Preventive chemotherapy for the control of strongyloidiasis in school-age children: Estimating the ivermectin need.

BACKGROUND: Strongyloides stercoralis is a soil-transmitted helminth (STH) that affects approximately 600 million people worldwide. Interventions targeting S. stercoralis have not been implemented yet. Specific treatment (ivermectin) could be included in already ongoing preventive chemotherapy (PC) campaigns targeting other STHs. The aim of this study was to estimate the quantity of ivermectin needed for an integrated STH/S. stercoralis control program. METHODODOLOGY/PRINCIPAL FINDINGS: Our study estimates the number of school- age children (SAC) (the main focus of STH deworming campaigns) in need of PC with ivermectin. The normal approximation of the binomial distribution was adopted to calculate the hypothetical prevalence distribution in each endemic country. Considering prevalence thresholds for PC equal to 10%, 15%, and 20%, we estimated the number of SAC in need of treatment. We adjusted the estimates accounting for ivermectin distributed in lymphatic filariasis and onchocerciasis elimination programs and excluded from our calculation areas where Loa loa is endemic. The global number of SAC that should be targeted in PC campaigns was estimated at 283.9 M (95% CI: 163.4-368.8), 207.2 M (95% CI: 160.9-380.7), and 160.7 M (95% CI: 86.6-225.7) when the threshold for intervention was set to 10%, 15%, and 20%, respectively. India, China, Indonesia, Bangladesh, and Nigeria accounted for about 50% of the global SAC would have to be covered by PC intervention. CONCLUSIONS/SIGNIFICANCE: Our analysis may support endemic countries to evaluate the ivermectin quantity needed for integrating strongyloidiasis in the existing STH programs. These estimates might also show to generic drug manufacturers the size of the potential market for ivermectin and encourage its production.

Donor-derived strongyloidiasis after organ transplantation in Norway.

Strongyloides stercoralis is an intestinal helminth which in humans can cause asymptomatic chronic infection maintained for decades through its auto-infective cycle. During solid organ transplantation, recipients may unintentionally receive an organ infected with strongyloides. This is a very rare complication but may have deadly outcome if not detected. We hereby report two transplant recipients whom developed Strongyloides hyperinfection syndrome after organ transplantation from the same deceased donor. Recipient 1 was kidney transplanted and presented at day 65 post engraftment with diarrhea and subsequent septicemia and gastric retention. Larvae were detected in gastric aspirate. Recipient 2 was simultaneously kidney and pancreas transplanted and presented at day 90 post engraftment also with gastric retention and septicemia. Larvae were demonstrated on duodenal biopsy and stool sample. The clinical course was complicated with severe duodenal bleedings, gastric retention, meningitis, and prolonged hospitalization. Retrospective testing of pre-transplant donor serum was positive for Strongyloides stercoralis antibodies. As a result of disease severity and gastric retention albenazole was administered via a jejunal tube and ivermectin subcutaneously in both recipients. S stercoralis was successfully eradicated and the transplants ended up with unaffected graft function. Following these two cases, we started systematic screening of all deceased donors for serum Strongyloides IgG in October 2016. After having screened 150 utilized donors one tested positive for Strongyloides, which initiated prophylactic ivermectin treatment to organ recipients. No symptoms or disease developed. Our center will continue to screen all donors as prophylactic treatment may avert this potentially lethal complication in cases of donor-derived Strongyloides infection.

Synchronous MALT lymphoma of the colon and stomach and regression after eradication of Strongyloides stercoralis and Helicobacter pylori.

Mucosa-associated lymphoid tissue (MALT) is vital for host immunological surveillance against pathogens. MALT lymphoma, also known as extranodal marginal zone B cell lymphoma, is a non-Hodgkin's lymphoma subtype that predominantly arises in the gastrointestinal tract. Chronic Helicobacter pylori (H. pylori) infection is a common cause of gastric MALT lymphoma, although other infections are reported in association with extragastric MALT lymphomas. To our knowledge, here we report the first case of synchronous MALT lymphomas of the colon and stomach in the presence of Strongyloides stercoralis and H. pylori infections that resolved after eradication of both organisms.

