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Abstract Background Post malaria neurologic syndrome (PMNS) is a rare complication of malaria, usually caused by Plasmodium falciparum. The clinical picture is highly variable and ranges from qualitative disturbances of consciousness and psychosis to damage to the peripheral nerves, usually occurring three to eight weeks after treated malaria. Case presentation We report the case of a 54-year-old male who presented with recurrent clinical symptoms three and a half weeks after severe falciparum malaria. After ruling out recurrent malaria, autoimmune encephalitis was suspected. Corticosteroid therapy led to a rapid improvement of the clinical symptoms. The extended examinations (including cranial MRI and FDG-PET/CT) revealed no pathological findings. Routine serologic autoimmune diagnostics remained negative. However, anti-septin complex antibodies were detected in the serum in a cell-based and a tissue-based immunofluorescence assay. Twelve months after discontinuation of corticosteroid therapy, the patient was free of immunosuppressants and completely asymptomatic. Conclusion To our knowledge, this is the first case of septin complex autoimmunity with encephalitis associated with PMNS. All physicians treating malaria patients should therefore be aware of this rare condition and consider extended autoimmune diagnostics if routine panels remain unremarkable.

Background: Post malaria neurologic syndrome (PMNS) is a rare complication of malaria, usually caused by Plasmodium falciparum. The clinical picture is highly variable and ranges from qualitative disturbances of consciousness and psychosis to damage to the peripheral nerves, usually occurring three to eight weeks after treated malaria. Case presentation: We report the case of a 54-year-old male who presented with recurrent clinical symptoms three and a half weeks after severe falciparum malaria. After ruling out recurrent malaria, autoimmune encephalitis was suspected. Corticosteroid therapy led to a rapid improvement of the clinical symptoms. The extended examinations (including cranial MRI and FDG-PET/CT) revealed no pathological findings. Routine serologic autoimmune diagnostics remained negative. However, anti-septin complex antibodies were detected in the serum in a cell-based and a tissue-based immunofluorescence assay. Twelve months after discontinuation of corticosteroid therapy, the patient was free of immunosuppressants and completely asymptomatic. Conclusion: To our knowledge, this is the first case of septin complex autoimmunity with encephalitis associated with PMNS. All physicians treating malaria patients should therefore be aware of this rare condition and consider extended autoimmune diagnostics if routine panels remain unremarkable. [ABSTRACT FROM AUTHOR]

Background: Hypoglycaemia is a well recognized complication of falciparum malaria in children but its diagnosis may be overlooked because all the clinical features may be mimicked by other features of severe malaria. Objective: To determine the prevalence of hypoglycaemia at the point of hospital admission of under- fives with falciparum malaria and identify its risk factors in patients seen in a Nigerian secondary -healthcare institution. Methods: At the point of admission, venous blood sample was collected into an appropriate sample bottle (fluoride-oxalate bottle) from 502 children who were below 5 years of age for malaria parasite examination (Giemsa stain). The blood sample was analysed using the glucose-oxidase method. Results: Ninety two (18.3%) of 502 children below five years of age with falciparum malaria had hypoglycaemia (blood glucose below 2.6 mmol/L) at the point of hospital admission. Twenty three percent, 78 of 339 children below 36 months of age were hypoglycaemic compared to 8.6%, 14 of 163 children aged 36 months and above; p

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Introduction: Falciparum malaria remains one of the deadliest infectious diseases worldwide. In Germany, it is mainly an imported infection among travellers. Rates of coinfection are often unknown, and a clinical rationale for the beneficial use of calculated antibiotic therapy in patients with malaria and suspected coinfection is lacking. Methods: We conducted an analysis of all in-patients treated with falciparum malaria at a German infectious diseases centre in vicinity to one of Europe's major airports for 2010–2019. Logistic regression and time-to-event analysis were used to evaluate predictors for bacterial coinfection, the use of antibacterial substances, as well as their influence on clinical course. Results: In total, 264 patients were included. Of those, 64% received an additional antibacterial therapy (n = 169). Twenty-nine patients (11.0%) were found to have suffered from a relevant bacterial coinfection, while only a small fraction had relevant bacteremia (n = 3, 1.4%). However, patients with severe malaria did not suffer from coinfections more frequently (p = 0.283). CRP levels were not a reliable predictor for a bacterial coinfection (OR 0.99, 95% CI 0.94–1.06, p = 0.850), while another clinical focus of infection was positively associated (OR 3.86, 95% CI 1.45–11.55, p = 0.010). Conclusion: Although bacterial coinfections were rare in patients with malaria at our centre, the risk does not seem negligible. These data point rather towards individual risk assessment in respective patients than to general empiric antibiotic use. [ABSTRACT FROM AUTHOR]

