HelminthicDiseasesoftheDigestiveSystem

Figure 25.21
( ASCARIS LUMBRICOIDES)
 Ascariasis
Ascaris
lumbricoides
Lives in human
intestines
Transmitted by
ingesting Ascaris
eggs
Treated with
mebendazole

Figure 25.25
Ascaris lumbricoides
EPIDEMIOLOGI

TDP DI SLRH DUNIA : TROPIS,SUHU PANAS,

SANITASI JELEK
DI NEGARA MAJU ANGKA KJADIAN RENDAH,
NEGARA BERKEMBANG TINGGI. DI INDNESIA
HAMPIR SEMUA ANAK 1-10 TH TERINFEKSI
ANAK YG SERING KONTAK DG TANAH MU-
DAH TERINFEKSI ( SEMUA UMUR/DEWASA)
PREVALENSI CACING TINGGI PD TANAH BER-
PASIR. TELUR CACING RUSAK JIKA SINAR
MATAHARI LANGSUNG 12 JAM, SUHU DINGIN
TAK BERPENGARUH/BERTAHAN SLM.DINGIN
ETIOLOGI

STD INFEKTIF A.LUMBRICOIDES ADL TELUR

BERISI LARVA MATANG : OVAL,LEBAR,KULIT
TEBAL MAMILLATED , 40 X 60 uM
CACING DEWASA ( DI USUS KECIL MNS ) :
JANTAN 15-25 CM X 3 MM, BETINA 25-35 X 4
MM.
MASA HIDUP BETINA 1-2 TH , DAN MENGHA-
SILKAN 200.000 TELUR/HARI
 A. TELUR A.LUMBRICOIDES YG TELAH
DIBUAHI
B. TELUR YG TIDAK DIBUAHI
CACING A.LUMBRICOIDES DEWASA DI USUS KECIL
SIKLUS HIDUP A.LUMBRICOIDES

TELUR BERSAMA TINJA TERINFEKSI 5-10

HARI MATANG/INFEKTIF TERTELAN HOS-
PES/MNS,MENETAP DI BAG ATAS USUS
HALUS, LARVA LEPAS DR TELUR MENEM
BUS DD USUS VENA,PEMBULUH
LIMFE SIRKULASI PORTAL,HATI JANTUNG
KANAN PARU ALVEOLUS CABANG
BRONKUS
TRAKEA GLOTIS/EPIGLOTIS ESOFAGUS,
TELAN USUS :LARVA CACING DEWASA
MASA TELUR INFEKTIF DEWASA: 2 BULAN
PATOFISIOLOGI

INFEKSI DI MASYARAKAT OK.PEMBUANGAN

FESES DI TANAH :TELUR INFEKTIF LAGI
MIGRASI LARVA DI TUBUH REAKSI RADANG
INFILTRASI EOSINOFILIA,ANTIGEN CACING
MERANGSANG RESPONS IMUNOLOGIS : PE-
LEPASAN ANTIBODI, MEMBENTUK REAKSI
COMPLEMENT FIXATION DAN PRECIPITATING
PADA FASE INTESTINALIS : GEJALA OK.CA-
CING DLM/MIGRASI KE DALAM LUMEN USUS
YG LAIN,ATAU PERFORASI KE PERITONEUM
ASCARIS MENGELUARKAN ANTI-ENZIM,YG
AKAN BERMANIFESTASI TJD MALABSORBSI
ASCARIS LUMBRICOIDES ( GAMB. PATOFISIOLOGI )
 MANIFESTASI KLINIS

SIMTOMATIK JELAS : KOLIK DI EPIGASTRIUM ATAU

DAERAH PUSAT, PERUT BUNCIT ( POT BELLY ), MUAL,
MUNTAH, CENGENG, ANOREKSI, SUSAH TIDUR,DIARE

PENGELOMPOKAN BERDASAR MIGRASI ASCARIS :

A. SPOLIATIF ACTION
- DISTROFI / KURUS SEKALI : OK. DIARE DAN .
ANOREKSI, MALABSORBSI LEMAK,PROT,KH.
B. TOKSIN
. MASIH PERLU
PENELITIAN LEBIH LANJUT C. ALERGI
. ANTIGEN ASCARIS
AKAN MERANGSANG SISTEM . IMUNOLOGIS :
ANTIBODI SPESIFIK (IgG, IgA ). . REAKSI A.L.
ASMA BRONKIAL, URTIKARIA, HIPER . EOSINOFILIA,
SINDROMA LOFFLER
.
MANIFESTASI KLINIS (LANJUTAN)

