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Spatial and temporal trends of visceral leishmaniasis by mesoregion in a southeastern state of Brazil, 2002-2013

6 October 2017 - 9:00pm

by Thais Almeida Marques da Silva, Wendel Coura-Vital, David Soeiro Barbosa, Carla Sayuri Fogaça Oiko, Maria Helena Franco Morais, Bruna Dias Tourinho, Diogo Portella Ornelas de Melo, Ilka Afonso Reis, Mariângela Carneiro

Background

Visceral leishmaniasis (VL) is expanding in Brazil and in other South American countries, a process that has been associated with the urbanization of the disease. This study analyzes the spatial and temporal distribution of VL in the Brazilian state of Minas Gerais and identifies the areas with higher risks of transmission.

Methodology

An ecological study with spatial and time series analyzes of new confirmed cases of VL notified to the Brazilian Notifiable Disease Information System between 2002 and 2013, considering the 12 mesoregions of Minas Gerais. Two complementary methodologies were used: thematic maps of incidence and Poisson (log-linear) generalized linear model. Thematic maps using crude and smoothed cumulative incidences were generated for four trienniums. Poisson Regression measured the variation of the average number of cases from one year to the following, for each mesoregion.

Principal findings

The 5,778 cases analyzed revealed a heterogeneous spatial and temporal distribution of VL in Minas Gerais. Six mesoregions (Central Mineira, Jequitinhonha, Metropolitan area of Belo Horizonte, Northwest of Minas, North of Minas, and Vale do Rio Doce) were responsible for the expansion and maintenance of VL, with incidence rates as high as 26/100,000 inhabitants. The Vale do Rio Doce and Jequitinhonha mesoregions showed a considerable increase in the incidence rates in the last period studied. The other six mesoregions reported only sporadic cases and presented low and unsteady incidence rates, reaching a maximum of 1.2/100,000 inhabitants.

Conclusions/Significance

The results contribute to further the current understanding about the expansion of VL in Minas Gerais and may help guide actions for disease control.

Lymphatic filariasis transmission on Mafia Islands, Tanzania: Evidence from xenomonitoring in mosquito vectors

6 October 2017 - 9:00pm

by Yahya A. Derua, Susan F. Rumisha, Bernard M. Batengana, Demetrius A. Max, Grades Stanley, William N. Kisinza, Leonard E. G. Mboera

Introduction

Lymphatic filariasis (LF) is a chronic nematode infection transmitted by mosquitoes and in sub-Saharan Africa it is caused by Wuchereria bancrofti. The disease was targeted for global elimination by 2020 using repeated community-wide mass drug administration (MDA) distributed in endemic areas. However, recently, there has been a growing recognition of the potential role of including vector control as a supplement to MDA to achieve elimination goal. This study was carried out to determine mosquito abundance and transmission of bancroftian filariasis on Mafia Islands in Tanzania as a prerequisite for a search for appropriate vector control methods to complement the ongoing MDA campaign.

Methods

Mosquitoes were collected indoor and outdoor using Centre for Disease Control (CDC) light and gravid traps, respectively. Collected mosquitoes were identified based on their differential morphological features and Anopheles gambiae complex and An. funestus group were further identified to their respective sibling species by polymerase chain reaction (PCR). Filarial mosquito vectors were then examined for infection with Wuchereria bancrofti by microscopy and PCR technique.

Results

Overall, a total of 35,534 filarial mosquito vectors were collected, of which Anopheles gambiae complex, An. funestus group and Culex quinquefasciatus Say accounted for 1.3, 0.5 and 98.2%, respectively. Based on PCR identification, An. gambiae sensu stricto (s.s) and An. funestus s.s sibling species accounted for 88.3% and 99.1% of the identified members of the An. gambiae complex and An. funestus group, respectively. A total of 7,936 mosquitoes were examined for infection with W. bancrofti by microscopy. The infection and infectivity rates were 0.25% and 0.08%, respectively. Using pool screen PCR technique, analysis of 324 mosquito pools (each with 25 mosquitoes) resulted to an estimated infection rate of 1.7%.

Conclusion

The study has shown that Cx. quinquefasciatus is the dominant mosquito on Mafia Islands. By using mosquito infectivity as proxy to human infection, the study indicates that W. bancrofti transmission is still ongoing on Mafia Islands after more than a decade of control activities based on MDA.

Reappraisal of Leishmanin Skin Test (LST) in the management of American Cutaneous Leishmaniasis: A retrospective analysis from a reference center in Argentina

5 October 2017 - 9:00pm

by Alejandro Javier Krolewiecki, Maria Cristina Almazan, Marcelo Quipildor, Marisa Juarez, Jose Fernando Gil, Marco Espinosa, Maria Canabire, Silvana Pamela Cajal

