Recurrent Malaria Research Articles

Recurrence patterns and evolution of submicroscopic and asymptomatic Plasmodium vivax infections in malaria-endemic areas of the Peruvian Amazon.

In the Peruvian Amazon, Plasmodium vivax malaria transmission is maintained due to the high frequency of recurrences. By understanding the recurrence rates of submicroscopic and asymptomatic cases, we can develop informed strategies to prevent transmission more efficiently and disrupt the silent transmission cycle. A three-year, population-based cohort study was conducted in two sites, Cahuide and Lupuna, within the Loreto region in Peru from 2013 to 2015. The study included 385 individuals and aimed to examine the temporal dynamics of malaria recurrences and their impact on transmission and control. Individuals from Lupuna presented a higher risk of P. vivax infections compared to Cahuide, where most recurrences were asymptomatic and submicroscopic. It is estimated that a great proportion of these recurrences were due to relapses in both communities. The application of molecular diagnostic method proved to be significantly more effective, detecting 2.3 times more episodes during the follow-up (PCR, 1068; microscopy, 467). PCR identified recurrences significantly earlier, at 151 days after an initial infection, compared to microscopy, which detected them on average after 365 days. Community, occupation and previous malaria infections were factors associated with recurrences. Finally, potential infection evolution scenarios were described where one frequent scenario involved the transition from symptomatic to asymptomatic infections with a mean evolution time of 240 days. This study explores the contrast in malaria recurrence risk among individuals from two endemic settings, a consequence of prolonged exposure to the parasite. Through the analysis of the evolution scenarios of P. vivax recurrences, it is possible to have a more complete vision of how the transmission pattern changes over time and is conditioned by different factors.

Elevated levels of PDGF-BB and VEGF are associated with a decreased risk of readmission or death in children with severe malarial anemia.

Children with severe malarial anemia (SMA) typically have low in-hospital mortality but have a high risk of post-discharge readmission or death. We hypothesized that the dysregulation of hematopoiesis, vascular growth factors, and endothelial function that occurs in SMA might affect risk of readmission or death. Plasma was obtained from children 18 months to 12 years old with SMA (N=145) in Kampala, Uganda on admission, and outcomes were assessed over 12-month follow-up. Admission plasma levels of ten biomarkers of vascular growth, hematopoiesis, and endothelial function were compared to risk of readmission or death over 12-month follow-up. Over 12-month follow-up, 19 of 145 children with SMA were either readmitted or died: 15 children were readmitted (13 with malaria) and 4 children died. In multivariable analyses adjusted for age and sex, elevated plasma levels of platelet-derived growth factor-BB (PDGF-BB) and vascular endothelial growth factor (VEGF) on admission were independently associated with a decreased risk of all-cause readmission or death (adjusted hazard ratios [95% confidence intervals], 0.28 [0.16-0.51] and 0.19 [0.08-0.48], respectively) and a decreased risk of readmission due to severe malaria (0.27 [0.15, 0.51] and 0.16 [0.05, 0.47]) but not with risk of uncomplicated malaria (1.01 [0.53, 1.95] and 2.07 [0.93-4.64]). In children with severe malarial anemia, elevated plasma levels of PDGF-BB and VEGF, two factors that promote angiogenesis, are associated with a decreased risk of readmission or death in the year following admission, primarily driven by a decrease in the risk of recurrent severe malaria.