SINDROMA LOFFLER : .
INFILTRAT EOSINOFILI PARU MENYERUPAI BRON- .
KOPNEUMONI ATIPIK, YG CEPAT HILANG/TIMBUL .
DI BAG.PARU LAIN. .
GAMBARAN RADIOLOGIS SEPERTI TBC.MILIER

D. TRAUMATIC ACTION
. CACING BERKUMPUL MEMBENTUK BOLUS DLM LU-
. MEN USUS OBSTRUKSI (INSIDEN: 2 PER
1000/TH) . KEADAAN LAIN :PERFORASI
USUS,SUMBATAN SAL. . EMPEDU, PERITONITIS,
ABSES DD USUS
MANIFESTASI KLINIS ( LANJUTAN )

E. ERRATIC ACTION
. LAMBUNG : MUAL, MUNTAH, NYERI EPIGASTRIUM,
. KOLIK
. NASOFARING : KE TUBA EUSTACHII OMA.
. PERFORASI LARING-TRAKEA--
. BRONKUS SUMBATAN-
ASFIKSIA . INFEKSI SEKUNDER HATI: ABSES,
HEPATITIS . DLM KOLON: JUMLAH BANYAK
DIARE , APENDI- . SITIS AKUT
. OTAK : ABSES KECIL-KECIL
F. LAIN-LAIN
. NEFRITIS, OBSTRUKSI
SAL.EMPEDU/IKTERUS
 DIAGNOSIS

1. IDENT. TELUR ASKARIS DLM TINJA

(MIKROSKOPIK KHAS)
2. ADANYA CACING KELUAR BERSAMA
MUNTAH/TINJA PENDERITA
3. (PEMERIKS. SEROLOGIS/TAK KHAS)
TUBERKULOSIS MILIER ( =SINDROMA LOFFLER/ ASCARIS)
DIAGNOSIS BANDING

PNEUMONI : PADA ASCARIASIS

. TERDAPAT EOSINOFI-
. LIA DI DRH PERIFER

INFESTASI NEMATODA LAIN DLM

FASE MIGRASI KE DLM PARU

DI DAERAH DG PREVALENSI ASCA-

.RIS YG TINGGI : OBSTRUKSI OK.
ASCARIS
 PENGOBATAN

1. PYRANTEL PAMOATE : DOSIS

TUNGGAL 10 MG/KG BB
2. MEBENDAZOLE : DOSIS 100 MG
2 X SEHARI SELAMA 3 HARI
3. PIPERAZINE CITRATE (ANTEPAR )
DOSIS TUNGGAL 75-150 MG/KG BB
PD USUS OBSTRUKSI :75 MG/KG BB
SELAMA 2 HARI CUKUP EFEKTIF,
OK.OBAT INI PARALISIS MYONEU-
RAL JUNCTION ASKARIS
RELAKSASI BOLUS ASKARIS.
JANGAN BERSAMAAN PIRANTEL P.
PROGNOSIS :

= KEBANYAKAN KASUS, PROGNOSIS BAIK

= KASUS DG OBSTRUKSI ATAU PERFORASI,

. TERGANTUNG CEPATNYA PENANGANAN DAN
. PENOBATAN
Hookworms

Figure 12.30
ANKILOSTOMIASIS
(PENY AKIT CACING TAMB
ANG )

CACING PENYEBAB :
- ANCYLOSTOMA DUODENALE
- NECATOR AMERICANUS
- ( ANCYLOSTOMA BRAZILIENSIS )
EPIDEMIOLOGI

MASALAH KES.MASYARAKAT DAERAH SUB-

TROPIK DAN TROPIK
PREVALENSI DI INDONESIA TINGGI : A. IKLIM
TROPIK, B. KEBIASAAN HIDUP ( BUANG AIR
BESAR, TANPA ALAS KAKI ), C. SOS-EK.
AKIBAT INFEKSI TSB. : GIZI, ANEMI DAYA
TAHAN <, PRODUKTIVITAS <, BELAJAR <
INSIDENS DI SELURUH DUNIA / INDONESIA
CUKUP TINGGI
SEJARAH DAN GEOGRAFI

PAPYRUS EBER MESIR KUNO : 1600 S.M.

