The human intestine and its microbiota is the most common infection site for soil-transmitted helminths (STHs), which affect the well-being of ~ 1.5 billion people worldwide. The complex cross-kingdom interactions are not well understood. A cross-sectional analysis identified conserved microbial signatures positively or negatively associated with STH infections across Liberia and Indonesia, and longitudinal samples analysis from a double-blind randomized trial showed that the gut microbiota responds to deworming but does not transition closer to the uninfected state. The microbiomes of individuals able to self-clear the infection had more alike microbiome assemblages compared to individuals who remained infected. One bacterial taxon (Lachnospiracae) was negatively associated with infection in both countries, and 12 bacterial taxa were significantly associated with STH infection in both countries, including Olsenella (associated with reduced gut inflammation), which also significantly reduced in abundance following clearance of infection. Microbial community gene abundances were also affected by deworming. Functional categories identified as associated with STH infection included arachidonic acid metabolism; arachidonic acid is the precursor for pro-inflammatory leukotrienes that threaten helminth survival, and our findings suggest that some modulation of arachidonic acid activity in the STH-infected gut may occur through the increase of arachidonic acid metabolizing bacteria. For the first time, we identify specific members of the gut microbiome that discriminate between moderately/heavily STH-infected and non-infected states across very diverse geographical regions using two different statistical methods. We also identify microbiome-encoded biological functions associated with the STH infections, which are associated potentially with STH survival strategies, and changes in the host environment. These results provide a novel insight of the cross-kingdom interactions in the human gut ecosystem by unlocking the microbiome assemblages at taxonomic, genetic, and functional levels so that advances towards key mechanistic studies can be made.

Background: Given that helminth infections are thought to have strong immunomodulatory activity, the question whether helminth infections might affect responses to malaria antigens needs to be addressed. Different cross-sectional studies using diverse methodologies have reported that helminth infections might either exacerbate or reduce the severity of malaria attacks. The same discrepancies have been reported for parasitemia. Methods/Design: To determine the effect of geohelminth infections and their treatment on malaria infection and disease outcome, as well as on immunological parameters, the area of Nangapanda on Flores Island, Indonesia, where malaria and helminth parasites are co-endemic was selected for a longitudinal study. Here a Double-blind randomized trial will be performed, incorporating repeated treatment with albendazole (400 mg) or placebo at three monthly intervals. Household characteristic data, anthropometry, the presence of intestinal helminth and Plasmodium spp infections, and the incidence of malaria episodes are recorded. In vitro cultures of whole blood, stimulated with a number of antigens, mitogens and toll like receptor ligands provide relevant immunological parameters at baseline and following 1 and 2 years of treatment rounds. The primary outcome of the study is the prevalence of Plasmodium falciparum and P. vivax infection. The secondary outcome will be incidence and severity of malaria episodes detected via both passive and active follow-up. The tertiary outcome is the inflammatory cytokine profile in response to parasite antigens. The project also facilitates the transfer of state of the art methodologies and technologies, molecular diagnosis of parasitic diseases, immunology and epidemiology from Europe to Indonesia. Discussion: The study will provide data on the effect of helminth infections on malaria. It will also give information on anthelminthic treatment efficacy and effectiveness and could help develop evidence-based policymaking. Trial registration: This study was approved by The Ethical Committee of Faculty of Medicine, University of Indonesia, ref:194/PT02.FK/Etik/2006 and has been filed by ethics committee of the Leiden University Medical Center. Clinical trial number:ISRCTN83830814. The study is reported in accordance with the CONSORT guidelines for cluster-randomized studies.

Summary: A multicentre evaluation of the Brugia Rapid dipstick test was performed using 1263 serum samples in four international laboratories, i.e. T.D. Medical College (TDMC, India), National Institutes of Health (NIH, USA), Swiss Tropical Institute (STI, Switzerland) and Leiden University Medical Centre (LUMC, Netherlands). In comparison with microscopy, the dipstick demonstrated sensitivities of 97.2% (70 of 72) at TDMC, 91.6% (175 of 191) at LUMC and 100% (six of six) at STI. Sera of chronic patients showed a positivity rate of 11.3% (19 of 168) and 61.2% (71of 116) at TDMC and LUMC, respectively. All 266 sera of non‐endemic normals from STI, NIH and LUMC tested negative with the dipstick. At LUMC, sera of ‘endemic normals’ (amicrofilaraemics with no clinical disease) from an area with approximately 35% microfilaria positivity showed 60.8% positive results (31 of 51), thus demonstrating the likelihood of many cryptic infections occuring in this population. Specificities of the test with Onchocerca volvulus sera were 98.8% (80 of 81) and 100% (10 of 10) at the NIH and STI, respectively; while specificity with Loa loa sera at the NIH was 84.6% (44 of 52). At the STI, the dipstick test also demonstrated 100% specificity when tested with 75 sera from various protozoan and helminthic infections.

