Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-30 (of 44 Records) |
Query Trace: Haque R[original query] |
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Inconsequential role for chemerin-like receptor 1 in the manifestation of ozone-induced lung pathophysiology in male mice
Johnston RA , Pilkington AW , Atkins CL , Boots TE , Brown PL , Jackson WT , Spencer CY , Siddiqui SR , Haque IU . Physiol Rep 2024 12 (8) e16008 We executed this study to determine if chemerin-like receptor 1 (CMKLR1), a G(i/o) protein-coupled receptor expressed by leukocytes and non-leukocytes, contributes to the development of phenotypic features of non-atopic asthma, including airway hyperresponsiveness (AHR) to acetyl-β-methylcholine chloride, lung hyperpermeability, airway epithelial cell desquamation, and lung inflammation. Accordingly, we quantified sequelae of non-atopic asthma in wild-type mice and mice incapable of expressing CMKLR1 (CMKLR1-deficient mice) following cessation of acute inhalation exposure to either filtered room air (air) or ozone (O(3)), a criteria pollutant and non-atopic asthma stimulus. Following exposure to air, lung elastic recoil and airway responsiveness were greater while the quantity of adiponectin, a multi-functional adipocytokine, in bronchoalveolar lavage (BAL) fluid was lower in CMKLR1-deficient as compared to wild-type mice. Regardless of genotype, exposure to O(3) caused AHR, lung hyperpermeability, airway epithelial cell desquamation, and lung inflammation. Nevertheless, except for minimal genotype-related effects on lung hyperpermeability and BAL adiponectin, we observed no other genotype-related differences following O(3) exposure. In summary, we demonstrate that CMKLR1 limits the severity of innate airway responsiveness and lung elastic recoil but has a nominal effect on lung pathophysiology induced by acute exposure to O(3). |
Poliovirus type 1 systemic humoral and intestinal mucosal immunity induced by monovalent oral poliovirus vaccine, fractional inactivated poliovirus vaccine, and bivalent oral poliovirus vaccine: A randomized controlled trial
Snider CJ , Zaman K , Wilkinson AL , Binte Aziz A , Yunus M , Haque W , Jones KAV , Wei L , Estivariz CF , Konopka-Anstadt JL , Mainou BA , Patel JC , Lickness JS , Pallansch MA , Wassilak SGF , Steven Oberste M , Anand A . Vaccine 2023 41 (41) 6083-6092 BACKGROUND: To inform response strategies, we examined type 1 humoral and intestinal immunity induced by 1) one fractional inactivated poliovirus vaccine (fIPV) dose given with monovalent oral poliovirus vaccine (mOPV1), and 2) mOPV1 versus bivalent OPV (bOPV). METHODS: We conducted a randomized, controlled, open-label trial in Dhaka, Bangladesh. Healthy infants aged 5 weeks were block randomized to one of four arms: mOPV1 at age 6-10-14 weeks/fIPV at 6 weeks (A); mOPV1 at 6-10-14 weeks/fIPV at 10 weeks (B); mOPV1 at 6-10-14 weeks (C); and bOPV at 6-10-14 weeks (D). Immune response at 10 weeks and cumulative response at 14 weeks was assessed among the modified intention-to-treat population, defined as seroconversion from seronegative (<1:8 titers) to seropositive (≥1:8) or a four-fold titer rise among seropositive participants sustained to age 18 weeks. We examined virus shedding after two doses of mOPV1 with and without fIPV, and after the first mOPV1 or bOPV dose. The trial is registered at ClinicalTrials.gov (NCT03722004). FINDINGS: During 18 December 2018 - 23 November 2019, 1,192 infants were enrolled (arms A:301; B:295; C:298; D:298). Immune responses at 14 weeks did not differ after two mOPV1 doses alone (94% [95% CI: 91-97%]) versus two mOPV1 doses with fIPV at 6 weeks (96% [93-98%]) or 10 weeks (96% [93-98%]). Participants who received mOPV1 and fIPV at 10 weeks had significantly lower shedding (p < 0·001) one- and two-weeks later compared with mOPV1 alone. Response to one mOPV1 dose was significantly higher than one bOPV dose (79% versus 67%; p < 0·001) and shedding two-weeks later was significantly higher after mOPV1 (76% versus 56%; p < 0·001) indicating improved vaccine replication. Ninety-nine adverse events were reported, 29 serious including two deaths; none were attributed to study vaccines. INTERPRETATION: Given with the second mOPV1 dose, fIPV improved intestinal immunity but not humoral immunity. One mOPV1 dose induced higher humoral and intestinal immunity than bOPV. FUNDING: U.S. Centers for Disease Control and Prevention. |
Insecticide resistance status of Aedes aegypti in Bangladesh (preprint)
Al-Amin HM , Johora FT , Irish SR , Hossainey MRH , Vizcaino L , Paul KK , Khan WA , Haque R , Alam MS , Lenhart A . bioRxiv 2020 2020.07.31.231076 Background Arboviral diseases including dengue and chikungunya are major public health concern in Bangladesh, with unprecedented levels of transmission reported in recent years. The primary approach to control these diseases is control of Aedes aegypti using pyrethroid insecticides. Although chemical control is long-practiced, no comprehensive analysis of Ae. aegypti susceptibility to insecticides has previously been conducted. This study aimed to determine the insecticide resistance status of Ae. aegypti in Bangladesh and investigate the role of detoxification enzymes and altered target site sensitivity as resistance mechanisms.Methods Aedes eggs were collected using ovitraps from five districts across the country and in eight neighborhoods of the capital city Dhaka from August to November 2017. CDC bottle bioassays were conducted for permethrin, deltamethrin, malathion, and bendiocarb using 3-5-day old F0-F2 non-blood fed female mosquitoes. Biochemical assays were conducted to detect metabolic resistance mechanisms and real-time PCR was performed to determine the frequencies of the knockdown resistance (kdr) mutations Gly1016, Cys1534, and Leu410.Results High levels of resistance to permethrin were detected in all Ae. aegypti populations, with mortality ranging from 0 – 14.8% at the diagnostic dose. Substantial resistance continued to be detected against higher (2X) doses of permethrin (5.1 – 44.4% mortality). Susceptibility to deltamethrin and malathion varied between populations while complete