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The right to deworming: The case for girls and women of reproductive age

21 November 2018 - 10:00pm

by Theresa W. Gyorkos, Antonio Montresor, Vicente Belizario, Beverley-Ann Biggs, Mark Bradley, Simon J. Brooker, Martin Casapia, Philip Cooper, Sila Deb, Nicolas L. Gilbert, Rubina Imtiaz, Virak Khieu, Stefanie Knopp, Ornella Lincetto, Layla S. Mofid, Denise Mupfasoni, Cori Vail, Jozef Vercruysse

Modelling the cost-effectiveness of a rapid diagnostic test (IgMFA) for uncomplicated typhoid fever in Cambodia

19 November 2018 - 10:00pm

by Mari Kajiwara Saito, Christopher M. Parry, Shunmay Yeung

Typhoid fever is a common cause of fever in Cambodian children but diagnosis and treatment are usually presumptive owing to the lack of quick and accurate tests at an initial consultation. This study aimed to evaluate the cost-effectiveness of using a rapid diagnostic test (RDT) for typhoid fever diagnosis, an immunoglobulin M lateral flow assay (IgMFA), in a remote health centre setting in Cambodia from a healthcare provider perspective. A cost-effectiveness analysis (CEA) with decision analytic modelling was conducted. We constructed a decision tree model comparing the IgMFA versus clinical diagnosis in a hypothetical cohort with 1000 children in each arm. The costs included direct medical costs only. The eligibility was children (≤14 years old) with fever. Time horizon was day seven from the initial consultation. The number of treatment success in typhoid fever cases was the primary health outcome. The number of correctly diagnosed typhoid fever cases (true-positives) was the intermediate health outcome. We obtained the incremental cost effectiveness ratio (ICER), expressed as the difference in costs divided by the difference in the number of treatment success between the two arms. Sensitivity analyses were conducted. The IgMFA detected 5.87 more true-positives than the clinical diagnosis (38.45 versus 32.59) per 1000 children and there were 3.61 more treatment successes (46.78 versus 43.17). The incremental cost of the IgMFA was estimated at $5700; therefore, the ICER to have one additional treatment success was estimated to be $1579. The key drivers for the ICER were the relative sensitivity of IgMFA versus clinical diagnosis, the cost of IgMFA, and the prevalence of typhoid fever or multi-drug resistant strains. The IgMFA was more costly but more effective than the clinical diagnosis in the base-case analysis. An IgMFA could be more cost-effective than the base-case if the sensitivity of IgMFA was higher or cost lower. Decision makers may use a willingness-to-pay threshold that considers the additional cost of hospitalisation for treatment failures.

Vertical transmission of naturally occurring Bunyamwera and insect-specific flavivirus infections in mosquitoes from islands and mainland shores of Lakes Victoria and Baringo in Kenya

19 November 2018 - 10:00pm

by Yvonne Ukamaka Ajamma, Thomas Ogao Onchuru, Daniel O. Ouso, David Omondi, Daniel K. Masiga, Jandouwe Villinger

Background

Many arboviruses transmitted by mosquitoes have been implicated as causative agents of both human and animal illnesses in East Africa. Although epidemics of arboviral emerging infectious diseases have risen in frequency in recent years, the extent to which mosquitoes maintain pathogens in circulation during inter-epidemic periods is still poorly understood. This study aimed to investigate whether arboviruses may be maintained by vertical transmission via immature life stages of different mosquito vector species.

Methodology

We collected immature mosquitoes (egg, larva, pupa) on the shores and islands of Lake Baringo and Lake Victoria in western Kenya and reared them to adults. Mosquito pools (≤25 specimens/pool) of each species were screened for mosquito-borne viruses by high-resolution melting analysis and sequencing of multiplex PCR products of genus-specific primers (alphaviruses, flaviviruses, phleboviruses and Bunyamwera-group orthobunyaviruses). We further confirmed positive samples by culturing in baby hamster kidney and Aedes mosquito cell lines and re-sequencing.

Principal findings

Culex univittatus (2/31pools) and Anopheles gambiae (1/77 pools) from the Lake Victoria region were positive for Bunyamwera virus, a pathogenic virus that is of public health concern. In addition, Aedes aegypti (3/50), Aedes luteocephalus (3/13), Aedes spp. (2/15), and Culex pipiens (1/140) pools were positive for Aedes flaviviruses at Lake Victoria, whereas at Lake Baringo, three pools of An. gambiae mosquitoes were positive for Anopheles flavivirus. These insect-specific flaviviruses (ISFVs), which are presumably non-pathogenic to vertebrates, were found in known medically important arbovirus and malaria vectors.

