A Randomized Controlled Trial to Investigate Safety and Variability of Egg Excretion After Repeated Controlled Human Hookworm Infection

Hoogerwerf, Marie-Astrid; Koopman, J.; Janse, Jacqueline J.; Langenberg, Marijke C. C.; Schuijlenburg, Roos van; Kruize, Yvonne C. M.; Brienen, Eric A. T.; Manurung, Mikhael D.; Verbeek-Menken, Petra H.; Beek, Martha T. van der; Westra, Inge M.; Meij, Pauline; Visser, Leo G.; Lieshout, Lisette van; Vlas, Sake J. de; Yazdanbakhsh, Maria; Coffeng, Luc E.; Roestenberg, Meta

doi:10.1093/infdis/jiaa414

Cited by 11 publications

(19 citation statements)

References 22 publications

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“…Results of the clinical trial have been published elsewhere. 19 Briefly, of the 24 randomized volunteers, twenty completed follow-up and were included in the microbiota analysis, providing a total of 100 fecal samples. The primary aim of the clinical trial was to investigate the effect of repeated infectious dosages on hookworm egg excretion and variability.…”

Section: Resultsmentioning

confidence: 99%

“…All volunteers developed patent hookworm infection as shown by positive microscopy for hookworm eggs at a median of eight weeks (range five-nine) after first skin infection with L3 larvae. 19 Abdominal adverse events in many volunteers starting at three to four weeks after infection were paralleled by eosinophil increases which likely marked the timepoint of arrival and establishment of the hookworm in the duodenum. Abdominal adverse events consisted of bloating, nausea, vomiting, diarrhea or abdominal cramping.…”

Section: Resultsmentioning

confidence: 99%

“…Volunteers exposed to higher larval dosages (n = 6 volunteers with 50L3 larvae, n = 7 with 100L3 larvae and n = 7 with 150L3 larvae) generally had higher egg loads in feces, but there was no relation between cumulative larval dosage and number and severity of adverse events. 19 Based on the severity, number and duration of adverse events, nine volunteers were classified into the “hi” GI symptoms group, whereas eleven were categorized into the “lo” GI symptoms group by two independent physicians. All volunteers with severe adverse events were placed in the “hi” category, together with two volunteers who did not have severe adverse events but moderate adverse events of long duration (Table S1).…”

Section: Resultsmentioning

confidence: 99%

“…Recovery of stability in the “hi” symptoms groups leads us to believe that either volunteers with a more unstable microbiota in early weeks post-infection are more likely to experience GI symptoms during the infection, or the GI symptoms are caused by a more severe enteritis that also affects microbiota stability. The latter hypothesis seems most likely whereby symptoms are caused by an eosinophilic enteritis, with eosinophils having been described to correlate with severity of enteritis, 19 , 23 and the enteritis may in turn affect the gut microbiota. Although cause and effect cannot be determined, it does suggest an important bacterial-helminth-host interplay, which deserves further investigation.…”

Section: Discussionmentioning

confidence: 99%

“…18 In this study we infected individuals with 50–150 L3 larvae, after which we found mean egg counts of around 1500 eggs per gram feces at plateau level, which is more in line with the endemic situation where mild infection is defined by WHO as <2000 eggs per gram feces. 18 , 19 Still, infection levels in CHHIMs are not fully comparable to areas with a high infectious burden, defined as >4000 eggs per gram by WHO. The current study had two main aims.…”

Section: Introductionmentioning

confidence: 99%

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Dynamics of the bacterial gut microbiota during controlled human infection with Necator americanus larvae

et al. 2020

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Hookworms are soil-transmitted helminths that use immune-evasive strategies to persist in the human duodenum where they are responsible for anemia and protein loss. Given their location and immune regulatory effects, hookworms likely impact the bacterial microbiota. However, microbiota studies struggle to deconvolute the effect of hookworms from confounders such as coinfections and malnutrition. We thus used an experimental human hookworm infection model to explore temporal changes in the gut microbiota before and during hookworm infection. Volunteers were dermally exposed to cumulative dosages of 50, 100 or 150 L3 Necator americanus larvae. Fecal samples were collected for microbiota profiling through 16S rRNA gene amplicon sequencing at weeks zero, four, eight, fourteen and twenty. During the acute infection phase (trial week zero to eight) no changes in bacterial diversity were detected. During the established infection phase (trial week eight to twenty), bacterial richness (Chao1, p = .0174) increased significantly over all volunteers. No relation was found between larval dosage and diversity, stability or relative abundance of individual bacterial taxa. GI symptoms were associated with an unstable microbiota during the first eight weeks and rapid recovery at week twenty. Barnesiella, amongst other taxa, was more abundant in volunteers with more GI symptoms throughout the study. In conclusion, this study showed that clinical GI symptoms following N. americanus infection are associated with temporary microbiota instability and relative abundance of specific bacterial taxa. These results suggest a possible role of hookworm-induced enteritis on microbiota stability.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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