susceptibility to bendiocarb was observed in all populations. Significantly higher levels of esterase and oxidase activity were detected in most of the test populations as compared to the susceptible reference Rockefeller strain. A significant association was detected between permethrin resistance and the presence of Gly1016 and Cys1534 homozygotes. The frequency of kdr alleles varied across the Dhaka populations, and Leu410 was not detected in any of the tested populations.Conclusions The detection of widespread pyrethroid resistance and multiple mechanisms highlights the urgency for implementing alternate Ae. aegypti control strategies. In addition, implementing routine monitoring of insecticide resistance in Ae. aegypti in Bangladesh will lead to a greater understanding of susceptibility trends over space and time, thereby enabling the development of improved control strategies.Competing Interest StatementThe authors have declared no competing interest.AChEacetylcholine esterase;BIBreteau Index;β-ESTβ esterase;CIconfidence intervals;DDTdichlorodiphenyltrichloroethane;DTNBdithio-bis-2-nitrobenzoic acid;GSTsglutathione S-transferases;HWEHardy-Weinberg equilibrium;IRSindoor residual spraying;IACHEinsensitive acetylcholine esterase;icddr,bInternational Centre for Diarrhoeal Disease Research, Bangladesh;kdrknockdown resistance:LLINslong-lasting insecticidal nets:MFOsmixed-function oxidases;ODoptical density;ROCKRockefeller;CDCU.S. Centers for Disease Control and Prevention;VGSCvoltage-gated sodium channel;WHOWorld Health Organization |
Structural Elucidation of a Protective B cell Epitope on Outer Surface Protein C (OspC) of the Lyme disease spirochete, Borreliella burgdorferi (preprint)
Rudolph MJ , Davis SA , Emranul Haque HM , Weis DD , Vance DJ , Piazza CL , Ejemel M , Cavacini L , Wang Y , Lamine Mbow M , Gilmore RD , Mantis NJ . bioRxiv 2022 29 Outer surface protein C (OspC) plays a pivotal role in mediating tick-to-host transmission and infectivity of the Lyme disease spirochete, Borreliella burgdorferi. OspC is a helical-rich homodimer that interacts with tick salivary proteins, as well as components of the mammalian immune system. Several decades ago, it was shown that the OspC-specific monoclonal antibody, B5, was able to passively protect mice from experimental tick-transmitted infection by B. burgdorferi strain B31. However, B5's epitope has never been elucidated, despite widespread interest in OspC as a possible Lyme disease vaccine antigen. Here we report the crystal structure of B5 antigen-binding fragments (Fabs) in complex with recombinant OspC type A (OspCA). Each OspC monomer within the homodimer was bound by a single B5 Fab in a side-on orientation, with contact points along OspC's a-helix 1 and a-helix 6, as well as interactions with the loop between a-helices 5 and 6. In addition, B5's complementarity-determining region (CDR) H3 bridged the OspC-OspC' homodimer interface, revealing the quaternary nature of the protective epitope. To provide insight into the molecular basis of B5 serotype specificity, we solved the crystal structures of recombinant OspC types B and K and compared them to OspCA. This study represents the first structure of a protective B cell epitope on OspC and will aid in the rational design of OspC-based vaccines and therapeutics for Lyme disease. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Structural elucidation of a protective B cell epitope on outer surface protein C (OspC) of the Lyme disease spirochete, borreliella Burgdorferi
Rudolph MJ , Davis SA , Haque HME , Weis DD , Vance DJ , Piazza CL , Ejemel M , Cavacini L , Wang Y , Mbow ML , Gilmore RD , Mantis NJ . mBio 2023 14 (2) e0298122 Outer surface protein C (OspC) plays a pivotal role in mediating tick-to-host transmission and infectivity of the Lyme disease spirochete, Borreliella burgdorferi. OspC is a helical-rich homodimer that interacts with tick salivary proteins, as well as components of the mammalian immune system. Several decades ago, it was shown that the OspC-specific monoclonal antibody, B5, was able to passively protect mice from experimental tick-transmitted infection by B. burgdorferi strain B31. However, B5's epitope has never been elucidated, despite widespread interest in OspC as a possible Lyme disease vaccine antigen. Here, we report the crystal structure of B5 antigen-binding fragments (Fabs) in complex with recombinant OspC type A (OspC(A)). Each OspC monomer within the homodimer was bound by a single B5 Fab in a side-on orientation, with contact points along OspC's α-helix 1 and α-helix 6, as well as interactions with the loop between α-helices 5 and 6. In addition, B5's complementarity-determining region (CDR) H3 bridged the OspC-OspC' homodimer interface, revealing the quaternary nature of the protective epitope. To provide insight into the molecular basis of B5 serotype specificity, we solved the crystal structures of recombinant OspC types B and K and compared them to OspC(A). This study represents the first structure of a protective B cell epitope on OspC and will aid in the rational design of OspC-based vaccines and therapeutics for Lyme disease. IMPORTANCE The spirochete Borreliella burgdorferi is a causative agent of Lyme disease, the most common tickborne disease in the United States. The spirochete is transmitted to humans during the course of a tick taking a bloodmeal. After B. burgdorferi is deposited into the skin of a human host, it replicates locally and spreads systemically, often resulting in clinical manifestations involving the central nervous system, joints, and/or heart. Antibodies directed against B. burgdorferi's outer surface protein C (OspC) are known to block tick-to-host transmission, as well as dissemination of the spirochete within a mammalian host. In this report, we reveal the first atomic structure of one such antibody in complex with OspC. Our results have implications for the design of a Lyme disease vaccine capable of interfering with multiple stages in B. burgdorferi infection. |
Infection prevention and control in tertiary care hospitals of Bangladesh: results from WHO infection prevention and control assessment framework (IPCAF).