Conclusions

Our results suggest that not only ISFVs, but also a pathogenic arbovirus, are naturally maintained within mosquito populations by vertical transmission, even in the absence of vertebrate hosts. Therefore, virus and vector surveillance, even during inter-epidemics, and the study of vector-arbovirus-ISFV interactions, may aid in identifying arbovirus transmission risks, with the potential to inform control strategies that lead to disease prevention.

Antivirus effectiveness of ivermectin on dengue virus type 2 in <i>Aedes albopictus</i>

19 November 2018 - 10:00pm

by Tie-Long Xu, Yin Han, Wei Liu, Xing-Ya Pang, Bin Zheng, Yi Zhang, Xiao-Nong Zhou

Background

Dengue fever is the most rapidly spreading mosquito-borne viral disease over the past 50 years, with a 30-fold increase in global incidence. Dengue vector control is a key component for the dengue control strategy, since no absolutely effective vaccine or drug is available yet. However, the rapid rise and spread of mosquito insecticide resistance have become major threats to the efficiency of insecticide-based vector control activities. Thus, innovative vector control tools are badly needed. This study aims to confirm the antivirus effectiveness of ivermectin on dengue virus type 2 (DENV-2) in Aedes albopictus (Skuse, 1894), then to explore its potential use in the combating to the dengue epidemics.

Methods

Aedes albopictus were first infected with DENV-2 in human whole blood, and at the fourth day after infectious blood feeding, they were divided into eight groups. Seven of them were held for six days with access to 0, 2, 4, 8, 16, 32 and 64 ng/ml ivermectin, respectively, and the last one was set as a historical control group, which was stored at -80°C until being detected at the same time with the other groups. Each mosquito was detected using real-time fluorescent RT-PCR kit. DENV-2 RNA concentration (copies/ml) and infection rate in each group were compared.

Results

Both of quantitatively and qualitatively inhibiting effects of ivermectin have been detected in this study. Generally, DENV-2 replicated well in Aedes albopictus without ivermectin intervention, whose virus loads exhibited significantly higher when the mosquitoes were holding from 4 days to 10 days after infectious blood feeding. In contrast, with the treatment of ivermectin, the infection rate was reduced by as much as 49.63%. The regression equation between infection rates (Y2) and ivermectin concentration log2 values (X2) was obtained as Y2 = 91.41–7.21*X2 with R2 = 0.89.

Conclusion

Ivermectin can directly or indirectly inhibit DENV-2 multiplication in Aedes albopictus. Moreover, the actual concentration for application in zooprophylaxis needs to be confirmed in the further field trials.

CYP-mediated permethrin resistance in <i>Aedes aegypti</i> and evidence for <i>trans</i>-regulation

19 November 2018 - 10:00pm

by Letícia B. Smith, Rakshit Tyagi, Shinji Kasai, Jeffrey G. Scott

Aedes aegypti poses a serious risk to human health due to its wide global distribution, high vector competence for several arboviruses, frequent human biting, and ability to thrive in urban environments. Pyrethroid insecticides remain the primary means of controlling adult A. aegypti populations during disease outbreaks. As a result of decades of use, pyrethroid resistance is a global problem. Cytochrome P450 monooxygenase (CYP)-mediated detoxification is one of the primary mechanisms of pyrethroid resistance. However, the specific CYP(s) responsible for resistance have not been unequivocally determined. We introgressed the resistance alleles from the resistant A. aegypti strain, Singapore (SP), into the genetic background of the susceptible ROCK strain. The resulting strain (CKR) was congenic to ROCK. Our primary goal was to determine which CYPs in SP are linked to resistance. To do this, we first determined which CYPs overexpressed in SP are also overexpressed in CKR, with the assumption that only the CYPs linked to resistance will be overexpressed in CKR relative to ROCK. Next, we determined whether any of the overexpressed CYP(s) were genetically linked to resistance (cis-regulated) or not (trans-regulated). We found that CYP6BB2, CYP6Z8, CYP9M5 and CYP9M6 were overexpressed in SP as well as in CKR. Based on the genomic sequences and polymorphisms in each strain, none of these genes were linked to resistance, except for CYP6BB2, which was partially linked to the resistance locus. Hence, overexpression of these four CYPs is due to a trans-regulatory factor(s). Knowledge on the specific CYPs and their regulators involved in resistance is critical for resistance management strategies because it aids in the development of new control chemicals, provides information on potential environmental modulators of resistance, and allows for the detection of resistance markers before resistance becomes fixed in the population.

