Malaria-endemic Regions Research Articles

The Impact of Mobile Health (mHealth) Interventions on Malaria Diagnosis and Treatment Adherence among Pregnant Women: A Comprehensive Review

Malaria in pregnancy (MiP) poses a significant public health threat, particularly in sub-Saharan Africa, contributing to maternal anemia, preterm birth, low birth weight, and maternal and infant mortality. Early diagnosis and strict adherence to antimalarial treatments are essential to reduce these risks, yet access to timely care and consistent treatment adherence remain major challenges. Mobile health (mHealth) interventions, utilizing mobile technologies such as SMS reminders, diagnostic applications, and telemedicine platforms, have emerged as innovative tools to address these barriers. This comprehensive review examined the impact of mHealth interventions on malaria diagnosis and treatment adherence among pregnant women in malaria-endemic regions. Through case studies from Kenya, Nigeria, and Tanzania, we explore the effectiveness of mHealth solutions in improving maternal health outcomes by ensuring timely diagnosis and promoting adherence to treatment. Methodologically, the review drew on empirical studies, program evaluations, and case reports from peer-reviewed literature. Despite promising outcomes, challenges such as technological barriers, cultural resistance, and scalability concerns persist. Future research should focus on integrating emerging technologies like AI and machine learning to enhance mHealth’s effectiveness while prioritizing equitable access to digital health solutions. Policymakers must also prioritize the integration of mHealth into national health systems to ensure long-term sustainability. Keywords: mHealth interventions, Malaria in pregnancy (MiP), Treatment adherence, Malaria diagnosis, Sub-Saharan Africa

An Expression Quantitative Trait Locus of Fc Gamma Receptor Genes is Associated with Anti-Malarial IgG Responses and Infection Levels in Burkinabe Families.

The interaction between antibodies and Fc gamma receptors (FcγRs) plays a critical role in regulating immune responses to Plasmodium falciparum. Polymorphisms in genes encoding FcγRs influence the host's capacity to control parasite infection. This study investigates whether non-coding variants influencing FcγR expression are associated with anti-malarial immunization and infection traits. We utilized eQTL databases and functional annotations to identify non-coding variants, specifically rs1771575, rs2099684, and rs6700241, within the FCGR gene cluster. In addition, we examined the coding variants rs1801274 (p.His167Arg) and rs1050501 (p.Ile231Thr), which affect the affinity of FcγRIIa and FcγRIIb for IgG. These variants were genotyped in 163 individuals from Burkinabe families. Family-based linear mixed regression and Quantitative Transmission Disequilibrium Tests (QTDT) analyses were performed to assess associations with IgG levels and malaria infection, accounting for relevant covariates. Linear mixed models identified rs1771575 as associated with total IgG levels, while both rs1771575 and rs1801274 were linked to IgG2, and rs1050501 to IgG1 levels. A haplotype combining rs2099684 and rs6700241 was positively associated with IgG1. The rs1771575-CC and rs1050501-TT genotypes correlated with higher infection levels in children. QTDT models confirmed the association of rs1771575 with IgG2 and infection in children. Our findings suggest that the intergenic variant rs1771575 serves as an independent marker for IgG levels and blood infection in children. This highlights the interplay between regulatory variants and coding mutations in FCGR, which may influence immune function and antibody production. These results underscore the potential for personalized strategies to monitor humoral responses in malaria-endemic regions.

Presence of Plasmodium falciparum strains with artemisinin-resistant K13 mutation C469Y in Busia County, Western Kenya

Malaria remains a key health and economic problem, particularly in sub-Saharan Africa. The emergence of artemisinin drug resistance (ART-R) parasite strains poses a serious threat to the control and elimination of this scourge. This is because artemisinin-based combination therapies (ACTs) remain the first-line treatment in the majority of malaria-endemic regions in Sub-Saharan Africa. Certain single-nucleotide polymorphisms in the propeller domains of Plasmodium falciparum Kelch 13 protein (K13) have been associated with delayed parasite clearance in vivo and in vitro. These mutations serve as vital molecular markers for tracking the emergence and dispersion of resistance. Recently, there have been increasing reports of the emergence and spread of P. falciparum ART-R parasites in the Eastern Africa region. This necessitates continued surveillance to best inform mitigation efforts. This study investigated the presence of all reported mutations of K13 propeller domains in the parasite population in Busia County, Kenya, a known malaria-endemic region. Two hundred twenty-six participants with microscopically confirmed uncomplicated malaria were recruited for this study. They were treated with artemether–lumefantrine under observation for the first dose, and microscopic examination was repeated 1 day later after ensuring the participants had taken the second and third doses. P. falciparum DNA from all samples underwent targeted amplification of the K13 gene using a semi-nested PCR approach, followed by Sanger sequencing. The recently validated ART-R K13 mutation C469Y was identified in three samples. These three samples were among 63 samples with a low reduction in parasitemia on day 1, suggesting day 1 parasitemia reduction rate is a useful parameter to enrich the ART-R parasites for further analysis. Our findings highlight the need for continuous surveillance of ART-R in western Kenya and the region to determine the spread of ART-R and inform containment.