Leishmania (Viannia) braziliensis is the species most frequently implicated with cutaneous and mucosal leishmaniasis in the Americas; its diagnosis is based on the identification of amastigotes in lesions, which is limited by low parasite burden. Leishmanin Skin Test (LST) is a support tool for diagnosis, based on delayed type hypersensitivity responses to Leishmania antigens injected intradermally, used in endemic areas as a complement to diagnosis. A retrospective analysis of individuals evaluated for their first episode of tegumentary leishmaniasis at a reference center in Argentina during the period 2006–2015 was performed, with the goal of assessing its usefulness as a support tool in the diagnosis of leishmaniasis. Demographic, clinical and diagnostic work-up were analyzed in individuals with clinically compatible lesions, lesion`s smear and LST. A total of 733 cases that met the case definition were included in the analysis; 678 (93%) localized cutaneous cases, 50 (7%) with mucosal involvement and 5 (<1%) disseminated. Diagnostic confirmation was reached in 474 (65%) cases through positive smears from skin or mucosal lesions, with only 6 cases among this group having negative LST. Among smear negative cases, 190 were negative also by LST, but in 69 instances LST was positive. Across age groups, similar ratios of sensitivity between smear and LST were calculated. Lesions older than 21 days-old were found to correlate with positive results both for smear and LST significantly more than younger lesions. These findings support the clinical use of LST as a diagnostic complement for American Cutaneous Leishmaniasis across all age groups even in endemic areas. In this analysis, the correlation with smear was high. Standardization of this technique and further research into its most adequate preparation and utilization protocols across different sites will help in the management of suspicious clinical cases.

Efficacy of cryotherapy plus topical <i>Juniperus excelsa</i> M. Bieb cream versus cryotherapy plus placebo in the treatment of Old World cutaneous leishmaniasis: A triple-blind randomized controlled clinical trial

5 October 2017 - 9:00pm

by Mohammad Mahdi Parvizi, Farhad Handjani, Mahmoodreza Moein, Gholamreza Hatam, Majid Nimrouzi, Jafar Hassanzadeh, Nasrin Hamidizadeh, Hamid Reza Khorrami, Mohammad Mehdi Zarshenas

Background

Cutaneous leishmaniasis is one of the highly prevalent endemic diseases in the Middle East and North Africa. Many treatment modalities have been recommended for this condition but success rates remain limited. Herbal remedies have also been used for treatment but evidence-based clinical trials with these products are sparse. In-vitro and in-vivo studies have shown the anti-leishmanial and curative effects of extract of fruits and leaves of Juniperus excelsa (J. excelsa). The aim of this study was to determine the efficacy of topical J. excelsa M. Bieb extract as an adjuvant to cryotherapy for the treatment of human CL.

Materials and methods

This study was designed as a two-arm triple-blind randomized placebo-controlled clinical trial using a parallel design. Seventy-two patients with clinical diagnosis of CL confirmed by leishmania smears were allocated to receive either a topical formulation of leaf of J. excelsa extract (group A) or placebo (group B) for 3 months. Both groups received cryotherapy as baseline standard treatment. Patients were evaluated before and weekly after the intervention was initiated until complete cure.

Results

Overall, 82% of patients in group A, experienced complete cure and 9% of them had partial cure. On the other hand, 34% in group B reported complete cure, while 14% of them had partial cure at the end of treatment protocol with a significant difference between the two groups (P< 0.001). The mean duration to healing of the lesions in patients who received J. excelsa extract was statistically significantly shorter than the placebo group (p = 0.04). No significant side effect was seen in the J. excelsa extract group except for mild to moderate local irritation after a few weeks in a few numbers of patients.

Conclusion

The results of this study showed that topical J. excelsa extract can be used as an adjuvant treatment modality in addition to cryotherapy for accelerating the time to cure in addition to increasing the complete cure rate in CL.

Trial registration

ClinicalTrials.gov IRCT2015082523753N1

The cost-effectiveness of an eradication programme in the end game: Evidence from guinea worm disease

5 October 2017 - 9:00pm

by Christopher Fitzpatrick, Dieudonné P. Sankara, Junerlyn Farah Agua, Lakshmi Jonnalagedda, Filippo Rumi, Adam Weiss, Matthew Braden, Ernesto Ruiz-Tiben, Nicole Kruse, Kate Braband, Gautam Biswas

Background

Of the three diseases targeted for eradication by WHO, two are so-called Neglected Tropical Diseases (NTDs)–guinea worm disease (GWD) and yaws. The Guinea Worm Eradication Programme (GWEP) is in its final stages, with only 25 reported in 2016. However, global eradication still requires certification by WHO of the absence of transmission in all countries. We analyze the cost-effectiveness of the GWEP in the end game, when the number of cases is lower and the cost per case is higher than at any other time. Ours is the first economic evaluation of the GWEP since a World Bank study in 1997.

Methods

Using data from the GWEP, we estimate the cost of the implementation, pre-certification and certification stages. We model cost-effectiveness in the period 1986–2030. We compare the GWEP to two alternative scenarios: doing nothing (no intervention since 1986) and control (only surveillance and outbreak response during 2016–2030). We report the cost per case averted, cost per disability adjusted life year (DALY) averted and cost per at-risk life year averted. We assess cost-effectiveness against a threshold of about one half GDP per capita (less than US$ 500 in low income countries). All costs are expressed in US$ of 2015.