Harun MGD , Anwar MMU , Sumon SA , Hassan MZ , Haque T , Mah EMuneer S , Rahman A , Abdullah Sahm , Islam MS , Styczynski AR , Kaydos-Daniels SC . Antimicrob Resist Infect Control 2022 11 (1) 125 INTRODUCTION: Infection prevention and control (IPC) in healthcare settings is imperative for the safety of patients as well as healthcare providers. To measure current IPC activities, resources, and gaps at the facility level, WHO has developed the Infection Prevention and Control Assessment Framework (IPCAF). This study aimed to assess the existing IPC level of selected tertiary care hospitals in Bangladesh during the COVID-19 pandemic using IPCAF to explore their strengths and deficits. METHODS: Between September and December 2020, we assessed 11 tertiary-care hospitals across Bangladesh. We collected the information from IPC focal person and/or hospital administrator from each hospital using the IPCAF assessment tool.. The score was calculated based on eight core components and was used to categorize the hospitals into four distinct IPC levels- Inadequate, Basic, Intermediate, and Advanced. Key performance metrics were summarized within and between hospitals. RESULTS: The overall median IPCAF score was 355.0 (IQR: 252.5-397.5) out of 800. The majority (73%) of hospitals scored as 'Basic' IPC level, while only 18% of hospitals were categorized as 'Intermediate'. Most hospitals had IPC guidelines as well as environments, materials and equipments. Although 64% of hospitals had IPC orientation and training program for new employees, only 30% of hospitals had regular IPC training program for the staff. None of the hospitals had an IPC surveillance system with standard surveillance case definitions to track HAIs. Around 90% of hospitals did not have an active IPC monitoring and audit system. Half of the hospitals had inadequate staffing considering the workload. Bed occupancy of one patient per bed in all units was found in 55% of hospitals. About 73% of hospitals had functional hand hygiene stations, but sufficient toilets were available in only 37% of hospitals. CONCLUSION: The majority of sampled tertiary care hospitals demonstrate inadequate IPC level to ensure the safety of healthcare workers, patients, and visitors. Quality improvement programs and feedback mechanisms should be implemented to strengthen all IPC core components, particularly IPC surveillance, monitoring, education, and training, to improve healthcare safety and resilience. |
Interleukin-11 receptor subunit alpha-1 is required for maximal airway responsiveness to methacholine following acute exposure to ozone.
Johnston RA , Atkins CL , Siddiqui SR , Jackson WT , Mitchell NC , Spencer CY , Pilkington AWth , Kashon ML , Haque IU . Am J Physiol Regul Integr Comp Physiol 2022 323 (6) R921-R934 Interleukin (IL)-11, a multi-functional cytokine, contributes to numerous biological processes, including adipogenesis, hematopoiesis, and inflammation. Asthma, a respiratory disease, is notably characterized by reversible airway obstruction, persistent lung inflammation, and airway hyperresponsiveness (AHR). Nasal insufflation of IL-11 causes AHR in wild-type mice while lung inflammation induced by antigen sensitization and challenge, which mimics features of atopic asthma in humans, is attenuated in mice genetically deficient in IL-11 receptor subunit alpha-1 (IL-11Rα1-deficient mice), a transmembrane receptor that is required conjointly with glycoprotein 130 to transduce IL-11 signaling. Nevertheless, the contribution of IL-11Rα1 to characteristics of non-atopic asthma is unknown. Thus, based on the aforementioned observations, we hypothesized that genetic deficiency of IL-11Rα1 would attenuate lung inflammation and increases in airway responsiveness following acute inhalation exposure to ozone (O(3)), a criteria pollutant and non-atopic asthma stimulus. Accordingly, four- and/or twenty-four hours following cessation of exposure to filtered room air or O(3), we assessed lung inflammation and airway responsiveness in wild-type and IL-11Rα1-deficient mice. With the exception of bronchoalveolar lavage macrophages and adiponectin, which were significantly increased and decreased, respectively, in O(3)-exposed IL-11Rα1-deficient as compared to O(3)-exposed wild-type mice, no other genotype-related differences in lung inflammation indices that we quantified were observed in O(3)-exposed mice. However, airway responsiveness to acetyl-β-methylcholine chloride (methacholine) was significantly diminished in IL-11Rα1-deficient as compared to wild-type mice following O(3) exposure. In conclusion, these results demonstrate that IL-11Rα1 minimally contributes to lung inflammation but is required for maximal airway responsiveness to methacholine in a mouse model of non-atopic asthma. |
Head-to-head comparison of the immunogenicity of RotaTeq and Rotarix rotavirus vaccines and factors associated with seroresponse in infants in Bangladesh: a randomised, controlled, open-label, parallel, phase 4 trial
Velasquez-Portocarrero DE , Wang X , Cortese MM , Snider CJ , Anand A , Costantini VP , Yunus M , Aziz AB , Haque W , Parashar U , Sisay Z , Soeters HM , Hyde TB , Jiang B , Zaman K . Lancet Infect Dis 2022 22 (11) 1606-1616 BACKGROUND: A head-to-head comparison of the most widely used oral rotavirus vaccines has not previously been done, particularly in a high child mortality setting. We therefore aimed to compare the immunogenicity of RotaTeq (Merck, Kenilworth, NJ, USA) and Rotarix (GlaxoSmithKline, Rixensart, Belgium) rotavirus vaccines in the same population and examined risk factors for low seroresponse. METHODS: We did a randomised, controlled, open-label, parallel, phase 4 trial in urban slums within Mirpur and Mohakahli (Dhaka, Bangladesh). We enrolled eligible participants who were healthy infants aged 6 weeks and full-term (ie, >37 weeks' gestation). We randomly assigned participants (1:1), using block randomisation via a computer-generated electronic allocation with block sizes of 8, 16, 24, and 32, to receive either