The global burden of typhoid and paratyphoid fever from 1990 to 2021 and the impact on prevention and control | BMC Infectious Diseases

Global burden of typhoid and paratyphoid fevers

For typhoid fever worldwide, there were a total of 7,154,555 new cases in 2021, with 93,333 deaths and a total DALYs of 7,087,733 years. Regarding the trends, all of the incidence, mortality, and DALYs are decreasing from 1990 to 2021. The new cases decreased by 62.12%, with an EAPC of -3.92 (-4.14, -3.71); deaths decreased by 50.65%, EAPC − 2.83 (-2.99, -2.66), and DALYs decreased by 52.30%, EAPC − 2.82 (-3.00, -2.64) (Table 1). The highest incidence of new cases was in the less-than-1-year age group, with an ASR of 319.43 (195.03-472.62). The peaks for deaths and DALYs were also in the less-than-1-year age group, with corresponding ASR values of 6.11 (2.37–12.81) and 549.55 (214.87-1148.46), respectively (Fig. 1, Supplementary Table S1). Regarding sex differences, males had higher overall numbers of incidence, mortality, and DALYs compared to females (Fig. 2). However, the absolute numbers of new cases and DALYs were higher in females when the ages were over 80 years old (Supplementary Table S2).

The distribution of case numbers among different sex and age groups in 2021. (a) that of typhoid incidence; (b) that of typhoid mortality; (c) that of typhoid DALY; (d) that of paratyphoid incidence; (e) that of paratyphoid mortality; (f) that of paratyphoid DALY. (Data in details are listed in Supplementary Table S2.)

For paratyphoid fever, on a global scale, there were a total of 2,166,063 new cases in 2021, with 14,127 deaths and a total DALYs of 1,011,842 years. In terms of case numbers, severity after infection, and mortality, paratyphoid burden is lighter than typhoid burden. From 1990 to 2021, all of the incidence, mortality, and DALYs for paratyphoid fever are also decreasing. New cases decreased by 73.15%, with an EAPC of -4.77 (-5.29, -4.26); deaths decreased by 65.44%, EAPC − 3.74 (-4.24, -3.24), and DALYs decreased by 68.42%, EAPC − 3.87 (-4.42, -3.31) (Table 2), and the decline was greater than that of typhoid fever. Different with typhoid fever, the most common age group for new cases of paratyphoid fever was 2–4 years. But similar to typhoid fever, the peaks for DALYs and deaths were in the less-than-1-year age group, with an ASR of 64.04 (21.65-151.18) and 0.71 (0.24–1.69). (Fig. 1, Supplementary Table S1). Similar to typhoid fever, males had higher rates of incidence, mortality, and DALYs than females overall (Fig. 2). The absolute numbers of new cases, as well as deaths and DALYs, were higher than in females when ages were over 65 years old. Besides, in the age group of 10–14 years old, females have the larger number of deaths and DALYs (Supplementary Table S1 and S2).

Burden of typhoid and paratyphoid fevers by SDI

From 1990 to 2021, all of the globe and different SDI regions have decline trends of both typhoid and paratyphoid fevers, no matter of incidence, mortality or DALYs (Fig. 3). In the Spearman correlation analyses, all of incidence, mortality or DALYs of typhoid and paratyphoid fevers are negatively and significantly correlated to SDI (all P values < 0.001), which means more developed regions tend to have lighter burden. (Fig. 4, Supplementary Table S3) However, low-middle SDI regions seem to have higher ASR values and heavier burden of typhoid and paratyphoid fevers than low SDI regions (Fig. 3). A possible reason is that low SDI regions suffer more from other causes and diseases, and the burden attributing to typhoid and paratyphoid fevers is relatively lighter (but still heavier than middle-to-high SDI regions).

The fitted smooth curves (Fig. 4, Supplementary Table S4) are consistent with this finding, which also displays the specific values of SDI with peak ASRs (i.e. the worst disease burden). For typhoid fever, the SDI value with the highest incidence is 0.317, with the highest mortality is 0.318, and with the highest DALY is 0.326. For paratyphoid fever, the corresponding SDI is 0.388, 0.394, and 0.394, respectively.

The distribution and changes of ASRs in SDI areas from 1990 to 2021. (a) ASR of typhoid incidence; (b) ASR of typhoid mortality; (c) ASR of typhoid DALY; (d) ASR of paratyphoid incidence; (e) ASR of paratyphoid mortality; (f) ASR of paratyphoid DALY

The associations between ASRs and SDI among regions. (a) that of typhoid incidence; (b) that of typhoid mortality; (c) that of typhoid DALY; (d) that of paratyphoid incidence; (e) that of paratyphoid mortality; (f) that of paratyphoid DALY. (Data of scatters are listed in Supplementary Table S3. Data of fitted curves are in Supplementary Table S4.)