DOKTER PERSIA : TH 980 TH 1073
DUBINI ( TH 1843 ) : MENGGAMBARKAN
DENGAN TEPAT DARI OTOPSI
GRASSI & PARONA ( TH 1887 ) : DIAGNOSIS PE-
NYAKIT TELUR KHAS PD TINJA PEND.ANEMI
PEKERJA TAMBANG
GEOGRAFIS : MULANYA EROPA SEL. AFRIKA
UTARA,INDA UTARA, CINA UTARA, JEPANG.
SELANJUTNYA INDIA SEL. BIRMA,MALAYSIA,
FILIPINA,INDONESIA,POLINESIA,AFRIKA BAR.
N.AMERICANUS : TH 1902 DI TEXAS (STILES):
A.S., KARIBIA,AMERIKA TENGAH & SELATAN
MORFOLOGI

NEMATODA KECIL,SILINDER,KUMPARAN (FUSI-

FORM), PUTIH KEABU-ABUAN
BETINA :PANJANG 9-13 mm, DIAMETER 0,35-
0,6 mm . JANTAN: 5-11 mm; 0,3-0,45 mm
ANKILOSTOMA > BESAR DPD NEKATOR A.

TELUR : UJUNG-UJUNG BULAT DAN SELAPIS

KULIT TIPIS HIALIN TRANSPARAN. DLM TINJA
SEGAR TDP STADIUM MEMBAGI 2-8 SEL.
TELUR NEKATOR 64-76 mikron, ANKILOSTOMA
56-60 mikron; diameter sama = 36-40 mikron.
PRODUKSI TELOR 25.000-30.000 / HARI
MORFOLOGI ( Lanjutan )

C.TAMBANG MELEKAT PD MUKOSA USUS DG

RONGGA MULUTNYA : DI BAG ATAS USUS HA-
LUS DAN (BAG.KAUDAL ILEUM )
NEKATOR PD DUODENUM DAN JEJUNUM,
ANKILOSTOMA PD JEJUNUM DAN ILEUM PROX
MENGHISAP DARAH HOSPES 0,026-0,200 ml /
24 jam TIAP EKOR CACING.
INFEKSI ANKILOSTOMA 6 8 TAHUN,
NEKATOR MENGHILANG DLM 2 TAHUN ( KA-
DANG SP 4 5 TH
RONGGA MULUT NEKATOR : BENDA PEMO-
TONG BENTUK BULAN SABIT DAN SEGITIGA
SIKLUS HIDUP
TELOR (TINJA ) 1- 2 HARI LARVA RABDITI-
FORM (SUHU OPT.23-33 DER.C) DG UKURAN
275 X 16 MIKRON 5 HARI 500-700 MIK.
LARVA FILARIFORM
LARVA DI LAPISAN ATAS TANAH TEDUH BER-
PASIR,TANAH LIAT,LUMPUR MENEMBUS
HOSPES MEL.FOLIKEL RAMBUT & PORI-PORI
ALIRAN DARAH-JANTUNG-PARU-KAPILER-
ALVEOLI-BRONKUS-TRAKEA-TERTELAN KE
USUS (LAMA 1 MINGGU) MENJADI DEWASA
DLM 13 HARI.
DLM 5 6 MINGGU STL INFEKSI : BERTELUR
LAMA HIDUP SAMPAI LEBIH 15 TAHUN .
Life Cycle: A. duodenale & N. americanus

Eggs are passed in the stool (1), and

under favorable conditions (moisture,
warmth, shade), larvae hatch in 1 to
2 days.
The released rhabditiform larvae grow in
the feces and/or the soil (2), and
after 5 to 10 days (and two molts)
they become become filariform
(third-stage) larvae that are
infective (3).
These infective larvae can survive 3-4
weeks in favorable environmental
conditions. On contact with the human
host, the larvae penetrate the skin
and are carried through the veins to
the heart and then to the lungs.
They penetrate into the pulmonary
alveoli, ascend the bronchial tree to
the pharynx, and are swallowed (4).
The larvae reach the small intestine,
where they reside and mature into
adults. Adult worms live in the lumen
of the small intestine, where they
attach to the intestinal wall with
resultant blood loss by the host (5).
Most adult worms are eliminated in 1
to 2 years, but longevity records can
reach several years.
PATOGENESIS & GEJALA KLINIS
LARVA STD INFEKTIF MENEMBUS KULIT/
PENETRASI : GATAL, DLM BBRP JAM REAKSI
ALERGI ( PRURITIS,RASH,PAPULA ERITEMA-
TEUS, VESIKEL ). INFEKSI II KRN GARUKAN.
KDG NEKATOR KE DLM KULIT :CREEPING
ERUPTION ( CUTANEUS LARVA MIGRAN ).
KE DLM PEMB.LIMFE, VENA KECIL, ALIRAN
DRH-JANTUNG-PARU-ALVEOLI-PERDARAHAN
PNEUMONITIS.
LARVA TERTELAN KE USUS HALUS :MUAL,MUN-
TAH,HIPERSALIVASI,GATAL DI FARING, SUARA
PARAU
DIAGNOSIS