Results

The GWEP cost an estimated US$ 11 (95% uncertainty interval, 4.70–12.49) per case averted in the period 1986–2030. The pre-certification and certification phases can cost as much as US$ 0.0041 and US$ 0.0015 per capita per year. The cost per DALY averted by the GWEP relative to doing nothing is estimated at US$ 222 (118–372) in 1986–2030. The GWEP is probably more cost-effective than control by the year 2030. The GWEP is certainly more cost-effective than control if willingness to pay for one year of life lived without the risk of GWD exceeds US$ 0.10.

Discussion

Even if economic costs are two times as high as the financial costs estimated for the period to 2020, the GWEP will still be cost-effective relative to doing nothing. Whether the GWEP turns out to be the most cost-effective alternative in the period beyond 2015 depends on the time horizon. When framed in terms of the number of years of life lived without the risk of GWD, a case can be made more easily for finishing the end game, including certification of the absence of transmission.

Hepatitis B virus infection as a neglected tropical disease

5 October 2017 - 9:00pm

by Geraldine A. O’Hara, Anna L. McNaughton, Tongai Maponga, Pieter Jooste, Ponsiano Ocama, Roma Chilengi, Jolynne Mokaya, Mitchell I. Liyayi, Tabitha Wachira, David M. Gikungi, Lela Burbridge, Denise O’Donnell, Connie S. Akiror, Derek Sloan, Judith Torimiro, Louis Marie Yindom, Robert Walton, Monique Andersson, Kevin Marsh, Robert Newton, Philippa C. Matthews

Protection of bats <i>(Eptesicus fuscus)</i> against rabies following topical or oronasal exposure to a recombinant raccoon poxvirus vaccine

4 October 2017 - 9:00pm

by Ben Stading, James A. Ellison, William C. Carson, Panayampalli Subbian Satheshkumar, Tonie E. Rocke, Jorge E. Osorio

Rabies is an ancient neglected tropical disease that causes tens of thousands of human deaths and millions of cattle deaths annually. In order to develop a new vaccine for potential use in bats, a reservoir of rabies infection for humans and animals alike, an in silico antigen designer tool was used to create a mosaic glycoprotein (MoG) gene using available sequences from the rabies Phylogroup I glycoprotein. This sequence, which represents strains more likely to occur in bats, was cloned into raccoonpox virus (RCN) and the efficacy of this novel RCN-MoG vaccine was compared to RCN-G that expresses the glycoprotein gene from CVS-11 rabies or luciferase (RCN-luc, negative control) in mice and big brown bats (Eptesicus fuscus). Mice vaccinated and boosted intradermally with 1 x 107 plaque forming units (PFU) of each RCN-rabies vaccine construct developed neutralizing antibodies and survived at significantly higher rates than controls. No significant difference in antibody titers or survival was noted between rabies-vaccinated groups. Bats were vaccinated either oronasally (RCN-G, RCN-MoG) with 5x107 PFU or by topical application in glycerin jelly (RCN-MoG, dose 2x108 PFU), boosted (same dose and route) at 46 days post vaccination (dpv), and then challenged with wild-type big brown variant RABV at 65 dpv. Prior to challenge, 90% of RCN-G and 75% of RCN-MoG oronasally vaccinated bats had detectable levels of serum rabies neutralizing antibodies. Bats from the RCN-luc and topically vaccinated RCN-MoG groups did not have measurable antibody responses. The RCN-rabies constructs were highly protective and not significantly different from each other. RCN-MoG provided 100% protection (n = 9) when delivered oronasally and 83% protection (n = 6) when delivered topically; protection provided by the RCN-G construct was 70% (n = 10). All rabies-vaccinated bats survived at a significantly (P ≤ 0.02) higher rate than control bats (12%; n = 8). We have demonstrated the efficacy of a novel, in silico designed rabies MoG antigen that conferred protection from rabies challenge in mice and big brown bats in laboratory studies. With further development, topical or oronasal administration of the RCN-MoG vaccine could potentially mitigate rabies in wild bat populations, reducing spillover of this deadly disease into humans, domestic mammals, and other wildlife.

Estimating sensitivity of the Kato-Katz technique for the diagnosis of <i>Schistosoma mansoni</i> and hookworm in relation to infection intensity

4 October 2017 - 9:00pm

by Oliver Bärenbold, Giovanna Raso, Jean T. Coulibaly, Eliézer K. N’Goran, Jürg Utzinger, Penelope Vounatsou

The Kato-Katz technique is the most widely used diagnostic method in epidemiologic surveys and drug efficacy trials pertaining to intestinal schistosomiasis and soil-transmitted helminthiasis. However, the sensitivity of the technique is low, particularly for the detection of light-intensity helminth infections. Examination of multiple stool samples reduces the diagnostic error; yet, most studies rely on a single Kato-Katz thick smear, thus underestimating infection prevalence. We present a model which estimates the sensitivity of the Kato-Katz technique in Schistosoma mansoni and hookworm, as a function of infection intensity for repeated stool sampling and provide estimates of the age-dependent ‘true’ prevalence. We find that the sensitivity for S. mansoni diagnosis is dominated by missed light infections, which have a low probability to be diagnosed correctly even through repeated sampling. The overall sensitivity strongly depends on the mean infection intensity. In particular at an intensity of 100 eggs per gram of stool (EPG), we estimate a sensitivity of 50% and 80% for one and two samples, respectively. At an infection intensity of 300 EPG, we estimate a sensitivity of 62% for one sample and 90% for two samples. The sensitivity for hookworm diagnosis is dominated by day-to-day variation with typical values for one, two, three, and four samples equal to 50%, 75%, 85%, and 95%, respectively, while it is only weakly dependent on the mean infection intensity in the population. We recommend taking at least two samples and estimate the ‘true’ prevalence of S. mansoni considering the dependence of the sensitivity on the mean infection intensity and the ‘true’ hookworm prevalence by taking into account the sensitivity given in the current study.

Effectiveness of 32 versus 20 weeks of prednisolone in leprosy patients with recent nerve function impairment: A randomized controlled trial

4 October 2017 - 9:00pm

by Inge Wagenaar, Erik Post, Wim Brandsma, Bob Bowers, Khorshed Alam, Vanaja Shetty, Vivek Pai, Sajid Husain, Cita Rosita Sigit Prakoeswa, Linda Astari, Deanna Hagge, Mahesh Shah, Kapil Neupane, Krishna Bahadur Tamang, The TENLEP study group , Peter Nicholls, Jan Hendrik Richardus

Background

While prednisolone is commonly used to treat recent nerve function impairment (NFI) in leprosy patients, the optimal treatment duration has not yet been established. In this “Treatment of Early Neuropathy in Leprosy” (TENLEP) trial, we evaluated whether a 32-week prednisolone course is more effective than a 20-week course in restoring and improving nerve function.

Methods

In this multi-centre, triple-blind, randomized controlled trial, leprosy patients who had recently developed clinical NFI (<6 months) were allocated to a prednisolone treatment regimen of either 20 weeks or 32 weeks. Prednisolone was started at either 45 or 60 mg/day, depending on the patient’s body weight, and was then tapered. Throughout follow up, NFI was assessed by voluntary muscle testing and monofilament testing. The primary outcome was the proportion of patients with improved or restored nerve function at week 78. As secondary outcomes, we analysed improvements between baseline and week 78 on the Reaction Severity Scale, the SALSA Scale and the Participation Scale. Serious Adverse Events and the need for additional prednisolone treatment were monitored and reported.

Results

We included 868 patients in the study, 429 in the 20-week arm and 439 in the 32-week arm. At 78 weeks, the proportion of patients with improved or restored nerve function did not differ significantly between the groups: 78.1% in the 20-week arm and 77.5% in the 32-week arm (p = 0.821). Nor were there any differences in secondary outcomes, except for a significant higher proportion of Serious Adverse Events in the longer treatment arm.

Conclusion

In our study, a 20-week course of prednisolone was as effective as a 32-week course in improving and restoring recent clinical NFI in leprosy patients. Twenty weeks is therefore the preferred initial treatment duration for leprosy neuropathy, after which likely only a minority of patients require further individualized treatment.

The rationale and cost-effectiveness of a confirmatory mapping tool for lymphatic filariasis: Examples from Ethiopia and Tanzania

4 October 2017 - 9:00pm

by Katherine M. Gass, Heven Sime, Upendo J. Mwingira, Andreas Nshala, Maria Chikawe, Sonia Pelletreau, Kira A. Barbre, Michael S. Deming, Maria P. Rebollo

Endemicity mapping is required to determining whether a district requires mass drug administration (MDA). Current guidelines for mapping LF require that two sites be selected per district and within each site a convenience sample of 100 adults be tested for antigenemia or microfilaremia. One or more confirmed positive tests in either site is interpreted as an indicator of potential transmission, prompting MDA at the district-level. While this mapping strategy has worked well in high-prevalence settings, imperfect diagnostics and the transmission potential of a single positive adult have raised concerns about the strategy’s use in low-prevalence settings. In response to these limitations, a statistically rigorous confirmatory mapping strategy was designed as a complement to the current strategy when LF endemicity is uncertain. Under the new strategy, schools are selected by either systematic or cluster sampling, depending on population size, and within each selected school, children 9–14 years are sampled systematically. All selected children are tested and the number of positive results is compared against a critical value to determine, with known probabilities of error, whether the average prevalence of LF infection is likely below a threshold of 2%. This confirmatory mapping strategy was applied to 45 districts in Ethiopia and 10 in Tanzania, where initial mapping results were considered uncertain. In 42 Ethiopian districts, and all 10 of the Tanzanian districts, the number of antigenemic children was below the critical cutoff, suggesting that these districts do not require MDA. Only three Ethiopian districts exceeded the critical cutoff of positive results. Whereas the current World Health Organization guidelines would have recommended MDA in all 55 districts, the present results suggest that only three of these districts requires MDA. By avoiding unnecessary MDA in 52 districts, the confirmatory mapping strategy is estimated to have saved a total of $9,293,219.

Local selection in the presence of high levels of gene flow: Evidence of heterogeneous insecticide selection pressure across Ugandan <i>Culex quinquefasciatus</i> populations

3 October 2017 - 9:00pm

by Walter Fabricio Silva Martins, Craig Stephen Wilding, Keith Steen, Henry Mawejje, Tiago Rodrigues Antão, Martin James Donnelly

Background

Culex quinquefasciatus collected in Uganda, where no vector control interventions directly targeting this species have been conducted, was used as a model to determine if it is possible to detect heterogeneities in selection pressure driven by insecticide application targeting other insect species.

