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Multibacillary leprosy by population groups in Brazil: Lessons from an observational study

PLoS Neglected Tropical Diseases News - 13 February 2017 - 10:00pm

by Mauricio Lisboa Nobre, Ximena Illarramendi, Kathryn Margaret Dupnik, Mariana de Andrea Hacker, José Augusto da Costa Nery, Selma Maria Bezerra Jerônimo, Euzenir Nunes Sarno

Background

Leprosy remains an important public health problem in Brazil where 28,761 new cases were diagnosed in 2015, the second highest number of new cases detected globally. The disease is caused by Mycobacterium leprae, a pathogen spread by patients with multibacillary (MB) leprosy. This study was designed to identify population groups most at risk for MB disease in Brazil, contributing to new ideas for early diagnosis and leprosy control.

Methods

A national databank of cases reported in Brazil (2001–2013) was used to evaluate epidemiological characteristics of MB leprosy. Additionally, the databank of a leprosy reference center was used to determine factors associated with higher bacillary loads.

Results

A total of 541,090 cases were analyzed. New case detection rates (NCDRs) increased with age, especially for men with MB leprosy, reaching 44.8 new cases/100,000 population in 65–69 year olds. Males and subjects older than 59 years had twice the odds of MB leprosy than females and younger cases (OR = 2.36, CI95% = 2.33–2.38; OR = 1.99, CI95% = 1.96–2.02, respectively). Bacillary load was higher in male and in patients aged 20–39 and 40–59 years compared to females and other age groups. From 2003 to 2013, there was a progressive reduction in annual NCDRs and an increase in the percentage of MB cases and of elderly patients in Brazil. These data suggest reduction of leprosy transmission in the country.

Conclusion

Public health policies for leprosy control in endemic areas in Brazil should include activities especially addressed to men and to the elderly in order to further reduce M. leprae transmission.

Improving access to Chagas disease diagnosis and etiologic treatment in remote rural communities of the Argentine Chaco through strengthened primary health care and broad social participation

PLoS Neglected Tropical Diseases News - 13 February 2017 - 10:00pm

by Paula Sartor, Ivana Colaianni, M. Victoria Cardinal, Jacqueline Bua, Héctor Freilij, Ricardo E. Gürtler

Background

Rural populations in the Gran Chaco region have large prevalence rates of Trypanosoma cruzi infection and very limited access to diagnosis and treatment. We implemented an innovative strategy to bridge these gaps in 13 rural villages of Pampa del Indio held under sustained vector surveillance and control.

Methodology

The non-randomized treatment program included participatory workshops, capacity strengthening of local health personnel, serodiagnosis, qualitative and quantitative PCRs, a 60-day treatment course with benznidazole and follow-up. Parents and healthcare agents were instructed on drug administration and early detection and notification of adverse drug-related reactions (ADR). Healthcare agents monitored medication adherence and ADRs at village level.

Principal findings

The seroprevalence of T. cruzi infection was 24.1% among 395 residents up to 18 years of age examined. Serodiagnostic (70%) and treatment coverage (82%) largely exceeded local historical levels. Sixty-six (85%) of 78 eligible patients completed treatment with 97% medication adherence. ADRs occurred in 32% of patients, but most were mild and manageable. Four patients showing severe or moderate ADRs required treatment withdrawal. T. cruzi DNA was detected by qPCR in 47 (76%) patients before treatment, and persistently occurred in only one patient over 20–180 days posttreatment.

Conclusions and significance

Our results demonstrate that diagnosis and treatment of T. cruzi infection in remote, impoverished rural areas can be effectively addressed through strengthened primary healthcare attention and broad social participation with adequate external support. This strategy secured high treatment coverage and adherence; effectively managed ADRs, and provided early evidence of positive therapeutic responses.

Review of 21 cases of mycetoma from 1991 to 2014 in Rio de Janeiro, Brazil

PLoS Neglected Tropical Diseases News - 13 February 2017 - 10:00pm

by Felipe Maurício Soeiro Sampaio, Bodo Wanke, Dayvison Francis Saraiva Freitas, Janice Mery Chicarino de Oliveira Coelho, Maria Clara Gutierrez Galhardo, Marcelo Rosandiski Lyra, Maria Cristina da Silva Lourenço, Rodrigo de Almeida Paes, Antonio Carlos Francesconi do Valle