Abstract Background The overlap in the epidemiology of malaria and helminths has been identified as a potential area to exploit for the development of an integrated control strategy that may help to achieve elimination of malaria and helminths. A randomized, controlled, observer-blind trial was conducted to assess the feasibility and safety of combining mass drug administration (MDA) for schistosomiasis and soil transmitted helminths (STH) with seasonal malaria chemoprevention (SMC) among children living in Senegal. Methods Female and male children aged 1–14 years were randomized 1:1:1, to receive Vitamin A and Zinc on Day 0, followed by SMC drugs (sulfadoxine-pyrimethamine and amodiaquine) on Days 1–3 (control group); or praziquantel and Vitamin A on Day 0, followed by SMC drugs on Days 1–3 (treatment group 1); or albendazole and praziquantel on Day 0, followed by SMC drugs on Days 1–3 (treatment group 2). Safety assessment was performed by collecting adverse events from all children for six subsequent days following administration of the study drugs. Pre- and post-intervention, blood samples were collected for determination of haemoglobin concentration, malaria microscopy, and PCR assays. Stool samples were analyzed using Kato-Katz, Merthiolate-iodine-formalin and PCR methods. Urine filtration, PCR and circulating cathodic antigen tests were also performed. Results From 9 to 22 June 2022, 627 children aged 1–14 years were randomized into the three groups described above. Mild, transient vomiting was observed in 12.6% (26/206) of children in treatment group 2, in 10.6% (22/207) in group 1, and in 4.2% (9/214) in the control group (p = 0.005). Pre-intervention, the geometric mean value of Plasmodium falciparum parasite density was highest among children who received albendazole, praziquantel with SMC drugs. Post-intervention, the parasite density was highest among children who received SMC drugs only. Children who received praziquantel and SMC drugs had a lower risk of developing severe anaemia than their counterparts who received SMC drugs alone (OR = 0.81, 95% CI 0.13–5.00, p = 0.63). Conclusions Integration of MDA for helminths with SMC drugs was safe and feasible among Senegalese children. These findings support further evaluation of the integrated control model. Trial registration: The study is registered at Clinical Trial.gov NCT05354258.

Background: Scientific information on the impact of malaria on the risk of developing type 2 diabetes mellitus (T2DM) after recovery from the coronavirus disease 2019 (COVID-19) is limited in the Ghanaian context. The purpose of this study was to examine the association between selected risk markers of T2DM in falciparum malaria patients post-COVID-19 or not at a tertiary hospital in Ghana. Methodology: This was a descriptive cross-sectional comparative study of 38-recovered COVID-19 adult participants with malaria and 40 unexposed COVID-19 adults with malaria at the Tamale Teaching Hospital, Ghana. Demographic, anthropometric and levels of glucose, insulin, C-reactive protein and lipid profiles were measured in the two groups of participants under fasting conditions. Parasitaemia was assessed microscopically but insulin resistance and beta-cell function were assessed by the homeostatic model. Results: The COVID-19 exposed participants were older (p=0.035) with lower parasitaemia (p=0.025) but higher mean levels of insulin, insulin resistance, and beta-cell function compared with their unexposed counterparts (p<0.05). Parasitaemia correlated positively with a number of the measured indices of diabetogenic risk markers in the COVID-19 exposed group only, and predicted (Adjusted R²=0.751; p=0.031) by beta-cell function, C-reactive protein and triglycerides with the model explaining about 75% of the observed variation. Parasitaemia could only be predicted (Adjusted R²=0.245; p=0.002) by C-reactive protein with the model explaining just about a quarter of the observed variation in the COVID-19 unexposed group. Insulin resistance and sub-optimal beta-cell function were detected in both groups of participants. Conclusion: Falciparum malaria is associated with risk markers for development of T2DM irrespective of COVID-19 exposure. Insulin resistance, inflammation and sub-optimal beta-cell secretory function may drive the risk. The observed diabetogenic risk is higher in the recovered COVID-19 participants. [ABSTRACT FROM AUTHOR]

