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Common occurrence of <i>Cryptosporidium hominis</i> in asymptomatic and symptomatic calves in France

PLoS Neglected Tropical Diseases News - 29 March 2018 - 9:00pm

by Romy Razakandrainibe, El Hadji Ibrahima Diawara, Damien Costa, Laetitia Le Goff, Denis Lemeteil, Jean Jacques Ballet, Gilles Gargala, Loïc Favennec

Background

Cryptosporidium spp. are infections the most frequent parasitic cause of diarrhea in humans and cattle. However, asymptomatic cases are less often documented than symptomatic cases or cases with experimentally infected animals. Cryptosporidium (C.) hominis infection accounts for the majority of pediatric cases in several countries, while C. parvum is a major cause of diarrhea in neonatal calves. In cattle Cryptosporidium spp. infection can be caused by C. parvum, C. bovis, C.andersoni and C. ryanae, and recently, reports of cattle cases of C. hominis cryptosporidiosis cases suggest that the presence of C. hominis in calves was previously underestimated.

Methodology/Principal findings

From February to November 2015, Cryptosporidium spp. infected calves were detected in 29/44 randomly included farms from 5 geographic regions of France. C. hominis and C. parvum were found in 12/44 and 26/44 farms, respectively with higher C. hominis prevalence in the western region. In 9 farms, both C. parvum and C. hominis were detected. Eighty-six of 412 (73/342 asymptomatic and 13/70 symptomatic) one to nine-week-old calves shed C. hominis or C. parvum oocysts (15 and 71 calves, respectively), with no mixed infection detected. The predominant C. hominis IbA9G3 genotype was present in all regions, and more frequent in the western region. An incompletely characterized Ib, and the IbA13G3, IbA9G2 and IbA14G2 genotypes were present only in the western region. For C. parvum, the most frequent genotype was IIaA16G3R1 with no geographic clustering. Most C. hominis infected calves were asymptomatic, with some exceptions of IbA9G2 and IbA9G3 isolates, while C. parvum IIaA16G3R1 was associated with symptoms.

Conclusions/Significance

Present results indicate for the first time that in several geographic regions of France, C. hominis was present in about one fifth of both asymptomatic and symptomatic infected calves, with isolated genotypes likely associated with human infection. Further investigations are aimed at documenting direct or indirect transmissions between livestock and humans.

Distinct inflammatory profile underlies pathological increases in creatinine levels associated with <i>Plasmodium vivax</i> malaria clinical severity

PLoS Neglected Tropical Diseases News - 29 March 2018 - 9:00pm

by Luís A. B. Cruz, Manoel Barral-Netto, Bruno B. Andrade

Background

Although Plasmodium vivax infection is a frequent cause of malaria worldwide, severe presentations have been more regularly described only in recent years. In this setting, despite clinical descriptions of multi-organ involvement, data associating it with kidney dysfunction are relatively scarce. Here, renal dysfunction is retrospectively analyzed in a large cohort of vivax malaria patients with an attempt to dissect its association with disease severity and mortality, and to determine the role of inflammation in its progression.

Methods

A retrospective analysis of a databank containing 572 individuals from the Brazilian Amazon, including 179 patients with P. vivax monoinfection (161 symptomatic malaria, 12 severe non-lethal malaria, and 6 severe lethal disease) and 165 healthy controls, was performed. Data on levels of cytokines, chemokines, C-reactive protein (CRP), fibrinogen, creatinine, hepatic enzymes, bilirubin levels, free heme, and haptoglobin were analyzed to depict and compare profiles from patients per creatinine levels.

Results

Elevated creatinine levels were found predominantly in women. Vivax malaria severity was highly associated with abnormal creatinine increases, and nonsurvivors presented the highest values of serum creatinine. Indication of kidney dysfunction was not associated with parasitemia levels. IFN-γ/IL-10 ratio and CRP values marked the immune biosignature of vivax malaria patients, and could distinguish subjects with elevated creatinine levels who did not survive from those who did. Patients with elevated serum creatinine or severe vivax malaria displayed indication of cholestasis. Biomarkers of hemolysis did not follow increases in serum creatinine.

Conclusion

These findings reinforce the hypothesis that renal dysfunction is a key component in P. vivax malaria associated with clinical severity and mortality, possibly through intense inflammation and immune imbalance. Our study argues for systematic evaluation of kidney function as part of the clinical assessment in vivax malaria patients, and warrants additional studies in experimental models for further mechanism investigations.

