Chronic Malaria Research Articles

Detection of P. malariae using a new rapid isothermal amplification lateral flow assay

BackgroundWhile Plasmodium falciparum and Plasmodium vivax cause the majority of malaria cases and deaths, infection by Plasmodium malariae and other Plasmodium species also causes morbidity and mortality. Current understanding of these infections is limited in part by existing point-of-care diagnostics that fail to differentiate them and have poor sensitivity for low-density infections. Accurate diagnosis currently requires molecular assays performed in well-resourced laboratories. This report describes the development of a P. malariae diagnostic assay that uses rapid, isothermal recombinase polymerase amplification (RPA) and lateral-flow-strip detection.MethodsMultiple combinations of custom RPA primers and probes were designed using publicly available P. malariae genomic sequences, and by modifying published primer sets. Based on manufacturer RPA reaction conditions (TwistDx nfo kit), an isothermal assay was optimized targeting the multicopy P. malariae 18S rRNA gene with 39 °C incubation and 30-min run time. RPA product was visualized using lateral strips (FAM-labeled, biotinylated amplicon detected by a sandwich immunoassay, visualized using gold nanoparticles). Analytical sensitivity was evaluated using 18S rRNA plasmid DNA, and clinical sensitivity determined using qPCR-confirmed samples collected from Tanzania, Ethiopia, and the Democratic Republic of the Congo.ResultsUsing 18S rRNA plasmid DNA, the assay demonstrates a detection limit of 10 copies/µL (~ 1.7 genome equivalents) and 100% analytical specificity. Testing in field samples showed 95% clinical sensitivity and 88% specificity compared to qPCR. Total assay time was less than 40 min.ConclusionCombined with simplified DNA extraction methods, the assay has potential for future field-deployable, point-of-care use to detect P. malariae infection, which remains largely undiagnosed but a neglected cause of chronic malaria. The assay provides a rapid, simple readout on a lateral flow strip without the need for expensive laboratory equipment.

Oral Malignant Burkitt’s Lymphoma and It’s Problems

A non-Hodgkin lymphoma with rapid growth and aggressive behavior is Burkitt's lymphoma. Burkitt's lymphoma (BL) is also an oral cancer of lymphoid origin with a high percentage of occurrences and includes an advanced B-cell neoplasm. Fundamentally, the exact cause of BL is unknown. This disease commonly occurs in people with weakened immune systems or children related to the Epstein-Barr virus (EBV) and chronic malaria. Burkitt lymphoma can be fatal. Burkitt lymphoma is a rare but highly aggressive (fast-growing) B-cell non-Hodgkin lymphoma (NHL). This disease may affect the jaw, central nervous system, bowel, kidneys, ovaries, or other organs Cancer cells in BL can spread to all parts of the body. Inhibiting the proliferation of BL oral cancer cells requires a viable and efficient plan. One of them is using medicinal plants whose antitumor potential needs to be scientifically tested. However, Burkitt lymphoma is often very responsive to the currently recommended intensive chemotherapy regimens, and cure rates for this disease remain high. Studies show people who receive treatment right away have high rates of remission, meaning after treatment they don’t have symptoms or signs of the condition. The aim of this review is to discuss Burkitt's lymphoma (BL) in diagnosis and treatment. Burkitt's lymphoma, or Raji cell, is a B-cell non-Hodgkin lymphoma that is very aggressive

Chronic malaria exposure is associated with inhibitory markers on T cells that correlate with atypical memory and marginal zone-like B cells.

