A hybrid transmission model for Plasmodium vivax accounting for superinfection, immunity and the hypnozoite reservoir.

Malaria is a vector-borne disease that exacts a grave toll in the Global South. The epidemiology of Plasmodium vivax, the most geographically expansive agent of human malaria, is characterised by the accrual of a reservoir of dormant parasites known as hypnozoites. Relapses, arising from hypnozoite activation events, comprise the majority of the blood-stage infection burden, with implications for the acquisition of immunity and the distribution of superinfection. Here, we construct a novel model for the transmission of P. vivax that concurrently accounts for the accrual of the hypnozoite reservoir, (blood-stage) superinfection and the acquisition of immunity. We begin by using an infinite-server queueing network model to characterise the within-host dynamics as a function of mosquito-to-human transmission intensity, extending our previous model to capture a discretised immunity level. To model transmission-blocking and antidisease immunity, we allow for geometric decay in the respective probabilities of successful human-to-mosquito transmission and symptomatic blood-stage infection as a function of this immunity level. Under a hybrid approximation-whereby probabilistic within-host distributions are cast as expected population-level proportions-we couple host and vector dynamics to recover a deterministic compartmental model in line with Ross-Macdonald theory. We then perform a steady-state analysis for this compartmental model, informed by the (analytic) distributions derived at the within-host level. To characterise transient dynamics, we derive a reduced system of integrodifferential equations, likewise informed by our within-host queueing network, allowing us to recover population-level distributions for various quantities of epidemiological interest. In capturing the interplay between hypnozoite accrual, superinfection and acquired immunity-and providing, to the best of our knowledge, the most complete population-level distributions for a range of epidemiological values-our model provides insights into important, but poorly understood, epidemiological features of P. vivax.

Fatal Strongyloides stercoralis hyperinfection syndrome in an alcoholic diabetic patient from México / Síndrome de hiperinfección mortal por Strongyloides stercoralis en un paciente diabético y alcohólico de México

Strongyloides stercoralis hyperinfection syndrome is a medical emergency that requires a high level of suspicion. Immunocompromised patients are at high risk of hyperinfection syndrome; however, malnutrition, alcoholism, and diabetes mellitus also need to be considered as predisposing factors. The diagnosis and treatment of Strongyloides hyperinfection are challenging and patients often have severe complications. Consequently, mortality is overwhelmingly high, with proportions above 60%. Herein, we report a case of Strongyloides hyperinfection in a 40-year-old alcoholic diabetic patient living in México. Unfortunately, the late diagnosis resulted in his death despite the treatment and supportive measures. Increased awareness is needed to prevent the dire consequences of strongyloidiasis.

El síndrome de hiperinfección por Strongyloides stercoralis es una emergencia médica que requiere una aguda sospecha clínica. Los pacientes inmunocomprometidos tienen alto riesgo de sufrir el síndrome de hiperinfección; sin embargo, la desnutrición, el alcoholismo y la diabetes mellitus también deben considerarse factores predisponentes. El diagnóstico y el tratamiento de la hiperinfección por S. stercoralis constituyen un desafío y los pacientes a menudo tienen complicaciones graves. Como consecuencia, la mortalidad es abrumadoramente alta, con proporciones superiores al 60 %. Se presenta un caso de hiperinfección por S. stercoralis en un paciente diabético y alcohólico de 40 años que vivía en México. Infortunadamente, el diagnóstico tardío causó su muerte a pesar del tratamiento y las medidas de soporte. Se necesita un mayor conocimiento para prevenir las terribles consecuencias de la estrongiloidiasis.

A Host-Parasite System with Multiple Parasite Strains and Superinfection Revisited: The Global Dynamics.

In this paper, we revisit a host-parasite system with multiple parasite strains and superinfection proposed by Nowak and May (Proc R Soc Lond B 255(1342):81-89, 1994), and study its global dynamics when we relax the two strict conditions assumed therein. As for system with two parasite strains, we derive that the basic reproduction number [Formula: see text] is the threshold condition for parasite extinction and the invasion reproduction number [Formula: see text] is the subthreshold condition for coexistence of two parasite strains. As for system with three parasite strains, we are surprised to discover the global stability of parasite-free and coexistence equilibrium, which is distinct from the previous result. Furthermore, for system with n strains, we obtain the global asymptotical stability of the parasite-free equilibrium, conjecture a general result on the global stability of coexistence equilibrium and provide two numerical examples to testify our conjecture.

