International Travel and Health 2008

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CHAPTER 7

Malaria

General considerationsMalaria is a common and life-threatening disease in many tropical and subtropicalareas. It is currently endemic in over 100 countries, which are visited by more than125 million international travellers every year.Each year many international travellers fall ill with malaria while visiting countrieswhere the disease is endemic, and well over 10 000 are reported to fall ill afterreturning home. Due to underreporting, the real gure may be as high as 30 000.International travellers from non-endemic areas are at high risk of malaria and itsconsequences because they lack immunity. Immigrants from endemic areas whonow live in non-endemic areas and return to their home countries to visit friendsand relatives are similarly at risk because of waning or absent immunity. Feveroccurring in a traveller within three months of leaving a malaria-endemic area isa medical emergency and should be investigated urgently.

Travellers who fall ill during travel may nd it difcult to access reliable medicalcare. Travellers who develop malaria upon return to a non-endemic country pres-ent particular problems: doctors may be unfamiliar with malaria, the diagnosismay be delayed, and effective antimalarial medicines may not be registered and/or available, resulting in progression to severe and complicated malaria and, con-sequently, high case-fatality rates.

CauseHuman malaria is caused by four different species of the protozoan parasite Plas-

modium: Plasmodium falciparum, P. vivax, P. ovale and P. malariae .

TransmissionThe malaria parasite is transmitted by female Anopheles mosquitoes, which bitemainly between dusk and dawn.


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Nature of the diseaseMalaria is an acute febrile illness with an incubation period of 7 days or longer.Thus, a febrile illness developing less than one week after the rst possible expo-sure is not malaria.

The most severe form is caused by P. falciparum , in which variable clinical fea-tures include fever, chills, headache, muscular aching and weakness, vomiting,cough, diarrhoea and abdominal pain; other symptoms related to organ failuremay supervene, such as acute renal failure, generalized convulsions, circulatorycollapse, followed by coma and death. In endemic areas it is estimated thatabout 1% of patients with P. falciparum infection die of the disease; mortalityin non-immune travellers with falciparum infection is signicantly higher.The initial symptoms, which may be mild, may not be easy to recognize asbeing due to malaria. It is important that the possibility of falciparum malariais considered in all cases of unexplained fever starting at any time between7 days after the rst possible exposure to malaria and 3 months (or, rarely,later) after the last possible exposure. Any individual who experiences a feverin this interval should immediately seek diagnosis and effective treatment,and inform medical personnel of the possible exposure to malaria infection.Falciparum malaria may be fatal if treatment is delayed beyond 24 hours afterthe onset of clinical symptoms.

Young children, pregnant women, people living with HIV/AIDS, people whoare immunosuppressed and elderly travellers are particularly at risk. Malaria,particularly P. falciparum, in non-immune pregnant travellers increases the riskof maternal death, miscarriage, stillbirth and neonatal death.

The forms of malaria caused by other Plasmodium species cause signicant mor-bidity but are rarely life-threatening. P. vivax and P. ovale can remain dormantin the liver. Relapses caused by these persistent liver forms (hypnozoites) mayappear months, and rarely several years, after exposure. They are not preventedby current chemoprophylactic regimens, with the exception of primaquine. Latentblood infection with P. malariae may be present for many years, but it is veryrarely life-threatening.

Chemoprophylaxis and treatment of falciparum malaria are becoming more com-plex because P. falciparum is increasingly resistant to various antimalarial drugs.Chloroquine resistance of P. vivax is rare but increasing. It was rst reported inthe late 1980s in Indonesia and Papua New Guinea. Focal chloroquine resistanceor prophylactic and/or treatment failure have since also been observed in Brazil,Colombia, Ethiopia, Guyana, India, Myanmar, Peru, the Republic of Korea,


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Solomon Islands, Thailand and Turkey. Chloroquine-resistant P. malariae hasbeen reported from Indonesia.

Geographical distributionThe current distribution of malaria in the world is shown in the map. Affectedcountries and territories are listed at the end of this chapter, as well as in the Countrylist. The risk for travellers of contracting malaria is highly variable from countryto country and even between areas in a country and this must be considered inany discussion of appropriate preventive measures.

In many endemic countries, the main urban areas but not necessarily the out-skirts of towns are free of malaria transmission. However, malaria can occurin the main urban areas of Africa and, to a lesser extent, India. There is usuallyless risk at altitudes above 1500 metres but, in favourable climatic conditions, thedisease can occur at altitudes up to almost 3000 metres. The risk of infection mayalso vary according to the season, being highest at the end of the rainy season orsoon after.

There is no risk of malaria in many tourist destinations in South-East Asia, LatinAmerica and the Caribbean.

Risk for travellersDuring the transmission season in malaria-endemic areas, all non-immune travellersexposed to mosquito bites, especially between dusk and dawn, are at risk of malaria.This includes previously semi-immune travellers who have lost or partially losttheir immunity during stays of 6 months or more in non-endemic areas. Childrenof people who have migrated to non-endemic areas are particularly at risk whenthey return to malarious areas to visit friends and relatives.

Most cases of falciparum malaria in travellers occur because of poor adherence to,or complete failure to use, prophylactic drug regimens, or use of inappropriatemedicines, combined with failure to take adequate precautions against mosquito

bites. Studies on travellers behaviour have shown that adherence to treatmentcan be improved if travellers are informed of the risk of infection and believe inthe benet of prevention strategies. Late-onset vivax and ovale malaria may occurdespite effective prophylaxis, as they cannot be prevented with currently recom-mended prophylactic regimens.