Mycetoma is caused by the subcutaneous inoculation of filamentous fungi or aerobic filamentous bacteria that form grains in the tissue. The purpose of this study is to describe the epidemiologic, clinic, laboratory, and therapeutic characteristics of patients with mycetoma at the Oswaldo Cruz Foundation in Rio de Janeiro, Brazil, between 1991 and 2014. Twenty-one cases of mycetoma were included in the study. There was a predominance of male patients (1.3:1) and the average patient age was 46 years. The majority of the cases were from the Southeast region of Brazil and the feet were the most affected anatomical region (80.95%). Eumycetoma prevailed over actinomycetoma (61.9% and 38.1% respectively). Eumycetoma patients had positive cultures in 8 of 13 cases, with isolation of Scedosporium apiospermum species complex (n = 3), Madurella mycetomatis (n = 2) and Acremonium spp. (n = 1). Two cases presented sterile mycelium and five were negative. Six of 8 actinomycetoma cases had cultures that were identified as Nocardia spp. (n = 3), Nocardia brasiliensis (n = 2), and Nocardia asteroides (n = 1). Imaging tests were performed on all but one patients, and bone destruction was identified in 9 cases (42.68%). All eumycetoma cases were treated with itraconazole monotherapy or combined with fluconazole, terbinafine, or amphotericin B. Actinomycetoma cases were treated with sulfamethoxazole plus trimethoprim or combined with cycles of amikacin sulphate. Surgical procedures were performed in 9 (69.2%) eumycetoma and in 3 (37.5%) actinomycetoma cases, with one amputation case in each group. Clinical cure occurred in 11 cases (7 for eumycetoma and 4 for actinomycetoma), and recurrence was documented in 4 of 21 cases. No deaths were recorded during the study. Despite of the scarcity of mycetoma in our institution the cases presented reflect the wide clinical spectrum and difficulties to take care of this neglected disease.

Holding back the tiger: Successful control program protects Australia from <i>Aedes albopictus</i> expansion

PLoS Neglected Tropical Diseases News - 13 February 2017 - 10:00pm

by Mutizwa Odwell Muzari, Gregor Devine, Joseph Davis, Bruce Crunkhorn, Andrew van den Hurk, Peter Whelan, Richard Russell, James Walker, Peter Horne, Gerhard Ehlers, Scott Ritchie

Background

The Asian tiger mosquito, Aedes albopictus, is an important vector of dengue, chikungunya and Zika viruses and is a highly invasive and aggressive biter. Established populations of this species were first recognised in Australia in 2005 when they were discovered on islands in the Torres Strait, between mainland Australia and Papua New Guinea. A control program was implemented with the original goal of eliminating Ae. albopictus from the Torres Strait. We describe the evolution of management strategies that provide a template for Ae. albopictus control that can be adopted elsewhere.

Methodology / Principal findings

The control strategy implemented between 2005 and 2008 targeted larval habitats using source reduction, insect-growth regulator and pyrethroid insecticide to control larvae and adults in the containers. However, the infrequency of insecticide reapplication, the continual accumulation and replacement of containers, and imminent re-introduction of mosquitoes through people’s movement from elsewhere compromised the program. Consequently, in 2009 the objective of the program changed from elimination to quarantine, with the goal of preventing Ae albopictus from infesting Thursday and Horn islands, which are the transport hubs connecting the Torres Strait to mainland Australia. However, larval control strategies did not prevent the species establishing on these islands in 2010. Thereafter, an additional strategy adopted by the quarantine program in early 2011 was harborage spraying, whereby the vegetated, well shaded resting sites of adult Ae. albopictus were treated with a residual pyrethroid insecticide. Inclusion of this additional measure led to a 97% decline in Ae. albopictus numbers within two years. In addition, the frequency of container treatment was increased to five weeks between treatments, compared to an average of 8 weeks that occurred in the earlier iterations of the program. By 2015 and 2016, Ae. albopictus populations on the two islands were undetectable in 70–90% of surveys conducted. Importantly, a comprehensive surveillance network in selected strategic areas has not identified established populations of this species on the Australian mainland.

Conclusions / Significance

The program has successfully reduced Ae. albopictus populations on Thursday Island and Horn Island to levels where it is undetectable in up to 90% of surveys, and has largely removed the risk of mainland establishment via that route. The vector management strategies adopted in the later years of the program have been demonstrably successful and provide a practical management framework for dengue, chikungunya or Zika virus outbreaks vectored by Ae. albopictus. As of June 2016, Ae. albopictus had not established on the Australian mainland and this program has likely contributed significantly to this outcome.

Mosquito cell-derived West Nile virus replicon particles mimic arbovirus inoculum and have reduced spread in mice

PLoS Neglected Tropical Diseases News - 10 February 2017 - 10:00pm

by Brendan T. Boylan, Fernando R. Moreira, Tim W. Carlson, Kristen A. Bernard

Half of the human population is at risk of infection by an arthropod-borne virus. Many of these arboviruses, such as West Nile, dengue, and Zika viruses, infect humans by way of a bite from an infected mosquito. This infectious inoculum is insect cell-derived giving the virus particles distinct qualities not present in secondary infectious virus particles produced by infected vertebrate host cells. The insect cell-derived particles differ in the glycosylation of virus structural proteins and the lipid content of the envelope, as well as their induction of cytokines. Thus, in order to accurately mimic the inoculum delivered by arthropods, arboviruses should be derived from arthropod cells. Previous studies have packaged replicon genome in mammalian cells to produce replicon particles, which undergo only one round of infection, but no studies exist packaging replicon particles in mosquito cells. Here we optimized the packaging of West Nile virus replicon genome in mosquito cells and produced replicon particles at high concentration, allowing us to mimic mosquito cell-derived viral inoculum. These particles were mature with similar genome equivalents-to-infectious units as full-length West Nile virus. We then compared the mosquito cell-derived particles to mammalian cell-derived particles in mice. Both replicon particles infected skin at the inoculation site and the draining lymph node by 3 hours post-inoculation. The mammalian cell-derived replicon particles spread from the site of inoculation to the spleen and contralateral lymph nodes significantly more than the particles derived from mosquito cells. This in vivo difference in spread of West Nile replicons in the inoculum demonstrates the importance of using arthropod cell-derived particles to model early events in arboviral infection and highlights the value of these novel arthropod cell-derived replicon particles for studying the earliest virus-host interactions for arboviruses.

Asymptomatic leishmaniasis in kala-azar endemic areas of Malda district, West Bengal, India

PLoS Neglected Tropical Diseases News - 10 February 2017 - 10:00pm

by Pabitra Saha, Swagata Ganguly, Moytrey Chatterjee, Soumendu Bikash Das, Pratip K. Kundu, Subhasish K. Guha, Tamal K. Ghosh, Dilip K. Bera, Nandita Basu, Ardhendu K. Maji

Asymptomatic leishmaniasis may drive the epidemic and an important challenge to reach the goal of joint Visceral Leishmaniasis (VL) elimination initiative taken by three Asian countries. The role of these asymptomatic carriers in disease transmission, prognosis at individual level and rate of transformation to symptomatic VL/Post Kala-azar Dermal Leishmaniasis (PKDL) needs to be evaluated. Asymptomatic cases were diagnosed by active mass survey in eight tribal villages by detecting antileishmanial antibody using rK39 based rapid diagnostic kits and followed up for three years to observe the pattern of sero-conversion and disease transformation. Out of 2890 total population, 2603 were screened. Antileishmanial antibody was detected in 185 individuals of them 96 had a history of VL/PKDL and 89 without such history. Seventy nine such individuals were classified as asymptomatic leishmaniasis and ten as active VL with a ratio of 7.9:1. Out of 79 asymptomatic cases 2 were lost to follow up as they moved to other places. Amongst asymptomatically infected persons, disease transformation in 8/77 (10.39%) and sero-conversion in 62/77 (80.52%) cases were noted. Seven (9.09%) remained sero-positive even after three years. Progression to clinical disease among asymptomatic individuals was taking place at any time up to three years after the baseline survey. If there are no VL /PKDL cases for two or more years, it does not mean that the area is free from leishmaniasis as symptomatic VL or PKDL may appear even after three years, if there are such asymptomatic cases. So, asymptomatic infected individuals need much attention for VL elimination programme that has been initiated by three adjoining endemic countries.

Podoconiosis, trachomatous trichiasis and cataract in northern Ethiopia: A comparative cross sectional study

PLoS Neglected Tropical Diseases News - 10 February 2017 - 10:00pm

by Helen Burn, Sintayehu Aweke, Tariku Wondie, Esmael Habtamu, Kebede Deribe, Saul Rajak, Stephen Bremner, Gail Davey

Background

Rural populations in low-income countries commonly suffer from the co-morbidity of neglected tropical diseases (NTDs). Podoconiosis, trachomatous trichiasis (both NTDs) and cataract are common causes of morbidity among subsistence farmers in the highlands of northern Ethiopia. We explored whether podoconiosis was associated with cataract or trachomatous trichiasis (TT) among this population.

Methods

A comparative cross-sectional study was conducted in East Gojam region, Amhara, Ethiopia in May 2016. Data were collected from patients previously identified as having podoconiosis and from matched healthy neighbourhood controls. Information on socio-demographic factors, clinical factors and past medical history were collected by an interview-administered questionnaire. Clinical examination involved grading of podoconiosis by examination of both legs, measurement of visual acuity, direct ophthalmoscopy of dilated pupils to grade cataract, and eyelid and corneal examination to grade trachoma. Multiple logistic regression was conducted to estimate independent association and correlates of podoconiosis, TT and cataract.

Findings

A total of 700 participants were included in this study; 350 podoconiosis patients and 350 healthy neighbourhood controls. The prevalence of TT was higher among podoconiosis patients than controls (65 (18.6%) vs 43 (12.3%)) with an adjusted odds ratio OR 1.57 (95% CI 1.02–2.40), p = 0.04. There was no significant difference in prevalence of cataract between the two populations with an adjusted OR 0.83 (95% CI 0.55–1.25), p = 0.36. Mean best visual acuity was 0.59 (SD 0.06) in podoconiosis cases compared to 0.44 (SD 0.04) in controls, p<0.001. The proportion of patients classified as blind was higher in podoconiosis cases compared with healthy controls; 5.6% vs 2.0%; adjusted OR 2.63 (1.08–6.39), P = 0.03.

Conclusions

Individuals with podoconiosis have a higher burden of TT and worse visual acuity than their matched healthy neighbourhood controls. Further research into the environmental and biological reasons for this co-morbidity is required. A shared approach to managing these two NTDs within the same population could be beneficial.

