IFNγ, TNFα polymorphisms and IFNγ serum levels are associated with the clearance of drug-resistant P. falciparum in Malian children.

Host immunity has been suggested to clear drug-resistant parasites in malaria-endemic settings. However, the immunogenetic mechanisms involved in parasite clearance are poorly understood. Characterizing the host's immunity and genes involved in controlling the parasitic infection can inform the development of blood-stage malaria vaccines. This study investigates host regulatory cytokines and immunogenomic factors associated with the clearance of Plasmodium falciparum carrying a chloroquine resistance genotype. Biological samples from participants of previous drug efficacy trials conducted in two Malian localities were retrieved. The P. falciparum chloroquine resistance transporter (Pfcrt) gene was genotyped using parasite DNA. Children carrying parasites with the mutant allele (Pfcrt-76T) were classified based on their ability to clear their parasites. The levels of the different cytokines were measured in serum. The polymorphisms of specific human genes involved in malaria susceptibility were genotyped using human DNA. The prevalence of the Pfcrt-76T was significantly higher in Kolle than in Bandiagara (81.6 % vs 38.6 %, p < 10-6). The prevalence of children who cleared their mutant parasites was significantly higher in Bandiagara than in Kolle (82.2 % vs 67.4 %, p < 0.05). The genotyping of host genes revealed that IFN-γ -874 T and TNF-α -308A alleles were positively associated with parasite clearance. Cytokine profiling revealed that IFN-γ level was positively associated with parasite clearance (p = 0.04). This study highlights the role of host's immunity and immunogenetic factors to clear resistant parasites, suggesting further characterization of these polymorphisms may help to develop novel approaches to antiparasitic treatment strategies.

Current beliefs and attitudes regarding epilepsy in Mali.

PURPOSE: In Mali, epilepsy affects 15 individuals per thousand. Perceptions and attitudes have not seemingly evolved with advancing medical knowledge. The objective of this study was to assess parental beliefs and attitudes in families with and without affected children. METHODS: We enrolled 720 pediatric patients, half of whom had epilepsy, at Mali's largest hospital. We conducted semistructured interviews with the accompanying parent. Control families with unaffected patients and also had affected children were excluded. RESULTS: In total, 67% and 24% of families with and without epilepsy, respectively, lived in rural environments. Interviewees were mostly mothers in their 30s; 80% had not completed high school. About 22% of parents without an affected child had witnessed a seizure. During a seizure, 94% of parents with an affected child and 49% of parents without an affected child, respectively, would intervene; 7.5% and 21%, respectively, would wet the patient's face with cool water. Although parents with an affected child had more intimate knowledge of seizures, misconceptions prevailed, perhaps more so than in families without epilepsy: 79% and 66% of parents, respectively, considered epilepsy contagious; 43% vs. 69% thought that it inevitably led to psychosis; and 53% vs. 29% attributed epilepsy to supernatural causes. Finally, 63% of parents with an affected child reported consulting a traditional healer as first-line management for epilepsy. CONCLUSIONS: Our study demonstrates widespread misconceptions in Mali regarding epilepsy. Our findings argue for more education initiatives focused on the entire population, including traditional healers, to provide knowledge, reduce stigma, and improve quality of life for individuals living with epilepsy.

[Ear tuberculosis concomitant with pulmonary localization in an HIV-immunosuppressed patient, in Bamako, Mali]. / Tuberculose auriculaire concomitante à une localisation pulmonaire chez un patient immunodéprimé par le VIH, à Bamako, Mali.

