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Abstract
Background & objectives: Malaria and typhoid fever still remain diseases of major public health importance in the tropics. Individuals in areas endemic for both the diseases are at substantial risk of contracting both these diseases, either concurrently or an acute infection superimposed on a chronic one.
The objective of this report was to systematically review scientific data from studies conducted in the
tropics on concurrent malaria and typhoid fever within the last two decades (19872007), to highlight
the diagnostic challenges and the public health implications.
Methods: Using the MedLine Entrez-PubMed search, relevant publications were identified for the review via the key words Malaria and Typhoid fever, which yielded 287 entries as of January 2008.
Results: Most of the studies reviewed expressed concern that poor diagnosis continues to hinder effective control of concurrent malaria and typhoid fever in the tropics due to: non-specific clinical presentation of the diseases; high prevalence of asymptomatic infections; lack of resources and insufficient access to trained health care providers and facilities; and widespread practice of self-treatment
for clinically suspected malaria or typhoid fever.
Interpretation & conclusion: There were considerably higher rates of concurrent malaria and typhoid
fever by Widal test compared to the bacteriological culture technique. Although culture technique
remains the gold standard in typhoid fever diagnosis, Widal test is still of significant diagnostic value
provided judicious interpretation of the test is made against a background of pertinent information.
Malaria could be controlled through interventions to minimize human-vector contact, while improved
personal hygiene, targeted vaccination campaigns and intensive community health education could
help to control typhoid fever in the tropics.
Key words Coinfection concurrent diagnosis malaria public health tropics typhoid fever
Introduction
Malaria and typhoid fever are among the most endemic diseases in the tropics. Both diseases have been
associated with poverty and underdevelopment with
significant morbidity and mortality. An association
between malaria and typhoid fever was first described in the medical literature in the middle of the
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Malaria remains the most complex and overwhelming health problem, facing humanity in vast majority
of tropical and sub-tropical regions of the world, with
300 to 500 million cases and 2 to 3 million deaths per
year7. About 90% of all malaria deaths in the world
today occur in the sub-Saharan Africa and this is
because majority of infections are caused by Plasmodium falciparum, the most dangerous of the four
human malaria parasites (P. falciparum, P. ovale, P.
vivax, P. malariae), accounting for an estimated 1.4
to 2.6 million deaths per year in this region8,9. In
addition, the most effective malaria vector, Anopheles gambiae is the most wide spread in the region
and the most difficult to control9. In areas where
malaria is highly endemic, a protective semi-immunity against P. falciparum is acquired during the first
1015 years of life, and the majority of malariarelated morbidity and mortality happen in young
children10.
On the other hand, typhoid fever is widely recognized
as a major public health problem in most developing
tropical countries. It is a systemic infectious disease
characterized by an acute illness, the first typical
manifestations of which are fever, headache, abdominal pain, relative bradycardia, splenomegaly, and
leukopenia11,12. The etiological agent of typhoid fever is Salmonella enterica sub-sp enterica serotype
Typhi. Typhoid fever is an important cause of morbidity in many regions of the world, with an estimated
12 to 33 million cases occurring annually13. Cases are
more likely to be seen in areas like India, South and
Central America, and Africa with rapid population
growth, increased urbanization, and limited safe
water, infrastructure, and health systems. It is estimated that there are more than 13 million cases
occurring annually in Asia alone of which a large proportion occur during childhood14, and in the wake of
emerging multidrug-resistant strains of bacteria causing typhoid fever, the disorder is known to be associated with significant morbidity and mortality15,16.
Human beings are the only reservoir and host for
typhoid fever and is transmitted by faecally contami-
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50 with fever
189 with malaria
1891 with malaria
107 with malaria
Lagos Nigeria
Benin City Nigeria
Karachi Pakistan
Lagos Nigeria
Results
2004
2004
2005
2007
Smith et al (31)
Ibadin & Ogbimi (25)
Khan et al (29)
Akinyemi et al (28)
Case control
Case control
Case control
Case control
23 with malaria
270 with fever
218 with malaria
2001
2003
2003
Tanyigna et al (26)
Ohanu et al (3)
Mbuh et al (21)
Case control
Case control
Case control
Jos Nigeria
Enugu Nigeria
Zaria Nigeria
Prevalence of coinfection/
Typhoid fever laboratory test
Number/Patient
category
Study
location
Type of
study
Year of
publication
Authors (Ref)
Table 1. Summary of studies reporting concurrent malaria and typhoid fever in the tropics
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In all thirteen studies, which provided sufficient information on concurrent malaria and typhoid fever to
enable meaningful and reasonable comparisons, were
identified and reviewed. These 13 studies fulfilled the
following inclusion criteria: (i) Study conducted between 1987 and 2007; (ii) Study conducted in tropical countries endemic for malaria and typhoid fever;
(iii) Study design is case-control investigation; (iv)
Both malaria and typhoid fever screening conducted
on the study population; and (v) Laboratory diagnosis of malaria using blood smear microscopy and typhoid fever using either Widal test or bacterial culture or both. The summary of findings is presented in
Table 1. All the 13 studies reviewed were case-control investigations and made use of thick and thin
blood smear microscopy for laboratory diagnosis of
malaria. Two studies used both Widal and bacteriological culture techniques2,21, five studies used only
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the bacteriological culture techniques, while the remaining six studies used only the Widal technique
(Table 1). Eight of the studies were conducted in
Nigeria, two from India, one each from Cameroon,
Gambia and Pakistan.