Late post-kidney transplant Strongyloides hyperinfection syndrome.

Disseminated strongyloidiasis is a potentially life-threatening infection in organ transplant recipients that typically occurs within the first 6 months of transplantation. We discuss a patient from the Appalachia region of Virginia who appeared to acquire Strongyloides stercoralis domestically years after kidney transplantation and then develop disseminated strongyloidiasis.

Successful Treatment of Strongyloides stercoralis Hyperinfection in a Kidney Transplant Recipient: Case Report.

Strongyloides stercoralis (SS) can cause hyperinfection and disseminated infection in immunosuppressed individuals, with risk of mortality. We report the case of a cadaveric kidney transplant recipient who developed gastrointestinal symptoms and eosinophilia, approximately 3 months after transplantation. Stool examination and esophagogastroduodenoscopy with biopsies were positive for SS larvae. The patient was started on oral ivermectin and immunosuppression was reduced, but still the clinical picture got worse with metabolic ileus and respiratory symptoms, with the need for administration of subcutaneous ivermectin and combined therapy with albendazol. The patient survived and graft function was preserved. The patient was unlikely to be the source of infection. We also present a review of cases of SS infection in kidney transplant recipients.

Exposing the diversity of multiple infection patterns.

Natural populations often have to cope with genetically distinct parasites that can coexist, or not, within the same hosts. Theoretical models addressing the evolution of virulence have considered two within host infection outcomes, namely superinfection and coinfection. The field somehow became limited by this dichotomy that does not correspond to an empirical reality as other infection patterns, namely sets of within-host infection outcomes, are possible. We indeed formally prove there are over one hundred different infection patterns solely for recoverable chronic infections caused by two genetically distinct horizontally-transmitted microparasites. We afterwards highlight eight infection patterns using an explicit modelling of within-host dynamics that captures a large range of ecological interactions, five of which have been neglected so far. To clarify the terminology related to multiple infections, we introduce terms describing these new relevant patterns and illustrate them with existing biological systems. These infection patterns constitute a new framework for linking within-host and between-host dynamics, which is a requirement to forward our understanding of the epidemiology and the evolution of parasites.

Superinfection exclusion and the long-term survival of honey bees in Varroa-infested colonies.

Over the past 50 years, many millions of European honey bee (Apis mellifera) colonies have died as the ectoparasitic mite, Varroa destructor, has spread around the world. Subsequent studies have indicated that the mite's association with a group of RNA viral pathogens (Deformed Wing Virus, DWV) correlates with colony death. Here, we propose a phenomenon known as superinfection exclusion that provides an explanation of how certain A. mellifera populations have survived, despite Varroa infestation and high DWV loads. Next-generation sequencing has shown that a non-lethal DWV variant 'type B' has become established in these colonies and that the lethal 'type A' DWV variant fails to persist in the bee population. We propose that this novel stable host-pathogen relationship prevents the accumulation of lethal variants, suggesting that this interaction could be exploited for the development of an effective treatment that minimises colony losses in the future.

Myiasis on squamous cell carcinoma of skin.

Advanced squamous cell carcinoma (SCC) is a challenge for treatment. It is also a risk factor for unintended infestation with diptera larvae (maggots) known as myiasis. We performed a retrospective investigation in our files from 2001 to 2014 and identified three patients with SCC-associated myiasis (three men). In all three cases, Lucilia spp. were found. A literature review using PUBMED revealed another 12 cases of SCC-associated myiasis due to different species. It is not only a disease of older age, as two of the patients were in their 20s. The male to female ratio was 2 to 1. Wound myiasis and cavity myiasis were seen in half of the cases each. Pain, bleeding, and infection were possible symptoms due to infestation but not all patients reported complaints. Treatment aims to completely remove all maggots and to prevent secondary tissue damage with blindness due to eye ball destruction as one of the worst.

Hyperinfection strongyloidiasis in renal transplant recipients.

