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Guideline Summary
Guideline Title
The prevention of malaria in pregnancy.
Bibliographic Source(s)
Royal College of Obstetricians and Gynaecologists (RCOG). The prevention of malaria in pregnancy. London (UK): Royal College of Obstetricians and Gynaecologists (RCOG); 2010 Apr. 14 p. (Green-top guideline; no. 54A).  [129 references]
Guideline Status

This is the current release of the guideline.

FDA Warning/Regulatory Alert

Note from the National Guideline Clearinghouse: This guideline references a drug(s) for which important revised regulatory and/or warning information has been released.

  • July 29, 2013 – Mefloquine Hydrochloride External Web Site Policy: The US Food and Drug Administration (FDA) is advising the public about strengthened and updated warnings regarding neurologic and psychiatric side effects associated with the antimalarial drug mefloquine hydrochloride. A boxed warning, the most serious kind of warning about these potential problems, has been added to the drug label. FDA has revised the patient Medication Guide dispensed with each prescription and wallet card to include this information and the possibility that the neurologic side effects may persist or become permanent.

Scope

Disease/Condition(s)

Malaria in pregnancy

Guideline Category
Counseling
Prevention
Risk Assessment
Clinical Specialty
Family Practice
Infectious Diseases
Internal Medicine
Obstetrics and Gynecology
Intended Users
Advanced Practice Nurses
Nurses
Physician Assistants
Physicians
Guideline Objective(s)

To provide clinicians with evidenced based, up-to-date information about the prevention of malaria in pregnancy in situations that are likely to be encountered in UK medical facilities

Target Population

Pregnant or breastfeeding women and women planning a pregnancy (UK-based residents visiting malaria endemic areas)

Note: These guidelines are not necessarily appropriate for those residing in endemic areas.

Interventions and Practices Considered
  1. Advising women to consider postponing trips to malaria endemic countries
  2. Advising women on malaria risks, avoidance strategies, and symptoms
  3. Informing women about bite prevention measures including skin repellents, knock-down mosquito sprays, insecticide-treated bed nets, clothing and room protection
  4. Advising women and their general practitioners about the risks and benefits of malaria chemoprophylaxis (mefloquine)
  5. Providing written instructions for pregnant travelers regarding emergency standby malaria treatment

Note: Atovaquone and proguanil (Malarone®) for prophylaxis in the second and third trimesters of pregnancy was considered but not recommended.

Major Outcomes Considered
  • Maternal and fetal/neonate morbidity and mortality
  • Risk of contracting malaria
  • Adverse effects of prevention measures
  • Efficacy of prevention measures

Methodology

Methods Used to Collect/Select the Evidence
Hand-searches of Published Literature (Primary Sources)
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases
Description of Methods Used to Collect/Select the Evidence

A literature search was performed using Medline (1983 to November 2009). The keywords used were 'malaria', 'prevention', 'travellers', 'UK', 'imported malaria', 'pregnancy' and 'breast feeding'. Reference lists of the articles identified were hand searched for additional articles. Other sources included malaria-related pages from the websites of the Health Protection Agency (www.hpa.org.uk/HPA External Web Site Policy), the National Travel Health Network and Centre (www.nathnac.org External Web Site Policy), European Network on Imported Infectious Disease Surveillance (www.tropnet.net External Web Site Policy), Centers for Disease Control and Prevention (www.cdc.gov/Malaria External Web Site Policy) and TOXBASE, the primary clinical toxicology database of the National Poisons Information Service (www.toxbase.org External Web Site Policy).

