International Journal of Infectious Diseases
January 2015 Volume 30, p1
http://www.ijidonline.com/current

Guidelines for treatment of patients with Ebola Virus Diseases are urgently needed
Eskild Petersen1, Boubacar Maiga2
1ProMED Moderator, Parasitic Diseases
2ProMED Moderator for Infectious Diseases, ProMED-FRA (Francophone Africa)
Open Access
DOI: http://dx.doi.org/10.1016/j.ijid.2014.12.002
The Ebola Virus Diseases, EVD, epidemic is still unfolding in West Africa with Guinea, Sierra Leone and Liberia most severely affected. This week it was estimated that there is at least 500 new cases every week and the total number of cases has passed 16,000, but there is probably a substantial underreporting of both cases and fatalities.1 There are some doubts about the mortality rate, but one recent case series reported a mortality of 72%.2

The outbreak is unprecedented in magnitude and few would have predicted that such an outbreak was possible. However, it seems clear that it is not due to a more pathogenic version of the Ebola virus and indeed low virus genetic diversity has been observed in person-to-person virus transmission.3, 4 Therefore, the current situation is most probable due to the poor status of the health care systems especially in Liberia and Sierra Leone, which has both recently suffered long civil wars, which have left the countries drained for educated health care staff and a dilapidated health infrastructure.

There is no approved, specific treatment of EVD. Several experimental anti-virals, immune-therapy5 and use of hyperimmune plasma from survivors have been proposed, but data from controlled clinical trials are lacking.6

After a slow start the international community including many Non Governmental Organizations, NGO’s, are managing treatment facilities in West Africa
But what are these treatment facilities offering?
Very little data has emerged. One published study reported a mortality of 72% but astonishingly the study contained no information of any treatment.2 Thus the question remains if the patients included in that study received any treatment at all. These patients were all from Sierra Leone and in contrast, nationals from industrialized countries are evacuated and treated in their home country and survived.7, 8 In particular, the case evacuated to Germany7 show very clearly that the treatment with classical tools used for patients in severe chock (bacterial septicemia, severe malaria) is expected to substantially reduce mortality. The patients received 30 liters of fluid intravenously over the first three days, had paralytic ileus and thus could not take oral fluid, had an fecal output of 14 liters over three days and severe hypokalemia. The same problems were seen in the two patients evacuated to the United States and one of these also had malaria.8

Is this a proper level of inpatient care in the Ebola treatment facilities or should we aim higher?
A mortality of 43% were reported in a case series of 80 patients with EVD from Guinea where 76% of the patients received intravenous fluid even though only 1 titer over 24 hours in average.9 If the difference in mortality between the report from Sierra Leone (72%)2 and Guinea (43%)9 are due to the use of intravenous fluid and even though one liter intravenous fluid seems very modest in view the need in the three expatriated cases7, 8, it seems that intravenous fluid replacement may significantly reduce mortality in the treatment centers perhaps by as much as 50%. This can be done in the conditions prevailing in West Africa using pulse, blood pressure, body weight and urine output as guidance and using simple point-of-care tests for measuring electrolytes, but require intravenous access, abundant fluid for intravenous administration and trained staff.

It is telling that the NGO’s have not published any treatment results and it is unclear if there is any control of treatment outcomes in EVD treatment facilities. Simply notifying confirmed cases and outcomes (fatal or not) and publishing weekly updates broken down to different NGO’s would allow quality control and allow adjustment of treatment algorithms adopting procedures identifying the highest survival rates. The difference in mortality between the two published case series2, 9 indicate that this is urgently needed.

We must to ensure that treatment is not palliation and that the so-called “Ebola hospitals” are hospitals and not hospices for untreated cases with the sole purpose of isolating cases from the community.

It is estimated in a study from Liberia, that only 25% of known Ebola patients had been admitted to an Ebola treatment facility as of August 14, 2014.10 The reasons for this low number are many, but a key point is probably that the chance of survival in these units does not differ significantly from patients staying at home.

The national governments in the affected countries does not have the resources nor the manpower to ensure the quality of the care provided by NGO’s and others. Thus the World Health Organization or others with the necessary resources should establish a notification system, to ensure that facilities are providing treatment and not only palliation and publish for instance weekly updates of survival figures broken down for each NGO to ensure quality control, transparency and optimization of treatment algorithms.

