High burden of typhoid disease in sub-Saharan Africa calls for urgent roll-out of typhoid conjugate vaccines
Authors: Samuel Kariuki, Robert S Onsare
Journal: The Lancet Global Health (2024)

By 2019, there were an estimated 9·24 million cases of typhoid fever and 110 000 deaths globally, with the greatest burden being in low-income and middle-income countries in sub-Saharan Africa and Asia1Stanaway JD Reiner RC Blacker BF et al.The global burden of typhoid and paratyphoid fevers: a systematic analysis for the Global Burden of Disease Study 2017.Lancet Infect Dis. 2019; 19: 369-381Summary Full Text Full Text PDF PubMed Scopus (384) Google Scholar where poor sanitation and a lack of safe drinking water, the primary modes of transmission, are common.2Meiring JE Khanam F Basnyat B et al.Typhoid fever.Nat Rev Dis Primers. 2023; 9: 71Crossref Scopus (1) Google Scholar If not treated promptly, complications such as intestinal perforation or neurological problems can arise with severe sequelae.3Marchello CS Birkhold M Crump JA Complications and mortality of typhoid fever: a global systematic review and meta-analysis.J Infect. 2020; 81: 902-910Summary Full Text Full Text PDF PubMed Scopus (26) Google Scholar Diagnosis of typhoid is difficult in low-resource settings due to limited adequate laboratory infrastructure, and clinical presentation can be non-specific and inconclusive. Commonly available rapid diagnostic kits are usually unreliable, and microbiological testing is required to confirm a diagnosis, with blood and bone marrow cultures considered the gold standard.4Sapkota J Hasan R Onsare R et al.Comparative analysis of commercially available typhoid point-of-care tests: results of a prospective and hybrid retrospective multicenter diagnostic accuracy study in Kenya and Pakistan.J Clin Microbiol. 2022; 60e0100022Crossref Scopus (5) Google Scholar However, blood cultures are expensive, have low sensitivity, and are not adequate for rapid patient management. These challenges add to the paucity of typhoid incidence data in endemic settings in sub-Saharan Africa. While typhoid can be effectively treated with antibiotics, the emergence of multidrug resistance in the past decade adds to the challenges of the management of infections.5Kariuki S Dyson ZA Mbae C et al.Multiple introductions of multidrug-resistant typhoid associated with acute infection and asymptomatic carriage, Kenya.eLife. 2021; 10e67852Crossref PubMed Scopus (13) Google Scholar The main multidrug-resistance epidemic strain, Salmonella enterica serovar Typhi (S Typhi) haplotype 58 or lineage 4.3.1, has been linked to the widespread transmission of typhoid, and coupled with climate change, might be driving the disease into new geographical areas.5Kariuki S Dyson ZA Mbae C et al.Multiple introductions of multidrug-resistant typhoid associated with acute infection and asymptomatic carriage, Kenya.eLife. 2021; 10e67852Crossref PubMed Scopus (13) Google Scholar, 6Wong VK Baker S Pickard DJ et al.Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events.Nat Genet. 2015; 47: 632-639Crossref PubMed Scopus (312) Google Scholar Thus, short-term to medium-term control of typhoid through vaccination could be the best strategy for reducing disease burden in endemic populations. New generation typhoid vaccines, based on conjugate technology and the Vi capsular antigen of S Typhi have been developed, licensed, and used in some countries. It is against this backdrop of limited epidemiological information on typhoid in Africa that the Severe Typhoid in Africa (SETA) programme, funded by the Bill & Melinda Gates Foundation and covering six countries—Burkina Faso, the Democratic Republic of the Congo, Ethiopia, Ghana, Madagascar, and Nigeria—was carried out between May, 2016, and May, 2020. In this issue of The Lancet Global Health, Florian Marks and colleagues7Marks F Im J Park SE et al.Incidence of typhoid fever in Burkina Faso, Democratic Republic of the Congo, Ethiopia, Ghana, Madagascar, and Nigeria (the Severe Typhoid in Africa programme): a population-based study.Lancet Glob Health. 