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You may use this brief for informational, non-commercial purposes with credit attribution: The Global Health Delivery Project, GHDonline.org, Jul 24, 2015. Please see our Terms of Use for more information.

Qualitative Evaluation of Interventions in the Ebola Zaire Makona Outbreak

Added on 24 Jul 2015
Last updated on 24 Jul 2015

Authors: Elizabeth Glaser; Reviewed by Maggie Sullivan

In December 2013, the first confirmed case of Ebola Zaire Makona in West Africa occurred in a remote village in Guinea. The initial case, that of a young boy, has been attributed to exposure to fluids or excreta from insectivorous bats in a tree proximal to the child’s play area. The child died within days of becoming ill, as did his immediate caregiver, his pregnant mother. Their burial, attended by family, local midwives, and community health workers, resulted in three transmission chains that silently spread into neighboring Liberia and Sierra Leone in the early days of 2014.

During the same period, local public health officials in Guinea and members of the international NGO Médecins Sans Frontières (MSF), reported suspect cases of a novel viral hemorrhagic fever in West Africa. MSF alerted national and international authorities seeking an organized response to identify the agent, treat the ill, and contain the outbreak. However, a comprehensive and sustained international response did not occur for months after the initial calls for assistance.

Beginning in January 2015, members of the GHDonline Ebola Response community participated in a wide-ranging discussion on the challenges of providing care to Ebola-infected individuals, and the effectiveness of current and potential interventions.

Although media descriptions of Ebola Virus Disease (EVD) emphasize high mortality in infected humans, the case fatality rate varies greatly by Ebola species and strain, resources to manage the disease, and expertise of those managing the outbreak.

The overall depth and breadth of the West African Ebola outbreak has been attributed to a number of factors from the household to the international level. These include poor international response from global health agencies, porous borders, weak infrastructure in low-resource and post-conflict settings, inadequately prepared health services, and community practices that inadvertently amplified the spread of disease.

This summary consists of discussions, suggestions and unanswered questions, respectively, grounded within thematic sections. The suggestions derived from the various discussion points may be supported by some or all of the GHDonline discussants, peer reviewed literature, or established protocols. This document is not meant to take the place of established guidelines; rather it represents the lived experience of numerous clinicians and researchers in their roles as observers and participants in the Ebola Zaire Makona outbreak of 2013-2015.


Hydration

Oral Rehydration Salts (ORS)