Introduction/Rationale: Tuberculosis remains a major public health issue. It is an opportunistic pathology, very common in HIV-immunocompromised persons, classifying it at the WHO stage 4. Ear tuberculosis remains a rare and under-diagnosed clinical form. We report here a case of ear tuberculosis concomitant with pulmonary localization in an HIV-immunosuppressed person on triple antiretroviral therapy aged 32 years hospitalized in Bamako (Mali) to discuss the diagnostic and therapeutic difficulties posed by this rare localization. Description of the case: The patient had a chronic productive cough, otalgia and right chronic purulent otorrhea. The search for acid-resistant bacilli was positive for direct examination in gastric casing fluid and swabbing of the ear pus, confirming the diagnosis of tuberculosis. Anti-tuberculosis treatment instituted for 6 months associated with adjuvants resulted in complete healing of the patient. Discussion/conclusion: Although rare, ear localization must be actively sought. Etiological treatment must be instituted upon confirmation of the diagnosis to avoid complications and sequelae.

The estimated burden of fungal diseases in Mali.

Mali is a developing country facing several health challenges with a high rate of tuberculosis (TB) and a moderate HIV infection burden. Little is known or done about fungal diseases, yet they represent a significant public health problem in certain populations. The aim of this study was to estimate the national burden of fungal disease, and summarize data, diagnostic and treatment gaps. We used national demographics and PubMed searches to retrieve articles on published data on these infections and at-risk populations (pulmonary TB, HIV/AIDS patients, patients receiving critical care etc.) in Mali. The estimated Malian population was 21,251,000 in 2020 (UN), of which 45% were children <14 years. Among HIV patients, we estimate an annual incidence of 611 cryptococcosis, 1393 Pneumocystis pneumonia, 180 histoplasmosis and >5,700 esophageal candidiasis and some microsporidiosis cases. Our prevalence estimates for tinea capitis are 2.3 million, for recurrent vulvovaginal candidiasis 272,460, ∼60,000 fungal asthma and 7,290 cases of chronic pulmonary aspergillosis (often mistaken for TB). Less common acute fungal infections are probably invasive aspergillosis (n=1230), fungal keratitis (n=2820), candidaemia (>1,060) and mucormycosis (n=43). Histoplasmin was found in 6% in general population. A few cases of mycetoma are described in Mali. Many WHO Essential medicines and Diagnostics are not available in Mali. This shows a marked disparity in documented and estimated cases of fungal diseases in Mali. These infections are underestimated due to the lack of accurate diagnosis tools and lack of support for fungal diseases diagnosis and management.

Neuromeningeal Cryptococcosis and Tuberculosis Coinfection in Bamako: A One-Year Case Series.

Cryptococcosis and tuberculosis are life-threatening opportunistic infections that occur in apparently immunocompetent or severely immunocompromised individuals worldwide. As both infections are strongly linked to HIV infection, they may share certain clinical manifestations, and the interaction of their treatments should be considered. However, despite their similarity, concurrent tuberculosis and cryptococcal infections have rarely been reported in West Africa. Herein, we present 3 cases of neuromeningeal cryptococcosis and lung tuberculosis coinfection collected prospectively over a year at the Department of Infectious Diseases of the Point G Teaching Hospital in Bamako. Two patients had HIV disease, and the third patient had no underlying immunosuppressive illnesses. Thus, active screening for tuberculosis and cryptococcosis, particularly in individuals with HIV, can reduce misdiagnosis and ensure appropriate coinfection management. Moreover, this may reduce mortality due to AIDS-related opportunistic infections in resource-limited settings.

Assessment of lung injury severity using ultrasound in critically ill COVID-19 patients in resource limited settings.

