Moving forward in the diagnosis of infectious diseases in developing countries: a focus on malaria Forum organized by Fondation Mérieux & the Roll Back.

Moving forward in the diagnosis of infectious diseases in developing countries: a focus on malaria

Forum organized by Fondation Mérieux & the Roll Back Malaria Partnership22 June 2009

Dr Sergio SpinaciGlobal Malaria Programme

2 |GLOBAL

MALARIA PROGRAMME

Estimated number of cases and deathsEstimated number of cases and deaths

Approximately 250 million cases per year: 85% in Africa, 9% in South-East Asia

Approximately 900 000 deaths: 91% in Africa, 85% in children under 5 years of ageSource: World Malaria Report, 2008

Africa 212 801 88%Americas 3 3 29%Eastern Mediterranean 8 38 76%Europe 0 0 0%South-East Asia 21 36 35%Western Pacific 2 4 40%

World 247 881 85%

Cases (millions)

Deaths (thousands)

% deaths under 5

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MALARIA PROGRAMME

Laboratory-confirmed diagnosis of malaria Laboratory-confirmed diagnosis of malaria

Africa Western Pacific

Eastern Mediterranean

South-East Asia

Americas Europe

0

20

40

60

80

100 Malaria patients with confirmed diagnosis (%)

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MALARIA PROGRAMME

Health centres in sub-district

District health system in GhanaDistrict health system in Ghana

...

...

District level

Sub-district level

Community level

District health management teams (DHMT)

Sub-district health management teams (SDHMT)

Community health committees

District hospital

supervision

Health centres in sub-district

CHPS zoneswith communitysupport systems

CHPS zoneswith communitysupport systems

CHPS zoneswith communitysupport systems

CHPS zoneswith communitysupport systems

...

...

supervision

patient referral

supervision

patient referral

supervision

patient referral

patient referral patient referral

5 |GLOBAL

MALARIA PROGRAMME

Trend of malaria cases compared to total OPDin Sene District, 2005–2008

Trend of malaria cases compared to total OPDin Sene District, 2005–2008

Malaria cases

Total OPD cases

Number of malaria cases

0

20 000

40 000

60 000

2005 2006 2007 2008

6 |GLOBAL

MALARIA PROGRAMME

Trend of laboratory-confirmed malaria cases in the Sene District, 2005–2008

Trend of laboratory-confirmed malaria cases in the Sene District, 2005–2008

1484

5463

4183

0

1000

2000

3000

4000

5000

6000

2005 2006 2007 2008

Number of laboratory-confirmed malaria cases

7 |GLOBAL

MALARIA PROGRAMME

Reduction in prescription of antimalarials after RDT implementation

Reduction in prescription of antimalarials after RDT implementation

A mean of 6-fold decrease in ALu consumption was observed (range: 2–26) in intervention facilities and 1.7-fold decrease in control health facilities

Proportion of patients tested negative who were still prescribed antimalarials decreased from 67% to 7%

Fever patients tested for malaria increased from 73% to 90%

8 |GLOBAL

MALARIA PROGRAMME

Mean test positivity rates in intervention and control health facilities

Mean test positivity rates in intervention and control health facilities

Routine microscopy: 41% in hospitals; 49% in health centres; 65% in dispensaries (range: 13–90%)

Routine RDTs: 7% in hospitals; 10% in health centres; 9% in dispensaries (range: 6–12%)

2006 2007 2008

Malaria test positivity rate before and after RDT implementation

9 |GLOBAL

MALARIA PROGRAMME

New development in 2007–2009New development in 2007–2009

Malaria decrease due to effective control

Systematic review: 24 studies conducted between 1989 and 2005

in 15 different African countriesincluding 15 331 patients

Proportion of malaria among fevers highly variable: 2% to 81% Median parasite rate = 26%

Median PfPR 1985-19992-10 = 37%Median PfPR 2000-20072-10 = 17%

D'Acrémont et. al. (2009). PLoS Med, 6 (1): e252

10 |GLOBAL

MALARIA PROGRAMME

New development in 2007–2009New development in 2007–2009

Evidence of benefits of health outcomes

1887 patients studied in Zanzibar in non randommized four-centre clinical trial with weekly cross-over validation comparing RDT-aided malaria diagnosis with symptom-based clinical diagnosis (CD)

RDT was associated with lower prescription rates of antimalarial treatment than CD alone, 361/1005 (36%) compared with 752/882 (85%).

Prescriptions of antibiotics were higher after RDT than CD alone, i.e., 372/1005 (37%) and 235/882 (27%); re-attendance due to perceived unsuccessful clinical cure was lower after RDT 25/1005 (2.5%), than CD alone 43/882 (4.9%). Total average cost per patient was similar: US$ 2.47 and 2.37 after RDT and CD alone, respectively

Msellem et. al. (2009). PLoS Med, 6 (4): e1000070

11 |GLOBAL

MALARIA PROGRAMME

Debate on abandoning presumptive antimalarial treatment for febrile African children

Debate on abandoning presumptive antimalarial treatment for febrile African children

Time to move to laboratory confirmed diagnosis

Proportion of fevers due to malaria has become significantly lower

We now have reliable RDTs (comparable to expert microscopy)

Risk of false negative test is smaller than risk of patient dying due to another severe disease because of the focus on malaria

Against rapid abandoning of presumptive treatment

Health systems and health workers not ready for this change

– Prescription of antimalarial to negative – Problematic drug supply system– No resources for treating other causes

of non-malaria fevers

Pre-requirements – More data on local epidemiology– Improved implementation in > 5 years – Evidence of safety of new policy

D'Acrémont V et. al. (2009). PLoS Med, 6 (1): e252 English M et. al. (2009). PLoS Med, 6 (1): e1000015

12 |GLOBAL

MALARIA PROGRAMME

New diagnostics at different levels of the health system

New diagnostics at different levels of the health system

Referencelabs

Regionallabs

Districtlevel

Sub-districtlevel

Recombinantpanel

TBMalariaHAT

Infant HIV DxMalariaHATTB

Communitylevel

TBMalariaHAT

LAMP Malaria

RDT lottesting

RTD lottesting

MalariaImprovedRDTs

LAMPiLED

PCWs

Specimenbank

Drug resistance

surveillance

FIND: Foundation for innovative new diagnostics

13 |GLOBAL

MALARIA PROGRAMME

ConclusionsConclusions

The quality of routine microscopy was as poor in hospitals and health centres as in dispensaries

Routine RDT implementation minimized over-diagnosis and significantly reduced ALu consumption

Without appropriate diagnosis the true burden of disease cannot be estimated

Well-trained clinicians with adequate supportive supervision comply with RDT results and improve on practice

RDTs should be used as first-line diagnostic tool for malaria in all settings and all health facility levels, including hospitals where the potential for saving lives is the greatest