Stéphane Jauréguiberry

Discordance Between Cerebral Spinal Fluid and Plasma HIV Replication in Patients with Neurological Symptoms Who Are Receiving Suppressive Antiretroviral Therapy

OBJECTIVE We report data on 11 patients with neurological symptoms and human immunodeficiency virus (HIV) cerebrospinal fluid (CSF) viremia contrasting with suppressed plasma HIV RNA during receipt of combined antiretroviral therapy. DESIGN We retrospectively identified instances of central nervous system (CNS) symptoms in patients who had been receiving stable combination antiretroviral therapy. Discordance between plasma and CSF HIV RNA levels was defined by any detectable CSF HIV RNA level >200 copies/mL while plasma levels were <50 copies/mL or by a CSF HIV RNA level that was 1 log greater than the plasma HIV RNA level. RESULTS Eleven patients had experienced acute or subacute neurological symptoms. All but one patient had CSF pleocytosis and/or elevated protein levels. The median CSF HIV RNA level was 880 copies/mL (range, 558-12,885 copies/mL). Patients had been receiving stable combination antiretroviral therapy for a median of 13 months (range, 10-32 months). Eight of 11 patients had a plasma HIV RNA level <50 copies/mL, and 3 had plasma HIV RNA blips with their CSF HIV RNA level >1 log higher than their plasma HIV RNA level. Resistance-associated mutations were detected in 7 of 8 CSF HIV RNA genotypic strains. The median number of resistance-associated mutations was 6 (range, 2-8) to nucleoside reverse-transcriptase inhibitors and 3 (range, 1-9) to protease inhibitors. One patient had a virus harboring nonnucleoside reverse-transcriptase inhibitor mutations. The median central nervous system penetration-effectiveness (CPE) rank was 2 (range, 1-3), and 5 patients had a CPE 1.5. After antiretroviral therapy optimization based on genotypes and CPE, all patients clinically improved, with normalization of CSF. CONCLUSIONS Despite successful suppression of plasma viremia with antiretroviral therapy, HIV may replicate in CSF, with development of CSF HIV resistance resulting in acute or subacute neurological manifestations.

Chikungunya infection in travelers.

The largest described outbreak of chikungunya virus has been occurring on the islands of the southwest Indian Ocean since March 2005. We describe the manifestations of chikungunya virus infection in travelers returning from these islands, with focus on skin manifestations.

Chagas disease, France.

Chagas Disease, France

Imported Crimean-Congo Hemorrhagic Fever

ABSTRACT Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease that may also be transmitted through person-to-person transmission by exposure to infected body fluids. Despite its wide geographic distribution in animals, CCHF virus is rarely associated with recognized human diseases. We report the first case of imported CCHF in France.

Plasmodium falciparum Clearance Is Rapid and Pitting Independent in Immune Malian Children Treated With Artesunate for Malaria

BACKGROUND In Plasmodium falciparum-infected patients treated with artemisinins, parasitemia declines through so-called pitting, an innate splenic process that transforms infected red blood cells (iRBCs) into once-infected RBCs (O-iRBCs). METHODS We measured pitting in 83 French travelers and 42 Malian children treated for malaria with artesunate. RESULTS In travelers, O-iRBCs peaked at 107.7% initial parasitemia. In Malian children aged 1.5-4 years, O-iRBCs peaked at higher concentrations than in children aged 9-13 years (91.60% vs 31.95%; P = .0097). The parasite clearance time in older children was shorter than in younger children (P = .0001), and the decline in parasitemia in children aged 1.5-4 years often started 6 hours after treatment initiation, a lag phase generally absent in infants and older children. A 6-hour lag phase in artificial pitting of artesunate-exposed iRBCs was also observed in vitro. The proportion of iRBCs recognized by autologous immunoglobulin G (IgG) correlated with the parasite clearance time (r = -0.501; P = .0006) and peak O-iRBC concentration (r = -0.420; P = .0033). CONCLUSIONS Antimalarial immunity correlates with fast artemisinin-induced parasite clearance and low pitting rates. In nonimmune populations, artemisinin-induced P. falciparum clearance is related to pitting and starts after a 6-hour lag phase. In immune populations, passively and naturally acquired immune mechanisms operating faster than pitting may exist. This mechanism may mitigate the emergence of artemisinin-resistant P. falciparum in Africa.

Delayed-Onset Hemolytic Anemia in Patients with Travel-Associated Severe Malaria Treated with Artesunate, France, 2011–2013

Hemolysis occurred in a low proportion of patients and did not increase transfusion requirements.