Dear Malaria: Deer Have Malaria! Prevalence ofPlasmodium odocoilei Infection in White-tailed deer in Pennsylvania

Abstract Background To combat antimalarial treatment resistance, better understanding of malaria pathogenesis is needed, but existing animal model have various limitations. Notably, prevailing murine models require laboratory infection of non-natural host species. In 2016, the parasite Plasmodium odocoilei was identified in white-tailed deer (Odocoileus virginianus). This was the first non-human mammalian malaria parasite identified in North America, representing a novel naturally occurring model system that allows for integrated examination of host, vector, and systems parasite biology. In addition, sickle hemoglobinopathy is exceptionally common among white-tailed deer, occurring in up to 60% of apparently healthy animals. In humans, the prevalence of sickle hemoglobinopathy in individuals with ancestry from malaria-endemic regions is due to the protective effects of sickle trait against severe malaria. Thus, the white-tailed deer-P. odocoilei system represents the only known naturally occurring model of the association between malaria parasite biology and sickle cell disease. Pennsylvania white-tailed deer have not previously been surveyed for infection. In this study, we determined P. odocoilei prevalence in a sample of 170 Pennsylvania white-tailed deer. Methods We amplified the CytB gene of P. odocoilei by nested PCR from DNA extracted from homogenized white-tailed deer tongue tissue obtained from the PennVet Wildlife Futures Program. We confirmed samples screening positive on gel electrophoresis via unprimed sequencing (Plasmidsaurus, USA) and NCBI-BLAST analysis. Results We estimate the prevalence of P. odocoilei infection in Pennsylvania white-tailed deer to be 0.6% (1 of 170 samples). Sequencing of the positive sample revealed a 621-bp sequence with close sequence identity to previous North American isolates of P. odocoilei (query cover 91-100%, percent identity 99.34-100.00%). Biobank metadata showed the positive sample originated from a roadkilled yearling male picked up at GPS coordinates (40.8423, -79.0409) on August 15, 2022. Conclusion P. odocoilei is endemic to Pennsylvania white-tailed deer. Our future directions include screening of additional samples, determination of host hemoglobin allele frequencies, detailed parasite genetic studies, and entomologic studies to elucidate vector biology. In addition, granular sample metadata collected by the PennVet Wildlife Futures Program will allow us to analyze the effects of geographic, demographic, and temporal variables on epidemiology. In sum, our survey data empowers future Pennsylvania-based studies to take advantage of the only known naturally occurring animal model of sickling and its association with protozoan infection.

Differences in seasonal dynamics and pyrethroid resistance development among Anopheles Hyrcanus group species

