Geostatistical modelling enables efficient safety assessment for mass drug administration with ivermectin in Loa loa endemic areas through a combined antibody and LoaScope testing strategy for elimination of onchocerciasis.

The elimination of onchocerciasis through community-based Mass Drug Administration (MDA) of ivermectin (Mectizan) is hampered by co-endemicity of Loa loa, as individuals who are highly co-infected with Loa loa parasites can suffer serious and occasionally fatal neurological reactions from the drug. The test-and-not-treat strategy of testing all individuals participating in MDA has some operational constraints including the cost and limited availability of LoaScope diagnostic tools. As a result, a Loa loa Antibody (Ab) Rapid Test was developed to offer a complementary way of determining the prevalence of loiasis. We develop a joint geostatistical modelling framework for the analysis of Ab and Loascope data to delineate whether an area is safe for MDA. Our results support the use of a two-stage strategy, in which Ab testing is used to identify areas that, with acceptably high probability, are safe or unsafe for MDA, followed by Loascope testing in areas whose safety status is uncertain. This work therefore contributes to the global effort towards the elimination of onchocerciasis as a public health problem by potentially reducing the time and cost required to establish whether an area is safe for MDA.

Assessment of a recombinant protein from Leishmania infantum as a novel tool for Visceral Leishmaniasis (VL) diagnosis in VL/HIV co-infection cases.

Visceral Leishmaniasis and HIV-AIDS coinfection (VL/HIV) is considered a life-threatening pathology when undiagnosed and untreated, due to the immunosuppression caused by both diseases. Serological tests largely used for the VL diagnosis include the direct agglutination test (DAT), ELISA and immunochromatographic (ICT) assays. For VL diagnosis in HIV infections, different studies have shown that the use of the DAT assay facilitates the VL diagnosis in co-infected patients, since the performance of the most widely used ELISA and ICT tests, based on the recombinant protein rK39, are much less efficient in HIV co-infections. In this scenario, alternative recombinant antigens may help the development of new serological diagnostic methods which may improve the VL diagnosis for the co-infection cases. This work aimed to evaluate the use of the recombinant Lci2 antigen, related to, but antigenically more diverse than rK39, for VL diagnosis in co-infected sera through ELISA assays. A direct comparison between recombinant Lci2 and rK39 was thus carried out. The two proteins were first tested using indirect ELISA with sera from VL afflicted individuals and healthy controls, with similar performances. They were then tested with two different sets of VL/HIV co-infected cases and a significant drop in performance, for one of these groups, was observed for rK39 (32% sensitivity), but not for Lci2 (98% sensitivity). In fact, an almost perfect agreement (Kappa: 0.93) between the Lci2 ELISA and DAT was observed for the coinfected VL/HIV patients. Lci2 then has the potential to be used as a new tool for the VL diagnosis of VL/HIV co-infections.

Assessment of syndromic management of curable sexually transmitted and reproductive tract infections among pregnant women: an observational cross-sectional study.