three RotaTeq vaccine doses at ages 6, 10, and 14 weeks or two Rotarix doses at ages 6 and 10 weeks without oral poliovirus vaccine. Coprimary outcomes were the rotavirus-specific IgA seroconversion in both vaccines, and the comparison of the rotavirus IgA seroconversion by salivary secretor phenotype in each vaccine arm. Seroconversion at age 18 weeks in the RotaTeq arm and age of 14 weeks in the Rotarix arm was used to compare the complete series of each vaccine. Seroconversion at age 14 weeks was used to compare two RotaTeq doses versus two Rotarix doses. Seroconversion at age 22 weeks was used to compare the immunogenicity at the same age after receiving the full vaccine series. Safety was assessed for the duration of study participation. This study is registered with ClinicalTrials.gov, NCT02847026. FINDINGS: Between Sept 1 and Dec 8, 2016, a total of 1144 infants were randomly assigned to either the RotaTeq arm (n=571) or Rotarix arm (n=573); 1080 infants (531 in the RotaTeq arm and 549 in the Rotarix arm) completed the study. Rotavirus IgA seroconversion 4 weeks after the full series occurred in 390 (73%) of 531 infants age 18 weeks in the RotaTeq arm and 354 (64%) of 549 infants age 14 weeks in the Rotarix arm (p=0·01). At age 14 weeks, 4 weeks after two doses, RotaTeq recipients had lower seroconversion than Rotarix recipients (268 [50%] of 531 vs 354 [64%] of 549; p<0·0001). However, at age 22 weeks, RotaTeq recipients had higher seroconversion than Rotarix recipients (394 [74%] of 531 vs 278 [51%] of 549; p<0·0001). Among RotaTeq recipients, seroconversion 4 weeks after the third dose was higher than after the second dose (390 [73%] of 531 vs 268 [50%] of 531; p<0·0001]. In the RotaTeq arm, rotavirus IgA seroconversion was lower in non-secretors than in secretors at ages 14 weeks (p=0·08), 18 weeks (p=0·01), and 22 weeks (p=0·02). Similarly, in the Rotarix arm, rotavirus IgA seroconversion was lower in non-secretors than in secretors at ages 14 weeks (p=0·02) and 22 weeks (p=0·01). 65 (11%) of 571 infants had adverse events in the RotaTeq arm compared with 63 (11%) of 573 infants in the Rotarix arm; no adverse events were attributed to the use of either vaccine. One death due to aspiration occurred in the RotaTeq arm, which was not related to the vaccine. INTERPRETATION: RotaTeq induced a higher magnitude and longer duration of rotavirus IgA response than Rotarix in this high child mortality setting. Additional vaccination strategies should be evaluated to overcome the suboptimal performance of current oral rotavirus vaccines in these settings. FUNDING: US Centers for Disease Control and Prevention. |
Viral etiology of acute gastroenteritis among forcibly displaced Myanmar nationals and adjacent host population in Bangladesh
Hossian ME , Islam MM , Miah M , Haque W , Vinjé J , Rahman MZ , Faruque ASG , Khan AI , Ahmed T , Rahman M . J Infect Dis 2021 224 S864-S872 BACKGROUND: Since August 2017 Myanmar nationals from Rakhine state have crossed the border into Bangladesh and settled in Cox's Bazar, the World's largest refugee camp. Due to overcrowding, poor sanitation, and hygienic practices they have been under significant health risks including diarrheal diseases. OBJECTIVE: To determine the viral etiology of acute gastroenteritis (AGE) among forcibly displaced Myanmar nationals (FDMN) and adjacent Bangladeshi local host population (AHP). METHODS: From April 2018 to April 2019, we collected stool specimens from 764 FDMN and 1159 AHP of all ages. We tested 100 randomly selected specimens from each group for the most common acute gastroenteritis viruses. RESULTS: Among 200 diarrhea patients, 55% and 64% of FDMN and AHP patients respectively had viral infections; the most common viruses were rotavirus (29% vs 44%), adenovirus (24% vs 31%) and norovirus (14% vs 10%). In both populations, viral infections were significantly higher in children less than five years; compared to bacterial infections which were higher in patients older than five years of age (p=<0.05). CONCLUSION: Disparities in viral and bacterial prevalence among various age groups warrant careful antibiotic usage, especially in children less than five years. |
Insecticide resistance status of Aedes aegypti in Bangladesh.
Al-Amin HM , Johora FT , Irish SR , Hossainey MRH , Vizcaino L , Paul KK , Khan WA , Haque R , Alam MS , Lenhart A . Parasit Vectors 2020 13 (1) 622 BACKGROUND: Arboviral diseases, including dengue and chikungunya, are major public health concerns in Bangladesh where there have been unprecedented levels of transmission reported in recent years. The primary approach to control these diseases is to control the vector Aedes aegypti using pyrethroid insecticides. Although chemical control has long been practiced, no comprehensive analysis of Ae. aegypti susceptibility to insecticides has been conducted to date. The aim of this study was to determine the insecticide resistance status of Ae. aegypti in Bangladesh and investigate the role of detoxification enzymes and altered target site sensitivity as resistance mechanisms. METHODS: Eggs of Aedes mosquitoes were collected using ovitraps from five districts across Bangladesh and in eight neighborhoods of the capital city Dhaka, from August to November 2017. CDC bottle bioassays were conducted for permethrin, deltamethrin, malathion, and bendiocarb using 3- to 5-day-old F(0)-F(2) non-blood-fed female mosquitoes. Biochemical assays were conducted to detect metabolic resistance mechanisms, and real-time PCR was performed to determine the frequencies of the knockdown resistance (kdr) mutations Gly1016, Cys1534, and Leu410. RESULTS: High levels of resistance to permethrin were detected in all Ae. aegypti populations, with mortality ranging from 0 to 14.8% at the diagnostic dose. Substantial resistance continued to be detected against higher (2×) doses of permethrin (5.1-44.4% mortality). Susceptibility to deltamethrin and malathion varied between populations while complete susceptibility to bendiocarb was observed in all populations. Significantly higher levels of esterase and oxidase activity were detected in most of the test populations as compared to the susceptible reference Rockefeller strain. A significant association was detected between permethrin resistance and the presence of Gly1016 and Cys1534 homozygotes. The frequency of kdr (knockdown resistance) alleles varied across the Dhaka Aedes populations. Leu410 was not detected in any of the tested populations. CONCLUSIONS: The detection of widespread pyrethroid resistance and multiple resistance mechanisms highlights the urgency for implementing alternate Ae. aegypti control strategies. In addition, implementing routine monitoring of insecticide resistance in Ae. aegypti in Bangladesh will lead to a greater understanding of susceptibility trends over space and time, thereby enabling the development of improved control strategies. |
