Typhoid Fever in South Africa in an Endemic HIV Setting

Abstract

BackgroundTyphoid fever remains an important disease in Africa, associated with outbreaks and the emerging multidrug resistant Salmonella enterica serotype Typhi (Salmonella Typhi) haplotype, H58. This study describes the incidence of, and factors associated with mortality due to, typhoid fever in South Africa, where HIV prevalence is high.Methods and FindingsNationwide active laboratory-based surveillance for culture-confirmed typhoid fever was undertaken from 2003–2013. At selected institutions, additional clinical data from patients were collected including age, sex, HIV status, disease severity and outcome. HIV prevalence among typhoid fever patients was compared to national HIV seroprevalence estimates. The national reference laboratory tested Salmonella Typhi isolates for antimicrobial susceptibility and haplotype. Unadjusted and adjusted logistic regression analyses were conducted determining factors associated with typhoid fever mortality. We identified 855 typhoid fever cases: annual incidence ranged from 0.11 to 0.39 per 100,000 population. Additional clinical data were available for 369 (46.8%) cases presenting to the selected sites. Among typhoid fever patients with known HIV status, 19.3% (29/150) were HIV-infected. In adult females, HIV prevalence in typhoid fever patients was 43.2% (19/44) versus 15.7% national HIV seroprevalence (P < .001); in adult males, 16.3% (7/43) versus 12.3% national HIV seroprevalence (P = .2). H58 represented 11.9% (22/185) of Salmonella Typhi isolates tested. Increased mortality was associated with HIV infection (AOR 10.7; 95% CI 2.3–50.3) and disease severity (AOR 9.8; 95% CI 1.6–60.0) on multivariate analysis.ConclusionsTyphoid fever incidence in South Africa was largely unchanged from 2003–2013. Typhoid fever mortality was associated disease severity. HIV infection may be a contributing factor. Interventions mandate improved health care access, including to HIV management programmes as well as patient education. Further studies are necessary to clarify relationships between HIV infection and typhoid fever in adults.

The Burden of Typhoid Fever in South Africa: The Potential Impact of Selected Interventions

“…Recent evidence has shown that South Africa has low endemicity for typhoid fever, with an estimated annual incidence rate of culture-confirmed disease of 0.1 cases per 100,000 population, 1 nonetheless, outbreaks occur in vulnerable populations, such as those living in informal settlements or in crowded conditions. 2 , 3 Previous studies have highlighted that 50 years ago, there was a very different pattern of disease, and in parts of the country, typhoid fever was highly endemic, with an estimated blood culture positivity rate of 500 per 100,000.…”

“…9 Secondly, the notification system is supported by a laboratory-based surveillance system, which has been supplemented in part by enhanced surveillance for enteric fever at selected sentinel sites. 1 In addition to confirming each culture-positive case of typhoid fever, this latter system collects information on clinical presentation, antimicrobial susceptibility patterns, and molecular epidemiology of Salmonella enterica serotype Typhi ( Salmonella Typhi) 10 and Salmonella Paratyphi A, Salmonella Paratyphi B, and Salmonella Paratyphi C ( Salmonella Paratyphi) isolates. 11 …”

“… 14 – 16 A recent publication has suggested that excessive mortality may occur in human immunodeficiency virus-infected (HIV) patients in South Africa with typhoid fever but data could not confirm that HIV infection was a risk factor for typhoid fever. 1 …”

“… 11 , 17 In a limited clinical series, collected through the GERMS-enhanced surveillance network (previously an acronym for Group for Enteric Respiratory and Meningeal disease in South Africa [GERMS-SA]), no cases of paratyphoid fever died, 11 although mortality due to typhoid fever remains high. 1 Between 1945 and 1977, the case fatality rate (CFR) due to typhoid fever reportedly decreased from 15.5% to 1.1% but recent laboratory-based surveillance studies between 2003 and 2013 suggested that this mortality may be around 6.8%. 1 …”

“… 1 Between 1945 and 1977, the case fatality rate (CFR) due to typhoid fever reportedly decreased from 15.5% to 1.1% but recent laboratory-based surveillance studies between 2003 and 2013 suggested that this mortality may be around 6.8%. 1 …”