Pitting of malaria parasites and spherocyte formation

BACKGROUND: A high prevalence of spherocytes was detected in blood smears of children enrolled in a case control study conducted in the malaria holoendemic Lake Victoria basin. It was speculated that the spherocytes reflect intraerythrocytic removal of malarial parasites with a concurrent removal of RBC membrane through a process analogous to pitting of intraerythrocytic inclusion bodies. Pitting and re-circulation of RBCs devoid of malaria parasites could be a host mechanism for parasite clearance while minimizing the anaemia that would occur were the entire parasitized RBC removed. The prior demonstration of RBCs containing ring-infected erythrocyte surface antigen (pf 155 or RESA) but no intracellular parasites, support the idea of pitting. METHODS: An in vitro model was developed to examine the phenomenon of pitting and spherocyte formation in Plasmodium falciparum infected RBCs (iRBC) co-incubated with human macrophages. In vivo application of this model was evaluated using blood specimens from patients attending Kisumu Ditrict Hospital. RBCs were probed with anti-RESA monoclonal antibody and a DNA stain (propidium iodide). Flow cytometry and fluorescent microscopy was used to compare RBCs containing both the antigen and the parasites to those that were only RESA positive. RESULTS: Co-incubation of iRBC and tumor necrosis factor-alpha activated macrophages led to pitting (14% ± 1.31% macrophages with engulfed trophozoites) as opposed to erythrophagocytosis (5.33% ± 0.95%) (P < 0.01). Following the interaction, 26.9% ± 8.1% of the RBCs were spherocytes as determined by flow cytometric reduction in eosin-5-maleimide binding which detects RBC membrane band 3. The median of patient RBCs with pitted parasites (RESA+, PI-) was more than 3 times (95,275/μL) that of RESA+, PI+ RBCs (28,365/μL) (P < 0.01). RBCs with pitted parasites showed other morphological abnormalities, including spherocyte formation. CONCLUSION: It is proposed that in malaria holoendemic areas where prevalence of asexual stage parasites approaches 100% in children, RBCs with pitted parasites are re-circulated and pitting may produce spherocytes

2020-04-17/18 DAILY UNM GLOBAL HEALTH COVID-19 BRIEFING

Executive Summary: Daily NM Recap. Stimulus checks. Whitehouse reopening guidelines. Increased suicide calls. Commentary on COVID and African Americans. NYC ventilation rate. 300K African deaths predicted. Thai horse virus outbreak. Europe eases lockdown. UK vaccine research. Chinese death undercount. Biosafety breaches. General wearing of masks. PPE for emergency physician. FDA approves safer swabs. Mental health lockdown impact. Intermittent social distancing. Undetected US cases. NYC hospitalization characteristics. Adapting veterinary surveillance. Infectious disease” hospital. NIH vaccine and treatment partnership. Repurposing anesthetic machines as ventilators. Guidance for psychiatrists. Elective surgery risk stratification. Hemodialysis facility. Pathologist on IgG/M tests. Abnormal coagulation and ECMO. Paramedic guidance. Dialysis and transplants. Critically ill management. GI guidance. Otorhinolaryngology head & neck surgery. Emergency nursing management. Lung surgery. Metabolic & bariatric surgery. Convalescent plasma therapy effectiveness. Potential antivirals. UK testing. Spike proteins for potential vaccine. Cytokines suggest IL-6 antagonist treatments. Mental health messaging. $483 million for mRNA-1273 vaccine trial. WHO unsure about antibody protection. Complications for IBD. Hospitalizations characterized. Social distancing and personality. Digital COVID-19 literature database available

Multiple introductions of multidrug-resistant typhoid associated with acute infection and asymptomatic carriage, Kenya.

BackgroundUnderstanding the dynamics of infection and carriage of typhoid in endemic settings is critical to finding solutions to prevention and control.MethodsIn a 3-year case-control study, we investigated typhoid among children aged Results148 S. Typhi isolates from cases and 95 from controls (stool culture) were identified; a carriage frequency of 1 %. Whole-genome sequencing showed 97% of cases and 88% of controls were genotype 4.3.1 (Haplotype 58), with the majority of each (76% and 88%) being multidrug-resistant strains in three sublineages of the H58 genotype (East Africa 1 (EA1), EA2, and EA3), with sequences from cases and carriers intermingled.ConclusionsThe high rate of multidrug-resistant H58 S. Typhi, and the close phylogenetic relationships between cases and controls, provides evidence for the role of carriers as a reservoir for the community spread of typhoid in this setting.FundingNational Institutes of Health (R01AI099525); Wellcome Trust (106158/Z/14/Z); European Commission (TyphiNET No 845681); National Institute for Health Research (NIHR); Bill and Melinda Gates Foundation (OPP1175797)