Chronic immune activation from persistent malaria infections can induce immunophenotypic changes associated with T-cell exhaustion. However, associations between T and B cells during chronic exposure remain undefined. We analyzed peripheral blood mononuclear cells from malaria-exposed pregnant women from Papua New Guinea and Spanish malaria-naïve individuals using flow cytometry to profile T-cell exhaustion markers phenotypically. T-cell lineage (CD3, CD4, and CD8), inhibitory (PD1, TIM3, LAG3, CTLA4, and 2B4), and senescence (CD28-) markers were assessed. Dimensionality reduction methods revealed increased PD1, TIM3, and LAG3 expression in malaria-exposed individuals. Manual gating confirmed significantly higher frequencies of PD1+CD4+ and CD4+, CD8+, and double-negative (DN) T cells expressing TIM3 in malaria-exposed individuals. Increased frequencies of T cells co-expressing multiple markers were also found in malaria-exposed individuals. T-cell data were analyzed with B-cell populations from a previous study where we reported an alteration of B-cell subsets, including increased frequencies of atypical memory B cells (aMBC) and reduction in marginal zone (MZ-like) B cells during malaria exposure. Frequencies of aMBC subsets and MZ-like B cells expressing CD95+ had significant positive correlations with CD28+PD1+TIM3+CD4+ and DN T cells and CD28+TIM3+2B4+CD8+ T cells. Frequencies of aMBC, known to associate with malaria anemia, were inversely correlated with hemoglobin levels in malaria-exposed women. Similarly, inverse correlations with hemoglobin levels were found for TIM3+CD8+ and CD28+PD1+TIM3+CD4+ T cells. Our findings provide further insights into the effects of chronic malaria exposure on circulating B- and T-cell populations, which could impact immunity and responses to vaccination.

Placental Malaria and Its Relationship with Neonatal Birth Weight among Primigravidae: An Analytical Cross-sectional Study.

Malaria can be fatal during pregnancy, posing a serious risk to both mothers and fetuses, especially in sub-Saharan Africa. Primigravidae are particularly susceptible to placental malaria in areas with high rates of transmission due to insufficient immunity. This study aimed to determine the prevalence of placental malaria infection, risk factors, types of Plasmodium causing malaria during pregnancy, and its relationship with neonatal birth weight among primigravidae. This was an analytical cross-sectional study involving 357 primigravidae who delivered at Abubakar Tafawa Balewa University Teaching Hospital, Bauchi, Nigeria. Placental blocks were taken from the pericentric area of the maternal surface of the placenta, and the birth weights of the neonates were recorded. The samples were fixed in 10% neutral-buffered formalin, and histopathological analysis was performed. The primary outcome measure was to determine the relationship between placental malaria and neonatal birth weight. Demographics and outcomes were analyzed using standard statistical tests. Multivariable regression models accounting for potential confounders were created for the primary and secondary outcomes with adjusted odds ratios as the measures of effect. The prevalence of placental malaria was 38.4%. Among the participants with positive placenta malaria parasitemia, 49.6%, 36.5%, and 13.9% had chronic, acute, and past placental malaria infections, respectively. Only Plasmodium falciparum was found in the placenta. According to the bivariate analysis, unbooked status (p = 0.001), non-use of intermittent preventive therapy for malaria (p < 0.001), and village dwelling (p = 0.020) were significantly associated with placental malaria. However, on multivariable logistic regression, only non-uptake of intermittent preventive therapy for malaria was independently associated with placental malaria (adjusted odds ratio, 2.2, 95% confidence interval: 1.20, 4.1, p = 0.011). There was a significant difference in the mean birth weight between those with placental malaria and those without placental malaria (2.8 ± 0.5 kg vs. 3.2 ± 0.4 kg, p = 0.001). Additionally, placental malaria was significantly associated with low birth weight among the primigravidae (p < 0.001). In Nigeria, there is a strong correlation between low birth weight and placental malaria in Primidravidae. Placental malaria was found to be independently correlated with non-uptake of intermittent preventive therapy for malaria.

Prevalence and risk factor of anemia among pregnant women admitted in antenatal ward in PBMH Bhubaneswar, Odisha.

Anemia is one of the contributing factors for morbidity and mortality during pregnancy in developing country including India, which eventually leads to fetal and maternal consequences. Growing fetus depends completely on mothers for all its growth and maturity. Anemia is one of the nutritional deficiency disorders and around 56% of women are suffering from anemia in India. It is one of the reasons for maternal deaths and fetal complication during pregnancy. The aim of the study was to assess the prevalence of anemia and to determine the risk factors of anemia among pregnant women in PBMH hospital, Bhubaneswar, Odisha. A descriptive cross-sectional study was conducted over a period of 1 month from October 11, 2022, to November 11, 2022, from the Department of Obstetrics and Gynecology of Pradyumna Bal Memorial Hospital KIMS, Bhubaneswar. A total sample comprised of 52 pregnant women who were interviewed by using self-structured questionnaire for data collection and classification of anemia was performed according to the Indian Council of Medical Research (ICMR) criteria. A total of 52 antenatal mothers were admitted during this study period (October 11, 2022, to November 11, 2022), and all were selected as study sample. The incidence of anemia among antenatal mother in PBM hospital was found as follows: 17 (33%) mild, 04 (07%) moderate, and 02 (04%) were severe in this present study. The most common indication of anemia among antenatal mother as per the present study was found to be H/O infection (21%), chronic malaria (15%), hook worm (27%), and birth interval (42%). The study implies that the prevalence rate of Anemia is high, that is, 44.2%. Spacing between pregnancy and H/O infection plays a significant role in considering anemia in pregnant women, which eventually affects both maternal and fetal condition.

Research on the Correlation Between Anemia and Chronic Malnutrition in School-Age Children in Rural Areas of the Toumodi Health District in Côte d’Ivoire

Introduction: Anemia and chronic malnutrition are widespread in sub-Saharan Africa and constitute public health problems. This study was carried out to assess the association between chronic malnutrition and anemia in rural school-age children. Method: This is a descriptive and analytical cross-sectional study carried out in the Toumodi health district in central Côte d’Ivoire. Study subjects were selected from children aged 6 to 15 years from rural school areas, according to inclusion and exclusion criteria, resulting in a sample of 588 pupils. The study was carried out in two stages: - The first step was to screen all consenting children for anemia using a Hemocue ®-System. - The second step was to collect anthropometric and biological data: the result of the presence of the malaria parasite in the blood by malaria test and the presence of helminths in the stools. Data entry and statistical analysis were carried out using Excel and SPSS version 12.0 software respectively. Results: Chronic malnutrition (weight-by-age) accounted for 22.4% of children, while the prevalence of anemia was 70.7%. The percentage of children with a positive malaria test was 57.5%. Helminths were observed in the stools of 52.8% of children. Anemia was correlated with chronic malnutrition and malaria. Moreover, chronically malnourished children were about twice (OR = 1.81) as likely to develop anemia as those who were not. Conclusion: This study revealed a strong association between chronic malnutrition and anemia.

Pernicious Plasmodium vivax as a Historical Cause of Malarial Cachexia?

Prior to the understanding of malaria as a parasitic disease, malaria cachexia was a loosely defined syndrome consisting of severe anemia and splenomegaly in a chronically wasted individual living in a malarious area. Entire rural populations in diverse areas such as the Thames estuary, Marseilles marshes, and the Mississippi valley were said to have cachexia on the basis of chronic malaria "poisoning," which accounted for their poor socioeconomic health. Malaria cachexia appeared to disappear as the marshes were drained, agriculture improved, and quinine or iron treatments were administered. Malaria cachexia's association with plasmodia in the blood was uncertain once blood smears were examined in the twentieth century. Modern studies have raised the question of chronic Plasmodium vivax in the spleen as a possible etiology; historical specimens could be examined to clarify malaria cachexia.

Mint (Mentha): A Herb and Used as a Functional Ingredient

Health never goes out of trend. There is increased interest in alternative medicines particularly those obtained from plants. Functional foods have the ability to prevent or lessen the severity of symptoms of disease. The world is gaining its interest in treatment through natural sources like foods and medicinal plants. Herbal medicines have already been utilized by various cultures around the world for several therapies including chronic pain, malaria, heart conditions, warts, skin diseases and bowel disorders. The need for functional foods is anticipated to increase as a result of three factors: changing laws, increased health care expenses, and scientific discoveries. Mint is a member of the Lamiaceae family. Mint is an excellent source of vitamins, minerals, phenolic compounds, dietary fiber and antioxidants. Mint is a mysterious herb because of its many unknown aspects through which it promotes good health that should be revealed. Mint is a rich source of Iron. Alkaloids, steroids, and tannins are among phytoconstituents found in mint essential oils that prevent the absorption of sugars and flavonoids.

Subdural hematoma following dural puncture epidural anesthesia for labor analgesia: two case reports

BackgroundNeuraxial anesthesia is widely used for labor analgesia in the USA, such as epidural, combined spinal–epidural, and dural puncture epidural (DPE). Post-dural puncture headache (PDPH) is a well-known complication of neuraxial anesthesia. However, a rare yet more serious complication is subdural hematomas. Untreated subdural hematomas can result in permanent disability and death, hence the need to better understand their development in the obstetric population receiving DPE.Case presentationCase one: A 34-year-old G6P3 female at 39-week gestation received a DPE for labor analgesia and underwent a cesarean section for arrest of descent. On postoperative day two, the patient developed a PDPH but opted for conservative treatment. Ten days post-discharge, the patient presented with a large subacute to chronic subdural hematoma with midline shift. The patient underwent a right fronto-temporal craniectomy, evacuation of subdural hematoma, and placement of a subdural drain. Case two: A 31-year-old G1P0 female at 41-week gestation with a past medical history of a chronic right parietal hemangioma and malaria at 29-week gestation received a DPE for induction of labor. She subsequently underwent a primary cesarean section for failure to progress and persistent category-two fetal heart rate tracing. On postoperative day 11, she experienced a severe non-positional right-sided headache. Imaging revealed a subdural hematoma overlying the right frontal temporal and parietal lobes, which was observed and managed non-operatively. On postoperative day 14, the patient received an epidural blood patch for symptomatic intracranial hypotension.ConclusionPDPH, a complication of neuraxial anesthesia, is typically benign and often self-resolves with conservative measures. However, to avoid increased morbidity and mortality, monitoring in patients with PDPH at a higher risk for development of subdural hematomas (especially those with known preexisting intracranial pathologies) is critical for prompt diagnosis. As exemplified by our second case, epidural blood patches continue to be effective and may be considered in patients with symptomatic intracranial hypotension.

Absence of Malaria-Associated Coagulopathy in Asymptomatic Plasmodium falciparum Infection: Results From a Cross-sectional Study in the Ashanti Region, Ghana.

Coagulopathy is common in acute symptomatic Plasmodium falciparum malaria, and the degree of coagulation abnormality correlates with parasitemia and disease severity. Chronic asymptomatic malaria has been associated with increased morbidity. However, the role of coagulation activation in asymptomatic, semi-immune individuals remains unclear. This study investigates the potential effect of asymptomatic P falciparum infection on coagulation activation in semi-immune Ghanaian adults. Blood from asymptomatic Ghanaian adults with P falciparum blood stage infection detectable by polymerase chain reaction (PCR) or by both PCR and rapid diagnostic test and from noninfected individuals, was investigated. Markers of coagulation activation including global coagulation tests, D-dimer, antithrombin III, fibrinogen, and von Willebrand factor antigen were tested. Furthermore, blood count, inflammation markers, and liver and kidney function tests were assessed. Acquired coagulopathy was not found in asymptomatic P falciparum infection. Asymptomatic malaria was associated with significantly lower platelet counts. Systemic inflammation markers and liver and kidney function tests were not altered compared to noninfected controls. There is no laboratory evidence for acquired coagulopathy in adults with asymptomatic P falciparum malaria in highly endemic regions. Lack of laboratory evidence for systemic inflammation and liver and kidney dysfunction indicates that asymptomatic malaria may not be associated with significant morbidity.

Allometric scaling relationships in mouse placenta.