Therapeutic efficacy of artemether–lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Arba Minch Zuria District, Gamo Zone, Southwest Ethiopia

BackgroundArtemether–lumefantrine (AL) has been the primary anti-malarial drug used to treat uncomplicated Plasmodium falciparum malaria in Ethiopia since 2004. However, there have been recent reports of AL resistance mutations in different African countries, including Ethiopia. This is concerning and requires periodic monitoring of anti-malarial drug resistance. Therefore, the current study aimed to evaluate the therapeutic efficacy of AL in treating uncomplicated P. falciparum malaria in the Arba Minch Zuria District, Gamo Zone, Southwest Ethiopia.MethodsA single-arm prospective study with a 28-day follow-up period was conducted from July to October 2022. Capillary blood samples were collected for RDT and microscopic examination. The study enrolled monoinfected P. falciparum patients aged ≥ 18 years at Ganta Sira Health Post. Sociodemographic and clinical data were recorded, and a dried blood spot (DBS) was prepared for each participant. Nested polymerase chain reaction (nPCR) genotyping of the msp-1 and msp-2 genes was only performed for recurrent cases to distinguish between recurrence and reinfection. Data entry and analysis were performed using the WHO Excel spreadsheet and SPSS version 26.ResultsA total of 89 patients were enrolled, and 67 adequately completed the 28-day follow-up period. AL showed a 100% clearance rate for fever on day 2 and asexual parasites on day 3. Gametocytes were detected in 13.5% (12/89) of the participants. The gametocyte clearance rate was 58.3% (7/12) until day 7 and 100% (12/12) until day 14. Five participants developed recurrent malaria, three of whom experienced relapse and two of whom experienced reinfection. Based on the Kaplan–Meier survival analysis, the PCR-uncorrected and PCR-corrected cumulative incidence of success were 93.7% (95% CI 85.5–97.3) and 96.2% (95% CI 85.5–98.7), respectively.ConclusionAL was efficacious in treating uncomplicated P. falciparum malaria in the study area. However, the detection of recurrent patients highlights the need for continuous efficacy studies in this area.

Anaphylactic Reaction to Penicillin in Malaria-Infected Patients: A Case Study and Implications for Clinical Management

Malaria remains a significant global health challenge, often necessitating a combination of antimalarial and antibiotic treatments to manage both the primary infection and secondary bacterial complications. This review focuses on a critical case study involving a 35-year-old male with recurrent malaria who experienced a severe anaphylactic reaction to penicillin, highlighting the complex interplay between malaria management and drug allergies. The patient, already compromised by malaria, developed anaphylaxis shortly after receiving penicillin for a suspected bacterial infection. Despite immediate treatment, including epinephrine, antihistamines, and corticosteroids, the patient’s condition worsened due to the exacerbation of symptoms of malaria, leading to a fatal outcome. This case underscores the diagnostic and management challenges of drug allergies in malaria-infected patients, emphasizing the need for improved allergy assessment protocols, better training for healthcare providers, and enhanced patient education. The review advocates for the development of comprehensive allergy management strategies, improved allergy history documentation, and ongoing research to refine drug allergy testing and treatment protocols. Effective management of drug allergies, particularly in complex infection scenarios, is essential for optimizing patient safety and treatment efficacy. Keywords: Anaphylaxis, Penicillin Allergy, Malaria, Drug Reactions, Allergy Management, Clinical Protocols.

Assessing receptivity to malaria using case surveillance and forest data in a near-elimination setting in northeast Thailand