The Lake Victoria Island Intervention Study on Worms and Allergy-related diseases (LaVIISWA): study protocol for a randomised controlled trial.

BACKGROUND: The Hygiene Hypothesis proposes that infection exposure protects against inflammatory conditions. Helminths possess allergen-like molecules and may specifically modulate allergy-related immunological pathways to inhibit responses which protect against them. Mass drug administration is recommended for helminth-endemic communities to control helminth-induced pathology, but may also result in increased rates of inflammation-mediated diseases in resource-poor settings. Immunological studies integrated with implementation of helminth control measures may elucidate how helminth elimination contributes to ongoing epidemics of inflammatory diseases. We present the design of the Lake Victoria Island Intervention Study on Worms and Allergy-related diseases (LaVIISWA), a cluster-randomised trial evaluating the risks and benefits of intensive versus standard anthelminthic treatment for allergy-related diseases and other health outcomes. METHODS/DESIGN: The setting is comprised of island fishing communities in Mukono district, Uganda. Twenty-six communities have been randomised in a 1:1 ratio to receive standard or intensive anthelminthic intervention for a three-year period. Baseline characteristics were collected immediately prior to intervention rollout, commenced in February 2013. Primary outcomes are reported wheeze in the past 12 months and atopy (skin prick test response and allergen-specific immunoglobulin (asIg) E concentration). Secondary outcomes are visible flexural dermatitis, helminth infections, haemoglobin, growth parameters, hepatosplenomegaly, and responses to vaccine antigens. The trial provides a platform for in-depth analysis of clinical and immunological consequences of the contrasting interventions. DISCUSSION: The baseline survey has been completed successfully in a challenging environment. Baseline characteristics were balanced between trial arms. Prevalence of Schistosoma mansoni, hookworm, Strongyloides stercoralis and Trichuris trichiura was 52%, 23%, 13%, and 12%, respectively; 31% of Schistosoma mansoni infections were heavy (>400 eggs/gram). The prevalence of reported wheeze and positive skin prick test to any allergen was 5% and 20%, respectively. Respectively, 77% and 87% of participants had Dermatophagoides- and German cockroach-specific IgE above 0.35 kUA/L. These characteristics suggest that the LaVIISWA study will provide an excellent framework for investigating beneficial and detrimental effects of worms and their treatment, and the mechanisms of such effects. TRIAL REGISTRATION: This trial was registered with Current Controlled Trials (identifier: ISRCTN47196031) on 7 September 2012.

Acute respiratory distress syndrome due to Strongyloides stercoralis infection in a patient with cervical cancer.

A 62-year-old woman complained of diarrhea and vomiting after receiving chemotherapy for cervical cancer in association with high doses of corticosteroids. Two months later, the patient developed acute respiratory distress syndrome, and numerous Strongyloides stercoralis parasites were found in the intrabronchial discharge. Ivermectin was administered daily until nematodes were no longer detected in the sputum, and the patient's condition was successfully rescued. Antibodies for human T-cell lymphotropic virus-1 (HTLV-1) were positive. HTLV-1 infection and the administration of corticosteroids are known risk factors for strongyloides hyperinfection syndrome. Therefore, physicians should consider this disease in the differential diagnosis of patients from endemic areas who present with gastrointestinal symptoms under these risk factors.

"Surprise" in the evolution of chronic membranoproliferative glomerulonephritis associated with severe strongyloidiasis under corticotherapy: "hygienic paradox"?

