Malaria & Comorbid

Agung Nugroho
Tropical & Infectious Disease Division, Department of Internal medicine
Faculty of Medicine Sam Ratulangi University Manado
Malaria & HIV
 Introduction

• HIV cases increased significantly in Indonesia that is

also an endemic malaria region
• Malaria and HIV may co-exist in same geographic
area like Sub-Sahara Africa co-infection is
common
• Interactions between these deadly infections may
pose grave effects over 3 million death in 2007
• Other important thing is drug interactions between
antimalaria and antiretrovirus
 Impact of malaria to HIV
• Acute malaria decreases CD4 + T cells of HIV patients transiently,
recover at day 28 after treatment
• Tagoe DA, Boachie J. study :
CD4+ > 600 = 0 % HIV+M+
= 12,9 % HIV+M –
• Acute malaria increase HIV viral load transiently, decreased back to
baseline after 4 – 9 weeks malaria treatment
– A German traveler with P. Knowlesi & HIV+ :
Viral load : 34.799 copies 102.000 10.000
7d 3 mo
– A study in Malawi : HIV- VL increased 0,25 log, recovery
faster in those with CD4 > 300

Tagoe DNA, Boachie J. J Infect Dev Ctries 2012 ; 6(9) : 660 – 663
Ehrhardt J, et al. Malaria journal 2013 ; 12 : 283
 Impact of malaria to HIV

• Frequent acute malaria might accelerate progression of HIV

– Inflammation of acute malaria
– Malaria upregulate CCR5 a co-receptor for HIV entry
• Malaria may increased HIV transmission due to higher viral load
• In pregnant HIV patients :
– Malaria increased mother to child transmission
– Increased risk of clinical malaria and severe malaria even in
multipara. May be related to loss of antibody against
placenta malaria in HIV patients
– Increased risk of placenta malaria low birth weight,
clinical malaria in infant
 Impact of malaria to HIV

• Acute malaria may cause false positive of HIV test

• However impact of malaria on HIV remain
inconclusive
– Some study report no VL and CD4 changes
 Impact of malaria to HIV

malaria HIV CD4

progression to AIDS ?
viral load

pregnant sexual partner

transmission to child transmission

 pathophysiology

Malaria hemozoin mononuclear cell

proinflammatory cytokines
TNFα , IFNγ , IL-8 , IP-10

Activation of apoptosis / pyroptosis uninfected

HIV infected CD4 CD4

Viral replication CD4

 Impact of HIV to malaria

• Increased malaria episode : frequent reinfection or

recrudescens
– Study by Koremkomp EL in Sub-Sahara Africa : incidence of
malaria increased by 28 %, death increased by 114 %
– Other study : risk of malaria 5,1 %, mortality 2,1 %
• Increased severe malaria : 2 – 3 fold risk
• Increased parasite burden
• Increased mortality of malaria

Koremkomp EL. Emerging Infectious Disease 2005; 51(9)

 Impact of HIV to malaria

• Increased treatment failure :

– Related to hyperparasitemia and reinfection
– CD4 < 200 and anemia increased > 3 fold risk of tx. Failure
( not in children )
• Increased placenta malaria
• Decreased haemoglobin ( anaemia )
• Malaria symptoms recover more slowly in HIV pos. due to
delayed parasite clearance
• Malaria Immune Recovery Inflammation Syndrome ( IRIS ) ?
• Risk related to the degree of immunosupression of HIV pts.
HIV increased risk of severe malaria
 pathophysiology

HIV CD4 cellular immunity

T- regulator
B cell antibody production reinfection

Proinflammatory malaria eradication Tx. failure

Cytokines
parasites density

Severe malaria
 Impact of HIV to malaria

• Impact of HIV to malaria in children :

– Increase prevalence of clinical malaria particulary those
with severe immunosupression
– Increase prevalence of severe malaria and its complication
bacteremia
– No different respons to antimalaria treatment
– Co-administrtion artesunate – amodiakuin with
cotrimozale increase risk of severe neutropenia
 Impact of HIV to malaria

• Impact of malaria to adults in stable malaria transmission :

– Increase risk of asymptomatic parasitemia,
hyperparasitemia, clinical malaria, particulary for those
with severe immunosupression
– Increase risk of anemia
– No clear evidence about risk of severe malaria and
mortality
– Increase risk of treatment failure due to reinfection that
more prominent during severe immunosupression
 Study by Mbale EW et al.
• 877 retinopathy – positive CM ; 14,4 % HIV positive
• aim o f study : compare parasitemia and cytokines ( TNF and IL-10 )

• no difference in parasitemia and parasite biomass between HIV (+) and HIV ( - )
• patient with HIV ( + ) have significant lower TNF and IL-10 compare to HIV ( - )

Mbale at al. Journal of Infection 2016 ; 73 : 189 - 191

 Impact of HIV to malaria

• Impact of HIV to malaria in adults living in unstable malaria

transmission and non-immune patient
– Increase risk of severe malaria and mortality
• Impact of HIV to malaria in pregnant and infant
– Increase prevalence of parasitemia, clinical malaria,
placenta malaria
– Higher parasite count in blood and placenta
– Increase risk of anemia and mortality in pregnant
– Increase low birth weight and prematurity
– No clear data on infant mortality
 Management of HIV – malaria co-infection

• Treatment of malaria in HIV patients principally same as

non-HIV with exception :
– Do not use Artesunate – amodiaquine in HIV patient
treated with efavirenz or zidovudin
Risk of anemia and neutropenia
– Do not use artesunate – SP in HIV patient on
cotrimoxazole prophylaxis
Risk of hepatotoxic and skin reaction
– Co-adminstration Arthemeter- lumefantrin ( AL ) with
efavirenz ( but not nevirapine ) may reduce
lumefantrin bioavailability, recommended to extend
treatment of AL to 5 days with same dose
 Management of HIV – malaria co-infection