BackgroundThailand aimed to eliminate malaria by 2024, and as such is planning for future prevention of re-establishment in malaria free provinces. Understanding the receptivity of local areas to malaria allows the appropriate targeting of interventions. Current approaches to assessing receptivity involve collecting entomological data. Forest coverage is known to be associated with malaria risk, as an environment conducive to both vector breeding and high-risk human behaviours.MethodsGeolocated, anonymized, individual-level surveillance data from 2011 to 2021 from the Thai Division of Vector-Borne Disease (DVBD) was used to calculate incidence and estimated Rc at village level. Forest cover was calculated using raster maps of tree crown cover density and year of forest loss from the publicly available Hansen dataset. Incidence and forest cover were compared graphically and using Spearman’s rho. The current foci classification system was applied to data from the last 5 years (2017–2021) and forest cover for 2021 compared between the classifications. A simple risk score was developed to identify villages with high receptivity.ResultsThere was a non-linear decrease in annual cases by 96.6% (1061 to 36) across the two provinces from 2011 to 2021. Indigenous Annual Parasite Index (API) and approximated Rc were higher in villages in highly forested subdistricts, and with higher forest cover within 5 km. Forest cover was also higher in malaria foci which consistently reported malaria cases each year than those which did not. An Rc > 1 was only reported in villages in subdistricts with > 25% forest cover. When applying a simple risk score using forest cover and recent case history, the classifications were comparable to those of the risk stratification system currently used by the DVBD.ConclusionsThere was a positive association between forest coverage around a village and indigenous malaria cases. Most local transmission was observed in the heavily forested subdistricts on the international borders with Laos and Cambodia, which are where the most receptive villages are located. These areas are at greater risk of importation of malaria due to population mobility and forest-going activities. Combining forest cover and recent case surveillance data with measures of vulnerability may be useful for prediction of malaria recurrence risk.

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.

Causal effect of severe and non-severe malaria on dyslipidemia in African Ancestry individuals: A Mendelian randomization study.

Dyslipidemia is becoming prevalent in Africa, where malaria is endemic. Observational studies have documented the long-term protective effect of malaria on dyslipidemia; however, these study designs are prone to confounding. Therefore, we used Mendelian randomization (MR, a method robust to confounders and reverse causation) to determine the causal effect of severe malaria (SM) and the recurrence of non-severe malaria (RNM) on lipid traits. We performed two-sample MR using genome wide association study (GWAS) summary statistics for recurrent non-severe malaria (RNM) from a Benin cohort (N=775) and severe malaria from the MalariaGEN dataset (N=17,000) and lipid traits from summary-level data of a meta-analyzed African lipid GWAS (MALG, N=24,215) from the African Partnership for Chronic Disease Research (APCDR) (N=13,612) and the Africa Wits-IN-DEPTH partnership for genomics studies (AWI-Gen) dataset (N=10,603). No evidence of significant causal association was obtained between RNM and high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol and triglycerides. However, a notable association emerged between severe malarial anaemia (SMA) which is a subtype of severe malaria and reduced HDL-C levels, suggesting a potential subtype-specific effect. Nonetheless, we strongly believe that the small sample size likely affects our estimates, warranting cautious interpretation of these results. Our findings challenge the hypothesis of a broad causal relationship between malaria (both severe and recurrent non-severe forms) and dyslipidemia. The isolated association with SMA highlights an intriguing area for future research. However, we believe that conducting larger studies to investigate the connection between malaria and dyslipidemia in Africa will enhance our ability to better address the burden posed by both diseases.

Diagnostic challenges of recurrent malaria in non-endemic areas†.

In Spain, a patient’s unexpected relapse with Plasmodium falciparum raises questions about genetic influences on treatment efficacy. Meanwhile, in a separate case, a recurrence of Plasmodium malariae prompts speculation on latent reservoirs and treatment strategies. Here, we delve into these complex cases that underscore the evolving landscape of malaria.

Operational effectiveness of tafenoquine and primaquine for the prevention of Plasmodium vivax recurrence in Brazil: a retrospective observational study