Travellers to countries where the degree of malaria transmission varies in differentareas should seek advice on the risk in the specic zones that they will be visiting.


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CHAPTER 7. MALARIA

If specic information is not available before travelling, then it is recommendedthat precautions appropriate for the highest reported risk for the area or countryshould be taken; these precautions can be adjusted when more information be-comes available on arrival. This applies particularly to individuals backpacking toremote places and visiting areas where diagnostic facilities and medical care are notreadily available. Travellers staying overnight in rural areas may be at highest risk.Culturally sensitive approaches are needed to advise different groups at risk.

PrecautionsTravellers and their advisers should note the four principles the ABCD of

malaria protection: Be Aware of the risk, the incubation period, the possibility of delayed onset,

and the main symptoms. Avoid being Bitten by mosquitoes, especially between dusk and dawn. Take antimalarial drugs (Chemoprophylaxis) when appropriate, to prevent

infection from developing into clinical disease. Immediately seek Diagnosis and treatment if a fever develops one week or

more after entering an area where there is a malaria risk and up to 3 months(or, rarely, later) after departure from a risk area.

Protection against mosquito bitesAll travellers should be advised that individual protection from mosquito bitesbetween dusk and dawn is their rst line of defence against malaria. Practicalmeasures for protection are described in Chapter 3, in the section Protectionagainst vectors.

ChemoprophylaxisThe most appropriate chemoprophylactic antimalarial drug(s) (if any) for the

destination(s) should be prescribed in the correct dosages (see Country list andTable 7.1).


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Travellers and their doctors should be aware that

NO ANTIMALARIAL PROPHYLACTIC REGIMEN GIVES COMPLETEPROTECTION,

but good chemoprophylaxis (adherence to the recommended drug regimen) doesreduce the risk of fatal disease. The following should also be taken into account: Dosing schedules for children should be based on body weight. Antimalarials that have to be taken daily should be started the day before arrival

in the risk area. Weekly chloroquine should be started 1 week before arrival.

Weekly meoquine should preferably be started 23 weeks before departure,to achieve higher pre-travel blood levels and to allow side-effects to be detectedbefore travel so that possible alternatives can be considered.

All prophylactic drugs should be taken with unfailing regularity for the durationof the stay in the malaria risk area, and should be continued for 4 weeks after thelast possible exposure to infection, since parasites may still emerge from the liverduring this period. The single exception is atovaquoneproguanil, which can bestopped 1 week after return because of its effect on early liver-stage parasites(liver schizonts). Premature interruption of the daily atovaquoneproguanilprophylaxis regimen may lead to loss of this causal prophylactic effect, in which

case atovaquoneproguanil prophylaxis should also be continued for 4 weeksupon return. Depending on the type of malaria at the destination, travellers should be advised

about possible late-onset P. vivax and P. ovale .

Depending on the malaria risk in the area visited (see Country list), the recom-mended prevention method may be mosquito bite prevention only, or mosquitobite prevention in combination with chemoprophylaxis, as follows.

See Table 7.1 for details on individual drugs.


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Malaria risk Type of preventionType I Very limited risk of malaria Mosquito bite prevention only

transmission

Type II Risk of P. vivax malaria only; Mosquito bite prevention plusor fully chloroquine-sensitive chloroquine chemoprophylaxisP. falciparum

Type III Risk of P. vivax and Mosquito bite preventionP. falciparum malaria plus chloroquine+proguaniltransmission, combined with chemoprophylaxisemerging chloroquineresistance

Type IV (1) High risk of P. falciparum Mosquito bite prevention plusmalaria, in combination meoquine, doxycycline orwith reported antimalarial atovaquoneproguanil chemopro-drug resistance; or phylaxis (select according to

(2) Moderate/low risk ofreported resistance pattern)

P. falciparum malaria, incombination with reportedhigh levels of drug resistance 1

1 Alternatively, when travelling to rural areas with multidrug-resistant malaria and only a very low riskof P. falciparum infection, mosquito bite prevention can be combined with stand-by emergencytreatment.

CHAPTER 7. MALARIA

All antimalarial drugs have specic contraindications and possible side-effects.Adverse reactions attributed to malaria chemoprophylaxis are common, but mostare minor and do not affect the activities of the traveller. Serious adverse events dened as constituting an apparent threat to life, requiring or prolonging hos-pitalization, or resulting in persistent or signicant disability or incapacity arerare and normally identied in post-marketing surveillance once a drug has beenin use for some time. Severe neuropsychiatric disturbances (seizures, psychosis,encephalopathy) occur in approximately 1 in 10 000 travellers receiving meoquineprophylaxis, and have also been reported for chloroquine at a similar rate. Formalaria prophylaxis with atovaquoneproguanil or doxycycline, the risks of rareserious adverse events have not yet been established. The risk of drug-associatedadverse events should be weighed against the risk of malaria, especiallyP. falciparum malaria, and local drug-resistance patterns.

Each of the antimalarial drugs is contraindicated in certain groups and individuals,and the contraindications should be carefully observed (see Table 7.1) to reduce therisk of serious adverse reactions. Pregnant women, people travelling with young


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children, and people with chronic illnesses should seek individual medical advice.Any traveller who develops severe side-effects to an antimalarial should stop takingthe drug and seek immediate medical attention. This applies particularly to neurologi-cal or psychological disturbances experienced with meoquine prophylaxis. Mildnausea, occasional vomiting or loose stools should not prompt discontinuation of prophylaxis, but medical advice should be sought if symptoms persist.

