Host-Parasite Interactions Promote Disease Tolerance to Intestinal Helminth Infection.

Parasitic helminths are among the most pervasive pathogens of the animal kingdom. To complete their life cycle, these intestinal worms migrate through host tissues causing significant damage in their wake. As a result, infection can lead to malnutrition, anemia and increased susceptibility to co-infection. Despite repeated deworming treatment, individuals living in endemic regions remain highly susceptible to re-infection by helminths, but rarely succumb to excessive tissue damage. The chronicity of infection and inability to resist numerous species of parasitic helminths that have co-evolved with their hosts over millenia suggests that mammals have developed mechanisms to tolerate this infectious disease. Distinct from resistance where the goal is to destroy and eliminate the pathogen, disease tolerance is an active process whereby immune and structural cells restrict tissue damage to maintain host fitness without directly affecting pathogen burden. Although disease tolerance is evolutionary conserved and has been well-described in plant systems, only recently has this mode of host defense, in its strictest sense, begun to be explored in mammals. In this review, we will examine the inter- and intracellular networks that support disease tolerance during enteric stages of parasitic helminth infection and why this alternative host defense strategy may have evolved to endure the presence of non-replicating pathogens and maintain the essential functions of the intestine.

Epidemiology of soil-transmitted helminthiases-related mortality in Brazil.

Soil-transmitted helminth (STH) infections are widely distributed in tropical and subtropical areas, including Brazil. We performed a nationwide population-based study including all deaths in Brazil from 2000 to 2011, in which STHs (ascariasis, trichuriasis and/or hookworm infection) were mentioned on death certificates, either as underlying or as associated causes of death. Epidemiological characteristics, time trends and spatial analysis of STH-related mortality were analysed. STHs was identified on 853/12 491 280 death certificates: 827 (97·0%) deaths related to ascariasis, 25 (2·9%) to hookworm infections, and 1 (0·1%) to trichuriasis. The average annual age-adjusted mortality rate was 0·34/1 000 000 inhabitants (95% confidence interval: 0·27-0·44). Females, children <10 years of age, indigenous ethnic groups and residents in the Northeast region had highest STH-related mortality rates. Nationwide mortality decreased significantly over time (annual percent change: -5·7%; 95% CI: -6·9 to -4·4), with regional differences. We identified spatial high-risk clusters for STH-related mortality mainly in the North, Northeast and South regions. Diseases of the digestive system and infectious/parasitic diseases were the most commonly associated causes of death mentioned in the STH-related deaths. Despite decreasing mortality in Brazil, a considerable number of deaths is caused by STHs, with ascariasis responsible for the vast majority. There were marked regional differences, affecting mainly children and vulnerable populations.

ACANTHOCEPHALANS PROSTHENORCHIS CF. ELEGANS (ARCHIACANTHOCEPHALA: OLIGACANTHORHYNCHIDAE), PARASITES OF PRIMATES IN THE MOSCOW ZOO.

Acanthocephalans Prosthenorchis cf. elegans were found in primates in the Moscow Zoo. The larvae of these parasites (cistacanths) were found in cockroaches Blattella germanica that had been captured near aviaries of infected animals. Descriptions and drawings of adult parasites and their larvae are given. Analysis of Prosthenorchis cf. elegans genes ITS 1 rDNA and CO 1 mtDNA shows phylogenetic relations of these parasites with several representatives of the class Archiacanthocephala. The obtained molecular data, however, do not support the monophyly of the family Oligacanthorhynchidae and the order Oligacanthorhynchida.

A review of mortality from parasitic and vector-borne diseases in the U.S. Air Force from 1970 to 2012.

We review a unique set of documents, death certificates, cataloged in the U.S. Air Force Mortality Registry database, which tracks deaths for all current and retired service members. We screened the records for all deaths caused by parasitic, vector-borne, or zoonotic diseases between 1970 and 2013. There were 78 deaths caused by a variety of diseases such as amebiasis, malaria, strongyloidiasis, schistosomiasis, and pneumocystosis. We compare these deaths to U.S. national deaths. U.S. Air Force service members are more likely to die from malaria, strongyloidiasis, and Q fever than the average American but are less likely to die from pneumocystosis.