Methodology/Principal findings

Population genetic structure was assessed through microsatellite analysis, and the impact of insecticide pressure by genotyping two target-site mutations, Vgsc-1014F of the voltage-gated sodium channel target of pyrethroid and DDT insecticides, and Ace1-119S of the acetylcholinesterase gene, target of carbamate and organophosphate insecticides. No significant differences in genetic diversity were observed among populations by microsatellite markers with HE ranging from 0.597 to 0.612 and low, but significant, genetic differentiation among populations (FST = 0.019, P = 0.001). By contrast, the insecticide-resistance markers display heterogeneous allelic distributions with significant differences detected between Central Ugandan (urban) populations relative to Eastern and Southwestern (rural) populations. In the central region, a frequency of 62% for Vgsc-1014F, and 32% for the Ace1-119S resistant allele were observed. Conversely, in both Eastern and Southwestern regions the Vgsc-1014F alleles were close to fixation, whilst Ace1-119S allele frequency was 12% (although frequencies may be underestimated due to copy number variation at both loci).

Conclusions/Significance

Taken together, the microsatellite and both insecticide resistance target-site markers provide evidence that in the face of intense gene flow among populations, disjunction in resistance frequencies arise due to intense local selection pressures despite an absence of insecticidal control interventions targeting Culex.

Feasibility of utilizing the SD BIOLINE Onchocerciasis IgG4 rapid test in onchocerciasis surveillance in Senegal

3 October 2017 - 9:00pm

by Yakou Dieye, Helen L Storey, Kelsey L. Barrett, Emily Gerth-Guyette, Laura Di Giorgio, Allison Golden, Dunia Faulx, Michael Kalnoky, Marie Khemesse Ngom Ndiaye, Ngayo Sy, Malang Mané, Babacar Faye, Mamadou Sarr, Elhadji Mamadou Dioukhane, Roger B. Peck, Philippe Guinot, Tala de los Santos

As effective onchocerciasis control efforts in Africa transition to elimination efforts, different diagnostic tools are required to support country programs. Senegal, with its long standing, successful control program, is transitioning to using the SD BIOLINE Onchocerciasis IgG4 (Ov16) rapid test over traditional skin snip microscopy. The aim of this study is to demonstrate the feasibility of integrating the Ov16 rapid test into onchocerciasis surveillance activities in Senegal, based on the following attributes of acceptability, usability, and cost. A cross-sectional study was conducted in 13 villages in southeastern Senegal in May 2016. Individuals 5 years and older were invited to participate in a demographic questionnaire, an Ov16 rapid test, a skin snip biopsy, and an acceptability interview. Rapid test technicians were interviewed and a costing analysis was conducted. Of 1,173 participants, 1,169 (99.7%) agreed to the rapid test while 383 (32.7%) agreed to skin snip microscopy. The sero-positivity rate of the rapid test among those tested was 2.6% with zero positives 10 years and younger. None of the 383 skin snips were positive for Ov microfilaria. Community members appreciated that the rapid test was performed quickly, was not painful, and provided reliable results. The total costs for this surveillance activity was $22,272.83, with a cost per test conducted at $3.14 for rapid test, $7.58 for skin snip microscopy, and $13.43 for shared costs. If no participants had refused skin snip microscopy, the total cost per method with shared costs would have been around $16 per person tested. In this area with low onchocerciasis sero-positivity, there was high acceptability and perceived value of the rapid test by community members and technicians. This study provides evidence of the feasibility of implementing the Ov16 rapid test in Senegal and may be informative to other country programs transitioning to Ov16 serologic tools.

Phylogenetic analysis of simian <i>Plasmodium</i> spp. infecting <i>Anopheles balabacensis</i> Baisas in Sabah, Malaysia

2 October 2017 - 9:00pm

by Tock H. Chua, Benny O. Manin, Sylvia Daim, Indra Vythilingam, Chris Drakeley

Background

Anopheles balabacensis of the Leucospyrus group has been confirmed as the primary knowlesi malaria vector in Sabah, Malaysian Borneo for some time now. Presently, knowlesi malaria is the only zoonotic simian malaria in Malaysia with a high prevalence recorded in the states of Sabah and Sarawak.

Methodology/Principal findings

Anopheles spp. were sampled using human landing catch (HLC) method at Paradason village in Kudat district of Sabah. The collected Anopheles were identified morphologically and then subjected to total DNA extraction and polymerase chain reaction (PCR) to detect Plasmodium parasites in the mosquitoes. Identification of Plasmodium spp. was confirmed by sequencing the SSU rRNA gene with species specific primers. MEGA4 software was then used to analyse the SSU rRNA sequences and bulid the phylogenetic tree for inferring the relationship between simian malaria parasites in Sabah.PCR results showed that only 1.61% (23/1,425) of the screened An. balabacensis were infected with one or two of the five simian Plasmodispp. found in Sabah, vi Plasmodium coatneyi, P. inui, P. fieldi, P. cynomolgi and P. knowlesi. Sequence analysis of SSU rRNA of Plasmodium isolates showed high percentage of identity within the same Plasmodium sp. group. The phylogenetic tree based on the consensus sequences of P. knowlesi showed 99.7%–100.0% nucleotide identity among the isolates from An. balabacensis, human patients and a long-tailed macaque from the same locality.