IntroductionMortality in pediatric cerebral malaria (CM) in low- and middle-income countries (LMICs) is associated with brain swelling on magnetic resonance imaging (MRI); however, MRI is unavailable in most LMICs. Optic nerve sheath diameter (ONSD) measurement is an inexpensive method of detecting increased intracranial pressure compared with the invasive opening pressure (OP). Our primary objective was to determine if increased ONSD correlated with brain swelling on MRI in pediatric CM. Our secondary objective was to determine if increased ONSD correlated with increased OP and/or poor neurological outcome in pediatric CM. We hypothesized that increased ONSD would correlate with brain swelling on MRI and increased OP and that ONSD would be higher in survivors with sequelae and non-survivors.MethodsWe performed a retrospective chart review of children aged 0–12 years in Blantyre, Malawi, from 2013 to 2022 with CM as defined by the World Health Organization. Brain swelling on admission MRI was characterized by brain volume scores (BVS); severe swelling was scored as 7–8, mild-to-moderate as 4–6, normal as 3. The admission ONSD was measured via ultrasound; it was defined as abnormal if it was >4.5 mm in children >1 year and >4 mm in children

Background: The overlap in the epidemiology of malaria and helminths has been identified as a potential area to exploit for the development of an integrated control strategy that may help to achieve elimination of malaria and helminths. A randomized, controlled, observer-blind trial was conducted to assess the feasibility and safety of combining mass drug administration (MDA) for schistosomiasis and soil transmitted helminths (STH) with seasonal malaria chemoprevention (SMC) among children living in Senegal. Methods: Female and male children aged 1–14 years were randomized 1:1:1, to receive Vitamin A and Zinc on Day 0, followed by SMC drugs (sulfadoxine-pyrimethamine and amodiaquine) on Days 1–3 (control group); or praziquantel and Vitamin A on Day 0, followed by SMC drugs on Days 1–3 (treatment group 1); or albendazole and praziquantel on Day 0, followed by SMC drugs on Days 1–3 (treatment group 2). Safety assessment was performed by collecting adverse events from all children for six subsequent days following administration of the study drugs. Pre- and post-intervention, blood samples were collected for determination of haemoglobin concentration, malaria microscopy, and PCR assays. Stool samples were analyzed using Kato-Katz, Merthiolate-iodine-formalin and PCR methods. Urine filtration, PCR and circulating cathodic antigen tests were also performed. Results: From 9 to 22 June 2022, 627 children aged 1–14 years were randomized into the three groups described above. Mild, transient vomiting was observed in 12.6% (26/206) of children in treatment group 2, in 10.6% (22/207) in group 1, and in 4.2% (9/214) in the control group (p = 0.005). Pre-intervention, the geometric mean value of Plasmodium falciparum parasite density was highest among children who received albendazole, praziquantel with SMC drugs. Post-intervention, the parasite density was highest among children who received SMC drugs only. Children who received praziquantel and SMC drugs had a lower risk of developing severe anaemia than their counterparts who received SMC drugs alone (OR = 0.81, 95% CI 0.13–5.00, p = 0.63). Conclusions: Integration of MDA for helminths with SMC drugs was safe and feasible among Senegalese children. These findings support further evaluation of the integrated control model. Trial registration: The study is registered at Clinical Trial.gov NCT05354258. [ABSTRACT FROM AUTHOR]

Infectious diseases and their imperative awareness gain major relevance through global warming and multi-continent refugee crises. Here, we demonstrate the challenges of malaria diagnosis, disease course, and treatment, including post-artesunate hemolysis in a Syrian refugee with severe falciparum malaria, most probably infected during migrant smuggling from Türkiye to Germany. [ABSTRACT FROM AUTHOR]

Rationale: Malaria and dengue are the most prevalent vector-borne diseases in tropical countries. Plasmodium parasite and dengue virus (DENV) concurrent infection is possible and often under-recognized in geographical areas where these infections are both endemic. Patients concern and diagnosis: We describe the first two cases of Plasmodium falciparum and DENV-3 co-infection in travelers returning to northeastern Italy from Burkina Faso during 2013-2014. Interventions: Malaria infection in both patients was treated with mefloquine. Due to the persistence of symptoms despite of the antimalaria treatment, dengue was also investigated; the treatment of dengue was symptomatic. Outcomes: The patients were discharged in good general condition. Lessons: The need for surveillance of potential malaria and dengue co-infection in travelers returning to Europe from endemic areas is highlighted, as infection with Plasmodium does not exclude arboviral co-infection.

