Vivax Mono-infection Research Articles

Efficacy and safety of chloroquine plus primaquine for the treatment of Plasmodium vivax malaria in Hamusit site, Northwestern Ethiopia

BackgroundPlasmodium vivax malaria is still an important public health problem in Ethiopia. Unlike Plasmodium falciparum, P. vivax has a dormant liver stage (hypnozoite) that can be a risk of recurrent vivax malaria unless treated by radical cure with primaquine. Drug resistance to chloroquine is threatening malaria control and elimination efforts. This study assessed the therapeutic efficacy and safety of chloroquine plus 14 days of primaquine on P. vivax infection based on parasitological, clinical, and haematological parameters.MethodsA single-arm in vivo prospective therapeutic efficacy study was conducted to assess the clinical and parasitological response to the first-line treatment of P. vivax in Ethiopia, chloroquine plus 14 days low dose of (0.25 mg/kg/day) primaquine between December 2022 and March 2023 at Hamusit Health Centre using the standard World Health Organization (WHO) protocol. A total of 100 study participants with P. vivax mono-infection who were over 6 months old were enrolled and monitored for adequate clinical and parasitological responses for 42 days. The WHO double-entry Excel sheet and SPSS v.25 software were used for Kaplan–Meier survival analysis, and a paired t-test was used for analysis of haemoglobin improvements between follow up days.ResultsA total of 100 patients were enrolled among those, 96% cases were rural residents, 93% had previous malaria exposure, and predominant age group was 5–15 years (61%). 92.6% (95% CI 85.1–96.4%) of enrolled patients were adequate clinical and parasitological response, and 7.4% (95% CI 3.6–14.9%) recurrences were observed among treated patients. The fever and parasite clearance rate on day 3 were 98% and 94%, respectively. The baseline haemoglobin levels improved significantly compared to those days 14 and 42 (p < 0.001). No serious adverse event was observed during the study period.ConclusionsIn this study, co-administration of chloroquine with primaquine was efficacious and well-tolerated with fast resolution of fever and high parasites clearance rate. However, the 7.4% failure is reported is alarming that warrant further monitoring of the therapeutic efficacy study of P. vivax.

Chloroquine has shown high therapeutic efficacy against uncomplicated Plasmodium vivax malaria in southern Ethiopia: seven decades after its introduction

BackgroundPlasmodium vivax malaria is a leading cause of morbidity in Ethiopia. The first-line treatment for P. vivax is chloroquine (CQ) and primaquine (PQ), but there have been local reports of CQ resistance. A clinical study was conducted to determine the efficacy of CQ for the treatment of P. vivax malaria in southern Ethiopia.MethodsIn 2021, patients with P. vivax mono-infection and uncomplicated malaria were enrolled and treated with 25 mg/kg CQ for 3 consecutive days. Patients were followed for 28 days according to WHO guidelines. The data were analysed using per-protocol (PP) and Kaplan‒Meier (K‒M) analyses to estimate the risk of recurrent P. vivax parasitaemia on day 28.ResultsA total of 88 patients were enrolled, 78 (88.6%) of whom completed the 28 days of follow-up. Overall, 76 (97.4%) patients had adequate clinical and parasitological responses, and two patients had late parasitological failures. The initial therapeutic response was rapid, with 100% clearance of asexual parasitaemia within 48 h.ConclusionDespite previous reports of declining chloroquine efficacy against P. vivax, CQ retains high therapeutic efficacy in southern Ethiopia, supporting the current national treatment guidelines. Ongoing clinical monitoring of CQ efficacy supported by advanced molecular methods is warranted to inform national surveillance and ensure optimal treatment guidelines.

Epidemiology of Plasmodium vivax in Duffy negatives and Duffy positives from community and health centre collections in Ethiopia.

Malaria remains a significant cause of morbidity and mortality in Ethiopia with an estimated 3.8 million cases in 2021 and 61% of the population living in areas at risk of malaria transmission. Throughout the country Plasmodium vivax and Plasmodium falciparum are co-endemic, and Duffy expression is highly heterogeneous. The public health significance of Duffy negativity in relation to P. vivax malaria in Ethiopia, however, remains unclear. This study seeks to explore the prevalence and rates of P. vivax malaria infection across Duffy phenotypes in clinical and community settings. A total of 9580 and 4667 subjects from community and health facilities from a malaria endemic site and an epidemic-prone site in western Ethiopia were enrolled and examined for P. vivax infection and Duffy expression from February 2018 to April 2021. Association between Duffy expression, P. vivax and P. falciparum infections were examined for samples collected from asymptomatic community volunteers and symptomatic subjects from health centres. Infection rate of P. vivax among Duffy positives was 2-22 fold higher than Duffy negatives in asymptomatic volunteers from the community. Parasite positivity rate was 10-50 fold higher in Duffy positives than Duffy negatives among samples collected from febrile patients attending health centres and mixed P. vivax and P. falciparum infections were significantly more common than P. vivax mono infections among Duffy negative individuals. Plasmodium vivax parasitaemia measured by 18sRNA parasite gene copy number was similar between Duffy positives and Duffy negatives. Duffy negativity does not offer complete protection against infection by P. vivax, and cases of P. vivax in Duffy negatives are widespread in Ethiopia, being found in asymptomatic volunteers from communities and in febrile patients from health centres. These findings offer evidence for consideration when developing control and intervention strategies in areas of endemic P. vivax and Duffy heterogeneity.

Dynamics of asymptomatic Plasmodium falciparum and Plasmodium vivax infections and their infectiousness to mosquitoes in a low transmission setting of Ethiopia: a longitudinal observational study

ObjectiveA 15-month longitudinal study was conducted to determine the duration and infectivity of asymptomatic qPCR-detected Plasmodium falciparum and Plasmodium vivax infections in Ethiopia. MethodTotal parasite and gametocyte kinetics were determined by molecular methods; infectivity to Anopheles arabiensis mosquitoes by repeated membrane feeding assays. Infectivity results were contrasted with passively recruited symptomatic malaria cases. ResultsFor P. falciparum and P. vivax infections detected at enrolment, median durations of infection were 37 days (95% confidence interval [CI], 15-93) and 60 days (95% CI, 18-213), respectively. P. falciparum and P. vivax parasite densities declined over the course of infections. From 47 feeding assays on 22 asymptomatic P. falciparum infections, 6.4% (3/47) were infectious and these infected 1.8% (29/1579) of mosquitoes. No transmission was observed in feeding assays on asymptomatic P. vivax mono-infections (0/56); one mixed-species infection was highly infectious. Among the symptomatic cases, 4.3% (2/47) of P. falciparum and 73.3% (53/86) of P. vivax patients were infectious to mosquitoes. ConclusionThe majority of asymptomatic infections were of short duration and low parasite density. Only a minority of asymptomatic individuals were infectious to mosquitoes. This contrasts with earlier findings and is plausibly due to the low parasite densities in this population.

Molecular surveillance of chloroquine resistance in Plasmodium vivax isolates from malaria cases in Yunnan Province of China using pvcrt-o gene polymorphisms

BackgroundThe efficacy of chloroquine treatment for vivax malaria has been rarely evaluated due to a lack of an appropriate testing method. The objective of this study was to conduct molecular monitoring of chloroquine resistance in Plasmodium vivax strains from vivax malaria patients in Yunnan Province, focusing on the analysis of polymorphism in the P. vivax chloroquine resistance transporter protein orthologous gene (pvcrt-o).MethodsIn accordance with the principles of a cohort study, blood samples were collected from malaria cases diagnosed with a P. vivax mono-infection in Yunnan Province from 2020 to 2022. Segmental PCR was used to amplify the whole pvcrt-o gene in the blood samples and their products were subsequently sequenced. The sequencing data were arranged to obtain the full coding DNA sequence (CDS) as well as the gene’s promoter region sequences. The CDSs were aligned with the reference sequence (XM_001613407.1) of the P. vivax SalI isolate to identify the mutant loci.ResultsFrom a total of 375 blood samples taken from vivax malaria cases, 272 both whole gene CDSs (1272–1275 bp) and promoter DNA sequences (707 bp) of pvcrt-o gene were obtained. Among the whole CDSs, there were 7 single nucleotide polymorphic sites in which c.7 A>G was the minor allele frequency (MAF) site with 4.4% (12/272) detection rate. The mutation detection rate showed a significant decrease from 9.8% (10/102) in 2020 to 1.1% (1/92) in 2021 and 1.3% (1/78) in 2022, indicating statistical significance (χ2 = 11.256, P < 0.05). Among the identified 12 haplotypes, the majority of which were wild type (75.7%; 206/272). These four mutant haplotypes (Hap_3, Hap_5, Hap_9, and Hap_10) were classified as “K10 insertion type” and accounted for 12.1% (33/272). The detection rate of Hap_3 increased from 1.0% (1/102) in 2020 to 13.0% (12/92) in 2021 and 14.1% (11/78) in 2022, indicating statistical significance. A total of 23.8% (65/272) of the samples exhibited 14 bp (bp) deletions in the promoter region, occurring most frequently in the wild type haplotype (Hap_1) samples at a rate of 28.6% (59/206).ConclusionsIn recent years in Yunnan Province, a notable proportion of vivax malaria patients are infected by P. vivax strains with a “K10 insertion” and partial sequence deletions in the promoter region of the pvcrt-o gene, necessitating vigilance.

Trends in clinical features and severity of Plasmodium vivax malaria among children at tertiary care center in North India.

Malaria is a significant cause of morbidity and mortality in adults and children. Plasmodium falciparum is the primary cause of severe malaria, but recently Plasmodium vivax is also recognized to cause severe malaria-associated morbidity and mortality. The study focuses on determining the mortality related to severity parameters in individuals under 12 years and their critical presentation in P.vivax malaria-infected children. A prospective cross-sectional hospital-based study was conducted at Safdarjung Hospital, New Delhi, and ICMR-NIMR, New Delhi. All clinically suspected cases were admitted for screening. Exclusion criteria (rapid malaria antigen test, microscopy and medication history) were applied to all the admitted patients (n = 221) to obtain P.vivax patients only. Patients aged ≤ 12 years were included in the study. DNA was extracted from dried blood spots and amplified by nested PCR, followed by visualization on gel electrophoresis. A total of 221 clinically suspected cases of malaria were screened for P.vivax. After implementing various exclusion criteria, 45/221 cases were enrolled for the study, among which 44.4% (20/45) of children had the symptoms of severe malaria in terms of cerebral malaria, thrombocytopenia, anemia, pancytopenia, acute respiratory distress syndrome and hemophagocytic lymphohistiocytosis. Plasmodium vivax mono-infection can cause severe manifestation and must be treated as P.falciparum without any delay because it may lead to increased morbidity and mortality. A changing trend in clinical symptoms has shown in P.vivax which was an earlier phenomenon of P.falciparum.

Significant number of Plasmodium vivax mono-infections by PCR misidentified as mixed infections (P. vivax/P. falciparum) by microscopy and rapid diagnostic tests: malaria diagnostic challenges in Ethiopia

BackgroundPlasmodium vivax malaria is now recognized as a cause of severe morbidity and mortality, resulting in a substantial negative effect on health especially in endemic countries. Accurate and prompt diagnosis and treatment of P. vivax malaria is vital for the control and elimination of the disease.MethodsA cross-sectional study was conducted from February 2021 to September 2022 at five malaria endemic sites in Ethiopia including Aribaminch, Shewarobit, Metehara, Gambella, and Dubti. A total of 365 samples that were diagnosed positive for P. vivax (mono and mixed infection) using RDT, site level microscopists and expert microscopists were selected for PCR. Statistical analyses were performed to calculate the proportions, agreement (k), frequencies, and ranges among different diagnostic methods. Fisher’s exact tests and correlation test were used to detect associations and relationship between different variables.ResultsOf the 365 samples, 324 (88.8%), 37(10.1%), 2 (0.5%), and 2 (0.5%) were P. vivax (mono), P. vivax/Plasmodium falciparum (mixed), P. falciparum (mono) and negative by PCR, respectively. The overall agreement of rapid diagnostic test (RDT), site level microscopy and expert microscopists result with PCR was 90.41% (k: 0.49), 90.96% (k: 0.53), and 80.27% (k: 0.24). The overall prevalence of sexual (gametocyte) stage P. vivax in the study population was 215/361 (59.6%). The majority of these 215 samples (180; 83.7%) had below 1000 parasites/µl, with only four samples (1.9%) had ≥ 5000 parasites/µl. The gametocyte density was found to be weakly positive but statically significant with asexual parasitaemia (r = 0.31; p < 0.001).ConclusionBoth microscopy and RDT showed moderate agreement with PCR in the detection and identification of P. vivax (mono) and P. vivax/P. falciparum (mixed) infections. Therefore, to achieve malaria elimination goals, strengthening routine malaria diagnostic methods by implementing diagnostic tools with a good performance in detecting and accurately identifying malaria species in clinical settings is recommended.

Magnitude and patterns of severe Plasmodium vivax monoinfection in Vietnam: a 4-year single-center retrospective study.

Infection with Plasmodium vivax is a recognized cause of severe malaria including deaths. The exact burden and patterns of severe P. vivax monoinfections is however still not well quantified, especially in P. vivax endemic regions. We examined the magnitude and patterns of severe malaria caused by monoinfections of P. vivax and associated predictors among patients admitted to a tertiary care center for malaria in Vietnam. A retrospective cohort study was conducted based on the patients' medical records at the Hospital for Tropical Diseases from January 2015 to December 2018. Extracted information included demographic, epidemiologic, clinical, laboratory and treatment characteristics. Monoinfections with P. vivax were found in 153 (34.5, 95% CI 30.3-39.1%) patients of whom, uncomplicated and severe malaria were documented in 89.5% (137/153, 95% CI 83.7-93.5%) and 10.5% (16/153, 95% CI 6.5-16.3%), respectively. Patterns of severe malaria included jaundice (8 cases), hypoglycemia (3 cases), shock (2 cases), anemia (2 cases), and cerebral malaria (1 case). Among 153 patients, 73 (47.7%) had classic malaria paroxysm, 57 (37.3%) had >7 days of illness at the time of admission, and 40 (26.1%) were referred from other hospitals. A misdiagnosis as having other diseases from malaria cases coming from other hospitals was up to 32.5% (13/40). Being admitted to hospital after day 7th of illness (AOR = 6.33, 95% CI 1.14-35.30, p = 0.035) was a predictor of severe malaria. Severe malaria was statistically associated with longer hospital length of stay (p = 0.035). Early and late treatment failures and recrudescence were not recorded. All patients recovered completely. This study confirms the emergence of severe vivax malaria in Vietnam which is associated with delayed hospital admission and increased hospital length of stay. Clinical manifestations of P. vivax infection can be misdiagnosed which results in delayed treatment. To meet the goal of malaria elimination by 2030, it is crucial that the non-tertiary hospitals have the capacity to quickly and correctly diagnose malaria and then provide treatment for malaria including P. vivax infections. More robust studies need to be conducted to fully elucidate the magnitude of severe P. vivax in Vietnam.

Molecular epidemiology of potential candidate markers for chloroquine resistance in imported Plasmodium vivax malaria cases in Iran

BackgroundThe spread of Plasmodium vivax strains resistant to chloroquine (CQ) has posed a challenge to control strategies aimed at eliminating malaria. Molecular analysis of candidate resistance markers is very important for monitoring the P. vivax resistance to CQ in different endemic regions. In the present study, the multidrug resistance 1 (pvmdr1) gene, a possible marker for CQ resistance in P. vivax, was evaluated by molecular methods.MethodsA simple PCR–RFLP method was developed for mutation analysis in pvmdr1 gene. A number of 120 blood spots were obtained from patients with P. vivax mono-infection in 2021. All of the samples were collected from Pakistani patients who travelled to Iran.ResultsNone of the samples had any mutation at codon 976 of pvmdr1, while the 1076 mutation was detected in 96.2% of the examined isolates. Only two pvmdr1 haplotypes were identified, including the single mutant (Y976/1076L) as the most prevalent haplotype (with 96.2% frequency) and the wild type (Y976/F1076; with 3.8% frequency).ConclusionsIn this study, the major CQ resistance-mediating mutation and multiple mutant haplotypes of the pvmdr1 gene was not detected. However, continuous monitoring of drug resistance markers and close supervision of the efficacy of CQ is essential to detect the potential emergence of CQ-resistant P. vivax isolates in Iran. This data is important for performing future epidemiological surveillance to monitor CQ resistance in this endemic area and the bordering regions.

Temporal Dynamics of Subclinical Malaria in Different Transmission Zones of Myanmar.

ABSTRACT.Countries in the Greater Mekong Subregion have committed to eliminate Plasmodium falciparum malaria by 2025. Subclinical malaria infections that can be detected by highly sensitive polymerase chain reaction (PCR) testing in asymptomatic individuals represent a potential impediment to this goal, although the extent to which these low-density infections contribute to transmission is unclear. To understand the temporal dynamics of subclinical malaria in this setting, a cohort of 2,705 participants from three epidemiologically distinct regions of Myanmar was screened for subclinical P. falciparum and P. vivax infection using ultrasensitive PCR (usPCR). Standard rapid diagnostic tests (RDTs) for P. falciparum were also performed. Individuals who tested positive for malaria by usPCR were followed for up to 12 weeks. Regression analysis was performed to estimate whether the baseline prevalence of infection and the count of repeated positive tests were associated with demographic, behavioral, and clinical factors. At enrollment, the prevalence of subclinical malaria infection measured by usPCR was 7.7% (1.5% P. falciparum monoinfection, 0.3% mixed P. falciparum and P. vivax, and 6.0% P. vivax monoinfection), while P. falciparum prevalence measured by RDT was just 0.2%. Prevalence varied by geography and was higher among older people and in those with outdoor exposure and travel. No difference was observed in either the prevalence or count of subclinical infection by time of year, indicating that even in low-endemicity areas, a reservoir of subclinical infection persists year-round. If low-density infections are shown to represent a significant source of transmission, identification of high-risk groups and locations may aid elimination efforts.

