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Atis Muehlenbachs

Centers for Disease Control and Prevention

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Patrick E. Duffy

National Institute of Malaria Research

Michal Fried

National Institute of Allergy and Infectious Diseases

Jana M. Ritter

Centers for Disease Control and Prevention

Julu Bhatnagar

Centers for Disease Control and Prevention

Theonest K. Mutabingwa

Hubert Kairuki Memorial University

Sherif R. Zaki

Centers for Disease Control and Prevention

Rose McGready

Mahidol Oxford Tropical Medicine Research Unit

Wun‐Ju Shieh

Centers for Disease Control and Prevention

Cynthia S. Goldsmith

Centers for Disease Control and Prevention

François Nosten

Shoklo Malaria Research Unit

Cooperative Institutions

Centers for Disease Control and Prevention

National Center for Emerging and Zoonotic Infectious Diseases

Center for Surveillance, Epidemiology, and Laboratory Services

University of Washington

New York State Department of Health

University of California, San Francisco

Epidemic Intelligence Service

New York City Department of Health and Mental Hygiene

Emory University

AID Atlanta

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Zika Virus RNA Replication and Persistence in Brain and Placental Tissue

Emerging infectious diseases (2016)

Julu Bhatnagar D. Brett Rabeneck Roosecelis B. Martines Sarah Reagan-Steiner Yokabed Ermias

Zika virus is causally linked with congenital microcephaly and may be associated with pregnancy loss. However, the mechanisms of Zika virus intrauterine transmission and replication and its tropism and persistence in tissues are poorly understood. We tested tissues from 52 case-patients: 8 infants with microcephaly who died and 44 women suspected of being infected with Zika virus during pregnancy. By reverse transcription PCR, tissues from 32 (62%) case-patients (brains from 8 infants with microcephaly and placental/fetal tissues from 24 women) were positive for Zika virus. In situ hybridization localized replicative Zika virus RNA in brains of 7 infants and in placentas of 9 women who had pregnancy losses during the first or second trimester. These findings demonstrate that Zika virus replicates and persists in fetal brains and placentas, providing direct evidence of its association with microcephaly. Tissue-based reverse transcription PCR extends the time frame of Zika virus detection in congenital and pregnancy-associated infections.

Zika Virus

Microcephaly

Tissue tropism

10.3201/eid2303.161499

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Citations (202)

Viruses and Man: A History of Interactions

Clinical Infectious Diseases (2015)

Atis Muehlenbachs

10.1093/cid/civ222

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Citations (20)

Submicroscopic malaria infection during pregnancy and the impact of intermittent preventive treatment

Malaria Journal (2014)

Lauren M. Cohee Linda Kalilani‐Phiri Sarah Boudová Sudhaunshu Joshi Rabia A. G. Mukadam

Malaria during pregnancy results in adverse outcomes for mothers and infants. Intermittent preventive treatment (IPT) with sulphadoxine-pyrimethamine (SP) is the primary intervention aimed at reducing malaria infection during pregnancy. Although submicroscopic infection is common during pregnancy and at delivery, its impact throughout pregnancy on the development of placental malaria and adverse pregnancy outcomes has not been clearly established. Quantitative PCR was used to detect submicroscopic infections in pregnant women enrolled in an observational study in Blantyre, Malawi to determine their effect on maternal, foetal and placental outcomes. The ability of SP to treat and prevent submicroscopic infections was also assessed. 2,681 samples from 448 women were analysed and 95 submicroscopic infections were detected in 68 women, a rate of 0.6 episodes per person-year of follow-up. Submicroscopic infections were most often detected at enrolment. The majority of women with submicroscopic infections did not have a microscopically detectable infection detected during pregnancy. Submicroscopic infection was associated with placental malaria even after controlling for microscopically detectable infection and was associated with decreased maternal haemoglobin at the time of detection. However, submicroscopic infection was not associated with adverse maternal or foetal outcomes at delivery. One-third of women with evidence of placental malaria did not have documented peripheral infection during pregnancy. SP was moderately effective in treating submicroscopic infections, but did not prevent the development of new submicroscopic infections in the month after administration. Submicroscopic malaria infection is common and occurs early in pregnancy. SP-IPT can clear some submicroscopic infections but does not prevent new infections after administration. To effectively control pregnancy-associated malaria, new interventions are required to target women prior to their first antenatal care visit and to effectively treat and prevent all malaria infections.

10.1186/1475-2875-13-274

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Routine argyrophil techniques detectRickettsia rickettsiiin tissues of patients with fatal Rocky Mountain spotted fever

Journal of Histotechnology (2016)

Christopher D. Paddock Jeanine H. Sanders Amy M. Denison Atis Muehlenbachs Sherif R. Zaki