Long-term use of chemoprophylaxisAdherence and tolerability are important aspects of chemoprophylaxis use inlong-term travellers. There are few studies on chemoprophylaxis use in travellasting more than 6 months. The risk of serious side-effects associated with long-term prophylactic use of chloroquine and proguanil is low, but retinal toxicity isof concern when a cumulative dose of 100 g of chloroquine is reached. Anyonewho has taken 300 mg of chloroquine weekly for more than 5 years and requiresfurther prophylaxis should be screened twice-yearly for early retinal changes. If daily doses of 100 mg chloroquine have been taken, screening should start after3 years. Data indicate no increased risk of serious side-effects with long-term useof meoquine if the drug is tolerated in the short-term. Pharmacokinetic dataindicate that meoquine does not accumulate during long-term intake. Availabledata on long-term chemoprophylaxis with doxycycline (i.e. more than 12 months)is limited but reassuring. There are few data on long-term use of doxycycline in

women, but use of this drug is associated with an increased frequency of Can-dida vaginitis. Atovaquoneproguanil is registered in European countries with arestriction on duration of use (varying from 5 weeks to 1 year); in the USA nosuch restrictions apply.

TreatmentEarly diagnosis and appropriate treatment can be life-saving. A blood sampleshould be taken from all travellers with suspected malaria and examined withoutdelay for malaria parasites in an experienced, reliable laboratory. If no parasitesare found in the rst blood lm, a series of blood samples should be taken at

612-hour intervals and examined very carefully. Malaria rapid diagnostic testscan be useful in centres where malaria microscopy is unavailable. When laboratoryanalysis is delayed, physicians should begin treatment if the clinical indicators andtravel history suggest malaria.

For travellers who are treated for malaria in non-endemic areas, the followingprinciples apply:


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Patients are at high risk of malaria and its consequences because they are non-immune.

If the patient has taken prophylaxis, the same medicine should not be used fortreatment.

The following antimalarials are suitable for treatment of uncomplicated falci-parum malaria in travellers returning to non-endemic countries:

artemetherlumefantrine atovaquoneproguanil quinine plus doxycycline or clindamycin.

The treatment for vivax malaria in travellers is as follows: Chloroquine combined with primaquine is the treatment of choice to achieve

radical cure (i.e. to cure both the blood stage and liver stage infections, andthereby prevent both recrudescence and relapse).

Amodiaquine combined with primaquine should be given for chloroquine-resistant vivax malaria. Where amodiaquine is not available, quinine orartemetherlumefantrine can be used instead.

Travellers must be tested for glucose-6-phosphate dehydrogenase (G6PD) de-ciency before receiving primaquine antirelapse treatment. In moderate G6PDdeciency, primaquine should be given in an adjusted regimen of 0.75 mg base/

kg body weight once a week for 8 weeks. In severe G6PD deciency, primaquineshould not be given. In mixed P. falciparumP. vivax infections, the treatment for P. falciparum will

usually also cure the attack of P. vivax , but primaquine should be added toachieve radical cure and prevent relapses.

Relapsing malaria caused by P. ovale should be treated with chloroquine andprimaquine. Malaria caused by P. malariae should be treated with the standardregimen of chloroquine as for vivax malaria, but it does not require radical cure withprimaquine because no hypnozoites are formed in infection with this species.

Returning travellers with severe falciparum malaria should be managed in an in-tensive care unit. Parenteral antimalarial treatment should be with artesunate (rstchoice), artemether or quinine. If these medicines are not available, use parenteralquinidine with careful clinical and electrocardiographic monitoring.

The dosage regimens for the treatment of uncomplicated malaria are provided inTable 7.2. The details of the clinical management of severe malaria are addressedin other WHO publications (see list of references).


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Treatment abroad and stand-by emergency treatmentAn individual who experiences a fever 1 week or more after entering an area of malaria risk should consult a physician or qualied malaria laboratory immediatelyto obtain a correct diagnosis and safe and effective treatment. In principle, travel-lers can be treated with artemisinin-based combination therapy (ACT) accordingto the national policy in the country they will be visiting. National antimalarialdrug policies for all endemic countries are listed at http://www.who.int/malaria/treatmentpolicies.html.

In light of the spread of counterfeit drugs in some resource-poor settings, travellersmay opt to buy a reserve antimalarial treatment before departure, so that they canbe condent of drug quality should they become ill.

Many travellers will be able to obtain proper medical attention within 24 hours of the onset of fever. For others, however, this may be impossible, particularly if theywill be staying in remote locations. In such cases, travellers are advised to carryantimalarial drugs for self-administration (stand-by emergency treatment).

Stand-by emergency treatment (SBET) may also be indicated for travellers insome occupational groups, such as aircraft crews, who make frequent short stopsin endemic areas over a prolonged period of time. Such travellers may choose toreserve chemoprophylaxis for high-risk areas and seasons only. However, theyshould continue to take measures to protect against mosquito bites and be prepared

for an attack of malaria: they should always carry a course of antimalarial drugsfor SBET, seek immediate medical care in case of fever, and take SBET if promptmedical help is not available.

Furthermore, SBET combined with protection against mosquito bites maybe indicated for those who travel for 1 week or more to remote rural areas wherethere is multidrug-resistant malaria but a very low risk of infection, and the riskof side-effects of prophylaxis may outweigh that of contracting malaria. Thismay be the case in certain border areas of Thailand and neighbouring countriesin South-East Asia, as well as parts of the Amazon basin.