Discussion
  • For those strong enough to drink independently, use of WHO-approved glucose based Oral Rehydration Solution (ORS) was encouraged and supported. Anti-emetics, both oral and IV, were usually available to help the patient maintain hydration and decrease fluid loss through vomiting.
  • In general, ORS was unpalatable per report of patients. ORS was also used by Ebola Treatment Unit (ETU) staff to rehydrate after several hours of working in hot conditions such as wearing PPE. ETU staff agreed that the taste of ORS was unpleasant and aggravated or triggered nausea in some who used it.
  • Special flavors of ORS were more palatable than the basic offering, but could be difficult to obtain. While there were reports that adding juice or flavor to ORS might enhance uptake, it was cautioned that changes to ORS solution could alter the balance of electrolytes and nutrients in the formula, potentially offsetting the benefits.
    • As one discussant found, there was conflicting literature on whether the addition of unsweetened Kool-aid flavoring to ORS alters the overall balance of electrolytes or makes very little difference in the balance.1 2
  • A NEJM article on the clinical care of the two initial Americans treated in the United States3 noted that the patients had, upon admission in the US, hypovolemia with lower than normal levels of potassium, calcium, sodium and albumin.
  • Oral rehydration with commercial sports drinks, which were used by the American patients while in Liberia, were not sufficient and likely led to hypokalemia, while WHO approved ORS solutions with oral potassium might avert hypokalemia.
  • One discussant suggested rice-based ORS, offering that there is over 20 years of evidence to support rice- based ORS as less likely to contribute to increased diarrhea as compared to sugar-based ORS.4
Suggestions
  • Access to rehydration in multiple settings: Ensure adequate ORS availability at home, at local health facilities, holding centers/Community Care centers (CCCs) and Ebola Treatment Units (ETUs) as well as in transit between any of these sites. Providing ORS in a variety of treatment settings might reduce the number of patients that present to the ETU severely dehydrated, and at increased risk for mortality. Use of ORS beginning at home is endorsed by WHO for Cholera, a disease similar to Ebola in terms of mortality from high volume fluid and electrolyte losses.5
  • Anti-emetics: Use oral and/or IV anti-emetics to help the patient have less nausea, maintain hydration, and decrease fluid loss through vomiting.
  • Adding diluted juice/flavoring to ORS: WHO advises against mixing ORS with fruit juice or carbonated soda as the higher osmolarity of these solutions could contribute to increased diarrhea. However, we have to consider the risk/benefit between increasing diarrhea and altering ORS solution by use of diluted juice to increase uptake of oral fluids.
    • Suggestions to mask ORS taste:
      • Adding powdered orange juice-type drink
      • Adding apple juice
      • Cooling ORS
      • Freezing ORS into “pops”
      • Consider cultural taste preferences
  • Temperature: Offering a cool/cold drink in a hot setting is more likely to improve uptake than offering a warm fluids.
  • Oral electrolyte supplementation:
  • As most intravenous fluids recommended for rehydration do not have substantial levels of potassium, calcium, or magnesium consider supplementing ORS with oral potassium, calcium, and magnesium, especially in patients with large-volume fluid losses from diarrhea.6
  • ORS-focused care: Use non-clinical staff, such as trained survivors, to assist patients with oral rehydration and nutrition. This allows patients who are weak but able to drink and eat to continue to do so, while allowing clinical staff to attend to IV lines and other issues given the limited time that any staff can stay within the high-risk zone. Consider appointing staff, both clinical and non-clinical, to an ORS team, exclusively focused on oral rehydration and nutrition from patient admission through discharge.
Unanswered Questions or Areas in Need of Further Study
  • What are the logistics of providing access to rehydration across multiple settings:
    • Providing ORS solution and safe water in the community.
    • Training community health workers (CHWs) and family caregivers to administer ORS as soon as possible, even if patient is in transport for evaluation.
  • Is rice-based ORS as a better option for rehydrating patients with EVD in West Africa:
    • Rice-based ORS might be more acceptable as Liberia and Sierra Leone are rice-based cultures.
    • As EVD is characterized by high volume diarrhea, rice-based ORS as less likely to contribute to increased diarrhea as compared to sugar-based ORS.
  • Additives to ORS:
    • Does the addition of flavoring or juices alter the basic ORS formulation enough to offset the benefit of enhanced uptake of fluids?
    • What additions might increase palatability of ORS while retaining overall therapeutic balance?

ORS Alternatives: Coconut Water

Discussion
  • Use of coconut water, the clear liquid found inside young green coconuts, was raised in conjunction with use of the rice-based ORS. It was suggested that rice could be cooked in coconut water/milk.
  • In some facilities, patients received oral nutrition with coconuts and oranges, especially during the recovery phase of EVD. Another discussant reported providing “jelly water,” or coconut water, to a small number of patients however it was unclear if this provided any substantial benefit.
  • Data on the overall benefit of using coconut water to rehydrate those with acute Ebola has not been established.
    • WHO classifies coconut milk/water and oranges as having high potassium, between 250–499 mg per 100 g edible portion, and lists both foods as sources of extra potassium for people ill or recovering from Ebola.7
    • A search of the WHO website did not provide any information that suggests coconut water is a WHO-endorsed viable alternative to ORS, but in Essential Clinical Global Health, Weil and colleagues do suggest both rice-based ORS as well as coconut water are reasonable alternatives to WHO-approved ORS.8 Murugaiah and colleagues (2013) noted plant-based ORS, derived from rice, coconut, sorghum, or especially plantain flour results in less overall fluid loss from secretory diarrhea than the glucose-based ORS endorsed by WHO.9
Suggestions
  • Accessibility: Coconut water is a palatable, affordable, and a locally available crop in West Africa.
  • Oral adjunct to IV hydration: Coconut water is a WHO-approved source of extra potassium for those ill or recovering from Ebola, therefore it could supplement IV hydration with Lactated Ringers solution that has low levels of potassium.
  • ORS alternative: Coconut water as a viable alternative to glucose-based ORS for malnourished children with diarrhea, based on textbooks and literature from peer-reviewed journal.
Unanswered Questions or Areas in Need of Further Study 
  • Could coconut water provide a viable, palatable, affordable, and locally-available alternative to ORS in adults with high volume fluid loss?