BACKGROUND: This study estimated the prevalence of curable sexually transmitted and reproductive tract infections (STIs/RTIs) among pregnant women attending antenatal care (ANC) in rural Zambia, evaluated the effectiveness of syndromic management of STIs/RTIs versus reference-standard laboratory diagnoses, and identified determinants of curable STIs/RTIs during pregnancy. METHODS: A total of 1086 pregnant women were enrolled at ANC booking, socio-demographic information and biological samples were collected, and the provision of syndromic management based care was documented. The Piot-Fransen model was used to evaluate the effectiveness of syndromic management versus etiological testing, and univariate and multivariate logistic regression analyses were used to identify determinants of STIs/RTIs. RESULTS: Participants had a mean age of 25.6 years and a mean gestational age of 22.0 weeks. Of 1084 women, 700 had at least one STI/RTI (64.6%; 95% confidence interval [CI], 61.7, 67.4). Only 10.2% of infected women received any treatment for a curable STI/RTI (excluding syphilis). Treatment was given to 0 of 56 women with chlamydia (prevalence 5.2%; 95% CI, 4.0, 6.6), 14.7% of participants with gonorrhoea (prevalence 3.1%; 95% CI, 2.2, 4.4), 7.8% of trichomoniasis positives (prevalence 24.8%; 95% CI, 22.3, 27.5) and 7.5% of women with bacterial vaginosis (prevalence 48.7%; 95% CI, 45.2, 51.2). An estimated 7.1% (95% CI, 5.6, 8.7) of participants had syphilis and received treatment. Women < 20 years old were more likely (adjusted odds ratio [aOR] = 5.01; 95% CI: 1.23, 19.44) to have gonorrhoea compared to women ≥30. The odds of trichomoniasis infection were highest among primigravidae (aOR = 2.40; 95% CI: 1.69, 3.40), decreasing with each subsequent pregnancy. Women 20 to 29 years old were more likely to be diagnosed with bacterial vaginosis compared to women ≥30 (aOR = 1.58; 95% CI: 1.19, 2.10). Women aged 20 to 29 and ≥ 30 years had higher odds of infection with syphilis, aOR = 3.96; 95% CI: 1.40, 11.20 and aOR = 3.29; 95% CI: 1.11, 9.74 respectively, compared to women under 20. CONCLUSIONS: Curable STIs/RTIs were common and the majority of cases were undetected and untreated. Alternative approaches are urgently needed in the ANC setting in rural Zambia.

Assessment of Coxiella burnetii presence after tick bite in north-eastern Poland.

PURPOSE: The aim of the study is to assess anti-Coxiella burnetii antibodies presence in inhabitants of north-eastern Poland, to assess the risk of Q fever after tick bite and to assess the percentage of co-infection with other pathogens. METHODS: The serological study included 164 foresters and farmers with a history of tick bite. The molecular study included 540 patients, hospitalized because of various symptoms after tick bite. The control group consisted of 20 honorary blood donors. Anti-Coxiella burnetii antibodies titers were determined by Coxiella burnetii (Q fever) Phase 1 IgG ELISA (DRG International Inc. USA). PCR was performed to detect DNA of C. burnetii, Borrelia burgdorferi and Anaplasma phagocytophilum. RESULTS: Anti-C. burnetii IgG was detected in six foresters (7.3%). All foresters with the anti-C. burnetii IgG presence were positive toward anti-B. burgdorferi IgG and anti-TBE (tick-borne encephalitis). Anti-C. burnetii IgG was detected in five farmers (6%). Four farmers with anti-C. burnetii IgG presence were positive toward anti-B. burgdorferi IgG and two with anti-TBE. Among them one was co-infected with B. burgdorferi and TBEV. Correlations between anti-C. burnetii IgG and anti-B. burgdorferi IgG presence and between anti-C. burnetii IgG presence and symptoms of Lyme disease were observed. C. burnetii DNA was not detected in any of the 540 (0%) patients. CONCLUSIONS: C. burnetii is rarely transmitted by ticks, but we proved that it is present in the environment, so it may be a danger to humans. The most common co-occurrence after tick bite concerns C. burnetii and B. burgdorferi.

Liver fluke in Irish sheep: prevalence and associations with management practices and co-infection with rumen fluke.

