Two cases of long-lasting, sub-microscopic Plasmodium malariae infections in adults from coastal Tanzania

Abstract

Background Malaria is endemic in Tanzania with majority of clinical cases caused by Plasmodium falciparum . Additionally, Plasmodium malariae and Plasmodium ovale spp. are also present and clinical manifestations caused by these infections are not well described. Clinical episodes caused by P. malariae infections are often characterized by a relatively mild illness with a low number of parasites, which can persist for long periods. In this report, two cases of P. malariae infections that were identified during a clinical trial evaluating the P. falciparum malaria vaccine candidate, PfSPZ Vaccine are described. The two participants were followed up and monitored for clinical and laboratory parameters to assess vaccine safety providing the opportunity to study clinical manifestations of P. malariae over 4 months. Case presentation Two young, healthy Tanzanian men infected with low density asexual blood stage P. malariae diagnosed by quantitative polymerase chain reaction (qPCR) are described. Retrospective analysis of collected and stored blood samples revealed that the two volunteers had constant asexual blood stage parasitaemia for more than 4 months. During the 132 days of infection, the volunteers’ vital signs, body temperature and serum biochemistry all remained within normal ranges. Haematological abnormalities, which were transiently outside normal ranges, were regarded as not clinically significant. During this time period, four consecutive evaluations of blood samples by thick blood smear microscopy conducted by an experienced microscopist were all negative, indicating the presence of low-density sub-microscopic infections. Conclusions The two cases of P. malariae infections presented here confirm the ability of this Plasmodium species to persist at low density in the human host for extended time periods without causing clinical symptoms. The presented data also demonstrate that clinical study sites in malaria endemic regions need to have a strong malaria diagnostic infrastructure, including the ability of capturing sub-microscopic parasitaemia and differentiation of Plasmodium species. Trial registration ClinicalTrials.gov: NCT02613520, https://clinicaltrials.gov/ct2/show/NCT02613520 , Registered: November 24th 2015, Enrolment of the first participant to the trial: December 15th 2015, Trial was registered before the first participant was enrolled

Mixed Plasmodium malariae Infections Were Underdetected in a Malaria Endemic Area in the Amazon Region, Brazil

“…[4][5][6] Plasmodium malariae infection is not associated with relapse but can cause chronic, low-grade infections that persist for several years, often at levels that are lower than microscopic detection limits. 2,7,8 Cases of chronic and submicroscopic P. malariae infections have been reported, and approximately 2% of patients develop severe complications. 9 As a case detected after a long period of infection, an asymptomatic 74-year-old Greek woman with splenomegaly was monitored, and the submicroscopic infection was confirmed by nested polymerase chain reaction (PCR) specific for P. malariae 18S ribosomal RNA (rRNA).…”

“…18 However, in natural infections the parasite density may be very low, and it has been described as submicroscopic infection confirmed by PCR. [6][7][8]10,17 In our study, the presence of P. malariae was revealed by molecular diagnostic with sensitivity and specificity to detect species-specific sequences of mtDNA as previously described. 14 In Colombia where malaria is also endemic a study using PCR has reported 43.8% P. malariae positive infections among 671 symptomatic patients.…”

A Japanese man with malaria tests negative for fever after spending 6 months in rural Kenya

“…In the current case study, malaria was the number one suspected disease among the probable differentials, and malaria tests, including the rapid diagnosis test and blood smear examination, were repeated and showed negative results. It is worth knowing that in the setting of travel medicine, sensitivity of rapid diagnosis tests for P. falciparum is significantly lower (median 74.1%) if the parasitemia level was below 100/μL compared with above 100/ μL (median 94.3%) [2] and that in cases of Plasmodium malariae infection, the parasitemia level remains very low; thus, the presence of parasitemia is often missed by malaria blood film tests [3,4]. Furthermore, the malaria rapid diagnosis test used in the current case is based on an immunochromatographic method with detection antibodies targeting both P. falciparum-specific histidine-richprotein-2 (PfHRP2) and a pan-malarial antigen, Plasmodium aldolase, but the sensitivity of this test is lower for non-falciparum malaria, especially in the detection of P. ovale and P. malariae, probably due to the lower affinity of some monoclonal antibodies to these species [5].…”

Malaria rapid diagnostic tests reliably detect asymptomatic Plasmodium falciparum infections in school-aged children that are infectious to mosquitoes

“…To investigate P. falciparum co-infections with other relevant parasite species in the Bagamoyo district [ 25 , 26 ], all Plasmodium -positive samples were subjected to further analysis using the PlasID qPCR assay as previously described [ 27 ]. Samples were analysed with reagents, volumes and instruments as described above.…”