The German patient7 had septicemia and one of the American patients had malaria.8 Both diagnosis can lead to disseminated intravascular coagulation and will thus easily be confused with Ebola. If diagnostics are not available perhaps every patients in this highly endemic malaria area should receive a malaria treatment course and an infusion of a broad spectrum antibiotic, for instance ceftriaxone.

It is important to know if a patient is HIV positive as a low CD4 T cell count is expected to increase the risk of a fatal outcome, and thus treatment efficacy if at all possible should be stratified according to HIV status.

It is urgently needed to develop guidelines for treatment of EVD patients and to distinguish treatment from palliation and hospitals from hospices.

We suggest that the World Health Organization take the leadership and develop guidelines for treatment including:
1. Diagnosis of EVD
2. Principles for intravenous fluid replacement
3. Principles for measurement of electrolyte imbalance
4. Principles for correction of electrolyte imbalance
5. Diagnosis and treatment of concomitant malaria
6. When to administer antibiotics based on suspicion of septicemia
7. HIV testing.
8. Implement a reporting system for all EVD treatment facilities

These measures can all be implemented under the field conditions in West Africa, provided the staff are trained in high volume fluid replacement. Participating should be a prerequisite for receiving financial support from governments and receiving permission to manage EVD treatment facilities.
The staffing of the treatment facilities is a crucial issue and it can be speculated that the NGO’s does not have access to physicians and nurses with knowledge and experience in high volume fluid replacement and correction of electrolyte imbalance.
One solution could be twinning with hospitals in industrialized countries where these hospitals adopt an EVD treatment facility and ensure staffing and training. This of course would need support from the national health authorities. Such a program would ensure effective intravenous fluid replacement therapy were provided, most probably significantly reduce mortality, ensure confidence in the treatment facilities from the local population and thus increase the use of these facilities (earlier admission and higher proportion of cases treated, isolated and recovered).
[References]

Estimating influenza vaccine effectiveness using routine surveillance data among children aged 6–59 months for five consecutive influenza seasons
Wei-Ju Su, Ta-Chien Chan, Pei-Hung Chuang, Yu-Lun Liu, Ping-Ing Lee, Ming-Tsan Liu1, Jen-Hsiang Chuang2
1Tel.: +886 2 2653 1108; fax: +886 2 2785 3944.
2Tel.: +886 2 2391 8471; fax: +886 2 2391 8543.
Open Access
DOI: http://dx.doi.org/10.1016/j.ijid.2014.11.011
Highlights
:: Multiyear studies are preferred for estimating robust influenza vaccine effectiveness over time.
:: An efficient way to evaluate the influenza vaccine effectiveness was used, through data linkage of two already established systems in the public health sector.
:: We applied both fixed-effects and random-effects meta-analysis of case–control studies to estimate the pooled vaccine effectiveness for children aged 6–59 months across five influenza seasons and considered the variation in antigenic match and epidemics year by year as the heterogeneity between studies.
Summary
Objectives
We aimed to estimate the pooled vaccine effectiveness (VE) in children over five winters through data linkage of two existing surveillance systems.
Methods
Five test-negative case–control studies were conducted from November to February during the 2004/2005 to 2008/2009 seasons. Sentinel physicians from the Viral Surveillance Network enrolled children aged 6–59 months with influenza-like illness to collect throat swabs. Through linking with a nationwide vaccination registry, we measured the VE with a logistic regression model adjusting for age, gender, and week of symptom onset. Both fixed-effects and random-effects models were used in the meta-analysis.
Results
Four thousand four hundred and ninety-four subjects were included. The proportion of influenza test-positive subjects across the five seasons was 11.5% (132/1151), 7.2% (41/572), 23.9% (189/791), 6.6% (75/1135), and 11.2% (95/845), respectively. The pooled VE was 62% (95% confidence interval (CI) 48–83%) in both meta-analysis models. By age category, VE was 51% (95% CI 23–68%) for those aged 6–23 months and 75% (95% CI 60–84%) for those aged 24–59 months.
Conclusions
Influenza vaccination provided measurable protection against laboratory-confirmed influenza among children aged 6–59 months despite variations in the vaccine match during the 2004/2005 to 2008/2009 influenza seasons in Taiwan.