Federico Gobbi

The Role of Rapid Diagnostic Tests in Managing Malaria

Zeno Bisoffi and colleagues discuss a new clinical trial in Zanzibar comparing symptom-based clinical diagnosis of malaria versus clinical diagnosis plus rapid diagnostic tests.

Severe strongyloidiasis: a systematic review of case reports

BackgroundStrongyloidiasis is commonly a clinically unapparent, chronic infection, but immuno suppressed subjects can develop fatal disease. We carried out a review of literature on hyperinfection syndrome (HS) and disseminated strongyloidiasis (DS), in order to describe the most challenging aspects of severe strongyloidiasis.MethodsWe conducted a structured search using PubMed to collect case reports and short case series on HS/DS published from 1991 to 2011. We restricted search to papers in English, Spanish, Italian and French. Case reports were classified as HS/DS according to given definitions.ResultsRecords screened were 821, and 311 were excluded through titles and abstract evaluation. Of 510 full-text articles assessed for eligibility, 213 were included in qualitative analysis. As some of them were short case series, eventually the number of cases analyzed was 244.Steroids represented the main trigger predisposing to HS and DS (67% cases): they were mostly administered to treat underlying conditions (e.g. lymphomas, rheumatic diseases). However, sometimes steroids were empirically prescribed to treat signs and symptoms caused by unsuspected/unrecognized strongyloidiasis. Diagnosis was obtained by microscopy examination in 100% cases, while serology was done in a few cases (6.5%). Only in 3/29 cases of solid organ/bone marrow transplantation there is mention of pre-transplant serological screening. Therapeutic regimens were different in terms of drugs selection and combination, administration route and duration. Similar fatality rate was observed between patients with DS (68.5%) and HS (60%).ConclusionsProper screening (which must include serology) is mandatory in high - risk patients, for instance candidates to immunosuppressive medications, currently or previously living in endemic countries. In some cases, presumptive treatment might be justified. Ivermectin is the gold standard for treatment, although the optimal dosage is not clearly defined in case of HS/DS.

Rapid malaria diagnostic tests vs. clinical management of malaria in rural Burkina Faso: safety and effect on clinical decisions. A randomized trial

Objectives  To assess if the clinical outcome of patients treated after performing a Rapid Diagnostic Test for malaria (RDT) is at least equivalent to that of controls (treated presumptively without test) and to determine the impact of the introduction of a malaria RDT on clinical decisions.

Randomized Clinical Trial on Ivermectin versus Thiabendazole for the Treatment of Strongyloidiasis

Background Strongyloidiasis may cause a life-threatening disease in immunosuppressed patients. This can only be prevented by effective cure of chronic infections. Direct parasitologic exams are not sensitive enough to prove cure if negative. We used an indirect immune fluorescent antibody test (IFAT) along with direct methods for patient inclusion and efficacy assessment. Methodology/Principal Findings Prospective, randomized, open label, phase III trial conducted at the Centre for Tropical Diseases (Verona, Italy) to compare efficacy and safety of ivermectin (single dose, 200 µg/kg) and thiabendazole (two daily doses of 25 mg/Kg for two days) to cure strongyloidiasis. The first patient was recruited on 6th December, 2004. Follow-up visit of the last patient was on 11th January, 2007. Consenting patients responding to inclusion criteria were randomly assigned to one of the treatment arms. Primary outcome was: negative direct and indirect (IFAT) tests at follow-up (4 to 6 months after treatment) or subjects with negative direct test and drop of two or more IFAT titers. Considering 198 patients who concluded follow-up, efficacy was 56.6% for ivermectin and 52.2% for thiabendazole (p = 0.53). If the analysis is restricted to 92 patients with IFAT titer 80 or more before treatment (virtually 100% specific), efficacy would be 68.1% for ivermectin and 68.9% for thiabendazole (p = 0.93). Considering direct parasitological diagnosis only, efficacy would be 85.7% for ivermectin and 94.6% for thiabendazole (p = 0.21). In ivermectin arm, mild to moderate side effects were observed in 24/115 patients (20.9%), versus 79/108 (73.1%) in thiabendazole arm (p = 0.00). Conclusion No significant difference in efficacy was observed, while side effects were far more frequent in thiabendazole arm. Ivermectin is the drug of choice, but efficacy of single dose is suboptimal. Different dose schedules should be assessed by future, larger studies. Trial Registration Portal of Clinical Research with Medicines in Italy 2004–004693–87

