Concurrent malaria and typhoid fever in the tropics: the diagnostic challenges and public health implications.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 (1987-2007), 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 bac·te·ri·ol·o·gy
The study of bacteria, especially in relation to medicine and agriculture.
bac·te 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
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 Morbidity and Mortality can refer to:
Major branch of the U.S. military forces, charged with preserving peace and security and defending the nation. The first regular U.S. fighting force, the Continental Army, was organized by the Continental Congress on June 14, 1775, to supplement local (1). However, by the end of 19th century, laboratory tests had eliminated this theory as they found that it was either one thing or the other, or in rare instances, co-infection with both Salmonella typhi and the Plasmodium plasmodium, name for a stage in the life cycle of a slime mold. Also, Plasmodium is the name given to the genus of the protozoan parasite that causes malaria. species (1). In the last two decades, this relationship between the two diseases has been substantiated by studies from Africa and India (2-6).
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 year (7). 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 vi·vax
1. The protozoan (Plasmodium vivax) that causes the most common form of malaria.
2. Vivax malaria. , P. malariae), accounting for an estimated 1.4 to 2.6 million deaths per year in this region (8,9). In addition, the most effective malaria vector, Anopheles gambiae is the most wide spread in the region and the most difficult to control (9). In areas where malaria is highly endemic, a protective semi-immunity against P. falciparum is acquired during the first 10-15 years of life, and the majority of malaria-related morbidity and mortality happen in young children (10).
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 splenomegaly /sple·no·meg·a·ly/ (-meg´ah-le) enlargement of the spleen.
congestive splenomegaly Banti's disease; splenomegaly secondary to portal hypertension. , and leukopenia leukopenia /leu·ko·pe·nia/ (-pe´ne-ah) reduction of the number of leukocytes in the blood below about 5000 per cubic mm.leukope´nic
basophilic leukopenia basophilopenia. (11,12). The etiological etiological
pertaining to etiology.
the name of a disease which includes the identification of the causative agent, e.g. Streptococcus agalactiae mastitis. agent of typhoid fever is Salmonella enterica sub-sp enterica serotype serotype /se·ro·type/ (ser´o-tip) the type of a microorganism determined by its constituent antigens; a taxonomic subdivision based thereon.
v. Typhi. Typhoid fever is an important cause of morbidity in many regions of the world, with an estimated 12 to 33 million cases occurring annually (13). 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 childhood (14), 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 mortality (15,16). Human beings are the only reservoir and host for typhoid fever and is transmitted by faecally contaminated water and food in endemic areas especially by carriers handling food (11). The disease has important socioeconomic impact because, most of the time, several months are necessary for a patient to recover and be able to work again.
Although typhoid and malaria are caused by very different organisms--one a gram negative bacilli, the other a protozoan protozoan (prō'təzō`ən), informal term for the unicellular heterotrophs of the kingdom Protista. Protozoans comprise a large, diverse assortment of microscopic or near-microscopic organisms that live as single cells or in simple , and transmitted via different mechanisms, both diseases share rather similar symptomatology symptomatology /symp·to·ma·tol·o·gy/ (simp?to-mah-tol´ah-je)
1. the branch of medicine dealing with symptoms.
2. the combined symptoms of a disease.
n. . However, the precise incidence of the concurrent malaria and typhoid fever in most geographical areas is largely uncertain. Because both typhoid and malaria share social circumstances which are imperative to their transmission, individuals in areas endemic for both diseases are at substantial risk of contracting both these diseases, either concurrently or an acute infection superimposed on a chronic one (17). While high prevalence of malaria is an established fact, it is only within the last decade that an unusually high number of illnesses have been diagnosed as malaria co-existing with typhoid fever (2-6). Malaria and typhoid fever often present with mimicking symptoms especially in the early stages of typhoid fever (2,3). The situation often presents a diagnostic problem and in some cases could lead to diagnostic confusion. As a result of this, the importance of definitive laboratory-based diagnosis cannot be overstated. Before an individual is said to have concurrent malaria and typhoid fever, the presence of Plasmodium species and Salmonella enterica sub-sp enterica serotype Typhi must be demonstrated in the patient's laboratory specimens.