2024; 12: e599-e610Google Scholar present the results of this study, which used a hybrid design—hospital-based prospective surveillance with population-based health-care utilisation surveys—to provide an estimate of severe typhoid in the six sub-Saharan African countries. Findings from this study indicated that typhoid fever remains a major cause of differentiated febrile illness, with incidence rates being more than 100 cases per 100 000 person-years of observation, with the Democratic Republic of the Congo and Madagascar bearing the highest burden. The study also identified the highest burden of typhoid as being in rural settings, consistent with the previous Typhoid Fever Surveillance in Africa Program studies. This finding contrasts with the trend in Asia where typhoid burden is highest in impoverished populations in densely populated urban areas. The study also reported that typhoid incidence was highest in children younger than 15 years across the sites. The number of suspected typhoid intestinal perforations was also high, particularly in the Democratic Republic of the Congo and Ghana, suggesting that a substantial proportion of typhoid infections could be undiagnosed and untreated. The high disease incidence recorded in four countries, the high prevalence of typhoid hospitalisations and complicated disease, and the threat of multidrug resistant S Typhi strains call for the urgent use of effective typhoid conjugate vaccines (TCV) in sub-Saharan Africa, along with measures designed to improve clean water, sanitation, and hygiene practices. Several countries including Malawi, Pakistan, Liberia, Zimbabwe, and Nepal have introduced TCV into routine immunisation, leading to the prevention of a huge burden of typhoid disease. New epidemiological data on typhoid disease and evidence of its high burden in sub-Saharan Africa has been reported from studies of TCV implementation through the Typhoid Vaccine Acceleration Consortium and the TCV Introduction in Africa programme, with evidence of high efficacy and protection. The key message is for typhoid control programmes to prioritise TCV introduction in endemic settings while undertaking further research for optimal vaccine delivery strategies. A possible challenge for rolling out TCV is to determine usefulness in low-income and middle-income countries, where disease burden varies greatly by region, and between urban and rural settings. There is also a paucity of data on cost-effectiveness and economic value of TCV use in these settings—these data will be a strong motivation for more countries to introduce TCV as an effective intervention in high burden settings. Recent data from Malawi, where a single dose of vaccine was efficacious for at least 4 years even among children aged 9 months to 12 years, strengthens the case for adoption of TCV.8Patel PD Liang Y Meiring JE et al.Efficacy of typhoid conjugate vaccine: final analysis of a 4-year, phase 3, randomised controlled trial in Malawian children.Lancet. 2024; 403: 459-468Summary Full Text Full Text PDF PubMed Google Scholar Outstanding questions remain on how the burden of typhoid varies from poor rural settings to congested urban informal settlements and whether risk factors are different. Are the available data adequate to persuade health policy makers to adopt TCV use more widely? A recent study in Malawi9Liang Y Driscoll AJ Patel PD et al.Typhoid conjugate vaccine effectiveness in Malawi: evaluation of a test-negative design using randomised, controlled clinical trial data.Lancet Glob Health. 2023; 11: e136-e144Summary Full Text Full Text PDF PubMed Scopus (7) Google Scholar showed that the test-negative design is suitable for assessing TCV effectiveness in post-introduction studies using blood culture surveillance. Such studies might be pivotal in generating more data to facilitate the deployment of TCV. We declare no competing interests. Incidence of typhoid fever in Burkina Faso, Democratic Republic of the Congo, Ethiopia, Ghana, Madagascar, and Nigeria (the Severe Typhoid in Africa programme): a population-based studyHigh disease incidence (ie, >100 per 100 000 person-years of observation) recorded in four countries, the prevalence of typhoid hospitalisations and complicated disease, and the threat of resistant typhoid strains strengthen the need for rapid dispatch and implementation of effective typhoid conjugate vaccines along with measures designed to improve clean water, sanitation, and hygiene practices. Full-Text PDF Open Access