A case of strongyloidiasis in a patient with membranoproliferative glomerulonephritis is reported. In our patient, strongyloidiasis evolved latently and became overt after corticotherapy, and it turned to be a very severe outcome and life-threatening complications, hyperinfection syndrome and upper digestive tract hemorrhage. Besides its well-known complications, steroid therapy may provide real surprises. The association of this therapy with strongyloidiasis may turn an undiagnosed inactive, chronic form of the disease into an active form within the framework of a hyperinfection syndrome which might lead to death. In our case, the diagnosis of strongyloidiasis was established only after duodenal biopsy was performed for upper digestive tract hemorrhage, which revealed the parasite. It should be underlined that under corticotherapy, the patient evolved favorably with regard to glomerular disease, while strongyloidiasis worsened. The outcome was positive after the patient was treated with albendazole and ivermectin. The diagnosis of strongyloidiasis is sometimes difficult to establish due to the fact that eosinophilia may be absent, while commonly utilized stool examinations may be negative. By analyzing our case, it may be assumed that the immune mechanisms involved in strongyloidiasis do not activate the glomerular nephropathy. On the contrary, these mechanisms seem to have an immunosuppressive effect. The "hygienic hypothesis" also needs to be considered. While on corticotherapy, patients with glomerulonephritis need immunologic and parasitologic monitoring. This is important for other immunodepressing diseases and for immunosuppressive drugs. If the patient has originated in a mining area, as is the case with our patient, or in endemic areas, this monitoring becomes mandatory. The case reflects the complexity of the interrelation between the immune mechanisms in glomerulonephritis and those in parasitic diseases, strongyloidiasis in our case.

Secondary Strongyloides stercoralis prophylaxis in patients with human T-cell lymphotropic virus type 1 infection: report of two cases.

Secondary ivermectin prophylaxis for strongyloidiasis in two patients with human T-cell lymphotropic virus type 1 (HTLV-1)-associated malignancies and fully treated complicated strongyloidiasis is described. Treatment was well tolerated and neither patient developed further manifestations of hyperinfection. As treatment failure for complicated strongyloidiasis has been documented in severely immunosuppressed patients, secondary prophylaxis may be indicated.

Tribendimidine and albendazole for treating soil-transmitted helminths, Strongyloides stercoralis and Taenia spp.: open-label randomized trial.

BACKGROUND: Tribendimidine is an anthelminthic drug with a broad spectrum of activity. In 2004 the drug was approved by Chinese authorities for human use. The efficacy of tribendimidine against soil-transmitted helminths (Ascaris lumbricoides, hookworm, and Trichuris trichiura) has been established, and new laboratory investigations point to activity against cestodes and Strongyloides ratti. METHODOLOGY/PRINCIPAL FINDINGS: In an open-label randomized trial, the safety and efficacy of a single oral dose of albendazole or tribendimidine (both drugs administered at 200 mg for 5- to 14-year-old children, and 400 mg for individuals > or = 15 years) against soil-transmitted helminths, Strongyloides stercoralis, and Taenia spp. were assessed in a village in Yunnan province, People's Republic of China. The analysis was on a per-protocol basis and the trial is registered with controlled-trials.com (number ISRCTN01779485). Both albendazole and tribendimidine were highly efficacious against A. lumbricoides and, moderately, against hookworm. The efficacy against T. trichiura was low. Among 57 individuals who received tribendimidine, the prevalence of S. stercoralis was reduced from 19.3% to 8.8% (observed cure rate 54.5%, p = 0.107), and that of Taenia spp. from 26.3% to 8.8% (observed cure rate 66.7%, p = 0.014). Similar prevalence reductions were noted among the 66 albendazole recipients. Taking into account "new" infections discovered at treatment evaluation, which were most likely missed pre-treatment due to the lack of sensitivity of available diagnostic approaches, the difference between the drug-specific net Taenia spp. cure rates was highly significant in favor of tribendimidine (p = 0.001). No significant adverse events of either drug were observed. CONCLUSIONS/SIGNIFICANCE: Our results suggest that single-dose oral tribendimidine can be employed in settings with extensive intestinal polyparasitism, and its efficacy against A. lumbricoides and hookworm was confirmed. The promising results obtained with tribendimidine against S. stercoralis and Taenia spp. warrant further investigations. In a next step, multiple-dose schedules should be evaluated.

Comparison of albendazole regimen for prophylaxis of strongyloides hyperinfection in nephrotic syndrome patients on long-term steroids in Cambodia.

Nephrotic syndrome patients on long-term steroids face the risk of having heavy uncomplicated strongyloidiasis or death from its extreme form, the strongyloides hyperinfection. The risk can be minimized if we eradicate the parasite first. We compare a once daily and twice daily albendazole regimen in preventing this potentially fatal complication in 122 patients with nephrotic syndrome.