Conventional light microscopy is the established method for the laboratory confirmation of malaria and is the most commonly used method for malaria diagnosis in the tropics. The careful examination by an expert microscopist of a well-prepared and well stained blood film remains currently the "gold standard" for detecting and identifying malaria parasites (18). In most settings, the procedure consists of: collecting a finger-prick blood sample; preparing a thick blood smear (in some settings a thin smear is also prepared); staining the smear (most frequently with Giemsa); and examining the smear through a microscope (preferably with a 100x oil immersion objective In light microscopy, an oil immersion objective is a specially designed objective lens used to increase the resolution of the microscope. This is achieved by immersing both the lens and the specimen in a transparent oil of high refractive index, thereby increasing the numerical ) for the presence of malaria parasites (19). Microscopy offers many advantages. It is sensitive, informative, relatively inexpensive, is a general diagnostic technique that can be shared with other disease control programmes, and can provide a permanent record (the smears) of the diagnostic findings and be subject to quality control (18).
The definitive diagnosis of typhoid fever requires the isolation of Salmonella enterica serotype Typhi from the patient. Cultures of blood, stool, urine, rose spots, blood mononuclear mononuclear /mono·nu·cle·ar/ (-noo´kle-er)
1. having but one nucleus.
2. a cell having a single nucleus, especially a monocyte of the blood or tissues.
adj. cell-platelet fraction, bone marrow, and gastric and intestinal secretions can all be useful for diagnosis11. However, this requires laboratory equipment and technical training that are beyond the means of most primary health care facilities in the developing world. Consequently, Widal test is the only specific diagnostic investigation available in most tropical regions. The Widal test which is readily available and inexpensive was introduced as a serologic se·rol·o·gy
n. pl. se·rol·o·gies
1. The science that deals with the properties and reactions of serums, especially blood serum.
2. technique to aid in diagnosis of typhoid fever and has been used for more than a century. The test was based on demonstrating the presence of agglutinin Agglutinin
A substance that will cause a clumping of particles such as bacteria or erythrocytes. Of major importance are the specific or immune agglutinins, which are antibodies that will agglutinate bacteria containing the corresponding antigens on their (antibody) in the serum of an infected patient, against the H (flagellar flagellar /fla·gel·lar/ (flah-jel´ar) of or relating to a flagellum.
of or pertaining to a flagellum. ) and O (somatic) antigens of Salmonella typhi. The role of the Widal test had been to increase the index of suspicion index of suspicion Medtalk A phrase broadly used to indicate how seriously a particular disease is being entertained as a diagnosis; as an example, there is a high IOS that rapid and unexplained weight loss in an elderly Pt is due to pancreas CA, and a low IOS that for the presence of typhoid fever by demonstrating a positive agglutination agglutination, in biochemistry
agglutination, in biochemistry: see immunity.
agglutination, in linguistics
agglutination, in linguistics: see inflection. during the acute and convalescent con·va·les·cent
Relating to convalescence.
A person who is recovering from an illness, an injury, or a surgical operation.
1. pertaining to or characterized by convalescence.
2. period of infection with evidence of a four-fold rise of antibody titre titre
titer. (20). The Widal test reaction involves the use of bacterial suspensions of S. typhi and S. paratyphi 'A' and 'B', treated to retain only the 'O' and 'H' antigens. These antigens are employed to detect corresponding antibodies in the serum of a patient suspected of having typhoid fever. The IgM somatic O antibody appears first and represents the initial serologic response in acute typhoid fever, while the IgG flagella flagella /fla·gel·la/ (flah-jel´ah) [L.] plural of flagellum.
(fl H antibody usually develops more slowly but persists for longer (11,20). Two types of agglutination techniques are available: the slide test and the tube test.
In most parts of the tropics, the specific diagnosis of concurrent malaria and typhoid fever is based on blood smear microscopy and Widal test and in rare cases with the inclusion of bacterial culture. However, it is of concern that poor diagnosis continues to hinder effective malaria and typhoid control in the tropics. This is due to a combination of factors, including non-specific clinical presentation of the diseases, high prevalence of asymptomatic infections in many areas, lack of resources and insufficient access to trained health care providers and health facilities, and widespread practice of self-treatment for clinically suspected malaria or typhoid fever.
Despite the importance of concurrent malaria and typhoid fever in the tropics, the challenges associated with the diagnosis and the public health implications have not been comprehensively reviewed. The objective of this report was to systematically review scientific data from studies conducted in the tropics that provided information on malaria and typhoid fever coinfection. The implications of findings from these studies and their association with the risk, management, and treatment of the concurrent infection, public health policy, and operational research needs in the endemic areas of the tropics are discussed.