Nasogastric tubes

Discussion
  • Several discussants suggested using nasogastric tubes (NG tubes) to quickly deliver fluids when an individual is too weak to take in fluids by mouth.
    • One person noted that when oral rehydration therapy for cholera was being developed in the late 1960s, NG tubes were used to administer fluids allowing accurate quantitation of intake and output. They considered that NG tubes should be as well-tolerated and safe as IVs.
    • Others weighed in that since Ebola can increase one’s risk of bleeding, NG tube placement might be risky. However one participant found no contraindications after a brief literature search focusing on NG tubes and bleeding risk.
  • One clinician used NG tubes to administer fluids to two children with Ebola. In each case, NG tubes were used when clinic staff members were unable to get IV access. The children required slow and careful administration of fluids to reduce the chance of vomiting, however the clinician reported that, at least in these two cases, the intervention was highly successful.
  • Another clinician noted that children receiving care in her ETU had what looked like painful oral mucosa, oozing blood and couldn't tolerate a cup touching their lips. She assumed that the nasal mucosa was in the same friable condition. Dripping in ORS was very time consuming for staff and painful for the children so an NG tube might be worth trying however, the clinician expressed concerns about aspiration, vomiting, and securing the tube to skin slick from sweat.
Suggestions
  • Contraindications: NG tubes are currently contraindicated by WHO, UNICEF, and the World Food Program for hydration and/or nutritional supplementation in Ebola-infected individuals.
    • WHO/UNICEF/WFP recommends against using NG tubes for the following reasons:
      • Difficult to verify placement in the ETU setting.
      • NG tubes are hard to monitor given the limited staffing available in the ETU setting.
      • Some patients report discomfort or pain from NG tubes.
      • Patients may attempt to self-remove the NG tube, which can lead to infection.
      • Placement of the tube in resistant, fearful, or confused patients can potentially cause harm to the patient (including bleeding) or harm to the provider (by breaching Personal Protective Equipment, PPE, or body fluid exposure).
      • ETUs may not have sufficiently trained staff to safely insert, maintain, and remove NG tubes.
Unanswered Questions or Areas in Need of Further Study
  • If an ETU had the capacity to check tube placement with ultrasound, trained staff to safely insert, maintain, and remove NG tubes and able to provide supervision of patients, would NG tubes be a viable alternative to ORS or IVs for rehydration?

Pediatric Hydration

Discussion
  • Pediatric care presented the challenge of rehydration without driving the patient into fluid overload. Finding an adequate fluid balance was further hampered by a lack of devices to control the volume of infusion. Intraosseous infusion (IO) may have benefitted children, however clinicians speculated that IO was perhaps underutilized. Staff that did use IO to obtain access reported that it frequently had to be removed after each use due to lack of staff to monitor the access site.
Suggestions
  • Training across age groups: Local and international staff might benefit from cross-training to increase competence in caring for patients across the age spectrum.
  • Volume control: Access to Minidrip or other devices would likely allow better control over rate and volume of fluid infusion. In the absence of such devices, staff without experience in low- resources settings should be trained in adjusting infusion rate without the benefit of special volume control devices.
  • Intraosseous (IO) access: Facilities with access to IO should evaluate the use of the device by frequency, time access was left in place, patient characteristics, then compare patients with similar characteristics and during the same period that did not receive the device. Assess for overall survival, and for over/underutilization of device.
  • Staffing: Increase number of shifts/staff coverage to allow more careful infusion in children and facilitate increased use of IO if data suggests efficacy and improved outcomes from use of the device.
Unanswered Questions or Areas in Need of Further Study
  • What was the protocol for using IO and how consistently were utilization criteria applied?
  • What experience did local and/or international staff have in titrating IV fluids without benefit of volume/rate control devices, particularly in the pediatric population?

