bluuebunny/crossref_metadata_2025 huggingface dataset:
Leishmania (Viannia) guyanensis Induces Low Immunologic Responsiveness in Leishmaniasis Patients from an Endemic Area of the Brazilian Amazon Highland
Authors: Matta Nubia Estela , Nogueira Ricardo S. , Franco Antonia Maria Ramos , de Souza e Souza Ilner , Mattos Marise S. , Oliveira-Neto Manoel P. , Coutinho Sergio G. , Leon Leonor L. , Da-Cruz Alda Maria
Published: September 2018

Cutaneous leishmaniasis caused by Leishmania (Viannia) guyanensis (CL-Lguy) is endemic in the Brazilian Amazon, differing from L. braziliensis infection in clinical, diagnostic, and therapeutic aspects. T-cell reactivity to leishmanial antigens possibly involved in the pathogenesis of CL-Lguy was studied herein. Variable lymphoproliferative responses (LPRs) to Leishmania antigens were found among the 23 studied patients, and 50% of them showed low or no response to these antigens. Active disease was associated with an enrichment of leishmanial-reactive T lymphocytes, mainly TCD4+. High and low interferon (IFN)-γ producers were observed. TNF-α, interleukin (IL)-10, and IL-5 were consistently detected. CL-Lguy displayed low antibody response in comparison to L. braziliensis patients. CL caused by L. braziliensis presented positive LPRs and higher IFN-γ production but undetectable IL-5. L. guyanensis seems to induce a down-regulation of the immune system compared with L. braziliensis. This finding could explain some aspects of clinical presentation of CL-Lguy, such as high tissue parasite burden and frequent resistance to therapy.
Longitudinal Seroepidemiologic Study of Visceral Leishmaniasis in Hyperendemic Regions of Bihar, India
Authors: Gidwani Kamlesh , Kumar Rajiv , Rai Madhukar , Sundar Shyam
Published: September 2018

We conducted a seroepidemiologic study of visceral leishmaniasis (VL) in hyperendemic communities in Bihar, India, to determine its seroprevalence. A direct agglutination test (DAT) and rK39 antigen strip test were used as serologic tests. Capillary blood samples were collected on filter papers from 870 healthy persons (574 and 296 from households with or without VL, respectively). Of these persons, 230 (26.43%) were positive by DAT (titer > 1:1,600) and 120 (13.79%) were positive by the rK39 antigen strip test. During a two-year follow-up, 25 persons developed VL; 1 and 8 persons were positive by the rK39 strip test and DAT, respectively, and 1 was positive by both tests. Fifteen (2.57%) persons who were seronegative at baseline also developed VL. Disease occurred more among persons living in the same household (24 of 25). However, there was no significant difference in disease conversion among children (5–15 years of age) and adults (> 15 years of age). Seropositivity among asymptomatic persons is not a predictor for development of VL.
Multilevel Modeling of Household Contextual Determinants of Tuberculin Skin Test Positivity among Contacts of Infectious Tuberculosis Patients, Umerkot, Pakistan
Authors: Akhtar Saeed , Rathi Suresh K.
Published: September 2018

This cross-sectional study sought to identify household contextual determinants that might be associated with Mycobacterium tuberculosis infection as assessed by tuberculin skin test (TST) positivity among familial contacts of index patients of infectious pulmonary tuberculosis (TB) while controlling for the effects of individual-level factors. We analyzed data on TST results on 359 household contacts of 77 index cases of acid-fast bacilli (AFB) sputum smear-positive pulmonary TB using multilevel logistic regression analysis with characteristics of household contacts at the first level and that of households at the second level. The prevalence of M. tuberculosis infection as assessed by TST positivity among household contacts of index TB patients was 49.9% (179/359). After taking into account the individual-level risk factors, household-level contextual determinants significantly associated with contact’s TST positivity were gender of index TB patient (adjusted odds ratio [OR] = 2.2; 95% confidence interval [CI]: 1.3–3.9%) and density of AFB sputum smear (adjusted OR = 3.2; 95% CI: 1.9–5.5%). Household variances in multilevel models indicated significant inter-household heterogeneity in TST positivity among contacts. This study provided the evidence for substantive effects of household-level contextual variables on the TST positivity among contacts of index TB patients. Thus, both individual-level and household-level characteristics need to be taken into account while prioritizing contacts for investigations to improve TB control and prevention in resource-constrained countries such as Pakistan.
Spatial Stratification of House Infestation by Triatoma infestans in La Rioja, Argentina
Authors: Gorla David E. , Porcasi Ximena , Hrellac Hugo , Catalá Silvia S.
Published: September 2018

Vectorial transmission of Chagas disease has been decreasing over the past few decades because of effective vector control programs in the southern cone of South America. However, the disease is still actively transmitted within the Gran Chaco region. In this area, vector populations are abundant and highly prevalent in poor rural houses. This study analyses the spatial pattern of rural house infestation by Triatoma infestans in a 56,000 km2 area in the province of La Rioja, Argentina, before the re-initiation of systematic activity on vector control intervention. Data on 5,045 rural houses show that infestation has high spatial heterogeneity, with highly infested localities concentrated in a few areas. House infestation has a negative significant relationship with locality size. Rural houses in the region are highly dispersed and this feature has been and will remain a challenge for any vigilance system to be installed in the region.
Simulation Models Examining the Effect of Brugian Filariasis on Dengue Epidemics
Authors: Vaughan Jefferson A. , Focks Dana A. , Turell Michael J.
Published: September 2018