Accuracy of a rapid diagnostic test on the diagnosis of malaria infection and of malaria - attributable fever during low and high transmission season in Burkina Faso

BackgroundMalaria management policies currently recommend that the treatment should only be administered after laboratory confirmation. Where microscopy is not available, rapid diagnostic tests (RDTs) are the usual alternative. Conclusive evidence is still lacking on the safety of a test-based strategy for children. Moreover, no formal attempt has been made to estimate RDTs accuracy on malaria-attributable fever. This study aims at estimating the accuracy of a RDT for the diagnosis of both malaria infection and malaria - attributable fever, in a region of Burkina Faso with a typically seasonal malaria transmission pattern.MethodsCross-sectional study. Subjects: all patients aged > 6 months consulting during the study periods. Gold standard for the diagnosis of malaria infection was microscopy. Gold standard for malaria-attributable fever was the number of fevers attributable to malaria, estimated by comparing parasite densities of febrile versus non-febrile subjects. Exclusion criteria: severe clinical condition needing urgent care.ResultsIn the dry season, 186/852 patients with fever (22%) and 213/1,382 patients without fever (15%) had a Plasmodium falciparum infection. In the rainy season, this proportion was 841/1,317 (64%) and 623/1,669 (37%), respectively. The attributable fraction of fever to malaria was 11% and 69%, respectively. The RDT was positive in 113/400 (28.3%) fever cases in the dry season, and in 443/650 (68.2%) in the rainy season. In the dry season, the RDT sensitivity and specificity for malaria infection were 86% and 90% respectively. In the rainy season they were 94% and 78% respectively. In the dry season, the RDT sensitivity and specificity for malaria-attributable fever were 94% and 75%, the positive predictive value (PPV) was 9% and the negative predictive value (NPV) was 99.8%. In the rainy season the test sensitivity for malaria-attributable fever was 97% and specificity was 55%. The PPV ranged from 38% for adults to 82% for infants, while the NPV ranged from 84% for infants to over 99% for adults.ConclusionsIn the dry season the RDT has a low positive predictive value, but a very high negative predictive value for malaria-attributable fever. In the rainy season the negative test safely excludes malaria in adults but not in children.

Imported Malaria in Immigrants to Italy: A Changing Pattern Observed in North Eastern Italy

BACKGROUND Seventy percent of imported malaria cases in Italy occur in immigrants, generally with milder clinical presentation due to premunition acquired through repeated infections. Nevertheless, premunition could be progressively lost after a long period of nonexposure. We investigated the changing pattern of malaria in immigrants in two definite 5-year periods one decade apart. METHODS We retrospectively examined the main laboratory findings of all malaria cases observed in immigrants from 1990 to 1994 and from 2000 to 2004. We stratified patients by reason for traveling: subjects in Italy who traveled to visit friends and relatives (VFR) or new immigrants (NI). RESULTS Forty-eight cases of malaria in immigrants occurred from 1990 to 1994, while 161 were observed from 2000 to 2004. Patients admitted in the latter period had a significantly higher parasitemia (median 6,298 vs 3,360 trophozoites/microL, p= 0.028) and lower platelet count (median 96.5 vs 132 x 10(9)/L, p= 0.012) and hemoglobin (median 12.6 vs 13.4 g/dL, p= 0.049). While NI did not show any significant difference in the two study periods, in the VFR subgroup a higher parasitemia (median 8,845 vs 2,690 trophozoites/microL, p= 0.003) and lower platelet count (median 96 vs 131 x 10(9)/L, p= 0.034) were observed during the second period, during which three cases of severe malaria occurred in VFR. A longer stay in Italy was reported in VFR admitted during the second study period (median 8.3 vs 5.7 years). CONCLUSIONS We found a changing pattern of malaria presentation in immigrants over a decade. The most likely explanation is the longer average stay outside endemic countries and subsequent loss of premunition observed in the second cohort. Immigrants living in Italy for some time and traveling to VFR should no more be considered a low-risk group for severe malaria. Pretravel advice should be particularly targeted to this group.