Identification and characterization of <i>Loa loa</i> antigens responsible for cross-reactivity with rapid diagnostic tests for lymphatic filariasis

16 November 2018 - 10:00pm

by Marla I. Hertz, Hugues Nana-Djeunga, Joseph Kamgno, Abdel Jelil Njouendou, Valerine Chawa Chunda, Samuel Wanji, Amy Rush, Peter U. Fischer, Gary J. Weil, Philip J. Budge

The Global Program to Eliminate Lymphatic Filariasis (LF) relies on rapid diagnostic tests (RDTs) to determine where annual mass drug administration for LF is required and when it can be stopped. These tests detect a Wuchereria bancrofti glycoprotein in the blood of infected persons via a carbohydrate moiety recognized by the monoclonal antibodies AD12 and DH6.5. Loiasis cross-reactivity with LF RDTs has recently been recognized as a serious obstacle to LF elimination in loiasis-endemic areas. To better understand the nature of this cross-reactivity, we used the DH6.5 antibody to immunoaffinity purify Loa loa antigens from the sera of individuals with a positive RDT due to loiasis. Immunoblot analysis revealed many circulating AD12/DH6.5-reactive antigens, and proteomic analysis identified multiple L. loa proteins in LF RDT-positive loiasis sera. These included both secreted and somatic proteins, suggesting that they may be released by dying L. loa adult worms and/or microfilariae. Unlike the single high molecular weight W. bancrofti circulating filarial antigen that is reliably present in the blood of persons with bancroftian filariasis, reactive L. loa antigens appeared to be only transiently present in the blood of a subset of persons with loiasis. These key differences between the circulating antigens of W. bancrofti and L. loa can be used to differentiate positive results generated by both species and may lead to improved diagnostic tests for LF and loiasis.

Liver ultrasound elastography for the evaluation of periportal fibrosis in schistosomiasis mansoni: A cross-sectional study

16 November 2018 - 10:00pm

by Joelma Carvalho Santos, Andrea Dória Batista, Carla Maria Mola Vasconcelos, Roberto Souza Lemos, Valter Romão de Souza Junior, Alain Dessein, Hélia Dessein, Silvia Maria Lucena Montenegro, Edmundo Pessoa Almeida Lopes, Ana Lúcia Coutinho Domingues

Background

ARFI elastrography has been used as a noninvasive method to assess the severity of liver fibrosis in viral hepatitis, although with few studies in schistosomiasis mansoni. We aimed to evaluate the performance of point shear wave elastography (pSWE) for predicting significant periportal fibrosis (PPF) in schistosomotic patients and to determine its best cutoff point.

Methodology/principal findings

This cross-sectional study included 358 adult schistosomotic patients subjected to US and pSWE on the right lobe. Two hundred two patients (62.0%) were women, with a median age of 54 (ranging 18–92) years. The pSWE measurements were compared to the US patterns of PPF, as gold standard, according to the Niamey classification. The performance of pSWE was calculated as the area under the ROC curve (AUC). Patients were further classified into two groups: 86 patients with mild PPF and 272 patients with significant PPF. The median pSWE of the significant fibrosis group was higher (1.40 m/s) than that of mild fibrosis group (1.14 m/s, p<0.001). AUC was 0.719 with ≤1.11 m/s as the best cutoff value for excluding significant PPF. Sensitivity and negative predictive values were 80.5% and 40.5%, respectively. Whereas, for confirming significant PPF, the best cutoff value was >1.39 m/s, with specificity of 86.1% and positive predictive value of 92.0%.

Conclusions/significance

pSWE was able to differentiate significant from mild PPF, with better performance to predict significant PPF.

Prevalence and distribution of <i>Taenia solium</i> cysticercosis in naturally infected pigs in Punjab, India

15 November 2018 - 10:00pm

by Satinder Pal Singh, Balbir Bagicha Singh, Deepali G. Kalambhe, Devendra Pathak, Rabinder Singh Aulakh, Navneet K. Dhand

Background

Taenia solium (T. solium) cysticercosis remains a neglected zoonotic disease in India. The current study was planned to estimate the prevalence of T. solium porcine cysticercosis in the Punjab state of India, to compare this prevalence with the disease prevalence in pigs reared outside Punjab and to assess the distribution of the parasite in pig carcasses.

Methods

Two slaughter shops were selected in each of the 22 districts of Punjab. Pigs slaughtered on the day/s of inspection were post-mortem inspected to identify the presence of T. solium cysts. Estimated true prevalence was estimated by taking into account the diagnostic sensitivity (38%) and specificity (100%) of post-mortem inspection using the Rogan-Gladen estimator. Positive carcasses were purchased and brought to the laboratory to assess the tissue distribution of T. solium cysts and to conduct PCR targeting large subunit rRNA gene, internal transcribed spacer 1 gene, ITS1 gene and Cytochrome oxidase I gene. The selected PCR products were submitted for sequencing and phylogenetic analyses were performed.