BACKGROUND: Lung ultrasound is a non-invasive tool available at the bedside for the assessment of critically ill patients. The objective of this study was to evaluate the usefulness of lung ultrasound in assessing the severity of SARS-CoV-2 infection in critically-ill patients in a low-income setting. METHODS: We conducted a 12-month observational study in a university hospital intensive care unit (ICU) in Mali, on patients admitted for COVID-19 as diagnosed by a positive polymerase chain reaction for SARS-CoV-2 and/or typical lung computed tomography scan findings. RESULTS: The inclusion criteria was met by 156 patients with a median age of 59 years. Almost all patients (96%) had respiratory failure at admission and many needed respiratory support (121/156, 78%). The feasibility of lung ultrasound was very good, with 1802/1872 (96%) quadrants assessed. The reproducibility was good with an intra-class correlation coefficient of elementary patterns of 0.74 (95% CI 0.65, 0.82) and a coefficient of repeatability of lung ultrasound score < 3 for an overall score of 24. Confluent B lines were the most common lesions found in patients (155/156). The overall mean ultrasound score was 23 ± 5.4, and was significantly correlated with oxygen saturation (Pearson correlation coefficient of - 0.38, p < 0.001). More than half of the patients died (86/156, 55.1%). The factors associated with mortality, as shown by multivariable analysis, were: the patients' age; number of organ failures; therapeutic anticoagulation, and lung ultrasound score. CONCLUSION: Lung ultrasound was feasible and contributed to characterize lung injury in critically-ill COVID-19 patients in a low income setting. Lung ultrasound score was associated with oxygenation impairment and mortality.

Hepatitis B Virus in West African Children: Systematic Review and Meta-Analysis of HIV and Other Factors Associated with Hepatitis B Infection.

While Hepatitis B virus (HBV) and the human immunodeficiency virus (HIV) are endemic in West Africa, the prevalence of HBV/HIV coinfection and their associated risk factors in children remains unclear. In this review, we sought to assess HBsAg seroprevalence among 0- to 16-year-olds with and without HIV in West African countries and the risk factors associated with HBV infection in this population. Research articles between 2000 and 2021 that reported the prevalence of HBV and associated risk factors in children in West Africa were retrieved from the literature using the Africa Journals Online (AJOL), PubMed, Google Scholar, and Web of Science databases as search tools. StatsDirect, a statistical software, was used to perform a meta-analysis of the retained studies. HBV prevalence and heterogeneity were then assessed with a 95% confidence interval (CI). Publication bias was evaluated using funnel plot asymmetry and Egger's test. Twenty-seven articles conducted across seven West African countries were included in this review. HBV prevalence among persons aged 0 to 16 years was 5%, based on the random analysis, given the great heterogeneity of the studies. By country, the highest prevalence was observed in Benin (10%), followed by Nigeria (7%), and Ivory Coast (5%), with Togo (1%) having the lowest. HBV prevalence in an HIV-infected population of children was (9%). Vaccinated children had lower HBV prevalence (2%) than unvaccinated children (6%). HBV prevalence with a defined risk factor such as HIV co-infection, maternal HBsAg positivity, undergoing surgery, scarification, or being unvaccinated ranged from 3-9%. The study highlights the need to reinforce vaccination of newborns, screening for HBV, and HBV prophylaxis among pregnant women in Africa, particularly in West Africa, to achieve the WHO goal of HBV elimination, particularly in children.

[Neuromeningeal cryptococcosis in an HIV-negative patient with pulmonary tuberculosis in the Infectious and tropical diseases department of the University teaching hospital Point G of Bamako, Mali]. / Cryptococcose neuroméningée chez une patiente séronégative pour le VIH atteinte de tuberculose pulmonaire au service de Maladies infectieuses et tropicales du CHU du Point G de Bamako, Mali.

Neuromeningeal cryptococcosis and pulmonary tuberculosis are respectively serious mycotic and bacterial infections occurring in a subject regardless of its HIV serological status. We report here a case of neuromeningeal cryptococcosis associated with pulmonary tuberculosis and malnutrition in an HIV-seronegative patient with a CD4 count of 750/mm3, to highlight some particularities opposed to certain literatures. This is an 18-year-old patient, housewife, from Bamako, admitted in the Infectious and tropical diseases department of the University teaching hospital Point G of Bamako on March 13, 2022 for fever and impaired consciousness. Her symptomatology appears to have gradually set in over a month, preceded by headache resistant to paracetamol, jet vomiting and irregular dry cough, initially treated with ceftriaxone, artesunate and paracetamol for confirmed malaria and suspicion of bacterial meningitis before admission. In whom no known medical-surgical history, no use of topical corticosteroids, no immunosuppressive therapy, no alcohol or tobacco, and no immunosuppressive pathology was found. The diagnoses of neuromeningeal cryptococcosis, pulmonary tuberculosis and undernutrition were retained in view of clinical and microbiological arguments. Diabetes, sickle cell disease, viral hepatitis B and C, kidney failure and cancer, which are immunosuppressive pathologies, were not found. She was successfully treated with first-line oral antituberculous drugs and fluconazole infusion. Three interests are drawn from this clinical case: neuromeningeal cryptococcosis is not only the prerogative of HIV-positive subjects, a high CD4 count does not always mean immunocompetence and fluconazole is an effective therapeutic alternative for neuromeningeal cryptococcosis.