BackgroundThe Anopheles Hyrcanus group, which transmits Plasmodium vivax, consists of six confirmed species in South Korea. An epidemiological study revealed differences in the seasonal occurrence patterns of each species. Pyrethroid resistance in An. sinensis dates back to the early 2000s, whereas information on pyrethroid resistance in other species is lacking despite their greater significance in malaria epidemiology.MethodsAnopheles mosquitoes were collected from two malaria-endemic regions in South Korea for 2 years and their knockdown resistance (kdr) mutations were genotyped. The larval susceptibility to λ-cyhalothrin was compared in six Anopheles species and its seasonal changes in three species were investigated. The full-length sequences of the voltage-sensitive sodium channel (VSSC) were compared across six species to evaluate potential target-site insensitivity. The contribution of the kdr mutation to phenotypic resistance was confirmed by comparing median lethal time (LT50) to λ-cyhalothrin between populations of Anopheles belenrae with distinct genotypes.ResultsThe composition and seasonal occurrence of rare species (Anopheles kleini, Anopheles lestri, and Anopheles sineroides) varied considerably, whereas An. sinensis occurs continuously throughout the season. A kdr mutation in the form of heterozygous allele was newly identified in An. belenrae, An. lesteri, An. pullus, and An. sineroides. The baseline susceptibility to λ-cyhalothrin was the highest in An. belenrae, followed by An. lesteri, An. sineroides, An. kleini, An. pullus, and An. sinensis, with median lethal concentration (LC50) values ranging from 6.0- to 73.5-fold higher than that of An. belenrae. The susceptibility of An. sinensis and An. pullus varied by season, whereas that of An. belenrae remained stable. The kdr-heterozygous An. belenare population exhibited 5.1 times higher LT50 than that of the susceptible population. Species-specific VSSC sequence differences were observed among the six species.ConclusionsOur findings suggest that the status and extent of pyrethroid resistance vary among Anopheles Hyrcanus group species. While An. sinensis, the predominant species, developed a considerable level of pyrethroid resistance through kdr mutation, the resistance levels of other species appeared to be less pronounced. Large-scale monitoring is crucial to fully understand species-specific seasonal occurrence and resistance status for effective management strategies, considering the ongoing impact of climate change on their vectorial capacity.Graphical

Frequency of chloroquine-resistant haplotype of Plasmodium falciparum (CVIET) in Ibadan, Southwest Nigeria 17 years post-chloroquine withdrawal

The replacement of chloroquine with artemisinin-based combination therapies (ACTs) for over a decade has had varying impacts on the ability of the malaria parasite to sustain its chloroquine resistance prowess in different malaria-endemic regions. We evaluated the frequency of Plasmodium falciparum chloroquine resistance transporter (PfCRT) mutations in Ibadan, Nigeria 17 years after the replacement of chloroquine with ACTs for malaria treatment. Fragments of PfCRT gene from genomic DNA of microscopically confirmed P. falciparum-infected patients were amplified and sequenced. There were 19% CVIET mutant and 81% CVMNK wild-type haplotypes on residues 72–76. A220S change were found in 16.7% of samples occurring concurrently with the CVIET haplotype, while a Q271E mutation occurred in a PfCRT wild-type isolate. The reduced prevalence of the PfCRT mutant alleles in this study compared to previous reports suggests a gradual disappearance of chloroquine-resistant malaria parasites following reduced drug pressure. It may also be a result of fitness demand on the parasites in attempts to evolve resistance against the current first-line regimen. However, evaluating the prevalence of other chloroquine resistance markers such as Plasmodium falciparum multidrug resistance 1 gene mutations in this population, and a more robust sample size will help to consolidate these findings.

Development and longevity of naturally acquired antibody and memory B cell responses against Plasmodium vivax infection.

Plasmodium vivax malaria causes significant public health problems in endemic regions. Considering the rapid spread of drug-resistant parasite strains and the development of hypnozoites in the liver with potential for relapse, development of a safe and effective vaccine for preventing, controlling, and eliminating the infection is critical. Immunity to malaria is mediated by antibodies that inhibit sporozoite or merozoite invasion into host cells and protect against clinical disease. Epidemiologic data from malaria endemic regions show the presence of naturally acquired antibodies to P. vivax antigens during and following infection. But data on the persistence of these antibodies, development of P. vivax-specific memory B cells (MBCs), and their relation to reduction of malaria severity and risk is limited. This review provides an overview of the acquisition and persistence of naturally acquired humoral immunity to P. vivax infection. Also, we summarize and discuss current progress in assessment of immune responses to candidate vaccine antigens in P. vivax patients from different transmission settings. Longitudinal studies of MBC and antibody responses to these antigens will open new avenues for developing vaccines against malaria infection and its transmission.

Seasonal dynamics, resting behaviour and insecticide susceptibility of Anopheles mosquitoes across two differentially malaria-endemic regions in Ethiopia

Seasonal dynamics, resting behaviour and insecticide susceptibility of Anopheles mosquitoes across two differentially malaria-endemic regions in Ethiopia

Plasmodium falciparum genetic diversity; implications for malaria control in Ethiopia: Systematic review and meta-analysis.