Findings

We contacted 71 shop owners to achieve a sample of 44 shops for the study. We inspected 642 pigs reared in Punjab and 450 imported from other states at these slaughter shops. In addition, we sampled 40 pigs from an abattoir located in the state capital. Of the 642 pigs reared in Punjab, 9 had T. solium cysts with an apparent prevalence of 1·40% (95% CI: 0·74%, 2·64%) and the estimated true prevalence of 3.69% (95% CI: 1·95%, 6·95%). Pigs imported from outside the state had a significantly higher prevalence (odds ratio: 2·58; 95% CI: 1·12, 5·98; p-value: 0·026) as 15 of the 450 imported pigs were positive (apparent prevalence: 3.33%; 95% CI: 2.03%, 5.43%; estimated true prevalence: 8.77%; 95% CI: 5.34%, 14.28%). None of samples was positive from the pigs sampled at the abattoir in the state capital. The PCR confirmed T. solium cysts from all the 24 positive samples. We counted a median of 897 (range 526–1964) cysts per infected pig from the 19 infected pig carcasses inspected. The phylogenetic tree based on the alignment of partial cytochrome oxidase 1 sequences indicated all positive samples to be clustered with the T. solium Asian genotype. The analysis did not indicate the presence of T. asiatica in the slaughter pigs.

Conclusions

Despite the underestimation of the prevalence due to missing mildly-infected carcasses, low participation and lack of representative sampling, the presence of heavily infected carcasses containing viable cysts, particularly those imported from outside the state, indicates that T. solium cysticercosis is an important food safety concern for pork consumers in Punjab, India. Measures should be taken to reduce the disease prevalence in pigs to reduce the disease burden in the public.

Accuracy of the WHO praziquantel dose pole for large-scale community treatment of urogenital schistosomiasis in northern Mozambique: Is it time for an update?

15 November 2018 - 10:00pm

by Pedro H. Gazzinelli-Guimaraes, Neerav Dhanani, Charles H. King, Carl H. Campbell, Herminio O. Aurelio, Josefo Ferro, Rassul Nala, Alan Fenwick, Anna E. Phillips

Background

A pioneering strategy developed by the World Health Organization (WHO) for the control of schistosomiasis was the concept of a height-based dose pole to determine praziquantel (PZQ) dosing in large-scale treatment campaigns. However, some recent studies have shown variable accuracy for the dose pole in terms of predicting correct mg/Kg dosing, particularly for treatment of adults. According to the WHO, 91 million adults in 52 countries are targeted to be treated by 2020.

Methods/Principal findings

The present study aimed to test the accuracy of the dose pole in determining PZQ dosage by comparing the number of tablets determined by the dose pole with the number of tablets determined according to total body weight. The analysis included height-for-weight data from 9,827 school-aged children (SAC) and adults from 42 villages in the province of Cabo Delgado in Mozambique. The results revealed that of the 7,596 SAC, 91.8% has received an appropriate dose (30-60mg/Kg), 6% received an insufficient dose (<30mg/Kg) and 2% an excessive dose (> 60mg/Kg). On the other hand, 13.7% out of 2,231 adults were treated inaccurately with 13.5% receiving an insufficient dose. When the percentage of insufficient dosing was disaggregated by gender, the frequency of adult females who were underdosed reached 18.3% versus 10.8% of adult males. Adult females aged 21–55 years were found to have an underdose frequency of 21.3%, compared to 11.8% of adult males in the same age range. The performance of a proposed modified dose pole was compared using the same dataset of adult Mozambicans. The results showed that the modified dose pole reduced the underdose frequency among adults from 13.5% to 10.4%, and subsequently increasing the percentage of optimal dosing from 33.7% to 45.3%.

Conclusions

Our findings highlight the need to update the WHO-dose pole to avoid administration of insufficient PZQ doses to adults and therefore minimize the potential emergence of PZQ-resistant strains.