Malarial Epidemiology among Patients in Al-Medina Al-Munawara, KSA

Worldwide, malaria is the most important disease caused by parasites and responsible for a yearly estimation of 225 million clinical cases. The risk of the disease covers almost half of the world’s population and the annual death has been estimated as 800.000. Children under five years of age are mainly affected. Pregnant women and adults with immunosuppression become victims of cerebral manifestations or anaemia and frequently die. Almost 40% of the world's population is at risk to acquire the infection. Human malaria is caused by four Plasmodium species among which the most prevalent is Plasmodium falciparum. Because of the higher global prevalence, morbidity and mortality rate of P. falciparum, most research efforts on malaria pathogenesis have been focused on this species. Recent studies have reported the clinical outcomes that originate from regions where P. falciparum and P. vivax are equally prevalent. This in turn could make the clinical tools inappropriate for use in managing vivax mono infections. Thus, the present study was aimed to identify the epidemiology and clinical features of the malarial cases of the Referral laboratory, Al Madinah, Saudi Arabia. A retrospective case series study was conducted among the patients reported from January 2016 to December 2016 using a specially designed data collection form. Out of the 182 confirmed cases, 143 were non-saudi and 39 were Saudi cases. Most of the cases reported in the month of September due to seasonal change. Gender distribution showed a higher dominance of male patients compared to females. No cases were reported to be caused due to P.malariae. The predominant species was found to be P.Vivax (87%) while P.falciparum with only 13% incidence. Further investigations in large sample sizes are recommended to explore the other aspects in reducing the malaria burden.

Higher-Dose Primaquine to Prevent Relapse of Plasmodium vivax Malaria

BackgroundIn most of the Americas, the recommended treatment to prevent relapse of Plasmodium vivax malaria is primaquine at a total dose of 3.5 mg per kilogram of body weight, despite evidence of only moderate efficacy.MethodsIn this trial conducted in Brazil, we evaluated three primaquine regimens to prevent relapse of P. vivax malaria in children at least 5 years of age and in adults with microscopy-confirmed P. vivax monoinfection. All the patients received directly observed chloroquine for 3 days (total dose, 25 mg per kilogram). Group 1 received a total primaquine dose of 3.5 mg per kilogram (0.5 mg per kilogram per day) over 7 days with unobserved administration; group 2 received the same regimen as group 1 but with observed administration; and group 3 received a total primaquine dose of 7.0 mg per kilogram over 14 days (also 0.5 mg per kilogram per day) with observed administration. We monitored the patients for 168 days.ResultsWe enrolled 63 patients in group 1, 96 in group 2, and 95 in group 3. The median age of the patients was 22.4 years (range, 5.4 to 79.8). By day 28, three P. vivax recurrences were observed: 2 in group 1 and 1 in group 2. By day 168, a total of 70 recurrences had occurred: 24 in group 1, 34 in group 2, and 12 in group 3. No serious adverse events were noted. On day 168, the percentage of patients without recurrence was 58% (95% confidence interval [CI], 44 to 70) in group 1, 59% (95% CI, 47 to 69) in group 2, and 86% (95% CI, 76 to 92) in group 3. Survival analysis showed a difference in the day 168 recurrence-free percentage of 27 percentage points (97.5% CI, 10 to 44; P<0.001) between group 1 and group 3 and a difference of 27 percentage points (97.5% CI, 12 to 42; P<0.001) between group 2 and group 3.ConclusionsThe administration of primaquine at a total dose of 7.0 mg per kilogram had higher efficacy in preventing relapse of P. vivax malaria than a total dose of 3.5 mg per kilogram through day 168. (Supported by the U.S. Agency for International Development; ClinicalTrials.gov number, NCT03610399.)

Prevalence of Malaria and Associated Factors among Malaria-Suspected Patients Attending Hamusit Health Center, Northwest Ethiopia: A Cross-Sectional Study.

Background Malaria is one of the major public health problems in developing countries like Ethiopia. Despite efforts to reduce the mortality and morbidity, the disease is still a prominent health problem in Ethiopia. This study, therefore, was undertaken to assess the prevalence of malaria and associated factors among symptomatic patients in Northwest Ethiopia. Methods A facility based cross-sectional study was conducted from February to March 2020 among 210 febrile patients attending Hamusit Health Center, Northwest Ethiopia. A structured questionnaire was used to collect data on sociodemographic characteristics and factors perceived to be associated with Plasmodium infection. Questionnaire data was collected through face to face interview. Thin and thick blood films were prepared from capillary blood buffy coat samples. Data were analyzed using Statistical Package for Social Sciences Software version 20. Results Out of 210 malaria-suspected participants, 61 (29.0%) were confirmed to be infected by Plasmodium species. Plasmodium falciparum and P. vivax monoinfections were detected in 41 (19.5%) and 10 (4.8%) participants, respectively. Mixed infection was detected in 10 (4.8%) participants. Female participants (AOR = 2.261; 95% CI: 1.118-4.571; P = 0.023) and those having family members with history of malaria (AOR =2.261; 95% CI: 1.264-5.340; P = 0.009) had higher odds of acquiring Plasmodium infection as compared to their counterparts. Using insecticide-treated bed net and draining stagnant water were the most commonly mentioned malaria prevention measures reported by 71.9% and 8.1% of the respondents, respectively. Conclusion Malaria contributes significantly for febrile illnesses in the study area. Therefore, community mobilization should be strengthen in order to improve implementation of malaria control activities and, hence, reducing the prevalence.

In vivo efficacy of anti-malarial drugs against clinical Plasmodium vivax malaria in Ethiopia: a systematic review and meta-analysis

BackgroundEthiopia is one of the few countries in Africa where Plasmodium vivax commonly co-exists with Plasmodium falciparum, and which accounts for ~ 40% of the total number of malaria infections in the country. Regardless of the growing evidence over many decades of decreasing sensitivity of this parasite to different anti-malarial drugs, there has been no comprehensive attempt made to systematically review and meta-analyse the efficacy of different anti-malarial drugs against P. vivax in the country. However, outlining the efficacy of available anti-malarial drugs against this parasite is essential to guide recommendations for the optimal therapeutic strategy to use in clinical practice. The aim of this study was to synthesize evidence on the efficacy of anti-malarial drugs against clinical P. vivax malaria in Ethiopia.MethodsAll potentially relevant, peer-reviewed articles accessible in PubMed, Scopus, Web of Science, and Clinical Trial.gov electronic databases were retrieved using a search strategy combining keywords and related database-specific subject terms. Randomized controlled trials (RCTs) and non-randomized trials aiming to investigate the efficacy of anti-malarial drugs against P. vivax were included in the review. Data were analysed using Review Manager Software. Cochrane Q (χ2) and the I2 tests were used to assess heterogeneity. The funnel plot and Egger’s test were used to examine risk of publication bias.ResultsOut of 1294 identified citations, 14 articles that presented data on 29 treatment options were included in the analysis. These studies enrolled 2144 clinical vivax malaria patients. The pooled estimate of in vivo efficacy of anti-malarial drugs against vivax malaria in Ethiopia was 97.91% (95% CI: 97.29–98.52%), with significant heterogeneity (I2 = 86%, p < 0.0001) and publication bias (Egger’s test = -12.86, p < 0.001). Different anti-malarial drugs showed varied efficacies against vivax malaria. The duration of follow-up significantly affected the calculated efficacy of any given anti-malarial drug, with longer duration of the follow-up (42 days) associated with significantly lower efficacy than efficacy reported on day 28. Also, pooled PCR-corrected efficacy and efficacy estimated from altitudinally lower transmission settings were significantly higher than PCR-uncorrected efficacy that estimated for moderate transmission settings, respectively.ConclusionThe overall efficacy of anti-malarial drugs evaluated for the treatment of vivax malaria in Ethiopia was generally high, although there was wide-ranging degree of efficacy, which was affected by the treatment options, duration of follow-up, transmission intensity, and the confirmation procedures for recurrent parasitaemia. Regardless of evidence of sporadic efficacy reduction reported in the country, chloroquine (CQ), the first-line regimen in Ethiopia, remained highly efficacious, supporting its continuous utilization for confirmed P. vivax mono-infections. The addition of primaquine (PQ) to CQ is recommended, as this is the only approved way to provide radical cure, and thus ensure sustained efficacy and longer protection against P. vivax. Continuous surveillance of the efficacy of anti-malarial drugs and clinical trials to allow robust conclusions remains necessary to proactively act against possible emergence and spread of drug-resistant P. vivax in Ethiopia.

The Effect of Socioeconomic Factors and Indoor Residual Spraying on Malaria in Mangaluru, India: A Case-Control Study.