Insulin resistance is a strong predictor of the development of type 2 diabetes mellitus. Chronic helminth infections might protect against insulin resistance via a caloric restriction state and indirectly via T-helper-2 polarization of the immune system. Therefore the elimination of helminths might remove this beneficial effect on insulin resistance. To determine whether soil-transmitted helminth infections are associated with a better whole-body insulin sensitivity and whether this protection is reversible by anthelmintic treatment, a household-based cluster-randomized, double blind, placebo-controlled trial was conducted in the area of Nangapanda on Flores Island, Indonesia, an area endemic for soil-transmitted helminth infections. The trial incorporates three monthly treatment with albendazole or matching placebo for one year, whereby each treatment round consists of three consecutive days of supervised drug intake. The presence of soil-transmitted helminths will be evaluated in faeces using microscopy and/or PCR. The primary outcome of the study will be changes in insulin resistance as assessed by HOMA-IR, while the secondary outcomes will be changes in body mass index, waist circumference, fasting blood glucose, 2 h-glucose levels after oral glucose tolerance test, HbA1c, serum lipid levels, immunological parameters, and efficacy of anthelmintic treatment. The study will provide data on the effect of helminth infections on insulin resistance. It will assess the relationship between helminth infection status and immune responses as well as metabolic parameters, allowing the establishment of a link between inflammation and whole-body metabolic homeostasis. In addition, it will give information on anthelmintic treatment efficacy and effectiveness. This study has been approved by the ethical committee of Faculty of Medicine Universitas Indonesia (ref: 549/H2.F1/ETIK/2013), and has been filed by the ethics committee of Leiden University Medical Center, clinical trial number: ISRCTN75636394 . The study is reported in accordance with the CONSORT guidelines for cluster-randomised trials.

Oral polio vaccine (OPV) is recommended to be given at birth together with BCG vaccine. While we were conducting two trials including low-birth-weight (LBW) and normal-birth-weight (NBW) infants in Guinea-Bissau, OPV was not available during some periods and therefore some infants did not receive OPV at birth, but only BCG. We investigated the effect of OPV given simultaneously with BCG at birth on the immune response to BCG vaccine. We compared the in vitro and the in vivo response to PPD in the infants who received OPV and BCG with that of infants who received BCG only. At age 6 weeks, the in vitro cytokine response to purified protein derivate (PPD) of M. Tuberculosis was reduced in LBW and NBW infants who had received OPV with BCG. In a pooled analysis receiving OPV with BCG at birth was associated with significantly lower IL-13 (p = 0.041) and IFN-γ (p = 0.004) and a tendency for lower IL-10 (p = 0.054) in response to PPD. Furthermore, OPV was associated with reduced in vivo response to PPD at age 2 months, the prevalence ratio (PR) of having a PPD reaction being 0.75 (0.58–0.98), p = 0.033, and with a tendency for reduced likelihood of having a BCG scar (0.95 (0.91–1.00), p = 0.057)). Among children with a scar, OPV was associated with reduced scar size, the regression coefficient being −0.24 (−0.43—0.05), p = 0.012. This study is the first to address the consequences for the immune response to BCG of simultaneous administration with OPV. Worryingly, the results indicate that the common practice in low-income countries of administering OPV together with BCG at birth may down-regulate the response to BCG vaccine.

DNA-based diagnostic methods have been shown to be highly sensitive and specific for the detection of malaria. An 18S-rRNA-based, real-time polymerase chain reaction (PCR) was used to determine the prevalence and intensity of Plasmodium infections on Flores Island, Indonesia. Microscopy and real-time multiplex PCR for the detection of Plasmodium species was performed on blood samples collected in a population-based study in Nangapanda Flores Island, Indonesia. A total 1,509 blood samples were analysed. Real-time PCR revealed prevalence for Plasmodium falciparum, Plasmodium vivax, and Plasmodium malariae to be 14.5%, 13.2%, and 1.9% respectively. Sub-microscopic parasitaemia were found in more than 80% of all positive cases. The prevalence of P. falciparum and P. vivax was significantly higher in subjects younger than 20 years (p ≤ 0.01). In the present study, among non-symptomatic healthy individuals, anaemia was strongly correlated with the prevalence and load of P. falciparum infections (p ≤ 0.01; p = 0.02) and with the load of P. vivax infections (p = 0.01) as detected with real-time PCR. Subjects with AB blood group tend to have a higher risk of being infected with P. falciparum and P. vivax when compared to other blood groups. The present study has shown that real-time PCR provides more insight in the epidemiology of Plasmodium infections and can be used as a monitoring tool in the battle against malaria. The unsurpassed sensitivity of real-time PCR reveals that sub microscopic infections are common in this area, which are likely to play an important role in transmission and control. Trials number http://www.controlled-trials.com/ISRCTN83830814