Recommendations for Managing and Preventing Cases of Malaria in Areas with Ebola

Key Points:

1. Malaria is a cause of considerable morbidity and mortality in Guinea, Liberia, and Sierra Leone and is a major killer of children less than 5 years of age.
2. Symptoms of malaria overlap considerably with symptoms of Ebola, which may result in misclassification of malaria as Ebola and Ebola as malaria.
3. The World Health Organization (WHO) recommends that blood samples for laboratory diagnosis of malaria not be collected in areas with Ebola unless adequate personal protective equipment (PPE) is used. If a malaria diagnostic test is not done, presumptive treatment of malaria should be provided whenever a patient presents with measured or reported fever.
4. During a time when the health care system is disrupted and access to malaria treatment may be compromised, efforts should be made to improve access to antimalarial drugs and other prevention measures, such as insecticide treated nets.
5. A treatment dose of an artemisinin combination therapy (ACT) will provide approximately 2 to 3 weeks of post-treatment chemoprophylaxis against malaria, protecting the patient from malaria illness and malarial fevers during that time period. This will potentially reduce the workload on the health system.

Background

Guinea, Liberia, Sierra Leone—the three countries most affected by the current Ebola virus disease (Ebola) epidemic—are also countries with high year-round malaria transmission. National estimates of Plasmodium falciparum parasite infection prevalence among children aged 6–59 months in Liberia, Sierra Leone, and Guinea are 45%¹, 46%² and 47%³, respectively. Before the Ebola epidemic, malaria was responsible for approximately 30% of pediatric consultations, 25% of hospitalizations, 14% of hospital deaths, and 12,000^{4, 5}, total deaths annually in Guinea. In Liberia, malaria was responsible for 40% of all outpatient and inpatient visits and 33% of inpatient deaths⁶. Malaria continues to be a life-threatening disease in the countries with Ebola, and the risk of malaria-associated morbidity and mortality in these countries is now made greater because of the reduction in healthcare services and access to those services. Increases in malaria morbidity, mortality, and transmission may worsen the current public health crisis. Symptoms of malaria and Ebola are non-specific and have considerable overlap. A patient can be infected at the same time with both malaria and Ebola. While a negative malaria diagnostic test should be reassuring that a patient does not have malaria, a positive malaria diagnostic test does not rule out Ebola, and these patients will still need to be screened for Ebola. Malaria complicates Ebola triage and management; because of overlapping symptoms, many patients suffering from malaria will meet the case definition for “suspect Ebola” and will require Ebola testing. Additionally, malaria-related deaths may get classified as Ebola, and contacts of the deceased listed and traced unnecessarily. The overall effect adds further stress to an already fragile and over-taxed health system. CDC, with substantial input from WHO malaria subject-matter experts, has drafted the following recommendations for managing and preventing malaria in countries with Ebola outbreaks. Individual countries have their own malaria control guidelines. These recommendations are provided for strategic guidance and may need to be adapted by the respective MOHs to in-country context. Improving access to presumptive malaria treatment and prevention measures are emphasized to reduce malaria fevers and death and to reduce burden on health systems.

Malaria Testing and Treatment in areas with Ebola

The US government supports the WHO/CDC recommendations for malaria testing and treatment in areas with Ebola outbreaks, as follows⁷:

Wherever PPE requirements^* cannot be met, rapid diagnostic tests (RDTs) for malaria should be suspended until either the required level of PPE and appropriate training has been received or the state of the National Ebola Health Emergency has been officially declared to have ended. In the absence of RDTs

1. Patients with suspect malaria cases should be treated empirically with a full dose of the recommended ACT, with a positive clinical response expected within 48 hours.
2. No positive response to ACT treatment (i.e., fever has not resolved within 48 hours of treatment) excludes malaria as a cause of fever and strengthens the likelihood of other aetiologies for the febrile illness, including Ebola.