India faces 0.5 million malaria cases annually, including half of all Plasmodium vivax malaria cases worldwide. This case–control study assessed socioeconomic determinants of urban malaria in coastal Mangaluru, Karnataka, southwestern India. Between June and December 2015, we recruited 859 malaria patients presenting at the governmental Wenlock Hospital and 2190 asymptomatic community controls. We assessed clinical, parasitological, and socioeconomic data. Among patients, p. vivax mono-infection (70.1%) predominated. Most patients were male (93%), adult (median, 27 years), had no or low-level education (70.3%), and 57.1% were daily labourers or construction workers. In controls (59.3% male; median age, 32 years; no/low-level education, 54.5%; daily labourers/construction workers, 41.3%), 4.1% showed asymptomatic Plasmodium infection. The odds of malaria was reduced among those who had completed 10th school grade (aOR, 0.3; 95% CI, 0.26–0.42), lived in a building with a tiled roof (aOR, 0.71; 95% CI, 0.53–0.95), and reported recent indoor residual spraying (aOR, 0.02; 95% CI, 0.01–0.04). In contrast, migrant status was a risk factor for malaria (aOR, 2.43; 95% CI, 1.60–3.67). Malaria in Mangaluru is influenced by education, housing condition, and migration. Indoor residual spraying greatly contributes to reducing malaria in this community and should be promoted, especially among its marginalised members.

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

Plasmodium malariae infections are often asymptomatic and long-lasting. Mixed infections are often underdetected in areas where P. malariae, P. vivax, and P. falciparum are coendemic. In this study, we described the occurrence of these species circulating as single or mixed infections in Pará state, Brazil, in the Amazon region, with the purpose of clarifying the impact of misidentification of parasite species based only on morphological description using thick blood smear. By using real-time polymerase chain reaction based on the amplification of the mitochondrial DNA, we detected a prevalence of 46% (58/126) mixed infections with 33.3% P. malariae/P. vivax which were read as P. vivax monoinfections by microscopy detection. Our findings confirmed the high circulation of P. malariae in a malaria endemic area in the Brazilian Amazon region.

CLINICAL PROFILE OF PLASMODIUM VIVAX MALARIA IN CHILDREN

Background: To study clinical presentations and complications of P. vivax malaria&#x0D; Methods: A prospective hospital-based clinical observational study was conducted on 100 patients under age of 14 years were enrolled in the study.&#x0D; Result: The most common presentation was fever followed by pallor. Among the total of 100 cases studied 2 cases died with a case fatality rate of 2%. Among the total of 100 cases studied 5 cases (10%) required ICU admission.&#x0D; Conclusion: P. vivax monoinfection tends to have severe complications in children. There is a need to review severity criteria for P. vivax malaria.&#x0D; Keywords: Vivax, Fever, ICU

The high risk of malarial recurrence in patients with Plasmodium-mixed infection after treatment with antimalarial drugs: a systematic review and meta-analysis

BackgroundMalaria mixed infections are often unrecognized by microscopists in the hospitals, and a delay or failure to treat Plasmodium-mixed infection may lead to aggravated morbidity and increased mortality. The present study aimed to quantify the pooled proportion and risk of malarial recurrences after the treatment of Plasmodium-mixed infection. The results of the study may provide benefits in the management of Plasmodium-mixed infection in co-endemic regions.MethodsThis systematic review and meta-analysis searched the international Prospective Register of Systematic Reviews (PROSPERO; ID = CRD42020199709), MEDLINE, Web of Science, and Scopus for potentially relevant studies in any language published between January 1, 1936, and July 20, 2020, assessing drug efficacy in patients with Plasmodium-mixed infection. The primary outcome was the pooled prevalence of Plasmodium parasitemia after initiating antimalarial treatment for Plasmodium-mixed infection. The secondary outcome was the pooled risk ratio (RR) of malarial recurrence in Plasmodium-mixed infection compared with those in Plasmodium falciparum and Plasmodium vivax mono-infection. The pooled analyses were calculated by random-effects meta-analysis. After the initial treatment in different days of recurrences (≤ 28 days or > 28 days), the risk of Plasmodium parasitemia was compared in subgroup analysis.ResultsOut of 5217 screened studies, 11 were included in the meta-analysis, including 4390 patients from six countries. The pooled prevalence of all recurrences of Plasmodium-mixed parasitemia was 30% (95% confidence interval (CI) 16–43; I2: 99.2%; 11 studies). The RR of malarial recurrence within 28 days after the initial treatment (clinical treatment failure) of Plasmodium-mixed parasitemia compared with the treatment of P. falciparum was 1.22 (p: 0.029; 95% CI 1.02–1.47; Cochran Q: 0.93; I2: 0%; six studies), while there was no significant difference in the risk of recurrence 28 days after initial treatment compared with the treatment of P. falciparum (p: 0.696, RR: 1.14; 95% CI 0.59–2.18; Cochran Q < 0.05; I2: 98.2%; four studies). The subgroup analysis of antimalarial drugs showed that significant malarial recurrence within 28 days was observed in patients treated with artemisinin-based combination therapies (ACTs) with no significant heterogeneity (p: 0.028, RR: 1.31; 95% CI 1.03–1.66; Cochran Q: 0.834; I2: 0%).ConclusionsThe present findings showed a high prevalence of malarial recurrence after the initial treatment of Plasmodium-mixed infection. Moreover, significant malaria recurrence of mixed infection occurred within 28 days after treatment with ACTs.Graphical