Material & Methods
This systematic review was designed to address the following key questions: (a) What are the challenges associated with the diagnosis of concurrent malaria and typhoid fever in the tropics?; (b) What are the limitations of the present conventional diagnostic techniques and tools employed in the diagnosis of malaria and typhoid fever in the tropics?; (c) What are the public health implications of misdiagnosis mis·di·ag·no·sis
n. pl. mis·di·ag·no·ses
An incorrect diagnosis.
mis·diag·nose (under-diagnosis or over-diagnosis) of concurrent malaria and typhoid fever in the tropics?; and (d) What are the appropriate public health measures required to address concurrent malaria and typhoid fever in the tropics? A Medline Entrez-PubMed search was performed and studies conducted in the tropics on concurrent malaria and typhoid in the last two decades (1987-2007) and reported in English were identified. Combinations of key words such as Malaria and Typhoid fever were used for the search which yielded 287 entries as of January 2008. Selected publications obtained from Google search using the key words Malaria, Typhoid fever, Coinfeclion and Tropics relevant to the topic were also identified and used as additional literature for the review. Bibliographies of all publications obtained were checked for additional relevant references and were obtained and included in the review. Particular attention was paid to articles providing information on the diagnosis of concurrent malaria and typhoid fever. The various reports were systematically reviewed with respect to the method of sample collection/analysis, location, population, the period, setting, and the type of study to enhance comparison between studies.
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 techniques (2,21), five studies used only 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.
The prevalence of malaria and typhoid coinfection using only the Widal technique ranged from 4.4% to 70% (22-27), on the other hand, the prevalence of concurrent malaria and typhoid fever using only the bacteriological culture technique ranged from 1.11% to 26.6% (3,28-31). The two studies that used both Widal and bacteriological culture techniques reported considerably higher rates of coinfection with Widal test as compared with the bacteriological culture technique, in Nigeria (10.1% vs 0.5%) (21) and in Cameroon (47.9% vs 17%) (2) (Table 1).
Because the knowledge about baseline titres of O and H antibodies in a population is necessary for accurate interpretation of results of the Widal test, the eight studies that employed the Widal technique reported the local cut-off titer values denoting a positive Widal test. Although there was no consensus on the diagnostic titer for a single Widal test, all the studies reported a "positive" Widal test based on a fourfold rise in O agglutinins in repeated tests or a titer of 1:80 or greater in a single test (Table 1).
Malaria and typhoid fever still remain diseases of major public health importance in the tropics. Both malaria and typhoid fever are major aetiological AE`ti`o`log´ic`al
a. 1. Pertaining to ætiology; assigning a cause.
Adj. 1. aetiological - of or relating to the philosophical study of causation
aetiologic, etiologic, etiological
2. considerations in both acute and prolonged fever of unknown origin Fever of Unknown Origin Definition
Fever of unknown origin (FUO) refers to the presence of a documented fever for a specified time, for which a cause has not been found after a basic medical evaluation. (PUO PUO
pyrexia of unknown (or uncertain) origin (used of fevers before diagnosis is determined)
pyrexia of unknown origin. ) in the tropics. Because of the high prevalence of typhoid fever and malaria in the tropics, co-infections are common. However, the actual and precise underlying mechanisms to explain the association between malaria and Salmonella species infection is still uncertain, although there are few postulations which may explain why malaria may predispose pre·dis·pose
To make susceptible, as to a disease. to salmonella bacteremia bacteremia: see septicemia.
Presence of bacteria in the blood. Short-term bacteremia follows dental or surgical procedures, especially if local infection or very high-risk surgery releases bacteria from isolated sites. and sepsis (17). It has been shown that antibody response to O antigen of S. typhi was markedly reduced in acute episode of malaria compared with that in controls where humoral immunity is transiently impaired (32). It has been demonstrated in a murine model of infection with Salmonella murium that haemolysis Hae`mol´y`sis
n. 1. (Physiol.) Same as Hæmatolysis, Hæmatolytic.
the breaking down of erythrocytes with liberation of hemoglobin in the blood. which occur in malaria may predispose to gram-negative organism as what has been seen in haemolytic Adj. 1. haemolytic - relating to or involving or causing hemolysis; "hemolytic anemia"
hemolytic disease caused by sickle-cell disease and bartonellosis (33).
Although the signs and symptoms of malaria and typhoid fever do overlap, it was observed in Pakistan that subjects with dual infection had significantly higher rates of nausea, vomiting, abdominal pain, and diarrhoea, all common presenting features of enteric fever (29). Furthermore, it was noted that unlike the intermittent fever pattern generally seen with malaria, patients with dual infection tended to exhibit a continuous fever more typical of enteric fever (29). This latter pattern, as well as the delayed resolution of fever (>24 hours) after starting antimalarial antimalarial /an·ti·ma·lar·i·al/ (-mah-lar´e-al) therapeutically effective against malaria, or an agent with this quality.