Concurrent ingestion of microfilariae (mf) and arboviruses by mosquitoes can enhance the transmission of virus compared with when virus is ingested alone. We studied the effect of mf enhancement on the extrinsic incubation period (EIP) of dengue 1 virus within Aedes aegypti mosquitoes by feeding mosquitoes on blood that either contained virus plus Brugia malayi mf or virus only. Mosquitoes were sampled over time to determine viral dissemination rates. Co-ingestion of mf and virus reduced viral EIP by over half. We used the computer simulation program, DENSiM, to compare the predicted patterns of dengue incidence that would result from such a shortened EIP versus the EIP derived from the control (i.e., virus only) group of mosquitoes. Results indicated that, over the 14-year simulation period, mf-induced acceleration of the EIP would generate more frequent (but not necessarily more severe) epidemics. Potential interactions between arboviruses and hematozoans deserve closer scrutiny.
A Pilot Program of Mass Surgery Weeks for Treatment of Hydrocele Due to Lymphatic Filariasis in Central Nigeria
Authors: Thomas Gail , Richards Frank O. , Eigege Abel , Dakum Nuhu K. , Azzuwut Martin P. , Sarki John , Gontor Ibrahim , Abimiku Jacob , Ogah Gladys , Jindau Munirah Y. , Jiya Jonathan Y. , Miri Emmanuel S.
Published: September 2018

In a pilot program of mass surgery weeks (MSW) to provide hydrocelectomy services to men with filarial scrotal hydrocele, local general practitioners performed 425 surgical repairs in 301 men in five MSW in three rural Nigerian community hospitals between 2002 and 2005. The most common (94%) procedure used was the eversion technique, which was most familiar to the practitioners. Postoperative complications included hematoma (3.7%) and infection (3%), and there was one death from infection in an elderly man with previously unrecognized diabetes. In 115 patients (38%) followed for 1 to 3 years, the hydrocele recurrence rate was 7%. The eversion technique gives an acceptable outcome, and MSW are safe and effective if strict attention is paid to preoperative screening of candidates and asepsis.
Childhood Coinfections with Plasmodium falciparum and Schistosoma mansoni Result in Lower Percentages of Activated T Cells and T Regulatory Memory Cells than Schistosomiasis Only
Authors: Mouk Erick M. O. , Mwinzi Pauline N. M. , Black Carla L. , Carter Jennifer M. , Ng’ang’a Zipporah W. , Gicheru Michael M. , Secor W. Evan , Karanja Diana M. S. , Colley Daniel G.
Published: September 2018

Flow cytometric analyses were performed to evaluate HLA-DR + activated T lymphocytes (Tact; CD3 +/CD4 +/CD25medium) and T regulatory cells (Treg; CD3 +/CD4+/CD25high) in the circulation of children 8–10 years of age living in an area endemic for both Plasmodium falciparum and Schistosoma mansoni in western Kenya. Those children with only S. mansoni had a higher mean percentage of HLA-DR + Tact than those who were co-infected with these two intravascular parasites. The proportion of circulating Treg was comparable in children with only schistosomiasis and both schistosomiasis and malaria. However, the mean level of memory Treg (Treg expressing CD45RO +) in those with dual infections was lower than in children with schistosomiasis alone. These imbalances in Tact and Treg memory subsets in children infected with both schistosomiasis and malaria may be related to the differential morbidity or course of infection attributed to coinfections with these parasites.
ADAMTS13 Deficiency with Elevated Levels of Ultra-Large and Active von Willebrand Factor in P. falciparum and P. vivax Malaria
Authors: de Mast Quirijn , Groot Evelyn , Asih Puji B. , Syafruddin Din , Oosting Marije , Sebastian Silvie , Ferwerda Bart , Netea Mihai G. , de Groot Philip G. , van der Ven Andre J. A. M. , Fijnheer Rob
Published: September 2018

A deficiency in ADAMTS13 (a von Willebrand factor [VWF] cleaving protease) is associated with accumulation of prothrombogenic unusually large VWF multimers (UL-VWF) in plasma. We studied VWF release and proteolysis in patients with symptomatic Plasmodium falciparum or P. vivax malaria on the Indonesian island Sumba. Malaria patients had significantly lower platelet counts and higher VWF concentrations and VWF activation factors than healthy hospital staff controls. The latter indicates that a higher amount of circulating VWF was in a conformation enabling spontaneous platelet binding. In addition, ADAMTS13 activity and antigen levels were reduced in both malaria groups, and this was associated with the appearance of UL-VWF. The mechanism behind this reduction and the role in malaria pathogenesis needs to be further elucidated. In malaria, endothelial cell activation with increased circulating amounts of active and ultra-large VWF, together with reduced VWF inactivation by ADAMTS13, may result in intravascular platelet aggregation, thrombocytopenia, and microvascular disease.
Monkeypox or Varicella? Lessons from a Rash Outbreak Investigation in the Republic of the Congo
Authors: MacNeil Adam , Reynolds Mary G. , Carroll Darin S. , Karem Kevin , Braden Zach , Lash Ryan , Moundeli Amba , Mombouli Jean-Vivien , Jumaan Aisha O. , Schmid D. Scott , Damon Inger K.
Published: September 2018

Monkeypox virus and varicellazoster virus (VZV) cause visually similar rash illnesses. Monkeypox is more virulent, with fatality rates up to 10%. In June 2007, reports were received of a rash illness outbreak in isolated villages in Likouala district, Republic of the Congo. Blood specimens were obtained from 142 individuals reporting rash illness between January and September 2007 from four villages in Likouala. Thirty-seven cases of probable VZV were identified based on low VZV IgG avidity; cases occurred in all four villages. No probable monkeypox cases with orthopoxvirus-positive IgM responses were observed; however, three possible monkeypox cases, in individuals < 26 years of age, with rash illness occurring > 56 days before sampling and positive orthopoxvirus-specific IgG responses, were identified. Remoteness and delays in reporting limited collection of acute diagnostic specimens. Improvements in rash illness surveillance and infection control, through training of health workers and timely acquisition of diagnostic specimens, are being undertaken.
Five-Year Surveillance of Molecular Markers of Plasmodium falciparum Antimalarial Drug Resistance in Korogwe District, Tanzania: Accumulation of the 581G Mutation in the P. falciparum Dihydropteroate Synthase Gene
Authors: Alifrangis Michael , Lusingu John P. , Mmbando Bruno , Dalgaard Michael B. , Vestergaard Lasse S. , Ishengoma Deus , Khalil Insaf F. , Theander Thor G. , Lemnge Martha M. , Bygbjerg Ib C.
Published: September 2018