Population deworming every 6 months with albendazole in 1 million pre-school children in North India: DEVTA, a cluster-randomised trial.

BACKGROUND: In north India many pre-school children are underweight, many have intestinal worms, and 2-3% die at ages 1·0-6·0 years. We used the state-wide Integrated Child Development Service (ICDS) infrastructure to help to assess any effects of regular deworming on mortality. METHODS: Participants in this cluster-randomised study were children in catchment areas of 8338 ICDS-staffed village child-care centres (under-5 population 1 million) in 72 administrative blocks. Groups of four neighbouring blocks were cluster-randomly allocated in Oxford between 6-monthly vitamin A (retinol capsule of 200,000 IU retinyl acetate in oil, to be cut and dripped into the child's mouth every 6 months), albendazole (400 mg tablet every 6 months), both, or neither (open control). Analyses of albendazole effects are by block (36 vs 36 clusters). The study spanned 5 calendar years, with 11 6-monthly mass-treatment days for all children then aged 6-72 months. Annually, one centre per block was randomly selected and visited by a study team 1-5 months after any trial deworming to sample faeces (for presence of worm eggs, reliably assessed only after mid-study), weigh children, and interview caregivers. Separately, all 8338 centres were visited every 6 months to monitor pre-school deaths (100,000 visits, 25,000 deaths at age 1·0-6·0 years [the primary outcome]). This trial is registered at ClinicalTrials.gov, NCT00222547. FINDINGS: Estimated compliance with 6-monthly albendazole was 86%. Among 2589 versus 2576 children surveyed during the second half of the study, nematode egg prevalence was 16% versus 36%, and most infection was light. After at least 2 years of treatment, weight at ages 3·0-6·0 years (standardised to age 4·0 years, 50% male) was 12·72 kg albendazole versus 12·68 kg control (difference 0·04 kg, 95% CI -0·14 to 0·21, p=0·66). Comparing the 36 albendazole-allocated versus 36 control blocks in analyses of the primary outcome, deaths per child-care centre at ages 1·0-6·0 years during the 5-year study were 3·00 (SE 0·07) albendazole versus 3·16 (SE 0·09) control, difference 0·16 (SE 0·11, mortality ratio 0·95, 95% CI 0·89 to 1·02, p=0·16), suggesting absolute risks of dying between ages 1·0 and 6·0 years of roughly 2·5% albendazole versus 2·6% control. No specific cause of death was significantly affected. INTERPRETATION: Existing ICDS village staff can be organised to deliver simple pre-school interventions sustainably for many years at low cost, but regular deworming had little effect on mortality in this lightly infected pre-school population. FUNDING: UK Medical Research Council, USAID, World Bank (albendazole donated by GlaxoSmithKline).

Worms, wisdom, and wealth: why deworming can make economic sense.

For those of us who have had worms, getting rid of them seems a good idea, and multiple studies demonstrate the simplicity and benefit of deworming children. In the past decade or so, there has been a dramatic increase in efforts to provide inexpensive deworming medications, but at the same time there have been calls to re-evaluate the impact of deworming programs. In this review, we examine the history of deworming and explore the evidence for effects of deworming on health, on child development, and on economic returns. Important policy conclusions include that a paucity of randomized trial data suggesting benefit does not equate to a lack of benefit and that a greater emphasis on documenting such benefit should be pursued.

From morbidity control to transmission control: time to change tactics against helminths on Unguja Island, Zanzibar.

