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Clinical profile of Plasmodium falciparum and Plasmodium vivax infections in low and unstable malaria transmission settings of Colombia.

ABSTRACT: Malaria transmission in Latin America is generally hypoendemic and unstable, with Plasmodium vivax as the most prevalent species. However, only a few studies have been carried out in areas with low and unstable transmission, whereas the clinical profile of malaria has been broadly described in hyperendemic areas. The pattern of clinical manifestations and laboratory findings in low to moderate endemic areas of Colombia is reported here.A passive surveillance study was conducted between 2011 and 2013 involving 1,328 patients with Plasmodium falciparum, P. vivax or mixed malaria infections attending malaria points-of-care of four malaria endemic-areas with distinct transmission intensities and parasite distribution. Trained physicians recorded clinical symptoms and signs as well as socio-demographic characteristics of study participants. Haematological, biochemical and urine tests were performed at the time of diagnosis.Out of 1,328 cases, 673 (50.7%) were caused by P. vivax; 650 (48.9%) were due to P. falciparum; and five (0.4%) patients had mixed infections (P. falciparum/P. vivax). Most patients (92.5%) presented with uncomplicated malaria characterized by fever, chills, headache, sweating, myalgia/arthralgia and parasitaemia ≤ 20,000 parasites/μL. Fever, tachycardia, pallor and abdominal pain on palpation were more frequent in P. falciparum patients, whereas mild hepatomegaly and splenomegaly were mostly observed with P. vivax. Non-severe anaemia (Hb 7.0-10.9 g/dL) was observed in 20% of the subjects, whereas severe anaemia (Hb < 7.0 g/dL) was present in four patients. Half of the patients presented thrombocytopaenia regardless of parasite species. Leukopaenia, neutrophilia and monocytosis were frequently observed in patients infected with P. falciparum. Mild-to-moderate biochemical alterations were present in ~25% of the patients, particularly abnormal bilirubin in those with P. falciparum and abnormal transaminases in P. vivax malaria patients. Proteinuria was present in ~50% of the patients regardless of parasite species, whereas haemoglobinuria was more common in P. vivax infections. Only 7.5% of the cases were classified as clinically severe malaria, caused by both P. vivax and P. falciparum.The high prevalence of uncomplicated malaria associated with moderate parasitaemia suggests the importance of timely diagnosis and effective treatment and encourages new activities to further decrease complicated malaria cases and mortality.

SUBMITTER: Arevalo-Herrera M

PROVIDER: S-EPMC4397685 | biostudies-other | 2015 Apr

REPOSITORIES: biostudies-other

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Project description:BackgroundAs countries move to malaria elimination, detecting and targeting asymptomatic malaria infections might be needed. Here, the epidemiology and detectability of asymptomatic Plasmodium falciparum and Plasmodium vivax infections were investigated in different transmission settings in Ethiopia.MethodA total of 1093 dried blood spot (DBS) samples were collected from afebrile and apparently healthy individuals across ten study sites in Ethiopia from 2016 to 2020. Of these, 862 were from community and 231 from school based cross-sectional surveys. Malaria infection status was determined by microscopy or rapid diagnostics tests (RDT) and 18S rRNA-based nested PCR (nPCR). The annual parasite index (API) was used to classify endemicity as low (API?>?0 and <?5), moderate (API???5 and <?100) and high transmission (API???100) and detectability of infections was assessed in these settings.ResultsIn community surveys, the overall prevalence of asymptomatic Plasmodium infections by microscopy/RDT, nPCR and all methods combined was 12.2% (105/860), 21.6% (183/846) and 24.1% (208/862), respectively. The proportion of nPCR positive infections that was detectable by microscopy/RDT was 48.7% (73/150) for P. falciparum and 4.6% (2/44) for P. vivax. Compared to low transmission settings, the likelihood of detecting infections by microscopy/RDT was increased in moderate (Adjusted odds ratio [AOR]: 3.4; 95% confidence interval [95% CI] 1.6-7.2, P?=?0.002) and high endemic settings (AOR?=?5.1; 95% CI?2.6-9.9, P?<?0.001). After adjustment for site and correlation between observations from the same survey, the likelihood of detecting asymptomatic infections by microscopy/RDT (AOR per year increase?=?0.95, 95% CI?0.9-1.0, P?=?0.013) declined with age.ConclusionsConventional diagnostics missed nearly half of the asymptomatic Plasmodium reservoir detected by nPCR. The detectability of infections was particularly low in older age groups and low transmission settings. These findings highlight the need for sensitive diagnostic tools to detect the entire parasite reservoir and potential infection transmitters.

Project description:BackgroundCross-border malaria transmission is an important problem for national malaria control programmes. The epidemiology of cross-border malaria is further complicated in areas where Plasmodium falciparum and Plasmodium vivax are both endemic. By combining passive case detection data with entomological data, a transmission scenario on the northwestern Thai-Myanmar border where P. falciparum is likely driven by importation was described, whereas P. vivax is also locally transmitted. This study highlights the differences in the level of control required to eliminate P. falciparum and P. vivax from the same region.MethodsMalaria case data were collected from malaria clinics in Suan Oi village, Tak Province, Thailand between 2011 and 2014. Infections were diagnosed by light microscopy. Demographic data, including migrant status, were correlated with concomitantly collected entomology data from 1330 mosquito trap nights using logistic regression. Malaria infection in the captured mosquitoes was detected by ELISA.ResultsRecent migrants were almost four times more likely to be infected with P. falciparum compared with Thai patients (OR 3.84, p < 0.001) and cases were significantly associated with seasonal migration. However, P. falciparum infection was not associated with the Anopheles mosquito capture rates, suggesting predominantly imported infections. In contrast, recent migrants were equally likely to present with P. vivax as mid-term migrants. Both migrant groups were twice as likely to be infected with P. vivax in comparison to the resident Thai population (OR 1.96, p < 0.001 and OR 1.94, p < 0.001, respectively). Plasmodium vivax cases were strongly correlated with age and local capture rates of two major vector species Anopheles minimus and Anopheles maculatus (OR 1.23, p = 0.020 and OR 1.33, p = 0.046, respectively), suggesting that a high level of local transmission might be causing these infections.ConclusionsOn the Thai-Myanmar border, P. falciparum infections occur mostly in the recent migrant population with a seasonality reflecting that of agricultural activity, rather than that of the local mosquito population. This suggests that P. falciparum was mostly imported. In contrast, P. vivax cases were significantly associated with mosquito capture rates and less with migrant status, indicating local transmission. This highlights the different timelines and requirements for P. falciparum and P. vivax elimination in the same region and underlines the importance of multinational, cross-border malaria control.

Project description:Knowledge about the relation of histopathological characteristics and mediators of physiological processes in the placenta malaria (PM) is poor, and that PM caused by Plasmodium vivax is almost null. The objective was to compare histopathological characteristics, cytokines and mediators of physiological processes in PM depending on the parasitic species, through a cross-sectional study in three groups: negative-PM, vivax-PM, falciparum-PM from Northwestern Colombia. The diagnosis of PM was made with thick blood smear, qPCR, and histopathology. Immuno-histochemical was made with EnVision system (Dako) and Zeiss Axio Imager M2 with light microscope. Cells in apoptosis were studied with the TUNEL technique. To measure the expression level of cytokines and mediators qRT-PCR was used. We included 179 placentas without PM and 87 with PM (53% P. vivax and 47% P. falciparum). At delivery, anemia was 25% in negative-PM, 60% in vivax-PM, and 44% in falciparum-PM group. The neonatal weight had an intense difference between groups with 3292±394g in negative-PM, 2,841±239 in vivax-PM, and 2,957±352 in falciparum-PM. The histopathological characteristics and CD+ cells in placenta with statistical differences (Dunn´s test) between negative-PM vs vivax-PM (P. falciparum was similar to P. vivax) were infarction, fibrinoid deposits, calcification, cells in apoptosis, immune infiltrates in decidua and intervillous space, CD4+, CD8+, CD14+, CD56+, CD68+. The expression levels of mediators in the placenta with statistical differences (Dunn´s test) between negative-PM vs vivax-PM (P. falciparum was similar to P. vivax) were Fas, FasL, HIF1α, Cox1, Cox2, VEGF, IL4, IL10, IFNγ, TNF, TGFβ, FOXP3, and CTLA4. PM with P. falciparum and P. vivax, damages this organ and causes significant alteration of various physiological processes, which cause maternal anemia and a reduction in neonatal weight in degrees that are statistically and clinically significant. It is necessary that the search for plasmodial infection in pregnant and placenta goes from passive to active surveillance with adequate diagnostic capacity.