Preventing or relieving the symptoms of malaria. treatment have clinical implication as it should raise the clinical suspicion of dual infection in areas endemic for the two diseases. However, it is imperative that definitive diagnosis be made to confirm the presence of coinfection by the demonstration of the presence of Plasmodium sp and Salmonella enlerica sub-sp enlerica serotype Typhi in the patient's laboratory specimens. This can most often be problematic particularly in local settings of the tropics.
Concerning malaria diagnosis, it is pertinent to state that two malaria diagnostic approaches currently used most often, do not allow a satisfactory diagnosis of malaria. Clinical diagnosis, the most widely used approach, is unreliable because the symptoms of malaria are very non-specific. Microscopic diagnosis, the established method for laboratory confirmation of malaria, presents technical and personnel requirements that often cannot be met, particularly in facilities at the periphery of the health care system. In addition, delays in the provision of the microscopy results to the clinician mean that decisions on treatment may be taken without the benefit of the results (18,19). 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 equipment (19). Compared to microscopy, the main disadvantages of currently available RDTs are: lack of sensitivity at low levels of parasitaemia Noun 1. parasitaemia - a condition in which parasites are present in the blood
blood disease, blood disorder - a disease or disorder of the blood ; inability to quantify parasite density; inability to differentiate between P. vivax, P. ovale and P. malariae, as well as between the sexual and asexual asexual /asex·u·al/ (a-sek´shoo-al) having no sex; not sexual; not pertaining to sex.
1. Having no evident sex or sex organs; sexless.
2. 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 PCR polymerase chain reaction.
polymerase chain reaction
Polymerase chain reaction (PCR) ) based tests and antibody detection by serology Serology
The division of biological science concerned with antigen-antibody reactions in serum. It properly encompasses any of these reactions, but is often used in a limited sense to denote laboratory diagnostic tests, especially for syphilis. (18).
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 collection (12). Although this test is highly specific, sensitivity varies from 48-78% (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 invasive (36). 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 value (37-40). Cross-reactions can occur as a consequence of latent and post-infectious diseases prevalent in the tropics namely tuberculosis, pneumonia, amoebiasis am·oe·bi·a·sis
Variant of amebiasis. , rickettsial rickettsial /rick·ett·si·al/ (ri-ket´se-al) pertaining to or caused by rickettsiae.
Relating to, or caused by a member of the genus Rickettsia. diseases, rheumatoid arthritis and chronic active hepatitis chronic active hepatitis 1. Obsolete term. See Chronic hepatitis2. Chronic viral hepatitis (38). In addition, the test has to be interpreted against a baseline titer in the same geographical area since titers of diagnostic significance differ in endemic and non-endemic areas (39).
As a result of the diagnostic challenge associated with malaria and typhoid fever, it is very common to see patients in many parts of the tropics, undergoing both typhoid and malarial treatment even if their diagnosis has not been confirmed (21). There appears to be more typhoid fever cases in areas of drug resistant malaria and a cross-reaction between malarial parasites and salmonella antigens may cause false positive Widal agglutination test (21,22). It seems that the outcome of the Widal reaction for patients with a clinical suspicion of typhoid and malaria depends on individual host immune responses, which become stimulated in febrile febrile /feb·rile/ (feb´ril) pertaining to or characterized by fever.
Of, relating to, or characterized by fever; feverish. conditions associated with malaria fever. This memory response could cause positive Widal reactions in previously sensitized patients and accounts for up to 35% of false positive Widal test which have been reported (21,41). This can be accounted for by the demonstrated high prevalence of Salmonella antibodies in local healthy population and the fact that 50% of the patients had detectable levels of antibodies to the somatic antigen (21,23,27).
It is interesting to note that an association between non-typhoidal salmonellosis and/or typhoidal salmonellosis and malaria was reported in the studies reviewed. The predominance of typhoidal salmonellosis over non-typhoidal salmonellosis as cause of salmonella bacteraemia bacteraemia
see bacteremia. was demonstrated in a study of dual malaria-salmonella infection in Karachi, Pakistan, in which 21 of 22 positive blood cultures for salmonellae grew S. typhi (16/21) or S. paralyphi A or B (5/21) (one patient with S. enlerilidis was excluded from analysis) (29). In Lagos, Nigeria, 16 Salmonella spp made up of seven each of S. typhi and S. enlerilidis, and two of S. paratyphi were isolated with Plasmodium spp from patients with complications (28). Two other studies in Nigeria that employed bacterial culture identified only typhoidal salmonellosis as responsible for the typhoid fever in coinfected cases (3,31). In contrast, the non-typhoidal salmonellosis predominated in the reports from Cameroon and Gambia. In the study of 200 febrile patients in Cameroon, Ammah el al (2) reported a 32.5% incidence of microbiologically-proven concurrent infection with malaria and S. lyphimurium (diagnosed via blood and/or stool positive for salmonellae) compared with S. typhi (17%) and S. paralyphi (2%) (p <0.05). In Gambia, malarial infection was present in 11% of patients with S. typhi septicaemia septicaemia or septicemia
an infection of the blood which develops in a wound [Greek sēptos decayed + haima blood]
septicemia, septicaemia and 42% of patients with non-typhoidal salmonellae (30). The implication of the high rate of the non-typhoidal Salmonella infection is increase in the rate of false positive Widal test results, due to the presence of cross-reacting antigens (42,43).