In January 2007, Tanzania replaced sulfadoxine-pyrimethamine (SP) with artemether-lumefantrine for treatment of uncomplicated malaria. This study examined the impact of widespread SP use on molecular markers of Plasmodium falciparum drug resistance in blood samples from persons living in two villages in Korogwe District, Tanzania, from 2003 through 2007. The prevalence of the P. falciparum dihydropteroate synthase (Pfdhps) gene 581G mutation increased from 12% in 2003 to 56% in 2007 (P < 0.001), resulting in an increase in the triple mutant Pfdhps haplotype SGEGA from 8% to 32% (P < 0.001). In contrast, the chloroquine-sensitive P. falciparum chloroquine resistance transporter (Pfcrt) CVMNK haplotype increased from 6% to 30% (P < 0.001). The dramatic increase of the triple Pfdhps mutant SGEGA haplotype may endanger the continued use of SP for intermittent presumptive treatment of pregnant women (IPTp). Further studies are needed to determine the importance of Pfdhps SGEGA haplotype parasites on the efficacy of SP for IPTp.
Cerebral Malaria Is Associated with Low Levels of Circulating Endothelial Progenitor Cells in African Children
Authors: Gyan Ben , Goka Bamenla Quarm , Adjei George O. , Tetteh John K. A. , Kusi Kwadwo Asamoah , Aikins Anastasia , Dodoo Daniel , Lesser Martin L. , Sison Cristina P. , Das Sanchita , Howard Marion E. , Milbank Elizabeth , Fischer Kimberly , Rafii Shahin , Jin David , Golightly Linnie M.
Published: September 2018

Damage to the cerebral microvasculature is a feature of cerebral malaria. Circulating endothelial progenitor cells are needed for microvascular repair. Based on this knowledge, we hypothesized that the failure to mobilize sufficient circulating endothelial progenitor cells to the cerebral microvasculature is a pathophysiologic feature of cerebral malaria. To test this hypothesis, we compared peripheral blood levels of CD34 +/VEGFR2+ and CD34 +/CD133+ cells and plasma levels of the chemokine stromal cell–derived growth factor 1 (SDF-1) in 214 children in Accra, Ghana. Children with cerebral malaria had lower levels of CD34 +/VEGFR2+ and CD34 +/CD133+ cells compared with those with uncomplicated malaria, asymptomatic parasitemia, or healthy controls. SDF-1 levels were higher in children with acute malaria compared with healthy controls. Together, these results uncover a potentially novel role for endothelial progenitor cell mobilization in the pathophysiology of cerebral malaria.
Effect of Oral Treatment with Pyrazole Carbohydrazide Derivatives against Murine Infection by Leishmania amazonensis
Authors: Charret Karen S. , Rodrigues Raquel F. , Bernardino Alice M. R. , Gomes Adriana O. , Carvalho Adriana V. , Canto-Cavalheiro Marilene M. , Leon Leonor , Amaral Veronica F.
Published: September 2018

Newly synthesized pyrazole carbohydrazide derivatives with substituents X = Br/Y = NO2 and X = NO2/Y = Cl were independently investigated in the CBA mouse model of cutaneous leishmaniasis. Animals were infected with Leishmania amazonensis and treated two weeks after the parasitic infection with the pyrazole carbohydrazides for 45 days. Oral treatment with both compounds controlled evolution of footpad cutaneous lesions and dissemination of parasites to draining lymph nodes. Nitric oxide generation was observed in supernatants of lymph node cells from infected CBA mice that were treated with these compounds. The pyrazole carbohydrazide derivatives did not show any toxicity or cause alterations in body weight, plasma concentrations of alanine aminotransferase and aspartate aminotransferase, and urinary creatinine levels, but promoted a small decrease in blood neutrophils. These results provide new perspectives on the development of drugs with activities against leishmaniasis.
Cotrimoxazole for Treatment of Cerebral Toxoplasmosis: An Observational Cohort Study during 1994–2006
Authors: Béraud Guillaume , Pierre-François Sandrine , Foltzer Adeline , Abel Sylvie , Liautaud Bernard , Smadja Didier , Cabié André
Published: September 2018

Cotrimoxazole (trimethoprim/sulfamethoxazole [TMP-SMX]) is an alternative treatment for toxoplasmic encephalitis because it is inexpensive, well-tolerated, and as effective as pyrimethamine-sulfadiazine, which is the first-line drug regimen). We report results of a large cohort study of patients with acquired immunodeficiency syndrome who were treated for toxoplasmic encephalitis with cotrimoxazole. The mean follow-up period was more than three years. Our results confirm that cotrimoxazole is effective (85.5%), with a relatively low incidence of side effects (22%; 7.4% requiring treatment interruption). Relapse occurred in 30.1% of the patients at a mean ± SD of 7.8 ± 16.2 months after the first episode. The only risk factor for relapse was poor treatment and/or prophylaxis adherence. Mortality was significantly higher (P < 0.05) before 1996 than after 1996 (the era of highly active antiretroviral therapy). There was a non-significant trend towards a higher rate of relapse among patients treated before 1996 (P = 0.06). Consequently, cotrimoxazole could be a first-line drug regimen for curative treatment and prophylaxis of toxoplasmic encephalitis.
First Report of Lutzomyia (Nyssomyia) neivai (Diptera: Psychodidae: Phlebotominae) Naturally Infected by Leishmania (Viannia) braziliensis in a Periurban Area of South Brazil Using a Multiplex Polymerase Chain Reaction Assay
Authors: Pita-Pereira Daniela , Souza Getúlio D. , Zwetsch Adriana , Alves Carlos Roberto , Britto Constança , Rangel Elizabeth F.
Published: September 2018