Intravenous (IV) Hydration

Discussion
  • Treatment practices varied widely by management, whether NGO, government or other agency.
  • Clinicians as a whole noted the high volume of diarrhea during acute infection with Ebola. In general, patients received Lactated Ringers for IV rehydration. Participants reported that some patients received between 10-14 liters of IV fluids per day to keep up with their output from diarrhea and vomiting.
  • Third-spacing was seen in a subset of patients. There was concern that these patients, some of whom were receiving 2-4 liters of fluid an hour, should be infused carefully. Another believed that third-spacing was an indication of end-stage Ebola which could be averted by IV fluid resuscitation.
  • Fluid tolerance was evaluated based on respiratory status. One clinician with access to ultrasound noted an end-stage patient evidenced small pleural effusions, dilated ventricles, flat inferior vena cava (IVC), hydronephrosis, and a severely edematous bowel wall.
  • Staff struggled to measure intake and output. Given the blocks of time in some facilities during which there were no staff on the unit to assist patients with toileting or emesis, this is not surprising.
  • Those who had access to an I-stat machine to check electrolyte values noted that virtually all patients had low potassium and required supplementation with potassium and magnesium. Facilities without the capacity to check electrolytes provided oral potassium supplementation based on signs and symptoms consistent with hypokalemia.
  • The mode of potassium administration varied. At some facilities, staff were not willing to put potassium into the Lactated Ringers solution whereas at other facilities, oral KCL was part of standing orders. In general, KCL was given orally. KCL tablets, however, can be difficult to tolerate even in the absence of severe nausea and vomiting. Lactated Ringers solution is not indicated for severe potassium deficiency; therefore if Lactated Ringers is used for IV hydration in patients with severe diarrhea, it must be supplement with either additional potassium in the IV bag, or oral potassium tablets, in conjunction with ORS, if tolerated.
  • In more than one facility, IV hydration was provided through a periodic fluid bolus. In some facilities, pressure infusions would be used to infuse as much fluid as possible given staffing time constraints in the ETU.
  • Some facilities inserted an IV upon admission to the ETU whereas, other facilities only inserted an IV if the patient was not maintaining oral hydration and displaying signs of dehydration.
  • Antibiotics, usually cefixime or ceftriaxone, were administered via IV, however some facilities administered antibiotics as a standing order for all admitted (Ebola PCR positive) patients, while others only administered antibiotics if the patient had significant diarrhea or was judged to be at risk for secondary bacterial infections.
  • Participants compared Ebola to cholera because both are characterized by high volume diarrhea. One participant with experience treating both diseases noted that patients with cholera usually rapidly responded to IV rehydration, however the course for Ebola patients was far less predictable. As she stated, “Aggressive rehydration was never a guarantee of survival.” Clinic staff clearly saw the benefits of IV hydration but expected fluid resuscitation to have more of an impact on mortality than was actually observed.
  • Schieffelin and colleagues (2014) evaluated outcomes in a cohort of Ebola infected patients in Sierra Leone. Of the 213 patients presenting with suspected Ebola, 106 (~50%) were positive for Ebola by PCR testing. Ebola-positive patients had significantly lower sodium, potassium, total CO2, chloride, calcium, total bilirubin, albumin, and total protein than Ebola-negative patients or healthy controls, and significantly higher BUN, creatinine, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase upon admission than Ebola-negative patients at admission.
  • All Ebola-positive patients in the study received IV hydration. Fatal outcomes (74%) in Ebola- positive patients were associated with elevated BUN, creatinine, and aspartate aminotransferase at admission. The authors suggested dehydration and worsening renal function as significant contributors to mortality, while hepatic failure was not believed to be a likely factor in most fatal outcomes.10
  • Ebola-infected clinicians treated in the US, UK, and Europe had quite low (10-20%) mortality as compared to those treated within West Africa. However those treated outside of West Africa had, in conjunction with IV hydration, a fairly short time from infection to treatment, around-the-clock nursing care, a cooler environment, more options for ORS, experimental regimens (medications and/or convalescent blood), and access to testing to evaluate and revise the treatment regimen. Given the constraints of the ETUs, it is encouraging that IV hydration had any positive benefit.
Suggestions
  • Electrolyte monitoring: I-stat machine or other means to monitor electrolytes and general metabolic panel within the ETU to inform treatment plan, and assess responsiveness to treatment.
  • Staffing: Increased clinician time in the ETU to assess intake and output, allow more careful infusion of fluids, support oral as well as IV hydration, and to improve record keeping with the ETU.
  • Training: Staff training in oral and IV electrolyte replacement to increase competency and comfort with administration of electrolytes, particularly potassium chloride (KCL).
  • Technology: Use of mhealth or wireless technologies to facilitate data extraction from the ETU.
Unanswered Questions or Areas in Need of Further Study
  • What existing IV solutions or new formulations can be used or developed to better address the fluid and electrolyte losses associated with Ebola?