Human exposures to by-products from animals suspected to have died of anthrax in Bangladesh: An exploratory study
Islam MS , Hasan SM , Salzer JS , Kadzik M , Haque F , Haider N , Hossain MB , Islam MA , Rahman M , Kennedy E , Gurley ES . Transbound Emerg Dis 2020 68 (4) 2514-2520 Anthrax is a zoonotic disease caused by the bacterium Bacillus anthracis that is considered endemic in Bangladesh, where cases among animals and people have been reported almost annually since 2009. Contaminated by-products from animals are suspected to play a role in transmission to people, but minimal information is known on the supply-chain of these potentially contaminated products. Between April 2013 and May 2016, we conducted a qualitative study in 17 villages located in 5 districts in Bangladesh, which had experienced suspected anthrax outbreaks. The study explored how by-products from suspected animal cases were collected, discarded, processed, distributed, and used by people. We conducted open-ended interviews, group discussions, and unstructured observations of people's exposure to animal by-products. The practice of slaughtering acutely ill domestic ruminants before they died was common. Respondents reported that moribund animals were typically butchered, and the waste products were discarded in nearby rivers, ditches, bamboo bushes, or on privately owned land. Regardless of health status before death, very few carcasses were buried, and none were incinerated or burned. The hides were reportedly used to make wallets, belts, shoes, balls, and clothing. Discarded bones were often ground into granular and powder forms to produce bone meal and fertilizer. Therefore, given anthrax is endemic in the study region, livestock with acute onset of fatal disease or found dead with no known cause of death may be an anthrax case and subsequently pose a health risk to those involved in the collection and processing of the carcass, as well as the end-user of these products. Improved bio-security practices and safe carcass disposal measures could reduce the risk of human exposure, but resource and other constraints make implementation a challenge. Therefore, targeting at-risk animal populations for vaccination may be the most effective strategy to reduce anthrax outbreaks, protect the supply chain, and reduce the risk of exposure to B. anthracis. |
The Clinical Presentation of Culture-positive and Culture-negative, Quantitative Polymerase Chain Reaction (qPCR)-Attributable Shigellosis in the Global Enteric Multicenter Study and Derivation of a Shigella Severity Score: Implications for Pediatric Shigella Vaccine Trials.
Pavlinac PB , Platts-Mills JA , Tickell KD , Liu J , Juma J , Kabir F , Nkeze J , Okoi C , Operario DJ , Uddin MJ , Ahmed S , Alonso PL , Antonio M , Becker SM , Breiman RF , Faruque ASG , Fields B , Gratz J , Haque R , Hossain A , Hossain MJ , Jarju S , Qamar F , Iqbal NT , Kwambana B , Mandomando I , McMurry TL , Ochieng C , Ochieng JB , Ochieng M , Onyango C , Panchalingam S , Kalam A , Aziz F , Qureshi S , Ramamurthy T , Roberts JH , Saha D , Sow SO , Stroup SE , Sur D , Tamboura B , Taniuchi M , Tennant SM , Roose A , Toema D , Wu Y , Zaidi A , Nataro JP , Levine MM , Houpt ER , Kotloff KL . Clin Infect Dis 2020 73 (3) e569-e579 BACKGROUND: Shigella is a leading cause of childhood diarrhea and target for vaccine development. Microbiologic and clinical case definitions are needed for pediatric field vaccine efficacy trials. METHODS: We compared characteristics of moderate to severe diarrhea (MSD) cases in the Global Enteric Multicenter Study (GEMS) between children with culture positive Shigella to those with culture-negative, qPCR-attributable Shigella (defined by an ipaH gene cycle threshold <27.9). Among Shigella MSD cases, we determined risk factors for death and derived a clinical severity score. RESULTS: Compared to culture-positive Shigella MSD cases (n=745), culture-negative/qPCR-attributable Shigella cases (n=852) were more likely to be under 12 months, stunted, have a longer duration of diarrhea, and less likely to have high stool frequency or a fever. There was no difference in dehydration, hospitalization, or severe classification from a modified Vesikari score. Twenty-two (1.8%) Shigella MSD cases died within the 14-days after presentation to health facilities, and 59.1% of these deaths were in culture-negative cases. Age < 12 months, diarrhea duration prior to presentation, vomiting, stunting, wasting, and hospitalization were associated with mortality. A model-derived score assigned points for dehydration, hospital admission, and longer diarrhea duration but was not significantly better at predicting 14-day mortality than a modified Vesikari score. CONCLUSIONS: A composite severity score consistent with severe disease or dysentery may be a pragmatic clinical endpoint for severe shigellosis in vaccine trials. Reliance on culture for microbiologic confirmation may miss a substantial number of Shigella cases but is currently required to measure serotype specific immunity. |
Outbreak of diarrhoea in piglets caused by novel rotavirus genotype G4P[49] in north-western district of Bangladesh, February 2014.