To identify Lutzomyia (Nyssomyia) neivai naturally infected by Leishmania a multiplex polymerase chain reaction (PCR) was used for the analysis of 450 specimens (270 females, 180 males) collected in an endemic periurban area of cutaneous leishmaniasis in Porto Alegre, Brazil. Insects were grouped into pools of 10 and positive results were achieved in 3/27 Lu. (N.) neivai female pools. Infection by L. (Viannia) braziliensis was confirmed after hybridizing PCR products with a subgenus–specific biotinylated probe. Considering the detection of three positive pools with at least one infected insect in each, an infection rate of 1.1% was estimated. Our results associated with epidemiologic data suggest a potential ability of Lu. (N.) neivai in transmitting L. braziliensis in Porto Alegre, where the first notifications of autochthonous cutaneous leishmaniasis in humans occurred in 2002, with an increase in the number of cases in recent years possibly as a consequence of deforestation and agricultural activities in the area.
Increasing Incidence of Rocky Mountain Spotted Fever among the American Indian Population in the United States
Authors: Holman Robert C. , McQuiston Jennifer H. , Haberling Dana L. , Cheek James E.
Published: September 2018

To examine trends of Rocky Mountain spotted fever (RMSF) incidence among American Indians compared with other race groups, a retrospective analysis of national RMSF surveillance data reported to the National Electronic Telecommunications System for Surveillance and the Tickborne Rickettsial Disease Case Report Forms system were used. The RMSF incidence for American Indians, which was comparable to those for other race groups during 1990–2000, increased at a disproportionate rate during 2001–2005. The average annual incidence of RMSF reported among American Indians for 2001–2005 was 16.8 per 1,000,000 persons compared with 4.2, 2.6, and 0.5 for white, black, and Asian/Pacific Islander persons, respectively. Most cases in American Indians were reported from Oklahoma (113.1 cases per 1,000,000), North Carolina (60.0), and Arizona (17.2). The incidence of RMSF increased dramatically among American Indians disproportionately to trends for other race groups. Education about tick-borne disease and prevention measures should be addressed for high-risk American Indian populations.
An Automated Dengue Virus Microneutralization Plaque Assay Performed in Human Fcγ Receptor-expressing CV-1 Cells
Authors: Shanaka W. W. , Rodrigo I. , Alcena Danielle C. , Rose Robert C. , Jin Xia , Schlesinger Jacob J.
Published: September 2018

We describe microneutralization assays that used automated 96-well enzyme-linked immunospot (ELI-SPOT) readout instrumentation to measure human anti-dengue virus (DENV) antibodies in CV-1 cells that were stably transfected to express human FcγRIIA (CD32) using conventional Vero cells as a comparator. Classic plaque reduction neutralization test (PRNT) end-point titers were determined by probit analysis. Neutralization titers against DENV measured in CV-1 transfectants were expressed in terms of both conventional 50% to 90% PRNT end-point titers and differential infectivity of antibody-treated virus in control and CD32-expressing CV-1 cells. Significantly reduced PRNT titers and strikingly heightened infectivity (up to 100-fold) of antibody-treated DENV was observed in CV-1 CD32 transfectants compared with that observed in control CV-1 or Vero cells. Because DENVs may preferentially replicate in CD32-expressing monocytes/macrophages and dendritic cells, in vivo, it is possible that CD32 introduced into a conventional DENV neutralization assay might provide results that better correlate with protection.
Cholera Outbreak in Kenyan Refugee Camp: Risk Factors for Illness and Importance of Sanitation
Authors: Shultz Alvin , Omollo Jared O. , Burke Heather , Qassim Mohamed , Ochieng John B. , Weinberg Michelle , Feikin Daniel R. , Breiman Robert F.
Published: September 2018

An outbreak of watery diarrhea struck within the Kakuma refugee camp in Kenya in April 2005; 418 people were treated, and 4 persons died. Vibrio cholerae O1 was isolated from 33 patients. In June 2005, we conducted a retrospective matched case-control study to define risk factors associated with cholera among camp residents and identify interventions that could prevent further cases and future outbreaks. We identified cases of cholera through medical records at the main health facility in the camp and matched controls (without watery diarrhea since November 2004) to the cases by age category (< 2, 2–4, 5–14, and > 14 years) and location of residence within the camp. Cases were defined as any person of any age with profuse, effortless watery diarrhea (three or more stools in 24 hours). A multivariate model showed that storing drinking water at home in sealed or covered containers was protective against cholera (matched odds ratio [MOR] = 0.49 [0.25, 0.96]), whereas “sharing a latrine with at least three households” (MOR = 2.17 [1.01, 4.68]) and arriving at the Kakuma camp on or after November 2004 (MOR = 4.66 [1.35, 16.05]) were risk factors. Improving sanitation and promoting methods to ensure safe drinking water are likely to be effective measures in moderating future cholera outbreaks in this setting. Higher risks for cholera illness among refugees recently “in-migrated” suggest that there may be value in targeting new arrivals in the camp for risk reduction messages and interventions, such as covered water storage containers, to prevent cholera.
Comparison of Two Active Surveillance Programs for the Detection of Clinical Dengue Cases in Iquitos, Peru
Authors: Rocha Claudio , Morrison Amy C. , Forshey Brett M. , Blair Patrick J. , Olson James G. , Stancil Jeffrey D. , Sihuincha Moises , Scott Thomas W. , Kochel Tadeusz J.
Published: September 2018