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ment may be taken without the benefit of the results18,19. The rapid diagnostic tests (RDTs) for malaria which use immunochromatographic methods to
detect Plasmodium-specific antigens in a finger prick
blood sample, can be performed in approximately 15
min by individuals with minimal training, using test
kits (available from several manufacturers) that require no electricity and no special equipment19. Compared to microscopy, the main disadvantages of currently available RDTs are: lack of sensitivity at low
levels of parasitaemia; inability to quantify parasite
density; inability to differentiate between P. vivax, P.
ovale and P. malariae, as well as between the sexual
and asexual stages of the parasite; persistently positive tests (for some antigens) in spite of parasite clearance following chemotherapy; and relatively high
cost per test 18,19,34. Other diagnostic methods are
available, but they are neither suitable for wide field
application nor for use in routine disease management and this include; microscopy using fluorochromes, polymerase chain reaction (PCR) based
tests and antibody detection by serology18.
Unlike the diagnosis of malaria, typhoid fever presents a greater diagnostic challenge. Typhoid fever
diagnosis is still based on clinical presentation and on
diagnostic tests that are associated with numerous
limitations. Blood culture, which is the gold standard
for diagnosis of typhoid fever, is not routinely requested by most physicians because it is expensive
and final results can be obtained at the earliest, three
days after specimen collection12. Although this test is
highly specific, sensitivity varies from 4878%35 and
the yield is affected by prior antibiotic intake and
stage of illness and alternative methods such as bone
marrow cultures may be required even though this
latter method is invasive36. The Widal test is inexpensive and readily available in most health care settings
in the tropics, but serious doubts have been raised
regarding its validity. It is now regarded as inaccurate, non-specific, poorly standardized, confusing and
of limited diagnostic value3740. Cross-reactions can
occur as a consequence of latent and post-infectious
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culty or errors in the performance of the test, previous antibiotic treatment, and variability in the preparation of commercial antigens. In fact, Ammah et al2
concluded from their study that the number of fever
cases diagnosed as malaria co-existing with typhoid
fever is actually overestimated. It is important therefore to state that erroneous interpretation of the test
result may lead to misdiagnosis and mismanagement
of the patient, resulting in major morbidity and mortality. This is because misdiagnosis of typhoid fever
leads to unnecessary expenditure and exposure of
patients to the side-effects of antibiotics. In addition,
misdiagnosis may result in delayed diagnosis and
treatment of malaria, and other acute febrile illness44.
As a public health measure, patients with malaria
who have marked gastrointestinal symptoms, continuous pattern of fever and persistence of fever for
more than 24 h after appropriate antimalarial therapy,
should be investigated or empirically treated for concurrent enteric fever. The absence of the above clinical features in patients with uncomplicated malaria
should reassure physicians that there is no concurrent
typhoid fever29. Although the Widal test is far from
being a perfect diagnostic tool, in endemic areas, the
Widal test is still of significant diagnostic value provided judicious interpretation of the test is made
against a background of pertinent information, especially data which relate to agglutinin levels in normal
individuals and in non-typhoidal fevers common in
the region45. A single Widal test has even being
pointed out to be of diagnostic value in the early stage
of disease and thus help in reducing morbidity and
mortality from typhoid42,45.
Smith DC. The rise and fall of typhomalarial fever. I: origins. J Hist Med Allied Sci 1982; 37: 182220.
2.
3.
Ohanu ME, Mbah AU, Okonkwo PO, Nwagbo FS. Interference by malaria in the diagnosis of typhoid using Widal
test alone. West Afr J Med 2003; 22: 2502.
4.
5.
8.
9.
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35. Tsang RS, Chau PV. Laboratory diagnosis of typhoid fever: strategies for the 90s. In: Pang T, Koh CL,
Puthucheary SD, editors. Singapore and London: World
Scientific Publishing 1991; p. 18894.
22. Jhaveri KN, Nandwani SK, Mehta PK, Surati RR, Parmar
BD. False positive modified Widal test in acute malaria. J
36. Gilman RH, Terminel M, Levine MM, HernandezMenodoze P, Hornick RB. Relative efficacy of blood,
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Correspondence: