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Urban villages as transfer stations for dengue fever epidemic: A case study in the Guangzhou, China

PLoS Neglected Tropical Diseases News - 25 April 2019 - 9:00pm

by Hongyan Ren, Wei Wu, Tiegang Li, Zhicong Yang

Background

Numerous urban villages (UVs) and frequent infectious disease outbreaks are major environmental and public health concerns in highly urbanized regions, especially in developing countries. However, the spatial and quantitative associations between UVs and infections remain little understood on a fine scale.

Methodology and principal findings

In this study, the relationships between reported dengue fever (DF) epidemics during 2012–2017, gross domestic product (GDP), the traffic system (road density, bus and/or subway stations), and UVs derived from high-resolution remotely sensed imagery in the central area of Guangzhou, were explored using geographically weighted regression (GWR) models based on a 1 km × 1 km grid scale. Accounting for 16.53%–18.07% of residential area and 16.84%–18.02% of population, UVs possessed 28.55%–38.24% of total reported DF cases in the core area of Guangzhou. The density of DF cases and the DF incidence rates in UVs were 1.81–3.13 and 1.82–3.06 times of that of normal construction land. Approximately 90% of the total cases were concentrated in the UVs and their buffering zones of radius ranged from 0 to 500 m. Significantly positive associations were observed between gridded DF incidence rates and UV area (r = 0.33, P = 0.000), the number of bus stops (r = 0.49, P = 0.000) and subway stations (r = 0.27, P = 0.000), and road density (r = 0.39, P = 0.000). About 60% of spatial variations in the gridded DF incidence rates were interpreted by the different variables of GDP, UVs, and bus stops integrated in GWR models.

Conclusions

UVs likely acted as special transfer stations, receiving and/or exporting DF cases during epidemics. This work increases our understanding of the influences of UVs on vector-borne diseases in highly urbanized areas, supplying valuable clues to local authorities making targeted interventions for the prevention and control of DF epidemics.

Central nervous system melioidosis: A systematic review of individual participant data of case reports and case series

PLoS Neglected Tropical Diseases News - 25 April 2019 - 9:00pm

by Monton Wongwandee, Patcharasarn Linasmita

Background

Central nervous system (CNS) melioidosis is rare. However, delayed diagnosis and treatment could lead to fatality. To identify knowledge of CNS melioidosis, we systematically review case reports and case series.

Methodology/Principal findings

We searched through PubMed, Web of Science and Thai-Journal Citation Index databases as well as Google Scholar with the last date on July 10, 2018. The diagnosis of CNS melioidosis had to be confirmed with culture, serology or polymerase chain reaction. We excluded the animal cases and the studies that the clinical data were not available. We identified 1170 relevant studies, while 70 studies with a total of 120 patients were analyzed. Ninety-three percent of patients were reported from the endemic area of melioidosis. Median age was 40 years (IQR 18–53), and 70% were men. A total of 60% had one or more risk factors for melioidosis. The median duration from clinical onset to diagnosis was ten days (IQR 5–25). Fever (82%), headache (54%), unilateral weakness (57%) and cranial nerve deficits (52%) are among the prominent presentation. Most patient (67%) had at least one extraneurological organ involvement. The CSF profile mostly showed mononuclear pleocytosis (64%), high protein (93%) and normal glucose (66%). The rim-enhancing pattern (78%) is the most frequent neuroimaging finding in encephalomyelitis and brain abscess patients. Both brainstem (34%) and frontal lobe (34%) are the most affected locations. Mortality rate was 20%.

Conclusions/Significance

This study is the most extensive systematic review of case reports and case series of CNS melioidosis in all age groups. However, the results should be cautiously interpreted due to the missing data issue. The propensity of brainstem involvement which correlates with prominent cranial nerve deficits is the characteristic of CNS melioidosis especially encephalomyelitis type. The presenting features of fever and neurological deficits (especially cranial nerve palsies) along with the mononuclear CSF pleocytosis in a patient who lives in the endemic area and also has the risk factor for melioidosis should raise the CNS melioidosis as the differential diagnosis.

Guidance on stakeholder engagement practices to inform the development of area-wide vector control methods

PLoS Neglected Tropical Diseases News - 25 April 2019 - 9:00pm

by Delphine Thizy, Claudia Emerson, Johanna Gibbs, Sarah Hartley, Lydia Kapiriri, James Lavery, Jeantine Lunshof, Janine Ramsey, Julie Shapiro, Jerome Amir Singh, Lea Pare Toe, Isabelle Coche, Benjamin Robinson

Trends in dengue research in the Philippines: A systematic review

PLoS Neglected Tropical Diseases News - 25 April 2019 - 9:00pm

by Kristal An Agrupis, Michelle Ylade, Josephine Aldaba, Anna Lena Lopez, Jacqueline Deen

Dengue is an important public health problem in the Philippines. We sought to describe the trends in dengue research in the country. We searched four databases and identified published studies on dengue research in the Philippines during the past 60 years. We reviewed 135 eligible studies, of which 33% were descriptive epidemiologic studies or case series, 16% were entomologic or vector control studies, 12% were studies on dengue virology and serologic response, 10% were socio-behavioral and economics studies, 8% were clinical trials, 7% were on burden of disease, 7% were investigations on markers of disease severity, 5% were on dengue diagnostics, and 2% were modeling studies. During the last decade, dengue research in the Philippines has increased and evolved from simple descriptive studies to those with more complex and diverse designs. We identified several key topics where more research would be useful.

Knowledge engagement in gene drive research for malaria control

PLoS Neglected Tropical Diseases News - 25 April 2019 - 9:00pm

by Sarah Hartley, Delphine Thizy, Katie Ledingham, Mamadou Coulibaly, Abdoulaye Diabaté, Bakara Dicko, Samba Diop, Jonathan Kayondo, Annet Namukwaya, Barry Nourou, Léa Paré Toé

Sustainable innovation in vector control requires strong partnerships with communities

PLoS Neglected Tropical Diseases News - 25 April 2019 - 9:00pm

by Frederic Bartumeus, Guilherme B. Costa, Roger Eritja, Ann H. Kelly, Marceline Finda, Javier Lezaun, Fredros Okumu, M. Megan Quinlan, Delphine C. Thizy, Léa Paré Toé, Megan Vaughan

Application of a targeted-enrichment methodology for full-genome sequencing of Dengue 1-4, Chikungunya and Zika viruses directly from patient samples

PLoS Neglected Tropical Diseases News - 25 April 2019 - 9:00pm

by Uma Sangumathi Kamaraj, Jun Hao Tan, Ong Xin Mei, Louise Pan, Tanu Chawla, Anna Uehara, Lin-Fa Wang, Eng Eong Ooi, Duane J. Gubler, Hasitha Tissera, Lee Ching Ng, Annelies Wilder-Smith, Paola Florez de Sessions, Timothy Barkham, Danielle E. Anderson, October Michael Sessions

The frequency of epidemics caused by Dengue viruses 1–4, Zika virus and Chikungunya viruses have been on an upward trend in recent years driven primarily by uncontrolled urbanization, mobility of human populations and geographical spread of their shared vectors, Aedes aegypti and Aedes albopictus. Infections by these viruses present with similar clinical manifestations making them challenging to diagnose; this is especially difficult in regions of the world hyperendemic for these viruses. In this study, we present a targeted-enrichment methodology to simultaneously sequence the complete viral genomes for each of these viruses directly from clinical samples. Additionally, we have also developed a customized computational tool (BaitMaker) to design these enrichment baits. This methodology is robust in its ability to capture diverse sequences and is amenable to large-scale epidemiological studies. We have applied this methodology to two large cohorts: a febrile study based in Colombo, Sri Lanka taken during the 2009–2015 dengue epidemic (n = 170) and another taken during the 2016 outbreak of Zika virus in Singapore (n = 162). Results from these studies indicate that we were able to cover an average of 97.04% ± 0.67% of the full viral genome from samples in these cohorts. We also show detection of one DENV3/ZIKV co-infected patient where we recovered full genomes for both viruses.

Clinical and molecular epidemiology of Crimean-Congo hemorrhagic fever in Oman

PLoS Neglected Tropical Diseases News - 25 April 2019 - 9:00pm

by Seif S. Al-Abri, Roger Hewson, Hanan Al-Kindi, Idris Al-Abaidani, Amina Al-Jardani, Amal Al-Maani, Samira Almahrouqi, Barry Atkinson, Adil Al-Wahaibi, Bader Al-Rawahi, Shyam Bawikar, Nicholas J. Beeching

Background

Crimean-Congo hemorrhagic fever (CCHF) is a serious disease with a high fatality rate reported in many countries. The first case of CCHF in Oman was detected in 1995 and serosurveys have suggested widespread infection of humans and livestock throughout the country.

Methodology

Cases of CCHF reported to the Ministry of Health (MoH) of Oman between 1995 and 2017 were retrospectively reviewed. Diagnosis was confirmed by serology and/or molecular tests in Oman. Stored RNA from recent cases was studied by sequencing the complete open reading frame (ORF) of the viral S segment at Public Health England, enabling phylogenetic comparisons to be made with other S segments of strains obtained from the region.

Findings

Of 88 cases of CCHF, 4 were sporadic in 1995 and 1996, then none were detected until 2011. From 2011–2017, incidence has steadily increased and 19 (23.8%) of 80 cases clustered around Eid Al Adha. The median (range) age was 33 (15–68) years and 79 (90%) were male. The major risk for infection was contact with animals and/or butchering in 73/88 (83%) and only one case was related to tick bites alone. Severe cases were over-represented: 64 (72.7%) had a platelet count < 50 x 109/L and 32 (36.4%) died. There was no intrafamilial spread or healthcare-associated infection. The viral S segments from 11 patients presenting in 2013 and 2014 were all grouped in Asia 1 (IV) lineage.

Conclusions

CCHF is well-established throughout Oman, with a single strain of virus present for at least 20 years. Most patients are men involved in animal husbandry and butchery. The high mortality suggests that there is substantial under-diagnosis of milder cases. Preventive measures have been introduced to reduce risks of transmission to animal handlers and butchers and to maintain safety in healthcare settings.

Host immune responses induced by specific <i>Mycobacterium leprae</i> antigens in an overnight whole-blood assay correlate with the diagnosis of paucibacillary leprosy patients in China

PLoS Neglected Tropical Diseases News - 24 April 2019 - 9:00pm

by Xiaohua Chen, Yuan-Gang You, You-Hua Yuan, Lian C. Yuan, Yan Wen

Background

Leprosy, caused by Mycobacterium leprae, affects over 200,000 people annually worldwide and remains endemic in the ethnically diverse, mountainous and underdeveloped southwestern provinces of China. Delayed diagnosis of leprosy persists in China, thus, additional knowledge to support early diagnosis, especially early diagnosis of paucibacillary (PB) patients, based on the host immune responses induced by specific M. leprae antigens is needed. The current study aimed to investigate leprosy patients and controls in Southwest China by comparing supernatants after stimulation with specific M. leprae antigens in an overnight whole-blood assay (WBA) to determine whether host markers induced by specific M. leprae antigens improve the diagnosis or discrimination of PB patients with leprosy.

Methodology/Principal findings

Leprosy patients [13 multibacillary (MB) patients and 7 PB patients] and nonleprosy controls [21 healthy household contacts (HHCs), 20 endemic controls (ECs) and 19 tuberculosis (TB) patients] were enrolled in this study. The supernatant levels of ten host markers stimulated by specific M. leprae antigens were evaluated by overnight WBA and multiplex Luminex assays. The diagnostic value in PB patients and ECs and the discriminatory value between PB patients and HHCs or TB patients were evaluated by receiver operator characteristics (ROC) analysis. ML2044-stimulated CXCL8/IL-8 achieved the highest sensitivity of 100%, with a specificity of 73.68%, for PB diagnosis. Compared to single markers, a 3-marker combination model that included ML2044-induced CXCL8/IL-8, CCL4/MIP-1 beta, and IL-6 improved the diagnostic specificity to 94.7% for PB patients. ML2044-stimulated IL-4 and CXCL8/IL-8 achieved the highest sensitivity (85.71% and 100%) and the highest specificity (95.24% and 84.21%) for discriminating PB patients from HHCs and TB patients, respectively.

Conclusions

Our findings suggest that the host markers induced by specific M. leprae antigens in an overnight WBA increase diagnostic and discriminatory value in PB patients with leprosy, with a particularly strong association with interleukin 8.