Sarkar S , Dioh Esona M , Gautam R , Castro CJ , Ng TFF , Haque W , Khan SU , Hossain ME , Rahman MZ , Gurley ES , Kennedy ED , Bowen MD , Parashar UD , Rahman M . Transbound Emerg Dis 2019 67 (1) 442-449 Group A rotavirus (RVA) associated diarrhea in piglets represents one of the major causes of morbidity and mortality in pig farms worldwide. A diarrhea outbreak occurred among nomadic piglets in north-western district of Bangladesh in February 2014. Outbreak investigation was performed to identify the cause, epidemiologic and clinical features of the outbreak. Rectal swabs and clinical information were collected from diarrheic piglets (n=36). Rectal swabs were tested for RVA RNA by real time reverse transcription polymerase chain reaction (rRT-PCR) using NSP3-specific primers. The G (VP7) and P (VP4) genes were typed by conventional RT-PCR and sanger sequencing and full genome sequences were determined using next generation sequencing. We found the attack rate was 61% (50/82) among piglets in the nomadic pig herd and the case fatality rate was 20% (10/50) among piglets with diarrhea. All study piglets cases had watery diarrhea, lack of appetite or reluctance to move. A novel RVA strain with a new P[49] genotype combined with G4 was identified among all piglets with diarrhea. The genome constellation of the novel RVA strains was determined to be G4-P [49]-I1-R1-C1-M1-A8-N1-T7-E1-H1. Genetic analysis shows that the novel G4P[49] strain is similar to Indian and Chinese porcine or porcine-like G4 human strains and is genetically distant from Bangladeshi human G4 strains. Identification of this novel RVA strain warrants further exploration for disease severity and zoonotic potential. This article is protected by copyright. All rights reserved. |
Fecal IgA against a sporozoite antigen at 12 months is associated with delayed time to subsequent cryptosporidiosis in urban Bangladesh: a prospective cohort study
Steiner KL , Kabir M , Priest JW , Hossain B , Gilchrist CA , Cook H , Ma JZ , Korpe PS , Ahmed T , Faruque ASG , Haque R , Petri WA . Clin Infect Dis 2019 70 (2) 323-326 In this prospective cohort study of Bangladeshi children, greater fecal IgA, but not plasma IgG, directed against the Cryptosporidium sporozoite-expressed antigen Cp23 at 12 months of age was associated with delayed time to subsequent cryptosporidiosis. This finding suggests a protective role for mucosal antibody-mediated immunity in naturally exposed children. |
An epidemic of chikungunya in northwestern Bangladesh in 2011.
Haque F , Rahman M , Banu NN , Sharif AR , Jubayer S , Shamsuzzaman A , Alamgir A , Erasmus JH , Guzman H , Forrester N , Luby SP , Gurley ES . PLoS One 2019 14 (3) e0212218 BACKGROUND: In November 2011, a government hospital physician in Shibganj sub-district of Bangladesh reported a cluster of patients with fever and joint pain or rash. A multi-disciplinary team investigated to characterize the outbreak; confirm the cause; and recommend control and prevention measures. METHODS: Shibganj's residents with new onset of fever and joint pain or rash between 1 September and 15 December 2011 were defined as chikungunya fever (CHIKF) suspect cases. To estimate the attack rate, we identified 16 outpatient clinics in 16 selected wards across 16 unions in Shibganj and searched for suspect cases in the 80 households nearest to each outpatient clinic. One suspect case from the first 30 households in each ward was invited to visit the nearest outpatient clinic for clinical assessment and to provide a blood sample for laboratory testing and analyses. RESULTS: We identified 1,769 CHIKF suspect cases from among 5,902 residents surveyed (30%). Their median age was 28 (IQR:15-42) years. The average attack rate in the sub-district was 30% (95% CI: 27%-33%). The lowest attack rate was found in children <5 years (15%). Anti-CHIKV IgM antibodies were detected by ELISA in 78% (264) of the 338 case samples tested. In addition to fever, predominant symptoms of serologically-confirmed cases included joint pain (97%), weakness (54%), myalgia (47%), rash (42%), itching (37%) and malaise (31%). Among the sero-positive patients, 79% (209/264) sought healthcare from outpatient clinics. CHIKV was isolated from two cases and phylogenetic analyses of full genome sequences placed these viruses within the Indian Ocean Lineage (IOL). Molecular analysis identified mutations in E2 and E1 glycoproteins and contained the E1 A226V point mutation. CONCLUSION: The consistently high attack rate by age groups suggested recent introduction of chikungunya in this community. Mosquito control efforts should be enhanced to reduce the risk of continued transmission and to improve global health security. |
Using video technology to increase treatment completion for patients with latent tuberculosis infection on 3-month isoniazid and rifapentine: An implementation study
Lam CK , McGinnis Pilote K , Haque A , Burzynski J , Chuck C , Macaraig M . J Med Internet Res 2018 20 (11) e287 BACKGROUND: Since January 2013, the New York City (NYC) Health Department Tuberculosis (TB) Program has offered persons diagnosed with latent TB infection (LTBI) the 3-month, once-weekly isoniazid and rifapentine (3HP) treatment regimen. Patients on this treatment are monitored in-person under directly observed therapy (DOT). To address patient and provider barriers to in-person DOT, we piloted the use of a videoconferencing software app to remotely conduct synchronous DOT (video directly observed therapy; VDOT) for patients on 3HP. OBJECTIVE: The objective of our study was to evaluate the implementation of VDOT for patients on 3HP and to assess whether treatment completion for these patients increased when they were monitored using VDOT compared with that using the standard in-person DOT. METHODS: Between February and October 2015, patients diagnosed with LTBI at any of the four NYC Health Department TB clinics who met eligibility criteria for treatment with 3HP under VDOT (V3HP) were followed until 16 weeks after treatment initiation, with treatment completion defined as ingestion of 11 doses within 16 weeks. Treatment completion of patients on V3HP was compared with that of patients on 3HP under clinic-based, in-person DOT who were part of a prior study in 2013. Furthermore, outcomes of video sessions with V3HP patients were collected and analyzed. RESULTS: During the study period, 70% (50/71) of eligible patients were placed on V3HP. Treatment completion among V3HP patients was 88% (44/50) compared with 64.9% (196/302) among 3HP patients on clinic DOT (P<.001). A total of 360 video sessions were conducted for V3HP patients with a median of 8 (range: 1-11) sessions per patient and a median time of 4 (range: 1-59) minutes per session. Adherence issues (eg, >15 minutes late) during video sessions occurred 104 times. No major side effects were reported by V3HP patients. CONCLUSIONS: The NYC TB program observed higher treatment completion with VDOT than that previously seen with clinic DOT among patients on 3HP. Expanding the use of VDOT may improve treatment completion and corresponding outcomes for patients with LTBI. |
Genetic diversity of noroviruses circulating in a pediatric cohort in Bangladesh.