Project description:BACKGROUND:The use of molecular diagnostics has revealed an unexpectedly large number of asymptomatic low-density malaria infections in many malaria endemic areas. This study compared the gains in parasite prevalence obtained by the use of ultra-sensitive (us)-qPCR as compared to standard qPCR in cross-sectional surveys conducted in Thailand, Brazil and Papua New Guinea (PNG). The compared assays differed in the copy number of qPCR targets in the parasite genome. METHODS:Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) parasites were quantified by qPCR amplifying the low-copy Pf_ and Pv_18S rRNA genes or the multi-copy targets Pf_varATS and Pv_mtCOX1. Cross-sectional surveys at the three study sites included 2252 participants of all ages and represented different transmission intensities. RESULTS:In the two low-transmission areas, P. falciparum positivity was 1.3% (10/773) (Thailand) and 0.8% (5/651) (Brazil) using standard Pf_18S rRNA qPCR. In these two countries, P. falciparum positivity by Pf_varATS us-qPCR increased to 1.9% (15/773) and 1.7% (11/651). In PNG, an area with moderate transmission intensity, P. falciparum positivity significantly increased from 8.6% (71/828) by standard qPCR to 12.2% (101/828) by us-qPCR. The proportions of P. falciparum infections not detected by standard qPCR were 33%, 55% and 30% in Thailand, Brazil and PNG. Plasmodium vivax was the predominating species in Thailand and Brazil, with 3.9% (30/773) and 4.9% (32/651) positivity by Pv_18S rRNA qPCR. In PNG, P. vivax positivity was similar to P. falciparum, at 8.0% (66/828). Use of Pv_mtCOX1 us-qPCR led to a significant increase in positivity to 5.1% (39/773), 6.4% (42/651) and 11.5% (95/828) in Thailand, Brazil, and PNG. The proportions of P. vivax infections missed by standard qPCR were similar at all three sites, with 23%, 24% and 31% in Thailand, Brazil and PNG. CONCLUSION:The proportional gains in the detection of P. falciparum and P. vivax infections by ultra-sensitive diagnostic assays were substantial at all three study sites. Thus, us-qPCR yields more precise prevalence estimates for both P. falciparum and P. vivax at all studied levels of endemicity and represents a significant diagnostic improvement. Improving sensitivity in P. vivax surveillance by us-qPCR is of particular benefit, because the additionally detected P. vivax infections signal the potential presence of hypnozoites and subsequent risk of relapse and further transmission.