Endemic dengue transmission has been documented in the Amazonian city of Iquitos, Peru, since the early 1990s. To better understand the epidemiology of dengue transmission in Iquitos, we established multiple active surveillance systems to detect symptomatic infections. Here we compare the efficacy of distinct community-based (door to door) and school absenteeism–based febrile surveillance strategies in detecting active cases of dengue. Febrile episodes were detected by both systems with equal rapidity after disease onset. However, during the period that both programs were running simultaneously in 2004, a higher number of febrile cases in general (4.52/100 versus 1.64/100 person-years) and dengue cases specifically (2.35/100 versus 1.29/100 person-years) were detected in school-aged children through the community-based surveillance program. Similar results were obtained by direct comparison of 435 participants concurrently enrolled in both programs (P < 0.005). We conclude that, in Iquitos, community-based door-to-door surveillance is a more efficient and sensitive design for detecting active dengue cases than programs based on school absenteeism.
Predicting the Risk of Hantavirus Infection in Beijing, People’s Republic of China
Authors: Zhang Wen-Yi , Fang Li-Qun , Jiang Jia-Fu , Hui Feng-Ming , Glass Gregory E. , Yan Lei , Xu You-Fu , Zhao Wen-Juan , Yang Hong , Liu Wei , Cao Wu-Chun
Published: September 2018

To understand the spatial distribution of hantavirus infections across landscapes and its influencing environment factors in Beijing, People’s Republic of China, rodents captured in this region were examined for hantavirus by reverse transcription–polymerase chain reaction. A total of 1,639 rodents were trapped at 86 randomly selected sites. The overall infection rate for hantavirus was 7.14% in the rodents. Multivariate logistic regression analysis indicated that the natural infection rates for hantavirus in rodents were significantly associated with rice agriculture (odds ratio [OR] = 2.88, 95% confidence interval [CI] = 1.27–30.70), orchards (OR = 1.12, 95% CI = 1.02–5.96), and moderate elevation (OR = 9.83, 95% CI = 2.22–43.55). A risk map was constructed on the basis of these significant factors to predict extension and transmission of infection with hantavirus in this region.
Nigeria’s War on Terror: Fighting Dracunculiasis, Onchocerciasis, Lymphatic Filariasis, and Schistosomiasis at the Grassroots
Authors: Njepuome Ngozi A. , Hopkins Donald R. , Richards Frank O. , Anagbogu Ifeoma N. , Pearce Patricia Ogbu , Jibril Mustapha Muhammed , Okoronkwo Chukwu , Sofola Olayemi T. , Withers P. Craig , Ruiz-Tiben Ernesto , Miri Emmanuel S. , Eigege Abel , Emukah Emmanuel C. , Nwobi Ben C. , Jiya Jonathan Y.
Published: September 2018

Africa’s populous country, Nigeria, contains or contained more cases of dracunculiasis, onchocerciasis, lymphatic filariasis, and schistosomiasis than any other African nation and ranks or ranked first (dracunculiasis, onchocerciasis, schistosomiasis) or third (lymphatic filariasis) in the world for the same diseases. After beginning village-based interventions against dracunculiasis 20 years ago and confronting onchocerciasis a few years later, Nigeria has nearly eliminated dracunculiasis and has provided annual mass drug administration for onchocerciasis to over three quarters of that at-risk population for 7 years. With assistance from The Carter Center, Nigeria began treating lymphatic filariasis and schistosomiasis in two and three states, respectively, over the past decade, while conducting pioneering operational research as a basis for scaling up interventions against those diseases, for which much more remains to be done. This paper describes the status of Nigeria’s struggles against these four neglected tropical diseases and discusses challenges and plans for the future.
Accuracy of Malaria Diagnosis by Microscopy, Rapid Diagnostic Test, and PCR Methods and Evidence of Antimalarial Overprescription in Non-Severe Febrile Patients in Two Tanzanian Hospitals
Authors: Nicastri Emanuele , Bevilacqua Nazario , Schepisi Monica Sañé , Paglia Maria G. , Meschi Silvia , Ame Shaali M. , Mohamed Jape A. , Mangi Sabina , Fumakule Robert , Di Caro Antonino , Capobianchi Maria R. , Kitua Andrew , Molteni Fabrizio , Racalbuto Vincenzo , Ippolito Giuseppe
Published: September 2018

The study was aimed to evaluate the malaria over/underdiagnosis and over/underprescription of antimalarial drugs. Between February and March 2007 blood samples were collected from 336 non-severe febrile outpatients attended in two peripheral Tanzanian hospitals. Microscopy and a rapid diagnostic test (RDT) were done locally and the accuracy evaluated by qualitative polymerase chain reaction (PCR) for Plasmodium spp. The testing was performed at National Institute for Infectious Diseases Lazzaro Spallanzani (INMI), Rome, Italy. As a result of PCR, we identified 26 malaria cases out of 336 (7.7%) patients. Microscopy and RDT accuracies were 93.5% and 97.6%, respectively. Overprescription and underdiagnosis rates were 29.3% and 30.8%, respectively. On-field training, clinical management of febrile illness, and malaria microscopy in remote settings should be considered.
Spatial Clustering by Disease Severity among Reported Rocky Mountain Spotted Fever Cases in the United States, 2001–2005
Authors: Adjemian Jennifer Zipser , Krebs John , Mandel Eric , McQuiston Jennifer
Published: September 2018