OBJECTIVES To determine the association between the severity of thrombocytopenia and the pattern of malaria. METHODOLOGY This descriptive cross-sectional study included 194 patients who tested positive for malarial parasites on peripheral smear examination. The study comprised smear-positive malaria cases, both males and females, who were Pakistani nationals aged between 8 and 50. Exclusion criteria were individuals with dengue, typhoid, immunocompromised status, liver disease, and pregnancy. Data were recorded for age, gender, the pattern of malaria (Plasmodium (P). vivax, P. falciparum, or mixed), and type of thrombocytopenia (mild, moderate, and severe). The association between the severity of thrombocytopenia and the pattern of malaria was determined using a chi-square test, with the analysis stratified by gender. RESULTS The mean age of the participants was 28.58±11.70 years, with 114 (58.76%) being male. The lowest platelet count (64,627 ± 43,062) was found in cases of falciparum malaria, while the highest mean platelet count was found in cases of vivax malaria (130,919 ± 107,723), and this difference was statistically significant (p=0.004). The most common occurrence of severe thrombocytopenia was in falciparum malaria cases (n=11, 42.31%), and the difference was statistically significant (p=0.024). CONCLUSION Falciparum malaria has the lowest mean platelet count and more severe thrombocytopenia than vivax and mixed type.

Jaundice commonly occurs in severe malaria, seen in approximately 2.5% patients with falciparum malaria infection. Jaundice in malaria can be caused by intravascular hemolysis, disseminated intravascular coagulation (DIC) or malaria-related liver disorders. Malarial hepatopathy is a term that is often used to describe hepatocytic dysfunction in severe malaria, although inflammation does not occur in the liver parenchyma. Malarial hepatopathy also characterized by a rise in serum bilirubin along with the rise in serum glutamate pyruvate transaminase levels. This two condition are similar but must be distinguished because of different treatment required. [ABSTRACT FROM AUTHOR]

Abstract Background Malaria burden among under-five children living in endemic areas of Yemen is largely unknown due to the lack of community-based studies. Therefore, this study determined the prevalence and risk factors associated with falciparum malaria among under-five children in rural communities of Al-Mahweet governorate, Yemen. Methods This community-based, cross-sectional study recruited 400 under-five children from two rural districts of Al-Mahweet governorate in December 2019. Demographic characteristics (gender, age, education and occupation of the child’s parents, and household size) and risk factors associated with malaria were collected through interviews with children’s caregivers using a structured questionnaire. Finger-prick blood was screened for Plasmodium falciparum and non-falciparum species using rapid diagnostic tests (RDTs), and duplicate Giemsa-stained thick and thin blood films were examined for malaria parasites. The density of asexual P. falciparum stages was also estimated. Data were then analysed, and the agreement between the results of thick-film microscopy and RDTs for diagnosing falciparum malaria was assessed using the kappa index. Statistical significance was set at a P-value of

Abstract Background Plasmodium vivax forms dormant liver stages that can reactivate weeks or months following an acute infection. Recurrent infections are often associated with a febrile illness and can cause a cumulative risk of severe anaemia, direct and indirect mortality, and onward transmission of the parasite. There is an increased risk of P. vivax parasitaemia following falciparum malaria suggesting a rationale for universal use of radically curative treatment in patients with P. falciparum malaria even in the absence of detectable P. vivax parasitaemia in areas that are co-endemic for both species. Methods This is a multicentre, health care facility-based, randomized, controlled, open-label trial in Bangladesh, Indonesia and Ethiopia. Patients with uncomplicated falciparum malaria, G6PD activity of ≥70% of the adjusted male median (AMM) and haemoglobin levels ≥8g/dl are recruited into the study and randomized to either receive standard schizonticidal treatment plus 7-day high dose primaquine (total dose 7mg/kg) or standard care in a 1:1 ratio. Patients are followed up weekly until day 63. The primary endpoint is the incidence risk of any P. vivax parasitemia on day 63. Secondary endpoints include incidence risk on day 63 of symptomatic P. vivax malaria and the risk of any P. falciparum parasitaemia. Secondary safety outcomes include the proportion of adverse events and serious adverse events, the incidence risk of severe anaemia (Hb