• Caution of drug interaction :

– Halofantrin / lumefantin with NNRTI ( efavirenz /
nevirapine ) or Protease inhibitor ( PI )
• Increased risk of cardiotoxicity ( long QT )
• Avoid if possible or close monitoring
– Quinine with NNRTI or PI : risk cardiotoxicity, avoid if
possible
– SP with cotrimoxazole : avoid
– SP with nevirapine : don’t use simultant
 Management of HIV – malaria co-infection

• To reduced risk of malaria :

– Advise to use ITN
– Early antiretrovirus treatment ( ART ) for HIV
– Cotrimoxazole prophylaxis
Reduced risk of malaria by 75 %
– More frequent IPTp for pregnant HIV pts.
• PI drugs ( lopinavir / ritonavir boosted ) have
antimalaria
First line choice ARV in high endemic malaria area ?
 Pedoman Nasional tatalaksana HIV 2019

• Tidak ada perbedaaan penegakkan diagnosis malaria

pada pasien dengan atau tanpa HIV, harus dengan
pemeriksaan RDT atau mikroskopis
• Pilihan obat malaria program tidak berinteraksi dengan
obat ARV
• Pemerian obat antimalaria dilakukan segera setelah
diagnosis ditegakkan tanpa mempertimbangkan infeksi
HIV
• Tidak ada perbedaan dalam pemantauan respons
pengobatan malaria yaitu dengan hitung parasit secara
mikroskopis
 Take home massage
• Every HIV patients with fever who lived or have history of
travel to malaria endemic area should have malaria test.
• Beware, HIV patient with malaria smear positive may have
another cause of infection like oportunistic infections
i.e : coma in HIV and malaria positive, may be caused by
meningitis TB, toxoplasmosis cerebri
• Do every malaria patients should be tested for HIV ?
– At present , No recommendation in Indonesia
– Offer HIV test in high HIV prevalance area
– Offer test for high risk group ( ask sexual behaviour )
– Offer HIV test for malaria treatment failure, frequent
malaria attack, severe anaemia ?
 Case
• Male, 27 year old, HIV positive on ARV 6 for months, CD4 : 69
• Hospitalized due to massive bleeding of giant condyloma
accuminata in anorectal and genital area ; Hb : 4,2 gr/dl
• Received large volume blood transfusion, followed by surgery
• Day 18 th, patient develop fever, headache, jaundice
• Hb 12,6 ; WBC : 8500 ; neutrophils 82 % ; platellet : 87.000 ; Total
bilirubin 4,6, direk 3,2 ; SGOT 118 , SGPT 92 ; ureum , creatinin
normal
• Early working diagnosis : sepsis nosocomial with complication
hepatitis reactive. Tx. ceftriaxone
• Day 3 of fever : malaria smear positive P. falciparum
• Tx. Artesunate iv.. Patient recovery
 Malaria & Diabetes
• Type 2- Diabetes mellitus ( T2-DM ) patients have
higher risk of malaria
• A study in Ghana reveal higher malaria cases in DM
patients group
• Every mg/dl increase of blood sugar will increase risk
of P. falciparum by 5 %
• Blood sugar 155 mg/dl is threashold increased risk of
malaria ( OR 1,63 )
• Complications : Diabetic ketoacidosis
lower risk of hypoglycemia
• Higher mortality rate
 Malaria & Diabetes

• A study by Pravat K, Thotdi SR et al. :

– 200 severe malaria patients in India
– 54 patients have DM
– More mixed P. falsiparum & P. vivax
– Earlyer onset and longer duration of coma
– More malaria with complications
– Mortality : Diabetes : non-DM = 35,5 % : 13,69 %
– DM pts have higher mortality and severe malaria
compared to non-DM

Pravat K, Thotdi SR. Diabetes 2018 ; 67 ( Suppl 1 )

 Malaria & Diabetes

• Pathomechanisms :
– Altered immune response to parasites liver stage
and blood stage in DM patients
– Decreased T cell mediated – immunity in DM
patient
– Higher glucose utility as nutrient by plasmodium
– DM patient with high glucose are more attractive
to mosquitoes due to olfactory odors
 Malaria & Diabetes

• Possibly malaria during pregnancy may increase the

children,s risk of DM in later life
• Clinical manifestation of malaria in DM :
– Sometimes have atypical clinical manifestation
such as abscence of fever, vomiting as chief
complaint
– Multiple organ involvement
– Shorter onset but Longer duration of coma
– Relative bradycardia
– Higher risk of AKI and jaundice
– Lower parasites count
 Malaria & Diabetes

• Management of Malaria in DM patients

– Principally no difference in the treatment of both
malaria and DM
– Metformin is protective against malaria
– Modification of antidiabetic drugs dependt on the
ability of patient to take a meal
– Monitoring blood glucose more often
– Monitoring organ dysfunction strictly
 Malaria & Diabetes

Adjusment of antidiabetes drugs base on oral intake

status
 Malaria & Obesity

• There are conflicting data of relationship between

malaria and obesity
• A Swiss study : obesity have higher risk for severe P.
falsiparum malaria
• A Brazil study : obesity have lower risk for P. vivax
• A obese mice study : protective to cerebral
complication of P. berghei ANKA
• Further studies are needed to revealed the
relationship between malaria and obesity
Malaria & Obesity
Malaria & obesity
Thank You