In Zanzibar, the prevalence and intensity of helminth infections have markedly declined over the past 25 years, which is generally attributed to morbidity control programmes emphasising 'preventive chemotherapy'. Here we provide an update of the current situation of soil-transmitted helminthiasis and urinary schistosomiasis on Unguja Island, and highlight socioeconomic development, improvement in sanitation and health education as additional drivers against helminthiases. Our data were obtained from cross-sectional surveys carried out between 2006 and 2009 with stool and urine samples from 2858 and 879 individuals, respectively, examined for helminth eggs and larvae. Additionally, several hundred people were interviewed on sanitation and hygienic behaviour. Data on Unguja's economic growth and improvements in access to clean water and household latrines in the recent past were derived from the extant literature. Pooled prevalences of Trichuris trichiura, Schistosoma haematobium, Ascaris lumbricoides, hookworm and Strongyloides stercoralis were 35%, 29%, 12%, 10% and 6%, respectively. However, there were considerable differences in prevalences between different age-groups and at village and district level. Moreover, some hotspots for A. lumbricoides, T. trichiura and S. haematobium were identified with prevalences above 60% among school-aged children. Availability of a latrine and washing hands before eating did not significantly lower the risk of helminth infections in our study population. Nevertheless, a considerable increase in access to household latrines (from 49% to 72%) and piped water (from 45% to 71%) between 1991 and 2005 is likely to have contributed to reducing the force of transmission of helminthiases in Zanzibar. The next logical step in Unguja is to change the tactics from morbidity control to interruption of helminth transmission and ultimately local elimination. Hence, 'preventive chemotherapy' needs to be further consolidated, placing particular emphasis on health education and improved access to clean water and sanitation.

The nature and consequences of coinfection in humans.

OBJECTIVE: Many fundamental patterns of coinfection (multi-species infections) are undescribed, including the relative frequency of coinfection by various pathogens, differences between single-species infections and coinfection, and the burden of coinfection on human health. We aimed to address the paucity of general knowledge on coinfection by systematically collating and analysing data from recent publications to understand the types of coinfection and their effects. METHODS: From an electronic search to find all publications from 2009 on coinfection and its synonyms in humans we recorded data on i) coinfecting pathogens and their effect on ii) host health and iii) intensity of infection. RESULTS: The most commonly reported coinfections differ from infections causing highest global mortality, with a notable lack of serious childhood infections in reported coinfections. We found that coinfection is generally reported to worsen human health (76% publications) and exacerbate infections (57% publications). Reported coinfections included all kinds of pathogens, but were most likely to contain bacteria. CONCLUSIONS: These results suggest differences between coinfected patients and those with single infections, with coinfection having serious health effects. There is a pressing need to quantify the tendency towards negative effects and to evaluate any sampling biases in the coverage of coinfection research.

Enteroparasitosis prevalence and parasitism influence in clinical outcomes of tuberculosis patients with or without HIV co-infection in a reference hospital in Rio de Janeiro (2000-2006)

Tuberculosis and intestinal parasites affect primarily low social and economic level populations, living clustered in precarious habitational settings. One of the interesting aspects of this interaction is the parasitism influence in cellular response to tuberculosis. In the present study, we evaluated the prevalence of enteroparasitosis in tuberculosis patients, HIV-infected and non HIV infected, and we observed the influence of helminth presence in the response to tuberculin skin test (TST) and tuberculosis clinical outcomes. From 607 clinical records reviewed, 327 individuals met the study inclusion criteria and did not present any exclusion criteria. The prevalence of enteroparasites observed was 19.6 percent. There was no significant association among TST result and the variables related to the presence of: helminthes, protozoa, and stool test for parasites result (p>0.5). Considering the survival of this cohort, we may observe that there is no significant difference (p>0.05) between the survival curves of parasited and non parasited individuals. Solely the variable "eosinophils" presents a statistically significant association (p<0.001) with helminthes, all other associations are considered not significant. Our findings neither show an association between helminthic infection and a favorable tuberculosis outcome, nor between parasitism and TST response, unlike other in vitro studies. Apparently, experimental data do not correspond to the clinical findings.

Enteroparasitosis prevalence and parasitism influence in clinical outcomes of tuberculosis patients with or without HIV co-infection in a reference hospital in Rio de Janeiro (2000-2006).

Tuberculosis and intestinal parasites affect primarily low social and economic level populations, living clustered in precarious habitational settings. One of the interesting aspects of this interaction is the parasitism influence in cellular response to tuberculosis. In the present study, we evaluated the prevalence of enteroparasitosis in tuberculosis patients, HIV-infected and non HIV infected, and we observed the influence of helminth presence in the response to tuberculin skin test (TST) and tuberculosis clinical outcomes. From 607 clinical records reviewed, 327 individuals met the study inclusion criteria and did not present any exclusion criteria. The prevalence of enteroparasites observed was 19.6%. There was no significant association among TST result and the variables related to the presence of: helminthes, protozoa, and stool test for parasites result (p>0.5). Considering the survival of this cohort, we may observe that there is no significant difference (p>0.05) between the survival curves of parasited and non parasited individuals. Solely the variable "eosinophils" presents a statistically significant association (p<0.001) with helminthes, all other associations are considered not significant. Our findings neither show an association between helminthic infection and a favorable tuberculosis outcome, nor between parasitism and TST response, unlike other in vitro studies. Apparently, experimental data do not correspond to the clinical findings.