Because typhoidal Salmonella antibodies are known to cross-react with other antigens including those from non-typhoidal Salmonella and malaria antigens, the use of Widal test as diagnostic tool in patients with malaria may lead to misleading results as demonstrated by some studies from Nigeria. Although, in Benin City, Nigeria, Widal agglutination reaction at >1.80 were significantly more in malaria patients (27.5%) than in controls (16%) (p <0.05) and also significantly higher in controls with malaria parasitaemia (27.8%) than those without parasitaemia (12.9%) (p <0.02) (25), a correlation analysis in a similar study in Zaria, Nigeria, showed that the presence of malaria parasites had no specific relationship with S. typhi O and H antibody levels in malaria patients and carriers of malaria parasites using Widal test (21). Furthermore, in another study in Enugu, Nigeria, there was no statistical significant difference (p >0.05) between Widal titres of malaria and culture-proven typhoid cases, and the study indicated that using Widal test alone, one cannot differentiate typhoid fever from malaria (3). In yet another study in Lagos, Nigeria, which investigated Widal agglutinin in malaria-infected individuals, it was found that 85% of patients with a negative S. typhi culture but positive malaria smear had Widal titers of 1:40, 12% had titers of 1:80, and 3% had titers of 1:160; in contrast, 45% of patients with both S. typhi cultures and malaria smears negative had Widal titers of 1:40, 15% had titers of 1:80, and 10% had titers of 1:160 (23). The study noted that the presence of Widal agglutinin under conditions of positive malaria smear, negative S. typhi culture and negative prior typhoid immunization immunization: see immunity; vaccination. would suggest that malaria parasite may have some undefined antigenic determinants similar to S. typhi which can induce antibody production and could explain the febrile condition seen in some of the patients. Furthermore, the presence of Widal agglutinin under conditions of negative malaria smear, negative S. typhi culture and negative prior immunisation against typhoid fever suggests that other infectious agents, in addition to Salmonella and malaria parasite, may also share common antigenic determinants with S. typhi. Hence, malaria could interfere with diagnosis of typhoid fever using Widal test and thereby lead to over diagnosis of typhoid fever.
The interpretation of Widal test results, when diagnosing concurrent malaria and typhoid fever must therefore be done with a lot of caution. This is because negative or positive Widal agglutination test is neither definitive nor completely informative. Apart from the influence of the results by malaria, Olopoenia and King (20), have identified the following as causes of a positive Widal agglutination test; the patient being tested has typhoid fever, previous immunisation with Salmonella antigen, cross-reaction with non-typhoidal Salmonella, variability and poorly standardized commercial antigen preparation, infection with other enterobacteriaceae and other diseases such as dengue dengue
or breakbone fever or dandy fever
Infectious, disabling mosquito-borne fever. Other symptoms include extreme joint pain and stiffness, intense pain behind the eyes, a return of fever after brief pause, and a characteristic rash. . Also identified are the following as causes of a negative Widal agglutination test; absence of infection by S. typhi, the carrier state, an inadequate inoculum inoculum /in·oc·u·lum/ (-ok´u-lum) pl. inoc´ula material used in inoculation.
n. pl. of bacterial, antigen in the host to induce antibody production, technical difficulty or errors in the performance of the test, previous antibiotic treatment, and variability in the preparation of commercial antigens. In fact, Ammah el al (2) 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 mis·man·age
tr.v. mis·man·aged, mis·man·ag·ing, mis·man·ag·es
To manage badly or carelessly.
mis·manage·ment n. 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 illness acute febrile illness A nonspecific term for an illness of sudden onset accompanied by fever (44).
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 fever (29). 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 region (45). 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 typhoid (42,45).