In malaria endemic regions, Plasmodium falciparum infection is characterized by variable genetic diversity at different settings. The parasite's various forms are found at varied frequency in different geographic areas. Understanding malaria parasite diversity and transmission is vital to evaluate control interventions. The aim of this study was under taken to determine the status of P. falciparum genetic diversity and MOI in different regions of Ethiopia. Relevant publications were identified from electronic databases such as; PubMed, EMBASE, Google scholar and Google. Besides, an online search was done using the above databases for all articles published in English on genetic diversity of P. falciparum in Ethiopia. STATA software was used for data analysis. The pooled estimates were calculated using random effect model. The summary estimates were presented using forest plots and tables. A total of 11 studies were included in the systematic review. However, only 8, 10 and 2 studies were included for Pfmsp-1, Pfmsp-2 and glurp gene meta-analysis, respectively. However, the meta-analysis result showed that the pooled prevalence of Pfmsp-1, msp-2 and glurp gene were 84% for both msp-1/2% and 51%, respectively. The pooled prevalence of msp-1 gene was higher in Amhara followed by Oromia region and lower in SNNPR while, for msp-2 gene the pooled prevalence was higher in Benshangul gumez region. Among the allelic family of msp-1 and msp-2 genes, MAD20 (34%) and FC27 (44%) were the most predominant respectively. Based on the review, there is evidence of the presence of high genetic diversity of P. falciparum parasites in Ethiopia, suggesting that malaria transmission remain high and that strengthened control efforts are needed. The approaches and methods used for investigation of diversified parasites have similarity between studies and should use advanced molecular techniques, like microsatellite, to assess the genetic diversity of P. falciparum for better results.

Association of first-line combination antiretroviral therapy with malaria among adult HIV-infected persons in Jos, Nigeria: a pilot cross sectional study

BackgroundMalaria and human immunodeficiency virus (HIV) infection coexist in significant numbers in some geographic areas including sub-Sahara Africa (SSA). HIV-infected patients are a World Health Organization (WHO) recognized high risk group for increased malaria morbidity. Majority of HIV-infected patients undertaking treatment in SSA are on WHO recognized first-line combination antiretroviral therapy (cART). Considering the immunity-enhancing capacity of antiretroviral therapies on people living with HIV, this study aimed to explore the association between first-line combination antiretroviral therapy (cART) with malaria parasitaemia and antigenaemia in adult HIV-infected persons and to determine the predictors of malaria antigenaemia in adult persons living with HIV.MethodsThe study was conducted at the AIDS Prevention Initiative in Nigeria (APIN) Centre, Jos University Teaching Hospital, Jos, Plateau State, from August 2018 to February 2019. Epi Info statistical tool was used to determine the sample size and power of the study. The study population consisted of three groups. The first group comprised first-line cART-experienced adult HIV-seropositive subjects, the second group comprised ARV-naïve HIV-seropositive adults and the third group comprised HIV-seronegative adults. For this pilot study, 60 persons were recruited into each group via convenience sampling. Malaria rapid diagnostic test (RDT) was performed according to manufacturer’s instruction for all the study participants using SD Bioline Malaria Ag P.f (HRP2/pLDH) (Standard Diagnostics, Hagal-Dong, Korea). All the study participants also had thick and thin blood film malaria microscopy. Data collected was processed and analyzed using the Stata statistical software version 15 (StataCorp, College Station, Texas). Chi square was used to test the association between malaria and first-line cART exposure. Univariate and multivariate analysis were also done to identify factors that were independently associated with malaria antigenaemia.ResultsA total of 180 persons participated in the study and involved 60 participants recruited in each of the three study groups. Overall, the predominant study participants were females (56.67%), traders (27.78%), secondary school leavers (43.33%) and urban dwellers (88.89%). Their mean age and standard deviation was 37.07 ± 11.53 years. Using malaria microscopy, the prevalence of malaria parasitaemia in ARV-naïve HIV-infected persons was 5% and 0% in the first-line cART-experienced HIV-infected persons as well as the HIV-negative persons. Malaria RDT result was positive in 7/60 (11.67%) of the first-line cART experienced HIV-infected participants, 6/60 (10%) of the ARV-naïve HIV-infected group and 1/60 (1.67%) of the HIV-negative group. Of the seven positive malaria RDT results in those on first-line cART, five persons were receiving zidovudine/lamivudine/nevirapine (AZT/3TC/NVP) while the remaining two were receiving tenofovir disoproxil fumarate/lamivudine/efavirenz (TDF/3TC/EFV), thus making an antigenaemia proportion of 16.67% and 6.67% respectively. Being an HIV-infected person on first-line cART (OR = 16.20, p = 0.04), having a headache (OR = 6.21, p = 0.03) and non-usage of window nets (OR = 3.74, p = 0.05) were found to be predictors of malaria antigenaemia.ConclusionMalaria parasite burden in HIV-infected persons on first-line cART is lower than that observed in ARV-naïve HIV-infected persons. Our study suggests that TDF/3TC/EFV may be associated with lower malaria antigenaemia when compared with AZT/3TC/NVP and can be considered an alternative first-line antiretroviral regimen in malaria-endemic regions.