Chronic helminth infections induce immunomodulation: consequences and mechanisms.

Worldwide, more than a billion people are infected with helminths. These worm infections generally do not lead to mortality, however, they are chronic in nature and can lead to considerable morbidity. Immunologically these infections are interesting; chronic helminth infections are characterized by skewing towards a T helper 2 type response as well as regulatory responses. The regulatory network is associated with chronic helminth infections and is thought to prevent strong immune responses against parasitic worms, allowing their long-term survival and restricting pathology. This regulatory network is thought to also temper responses to non-helminth antigens, like allergens or self-antigens, possibly leading to lower prevalence of allergies and autoimmune diseases in subjects that are chronically infected with helminths. This raises the interesting idea that helminths may bear molecules that have potential therapeutic action against allergies and possibly other inflammatory diseases. However, on the other side of the coin, this would predict that helminth infected subjects might not respond strongly to third party antigens like vaccines. This is an important issue, since most vaccines that are being developed against diseases such as HIV, tuberculosis or malaria will be introduced in areas where helminth infections are highly prevalent. Moreover, these vaccines are proving difficult to develop and are often weak, thus any confounder that would affect their efficacy needs to be taken into consideration. Helminth derived molecules have been identified that induce T helper 2 and regulatory responses via modulation of dendritic cells and some appear to do so via Toll like receptor (TLR) signaling. New insights into these pathways could be useful to antagonize suppression and hence boost vaccine efficacy or to optimize suppression induced by helminth derived molecules and control inflammatory diseases.

The role of residential location in apparent helminth and malaria associations.

Conflicting opinions on the nature of malaria and helminth coinfections in humans have highlighted the need for a rational approach to study the effects of coinfections on morbidity. Here, it is argued that a variety of factors have led to this confusion but that many problems might be helped by more deliberate consideration of residential location and spatial aspects of exposure in parasitological surveys.

Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm.

The three main soil-transmitted helminth infections, ascariasis, trichuriasis, and hookworm, are common clinical disorders in man. The gastrointestinal tract of a child living in poverty in a less developed country is likely to be parasitised with at least one, and in many cases all three soil-transmitted helminths, with resultant impairments in physical, intellectual, and cognitive development. The benzimidazole anthelmintics, mebendazole and albendazole, are commonly used to remove these infections. The use of these drugs is not limited to treatment of symptomatic soil-transmitted helminth infections, but also for large-scale prevention of morbidity in children living in endemic areas. As a result of data showing improvements in child health and education after deworming, and the burden of disease attributed to soil-transmitted helminths, the worldwide community is awakening to the importance of these infections. Concerns about the sustainability of periodic deworming with benzimidazole anthelmintics and the emergence of resistance have prompted efforts to develop and test new control tools.

Aging and infectious diseases in the developing world.

Although demographic aging does not remain restricted to industrialized countries, the medical challenge arising from the aging population will be distinct in the developing world. This is particularly true with respect to infectious diseases, which have a distinct spectrum in the elderly population, as well as a greater overall relevance in the developing world. Tropical diseases have a specific presentation and epidemiology in elderly patients. Infectious diseases with a worldwide distribution impact elderly patients in the developing world in a specific manner, which is most obvious with respect to human immunodeficiency virus and tuberculosis but is also true with respect to "trivial" manifestations of infection, such as diarrhea and pneumonia. Malnutrition contributes in a major way to the immunodeficiency of elderly patients in the developing world. Poorly controlled use of antimicrobial drugs leads to multidrug-resistant microorganisms, which, together with the limited resources available for drug treatment, makes appropriate treatment of infections in elderly patients in developing countries very difficult. Infections in elderly patients will have an increasing impact on the public health and economy of developing countries.