Raoultella planticola and urinary tract infection: The first laboratory-confirmed case in an HIV-infected patient in Mali.

Raoultella planticola is a Gram-negative, aerobic, non-motile bacterium, abundant in the environment, but rarely associated with pathology in humans. Notably, few urinary tract infections caused by R. planticola have been reported. To our knowledge, we are presenting here the first case of urinary tract infection caused by R. planticola in an HIV-infected individual. It is a 50-year-old female, with a history of HIV-1 infection treated for three years. At admission, her CD4 count was 70 cells/mL, and the main complaints were severe diarrhea and cough. She was diagnosed and treated for pulmonary tuberculosis (TB) and E. Coli enteritis. Initially, we observed a good evolution. However, on day 21 of hospitalization, she presented with fever and dysuria. Urinalysis revealed the presence of R. planticola with resistance to multiple antibiotics. We also detected that she has an HIV-2 but not HIV-1 infection. After receiving the right regimen, she was confirmed cured of her bacterial infections.

Incidence and Predictors of Imported Cases of COVID-19 in Burkina Faso.

BACKGROUND: To limit the spread of COVID-19 due to imported cases, Burkina Faso has set up quarantine measures for arriving passengers. We aimed to determine the incidence and predictors of imported cases of COVID-19 in Burkina Faso. METHODS: A prospective cohort study was performed using data from passengers arriving at the airport from April 9 to August 31, 2020. The data was extracted from the District Health Information Software 2 (DHIS2) platform. Cox regression was used to identify predictors of imported cases of COVID-19. RESULTS: Among 6,332 travelers who arrived in the study period, 173 imported cases (2.7%) were recorded. The incidence rate was 1.9 cases per 1,000 traveler-days (95%CI: 1.6-2.2 per 1,000). Passengers arriving in April (Adjusted hazard ratio [aHR] = 3.56; 95%CI: 1.62-7.81) and May (aHR = 1.92; 95% CI: 1.18-3.12) were more at risk of being tested positive compared to those arriving in August, as well as, passengers presenting with one symptom (aHR = 3.71; 95% CI: 1.63-8.43) and at least two symptoms (aHR = 10.82; 95% CI: 5.24-22,30) compared to asymptomatic travelers. CONCLUSIONS: The incidence of imported cases was relatively low in Burkina Faso between April and August 2020. The period of travel and the presence of symptoms at arrival predicted the risk of being tested positive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This is essential in the context of the high circulation of virus variants worldwide and the low local capacity to perform genotyping tests to strengthen the surveillance and screening capacities at the points of entry into the country.

Point-of-care ultrasound for tuberculosis management in Sub-Saharan Africa-a balanced SWOT analysis.