Studies on the use of rapid diagnostic tests (dipsticks) have shown that untrained

travellers experience major problems in the performance and interpretation of these tests, with an unacceptably high number of false-negative results. In addi-tion, dipsticks can be degraded by extremes of heat and humidity, becoming lesssensitive.

Successful SBET depends crucially on travellers behaviour, and health advisersneed to spend time explaining the strategy. Travellers provided with SBET shouldbe given clear and precise written instructions on the recognition of symptoms,


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when and how to take the treatment, possible side-effects, and the possibility of drug failure. If several people travel together, the individual dosages for SBETshould be specied. Weight-based dosages for children need to be clearly indicated.Travellers should realize that self-treatment is a rst-aid measure, and thatthey should still seek medical advice as soon as possible.

In general, travellers carrying SBET should observe the following guidelines: Consult a physician immediately if fever occurs 1 week or more after entering

an area with malaria risk. If it is impossible to consult a physician and/or establish a diagnosis within 24

hours of the onset of fever, start the stand-by emergency treatment and seek

medical care as soon as possible for complete evaluation and to exclude otherserious causes of fever. Do not treat suspected malaria with the same drugs used for prophylaxis. Vomiting of antimalarial drugs is less likely if fever is rst lowered with an-

tipyretics. A second full dose should be taken if vomiting occurs within 30minutes of taking the drug. If vomiting occurs 3060 minutes after a dose, anadditional half-dose should be taken. Vomiting with diarrhoea may lead totreatment failure because of poor drug absorption.

Complete the stand-by treatment course and resume antimalarial prophylaxis1 week after the rst treatment dose. To reduce the risk of drug interactions,at least 12 hours should elapse between the last treatment dose of quinine andresumption of meoquine prophylaxis.

The drug options for SBET are in principle the same as for treatment of uncom-plicated malaria (see above). The choice will depend on the type of malaria in thearea visited and the chemoprophylaxis regimen taken. Artemetherlumefantrinehas been registered (in Switzerland and the United Kingdom) for use as SBET fortravellers. Table 7.2 provides details on individual drugs.

Multidrug-resistant malaria

Multidrug-resistant malaria has been reported from South-East Asia (Cambodia,Myanmar, Thailand, Viet Nam) and the Amazon basin of South America, whereit occurs in parts of Brazil, French Guiana and Suriname.

In border areas between Cambodia, Myanmar and Thailand, P. falciparum infec-tions do not respond to treatment with chloroquine or sulfadoxinepyrimethamine,sensitivity to quinine is reduced, and treatment failures in excess of 50% with


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meoquine are being reported. In these situations, malaria prevention consistsof personal protection measures in combination with atovaquoneproguanilor doxycycline as chemoprophylaxis. SBET with atovaquoneproguanil orartemetherlumefantrine can be used in situations where the risk of infection isvery low. However, these drugs cannot be given to pregnant women and youngchildren. Since there is no prophylactic or SBET regimen that is both effective andsafe for these groups in areas of multidrug-resistant malaria, pregnant women andyoung children should avoid travelling to these malarious areas.

Special groupsSome groups of travellers, especially young children, pregnant women and im-munosuppressed travelers, are at particular risk of serious consequences if theybecome infected with malaria. Recommendations for these groups are difcult toformulate because safety data are limited. The special concerns for immigrants fromendemic areas who live in non-endemic areas and return to their home countriesto visit friends and relatives are addressed in Chapter 9.

Pregnant womenMalaria in a pregnant woman increases the risk of maternal death, miscarriage,stillbirth and low birth weight with associated risk of neonatal death.

Pregnant women should be advised to avoid travelling to areas where malariatransmission occurs. When travel cannot be avoided, it is very important to takeeffective preventive measures against malaria, even when travelling to areas withtransmission only of vivax malaria. Pregnant women should seek medical helpimmediately if malaria is suspected; if this is not possible, they should take stand-by emergency treatment. Medical help must be sought as soon as possible afterstarting stand-by treatment. There is very limited information on the safety andefcacy of most antimalarials in pregnancy, particularly during the rst trimester.However, inadvertent exposure to antimalarials is not an indication for termina-tion of the pregnancy.

Mosquito bite preventionPregnant women are particularly susceptible to mosquito bites and should thereforebe vigilant in using protection measures, including insect repellents and insecticide-treated mosquito nets. They should take care not to exceed the recommendeddosage of insect repellents.


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ChemoprophylaxisIn type II areas, with exclusively P. vivax transmission or where P. falciparum canbe expected to be fully sensitive to chloroquine, prophylaxis with chloroquine alonemay be used. In type III areas, prophylaxis with chloroquine plus proguanil can besafely prescribed, including during the rst 3 months of pregnancy. In type IV areas,meoquine prophylaxis may be given during the second and third trimesters, butthere is limited information on the safety of meoquine during the rst trimester.In light of the danger of malaria to mother and fetus, experts increasingly agreethat travel to a chloroquine-resistant P. falciparum area during the rst trimester of pregnancy should be avoided or delayed at all costs; if this is truly impossible, goodpreventive measures should be taken, including prophylaxis with meoquine where

this is indicated. Doxycycline is contraindicated during pregnancy. Atovaquoneproguanil has not been sufciently investigated to be prescribed in pregnancy.