2020-04-15 DAILY UNM GLOBAL HEALTH COVID-19 BRIEFING

Executive Summary: Daily NM recap. NM Hospital financial challenges. NM absentee voting. NM dairy farmers impact. 19-20 states open May 1? USA halts WHO funding. More NYC deaths. 250K tests AZ first responders. Global pandemic updates. Imported cases China. Masked South Korea elections. Danish children school return. PPE angiography. NYC cancels healthcare workers. GI shedding endoscopes. Blockade reduces transmission. Fever screening. Viral shedding post seroconversion. Radiology mitigations. Endoscopy units. Tracheostomy reduced transmission. Survivors plasma. Medical Imaging. Useful CTs. Electrophysiology procedures. Renin angiotensin blockers. Hemostasis. Dermatologic surgery. Pediatric gastroenterology. Autoimmune liver disease. Orthopedic surgical care. Updated treatment evidence. Asymptomatic detection. CVD pharmacology. Bleach disinfection. Arbidol beats lopinavir/ritonavir. IV immunoglobulin therapy. No HCQ clinical efficacy. Cepharantine inhibition pangolins. Machine learning antivirals. Eat bitter substances. 59 new trials. Combining RNA and antibody tests. No SARS-CoV-2 in patient ward air. Influenza impact prevention. Encephalitis. Low CD4+ and CD8+ severe. G6PD-deficient issues. Cytokine storm. Biosensor detection. Immunopathogenesis

2020-04-14 DAILY UNM GLOBAL HEALTH COVID-19 BRIEFING

Executive Summary: NMDOH county demographics online. NM emergency business loans. ABQ businesses violations. NM 5 new deaths 62 more cases. May 1 reopening too optimistic. MA contract tracing. Federal Ventilator Reserve. GM mass ventilator production. Ventilator-sharing device. $400M N-95 mask sterilization 60 sites. UNM PPE reprocessing online. Drug quality vulnerable. Managing urgent airway calls. Social distancing until 2022. SARS-Cov-2 blood supply. Contact tracing national blueprint. Mental health endangered. Successful surgical rapid response. Contact tracing medical ethics. Animal coronaviruses: human lessons. IDSA management guidelines. Ophthalmic practice. Pain management. Obstetrics management. Oncology practice. Forward triage. Scoring time-sensitive procedures. Outpatient structural heart disease. Thoracic surgery outcomes. Chest CT screening: epidemics. Sarcoma management. Endocrine diseases. Clinical pharmacists\u27 strategies. Non-invasive ventilation benefits. Essential laboratory testing. Psychiatric service. Hydroxychloroquine negative RCT. JAMA pharmacologic Tx review. Convalescent plasma. Promising antivirals. 55 clinical trials today. NYC hospitalization risk factors. Children milder disease. Blood morphology anomalies. No antimalarial consensus

2020-04-11/12 DAILY UNM GLOBAL HEALTH COVID-19 BRIEFING

Executive Summary: No NM church gatherings. NM a testing champ. Consolidation of elderly care. NM case update. 50-state disaster. Ventilator haggling. Economy reopening planning. PPE decontamination. Hospital ward contamination. Prolonged return to normal. FEMA projections. WHO tracking app. China SEIR model. Hubei epi. Mortality best measure. Covid-19 wave 2. Public should wear masks. Civil liberties. Safe grocery shopping. School closure impact. CDC caretaker guidelines. Psychiatric mobilization. Keep newborns with mom. C-section protocol. Italian obstetrics. Pediatric cardiac catherization. Chinese anesthesiology consensus. Cancer guidelines. Neuro-oncologic Tx. Radiology algorithm. Lung ultrasonography. ARF care. VTE common and predictable. Liver transplantation. Auto-immune treatments. Extracorporeal kidney involvement. Nutrition support. GI endoscopy. No stay-at-home for stroke. Intensive care collaboration. Supine swab collection. Lab tests for severity. Testing assay performance. False negative RT-PCR tests. IgM and IgG serum tests. FDA convalescent plasma. Blood purification device approval. Erythropoietin treatment. Tissue plasminogen activator. ECMO. Lopinavir/ritonavir study results. Immunotherapy review. Vaccine development. Hydroxychloroquine review. Candidates from in silico/virtual screening. Traditional Indian therapies. US trials update. Pathways and risk factors for death. ACE2 polymorphism. Severity in children. Lung tissue replication. Phylogenetic tracing. Text mining dataset. Risk by blood type

2020-04-10 DAILY UNM GLOBAL HEALTH COVID-19 BRIEFING

Executive Summary: Extra NM HSD SNAP benefits. NM cases \u3e1000. Meds supply chain threatened. Mass graves in NY. Surgeon General screening app. Presidential briefing. Italian healthcare worker deaths. Taiwan tiered care model. Communicating risks to public. French public demand hydroxychloroquine. Vaccination pause dangers. Retesting needed after discharge. CDC report geography and incidence. UW clinical informatics response. UW preparedness guidelines. Wuhan outbreak control. CDC asymptomatic exposed worker guidelines. Mask innovation. Unemployment spikes. Workforce gaps. Workspace modifications reduce transmission. Guidelines and recommendations: ER physician, surgery, cardiopulmonary resuscitation, chest imaging, geriatrics, critically ill children, postpyloric tube placement, genitourinary malignancies, obstetrics, and home work health. Remdesivir clinically promising. Hydroxychloroquine safe but higher mortality with azithromycin. Lockdown health risks. Post-ICU syndrome. Tetracyline therapy potential. ACE2 review. Repurposing candidates. Patient self-triage tool. Video of aerosol spread and lingering. Modeling challenges. 34 new clinical trials registered today

