dacremont2_oct202011

Management of malaria

and non-malaria febrile illnesses

Valérie D'Acremont

Swiss Tropical & Public Health Institute

Global Malaria Programme, WHO

Seattle, 20 Oct 2011

2

Background

Prescription of antimicrobials for children underfive

in Dar es Salaam, Tanzania

Antimalarials AntibioticsAND

Routine microscopy

(or no malaria tests)

Rapid Diagnostic Tests

75%

15%

57%79%

3

Dar Es Salam

3 mio d’habitants

Ifakara, 50.000 hab.

To determine the etiology of fever episodes

in children living in urban and rural Tanzania

Objective

4

Methodology

• Prospective study including children

attending two outpatient clinics

(one urban and one rural) in Tanzania

• Inclusion criteria:

- aged 2 months - 10 yrs

- temperature > 38°C

- no antimicrobials for > 1week

• Full clinical assessment

• Investigations based on pre-defined algorithms:

FBC; ALT; creat.; RDT for malaria, typhoid, strepto A,

adeno/rotavirus; BS malaria and borrelia; urine dipstick;

amoeba in stool; blood/urine/stool cultures; chest X-ray

5

Diarrhea (>3 stools/day):

POS

NEGRapid test

Rota/adeno

Amoebic

GASTRO-ENTERITIS

Viral

GASTRO-ENTERITIS

Possible bacterial

GASTRO-ENTERITIS

Metronidazole

POS

NEGCiprofloxacine

Follow-up

Day 7

Blood

culture

Investigation

for diarrhea

Stool

examination

for amoeba

TYPHOIDPOS

NEGFollow-up

Day 7

Ciprofloxacine

Rapid Test

for Typhoid

2)

1)

3)

No antibiotic

STOP

STOP

STOP

Methodology

Example of a pre-defined algorithm:

6

Methodology

• Real-time (RT-)PCR of naso-pharyngeal swabs for 15 virus:

FLUAV, FLUBV, RSV, HMPV, HPIV 1/3,

PIC (rhino, entero, coxsackie), HBoV,

HCoV OC43 229E NL63 HKU1, HAdV

• Real-time PCR on blood:

Dengue, Chikungunya, West Nile, Rift Valley

HHV6, parvovirus B19

• Serologies on blood :

EBV, CMV, Toxoplasma, Rickettsia, Coxiella, Leptospira

Computer-based diagnosis with levels of probability

7

Baseline characteristics

From April to December 2008:

• 1005 children were included (informed consent, 2 refusals)

507 in Dar es Salaam and 498 in Ifakara

• median age was 18 months

• 49% were females

• 78 (8%) children were admitted in the ward

• 133 (13%) had WHO criteria for severe disease (4 deaths)

8

Skin infection

TyphoidMalaria

Fever?

Systemic infections

Gastroenteritis

Acute

respiratory

infectionUrinary tract infection

50%

13%

8%

5%

1%

11%

0.2%3%

9%Meningitis

Etiologies of fever in 1005 Tanzanian children

1212 diagnoses

9

Overlap of diseases

ARI52.8%

Clinical pneumonia*

14.6%

0.2%

4%

3.6

%

Gastro-

enteritis5.9%

Malaria6.7%

19.6% had 2 or more diagnoses of high probability

*Pneumonia as defined by WHO

(documented or not by chest X-ray)

10

Skin infection

TyphoidMalaria

Fever?

Systemic infections

Gastroenteritis

ARI

Urinary tract infection

50%

13%

8%

5%

1%

11%

0.2%3%

9%Meningitis

Etiologies of Acute Respiratory Infections (ARI)

11

ARI

50%

URTI

Clinical

pneumonia

Bronchiolitis

Radiological pneumonia

Viruses

5%

22%

7% 65%


81%

12

ARI

50%

URTI

Clinical

pneumonia

Bronchiolitis

Radiological pneumonia

5%

22%

7% 65%

Influenza

RSV

Metapneumovirus

Parainfluenza 1/3

RhinovirusEnterovirus

Coronavirus

Bocavirus

Adenovirus


81%

13

Seasonality of influenza

0%

10%

20%

30%

40%

50%

Apr May Jun Jul Aug

Influenza A

Influenza B

0%

10%

20%

30%

40%

50%

Jul Aug Sep Oct Nov

Dar es Salaam

Ifakara

14

Skin infection

TyphoidMalaria

Fever?