1. BERDASARKAN GEJALA KLINIS :

A.L. ANEMI DAN EDEMA OK.DEFISIENSI MA-
KANAN/ INFEKSI CACING

2. DITEMUKANNYA TELUR DLM TINJA PENDE-

RITA, BAIK KUALITATIF MAUPUN KUANTITA-
TIF.
PRAKTIS TELUR ANKILOSTOMA TIDAK DA-
PAT DIBEDAKAN DG NEKATOR AMERIKANUS
PENGOBATAN
MEBENDAZOLE : DRUG OF CHOICE BAIK NEKATOR
MAUPUN ANKILOSTOMA.
DOSIS 100 MG, 2 X SEHARI SELAMA 3 HARI
PYRANTEL PAMOATE : 10 MG/KG BB
ANKILOSTOMA 1 X (TUNGGAL),NEKATOR 3 HARI
BEPHENIUM HIDROKSINAPTOAT:
DOSIS 5 GR TUNGGAL, BB < 22 KG 2,5 GR
TETRAKLORETIL : EFEKTIF UTK NEKATOR
DOSIS 0,12 ML/KG BB TUNGGAL, ULANGAN > 2 X DG
INTERVAL 4 HARI
ALBENDAZOLE : EFEKTIF UTK CACING DEWASA, LAR-
VA, TELUR. DOSIS TUNGGAL 400 MG DEWASA,UNTUK
ANAK 200 MG
TIABENDAZOLE: SPEKTRUM > ,25 MG/KG BB 2X/HR
PENCEGAHAN

DI INDONESIA, PEMBRANTASAN SEJAK TH.

1978 ( Lokakarya Pemberantasan Penyakit
Cacing ) , PRIORITAS ANAK BALITA, WANI-TA
HAMIL DAN MENYUSUI :
1. PENGOBATAN MASAL
2. PERBAIKAN SANITASI LINGKUNGAN
3. PENYULUHAN KESEHATAN
PENGOBATAN MASAL : BILA PREVALENSI DAN
INTENSITAS INFEKSI CACING > 10%.
Keadaan klinis anak tersebut
Anak penggugup, susah tidur
(tidak pulas) , mimpi yg
menakutkan (nightmare) sehingga
di bawah kelopak mata bag.bawah
tampak bayangan kulit yg gelap .
Pada keadaan serius, rasa gatal di
anus. Akibat garuk-an ,terjadi
eksim & infeksi sekunder,
selanjutnya terjadi ggn
pertumbuhan pd anak.
OKSIURIASIS

Oxyuris vermicularis
nama lain :
Enterobius vermicularis
Thread pin
Seat worm
Cacing keremi
PENDAHULUAN
Oxyuriasis adl infeksi yg terjadi pd kelompok
/sering terjadi dlm satu keluarga/tinggal dlm satu
rumah.
Sering ditemukan pada anak.
Cacing betina dewasa 8-13 mm x 0,3-0,5 mm dg
ekor yg runcing, jantan 2-5 mm x 0,1-0,2 mm.
Seekor cacing 11.000 telur, bentuk ovoid 50-60
mm x 20-30 mm,salah satu sisi datar- spt sampan.
Manusia terinfeksi krn tertelan telur infektif,mene-
tas di sekum dewasa. Siklus hidup +/- 1 bulan.
Pinworms

Figure 12.29
 Siklus hidup E.vermicularis
Setelah membuahi, cacing jantan akan
mati, dikeluarkan mel.tinja. Cacing betina
yg gra-vid pd malam hari turun ke
bag.bawah ko-on ke anus, telur diletakan
di perianal dan kulit perineum ( rasa
gatal ? ). Kmd.cacing betina kembali ke
usus.
Enterobius vermicularis
brneorm
 Empat cara terjadinya infeksi :
(1) langsung anus mulut, mel.tangan yg terkon -
taminasi waktu menggaruk
(2) penularan pd orang setempat tidur, mel. telur
di tempat tidur, bantal, selimut
(3) mel.udara terhirup (mis.pada waktu mem -
bersihkan tempat tidur)
(4) retroinfection :telur di anus menetas, larva
masuk kembali ke usus mel.anus.
DIAGNOSIS

Dg melihat anus anak pd malam hari,

dan menemukan cacing dewasa yg
sedang keluar untuk bertelur.
Atau menggunakan
anal swab atau cellophane swab, segera
diperiksa dg mikroskop dijumpai telur
cacing keremi.
Enterobius vermicularis
Brneorm
PENGOBATAN

Semua obat cacing dpt digunakan.