Rocky Mountain spotted fever (RMSF) occurs throughout much of the United States, ranging in clinical severity from moderate to fatal infection. Yet, little is known about possible differences among severity levels across geographic locations. To identify significant spatial clusters of severe and non-severe disease, RMSF cases reported to Centers for Disease Control and Prevention (CDC) were geocoded by county and classified by severity level. The statistical software program SaTScan was used to detect significant spatial clusters. Of 4,533 RMSF cases reported, 1,089 hospitalizations (168 with complications) and 23 deaths occurred. Significant clusters of 6 deaths (P = 0.05, RR = 11.4) and 19 hospitalizations with complications (P = 0.02, RR = 3.45) were detected in southwestern Tennessee. Two geographic areas were identified in north-central North Carolina with unusually low rates of severity (P = 0.001, RR = 0.62 and P = 0.001, RR = 0.45, respectively). Of all hospitalizations, 20% were clustered in central Oklahoma (P = 0.02, RR = 1.43). Significant geographic differences in severity were observed, suggesting that biologic and/or anthropogenic factors may be impacting RMSF epidemiology in the United States.
Treatment of Severe Sepsis with Artemether-Lumefantrine Is Associated with Decreased Mortality in Ugandan Patients without Malaria
Authors: Moore Christopher C. , Jacob Shevin T. , Pinkerton Relana , Banura Patrick , Meya David B. , Reynolds Steven J. , Kenya-Mugisha Nathan , Mayanja-Kizza Harriet , _ _
Published: September 2018

We enrolled 382 patients at two hospitals in Uganda in a prospective observational study of severe sepsis. Because artemisinins improve survival in murine sepsis models, we performed a post hoc analysis of the association between the use of artemether-lumefantrine (A-L) and mortality in patients with or without malaria. In patients with negative malaria smears (N = 328 of 379), Kaplan–Meier curves revealed decreased combined inpatient and 30-day mortality among patients receiving A-L versus those who did not (20.6%, SE = 10.6 versus 48.8%, SE = 3.2; Log rank χ2 = 3.93, P = 0.048). The decrease in mortality associated with A-L was maintained in the most clinically ill patients determined by Karnofsky Performance Scores ≤ 50 (16.7%, SE = 15.2 versus 58.3%, SE = 3.7; Log rank χ2 3.94, P = 0.041). Research into the properties of A-L is needed to improve treatment of sepsis without compromising malarial susceptibility.
Novel dhps and pfcrt Polymorphisms in Plasmodium falciparum Detected by Heteroduplex Tracking Assay
Authors: Juliano Jonathan J. , Bacon David J. , Mu Jianbing , Wang Xinhua , Meshnick Steven R.
Published: September 2018

Several single nucleotide polymorphisms (SNPs) have been linked to antimalarial drug resistance in Plasmodium falciparum. However, standard polymerase chain reaction (PCR) methods to detect these polymorphisms are unable to detect SNPs in variants representing < 20% of the parasites in a mixed infection, nor can they detect polymorphisms at nearby loci. Here we use heteroduplex tracking assays (HTAs) to analyze dhps540 mutations in 96 samples from Peru and pfcrt76 mutations in 70 samples from China. All samples had been previously analyzed by standard PCR. We detected drug-resistant minority variants and two novel non-synonymous pfcrt mutations in China. In Peru, we found no drug-resistant minority variants and a synonymous mutation in dhps. Thus, even in regions of low malaria transmission, HTA assays are more informative than PCR with agarose gel electrophoresis.
Malaria Drug Shortages in Kenya: A Major Failure to Provide Access to Effective Treatment
Authors: Kangwana Beth B. , Njogu Julius , Wasunna Beatrice , Kedenge Sarah V. , Memusi Dorothy N. , Goodman Catherine A. , Zurovac Dejan , Snow Robert W.
Published: September 2018

A key bench mark of successful therapeutic policy implementation, and thus effectiveness, is that the recommended drugs are available at the point of care. Two years after artemether-lumefathrine (AL) was introduced for the management of uncomplicated malaria in Kenya, we carried out a cross-sectional survey to investigate AL availability in government facilities in seven malaria-endemic districts. One of four of the surveyed facilities had none of the four AL weight-specific treatment packs in stock; three of four facilities were out of stock of at least one weight-specific AL pack, leading health workers to prescribe a range of inappropriate alternatives. The shortage was in large part caused by a delayed procurement process. National ministries of health and the international community must address the current shortcomings facing antimalarial drug supply to the public sector.
Xenomonitoring of Wuchereria bancrofti and Dirofilaria immitis Infections in Mosquitoes from American Samoa: Trapping Considerations and a Comparison of Polymerase Chain Reaction Assays with Dissection
Authors: Chambers Eric W. , McClintock Shannon K. , Avery Melissa F. , King Jonathan D. , Bradley Mark H. , Schmaedick Mark A. , Lammie Patrick J. , Burkot Thomas R.
Published: September 2018

Entomologic monitoring of filarial infections, xenomonitoring, may have advantages in certain epidemiologic situations to assess the presence of infections in humans. Hemalum staining and dissection and polymerase chain reaction (PCR) were compared to determine the filarial infection status of Aedes (Stegomyia) mosquitoes in American Samoa. The overall prevalences of Wuchereria bancrofti and Dirofilaria immitis infections in Ae. polynesiensis were, respectively, 0.16% and 1.06% by dissection and 0.69% and 1.77% by PCR. Human filarial worm DNA rates in Aedes aegypti and Aedes upolensis were 1.16% and 0.38%, respectively. The results suggest that W. bancrofti transmission to humans may be continuing at low levels in some villages despite recent completion of 5 years of mass drug administration. PCR testing of mosquitoes collected using the BG-Sentinel traps represents a promising alternative to landing catches for assessing the transmission of filariasis in areas where Ae. polynesiensis and related species are the primary vectors.
Close Relationship between Clinical Regression and Specific Serology in the Follow-up of Patients with Alveolar Echinococcosis in Different Clinical Stages
Authors: Tappe Dennis , Frosch Matthias , Sako Yasuhito , Itoh Sonoyo , Grüner Beate , Reuter Stefan , Nakao Minoru , Ito Akira , Kern Peter
Published: September 2018