Pattern of severe malaria with special reference to Plasmodium vivax in pediatric population of the most aspirational region of North India

Introduction: Malaria is one of the major life-threatening health problems in most of the tropical countries. Children are the most vulnerable group accounting for 67% of all malaria-associated deaths worldwide. Southern Haryana is typically endemic for malaria. Therefore, the present study was undertaken to describe the clinical presentation of complicated malaria and correlate clinical complications with malarial species. Materials and Methods: It was an observational cross-sectional study conducted in the Department of Microbiology along with Department of Pediatrics, Shaheed Hasan Khan Mewati Government Medical College, Nalhar, Nuh, Haryana. A total of 100 children with severe malaria admitted in the pediatric ward, confirmed by peripheral blood smear and rapid diagnostic test, were included. Results: Out of 100 cases admitted, majority were due to Plasmodium vivax (73%), followed by mixed (18%) and Plasmodium falciparum (9%) infection. Children below 5 years were more infected (57%). Male preponderance was seen (55%). Fever was the most common symptom observed (95%). Pallor was the most common sign observed (85%). Among severity parameters, the most common were severe anemia (41%), jaundice (17%), abnormal bleeding (17%), convulsions (15%), and acute respiratory distress syndrome (7%). The case fatality rate was 3%. Conclusion: P. vivax was previously known to cause benign malaria. The present study found that P. vivax mono-infection can cause severe malaria in children and should no longer be considered as benign malaria.

Molecular surveillance of the Plasmodium vivax multidrug resistance 1 gene in Peru between 2006 and 2015

BackgroundThe high incidence of Plasmodium vivax infections associated with clinical severity and the emergence of chloroquine (CQ) resistance has posed a challenge to control efforts aimed at eliminating this disease. Despite conflicting evidence regarding the role of mutations of P. vivax multidrug resistance 1 gene (pvmdr1) in drug resistance, this gene can be a tool for molecular surveillance due to its variability and spatial patterns.MethodsBlood samples were collected from studies conducted between 2006 and 2015 in the Northern and Southern Amazon Basin and the North Coast of Peru. Thick and thin blood smears were prepared for malaria diagnosis by microscopy and PCR was performed for detection of P. vivax monoinfections. The pvmdr1 gene was subsequently sequenced and the genetic data was used for haplotype and diversity analysis.ResultsA total of 550 positive P. vivax samples were sequenced; 445 from the Northern Amazon Basin, 48 from the Southern Amazon Basin and 57 from the North Coast. Eight non-synonymous mutations and three synonymous mutations were analysed in 4,395 bp of pvmdr1. Amino acid changes at positions 976F and 1076L were detected in the Northern Amazon Basin (12.8%) and the Southern Amazon Basin (4.2%) with fluctuations in the prevalence of both mutations in the Northern Amazon Basin during the course of the study that seemed to correspond with a malaria control programme implemented in the region. A total of 13 pvmdr1 haplotypes with non-synonymous mutations were estimated in Peru and an overall nucleotide diversity of π = 0.00054. The Northern Amazon Basin was the most diverse region (π = 0.00055) followed by the Southern Amazon and the North Coast (π = 0.00035 and π = 0.00014, respectively).ConclusionThis study showed a high variability in the frequencies of the 976F and 1076L polymorphisms in the Northern Amazon Basin between 2006 and 2015. The low and heterogeneous diversity of pvmdr1 found in this study underscores the need for additional research that can elucidate the role of this gene on P. vivax drug resistance as well as in vitro and clinical data that can clarify the extend of CQ resistance in Peru.