Malaria control is too complex to be addressed by a single approach, and any attempt to do so is fraught with danger. It is important to tailor control and preventive strategy to the prevailing ecological and epidemiological conditions. The strategy of mortality control involves detecting presumptive cases, determining which cases are parasite positive, and administering effective treatment. Focal interventions to minimize human-vector contact can be effected by the use of insecticide-treated mosquito nets as well as indoor spraying of insecticide (7). On the other hand, improved personal hygiene, targeted vaccination campaigns and intensive community health education have been identified as public health measures that could help to prevent and control typhoid (5). The financial and human resource constraints of health systems in the tropics most affected by malaria and typhoid fever, and the shared determinants of vulnerability for both diseases, indicate the need for integration of preventive and curative services for malaria and typhoid fever and strengthening the health systems that deliver these services. Delivery of malaria and typhoid fever interventions within existing health services may permit effective utilization of human resources and address serious resource constraints. The challenge is to ensure coherence at each level of the health system, and to maximize the use of available resources for integrated service delivery.
Received: 9 January 2008 Accepted in revised form: 27 February 2008
(1.) Smith DC. The rise and fall of typhomalarial fever. I: origins. J Hist Med Allied Sci 1982; 37: 182-220.
(2.) Ammah A, Nkujo-Akenji T, Ndip R, Deas JE. An update on concurrent malaria and typhoid fever in Cameroon. Trans R Soc Trop Med Hyg 1999; 2: 127-9.
(3.) Ohanu ME, Mbah AU, Okonkwo PO, Nwagbo FS. Interference by malaria in the diagnosis of typhoid using Widal test alone. Wesl Afr J Med 2003; 22: 250-2.
(4.) Samal KK, Sahu CS. Malaria and Widal reaction. J Assoc Physicians India 1991; 10: 745-7.
(5.) Sur D, von Seidlein L, Manna B, Dutta S, Deb AK, Sarkar Sarkar could mean:
(6.) Kanjilal SD, Dutta A, Mondal RK, Chakravorti S. Uncomplicated falciparum malaria fal·cip·a·rum malaria
Malaria caused by Plasmodium falciparum and characterized by severe malarial paroxysms that recur about every 48 hours and often by acute cerebral, renal, or gastrointestinal manifestations. complicated by salmonella septicaemia: cause not coincidence. J Indian Med Assoc 2006; 104: 646-8.
(7.) Expert committee on malaria. WHO Tech Rep Ser 2000; No. 892: i-v.
(8.) World malaria situation in 1994. WHO Weekly Epidemiol Rec 1997; 72: 285-90.
(9.) World malaria situation, 1990. WHO Weekly Epidemiol Rec 1992; 67: 161-7.
(10.) Riley EM, Hviid L, Theander TG. Malaria. In: Kierszenbaum F, editor. Parasitic infections and the immune system. New York: Academic Press 1994; p. 119- 43.
(11.) Butter T. Typhoid fever. In: Wyngaarden JB, Smith LH, Bennett JC, editors. Cecil textbook of medicine, XIX edn. Philadelphia, USA: W.B. Saunders Co, 1992; p. 1690-2.
(12.) Pearson RD, Guerrant RL. Enteric fever and other causes of abdominal symptoms with fever. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases, V edn. New York: Churchill Livingstone 2000; p. 1136-50.
(13.) Pang TZ, Bhutta A, Finlay BB, Altwegg M. Typhoid fever and other salmonellosis: a continuing challenge. Trends Microbiol 1995; 3: 253-5.
(14.) Ivanoff B, Levine MM, Lambert PH. Vaccination against typhoid fever: present status. Bull Wld Health Org 1994; 72: 957-71.
(15.) Gupta A. Multidrug-resistant typhoid fever in children: epidemiology and therapeutic approach. Pediatr Infect Dis J 1994; 13: 134-40.
(16.) Bhutta ZA. Impact of age and drug resistant on mortality in typhoid fever. Arch Dis Child 1996; 75: 214-7.
(17.) Keong BCM BCM Baylor College of Medicine
BCM Business Communications Manager (Nortel)
BCM Broadcom Corporation
BCM Business Continuity Management
BCM Business Contact Manager (Microsoft) , Sulaiman W. Typhoid and malaria co-infection --an interesting finding in the investigation of a tropical fever. Malaysian J Med Sci 2006; 13: 74-5.
(18.) Malaria diagnosis new perspectives: report of a joint WHO/ USAID USAID United States Agency for International Development
USAID Agencia de los Estados Unidos para el Desarrollo Internacional (Spanish) informal consultation. Geneva Geneva, canton and city, Switzerland
Geneva (jənē`və), Fr. Genève, canton (1990 pop. 373,019), 109 sq mi (282 sq km), SW Switzerland, surrounding the southwest tip of the Lake of Geneva. : World Health Organization 2000; p. 1-57.