Protecting maternal health: Strategies against HIV and malaria in pregnancy.

Maternal health remains a global priority, with particular emphasis on combating infectious diseases such as HIV and malaria during pregnancy. Despite significant progress in prevention and treatment efforts, both HIV and malaria continue to pose significant risks to maternal and fetal well-being, particularly in resource-limited settings. The prevention of mother-to-child transmission (PMTCT) programs for HIV and intermittent preventive treatment (IPTp) for malaria represent cornerstone strategies in mitigating the impact of these infections on pregnancy outcomes. PMTCT programs focus on early HIV diagnosis, antiretroviral therapy initiation, and promoting safe infant feeding practices to reduce the risk of mother-to-child transmission. Similarly, IPTp involves the administration of antimalarial medication to pregnant women in malaria-endemic regions to prevent maternal and fetal complications associated with malaria infection. Integration of HIV and malaria prevention and treatment services within existing maternal and child health programs is crucial for maximizing impact and minimizing healthcare system strain. Strengthening health systems, improving access to antenatal care services, and enhancing community engagement are essential components of comprehensive maternal health strategies. Furthermore, promoting awareness, education, and empowerment of pregnant women and communities are vital in fostering health-seeking behaviors and adherence to preventive measures against HIV and malaria. In conclusion, protecting maternal health from the dual threat of HIV and malaria requires a multifaceted approach that encompasses prevention, screening, treatment, and community engagement.

Hemoglobinopathy for Malaria Protection: A Comprehensive Review

Hemoglobinopathies, including sickle cell disease (SCD) and thalassemia, are inherited disorders that affect hemoglobin structure and function, leading to significant health implications. However, these genetic conditions also confer a degree of protection against malaria, particularly Plasmodium falciparum, the most virulent malaria parasite. This comprehensive review examines the relationship between hemoglobinopathies and malaria protection, exploring how genetic mutations in hemoglobin subunits influence susceptibility to malaria. Sickle cell trait (HbAS) provides notable protection against severe malaria, with mechanisms including reduced parasite growth, enhanced immune clearance, and microvascular obstruction. Although homozygous sickle cell disease (HbSS) does not confer protection and leads to severe complications, the high prevalence of HbS in malaria-endemic regions underscores an evolutionary balance. Thalassemia, both alpha and beta types, also offers partial malaria protection by altering the red blood cell environment, though the precise mechanisms remain less understood. Additionally, other hemoglobin variants, such as hemoglobin C (HbC) and hemoglobin E (HbE), demonstrate varying degrees of malaria resistance. The review highlights the evolutionary and epidemiological evidence supporting the protective effects of these genetic traits, emphasizing their role in malaria-endemic regions. Public health implications include the need for genetic counseling and targeted malaria control strategies. Future research directions include elucidating mechanistic pathways, exploring regional variations, and assessing the impact on malaria vaccine efficacy. By integrating insights from hemoglobinopathy research into public health interventions, more effective malaria control strategies can be developed, ultimately improving health outcomes for affected populations. Keywords: Hemoglobinopathies, Sickle Cell Disease, Thalassemia, Malaria Protection, Plasmodium falciparum.

Hepcidin: A missing link at the interface of malaria and hypertension

Malaria and hypertension are seemingly unrelated communicable and non-communicable diseases, both highly pervasive in the global south. There is a debate about the potential connection between these two disorders beyond any obvious factors. The emerging evidence suggests an emerging genetic selection pressure for hypertension in malaria-endemic regions. Furthermore, the impact of the liver hormone hepcidin, which has been overlooked, is significant in the development of hypertension due to malaria. Malaria exposure leads to changes in iron metabolism through the regulation of hepcidin, resulting in iron deficiency and, consequently, the development of hypertension.