Conclusions/Significance

This is the first study showing high molecular identity between the P. knowlesi isolates from An. balabacensis, human patients and a long-tailed macaque in Sabah. The other common simian Plasmodium spp. found in long-tailed macaques and also detected in An. balabacensis were P. coatneyi, P. inui, P. fieldi and P. cynomolgi. The high percentage identity of nucleotide sequences between the P. knowlesi isolates from the long-tailed macaque, An. balabacensis and human patients suggests a close genetic relationship between the parasites from these hosts.

Perceptions about interventions to control schistosomiasis among the Lake Victoria island communities of Koome, Uganda

2 October 2017 - 9:00pm

by Richard E. Sanya, Edward Tumwesige, Alison M. Elliott, Janet Seeley

Background

Praziquantel-based mass treatment is the main approach to controlling schistosomiasis mansoni in endemic areas. Interventions such as provision and use of safe water, minimising contact with infested water, disposal of stool in latrines and snail control provide key avenues to break the transmission cycle and can sustain the benefits of mass treatment in the long term. Efforts are also being made to develop a schistosomiasis vaccine which, if effective, might reduce the incidence of re-infection after treatment. However, any interventions deployed need to be acceptable to, and sustainable by, the target communities.

Methods

In this qualitative study, we investigated the perceptions of six Lake Victoria island communities of Koome, Uganda, about interventions to control Schistosoma mansoni infection and their willingness to participate in Schistosoma vaccine trials. Thirty-two in-depth interviews, 12 key informant interviews and 10 focus group discussions were conducted. Data were analysed using a thematic content approach.

Findings

Intestinal schistosomiasis was not regarded as a serious health problem because a mass treatment programme is in place. However, the communities lack safe water sources and latrines. Mass treatment with praziquantel, safe water supplies and use of toilets were deemed the most acceptable interventions by the participants. The communities are willing to participate in Schistosoma vaccine trials.

Conclusion/Significance

Knowledge of a community’s perception about interventions to control schistosomiasis can be valuable to policy makers and programme implementers intending to set up interventions co-managed by the community members. In this study, the views of the Lake Victoria island communities of Koome are presented. This study also provides data to guide further work on alternative interventions such as Schistosoma vaccine trials in these communities.

A longitudinal study of the infant nasopharyngeal microbiota: The effects of age, illness and antibiotic use in a cohort of South East Asian children

2 October 2017 - 9:00pm

by Susannah J. Salter, Claudia Turner, Wanitda Watthanaworawit, Marcus C. de Goffau, Josef Wagner, Julian Parkhill, Stephen D. Bentley, David Goldblatt, Francois Nosten, Paul Turner

A longitudinal study was undertaken in infants living in the Maela refugee camp on the Thailand-Myanmar border between 2007 and 2010. Nasopharyngeal swabs were collected monthly, from birth to 24 months of age, with additional swabs taken if the infant was diagnosed with pneumonia according to WHO clinical criteria. At the time of collection, swabs were cultured for Streptococcus pneumoniae and multiple serotype carriage was assessed. The bacterial 16S rRNA gene profiles of 544 swabs from 21 infants were analysed to see how the microbiota changes with age, respiratory infection, antibiotic consumption and pneumococcal acquisition. The nasopharyngeal microbiota is a somewhat homogenous community compared to that of other body sites. In this cohort it is dominated by five taxa: Moraxella, Streptococcus, Haemophilus, Corynebacterium and an uncharacterized Flavobacteriaceae taxon of 93% nucleotide similarity to Ornithobacterium. Infant age correlates with certain changes in the microbiota across the cohort: Staphylococcus and Corynebacterium are associated with the first few months of life while Moraxella and the uncharacterised Flavobacteriaceae increase in proportional abundance with age. Respiratory illness and antibiotic use often coincide with an unpredictable perturbation of the microbiota that differs from infant to infant and in different illness episodes. The previously described interaction between Dolosigranulum and Streptococcus was observed in these data. Monthly sampling demonstrates that the nasopharyngeal microbiota is in flux throughout the first two years of life, and that in this refugee camp population the pool of potential bacterial colonisers may be limited.

Correlates of multi-drug non-susceptibility in enteric bacteria isolated from Kenyan children with acute diarrhea

2 October 2017 - 9:00pm

by Rebecca L. Brander, Judd L. Walson, Grace C. John-Stewart, Jacqueline M. Naulikha, Janet Ndonye, Nancy Kipkemo, Doreen Rwigi, Benson O. Singa, Patricia B. Pavlinac

Background

Reduced antimicrobial susceptibility threatens treatment efficacy in sub-Saharan Africa, where data on the burden and correlates of antibiotic resistance among enteric pathogens are limited.

Methods

Fecal samples from children aged 6 mos—15 yrs presenting with acute diarrhea in western Kenya were cultured for bacterial pathogens. HIV-uninfected children with identified Shigella or Salmonella species or pathogenic Escherichia coli (EPEC, ETEC, EAEC or EIEC) were included in this cross-sectional sub-study. Non-susceptibility to ampicillin, ceftriaxone, ciprofloxacin, cotrimoxazole, and tetracycline was determined using MicroScan Walkaway40 Plus. Multivariable log-binomial regression was used to identify correlates of multi-drug non-susceptibility (MDNS, non-susceptibility to ≥ 3 of these antibiotics).