Neurological involvement during Katayama syndrome

We read with interest the Review on acute schistosomiasis (ie, invasive schistososomiasis, Katayama syndrome) by Allen Ross and colleagues. The neurological involvement that is sometimes observed during this phase of schistosomiasis calls for specifi c comments regarding its clinical presentation, pathophysiology, and treatment. Neurological manifestations rarely occur during the invasive phase of schistosomiasis. Indeed, in the largest series to date, during the Philippines campaign (1944–45) of World War II, neurological manifestations were observed in only about 2% of cases during the invasive phase. Of the 1200 American soldiers infected with Schistosoma japonicum, 27 presented with a neurological involvement during this phase. Headache, disturbances of sensorium, and weakness were all present, and about 84% of patients were febrile at one time or another; 44% presented with a transient hemiplegia or tetraplegia, 60% complained of visual impairment, and 50% reported incontinence, speech impairment, and ataxia. Neurological manifestations have also been described in case reports of the acute phase of S japonicum, Schistosoma mansoni, and Schistosoma haematobium infections in travellers, contributing to a better understanding of the clinical manifestations during this stage. For example, the brain involvement during the acute phase of schistosomiasis may be revealed by headache, confusion, seizures, loss of consciousness, focal defi ciencies, visual impairment, ataxia, urinary incontinence, and motor paralysis. This neurological involvement diff ers from that observed during the chronic phase of the disease. Clinical manifestations occur within 6 weeks after infection, as reported in small outbreaks in exposed travellers. During this phase of the disease cycle, schistosomulae have not reached their adult stage. Therefore, egg laying—which usually starts at least 2 months after the infestation—is not possible. Consequently, eggs cannot be responsible for the neurological manifestations. Nevertheless, these life-threatening neurological manifestations are always associated with marked eosinophilia, which reaches a peak during the invasive phase. The most likely pathophysiological mechanism to explain such manifestations is, therefore, eosinophil-mediated toxicity leading to vasculitis and small vessel thrombosis. By contrast with what is recommended by Ross and colleagues, praziquantel should be contraindicated during the acute phase. First, praziquantel is not effi cient, as shown by studies in travellers. Second, the drug may lead to complications (paradoxical reactions), as described in four (40%) of ten treated patients in a recent outbreak in French travellers. Instead, corticosteroids are the recommended treatment, especially in emergency situations. It is therefore important to distinguish the two pathophysiological mechanisms of neurological involvement during schistosomiasis. Whereas the neurological involvement seen during the acute phase is caused by vasculitis and calls for corticosteroids, that observed during the chronic phase is caused by granuloma developing around eggs that migrated accidentally in the brain and calls for specifi c treatment with praziquantel and sometimes surgery.

Travel-Related Leptospirosis: A Series of 15 Imported Cases

BACKGROUND Leptospirosis belongs to the spectrum of travel-related infections. METHODS We retrospectively studied all the consecutive cases of travel-related leptospirosis seen in our department between January 2008 and September 2011. Patients were included with a clinical picture compatible with the disease within 21 days after return, the presence of a thermoresistant antigen or IgM antibodies, Elisa ≥ 1 /400, and a positive microagglutination test (MAT) ≥ 1/100. RESULTS Fifteen leptospirosis cases were evaluated. Exposure occurred in Asia (47%), Africa (20%), the Caribbean (20%), and Indian Ocean (13%). Fourteen patients were infected during water-related activities. On admission the most frequent symptoms were fever (100%), headache (80%), and digestive disorders (67%). Relevant laboratory findings included impaired liver function tests (100%), lymphocytopenia (80%), thrombocytopenia (67%), and elevated C-reactive protein (CRP) (67%). Our cases were confirmed by MAT that found antibodies against nine different serovars. Seven patients were cured with amoxicillin, four with doxycycline, two with ceftriaxone, one with ceftriaxone, doxycycline, and spiramycin, whereas one recovered spontaneously (retrospective diagnosis). Eight patients were hospitalized. All patients recovered. CONCLUSION Our cases involved nine different serovars. They were related to travel in Asia, Africa, and the Caribbean. Bathing or other fresh-water leisure activities (canoeing, kayaking, rafting) are the most likely at-risk exposure. Any traveler with fever and at-risk exposure should be investigated for leptospirosis.

Myocarditis during Acute Schistosomiasis in Two Travelers

We report two cases of myocarditis complicating acute schistosomiasis in returning travelers. Treatment with corticosteroids led to full recovery in both cases. Although the pathophysiology of this complication remains unclear, we recommend treating such patients with corticosteroids rather than praziquantel, which can be associated with clinical deterioration.

Disseminated cryptococcosis, invasive aspergillosis, and mucormycosis in a patient treated with alemtuzumab for chronic lymphocytic leukaemia

Abstract We report the case of a 42-y-old man treated with alemtuzumab for chronic lymphocytic leukaemia, who developed 3 successive deep fungal infections. Despite being treated with liposomal amphotericin B and 5-flucytosine for disseminated cryptococcosis, he developed pulmonary invasive aspergillosis, followed by pulmonary mucormycosis. Several deep fungal infections may occur in association in an immunocompromised host after treatment with alemtuzumab.