The arginine sensing and transport binding sites are distinct in the human pathogen <i>Leishmania</i>

PLoS Neglected Tropical Diseases News - 24 April 2019 - 9:00pm

by Harsh Pawar, Madhu Puri, Renana Fischer Weinberger, Rentala Madhubala, Dan Zilberstein

The intracellular protozoan parasite Leishmania donovani causes human visceral leishmaniasis. Intracellular L. donovani that proliferate inside macrophage phagolysosomes compete with the host for arginine, creating a situation that endangers parasite survival. Parasites have a sensor that upon arginine deficiency activates an Arginine Deprivation Response (ADR). L. donovani transport arginine via a high-affinity transporter (LdAAP3) that is rapidly up-regulated by ADR in intracellular amastigotes. To date, the sensor and its ligand have not been identified. Here, we show that the conserved amidino group at the distal cap of the arginine side chain is the ligand that activates ADR, in both promastigotes and intracellular amastigotes, and that arginine sensing and transport binding sites are distinct in L. donovani. Finally, upon addition of arginine and analogues to deprived cells, the amidino ligand activates rapid degradation of LdAAP3. This study provides the first identification of an intra-molecular ligand of a sensor that acts during infection.

(De)glutamylation and cell death in <i>Leishmania</i> parasites

PLoS Neglected Tropical Diseases News - 24 April 2019 - 9:00pm

by Louise Basmaciyan, Derrick R. Robinson, Nadine Azas, Magali Casanova

Trypanosomatids are flagellated protozoan parasites that are very unusual in terms of cytoskeleton organization but also in terms of cell death. Most of the Trypanosomatid cytoskeleton consists of microtubules, forming different substructures including a subpellicular corset. Oddly, the actin network appears structurally and functionally different from other eukaryotic actins. And Trypanosomatids have an apoptotic phenotype under cell death conditions, but the pathways involved are devoid of key mammal proteins such as caspases or death receptors, and the triggers involved in apoptotic induction remain unknown. In this article, we have studied the role of the post-translational modifications, deglutamylation and polyglutamylation, in Leishmania. We have shown that Leishmania apoptosis was linked to polyglutamylation and hypothesized that the cell survival process autophagy was linked to deglutamylation. A balance seems to be established between polyglutamylation and deglutamylation, with imbalance inducing microtubule or other protein modifications characterizing either cell death if polyglutamylation was prioritized, or the cell survival process of autophagy if deglutamylation was prioritized. This emphasizes the role of post-translational modifications in cell biology, inducing cell death or cell survival of infectious agents.

Systematic sampling of adults as a sensitive means of detecting persistence of lymphatic filariasis following mass drug administration in Sri Lanka

PLoS Neglected Tropical Diseases News - 22 April 2019 - 9:00pm

by Ramakrishna U. Rao, Sandhya D. Samarasekera, Kumara C. Nagodavithana, Manjula W. Punchihewa, Udaya S. B. Ranasinghe, Gary J. Weil

Background

Sri Lanka’s Anti-Filariasis Campaign conducted 5 annual rounds of mass drug administration (MDA) with diethylcarbamazine (DEC) plus albendazole to eliminate lymphatic filariasis (LF) in all endemic districts between 2002 and 2006. Post-MDA surveillance has consistently documented Wuchereria bancrofti microfilaremia (Mf) rates below 1% in all sentinel and spot check sites since that time, and all implementation units easily satisfied WHO’s target for school-based transmission assessment surveys (school-TAS) in 2013. However, more detailed studies have identified foci of persistent infection in the large coastal evaluation unit (EU) (population about 0.6 million) in Galle district. Therefore, the purpose of this study was to assess the sensitivity and feasibility of community-based TAS in adults (adult-TAS) and to compare results obtained by adult-TAS with prior school-TAS and molecular xenomonitoring (MX, molecular detection of filarial DNA in systematically sampled mosquitoes) results in this known problem area.

Methodology and principal findings

Two cluster surveys were performed in independent samples of 30 evaluation areas (EAs) in the coastal Galle EU in 2015. Each survey tested approximately 1,800 adults for circulating filarial antigenemia (CFA) with the Alere Filariasis Test Strip. The CFA prevalence for all persons tested (N = 3,612) was 1.8% (CI 1.4–2.2), and this was significantly higher than the CFA rate of 0.4% obtained by school-TAS in 2013. CFA prevalences in the two samples were similar [1.5% (CI 1.0–2.2), and 2.0% (CI 1.4–2.7)]. Antigenemia prevalence in sampled EUs was highly variable (range 0–11%), and it exceeded 5% in 6 EAs. The 30 EAs sampled in one of our adult-TAS surveys had recently been assessed for persistent filariasis by molecular xenomonitoring (MX). CFA prevalence in adults and filarial DNA prevalence in mosquitoes in these EAs were significantly correlated (r = 0.43; P = 0.02).

