Typhoid fever among febrile Nigerian patients: Prevalence, diagnostic performance of the Widal test and antibiotic multi-drug resistance

BACKGROUND: Over-dependence on clinical presentation and/or the Widal agglutination test for the diagnosis of typhoid fever in developing countries can lead to antibiotic abuse. In Nigeria, the antibiotic resistance of typhoid organisms is poorly characterized. In this study, we determined the prevalence of culture positivity among patients suspected of having typhoid fever, evaluated the diagnostic value of the Widal test and the burden created by the multi-drug resistance of typhoid organisms in South-East Nigeria. METHODOLOGY: This was a prospective and case-controlled study carried out between 2013 and 2016. We acquired samples of blood/stool/urine cultures, and data relating to the Widal agglutination test and malaria parasites from 810 febrile patients (suspected of having typhoid) and 288 apparently healthy controls. Individuals with a history of antibiotic use within the previous 14 days were excluded. We then carried out antibiotic susceptibility tests on all isolates. Multi-drug resistance was defined as a resistance to ≥3 of the antibiotics tested. We determined the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of Widal test for typhoid laboratory diagnosis compared to bacterial culture which is the gold standard. A P-value <0.05 was considered to be statistically significant. RESULTS: The mean age of typhoid suspects was 33.1±6.5 years and 50.7% were women. Of the 810 typhoid suspects tested, 114 (14.1%) had positive cultures for the typhoid organisms Salmonella enterica serovar paratyphi (72) and S. enterica serovar Typhi (42). Sample-specific rates of culture positivity were as follows: stool (72; 8.9%), blood (21; 2.6%) and urine (21; 2.6%), P<0.001. None of the controls had typhoid isolates. The sensitivity, specificity, PPV and NPV of the Widal test were 49.1%, 90.7%, 46.2% and 91.6%, respectively. Malaria parasitaemia was detected in 180 (22.2%) febrile patients, out of whom 115 (63.9%) had a positive Widal test for O/H antigens vs. 1% (6/630) in those with negative malaria parasite test results (P<0.001). The rate of false-positive Widal titres was 48%. Antibiotic multi-drug resistance was detected in 52.6% of patients. The antibiotics with the highest susceptibility were ciprofloxacin, levofloxacin and meropenem (all 100% susceptibility) and ceftriaxone (95.6% susceptibility). CONCLUSION: Our data showed that while typhoid fever is common in Nigeria, malaria is more prevalent. Our analysis showed that the Widal test performed poorly as a diagnostic test and that the burden created by multi-drug resistance was high. Our data indicate that periodic surveillance of antibiotic susceptibility is critical for optimal typhoid therapy.