BACKGROUND: The present study aimed to identify the national prevalence of Fasciola hepatica in Irish sheep and to conduct a risk analysis assessment based on management and treatment practices in participating flocks. Also, co-infection with rumen fluke was quantified and its association with liver fluke and management practices was assessed. METHODS: A total of 305 sheep flocks were selected ensuring even national representation of the sheep population. Participating farms were asked to complete a survey questionnaire on farm management practices and submit faecal samples during the winter of 2014-2015. Pooled faecal samples were analysed for the presence of F. hepatica and co-infection with rumen fluke. Apparent and true prevalence were calculated, additionally, the rate of co-infection with rumen fluke was also obtained. Correlation and regression analyses were used for assessing associations between management practices, liver fluke infection and co-infection with rumen fluke. RESULTS: The national true prevalence of F. hepatica was 50.4% (n = 305). Regional prevalence varied from 41% in the east to 52% in the south. Co-infection with rumen fluke was observed in 40% of the studied population and correlated with increased F. hepatica egg counts (OR = 2.9; P ≤ 0.001). Predominant breeds were Suffolk, Texel and Horned Mountain breeds. Beef cattle were the most frequent type of other livestock present on farms and mixed species grazing was frequently reported (73%). More than half of the flocks reported a mid-to-late lambing period (March-April). Use of mountain land for grazing was of 32%. Flukicides were most commonly used twice over the autumn-winter period. Regression analyses highlighted significant association of F. hepatica status, with the presence of other livestock on farm, frequency of flukicides used during the winter and clinical presentation of liver fluke. A significant increase in eggs per gram of faeces was observed in Charollais sheep in comparison with all other breeds. Co-infection with F. hepatica and Calicophoron daubneyi was also significantly associated with the presence of other livestock on the farm, type of flukicide used and clinical fasciolosis. CONCLUSIONS: The present study provides up-to-date information on the prevalence of F. hepatica in Irish sheep and adds insight to the epidemiology of the disease. These findings will be useful for designing new holistic control measures for F. hepatica infection.

Exogenous glucocorticoids amplify the costs of infection by reducing resistance and tolerance, but effects are mitigated by co-infection.

Individual variation in parasite defences, such as resistance and tolerance, can underlie heterogeneity in fitness and could influence disease transmission dynamics. Glucocorticoid hormone concentrations often change in response to fluctuating environmental conditions and mediate changes in immune function, resource allocation and tissue repair. Thus, changes in glucocorticoid hormone concentrations might mediate individual variation in investment in resistance versus tolerance. In this study, we experimentally increased glucocorticoid concentrations in red-winged blackbirds ( Agelaius phoeniceus) that were naturally infected with haemosporidian parasites, and assessed changes in resistance and tolerance of infection. Glucocorticoid treatment increased burdens of Plasmodium, the parasite causing avian malaria, but only in the absence of co-infection with another Haemosporidian, Haemoproteus. Thus, glucocorticoids might reduce resistance to infection, but co-infection can mitigate the negative consequences of increased hormone concentrations. Glucocorticoid treatment also decreased tolerance of infection. We found no evidence that the inflammatory immune response or rate of red blood cell production underlie the effects of glucocorticoids on resistance and tolerance. Our findings suggest that exogenous glucocorticoids can increase the costs of haemosporidian infections by both increasing parasite numbers and reducing an individual's ability to cope with infection. These effects could scale up to impact populations of both host and parasite.

Liver fluke (Fasciola hepatica) co-infection with bovine tuberculosis in cattle: A prospective herd-level assessment of herd bTB risk in dairy enterprises.

Co-infection of tuberculosis (TB) and helminths is recognized as a significant problem in regions where such pathogens are endemic and chronic cases exist. Co-infection can modulate the immune system leading to interference with diagnostic tests, increased pathological impacts and pathogen persistence. However, research has found that such interactions between pathogens can be context and species specific. Recent studies have suggested that liver fluke, Fasciola hepatica, infection may impact on immunological responses and diagnostics for bovine tuberculosis (bTB; caused by Mycobacterium bovis) in cattle. Where evidence of such interaction exists, there would be an onus on policy makers to adjust eradication programs to minimize impacts. We assessed the association between herd-level bTB breakdown risk and seasonal variation in liver fluke exposure based on 5,753 bulk tank milk (BTM) samples from 1,494 dairy herds across Northern Ireland. BTM was tested by an IDEXX antibody specific enzyme-linked immunosorbent assay (ELISA) using the 'f2' antigen as a detection agent. The ELISA determined the result based on a sample to (known) positive ratio (S/P%) from which binary status and categories of exposure were derived. Associations were tested using multivariable random effects models. Models predicting bTB risk were not improved with the inclusion of liver fluke exposure levels. Variations in modelling liver fluke exposure (S/P%, binary, categories of exposure) and bTB risk (skin test breakdowns, post-mortem confirmed breakdowns, breakdown size and lag effects) also failed to support associations (neither positive nor negative) between the pathogens at herd-level. These results, along with previously published animal-level data from Northern Ireland, suggest that the nexus between bTB and F. hepatica may have small size effects at the population-level. However, our results also highlight the high prevalence of F. hepatica in cattle in our study population, and therefore we cannot fully discount the potential hypothesis of population-level depression of immune response to M. bovis due to co-infection.