Conclusions

Community based adult-TAS provided a reproducible measure of persistent W. bancrofti infection in a large evaluation unit in Sri Lanka that has low-level persistence of LF following multiple rounds of MDA. In addition, adult-TAS and MX results illustrate the focality of persistent LF in this setting. Adult-TAS may be more sensitive than school-TAS for this purpose. Adult-TAS and MX are potential options for post-MDA and post-validation surveillance programs to identify problem areas that require mop-up activities. Adult-TAS should also be useful for remapping areas with uncertain LF endemicity for possible inclusion in national LF elimination programs.

A highly expressed intestinal cysteine protease of <i>Ancylostoma ceylanicum</i> protects vaccinated hamsters from hookworm infection

PLoS Neglected Tropical Diseases News - 22 April 2019 - 9:00pm

by Jason B. Noon, Erich M. Schwarz, Gary R. Ostroff, Raffi V. Aroian

Background

Human hookworms (Necator americanus, Ancylostoma duodenale, and Ancylostoma ceylanicum) are intestinal blood-feeding parasites that infect ~500 million people worldwide and are among the leading causes of iron-deficiency anemia in the developing world. Drugs are useful against hookworm infections, but hookworms rapidly reinfect people, and the parasites can develop drug resistance. Therefore, having a hookworm vaccine would be of tremendous benefit.

Methodology/Principal findings

We investigated the vaccine efficacy in outbred Syrian hamsters of three A. ceylanicum hookworm antigen candidates from two classes of proteins previously identified as promising vaccine candidates. These include two intestinally-enriched, putatively secreted cathepsin B cysteine proteases (AceyCP1, AceyCPL) and one small Kunitz-type protease inhibitor (AceySKPI3). Recombinant proteins were produced in Pichia pastoris, and adsorbed to Alhydrogel. Recombinant AceyCPL (rAceyCPL)/Alhydrogel and rAceySKPI3/Alhydrogel induced high serum immunoglobulin G (IgG) titers in 8/8 vaccinates, but were not protective. rAceyCP1/Alhydrogel induced intermediate serum IgG titers in ~60% of vaccinates in two different trials. rAceyCP1 serum IgG responders had highly significantly decreased hookworm burdens, fecal egg counts and clinical pathology compared to Alhydrogel controls and nonresponders. Protection was highly correlated with rAceyCP1 serum IgG titer. Antisera from rAceyCP1 serum IgG responders, but not nonresponders or rAceyCPL/Alhydrogel vaccinates, significantly reduced adult A. ceylanicum motility in vitro. Furthermore, rAceyCP1 serum IgG responders had canonical Th2-specific recall responses (IL4, IL5, IL13) in splenocytes stimulated ex vivo.

Conclusions/Significance

These findings indicate that rAceyCP1 is a promising vaccine candidate and validates a genomic/transcriptomic approach to human hookworm vaccine discovery.

Prevalence, intensity and associated risk factors of soil transmitted helminth infections: A comparison between Negritos (indigenous) in inland jungle and those in resettlement at town peripheries

PLoS Neglected Tropical Diseases News - 22 April 2019 - 9:00pm

by Azdayanti Muslim, Sakinah Mohd Sofian, Syahrul Azlin Shaari, Boon-Peng Hoh, Yvonne Ai-Lian Lim

Background

Formerly known as the Malaysian hunter gatherers, the Negrito Orang Asli (OA) were heavily dependent on the forest for sustenance and early studies indicated high prevalence of intestinal parasitism. Initiation of a redevelopment program in the 1970s aimed to demarginalize the OA was expected to reduce soil transmitted helminth (STH) infections. Gradually, the OA were relocated to new resettlement areas at the peripheries. The aim of this study was to compare STH infections between Negritos who are still living in the inland jungle with those living in resettlements.

