Saraiva da Cunha

Screening for Mutations Related to Atovaquone/ Proguanil Resistance in Treatment Failures and Other Imported Isolates of Plasmodium falciparum in Europe

BACKGROUND Two single-point mutations of the Plasmodium falciparum cytochrome b gene (Tyr268Asn and Tyr268Ser) were recently reported in cases of atovaquone/proguanil (Malarone) treatment failure. However, little is known about the prevalence of codon-268 mutations and their quantitative association with treatment failure. METHODS We set out to assess the prevalence of codon-268 mutations in P. falciparum isolates imported into Europe and to quantify their association with atovaquone/proguanil treatment failure. Isolates of P. falciparum collected by the European Network on Imported Infectious Disease Surveillance between April 2000 and August 2003 were analyzed for codon-268 mutations, by use of polymerase chain reaction-restriction fragment-length polymorphism. RESULTS We successfully screened 504 samples for the presence of either Tyr268Ser or Tyr268Asn. One case of Ser268 and no cases of Asn268 were detected. Therefore, we can be 95% confident that the prevalence of Ser268 in the European patient pool does not exceed 0.96% and that Asn268 is less frequent than 0.77%. In 58 patients treated with atovaquone/proguanil, Tyr268Ser was present in 1 of 5 patients with treatment failure but in 0 of 53 successfully treated patients. CONCLUSIONS Tyr268Ser seems to be a sufficient, but not a necessary, cause for atovaquone/proguanil treatment failure. The prevalence of both codon-268 mutations is currently unlikely to be >1% in the European patient pool.

Molecular surveillance of drug resistance through imported isolates of Plasmodium falciparum in Europe

BackgroundResults from numerous studies point convincingly to correlations between mutations at selected genes and phenotypic resistance to antimalarials in Plasmodium falciparum isolates. In order to move molecular assays for point mutations on resistance-related genes into the realm of applied tools for surveillance, we investigated a selection of P. falciparum isolates that were imported during the year 2001 into Europe to study the prevalence of resistance-associated point mutations at relevant codons. In particular, we tested for parasites which were developing resistance to antifolates and chloroquine. The screening results were used to map the prevalence of mutations and, thus, levels of potential drug resistance in endemic areas world-wide.Results337 isolates have been tested so far. Prevalence of mutations that are associated with resistance to chloroquine on the pfcrt and pfmdr genes of P. falciparum was demonstrated at high levels. However, the prevalence of mutations associated with resistance to antifolates at the DHFR and DHPS genes was unexpectedly low, rarely exceeding 60% in endemic areas.ConclusionsConstant screening of imported isolates will enable TropNetEurop to establish a screening tool for emerging resistance in endemic areas.

Molecular surveillance of the antifolate-resistant mutation I164L in imported african isolates of Plasmodium falciparum in Europe: sentinel data from TropNetEurop

BackgroundMalaria parasites that carry the DHFR-mutation I164L are not only highly resistant to sulfadoxine-pyrimethamine but also to the new antimalarial drug chlorproguanil-dapsone. The spread of this mutation in Africa would result in a public health disaster since there is a lack of effective alternatives that are both affordable and safe. Up to now, this mutation has only been described in Asian and Latin-American countries. The objective of this study was to assess the prevalence of this mutation in African isolates of Plasmodium falciparum that have been imported into Europe through travellers.MethodsTropNetEurop is a network for the surveillance of travel-associated diseases and seems to cover approximately 12% of all malaria cases imported into Europe. Within this network we screened 277 imported African isolates of P. falciparum with the help of PCR- and enzyme-digestion-methods for the antifolate-resistant mutation I164L.ResultsThe I164L mutation was not detected in any of the isolates tested.DiscussionContinuous molecular surveillance of mutations in P. falciparum, as it is practised within TropNetEurop, is an essential tool for the understanding and early detection of the spread of antimalarial drug resistance in Africa.

Rickettsia slovaca Infection in Humans, Portugal

Fifteen years after the initial detection of Rickettsia slovaca in ticks in Portugal, 3 autochthonous cases of R. slovaca infection were diagnosed in humans. All patients had an eschar on the scalp and lymphadenopathy; 2 patients had facial edema. R. slovaca infection was confirmed by serologic testing, culture, and PCR.

Spondylodiscitis associated with recurrent Serratia bacteremia due to a transjugular intrahepatic portosystemic shunt (TIPS): a case report

We report a case of spondylodiscitis caused by multiresistant Serratia marcescens in a cirrhotic patient who had several Serratia bacteremias after the placement of a transjugular intrahepatic portosystemic shunt (TIPS) device. We concluded that an endovascular stent that can not be removed makes management of recurrent bacteremia difficult. Furthermore, back pain due to bacteremia is indicative of spondylodiscitis. Serratia marcescens can be an aggressive pathogen, causing spinal infection.

Cervical abscess in an immunocompetent patient with Mycobacterium malmoense pulmonary disease

BackgroundMycobacterium malmoense is a nontuberculous mycobacteria seen mainly in two age groups and with different clinical presentations. Most patients are male adults presenting clinical symptoms and signs similar to those of pulmonary tuberculosis. The second group is formed by immunocompetent children with localized cervical lymphadenitis. Although cervical adenitis is the main extrapulmonary manifestation of M. malmoense, virtually all cases of cervical disease were documented in children. Disseminated disease is rare and has been reported in patients with severely impaired immunity.Case reportWe report a case of a 47-year-old immunocompetent man with a cervical abscess, in whom we identified a M. malmoense pulmonary disease with multiple cervical, thoracic and abdominal adenopathies.ConclusionExtrapulmonary infection due to M. Malmoense needs to be considered on the differential diagnosis of cervical masses and adenopathies, not only in pediatric patients but also in adults with no impaired immunity. A high index of suspicion for nontuberculous mycobacteria is essential for the diagnosis and prognosis.