Liver fluke (Fasciola hepatica) co-infection with bovine tuberculosis (bTB) in cattle: A retrospective animal-level assessment of bTB risk in dairy and beef cattle.

Bovine tuberculosis (bTB), caused by Mycobacterium bovis, remains a persistent problem for cattle industries in endemic countries. The frequency, quality, and performance of tests, and the presence of wildlife reservoirs, have been identified as impediments to eradication. Recently, exposure to helminth infection (Fasciola hepatica) has been associated negatively with the disclosure of bTB. Here, for the first time, we assess impact of concurrent infections of Fasciola hepatica and the disclosure of bTB at the animal-level using large surveillance datasets. We utilized a dataset of 138,566 animal records from an abattoir from Northern Ireland (2011-2013). The presence of F. hepatica infection was assessed from macroscopic tissue inspection at abattoir. Multivariable models were developed to assess co-infection associations with bTB status based on: Single Intradermal Comparative Tuberculin Test (SICTT), lesion, bacteriological confirmation, including either all animals, or only skin-test negative animals (lesions at routine slaughter; LRS; confirmed nonreactors at routine slaughter; cNRs) or positive (reactors) animals alone, respectively. The relationship between skin tuberculin reaction sizes and fluke status was also explored for a subset of animals with field recordings (n = 24,680). Controlling for known risk factors (e.g., climatic, herd, and individual level characteristics), we did not find significant associations between the SICTT (standard or severe interpretation), lesion, nor confirmation status of animals and their liver fluke status. The only exception was a negative association between liver fluke positivity, and LRS or cNRs, respectively; though effect-sizes were small (e.g., LRS Odds-Ratio: 0.87; 95% CI: 0.76-1.00). There was limited evidence of a relationship between tuberculin reaction sizes during SICTT testing and liver fluke infection status. These data do not support the contention that the detection of bTB using skin-tests or reactor postmortem follow-up may be compromised by co-infection at a population level, but the relationship with lesion formation (pathogenesis) may indicate an impact for postmortem surveillance.

Can Wolbachia modulate the fecundity costs of Plasmodium in mosquitoes?

Vertically transmitted parasites (VTPs) such as Wolbachia are expected not only to minimize the damage they inflict on their hosts, but also to protect their hosts against the damaging effects of coinfecting parasites. By modifying the fitness costs of the infection, VTPs can therefore play an important role in the evolution and epidemiology of infectious diseases.Using a natural system, we explore the effects of a Wolbachia-Plasmodium co-infection on mosquito fecundity. While Plasmodium is known to frequently express its virulence by partially castrating its mosquito vectors, the effects of Wolbachia infections on mosquito fecundity are, in contrast, highly variable. Here, we show that Plasmodium drastically decreases the fecundity of mosquitoes by ca. 20%, and we provide the first evidence that this decrease is independent of the parasite's burden. Wolbachia, on the other hand, increases fecundity by roughly 10%, but does not alter the tolerance (fecundity-burden relationship) of mosquitoes to Plasmodium infection.Although Wolbachia-infected mosquitoes fare overall better than uninfected ones, Wolbachia does not confer a sufficiently high reproductive boost to mosquitoes to compensate for the reproductive losses inflicted by Plasmodium. We discuss the potential mechanisms and implications underlying the conflicting effects of these two parasites on mosquito reproduction.

Environmental and socio-demographic individual, family and neighborhood factors associated with children intestinal parasitoses at Iguazú, in the subtropical northern border of Argentina.