Prevention of Plasmodium vivax malaria recurrence is essential for malaria elimination in Brazil. We evaluated the real-world effectiveness of an updated treatment algorithm for P vivax radical cure in the Brazilian Amazon. In this non-interventional observational study, we used retrospective data from the implementation of a P vivax treatment algorithm at 43 health facilities in Manaus and Porto Velho, Brazil. The treatment algorithm consisted of chloroquine (25 mg/kg over 3 days) and point-of-care quantitative glucose-6-phosphate dehydrogenase (G6PD) testing followed by single-dose tafenoquine 300 mg (G6PD normal, aged ≥16 years, not pregnant and not breastfeeding), 7-day primaquine 0·5 mg/kg per day (G6PD intermediate or normal, aged ≥6 months, not pregnant, and not breastfeeding or breastfeeding for >1 month), or primaquine 0·75 mg/kg per week for 8 weeks (G6PD deficient, aged ≥6 months, not pregnant, and not breastfeeding or breastfeeding for >1 month). P vivax recurrences were identified from probabilistic linkage of routine patient records from the Brazilian malaria epidemiological surveillance system. Recurrence-free effectiveness at day 90 and day 180 was estimated using Kaplan-Meier analysis and hazard ratios (HRs) by multivariate analysis. This clinical trial is registered with ClinicalTrials.gov, NCT05096702, and is completed. Records from Sept 9, 2021, to Aug 31, 2022, included 5554 patients with P vivax malaria. In all treated patients of any age and any G6PD status, recurrence-free effectiveness at day 180 was 75·8% (95% CI 74·0-77·6) with tafenoquine, 73·4% (71·9-75·0) with 7-day primaquine, and 82·1% (77·7-86·8) with weekly primaquine. In patients aged at least 16 years who were G6PD normal, recurrence-free effectiveness until day 90 was 88·6% (95% CI 87·2-89·9) in those who were treated with tafenoquine (n=2134) and 83·5% (79·8-87·4) in those treated with 7-day primaquine (n=370); after adjustment for confounding factors, the HR for recurrence following tafenoquine versus 7-day primaquine was 0·65 (95% CI 0·49-0·86; p=0·0031), with similar outcomes between the two treatments at day 180 (log-rank p=0·82). Over 180 days, median time to recurrence in patients aged at least 16 years who were G6PD normal was 92 days (IQR 76-120) in those treated with tafenoquine and 68 days (52-94) in those treated with 7-day primaquine. In this real-world setting, single-dose tafenoquine was more effective at preventing P vivax recurrence in patients aged at least 16 years who were G6PD normal compared with 7-day primaquine at day 90, while overall efficacy at 180 days was similar. The public health benefits of the P vivax radical cure treatment algorithm incorporating G6PD quantitative testing and tafenoquine support its implementation in Brazil and potentially across South America. Brazilian Ministry of Health, Municipal and State Health Secretariats; Fiocruz; Medicines for Malaria Venture; Bill & Melinda Gates Foundation; Newcrest Mining; and the UK Government. For the Portuguese translation of the abstract see Supplementary Materials section.

Current Trends in Nanotechnology-based Drug Delivery Systems for the Diagnosis and Treatment of Malaria: A Review.

Malaria is still a major endemic disease transmitted in humans via Plasmodium-infected mosquitoes. The eradication of malarial parasites and the control measures have been rigorously and extensively deployed by local and international health organizations. Malaria's recurrence is a result of the failure to entirely eradicate it. The drawbacks related to malarial chemotherapy, non-specific targeting, multiple drug resistance, requirement of high doses, intolerable toxicity, indefinable complexity of Plasmodium's life cycle, and advent of drug-resistant strains of P. falciparum are the causes of the ineffective eradication measures. With the emergence of nanotechnology and its application in various industrial domains, the rising interest in the medical field, especially in epidemiology, has skyrocketed. The applications of nanosized carriers have sparked special attention, aiming towards minimizing the overall side effects caused due to drug therapy and avoiding bioavailability. The applications of concepts of nanobiotechnology to both vector control and patient therapy can also be one of the approaches. The current study focuses on the use of hybrid drugs as next-generation antimalarial drugs because they involve fewer drug adverse effects. The paper encompasses the numerous nanosized delivery-based systems that have been found to be effective among higher animal models, especially in treating malarial prophylaxis. This paper delivers a detailed review of diagnostic techniques, various nanotechnology approaches, the application of nanocarriers, and the underlying mechanisms for the management of malaria, thereby providing insights and the direction in which the current trends are imparted from the innovative and technological perspective.