Pengobatan harus diberikan ke seluruh
ang-gata keluarga/serumah.
Pengobatan secara periodik.
Penerangan /penyuluhan mengenai
keber-sihan pribadi.
Pengobatan ( lanjutan )

Mebendazole or abendazole
Regular bathing and changing of underclothes
Keeping fingernails short
Treat the whole family
Selamat Bel
ajar
Statistics
In 2004, 18.48 million laboratory confirmed cases;
but estimates of actual cases run as high as 500
million.
In 2004, 99,600 confirmed deaths; estimates of
actual deaths approach one million.
Most deaths are of infants, young children and
pregnant women; most in Africa.
A child dies of malaria every 30 seconds.
40% of the worlds population, mostly in the worlds
poorest countries, are at risk.
Most cases and deaths are in sub-Saharan Africa.
However, Asia, Latin America, the Middle East and
parts of Europe are also affected.
 Distribution of species (%) in following areas

Central
Asia (all) South
America
Sub-Saharan Africa
and
Caribbean America
West and East and
Species
Central South

4.2 (but in SE
P. falciparum 88.2 78.8 Asia, 48%) 12.9 29.2

P. vivax 1.2 9.8 95.6 87.1 70.6

P. malariae 2.2 3 0 0 0.2

P. ovale 8.4 8.4 0.2 0 0

Carter and Mendis, Clin Microbiol Rev 2002

 Africa
~ 1,136,000 deaths from malaria in Africa in 2002
(The World Health Report, WHO, 2004)
Malaria causes half the deaths of African children
under the age of five
Sub Saharan Africa: 275 million of total 530 million
people may have malaria parasites in their blood
Up to 30% of malaria deaths in Africa related to
war, local violence or other emergencies. Displaced
people in makeshift housing are vulnerable: more
likely to be bitten by mosquitoes, often ill with other
infections, and lack access to health care.
Latin America
Countries in region w/ greatest number of malaria cases
overall (top 10 in order): Brazil, Colombia, Peru,
Ecuador, Guatemala, Venezuela, Guyana, Bolivia,
Honduras, Suriname
Greatest number of cases of falciparum: Colombia,
Brazil, Peru, Guyana, Suriname, Ecuador, Haiti,
Venezuela, French Guyana
Mortality rate:
816 (8.3/100,000
(8.3/ of at-risk population) in 1994
68 (7.5/1,000,000
(7.5/ of high risk population) in 2003
Population living in
Low risk areas: 26%
Moderate risk areas: 5%
High risk areas: 4%
SE Asia
30% of worldwide malaria morbidity; about 4% of mortality
In 2004
2.53 million (provisional) laboratory confirmed malaria cases
3,768 malaria deaths
In 1977, much more vivax than falciparum, now about equal;
many areas w/ drug resistant falciparum
2004, % of Total Cases:
India 75%
Indonesia 12%
Myanmar 6%
Bangladesh 2.4%
Timor 1.6%
Thailand 1.1%
2004, % of Total Deaths
Myanmar 52%
India 25%
Bangladesh 13%
Thailand 6%
Types of Transmission
Stable Transmission
Sub Saharan Africa and parts of Oceania
Entomological inoculation rate (EIR) >10/year
Worst disease in children less than 5, pregnancy
Children at risk of severe disease/death
Adults with partial immunity, lesser symptoms

