Key Points
After being killed by artesunate, malaria parasites are expelled from red cells and then these pitted red cells reenter the circulation. When many pitted red cells are produced during therapy, their delayed clearance a few weeks later triggers hemolytic episodes.
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.
In this population of CL patients displaying variable degrees of complexity and severity, almost two-thirds of patients could be initially managed without systemic therapy. Of these, 60 were cured before day 60. The WHO-recommended stepwise approach favoring initial local therapy therefore resulted in at least 44% of all patients being cured without exposure to the risk of systemic adverse events. Efforts are needed to further simplify local therapy of CL and to improve the management of patients with complex lesions and/or preexisting comorbidities.
Artesunate, the recommended drug for severe malaria, rapidly clears the malaria parasite from infected patients but frequently induces anemia-called post-artesunate delayed hemolysis (PADH)-for which a simple predictive test is urgently needed. The underlying event in PADH is the expulsion of artesunate-exposed parasites from their host erythrocytes by pitting. We show that the histidine-rich protein 2 (HRP2) of the malaria parasite persists in the circulation of artesunate-treated malaria patients in Bangladesh and in French travelers who became infected with malaria in Africa. HRP2 persisted in whole blood (not plasma) of artesunate-treated patients with malaria at higher levels compared to quinine-treated patients. Using an optimized membrane permeabilization method, HRP2 was observed by immunofluorescence, Western blotting, and electron microscopy to persist in once-infected red blood cells from artesunate-treated malaria patients. HRP2 was deposited at the membrane of once-infected red blood cells in a pattern similar to that for ring erythrocyte surface antigen (RESA), a parasite invasion marker. On the basis of these observations, we developed a semiquantitative titration method using a widely available HRP2-based rapid diagnostic dipstick test. Positivity on this test using a 1:500 dilution of whole blood from artesunate-treated patients with malaria collected shortly after parasite clearance predicted subsequent PADH with 89% sensitivity and 73% specificity. These results suggest that adapting an existing HRP2-based rapid diagnostic dipstick test may enable prediction of PADH several days before it occurs in artesunate-treated patients with malaria.
BackgroundCutaneous leishmaniasis is caused by several Leishmania species that are associated with variable outcomes before and after therapy. Optimal treatment decision is based on an accurate identification of the infecting species but current methods to type Leishmania isolates are relatively complex and/or slow. Therefore, the initial treatment decision is generally presumptive, the infecting species being suspected on epidemiological and clinical grounds. A simple method to type cultured isolates would facilitate disease management.MethodologyWe analyzed MALDI-TOF spectra of promastigote pellets from 46 strains cultured in monophasic medium, including 20 short-term cultured isolates from French travelers (19 with CL, 1 with VL). As per routine procedure, clinical isolates were analyzed in parallel with Multilocus Sequence Typing (MLST) at the National Reference Center for Leishmania.Principal FindingsAutomatic dendrogram analysis generated a classification of isolates consistent with reference determination of species based on MLST or hsp70 sequencing. A minute analysis of spectra based on a very simple, database-independent analysis of spectra based on the algorithm showed that the mutually exclusive presence of two pairs of peaks discriminated isolates considered by reference methods to belong either to the Viannia or Leishmania subgenus, and that within each subgenus presence or absence of a few peaks allowed discrimination to species complexes level.Conclusions/SignificanceAnalysis of cultured Leishmania isolates using mass spectrometry allows a rapid and simple classification to the species complex level consistent with reference methods, a potentially useful method to guide treatment decision in patients with cutaneous leishmaniasis.
Key Points
Question
Could changes in the population experiencing imported malaria in France over
the past 2 decades explain the persistence of the high number of malaria
cases despite national preventive measures?
Findings
In this cross-sectional study of 43 333 malaria cases from travelers
returning to France from a malaria-endemic area, the proportion of malaria
cases among African individuals has increased significantly from 1996
through 2016 (53.5% vs 83.4%).
Meaning
Although prophylactic measures appeared to be efficient among European
individuals traveling for tourism or business purposes, progress is needed
to ensure better protection for African individuals visiting friends or
relatives.
We report on 4 patients (1 immunocompetent, 3 immunosuppressed) in whom visceral leishmaniasis had become unresponsive to (or had relapsed after) treatment with appropriate doses of liposomal amphotericin B. Under close follow-up, full courses of pentavalent antimony were administered without life-threatening adverse events and resulted in rapid and sustained clinical and parasitological cure.
BackgroundHIV and malaria are among the leading causes of morbidity and mortality during pregnancy in Africa. However, data from Congolese pregnant women are lacking. The aim of the study was to determine the magnitude, predictive factors, clinical, biologic and anthropometric consequences of malaria infection, HIV infection, and interactions between malaria and HIV infections in pregnant women.MethodsA cross-sectional study was conducted among pregnant women admitted and followed up at Camp Kokolo Military Hospital from 2009 to 2012 in Kinshasa, the Democratic Republic of Congo. Differences in means between malaria-positive and malaria-negative cases or between HIV-positive and HIV-negative cases were compared using the Student’s t-test or a non-parametric test, if appropriate. Categorical variables were compared using the Chi-square or Fisher’s exact test, if appropriate. Backward multivariable analysis was used to evaluate the potential risk factors of malaria and HIV infections. The odds ratios with their 95% confidence interval (95% CI) were estimated to measure the strengths of the associations. Analyses resulting in values of P < 0.05 were considered significant.ResultsA malaria infection was detected in 246/332 (74.1%) pregnant women, and 31.9% were anaemic. Overall, 7.5% (25/332) of mothers were infected by HIV, with a median CD4 count of 375 (191; 669) cells/μL. The mean (±SD) birth weight was 2,613 ± 227 g, with 35.7% of newborns weighing less than 2,500 g (low birth weight). Low birth weight, parity and occupation were significantly different between malaria-infected and uninfected women in adjusted models. However, fever, anemia, placenta previa, marital status and district of residence were significantly associated to HIV infection.ConclusionThe prevalence of malaria infection was high in pregnant women attending the antenatal facilities or hospitalized and increased when associated with HIV infection.
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