Impact of RTS,S/AS02A and RTS,S/AS01B on Genotypes of P. falciparum in Adults Participating in a Malaria Vaccine Clinical Trial

Objective:RTS,S, a candidate vaccine for malaria, is a recombinant protein expressed in yeast containing part of the circumsporozoite protein (CSP) sequence of 3D7 strain of Plasmodium falciparum linked to the hepatitis B surface antigen in a hybrid protein. The RTS,S antigen is formulated with GSK Biologicals\u27 proprietary Adjuvant Systems AS02A or AS01B. A recent trial of the RTS,S/AS02A and RTS,S/AS01B vaccines evaluated safety, immunogenicity and impact on the development of parasitemia of the two formulations. Parasite isolates from this study were used to determine the molecular impact of RTS,S/AS02A and RTS,S/AS01B on the multiplicity of infection (MOI) and the csp allelic characteristics of subsequent parasitemias.Design:The distribution of csp sequences and the MOI of the infecting strains were examined at baseline and in break-through infections from vaccinated individuals and from those receiving a non-malarial vaccine.Setting:The study was conducted in Kombewa District, western Kenya.Participants:Semi-immune adults from the three study arms provided isolates at baseline and during break-through infections.Outcome:Parasite isolates used for determining MOI and divergence of csp T cell&ndash;epitopes were 191 at baseline and 87 from break-through infections.Results:Grouping recipients of RTS,S/AS01A and RTS,S/AS02B together, vaccine recipients identified as parasite-positive by microscopy contained significantly fewer parasite genotypes than recipients of the rabies vaccine comparator (median in pooled RTS,S groups: 3 versus 4 in controls, P = 0.0313). When analyzed separately, parasitaemic individuals in the RTS,S/AS01B group, but not the RTS,S/AS02A group, were found to have significantly fewer genotypes than the comparator group. Two individual amino acids found in the vaccine construct (Q339 in Th2R and D371 in Th3R) were observed to differ in incidence between vaccine and comparator groups but in different directions; parasites harboring Q339 were less common among pooled RTS,S/AS vaccine recipients than among recipients of rabies vaccine, whereas parasites with D371 were more common among the RTS,S/AS groups.Conclusions:It is concluded that both RTS,S/AS vaccines reduce multiplicity of infection. Our results do not support the hypothesis that RTS,S/AS vaccines elicit preferential effects against pfcsp alleles with sequence similarity to the 3D7 pfcsp sequence employed in the vaccine construct

Reframing Non-Communicable Diseases and Injuries for Equity in the Era of Universal Health Coverage: Findings and Recommendations from the Kenya NCDI Poverty Commission.

Background: Kenya has implemented a robust response to non-communicable diseases and injuries (NCDIs); however, key gaps in health services for NCDIs still exist in the attainment of Universal Health Coverage (UHC). The Kenya Non-Communicable Diseases and Injury (NCDI) Poverty Commission was established to estimate the burden of NCDIs, determine the availability and coverage of health services, prioritize an expanded set of NCDI conditions, and propose cost-effective and equity-promoting interventions to avert the health and economic consequences of NCDIs in Kenya. Methods: Burden of NCDIs in Kenya was determined using desk review of published literature, estimates from the Global Burden of Disease Study, and secondary analysis of local health surveillance data. Secondary analysis of nationally representative surveys was conducted to estimate current availability and coverage of services by socioeconomic status. The Commission then conducted a structured priority setting process to determine priority NCDI conditions and health sector interventions based on published evidence. Findings: There is a large and diverse burden of NCDIs in Kenya, with the majority of disability-adjusted life-years occurring before age of 40. The poorest wealth quintiles experience a substantially higher deaths rate from NCDIs, lower coverage of diagnosis and treatment for NCDIs, and lower availability of NCDI-related health services. The Commission prioritized 14 NCDIs and selected 34 accompanying interventions for recommendation to achieve UHC. These interventions were estimated to cost $11.76 USD per capita annually, which represents 15% of current total health expenditure. This investment could potentially avert 9,322 premature deaths per year by 2030. Conclusions and Recommendations: An expanded set of priority NCDI conditions and health sector interventions are required in Kenya to achieve UHC, particularly for disadvantaged socioeconomic groups. We provided recommendations for integration of services within existing health services platforms and financing mechanisms and coordination of whole-of-government approaches for the prevention and treatment of NCDIs