6. MANAGEMENT OF VHF PATIENTS

6.1  Medical management of VHF patients

The medical management of VHF patients is a subject on which it is difficult to obtain consensus of opinion, and detailed analysis lies beyond the scope of the present document. The following remarks represent an attempt to summarize experience gained mainly in the management of Congo fever patients in South Africa.

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6.1.1   Antiviral therapy

Antiviral compounds

Ribavirin is a synthetic nucleoside analogue, which has been shown to be of use in treating hantavirus and arenavirus (Lassa fever) infections. There is evidence to suggest that it is of benefit in treating Congo fever patients but the findings are not conclusive, mainly because too few patients have been placed on therapy sufficiently early in the course of the disease for meaningful analysis: since deaths occur from day 5 of illness onwards the disease must be recognized and treated early.

In practice, ribavirin therapy has only been attempted in patients with severe disease and a poor prognosis. In order to reach an early decision to institute therapy, it should be noted that during the first 5 days of illness in Congo fever any of the following pathological values are predictive of fatal outcome: leucocyte count ≥10x109/L; platelet count ≤20x109/L; AST ≥200U/L; ALT ≥150U/L; APTT ≥60 seconds; and fibrinogen ≤110mg/dL. After day 5 of illness any value may be grossly abnormal without necessarily being indicative of a poor prognosis.

The oral preparation of ribavirin is registered in South Africa for the treatment of viral hepatitis. The drug would therefore be used ‘off- label’ for the treatment of CHF or Lassa fever. The trade name is Copegus, a Roche product, available in 200mg tablets. Ideally all severely ill patients should be treated with the intravenous formulation of ribavirin, but unfortunately it is not currently available in South Africa. It generally has to be sourced and imported when required. Table 6.1 and 6.2 shows the recommended dosage for adults and children.

Oral ribavirin treatment of CCHF reported by Fisher-Hoch et al. (14): 4000 mg/d d1-4, 2400 mg/d d5-10.

Ribavirin can cause bone marrow depression, raised serum bilirubin values, nausea and malaise, but these effects are generally overshadowed by the signs and symptoms of VHF. Moreover, the drug is teratogenic in animal models, but its use should still be considered in pregnant patients given the potential for lethality in severe infections.

Congo fever patients have generally succumbed or recovered before completion of 10 days of treatment, resulting in early termination of the treatment.

No other chemotherapeutics are available for the treatment of VHFs, and the use of ribavirin is indicated only for the treatment of hantavirus, arenavirus and Congo fever virus infections. Use of ribavirin is considered to be contraindicated in Rift Valley fever as some patients treated  in  Saudi  Arabia  in  2000  succumbed  to  late-onset  viral  encephalitis,  but  the association with ribavirin is not clear.

Prophylactic use of ribavirin

Oral ribavirin has been used prophylactically in persons deemed to have been exposed to infection with hantaviruses, arenaviruses and Congo fever virus, but the side effects of the drug can cause confusing and distressing illness which is particularly inconvenient when several people are affected. Hence it is advised that prophylaxis should be strictly limited to instances where there are strong indications that there has been exposure to infection, such as needle stick with blood known to be infected. The dosage for prophylaxis is the same as for treatment of infection.

Interferon

It has been demonstrated that interferons have significant antiviral activitiy against VHF agents in vitro and in animal models, and that there may be high levels of interferon expression in VHF patients. There appears to be no information on the value of interferon therapy in VHFs, but it is cautioned that its use in VHF patients poses difficult clinical challenges.

6.1.2   Immune plasma therapy

There is no controlled experimental evidence to indicate that the use of immune plasma is of benefit in VHF, and persons who have recovered from Congo fever generally have low neutralizing antibody activity in their serum which is unlikely to be of therapeutic value.

6.1.3   Supportive treatment

The use of heparin is considered to be useful in the early hypercoaguable stage of DIC, when there is accelerated partial thromboplastin time (PTT) and decreased prothrombin ratio (PR), but is of no value once the fibrinogen level falls. However, most cases of VHF are not diagnosed sufficiently early for use of heparin to be of value. Moreover, the use of the drug requires constant monitoring of the response and is best avoided by the inexperienced.

Thrombocytopaenia is a common feature of VHFs and occurs regularly in CCHF. There is agreement on the need for replacement of platelets, but this should be done only if thrombocytopaenia is accompanied by purpura and active bleeding such as epistaxis, or if platelet counts fall below 20x109/L.

A bag of platelet concentrate contains approximately 0.5 - 1.0X10 11 platelets in about 50 ml of plasma. The dosage of platelet concentrate is 1 bag/10kg body mass and transfusion services can be requested to pool the total dose, e.g. 7 bags can be supplied as 1 bag of 350 ml, which can be administered rapidly (10 minutes). Transfusion services ordinarily supply platelets of appropriate ABO group specificity. The treatment may be repeated over a period of days if the patient's platelet level continues to decline or remains critically low.

