METHODS: We measured PS immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies in Malaysian patients with vivax, falciparum, knowlesi, and malariae malaria, and in healthy controls, and correlated antibody titres with hemoglobin. PS antibodies were also measured in volunteers experimentally infected with Plasmodium vivax and Plasmodium falciparum.
RESULTS: PS IgM and IgG antibodies were elevated in patients with vivax, falciparum, knowlesi, and malariae malaria (P < .0001 for all comparisons with controls) and were highest in vivax malaria. In vivax and falciparum malaria, PS IgM and IgG on admission correlated inversely with admission and nadir hemoglobin, controlling for parasitemia and fever duration. PS IgM and IgG were also increased in volunteers infected with blood-stage P. vivax and P. falciparum, and were higher in P. vivax infection.
CONCLUSIONS: PS antibodies are higher in vivax than falciparum malaria, correlate inversely with hemoglobin, and may contribute to the early loss of uninfected red blood cells found in malarial anemia from both species.
METHODS: The expression of CRP CR1, CD55, CD59, and the phagocytic regulator CD47, on uninfected normocytes and reticulocytes were assessed in individuals from two study populations: (1) P. falciparum and P. vivax-infected patients from a low transmission setting in Sabah, Malaysia; and, (2) malaria-naïve volunteers undergoing P. falciparum induced blood-stage malaria (IBSM). For clinical infections, individuals were categorized into anaemia severity categories based on haemoglobin levels. For IBSM, associations between CRPs and haemoglobin level were investigated.
RESULTS: CRP expression on RBC was lower in Malaysian individuals with P. falciparum and P. vivax mild malarial anaemia compared to healthy controls. CRP expression was also reduced on RBCs from volunteers during IBSM. Reduction occurred on normocytes and reticulocytes. However, there was no significant association between reduced CRPs and haemoglobin during IBSM.
CONCLUSIONS: Removal of CRPs occurs on both RBCs and reticulocytes during Plasmodium infection even in mild malarial anaemia and at low levels of parasitaemia.
MAIN BODY: A systematic review and meta-analysis of the available literature on thrombocytopaenia in P. vivax malaria patients was undertaken. Relevant studies in health-related electronic databases were identified and reviewed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Fifty-eight observational studies (n = 29 664) were included in the current review. Severe thrombocytopaenia (vivax infection. A meta-analysis of 11 observational studies showed an equal risk of developing severe/very severe thrombocytopaenia between the patients with P. vivax malaria and those with P. falciparum malaria (OR: 1.98, 95% CI: 0.92-4.25). This indicates that thrombocytopaenia is as equally a common manifestation in P. vivax and P. falciparum malaria patients. One study showed a higher risk of developing very severe thrombocytopaenia in children with severe P. vivax malaria than with severe P. falciparum malaria (OR: 2.80, 95% CI: 1.48-5.29). However, a pooled analysis of two studies showed an equal risk among adult severe cases (OR: 1.19, 95% CI: 0.51-2.77). This indicates that the risk of developing thrombocytopaenia in P. vivax malaria can vary with immune status in both children and adults. One study reported higher levels of urea and serum bilirubin in patients with P. vivax malaria and severe thrombocytopaenia compared with patients mild thrombocytopaenia or no thrombocytopaenia, (P vivax patients and severe P. falciparum patients (P = 0.09). This implied that both P. vivax and P. falciparum infections could present with bleeding episodes, if there had been a change in platelet counts in the infected patients. A pooled analysis of another two studies showed an equal risk of mortality with severe thrombocytopaenia in both P. vivax and P. falciparum malaria patients (OR: 1.16, 95% CI: 0.30-4.60). However, due to the low number of studies with small sample sizes within the subset of studies that provided clinically relevant information, our confidence in the estimates is limited.
CONCLUSION: The current review has provided some evidence of the clinical relevance of severe thrombocytopaenia in P. vivax malaria. To substantiate these findings, there is a need for well designed, large-scale, prospective studies among patients infected with P. vivax. These should include patients from different countries and epidemiological settings with various age and gender groups represented.
METHODS: A systematic review identified P. vivax efficacy studies of chloroquine with or without primaquine published between January 2000 and March 2017. Individual patient data were pooled using standardised methodology, and the haematological response versus time was quantified using a multivariable linear mixed effects model with non-linear terms for time. Mean differences in haemoglobin between treatment groups at day of nadir and day 42 were estimated from this model.
RESULTS: In total, 3421 patients from 29 studies were included: 1692 (49.5%) with normal G6PD status, 1701 (49.7%) with unknown status and 28 (0.8%) deficient or borderline individuals. Of 1975 patients treated with chloroquine alone, the mean haemoglobin fell from 12.22 g/dL [95% CI 11.93, 12.50] on day 0 to a nadir of 11.64 g/dL [11.36, 11.93] on day 2, before rising to 12.88 g/dL [12.60, 13.17] on day 42. In comparison to chloroquine alone, the mean haemoglobin in 1446 patients treated with chloroquine plus primaquine was - 0.13 g/dL [- 0.27, 0.01] lower at day of nadir (p = 0.072), but 0.49 g/dL [0.28, 0.69] higher by day 42 (p 25% to 5 g/dL.
CONCLUSIONS: Primaquine has the potential to reduce malaria-related anaemia at day 42 and beyond by preventing recurrent parasitaemia. Its widespread implementation will require accurate diagnosis of G6PD deficiency to reduce the risk of drug-induced haemolysis in vulnerable individuals.
TRIAL REGISTRATION: This trial was registered with PROSPERO: CRD42016053312. The date of the first registration was 23 December 2016.
METHODS: In a systematic study of the presentation and course of patients with acute P. knowlesi infection, clinical and laboratory data were collected from previously untreated, nonpregnant adults admitted to the hospital with polymerase chain reaction-confirmed acute malaria at Kapit Hospital (Sarawak, Malaysia) from July 2006 through February 2008.
RESULTS: Of 152 patients recruited, 107 (70%) had P. knowlesi infection, 24 (16%) had Plasmodium falciparum infection, and 21 (14%) had Plasmodium vivax. Patients with P. knowlesi infection presented with a nonspecific febrile illness, had a baseline median parasitemia value at hospital admission of 1387 parasites/microL (interquartile range, 6-222,570 parasites/microL), and all were thrombocytopenic at hospital admission or on the following day. Most (93.5%) of the patients with P. knowlesi infection had uncomplicated malaria that responded to chloroquine and primaquine treatment. Based on World Health Organization criteria for falciparum malaria, 7 patients with P. knowlesi infection (6.5%) had severe infections at hospital admission. The most frequent complication was respiratory distress, which was present at hospital admission in 4 patients and developed after admission in an additional 3 patients. P. knowlesi parasitemia at hospital admission was an independent determinant of respiratory distress, as were serum creatinine level, serum bilirubin, and platelet count at admission (p < .002 for each). Two patients with knowlesi malaria died, representing a case fatality rate of 1.8% (95% confidence interval, 0.2%-6.6%).
CONCLUSIONS: Knowlesi malaria causes a wide spectrum of disease. Most cases are uncomplicated and respond promptly to treatment, but approximately 1 in 10 patients develop potentially fatal complications.