Fetal growth and maturation are highly intertwined with placental development during pregnancy. Here we used placental vascular morphology measurements (depth and span) as well as the umbilical artery (UA) diameter of previously published studies on three different mouse strains (C57BL6/J, CD-1 and BALB/c), which were exposed to different conditions (combination antiretroviral therapy, chronic maternal hypoxia and malaria infection) at different embryonic days, to test the hypothesis that placental vascularization and specifically the UA size affect conceptus weight. Interaction of each study parameter with embryonic day, strain and exposure to treatments are studied to investigate the stability of the scaling relationships across and/or within strains and conditions. In addition, the effect of UA diameter on the placental growth measurements (depth and span) is studied. These results show that the power-law scaling relationship of conceptus weight and placental depth with the UA diameter is conserved across strains and conditions with the scaling exponent of approximately 3/8 and 5/8, respectively. By contrast, the relationship between conceptus weight and either the placental span or depth is different between strains and conditions, suggesting multiple mechanisms of vascular adaptation.

Life Cycle Analysis and Cost–Benefit Assessment of the Waste Collection System in Anyama, Cote d’Ivoire

Municipal solid waste collection system in Anyama is in a critical state and is compounded by high population density. Household residents need about 30 minutes’ walk to the designated waste collection point. Waste is dumped openly along the roadside, which serves as breeding grounds for chronic diseases, malaria, diarrhea, and acute respiratory disease. Could the perception and attitude of residents change if the distance between their homes and the collection points is reduced? This study evaluated the current waste management system in Anyama. Life Cycle Assessment (LCA) and cost–benefit analysis were conducted on four different waste collection scenarios, to propose an alternative, feasible, and integrated solid waste management system. Results showed that the kerbside recycling scenario has the highest benefit (5.8 billion CFA) compared to its cost (1.9 billion CFA), proving to be more economically sustainable. In environmental terms, the kerbside recycling scenario emitted lower emissions such as global warming potential (GWP 4967 tons) and carbon dioxide (CO2eq 550 tons). The kerbside recycling obviously had the highest potential for recycling and thus is more environmentally sustainable. Therefore, the kerbside scenario is the most suitable and recommended policy that should be adopted and implemented in Anyama. We recommend the introduction of waste banks specifically for recyclable waste and the setting up of more kerbside collection points in order to reduce the distance from households to collection points, thus improving residents’ attitude towards effective waste disposal.

The controversial case of Cosimo I de’ Medici (1519-1574): reflections on the interaction between anatomy and art (iconodiagnosis vs misdiagnosis)

A recent study maintains to have identified a case of severe Graves’ disease in the bronze statue of Cosimo I de’ Medici forged by Benevenuto Cellini (between 1545 and 1547). We carefully examined the artistic sources, the medical primary sources and the paleopathological findings with the aim of showing that Cosimo I de’ Medici (1519-1574) was not affected by severe Graves’ disease. The artistic analysis of different statues and portraits of the Grand-Duke of Tuscany confirms the medical interpretation. Cosimo I was thick-necked with a well-developed laryngeal prominence of the thyroid cartilage (Adam’s Apple) and slightly bulging eyes. Plagued by obesity, Cosimo I was affected by DISH (diffuse idiopathic skeletal hyperostosis), chronic malaria, and severe osteoarthritis. The Grand Duke had a stroke on February 18th 1568, aged 49, and suffered from the sequelae for six years. Previous scholars proposed chronic cerebral vasculopathy as a possible diagnosis. We surmise that, as in modern day obese patients with DISH, he had increased risk for cardiovascular morbidity. The presence of a familiar thick-neck and a well-developed Adam’s Apple can be observed in several other members of the Medici family such Giovanni dalle Bande Nere, Cosimo I de’ Medici’s father. The same features can also be found in several other predecessors of Cosimo I such as Piero the Gouty and his sons Lorenzo the Magnificent and Giuliano de’ Medici, Pope Leo X, Giuliano de’ Medici, Duke of Nemours and Lorenzo de’ Medici, Duke of Urbino. This paper shows that the combination of literary, artistic, paleopathological sources is fundamental to correctly assess disease manifestation. A constant interaction between anatomy and art is recommended so to avoid over-interpretation of pathologic conditions in personages of the past.