Epidemic or seasonal transmission

Most of Latin America/much of Asia
EIR 1-5/year
All ages at risk of severe disease/death
May overwhelm health system in epidemic
 Protozoa Plasmodium
Female anopheline mosquito transmits (many species)
6-12 days after biting an infected person
P. falciparum
Responsible for 95% of malaria related deaths; 1 to 3% mortality rate
P. vivax
Most dominant species outside Africa (none in W. Africa)
Affects all ages b/c common in areas of low transmission
Like falciparum, reduces birth weight (but not as severely)
Rare complication is splenic rupture (but mortality rate of this 80%)
Can cause post-malaria cerebellar syndrome
P. ovale
Only P. vivax and P. ovale have hypnozoites, latent liver stage
resulting in relapses weeks to months later, up to 5 years
Relapses affect local educational and economic development
P. malariae
May lead to glomerulonephritis and nephrotic syndrome (but
uncommon)
Co-infection of more than one species common in some
regions
Uncomplicated Malaria
First symptoms nonspecific: HA, fatigue,
abdominal discomfort, muscle and joint aches,
followed by fever, chills, perspiration anorexia,
vomiting and worsening malaise.
Residents of endemic areas may self-diagnose.
Sometimes overdiagnosed on basis of
symptoms.
No evidence of end-organ dysfunction.
P. vivax and P. ovale, more than other species
have malarial paroxysmsfever spikes, chills,
and rigors at regular intervals.
Fatality rate low at this stage (0.1% for
falciparum, the other malarias are rarely fatal.)
Severe Malaria (Falciparum almost
always)
If ineffective drugs given or treatment delayed in
falciparum, parasite burden may increase and change to
severe malaria
May progress within a few hours
Coma (cerebral malaria)
Metabolic acidosis
Severe anemia
Hypoglycemia
In adults, acute renal failure or acute pulmonary edema
In this stage, mortality in people receiving treatment is
15-20% (has increased in recent years due to
resistance)
If untreated, almost always fatal.
Clinical Diagnosis:
In settings where the risk of malaria is low:
dx based on degree of exposure to malaria and h/o
fever for 3 days or more w/out features of other severe
diseases
In setting where risk high:
fever in previous 24 hours and/or presence of anemia
Pallor of the palms most reliable sign of anemia in
young children
See WHO algorithms for IMCI (Integrated
Management of Childhood Illness)
Laboratory Diagnosis:
Light microscopy
Low cost if case-load is high of fever Pts
High sensitivity
Need training/experience (see Oxford Tropical Medicine Handbook re
preparing smears)
Rapid Detection Tests (RDTs)
More expensive
May be affected by heat/humidity
More feasible in community settings
Low to moderate/unstable transmissionshould confirm dx w/
laboratory before treating
Very low riskconfirm exposure before laboratory test
Stable high-transmission
Malaria most common cause of fever in children under 5give treatment if
fever and no other obvious cause--benefits of lab dx do not outweigh
benefit of not treating false negatives
Above 5 y/o and especially in pregnancy given risks of drugs should first
get laboratory diagnosis
Where high prevalence of AIDS, lab dx important b/c many other causes
of fever in AIDS
In severe malaria, ok to treat based on clinical dx if delay in lab dx
Treatment

Below per WHO guidelinesbig

emphasis on trying to avoid increased
drug resistance through Artemisinin
Combination Therapies (ACT)

For Country-specific policies,

http://www.who.int/malaria/treatmentpolicies.
html
Drug names

Fansidar (brand name) =

pyrimethamine/sulfadoxine
Malarone = atovaquone/proguanil
Lariam = mefloquine
ACTavoiding drug
resistance
In various areas, falciparum observed resistant to almost
all antimalarials (amodiaquine, chloroquine, mefloquine,
quinine, and sulfadoxine-pyrimethamine); spreading.
Except artemisinin and its derivatives (artesunate,
artemether, artemotil, dihydroartemisinin)
From traditional Chinese medicine; provides rapid
clearance of parasite
New WHO policy for artemisinin combination therapy
(ACT) to avoid resistance (think TB, HIV)
Combination tx w/out artemisinin does not offer addtl
benefit b/c high resistance to one of the compounds; not
considered combination therapy b/c do not attack different
targets on the parasite
Evidence of neurotoxicity in animals, but none in large
human studies
Recommended ACTs
When given with a slowly-eliminated partner medicine,
3 day treatment possible
When given w/ rapidly eliminated compounds
(tetracycline, clindamycin), 7 days needed
These 2 may have lower cure rates b/c resistance to the
partner medicine
Artesunate + amodiaquine
Artesunate + sulfadoxine-pyrimethamine
Resistance particularly a problem for SP where used for intermittent
preventive tx in pregnancy
These 2 less affordable and available but more
recommended where multi-drug resistance (SE Asia)
Artemether-lumefantrine
also recommened in Africa if available
6 dose regimen
Artesunate + mefloquine
Insufficient data on treatment in children
 Incorrect to treat semi-immune patients with
medications with known resistance or to give
partial treatment
Also potentially dangerous to give only first dose
of tx while waiting for lab dx; if tx started should
be finished
In some areas where ACT not available, AQ and
SP (amodiaquine and sulfadoxine-
pyrimethamine) may be used in the interim, if
effective in that area
however in some areas failure rates of this
combination have increased rapidly
Artemisins and partner medicines should not be
available as monotherapies
 WHO has called for a ban on the use of oral
artemisinin monotherapies worldwide
(rectal therapy used in severe malaria cases, before
transfer, if possible, for IV therapy)
Recently proposed globally administered
subsidy for ACTs
combination therapies sold to both governments and
private wholesalers at the same price as artemisinin
alone
about US $0.10 per treatment course (some ACTs are
more expensive, up to $2.40/treatment course)
Globally, would cost donors and development
agencies US$150-200 million each year
Children
ACTs still first line treatment for falciparum
Antipyretic (paracetamol/acetaminophen or
ibuprofen, not aspirin b/c of Reyes syndrome) or
baths in tepid water for fever reduction
Seizure management
Overlap between febrile seizures and seizures of
cerebral malaria
parenteral or rectal benzodiazepines or IM
paraldehyde
No benefit for prophylactic anticonvulsants
Beware of treating children with high levels of
parasitemia outpatient, as they may deteriorate
rapidly
Insufficient data on use of mefloquine in children
Pregnancy