We compared four enzyme-linked immunosorbent assays (ELISAs) with 172 serum samples from 28 patients with alveolar echinococcosis in different clinical stages according to the World Health Organization–PNM (P = parasitic mass in the liver, N = involvement of neighboring organs, M = metastasis) staging system. The sequential antibody responses against Em 2plus, Em10, and Em18 antigens, and a crude antigen extract were measured in cohorts with resected and unresected lesions. Antibody levels in all assays correlated with the PNM stage before treatment, and the highest correlation was shown for the Em18 assay. The PNM stage did not influence the antibody kinetics, but changes in antibody levels depended on the treatment. In patients after curative surgery, seroreversion in the Em 2plus ELISA indicated successful resection of lesions in more patients than any other assay, irrespective of the clinical stage. There were no significant differences in the time before assays that use recombinant or purified antigens became unreactive. Antibodies directed against crude antigens were detectable longer than other antibodies in all patient cohorts and stages.
Morphologic Organization of Pulmonary Granulomas in Mice Infected with Paracoccidioides brasiliensis
Authors: Da Silva Fernanda C. , Svidzinski Terezinha I. E. , Patussi Eliana V. , Cardoso Cristina P. , De Oliveira Dalalio Márcia M. , Hernandes Luzmarina
Published: September 2018

A morphologic study of the lungs was carried out in Swiss mice infected with yeast isolated from Paracoccidioides brasiliensis (Pb18). The lung was processed 1, 2, 4, and 8 weeks after inoculation for histologic staining with hematoxylin and eosin (H&E), methenamine silver nitrate (Gomori–Grocott), and picrosirius to qualitative and quantitative analyses of the granulomas and the presence of fungal lesions. The numbers of CFUs/g counted in the lungs were 189.8 ± 20.64, 353.6 ± 46.21, 547.2 ± 108.1, and 295.2 ± 89.17 in the first, second, fourth, and eighth weeks, respectively. One week after infection, inflammatory cells and reticular and collagens fibers, the latest typical of fibrosis, were detected. After 2 and 4 weeks, a progressive intensification of the infection and fibrosis was observed, but in week 8 a more organized granuloma was evident, with macrophages, epithelioid cells, and yeasts in the central portion, and intense peripheral basophilia. Pycnotic structures typical of apoptotic bodies were observed in weeks 1 and 8. The different histologic staining used acted as a fundamental tool for the study of the morphologic organization of granuloma formation.
Population-Based Study of a Widespread Outbreak of Diarrhea Associated with Increased Mortality and Malnutrition in Botswana, January–March, 2006
Authors: Mach Ondrej , Lu Lydia , Creek Tracy , Bowen Anna , Arvelo Wences , Smit Molly , Masunge Japhter , Brennan Muireann , Handzel Thomas
Published: September 2018

In early 2006, coinciding with heavy rains, Botswana health facilities reported increases in diarrhea, mortality, and acute malnutrition among young children. Data on diarrhea, human immunodeficiency virus, feeding, mortality, and water/sanitation were collected by random cluster survey. Anthropometric data were measured and drinking water samples were tested. Of 537 surveyed children less than five years of age, one-third experienced ≥ 1 episode of diarrhea. Prevalence of acute malnutrition was 7.9%, and the mortality rate for children less than five years of age was 2.6/10,000/day during the outbreak. Significant risk factors for diarrhea included an age less than two years; breastfeeding was protective. Diarrhea lasting for more than 14 days and failure to thrive were risk factors for acute malnutrition. Prevalence of acute malnutrition was higher than previously documented and the mortality rate in children less than five years of age during the outbreak was above the international threshold for emergency action with an estimated 547 excess deaths. This survey highlights the need for safe infant feeding and effective treatment of malnutrition and diarrhea in young children.
Comparison of Indirect Immunofluorescence Assays for Diagnosis of Scrub Typhus and Murine Typhus Using Venous Blood and Finger Prick Filter Paper Blood Spots
Authors: Phetsouvanh Rattanaphone , Blacksell Stuart D. , Jenjaroen Kemajittra , Day Nicholas P. J. , Newton Paul N.
Published: September 2018

We performed indirect immunofluorescence assays (IFAs) to compare levels of IgM and IgG antibodies to Orientia tsutsugamushi and Rickettsia typhi in admission-phase serum samples and filter paper blood spots (assayed immediately and stored at 5.4°C and 29°C for 30 days) collected on the same day from 53 adults with suspected scrub typhus and murine typhus admitted to Mahosot Hospital Vientiane, Lao People’s Democratic Republic. The sensitivities and specificities of admission-phase filter paper blood spots in comparison to paired sera were between 91% and 95% and 87% and 100%, respectively, for the diagnosis of scrub typhus and murine typhus. The classification of patients as having or not having typhus did not significantly differ after storage of the blood spots for 30 days (P > 0.4) at 5.4°C and 29°C. Because filter paper blood samples do not require sophisticated and expensive storage and transport, they may be an appropriate specimen collection technique for the diagnosis of rickettsial disease in the rural tropics.
Increased Phagocytosis of Platelets from Patients with Secondary Dengue Virus Infection by Human Macrophages
Authors: Honda Shoko , Saito Mariko , Dimaano Efren M. , Morales Philip A. , Alonzo Maria T. G. , Suarez Lady-Anne C. , Koike Natsuki , Inoue Shingo , Kumatori Atsushi , Matias Ronald R. , Natividad Filipinas F. , Oishi Kazunori
Published: September 2018