Results

Of 292 included children, median age was 22.5 mos. MDNS was identified in 62.5% of 318 isolates. Non-susceptibility to cotrimoxazole (92.8%), ampicillin (81.3%), and tetracycline (75.0%) was common. Young age (6–24 mos vs. 24–59 mos adjusted prevalence ratio [aPR] = 1.519 [95% confidence interval: 1.19, 1.91]), maternal HIV (aPR = 1.29 [1.01, 1.66]); and acute malnutrition (aPR = 1.28 [1.06, 1.55]) were associated with higher prevalence of MDNS, as were open defecation (aPR = 2.25 [1.13, 4.50]), household crowding (aPR = 1.29 [1.08, 1.53]) and infrequent caregiver hand-washing (aPR = 1.50 [1.15, 1.95]).

Conclusions

Young age, HIV exposure, acute malnutrition and poor sanitation may increase risk of antibiotic non-susceptible enteric pathogen infections among children in Kenya.

Distribution of triatomine species in domestic and peridomestic environments in central coastal Ecuador

2 October 2017 - 9:00pm

by Mario J. Grijalva, Anita G. Villacís, Ana L. Moncayo, Sofia Ocaña-Mayorga, Cesar A. Yumiseva, Esteban G. Baus

Background

Although the central coast of the Ecuador is considered endemic for Chagas disease, few studies have focused on determining the risk of transmission in this region. In this study we describe the triatomine household infestation in Manabí province (Central Coast region), determine the rate of Trypanosoma cruzi infection and study the risk factors associated with infestation by Rhodnius ecuadoriensis.

Methodology/Principal findings

An entomological survey found three triatomine species (Rhodnius ecuadoriensis, Panstrongylus rufotuberculatus and P. howardi) infesting domiciles in 47.4% of the 78 communities visited (total infestation rate of 4.5%). Four percent of domiciles were infested, and nymphs were observed in 77% of those domiciles. The three species were found in altitudes below 500 masl and in all ecological zones except cloud forest. Within the domicile, we found the three species mostly in bedrooms. Rhodnius ecuadoriensis and P. rufotuberculatus were abundant in bird nests, including chicken coops and P. howardi associated with rats in piles of bricks, in the peridomicile. Triatomine infestation was characterized by high rates of colonization, especially in peridomicile. Flagelates infection was detected in only 12% of the samples by microscopy and Trypanosoma cruzi infection in 42% of the examined triatomines by PCR (n = 372). The most important risk factors for house infestation by R. ecuadoriensis were ecological zone (w = 0.99) and presence of chickens (w = 0.96). Determinants of secondary importance were reporting no insecticide applications over the last twelve months (w = 0.86) and dirt floor (w = 0.70). On the other hand, wood as wall material was a protective factor (w = 0.85).

Conclusion/Significance

According the results, approximately 571,000 people would be at high risk for T. cruzi infection in Manabí province. A multidisciplinary approximation and the adhesion to a periodic integrated vector management (IVM) program are essential to guarantee sustainable preventive and control strategies for Chagas disease in this region.

A clinical severity scoring system for visceral leishmaniasis in immunocompetent patients in South Sudan

2 October 2017 - 9:00pm

by Suzette S. Kämink, Simon M. Collin, Tim Harrison, Francis Gatluak, Abdul Wasay Mullahzada, Koert Ritmeijer

Background

South Sudan is one of the most endemic countries for visceral leishmaniasis (VL), and is frequently affected by large epidemics. In resource-limited settings, clinicians require a simple clinical tool to identify VL patients who are at increased risk of dying, and who need specialised treatment with liposomal amphotericin B and other supportive care. The aim of this study was to develop and validate a clinical severity scoring system based on risk factors for death in VL patients in South Sudan.

Methods

A retrospective analysis was conducted of data from a cohort of 6,633 VL patients who were treated in the Médecins Sans Frontières (MSF) hospital in Lankien between July 2013 and June 2015. Risk factors for death during treatment were identified using multivariable logistic regression models, and the regression coefficients were used to develop a severity scoring system. Sensitivity and specificity of score cut-offs were assessed by receiver operating characteristic (ROC) analysis.

Results

In multivariable models, risk factors for death in adult VL patients were: anaemia (odds ratio (OR) 4.46 (95% CI 1.58–12.6) for Hb <6g/dL compared with ≥9g/dL), nutritional status (OR 4.84 (2.09–11.2) for BMI <13 kg/m2 compared with ≥16 kg/m2), weakness (OR 4.20 (1.82–9.73) for collapsed compared with normal weakness), jaundice (OR 3.41 (1.17–9.95)), and oedema/ascites (OR 4.86 (1.67–14.1)). For children and adolescents the risk factors were: age (OR 10.7 (6.3–18.3) for age <2 years compared with 6–18 years), anaemia (OR 7.76 (4.15–14.5) for Hb <6g/dL compared with ≥9g/dL), weakness (OR 3.13 (22.8–105.2) for collapsed compared with normal weakness), and jaundice (OR 12.8 (4.06–40.2)). Severity scoring predictive ability was 74.4% in adults and 83.4% in children and adolescents.