BACKGROUND: Intestinal parasitoses are a major concern for public health, especially in children from middle and low-income populations of tropical and subtropical areas. We examined the presence and co-infection of parasites in humans as well as parasitic environmental contamination in Puerto Iguazú, Argentina. We explored the environmental and socio-demographic characteristics of the persistence of parasites in children and their environment. METHODOLOGY/PRINCIPAL FINDINGS: This cross-section survey was conducted among children population comprised into the area of the public health care centers of Iguazú during June 2013 to May 2016. Copro-parasitological status of 483 asymptomatic children was assessed. Simultaneously, a design-based sampling of 744 soil samples and 530 dog feces was used for characterize the environmental contamination. The 71.5% of these sites were contaminated. Sixteen genera were detected in the environment being hookworms (62.0%) the main pathogens group detected followed by Toxocara spp (16.3%), Trichuris spp (15.2%) and Giardia (6.5%). Total children prevalence raised 58.8%, detecting twelve genera of parasite with Giardia intestinalis as the most prevalent pathogen (29.0%) followed by Enterobius vermicularis (23.0%), Hymenolepis nana (12.4%) and hookworms (4.4%). Through questionnaires and census data, we characterized the socio-demographics conditions at an individual, family and neighborhood levels. A multi-level analysis including environmental contamination data showed that the ´presence of parasites´ was mostly determined by individual (e.g. age, playing habits, previous treatment) and household level (e.g. UBN, WASH, mother's literacy) determinants. Remarkably, to define the level of 'parasite co-infection', besides individual and household characteristics, environmental factors at a neighborhood level were important. CONCLUSION/SIGNIFICANCE: Our work represents the major survey of intestinal parasites in human and environmental samples developed in the region. High prevalence was detected in the children population as well as in their environment. This work shows the importance of considering and promoting multi-level actions over the identified determinants to face this public health problem from integrative approaches.

The burden, pattern and factors that contribute to periportal fibrosis in HIV-infected patients in an S. mansoni endemic rural Uganda.

INTRODUCTION: Both Human Immunodeficiency Virus (HIV) and S.mansoni infections are common in Uganda and can cause liver disease. No study has determined co-infection significance in Uganda. We carried out a study on the burden, pattern and factors that contribute to peri-portal fibrosis (PPF) in HIV infected patients attending a Primary healthcare setting at Pakwach. METHODOLOGY: We conducted a cross-sectional study in the HIV clinic at Pakwach health centre IV. Data on demographics, contact with the Nile, CD4+ cell count, ART and alcohol use were collected. Urinary Circulating Cathodic Antigen (CCA), was done for S. Mansoni detection. Liver scan was done for presence and pattern of PPF. HBsAg testing was performed on all participants. Data was analyzed using Stata Version 10. RESULTS: We enrolled 299 patients, median age 39 years (IQR 16), most were female, 210 (73%). Overall, 206 (68.9%) had PPF, majority 191 (92.7%) had pattern c, either alone (63 participants) or in combination with pattern d (128 participants). Age of 30-50 years was significantly associated with PPF (OR 2.28 p-value-0.003). CONCLUSION: We found high prevalence of S. mansoni and PPF in the HIV infected population and age was a significant factor for PPF. We recommend all HIV infected patients be examined routinely for S. mansoni infection for early anti-schistosomal treatment.

Burden of influenza among hospitalized febrile children in Ghana.

BACKGROUND: Influenza surveillance data from Africa indicate a substantial disease burden with high mortality. However, local influenza data from district hospitals with limited laboratory facilities are still scarce. OBJECTIVES: To identify the frequency and seasonal distribution of influenza among hospitalized febrile children in a rural hospital in Ghana and to describe differential diagnoses to other severe febrile infections. METHODS: Between January 2014 and April 2015, all children with a temperature of ≥38°C admitted to a district hospital in Ghana were screened for influenza A and B by RT-PCR and differentiated to subtypes A(H1N1)pdm09 and A(H3N2). Malaria microscopy and blood cultures were performed for each patient. RESULTS: A total of 1063 children with a median age of 2 years (IQR: 1-4 years) were recruited. Of those, 271 (21%) were classified as severe acute respiratory infection (SARI) and 47 (4%) were positive for influenza, namely 26 (55%) influenza B, 15 (32%) A(H1N1)pdm09, and 6 (13%) A(H3N2) cases. Influenza predominantly occurred in children aged 3-5 years and was more frequently detected in the major rainy season (OR = 2.9; 95% CI: 1.47-6.19) during the first half of the year. Two (4%) and seven (15%) influenza-positive children were co-diagnosed with an invasive bloodstream infection or malaria, respectively. CONCLUSION: Influenza contributes substantially to the burden of hospitalized febrile children in Ghana being strongly dependent on age and corresponds with the major rainy season during the first half-year.