If there is manifest consumption of other coagulation factors (abnormal PTT and PR levels, fibrinogen level <0.8g/L), administer fresh frozen plasma (FFP) or fresh dried plasma (FDP)at the rate of 10ml/kg body mass for the first dose. The treatment may be repeated if the patient continues to bleed or if coagulation factor levels remain markedly abnormal. As a general rule, 2-3 units of FFP or FDP should be administered to augment coagulation factors for every 10 units of red cell concentrate given to the patient.

Fibrinogen is not available as a separate product, but apart from its administration in FFP and FDP, it (and other factors) can also be administered in the form of cryoprecipitate. One bag of wet cryoprecipitate contains about 250 mg of fibrinogen and a bottle of dried cryoprecipitate, called anti-haemophilia factor (AHF), which is derived from a pool of 4-6 units of wet cryoprecipitate, contains approximately 1 g of fibrinogen. About 1-2 g fibrinogen (10 bags of wet cryoprecipitate) may be administered as a first dose.

Prothrombin complex concentrate (PCC, factor IX complex, Proplex) may be indicated following liver damage. It contains 200 units factor IX in a10 ml volume and a dose of 1 U/kg should increase the blood level of the factor by approximately 1%. Vitamin K should also be administered.

Intravenous fluids

Plasma is used to replace coagulation factors, not merely for volume expansion, but it is expensive and haemodynamic goals can be achieved with artificial colloids or even crystalloids. Iso-osmotic albumin solution (4%) may be used for volume expansion. Although

20% albumin has been used to treat hypoproteinaemia following liver damage in CCHF, it is considered  better  to  use  an  enteral  feed  that  provides  sufficient  calories  and  protein according to body mass. If the gut is unavailable for enteral nutrition parenteral feeding may be necessary.

Hypoglycaemia was thought to be of critical importance in a number of CCHF patients in South Africa and blood glucose levels should be monitored carefully in severely ill patients.

Other therapy

There  is  no  information  on  the  effectiveness  of  steroids  to  allay  the  ‘cytokine  storm’ underlying the DIC in VHF patients, but there is some support for this approach from animal models. If used, the dose should not exceed 200-300mg hydrocortisone daily. The use of non-steroidal anti-inflammatory drugs is not recommended.

Antacids, painkillers, relaxants and tranquillisers are administered as indicated.

Antibiotic prophylaxis is generally not indicated, however many patients will have received antibiotics prior to the diagnosis having been made. As with all patients in the ICU regular screening for colonization and infection is necessary.

Counselling of patients and relatives is mandatory as this is a highly stressful situation.

6.2  Clinical pathology monitoring of VHF patients

Requirements

Hospitals which manage suspected or confirmed cases of VHF should have available the services of a laboratory able to conduct the following tests:

●   A minimum range of screening tests to eliminate non-VHF diseases:

§  Full blood count.

§  Examination of blood smears for parasites and bacteria.

§   Blood cultures for septicaemia.

●    Haematological  and  clinical  chemistry  tests  to  monitor  treatment  and  progress  of patients:

§  Full blood counts (including platelet and haemoglobin values).

§  Coagulation studies.

§  Liver function tests.

§  Blood glucose tests.

§  Creatinine, urea, electrolyte determinations.

§  Blood gases and pH determinations.

§  Cross matching studies for transfusions.

Ideally  the  tests  should  be  conducted  by  a  small  team  of  experienced  volunteer technologists in a room set aside for the purpose within an existing laboratory, but since the occurrence of VHF is sporadic the expenditure to equip a dedicated unit is not justified. Consequently, the required tests are often conducted within routine laboratory facilities temporarily set aside for the purpose as required.

Operational procedures

Technologists who conduct clinical pathology tests on specimens from VHF patients should be trained in the donning, removal, and disposal of personal protective equipment (PPE), and entry and exit procedures from infected areas, as described under isolation precautions for VHF patients (see section 6,3).

Only volunteer team members should be present during the testing of specimens from suspected or confirmed VHF patients, and as far as possible manipulation of specimens should be performed in biohazard laminar flow safety cabinets (class IIA).

Duty registers should be kept, with staff subjected to the same monitoring as other medical personnel  dealing  with  VHF  patients,  and  incidents  constituting  potential  exposure  to infection, including injuries and spillages, should be dealt with as described in sections 6.4 and 7.

Decontamination of laboratory equipment including auto analyzers should follow standard operating procedures developed from manufacturer’s instructions.

Decontamination of laboratory floors, walls and work surfaces, and disposal of waste materials, should follow procedures described in section 6.4.

Specimens for monitoring of VHF patients should be preserved at least until the patient is discharged or a diagnosis is established in a deceased patient, and should then be disposed of in a safe manner (autoclaved or sent for incineration). However, specimens should be offered to the Special Pathogens Unit (SPU) at the National Institute for Communicable Diseases (NICD) rather than destroyed, since much valuable information is gained from the examination of serial samples from VHF patients.

Ideally a separate clotted blood sample should be taken daily from confirmed VHF patients for submission to NICD, but these can be submitted together when the patient is discharged.

6.3 Isolation precautions (formerly known as barrier-nursing procedures)

Although the VHFs are seldom encountered, the consequences of being unprepared can be extremely serious. All medical institutions should formulate and implement contingency plans for isolating and managing VHF patients, even on a temporary basis. The aims should be to:

●   Identify facilities and resources which can be utilized for isolating and managing VHF patients.