Treatment Clindamycin and quinine are considered safe, including during the rst trimesterof pregnancy; artemisinin derivatives can be used to treat uncomplicated malaria inthe second and third trimesters, and in the rst trimester only if no other adequatemedicines are available. Amodiaquine and chloroquine can be safely used for treat-ment of vivax malaria in pregnancy, but primaquine anti-relapse treatment should bepostponed until after delivery. Atovaquoneproguanil and artemetherlumefantrine

have not been sufciently investigated to be prescribed in pregnancy.The recommended treatment for uncomplicated falciparum malaria in the rsttrimester is quinine +/ clindamycin. For the second and third trimesters , theoptions are: ACT in accordance with national policy; artesunate +/ clindamycin;or quinine +/ clindamycin.

Pregnant women with falciparum malaria, particularly in the second and thirdtrimesters of pregnancy, are more likely than other adults to develop severe malaria,often complicated by hypoglycaemia and pulmonary oedema. Maternal mortal-ity in severe malaria is approximately 50%, which is higher than in non-pregnantadults. Fetal death and premature labour are common. Pregnant women with

severe malaria must be treated without delay with full doses of parenteral anti-malarial treatment. In the rst trimester , either quinine or artesunate can be used.In the second and third trimesters , artesunate is the rst option and artemetherthe second option. Treatment must not be delayed, so if only one of the drugsartesunate, artemether, or quinine is available it should be started immediately.

Information on the safety of antimalarial drugs during breastfeeding is providedin Tables 7.1 and 7.2.


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Women who may become pregnant during or after travelMalaria prophylaxis may be taken, but pregnancy should preferably be avoidedduring the period of drug intake and for 1 week after doxycycline, 3 weeks afteratovaquoneproguanil, and 3 months after meoquine prophylaxis is stopped. If pregnancy occurs during antimalarial prophylaxis, this is not considered to be anindication for pregnancy termination.

Young childrenFalciparum malaria in a young child is a medical emergency. It may be rapidlyfatal. Early symptoms are atypical and difcult to recognize, and life-threatening

complications can occur within hours of the initial symptoms. Medical help shouldbe sought immediately if a child develops a febrile illness within 3 months (or,rarely, later) of travelling to an endemic area. Laboratory conrmation of diagnosisshould be requested immediately, and treatment with an effective antimalarialdrug initiated as soon as possible. In infants, malaria should be suspected even innon-febrile illness.

Parents should be advised not to take babies or young children to areas with riskof falciparum malaria. If travel cannot be avoided, children must be very carefullyprotected against mosquito bites and be given appropriate chemoprophylacticdrugs. Long-term travelers and expatriates should adjust the chemoprophylaxisdosage according to the increasing weight of the growing child.

Mosquito bite preventionBabies should be kept under insecticide-treated mosquito nets as much as possiblebetween dusk and dawn. The manufacturers instructions on the use of insectrepellents should be followed diligently, and the recommended dosage must notbe exceeded.

ChemoprophylaxisChloroquine, proguanil and meoquine are considered compatible with breastfeed-ing. Breastfed, as well as bottle-fed, babies should be given chemoprophylaxis sincethey are not protected by the mothers prophylaxis. Dosage schedules for childrenshould be based on body weight, and tablets should be crushed and ground asnecessary. The bitter taste of the tablets can be disguised with jam or other foods.Chloroquine and proguanil are safe for babies and young children but their useis now very limited, because of spreading chloroquine resistance. Meoquinemay be given to infants of more than 5 kg body weight. Atovaquoneproguanil


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is generally not recommended for prophylaxis in children who weigh less than 11kg, because of limited data; in Belgium and the USA it is given for prophylaxis ininfants of more than 5 kg body weight. Doxycycline is contraindicated in childrenbelow 8 years of age. All antimalarial drugs should be kept out of the reach of children and stored in childproof containers: chloroquine is particularly toxic incase of overdose.

Treatment Acutely ill children with falciparum malaria require careful clinical monitoring astheir condition may deteriorate rapidly. Every effort should be made to give oraltreatment and ensure that it is retained. ACT as per national policy may be used asrst-line treatment while abroad. Oral treatment options for SBET and returningtravellers are: artemether-lumefantrine (not recommended under 5 kg because of lack of data), atovaquoneproguanil (apparently safe in children weighing 5 kgor more, but limited data), and quinine plus clindamycin (safe, but limited dataon clindamycin). Quinine plus doxycycline is an option for children of 8 yearsand older. Parenteral treatment and admission to hospital are indicated for youngchildren who cannot swallow antimalarials reliably.

Chloroquine and amodiaquine can be safely given to treat P. vivax , P. ovale orP. malariae infections in young children. The lower age limit for anti-relapse treat-ment with primaquine has not been established; it is generally contraindicated in

young infants.Information on the safety of drugs for prophylaxis and treatment of young childrenis provided in Tables 7.1 and 7.2.

Immunosuppressed travellersImmunosuppressed travellers are at increased risk of malaria, and prevention of malaria through avoidance of mosquito bites and use of chemoprophylaxis isparticularly important. Individual pre-travel advice should be carefully sought.There may be an increased risk of antimalarial treatment failure in people livingwith HIV/AIDS. However, at present, there is insufcient information to per-mit modications to treatment regimens to be recommended. Pharmacokineticinteractions between certain antimalarials (including artemetherlumefantrine),and antiretrovirals (non-nucleoside reverse transcriptase inhibitors and proteaseinhibitors) are theoretically possible and should be avoided as they could leadto toxicity. Cutaneous drug reactions following treatment with sulfadoxinepyrimethamine are more common in people infected with HIV. Treatment withACT containing sulfadoxinepyrimethamine should be avoided in HIV-infectedpatients receiving co-trimoxazole prophylaxis.