Non-immune pregnant women: up to

60% fetal loss and over 10% maternal
deaths; 50% mortality for severe disease
Immunity reduced during pregnancy
Associated w/ low birth weight, increased
anemia, and in low transmission areas,
more severe malaria
 Treatment in Pregnancy
Mefloquine should not be used in pregnancy
More and more experience w/ artemisinin derivatives in 2nd
and 3rd trimester
Sulfadoxine-pyrimethamine used intermittently to clear
placenta in highly endemic areas to reduce asymptomatic
effects of malaria
Safe in 1st trimester:
Quinine, chloroquine, proquanil, pyrimethamine and sulfadoxine-
pyrimethamine (most effective is quinine)
First trimester: quinine plus/minus clindamycin
Second/Third trimester
ACT being used in that country/region
Or artesunate + clindamycin
Or quinine + clindamycin
Travelers: Prophylaxis
Malaria Risk Prophylaxis

Type I--Very limited risk of Mosquito bite prevention only

malaria transmission
Type II--Risk of P. vivax Mosquito bite prevention plus chloroquine
malaria or fully chloroquine- chemoprophylaxis
sensitive P. falciparum only
Type III--Risk of malaria Mosquito bite prevention plus
transmission and emerging chloroquine+proguanil chemoprophylaxis
chloroquine resistance

Type IV--High risk of Mosquito bite prevention plus either

falciparum malaria plus drug mefloquine, doxycycline or atovaquone/
resistance, or moderate/low proguanil (take one that no resistance is
risk falciparum malaria but reported for in the specific areas to be
high drug resistance visited)
 Remember, prophylaxis is NOT the same medicines/doses as
treatment. Prophylaxis doses:
Chloroquine 500 mg weekly, 1-2 weeks prior to exposure (500 mg
Q6hx2 if started after) to 4 weeks after exposure. Side effects:
N/V/D, vision changes/HA, rarely aplastic anemia. Need periodic
eye exams, CBCs if long term use. 30 tabs for $70 (in US but
cheaper in other places).
Mefloquine (Lariam): 250 mg/wk starting 1 wk before and 4 wks
after. N/V, dizziness, rarely depression/psychosis, seizuresmuch
talked about but more recently several studies showed no
significant difference in terms of neurologic effects. $300 for 25
tabs.
Doxycycline 100 mg daily 1-2 days before until 4 wk after. Tooth
discoloration if <8 y/o, photosensitivity, headache,
nausea/diarrhea, vaginal candidiasis, may affect oral
contraceptives. 200 capsules for $55.
Atovaquone/proquanil (Malarone): 250/100 mg daily starting 1-2
days prior through 7 days after. N/V/D/abd pain/HA, renally
excreted so consider baseline creatinine. $45 for 7 tabs.
Per one survey, the average cost of malaria prophylaxis for a two-
week trip would be $34 for doxycycline, $74 for Lariam, and $127
for Malarone.
 http://www.who.int/ith/countries/en/index.html for
country-specific information on risk level
Many major cities in endemic areas safe, except for
outskirts
Many tourist destinations are safe
SBET (Stand-by Emergency Treatment): Bringing this
may be recommended (in combination with mosquito bite
protection)
for frequent short trips (i.e. airline crews)
those who travel 1 week or more to remote rural areas, where
multidrug-resistant malaria but very low risk of infection, and risk
of side-effects of prophylaxis may outweigh risk of contracting
malaria. (i.e. certain border areas of Thailand/ other countries in
SE Asia, the Amazon basin.)
Travelers taking prophylaxis may bring if fake drugs common
where they are going or going to very remote areas where
treatment in < 24 hours not available
still need to seek medical attention as soon as possible
Travelers: Bite-
Avoidance
Long pants/sleeves at night, avoid dark colors
(which attract mosquitoes)
Insect repellant with Deet or dimethyl phthalate;
higher the concentration, the longer the
protection lasts:
23.8% DEET -- an average of 5 hours protection
20% DEET -- almost 4 hours of protection
6.65% DEET -- almost 2 hours of protection
4.75% DEET or 2% soybean oil -- 1 1/2 hour
Screens/mosquito nets
Travelers: Treatment
Fever 1 week after and up to 3 months
after exposure should be investigated
Prophylaxis should be stopped while
investigating active infection
Artemether-lumefantrine (6-dose
regimen)
Or atovaquone-proguanil
Or quinine + doxycycline or clindamycin
Severe Malaria
IV artesunate or IV quinine
Quinidine w/ careful cardiac monitoring in
areas (like non-malaria areas) where quinine,
etc. not available
Hemodialysis early in acute renal failure or
severe metabolic acidosis
Positive pressure ventilation should be started
early if breathing pattern abnormality,
intractable seizure, or ARDS
Pre-referral Treatment