(19.) Payne D. Use and limitations of light microscopy for diagnosing malaria at the primary health care level. Bull Wld Health Org 1988; 66: 621-6.
(20.) Olopoenia LA, King AL. Widal agglutination test--100 years later: still plagued by controversy. Postgrad Med J 2000; 76: 80-4.
(21.) Mbuh FA, Galadima M, Ogbadu L. Rate of coinfection with malaria parasites and Salmonella typhi in Zaria, Kaduna State, Nigeria. Ann Afr Med 2003; 2: 64-7.
(22.) Jhaveri KN, Nandwani SK, Mehta PK, Surati RR, Parmar BD. False positive modified Widal test in acute malaria. J Assoc Physicians India 1995; 43: 754-5.
(23.) Olopoenia L, Oyewole F, Onafowokan R1. Widal agglutination in malaria infection. Med Rev 1996; 3: 5-6.
(24.) Samal KK, Sahu JCS JCS
Joint Chiefs of Staff
JCS (US) n abbr (= Joint Chiefs of Staff) → Stabschefs pl . Malaria and Widal reaction. J Assoc Physicians India 1991; 39: 745-7.
(25.) Ibadin MO, Ogbimi A. Antityphoid agglutinins in African school aged children with malaria. West Afr J Med 2004; 23: 276-9.
(26.) Tanyigna KB, Bello CS, Okeke N, Onwukeme KE. Comparison of blood, bone marrow aspirate as·pi·rate
To take in or remove by aspiration.
A substance removed by aspiration.
The removal by suction of a fluid from a body cavity using a needle. , stool and urine cultures in the diagnosis of enteric fever. Niger J Med 2001; 10: 21-4.
(27.) Onuigbo MA. Diagnosis of typhoid fever in Nigeria: misuse of the Widal test. Trans R Soc Trop Med Hyg 1990; 84:129-31.
(28.) Akinyemi KO, Bamiro BS, Coker AO. Salmonellosis in Lagos, Nigeria: incidence of Plasmodium falciparum-associated co-infection, patterns of antimicrobial resistance, and emergence of reduced susceptibility to fluoroquinolones. J Health Popul Nutr 2007; 25: 351-8.
(29.) Khan MA, Mekan SF, Abbas Z, Smego RA Jr. Concurrent malaria and enteric fever in Pakistan. Singapore Med J 2005; 46: 635-8.
(30.) Mabey DC, Brown A, Greenwood BM. Plasmodium falciparum malaria and Salmonella infections in Gambian children. J Infect Dis 1987; 155: 1319-21.
(31.) Smith SI, Odunukwe NN, Niemogha MT, Ahmed AO, Efienemokwu CA, Otuonye MN, Bankole M, Junaid M, Agomo C, Mafe AG, Idigbe EO. Diagnostic methods for typhoid fever in Nigeria. Br J Biomed Sci 2004; 61: 179-81.
(32.) Greenwood BM, Bradley-Moore AM, Palit A, Bryceson ADM See add/drop multiplexer.
(language) ADM - A picture query language, extension of Sequel2.
["An Image-Oriented Database System", Y. Takao et al, in Database Techniques for Pictorial Applications, A. Blaser ed, pp. 527-538]. . Immunosuppression immunosuppression
Suppression of immunity with drugs, usually to prevent rejection of an organ transplant. Its aim is to allow the recipient to accept the organ permanently with no unpleasant side effects. in children with malaria. Lancet 1972; 1: 169-72.
(33.) Kaye D, Hook EW. The influence of hemolysis hemolysis (hĭmŏl`ĭsĭs), destruction of red blood cells in the bloodstream. Although new red blood cells, or erythrocytes, are continuously created and old ones destroyed, an excessive rate of destruction sometimes occurs. or blood loss on susceptibility to infection. J Immunol 1963; 91: 65-75.
(34.) Moody A. Rapid diagnostic tests for malaria parasites. Clin Microbiol Rev 2002; 15: 66-78.
(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 Established in 1981, World Scientific Publishing Company (WSPC) is one of the leading scientific publishers in the world, and the largest international scientific publisher in the Asia-Pacific region. 1991; p. 188-94.
(36.) Gilman RH, Terminel M, Levine MM, Hernandez-Menodoze P, Hornick RB. Relative efficacy of blood, urine, rectal swab, bone-marrow and rose spot cultures for recovery of Salmonella typhi in typhoid fever. Lancet 1975; 1: 1211-3.
(37.) Chew SK. Diagnostic value of Widal test for typhoid fever in Singapore. J Trop Med Hyg 1992; 95: 288-91.