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t u r e

h i s t o r y o f e p

i l e p s y ; p s o r i a s

i s .

r e d u c e

t h e a n

t i b o d y r e s p o n s e

t o

w e e

k l y

d i v i d e d

i n 6 d a i

l y d o s e s a n

d c o n

t i n u e

f o r

i n t r a d e r m a l

l y a d m

i n i s t e r e

d h u m a n

A d u

l t d o s e :

3 0 0 m g

4 w e e

k s a f

t e r

d i p l o i d

- c e l

l r a

b i e s v a c c

i n e .

c h l o r o q u

i n e

b a s e w e e

k l y

i n

r e t u r n .

o n e

d o s e , o r

I f d a i

l y d o s e s :

6 0 0 m g c h

l o r o q u

i n e

s t a r

t 1 d a y

b e f o r e

b a s e w e e

k l y

d i v i

d e d

d e p a r

t u r e

o v e r

6 d a i

l y d o s e s o f

1 0 0 m g

b a s e

( w i t h o n e

d r u g -

f r e e

d a y p e r w e e

k )

C h l o r o q u

i n e

> 5

0 k g :

1 0 0 m g

S t a r t

1 d a y

S a f e

S a f e

T a b l e t s i z e

H y p e r s e n s i

t i v i

t y t o c h

l o r o q u

i n e

C o n c u r r e n

t u s e o f c h

l o r o q u

i n e m a y

p r o g u a n

i l

c h l o r o q u

i n e

b a s e

b e f o r e

d e p a r

t u r e

n o t s u

i t a b

l e a n

d / o r p r o g u a n

i l ; l i v e r o r

r e d u c e

t h e a n


t o

c o m

b i n a t

i o n

p l u s

2 0 0 m g p r o g u a n

i l

a n d c o n

t i n u e

f o r

f o r p e r s o n s

k i d n e y

i n s u

f c i e n c y ;

h i s t o r y o f


l y a d m

i n i s t e r e

d h u m a n

t a b l e t

( 1 t a b l e t ) d a i l y

4 w e e

k s a f

t e r

o f 5

k g ,

b u

t

c l e a r a n c e 4

0 k g :

4 a d u

l t t a b l e t s ( 1 g a t o v a q u o n e

p l u s

4 0 0 m g p r o g u a n

i l ) d a i

l y

a P l e a s e s e e p a c

k a g e

i n s e r t

f o r f u l l i n f o r m a t

i o n o n c o n

t r a i n

d i c a t

i o n s a n

d p r e c a u t i o n s .


18/22

163

T a b l e 7

. 2 U s e o

f a n

t i m a l a r

i a l d r u g s

f o r

t r e a t m e n

t o

f u n c o m

p l i c a t e

d m a l a r

i a i n t r a v e

l l e r s

( c o n t i n u e d )

U s e

i n s p e c

i a l g r o u p s


B r e a s t -

M a

i n c o n

t r a

i n d i c a

t i o n s a


P r e g n a n c y

f e e d

i n g

C h i l d r e n

C o m m e n

t s a

C h o r o q u

i n e

2 5 m g

b a s e /

k g

d i v i d e d

i n d a i

l y d o s e

S a f e

S a f e

S a f e

H y p e r s e n s i

t i v i

t y t o c h

l o r o q u

i n e ;

U s e o n

l y f o r m a l a r

i a c a u s e

d b y

P . v i v a x ,

( 1 0

, 1 0

, 5 m g

b a s e /

k g )

h i s t o r y o f e p

i l e p s y ; p s o r i a s

i s .

P . o v a l e o r

P . m a l a r

i a e .

f o r

3 d a y s

C o n c u r r e n

t u s e o f c h

l o r o q u

i n e m a y

r e d u c e

t h e a n


t o


l y a d m

i n i s t e r e

d h u m a n

d i p l o i d

- c e l

l r a

b i e s v a c c

i n e .

C l i n d a m y c

i n

U n

d e r

6 0 k g : 5

m g

b a s e /

k g 4 t i m e s

A p p a r e n

t l y

A p p a r e n

t l y

A p p a r e n

t l y

H y p e r s e n s i

t i v i

t y t o c l

i n d a m y c

i n

U s e

d i n c o m

b i n a t

i o n w

i t h q u

i n i n e

i n

d a i

l y f o r

5 d a y s

s a f e b u

t

s a f e b u

t

s a f e b u

t

o r l i n c o m y c

i n ;

h i s t o r y o

f g a s t r o -

a r e a s o f e m e r g i n g q u

i n i n e r e s i s t a n c e .

6 0 k g a n

d o v e r :

3 0 0 m g

b a s e

4 t i m e s

l i m i t e d

d a t a

l i m i t e d

d a t a

l i m i t e d

d a t a

i n t e s t

i n a l

d i s e a s e ,

p a r t

i c u

l a r l y

d a i

l y f o r

5 d a y s

c o l i t i s ; s e v e r e

l i v e r o r

k i d n e y

i m p a i r m e n

t .