Gene expression levels and inhibitory effect of 7-[(7-methoxy-4,5-dihydro-1H-benzo[g]indazol-3-yl)carbonyl]-2-phenyl-5,6,7,8-tetrahydropyrazolo[1,5-a]pyrido[4,3-d]Pyrimidin-9(1H)-one (MCL) against AP2-I and BDP1 in malaria experimental models

Resistance to antimalarial drugs leads a global recurrence of malaria, posing a significant challenge to malaria control. This study aimed to assess gene expression and resistance profiles in clinical isolates, and validate the inhibitory effect of MCL compound against PbAP2-I and PbBDP1 genes in vivo. Malaria prevalence rate throughout the clinical study period stood at 12.24%. Blood samples were obtained from 182 malaria outpatients and 30 P. berghei-infected mice treated with varying MCL concentrations. DNA and RNA were extracted. PfAP2-I, PfBDP1, PfMDR1, and PfK13 genes were amplified using Real-time qPCR and sequenced for mutation profiling. Relative gene expression of AP2-I and BDP1 genes in P. falciparum and P. berghei-treated mice was carried out by Reverse-transcription PCR. The data were analyzed using ANOVA at P<0.05 indicating a significant difference. Relative gene expression results from clinical isolates showed PfAP2-I and PfBDP1 are highly expressed in the trophozoite and schizont stages. The clinical isolates show conserved nucleotide sequences for PfAP2-I, PfBDP1, and PfK13 genes compared to the 3D7 strain. However, Asn86Tyr mutation implicated in antimalarial drug resistance and Leu1312Iso mutation not previously reported to be associated with antimalarial drug resistance were observed for the PfMDR1 gene. MCL inhibited the expression of PbAP2-I (by 4.52 and 8.08 folds) and PbBDP1 (by 37.92 and 79.07 folds) at 40µM and 50µM concentrations after a 7-day, single oral daily dose. Our findings validate MCL's inhibitory activity against AP2-I and BDP1 genes, hence representing potential new targets of antimalarial therapy for controlling malaria parasite invasion.

Impact of host stress on the replication rate of Plasmodium: take it easy to avoid malaria recurrences

Malaria is widespread throughout the world and affects many animal species. Although the origin of this vector-borne disease was discovered more than a century ago, several aspects of the within-host infection dynamic are still poorly understood. Among them, the factors triggering parasite recurrences – episodes of brief increase in parasite number following a period when the parasite was either absent or present at very low levels in the blood – have still not been clearly identified. Yet, recurrences may contribute significantly to overall infection prevalence in vertebrate host populations. Here, we investigated whether artificial or natural increases in stress hormone levels in chronically infected birds influence the replication rate of Plasmodium relictum and transmission to its natural vector, the mosquito Culex pipiens. Our results provide evidence that increased levels of corticosterone, either induced by oral ingestion or caused by handling stress, can trigger malaria recurrences. However, we did not observe any effect on the transmission rate of the parasite to the mosquito vector. Our study is a first fundamental step in understanding the mechanisms underlying malaria recurrences. It remains to be ascertained whether this feature extends to other malaria system and in particular to human malaria.

Adherence to 14-day radical cure for Plasmodium vivax malaria in Papua, Indonesia: a mixed-methods study

