Malaria Prevention

&
Chemoprophylaxis
Agung Nugroho
Department of Internal Medicine
Tropical & Infectious Disease Division
Sam Ratulangi University Manado
 Introduction

• Malaria endemic in the eastern part of Indonesia

particulary hyperendemic in Papua
• Increasing visitors or tourists come to Papua for short
or long term stay or transmigrants for permanent
stay
• They considered non-immune and vunerable to
malaria with risk of death
• This high risk groups need malaria prevention to
reduced morbidity and mortality
 Risk of malaria for travelers

• A study of Denmark travelers to Indonesia :

– 76 per 100.000 travelers contracted malaria
• Risk of exposure to malaria for travelers to Southeast
Asia : 3,4 %
 Malaria prevention for travelers in general

• “ ABCD “ approach :
– Awareness of risk
– Bite prevention
– Chemoprophylaxis
– Diagnosis promptly and treat without delay
• Education : all about malaria
benefit of prevention measures
benefit and risks of chemoprophylaxis
 Awareness of risk

• Risk related to endemicity of the visiting area :

– Annual incidence of malaria cases in local population
– Annual parasite rate of indigenous population
• Length of stay : longer stay risk
• Reasons of visit : bussiness, occupation ( miner risk )
• Activity : outdoor at dawn / night risk
• Season : rainy season risk
• Accomodation : room with AC, cycling fan risk
• Visiting Area : capital, downtown, country side
 Bite Prevention
• Physical barrier :
– mosquitoes screen to cover ventilation, door, window
– Close the door and window after dawn
– Use air condition or cycling fan in the living room /
bedroom
– Insecticide-treated mosquito nets ( ITN )
• Personal protective measures :
– Apply skin with DEET 30 – 50 % repellent
– Use long sleeves shirts or pants, socks, full- covered
footwear for outdoor activities at night
– Use knockdown sprays / aerosolized or insecticide coils
• Indoor residual-insecticide sprays
 Insecticide-treated nets ( ITN )

• WHO recommended Long-lasting insecticide-treated

nets ( LLITN ) that effective for 3 years
• Indications :
– In unstable malaria area : total population
– Recommended for travelers sleep outdoor
or unscreen accommodation
– Priority to pregnant woman and children
• ITN must free of tears, tucked in under the mattres
 Repellent DEET

• Repell insect, not kill them

• ACPM recommended DDET 30 – 50 %
• For outdoor use, apply on exposed skin
• Commonly safe even for pregnant women
• Side effect : skin rashes
skin, mucous membrane iritation
• Precautions :
– Use for adult, children, infant > 2 month of age
– Avoid contact to eye, mucous membrane, wound / iritated skin
– Wash hand after handling repellent
– Avoid over-appliance especially for children
 Indoor- Residual insecticide spraying ( IRS )

• The most popular Insecticide is DDT : cheapest, longest

duration, relatively safe
• Problems :
– Developing resistance by insects to DDT
– Mosquitos behaviour : outdoors bitting and resting habits
– Inadequate sprayingable surface / suitability of wall or roof
surface for spraying
– Custom of people in some areas to sleep outdoor during
the hot season
– Poor acceptance by community
 Chemoprophylaxis
• Administration of antimalaria drugs for prevention
• Lower dose, longer duration
• Antimalaria drugs for chemoprophylaxis :
– Blood - stage prophylaxis :
• Chloroquin + proguanil
• Mefloquin
• Doxycycline
– Live- stage prophylaxis :
• Atovaquone / proguanil
• Primaquine : for P. vivax only
• Chemoprohylaxis is not 100 % effective, efficacy rate 75 – 95 %
Chemoprophylaxis
Chemoprophylaxis
Chemoprophylaxis
Chemoprophylaxis for children
 Chemoprophylaxis