Detection of the mosquito-borne flaviviruses, West Nile, Dengue, Saint Louis Encephalitis, Ilheus, Bussuquara, and Yellow Fever in free-ranging black howlers (<i>Alouatta caraya</i>) of Northeastern Argentina

PLoS Neglected Tropical Diseases News - 10 February 2017 - 10:00pm

by María A. Morales, Cintia M. Fabbri, Gabriel E. Zunino, Martín M. Kowalewski, Victoria C. Luppo, Delia A. Enría, Silvana C. Levis, Gladys E. Calderón

Several medically important mosquito-borne flaviviruses have been detected in Argentina in recent years: Dengue (DENV), St. Louis encephalitis (SLEV), West Nile (WNV) and Yellow Fever (YFV) viruses. Evidence of Bussuquara virus (BSQV) and Ilheus virus (ILHV) activity were found, but they have not been associated with human disease. Non-human primates can act as important hosts in the natural cycle of flaviviruses and serological studies can lead to improved understanding of virus circulation dynamics and host susceptibility. From July–August 2010, we conducted serological and molecular surveys in free–ranging black howlers (Alouatta caraya) captured in northeastern Argentina. We used 90% plaque-reduction neutralization tests (PRNT90) to analyze 108 serum samples for antibodies to WNV, SLEV, YFV, DENV (serotypes 1and 3), ILHV, and BSQV. Virus genome detection was performed using generic reverse transcription (RT)-nested PCR to identify flaviviruses in 51 antibody-negative animals. Seventy animals had antibodies for one or more flaviviruses for a total antibody prevalence of 64.8% (70/108). Monotypic (13/70, 19%) and heterotypic (27/70, 39%) patterns were differentiated. Specific neutralizing antibodies against WNV, SLEV, DENV-1, DENV-3, ILHV, and BSQV were found. Unexpectedly, the highest flavivirus antibody prevalence detected was to WNV with 9 (8.33%) monotypic responses. All samples tested by (RT)-nested PCR were negative for viral genome. This is the first detection of WNV-specific antibodies in black howlers from Argentina and the first report in free-ranging non-human primates from Latin-American countries. Given that no animals had specific neutralizing antibodies to YFV, our results suggest that the study population remains susceptible to YFV. Monitoring of these agents should be strengthened to detect the establishment of sylvatic cycles of flaviviruses in America and evaluate risks to wildlife and human health.

Killing of diverse eye pathogens (<i>Acanthamoeba spp</i>., <i>Fusarium solani</i>, and <i>Chlamydia trachomatis</i>) with alcohols

PLoS Neglected Tropical Diseases News - 9 February 2017 - 10:00pm

by Yousuf Aqeel, Raquel Rodriguez, Aparajita Chatterjee, Robin R. Ingalls, John Samuelson

Background

Blindness is caused by eye pathogens that include a free-living protist (Acanthamoeba castellanii, A. byersi, and/or other Acanthamoeba spp.), a fungus (Fusarium solani), and a bacterium (Chlamydia trachomatis). Hand-eye contact is likely a contributor to the spread of these pathogens, and so hand washing with soap and water or alcohol–based hand sanitizers (when water is not available) might reduce their transmission. Recently we showed that ethanol and isopropanol in concentrations present in hand sanitizers kill walled cysts of Giardia and Entamoeba, causes of diarrhea and dysentery, respectively. The goal here was to determine whether these alcohols might kill infectious forms of representative eye pathogens (trophozoites and cysts of Acanthamoeba, conidia of F. solani, or elementary bodies of C. trachomatis).

Methodology/Principal findings

We found that treatment with 63% ethanol or 63% isopropanol kills >99% of Acanthamoeba trophozoites after 30 sec exposure, as shown by labeling with propidium iodide (PI) and failure to grow in culture. In contrast, Acanthamoeba cysts, which contain cellulose fibers in their wall, are relatively more resistant to these alcohols, particularly isopropanol. Depending upon the strain tested, 80 to 99% of Acanthamoeba cysts were killed by 63% ethanol after 2 min and 95 to 99% were killed by 80% ethanol after 30 sec, as shown by PI labeling and reduced rates of excystation in vitro. Both ethanol and isopropanol (63% for 30 sec) kill >99% of F. solani conidia, which have a wall of chitin and glucan fibrils, as demonstrated by PI labeling and colony counts on nutrient agar plates. Both ethanol and isopropanol (63% for 60 sec) inactivate 96 to 99% of elementary bodies of C. trachomatis, which have a wall of lipopolysaccharide but lack peptidoglycan, as measured by quantitative cultures to calculate inclusion forming units.

Conclusions/Significance

In summary, alcohols kill infectious forms of Acanthamoeba, F. solani, and C. trachomatis, although longer times and higher ethanol concentrations are necessary for Acanthamoeba cysts. These results suggest the possibility that expanded use of alcohol-based hand sanitizers in places where water is not easily available might reduce transmission of these important causes of blindness.

Improving our forecasts for trachoma elimination: What else do we need to know?

