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Malaria Prevention

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

• Malaria are endemic in most the eastern part of


Indonesia particulary in Papua
• Nowdays globalization drives peoples to go abroad
including to endemic malaria areas
• This visitors are considered as non-immune and
vunerable to malaria with high risk of death
• This high risk groups need malaria prevention to
reduced morbidity and mortality
Risk of malaria for travelers

• Risk of exposure to malaria for travelers to :


– Western Africa : 302 - 1300 / 100.000 visitors
– South Africa : 46 /100.000 visitors
– South America : 1 - 7,2 / 100.000 visitors
– Thailand and Vietnam : 2 – 19,2 /100.000 visitors
• A study of Denmark travelers to Indonesia :
– 76 per 100.000 travelers contracted malaria

Schlagenhauf P, Petersen E. Clin Microbiol Rev 2008 ; 21(3) : 466


Malaria prevention for travelers in general

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

• Risk of malaria 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 , risk , miner risk
• Activity : outdoor at dawn / night risk
• Season : rainy season risk
• Accomodation : room with AC, cycling fan risk
• Visiting Area : capital or downtown risk , 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
Efficacy of repellent

Conclusion : among repellents : DEET is still the best


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 some community
Chemoprophylaxis
• Administration of antimalaria drugs for prevention
• Use lower dose, but for 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 :
– Could be used short or long-term travelers
– Visiting low malaria transmission areas
– Visit remote area with no prompt 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 by IRS and ITN
– Early diagnosis and prompt treatment
– 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 travellers

• 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 for short-term travelers
Risk to get malaria in travellers
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 like pilot
• 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


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 efficacy : 30 %
– 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
– IPTp with DHP 3 tab. Every month or every week ( under development )
Prevention of malaria in pregnant women

• Disadvantage of IPTp :
– Increased resistance to SP -- change to DHP (? )
• 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, controversial
• 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

Primary Prophylaxis
Summary

• Choice of malaria prevention depend on :


– Endemic area : high endemic or low endemic
– Length of stay : short – term or long – term
– Purpose of visit : high or low – risk,
– Access to health facility : available or not
• Categorized to high or low risk
• Chemoprophylaxis indicated to high risk travellers
• Chemoprophylaxis usually not indicated to low risk
travellers
• Patients preference
Kasus

• Seorang Dokter akan bertugas di puskesmas 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 pedalaman
Papua, selama 2 minggu. Anjuran pencegahannya ?
• Seorang pengusaha akan berkunjung ke kota Labuhan Bajo, NTT
untuk urusan bisnis. Beliau tinggal di Hotel di tengah kota,
namun pada siang hari sering pergi ke pinggiran kota tempat
proyeknya. Rencana berkunjung selama 14 hari. Advis ?
Kasus

• Seorang dokter puskesmas di pedalaman Waingapu, NTT.


Beliau ikatan dinas selama 3 tahun. Hamil G1P0 A1 10-12
minggu. Keguguran 2 tahun lalu. Advis pencegahan ?
• Seorang wanita hamil G1P0A0 hamil 26 minggu. Ingin pergi
menyusul suaminya yang sedang bertugas di puskesmas
terpencil di pulau Buru, Maluku. Beliau bersikeras berangkat
karena khawatir suaminya selingkuh. Lama tinggal belum
tahu. Advis pencegahan malaria ?
Thank you