Drug advantage disadvantage contraindication

chloroquin Take weekly Resistant -
Cheap, widely GI side effect
available
pregnancy
Mefloquin Weekly Side effect : Psychiatric
pregnancy Neuropsychiatry
Nausea, dizziness
Atovaquone - Most tolerable Expensive Kidney failure ( Cr
proguannil For chloroquin Daily clerance < 30 ml/m )
resistant pregnant
Doxycycline cheap Daily Pregnant
GI side effect
Photosensitivity
Candida vaginal
 Evidence of efficacy
Interventions Evidence benefits
Insecticide treated nets 18 RCTs Reduced malaria episodde 39 %
Ruduced child mortality ( RR 0,83 )
Air conditioning , electric 1 questionnaire Reduced the incidence of malaria
fans Survey, Fan did not reduce catches of
1 observational Anopheles
study
Insecticide treated clothing 1 controled trial Reduced mosquito bites
DEET 1 controled trial Reduced malaria bites ( RR 99,9 % )
Doxycycline 2 RCT 1/67 cases vs 53/69 ( RR 99 % )
Protective efficacy 96,3 % P.
falciparum, 98 % P. vivax
mefloquin 5 RCT Efficacy 100 %
Aerosol insecticide 1 survey Not reduce the incidence of malaria
clothing 1 survey Reduced the incidence of malaria
Insects electrocuters, 1 observasional Not reduced bites
buzzers, smoke study
Croft A. BMJ 2000 ; 321 : 154 - 160
 Early diagnosis and prompt treatment

• Stand-by Emergency Treatment ( SBET ) :

Use of antimalarial drugs carried by the traveler for
self- administration when malaria is suspected and
prompt medical attention is unavailable within 24
hours of onset of symptoms
• Indications :
– short or long-term travelers
– Visiting low malaria transmission
– Visit remote area with no diagnostic and therapeutic
facilities
 Stand-by Emergency Treatment

• Not indicated for very-short visit ( < 6 days )

• Need written instructions
• Need good education, responsible travelers
• Drugs used for SBET different with chemoprophylaxis drugs
• Disadvantages :
– Overuse antimalarial drugs
– Patients tend to miss medical attention as advised
– Delay in diagnosis & treatment of others non-malaria
illness
– Errors SBET dosage and regimen is high ( 88 % )
Antimalarial drugs for SBET
 Malaria prevention

• Prevention for visitors / travelers to endemic area :

– Prevention for short – term travelers
– Prevention for long-term travelers
• Prevention of malaria for resident
– vector control
– Vaccine
– Prevention for pregnant and breastfeeding
women and children
 Prevention of malaria for short-term travelers

• Short-term travelers have substantial risk of contracted

malaria
• Short-term travelers : 3 weeks or less
• Risk depend on endemicity area, activities
• Prevention measures :
– Bite prevention with personal protection measures
– Chemoprophylaxis

Freedman DO. N Engl J Med 2008; 359 (6)

 Prevention of malaria for short-term travelers

• Personal protection against mosquitoes :

– Wear long sleeves, long pants, fully closed shoes
with socks after dark
– Use ITN if room is not well screened or air-
conditioned
– Use DEET 30 – 50 % every 4 – 6 hours or more
frequent if use lower concentration
 Chemoprophylaxis for short-term prophylaxis

• Drug choices depent on :

– Risks of malaria
– Comorbidities
– Cost
• Safety :
– Atovaquone – proguanil : most tolerable
– Followed by doxycycline
– Mefloquin : rare, notorious side efect ( neurophsychiatry )
• Indonesia : only doxycycline is available , recommended

Sclagenhauf P, Tschopp A, et al. BMJ 2003 ; 327 : 1078

 Prevention of malaria in long-term travelers

• Long term travelers are non-immune travelers visiting endemic

areas for longer than 6 months
• Also include :
– Visiting of less than 6 months
– Frequent transient stays
• Long- term travellers have higher risk of infection
– P. falciparum OR = 1, 5 ; P. vivax OR = 2,44
• Specific problems for long-term travelers :
– Lower adherence to long term chemoprophylaxis
– Worried about long-term chemoprophylaxis side effect
– Confidence that infection could be managed effectively
Schlagenhauf P, Petersen E. Clinical Microbiology review 2008 ;
Chen LH, wilson ME, Schlagenhauf P. JAMA 2006
Chen LH, wilson ME, Schlagenhauf P. JAMA 2006
Chen LH, wilson ME, Schlagenhauf P. JAMA 2006
 Chemoprophylaxis for long-term travelers

