Decades of research have proven that typhoid prevention and control solutions are efficacious and yield health impact. Ongoing global research continues to build our strong knowledge base, but there is still more we need to know to continue efforts to #TakeOnTyphoid.
What we know
Typhoid disproportionately affects children and adolescents in low- and middle-income countries. The Global Burden of Disease Study estimates more than 9 million cases of typhoid and more than 110,000 typhoid-related deaths worldwide in 2019, largely concentrated in South Asia and sub-Saharan Africa. However, the burden is thought to be underestimated given diagnostic challenges and difficulties with surveillance.
Increasing drug resistance is a persistent threat. While typhoid can be treated successfully with appropriate antibiotics, the rate of cases resistant to available treatments is increasing globally. Resistance to newer, more efficacious antibiotics for typhoid is becoming more prevalent, particularly in low- and middle-income countries where accurate diagnosis and treatment are difficult.
Typhoid is preventable. The best way to take on typhoid is through an integrated prevention and treatment approach including typhoid conjugate vaccines (TCVs); improvements in water, sanitation, and hygiene (WASH); improved typhoid diagnostics; and appropriate antibiotics. We currently have two World Health Organization prequalified TCVs: Typbar TCV® manufactured by Bharat Biotech, India, and TYPHIBEV manufactured by Biological E, India. Interim results from a Phase 3 study in Nepal found Typbar TCV to be safe and efficacious in an endemic setting, preventing over 81 percent of typhoid cases in vaccinated children. Results from a Phase 2/3 study in India found TYPHIBEV to be safe and immunogenic, with an immune response profile similar to that of Typbar TCV.
What we’re learning
Surveillance: Typhoid is more prevalent than originally thought. Surveillance studies aim to create an accurate, comprehensive estimate of the global burden of typhoid. Continued surveillance enables us to gather better data to inform vaccine programs, as well as monitor drug resistance and new or ongoing outbreaks.
Past and ongoing surveillance studies include:
- The Typhoid Surveillance in Africa Project (TSAP), which has concluded. The project identified a much larger burden in sub-Saharan Africa than previously understood.
- Following TSAP, several multi-country, multi-phase surveillance studies are currently being conducted in Asia and sub-Saharan Africa, including the Surveillance of Enteric Fever in Asia Project (SEAP) and the Severe Typhoid Fever Surveillance in Africa (SETA) Program.
In addition to morbidity and mortality data, these studies will provide information on risk factors, socioeconomic impact, and the long-term implications of typhoid.
Diagnosis: Typhoid diagnosis is best confirmed through blood or bone marrow cultures, which require laboratory equipment and are difficult in low-resource settings. Without access to laboratory equipment, typhoid tends to be diagnosed based on clinical symptoms, which can be mistaken for malaria, influenza, pneumonia, and other febrile illnesses. New research and development for more reliable point of care diagnostic tests will help improve diagnoses, reduce over-prescription of antibiotics, and increase accuracy of disease burden estimates.
Prevention with vaccines: The Typhoid Vaccine Acceleration Consortium (TyVAC) works with governments in low- and middle-income countries to introduce vaccine solutions in high-burden typhoid areas. TyVAC is leading research to assess existing data and generate new evidence related to typhoid disease burden, drug resistance, vaccine cost-effectiveness, health impact analyses, and TCVs. TyVAC is conducting clinical studies with Typbar TCV in Bangladesh, Burkina Faso, Malawi, and Nepal, as well as performing country-level analyses to understand the economics behind vaccine rollouts and inform national decision-makers.
TCVs have the potential to overcome many of the challenges that impeded uptake of earlier vaccines, including longer-lasting protection*, fewer doses, and suitability for children younger than two years of age, allowing for inclusion in routine childhood immunization programs. In 2018, the World Health Organization recommended that typhoid-endemic countries introduce prequalified TCVs into routine childhood immunization programs as a single dose for infants and children older than 6 months of age, accompanied by catch-up vaccination campaigns for children up to 15 years of age, where feasible. Pakistan began a phased national introduction of TCV in Sindh Province in November 2019 with nearly 10 million children vaccinated during a three-week campaign. Pakistan will continue with its phased introduction until the vaccine is available nationally for all children at nine months of age. Liberia and Zimbabwe also plan to introduce TCV into their routine childhood immunization programs in 2021.
Monitoring drug resistance: Monitoring the spread and patterns of drug-resistant typhoid is important to inform effective prevention and control efforts. In 2015, the World Health Assembly endorsed a global action plan to tackle drug resistance that focuses on prevention, surveillance, and research. The Wellcome Trust and current surveillance projects including SEAP and SETA are conducting research to identify typhoid drug resistance trends and monitor antibiotic use across Asia and Africa.
*Interim data from ongoing TyVAC studies indicate protection greater than two years.
Photo: PATH/Will Boase