Point-of-care ultrasound (POCUS) is an increasingly accessible skill, allowing for the decentralization of its use to nonspecialist healthcare workers to guide routine clinical decision-making. The advent of ultrasound-on-a-chip has transformed the technology into a portable mobile health device. Because of its high sensitivity to detect small consolidations, pleural effusions, and subpleural nodules, POCUS has recently been proposed as a sputum-free likely triage tool for tuberculosis (TB). To make an objective assessment of the potential and limitations of POCUS in routine TB management, we present a Strengths, Weaknesses, Opportunities and Threats (SWOT) analysis based on a review of the relevant literature and focusing on Sub-Saharan Africa (SSA). We identified numerous strengths and opportunities of POCUS for TB management, e.g., accessible, affordable, easy to use and maintain, expedited diagnosis, extrapulmonary TB detection, safer pleural/pericardial puncture, use in children/pregnant women/people living with HIV, targeted screening of TB contacts, monitoring TB sequelae, and creating artificial intelligence decision support. Weaknesses and external threats such as operator dependency, lack of visualization of central lung pathology, poor specificity, lack of impact assessments and data from SSA must be taken into consideration to ensure that the potential of the technology can be fully realized in research as in practice.

High SARS-CoV-2 Seroprevalence among Healthcare Workers in Bamako, Mali.

In Mali, a country in West Africa, cumulative confirmed COVID-19 cases and deaths among healthcare workers (HCWs) remain enigmatically low, despite a series of waves, circulation of SARS-CoV-2 variants, the country's weak healthcare system, and a general lack of adherence to public health mitigation measures. The goal of the study was to determine whether exposure is important by assessing the seroprevalence of anti-SARS-CoV-2 IgG antibodies in HCWs. The study was conducted between November 2020 and June 2021. HCWs in the major hospitals where COVID-19 cases were being cared for in the capital city, Bamako, Mali, were recruited. During the study period, vaccinations were not yet available. The ELISA of the IgG against the spike protein was optimized and quantitatively measured. A total of 240 HCWs were enrolled in the study, of which seropositivity was observed in 147 cases (61.8%). A continuous increase in the seropositivity was observed, over time, during the study period, from 50% at the beginning to 70% at the end of the study. HCWs who provided direct care to COVID-19 patients and were potentially highly exposed did not have the highest seropositivity rate. Vulnerable HCWs with comorbidities such as obesity, diabetes, and asthma had even higher seropositivity rates at 77.8%, 75.0%, and 66.7%, respectively. Overall, HCWs had high SARS-CoV-2 seroprevalence, likely reflecting a "herd" immunity level, which could be protective at some degrees. These data suggest that the low number of cases and deaths among HCWs in Mali is not due to a lack of occupational exposure to the virus but rather related to other factors that need to be investigated.

Fighting COVID-19 in the West Africa after experiencing the Ebola epidemic.

Coronavirus disease 2019 (COVID-19) dissemination occurred from December 2019 and quickly spread to all countries. Infected patients with COVID-19 have had a wide range of symptoms, ranging from mild to severe illness. The most mortality was observed in patients with underlying disease and over 45 years. World statistics have shown that the COVID-19 outbreak is most expanded in Middle Eastern, West Asian, European, North, and South American countries, and is least expanded in African countries. Therefore, the aim of the paper was the evaluation of six African countries including Mali, Mauritania, Niger, Guinea, Togo, and Djibouti to find why this disease is least expanded in African countries. Study was conducted by Questioner for countries health organizers to define their different aspect exposure and fight with COVID-19 including epidemiology, clinical aspects of the disease, case definitions, diagnosis laboratory confirmation, and referral of cases by the portal of entry, case management, and disease prevention in these countries. According to this opinion review, due to the low international flights and low domestic travel, the spread, and prevalence of COVID-19 was low and the return of the immigrants of these countries has caused the spread of COVID-19 among these countries. Experience, preparation, and impact of previous infections epidemic such as the Ebola virus epidemic would have beneficial, which have promoted certain reflexes among people that cause low dissemination in these countries.

Peoples' attitude toward COVID-19 vaccine, acceptance, and social trust among African and Middle East countries.