One Haemolytic Anaemia May Hide Another: Paroxysmal Nocturnal Haemoglobinuria Masquerading As Plasmodium Falciparum Infection.

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, genetic and acquired haematologic disease that causes complement-mediated intravascular haemolytic anaemia, thrombosis and bone marrow failure. A 27-year-old migrant patient attended the emergency department in a context of fever and chills over the previous few days as well as chronic fatigue, dyspnoea and chest pain. His medical history included chronic anaemia and erectile dysfunction. Initial biology showed a haemoglobin of 6.3 g/dl, platelets of 25,000/μl, total leucocytes of 3,500/μl with 1,500 neutrophils. B12 vitamin, folic acid, ferritin and thyroid stimulating hormone were normal. Lactate dehydrogenase levels were high and haptoglobin was non-measurable. C-reactive protein was 46.1 mg/l. A thick blood smear revealed Plasmodium falciparum infection with 0.1% parasitaemia. The patient was treated with an oral combination of artemether and lumefantrine. Three weeks later, the patient consulted the infectious disease department given the lack of clinical improvement. The cytopenias worsened, and lactate dehydrogenase (LDH) and reticulocytes increased. Tests for schistocytes, a thick blood smear for malaria and a direct Coombs test were negative; a myelogram was reassuring. An abdominal, pelvic and thoracic CT scan showed a mild hepatomegaly with no focal lesion and no splenomegaly or adenomegaly. A 12-colour flow cytometry unveiled a PNH clone on 90.9545% of neutrophils and 80.7371% of monocytes. PNH patients can be vulnerable to parasites infection (such as P. falciparum) as it may trigger breakthrough haemolysis through uncontrolled resurgence of activity of the complement system. In our patient, P. falciparum infection was a confounding factor, as it commonly causes haemolytic anaemia and thrombocytopenia, and patients living in malaria-endemic regions can carry low parasitaemia while being slightly symptomatic or asymptomatic. Plasmodium falciparum infection can cause breakthrough haemolysis in patients with paroxysmal nocturnal haemoglobinuria.Low P. falciparum parasitemia in patients living in malaria-endemic regions is not always significant as these patients often carry acquired immunity.Patients from malaria-endemic regions presenting with severe sickness and low P. falciparum parasitemia must be assessed for other diseases, as it cannot explain heavy illness.Patients presenting with haemolytic anaemia, no schistocytes, a negative direct Coombs test and other unexplained cytopenia such as thrombocytopenia/neutropenia and other unexplained clinical manifestations such as dyspnoea, chest pain or erectile dysfunction should be assessed for paroxysmal nocturnal haemoglobinuria.

Association between Epstein-Barr virus reactivation and severe malaria in pregnant women living in a malaria-endemic region of Cameroon.

Malaria kills nearly 619,000 people each year. Despite the natural immunity acquired to malaria, pregnant women and children under five die from severe forms of the disease in sub-Saharan Africa. Co-infection with acute Epstein-Barr Virus (EBV) infection has been shown to suppress the anti-malarial humoral responses, but little is known about the impact of EBV reactivation on malaria-associated morbidity. This study investigated the association between EBV reactivation and malaria severity in pregnant women living in a malaria-endemic region in Cameroon. A cross-sectional study was conducted on 220 pregnant women attending antenatal consultations in three health facilities in the West region of Cameroon. Malaria was diagnosed by microscopy, and Plasmodium species were identified by Nested PCR. Plasma samples were analyzed by ELISA for the presence of EBV nuclear antigen, EBV viral capsid antigen, and EBV early antigen to determine EBV reactivation. All statistics were performed using GraphPad Prism and SPSS software. The prevalence of malaria among pregnant women was 23.2%, of which 18.6% were P. falciparum mono-infections and 4.5% mixed infections (3.6% P. falciparum and P. malariae; 0.9% P. falciparum and P. ovale). 99.5% of the women were EBV seropositive, and 13.2% had EBV reactivation. Pregnant women with reactivated EBV were more likely to develop severe malaria than pregnant women with latent EBV (OR 4.33, 95% CI 1.08-17.25, p = 0.03). The median parasitemia in pregnant women with latent EBV was lower than in those with EBV reactivation (2816 vs. 19002 parasites/μL, p = 0.02). Our study revealed that lytic reactivation of EBV may be associated with the severity of malaria in pregnant women. Suggesting that, like acute infection, EBV reactivation should be considered a risk factor for severe malaria in pregnant women in malaria-endemic regions or could serve as a hallmark of malaria severity during pregnancy. Further detailed studies are needed.