Taking a bite out of nutrition and arbovirus infection

PLoS Neglected Tropical Diseases News - 29 March 2018 - 9:00pm

by James Weger-Lucarelli, Heidi Auerswald, Marco Vignuzzi, Phillipe Dussart, Erik A. Karlsson

Nutrition is a key factor in host–pathogen defense. Malnutrition can increase both host susceptibility and severity of infection through a number of pathways, and infection itself can promote nutritional deterioration and further susceptibility. Nutritional status can also strongly influence response to vaccination or therapeutic pharmaceuticals. Arthropod-borne viruses (arboviruses) have a long history of infecting humans, resulting in regular pandemics as well as an increasing frequency of autochthonous transmission. Interestingly, aside from host-related factors, nutrition could also play a role in the competence of vectors required for transmission of these viruses. Nutritional status of the host and vector could even influence viral evolution itself. Therefore, it is vital to understand the role of nutrition in the arbovirus lifecycle. This Review will focus on nutritional factors that could influence susceptibility and severity of infection in the host, response to prophylactic and therapeutic strategies, vector competence, and viral evolution.

Isolated iliac cryptococcosis in an immunocompetent patient

PLoS Neglected Tropical Diseases News - 29 March 2018 - 9:00pm

by Junjun Sang, Yali Yang, Yibin Fan, Guizhen Wang, Jiu Yi, Wei Fang, Weihua Pan, Jinhua Xu, Wanqing Liao

Prospective evaluation of a rapid diagnostic test for <i>Trypanosoma brucei gambiense</i> infection developed using recombinant antigens

PLoS Neglected Tropical Diseases News - 28 March 2018 - 9:00pm

by Crispin Lumbala, Sylvain Biéler, Simon Kayembe, Jacquies Makabuza, Stefano Ongarello, Joseph Mathu Ndung’u

Background

Diagnosis and treatment are central elements of strategies to control Trypanosoma brucei gambiense human African trypanosomiasis (HAT). Serological screening is a key entry point in diagnostic algorithms. The Card Agglutination Test for Trypanosomiasis (CATT) has been the most widely used screening test for decades, despite a number of practical limitations that were partially addressed by the introduction of rapid diagnostic tests (RDTs). However, current RDTs are manufactured using native antigens, which are challenging to produce.

Methodology/Principal findings

The objective of this study was to evaluate the accuracy of a new RDT developed using recombinant antigens (SD BIOLINE HAT 2.0), in comparison with an RDT produced using native antigens (SD BIOLINE HAT) and CATT. A total of 57,632 individuals were screened in the Democratic Republic of the Congo, either passively at 10 health centres, or actively by 5 mobile teams, and 260 HAT cases were confirmed by parasitology. The highest sensitivity was achieved with the SD BIOLINE HAT 2.0 (71.2%), followed by CATT (62.5%) and the SD BIOLINE HAT (59.0%). The most specific test was CATT (99.2%), while the specificity of the SD BIOLINE HAT and SD BIOLINE HAT 2.0 were 98.9% and 98.1%, respectively. Sensitivity of the tests was lower than previously reported, as they identified cases from partially overlapping sub-populations. All three tests were significantly more sensitive in passive than in active screening. Combining two or three tests resulted in a markedly increased sensitivity: When the SD BIOLINE HAT was combined with the SD BIOLINE HAT 2.0, sensitivity reached 98.4% in passive and 83.0% in active screening.

Conclusions/Significance

The recombinant antigen-based RDT was more sensitive than, and as specific as, the SD BIOLINE HAT. It was as sensitive as, but slightly less specific than, CATT. While the practicality and cost-effectiveness of algorithms including several screening tests would need to be investigated, using two or more tests appears to enhance sensitivity of diagnostic algorithms, although some decrease in specificity is observed as well.

The associations between water and sanitation and hookworm infection using cross-sectional data from Togo's national deworming program

PLoS Neglected Tropical Diseases News - 28 March 2018 - 9:00pm

by Julia M. Baker, Victoria Trinies, Rachel N. Bronzan, Ameyo M. Dorkenoo, Joshua V. Garn, Sêvi Sognikin, Matthew C. Freeman

Background

Sustainable control of soil-transmitted helminths requires a combination of chemotherapy treatment and environmental interventions, including access to safe drinking water, sufficient water for hygiene, use of clean sanitation facilities, and handwashing (WASH). We quantified associations between home-, school-, and community-level WASH characteristics and hookworm infection—both prevalence and eggs per gram of stool (intensity)—among Togolese school children in the context of community-based chemotherapy treatments administered in the country from 2010 through 2014.