Rationale: Malaria and dengue are the most prevalent vector-borne diseases in tropical countries. Plasmodium parasite and dengue virus (DENV) concurrent infection is possible and often under-recognized in geographical areas where these infections are both endemic. Patients concern and diagnosis: We describe the first two cases of Plasmodium falciparum and DENV-3 co-infection in travelers returning to northeastern Italy from Burkina Faso during 2013-2014. Interventions: Malaria infection in both patients was treated with mefloquine. Due to the persistence of symptoms despite of the antimalaria treatment, dengue was also investigated; the treatment of dengue was symptomatic. Outcomes: The patients were discharged in good general condition. Lessons: The need for surveillance of potential malaria and dengue co-infection in travelers returning to Europe from endemic areas is highlighted, as infection with Plasmodium does not exclude arboviral co-infection. [ABSTRACT FROM AUTHOR]

Background: Malaria burden among under-five children living in endemic areas of Yemen is largely unknown due to the lack of community-based studies. Therefore, this study determined the prevalence and risk factors associated with falciparum malaria among under-five children in rural communities of Al-Mahweet governorate, Yemen. Methods: This community-based, cross-sectional study recruited 400 under-five children from two rural districts of Al-Mahweet governorate in December 2019. Demographic characteristics (gender, age, education and occupation of the child's parents, and household size) and risk factors associated with malaria were collected through interviews with children's caregivers using a structured questionnaire. Finger-prick blood was screened for Plasmodium falciparum and non-falciparum species using rapid diagnostic tests (RDTs), and duplicate Giemsa-stained thick and thin blood films were examined for malaria parasites. The density of asexual P. falciparum stages was also estimated. Data were then analysed, and the agreement between the results of thick-film microscopy and RDTs for diagnosing falciparum malaria was assessed using the kappa index. Statistical significance was set at a P-value of < 0.05. Results: Plasmodium falciparum was prevalent among 9.8% (95% CI 7.0–13.1) of under-five children in the rural communities of Al-Mahweet, with a median asexual parasite density of 763 ± 2606 parasites/μl of blood (range: 132–4280) and low-to-moderate parasitaemia levels. Approximately one-third of microscopy-confirmed cases were gametocyte carriers. Multivariable logistic regression analysis confirmed that age of three years or older (AOR = 5.6, 95% CI 1.6–19.8; P = 0.007), not sleeping under a mosquito net the previous night of the survey (AOR = 8.0, 95% CI 2.4–27.4; P = 0.001), sleeping outdoors at night (AOR = 4.4, 95% CI 2.0–10.0; P < 0.001), and absence of indoor residual spraying (IRS) during the last year (AOR = 4.2, 95% CI 1.9–9.4; P < 0.001) were the independent predictors of falciparum malaria among under-five children in the rural communities of Al-Mahweet. The observed percentage agreement between thick-film microscopy and RDTs was 98.5%, with a very good agreement (k-index = 0.9) between the two methods for falciparum malaria diagnosis that was statistically significant. Conclusion: Approximately one in ten under-five children in rural communities of Al-Mahweet is infected with P. falciparum based on microscopy and RDTs. Age of three years or older, not sleeping under mosquito nets, sleeping outdoors at night and absence of IRS can independently predict falciparum malaria among them. The very good agreement between thick-film microscopy and RDTs for diagnosing falciparum malaria in children supports the usefulness of using RDTs in such resource-limited rural communities. [ABSTRACT FROM AUTHOR]