Chen LH, wilson ME, Schlagenhauf P. JAMA 2006

Summary of malaria prevention for long term travelers

• Awareness of risk : Essential

• Prevention of bite : Essential
• Seasonal chemoprophylaxis :
– Limited applicability, limited data
– Not recommended in Indonesia
• Continous chemoprophylaxis :
– High risk area in Africa, PNG
– Not recommended in Indonesia
• Stand-by Emergency self treatment ( SBET ) :
– Remote, low risk areas
– Limited medical resources
– Supplemented with rapid diagnostic test ( RDT )
 Prevention of malaria in resident
• WHO rercommended 3 measures :
– Indoor-residual insecticide sprays
– Long-lasting insecticide-treated nets
– Diagnosis and treatment of malaria cases
• Other strategies :
– Malaria Vaccine : RTS,S /ASO1
– Intermitten prevention treatment in infant ( IPTi ) : give SP
to infant ( < 12 mo of age ) at 2nd and 3 th round of
vaccination against DPT and measles.
– Seasonal malaria chemoprophylaxis ( SMC ) for children
age < 6 year with Amodiaquin + SP monthy during peak
malaria season
 Prevention of malaria in pregnant and
breastfeeding women
• Malaria during pregnancy is dangerous significant
high maternal and child morbidity and mortality
• P. falciparum is the main culprit of malaria in pregnant
women severe malaria maternal death
stillbirths, spontaneous abortion
• Pregnant women adviced not to visit endemic area
• Personal protection measures is essensial :
– ITN is an important measure
– 20 % DEET are safe for both mother and the fetus, but need to applied
more frequently
• For chemoprophylaxis only mefloquin and chloroquin are safe
for pregnant women
 Prevention of malaria in pregnant and breastfeeding women

• Breastfeeding women :
– Chloroquin and mefloquin are safe
– Alternative : atovaquone – proguanil ( infant weigh > 5 kg )
– Infant who are breastfeed need his own chemoprophylaxis
• For pregnant women who lived in stable endemic area :
 Intermitten Preventive Treatment of pregnancy ( IPTp ) :
– Give treatment dose of antimalaria ( Sulfadoxine – pyrimethamine / SP )
in asymptomatic pregnant women for prevention
– Indications : all pregnant women in areas of stable malaria transmission
– 2 or 3 doses of SP at least 1 month apart start from second trimester,
given during antenatal visit under direct observation
 Prevention of malaria in pregnant women

• Disadvantage of IPTp :
– Increased resistance to SP
• Systemic review by Feike O, et al revealed even in area
with resistance to SP, IPTp still provide benefit
– Low coverage and acceptance in some area
• Indonesia : no IPTp program
 Intermitten Screening and Treatment of pregnancy ( ISTp )
– Screening pregnant women with RDT during antenatal visit
and treat those who are positive with ACT.
– Performed in low endemic area or as alternatif to IPTp
– ISTp at least as effective as IPTp
Feike O, et al. JAMA 2007 ; 297 (23 ) : 2603
Tagbor H, Cairn M, et al. PloS ONE 2015 : doi : 10.1371/journal.pone.0132247
 Prevention of vivax malaria

• P. vivax is high endemic in Southeast Asia including Papua

• Vivax malaria have lower mortality but higher morbidity due
to relaps of dormant hypnozoit in Liver
• Vivax malaria for traveler responsible to late onset malaria ( 2
– 3 months after leaving endemic area )
• Althrough less common, P. vivax can cause severe malaria
• The only drugs to prevent relaps is primaquin
• Increasing resistance of P. vivax to primaquin in Papua.
• Side efect of primaquin : hemolysis due to G6PD deficiency
methaemoglobulinemia
 Prevention of vivax malaria

• Primary prophylaxis : 30 mg base once daily taken with meal,

start 1 day before until 7 days after leaving endemic area.
– Indications : brief trip
• Presumptive antirelapse therapy / terminal prophylaxis : 30
mg base once daily for 14 days (combined with blood stage
chemoprophylaxis ) , usually given at the last 2 weeks of
chemoprophylaxis
– Indications : long term trip to high P. vivax areas
• G6PD test is mandatory before treatment
• Indonesia : no recommendation
Prevention of vivax malaria
 Kasus

• Seorang Dokter akan bertugas di Tanah Merah, Digul, selama

1 tahun. Anjuran pencegahan malaria ?
• Seorang Penginjil, 35 th, akan bertugas di Nabire, berkunjung
ke pedalaman, selama 2 minggu. Anjuran pencegahan ?
• Prajurit TNI dari Jawa, bertugas pengintaian di hutan
pedalama Papua, selama 2 minggu. Anjuran pencegahannya ?
Terima kasih