Background: To end the COVID-19 pandemic, a large part of the world must be immune to the virus by vaccination. Therefore, this study aimed to gauge intent to be vaccinated against COVID-19 among ordinary people and to identify attitudes towards vaccines and barriers for vaccine acceptance. Methods: The study population comprises 1880 people residing in different countries that answer a prepared questionnaire. The questionnaire topics are demographics, historical issues, participants' attitudes and beliefs regarding vaccines, concerns, and vaccine hesitancy. Results: Attitudes and beliefs relating to vaccines in general, and the COVID-19 vaccine, were ascertained. Overall, 66.81% of the contributors would like to be vaccinated against COVID-19, while %33.19 did not intend to be vaccinated. Reasons for COVID-19 vaccine hesitancy included concern regarding vaccine side effects, fear of getting sick from the uptake of the vaccine, and the absence of accurate vaccine promotion news. Individuals with higher education believe that India (68.6%) produces the best vaccine (P <0.001), while healthcare workers think the Chinese vaccine (44.2%) is the best (P =0.020). Individuals with higher education have not been vaccinated, not be healthcare workers, and females were the most contributors to effective of the vaccine in reducing mortality from COVID-19 disease. Conclusion: Given the degree of hesitancy against COVID-19 vaccination, a multifaceted approach to facilitate vaccine uptake that includes vaccine education, behavioral change strategies, and health promotion, is paramount.

[Tuberculosis and HIV coinfection complicated by nosocomial infection caused by Klebsiella pneumoniae: about 4 cases in a Department of Infectious diseases in Mali]. / Co-infection tuberculose-VIH compliquée d'une sur infection nosocomiale à Klebsiella pneumoniae: à propos de 4 observations dans un Service de Maladies Infectieuses au Mali.

Nosocomial infections are a real global public health problem. Pulmonary tuberculosis and HIV co-infection increases the incidence of nosocomial infections because of immunosuppression and iterative hospitalizations. We here report four cases of patients aged 28, 36, 42 and 52 years co-infected with HIV and tuberculosis (multifocal tuberculosis in 2 patients, miliary tuberculosis, bacteriologically confirmed tuberculosis), all with CD4 < 100 cells/mm3. During the intensive-phase, patients received antitubercular drugs and antiretroviral therapy (ART). They had been admitted to the Department of Infectious Diseases at the G-Point University Hospital with productive cough and/or hyperthermia following hospital stay greater than 48 hours. Patients' history revealed that one patient had not been compliant with tuberculosis treatment because of adverse reactions classified as minor. There had been no clinical improvement in the three remaining patients despite their optimal compliance to different treatments. Cytobacteriological examination of sputum and/or testing of the feeding tubes, blood cultures and specific samples allowed to identify multidrug-resistant Klebsiella pneumoniae. The clinical course of these patients was favorable under specific antibiotic therapy. Nosocomial infections may be misinterpreted and associated with poor therapeutic response in patients receiving TB treatment. Cytobacteriological examination of the biological fluids should be systematic in patients co-infected with HIV and tuberculosis and hospitalized for at least 48 hours, in whom pulmonary signs and/or fever persist despite their good compliance to treatment.

[Localised tetanus with no obvious entry site: about a case in Bamako (Mali)]. / Tétanos localisé sans porte d´entrée apparente: à propos d´un cas à Bamako (Mali).

Tetanus is a major public health problem in sub-Saharan Africa. Localised tetanus is rare, unlike generalized tetanus which has been sufficiently described in the literature. We report a case of localised tetanus with no obvious entry site managed in the Department of Infectious Diseases in Bamako. The study involved a retired nurse aged 59 years who had not undergone tetanus booster immunisation within the last 10 years, corresponding to the date of her last delivery. She was referred to our Hospital with dysphagia associated with inability to open the buccal cavity. Patient's history was characterized by long-term therapy associated with many specialized consultations without any improvement. The diagnosis of localised tetanus with no obvious entry site was retained after having excluded any other local disorder. Outcome was favorable ten days after adequate management. Underdiagnosed or unknown to health-care providers, localised tetanus may mimic other diseases delaying diagnosis and management. Targeted campaign to build awareness should be implemented in order to improve adherence with immunization schedules.