Systemic infections

ARI


50%

13%

5%

1%

11%

0.2%3%

9%Meningitis

Etiologies of gastroenteritis

Gastroenteritis

8%

15

Amoeba

Rotavirus

Adenovirus

Salmonella

Shigella

Unknown

pathogen

8%

Gastroenteritis

51%

4%

28%

18%

Etiologies of gastroenteritis

16

Skin infection

TyphoidMalaria

Fever?

Gastroenteritis

ARI


50%

13%

8%

5%

0.2%3%

9%Meningitis

Etiologies of systemic infections

Systemic infections

11%

17

8%

11%

Systemic infections

Viruses

75%


18

8%

11%

Systemic infections

Viruses

HHV6

CMV

EBV

Parvovirus B19

VZVMumps

Common

bacteremia

Rickettsia

Leptospira

Coxiella

Toxoplasma

75%

No Dengue, No Chikungunya, No West Nile, No Rift Valley


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Summary of findings

• In Tanzanian children, half of fevers are due to acute respiratory

infections (ARI)

• A quarter of ARI were due to influenza

• 81% of the children were infected with one or more viruses

• Malaria (9%), urinary tract infection (5%) and typhoid (3%) were

much less prevalent than clinicians think

• In children: cosmopolitan >>> tropical vector-borne pathogens

• Children rarely had more than one significant diseases at a time

• 47% of severe patients were not admitted to the ward

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Guidelines: IMCI and iCCM

NO

Blood in stool

Malaria Dysentery

ACT

Fever

<7 days Cough

Pneumonia

Diarrhea

Cold

Fast breathing

‘Watery’ diarrhea

Amoxicillin

Antimalarials and antibioticsYES

NO

No drug Ciprofloxacin ORS+

Zinc

Ear pain

Amoxicillin

YES NO YES NO

REFER

Acute otitis

media

Danger signs

Malaria test

No drug

POS NEG

Salbutamol

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The way forward

• In our study, only 27% had a disease that needs antibiotics

• If we had applied the IMCI algorithm to these children, 25% would

have received antibiotics, BUT:

Our study IMCI13%12%15%

22

ALMANACH

How can we improve the IMCI clinical algorithm with available tools?

1) including the clinical predictors found in the fever study

2) adding diagnostic tests to RDT for malaria :

- RDT for influenza or RSV (cough) ?

- chest Xray (clinical pneumonia) ?

- urine dipstick (children <2 years) ?

- RDT for typhoid (children >2 years) ?

The way forward in diagnostics

Our study 17%18%9%

23

We need a rapid and portable test that detects

(malaria and) ONLY patients in need for antibiotics:

BUT who are they?

� All patients who have no respiratory virus?

� All patients who have a ‘respiratory bacteria’?

� All patients who have a bacteria in blood (including typhoid)?

NO, so what?

Biomarkers of severity…

… with a clever combination of the above.

The ‘fever stick’

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Implications for treatment of febrile illnesses

Based on what we are presently able to diagnose:

(excluding severe and immunosuppressed children)

• Amoxicillin for clinical pneumonia and acute otitis media

• Oseltamivir for influenza (children <2 years, chronic condition)

• Inhaled salbutamol + spacer for wheezing

• ORS + Zinc for diarrhea

• Ciprofloxacin for UTI, bloody diarrhea (and typhoid)

• Cloxacillin for significant skin infection

• Tetracyclin eye ointment + vitamine A for measles

64%18%

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DSM City Medical Office of Health, Tanzania

Judith Kahama (co-researcher)

Ndeniria Swai (research assistant)

Gerumana Mpawa (logistics and data entry)

Ministry of health and Welfare, Tanzania

Deo Mtasiwa (Chief Medical Officer)

Ifakara Health Institute, Tanzania

Hassan Mshinda (ex-director)

Amana and St Francis hospital, Tanzania

Willy Sangu and P. Kibatala (directors)

Swiss Tropical and Public Health Institute

Blaise Genton and Christian Lengeler

Hôpitaux Universitaires de Genève

Laurent Kaiser, Pascal Cherpillod, Yves Thomas, C. Tapparel

Financial support from the Swiss National Science Foundation

Acknowledgements

Special thanks to lab

technicians who

performed 28’352

microbiological tests

…

dacremont2_oct202011

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