Cost-effectiveness of malaria preventive treatment for HIV-infected pregnant women in sub-Saharan Africa.

BACKGROUND: Malaria is a leading cause of morbidity and mortality among HIV-infected pregnant women in sub-Saharan Africa: at least 1 million pregnancies among HIV-infected women are complicated by co-infection with malaria annually, leading to increased risk of premature delivery, severe anaemia, delivery of low birth weight infants, and maternal death. Current guidelines recommend either daily cotrimoxazole (CTX) or intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) for HIV-infected pregnant women to prevent malaria and its complications. The cost-effectiveness of CTX compared to IPTp-SP among HIV-infected pregnant women was assessed. METHODS: A microsimulation model of malaria and HIV among pregnant women in five malaria-endemic countries in sub-Saharan Africa was constructed. Four strategies were compared: (1) 2-dose IPTp-SP at current IPTp-SP coverage of the country ("2-IPT Low"); (2) 3-dose IPTp-SP at current coverage ("3-IPT Low"); (3) 3-dose IPTp-SP at the same coverage as antiretroviral therapy (ART) in the country ("3-IPT High"); and (4) daily CTX at ART coverage. Outcomes measured include maternal malaria, anaemia, low birth weight (LBW), and disability-adjusted life years (DALYs). Sensitivity analyses assessed the effect of adherence to CTX. RESULTS: Compared with the 2-IPT Low Strategy, women receiving CTX had 22.5% fewer LBW infants (95% CI 22.3-22.7), 13.5% fewer anaemia cases (95% CI 13.4-13.5), and 13.6% fewer maternal malaria cases (95% CI 13.6-13.7). In all simulated countries, CTX was the preferred strategy, with incremental cost-effectiveness ratios ranging from cost-saving to $3.9 per DALY averted from a societal perspective. CTX was less effective than the 3-IPT High Strategy when more than 18% of women stopped taking CTX during the pregnancy. CONCLUSION: In malarious regions of sub-Saharan Africa, daily CTX for HIV-infected pregnant women regardless of CD4 cell count is cost-effective compared with 3-dose IPTp-SP as long as more than 82% of women adhere to daily dosing.

Intestinal parasites, growth and physical fitness of schoolchildren in poor neighbourhoods of Port Elizabeth, South Africa: a cross-sectional survey.

BACKGROUND: As traditional lifestyle and diets change with social and economic development, disadvantaged communities in low- and middle-income countries increasingly face a double burden of communicable and non-communicable diseases. We studied the relationship between physical fitness and infections with soil-transmitted helminths (STHs), intestinal protozoa and Helicobacter pylori among schoolchildren in Port Elizabeth, South Africa. METHODS: We conducted a cross-sectional survey among 1009 children, aged 9 to 12 years, from eight primary schools in socioeconomically disadvantaged neighbourhoods of Port Elizabeth. Physical fitness was determined using field-deployable tests of the Eurofit fitness test battery. Stool samples were analysed with the Kato-Katz thick smear technique to diagnose STHs and with rapid diagnostic tests (RDTs) to detect intestinal protozoa and H. pylori infections. Haemoglobin (Hb) levels were assessed and anthropometric indicators determined. RESULTS: Complete data were available for 934 children (92 %). In two schools, high STH prevalences were found (Ascaris lumbricoides 60 and 72 %; Trichuris trichiura 65 % each). For boys and girls co-infected with A. lumbricoides and T. trichiura (n = 155) the maximal oxygen uptake (VO2 max) was estimated to be 50.1 and 47.2 ml kg(-1) min(-1), compared to 51.5 and 47.4 ml kg(-1) min(-1) for their non-infected peers (n = 278), respectively. On average, children without helminth infections had greater body mass (P = 0.011), height (P = 0.009) and a higher body mass index (P = 0.024) and were less often stunted (P = 0.006), but not significantly less wasted compared to their peers with a single or dual species infection. Among 9-year-old boys, a negative correlation between helminth infections and VO2 max, grip strength and standing broad jump distance was observed (P = 0.038). The overall mean Hb level was 122.2 g l(-1). In the two schools with the highest prevalence of STHs the Hb means were 119.7 and 120.5 g l(-1), respectively. CONCLUSIONS: Intestinal parasite infections appear to have a small but significant negative effect on the physical fitness of infected children, as expressed by their maximal oxygen uptake. We observed a clear impact on anthropometric indicators.