Conclusion

Our evidenced-based severity scoring system demonstrated sufficient predictive ability to be operationalised as a clinical tool for rational allocation of treatment to VL patients at MSF centres in South Sudan.

High-resolution profiling of linear B-cell epitopes from mucin-associated surface proteins (MASPs) of <i>Trypanosoma cruzi</i> during human infections

29 September 2017 - 9:00pm

by Ignacio M. Durante, Pablo E. La Spina, Santiago J. Carmona, Fernán Agüero, Carlos A. Buscaglia

Background

The Trypanosoma cruzi genome bears a huge family of genes and pseudogenes coding for Mucin-Associated Surface Proteins (MASPs). MASP molecules display a ‘mosaic’ structure, with highly conserved flanking regions and a strikingly variable central and mature domain made up of different combinations of a large repertoire of short sequence motifs. MASP molecules are highly expressed in mammal-dwelling stages of T. cruzi and may be involved in parasite-host interactions and/or in diverting the immune response.

Methods/Principle findings

High-density microarrays composed of fully overlapped 15mer peptides spanning the entire sequences of 232 non-redundant MASPs (~25% of the total MASP content) were screened with chronic Chagasic sera. This strategy led to the identification of 86 antigenic motifs, each one likely representing a single linear B-cell epitope, which were mapped to 69 different MASPs. These motifs could be further grouped into 31 clusters of structurally- and likely antigenically-related sequences, and fully characterized. In contrast to previous reports, we show that MASP antigenic motifs are restricted to the central and mature region of MASP polypeptides, consistent with their intracellular processing. The antigenicity of these motifs displayed significant positive correlation with their genome dosage and their relative position within the MASP polypeptide. In addition, we verified the biased genetic co-occurrence of certain antigenic motifs within MASP polypeptides, compatible with proposed intra-family recombination events underlying the evolution of their coding genes. Sequences spanning 7 MASP antigenic motifs were further evaluated using distinct synthesis/display approaches and a large panel of serum samples. Overall, the serological recognition of MASP antigenic motifs exhibited a remarkable non normal distribution among the T. cruzi seropositive population, thus reducing their applicability in conventional serodiagnosis. As previously observed in in vitro and animal infection models, immune signatures supported the concurrent expression of several MASPs during human infection.

Conclusions/Significance

In spite of their conspicuous expression and potential roles in parasite biology, this study constitutes the first unbiased, high-resolution profiling of linear B-cell epitopes from T. cruzi MASPs during human infection.

Chikungunya virus dissemination from the midgut of <i>Aedes aegypti</i> is associated with temporal basal lamina degradation during bloodmeal digestion

29 September 2017 - 9:00pm

by Shengzhang Dong, Velmurugan Balaraman, Asher M. Kantor, Jingyi Lin, DeAna G. Grant, Nicole L. Held, Alexander W. E. Franz

In the mosquito, the midgut epithelium is the initial tissue to become infected with an arthropod-borne virus (arbovirus) that has been acquired from a vertebrate host along with a viremic bloodmeal. Following its replication in midgut epithelial cells, the virus needs to exit the midgut and infect secondary tissues including the salivary glands before it can be transmitted to another vertebrate host. The viral exit mechanism from the midgut, the midgut escape barrier (MEB), is poorly understood although it is an important determinant of mosquito vector competence for arboviruses. Using chikungunya virus (CHIKV) as a model in Aedes aegypti, we demonstrate that the basal lamina (BL) of the extracellular matrix (ECM) surrounding the midgut constitutes a potential barrier for the virus. The BL, predominantly consisting of collagen IV and laminin, becomes permissive during bloodmeal digestion in the midgut lumen. Bloodmeal digestion, BL permissiveness, and CHIKV dissemination are coincident with increased collagenase activity, diminished collagen IV abundance, and BL shredding in the midgut between 24–32 h post-bloodmeal. This indicates that there may be a window-of-opportunity during which the MEB in Ae. aegypti becomes permissive for CHIKV. Matrix metalloproteinases (MMPs) are the principal extracellular endopeptidases responsible for the degradation/remodeling of the ECM including the BL. We focused on Ae. aegypti (Ae)MMP1, which is expressed in midgut epithelial cells, is inducible upon bloodfeeding, and shows collagenase (gelatinase) activity. However, attempts to inhibit AeMMP activity in general or specifically that of AeMMP1 did not seem to affect its function nor produce an altered midgut escape phenotype. As an alternative, we silenced and overexpressed the Ae. aegypti tissue inhibitor of metalloproteinases (AeTIMP) in the mosquito midgut. AeTIMP was highly upregulated in the midgut during bloodmeal digestion and was able to inhibit MMP activity in vitro. Bloodmeal-inducible, midgut-specific overexpression of AeTIMP or its expression via a recombinant CHIKV significantly increased midgut dissemination rates of the virus. Possibly, AeTIMP overexpression affected BL degradation and/or restoration thereby increasing the midgut dissemination efficiency of the virus.

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