The relationship between the percent phagocytosis of platelets by differentiated THP-1 cells was examined using flowcytometry and the peripheral platelet counts as well as platelet-associated IgG (PAIgG) in 36 patients with secondary dengue virus (DV) infections. The percent phagocytosis and the levels of PAIgG were significantly increased in these patients during the acute phase compared with the healthy volunteers. The increased percent phagocytosis and PAIgG found during the acute phase significantly decreased during the convalescent phase. An inverse correlation between platelet count and the percent phagocytosis (P = 0.011) and the levels of PAIgG (P = 0.041) was found among these patients during the acute phase. No correlation was found, however, between the percent phagocytosis and the levels of PAIgG. Our present data suggest that accelerated platelet phagocytosis occurs during the acute phase of secondary DV infections, and it is one of the mechanisms of thrombocytopenia in this disease.
Comparative Thermostability of West Nile, St. Louis Encephalitis, and Western Equine Encephalomyelitis Viruses during Heat Inactivation for Serologic Diagnostics
Authors: Fang Ying , Brault Aaron C. , Reisen William K.
Published: September 2018

During the monitoring of arbovirus seroprevalence in wild birds collected in California, we inadvertently made two isolates of western equine encephalomyelitis virus (WEEV) from California quail sera being tested by plaque reduction neutralization assay for antibodies against St Louis encephalitis (SLEV) and West Nile (WNV) viruses despite heating the sera at 56°C for 30 minutes. These data prompted us to examine the thermostability of these viruses during heat treatment. The flaviviruses, SLEV and WNV, at titers up to 106 plaque-forming units (PFU), were readily inactivated by the standard protocol of heating at 56°C for 30 minutes. In contrast, solutions containing 105 and 106 PFU of WEEV required 2 hours for complete inactivation. Occasional presence of live virus within sera could lead to false negatives using standard plaque reduction neutralization test protocols.
Marked Increase in Child Survival after Four Years of Intensive Malaria Control
Authors: Kleinschmidt Immo , Schwabe Christopher , Benavente Luis , Torrez Miguel , Ridl Frances C. , Segura Jose Luis , Ehmer Paul , Nchama Gloria Nseng
Published: September 2018

In malaria-endemic countries in Africa, a large proportion of child deaths are directly or indirectly attributable to infection with Plasmodium falciparum. Four years after high coverage, multiple malaria control interventions were introduced on Bioko Island, Equatorial Guinea, changes in infection with malarial parasites, anemia, and fever history in children were estimated and assessed in relation to changes in all-cause under-5 mortality. There were reductions in prevalence of infection (odds ratio [OR] = 0.31, 95% confidence interval [CI] = 0.2–0.46), anemia (OR = 0.11, 95% CI = 0.07–0.18), and reported fevers (OR = 0.41, 95% CI = 0.22–0.76) in children. Under-5 mortality fell from 152 per 1,000 births (95% CI = 122–186) to 55 per 1,000 (95% CI = 38–77; hazard ratio = 0.34 [95% CI = 0.23–0.49]). Effective malaria control measures can dramatically increase child survival and play a key role in achieving millennium development goals.
The Participation of Secondary Clinical Episodes in the Epidemiology of Vivax Malaria during Pre- and Post-Implementation of Focal Control in the State of Oaxaca, Mexico
Authors: Rodriguez Mario H. , Betanzos-Reyes Ángel F. , Hernández-Ávila Juan E. , Méndez-Galván Jorge F. , Danis-Lozano Rogelio , Altamirano-Jiménez Armando
Published: September 2018

The participation of vivax malaria secondary clinical was researched in a retrospective cohort of 33,414 confirmed cases occurring between 1994 and 2005 in the state of Oaxaca, Mexico. Secondary episodes occurred in 23.4% of all primary cases. An increase in secondary episodes was associated with primary cases occurring during the dry seasons (risk ratio [RR] = 1.68, 95% CI: 1.45–1.96). The incidence of secondary episodes peaked at an older age, occurred similarly in men and women mostly during low mosquito abundance, and had a uniform distribution among localities. A reduction in secondary episodes was associated with the administration of an increased dose and early administration of primaquine (RR = 0.32, 95% CI: 0.26–0.38). However, limitations to distinguish relapses from re-infections impede assessment of the new treatment effect on relapses and its contribution to malaria control in the area. These findings highlight the need for new therapeutic schemes to radical cure of P. vivax infections and operational research aimed at parasite pool elimination.
Impact of Ministry of Health Interventions on Private Medicine Retailer Knowledge and Practices on Anti-Malarial Treatment in Kenya
Authors: Abuya Timothy , Fegan Greg , Rowa Yvone , Karisa Baya , Ochola Sam , Mutemi Wilfred , Marsh Vicki
Published: September 2018

Small-scale interventions on training medicine retailers on malaria treatment improve over-the-counter medicine use, but there is little evidence on effectiveness when scaled up. This study evaluated the impact of Ministry of Health (MoH) training programs on the knowledge and practices of medicine retailers in three districts in Kenya. A cluster randomized trial was planned across 10 administrative divisions. Findings indicated that 30.7% (95% confidence interval [CI]: 23.3, 39.0) and 5.2% (95% CI: 2.1, 10.3) of program and control retailers, respectively, sold MoH amodiaquine with correct advice on use to surrogate clients (OR = 8.8; 95% CI: 2.9, 26.9; P < 0.001). Similarly, 61.8% (95% CI: 54.2, 69.1) and 6.3% (95% CI: 2.7, 12.1) of program and control retailers, respectively, reported correct knowledge on dosing with amodiaquine (OR = 29.8; 95% CI: 8.2, 108.8). Large-scale retailer training programs within the national malaria control framework led to significant improvements in retailers’ practices across three districts.