Markov chain Monte Carlo and expectation maximization approaches for estimation of haplotype frequencies for multiply infected human blood samples.

BACKGROUND: Haplotypes are important in anti-malarial drug resistance because genes encoding drug resistance may accumulate mutations at several codons in the same gene, each mutation increasing the level of drug resistance and, possibly, reducing the metabolic costs of previous mutation. Patients often have two or more haplotypes in their blood sample which may make it impossible to identify exactly which haplotypes they carry, and hence to measure the type and frequency of resistant haplotypes in the malaria population. RESULTS: This study presents two novel statistical methods expectation-maximization (EM) and Markov chain Monte Carlo (MCMC) algorithms to investigate this issue. The performance of the algorithms is evaluated on simulated datasets consisting of patient blood characterized by their multiplicity of infection (MOI) and malaria genotype. The datasets are generated using different resistance allele frequencies (RAF) at each single nucleotide polymorphisms (SNPs) and different limit of detection (LoD) of the SNPs and the MOI. The EM and the MCMC algorithm are validated and appear more accurate, faster and slightly less affected by LoD of the SNPs and the MOI compared to previous related statistical approaches. CONCLUSIONS: The EM and the MCMC algorithms perform well when analysing malaria genetic data obtained from infected human blood samples. The results are robust to genotyping errors caused by LoDs and function well even in the absence of MOI data on individual patients.

Helminth Interaction with the Host Immune System: Short-Term Benefits and Costs in Relation to the Infectious Environment.

Chronic infections imply that the parasite and the host immune system closely interact for a long time without a fatal outcome. Environmental changes encountered by hosts and parasites, such as coinfections, can deeply affect the stability of this apparent equilibrium. Our study aimed to determine the effect of the infectious environment on the costs and benefits of chronic infection with the gut nematode Heligmosomoides polygyrus in mice. Heligmosomoides polygyrus is known for its capacity to actively interfere with the host immune response by secreting molecules that can dampen immunity. We simulated bacterial coinfection of H. polygyrus-infected CBA-strain mice during the chronic phase of the infection by injecting them with Escherichia coli lipopolysaccharide. We found that infection by H. polygyrus induced only weak costs for the host (in terms of reproductive investment) and was characterized by the upregulation of both Th1 (interferon-γ) and anti-inflammatory (transforming growth factor-ß) cytokines, which is favorable to parasite persistence. However, when co-occurring with the simulated bacterial infection, H. polygyrus infection was associated with a pronounced shift toward a pro-inflammatory status, which was deleterious to both the parasite and the host. Our study highlights the dynamic equilibrium reached during chronic infection, where a rapid environmental change, such as a concomitant bacterial infection, can deeply affect the outcome of the host-parasite interaction.

Toxoplasmosis and Toxocariasis: An Assessment of Human Immunodeficiency Virus Comorbidity and Health-Care Costs in Canada.