Nelson MI , Mahfuz M , Chhabra P , Haque R , Seidman JC , Hossain I , McGrath M , Ahmed AMS , Knobler S , Vinje J , Ahmed T . J Infect Dis 2018 218 (12) 1937-1942 Noroviruses are a leading cause of diarrhea in children <5yo worldwide. We genotyped 88 viruses collected by active surveillance in a birth cohort of children <2yo in Dhaka, Bangladesh, during 2010-2013. Twenty-five (81%) of 31 established GI and GII genotypes were detected, with GII.4 as the predominant genotype (20%). Our results show that children in Bangladesh are infected with a great diversity of norovirus strains. Re-infections are common, but not with closely related genotypes. Birth cohort studies are critical to understand cross-protective immunity and advance the development of pediatric norovirus vaccines. |
An update from hospital-based surveillance for rotavirus gastroenteritis among young children in Bangladesh, July 2012 to June 2017
Satter SM , Aliabadi N , Gastanaduy PA , Haque W , Mamun A , Flora MS , Zaman K , Rahman M , Heffelfinger JD , Luby SP , Gurley ES , Parashar UD . Vaccine 2018 36 (51) 7811-7815 INTRODUCTION: In preparation for the introduction of a rotavirus vaccine into the routine immunization program of Bangladesh in 2018, we report data and highlight evolving genotypes from five years of active hospital-based rotavirus surveillance which began in July 2012. METHODS: We enrolled and collected fresh stool from every fourth child<5years admitted with acute gastroenteritis (AGE) at 8 participating surveillance hospitals. Rotavirus infections were detected by enzyme immune assay. Twenty-five percent of rotavirus isolates were genotyped using reverse transcription polymerase chain reaction. RESULTS: We found that 64% (4832/7562) of children<5years of age admitted with AGE had evidence of rotavirus infection. The majority (57%) of patients with rotavirus infection were <12months of age. The most common strains were G1P[8] (43%), G12P[8] (15%) and G9P[8] (9%); 11% of children had mixed infection.G3P[8], which has not been reported in Bangladesh since 2001, was documented for the first time in our surveillance system. CONCLUSIONS: The high burden of rotavirus-associated hospitalizations highlights the potential value of rotavirus vaccination in Bangladesh. Continued surveillance is important for monitoring the impact of vaccination as well as monitoring evolving genotypes. |
Modeling the environmental suitability for Aedes (Stegomyia) aegypti and Aedes (Stegomyia) albopictus (Diptera: Culicidae) in the contiguous United States
Johnson TL , Haque U , Monaghan AJ , Eisen L , Hahn MB , Hayden MH , Savage HM , McAllister J , Mutebi JP , Eisen RJ . J Med Entomol 2017 54 (6) 1605-1614 The mosquitoes Aedes (Stegomyia) aegypti (L.)(Diptera:Culicidae) and Ae. (Stegomyia) albopictus (Skuse) (Diptera:Culicidae) transmit dengue, chikungunya, and Zika viruses and represent a growing public health threat in parts of the United States where they are established. To complement existing mosquito presence records based on discontinuous, non-systematic surveillance efforts, we developed county-scale environmental suitability maps for both species using maximum entropy modeling to fit climatic variables to county presence records from 1960-2016 in the contiguous United States. The predictive models for Ae. aegypti and Ae. albopictus had an overall accuracy of 0.84 and 0.85, respectively. Cumulative growing degree days (GDDs) during the winter months, an indicator of overall warmth, was the most important predictive variable for both species and was positively associated with environmental suitability. The number (percentage) of counties classified as environmentally suitable, based on models with 90 or 99% sensitivity, ranged from 1,443 (46%) to 2,209 (71%) for Ae. aegypti and from 1,726 (55%) to 2,329 (75%) for Ae. albopictus. Increasing model sensitivity results in more counties classified as suitable, at least for summer survival, from which there are no mosquito records. We anticipate that Ae. aegypti and Ae. albopictus will be found more commonly in counties classified as suitable based on the lower 90% sensitivity threshold compared with the higher 99% threshold. Counties predicted suitable with 90% sensitivity should therefore be a top priority for expanded mosquito surveillance efforts while still keeping in mind that Ae. aegypti and Ae. albopictus may be introduced, via accidental transport of eggs or immatures, and potentially proliferate during the warmest part of the year anywhere within the geographic areas delineated by the 99% sensitivity model. |
Experiences and lessons learned for delivery of micronutrient powders interventions
Reerink I , Namaste SM , Poonawala A , Nyhus Dhillon C , Aburto N , Chaudhery D , Kroeun H , Griffiths M , Haque MR , Bonvecchio A , Jefferds ME , Rawat R . Matern Child Nutr 2017 13 Suppl 1 An effective delivery strategy coupled with relevant social and behaviour change communication (SBCC) have been identified as central to the implementation of micronutrient powders (MNP) interventions, but there has been limited documentation of what works. Under the auspices of "The Micronutrient Powders Consultation: Lessons Learned for Operational Guidance," three working groups were formed to summarize experiences and lessons across countries regarding MNP interventions for young children. This paper focuses on programmatic experiences related to MNP delivery (models, platforms, and channels), SBCC, and training. Methods included a review of published and grey literature, interviews with key informants, and deliberations throughout the consultation process. We found that most countries distributed MNP free of charge via the health sector, although distribution through other platforms and using subsidized fee for product or mixed payment models have also been used. Community-based distribution channels have generally shown higher coverage and when part of an infant and young child feeding approach, may provide additional benefit given their complementarity. SBCC for MNP has worked best when focused on meeting the MNP behavioural objectives (appropriate use, intake adherence, and related infant and young child feeding behaviours). Programmers have learned that reincorporating SBCC and training throughout the intervention life cycle has allowed for much needed adaptations. Diverse experiences delivering MNP exist, and although no one-size-fits-all approach emerged, well-established delivery platforms, community involvement, and SBCC-centred designs tended to have more success. Much still needs to be learned on MNP delivery, and we propose a set of implementation research questions that require further investigation. |
Non-specific effects of oral polio vaccine on diarrheal burden and etiology among Bangladeshi infants
Upfill-Brown A , Taniuchi M , Platts-Mills JA , Kirkpatrick B , Burgess SL , Oberste MS , Weldon W , Houpt E , Haque R , Zaman K , Petri WA Jr . Clin Infect Dis 2017 Background: As the global polio eradication initiative prepares to cease use of oral polio vaccine (OPV) in 2020, there is increasing interest in understanding if oral vaccination provides non-specific immunity to other infections so that the consequences of this transition can be effectively planned for and mitigated. Methods: Data was collected from infants in an urban slum in Bangladesh (Mirpur, Dhaka) as part of the PROVIDE study. Following vaccination with tOPV at 6,10, and 14 weeks, infants were randomly assigned to receive tOPV (n=315) or IPV (n=299) at 39 weeks. Episodes of diarrhea were documented through clinic visits and twice-weekly house visits through 52 weeks. 14 pathogens associated with diarrhea were analyzed with TaqMan Array Cards. Results: While the proportion of children experiencing diarrhea was not different between the tOPV and IPV groups (p=0.18), the number of days with diarrhea (p=0.0037) and the number of separate diarrheal episodes (p=0.054) trended lower in the OPV arm. Etiological analysis revealed that male tOPV recipients were less likely to have diarrhea of bacterial etiology (p=0.0099) compared to male IPV recipients, but equally likely to experience diarrhea due to viruses (p=0.57) or protozoa (p=0.14). Among the 6 bacterial enteric pathogens tested, only Campylobacter jejuni/coli detection was significantly reduced in the OPV arm (p=0.0048). Conclusions: Our results suggest that OPV may cause non-specific reductions in mortality, as has been studied elsewhere, by reducing etiology-specific diarrheal burden. This is likely driven by reductions in bacterial diarrhea. Further study of non-specific OPV effects before global cessation is supported. |
Use of quantitative molecular diagnostic methods to identify causes of diarrhoea in children: a reanalysis of the GEMS case-control study.