Methodology/Principal findings

We analyzed data from two surveys conducted by the Togo Ministry of Health: a school-based survey of students aged 6–9 years across Togo conducted in 2009 and a follow-up survey in 2015, after four to five years of preventive chemotherapy. Data were available for 16,473 students attending 1,129 schools in 2009 and for 16,890 students from 1,126 schools in 2015. Between surveys, children in study schools received 0 to 8 rounds of deworming chemotherapy treatments. Few WASH conditions (only unimproved drinking water) were found to be significantly associated with the presence or absence of hookworms in an individual; however, quantitative eggs per gram of feces was associated with availability of unimproved drinking water, availability of improved drinking water either on or off school grounds, having a handwashing station with water available, and access to a sex-separate non-private or private latrine. The association between school WASH conditions and hookworm infection or burden often depended on the 2009 prevalence of infection, as more WASH characteristics were found to be significant predictors of infection among schools with high underlying endemicity of hookworm.

Conclusions/Significance

Our findings emphasize the complex and often inconsistent or unpredictable relationship between WASH and hookworm. Specifically, we found that while preventive chemotherapy appeared to dramatically reduce hookworm infection, WASH was associated with infection intensity.

Diet and hygiene practices influence morbidity in schoolchildren living in Schistosomiasis endemic areas along Lake Victoria in Kenya and Tanzania—A cross-sectional study

PLoS Neglected Tropical Diseases News - 28 March 2018 - 9:00pm

by Iman Mohamed, Safari Kinung’hi, Pauline N. M. Mwinzi, Isaac O. Onkanga, Kennedy Andiego, Geoffrey Muchiri, Maurice R. Odiere, Birgitte Jyding Vennervald, Annette Olsen

Background

Since 2011, cohorts of schoolchildren in regions bordering Lake Victoria in Kenya and Tanzania have been investigated for morbidity caused by Schistosoma mansoni infection. Despite being neighbouring countries with similar lifestyles and ecological environments, Tanzanian schoolchildren had lower S. mansoni prevalence and intensity and they were taller and heavier, fewer were wasted and anaemic, and more were physical fit compared to their Kenyan peers. The aim of the present study was to evaluate whether diet and school-related markers of socioeconomic status (SES) could explain differences in morbidity beyond the effect of infection levels.

Methods and principal findings

Parasitological and morbidity data from surveys in 2013–2014 were compared with information on diet and school-related markers of SES collected in 2015 using questionnaires. A total of 490 schoolchildren (163 Kenyans and 327 Tanzanians) aged 9–11 years provided data. A higher proportion of Tanzanian pupils (69.4%, 95% CI: 64.3–74.5) knew where to wash hands after toilet visits compared to Kenyan pupils (48.5%, 95% CI: 40.9–56.1; P<0.0005). Similar proportions of children in the two countries ate breakfast, lunch and dinner, but the content of the meals differed. At all three meals, a higher proportion (95% CI) of Tanzanian pupils consumed animal proteins (mostly fish proteins) compared to their Kenyan peers (35.0% (28.3–41.7) vs. 0%; P<0.0005 at breakfast; 69.0% (63.9–74.1) vs. 43.6% (35.8–51.4); P<0.0005 at lunch; and 67.2% (62.1–72.3) vs. 53.4% (45.8–61.0); P = 0.003 at dinner). Multivariable analyses investigating risk factors for important morbidity markers among individuals revealed that after controlling for schistosome and malaria infections, eating animal proteins (fish) and knowing where to wash hands after toilet visits were significant predictors for both haemoglobin levels and physical fitness (measured as VO2 max).

Conclusions

These results suggest that the differences in morbidity may be affected by factors other than S. mansoni infection alone. Diet and hygiene practice differences were associated with health status of schoolchildren along Lake Victoria in Kenya and Tanzania.

Trial registration

Trials Registration numbers: ISRCT 16755535 (Kenya), ISRCT 95819193 (Tanzania).

Emergence of <i>Orientia tsutsugamushi</i> as an important cause of Acute Encephalitis Syndrome in India

PLoS Neglected Tropical Diseases News - 28 March 2018 - 9:00pm

by Parul Jain, Shantanu Prakash, Piyush K. Tripathi, Archana Chauhan, Shikha Gupta, Umesh Sharma, Anil K. Jaiswal, Devraj Sharma, Amita Jain

Background

Acute Encephalitis Syndrome (AES) is a major seasonal public health problem in Bihar, India. Despite efforts of the Bihar health department and the Government of India, burden and mortality of AES cases have not decreased, and definitive etiologies for the illness have yet to be identified.

Objectives

The present study was undertaken to study the specific etiology of AES in Bihar.

Methods

Cerebrospinal fluid and/or serum samples from AES patients were collected and tested for various pathogens, including viruses and bacteria by ELISA and/or Real Time PCR.