BackgroundReducing the risk of recurrent Plasmodium vivax malaria is critical for malaria control and elimination. Primaquine (PQ) is the only widely available drug against P. vivax dormant liver stages, but is recommended as a 14-day regimen, which can undermine adherence to a complete course of treatment.MethodsThis is a mixed-methods study to assess socio-cultural factors influencing adherence to a 14-day PQ regimen in a 3-arm, treatment effectiveness trial in Papua, Indonesia. The qualitative strand, consisting of interviews and participant observation was triangulated with a quantitative strand in which trial participants were surveyed using a questionnaire.ResultsTrial participants differentiated between two types of malaria: tersiana and tropika, equivalent to P. vivax and Plasmodium falciparum infection, respectively. The perceived severity of both types was similar with 44.0% (267/607) perceiving tersiana vs. 45.1% (274/607) perceiving tropika as more severe. There was no perceived differentiation whether malaria episodes were due to a new infection or relapse; and 71.3% (433/607) acknowledged the possibility of recurrence. Participants were familiar with malaria symptoms and delaying health facility visit by 1–2 days was perceived to increase the likelihood of a positive test. Prior to health facility visits, symptoms were treated with leftover drugs kept at home (40.4%; 245/607) or bought over the counter (17.0%; 103/607). Malaria was considered to be cured with ‘blue drugs’ (referring to dihydroartemisinin-piperaquine). Conversely, ‘brown drugs,’ referring to PQ, were not considered malaria medication and instead were perceived as supplements. Adherence to malaria treatment was 71.2% (131/184), in the supervised arm, 56.9% (91/160) in the unsupervised arm and 62.4% (164/263) in the control arm; p = 0.019. Adherence was 47.5% (47/99) among highland Papuans, 51.7% (76/147) among lowland Papuans, and 72.9% (263/361) among non-Papuans; p < 0.001.ConclusionAdherence to malaria treatment was a socio-culturally embedded process during which patients (re-)evaluated the characteristics of the medicines in relation to the course of the illness, their past experiences with illness, and the perceived benefits of the treatment. Structural barriers that hinder the process of patient adherence are crucial to consider in the development and rollout of effective malaria treatment policies.

Prevalence of mutations in the cysteine desulfurase IscS (Pfnfs1) gene in recurrent Plasmodium falciparum infections following artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) treatment in Matayos, Western Kenya

BackgroundMalaria remains a public health concern globally. Resistance to anti-malarial drugs has consistently threatened the gains in controlling the malaria parasites. Currently, artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) are the treatment regimens against Plasmodium falciparum infections in many African countries, including Kenya. Recurrent infections have been reported in patients treated with AL or DP, suggesting the possibility of reinfection or parasite recrudescence associated with the development of resistance against the two therapies. The Plasmodium falciparum cysteine desulfurase IscS (Pfnfs1) K65 selection marker has previously been associated with decreased lumefantrine susceptibility. This study evaluated the frequency of the Pfnfs1 K65 resistance marker and associated K65Q resistant allele in recurrent infections collected from P. falciparum-infected individuals living in Matayos, Busia County, in western Kenya.MethodsArchived dried blood spots (DBS) of patients with recurrent malaria infection on clinical follow-up days after treatment with either AL or DP were used in the study. After extraction of genomic DNA, PCR amplification and sequencing analysis were employed to determine the frequencies of the Pfnfs1 K65 resistance marker and K65Q mutant allele in the recurrent infections. Plasmodium falciparum msp1 and P. falciparum msp2 genetic markers were used to distinguish recrudescent infections from new infections.ResultsThe K65 wild-type allele was detected at a frequency of 41% while the K65Q mutant allele was detected at a frequency of 22% in the recurrent samples. 58% of the samples containing the K65 wild-type allele were AL treated samples and while 42% were DP treated samples. 79% of the samples with the K65Q mutation were AL treated samples and 21% were DP treated samples. The K65 wild-type allele was detected in three recrudescent infections (100%) identified from the AL treated samples. The K65 wild-type allele was detected in two recrudescent DP treated samples (67%) while the K65Q mutant allele was identified in one DP treated (33%) recrudescent sample.ConclusionsThe data demonstrate a higher frequency of the K65 resistance marker in patients with recurrent infection during the study period. The study underscores the need for consistent monitoring of molecular markers of resistance in regions of high malaria transmission.