Liu J , Platts-Mills JA , Juma J , Kabir F , Nkeze J , Okoi C , Operario DJ , Uddin J , Ahmed S , Alonso PL , Antonio M , Becker SM , Blackwelder WC , Breiman RF , Faruque AS , Fields B , Gratz J , Haque R , Hossain A , Hossain MJ , Jarju S , Qamar F , Iqbal NT , Kwambana B , Mandomando I , McMurry TL , Ochieng C , Ochieng JB , Ochieng M , Onyango C , Panchalingam S , Kalam A , Aziz F , Qureshi S , Ramamurthy T , Roberts JH , Saha D , Sow SO , Stroup SE , Sur D , Tamboura B , Taniuchi M , Tennant SM , Toema D , Wu Y , Zaidi A , Nataro JP , Kotloff KL , Levine MM , Houpt ER . Lancet 2016 388 (10051) 1291-301 BACKGROUND: Diarrhoea is the second leading cause of mortality in children worldwide, but establishing the cause can be complicated by diverse diagnostic approaches and varying test characteristics. We used quantitative molecular diagnostic methods to reassess causes of diarrhoea in the Global Enteric Multicenter Study (GEMS). METHODS: GEMS was a study of moderate to severe diarrhoea in children younger than 5 years in Africa and Asia. We used quantitative real-time PCR (qPCR) to test for 32 enteropathogens in stool samples from cases and matched asymptomatic controls from GEMS, and compared pathogen-specific attributable incidences with those found with the original GEMS microbiological methods, including culture, EIA, and reverse-transcriptase PCR. We calculated revised pathogen-specific burdens of disease and assessed causes in individual children. FINDINGS: We analysed 5304 sample pairs. For most pathogens, incidence was greater with qPCR than with the original methods, particularly for adenovirus 40/41 (around five times), Shigella spp or enteroinvasive Escherichia coli (EIEC) and Campylobactor jejuni o C coli (around two times), and heat-stable enterotoxin-producing E coli ([ST-ETEC] around 1.5 times). The six most attributable pathogens became, in descending order, Shigella spp, rotavirus, adenovirus 40/41, ST-ETEC, Cryptosporidium spp, and Campylobacter spp. Pathogen-attributable diarrhoeal burden was 89.3% (95% CI 83.2-96.0) at the population level, compared with 51.5% (48.0-55.0) in the original GEMS analysis. The top six pathogens accounted for 77.8% (74.6-80.9) of all attributable diarrhoea. With use of model-derived quantitative cutoffs to assess individual diarrhoeal cases, 2254 (42.5%) of 5304 cases had one diarrhoea-associated pathogen detected and 2063 (38.9%) had two or more, with Shigella spp and rotavirus being the pathogens most strongly associated with diarrhoea in children with mixed infections. INTERPRETATION: A quantitative molecular diagnostic approach improved population-level and case-level characterisation of the causes of diarrhoea and indicated a high burden of disease associated with six pathogens, for which targeted treatment should be prioritised. FUNDING: Bill & Melinda Gates Foundation. |
Influenza B virus outbreak at a religious residential school for boys in northern Bangladesh, 2011
Haque F , Sturm-Ramirez K , Homaira N , Gurley ES , Hossain MJ , Hasan SM , Chowdhury S , Sarkar S , Khan AK , Rahman M , Rahman M , Luby SP . Influenza Other Respir Viruses 2016 11 (2) 165-169 BACKGROUND: National media reported a febrile illness among dormitory residents of a boys' religious school. We investigated the outbreak to identify cause. METHODS: Individuals with fever (>100 degrees F) and cough or sore throat between 1-13 August 2011 were influenza-like-illness (ILI) case-patients. We collected histories and specimens from hospitalized case-patients, and visited campus to explore environmental context. RESULTS: All 28 case-patients were dormitory residents including 27 hospitalizations. Accommodation space per resident was <0.8 square metres. Nasal and oropharyngeal swabs from 22 case-patients were positive for influenza B virus using real-time reverse transcription polymerase chain reaction (rRT-PCR). CONCLUSIONS: Overcrowding likely facilitated transmission leading to this dormitory outbreak. |
Genetically Diverse Low Pathogenicity Avian Influenza A Virus Subtypes Co-Circulate among Poultry in Bangladesh.
Gerloff NA , Khan SU , Zanders N , