Editorial

Would rational use of antibiotics be compromised in the era

of test-based management of malaria?
Frank Baiden
1
, Jayne Webster
2
, Seth Owusu-Agyei
1,2
and Daniel Chandramohan
2
1 Kintampo Health Research Center, Kintampo, BAR, Ghana
2 London School of Hygiene and Tropical Medicine, London, UK
keywords malaria, therapy, presumptive diagnosis, rational use, antimalarials, Africa, WHO guidelines
WHOs revised malaria treatment guidelines (WHO 2010)
recommend parasitological conrmation by microscopy or
by rapid diagnostic test (RDT) in all patients including
children suspected of malaria before starting treatment.
Presumptive treatment of fever in children <5 years of age
with antimalarial drugs, unless an alternative cause for the
fever is diagnosed, was for many years recommended in
malaria-endemic countries of sub-Saharan Africa. This
approach to diagnosis of febrile illness in children, incor-
porated within the Integrated Management of Childhood
Illness (IMCI), is part of the reason why nearly 80% of all
malaria cases reported are unconrmed (WHO 2009).
Endorsement of the presumptive approach to diagnosis
contributed to an overemphasis on malaria and the under-
diagnosis of non-malaria fevers, leading to wastage of
antimalarial drugs, with possible adverse medical and
economic consequences (Amexo et al. 2004). The new
WHO guidelines, if adhered to by health workers, would
address this problem. However, this strategy could accen-
tuate the challenge of how to appropriately manage the
conrmed non-malaria febrile illnesses.
A declining trend in malaria transmission has been
observed in many countries particularly in east and
southern Africa. Areas previously known to be high
transmission malaria settings are now recording malaria
slide positivity rates of 511% in febrile children (Ceesay
et al. 2008; OMeara et al. 2008). Adherence to the new
WHO guidelines would lead to a large number of febrile
illnesses to be conrmed as non-malaria cases. In health
systems that have for many years focused attention heavily
on malaria, the capacity to appropriately manage non-
malaria cases cannot be assumed. A shift in the mix of
diagnosis will pose a challenge to the abilities of clinicians
in peripheral health facilities who will continue to rely on
little or no resources to distinguish between the causes of
non-malaria fevers.
The many years of over-emphasis on malaria have been
at the expense of attention to other causes of acute
childhood febrile illnesses in malaria-endemic countries.
This is evident in both research and national disease
control programmes. Very little is known about the causes
of non-malarial fevers in most malaria-endemic countries
(Perkins & Bell 2008). Although viral and bacterial
aetiologies are commonly implicated, empirical data on the
distribution of non-malarial causes of fever in children are
scarce. While there is substantial evidence of the over-
diagnosis of malaria, very little is reported on the alterna-
tive diagnoses. Unless targeted interventions to manage
non-malaria febrile illness are instituted, the coming era of
test-based management of malaria would increase the
inappropriate treatment of febrile children.
Of particular concern is the extent to which antibiotics
will be used appropriately. Given that skilled human
resources are scarce while being faced with increasing
demand for health care and a continued lack of point-of-
care laboratory support, the effortless approach of simply
substituting the presumptive use of antimalarials with the
presumptive use of antibiotics whenever a rapid test for
malaria returns a negative result is likely to emerge. A
dogma that would translate as antimalarial for RDT
positive, antibiotic for RDT negative is in the ofng. This
is likely to be applied with little or no attempt at
establishing the aetiology of the non-malaria fevers.
A few non-malaria infections such as diarrhoea and skin
infections are relatively easy to differentiate but many
other infections such as pneumonia, typhoid, hepatitis and
viral infections are not easily distinguished solely on the
basis of clinical judgment. In the absence of point-of-care
diagnostics, these infections are likely to be classied
within the large group of non-malarial acute undifferenti-
ated fever (NMAUF) (Joshi et al. 2008). Presently, an
accurate estimate of the burden of NMAUF for developing
countries and Africa in particular is difcult to ascertain
because of inadequate diagnostic aides, poor disease
surveillance systems and widespread presumptive man-
agement of malaria. Without the capacity to differentiate
Tropical Medicine and International Health doi:10.1111/j.1365-3156.2010.02692.x
volume 16 no 2 pp 142144 february 2011
142 2010 Blackwell Publishing Ltd
the causes of non-malarial febrile illnesses, the tendency
would be to use broad-spectrum antibiotics in all
RDT-negative cases. This has been shown in recent studies
in Tanzania and Zanzibar where RDT was used along-
side routine case management (Msellem et al. 2009;
Mosha et al. 2010).
A signicant increase in the indiscriminate use of
antibiotics in sub-Saharan Africa is likely to add to the
global problem of antibiotic resistance. Methicillin-resis-
tant Staphylococcus aureus alone infects more than 94 000
people and kills nearly 19 000 in the United States every
year. In the European Union, about 25 000 patients die
every year from infection with multidrug-resistant bacteria
(Anonymous 2009). Although empirical data on the impact
of antibiotic resistance on mortality in sub-Saharan Africa
are not available, there is clear evidence of the problem in
many parts of the region. In a study in Tanzania, only 47%
of the isolated organisms in children with invasive bacterial
disease were susceptible to the rst recommended antimi-
crobial agent (Nadjm et al. 2010). About 20% prevalence
of methicillin-resistant S. aureus (MRSA) has been detected
in Southwest Nigeria, with 48% of isolates fullling the
denition of community-acquired MRSA. Eighty-eight per
cent of MRSA isolates collected from Dakar and ve other
African cities belonged to the three major clones with
potential for pandemic spread (Breurec et al. 2010). While
the development of resistance to the artemisinins would
pose a signicant threat to global health, widespread
resistance to antibiotics in resource-poor settings would
have more devastating consequences. The development of
multidrug-resistant bacterial strains crosses geographic and
racial borders (Obaro 2000).
There is a critical need to improve the capacity in
primary care facilities to appropriately use antibiotics in
the management of non-malaria fevers. For health systems
that have for many years practiced a policy of equating
fever with malaria, the transition to test-based malaria
treatment management would require re-orientation. The
ideal would be a point of care test that distinguishes
malaria, bacterial and viral illnesses. While awaiting the
development of such a technology, clinical care in periph-
eral health facilities needs to be improved through (i)
revising the IMCI guidelines to incorporate malaria RDT,
(ii) refresher training and supportive supervision to
strengthen adherence to the revised IMCI guidelines, (iii)
encouraging clinicians to avoid merely diagnosing NMAUF
by documenting comprehensive history and systematic
physical examination, (iv) enforcing the use of antibiotics
only when absolutely indicated for the appropriate length
of time at the optimum dose (Vento & Cainelli 2010),
(v) establishing disease surveillance systems to determine
the aetiology of NMAUF in children and antibiotic
sensitivity patterns and (vi) effective dissemination of the
information on aetiology of NMAUF and antibiotic
sensitivity patterns to all clinicians, particularly to those
working in peripheral health facilities.
Revision to current IMCI case management guidelines
should take into account evidence on updated antibiotic
susceptibility patterns, including the impact of conjugate
pneumococcal vaccines on the carriage of pneumococcal
serotypes in sub-Saharan Africa. An IMCI quality
management system that makes it possible to track and
audit the ndings of clinical examination relative to the
management approach needs to be instituted.
The majority of primary care facilities in sub-Saharan
Africa are manned by cadres other than doctors who are
taught to manage childhood fevers using simple
algorithms. As part of re-orienting these personnel to meet
the demand of appropriate management of non-malaria
cases, there is the need to ensure the availability and skilled
use of simple, yet important clinical diagnostic aides such
as child stethoscopes, tongue depressors, otoscopes and
oroscopes.
This is the time to focus attention on how to appropri-
ately manage non-malaria fevers in Sub-Saharan Africa. To
this end, it is imperative for studies designed to make the
case for the deployment of rapid tests for malaria to
simultaneously address the question, if it is not malaria,
then what is it? Improving the management of febrile
illness in children requires effort and resources beyond the
availability of rapid tests for malaria.
References
Amexo M, Tolhurst R, Barnish G & Bates I (2004) Malaria mis-
diagnosis: effects on the poor and vulnerable. Lancet 364, 1896
1898.
Anonymous (2009) Urgently needed: new antibiotics (Editorial).
Lancet 374, 1868.
Breurec S, Zriouil SB, Fall C et al. (2010) Epidemiology of meth-
icillin-resistant Staphylococcus aureus lineages in ve major
African towns: emergence and spread of atypical clones. Clinical
Microbiology and Infection DOI:10.1111/j.1469-0691.2010.
03219.x.
Ceesay SJ, Casals-Pascual C, Erskine J et al. (2008) Changes in
malaria indices between 1999 and 2007 in The Gambia: a
retrospective analysis. Lancet 372, 15451554.
Joshi R, Colford JM Jr, Reingold AL & Kalantri S (2008) Non-
malarial acute undifferentiated fever in a rural hospital in
central India: diagnostic uncertainty and overtreatment with
antimalarial agents. American Journal of Tropical Medicine 78,
393399.
Mosha JF, Conteh L, Tediosi F et al. (2010) Cost implications of
improving malaria diagnosis: ndings from north-eastern
Tanzania. PLoS ONE 5, e8707.
Tropical Medicine and International Health volume 16 no 2 pp 142144 february 2011
F. Baiden et al. Editorial
2010 Blackwell Publishing Ltd 143
Msellem MI, Ma rtensson A, Rotllant G et al. (2009) Inuence of
rapid malaria diagnostic tests on treatment and health outcome
in fever patients, Zanzibar: a crossover validation study. PLoS
Med 6, e1000070.
Nadjm B, Amos B, Mtove G et al. (2010) WHO guidelines for
antimicrobial treatment in children admitted to hospital in
an area of intense Plasmodium falciparum transmission:
prospective study. British Medical Journal 340, c1350. Doi:
10.1136/bmj.c1350.
Obaro SK (2000) Prospects for pneumococcal vaccination in
African children. Acta Tropica 75, 141153.
OMeara WP, Bejon P, Mwangi TW et al. (2008) Effect of a fall
in malaria transmission on morbidity and mortality in Kili,
Kenya. Lancet 372, 15551562.
Perkins M & Bell D (2008) Working without a blindfold: the
critical role of diagnostics in malaria control. Malaria Journal
7(Suppl. 1), S5.
Vento S & Cainelli F (2010) The need for new antibiotics. Lancet
375, 637.
WHO (2009) World Malaria Report 2009. WHO, Geneva.
WHO (2010) Guidelines for the Treatment of Malaria, 2nd edn.
WHO, Geneva.
Corresponding Author Frank E. Baiden, Kintampo Health Research Center, PO Box 200, Kintampo, BAR, Ghana.
Tel.: +233 244 591181; E-mail: baidenf@yahoo.co.uk
Tropical Medicine and International Health volume 16 no 2 pp 142144 february 2011
F. Baiden et al. Editorial
144 2010 Blackwell Publishing Ltd