Intravenous (IV) Line Management

Discussion
  • Multiple clinicians reported that delirious, fearful, agitated, and confused patients pulled out IVs. In their estimation, one of the major challenges of IV therapy was simply averting traumatic self-removal of the catheter. As one discussant pointed out, neurologic status appeared to be directly related to the duration and security of the IV catheter.
  • Traumatic self-removal of the catheter led to bleeding at the catheter site, ranging from oozing to what one clinician characterized as “profuse” bleeding. These signs are consistent with the endothelial dysfunction and hemorrhagic changes associated with Ebola.
  • Taping and bandaging, in general, did not adequately secure the IV enough to keep it from being pulled. In some cases, efforts to secure the line led to further complications from infiltration and infection.
  • If an IV came out near dusk or after dark, staff at one facility would not reinsert a new IV at that time due to increased risk of needle sticks from poor lighting, thus delaying access to IV fluids until the next morning.
  • At one facility, diazepam was used for sedation of delirious, confused, or agitated patients to allow infusion of IV fluids, in the hope that rehydration would improve their overall condition. Staff at that facility, particularly local staff, expressed concern with this practice.
  • One consequence of catheter self-removal was that it was difficult to know how much fluid volume had been administered prior to the IV being pulled.
  • In facilities that inserted an IV catheter upon admission, cannulas were not necessarily flushed on a daily basis. In this situation, if a patient later required IV hydration, the IV was longer patent and had to be reinserted, requiring another stick.
  • Catheter hubs were not necessarily cleaned prior to the line being accessed. Since bags were only hung when staff were in the ETU, the lines might be accessed several times a day, each time presenting an opportunity to introduce microorganisms into an already compromised patient.
  • There were patients that evidenced phlebitis, extravasation, or infiltration at or above the IV insertion site. Those changes may have been due to general irritation, catheter movement, bacterial infection at the site, changes in endothelial tissue as a complication of Ebola, thrombosis, or all of the above, but regardless, it made for painful and problematic IVs. Other clinicians did not see much evidence of phlebitis but admitted this may have been because IVs were in place for less than 24 hours.
  • Pressure infusion would be used to shorten infusion times. This was done to accommodate staffing time limits in the ETU. While fluid bolus may not be an issue in general, Ebola-related endothelial changes might increase the risk for complications from this practice.
  • Staffing in the ETUs varied greatly by facility: some had staff present during the night, whereas others had no staff in the isolation unit for up to 10 hours at a time. This limited infusion time.
  • Clinicians discussed various options for IV access aside from peripheral IV and intraosseous routes, including subcutaneous (SC) access and Peripherally Inserted Central catheters (PICC lines), however no one was aware of SC or PICC line access being used to deliver fluids in Ebola patients.
Suggestions
  • Training and critical thinking (troubleshooting): Given the difficulties of inserting and maintaining lines, ongoing training and trouble-shooting with local and international staff in IV insertion, line care for infection control, and securing the line using low tech as well as high tech methods, may help patients retain IV access over the long term.
  • Environmental controls: Cooling health facilities would allow staff increased time within the isolation unit to manage IV lines, titrate infusions, attend to confused, fearful patients, and decrease the need for pressure infusions.
  • IV stabilization: Explore interventions to decrease accidental dislodgement and traumatic removal of the cannula such as use of an IV statlock or similar device, while a cheaper intervention would be to tape a longitudinally cut plastic cup over the IV hub.
  • Line infections: Infection control practices must be used to avert line infections or other secondary infections in patients.
  • Adapt staffing: Frequent, short, overlapping shifts to decrease heat stress on staff but allow longer infusion times.
  • Sedation: Short-term use of mild sedation may decrease the risk of traumatic self-removal of IVs in confused/delirious patients.
  • According to a recent Cochrane Review focusing on parenteral access for management of patient with Ebola, the authors cautiously concluded:
    • Peripheral IV access allows infusion of larger volumes of fluid than other routes.
    • If peripheral IV access cannot be obtained, intraosseous access or subcutaneous access are acceptable routes to deliver fluids.
    • Subcutaneous access may be preferable to use for patients unable to orally rehydrate but who are not yet severely dehydrated.
Unanswered Questions or Areas in Need of Further Study
  • Have any ETUs used the subcutaneous route to deliver fluids?
  • Would use of subcutaneous access reduce risk of bleeds from traumatic removal?
  • Would subcutaneous access be more tolerated by confused and agitated patients?