Project description:BackgroundMalaria-associated anaemia, arising from symptomatic, asymptomatic and submicroscopic infections, is a significant cause of morbidity worldwide. Induced blood stage malaria volunteer infection studies (IBSM-VIS) provide a unique opportunity to evaluate the haematological response to early Plasmodium falciparum and Plasmodium vivax infection.MethodsThis study was an analysis of the haemoglobin, red cell counts, and parasitaemia data from 315 participants enrolled in IBSM-VIS between 2012 and 2019, including 269 participants inoculated with the 3D7 strain of P. falciparum (Pf3D7), 15 with an artemisinin-resistant P. falciparum strain (PfK13) and 46 with P. vivax. Factors associated with the fractional fall in haemoglobin (Hb-FF) were evaluated, and the malaria-attributable erythrocyte loss after accounting for phlebotomy-related losses was estimated. The relative contribution of parasitized erythrocytes to the malaria-attributable erythrocyte loss was also estimated.ResultsThe median peak parasitaemia prior to treatment was 10,277 parasites/ml (IQR 3566-27,815), 71,427 parasites/ml [IQR 33,236-180,213], and 34,840 parasites/ml (IQR 13,302-77,064) in participants inoculated with Pf3D7, PfK13, and P. vivax, respectively. The median Hb-FF was 10.3% (IQR 7.8-13.3), 14.8% (IQR 11.8-15.9) and 11.7% (IQR 8.9-14.5) in those inoculated with Pf3D7, PfK13 and P. vivax, respectively, with the haemoglobin nadir occurring a median 12 (IQR 5-21), 15 (IQR 7-22), and 8 (IQR 7-15) days following inoculation. In participants inoculated with P. falciparum, recrudescence was associated with a greater Hb-FF, while in those with P. vivax, the Hb-FF was associated with a higher pre-treatment parasitaemia and later day of anti-malarial treatment. After accounting for phlebotomy-related blood losses, the estimated Hb-FF was 4.1% (IQR 3.1-5.3), 7.2% (IQR 5.8-7.8), and 4.9% (IQR 3.7-6.1) in participants inoculated with Pf3D7, PfK13, and P. vivax, respectively. Parasitized erythrocytes were estimated to account for 0.015% (IQR 0.006-0.06), 0.128% (IQR 0.068-0.616) and 0.022% (IQR 0.008-0.082) of the malaria-attributable erythrocyte loss in participants inoculated with Pf3D7, PfK13, and P. vivax, respectively.ConclusionEarly experimental P. falciparum and P. vivax infection resulted in a small but significant fall in haemoglobin despite parasitaemia only just at the level of microscopic detection. Loss of parasitized erythrocytes accounted for < 0.2% of the total malaria-attributable haemoglobin loss.

Project description:Understanding naturally acquired immunity to infections caused by Plasmodia in different malaria endemicity settings is needed for better vaccine designs and for exploring antibody responses as a proxy marker of malaria transmission intensity. This study investigated the sero-epidemiology of malaria along the international border between China and Myanmar, where malaria elimination action plans are in place. This study recruited 233 P. vivax and 156 P. falciparum infected subjects with acute malaria at the malaria clinics and hospitals. In addition, 93 and 67 healthy individuals from the same endemic region or from non-endemic region, respectively, were used as controls. Acute malaria infections were identified by microscopy. Anti-recombinant PfMSP119 and PvMSP119 antibody levels were measured by ELISA. Antibody responses to respective MSP119 were detected in 50.9% and 78.2% patients with acute P. vivax and P. falciparum infections, respectively. There were cross-reacting antibodies in Plasmodium patients against these two recombinant proteins, though we could not exclude the possibility of submicroscopic mixed-species infections. IgG1, IgG3 and IgG4 were the major subclasses. Interestingly, 43.2% of the healthy endemic population also had antibodies against PfMSP119, whereas only 3.9% of this population had antibodies against PvMSP119. Higher antibody levels were correlated with age and parasite density, but not with season, gender or malaria history. Both total IgG and individual IgG subclasses underwent substantial declines during the convalescent period in three months. This study demonstrated that individuals in a hypoendemic area with coexistence of P. vivax and P. falciparum can mount rapid antibody responses against both PfMSP119 and PvMSP119. The significantly higher proportion of responders to PfMSP119 in the healthy endemic population indicates higher prevalence of P. falciparum in the recent past. Specific antibodies against PvMSP119 could serve as a marker of recent exposure to P. vivax in epidemiological studies.

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Clinical profile of Plasmodium falciparum and Plasmodium vivax infections in low and unstable malaria transmission settings of Colombia.

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