●    Provide health care workers with training and instructions specific to their duties so that they are able to act in an informed manner when suspected cases of VHF are encountered.

●    Train all staff members to recognize potential cases of VHF, but ensure that critical assessment of such cases is performed by experienced clinicians and infection control personnel.

●   Train suitable volunteers in isolation precautions. Experience has shown that when VHF occurs in an institution where        there has been no prior discussion of VHFs and  training  in  isolation  precautions  it  may  be  extremely  difficult  to     obtain volunteers. Do not be caught unprepared.

●    Ensure  that  infection  control  personnel  monitor  safety  practices  during  isolation precautions and place staff who are in contact with VHF patients or fomites under observation (see section 7.3).

●    Establish proper channels of communication so that relevant members of staff at all levels are informed promptly of the existence of a suspected case of VHF, or of the impending arrival at a hospital of such a patient, and of all key developments in the handling of the case.

●    Extend the system of communication to outside officials who need to be kept informed, such as Communicable Disease Control officials of the national and provincial Departments of Health (see section 7).

●   Make provision for well-informed responses to enquiries from news media (see section 7).

Facilities

The minimum accommodation required for isolation precautions consists of one room in which the patient may be isolated and an ante-room or adjacent room where staff can don and remove personal protective equipment (PPE). Ideally, isolation units should have separate entrance and exit (‘clean and dirty’) channels, and it is advantageous if the ante- room has a hand-basin and if ablution facilities are located in convenient proximity to the patient's room. The equipments and supplies required in the patient isolation room are listed in Table 6.3 below. Since VHF patients are often in need of intensive care, the isolation unit may need to consist of a cubicle or section of an ICU ward which can be closed off.

In addition to the patient room and ante-room there should be:

●    An area suitable for a nursing station where staff wait when not in direct attendance on the patient.

●   An area or room for storing supplies and equipment.

●    A  room  or  enclosed  area  for  changing  from  street  clothes  into  surgical  theatre  or equivalent clothing.

●    An observation room/ward in which to place high risk contacts of VHF patients who become sick, i.e. potential but unconfirmed secondary cases (such a facility is seldom

required).

●    A two-way communications system between the patient isolation room and the nursing station if necessary.

Much of the PPE is available in disposable plastic or paper form at all hospitals and clinics. Up to 25 changes of protective clothing may be required per day in nursing a patient during the critical phase of VHF illness (not all patients become severely ill or exhibit bleeding tendencies). Some hospitals utilize mended and condemned linen and theatre clothes for nursing VHF patients, but dye the items an obvious colour to help ensure that they are disposed of safely. Ideally, hospitals should keep stocks of the essential items in readiness, but this involves dedication of funds and secure storage space, plus rotation of perishable items. Alternatively, stocks should be secured immediately an emergency arises. Formidable epidemic disease packs (FED packs) containing virtually all of the above PPE items are available  commercially,  and  customized  packs  can  be  prepared  to  order  or  within  the hospital.

Safety equipment

It is notable that international teams operating under the auspices of the World Health Organization to control outbreaks of Marburg and Ebola haemorrhagic fevers in Africa use only standard PPE items specified above. Almost all VHF patients in South Africa have been nursed without special safety equipment, and all nosocomial infections occurred before the patients were placed under conditions of isolation precautions.

In the past, some hospitals in South Africa acquired special safety equipment for protection of staff against nosocomial infection, ranging from containment bed isolators, full-face respirators (gas masks) to battery-operated positive-pressure ventilated respirators (‘pappers’). There are disadvantages associated with each of these items: bed isolators are very expensive and occupy a large floor space; gas masks are tiring to use and tend to become fogged, thus reducing visibility and efficiency; pappers require expensive semi- disposable hoods and interfere with the use of stethoscopes.

Nevertheless, the use of pappers may be warranted for particularly hazardous procedures, such as intubation of VHF patients under intensive care. Hoods may be re-used by the same staff member for successive entries into the patient isolation room provided they are disinfected on exit from the isolation room as described below (they should be marked with the name of the user). Power supply points will be required in the ante-room for re-charging batteries, plus a rack or coat hooks for hanging respirators and hoods when not in use.

Personnel

Ideally, specifically trained, volunteer staff should be used for nursing VHF patients, and personnel who were in contact with the VHF patient/s before isolation precautions were implemented should be utilized first to limit potential exposure of further members of staff. Select persons of calm disposition able to cope with the stress of nursing VHF patients under strict isolation precautions.

Nosocomial infections can almost invariably be traced to fundamental lapses in technique, such as needle-sticks, against which most safety equipment cannot protect. Fatigue causes mistakes and hence adequate numbers of staff should be delegated to nursing patients under conditions of strict isolation precautions without seriously depleting the rest of the hospital or unnecessarily exposing too many individuals to VHF. If the nursing load is too heavy, as when multiple patients are involved, it may be necessary to suspend some or all- routine functions of the hospital. Counselling of staff (plus patients and families) should be offered to alleviate stress.