Rickettsia rickettsii, a bacterial tickborne pathogen that causes Rocky Mountain spotted fever (RMSF), stains poorly or not at all with conventional tissue Gram techniques, and contemporary visualization of the pathogen in formalin-fixed, paraffin-embedded tissues has relied almost entirely on immunohistochemical staining methods that are generally limited to specialized research laboratories or national reference centers. To our knowledge, previously described argyrophil-based histochemical techniques have not successfully detected rickettsiae in formalin-fixed, paraffin-embedded tissues. To investigate the ability of standard silver impregnation techniques to demonstrate the occurrence and distribution of R. rickettsii in tissues of patients with RMSF confirmed by molecular and immunohistochemical methods, three widely recognized and commercially available silver impregnation methods (Warthin–Starry, Steiner, and Dieterle's) were applied to various tissues obtained at autopsy from 10 patients with fatal RMSF. R. rickettsii bacteria were demonstrated in one or more tissues of all patients, using each of the argyrophil-based methods, and appeared as small, dark brown-to-black lanceolate rods, often in pairs and occasionally surrounded by a faint halo. Rickettsiae were identified most consistently in small arteries and arterioles of liver, kidney, and leptomeninges, and were localized predominantly to the cytoplasm of endothelial cells and less often within the internal elastic lamella and smooth muscle of the media. This validation of argyrophilic techniques to detect R. rickettsii demonstrates the utility of inexpensive core histochemical methods in the diagnosis of infectious agents in pathology specimens and may have utility in certain resource-limited settings where RMSF is endemic.

Rickettsia rickettsii

10.1080/01478885.2016.1196868

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Citations (2)

Heartland Virus-Associated Death in Tennessee

Clinical Infectious Diseases (2014)

Atis Muehlenbachs Cynthia Fata Amy J. Lambert Christopher D. Paddock Jason O. Velez

Heartland virus (HRTV) is a novel pathogen associated with fever, leukopenia, and thrombocytopenia. An unexplained death investigation identified the first fatal HRTV disease case and first case outside Missouri, broadening the known geographic location and disease severity of HRTV. Background. Heartland virus (HRTV) is a tick-borne phlebovirus recently described in Missouri that is associated with fever, leukopenia, and thrombocytopenia. The virus has also been detected in Ambylomma americanum ticks. Methods. Here we report the first fatal case of HRTV disease in an 80-year-old Tennessee resident. He was hospitalized with fever, confusion, leukopenia, and thrombocytopenia and developed multiorgan failure and hemorrhage. A tick-borne illness was suspected and testing for ehrlichiosis was negative. He died on hospital day 15, and autopsy specimens were tested for various pathogens as part of an unexplained death evaluation. Results. HRTV antigens were detected in postmortem spleen and lymph nodes by immunohistochemistry, and HRTV was detected in premortem blood by reverse transcription polymerase chain reaction and by isolation in cell culture. Conclusions. This case demonstrates that HRTV infection can cause severe disease and death and expands the geographic range of HRTV within the United States.

Leukopenia

Phlebovirus

Ehrlichiosis

myalgia

10.1093/cid/ciu434

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Citations (86)

Hypertension and Maternal–Fetal Conflict during Placental Malaria

PLoS Medicine (2006)

Atis Muehlenbachs Theonest K. Mutabingwa Sally Edmonds Michal Fried Patrick E. Duffy

Malaria and hypertension are major causes of maternal mortality in tropical countries, especially during first pregnancies, but evidence for a relationship between these syndromes is contradictory.In a cross-sectional survey of Tanzanian parturients, the rate of hypertension was similar in placental malaria (PM)-positive (11/85 = 13%) and PM-negative (73/602 = 12%) individuals. However, we found that PM was associated with hypertension in first-time mothers aged 18-20 y but not other mothers. Hypertension was also associated with histologic features of chronic malaria, which is common in first-time mothers. Levels of soluble vascular endothelial growth factor receptor 1 (sVEGFR1), a preeclampsia biomarker, were elevated in first-time mothers with either PM, hypertension, or both, but levels were not elevated in other mothers with these conditions. In first-time mothers with PM, the inflammatory mediator vascular endothelial growth factor (VEGF) was localized to maternal macrophages in the placenta, while sVEGFR1, its soluble inhibitor, was localized to the fetal trophoblast.The data suggest that maternal-fetal conflict involving the VEGF pathway occurs during PM, and that sVEGFR1 may be involved in the relationship between chronic PM and hypertension in first-time mothers. Because placental inflammation causes poor fetal outcomes, we hypothesize that fetal mechanisms that promote sVEGFR1 expression may be under selective pressure during first pregnancies in malaria-endemic areas.

Trophoblast

Endothelial Activation

10.1371/journal.pmed.0030446

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Citations (116)

Exserohilum Infections Associated with Contaminated Steroid Injections

American Journal Of Pathology (2013)

Jana M. Ritter Atis Muehlenbachs Dianna M. Blau Christopher D. Paddock Wun‐Ju Shieh

Exserohilum

10.1016/j.ajpath.2013.05.007

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Citations (53)

Multicompartmental distribution of the tuberous sclerosis gene products, hamartin and tuberin

Archives of Biochemistry and Biophysics (2002)

Yuji Yamamoto Kathryn A Jones Baldwin Mak Atis Muehlenbachs Raymond S. Yeung

TSC1

TSC2

Cell fractionation

10.1016/s0003-9861(02)00300-4

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Citations (37)

Viral Encephalomyelitis

Elsevier eBooks (2015)

Clifton P. Drew Atis Muehlenbachs Sherif R. Zaki

Encephalomyelitis

10.1016/b978-1-4377-0762-5.00008-5

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High-Quality Parasitic Disease Laboratory Services Are a Priority at the CDC

American Journal of Tropical Medicine and Hygiene (2022)

Anne Purfield Jay C. Butler Kevin P. Cain Wendi L. Kuhnert Atis Muehlenbachs

10.4269/ajtmh.22-0235

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