Absence of developmental and reproductive toxicity in rats, rabbits, and zebrafish embryos exposed to antimalarial drug cabamiquine.

When developing new antimalarial drugs, considering their potential use during pregnancy as preventive or curative therapy is crucial. This prevents the parasite from affecting embryonic development and reduces maternal and fetal death risks. Consequently, understanding the exposure and safety of antimalarial drugs during pregnancy is crucial, with well-designed animal studies playing a key role in this assessment. As part of the drug development program for cabamiquine, a series of developmental and reproductive toxicity studies were conducted in rats and rabbits. Additionally, the zebrafish embryo model was used to further improve embryo exposure, minimize confounding factors related to maternal toxicity, and assess developmental risks of cabamiquine. In these studies, although maternal toxicity was observed, there were no cabamiquine-related adverse effects on fertility, embryonic, or fetal development at maternal exposures representing significant multiples (up to five and 10 times higher in rabbit and rats, respectively) than the exposure at the anticipated efficacious human dose. Similarly, no adverse effects were observed on ZF embryonic development, even though cabamiquine concentrations in the embryos were 10-fold higher than nominal concentrations. The results obtained in a full set of reproductive toxicity studies did not provide evidence of detrimental effects on the conceptuses and progeny at maternally nontoxic doses and exposures, still representing a multiple of the anticipated systemic exposures in women of childbearing potential (WOCBP). Cabamiquine can therefore be considered a suitable therapeutic option for WOCBP and pregnant women living in malaria-endemic regions by significantly reducing maternal and infant malaria death rates.

Possible alteration in serum ferritin level in malaria infected HIV seropositive individuals in Nauth, Nnewi, Nigeria

The role of Ferritin in monitoring disease progression in immune compromised HIV individuals with an underlying active infection like malaria is a subject of growing research. Ferritin being an acute phase protein, plays important role in assessing the range of damage due to inflammation in immunosuppressed patients leaving in highly endemic malaria regions. The levels of serum ferritin in malaria infected HIV positive individuals in Nnamdi Azikiwe University teaching hospital (NAUTH), Nnewi, Anambra State, Nigeria, was assessed. Questionnaire was used to obtain the demographic details of the participants, and to rule out other inflammatory infections. 88 participants of the age group 18 - 65 years, comprising 24 with HIV infection, 22 with HIV and Malaria co-infection, 22 with Malaria infection, and a control group of 22 individuals with neither HIV nor malaria infection were randomly recruited. Ferritin level was determined using enzyme linked immunosorbent assay technique and a cross sectional prospective study design was used. A significantly high mean serum ferritin level was observed in HIV infected individuals with and/ or without malaria co-infection than in malaria positive and control group (p<0.05 respectively). Serum ferritin level was significantly higher in female participants than in male counterparts (p < 0.05). Serum ferritin level was significantly higher in individuals with CD4 count >500 than in CD4 count ≤ 500 (p < 0.05). Blood pressure was significantly higher in HIV infected and malaria positive individuals when compared with controls. The increased serum ferritin level and higher blood pressure in HIV infected participants suggests active inflammatory process, reduced immunity and hypertension which may have worsened by malaria co-infection. This may subsequently lead to vascular and endothelia damage causing disease severity.

Indoor residual spraying of experimental huts in Cameroon highlights the potential of Fludora® Fusion to control wild pyrethroid-resistant malaria vectors

Elevated resistance to pyrethroids in major malaria vectors has led to the introduction of novel insecticides including neonicotinoids. There is a fear that efficacy of these new insecticides could be impacted by cross-resistance mechanisms from metabolic resistance to pyrethroids. In this study, after evaluating the resistance to deltamethrin, clothianidin and mixture of clothianidin + deltamethrin in the lab using CDC bottle assays, the efficacy of the new IRS formulation Fludora® Fusion was tested in comparison to clothianidin and deltamethrin applied alone using experimental hut trials against wild free-flying pyrethroid-resistant Anopheles funestus from Elende and field An. gambiae collected from Nkolondom reared in the lab and released in the huts. Additionally, cone tests on the treated walls were performed each month for a period of twelve months to evaluate the residual efficacy of the sprayed products. Furthermore, the L1014F-kdr target-site mutation and the L119F-GSTe2 mediated metabolic resistance to pyrethroids were genotyped on a subset of mosquitoes from the EHT to assess the potential cross-resistance. All Anopheles species tested were fully susceptible to clothianidin and clothianidin + deltamethrin mixture in CDC bottle assay while resistance was noted to deltamethrin. Accordingly, Fludora® Fusion (62.83% vs 42.42%) and clothianidin (64.42% vs 42.42%) induced significantly higher mortality rates in EHT than deltamethrin (42.42%) against free flying An. funestus from Elende in month 1 (M1) and no significant difference in mortality was observed between the first (M1) and sixth (M6) months of the evaluation (P > 0.05). However, lower mortality rates were recorded against An. gambiae s.s from Nkolondom (mortality rates 50%, 45.56% and 26.68%). In-situ cone test on the wall showed a high residual efficacy of Fludora® Fusion and clothianidin on the susceptible strain KISUMU (> 12 months) and moderately on the highly pyrethroid-resistant An. gambiae strain from Nkolondom (6 months). Interestingly, no association was observed between the L119F-GSTe2 mutation and the ability of mosquitoes to survive exposure to Fludora® Fusion, whereas a trend was observed with the L1014F-kdr mutation. This study highlights that Fludora® Fusion, through its clothianidin component, has good potential of controlling pyrethroid-resistant mosquitoes with prolonged residual efficacy. This could be therefore an appropriate tool for vector control in several malaria endemic regions.

Dose-dependent inactivation of Plasmodium falciparum in red blood cell concentrates by treatment with short-wavelength ultraviolet light.

Plasmodium species are naturally transmitted by Anopheles mosquitos. The parasite infects red blood cells (RBCs) and can be transfused with blood products. In non-endemic areas, the main risk of infection arises from travellers coming back and people immigrating from malaria-endemic regions. Endemic countries face a permanent risk of infection from transfusion-transmitted malaria (TTM). TTM may cause life-threatening complications in patients dependent on blood donations. This study aimed to investigate the efficacy of Plasmodium falciparum inactivation in RBC units by treatment with short-wavelength ultraviolet C (UVC) light in the absence of photochemical additives. RBC units were spiked with P. falciparum to a parasite density of 0.1%-1% and irradiated with up to 4.5 J/cm2 UVC. The parasite density of UVC-treated dilution series and untreated controls were compared over 3 weeks after irradiation. The lowest dose of 1.5 J/cm2 UVC led to a 3.1 log reduction in parasite load compared with the untreated control. The inactivation capacity was dose-dependent. Strikingly, 4.5 J/cm2 led to ≥5.3 log unit reduction, which was equivalent to a complete inactivation in two out of three experiments. Pathogen reduction with UVC light was previously shown to be effective for different bacteria and viruses, but the inactivation of parasites in RBC concentrates was not addressed until now. The present study provides evidence for significant inactivation of P. falciparum-infected RBCs by UVC light.

Maternal Malaria and the Risk of Subsequent Pregnancy Complications

Maternal malaria, primarily caused by Plasmodium falciparum, has well-documented immediate effects on pregnancy, including preterm birth, low birth weight, and placental dysfunction. However, its impact extends beyond the current pregnancy, potentially influencing outcomes in subsequent pregnancies. This review examines how maternal malaria affects future pregnancies, focusing on the mechanisms through which previous malaria infections contribute to subsequent complications. Key mechanisms include chronic placental damage, immune system alterations, and persistent inflammation, which can disrupt placental function and increase the risk of adverse outcomes such as preterm labor and placental abruption in future pregnancies. The review highlights evidence that women with a history of maternal malaria are at an elevated risk for complications in subsequent pregnancies, including an increased likelihood of preterm birth and low birth weight. Persistent placental damage and immune dysregulation resulting from past malaria infections contribute to these risks. Understanding these long-term effects is crucial for developing effective public health strategies and interventions aimed at mitigating the risks of adverse pregnancy outcomes in malaria-endemic regions. Keywords: Maternal malaria, Plasmodium falciparum, pregnancy complications, placental damage, immune dysregulation, chronic inflammation, preterm birth