Nutrition

Ready to Use Therapeutic Food (RTUs)

Discussion
  • A discussant reported successfully using BP 100 biscuits diluting in 500 ml of water for fluid resuscitation in their ETU. BP 100 and F-75 biscuits are a ready to use therapeutic food endorsed by WHO and the government of Liberia for ill or convalescent individuals that are not severely dehydrated, have some or good appetite and can tolerate a soft to solid diet. One and one half biscuits (BP100 as a porridge) provide 750 kcals to an ill person and two biscuits provide 1000 kcals to a convalescent person. This should only be administered if the person can drink a minimum 1ml of water for each kcal of the diet.
Suggestions
  • Milk biscuits and other forms of ready-to-use supplementary food and ready to use therapeutic food are endorsed by WHO for nutrition in Ebola-infected individuals.
Unanswered Questions or Areas in Need of Further Study
  • What easy to access, affordable, local staples can be used as therapeutic food?

Other Considerations

Treatment Environment

Discussion
  • All participants agreed that PPE imposed limitations to effective practice. Double-gloving restricted fine motor activities such as IV insertion; goggles fogged over, obscuring vision; mask and head coverings muffled speech and hearing, making communication with patients and other staff difficult; the extreme heat could affect cognition and concentration, placing staff at risk for exposure and affect the quality and quantity of patient care.
  • The heat and humidity in ETUs likely worsened patient hydration status in patients already quite ill. Additionally, the tedious process of removing (doffing) PPE after an exhausting session in the ETU created another point at which there was increased risk for exposure and created a bottleneck to transitioning staff in and out of the ETU.
  • Lighter PPE and cooler environment will allow longer times in the ETU, and may facilitate around-the- clock nursing care.
Suggestions
  • PPE redesign: PPE must be designed to be lighter, easier to don, less restrictive, and cooler, yielding garments and gear that can be worn safely for longer periods of time.
    • PPE should be designed to be doffed quickly and safely, to reduce the risk for exposure in very hot tired people, and decrease a staffing bottleneck.
  • Environmental controls: Health facilities must have better environmental controls, either via air conditioning or fans, to enhance air-cooling and circulation. These environmental controls can be facilitated with access to electrical generators and support to maintain the physical plant of the facilities.
Unanswered Questions or Areas in Need of Further Study
  • Are there affordable materials that can be used to create improved PPE?

Alternative Treatments

Discussion
  • A number of medications are in development or active clinical trials to either prevent Ebola (e.g. vaccines) or spur a healthy immune response (e.g. ZMapp). During the course of the illness Ebola produces a cascade of effects, including upregulation of proinflammatory cytokines as a precursor to endothelial dysfunction, as manifested by vascular leakage, third spacing, hypovolemia, multiple organ failure, and death.
  • To counter the impact of the disease, clinicians have been advised to use sepsis protocols, including IV rehydration to ameliorate some signs and symptoms, however, once third-spacing is evident, little treatment aside from ZMapp has shown efficacy in reversing the effects of the disease.
    • Previous peer-reviewed research in influenza suggested that statins in conjunction with angiotensin receptor blockers might act as immunomodulatory agents to reduce endothelial dysfunction, and decrease the sepsis-like impact of severe influenza.11
    • One participant with extensive experience in off-label use of statins and angiotensin receptor blockers in infectious diseases reported the results of a non-randomized, non-blinded trial of statins and angiotensin receptor blockers in Sierra Leone to treat the immediate effects of Ebola with positive response. Although the statin-angiotensin receptor blocker combination must undergo full clinical trials before efficacy can be firmly established, it may be a promising treatment.
  • Convalescent blood is an intervention that has been used since the first outbreak of Ebola in 1976. In the 1995 outbreak of Ebola Zaire in Kikwit, Democratic Republic of the Congo. Mupapa and colleagues transfused convalescent blood from five Ebola survivors into eight patients ill with presumed Ebola. The case fatality rate for the study cohort was 12.5% versus 80% for all cases in the population, however lower mortality may simply been a function of better overall care than due to any therapeutic effects from the intervention.12
    • It is thought that antibodies still present in the blood of survivors, approximately 1-2 months post infection, help an ill person’s immune system mount a response against the virus. In this epidemic, convalescent blood has been administered in Stage II and III clinical trials in Liberia, Sierra Leone, and, in the largest trial to date, 89 people have received infusions in Guinea.13 No results have been reported.
Suggestions
  • WHO should continue to explore novel therapeutic uses for generic, pre-approved medications as, if efficacious against Ebola, such medications may present an affordable option for treatment.
  • Convalescent blood, if efficacious against Ebola, could present an opportunity to allow affected countries to build up their health infrastructure to allow for increased whole blood and plasma donations in general while also funding the collection, testing, and storage of blood from survivors to provide convalescent blood.
Unanswered Questions or Areas in Need of Further Study
  • What existing medications may have efficacy against Ebola?
  • What are the ethical implications of therapeutic trials in such a situation?
  • In this context, can there be truly informed consent?