Findings

Of 540 enrolled patients, 33.3% (180) tested positive for at least one pathogen of which 23.3% were co-positive for more than one pathogen. Most samples were positive for scrub typhus IgM or PCR (25%), followed by IgM positivity for JEV (8.1%), WNV (6.8%), DV (6.1%), and ChikV (4.5%).M. tuberculosis and S. pneumoniae each was detected in ~ 1% cases. H. influenzae, adenovirus, Herpes Simplex Virus -1, enterovirus, and measles virus, each was detected occasionally. The presence of Scrub typhus was confirmed by PCR and sequencing. Bihar strains resembled Gilliam-like strains from Thailand, Combodia and Vietnam.

Conclusion

The highlights of this pilot AES study were detection of an infectious etiology in one third of the AES cases, multiple etiologies, and emergence of O. tsutsugamushi infection as an important causative agent of AES in India.

Developing a Buruli ulcer community of practice in Bankim, Cameroon: A model for Buruli ulcer outreach in Africa

PLoS Neglected Tropical Diseases News - 27 March 2018 - 9:00pm

by Paschal Kum Awah, Alphonse Um Boock, Ferdinand Mou, Joseph Tohnain Koin, Evaristus Mbah Anye, Djeunga Noumen, Mark Nichter, Stop Buruli Consortium

Background

In the Cameroon, previous efforts to identify Buruli ulcer (BU) through the mobilization of community health workers (CHWs) yielded poor results. In this paper, we describe the successful creation of a BU community of practice (BUCOP) in Bankim, Cameroon composed of hospital staff, former patients, CHWs, and traditional healers.

Methods and principle findings

All seven stages of a well-defined formative research process were conducted during three phases of research carried out by a team of social scientists working closely with Bankim hospital staff. Phase one ethnographic research generated interventions tested in a phase two proof of concept study followed by a three- year pilot project. In phase three the pilot project was evaluated. An outcome evaluation documented a significant rise in BU detection, especially category I cases, and a shift in case referral. Trained CHW and traditional healers initially referred most suspected cases of BU to Bankim hospital. Over time, household members exposed to an innovative and culturally sensitive outreach education program referred the greatest number of suspected cases. Laboratory confirmation of suspected BU cases referred by community stakeholders was above 30%. An impact and process evaluation found that sustained collaboration between health staff, CHWs, and traditional healers had been achieved. CHWs came to play a more active role in organizing BU outreach activities, which increased their social status. Traditional healers found they gained more from collaboration than they lost from referral.

Conclusion/ Significance

Setting up lines of communication, and promoting collaboration and trust between community stakeholders and health staff is essential to the control of neglected tropical diseases. It is also essential to health system strengthening and emerging disease preparedness. The BUCOP model described in this paper holds great promise for bringing communities together to solve pressing health problems in a culturally sensitive manner.

Sensitive and specific detection of Crimean-Congo Hemorrhagic Fever Virus (CCHFV)—Specific IgM and IgG antibodies in human sera using recombinant CCHFV nucleoprotein as antigen in μ-capture and IgG immune complex (IC) ELISA tests

PLoS Neglected Tropical Diseases News - 26 March 2018 - 9:00pm

by Petra Emmerich, Angela Mika, Ronald von Possel, Anne Rackow, Yang Liu, Herbert Schmitz, Stephan Günther, Kurtesh Sherifi, Barie Halili, Xhevat Jakupi, Lindita Berisha, Salih Ahmeti, Christina Deschermeier

As the most widespread tick-borne arbovirus causing infections in numerous countries in Asia, Africa and Europe, Crimean-Congo Hemorrhagic Fever Virus (CCHFV, family Nairoviridae) was included in the WHO priority list of emerging pathogens needing urgent Research & Development attention. To ensure preparedness for potential future outbreak scenarios, reliable diagnostic tools for identification of acute cases as well as for performance of seroprevalence studies are necessary. Here, the CCHFV ortholog of the major bunyavirus antigen, the nucleoprotein (NP), was recombinantly expressed in E.coli, purified and directly labeled with horseradish peroxidase (HRP). Employing this antigen, two serological tests, a μ-capture ELISA for the detection of CCHFV-specific IgM antibodies (BLACKBOX CCHFV IgM) and an IgG immune complex (IC) ELISA for the detection of CCHFV-specific IgG antibodies (BLACKBOX CCHFV IgG), were developed. Test performance was evaluated and compared with both in-house gold standard testing by IgM/IgG indirect immunofluorescence (IIFT) and commercially available ELISA tests (VectoCrimean-CHF-IgM/IgG, Vector-Best, Russia) using a serum panel comprising paired samples collected in Kosovo during the years 2013–2016 from 15 patients with an acute, RT-PCR-confirmed CCHFV infection, and 12 follow-up sera of the same patients collected approximately one year after having overcome the infection. Reliably detecting IgM antibodies in all acute phase sera collected later than day 4 after onset of symptoms, both IgM ELISAs displayed excellent diagnostic and analytical sensitivity (100%, 95% confidence interval (CI): 85.2%–100.0%). While both IgG ELISAs readily detected the high IgG titers present in convalescent patients approximately one year after having overcome the infection (sensitivity 100%, 95% CI: 73.5%–100.0%), the newly developed BLACKBOX CCHFV IgG ELISA was superior to the commercial IgG ELISA in detecting the rising IgG titers during the acute phase of the disease. While all samples collected between day 11 and 19 after onset of symptoms tested positive in both the in-house gold standard IIFT and the BLACKBOX CCHFV IgG ELISA (sensitivity 100%, 95% CI: 71.5%–100.0%), only 27% (95% CI: 6.0%–61.0%) of those samples were tested positive in the commercial IgG ELISA. No false positive signals were observed in either IgM/IgG ELISA when analyzing a priori CCHFV IgM/IgG negative serum samples from healthy blood donors, malaria patients and flavivirus infected patients as well as CCHFV IgM/IgG IIFT negative serum samples from healthy Kosovar blood donors (for BLACKBOX CCHFV IgM/IgG: n = 218, 100% specificity, 95% CI: 98.3%–100.0%, for VectoCrimean-CHF-IgM/IgG: n = 113, 100% specificity, 95% CI: 96.8%–100.0%).

Cardiac findings in infants with in utero exposure to Zika virus- a cross sectional study

PLoS Neglected Tropical Diseases News - 26 March 2018 - 9:00pm

by Dulce H. G. Orofino, Sonia R. L. Passos, Raquel V. C. de Oliveira, Carla Verona B. de Farias, Maria de Fatima M. P. Leite, Sheila M. Pone, Marcos V. da S. Pone, Helena A. R. Teixeira Mendes, Maria Elizabeth L. Moreira, Karin Nielsen-Saines

Background

Antenatal exposure to Zika virus (ZIKV) is related to severe neurological manifestations. A previous study in Brazil reported an increased incidence of non-severe congenital heart defects in infants with diagnosis of congenital Zika syndrome but without laboratory confirmation of ZIKV infection in the mother or infant. The objective of this study is to report echocardiographic (ECHO) findings in infants with laboratory confirmed antenatal exposure to ZIKV.

Methodology

Cross sectional study of cardiologic assessments of infants born between November 2015 and January 2017 with confirmed vertical exposure to ZIKV in Rio de Janeiro, Brazil.

Results

The study enrolled 120 children with a median age of 97 days (1 to 376 days). In utero exposure to ZIKV was confirmed in 97 children (80,8%) through positive maternal polymerase chain reaction (PCR) results during pregnancy or a positive PCR result at birth; 23 additional children (19.2%) had maternal positive PCR results during pregnancy and postnatally. Forty- eight infants (40%) had cardiac defects noted on ECHO. Thirteen infants (10.8%) had major cardiac defects (atrial septal defect, ventricular septal defect, patent ductus arteriosus). None of the defects were severe. The frequency of major defects was higher in infants whose mothers had a rash in the 2nd trimester of pregnancy, or who had altered Central Nervous System (CNS) imaging postnatally or were preterm.

Conclusions

Infants with in utero ZIKV exposure have a higher prevalence of major cardiac defects, however none were severe enough to require immediate intervention. For this reason, guidelines for performance of postnatal ECHO in this population should follow general newborn screening guidelines, which significantly reduces the burden of performing emergent fetal or neonatal ECHOs in a setting where resources are not available, such as most Brazilian municipalities.

Eutrophication and predator presence overrule the effects of temperature on mosquito survival and development

PLoS Neglected Tropical Diseases News - 26 March 2018 - 9:00pm

by Maarten Schrama, Erin E. Gorsich, Ellard R. Hunting, S. Henrik Barmentlo, Brianna Beechler, Peter M. van Bodegom

Adequate predictions of mosquito-borne disease risk require an understanding of the relevant drivers governing mosquito populations. Since previous studies have focused mainly on the role of temperature, here we assessed the effects of other important ecological variables (predation, nutrient availability, presence of conspecifics) in conjunction with the role of temperature on mosquito life history parameters. We carried out two mesocosm experiments with the common brown house mosquito, Culex pipiens, a confirmed vector for West Nile Virus, Usutu and Sindbis, and a controphic species; the harlequin fly, Chironomus riparius. The first experiment quantified interactions between predation by Notonecta glauca L. (Hemiptera: Notonectidae) and temperature on adult emergence. The second experiment quantified interactions between nutrient additions and temperature on larval mortality and adult emergence. Results indicate that 1) irrespective of temperature, predator presence decreased mosquito larval survival and adult emergence by 20–50%, 2) nutrient additions led to a 3-4-fold increase in mosquito adult emergence and a 2-day decrease in development time across all temperature treatments, 3) neither predation, nutrient additions nor temperature had strong effects on the emergence and development rate of controphic Ch. riparius. Our study suggests that, in addition to of effects of temperature, ecological bottom-up (eutrophication) and top-down (predation) drivers can have strong effects on mosquito life history parameters. Current approaches to predicting mosquito-borne disease risk rely on large-scale proxies of mosquito population dynamics, such as temperature, vegetation characteristics and precipitation. Local scale management actions, however, will require understanding of the relevant top-down and bottom-up drivers of mosquito populations.

Seroepidemiology of helminths and the association with severe malaria among infants and young children in Tanzania

PLoS Neglected Tropical Diseases News - 26 March 2018 - 9:00pm

by Jennifer L. Kwan, Amy E. Seitz, Michal Fried, Kun-Lin Lee, Simon Metenou, Robert Morrison, Edward Kabyemela, Thomas B. Nutman, D. Rebecca Prevots, Patrick E. Duffy

The disease burden of Wuchereria bancrofti and Plasmodium falciparum malaria is high, particularly in Africa, and co-infection is common. However, the effects of filarial infection on the risk of severe malaria are unknown. We used the remaining serum samples from a large cohort study in Muheza, Tanzania to describe vector-borne filarial sero-reactivity among young children and to identify associations between exposure to filarial parasites and subsequent severe malaria infections. We identified positive filarial antibody responses (as well as positive antibody responses to Strongyloides stercoralis) among infants as young as six months. In addition, we found a significant association between filarial seropositivity at six months of age and subsequent severe malaria. Specifically, infants who developed severe malaria by one year of age were 3.9 times more likely (OR = 3.9, 95% CI: 1.2, 13.0) to have been seropositive for filarial antigen at six months of age compared with infants who did not develop severe malaria.

Scrub typhus point-of-care testing: A systematic review and meta-analysis

PLoS Neglected Tropical Diseases News - 26 March 2018 - 9:00pm

by Kartika Saraswati, Nicholas P. J. Day, Mavuto Mukaka, Stuart D. Blacksell

Background

Diagnosing scrub typhus clinically is difficult, hence laboratory tests play a very important role in diagnosis. As performing sophisticated laboratory tests in resource-limited settings is not feasible, accurate point-of-care testing (POCT) for scrub typhus diagnosis would be invaluable for patient diagnosis and management. Here we summarise the existing evidence on the accuracy of scrub typhus POCTs to inform clinical practitioners in resource-limited settings of their diagnostic value.

Methodology/principal findings

Studies on POCTs which can be feasibly deployed in primary health care or outpatient settings were included. Thirty-one studies were identified through PubMed and manual searches of reference lists. The quality of the studies was assessed with the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). About half (n = 14/31) of the included studies were of moderate quality. Meta-analysis showed the pooled sensitivity and specificity of commercially available immunochromatographic tests (ICTs) were 66.0% (95% CI 0.37–0.86) and 92.0% (95% CI 0.83–0.97), respectively. There was a significant and high degree of heterogeneity between the studies (I2 value = 97.48%, 95% CI 96.71–98.24 for sensitivity and I2 value = 98.17%, 95% CI 97.67–98.67 for specificity). Significant heterogeneity was observed for total number of samples between studies (p = 0.01), study design (whether using case-control design or not, p = 0.01), blinding during index test interpretation (p = 0.02), and QUADAS-2 score (p = 0.01).

Conclusions/significance

There was significant heterogeneity between the scrub typhus POCT diagnostic accuracy studies examined. Overall, the commercially available scrub typhus ICTs demonstrated better performance when ‘ruling in’ the diagnosis. There is a need for standardised methods and reporting of diagnostic accuracy to decrease between-study heterogeneity and increase comparability among study results, as well as development of an affordable and accurate antigen-based POCT to tackle the inherent weaknesses associated with serological testing.

Results of a confirmatory mapping tool for <i>Lymphatic filariasis</i> endemicity classification in areas where transmission was uncertain in Ethiopia

PLoS Neglected Tropical Diseases News - 26 March 2018 - 9:00pm

by Heven Sime, Katherine M. Gass, Sindew Mekasha, Ashenafi Assefa, Adugna Woyessa, Oumer Shafi, Kadu Meribo, Biruck Kebede, Kisito Ogoussan, Sonia Pelletreau, Moses J. Bockarie, Amha Kebede, Maria P. Rebollo

Background

The goal of the global lymphatic filariasis (LF) program is to eliminate the disease as a public health problem by the year 2020. The WHO mapping protocol that is used to identify endemic areas in need of mass drug administration (MDA) uses convenience-based sampling. This rapid mapping has allowed the global program to dramatically scale up treatment, but as the program approaches its elimination goal, it is important to ensure that all endemic areas have been identified and have received MDA. In low transmission settings, the WHO mapping protocol for LF mapping has several limitations. To correctly identify the LF endemicity of woredas, a new confirmatory mapping tool was developed to test older school children for circulating filarial antigen (CFA) in settings where it is uncertain. Ethiopia is the first country to implement this new tool. In this paper, we present the Ethiopian experience of implementing the new confirmatory mapping tool and discuss the implications of the results for the LF program in Ethiopia and globally.