PLoS Neglected Tropical Diseases News - 9 February 2017 - 10:00pm

by Amy Pinsent, Manoj Gambhir

The World Health Organization (WHO) has targeted trachoma for elimination as a public health concern by 2020. Mathematical modelling is used for a range of infectious diseases to assess the impact of different intervention strategies on the prevalence of infection or disease. Here we evaluate the performance of four different mechanistic mathematical models that could all realistically represent trachoma transmission. We fit the four different mechanistic models of trachoma transmission to cross-sectional age-specific Polymerase Chain Reaction (PCR) and Trachomatous inflammation, follicular (TF) prevalence data. We estimate 4 or 3 parameters within each model, including the duration of an individual’s infection and disease episode using Markov Chain Monte Carlo. We assess the performance of each models fit to the data by calculating the deviance information criterion. We then model the implementation of different interventions for each model structure to assess the feasibility of elimination of trachoma with different model structure. A model structure which allowed some re-infection in the disease state (Model 2) was statistically the most well performing model. All models struggled to fit to the very high prevalence of active disease in the youngest age group. Our simulations suggested that for Model 3, with annual antibiotic treatment and transmission reduction, the chance of reducing active disease prevalence to < 5% within 5 years was very low, while Model 2 and 4 could ensure that active disease prevalence was reduced within 5 years. Model 2 here fitted to the data best of the models evaluated. The appropriate level of susceptibility to re-infection was, however, challenging to identify given the amount and kind of data available. We demonstrate that the model structure assumed can lead to different end points following the implementation of the same interventions. Our findings are likely to extend beyond trachoma and should be considered when modelling other neglected tropical diseases.

Metformin exhibits preventive and therapeutic efficacy against experimental cystic echinococcosis

PLoS Neglected Tropical Diseases News - 9 February 2017 - 10:00pm

by Julia A. Loos, Valeria A. Dávila, Christian R. Rodrígues, Romina Petrigh, Jorge A. Zoppi, Fernando A. Crocenzi, Andrea C. Cumino

Metformin (Met) is an anti-hyperglycemic and potential anti-cancer agent which may exert its anti-proliferative effects via the induction of energetic stress. In this study we investigated the in vitro and in vivo efficacy of Met against the larval stage of Echinococcus granulosus. Metformin showed significant dose- and time-dependent killing effects on in vitro cultured protoscoleces and metacestodes. Notably, the combination of Met together with the minimum effective concentration of ABZSO had a synergistic effect after days 3 and 12 on metacestodes and protoscoleces, respectively. Oral administration of Met (50 mg/kg/day) in E. granulosus-infected mice was highly effective in reducing the weight and number of parasite cysts, yet its combination with the lowest recommended dose of ABZ (5 mg/kg/day) was even more effective. Coincidentally, intracystic Met accumulation was higher in animals treated with both drugs compared to those administered Met alone. Furthermore, the safe plant-derived drug Met exhibited remarkable chemopreventive properties against secondary hydatidosis in mice. In conclusion, based on our experimental data, Met emerges as a promising anti-echinococcal drug as it has proven to efficiently inhibit the development and growth of the E. granulosus larval stage and its combination with ABZ may improve the current anti-parasitic therapy.

Dihydrobenz[<i>e</i>][1,4]oxazepin-2(3<i>H</i>)-ones, a new anthelmintic chemotype immobilising whipworm and reducing infectivity <i>in vivo</i>

PLoS Neglected Tropical Diseases News - 9 February 2017 - 10:00pm

by Frederick A. Partridge, Emma A. Murphy, Nicky J. Willis, Carole J. R. Bataille, Ruth Forman, Narinder Heyer-Chauhan, Bruno Marinič, Daniel J. C. Sowood, Graham M. Wynne, Kathryn J. Else, Angela J. Russell, David B. Sattelle

Trichuris trichiura is a human parasitic whipworm infecting around 500 million people globally, damaging the physical growth and educational performance of those infected. Current drug treatment options are limited and lack efficacy against the worm, preventing an eradication programme. It is therefore important to develop new treatments for trichuriasis. Using Trichuris muris, an established model for T. trichiura, we screened a library of 480 novel drug-like small molecules for compounds causing paralysis of the ex vivo adult parasite. We identified a class of dihydrobenz[e][1,4]oxazepin-2(3H)-one compounds with anthelmintic activity against T. muris. Further screening of structurally related compounds and resynthesis of the most potent molecules led to the identification of 20 active dihydrobenzoxazepinones, a class of molecule not previously implicated in nematode control. The most active immobilise adult T. muris with EC50 values around 25–50μM, comparable to the existing anthelmintic levamisole. The best compounds from this chemotype show low cytotoxicity against murine gut epithelial cells, demonstrating selectivity for the parasite. Developing a novel oral pharmaceutical treatment for a neglected disease and deploying it via mass drug administration is challenging. Interestingly, the dihydrobenzoxazepinone OX02983 reduces the ability of embryonated T. muris eggs to establish infection in the mouse host in vivo. Complementing the potential development of dihydrobenzoxazepinones as an oral anthelmintic, this supports an alternative strategy of developing a therapeutic that acts in the environment, perhaps via a spray, to interrupt the parasite lifecycle. Together these results show that the dihydrobenzoxazepinones are a new class of anthelmintic, active against both egg and adult stages of Trichuris parasites. They demonstrate encouraging selectivity for the parasite, and importantly show considerable scope for further optimisation to improve potency and pharmacokinetic properties with the aim of developing a clinical agent.

