Tropical ID (Update)

Dr P Senthur Nambi
Consultant – Infectious Diseases
Apollo Hospitals, Chennai Region
 Tropical Infections
Common & often considered
Eg: Typhoid, Malaria, Dengue, Lepto

Common but considered less often

Eg: Scrub typhus

Not so common but not to be ignored

Eg: Meliodosis

Uncommon but not to forget

Eg: JE, Rabies, Anthrax

Newer ones
Eg: WNV, CCHF, Zika
 Approach to fever

Differentiated fever Undifferentiated fever

• Pneumonia • Enteric fever

• Meningoencephalitis • Leptospirosis
• UTI • Malaria
• Intraabdominal • Dengue
infections • Scrub typhus
What’s the prevalence of malaria in Tamil
Nadu?

• High

• Low

• Very high

• Not so high
How would you diagnose malaria?

1. Clinically

2. Rapid diagnostic test (Card test)

3. Peripheral smear

4. QBC
 Blood film examination

• Thick film – 15 times • Thin film – provides

more sensitive than thin specificity by confirming
film the plasmodium species

• Detect parasitemia at a • Monitoring of

level as low as 50 treatment
parasites/microlitre
• Two or three negative
smears r/o malaria
 Detection of malarial antigen(RDT)
HRP-2 detection (molecule present throughout the
erythrocytic cycle)
• First rapid malaria detection test to be developed
• sensitivity – 96%, specificity - >95%

pLDH detection
• Not species specific
• Can detect parasitaemia as low as 0.1% (100 parasites
per microlitre)
• sensitivity – 94%, specificity – 99%
Minimal risk
of resistance
National Guidelines on Malaria
Artesunate vs Quinine – SEAQUAMAT study

SEAQUAMAT group. Lancet 2005;366:717-725.

WHO guidelines for severe falciparum malaria

• Artesunate 2.4 mg/kg IV or IM given on

admission (time = 0), then at 12 h and 24 h, then
once a day for total 7 days

• Add doxycycline or clindamycin

• Avoid mefloquine if altered sensorium

 Severe falciparum malaria

• Parenteral for atleast 24h

• Complete with either

artemether + lumefantrine
artesunate + SP
artesunate + clinda / doxy
 Vivax malaria
• Chloroquine 25mg/kg over 3 days

• + Primaquine 0.25mg/kg od x 14d

• ACT with primaquine for chloroquine resistance

• Avoid ACT with SP

 P. knowlesi – the fifth malaria species

• Macaques natural host for P.

knowlesi, lives in forest areas in South
East Asia

• In a study from Malaysia 28% (n=960)

malaria patients were confirmed by
PCR to be P. knowlesi, mainly
misdiagnosed as P. malaria*

• Potentially severe malaria like P.

falciparum

• Malaria diagnosed as P. malariae

from Asia should be suspected to be
P. knowlesi and managed as severe
malaria

Thin blood slide from one of four patients who

died with the diagnosis ”P. malariae” in Sarawak *Cox-Singh J et. al. Plasmodium knowlesi Malaria in Humans is Widely
in Malaysia; later confirmed by PCR to be P. knowlesi. Distributed and Potentially Life Threatening.CID2008:46
Artesunate resistance
Poor-quality antimalarial drugs in Southeast Asia and
sub-Saharan Africa
Lancet Infect Dis 2012,12: 488–96

1437 samples, five classes tested

7 countries in southeast Asia

➢ 497 (35%) failed chemical analysis

➢ 423 (46%) of 919 failed packaging analysis
➢ 450 (36%) of 1260 were falsified
Typhoid worldwide
Widal & Enteric fever
Source: WHO Guidelines on typhoid - 2003

• Endemic area (?Cut-off)

• Negative in up to 30% of culture-proven cases

• False Positive – Previous inf, anamnestic, auto-immune

diseases, malaria, typhus, bacteremia, cirrhosis, vaccination

• False Negative – Too early, antibiotic use, kit used

• The Widal test can be dangerously misleading and should

no longer be used in clinical practice (WHO – Good Clinical
Diagnostic Practice Guidelines)
 When to suspect enteric fever?
• Fever > 72 hrs

• Normal WBC, Eosinopenia

• Normal ESR

• Young individuals, outside food intake

S.Typhi senstivities
Time to defervescence with ceftriaxone+azithromycin
3.2 days vs 6.6 days for ceftriaxone
Dengue Incidence

Nature 2013 Apr 25; 496(7446): 504–507507.