Toxoplasma gondii and Toxocara spp. are zoonotic parasites with potentially severe long-term consequences for those infected. We estimated incidence and investigated distribution, risk factors, and costs associated with these parasites by examining hospital discharge abstracts submitted to the Canadian Institute for Health Information (2002-2011). Annual incidence of serious toxoplasmosis and toxocariasis was 0.257 (95% confidence interval [CI]: 0.254-0.260) and 0.010 (95% CI: 0.007-0.014) cases per 100,000 persons, respectively. Median annual health-care costs per serious case of congenital, adult-acquired, and human immunodeficiency virus (HIV)-associated toxoplasmosis were $1,971, $763, and $5,744, respectively, with an overall cost of C$1,686,860 annually (2015 Canadian dollars). However, the total economic burden of toxoplasmosis is likely much higher than these direct health-care cost estimates. HIV was reported as a comorbidity in 40% of toxoplasmosis cases and accounted for over half of direct health-care costs associated with clinical toxoplasmosis. A One Health approach, integrating physician and veterinary input, is recommended for increasing public awareness and decreasing the economic burden of these preventable zoonoses.

What is the price of neglecting parasite groups when assessing the cost of co-infection?

Although co-infection by multiple groups of pathogens is the norm rather than the exception in nature, most research on the effects of pathogens on their hosts has been largely based on a single or few pathogen species. Nevertheless, the health impact of co-occurring infections is evident, and it is important that scientists should consider pathogen communities rather than single relevant pathogen species when assessing the impact of multiple infections. In this work we illustrate the consequences of neglecting different pathogen taxa (viruses, protozoa, helminths, arthropods) in the explanatory power of a set of Partial Least Squares Regression (PLS-R) models used for exploring the impact of co-infections on the body condition of 57 adult feral cats; 71·5% cats were co-infected by ≥3 groups of pathogens. The best two PLS-R models provided a first component based on the combination of helminths, protozoa and viruses, explaining 29·15% of body-condition variability. Statistical models, partially considering the pathogen community, lost between 24% and 94% of their explanatory power for explaining the cost of multiple infections. We believe that in the future, researchers assessing the impact of diseases on host life-history traits should take into account a broad representation of the pathogen community, especially during early assessment of the impact of diseases on host health.

Molecular assessment of trematode co-infection and intraspecific competition in molluscan intermediate hosts.

In natural populations of the human parasite Schistosoma mansoni, parasite distribution among snail intermediate hosts is generally overdispersed, such that a small proportion of hosts harbor the majority of parasite genotypes. Within these few infected snails, researchers have found that it can be common for hosts to harbor multiple parasite genotypes, creating circumstances in which co-infecting parasites are faced with potential competition over limited host resources. Much theoretical modeling has focused on parasite competition, especially regarding the influence of co-infection on parasite exploitation strategy evolution. However, particularly in the case of intra-molluscan intermediate stages, empirical investigations of parasite-parasite competition have often hinged on the untested assumption that co-exposure produces co-infection. That is, infected hosts exposed to multiple strains have been assumed to harbor multiple strains, regardless of the true nature of the infection outcome. Here we describe a real-time quantitative PCR method to distinguish the conditions of multiple- versus single-strain infection, as well as quantify the relative larval output of co-infecting strains. We applied the method to an empirical investigation of intraspecific parasite competition between S. mansoni strains within the intermediate snail host Biomphalaria glabrata, assessing co-exposure's effects on parasite infectivity and productivity and the concomitant effects on host fitness. Overall, there was no effect of parasite co-infection on snail life history traits relative to single-strain infection. Parasite infectivity significantly increased as a result of increasing overall miracidial dose, rather than co-exposure, though strain-specific productivity was significantly reduced in co-infections in manner consistent with resource competition. Moreover, we show that less than half of infected, co-exposed hosts had patent co-infections and demonstrate the utility of this molecular tool for the study of trematode life history variation in molluscan hosts.

Scabies in the developing world--its prevalence, complications, and management.

Scabies remains one of the commonest of skin diseases seen in developing countries. Although its distribution is subject to a cycle of infection, with peaks and troughs of disease prevalence, this periodicity is often less obvious in poor communities. Scabies is a condition that affects families, particularly the most vulnerable; it also has the greatest impact on young children. Largely through the association with secondary bacterial infection caused by group A streptococci and Staphylococcus aureus, the burden of disease is compounded by nephritis, rheumatic fever and sepsis in developing countries. However, with a few notable exceptions, it remains largely neglected as an important public health problem. The purpose of this review is to provide an update on the current position of scabies with regard to its complications and control in resource-poor countries.