Purpose of Review: To discuss the neurological complications and pathophysiology of organ damage following malaria infection. Recent Findings: The principal advancement made in malaria research has been a better understanding of the pathogenesis of cerebral malaria (CM), the most dreaded neurological complication generally caused by Plasmodium falciparum infection. However, no definitive treatment has yet been evolved other than the use of antimalarial drugs and supportive care. The development of severe cerebral edema in CM results from two distinct pathophysiologic mechanisms. First, the development of "sticky" red blood cells (RBCs) leads to cytoadherence, where red blood cells (RBCs) get stuck to the endothelial walls and between themselves, resulting in clogging of the brain microvasculature with resultant hypoxemia and cerebral edema. In addition, the P. falciparum-infected erythrocyte membrane protein 1 (PfEMP1) molecules protrude from the raised knob structures on the RBCs walls and are in themselves made of a combination of human and parasite proteins in a tight complex. Antibodies to surfins, rifins, and stevors from the parasite are also located in the RBC membrane. On the human microvascular side, a range of molecules involved in host–parasite interactions, including CD36 and intracellular adhesion molecule 1, is activated during interaction with other molecules such as endothelial protein C receptor and thrombospondin. As a result, an inflammatory response occurs with the dysregulated release of cytokines (TNF, interleukins 1 and 10) which damage the blood–brain barrier (BBB), causing plasma leakage and brain edema. This second mechanism of CNS injury often involves multiple organs in adult patients in endemic areas but remains localized only to the central nervous system (CNS) among African children. Summary: Neurological sequelae may follow both P. falciparum and P. vivax infections. The major brain pathology of CM is brain edema with diffuse brain swelling resulting from the combined effects of reduced perfusion and hypoxemia of cerebral neurons due to blockage of the microvasculature by parasitized RBCs as well as the neurotoxic effect of released cytokines from a hyper-acute immune host reaction. A plethora of additional neurological manifestations have been associated with malaria, including posterior reversible encephalopathy syndrome (PRES), reversible cerebral vasoconstriction syndrome (RCVS), malarial retinopathy, post-malarial neurological syndrome (PMNS), acute disseminated encephalomyelitis (ADEM), Guillain-Barré syndrome (GBS), and cerebellar ataxia. Lastly, the impact of the COVID-19 pandemic on worldwide malaria control programs and the possible threat from co-infections is briefly discussed. [ABSTRACT FROM AUTHOR]

Malaria is a vector-borne tropical disease well known for causing a multitude of complications. One such rare but familiar complication is symmetrical peripheral gangrene (SPG). SPG is a distinct entity resulting from a horde of infectious and non-infectious illnesses. We report the case of a 32-year-old male infected with Plasmodium falciparum malaria and Human Immunodeficiency Virus who presented to us with renal failure and developed SPG of both feet 3 days into admission. [ABSTRACT FROM AUTHOR]

Background: Plasmodium vivax forms dormant liver stages that can reactivate weeks or months following an acute infection. Recurrent infections are often associated with a febrile illness and can cause a cumulative risk of severe anaemia, direct and indirect mortality, and onward transmission of the parasite. There is an increased risk of P. vivax parasitaemia following falciparum malaria suggesting a rationale for universal use of radically curative treatment in patients with P. falciparum malaria even in the absence of detectable P. vivax parasitaemia in areas that are co-endemic for both species.Methods: This is a multicentre, health care facility-based, randomized, controlled, open-label trial in Bangladesh, Indonesia and Ethiopia. Patients with uncomplicated falciparum malaria, G6PD activity of ≥70% of the adjusted male median (AMM) and haemoglobin levels ≥8g/dl are recruited into the study and randomized to either receive standard schizonticidal treatment plus 7-day high dose primaquine (total dose 7mg/kg) or standard care in a 1:1 ratio. Patients are followed up weekly until day 63. The primary endpoint is the incidence risk of any P. vivax parasitemia on day 63. Secondary endpoints include incidence risk on day 63 of symptomatic P. vivax malaria and the risk of any P. falciparum parasitaemia. Secondary safety outcomes include the proportion of adverse events and serious adverse events, the incidence risk of severe anaemia (Hb<5g/dl and <7g/dl) and/or the risk for blood transfusion, the incidence risk of ≥ 25% fall in haemoglobin with and without haemoglobinuria, and the incidence risk of ≥ 25% fall in haemoglobin to under 7g/dl with and without haemoglobinuria.Discussion: This study evaluates the potential benefit of a universal radical cure for both P. vivax and P. falciparum in different endemic locations. If found safe and effective universal radical cure could represent a cost-effective approach to clear otherwise unrecognised P. vivax infections and hence accelerate P. vivax elimination.Trial Registration: NCT03916003 . Registered on 12 April 2019. [ABSTRACT FROM AUTHOR]

Background Cipargamin (KAE609) is a potent antimalarial in a phase II trial. Here we report efficacy, pharmacokinetics, and resistance marker analysis across a range of cipargamin doses. These were secondary endpoints from a study primarily conducted to assess the hepatic safety of cipargamin (hepatic safety data are reported elsewhere). Methods This phase II, multicenter, randomized, open-label, dose-escalation trial was conducted in sub-Saharan Africa in adults with uncomplicated Plasmodium falciparum malaria. Cipargamin monotherapy was given as single doses up to 150 mg or up to 50 mg once daily for 3 days, with artemether-lumefantrine as control. Key efficacy endpoints were parasite clearance time (PCT), and polymerase chain reaction (PCR)–corrected and uncorrected adequate clinical and parasitological response (ACPR) at 14 and 28 days. Pharmacokinetics and molecular markers of drug resistance were also assessed. Results All single or multiple cipargamin doses ≥50 mg were associated with rapid parasite clearance, with median PCT of 8 hours versus 24 hours for artemether-lumefantrine. PCR-corrected ACPR at 14 and 28 days was >75% and 65%, respectively, for each cipargamin dose. A treatment-emerging mutation in the Pfatp4 gene, G358S, was detected in 65% of treatment failures. Pharmacokinetic parameters were consistent with previous data, and approximately dose proportional. Conclusions Cipargamin, at single doses of 50 to 150 mg, was associated with very rapid parasite clearance, PCR-corrected ACPR at 28 days of >65% in adults with uncomplicated P. falciparum malaria, and recrudescent parasites frequently harbored a treatment-emerging mutation. Cipargamin will be further developed with a suitable combination partner. Clinical Trials Registration ClinicalTrials.gov (NCT03334747). [ABSTRACT FROM AUTHOR]

Introduction: Understanding the human immune response to Plasmodium falciparum gametocytes and its association with gametocytemia is essential for understanding the transmission of malaria as well as progressing transmission blocking vaccine candidates. Methods: In a multi-national clinical efficacy trial of artemisinin therapies (13 sites of varying transmission over South-East Asia and Africa), we measured Immunoglobulin G (IgG) responses to recombinant P. falciparum gametocyte antigens expressed on the gametocyte plasma membrane and leading transmission blocking vaccine candidates Pf s230 (Pf s230c and Pf s230D1M) and Pf s48/45 at enrolment in 1,114 participants with clinical falciparum malaria. Mixed effects linear and logistic regression were used to determine the association between gametocyte measures (gametocytemia and gametocyte density) and antibody outcomes at enrolment. Results: Microscopy detectable gametocytemia was observed in 11% (127/1,114) of participants at enrolment, and an additional 9% (95/1,114) over the follow-up period (up to day 42) (total 20% of participants [222/1,114]). IgG levels in response to Pf s230c, Pf s48/45 and Pf s230D1M varied across study sites at enrolment (p < 0.001), as did IgG seroprevalence for anti- Pf s230c and D1M IgG (p < 0.001), but not for anti- Pf s48/45 IgG (p = 0.159). In adjusted analyses, microscopy detectable gametocytemia at enrolment was associated with an increase in the odds of IgG seropositivity to the three gametocyte antigens (Pf s230c OR [95% CI], p : 1.70 [1.10, 2.62], 0.017 ; Pf s48/45: 1.45 [0.85, 2.46], 0.174 ; Pf s230D1M: 1.70 [1.03, 2.80], 0.037), as was higher gametocyte density at enrolment (per two-fold change in gametocyte density Pf s230c OR [95% CI], p : 1.09 [1.02, 1.17], 0.008 ; Pf s48/45: 1.05 [0.98, 1.13], 0.185 ; Pf s230D1M: 1.07 [0.99, 1.14], 0.071). Conclusion: Pf s230 and Pf s48/45 antibodies are naturally immunogenic targets associated with patent gametocytemia and increasing gametocyte density across multiple malaria endemic settings, including regions with emerging artemisinin-resistant P. falciparum. [ABSTRACT FROM AUTHOR]

Post-artesunate delayed haemolysis (PADH) is thought to occur because of delayed clearance of previously malarial infected erythrocytes spared by ‘pitting’ during treatment. We report a case of PADH following the treatment of Plasmodium (P.) falciparum malaria (32% parasitaemia), with a positive direct antiglobulin (DAT) test, suggesting an immune mechanism.

IntroductionUnderstanding the human immune response to Plasmodium falciparum gametocytes and its association with gametocytemia is essential for understanding the transmission of malaria as well as progressing transmission blocking vaccine candidates.MethodsIn a multi-national clinical efficacy trial of artemisinin therapies (13 sites of varying transmission over South-East Asia and Africa), we measured Immunoglobulin G (IgG) responses to recombinant P. falciparum gametocyte antigens expressed on the gametocyte plasma membrane and leading transmission blocking vaccine candidates Pfs230 (Pfs230c and Pfs230D1M) and Pfs48/45 at enrolment in 1,114 participants with clinical falciparum malaria. Mixed effects linear and logistic regression were used to determine the association between gametocyte measures (gametocytemia and gametocyte density) and antibody outcomes at enrolment.ResultsMicroscopy detectable gametocytemia was observed in 11% (127/1,114) of participants at enrolment, and an additional 9% (95/1,114) over the follow-up period (up to day 42) (total 20% of participants [222/1,114]). IgG levels in response to Pfs230c, Pfs48/45 and Pfs230D1M varied across study sites at enrolment (p < 0.001), as did IgG seroprevalence for anti-Pfs230c and D1M IgG (p < 0.001), but not for anti-Pfs48/45 IgG (p = 0.159). In adjusted analyses, microscopy detectable gametocytemia at enrolment was associated with an increase in the odds of IgG seropositivity to the three gametocyte antigens (Pfs230c OR [95% CI], p: 1.70 [1.10, 2.62], 0.017; Pfs48/45: 1.45 [0.85, 2.46], 0.174; Pfs230D1M: 1.70 [1.03, 2.80], 0.037), as was higher gametocyte density at enrolment (per two-fold change in gametocyte density Pfs230c OR [95% CI], p: 1.09 [1.02, 1.17], 0.008; Pfs48/45: 1.05 [0.98, 1.13], 0.185; Pfs230D1M: 1.07 [0.99, 1.14], 0.071).ConclusionPfs230 and Pfs48/45 antibodies are naturally immunogenic targets associated with patent gametocytemia and increasing gametocyte density across multiple malaria endemic settings, including regions with emerging artemisinin-resistant P. falciparum.

Malaria remains a significant global health challenge, particularly in endemic regions of Africa, with Plasmodium falciparum being the most virulent species. This case report details the presentation of a 24-year-old Caucasian woman who collapsed at a train station in the United Kingdom after experiencing a week of fever, malaise, abdominal pain, and gastrointestinal symptoms. At emergency care, she was initially resuscitated with intravenous fluids and antipyretics. Laboratory investigations indicated a normal hemoglobin level but a markedly low platelet count. Initial differentials included sepsis, viral infection, and idiopathic thrombocytopenic purpura. Following her transfer to the medical ward, her travel history elicited a month-long trip to Nigeria. A malaria screen subsequently tested positive for P. falciparum , leading to the initiation of intravenous artesunate. The diagnosis was confirmed through thick and thin blood films, and treatment was adjusted to oral artemether and lumefantrine. The patient showed significant clinical improvement, with normalization of platelet counts and a decrease in inflammatory markers. This case underscores the importance of thorough history-taking, particularly regarding travel to endemic areas, for the timely diagnosis of malaria. It highlights the necessity for healthcare professionals to maintain a high index of suspicion for malaria in returning travelers presenting with fever, regardless of any prophylactic measures taken. The report emphasizes the critical need for awareness and education surrounding malaria, especially in non-endemic regions, to prevent severe complications and improve patient outcomes., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Samuel et al.)

Gilbert's syndrome and G6PD deficiency are common genetic disorders. They both give rise to unconjugated hyperbilirubinemia through different mechanisms. Falciparum malaria-induced hemolysis is another cause of unconjugated hyperbilirubinemia. We have reported a 51-year-old Asian male who presented with a four-day history of fever and sweating just after a holiday in Kenya. He admitted to not taken malaria prophylaxis while on holiday. Initial investigations revealed that he had falciparum malaria along with co-existing severe G6PD deficiency and Gilbert's syndrome, which we believe, all contributed to an exacerbation of unconjugated hyperbilirubinemia (four-fold rise). He was treated with intravenous fluids, paracetamol and oral artemether/lumefantrine combination therapy. He made a good clinical recovery. After a month, he still exhibited chronic unconjugated hyperbilirubinemia with recurrent elevation in his reticulocyte count but no anaemia, suggesting further episodes of compensated hemolysis. We also discuss the differential diagnosis for unconjugated hyperbilirubinemia in relation to this interesting case., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Not applicable issued approval Not applicable. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Mon et al.)