The extent, nature, and pathogenic consequences of helminth polyparasitism in humans: A meta-analysis

Abstract

Background: Individual helminth infections are ubiquitous in the tropics; geographical overlaps in endemicity and epidemiological reports suggest areas endemic for multiple helminthiases are also burdened with high prevalences of intestinal protozoan infections, malaria, tuberculosis (TB), and human immunodeficiency virus (HIV). Despite this, pathogens tend to be studied in isolation, and there remains a need for a better understanding of the community ecology and health consequences of helminth polyparasitism to inform the design of effective parasite control programs.

Methodology: We performed meta-analyses to (i) evaluate the commonality of polyparasitism for helminth-helminth, helminth-intestinal protozoa, helminth-malaria, helminth-TB, and helminth-HIV co-infections, (ii) assess the potential for interspecies interactions among helminth-helminth and helminth-intestinal protozoan infections, and (iii) determine the presence and magnitude of association between specific parasite pairs. Additionally, we conducted a review of reported health consequences of multiply-infected individuals compared to singly- or not multiply-infected individuals.

Principal findings: We found that helminth-helminth and helminth-intestinal protozoan multiple infections were significantly more common than single infections, while individuals with malaria, TB, and HIV were more likely to be singly-infected with these infections than co-infected with at least one helminth. Most observed species density distributions significantly differed from the expected distributions, suggesting the potential presence of interspecies interactions. All significant associations between parasite pairs were positive in direction, irrespective of the combination of pathogens. Polyparasitized individuals largely exhibited lower hemoglobin levels and higher anemia prevalence, while the differences in growth-related variables were mostly statistically insignificant.

Conclusions: Our findings confirm that helminth polyparasitism and co-infection with major diseases is common in the tropics. A multitude of factors acting at various hierarchical levels, such as interspecies interactions at the within-host infra-parasite community level and environmental variables at the higher host community level, could explain the observed positive associations between pathogens; there remains a need to develop new frameworks which can consider these multilevel factors to better understand the processes structuring parasite communities to accomplish their control.

Fig 1. Flowchart of study selection process.

Fig 2. Forest plot of the mean community prevalence difference between humans infected with multiple helminth infections compared to humans infected with a single helminth infection.

RE = random effects.

Fig 3

Summary effect sizes and 95% confidence interval plots of (a) the mean prevalence difference between polyparasitized and monoparasitized human hosts with helminth-helminth, helminth-intestinal protozoa, helminth malaria, helminth-HIV, and helminth-TB infections and (b) the proportion of malaria-, HIV- and TB-infected individuals concurrently infected with at least 1 helminth. Open circles indicate studies evaluated community-based differences in prevalence between multiply- and singly- infected individuals, while closed circles indicate studies evaluated the difference in prevalence between helminth co-infected and singly infected malaria, HIV, and TB positive individuals only, respectively. An asterisk denotes statistical significance at the 5% level.

Fig 4. Random-effects univariate meta-regression between publication year and the mean difference between helminth-polyparasitized and helminth-monoparasitized individuals.

Each circle represents a study and the circle size is representative of its weight (inversely proportional to the variance of that study) in the meta-regression analysis. The solid line indicates the regression prediction (coefficient -0.008 [95% CI -0.017–0.001], p = 0.072). The dashed line indicates an equal number of polyparasitized and monoparasitized individuals in the study, while study estimates above or below zero indicate a greater or lesser number of polyparasitized individuals when compared to monoparasitized individuals, respectively.

Fig 5

Number of studies finding fewer or greater individuals harboring the specified number of parasites compared to the expected number of individuals calculated using the Janovy null model for (a) helminth-only studies and (b) helminth-intestinal protozoa studies.

Fig 6. Forest plot of the association between A. lumbricoides and hookworm infections stratified by studies reporting unadjusted and adjusted odds ratios.

a = AL+/HW+; b = AL+/HW-; c = AL-/HW+; d = AL-/HW-; RE = random effects. Odds ratio compares the odds of A. lumbricoides infection among hookworm-positive individuals (a/c) to the odds of A lumbricoides infection among hookworm-negative individuals (b/d).

Fig 7. Forest plots for the meta-analyses comparing the association between the helminth infections A. lumbricoides, hookworm, T. trichiura, S. stercoralis, S. mansoni and HIV infection.

FE = fixed effects; RE = random effects.

Fig 8. Forest plots for the meta-analyses comparing the association between the helminth infections A. lumbricoides, hookworm, S. stercoralis and tuberculosis (TB) infection.

FE = fixed effects; RE = random effects.

Fig 9

Direction of reported health outcomes of helminth co-infections for (a) hemoglobin levels, (b) anemia prevalence, and (c) growth-related variables. Horizontal line indicates expected value assuming the null hypothesis of equal proportions.