Efficiency and economic analysis of intervention strategies for recurrent malaria transmission

Efficiency and economic analysis of intervention strategies for recurrent malaria transmission

Renal and hepatic dysfunction parameters correlate positively with gender among patients with recurrent malaria cases in Birnin Kebbi, Northwest Nigeria

BackgroundSimultaneous increase in transaminases and bilirubin is an indicator of hepatic dysfunction in malaria. Malaria-induced hyperbilirubinemia has been associated with acute kidney injury and pathogenesis of cerebral malaria which are significantly associated with mortality in malaria infection. This retrospective study was designed to assess the lipid profile, and hematological, renal and hepatic function data of malaria patients in Sir Yahaya Memorial hospital Birnin Kebbi from 2016 to 2020 who are 18 years and above.MethodsThe data of all patients between 2016 and 2020 who are 18 years and above were collected. Complete data of 370 subjects who met the inclusion criteria which consist of 250 malaria subjects and 120 control subjects were analyzed.ResultsThe results showed that females constitute 65.2% of malaria patients with complete records while the remaining 34.8% were males. Age distribution of the patients showed that the infection was more prevalent among 26–45 years and least among 65 years and above. Anemia and thrombocytopenia were prevalent among the female malaria patients compared to the male patients. Liver and kidney function parameters analyzed correlate positively with the gender. The infected male showed higher dysfunction in liver parameters while infected female patients showed significant dysfunction in kidney function parameters and lipid profile.ConclusionsIn conclusion, to prevent the potential widespread of acute renal and hepatic failure with the attendant morbidity and mortality among malaria patients, it is recommended that liver and kidney function tests be mandated for patients with recurring malaria and those with a history of treatment failure in the endemic area to ensure early diagnosis of malarial induced kidney and liver injury among malaria patients.

International Research and Philanthropy

International Research and Philanthropy

Association between CYP2D6 phenotype and recurrence of Plasmodium vivax infection in south Korean patients

BackgroundPrimaquine is activated by CYP2D6 in the hepatocytes. In Korea, primaquine is the only hypnozoitocidal agent used for patients with vivax malaria. Thus, patients with poor CYP2D6 activity could have an increased risk of primaquine failure and subsequent relapse. The study sought to identify the association between CYP2D6 phenotype and recurrence of malaria in Korean patients.MethodsA total of 102 patients with vivax malaria were prospectively enrolled from eight institutions in Korea. An additional 38 blood samples from patients with recurred vivax malaria were provided by the Korea Disease Control and Prevention Agency. Malaria recurrence was defined as more than one episode of vivax malaria in the same or consecutive years. CYP2D6 star alleles, phenotypes, and activity scores were examined.ResultsGenotyping for CYP2D6 was successful in 101 of the prospectively enrolled patients and 38 samples from the Korea Disease Control and Prevention Agency, of which 91 were included in the no-recurrence group and 48 were included in the recurrence group. Reduced CYP2D6 activity (intermediate metabolizer) phenotype was more common in the recurrence group than in the no-recurrence group (OR, 2.33 (95% CI, 1.14–4.77); p = 0.02). Patients with lower CYP2D6 activity had a higher probability of recurrence (p = 0.029).ConclusionThis study suggests that CYP2D6 polymorphism may affect primaquine efficacy and thus Plasmodium vivax recurrence in Korea.

Analysis of Recurrent Times-to-Clinical Malaria Episodes and Plasmodium falciparum Parasitemia: A Joint Modeling Approach Applied to a Cohort Data.