Methodology/Principal findings

A total of 416 Negrito participants were grouped into two categories of communities based on location; Inland Jungle Villages (IJV); and Resettlement Plan Scheme (RPS). Iodine wet mount, formalin-ether sedimentation, modified Trichrome and modified Ziehl-Neelsen staining and Kato-Katz methods were performed on stool samples. A questionnaire was used to collect information regarding demographic, socioeconomic, environmental and hygiene behaviors. Prevalence of STH was significantly higher in IJV (91.3%) versus RPS (83.1%) (P = 0.02). However, the percentage of individuals with severe intensity of Trichuris trichiura infections was significantly higher in the RPS (17.2%) compared to IJV (6.5%) (P = 0.01). Severe Ascaris lumbricoides infection was observed at 20.0% amongst RPS Negritos and 15.0% amongst IJV (P = 0.41). Whilst for hookworm infection, both prevalence and individuals with moderate to severe infections were higher in the IJV (26.2%, 41.0%) versus RPS (18.7%, 24.0%) (P values = 0.08, 0.09), accordingly. The prevalence other intestinal parasitic infections (e.g. Entamoeba sp., Blastocystis and flukes) was also higher in IJV versus RPS. Apart from poor hygienic behaviors as significant risk factors in both communities, low socio-economic status was highly associated with STH infections in RPS (P<0.001) but not significantly associated in IJV.

Conclusions

The findings showed that ex situ development plan by RPS has not profoundly contributed to the STH reduction among the OA. Conversely, burden rate of T. trichiura infections increased due to their extreme poverty and poor hygienic behaviors. Here, we are suggesting biannual mass albendazole intervention (triple dose regimens in RPS, but a single dose in IJV) and community empowerment to both communities. For a long-term and better uptake, these strategies must be done together with the community input and participation, respecting their traditional customs and accompanied by recruitment of more OA people in the health-care taskforce.

The spatial epidemiology of leprosy in Kenya: A retrospective study

PLoS Neglected Tropical Diseases News - 22 April 2019 - 9:00pm

by Fatihiyya Wangara, Hillary Kipruto, Oscar Ngesa, James Kayima, Enos Masini, Joseph Sitienei, Faith Ngari

Background

Leprosy elimination defined as a registered prevalence rate of less than 1 case per 10,000 persons was achieved in Kenya at the national level in 1989. However, there are still pockets of leprosy in some counties where late diagnosis and consequent physical disability persist. The epidemiology of leprosy in Kenya for the period 2012 through to 2015 was defined using spatial methods.

Methods

This was a retrospective ecological correlational study that utilized leprosy case based data extracted from the National Leprosy Control Program database. Geographic information system and demographic data were obtained from Kenya National Bureau of Statistics (KNBS). Chi square tests were carried out to check for association between sociodemographic factors and disease indicators. Two Spatial Poisson Conditional Autoregressive (CAR) models were fitted in WinBUGS 1.4 software. The first model included all leprosy cases (new, retreatment, transfers from another health facility) and the second one included only new leprosy cases. These models were used to estimate leprosy relative risks per county as compared to the whole country i.e. the risk of presenting with leprosy given the geographical location.

Principal findings

Children aged less than 15 years accounted for 7.5% of all leprosy cases indicating active leprosy transmission in Kenya. The risk of leprosy notification increased by about 5% for every 1 year increase in age, whereas a 1% increase in the proportion of MB cases increased the chances of new leprosy case notification by 4%. When compared to the whole country, counties with the highest risk of leprosy include Kwale (relative risk of 15), Kilifi (RR;8.9) and Homabay (RR;4.1), whereas Turkana had the lowest relative risk of 0.005.

Conclusion

Leprosy incidence exhibits geographical variation and there is need to institute tailored local control measures in these areas to reduce the burden of disability.

