High incidences of typhoid and invasive Salmonella infection confirmed in sub-Saharan Africa

2017-02-27 07:17
- Findings of IVI-led study in 10 African countries published in The Lancet Global Health

- High disease burden findings support the introduction of typhoid conjugate vaccines in high-incidence settings

February 27, 2017 - An IVI-led study found that typhoid fever and invasive non-typhoidal Salmonella (iNTS) disease are major causes of invasive bacterial febrile illness in some African countries, and they most commonly afflict children in low and high population density settings.

Large variations exist in the disease burden of Salmonella Typhi and non-typhoidal Salmonella in sub-Saharan Africa, with rates of disease reaching as high as 383 per 100,000 persons per years (PY) for S. Typhi and 237 per 100,000 PY for iNTS disease in Burkina Faso. A rate of more than 100 per 100,000 is considered “high” as defined by the World Health Organization (WHO). Typhoid was found in both infants and school-age children, with a higher incidence in children below 15 years old, according to the study recently published in The Lancet Global Health.

The varying incidence of disease-causing Salmonella suggests a complex epidemiology and a highly diverse disease distribution pattern in sub-Saharan Africa. Worryingly, significant levels of multidrug resistance were found in S. Typhi and iNTS strains in several settings. The findings support the rationale for the development and deployment of new vaccines against typhoid and iNTS disease.

“The development of iNTS vaccines and the introduction of S. Typhi conjugate vaccines currently under clinical development should be considered for high-incidence settings, such as those identified in this study,” said Dr. Florian Marks, IVI senior scientist and lead investigator of the study.

Typhoid fever is a relatively common disease in many low- and middle-income countries where clean water and basic sanitation facilities are scarce. The disease is characterized by chronic fever that can lead to serious complications including intestinal perforation or neurological problems if untreated. It is estimated there are more than 20 million cases of invasive Salmonella infections globally, most of which are caused by S. Typhi, and 200,000 to 600,000 deaths per year.

While previous evidence suggested typhoid is a public health problem in Africa, there was limited scientific data to back up those claims. Consequently, IVI, with a network of partners, conducted the Typhoid Fever Surveillance in Africa Program (TSAP), the first multi-country population-based typhoid surveillance study in Africa. TSAP, which ran from 2011 to 2014, aimed to measure the incidence of typhoid fever and iNTS disease in sub-Saharan Africa, as well as the antimicrobial susceptibility of these causative agents. The program was funded by the Bill & Melinda Gates Foundation.

IVI established a standardized surveillance network for invasive bacterial bloodstream infections consisting of 13 field sites in ten sub-Saharan African countries. Blood cultures were conducted on a total of 13,431 febrile patients. The study found the incidence rates of S. Typhi ranged from 0 per 100,000 person-years in Sudan to 383 per 100,000 PY in Burkina Faso; while the incidence of iNTS ranged from 0 in Sudan, Ethiopia, Madagascar, and South Africa to 237 per 100,000 in Burkina Faso. The Salmonella spp. strain accounted for 33% or more of all bacterial pathogens at nine sites.

Multidrug-resistant S. Typhi was isolated at sites in Ghana, Kenya, and Tanzania, and multidrug-resistant iNTS was isolated at sites in Burkina Faso, Ghana, Kenya, and Guinea-Bissau.

“A key challenge is to determine how useful an efficacious vaccine might be in low to middle-income countries, where the levels of disease vary so greatly between different regions. Such studies might be pivotal to facilitate the deployment of such vaccines,” Prof. Gordon Dougan of the Wellcome Trust Sanger Institute said in his comment in The Lancet Global Health. “The changing epidemiological pattern, the emergence of a potentially more aggressive multidrug resistant strains, and the likelihood of increased antibiotic usage in communities affected by the disease are creating a sense of urgency (for the development and subsequent deployment of vaccines).”

Building upon these findings, IVI scientists are currently investigating severe typhoid cases in Africa by collecting additional information such as long-term manifestations of illness and socio-economic burden. This new program, Severe Typhoid in Africa (SETA), is also funded by the Bill & Melinda Gates Foundation. Such novel evidence will help strengthen the case for disease prevention and control measures, including the development and introduction of new vaccines.