Trial registration

International Standard Randomized Controlled Trial registry under ISRTC number 14117624

Geostatistical mapping of the seasonal spread of under-reported dengue cases in Bangladesh

15 November 2018 - 10:00pm

by Sifat Sharmin, Kathryn Glass, Elvina Viennet, David Harley

Geographical mapping of dengue in resource-limited settings is crucial for targeting control interventions but is challenging due to the problem of zero-inflation because many cases are not reported. We developed a negative binomial generalised linear mixed effect model accounting for zero-inflation, spatial, and temporal random effects to investigate the spatial variation in monthly dengue cases in Bangladesh. The model was fitted to the district-level (64 districts) monthly reported dengue cases aggregated over the period 2000 to 2009 and Bayesian inference was performed using the integrated nested Laplace approximation. We found that mean monthly temperature and its interaction with mean monthly diurnal temperature range, lagged by two months were significantly associated with dengue incidence. Mean monthly rainfall at two months lag was positively associated with dengue incidence. Densely populated districts and districts bordering India or Myanmar had higher incidence than others. The model estimated that 92% of the annual dengue cases occurred between August and September. Cases were identified across the country with 94% in the capital Dhaka (located almost in the middle of the country). Less than half of the affected districts reported cases as observed from the surveillance data. The proportion reported varied by month with a higher proportion reported in high-incidence districts, but dropped towards the end of high transmission season.

Validation of SYBR green I based closed tube loop mediated isothermal amplification (LAMP) assay and simplified direct-blood-lysis (DBL)-LAMP assay for diagnosis of visceral leishmaniasis (VL)

15 November 2018 - 10:00pm

by Keerti Kaumudee Dixit, Sandeep Verma, Om Prakash Singh, Dharmendra Singh, Akhil Pratap Singh, Ratan Gupta, Narendra Singh Negi, Pradeep Das, Shyam Sundar, Ruchi Singh, Poonam Salotra

Background

The World Health Organization has targeted elimination of visceral leishmaniasis (VL) in the Indian subcontinent (ISC) by 2020. Despite distinctive decline seen in the number of VL cases in ISC, there is still a quest for development of a diagnostic test which has the utility for detection of active infection and relapse cases and as a test of cure. The present study validated the sensitivity and specificity of SYBR Green I based closed tube LAMP assay reported by us for diagnosis of VL.

Methodology

The validation study was carried out at two endemic sites in India, located at Rajendra Memorial Research Institute of Medical Sciences (RMRIMS), Patna and Institute of Medical Sciences (IMS), Banaras Hindu University (BHU), Varanasi. Standard operating protocols were provided at the two sites for applying LAMP assay on confirmed VL cases. The diagnostic accuracy of LAMP assay was evaluated by Receiver operator curve (ROC) analysis. Furthermore, a simplified LAMP assay based on direct blood lysis, DBL-LAMP, was developed and verified for its diagnostic accuracy.

Principal findings

A total of 267 eligible participants were included in the study which comprised of 179 VL cases and 88 controls. Sensitivity and specificity of the LAMP assay were 98.32% (95% C.I– 95.2–99.7%) and 96.59% (95% C.I.-90.4–99.3%), respectively. ROC curve analysis depicted no significant difference between area under curve (AUCROC) for LAMP assay and rK39 RDT, indicative of LAMP as an excellent diagnostic test. DBL-LAMP assay, performed on 67 VL and 100 control samples, yielded a sensitivity of 93.05% (95% C.I- 84.75–97%) and specificity of 100% (95% C.I.- 96.30–100%).

Conclusions/Significance

The validated closed tube LAMP for diagnosis of VL will provide impetus to the ongoing VL elimination programme in ISC. The assay based on direct blood lysis promotes its scope for application in field settings by further reducing time and cost.

Global fingerprint of humans on the distribution of <i>Bartonella</i> bacteria in mammals

15 November 2018 - 10:00pm

by Hannah K. Frank, Scott D. Boyd, Elizabeth A. Hadly

As humans move and alter habitats, they change the disease risk for themselves, their commensal animals and wildlife. Bartonella bacteria are prevalent in mammals and cause numerous human infections. Understanding how this genus has evolved and switched hosts in the past can reveal how current patterns were established and identify potential mechanisms for future cross-species transmission. We analyzed patterns of Bartonella transmission and likely sources of spillover using the largest collection of Bartonella gltA genotypes assembled, including 67 new genotypes. This pathogenic genus likely originated as an environmental bacterium and insect commensal before infecting mammals. Rodents and domestic animals serve as the reservoirs or at least key proximate host for most Bartonella genotypes in humans. We also find evidence of exchange of Bartonella between phylogenetically distant domestic animals and wildlife, likely due to increased contact. Care should be taken to avoid contact between humans, domestic animals and wildlife to protect the health of all.