Spatio-temporal dynamics of dengue in Brazil: Seasonal travelling waves and determinants of regional synchrony

PLoS Neglected Tropical Diseases News - 22 April 2019 - 9:00pm

by Mikhail Churakov, Christian J. Villabona-Arenas, Moritz U. G. Kraemer, Henrik Salje, Simon Cauchemez

Dengue continues to be the most important vector-borne viral disease globally and in Brazil, where more than 1.4 million cases and over 500 deaths were reported in 2016. Mosquito control programmes and other interventions have not stopped the alarming trend of increasingly large epidemics in the past few years. Here, we analyzed monthly dengue cases reported in Brazil between 2001 and 2016 to better characterise the key drivers of dengue epidemics. Spatio-temporal analysis revealed recurring travelling waves of disease occurrence. Using wavelet methods, we characterised the average seasonal pattern of dengue in Brazil, which starts in the western states of Acre and Rondônia, then travels eastward to the coast before reaching the northeast of the country. Only two states in the north of Brazil (Roraima and Amapá) did not follow the countrywide pattern and had inconsistent timing of dengue epidemics throughout the study period. We also explored epidemic synchrony and timing of annual dengue cycles in Brazilian regions. Using gravity style models combined with climate factors, we showed that both human mobility and vector ecology contribute to spatial patterns of dengue occurrence. This study offers a characterization of the spatial dynamics of dengue in Brazil and its drivers, which could inform intervention strategies against dengue and other arboviruses.

Loss of cytoplasmic incompatibility in <i>Wolbachia</i>-infected <i>Aedes aegypti</i> under field conditions

PLoS Neglected Tropical Diseases News - 19 April 2019 - 9:00pm

by Perran A. Ross, Scott A. Ritchie, Jason K. Axford, Ary A. Hoffmann

Wolbachia bacteria are now being introduced into Aedes aegypti mosquito populations for dengue control. When Wolbachia infections are at a high frequency, they influence the local transmission of dengue by direct virus blocking as well as deleterious effects on vector mosquito populations. However, the effectiveness of this strategy could be influenced by environmental temperatures that decrease Wolbachia density, thereby reducing the ability of Wolbachia to invade and persist in the population and block viruses. We reared wMel-infected Ae. aegypti larvae in the field during the wet season in Cairns, North Queensland. Containers placed in the shade produced mosquitoes with a high Wolbachia density and little impact on cytoplasmic incompatibility. However, in 50% shade where temperatures reached 39°C during the day, wMel-infected males partially lost their ability to induce cytoplasmic incompatibility and females had greatly reduced egg hatch when crossed to infected males. In a second experiment under somewhat hotter conditions (>40°C in 50% shade), field-reared wMel-infected females had their egg hatch reduced to 25% when crossed to field-reared wMel-infected males. Wolbachia density was reduced in 50% shade for both sexes in both experiments, with some mosquitoes cleared of their Wolbachia infections entirely. To investigate the critical temperature range for the loss of Wolbachia infections, we held Ae. aegypti eggs in thermocyclers for one week at a range of cyclical temperatures. Adult wMel density declined when eggs were held at 26–36°C or above with complete loss at 30–40°C, while the density of wAlbB remained high until temperatures were lethal. These findings suggest that high temperature effects on Wolbachia are potentially substantial when breeding containers are exposed to partial sunlight but not shade. Heat stress could reduce the ability of Wolbachia infections to invade mosquito populations in some locations and may compromise the ability of Wolbachia to block virus transmission in the field. Temperature effects may also have an ecological impact on mosquito populations given that a proportion of the population becomes self-incompatible.

Prevalence and genetic diversity of <i>Burkholderia pseudomallei</i> isolates in the environment near a patient’s residence in Northeast Thailand

PLoS Neglected Tropical Diseases News - 19 April 2019 - 9:00pm

by Rathanin Seng, Natnaree Saiprom, Rungnapa Phunpang, Christine Joy Baltazar, Sarika Boontawee, Thanatchanan Thodthasri, Wirayut Silakun, Narisara Chantratita

Background

Burkholderia pseudomallei is the causative agent of melioidosis, a severe infectious disease in tropical regions. It is necessary to understand the risk of acquiring this infection from the environment.

Methodology /Principal Findings

The prevalence, concentration and genetic diversity of B. pseudomallei isolates collected from two sites in Buriram, Northeast Thailand were investigated. Forty-four environmental samples (18 from soil, 14 from rice rhizosphere, and 12 from water) were collected; of those 44 samples, 19 were collected from near a patient’s residence and 25 from suspected exposure sites and compared with 10 clinical isolates of the patient. Quantitative culture was performed, and B. pseudomallei was identified using the latex agglutination test and matrix-laser absorption ionisation mass spectrometry. Genotyping was performed in 162 colonies from clinical (N = 10) and environmental samples (N = 152) using pulse-field gel electrophoresis (PFGE) followed by multi-locus sequence typing (MLST) of the clinical strain. B. pseudomallei was detected in 11 of the 44 environmental samples (1 from soil, 4 from rice rhizosphere, and 6 from water). The bacterial count in the positive soil sample was 115 CFU/g. The mean concentrations ± SDs of B. pseudomallei in the positive water and rhizosphere samples were 5.1 ± 5.5 CFU/ml and 80 ± 49 CFU/g, respectively. Six water samples with positive results were collected from a pond and water sources for drinking and daily use. All colonies isolated from the patient shared the same PFGE type (PT) indicating monoclonal infection of ST99. Although the 152 colonies from environmental isolates exhibited 25 PTs, none were identical to the patient’s isolates. PT5 and PT7 were most common genotype among the environmental samples.

Conclusions/Significance

Diverse genotypes of B. pseudomallei were prevalent in the environment. However, the patient may have been infected with a low-density genotype. Intervention strategies for preventing B. pseudomallei infection are required.

Genetic landscape and macro-evolution of co-circulating Coxsackieviruses A and Vaccine-derived Polioviruses in the Democratic Republic of Congo, 2008-2013

PLoS Neglected Tropical Diseases News - 19 April 2019 - 9:00pm

by Serge Alain Sadeuh-Mba, Hugo Kavunga-Membo, Marie-Line Joffret, Riziki Yogolelo, Marie Claire Endegue-Zanga, Maël Bessaud, Richard Njouom, Jean-Jacques Muyembe-Tamfu, Francis Delpeyroux

Enteroviruses (EVs) are among the most common viruses infecting humans worldwide but only a few Non-Polio Enterovirus (NPEV) isolates have been characterized in the Democratic Republic of Congo (DR Congo). Moreover, circulating vaccine-derived polioviruses (PVs) [cVDPVs] isolated during multiple outbreaks in DR Congo from 2004 to 2018 have been characterized so far only by the sequences of their VP1 capsid coding gene. This study was carried to i) investigate the circulation and genetic diversity of NPEV and polio vaccine isolates recovered from healthy children and Acute Flaccid Paralysis (AFP) patients, ii) evaluate the occurrence of genetic recombination among EVs belonging to the Enterovirus C species (including PVs) and iii) identify the virological factors favoring multiple emergences of cVDPVs in DR Congo. The biological material considered in this study included i) a collection of 91 Sabin-like PVs, 54 cVDPVs and 150 NPEVs isolated from AFP patients between 2008 and 2012 in DR Congo and iii) a collection of 330 stool specimens collected from healthy children in 2013 in the Kasai Oriental and Maniema provinces of DR Congo. Studied virus isolates were sequenced in four distinct sub-genomic regions 5’-UTR, VP1, 2CATPase and 3Dpol. Resulting sequences were compared through comparative phylogenetic analyses. Virus isolation showed that 19.1% (63/330) healthy children were infected by EVs including 17.9% (59/330) of NPEVs and 1.2% (4/330) of type 3 Sabin-like PVs. Only one EV-C type, EV-C99 was identified among the NPEV collection from AFP patients whereas 27.5% of the 69 NPEV isolates typed in healthy children belonged to the EV-C species: CV-A13 (13/69), A20 (5/69) and A17 (1/69). Interestingly, 50 of the 54 cVDPVs featured recombinant genomes containing exogenous sequences in at least one of the targeted non-structural regions of their genomes: 5’UTR, 2CATPase and 3Dpol. Some of these non-vaccine sequences of the recombinant cVDPVs were strikingly related to homologous sequences from co-circulating CV-A17 and A20 in the 2CATPase region as well as to those from co-circulating CV-A13, A17 and A20 in the 3Dpol region. This study provided the first evidence uncovering CV-A20 strains as major recombination partners of PVs. High quality AFP surveillance, sensitive environmental surveillance and efficient vaccination activities remain essential to ensure timely detection and efficient response to recombinant cVDPVs outbreaks in DR Congo. Such needs are valid for any epidemiological setting where high frequency and genetic diversity of Coxsackieviruses A13, A17 and A20 provide a conducive viral ecosystem for the emergence of virulent recombinant cVDPVs.

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