-Stamm1 festgestellt.

5-Auch in den noch endemischen Ländern werden immer mehr Kinder von der oralen Massen- Impfung erreicht (ORAL POLIOVIRUS VACCINE OPV).

6-Jedes Jahr werden mehr als 400 Mio Kinder mehrfach mit 2.2 Billionen Impfdosen geimpft.

7-die Impfung immunisiert das Kind und unterbricht auch die Weitergabe des Virus in der Gemeinschaft, mit dem ultimativen Ziel der Eradikation der Infektion

8- In seltenen Fällen kann das attenuierte Virus in dem Impfstoff die sog. Serotyp 2 -Vakzin-assozierte paralytische Poliomyelitis in den behandelten Kindern verursachen und kann zum Vakzine-derived zirkulierenden Poliovirus werden.Ca 40% der Vakzine-assozierten paralytischen Poliomyelitiden(ca 200 Fälle/Jahr) und 90% der Ausbrüche von zirkulierenden Vakzine-derived Polioviren der letzten 10 Jahre waren durch den Serotyp 2 der trivalenten OPV-Vakzine verursacht.

9- Es ist daher unbedingt erforderlich, dass die Anwendung der trivalenten OPV-Vakzine beendet wird.

10- Dieses Verfahren ist bereits eingeleitet worden und sollte stufenweise weiterlaufen.

11-Nach der Erklärung der Eradikation des Polio-Stammes 2 im September 2015 sind alle Länder ab der zweiten Hälfte April 2016 von dem trivalenten OPV-Impfstoff (alle Serotypen 1,2,3) zum bivalenten Impfstoff (Serotypen 1,3 aber nicht Serotyp 2) übergegangen.

 Alle 155 Länder der Welt haben innerhalb von 2 Wochen alle trivalenten OPV- Impfstoffe durch die bivalenten ersetzt. Dadurch sollte die Vakzine-assozierte Poliomyelitis nicht mehr vorkommen.

12-Da aber die Vollständigkeit des Überganges vom trivalenten in den bivalenten OPV in manchen Ländern nicht überprüft werden kann und ein Abfall der Immunität gegen den Serotyp 2 nicht immer

ausgeschlossen werden kann, ist ein weiteres Auftreten der Vakzine-induzierten (Stamm 2)-Poliomyelitis in der Zeit unmittelbar nach der Umstellung der OPV  nicht ausgeschlossen . In der Tat sind Serotyp 2-Fälle im Jahr 2016 (aber kein Fall in 2017) in Nigeria und in Pakistan gemeldet worden.

13-Neu Ausbrüche von zirkulierendem Vakzine-derived Serotyp 2-Poliovirus sind in Mai 2017 in Syrien (74 Fälle bis 27 Dez 2017) und in der Republik Congo (12 Fälle) festgestellt worden. Die Paralyse bei den 86 Kindern macht klar wie notwendig es ist, dass alle trivalenten Vakzinen zerstört werden und dadurch nicht mehr zur Anwendung kommen.

14-Als internationale Antwort auf diese Gefahr in der post-Switch-Era, werden OPV-2-Vakzine-Stocks bereitgehalten, um durch eine monovalente Impfung die Ausbrüche zu beenden. Diese Strategie wird in beiden Ländern derzeit praktiziert. Ähnlich ist in Syrien 2013-2014 vorgegangen worden, als ein Serotyp1-Ausbruch mit einer Serotyp-1 monovalenten Impfung, erfolgreich beendet werden konnte.

15-Um eine definitive Eradikation zu erreichen, ist es sehr wichtig, das Risiko von Laborfehlern zu minimieren und die Entdeckung, die Überwachung und Behandlung von immunsupprimierten Langzeitausscheidern, die eine Vakzine-assozierte paralytische Poliomyelitis hatten zu gewährleisten.

Das Ziel einer definitiven Eradikation kann nur erreicht werden, wenn alle Länder daran mitwirken

indem sie alle Stufen der Diagnostik, Prävention und Überwachung apparativ und personell unterstützen und umsetzen

Übersetzung aus dem Bericht in der Zeitschrift Lancet von G.Ramadori.

Autoren des Berichtes sind:

Michel Zaffran,Michael Mc Govern,Reza Hossaini,Rebecca Martin,Jay Wenger Lancet Vol 391, January 6,2018:11-13

Es wurden Angaben aus der Zeitschrift Ochsener Journal 2017 aus den Artikeln

1) Mahmood SU et al.Vol 17:13-14 und 2) Ullah MA und Husseini AM,2017,17:306