Outcomes Measurement

Discussion
  • Participants reported poor record keeping due to time constraints, lack of information on some patients and the difficulty in exporting data out of the ETU.
  • Clinicians could only speculate as to what treatments did or did not have a benefit. One opined that the antibiotic protocol for Ebola-confirmed patients may have imposed more damage to gut flora than any prophylactic benefit for which it was intended.
  • Others pointed out that a number of pre-hospital factors, such as malnutrition, or time and distance to treatment, might play as important a role in mortality as any factors within the ETU.
  • One participant with past work experience with the United States Center for Disease Control and Prevention made invaluable suggestions about requirements used to adequately assess factors influencing mortality with and between facilities and treatment modalities.
Suggestions
  • Person-level characteristics: To be able to compare outcomes between various sites, facilities should gather person-level characteristics that have already been identified as associated with mortality–for example, viral load on presentation, age, gender, time since onset of symptoms, electrolyte and metabolic labs, and signs and symptoms at presentation (Schieffelin et al, 2014).
    • Other important patient-level data would include distance and time traveled to facility, and information on any treatments, standard or nonstandard, prior to admission to the ETU, intake and output, treatments received during stay, length of stay, renal, hepatic nutritional status and cardiac function, co-morbidities, and final outcomes.
  • Facility-level characteristics: Researchers will require data on facility-level characteristics to control for potential bias in the analysis. Facility-level data would optimally include date facility opened; number of confirmed and suspect beds; direct care staff to patient ratio during stay; average minutes per clinician per day in the ETU; type of facility (MOH, NGO); rural, peri-urban, or urban setting; type of protocol (medications); and average length of stay.
  • Methods: As a necessity, one would need to stratify the patient population by these indicators when evaluating efficacy to allow comparisons between sites, or within sites using different treatment regimens.
    • Sufficient characteristics/unique factors might allow researchers to estimate average treatment effects within and between facilities using propensity score or near-neighbor matching.
Unanswered Questions or Areas in Need of Further Study
  • What extant data is publicly accessible to evaluate the efficacy of various treatments protocols for Ebola?

Conclusion

This paper is comprised of the experiences of less than two-dozen individuals, participants in an Ebola response that has involved the collective efforts of thousands of men and women across the globe. The rich content derived from our GHDonline discussion thread suggests that qualitative analyses from a variety of sources including online fora, focus groups, or oral histories, could inform future approaches to Ebola prevention, diagnosis, and care.

References

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  • 5 World Health Organization (2008) WHO position paper on Oral Rehydration Salts to reduce mortality from cholera. http://www.who.int/cholera/technical/en/
  • 6 Lyon, G. M., Mehta, A. K., Varkey, J. B., Brantly, K., Plyler, L., McElroy, A. K., ... & Ribner, B. S. (2014). Clinical care of two patients with Ebola virus disease in the United States. New England Journal of Medicine, 371(25), 2402-2409.
  • 7 WHO/UNICEF/WFP(2014) Interim guideline: Nutritional care of children and adults with Ebola virus disease in treatment centres. Geneva: World Health Organization; 2014.
  • 8 Weil, A. A., Chisti, M. J., & Harris, J. B. (2014). Diarrheal Illness and Rehydration. Essential Clinical Global Health, 104.
  • 9 Murugaiah, C., Aye, T. S., Soelyoadikoesoemo, B. S., Radhakrishna, H., & Bilung, L. M. (2013). The burden of diarrhoeal disease in malnourished children. Reviews in Medical Microbiology, 24(3), 55-62.
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