Number of Source Documents

Not stated

Methods Used to Assess the Quality and Strength of the Evidence
Weighting According to a Rating Scheme (Scheme Given)
Rating Scheme for the Strength of the Evidence

Classification of Evidence Levels

1++ High-quality meta-analyses, systematic reviews of randomised controlled trials or randomised controlled trials with a very low risk of bias

1+ Well-conducted meta-analyses, systematic reviews of randomised controlled trials or randomised controlled trials with a low risk of bias

1– Meta-analyses, systematic reviews of randomised controlled trials or randomised controlled trials with a high risk of bias

2++ High-quality systematic reviews of case–control or cohort studies or high-quality case–control or cohort studies with a very low risk of confounding, bias or chance and a high probability that the relationship is causal

2+ Well-conducted case–control or cohort studies with a low risk of confounding, bias or chance and a moderate probability that the relationship is causal

2– Case–control or cohort studies with a high risk of confounding, bias or chance and a significant risk that the relationship is not causal

3 Non-analytical studies; e.g., case reports, case series

4 Expert opinion

Methods Used to Analyze the Evidence
Review of Published Meta-Analyses
Systematic Review
Description of the Methods Used to Analyze the Evidence

Reviewing and Grading of Evidence

Once the evidence has been collated for each clinical question it needs to be appraised and reviewed (refer to section 3 in "Development of RCOG Green-top guidelines: producing a clinical practice guideline" for information on the formulation of the clinical questions; see the "Availability of Companion Documents" field). For each question, the study type with least chance of bias should be used. If available, randomised controlled trials (RCTs) of suitable size and quality should be used in preference to observational data. This may vary depending on the outcome being examined.

The level of evidence and the grade of the recommendations used in this guideline originate from the guidance by the Scottish Intercollegiate Guidelines Network (SIGN) Grading Review Group, which incorporates formal assessment of the methodological quality, quantity, consistency, and applicability of the evidence base. The methods used to appraise individual study types are available from the SIGN Web site (www.sign.ac.uk/methodology/checklists.html External Web Site Policy). An objective appraisal of study quality is essential, but paired reviewing by guideline leads may be impractical because of resource constraints.

Once evidence has been collated and appraised, it can be graded. A judgement on the quality of the evidence will be necessary using the grading system (see the "Rating Scheme for the Strength of the Evidence" field). Where evidence is felt to warrant 'down-grading', for whatever reason, the rationale must be stated. Evidence judged to be of poor quality can be excluded. Any study with a high chance of bias (either 1– or 2–) will be excluded from the guideline and recommendations will not be based on this evidence. This prevents recommendations being based on poor-quality RCTs when higher-quality observational evidence is available.

Methods Used to Formulate the Recommendations
Expert Consensus
Informal Consensus
Description of Methods Used to Formulate the Recommendations

Guideline Development

The development of guidelines involves more than the collation and reviewing of evidence. Even with high-quality data from systematic reviews of randomised controlled trials, a value judgement is needed when comparing one therapy with another. This will therefore introduce the need for consensus.

Royal College of Obstetricians and Gynaecologists (RCOG) Green-top guidelines are drafted by nominated developers, in contrast to other guideline groups such as the National Institute for Health and Clinical Excellence (NICE) and the Scottish Intercollegiate Guidelines Network (SIGN), who use larger guideline development groups. Equally, in contrast to other guideline groups, the topics chosen for development as Green-top guidelines are concise enough to allow development by a smaller group of individuals.

In agreeing the precise wording of evidence-based guideline recommendations and in developing consensus-based 'good practice points', the Guidelines Committee (GC) will employ an informal consensus approach through group discussion. In line with current methodologies, the entire development process will follow strict guidance and be both transparent and robust. The RCOG acknowledges that formal consensus methods have been described but these require further evaluation in the context of clinical guideline development. It is envisaged that this will not detract from the rigor of the process but prevent undue delays in development.

Rating Scheme for the Strength of the Recommendations

Grades of Recommendations

A - At least one meta-analysis, systematic review, or randomised controlled trial rated as 1++ and directly applicable to the target population; or

A systematic review of randomised controlled trials or a body of evidence consisting principally of studies rated as 1+ directly applicable to the target population and demonstrating overall consistency of results

B - A body of evidence including studies rated as 2++ directly applicable to the target population, and demonstrating overall consistency of results; or

Extrapolated evidence from studies rated as 1++ or 1+

C - A body of evidence including studies rated as 2+ directly applicable to the target population and demonstrating overall consistency of results; or

Extrapolated evidence from studies rated as 2++

D - Evidence level 3 or 4; or

Extrapolated evidence from studies rated as 2+

Good Practice Point - Recommended best practice based on the clinical experience of the guideline development group

Cost Analysis

A formal cost analysis was not performed and published cost analyses were not reviewed.