Malaria Testing and Treatment in Ebola Treatment Units (ETU), Ebola Wards, or Ebola Care Centers Where Care Is Provided to Patients with Confirmed or Suspected Cases of Ebola and Appropriate PPE and Waste Disposal Is in Place

1. All suspected and confirmed Ebola patients should be treated presumptively for malaria on presentation to the ETU, Ebola ward, or Ebola Care Center, unless there is a reliable history that the patient had already received malaria treatment with an ACT during the 2 weeks before admission.
2. Malaria testing by RDT or blood smear microscopy should be done, if possible, at the time of Ebola testing or when other blood tests are done. Although a positive malaria test does not rule out Ebola, and the patient will receive malaria treatment regardless of the result, diagnosing malaria may be helpful if malaria treatment becomes difficult (e.g., inability to tolerate oral antimalarial therapy due to vomiting or loss of consciousness). In these situations, a positive malaria test result would justify providing rectal artesunate for children younger than 5 years, or intravenous (IV) artesunate or intramuscular (IM) artemether for patients of any age.

Rationale: Patients living in the three countries most affected by Ebola are at risk for malaria, whether or not they have Ebola. Malaria can be a life-threatening illness that is readily treated with effective antimalarial drugs. RDT and microscopy results may initially be negative but become positive as parasite densities increase. Repeated blood draws may not be possible or desirable in patients with suspected or confirmed cases of Ebola. ACTs are well tolerated and have few serious side effects, even for those who do not have malaria. A treatment dose of an ACT will provide approximately 2 to 3 weeks of post-treatment chemoprophylaxis against malaria, protecting the patient from malaria illness and malarial fevers during that time period.

Malaria Case Management at Peripheral Health Facilities

1. Presumptively treat all patients with suspect cases of Ebola with the first-line ACT at first contact.
2. All persons with fever or a recent history of fever, regardless of age, should receive presumptive treatment for malaria with an ACT or a malaria diagnostic test (if appropriate PPE available). Ensuring the availability of malaria treatment to those requiring treatment is important to prevent unnecessary severe disease and deaths.
   • To ensure prompt treatment and avoid missed treatments, ACTs should be administered at the point of triage, before isolation or transport.
   • Presumptive oral ACTs should be provided to those who are able to take oral medications. For those who are vomiting or who have other symptoms that prevent the administration of oral ACTs, pre-referral RA for children under 5 years of age or IM artemether for all ages should be provided, using appropriate PPE.
3. Patients with suspected severe malaria should be provided pre-referral treatment with oral ACTs, if able to take oral medications, or with IM artemether, using appropriate PPE.
4. For children under 5 years of age with suspected cases of severe malaria in, consider scaling up the use of presumptive pre-referral treatment with RA. RA should be administered by trained health workers, using appropriate PPE.

Malaria Case Management in the Community, Outside of Health Facility Settings, Using a No-Touch Policy

A no-touch policy should be implemented when sufficient PPE and training are not available. Whenever possible, there should be no contact between the community health worker (CHW) and the patient. Presumptive diagnoses are made from history and visual inspection only, maintaining a distance of at least three feet from the patient at all times. Medication is provided by placing the medicine in a cup or other container and placing the cup on a table for the patient to retrieve.

1. Presumptively treat all patients identified in the community with suspect cases of Ebola with the first-line ACT at first contact.
2. Presumptively treat all persons with fever or a recent history of fever for malaria with the first-line ACT.
3. Where feasible, consider treating all contacts of Ebola cases with the first-line ACT at first contact. Consider having surveillance officers or contact tracers provide the presumptive treatment.
4. Where prompt treatment for malaria is not accessible because of health facility closures, poor drug supply chain, or fear, alternative means to improve access to ACTs should be explored with MOHs. Any person with fever or a recent history of fever should receive presumptive treatment for malaria.
   • Train and employ CHWs or traditional birth attendants (TBAs) to provide ACTs in the community to anyone with reported fever.
   • With the cooperation of drug providers, consider stationing MOH nurses from closed health facilities at fixed drug distribution sites where community members are likely to seek care for febrile illness, such as chemists or pharmacies, to provide ACTs free of charge, using a no touch policy. ACTs can be provided to the healthy caregiver of a reportedly febrile patient in the home, with instructions on how to administer the ACTs and information that the patient should return for follow up if she or he does not improve. If the fever is due to malaria, fever should resolve within 48 hours of ACT administration. If fever has not resolved within 48 hours, the patient should be re-evaluated for other sources of fever, including Ebola.

Rationale: In some areas of the countries most affected by Ebola, the health system is either overburdened or nonfunctional. In addition, many febrile patients may avoid accessing a health facility even if it is open and functioning because of the fear of getting infected by Ebola. Creative temporary means to bring malaria treatment to the patient are required.

Providing malaria treatment at first contact treats malaria infection if present and prevents progression to severe disease. It also reduces the risk of a subsequent malarial fever being misclassified as fever caused by Ebola. Malaria treatment with the first-line ACT will provide approximately 2 to 3 weeks of post-treatment chemoprophylaxis against malaria, reducing the risk of malarial fever through most of the contact tracing follow-up period. This will potentially reduce the workload on the health system.

Mass Drug Administration (MDA) with Antimalarial Drugs

Organizations that are considering MDA should coordinate with the respective MOH and should consult technical partners for guidance on how to implement this strategy. MDA is a strategy that has been used in malaria control; a treatment dose of an antimalarial drug is provided to all eligible persons in a given geographic area without prior testing for malaria and regardless of whether symptoms of malaria are present. In settings where malaria transmission is high and MDA is feasible, MDA might be useful for the treatment of malaria and the prevention of new malaria infections. Depending on the antimalarial drugs, the chemoprophylactic effect may last up to 21 days or more and could be implemented monthly during a high transmission season or monthly until ACTs reliably become available through the health system or other outlets. After two to three rounds of MDA, the need for continued MDA rounds should be assessed.

Treatment of malaria (suspected or proven malaria)

Treatment options include

1. Oral ACTs for uncomplicated or severe malaria
   • In areas with Ebola outbreaks, oral ACTs can be used, even for severe illness, if the patient is able to retain oral medication.
2. Oral quinine for severe malaria if the patient is able to retain oral medication
3. IV/IM artesunate or IM artemether or IV/IM quinine if the patient is not bleeding excessively and appropriate PPE and waste management available
4. RA for children 5 years of age or younger and appropriate PPE available

Refer to national guidelines for drug dosing.

Long Lasting Insecticide Treated Nets (LLINs)

1. High LLIN coverage will reduce malaria illness and death. Two complementary means are used to achieve high coverage: 1. mass LLIN distribution campaigns, and 2. routine distribution systems. The need for mass campaigns in the Liberia, Sierra Leone, or Guinea is based on the LLIN coverage in each individual country and on the time since the last mass distribution campaign.
2. Where maternal child health (MCH) clinics or antenatal clinics (ANC) are operating, LLINs should be distributed free of charge through these outlets.
3. Where MCH clinics and ANC clinics have closed, alternative outlets should be identified for routine LLIN distribution to vulnerable groups (children under 5 years of age and pregnant women), e.g. by CHWs or TBAs.
4. LLINs used by an Ebola patient should be burned to reduce fomite spread of Ebola. A new LLIN should be provided to survivors and can be provided upon leaving the ETU.

To avoid crowding at sites of LLIN distribution, LLIN campaigns might rely on a voucher system, providing LLINs free of charge at distribution points.

Rationale: Preventing malaria will reduce the malaria burden overall as well as fever incidence in the community, thus reducing the number of febrile patients presenting for Ebola assessment/diagnosis. Additional guidance for mass distribution and disposal of LLINs are available⁸.

Laboratory Diagnosis of Malaria in Areas with Ebola

Laboratory diagnosis should only be done if appropriate PPE is available^*

1. RDT testing of malaria
   Testing can be performed on either finger-prick blood or blood collected in EDTA containing tube. The effect of Ebola virus inactivating agents could affect the performance of malaria RDTs, and until further evidence is available, RDTs should not be performed on inactivated samples.
2. Microscopic testing of malaria
   Preparation and staining of blood films should be done in compliance with Ebola virus inactivation procedures. See https://www.cdc.gov/malaria/new_info/2014/malaria_ebola.htm

Note: Formalin will fix the thick film and may alter the parasite morphology and therefore should not be used.

Clinical Management

• Guidance for clinical management of patients with malaria
• Guidance for clinical management of patients with viral hemorrhagic fever