D o x y c y c

l i n e

A d u

l t s >

5 0 k g :

8 0 0 m g s a

l t o v e r

7 d a y s ,

C o n

t r a -

C o n t r a -

C o n

t r a -

H y p e r s e n s i

t i v i

t y t o t e t r a c y c l

i n e s ;

U s e

d i n c o m

b i n a t

i o n w

i t h q u

i n i n e

i n

t a k e n a s

2 t a b l e t s ( 1 0 0 m g s a

l t e a c h

)

i n d i c a t e d

i n d i c a t e d

i n d i c a t e d

l i v e r

d y s

f u n c t

i o n .

a r e a s o f e m e r g i n g q u

i n i n e r e s i s t a n c e .

1 2 h o u r s a p a r t

o n d a y

1 ,

f o l l o w e d

b y

u n

d e r

8 y e a r s

1 t a b l e t d a i

l y f o r

6 d a y s

o f a g e

C h i l d r e n

8 y e a r s a n

d o l

d e r :

2 5

3 5 k g :

0 . 5

t a b l e t p e r

d o s e

3 6

5 0 k g :

0 . 7 5 t a b l e t p e r

d o s e

> 5

0 k g :

1 t a b l e t p e r

d o s e


k a g e

i n s e r t


i o n o n c o n

t r a i n

d i c a t

i o n s a n


CHAPTER 7. MALARIA


19/22


164

T a b l e 7

. 2 U s e o

f a n

t i m a l a r

i a l d r u g s

f o r

t r e a t m e n

t o

f u n c o m

p l i c a t e

d m a l a r

i a i n t r a v e

l l e r s


U s e

i n s p e c

i a l g r o u p s


B r e a s t -

M a

i n c o n

t r a

i n d i c a

t i o n s a


P r e g n a n c y

f e e d

i n g

C h i l d r e n

C o m m e n

t s a

M e o q u

i n e

2 5 m g

b a s e /

k g

a s s p

l i t d o s e

( 1 5 m g /

k g

N o t r e c o m -

S a f e

N o t r e c o m -

H y p e r s e n s i

t i v i

t y t o m e o q u

i n e ;

D o n o t g i v e m e o q u

i n e w

i t h i n 1 2 h o u r s

p l u s

1 0 m g /

k g 6

2 4 h o u r s a p a r

t )

m e n

d e d

i n

m e n

d e d

p s y c h

i a t r i c ( i n c l u

d i n g d e p r e s -

o f l a s t

d o s e o f q u

i n i n e

t r e a

t m e n

t .

r s t

t r i m e s

t e r

u n

d e r

5 k g

s i o n

) o r c o n v u

l s i v e

d i s o r d e r s ;

M e o q u

i n e a n

d o t

h e r r e

l a t e d

b e c a u s e o f

b e c a u s e o f

h i s t o r y o f s e v e r e n e u r o p s y c h

i a -

c o m p o u n

d s

( s u c h a s q u

i n i n e , q u

i n i d i n e ,

l a c k o f

d a

t a

l a c k o f

d a t a

t r i c d i s e a s e ; c o n c o m

i t a n

t

c h l o r o q u

i n e ) m a y

b e g i v e n c o n c o m

i t a n t l y

h a l o f a n

t r i n e

t r e a

t m e n

t ; t r e a

t -

o n l y u n

d e r c l o s e m e d

i c a l s u p e r v i s i o n

m e n

t w

i t h m e o q u

i n e

i n

b e c a u s e o f p o s s i

b l e a d

d i t i v e c a r d

i a c

p r e v i o u s

4 w e e

k s ; u s e w

i t h

t o x i c i

t y a n

d i n c r e a s e

d r i s k o f

c a u

t i o n

i n p e o p

l e w

h o s e

c o n v u

l s i o n s ; c o - a

d m

i n i s t r a t

i o n o f

a c t i v i

t i e s r e q u

i r e

n e c o o r

d i n a -

m e o q u

i n e w

i t h a n

t i - a

r r h y t

h m

i c a g e n

t s ,

t i o n a n

d s p a t

i a l d i s c r

i m i n a t

i o n ,

b e t a - a d r e n e r g i c

b l o c k

i n g a g e n

t s ,

e . g . p

i l o t s a n

d m a c h

i n e

c a l c i u m

c h a n n e l

b l o c k e r s , a n

t i h i s t a m i n e s

o p e r a t o r s .

i n c l u

d i n g

H 1

- b l o c k

i n g a g e n

t s ,

a n d p

h e n o -

t h i a z i n e s m a y c o n

t r i b u

t e t o p r o

l o n g a

t i o n

o f Q T c i n t e r v a

l . A m p

i c i l l i n

, t e t r a c y c

l i n e

a n d m e t o c

l o p r a m

i d e m a y

i n c r e a s e

m e o q u

i n e

b l o o d

l e v e

l s .

P r i m a q u

i n e

0 . 2

5 m g

b a s e /

k g ,

t a k e n

C o n

t r a -

S a f e

L o w e r a g e

G 6 P D d e c i e n c y ; a c

t i v e

U s e

d a a n

t i - r

e l a p s e

t r e a

t m e n

t

w i t h f o o d o n c e

d a i

l y f o r

1 4 d a y s

i n d i c a t e d

l i m i t n o t

r h e u m a t o i

d a r

t h r i

t i s ;

l u p u s

f o r

P . v i v a x a n

d P . o v a l e

i n f e c t

i o n s .

