Clinical aspects of visceral leishmaniasis caused by L. infantum in adults. Ten years of experience of the largest outbreak in Europe: what have we learned?

BACKGROUND: An outbreak of leishmaniasis caused by Leishmania infantum was declared in the southwest of the Madrid region (Spain) in June 2009. This provided a unique opportunity to compare the management of visceral leishmaniasis (VL) in immunocompetent adults (IC-VL), patients with HIV (HIV-VL) and patients receiving immunosuppressants (IS-VL). METHODS: A cohort of adults with VL, all admitted to the Hospital Universitario de Fuenlabrada between June 2009 and June 2018, were monitored in this observational study, recording their personal, epidemiological, analytical, diagnostic, treatment and outcome variables. RESULTS: The study population was made up of 111 patients with VL (10% HIV-VL, 14% IS-VL, 76% IC-VL). Seventy-one percent of the patients were male; the mean age was 45 years (55 years for the IS-VL patients, P = 0.017). Fifty-four percent of the IC-VL patients were of sub-Saharan origin (P = 0.001). Fever was experienced by 98% of the IC-VL patients vs 73% of the LV-HIV patients (P = 0.003). Plasma ferritin was > 1000 ng/ml in 77% of the IC-VL patients vs 17% of the LV-HIV patients (P = 0.007). Forty-two percent of patients fulfilled the criteria for haemophagocytic lymphohistiocytosis. RDT (rK39-ICT) serological analysis returned sensitivity and specificity values of 45% and 99%, respectively, and ELISA/iIFAT returned 96% and 89%, respectively, with no differences in this respect between patient groups. Fourteen (13.0%) patients with VL experienced treatment failure, eight of whom were in the IC-VL group. Treatment with < 21 mg/kg (total) liposomal amphotericin B (LAB) was associated with treatment failure in the IC-VL patients [P = 0.002 (OR: 14.7; 95% CI: 2.6-83.3)]. CONCLUSIONS: IS-VL was more common than HIV-VL; the lack of experience in dealing with IS-VL is a challenge that needs to be met. The clinical features of the patients in all groups were similar, although the HIV-VL patients experienced less fever and had lower plasma ferritin concentrations. RDT (rK39-ICT) analysis returned a good specificity value but a much poorer sensitivity value than reported in other scenarios. The patients with HIV-VL, IS-VL and IC-VL returned similar serological results. Current guidelines for treatment seem appropriate, but the doses of LAB required to treat patients with HIV-VL and IS-VL are poorly defined.

Prevalence of submicroscopic malaria infection in immigrants living in Spain.

BACKGROUND: The importance of submicroscopic malaria infections in high-transmission areas could contribute to maintain the parasite cycle. Regarding non-endemic areas, its importance remains barely understood because parasitaemia in these afebrile patients is usually below the detection limits for microscopy, hence molecular techniques are often needed for its diagnosis. In addition to this, the lack of standardized protocols for the screening of submicroscopic malaria in immigrants from endemic areas may underestimate the infection with Plasmodium spp. The aim of this study was to assess the prevalence of submicroscopic malaria in afebrile immigrants living in a non-endemic area. METHODS: A prospective, observational, multicentre study was conducted. Afebrile immigrants were included, microscopic observation of Giemsa-stained thin and thick blood smears, and two different molecular techniques detecting Plasmodium spp. were performed. Patients with submicroscopic malaria were defined as patients with negative blood smears and detection of DNA of Plasmodium spp. with one or both molecular techniques. Demographic, clinical, analytical and microbiological features were recorded and univariate analysis by subgroups was carried out with STATA v15. RESULTS: A total of 244 afebrile immigrants were included in the study. Of them, 14 had a submicroscopic malaria infection, yielding a prevalence of 5.7% (95% confidence interval 3.45-9.40). In 71.4% of the positive PCR/negative microscopy cases, Plasmodium falciparum alone was the main detected species (10 out of the 14 patients) and in 4 cases (28.6%) Plasmodium vivax or Plasmodium ovale were detected. One patient had a mixed infection including three different species. CONCLUSIONS: The prevalence of submicroscopic malaria in afebrile immigrants was similar to that previously described in Spain. Plasmodium vivax and P. ovale were detected in almost a third of the submicroscopic infections. Screening protocols for afebrile immigrants with molecular techniques could be useful for a proper management of these patients.

Study of the diagnostic accuracy of microbiological techniques in the diagnosis of malaria in the immigrant population in Madrid.

BACKGROUND: Malaria is currently the most important human parasitic disease in the world responsible for high morbidity and mortality. Appropriate diagnostic methods are essential for early detection. Microscopy examination remains the gold standard, although molecular techniques have higher sensitivity and are very useful in cases of low parasitaemia and mixed infections. The objective of this study was to evaluate a new commercial molecular diagnostic technique. METHODS: A prospective, observational, multicentre study was performed between January 2015 and April 2017. All participants were immigrants from malaria-endemic areas, who were divided into two groups: asymptomatic group and symptomatic. Samples from both groups were evaluated by a rapid diagnostic test (ImmunoQuick® Malaria + 4 RDT), microscopy examination, and two commercial molecular malaria tests (FTD Malaria and FTD Malaria Differentiation), then compared against an in-house reference PCR technique. RESULTS: In all, 250 patients were included: 164 (65.6%) in the asymptomatic group, and 86 (34.4%) in the symptomatic group. There were seven cases of asymptomatic parasitaemia (prevalence = 2.8%) that were detected only by molecular methods. In the symptomatic group, there were seven cases of submicroscopic malaria. The main species detected was Plasmodium falciparum (96.6%). The commercial molecular technique had higher sensitivity than the other methods (S = 96%) and a high rate of concordance with the in-house reference PCR technique (Kappa score = 0.93). CONCLUSIONS: The molecular techniques, although slower than microscopy, have adequate diagnostic accuracy and are very useful for the detection of P. falciparum in cases with low parasitaemia.

Self-reported history of vaccination and disease and immunity against hepatitis A, hepatitis B, tetanus, diphtheria and varicella among Spanish military recruits.

This study aims to evaluate the immune status against hepatitis A, hepatitis B, tetanus, diphtheria and varicella in military recruits and the validity of self-reporting of their disease and vaccination history. A total of 226 participants were studied (mean age, 20.2 years; SD 1.7). 10.4% presented antibodies to hepatitis A, 78.3% to hepatitis B, 94.2% to tetanus, 77.4% to diphtheria and 81.9% to varicella. The relationship between self-reporting of vaccination history and seroprotection showed a high Positive Predictive Value for tetanus (98.8%) and a high Negative Predictive Value for hepatitis A (91%). Hepatitis A vaccination and serology testing for varicella and Hepatitis B on joining the Spanish armed forces are recommended.