Methods

Confirmatory LF mapping was conducted in 1,191 schools in 45 woredas, the implementation unit in Ethiopia, in the regions of Tigray, Amhara, Oromia, SNNP, Afar and Harari, where the results of previous mapping for LF using the current WHO protocol indicated that LF endemicity was uncertain. Within each woreda schools were selected using either cluster or systematic sampling. From selected schools, a total of 18,254 children were tested for circulating filarial antigen (CFA) using the immuno-chromatographic test (ICT).

Results

Of the 18,254 children in 45 woredas who participated in the survey, 28 (0.16%) in 9 woredas tested CFA positive. According to the confirmatory mapping threshold, which is ≥2% CFA in children 9–14 years of age, only 3 woredas out of the total 45 had more CFA positive results than the threshold and thus were confirmed to be endemic; the remaining 42 woredas were declared non-endemic. These results drastically decreased the estimated total population living in LF-endemic woredas in Ethiopia and in need of MDA by 49.1%, from 11,580,010 to 5,893,309.

Conclusion

This study demonstrated that the new confirmatory mapping tool for LF can benefit national LF programs by generating information that not only can confirm where LF is endemic, but also can save time and resources by preventing MDA where there is no evidence of ongoing LF transmission.

Community-based mass treatment with azithromycin for the elimination of yaws in Ghana—Results of a pilot study

PLoS Neglected Tropical Diseases News - 22 March 2018 - 9:00pm

by Abdul Aziz Abdulai, Patrick Agana-Nsiire, Frank Biney, Cynthia Kwakye-Maclean, Sardick Kyei-Faried, Kwame Amponsa-Achiano, Shirley Victoria Simpson, George Bonsu, Sally-Ann Ohene, William Kwabena Ampofo, Yaw Adu-Sarkodie, Kennedy Kwasi Addo, Kai-Hua Chi, Damien Danavall, Cheng Y. Chen, Allan Pillay, Sergi Sanz, Ye Tun, Oriol Mitjà, Kingsley Bampoe Asiedu, Ronald C. Ballard

Introduction

The WHO yaws eradication strategy consists of one round of total community treatment (TCT) of single-dose azithromycin with coverage of > 90%.The efficacy of the strategy to reduce the levels on infection has been demonstrated previously in isolated island communities in the Pacific region. We aimed to determine the efficacy of a single round of TCT with azithromycin to achieve a decrease in yaws prevalence in communities that are endemic for yaws and surrounded by other yaws-endemic areas.

Methods

Surveys for yaws seroprevalence and prevalence of skin lesions were conducted among schoolchildren aged 5–15 years before and one year after the TCT intervention in the Abamkrom sub-district of Ghana. We used a cluster design with the schools as the primary sampling unit. Among 20 eligible primary schools in the sub district, 10 were assigned to the baseline survey and 10 to the post-TCT survey. The field teams conducted a physical examination for skin lesions and a dual point-of-care immunoassay for non-treponemal and treponemal antibodies of all children present at the time of the visit. We also undertook surveys with non-probabilistic sampling to collect lesion swabs for etiology and macrolide resistance assessment.

Results

At baseline 14,548 (89%) of 16,287 population in the sub-district received treatment during TCT. Following one round of TCT, the prevalence of dual seropositivity among all children decreased from 10.9% (103/943) pre-TCT to 2.2% (27/1211) post-TCT (OR 0.19; 95%CI 0.09–0.37). The prevalence of serologically confirmed skin lesions consistent with active yaws was reduced from 5.7% (54/943) pre-TCT to 0.6% (7/1211) post-TCT (OR 0.10; 95% CI 0.25–0.35). No evidence of resistance to macrolides against Treponema pallidum subsp. pertenue was seen.

Discussion

A single round of high coverage TCT with azithromycin in a yaws affected sub-district adjoining other endemic areas is effective in reducing the prevalence of seropositive children and the prevalence of early skin lesions consistent with yaws one year following the intervention. These results suggest that national yaws eradication programmes may plan the gradual expansion of mass treatment interventions without high short-term risk of reintroduction of infection from contiguous untreated endemic areas.

