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Malaria and typhoid are the recurrent infectious diseases with different etiological and vector agents in the endemic tropical regions of the world, yet, both infections display significant similarities in symptomological manifestations. Malaria is caused by a Plasmodium parasite transmitted by anopheles mosquitoes. It occurs mainly in the tropical regions of the world, while typhoid fever is caused by Salmonella enterica serotype typhi, and occurs worldwide. Nevertheless, both malaria and typhoid are known as the major causes of morbidity and mortality in endemic regions of world especially in the Indian subcontinent, Africa, Asia, or Latin America. The majority of malaria cases are found in countries where cost-effectiveness is an important factor and ease of diagnostic test performance and training of personnel are also major considerations. However, in Africa, it is endemic in the regions, south of the Sahara especially in West Africa. In Nigeria for example, malaria alone is one of the most persistent infections that adversely affect socioeconomic productivity and wellness of the population. What makes the coexistence of malaria and typhoid fever unique is the fact that they possess similar symptomology with multiple variable complication, yet, share the same pathological outcomes, which make sustained management and prevention difficult. One of the major problems in managing malaria and typhoid fever in Nigeria for example, is the inherent problem of misdiagnosis and confusion in the physiological and behavioral manifestations of the two separate etiological infections. Both exhibit similarities in the signs and symptoms of the two diseases. Furthermore, most of the sufferers have the tendency to erroneously conclude that they have malaria when they have typhoid fever. Consequently, they resort to self-medication, which could put them at risk of more adverse outcomes. Some healthcare managers casually assume this erroneous diagnostic method and immediately prescribe malaria drug without proper investigation. The objective of this article is to review the scientific data from studies conducted in the tropics that provided information on malaria and typhoid fever infection in order to assess the challenges associated with diagnosis, manifestations and the management of these important infections in a view to have a better understanding on how to effectively control these infections.