Human hookworm infection in the 21st century

Abstract

The scientific study of human hookworm infection began at the dawn of the twentieth century. In recent years, there have been dramatic improvements in our understanding of many aspects of this globally widespread parasite. This chapter reviews recent advances in our understanding in the biology, immunology, epidemiology, public health significance and control of hookworm, and to look forward to the study of this important parasite in the 21st century. Advances in molecular biology has lead to the identification of a variety of new molecules from hookworms, which have importance either in the molecular pathogenesis of hookworm infection or in the host-parasite relationship; some are also promising vaccine targets. At present, relatively little is known about the immune responses to hookworm infection, although it has recently been speculated that hookworm and other helminths may modulate specific immune responses to other pathogens and vaccines. Our epidemiological understanding of hookworm has improved through the development of mathematical models of transmission dynamics, which coupled with decades of field research across multiple epidemiological settings, have shown that certain population characteristics can now be recognised as common to the epidemiology, population biology and control of hookworm and other helminth species. Recent recognition of the subtle, but significant, impact of hookworm on health and education, together with the simplicity, safety, low cost and efficacy of chemotherapy has spurred international efforts to control the morbidity due to infection. Large-scale treatment programmes are currently underway, ideally supported by health education and integrated with the provision of improved water and sanitation. There are also on-going efforts to develop novel anthelmintic drugs and anti-hookworm vaccines.

Figure 1

(a) Typical age-prevalence profiles of hookworm and other STH. Data from Bundy (1988a) and Behnke et al. (2000) (females only). (b) Recent age-prevalence data from China (Lili et al., 2000; Gandi et al., 2001; Bethony et al., 2002a)

Figure 2

The relationship between host age and mean N. americanus worm burden obtained by anthelmintic expulsion: India (Haswell-Elkins et al., 1988), Papua New Guinea (Pritchard et al., 1990), Zimbabwe (Bradley et al., 1991), Puerto Rico (Hill, 1926) and China (Ye et al., 1994). No comparable data are currently available for A. duodenale (Bundy & Keymer, 1991).

Figure 3

Frequency distribution of differences in the prevalence of infection between male and female school-aged children for (a) A. lumbricoides, (b) T. trichiura, and (c) hookworm. Analysis follows that used by Poulin (1996) who employed a fixed effects meta-analysis. In brief, differences in prevalence were calculated using the following formula: $$(p_f-p_m)\left(J\right),\text{where}J=1-\frac{3}{4(N_f+N_m-2)-1}$$ which is the difference between prevalence in females (P_f) and that in males (P_m) weighted by a correction for small sample sizes (J). If there is no sex bias in levels of infection, differences in prevalence expected to be normally distributed around a mean of zero. Frequency distributions of differences were compared with χ² test. Values to the left of the line represent indicate higher prevalence in males, and values to the right indicate higher prevalence in females. Data sources available from authors.

Figure 4

The geographical distribution of hookworm in Cameroon (18,260 schoolchildren in 402 schools) and Uganda (13,378 children in 235 schools). Data source: Ratard et al., (1992); Brooker et al., in press).

Figure 5

Proportion of Zanzibari (aged 30 months or greater) and Kenyan (aged 6-76 months) pre-schoolchildren with severe anaemia (Hb<80 g/L) by hookworm egg counts. Taken from Brooker et al. (1999) and Stoltfuz et al. (2000) Chi-square test for trends of association were p=0.007 and p=0.0002, respectively.

Figure 6

The ways which intestinal nematodes may affect either (a) current productivity through causing anaemia and undernutrition or (b) future potential productivity mediated anaemia and undernutrition and their effect on cognitive function and school performance. The link between cognitive function and productivity is less clear (as indicated by dashed line). Taken from Guyatt (2000).

Figure 7

Map showing the global distribution of hookworm. Taken from a global WHO update by de Silva et al. (2003), which included 494 publications from 1990 onward reporting community-based studies incorporating data from 112 countries.

Figure 8

Intensity of hookworm infection at multiple sampling rounds following initial treatment.