Burden of typhoid and paratyphoid fevers by regions

According to Fig. 4, The burden of typhoid fever concentrates on South Asia, Southeast Asia, and Oceania, while only South Asia suffers from paratyphoid fever severely. Regarding the typhoid EAPCs of 21 GBD regions, the majority of regions have decreasing burden following the definition in Method section. However, Australasia (incidence, mortality, and DALYs) and southern Sub-Saharan Africa (mortality and DALYs) have increasing trends, although the incidence of southern Sub-Saharan Africa is decreasing. The trends of deaths and DALYs of high-income North America and central Europe is regarded as stable, because the 95% CIs cross 0, while the incidence trend of central European is decreasing. (Fig. 5a) As comparison, regarding the paratyphoid EAPCs of 21 GBD regions, the increasing trends can be seen in incidence of Australasia and Western Europe, and all three results of high-income North America, and mortality and DALYs of southern Sub-Saharan Africa. Stable findings include all three results of Caribbean areas, deaths and DALYs of Andean Latin America, Eastern Sub-Saharan Africa, Eastern and Western Europe, and incidence of high-income Asia Pacific, Central Europe, and Southern Sub-Saharan Africa. (Fig. 5b)

However, it worths to note that it is the trend of ASRs. Some regions with increasing trends have very small absolute numbers, especially for those high-SDI regions. For example, Australasia and Western Europe have multiple increasing trend results. But the absolute case numbers are small. By contrast, South Asia has significant decreasing trends in all results of both diseases, but the ASRs of South Asia are still apparently higher than other regions. (Fig. 4)

Trends in incidence, mortality, and DALYs in global, SDI areas and geographic regions from 1990 to 2021. (a) typhoid fever; (b) paratyphoid fever.

Burden of typhoid and paratyphoid fevers by countries

The world maps were labeled with colors according to ASRs (Fig. 6, Supplementary Table S5) and EAPCs (Supplementary Figure S1, Supplementary Table S5) of incidence, mortality and DALYs.

Regarding typhoid fever, the top three countries with the highest ASRs of incidence are Burkina Faso (328.48) (SDI: 0.285), Bangladesh (303.14) (SDI: 0.492), and Papua New Guinea (299.45) (SDI: 418) which are in Western Sub-Saharan, South Asia, and Oceania. The top three of mortality and DALYs are Bhutan (5.61; 434.23) (SDI: 0.473) (a country in South Asia), Bangladesh (5.06; 382.38), and Burkina Faso (4.64;352.57). As for absolute numbers, the highest deaths and DALYs were India (SDI: 0.575), Pakistan (SDI: 0.504), and Bangladesh, which are all in South Asia. The highest number of incidences was found in India, Bangladesh, and Philippines (SDI: 0.651) (a country in Southest Asia). As it is found Southeast Asia and Oceania also suffer from typhoid, further comparisons are performed. The top three ASRs of incidence in Oceania are Papua New Guinea (299.45), Palau (182.25) (SDI: 0.754), and Solomon Islands (75.62) (SDI: 0.429). The top three ASRs of mortality in Oceania are Papua New Guinea (4.19;), Tokelau (3.66) (SDI: 0.686), and Niue (2.36) (SDI: 0.726). The top three ASRs of DALYs in Oceania are Tokelau (305.36), Papua New Guinea (303.68), and Niue (195.24). The top three ASRs of incidence in Southeast Asia are Indonesia (183.19) (SDI: 0.657), Timor-Leste (172.59) (SDI: 0.445), and Laos (157.19) (SDI: 0.489). The top three ASRs of mortality and DALYs in Southeast Asia are Indonesia (2.41; 177.66), Myanmar (2.13; 161.27) (SDI: 0.534), and Timor-Leste (2.09; 154.96).

Regarding paratyphoid fever, the top three countries with the highest ASRs of mortality and DALYs are the same, which are Pakistan (1.05; 72.66), India (0.75; 53.42) and Nepal (0.72; 50.65) (SDI: 0.433), which are all in South Asia. The top three countries with the highest ASRs of incidence rank as India (124.45), Pakistan (114.69), and Nepal (98.33) (Fig. 6).

The distribution of ASRs at the national level in 2021. (a) ASR of typhoid incidence; (b) ASR of typhoid mortality; (c) ASR of typhoid DALY; (d) ASR of paratyphoid incidence; (e) ASR of paratyphoid mortality; (f) ASR of paratyphoid DALY