Treatment of human disseminated strongyloidiasis with a parenteral veterinary formulation of ivermectin.

There are no parenteral antihelminthic drugs licensed for use in humans. We report the successful treatment of disseminated strongyloidiasis with a parenteral veterinary formulation of ivermectin in a patient presenting with severe malabsorption and paralytic ileus. To our knowledge, ivermectin levels are reported for the first time in this situation.

Disseminated strongyloidiasis arising from a single dose of dexamethasone before stereotactic radiosurgery.

A fatal case of disseminated strongyloidiasis is described, abruptly following a single high dose of dexamethasone before stereotactic radiosurgery. The mechanism of steroid-induced dysregulation of Strongyloides infection is unclear. Treatment failure and the use of rectal thiabendazole in the presence of bowel obstruction is discussed. This case reinforces the need to screen selected patients for strongyloidiasis before any high-dose steroid therapy, particularly in the presence of persistent eosinophilia.

Disseminated Strongyloides stercoralis infection in an AIDS patient: The role of suppressive therapy

Patients with AIDS are prome to develop infections caused by opportunistic pathogens. Unusual agents, such as Stongyloides stercoralis, are being described in this syndrome, resulting in disseminated disease which is always severe and, in some cases, fatal. We describe a case of patient with AIDS and Strongyloides stercoralis infection involving the gastrointestinal tract and lungs. Therapy with thiabendazole for ten days led to resolution of the acute episode. Preventive therapy with 3g of thiabendazole once a week was then prescribed, and repeated fecal examinations were negative for larvae. Following discontinuation of treatment, however, the patient again had a positive fecal examination for Strongyloides stercoralis larvae, even though reinfection was considered to be very unlikely. The patient was retreated with a shorter course of therapy and once per week preventive therapy was reintroduced. After four months of follow-up, repeated fecal examinations were negative. When the treatment was changed to thiabendazole given once every two weeks, however, pulmonary Strongyloides stercoralis recurred. Subsequently, because of intolerance to thiabendazole, the patient was treated with cambendazole. The patient died three months later due to Pseudomonas aeruginosa pneumonia. Prolonged therapy for Strongyloides stercoralis infection may be necessary. Although further evaluation is needed, 3g of thiabendazole once a week may be adequate for this purpose. Cambendazole may be a useful alternative for disseminated Strongyloides stercoralis.

[Clinical study on ivermectin against 125 strongyloidiasis patients].

We treated 125 patients with strongyloidiasis (78 males and 47 females) by 2 oral doses of ivermectin (6 mg) at 2-week interval, and obtained the following results: 1. Eradication rate after treatment was 86.4% (108 of 125 patients), responsively. Out of the total 17 patients were resistant (non-responsive) to treatment, 8 patients received a further course of ivermectin and all Strongyloides stercoralis in their feces were eradicated. 2. Side effects were observed in 7.2% of the patients after the first dose treatment and in 3.2% after the second dose. But all symptoms were mild and self-limited. Although liver disfunction developed in 13.6% of the patients, no symptoms occurred and no special treatment was required. 3. Positive rate of anti-HTLV-I antibody in the resistant group was significantly higher (80.0%) than in the eradicated group (29.2%) and in the stool-negative group (0%). 4. Although eosinophils before treatment in the eradicated group was significantly higher than that of controls, there was no significant difference between the resistant group and controls. IgE levels in the resistant group was significantly lower than in the eradicated group. We would like to conclude that IVM is the best drug for treatment of the patient with Strongyloides stercoralis not only from this results but also our previous reports which had investigated the clinical efficacy on thiabendazole, mebendazole and albendazole.

Strongyloidiasis. Métodos Diagnósticos

La strongyloidiasis se diagnostica rutinariamente por el examen directo de las heces del paciente. Esta no es la mejor ni la única manera de dilucidar la enfermedad, pues actualmente se cuenta con métodos inmunológicos indirectos y técnicas directas más sensibles y confiables que permiten la mayor captación de casos agudos y portadores crónicos de la infección