I n O c e a n

i a a n d

S o u

t h - E

a s t A s i a

e s t a b l i s h e d .

e r y t

h e m a t o s u s ; c o n

d i t i o n s

t h a

t

t h e

d o s e s h o u l

d b e

0 . 5

m g

b a s e /

k g

G e n e r a l

l y

p r e

d i s p o s e

t o g r a n u

l o c y t o p e n

i a ;

c o n

t r a i n

d i c a -

c o n c o m

i t a n

t u s e o f

d r u g s

t h a t

t e d i n y o u n g

m a y

i n d u c e

h a e m a t o l o g i c a

l d i s

-

i n f a n

t s

o r d e r s .


k a g e

i n s e r t


i o n o n c o n

t r a i n

d i c a t

i o n s a n



20/22

165

T a b l e 7

. 2 U s e o

f a n

t i m a l a r

i a l d r u g s

f o r

t r e a t m e n

t o

f u n c o m

p l i c a t e

d m a l a r

i a i n t r a v e

l l e r s


U s e

i n s p e c

i a l g r o u p s


B r e a s t -

M a

i n c o n

t r a

i n d i c a

t i o n s a


P r e g n a n c y

f e e d

i n g

C h i l d r e n

C o m m e n

t s a

Q u

i n i n e

8 m g

b a s e /

k g 3

t i m e s

d a i

l y f o r

7 d a y s

S a f e

S a f e

S a f e

H y p e r s e n s i

t i v i

t y t o q u i n

i n e o r

I n a r e a s o f e m e r g i n g r e s i s t a n c e

t o

q u

i n i d i n e ;

t i n n

i t u s ; o p t

i c n e u r i

t i s ; q u

i n i n e , g i v e

i n c o m

b i n a t

i o n w

i t h

h a e m o l y s

i s ; m y a s t

h e n i a g r a v

i s .

d o x y c y c

l i n e ,

t e t r a c y c

l i n e o r c l

i n d a m y c

i n .

U s e w

i t h c a u

t i o n

i n p e r s o n s w

i t h Q u

i n i n e m a y

i n d u c e

h y p o g

l y c a e m

i a ,

G 6 P D d e c i e n c y a n

d i n

p a r

t i c u

l a r l y

i n ( m a

l n o u r i s h e d

) c h

i l d r e n ,

p a t

i e n

t s w

i t h a t r i a l

b r i l l a t

i o n ,

p r e g n a n

t w o m e n a n

d p a t

i e n

t s w

i t h

c a r d

i a c c o n

d u c t

i o n

d e f e c

t s o r

s e v e r e

d i s e a s e .

h e a r t

b l o c k .

Q u

i n i n e m a y e n -

h a n c e e f

f e c t o f c a r d

i o s u p p r e s -

s a n

t d r u g s .

U s e w

i t h c a u

t i o n

i n

p e r s o n s u s i n g

b e t a -

b l o c k e r s ,

d i g o x

i n ,

c a l c i u m

c h a n n e l

b l o c k e r s , e t c .


k a g e

i n s e r t


i o n o n c o n

t r a i n

d i c a t

i o n s a n


CHAPTER 7. MALARIA


21/22


166

AfghanistanAlgeria*AngolaArgentina*Armenia*Azerbaijan*BangladeshBelizeBeninBhutanBoliviaBotswanaBrazilBurkina FasoBurundiCambodiaCameroonCape VerdeCentral African

RepublicChadChinaColombiaComorosCongoCongo, Democratic

Republic of the(former Zaire)

Costa RicaCte dIvoireDjiboutiDominican RepublicEcuadorEgyptEl SalvadorEquatorial GuineaEritreaEthiopiaFrench GuianaGabon

GambiaGeorgia*GhanaGuatemalaGuineaGuinea-BissauGuyanaHaitiHondurasIndiaIndonesiaIran, Islamic Republic of Iraq* JamaicaKenyaKorea, Democratic

Peoples Republic of*Korea, Republic of*Kyrgyzstan*Lao Peoples Democratic

RepublicLiberiaMadagascarMalawiMalaysiaMaliMauritaniaMauritius*MayotteMexicoMorocco*MozambiqueMyanmarNamibiaNepalNicaraguaNigerNigeriaOmanPakistan

PanamaPapua New GuineaParaguay*PeruPhilippinesRussian Federation*RwandaSao Tome and PrincipeSaudi ArabiaSenegalSierra LeoneSolomon IslandsSomaliaSouth AfricaSri LankaSudanSurinameSwazilandSyrian Arab

Republic*TajikistanThailandTimor-LesteTogoTurkey*Turkmenistan*UgandaUnited Republic

of TanzaniaUzbekistan*VanuatuVenezuela, Bolivarian

Republic of Viet NamYemenZambiaZimbabwe

Countries and territories with malarious areasThe following list shows all countries/territories where malaria occurs. In some of these countries/territories, malaria is present only in certain areas or up to a particularaltitude. In many countries, malaria has a seasonal pattern. These details as well asinformation on the predominant malaria species, status of resistance to antimalarialdrugs and recommended type of prevention are provided in the Country list.

(* = P. vivax risk only)


22/22

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CHAPTER 7. MALARIA

Further readingGuidelines for the treatment of malaria . Geneva, World Health Organization, 2006 (WHO/HTM/MAL/2006.1108).

Malaria vector control and personal protection: report of a WHO Study Group . Geneva,World Health Organization, 2006 (WHO Technical Report Series, No. 936).

Management of severe malaria: a practical handbook , 2nd ed. Geneva, World Health Or-ganization, 2000.

These documents are available on the WHO Global Malaria Programme web site:http://www.who.int/malaria.

International Travel and Health 2008

Documents

Transcript of International Travel and Health 2008