Modeling the Potential for Vaccination to Diminish the Burden of Invasive Non-typhoidal <i>Salmonella</i> Disease in Young Children in Mali, West Africa

PLoS Neglected Tropical Diseases News - 9 February 2017 - 10:00pm

by Kristin Bornstein, Laura Hungerford, David Hartley, John D. Sorkin, Milagritos D. Tapia, Samba O. Sow, Uma Onwuchekwa, Raphael Simon, Sharon M. Tennant, Myron M. Levine

Background

In sub-Saharan Africa, systematic surveillance of young children with suspected invasive bacterial disease (e.g., septicemia, meningitis) has revealed non-typhoidal Salmonella (NTS) to be a major pathogen exhibiting high case fatality (~20%). Where infant vaccination against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae has been introduced to prevent invasive disease caused by these pathogens, as in Bamako, Mali, their burden has decreased markedly. In parallel, NTS has become the predominant invasive bacterial pathogen in children aged <5 years. While NTS is believed to be acquired orally via contaminated food/water, epidemiologic studies have failed to identify the reservoir of infection or vehicles of transmission. This has precluded targeting food chain interventions to diminish disease transmission but conversely has fostered the development of vaccines to prevent invasive NTS (iNTS) disease. We developed a mathematical model to estimate the potential impact of NTS vaccination programs in Bamako.

Methodology/Principal Findings

A Markov chain transmission model was developed utilizing age-specific Bamako demographic data and hospital surveillance data for iNTS disease in children aged <5 years and assuming vaccine coverage and efficacy similar to the existing, successfully implemented, Hib vaccine. Annual iNTS hospitalizations and deaths in children <5 years, with and without a Salmonella Enteritidis/Salmonella Typhimurium vaccine, were the model’s outcomes of interest. Per the model, high coverage/high efficacy iNTS vaccination programs would drastically diminish iNTS disease except among infants age <8 weeks.

Conclusions/Significance

The public health impact of NTS vaccination shifts as disease burden, vaccine coverage, and serovar distribution vary. Our model shows that implementing an iNTS vaccine through an analogous strategy to the Hib vaccination program in Bamako would markedly reduce cases and deaths due to iNTS among the pediatric population. The model can be adjusted for use elsewhere in Africa where NTS epidemiologic patterns, serovar prevalence, and immunization schedules differ from Bamako.

Investigation on predominant <i>Leptospira</i> serovars and its distribution in humans and livestock in Thailand, 2010-2015

PLoS Neglected Tropical Diseases News - 9 February 2017 - 10:00pm

by Sudarat Chadsuthi, Dominique J. Bicout, Anuwat Wiratsudakul, Duangjai Suwancharoen, Wimol Petkanchanapong, Charin Modchang, Wannapong Triampo, Parntep Ratanakorn, Karine Chalvet-Monfray

Background

Leptospirosis is a worldwide zoonotic bacterial disease caused by infection with leptospires. Leptospirosis in humans and livestock is an endemic and epidemic disease in Thailand. Livestock may act as reservoirs for leptospires and source for human infection.

Methodology/Principal findings

Data on leptospirosis infection in humans and livestock (Buffaloes, Cattle, and Pigs) species during 2010 to 2015 were analyzed. Serum samples were examined using Microscopic Agglutination Test (MAT) to identify antibodies against Leptospira serovars using a cut-off titer ≥ 1:100. The seroprevalence was 23.7% in humans, 24.8% in buffaloes, 28.1% in cattle, and 11.3% in pigs. Region specific prevalence among humans and livestock was found in a wide range. The most predominant serovars were Shermani, followed by Bratislava, Panama, and Sejroe in human, Shermani, Ranarum, and Tarassovi in buffaloes, and Shermani and Ranarum in cattle and pigs. Equally highest MAT titers against multiple serovars per one sample were found mainly in buffaloes and cattle showing equally titers against Ranarum and Shermani. The correlations of distribution of serovars across Thailand’s regions were found to be similar in pattern for cattle but not for buffaloes. In humans, the serovar distribution in the south differed from other regions. By logistic regression, the results indicated that livestock is more susceptible to infection by serovar Shermani when compared to humans.

Conclusions/Significance

This study gives a detailed picture of the predominance of Leptospira serovars in relation to region, humans and typical livestock. The broad spatial distribution of seroprevalence was analyzed across and within species as well as regions in Thailand. Our finding may guide public health policy makers to implement appropriate control measures and help to reduce the impact of leptospirosis in Thailand.

Nakalanga Syndrome: Clinical Characteristics, Potential Causes, and Its Relationship with Recently Described Nodding Syndrome

PLoS Neglected Tropical Diseases News - 9 February 2017 - 10:00pm

by Kathrin Föger, Gina Gora-Stahlberg, James Sejvar, Emilio Ovuga, Louise Jilek-Aall, Erich Schmutzhard, Christoph Kaiser, Andrea S. Winkler

Nakalanga syndrome is a condition that was described in Uganda and various other African countries decades ago. Its features include growth retardation, physical deformities, endocrine dysfunction, mental impairment, and epilepsy, amongst others. Its cause remains obscure. Nodding syndrome is a neurological disorder with some features in common with Nakalanga syndrome, which has been described mainly in Uganda, South Sudan, and Tanzania. It has been considered an encephalopathy affecting children who, besides head nodding attacks, can also present with stunted growth, delayed puberty, and mental impairment, amongst other symptoms. Despite active research over the last years on the pathogenesis of Nodding syndrome, to date, no convincing single cause of Nodding syndrome has been reported. In this review, by means of a thorough literature search, we compare features of both disorders. We conclude that Nakalanga and Nodding syndromes are closely related and may represent the same condition. Our findings may provide new directions in research on the cause underlying this neurological disorder.

Environmental and Social Change Drive the Explosive Emergence of Zika Virus in the Americas

PLoS Neglected Tropical Diseases News - 9 February 2017 - 10:00pm

by Sofia Ali, Olivia Gugliemini, Serena Harber, Alexandra Harrison, Lauren Houle, Javarcia Ivory, Sierra Kersten, Rebia Khan, Jenny Kim, Chris LeBoa, Emery Nez-Whitfield, Jamieson O’Marr, Emma Rothenberg, R. Max Segnitz, Stephanie Sila, Anna Verwillow, Miranda Vogt, Adrienne Yang, Erin A. Mordecai

Since Zika virus (ZIKV) was detected in Brazil in 2015, it has spread explosively across the Americas and has been linked to increased incidence of microcephaly and Guillain-Barré syndrome (GBS). In one year, it has infected over 500,000 people (suspected and confirmed cases) in 40 countries and territories in the Americas. Along with recent epidemics of dengue (DENV) and chikungunya virus (CHIKV), which are also transmitted by Aedes aegypti and Ae. albopictus mosquitoes, the emergence of ZIKV suggests an ongoing intensification of environmental and social factors that have given rise to a new regime of arbovirus transmission. Here, we review hypotheses and preliminary evidence for the environmental and social changes that have fueled the ZIKV epidemic. Potential drivers include climate variation, land use change, poverty, and human movement. Beyond the direct impact of microcephaly and GBS, the ZIKV epidemic will likely have social ramifications for women’s health and economic consequences for tourism and beyond.

<i>Trypanosoma cruzi</i> High Mobility Group B (<i>Tc</i>HMGB) can act as an inflammatory mediator on mammalian cells

PLoS Neglected Tropical Diseases News - 8 February 2017 - 10:00pm

by Pamela Cribb, Virginia Perdomo, Victoria L. Alonso, Romina Manarin, Jorge Barrios-Payan, Brenda Marquina-Castillo, Luis Tavernelli, Rogelio Hernández-Pando

Background

High Mobility Group B (HMGB) proteins are nuclear architectural factors involved in chromatin remodeling and important nuclear events. HMGBs also play key roles outside the cell acting as alarmins or Damage-associated Molecular Patterns (DAMPs). In response to a danger signal these proteins act as immune mediators in the extracellular milieu. Moreover, these molecules play a central role in the pathogenesis of many autoimmune and both infectious and sterile inflammatory chronic diseases.

Principal findings

We have previously identified a High mobility group B protein from Trypanosoma cruzi (TcHMGB) and showed that it has architectural properties interacting with DNA like HMGBs from other eukaryotes. Here we show that TcHMGB can be translocated to the cytoplasm and secreted out of the parasite, a process that seems to be stimulated by acetylation. We report that recombinant TcHMGB is able to induce an inflammatory response in vitro and in vivo, evidenced by the production of Nitric Oxide and induction of inflammatory cytokines like TNF-α, IL-1β and IFN-γ gene expression. Also, TGF-β and IL-10, which are not inflammatory cytokines but do play key roles in Chagas disease, were induced by rTcHMGB.

Conclusions

These preliminary results suggest that TcHMGB can act as an exogenous immune mediator that may be important for both the control of parasite replication as the pathogenesis of Chagas disease and can be envisioned as a pathogen associated molecular pattern (PAMP) partially overlapping in function with the host DAMPs.

Prevalence and clinical relevance of helminth co-infections among tuberculosis patients in urban Tanzania

PLoS Neglected Tropical Diseases News - 8 February 2017 - 10:00pm

by Francis Mhimbira, Jerry Hella, Khadija Said, Lujeko Kamwela, Mohamed Sasamalo, Thomas Maroa, Magreth Chiryamkubi, Grace Mhalu, Christian Schindler, Klaus Reither, Stefanie Knopp, Jürg Utzinger, Sébastien Gagneux, Lukas Fenner

Background

Helminth infections can negatively affect the immunologic host control, which may increase the risk of progression from latent Mycobacterium tuberculosis infection to tuberculosis (TB) disease and alter the clinical presentation of TB. We assessed the prevalence and determined the clinical relevance of helminth co-infection among TB patients and household contact controls in urban Tanzania.

Methodology

Between November 2013 and October 2015, we enrolled adult (≥18 years) sputum smear-positive TB patients and household contact controls without TB during an ongoing TB cohort study in Dar es Salaam, Tanzania. We used Baermann, FLOTAC, Kato-Katz, point-of-care circulating cathodic antigen, and urine filtration to diagnose helminth infections. Multivariable logistic regression models with and without random effects for households were used to assess for associations between helminth infection and TB.

Principal findings

A total of 597 TB patients and 375 household contact controls were included. The median age was 33 years and 60.2% (585/972) were men. The prevalence of any helminth infection among TB patients was 31.8% (190/597) and 25.9% (97/375) among controls. Strongyloides stercoralis was the predominant helminth species (16.6%, 161), followed by hookworm (9.0%, 87) and Schistosoma mansoni (5.7%, 55). An infection with any helminth was not associated with TB (adjusted odds ratio (aOR) 1.26, 95% confidence interval (CI): 0.88–1.80, p = 0.22), but S. mansoni infection was (aOR 2.15, 95% CI: 1.03–4.45, p = 0.040). Moreover, S. mansoni infection was associated with lower sputum bacterial load (aOR 2.63, 95% CI: 1.38–5.26, p = 0.004) and tended to have fewer lung cavitations (aOR 0.41, 95% CI: 0.12–1.16, p = 0.088).

Conclusions/Significance

S. mansoni infection was an independent risk factor for active TB and altered the clinical presentation in TB patients. These findings suggest a role for schistosomiasis in modulating the pathogenesis of human TB. Treatment of helminths should be considered in clinical management of TB and TB control programs.

The impact of prenatal exposure to parasitic infections and to anthelminthic treatment on antibody responses to routine immunisations given in infancy: Secondary analysis of a randomised controlled trial

PLoS Neglected Tropical Diseases News - 8 February 2017 - 10:00pm

by Stephen Nash, Alexander J. Mentzer, Swaib A. Lule, Dennison Kizito, Gaby Smits, Fiona R. M. van der Klis, Alison M. Elliott

Background

Chronic parasitic infections are associated with active immunomodulation which may include by-stander effects on unrelated antigens. It has been suggested that pre-natal exposure to parasitic infections in the mother impacts immunological development in the fetus and hence the offspring’s response to vaccines, and that control of parasitic infection among pregnant women will therefore be beneficial.

Methodology/Principal findings

We used new data from the Entebbe Mother and Baby Study, a trial of anthelminthic treatment during pregnancy conducted in Uganda, to further investigate this hypothesis. 2705 mothers were investigated for parasitic infections and then randomised to albendazole (400mg) versus placebo and praziquantel (40mg/kg) during pregnancy in a factorial design. All mothers received sulfadoxine/pyrimethamine for presumptive treatment of malaria. Offspring received Expanded Programme on Immunisation vaccines at birth, six, 10 and 14 weeks. New data on antibody levels to diphtheria toxin, three pertussis antigens, Haemophilus influenzae type B (HiB) and Hepatitis B, measured at one year (April 2004 –May 2007) from 1379 infants were analysed for this report. Additional observational analyses relating maternal infections to infant vaccine responses were also conducted. Helminth infections were highly prevalent amongst mothers (hookworm 43.1%, Mansonella 20.9%, Schistosoma mansoni 17.3%, Strongyloides 11.7%, Trichuris 8.1%) and 9.4% had malaria at enrolment. In the trial analysis we found no overall effect of either anthelminthic intervention on the measured infant vaccine responses. In observational analyses, no species was associated with suppressed responses. Strongyloidiasis was associated with enhanced responses to pertussis toxin, HiB and Hep B vaccine antigens.

Conclusions/Significance

Our results do not support the hypothesis that routine anthelminthic treatment during pregnancy has a benefit for the infant’s vaccine response, or that maternal helminth infection has a net suppressive effect on the offspring’s response to vaccines.

Trial Registration

ISRCTN.com ISRCTN32849447

Risk analysis and prediction of visceral leishmaniasis dispersion in São Paulo State, Brazil

PLoS Neglected Tropical Diseases News - 6 February 2017 - 10:00pm

by Anaiá da Paixão Sevá, Liang Mao, Fredy Galvis-Ovallos, Joanna Marie Tucker Lima, Denis Valle

Visceral leishmaniasis (VL) is an important neglected disease caused by a protozoan parasite, and represents a serious public health problem in many parts of the world. It is zoonotic in Europe and Latin America, where infected dogs constitute the main domestic reservoir for the parasite and play a key role in VL transmission to humans. In Brazil this disease is caused by the protozoan Leishmania infantum chagasi, and is transmitted by the sand fly Lutzomyia longipalpis. Despite programs aimed at eliminating infection sources, the disease continues to spread throughout the Country. VL in São Paulo State, Brazil, first appeared in the northwestern region, spreading in a southeasterly direction over time. We integrate data on the VL vector, infected dogs and infected human dispersion from 1999 to 2013 through an innovative spatial temporal Bayesian model in conjunction with geographic information system. This model is used to infer the drivers of the invasion process and predict the future progression of VL through the State. We found that vector dispersion was influenced by vector presence in nearby municipalities at the previous time step, proximity to the Bolívia-Brazil gas pipeline, and high temperatures (i.e., annual average between 20 and 23°C). Key factors affecting infected dog dispersion included proximity to the Marechal Rondon Highway, high temperatures, and presence of the competent vector within the same municipality. Finally, vector presence, presence of infected dogs, and rainfall (approx. 270 to 540mm/year) drove the dispersion of human VL cases. Surprisingly, economic factors exhibited no noticeable influence on disease dispersion. Based on these drivers and stochastic simulations, we identified which municipalities are most likely to be invaded by vectors and infected hosts in the future. Prioritizing prevention and control strategies within the identified municipalities may help halt the spread of VL while reducing monitoring costs. Our results contribute important knowledge to public and animal health policy planning, and suggest that prevention and control strategies should focus on vector control and on blocking contact between vectors and hosts in the priority areas identified to be at risk.

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