Epidemiological and clinical features of epileptic patients in Goma, Democratic Republic of the Congo

Introduction: Epilepsy is one of the most common neurological conditions but the majority of epileptic patients in sub-Saharan African countries do not receive appropriate treatment. In the Democratic Republic of the Congo (DRC), very few epidemiological studies have been conducted on epilepsy. The objective of this study was to describe socio-demographic characteristics, the type of epileptic seizures, and etiological factors of these seizures in a hospital cohort of epileptic patients followed at the Neuropsychiatric Hospital Center in Goma (in the DRC). Materials and methods: This was a cross-sectional study of 917 epileptic patients received in neurology consultation at the Neuropsychiatric Hospital Center in Goma (in the DRC) from January 1st, 2017 to December 31st, 2021. Results: The median age of patients was 16 years, the median age of the patients at onset of seizures was 13 years and the median time between onset of seizures and consultation was 8.0 months; 14.2% of had a family history of epilepsy. Generalized tonic-clonic seizures were the most frequent (76.7%), followed by motor focal impaired awareness seizures (5.2%) and non-motor focal aware seizures (3.6%). The etiologic factor was found in 444 (48.4%) patients and was dominated by chronic alcoholism (20.9%), neurocysticercosis (17.6%), meningitis (14.6%), malnutrition (11.3%), cerebral malaria (8.3%), and head injury (7.7%). Conclusion: This study provides an epidemiological overview of epilepsy in Goma city. The etiological factors and types of seizures will dictate the best possible treatment options.

Asymptomatic malaria infection impact on maternal anemia in Delta State, Nigeria

Background and Purpose: Pregnant women are vulnerable due to the pregnancy-induced suppressed immunity in malaria-endemic areas. Asymptomatic malaria in pregnancy (MiP) threatens both the mother, fetus, and neonate via chronic placental malaria which impacts maternal-neonatal exchange. Some studies reported that MiP risk factors vary across locations, however, there are few studies on MiP and maternal anemia in Nigeria. The purpose of this study was to investigate the association between asymptomatic placental malaria infection and maternal anemia among parturients in Asaba, Delta State, Nigeria.&#x0D; Method: This study was developed with a quantitative methodology that utilized primary and secondary healthcare data from 483 subjects aged 18–49 years from four healthcare facilities between May and July 2021. The Socio-Ecological Model (SEM) framework was used to explain how parturients can achieve improved pregnancy outcome via the mobilization of multi-levels supports to enhance the compliance of parturients to malaria interventions. The research question and hypothesis were tested with the binomial logistic regression test.&#x0D; Result: The findings showed a statistically significant association between placental malaria parasitemia by microscopy (PMPM), intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine, use of complementary and alternative medicine (CAM), and maternal anemia in the study population. Also, the study revealed that positive PMPM, use of CAM, insecticides treated net (ITN) ownership, ITN frequent use, and antenatal care (ANC) attendance were the risk factors of maternal anemia among the study population.&#x0D; Conclusion: The findings of this study could inform malaria control policymaking in Asaba and Delta State on tracking and treating asymptomatic placenta malaria among underserved parturient accessing antenatal services.

Chronic Vaccine Boost Prolongs Malaria Vaccine Immunity and CD4 Effector and Memory T cells