Creative use of the priority review voucher by public and not-for-profit actors delivers the first new FDA-approved treatment for river blindness in 20 years

15 November 2018 - 10:00pm

by Piero L. Olliaro, Annette C. Kuesel, Christine M. Halleux, Mark Sullivan, John C. Reeder

Removal of adult subconjunctival Loa loa amongst urban dwellers in Nigeria

14 November 2018 - 10:00pm

by Ogugua Ndubuisi Okonkwo, Adekunle Olubola Hassan, Taofik Alarape, Toyin Akanbi, Olufemi Oderinlo, Ayodele Akinye, Idris Oyekunle

Loiasis is a neglected tropical disease caused by infection with the filarial parasite Loa loa. It is a disease considered by many to be benign. Several reports of trans border importation of the Loa loa worm amongst immigrants and visitors from endemic regions of the world exist. In most cases an adult subconjunctival worm is removed from the patient. An interventional case series is reported and examines the practice of removal of subconjunctival adult Loa loa worms amongst urban dwellers in Nigeria. Four cases of ocular loiasis seen amongst urban dwellers in Nigeria exemplify the different presentations and removal methods of the subconjunctival adult worm. There were 2 males and 2 females aged 35years, 23years, 25years and 30years respectively. Each patient gave a history of having been raised in a rural community in childhood years, during which they were exposed to streams and muddy farm land; and then migrated to the urban community in later years. They all present with the finding of a subconjunctival adult worm, which was successfully removed and identified to be Loa loa. There are more urban dwellers in Nigeria who present with symptoms of foreign body sensation that may be related to the manifestation of a subconjunctival worm and are not recognized. This is because the emphasis on this disease has erstwhile been on the rural, village dwellers and not on urban dwellers. Eye care practitioners working in urban centers need to be aware of the possibility of this presentation, and be ready to remove any subconjunctival worm when it presents.

On-going transmission of human onchocerciasis in the Massangam health district in the West Region of Cameroon: Better understanding transmission dynamics to inform changes in programmatic interventions

14 November 2018 - 10:00pm

by Didier Bakajika, Laura Senyonjo, Peter Enyong, Joseph Oye, Benjamin Biholong, Elizabeth Elhassan, Daniel Boakye, Ruth Dixon, Elena Schmidt

Background

Massangam health district (HD), in the West Region of Cameroon, has received ivermectin mass drug administration (MDA) for 20 years, however there is evidence of continued high transmission of Onchocerca volvulus. In order to better understand the transmission dynamics in the HD and inform intervention strategies there is a need to delineate the boundaries of the suspected area of high transmission within the wider transmission zone.

Methodology/Principal findings

Parasitological and entomological surveys were conducted to map out the breeding sites of Simulium damnosum and evaluate the prevalence of onchocerciasis in neighbouring communities, including Makouopsap sentinel community. Potential rapids were prospected for identification of S. damnosum larvae and black flies collected to determine infectivity rates. Adults were assessed for the presence of O. volvulus microfilariae through a skin snip biopsy and examined for the presence of nodules. Anti Ov-16 antibodies were tested for in children. Four perennial breeding sites were identified on the Rivers Mbam and Nja. Large number of flies were collected along the River Mbam, especially in the rainy season, with up to 955 flies per day, suggesting this river is a perennial source of black flies. A total of 0.8% of parous flies were infective across the study area. Parasitological studies provided evidence of high rates of infection in the sentinel community and three neighbouring communities, with 37.1% of adults microfilariae positive in Makouopsap. High Ov-16 seropositivity in children also provided evidence of recent on-going transmission. In comparison, communities sampled further away from the sentinel community and neighbouring breeding sites were much closer to reaching onchocerciasis elimination targets.

Conclusions/Significance

This study provides evidence of a particular geographic area of high transmission in an approximate 12 km range around the sentinel community of Makouopsap and the neighbouring breeding sites on the River Nja. To eliminate onchocerciasis by 2025, there is a need to explore alternative intervention strategies in this area of high transmission.

Continuing evidence of Chagas disease along the Texas-Mexico border

14 November 2018 - 10:00pm

by Melissa S. Nolan, David Aguilar, Eric L. Brown, Sarah M. Gunter, Shannon E. Ronca, Craig L. Hanis, Kristy O. Murray

Background

Chagas disease is a chronic parasitic infection that progresses to dilated cardiomyopathy in 30% of human cases. Public health efforts target diagnosing asymptomatic cases, as therapeutic efficacy diminishes as irreversible tissue damage progresses. Physician diagnosis of Chagas disease cases in the United States is low, partially due to lack of awareness of the potential burden in the United States.

Methodology/Principal findings

The current study tested a patient cohort of 1,196 Starr County, Texas residents using the Hemagen Chagas ELISA Kit as a preliminary screening assay. Samples testing positive using the Hemagen test were subjected to additional confirmatory tests. Two patients (0.17%) without previous Chagas disease diagnosis were identified; both had evidence of acquiring disease in the United States or along the Texas-Mexico border.

Conclusions/Significance

The Texas-Mexico border is a foci of Chagas disease human cases, with a local disease burden potentially twice the national estimate of Hispanic populations. It is imperative that physicians consider persons with residential histories along the Texas-Mexico border for Chagas disease testing.