(38.) Koeleman JG. Retrospective study to determine the diagnostic value of Widal test in nonendemic country. Eur J Clin Microbiol Infect Dis 1992; 167-70.
(39.) Buck RL, Escanilla J, Sangalang RP, Cabangan AB, Santiago LT. Diagnostic value of single, pre-treatment Widal test in suspected enteric fever cases in the Philippines. Trans R Soc Trop Med Hyg 1987; 81: 871-3.
(40.) Choo KE. Usefulness of Widal test in diagnosing childhood typhoid fever in endemic area. J Pediatr Child Health Care 1993; 29: 36-42.
(41.) Petit PLC, Wamola IA. Typhoid fever: a review of its impact and diagnostic problems. East African Med J 1994; 11: 183-8.
(42.) Parry CM, Hoa NT, Diep TS, Wain J, Chinh NT, Vinh H, Hien TT, White NJ, Farrar JJ. Value of a single-tube Widal test in diagnosis of typhoid fever in Vietnam. J Clin Microbiol 1999; 37: 2882-6.
(43.) Willke A, Ergonul O, Bayar B. Widal test in diagnosis of typhoid fever in Turkey. Clin Diagn Lab Immunol 2002; 9: 938-41.
(44.) Nsutebu EF, Ndumbe PM, Koulla S. The increase in occurrence of typhoid fever in Cameroon: overdiagnosis due to misuse of the Widal test? Trans R Soc Trop Med Hyg 2002; 96: 64-7.
(45.) Pang T, Puthucheary SD. Significance and value of the Widal test in the diagnosis of typhoid fever in an endemic area. J Clin Palhol 1983; 36: 471-5.
Correspondence: C.J. Uneke, Department of Medical Microbiology/Parasitology, Faculty of Clinical Medicine, Ebonyi State University, P.M.B. 053, Abakaliki, Nigeria. e-mail: email@example.com
C. J. Uneke
Department of Medical Microbiology/Parasitology, Faculty of Clinical Medicine, Ebonyi State University, Abakaliki, Nigeria
Table 1. Summary of studies reporting concurrent malaria and typhoid fever in the tropics Authors (Ref) Year of Type of publication study Mabey et al (30) 1987 Case control Onuigbo (27) 1990 Case study Samal & Sahu (24) 1991 Case study Jhaveri et al (22) 1995 Case control Olopoenia et al (23) 1996 Case control Ammah et al (2) 1999 Case control Tanyigna et al (26) 2001 Case control Ohanu et al (3) 2003 Case control Mbuh et al (21) 2003 Case control Smith et al (31) 2004 Case control Ibadin & Ogbimi (25) 2004 Case control Khan et al (29) 2005 Case control Akinyemi et al (28) 2007 Case control Authors (Ref) Study Number/Patient location category Mabey et al (30) Gambia NA Onuigbo (27) Enugu Nigeria 15 with fever Samal & Sahu (24) Burla India 52 with malaria Jhaveri et al (22) Surat India 90 with malaria Olopoenia et al (23) Lagos Nigeria 45 with malaria Ammah et al (2) Beau Cameroon 200 with fever Tanyigna et al (26) Jos Nigeria 23 with malaria Ohanu et al (3) Enugu Nigeria 270 with fever Mbuh et al (21) Zaria Nigeria 218 with malaria Smith et al (31) Lagos Nigeria 50 with fever Ibadin & Ogbimi (25) Benin City Nigeria 189 with malaria Khan et al (29) Karachi Pakistan 1891 with malaria Akinyemi et al (28) Lagos Nigeria 107 with malaria Authors (Ref) Prevalence of coinfection/ Typhoid fever laboratory test Mabey et al (30) 11%; Bacterial culture Onuigbo (27) 70%; Widal test (>1:80 for O antigens) Samal & Sahu (24) 15.4%; Widal test (>1:80 for O antigens) Jhaveri et al (22) 14.58%; Widal test (>1:80 for O antigens) Olopoenia et al (23) 12%; Widal test (>1:80 for O antigens) Ammah et al (2) 17%; Bacterial culture 47.9%; Widal test (>1:80 for O antigens) Tanyigna et al (26) 4.4%; Widal test (>1:80 for O antigens) Ohanu et al (3) 26.6%; Bacterial culture Mbuh et al (21) 0.5%; Bacterial culture 10.1%; Widal test (>1:160 for O antigens) Smith et al (31) 18%; Bacterial culture Ibadin & Ogbimi (25) 27.5%; Widal test (>1:80 for O antigens) Khan et al (29) 1.11%; Bacterial culture Akinyemi et al (28) 14.95%; Bacterial culture NA: Information not accessible.