Dengue serology
Antigen (NS-1) detection test :

• Glycoprotein produced by all • IgM circulates for up to

flaviviruses three months or longer, its
presence might not be
diagnostic of a current
• Appears as early as Day 1 after illness
the onset of the fever and
declines to undetectable levels
by 5–6 days
• To diagnose a current
• Can be detected in both dengue infection, the
patients with primary and demonstration of a
secondary dengue infections seroconversion (four fold
or greater changes in
antibody titres) in paired
• Good sensitivity and specificity, sera is required
but not yet approved by WHO
 DF: Clinical Characteristics

• Fever
• Headache
• Muscle and joint pain
• Nausea/vomiting
• Rash
• Hemorrhagic
manifestations

NEJM 2005;353:924-932
 Treatment
• No specific antiviral drug available

• Avoid aspirin, NSAID

• Prompt fluid replacement

– 0.9% NS as effective as colloids for initial resuscitation

• Blood transfusion only with overt bleeding

• Avoid IM injections

NEJM 2005;353:877-889
• Dengue - Who needs admission ?

- Presence of Shock
- Dangerously low platelets
- Progressive disease & warning signs
- High risk patients esp children and comorbidities

- Indication of platelets transfusion ?

- if < 10,000
- if any overt bleeding
 Are prophylactic platelet transfusions
necessary?
• Doesnt shorten period of
thrombocytopenia What is an effective way to
prevent bleeding?
• Bleeding risk not correlated
with platelet count • Prevent prolonged shock
– recognize and treat it
• Limited data on EARLY
effectiveness of platelet
transfusions to prevent
bleeding complications • Avoid trauma (provokes
bleeding) – CVP insertion
• May lead to fluid overload by experienced persons
& prolonged hospitalization
Chuansumrit et al. Transfusion requirements in patients with DHF. SE
Asian J Trop Med Public Health, 2000, 3:10-14.
Lye et al. Lack of efficacy of prophylactic platelets for severe
thrombocytopenia in adult with dengue. CID, 2009, 48:1262-1265.
Chairulfatah et al. Thrombocytopenia and platelet transfusions in DHF and
DSS. Dengue Bulletin, 2003, 27:138-143.
• Insufficient evidence to
use corticosteroids

• Corticosteroids can
potentially do harm

• Clinicians should not

use them
 Discharge criteria - Dengue
• Absence of fever for at least 24 hours without the use of anti-fever
therapy

• Return of appetite

• Visible clinical improvement

• Good urine output

• Minimum of 2/3 days after recovery from shock

• No respiratory distress from pleural effusion or ascites

• Platelet count > 50,000/ cumm

 Dengue vaccine!
• CYD-TDV (Dengvaxia®) registered in several countries
for use in people 9-45 years of age

• Live attenuated (recombinant) tetravalent vaccine

• Other 2 most advanced candidates are also tetravalent

live attenuated (recombinant) vaccines & are currently
under evaluation in Phase 3 trials

Lancet 2014, NEJM 2014

 Leptospira under the Microscope

Dark Field Microscopy FL

Long, Thin, Highly Coiled

 Clinical Illnesses
Types Anicteric (common 95% recover)
Icteric ( Weil’s Syndrome) (rare, fatal)
Hepato-renal syndrome
Hemorrhagic syndrome with ARF
Atypical pneumonia syndrome
Aseptic meningo-encephalitis
Myocarditis, Chronic uveitis
Diagnosis

✓ Dark field microscopy

sensitivity 40 %, specificity 60%

✓ Culture
EMJH medium
Availability?
✓ MAT

✓ IgM antibodies
✓ ELISA
✓ Detectable after 5th day
 Microscopic agglutination test (MAT) - Lepto

• Sensitivity within the first 15 days only 17%

• Persists longer (5 to 10 yrs)

• Technically challenging

• Requires demonstration of seroconversion or a ≥4-fold MAT

titer increase between paired acute & convalescent phase
specimens

• WHO recently defined MAT titer of ≥1:400 in a single serum

specimen as significant
 Interpretation of Tests
IgM ELISA MAT Interpretation

Positive Positive Current Infection

Positive Negative Current Infection

Negative Positive Past Infection

Negative Negative R/o Leptospirosis

Not available Rising titers Current Infection

Panaput T, et al. CID 2003;36:1507-13.
 Leptospirosis – Treatment
Mild
✓ Doxy 100mg BD
✓ Ampicillin 500-750 mg q6h; Amox 500 mg q 6h
✓ Azithromycin 500mg OD

Moderate to severe
✓ Penicillin G 1.5 million units IV q6h
✓ Ceftriaxone 1 gm IV q 24h (as good as CP)
✓ Ampicillin 0.5-1gm IV q 6h

Watt G et al. Lancet 1988; 1(8583):433–5; ; Supputamongkol Y et al. Clin Infect Dis.
2004;39:1417–1424; Panaphut T et al. Clin Infect Dis 2003; 36:1507–13
 Scrub typhus
✓ Causative agent – O. tsutsugamushi
✓ Transmitted by larval mites
Scrub typhus endemic areas
Diagnosis
➢ IgM ELISA
✓ IFA, Immunoperoxidase test
✓ PCR
✓ Weil-Felix

Treatment
➢doxycycline
✓azithromycin, chloramphenicol, rifampicin
 Typhus - pointers
• Scrub typhus is a re emerging infection
• Look carefully for an eschar

• Typical clinical situations:

– Leukocytosis with thrombocytopenia
– Cholestatic hepatitis with fever
– Acute or subacute meningitis
– Atypical pneumonia
– Sepsis syndrome with multi-organ involvement

• Specific serology available

• Start doxycycline as soon as diagnosis considered
Spotted fevers – Tick borne (Ixodid and others)
50 yrs male from Chennai, poorly controlled
DM, consumes alcohol daily

• Has received
ceftriaxone,
azithromycin,
piperacillin
tazobactam

• Continues to have
fever
 Blood cultures (2 sets) grew
Non fermenting gram negative bacilli

Sensitive Resistant
Cotrimoxazole Cefuroxime
Cefotaxime Gentamycin
Cef-sulbactam Cipro
Ceftazidime Amikacin
Imipenem
Meropenem
Distribution of Melioidosis
 Melioidosis
• Spread by inhalation, • Acute (88%) & chronic
percutaneous presentation (12%)
inoculation
• Septicemic/localized
• Risk factors:
➢ Diabetes • Pneumonia, skin
➢ Alcohol consumption abscesses,
➢ Chronic renal failure genitourinary, arthritis
➢ Chronic lung disease or osteomyelitis
 Melioidosis - Treatment
Intensive therapy (2 weeks)
✓ Ceftazidime
✓ Meropenem
✓ Imipenem
With or without cotrimoxazole

Eradication therapy (3-6 months)

✓ Cotrimoxazole plus
✓ Doxy
Zika..
Zika & India
 Zika - Symptoms
▪ Flavivirus; Vector – Aedes; Incubation period: 2 -12
days
▪ Symptomatic in 20 – 25%

▪ Low-grade fever (37.8 to 38.5°C)

▪ Maculopapular rash
▪ Arthralgia (notably the small joints of hands and feet)
▪ Conjunctivitis (nonpurulent)

▪ Other clinical manifestations include myalgia,

headache, retro orbital pain & asthenia
 Zika & Pregnancy
• No evidence to suggest that pregnant women are more
susceptible or experience more severe disease

• Greatest risk of microcephaly & malformations appears to

be associated during the first trimester

• Rate of vertical transmission & the rate with which infected

fetuses manifest complications are unknown

• No developmental complications have been observed in

otherwise healthy infants with postnatal Zika virus infection
 Diagnosis
• Reverse-transcription polymerase chain reaction
(RT-PCR) – In the first 7 days of the illness

• Zika virus IgM and neutralizing antibody titers that

are ≥4-fold higher than dengue virus neutralizing
antibody titers in serum

• Testing is considered inconclusive if Zika virus

neutralizing antibody titers are <4-fold higher
than dengue virus neutralizing antibody titers
Global air travel map