Rabies vaccine initiation and adherence among animal-bite patients in Haiti, 2015

13 November 2018 - 10:00pm

by Cuc H. Tran, Maxwell Kligerman, Lesly L. Andrecy, Melissa D. Etheart, Paul Adrien, Jesse D. Blanton, Max Millien, Ryan M. Wallace

Background

Approximately 59,000 people die from rabies worldwide annually. Haiti is one of the last remaining countries in the Western Hemisphere with endemic canine rabies. Canine-mediated rabies deaths are preventable with post-exposure prophylaxis (PEP): wound treatment, immunoglobulin, and vaccination. In countries where PEP is available, variability in healthcare seeking behaviors and lack of adherence to recommended treatment guidelines could also contribute to these deaths. Yet, few studies have addressed these issues.

Methods

We examined animal-bite reporting and assessed adherence to treatment guidelines at nine healthcare facilities in Haiti. We analyzed individual-level, de-identified patient data (demographic characteristics, geographic location, healthcare facility type, vaccine administration, and bite injury information) using descriptive analyses and logistic regression to examine factors associated with receiving PEP.

Findings

During the 6 month study period, we found 2.5 times more animal-bite case-patients than reported by the national surveillance system (690 versus 274). Of the 690 animal-bite patients identified, 498 (72%) sought care at six PEP providing facilities. Of the case-patients that sought care, 110 (22%) received at least one rabies vaccine. Of the 110 patients, 60 (55%) received all five doses. Delays were observed for three events: when patients presented to a facility after an animal-bite (3.0 days, range: 0–34 days), when patients received their fourth dose (16.1 days, range: 13–52 days), and when patients received their fifth dose (29 days, range: 26–52). When comparing vaccination status and patient characteristics, we found a significant association for bite location (p < .001), severity rank score (p < .001), geographic location (p < .001), and healthcare facility type (p = .002) with vaccination.

Conclusion

High levels of underreporting identified here are of concern since vaccine distribution may, in part, be based on the number of animal-bite cases reported. Given that the Haitian government provides PEP to the population for free and we found animal-bite victims are seeking care in a timely manner─ reducing rabies deaths is an achievable goal.

Rabies post-exposure prophylaxis started during or after travel: A GeoSentinel analysis

13 November 2018 - 10:00pm

by Philippe Gautret, Kristina M. Angelo, Hilmir Asgeirsson, David G. Lalloo, Marc Shaw, Eli Schwartz, Michael Libman, Kevin C. Kain, Watcharapong Piyaphanee, Holly Murphy, Karin Leder, Jean Vincelette, Mogens Jensenius, Jesse Waggoner, Daniel Leung, Sarah Borwein, Lucille Blumberg, Patricia Schlagenhauf, Elizabeth D. Barnett, Davidson H. Hamer, GeoSentinel Global Surveillance Network

Background

Recent studies demonstrate that rabies post-exposure prophylaxis (RPEP) in international travelers is suboptimal, with only 5–20% of travelers receiving rabies immune globulin (RIG) in the country of exposure when indicated. We hypothesized that travelers may not be receiving RIG appropriately, and practices may vary between countries. We aim to describe the characteristics of travelers who received RIG and/or RPEP during travel.

Methodology/Principal findings

We conducted a multi-center review of international travelers exposed to potentially rabid animals, collecting information on RPEP administration. Travelers who started RPEP before (Group A) and at (Group B) presentation to a GeoSentinel clinic during September 2014–July 2017 were included. We included 920 travelers who started RPEP. About two-thirds of Group A travelers with an indication for rabies immunoglobulin (RIG) did not receive it. Travelers exposed in Indonesia were less likely to receive RIG in the country of exposure (relative risk: 0.30; 95% confidence interval: 0.12–0.73; P = 0.01). Travelers exposed in Thailand [Relative risk (RR) 1.38, 95% Confidence Interval (95% CI): 1.0–1.8; P = 0.02], Sri Lanka (RR 3.99, 95% CI: 3.99–11.9; P = 0.013), and the Philippines (RR 19.95, 95% CI: 2.5–157.2; P = 0.01), were more likely to receive RIG in the country of exposure.

Conclusions/Significance

This analysis highlights gaps in early delivery of RIG to travelers and identifies specific countries where travelers may be more or less likely to receive RIG. More detailed country-level information helps inform risk education of international travelers regarding appropriate rabies prevention.