First case of human infection with <i>Plasmodium knowlesi</i> in Laos

PLoS Neglected Tropical Diseases News - 22 March 2018 - 9:00pm

by Moritoshi Iwagami, Masami Nakatsu, Phonepadith Khattignavong, Pheovaly Soundala, Lavy Lorphachan, Sengdeuane Keomalaphet, Phonepadith Xangsayalath, Satoru Kawai, Bouasy Hongvanthong, Paul T. Brey, Shigeyuki Kano

Blood coagulation abnormalities in multibacillary leprosy patients

PLoS Neglected Tropical Diseases News - 22 March 2018 - 9:00pm

by Débora Santos da Silva, Lisandra Antonia Castro Teixeira, Daniela Gois Beghini, André Teixeira da Silva Ferreira, Márcia de Berredo Moreira Pinho, Patricia Sammarco Rosa, Marli Rambaldi Ribeiro, Monica Di Calafiori Freire, Mariana Andrea Hacker, José Augusto da Costa Nery, Maria Cristina Vidal Pessolani, Ana Maria Freire Tovar, Euzenir Nunes Sarno, Jonas Perales, Fernando Augusto Bozza, Danuza Esquenazi, Robson Queiroz Monteiro, Flavio Alves Lara

Background

Leprosy is a chronic dermato-neurological disease caused by Mycobacterium leprae infection. In 2016, more than 200,000 new cases of leprosy were detected around the world, representing the most frequent cause of infectious irreversible deformities and disabilities.

Principal findings

In the present work, we demonstrate a consistent procoagulant profile on 40 reactional and non-reactional multibacillary leprosy patients. A retrospective analysis in search of signs of coagulation abnormalities among 638 leprosy patients identified 35 leprosy patients (5.48%) which displayed a characteristic lipid-like clot formed between blood clot and serum during serum harvesting, herein named ‘leprosum clot’. Most of these patients (n = 16, 45.7%) belonged to the lepromatous leprosy pole of the disease. In addition, formation of the leprosum clot was directly correlated with increased plasma levels of soluble tissue factor and von Willebrand factor. High performance thin layer chromatography demonstrated a high content of neutral lipids in the leprosum clot, and proteomic analysis demonstrated that the leprosum clot presented in these patients is highly enriched in fibrin. Remarkably, differential 2D-proteomics analysis between leprosum clots and control clots identified two proteins present only in leprosy patients clots: complement component 3 and 4 and inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP). In agreement with those observations we demonstrated that M. leprae induces hepatocytes release of IHRP in vitro.

Conclusions

We demonstrated that leprosy MB patients develop a procoagulant status due to high levels of plasmatic fibrinogen, anti-cardiolipin antibodies, von Willebrand factor and soluble tissue factor. We propose that some of these components, fibrinogen for example, presents potential as predictive biomarkers of leprosy reactions, generating tools for earlier diagnosis and treatment of these events.

India’s neglected tropical diseases

PLoS Neglected Tropical Diseases News - 22 March 2018 - 9:00pm

by Peter J. Hotez, Ashish Damania

Xenosurveillance reflects traditional sampling techniques for the identification of human pathogens: A comparative study in West Africa

PLoS Neglected Tropical Diseases News - 21 March 2018 - 9:00pm

by Joseph R. Fauver, James Weger-Lucarelli, Lawrence S. Fakoli III, Kpehe Bolay, Fatorma K. Bolay, Joseph W. Diclaro II, Doug E. Brackney, Brian D. Foy, Mark D. Stenglein, Gregory D. Ebel

Background

Novel surveillance strategies are needed to detect the rapid and continuous emergence of infectious disease agents. Ideally, new sampling strategies should be simple to implement, technologically uncomplicated, and applicable to areas where emergence events are known to occur. To this end, xenosurveillance is a technique that makes use of blood collected by hematophagous arthropods to monitor and identify vertebrate pathogens. Mosquitoes are largely ubiquitous animals that often exist in sizable populations. As well, many domestic or peridomestic species of mosquitoes will preferentially take blood-meals from humans, making them a unique and largely untapped reservoir to collect human blood.

Methodology/Principal findings

We sought to take advantage of this phenomenon by systematically collecting blood-fed mosquitoes during a field trail in Northern Liberia to determine whether pathogen sequences from blood engorged mosquitoes accurately mirror those obtained directly from humans. Specifically, blood was collected from humans via finger-stick and by aspirating bloodfed mosquitoes from the inside of houses. Shotgun metagenomic sequencing of RNA and DNA derived from these specimens was performed to detect pathogen sequences. Samples obtained from xenosurveillance and from finger-stick blood collection produced a similar number and quality of reads aligning to two human viruses, GB virus C and hepatitis B virus.

Conclusions/Significance

This study represents the first systematic comparison between xenosurveillance and more traditional sampling methodologies, while also demonstrating the viability of xenosurveillance as a tool to sample human blood for circulating pathogens.

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