Comparing Treatment Outcomes of Antiretroviral Therapy in HIV-1 and HIV-2 Infected Patients, in Bamako, Mali.

BACKGROUND: HIV-2 leads to a less-severe disease than HIV-1 but is known to be resistant to Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs). We goaled to evaluate the clinical and biological outcomes of HIV-1 and HIV-2 infected-patients under Antiretroviral Therapy (ART) that do not include NNRTIs. METHODS: This is a case-control study of 100 participants (half in each group) to measure the frequency of clinical and biological adverse effects, and disease outcome at 6 and 12 months of treatment (M6 and M12) We included. RESULTS: Opportunistic infections were more frequent in HIV-1 infected patients with 82% when compared to HIV-2, 68%. However, the prevalence of treatment adverse events was slightly higher in HIV-2 infected patients. The average increase of CD4 cell count at M6 of treatment was 139.93 and 159.41 cells/mm3, for HIV-2 and HIV-1 groups respectively, and at 153 and 217 cells/mm3, at M12 for HIV-2 and HIV-1 respectively. A total of nine HIV-2 and six HIV-1 deaths were reported during the study. CONCLUSION: This study has shown that ART regimens that do not include NNRTIs are effective equally in the treatment of HIV-1 and HIV-2 infections. Nevertheless, we recommend regular and continuous laboratory monitoring for all HIV treated patients.

Serum antibody levels to glycosylphosphatidylinositols in specimens derived from matched Malian children with severe or uncomplicated Plasmodium falciparum malaria and healthy controls.

Neutralizing antibodies to glycosylphosphatidylinositols (GPIs), which are Plasmodium falciparum surface protein anchor molecules implicated in malaria pathogenesis, are thought to protect against symptomatic malaria. Index cases of severe malaria in Malian children 3 months to 14 years of age were matched by age and residence to uncomplicated malaria and healthy controls. Serum antibodies to GPI (IgM and IgG) were measured at the time of severe malaria and after the malaria transmission season. The mean optical density values for IgM and IgG antibodies were higher in children with severe or uncomplicated malaria compared with healthy controls. Similarly, higher percentages of children with IgM and IgG antibodies to GPI were observed in the severe malaria group compared with matched healthy controls. IgG antibody levels to GPI were highest among children with cerebral malaria and children who died. The IgG antibody levels to GPI peaked during periods of malaria transmission and decreased after malaria transmission ended. A direct correlation between age and parasitemia and IgG antibodies to GPI was observed. In summary, higher levels of IgM and IgG antibodies to GPI in young children were associated with disease severity and were short-lived.

Association of intraleukocytic Plasmodium falciparum malaria pigment with disease severity, clinical manifestations, and prognosis in severe malaria.

Peripheral parasite density of Plasmodium falciparum is used as an indicator of malaria disease severity, but does not quantify central sequestration, which is important in the pathogenesis of severe disease. Malaria pigment, recognizable within the cytoplasm of phagocytic cells by light microscopy may represent a peripheral marker for parasite biomass. One hundred seventy-two index cases of severe malaria and 172 healthy age-, residence-, and ethnicity-matched controls with uncomplicated malaria in Bandiagara, Mali were analyzed prospectively for presence of malaria pigment. The presence of polymorphonuclear cell (PMN) and monocyte pigment was strongly associated with severe disease compared with uncomplicated malaria. Total PMN pigment burden in children with severe malaria was higher in those with cerebral manifestations and with combined cerebral manifestations and severe anemia (hemoglobin < or = 5 g/dL) but was not associated with hyperparasitemia (> 500,000 asexual forms/mm3). Additionally, pigmented PMNs/mm3 was associated with a fatal outcome in patients with severe malaria. This study validates the presence of malaria pigment in monocytes and neutrophils as a marker for disease severity, and demonstrates that pigmented neutrophils are associated with cerebral malaria and with death in children with severe malaria.