Artesunate or artemisinin by rectal

administration
Artesunate or artemether IM
Quinine IM
HIV
No change in treatment recommended at
this time
Laboratory diagnosis of malaria or other
possible causes of fever recommended
b/c of many possible causes; lumbar
puncture if possible
In more resource rich settings, finding out
CD4 counts is very helpful to r/o some
opportunistic infections if count high
P. Vivax (also P. ovale)

Chloroquine over 3 days, w/ primaquine

once daily for 14 days to eliminate liver
phase
If chloroquine resistant, amodiaquine
over 3 days w/ primaquine for 14 days
Testing for G6PD deficiency if possible
if moderate, reduced dose primaquine; if
severe, should not be given
Prevention

For now, no longer an attempt to eliminate

malaria; to decrease morbidity and
mortality, especially in pregnant women
and young children
Vector reduction
Better access to treatment in vulnerable
populations
Vector reduction
Indoor Residual Spraying of long-acting insecticide (IRS)
use of DDT; in this case not environmentally damaging and
not shown to be dangerous to humans. Several
environmental groups formerly opposed to DDT now
endorse.
Spraying not helpful in areas where indoor mosquitoes are not the
major vector
Long-Lasting Insecticidal Nets (LLINs)
Previous nets needed to be redipped in insecticide every 6-12
monthsthese new nets supposedly last for 5 years
Debate whether selling them as a commodity to increase their
perceived value vs. giving them free. Current strategy a combination
of bothgiving free to high-risk groups (pregnant women/children).
Supporting the starting of small businesses of net-making.
Eliminating areas of standing water, etc.depends on type
of vectorobviously difficult to do in certain areas
Larvivorous fish (India, Indonesia, Myanmar, Sri Lanka and
Thailand)
Problems
Recent evidence from Africa indicates that
pyrethroid and DDT resistance is becoming more
widespread than anticipated. Thought to be more
of a problem for IRS than LLIN. Insecticide
resistance monitoring needs to be a part of
control programs.
? Changing area of stable transmission to an
area of seasonal or epidemic transmissionif
decreased exposure decreases immunitycould
result in worse disease in adults
 Vaccine development efforts are underway, but given that
people do not develop natural long-term immunity to
malaria, and such efforts are underfunded, this is difficult

Malaria, TB, African trypanosomiasis, Leishmaniasis, and

Chagas are the areas of greatest need for additional
research and development; malaria is the most needed
given the disease burden.

Unfortunately, most top pharmaceutical companies spend

2 to 3 times a much on marketing/administration as they
do on R&D; 22% of staff are employed in R&D, while 39%
are in marketing.

Almost no research is being done in malaria by

pharmaceutical corporations; most is through the NSF or
universities (University of Notre Dame is one).
Resources

http://www.who.int/malaria/
Oxford Handbook of Tropical Medicine
http://whqlibdoc.who.int/publications/200
7/9789241580397_7_eng.pdf