Method of Guideline Validation
External Peer Review
Internal Peer Review
Description of Method of Guideline Validation

Following discussion in the Guidelines Committee (GC), each Green-top guideline is formally peer reviewed. At the same time, the draft guideline is published on the Royal College of Obstetricians and Gynaecologists (RCOG) Web site for further peer discussion before final publication.

All comments will be collated by the RCOG and tabulated for consideration by the guideline leads. Each comment will require discussion. Where comments are rejected then justification will need to be made. Following this review, the document will be updated and the GC will then review the revised draft and the table of comments.

Once the GC signs-off on the guideline, it is submitted to the Standards Board for approval before final publication.

Recommendations

Major Recommendations

In addition to these evidence-based recommendations, the guideline development group also identifies points of best clinical practice in the original guideline document.

Classification of evidence levels (1++ to 4) and grades of recommendations (A-D) are defined at the end of the "Major Recommendations" field.

What Are the Medical Complications of Malaria in Pregnancy?

C - Malaria infection in pregnancy carries significant risks to mother and baby.

B - UK-based residents have low premunition and high susceptibility to malaria infection.

B - Malaria infection in pregnancy may result in reduced birth weight in the fetus and this may have health consequences in later life.

Prevention of Malaria Infection in Pregnancy

What Advice Should Pregnant Women Be Given if They Are Considering Travel to a Malaria Endemic Area?

C - Pregnant women should consider the risks of travel to malaria endemic countries and consider postponing their trip, unless travel is unavoidable.

A health professional advising a prospective UK resident who is pregnant or thinking about becoming pregnant and who is intending to go to a malaria endemic area should suggest that the woman consider not going or postponing her trip until she is no longer pregnant (see Table 1 in the original guideline document).

If Travel Is Unavoidable What Advice Should Pregnant Women Receive about Preventing Malaria Infection?

B - Advise the woman to seek guidance from a centre with expertise on malaria risks and avoidance strategies.

B - Advise women that a fever or flu-like illness while travelling or upon returning home, up to 1 year or more, may indicate malaria and requires medical attention.

B - Advise the woman on the risk of being exposed to malaria at her intended area of travel.

There are no measures specific to pregnancy that can be taken to prevent malaria beyond those that non-pregnant travellers can apply.

The 'ABCD' of malaria prevention is a useful formula to remember the components of malaria prevention:

  • Awareness of risk (see Section 5.2.1 in the original guideline document)
  • Bite prevention (see Section 5.3 in the original guideline document)
  • Chemoprophylaxis (see Section 5.4 in the original guideline document)
  • Diagnosis and treatment which must be prompt (see Section 5.5 in the original guideline document)

Women need to be educated about possible measures and, where possible, provided with written information in their own language.

What Needs to Be Done to Raise Pregnant Traveller's Awareness of the Risk of Malaria?

Despite applying effective anti-mosquito measures and good compliance to chemoprophylaxis, women can still contract malaria. Education about the symptoms of malaria (such as a fever or flu-like illness) is beneficial to travellers: it enables them to realise that they need to seek medical attention without delay and to state that they have travelled to a malarious area. Worryingly, some migrant groups and their families do not access effective antimalarial prophylaxis. Adult travellers born in Africa were reported to hold a belief that malaria was trivial or that they were protected from severe malaria. It is important to challenge and advise on misconceptions. Awareness of the risk is vital. Women may find the websites listed in Box 1 of the original guideline document useful to learn about malaria for travellers and to reinforce the points already made to them.

How Should Bites Be Prevented?

A - Inform women about bite prevention measures, including skin repellents, knock-down mosquito sprays, insecticide-treated bed nets, clothing and room protection.

The anopheline mosquito has different preferred biting times in different parts of the world but making the assumption that the risk period is from dawn to dusk will suffice. In pregnancy, other mosquito-borne diseases, such as dengue, which is caused by a daytime-biting mosquito, should be prevented, so applying mosquito bite prevention measures 24 hours a day is advisable.

Repellents – the Evidence Favours Skin Repellents Containing 50% DEET (N,N-diethyl-m-toluamide or N,N-diethly-3-methyl-benzamide)

As the consequences of malaria in pregnancy can be devastating and higher concentrations give longer protection, 50% DEET is recommended. In a sweaty environment, the effect of repellent is lowered and more frequent applications are required. [Evidence level 1]

Knock-Down Mosquito Sprays: Permethrin and Pyrethroids Sprays Kill Resting and Flying Mosquitoes

Whether women stay in air-conditioned hotel rooms or tents, a can of insect spray active against mosquitoes is useful to help clear the room of mosquitoes. Pyrethroids will quickly kill mosquitoes and are the preferred ingredient in sprays, while permethrin will both repel and kill mosquitoes when used regularly in the same room. [Evidence level 2+]

Insecticide Treated Bed Nets: Long Lasting Pyrethroid-Impregnated Bed Nets Offer Significant Protection

Women sleeping outdoors or in unscreened accommodation should use long-lasting pyrethroid-impregnated nets. If the net is not long-lasting it needs reimpregnating every 6 months, starting from the first date on which the net is used after purchase. Permethrin-impregnated hammocks are another possibility. [Evidence level 1++]

Clothing That Covers the Body and Forms a Barrier from Biting Mosquitoes Will Reduce the Risk of Malaria

After sunset, long sleeves, long trousers, loose-fitting clothing and socks, regardless of colour, are recommended. Clothes can be impregnated with permethrin or permethrin or DEET can be spayed on to the clothes. [Evidence level 1–]

Room Protection: Electrically Heated Mats Will Kill Mosquitoes in the Room

If electricity can be relied upon, an electrically heated device that vaporises synthetic pyrethroids from a mat tablet can kill mosquitoes. A supply of mats is required, as new mat is needed each night. While mosquito coils could be used as an alternative, they are not as effective and not recommended indoors. [Evidence level 2+]

Which Drug Can Be Recommended for Malaria Prevention in Pregnancy?

A - Inform women (and their general practitioner) of the risks and benefits of chemoprophylaxis versus the risks of malaria.

A - Remind women that there is no malaria prophylaxis regimen that is 100% protective.

The choice of drug and advice about chemoprophylaxis in pregnant women depends on the level of chloroquine-resistant Plasmodium falciparum and P. vivax malaria and the trimester of pregnancy. There are malaria prevention guidelines produced for travellers who are UK residents and these are detailed: by country and popular destination and updated regularly. It is not the aim of this guideline to reproduce these guidelines here. They can be directly accessed on the Health Protection Agency website (www.hpa.org.uk/HPA/Topics/InfectiousDiseases/InfectionsAZ External Web Site Policy) and clicking on malaria. Updates to guidelines, such as change in resistance or transmission, can be found at the same place.

Chemoprophylaxis for malaria can be causal or suppressive. Causal prophylaxis is directed against liver schizont stage, which takes approximately 7 days to develop so these drugs (for example, atovaquone-proguanil [Malarone®] need to be continued for 7 days after leaving a malarious area. Suppressive prophylaxis (such as mefloquine) is directed against the red blood cell stages of the malaria parasite and so should be continued for 4 weeks after leaving a malarious area. The full listings of drug actions, dosages, adverse effects, interactions and contraindications is contained in the British National Formulary (www.bnf.org External Web Site Policy) and will not be repeated here. Women should be warned that drugs purchased in endemic countries or over the internet may be cheaper but they may be fake. [Evidence level 1+]

Chemoprophylaxis for Women Planning a Pregnancy

Women planning pregnancy and travelling to a destination where there is a risk of contracting malaria should be advised there may be harmful consequences for the pregnancy. Prophylaxis is not 100% effective and malaria is associated with increased risk of miscarriage. Women should be advised not to travel or to choose an alternative destination. If it is not possible to delay either the pregnancy or the travel plan, advice from a specialist with current experience of malaria should be sought (Box 2). Chloroquine and proguanil are not efficacious in chloroquine-resistant areas and cannot be recommended because of this. There are very few chloroquine-sensitive areas remaining.

To avoid completely any potential adverse drug effects from preconceptual and first-trimester exposure, it is advisable to wait for complete excretion of the drug, if it was taken for prophylaxis, before becoming pregnant (see Table 3 in the original guideline document). Nevertheless, unplanned conception while taking malaria prophylaxis is not considered a reason to recommend termination of pregnancy, owing to the low risk of teratogenicity.

Chemoprophylaxis for Pregnant or Breastfeeding Women

Mefloquine (5mg/kg once a week) is the recommended drug of choice for prophylaxis in the second and third trimesters for chloroquine-resistant areas. With very few areas in the world free from chloroquine resistance, mefloquine is essentially the only drug considered safe for prophylaxis in pregnant travellers (see Table 4 in the original guideline document).

Emergency Standby Treatment in Pregnancy?

D - Written instructions should be given to a pregnant traveller regarding emergency standby malaria treatment in the event of suspected malaria without access to medical care.

Suspected malaria is a medical emergency and women should seek diagnosis and treatment at a health facility at the earliest opportunity. [Evidence level 3]

Definitions:

Grades of Recommendations

A - At least one meta-analysis, systematic review, or randomised controlled trial rated as 1++ and directly applicable to the target population; or

A systematic review of randomised controlled trials or a body of evidence consisting principally of studies rated as 1+ directly applicable to the target population and demonstrating overall consistency of results

B - A body of evidence including studies rated as 2++ directly applicable to the target population, and demonstrating overall consistency of results; or

Extrapolated evidence from studies rated as 1++ or 1+

C - A body of evidence including studies rated as 2+ directly applicable to the target population and demonstrating overall consistency of results; or

Extrapolated evidence from studies rated as 2++

D - Evidence level 3 or 4; or

Extrapolated evidence from studies rated as 2+

Good Practice Point - Recommended best practice based on the clinical experience of the guideline development group

Classification of Evidence Levels

1++ High-quality meta-analyses, systematic reviews of randomised controlled trials or randomised controlled trials with a very low risk of bias

1+ Well-conducted meta-analyses, systematic reviews of randomised controlled trials or randomised controlled trials with a low risk of bias

1– Meta-analyses, systematic reviews of randomised controlled trials or randomised controlled trials with a high risk of bias

2++ High-quality systematic reviews of case–control or cohort studies or high-quality case–control or cohort studies with a very low risk of confounding, bias or chance and a high probability that the relationship is causal

2+ Well-conducted case–control or cohort studies with a low risk of confounding, bias or chance and a moderate probability that the relationship is causal

2– Case–control or cohort studies with a high risk of confounding, bias or chance and a significant risk that the relationship is not causal

3 Non-analytical studies; e.g., case reports, case series

4 Expert opinion

Clinical Algorithm(s)

None provided

Evidence Supporting the Recommendations

Type of Evidence Supporting the Recommendations

The type of supporting evidence is identified and graded for each recommendation (see "Major Recommendations" field).

Benefits/Harms of Implementing the Guideline Recommendations

Potential Benefits

Appropriate prevention of malaria in pregnancy to reduce maternal mortality or pregnancy loss from miscarriage, stillbirth and premature labour

Potential Harms

The full listings of drug adverse effects and interactions and contraindications are contained in the British National Formulary (www.bnf.org External Web Site Policy).

Contraindications

Contraindications
  • The full listings of drug contraindications are contained in the British National Formulary (www.bnf.org External Web Site Policy).
  • There are strict contraindications to mefloquine, including current or previous history of depression, neuropsychiatric disorders, epilepsy, or hypersensitivity to quinine or mefloquine.
  • Doxycycline and primaquine are contraindicated as chemoprophylaxis in pregnant women.

Qualifying Statements

Qualifying Statements
  • These recommendations are not intended to dictate an exclusive course of management or treatment. They must be evaluated with reference to individual patient needs, resources and limitations unique to the institution and variations in local populations. It is hoped that this process of local ownership will help to incorporate these guidelines into routine practice. Attention is drawn to areas of clinical uncertainty where further research may be indicated.
  • The Royal College of Obstetricians and Gynaecologists (RCOG) produces guidelines as an educational aid to good clinical practice. They present recognised methods and techniques of clinical practice, based on published evidence, for consideration by obstetricians and gynaecologists and other relevant health professionals. The ultimate judgement regarding a particular clinical procedure or treatment plan must be made by the doctor or other attendant in the light of clinical data presented by the patient and the diagnostic and treatment options available within the appropriate health services.
  • This means that RCOG Guidelines are unlike protocols or guidelines issued by employers, as they are not intended to be prescriptive directions defining a single course of management. Departure from the local prescriptive protocols or guidelines should be fully documented in the patient's case notes at the time the relevant decision is taken. Once adapted for local use, these guidelines no longer represent the views of the RCOG.
  • Drug recommendations for malaria prophylaxis can change, owing to resistance, and up-to-date information on drugs can be obtained using online resources as described in the original guideline document.

Implementation of the Guideline

Description of Implementation Strategy

An implementation strategy was not provided.

Institute of Medicine (IOM) National Healthcare Quality Report Categories

IOM Care Need
Staying Healthy
IOM Domain
Effectiveness
Patient-centeredness

Identifying Information and Availability

Bibliographic Source(s)
Royal College of Obstetricians and Gynaecologists (RCOG). The prevention of malaria in pregnancy. London (UK): Royal College of Obstetricians and Gynaecologists (RCOG); 2010 Apr. 14 p. (Green-top guideline; no. 54A).  [129 references]
Adaptation

Not applicable: The guideline was not adapted from another source.

Date Released
2010 Apr
Guideline Developer(s)
Royal College of Obstetricians and Gynaecologists - Medical Specialty Society
Source(s) of Funding

Royal College of Obstetricians and Gynaecologists

Guideline Committee

Guidelines Committee

Composition of Group That Authored the Guideline

Authors: Dr R McGready, PhD, Dip, RANZCOG, Mae Sot, Thailand; Dr EA Ashley, PhD, London; Professor F Nosten, MD, PhD, Mae Sot, Thailand; Dr M Rijken, MD, PhD, Mae Sot, Thailand

Peer reviewers: Dr A Diaf, MRCOG, Birmingham; RCOG Consumers' Forum; Mr SA Walkinshaw, MRCOG, Liverpool; Dr C Whitty, FRCP, London; the Advisory Committee on Malaria Prevention in UK Travellers: Dr BA Bannister, FRCP, London; Dr D Lalloo, FRCP, Liverpool; Professor P Chiodini, FRCP, London

Guidelines Committee lead peer reviewers: Dr ALM David, MRCOG, London, and Professor F McAuliffe, FRCOG, Dublin

Financial Disclosures/Conflicts of Interest

Guideline authors are required to complete a "declaration of interests" form.

Guideline Status

This is the current release of the guideline.

Guideline Availability

Electronic copies: Available in Portable Document Format (PDF) from the Royal College of Obstetricians and Gynaecologists (RCOG) Web site External Web Site Policy.

Availability of Companion Documents

The following are available:

  • Development of RCOG green-top guidelines: policies and processes. Clinical Governance Advice No 1a. 2006 Nov. Available from the Royal College of Obstetricians and Gynaecologists (RCOG) Web site External Web Site Policy.
  • Development of RCOG green-top guidelines: producing a scope. Clinical Governance Advice No 1b. 2006 Nov. Available from the RCOG Web site External Web Site Policy.
  • Development of RCOG green-top guidelines: producing a clinical practice guideline. Clinical Governance Advice No 1c. 2006 Nov. Available from the RCOG Web site External Web Site Policy.
  • Development of RCOG green-top guidelines: consensus methods for adaptation of green-top guidelines. Governance Advice No. 1d. 2010 Feb. Available from the RCOG Web site External Web Site Policy.
Patient Resources

None available

NGC Status

This NGC summary was completed by ECRI Institute on June 16, 2011. The information was verified by the guideline developer on July 22, 2011. This summary was updated by ECRI Institute on August 2, 2013 following the U.S. Food and Drug Administration advisory on Mefloquine Hydrochloride.

Copyright Statement

This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions.

Disclaimer

NGC Disclaimer

The National Guideline Clearinghouse™ (NGC) does not develop, produce, approve, or endorse the guidelines represented on this site.

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