Community-wide effects of permethrin-treated bed nets on child mortality and malaria morbidity in western Kenya.

Spatial analyses of the effect of insecticide (permethrin)-treated bed nets (ITNs) on nearby households both with and without ITNs was performed in the context of a large-scale, group-randomized, controlled mortality trial in Asembo, western Kenya. Results illustrate a protective effect of ITNs on compounds lacking ITNs located within 300 meters of compounds with ITNs for child mortality, moderate anemia, high-density parasitemia, and hemoglobin levels. This community effect on nearby compounds without nets is approximately as strong as the effect observed within villages with ITNs. This implies that in areas with intense malaria transmission with high ITN coverage, the primary effect of insecticide-treated nets is via area-wide effects on the mosquito population and not, as commonly supposed, by simple imposition of a physical barrier protecting individuals from biting. The strength of the community effect depended upon the proportion of nearby compounds with treated nets. To maximize their public health impact, high coverage with treated nets is essential.

Immunity, antigenic heterogeneity, and aggregation of helminth parasites.

Empirical studies of helminth parasites reveal that the distribution of parasite burdens in their host populations is highly aggregated. This aggregation is fundamental to the ecology and epidemiology of helminth parasites. Results from a stochastic model predict that aggregation of helminth parasites is inversely related to the intensity of host immunity. Aggregation also decreases with antigenic heterogeneity and increases with heterogeneity in transmissibility among parasite strains. It is also found that the degree of aggregation is greater when immunity affects parasite fecundity than when immunity acts on host susceptibility. Potential relevance of this result for assessing the influence of vaccines that target either host susceptibility or parasite fecundity on the level of aggregation and consequent effects on drug resistance and disease prevalence are discussed.

The epidemiology of helminth infections of growing sheep in Argentina's western pampas.

Seasonal population trends of helminth parasites of growing lambs were investigated over 4 years. Successive worm-free lambs were grazed together with untreated lambs for 20-30 days and then slaughtered for helminth counts 2 weeks after their removal from pasture. Likewise untreated lambs from the same flock were slaughtered from 2 to 15 months of age for worm counts in the same way as tracer lambs. The predominant parasites were Haemonchus, Nematodirus and Trichostrongylus. Haemonchus contortus was found to be of major importance and the flock acquired massive worm burdens from summer to mid-autumn. Minimum burdens were seen from winter to early spring and maximum L4 stages were found from mid-autumn to early winter. Nematodirus burdens increased from December with a peak in late summer and then decreased to low values. Maximum larval availability was in autumn to early winter. Trichostrongylus (mainly T. colubriformis) populations increased in autumn and peaked in June-July, while the highest larval availability was in autumn. The minor genera recovered were Ostertagia, Cooperia, Trichuris, Oesophagostomum and Moniezia. Dictyocaulus, Chabertia and Teladorsagia were noted occasionally and liver flukes were not detected. No important and pathogenic numbers of L4 stages were seen and all predominant species were able to survive over summer or winter in pasture.

Effects of management system, legume feeding and anthelmintic treatment on the performance of lambs in north Sumatra.

Sixty-four lambs in North Sumatra were used in a factorial experiment comprising two systems of management (grazing and stall-feeding), four levels of legume supplementation (0, 250, 500 and 1,000 g/d Pueraria javanica) and two anthelmintic treatments (none and albendazole every four weeks). The experiment lasted five months. The mortality rate for lambs not given anthelmintic was 28%, significantly higher (P less than 0.05) than for animals given anthelmintic which had zero mortality. Anthelmintic treatment increased growth rate from only 2 g/d to 29 g/d (P less than 0.05) and reduced faecal egg count from 1,700 epg to 270 epg. When not given anthelmintic grazing lambs had a higher mortality rate (38%) than stall-fed lambs (19%) but this difference was not significant. When given anthelmintic grazing lambs has a slightly higher growth rate (32 g/d) than stall-fed lambs (26 g/d). System of management had no apparent effect on egg count. Legume supplementation reduced the egg count of lambs not given anthelmintic but had no significant effect on mortality or growth rate.