Strongyloidiasis is infection caused by the nematode Strongyloides stercoralis. Chronic uncomplicated strongyloidiasis is known to occur in immunocompetent individuals while hyperinfection and dissemination occurs in selective immunosuppressed hosts particularly those on corticosteroid therapy. We report two cases of hyperinfection strongyloidiasis in renal transplant recipients and document endoscopic and pathological changes in the involved small bowel. One patient presented with features of dehydration and malnutrition while another developed ileal obstruction and strangulation, requiring bowel resection. Oesophagogastroduodenoscopy showed erythematous and thickened duodenal mucosal folds. Histopathological examination of duodenal biopsies revealed S. stercoralis worms, larvae and eggs embedded in mucosa and submucosa. Wet mount stool preparation showed filariform larvae of S. stercoralis in both cases. Patients were managed with anthelmintic therapy (ivermectin/albendazole) and concurrent reduction of immunosuppression. Both patients had uneventful recovery. Complicated strongyloidiasis should be suspected in immunocompromised hosts who present with abdominal pain, vomiting and diarrhoea, particularly in endemic areas.

Borrelia hermsii acquisition order in superinfected ticks determines transmission efficiency.

Multilocus sequence typing of Borrelia hermsii isolates reveals its divergence into two major genomic groups (GG), but no differences in transmission efficiency or host pathogenicity are associated with these genotypes. To compare GGI and GGII in the tick-host infection cycle, we first determined if spirochetes from the two groups could superinfect the tick vector Ornithodoros hermsi. We infected mice with isolates from each group and fed ticks sequentially on these mice. We then fed the infected ticks on naive mice and measured GGI and GGII spirochete densities in vector and host, using quantitative PCR of genotype-specific chromosomal DNA sequences. Sequential feedings resulted in dual tick infections, showing that GGI or GGII primary acquisition did not block superinfection by a secondary agent. On transmission to naive mice at short intervals after acquisition, ticks with primary GGI and secondary GGII spirochete infections caused mixed GGI and GGII infections in mice. However, ticks with primary GGII and secondary GGI spirochete infections caused only GGII infections with all isolate pairs examined. At longer intervals after acquisition, the exclusion of GGI by GGII spirochetes declined and cotransmission predominated. We then examined GGI and GGII spirochetemia in mice following single inoculation and coinoculation by needle and found that GGI spirochete densities were reduced on multiple days when coinoculated with GGII. These findings indicate that dual GGI-GGII spirochete infections can persist in ticks and that transmission to a vertebrate host is dependent on the order of tick acquisition and the interval between acquisition and transmission events.

[High risk of strongyloïdes hyperinfection in a patient with sarcoidosis]. / Risque d'anguillulose maligne chez un patient présentant une sarcoïdose.

Strongyloïdes stercoralis infection is a polymorphic and non specific clinical presentation. Often asymptomatic, it can be not seen. However, in patients with immunodeficiency, high parasite load can be observed, consequence of self-infestation cycle, and can spread throughout the body. This presentation of malignant strongyloidiasis presents a mortality rate of 70%. The case report presents a 45 years old patient of Caribbean origin, long time treated with corticosteroids for sarcoidosis, and hospitalized for Strongyloïdes stercoralis colitis with high parasite load, raising fears an evolution to hyperinfection. His last visit to endemic area was in 2002. In conclusion, the potential severity of strongyloidiasis is strongly increased by immunosuppression, including corticosteroids. This risk should be notified prior to initiation of any treatment with corticosteroids, firstly by looking at a stay in endemic areas. The case of our patient illustrates the fact that a long time between risk of contamination and clinical manifestations is not a sufficient criterion for excluding an asymptomatic chronic infection with Strongyloïdes stercoralis. It is therefore recommended for patients who have lived in endemic areas to search the parasite in stool by a sensitive method.

Fulminant gastrointestinal hemorrhage due to Strongyloides stercoralis hyperinfection in an AIDS patient.

Strongyloides stercoralis is an endemic nematode to tropical and subtropical regions of the globe. The parasite is capable of autoinfection, which is limited by an intact immune response. In immunocompromised hosts, hyperinfection and dissemination can occur and have a high index of mortality. A hyperinfection syndrome with dissemination is frequently associated with corticosteroid administration and other conditions (malignancies and organ transplantation). Interestingly, although strongyloidiasis is common among AIDS patients in endemic areas, the hyperinfection syndrome is rarely noted. We report here on a rare manifestation of fulminant gastrointestinal hemorrhage due to hyperinfection of strongyloidiasis in a female drug-abusing, alcoholic HIV/AIDS patient.

Fulminant gastrointestinal hemorrhage due to Strongyloides stercoralis hyperinfection in an AIDS patient

Strongyloides stercoralis is an endemic nematode to tropical and subtropical regions of the globe. The parasite is capable of autoinfection, which is limited by an intact immune response. In immunocompromised hosts, hyperinfection and dissemination can occur and have a high index of mortality. A hyperinfection syndrome with dissemination is frequently associated with corticosteroid administration and other conditions (malignancies and organ transplantation). Interestingly, although strongyloidiasis is common among AIDS patients in endemic areas, the hyperinfection syndrome is rarely noted. We report here on a rare manifestation of fulminant gastrointestinal hemorrhage due to hyperinfection of strongyloidiasis in a female drug-abusing, alcoholic HIV/AIDS patient.

Strongyloides stercoralis hyperinfection syndrome in patients on prolonged steroid treatment: two case reports.

Two cases of Strongyloides hyperinfection have been reported who were on prolonged steroid therapy for frequent exacerbations of respiratory problems. One patient presenting with acute respiratory distress, rapidly deteriorated, did not give any time for management and died whereas the second patient survived because of early diagnosis of hyperinfection due to Strongyloides stercoralis.

Superinfection and the evolution of resistance to antimalarial drugs.

A major issue in the control of malaria is the evolution of drug resistance. Ecological theory has demonstrated that pathogen superinfection and the resulting within-host competition influences the evolution of specific traits. Individuals infected with Plasmodium falciparum are consistently infected by multiple parasites; however, while this probably alters the dynamics of resistance evolution, there are few robust mathematical models examining this issue. We developed a general theory for modelling the evolution of resistance with host superinfection and examine: (i) the effect of transmission intensity on the rate of resistance evolution; (ii) the importance of different biological costs of resistance; and (iii) the best measure of the frequency of resistance. We find that within-host competition retards the ability and slows the rate at which drug-resistant parasites invade, particularly as the transmission rate increases. We also find that biological costs of resistance that reduce transmission are less important than reductions in the duration of drug-resistant infections. Lastly, we find that random sampling of the population for resistant parasites is likely to significantly underestimate the frequency of resistance. Considering superinfection in mathematical models of antimalarial drug resistance may thus be important for generating accurate predictions of interventions to contain resistance.

Isospora belli superinfection in a patient with eosinophilic gastroenteritis--a diagnostic challenge.

Isospora belli infection, characterized by peripheral blood eosinophilia, is often seen as an opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS). It is also reported in patients with underlying lymphoproliferative disorders including lymphoma and leukemia. Eosinophil-associated gastrointestinal disorders (EGID), including eosinophilic gastroenteritis (EGE), is characterized by eosinophilic infiltration of the gastrointestinal (GI) tract with various GI symptoms. We report a case of a 50-year-old male who developed Isospora superinfection of the small bowel while receiving systemic corticosteroids for EGE. He presented with worsening diarrhea, abdominal pain, nausea and vomiting with worsening peripheral eosinophilia. I. belli infection was diagnosed by the detection of oocysts in stool samples and by the presence of the parasite on duodenal biopsy in the background of tissue eosinophilia. I. belli can cause severe chronic diarrhea in immunocompromised patients on corticosteroids. Trimethoprim-sulfamethoxazole often provided rapid cure. Even though peripheral blood eosinophilia was seen in both EGE and Isospora infection, the identification of subnuclear protozoal inclusions as a new histologic finding, as well as the absence of this finding in previous duodenal biopsies coupled with the continued presence of tissue eosinophilia, favored a parasitic superinfection in the setting of underlying EGE.

Superinfection in malaria: Plasmodium shows its iron will.

After the bite of a malaria-infected mosquito, the Plasmodium sporozoite infects liver cells and produces thousands of merozoites, which then infect red blood cells, causing malaria. In malaria-endemic areas, several hundred infected mosquitoes can bite an individual each year, increasing the risk of superinfection. However, in infants that are yet to acquire immunity, superinfections are infrequent. We have recently shown that blood-stage parasitaemia, above a minimum threshold, impairs the growth of a subsequent sporozoite infection of liver cells. Blood-stage parasites stimulate the production of the host iron-regulatory factor hepcidin, which redistributes iron away from hepatocytes, reducing the development of the iron-dependent liver stage. This could explain why Plasmodium superinfection is not often found in young nonimmune children. Here, we discuss the impact that such protection from superinfection might have in epidemiological settings or in programmes for controlling malaria, as well as how the induction of hepcidin and redistribution of iron might influence anaemia and the outcome of non-Plasmodium co-infections.