The <i>in vivo</i> and <i>in vitro</i> roles of <i>Trypanosoma cruzi</i> Rad51 in the repair of DNA double strand breaks and oxidative lesions

13 November 2018 - 10:00pm

by Danielle Gomes Passos Silva, Selma da Silva Santos, Sheila C. Nardelli, Isabela Cecília Mendes, Anna Cláudia Guimarães Freire, Bruno Marçal Repolês, Bruno Carvalho Resende, Héllida Marina Costa-Silva, Verônica Santana da Silva, Karla Andrade de Oliveira, Camila Franco Batista Oliveira, Liza Figueiredo Felicori Vilela, Ronaldo Alves Pinto Nagem, Glória Regina Franco, Andrea Mara Macedo, Sergio Danilo Junho Pena, Erich Birelli Tahara, Policarpo Ademar Sales Junior, Douglas Souza Moreira, Santuza Maria Ribeiro Teixeira, Richard McCulloch, Stela Virgilio, Luiz Ricardo Orsini Tosi, Sergio Schenkman, Luciana Oliveira Andrade, Silvane Maria Fonseca Murta, Carlos Renato Machado

In Trypanosoma cruzi, the etiologic agent of Chagas disease, Rad51 (TcRad51) is a central enzyme for homologous recombination. Here we describe the different roles of TcRad51 in DNA repair. Epimastigotes of T. cruzi overexpressing TcRAD51 presented abundant TcRad51-labeled foci before gamma irradiation treatment, and a faster growth recovery when compared to single-knockout epimastigotes for RAD51. Overexpression of RAD51 also promoted increased resistance against hydrogen peroxide treatment, while the single-knockout epimastigotes for RAD51 exhibited increased sensitivity to this oxidant agent, which indicates a role for this gene in the repair of DNA oxidative lesions. In contrast, TcRad51 was not involved in the repair of crosslink lesions promoted by UV light and cisplatin treatment. Also, RAD51 single-knockout epimastigotes showed a similar growth rate to that exhibited by wild-type ones after treatment with hydroxyurea, but an increased sensitivity to methyl methane sulfonate. Besides its role in epimastigotes, TcRad51 is also important during mammalian infection, as shown by increased detection of T. cruzi cells overexpressing RAD51, and decreased detection of single-knockout cells for RAD51, in both fibroblasts and macrophages infected with amastigotes. Besides that, RAD51-overexpressing parasites infecting mice also presented increased infectivity and higher resistance against benznidazole. We thus show that TcRad51 is involved in the repair of DNA double strands breaks and oxidative lesions in two different T. cruzi developmental stages, possibly playing an important role in the infectivity of this parasite.

Risk factors for childhood enteric infection in urban Maputo, Mozambique: A cross-sectional study

12 November 2018 - 10:00pm

by Jackie Knee, Trent Sumner, Zaida Adriano, David Berendes, Ellen de Bruijn, Wolf-Peter Schmidt, Rassul Nalá, Oliver Cumming, Joe Brown

Background

Enteric infections are common where public health infrastructure is lacking. This study assesses risk factors for a range of enteric infections among children living in low-income, unplanned communities of urban Maputo, Mozambique.

Methods & findings

We conducted a cross-sectional survey in 17 neighborhoods of Maputo to assess the prevalence of reported diarrheal illness and laboratory-confirmed enteric infections in children. We collected stool from children aged 1–48 months, independent of reported symptoms, for molecular detection of 15 common enteric pathogens by multiplex RT-PCR. We also collected survey and observational data related to water, sanitation, and hygiene (WASH) characteristics; other environmental factors; and social, economic, and demographic covariates.We analyzed stool from 759 children living in 425 household clusters (compounds) representing a range of environmental conditions. We detected ≥1 enteric pathogens in stool from most children (86%, 95% confidence interval (CI): 84–89%) though diarrheal symptoms were only reported for 16% (95% CI: 13–19%) of children with enteric infections and 13% (95% CI: 11–15%) of all children. Prevalence of any enteric infection was positively associated with age and ranged from 71% (95% CI: 64–77%) in children 1–11 months to 96% (95% CI: 93–98%) in children 24–48 months. We found poor sanitary conditions, such as presence of feces or soiled diapers around the compound, to be associated with higher risk of protozoan infections. Certain latrine features, including drop-hole covers and latrine walls, and presence of a water tap on the compound grounds were associated with a lower risk of bacterial and protozoan infections. Any breastfeeding was also associated with reduced risk of infection.

Conclusions

We found a high prevalence of enteric infections, primarily among children without diarrhea, and weak associations between bacterial and protozoan infections and environmental risk factors including WASH. Findings suggest that environmental health interventions to limit infections would need to be transformative given the high prevalence of enteric pathogen shedding and poor sanitary conditions observed.

Trial registration

ClinicalTrials.gov NCT02362932

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