Histoplasmosis infection in Spanish travelers to Latin America

The aim of the study presented here was to assess the incidence of histoplasma infection in a cohort of 342 individuals in Spain who had traveled to Latin America for the first time. The histoplasmin skin test was positive in 20% of the travelers, and Central America posed a higher risk for infection than South America (p=0.013). Sleeping outdoors (p=0.031) and the duration of travel (p=0.016) were also identified as significant risk factors. Serological testing demonstrated poor overall sensitivity for detecting infection in the travelers, but for the symptomatic acute cases the results were improved. Histoplasmosis must be considered in patients presenting with fever (odds ratio=3.51 [1.52–8.12]) or cough (odds ratio=4.24 [1.32–13.58]) after visiting Latin America. The results of this study have public health implications and indicate the risks of acquiring histoplasmosis should be included in pre-travel counseling.

Reemergence of strongyloidiasis, Northern Italy.

To the Editor: Strongyloidiasis is a helminth infection caused by Strongyloides stercoralis, a nematode ubiquitous in tropical and subtropical countries and occasionally reported in temperate countries, including Italy (1). Sources of infection are filariform strongyloid larvae present in soil contaminated by infected feces; the larvae penetrate through the skin of a human host. After the first life cycle, a process of autoinfection begins, which persists indefinitely in the host if the infection is not effectively treated. The infection can remain totally asymptomatic for many years or forever or cause cutaneous (itching and rash), abdominal (epigastric pain, pseudoappendicitis, diarrhea), respiratory (cough, recurrent asthma), and systemic (weight loss, cachexia) symptoms that can be enervating. More importantly, when host immunity is impaired because of a concurrent disease or immunosuppressive therapy (including corticosteroids, sometimes used to treat symptoms of the unrecognized infection or the concurrent eosinophilia), disseminated strongyloidiasis may occur (2–4), causing a massive and almost invariably fatal invasion of virtually all organs and tissues by filariform larvae and even adult worms (Figure), often combined with bacterial superinfection. This complication is believed to be rare but is probably underestimated because of the extreme variability of the clinical presentation.

Surveillance for West Nile, Dengue, and Chikungunya Virus Infections, Veneto Region, Italy, 2010

In 2010, in Veneto Region, Italy, surveillance of summer fevers was conducted to promptly identify autochthonous cases of West Nile fever and increase detection of imported dengue and chikungunya in travelers. Surveillance highlighted the need to modify case definitions, train physicians, and when a case is identified, implement vector control measures

Imported strongyloidiasis: epidemiology, presentations, and treatment.

Strongyloidiasis is extremely more frequent in immigrants than in travellers. Clinical presentations do not differ significantly between the two groups, and the most frequent picture is a chronic infection characterized by intermittent, mild, non-specific symptoms. Acute presentation is rare but it has been reported in travellers. Screening of asymptomatic subjects is not generally recommended, while a presumptive treatment with ivermectin might be justified for all travellers and immigrant patients presenting unexplained eosinophilia and/or compatible symptoms, even in case of negative test results. In fact, delayed diagnosis and treatment has life-threatening consequences in patients with conditions predisposing to development of hyperinfection and dissemination.