Abstract Vaccines to persistent parasite infections have been challenging to develop, and current iterations lack long-term protection. Persistent infection generates effector and effector memory T cells (Teff, Tem), and both contribute to protection, as we recently showed for Plasmodium infection. Sterilizing immunity from live P. chabaudi vaccination lasts less than 200 days. While specific antibody levels remain stable after the acute phase of infection, the decay of T cells corresponds with loss of protection from re-infection. Chronic vaccination with CMV has been shown to generate Tem and Teff, and so we tested MCMV for the ability to prolong protection to P. chabaudi. We generated MCMV encoding P. chabaudi MSP-1 epitope B5 (MCMV-B5), and used B5 TCR Transgenic CD4 T cells to follow the MCMV-B5 response. We showed that boosting the live malaria vaccine with MCMV-B5: i) prolonged vaccine protection to heterologous infection at day 200, ii) increased parasite-specific T cells and promoted a highly-differentiated Teff phenotype, including iii) IFN-γ+ and TNF+ T cells. Importantly, chronic MCMV infection itself improved protection from P. chabaudi infection and promoted generation of a T cell phenotype similar to P. chabaudi infection. Investigating the mechanisms of MCMV in prolonged vaccine-induced protection, we found an impressive role for IFN-γ, as its neutralization in vivo during MCMV latency is associated with loss of protection to P. chabaudi challenge. Blocking IFN-γ before challenge induced fewer Teff and less plasma IL-12 upon P. chabaudi challenge. Our findings suggest a mechanism to boost CD4 T cell immunity using chronic vaccines, which may be broadly applicable to infections that require T cell based immunity. Supported by R01AI135061

Ulysses S. Grant: Chronic Malaria and the myth of his alcoholism.

Ulysses S. Grant, Civil War general and twice-elected President of the United States, was highly respected in late-19th century America. Gradually however, it became the conventional wisdom that he was an alcoholic who had only succeeded as a general by using overwhelming force. This change began with his political enemies and those who resented his suppression of the Ku Klux Klan, his regard for the welfare of Native Americans and his support of Reconstruction. Jealous subordinates and those with an axe to grind added their voices to this and then the views of certain influential academic historians and romantic adherents of 'The Lost Cause' were unchallenged until the mid-1950s. Grant was undoubtedly an occasional binge drinker but this is not the same as being an alcoholic. Charles A. Dana is the most authoritative source for the claim that Grant was a frank alcoholic. In 1887 he wrote that Grant was drunk on a trip to Satartia, Mississippi in 1863 during the siege of Vicksburg. In this paper, the author shows that Grant was actually ill on that trip from the disease of malaria, alcohol was not involved at all, and that Grant suffered episodically from this disease both before and during the Civil War.

Malaria chronica larvata

The possibility of acute malaria becoming chronic is well known. It is also known that the manifestations of chronic malaria can be extremely atypical and unclear. In other words, malaria becomes latent. Descriptions of latent malaria have been repeatedly made (Laveran, Triantafillides, Nevyadomsky, Toporkov, Demyanov, etc.) However, its semiotics has not yet been developed clinically enough, while without knowledge of semiotics there is no way to catch and register latent malaria. And therefore it is impossible to form an idea of ​​its spread and the need to study it.

Malaria as a chronic infection

In the manuals on internal pathology, malaria is still considered mainly as an acute infectious disease, and chronic malaria is spoken of rather as a result of infection.

Swertia Chirata: A Comprehensive review of its abundant medicinal properties

Swertia chirata (S chirata), (Family Gentianaceae) is a well-known herbaceous plant. It is very popular in traditional systems of medicine like Unani, Ayurveda, and Siddha. It is commonly used in Unani medicine, for several pharmacological effects including Musaffi-i-Dam (blood purifier), Muqawwi-i-Mida (stomachic), Muhallil-i-Awram (anti-inflammatory), Muqawwi-i-Qalb wa Jigar (tonic to heart and liver), Mulattif (demulcent), Mudir (diuretic), Mulliyin (laxative) properties. It is used for chronic fever, malaria, anemia, liver disorders, hypertension, dyspepsia, gastritis, ulcers, constipation, and skin diseases, and is included in many pharmacopoeial and non-pharmacopoeial preparations. The entire plant contains ophelic acid, two bitter glycosides chiratin, and amarogentin. It also contains resins, tannin, gum, carbonate, and phosphate of potash, lime, and magnesia. Extensive studies on S. chirata have been carried out by various researchers and a wide spectrum of its pharmacological actions have been explored which includes anti-inflammatory, anti-diabetic, antimicrobial, and antioxidant properties. The present review is an effort to provide a detailed survey of the literature, scientific researches of pharmacognostical characteristics, chemical composition, and pharmacological activities of this plant.