Host biomarkers for early identification of severe imported Plasmodium falciparum malaria.

BACKGROUND: Severe imported P. falciparum malaria is a source of morbi-mortality in non-endemic regions. WHO criteria don't accurately classify patients at risk of complications. There is a need to evaluate new tools such as biomarkers to better identify patients with severe imported malaria. METHODS: A case-control study was conducted in Barcelona, from January 2011-January 2021. Adult patients with microbiologically confirmed P. falciparum malaria were classified according to WHO criteria. Patients with imported non-malarial fevers were included as controls. In each group, angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), soluble triggering receptor expressed on myeloid cells (sTREM-1), C-reactive protein (CRP) and platelets were measured and their concentrations were compared between groups. New groups were made with a modified WHO severity classification and biomarkers' performance was evaluated using multiple imputation models. RESULTS: 131 participants were included: 52 severe malaria, 30 uncomplicated malaria and 49 non-malarial fever cases. All biomarkers except sTREM-1 showed significant differences between groups. Using the modified WHO severity classification, Ang-2 and CRP presented the best AUROC; 0.79 (95%CI 0.64-0.94) and 0.80(95%CI 0.67-0.93). A model combining CRP and Ang-2 showed the best AUROC, of 0.84(95%CI 0.68-0.99), with the highest sensitivity and specificity: 84.6%(95%CI 58.9-98.1) and 77.4% (95%CI 65.9-87.7), respectively. CONCLUSIONS: The combination of Ang-2 and CRP may be a reliable tool for the early identification of severe imported malaria. The use of a rapid prognostic test including the mentioned biomarkers could optimize imported malaria management, with the potential to decrease the rate of complications and hospitalizations in patients with imported malaria.

Toxoplasma gondii-specific IgG avidity testing in pregnant women.

BACKGROUND: The parasite Toxoplasma gondii can cause congenital toxoplasmosis following primary infection in a pregnant woman. It is therefore important to distinguish between recent and past infection when both T. gondii-specific IgM and IgG are detected in a single serum in pregnant women. Toxoplasma gondii-specific IgG avidity testing is an essential tool to help to date the infection. However, interpretation of its results can be complex. OBJECTIVES: To review the benefits and limitations of T. gondii-specific avidity testing in pregnant women, to help practitioners to interpret the results and adapt the patient management. SOURCES: PubMed search with the keywords avidity, toxoplasmosis and Toxoplasma gondii for articles published from 1989 to 2019. CONTENT: Toxoplasma gondii-specific IgG avidity testing remains a key tool for dating a T. gondii infection in immunocompetent pregnant women. Several commercial assays are available and display comparable performances. A high avidity result obtained on a first-trimester serum sample is indicative of a past infection, which occurred before pregnancy. To date, a low avidity result must still be considered as non-informative to date the infection, although some authors suggest that very low avidity results are highly suggestive of recent infections depending on the assay. Interpretation of low or grey zone avidity results on a first-trimester serum sample, as well as any avidity result on a second-trimester or third-trimester serum sample, is more complex and requires recourse to expert toxoplasmosis laboratories. IMPLICATIONS: Although used for about 30 years, T. gondii-specific avidity testing has scarcely evolved. The same difficulties in interpretation have persisted over the years. Some authors have proposed additional thresholds to exclude an infection of <9 months, or in contrast to confirm a recent infection. Such thresholds would be of great interest to adapt management of pregnant women and avoid unnecessary treatment; however, they need confirmation and further studies.

Aetiology of traveller's diarrhoea: evaluation of a multiplex PCR tool to detect different enteropathogens.

Traveller's diarrhoea (TD) is the most common illness reported in international travellers. TD is caused by a wide range of pathogens, including bacteria, viruses and parasites. Multiplex PCR assays can be especially useful for studying the aetiology of TD. The first objective of this study was to evaluate the utility of the commercially available multiplex PCR (xTAG(®) Gastrointestinal Pathogen Panel (GPP)) for the diagnosis of TD. A total of 185 stool specimens obtained from 174 patients were processed using the GPP assay. This test detected 86 pathogens in 67 stool samples (67/185, 36.2%). Sixteen pathogens out of 86 were also detected by routine testing. The remaining pathogens (n = 70) required further confirmation by alternative techniques. Finally, 60 out of 70 pathogens were confirmed. The second objective of this study was to analyse the aetiology of TD based on the results obtained by the GPP test and routine methods. The primary pathogens causing TD were Shigella (24.2%) followed by enterotoxigenic Escherichia coli (ETEC) (23.2%), enteroaggregative E. coli (14.7%) and Giardia (13.7%). Significant regional differences were observed for ETEC with 19.4% of TD cases acquired in Africa, 11.3% in Asia and none in South Central (SC) America (p 0.01), Giardia was found in 1.5% of cases among those who had travelled to Africa, 14.1% of those who had travelled to Asia and 3% of those who had travelled to SC America (p 0.01). In conclusion, the GPP test improved the detection of enteropathogens and allowed better assessment of the aetiology of TD.

Extended spectrum ß-lactamase-producing Escherichia coli faecal carriage in Spanish travellers returning from tropical and subtropical countries.

The aim of this study was to investigate the prevalence of extended-spectrum ß-lactamase (ESBL) -producing Escherichia coli in stool samples from 457 patients with travellers' diarrhoea who had travelled to tropical and subtropical countries. Ninety-seven ESBL-producing E. coli strains were isolated from 17.9% of the patients (82/457). CTX-M-15 was the most prevalent enzyme (80%) and India was the most visited country and showed the highest prevalence of positive samples (37.4%).

Prevalence of dihydropteroate synthase mutants in HIV-infected South African children with Pneumocystis jiroveci pneumonia.

BACKGROUND: Pneumocystis jiroveci (formerly Pneumocystis carinii) pneumonia (PCP) is a major cause of mortality in human immunodeficiency virus (HIV)-infected infants in Africa, but the prevalence of mutations in the gene encoding dihydropteroate synthase (DHPS) in isolates from Africa has not been reported. METHODS: This study investigated the prevalence of DHPS mutations in P. jiroveci isolates from South African HIV-infected children with PCP by amplifying DNA using 2 different polymerase chain reactions. RESULTS: P. jiroveci DNA from 30 respiratory specimens was amplified; 26 specimens (86.7%) contained wild-type DHPS alleles. Of the 4 samples (13.3%) with DHPS mutations, 2 contained a homogenous population with single DHPS mutations, 1 contained a homogenous population with 2 DHPS mutations, and the fourth contained a heterogenous population of organisms with both wild-type and single-mutant DHPS genotypes. Only 1 child was receiving trimethoprim-sulphamethoxazole (TMP-SMZ) prophylaxis; this patient was infected with wild-type P. jiroveci. The mortality rate (overall, 20 [66.7%] of 30 children) was not significantly different between children infected with wild-type P. jiroveci (17 [65.4%] of 26) and those infected with mutant strains (3 [75%] of 4; P=.8). CONCLUSIONS: DHPS mutations are uncommon in P. jiroveci isolates from South Africa. However, increasing use of TMP-SMZ prophylaxis may result in widespread development of mutations.