Recurrent clinical malaria episodes due to Plasmodium falciparum parasite infection are common in endemic regions. With each infection, acquired immunity develops, making subsequent disease episodes less likely. To capture the effect of acquired immunity to malaria, it may be necessary to model recurrent clinical disease episodes jointly with P. falciparum parasitemia data. A joint model of longitudinal parasitemia and time-to-first clinical malaria episode (single-event joint model) may be inaccurate because acquired immunity is lost when subsequent episodes are excluded. This study's informativeness assessed whether joint modeling of recurrent clinical malaria episodes and parasitemia is more accurate than a single-event joint model where the subsequent episodes are ignored. The single event joint model comprised Cox Proportional Hazards (PH) sub-model for time-to-first clinical malaria episode and Negative Binomial (NB) mixed-effects sub-model for the longitudinal parasitemia. The recurrent events joint model extends the survival sub-model to a Gamma shared frailty model to include all recurrent clinical episodes. The models were applied to cohort data from Malawi. Simulations were also conducted to assess the performance of the model under different conditions. The recurrent events joint model, which yielded higher hazard ratios of clinical malaria, was more precise and in most cases produced smaller standard errors than the single-event joint model; hazard ratio (HR) = 1.42, [95% confidence interval [CI]: 1.22, 2.03] vs. HR = 1.29, [95% CI:1.60, 2.45] among participants who reported not to use LLINs every night compared to those who used the nets every night; HR = 0.96, [ 95% CI: 0.94, 0.98] vs. HR = 0.81, [95% CI: 0.75, 0.88] for each 1-year increase in participants' age; and HR = 1.36, [95% CI: 1.05, 1.75] vs. HR = 1.10, [95% CI: 0.83, 4.11] for observations during the rainy season compared to the dry season. The recurrent events joint model in this study provides a way of estimating the risk of recurrent clinical malaria in a cohort where the effect of immunity on malaria disease acquired due to P. falciparum parasitemia with aging is captured. The simulation study has shown that if correctly specified, the recurrent events joint model can give risk estimates with low bias.

Factors influencing severity of recurrent malaria in a conflict-affected state of South Sudan: an unmatched case-control study

BackgroundThe burden of malaria remains the highest in sub-Saharan Africa and South Sudan is not an exception. The country has borne the brunt of years of chronic warfare and remains endemic of malaria, with increasing mortality and morbidity. Limited data still exists on factors influencing the recurrence of severe malaria, especially in emergency contexts such as South Sudan, affected by various conflicts and humanitarian situations. This study therefore aimed to investigate factors influencing severity of occurrence malaria in selected primary healthcare centres in South Sudan. This would assist and guide in malaria prevention, treatment, and eradication efforts.MethodsWe conducted an unmatched case-control study using routinely collected clinic data for individuals aged 1 year and above who received a diagnosis of severe malaria at 3 primary healthcare centres (PHCC); Malual Bab PHCC, Matangai PHCC and Malek PHCC between September 15, 2019 to December 15, 2019 in South Sudan. Patient characteristics were analyzed using simple descriptive statistics. Inferential statistics were also conducted to identify the associated factors influencing recurrence of severe malaria. All analyses were conducted using R Version 3.6.2.ResultsA total of 289 recurrent malaria cases were included in this study. More than half of the participants were female. Overall, the prevalence of severe recurrent malaria was 66.1% (191) while 74.4% (215) did not complete malaria treatment. Among those who did not complete malaria treatment, 76.7% (165) had severe recurrent malaria, while among those who completed malaria treatment 35.1% (26) had severe recurrent malaria (p < 0.001). There is a significant association between marital status (OR 0.33, 95% CI 0.19–0.56, p < 0.001), employment status (OR 0.35, 95% CI 0.14–0.87, p = 0.024), the use of preventive measures (OR 3.82, 95% CI 1.81–8.43, p < 0.001) and nutrition status (OR 0.22, 95% CI 0.13–0.37, p < 0.001). When adjusted for employment, marital status, nutritional and prevention measures in turns using Mantel–Haenszel test of association, this effect remained statistically significant.ConclusionsOur study showed that there is a high prevalence of severe recurrent malaria in South Sudan and that a significant relationship exists between severe recurrent malaria and antimalarial treatment dosage completion influenced by certain personal and social factors such as marital status, employment status, the use of preventive measures and nutrition status. Findings from our study would be useful for effective response to control and prevent malaria in endemic areas of South Sudan.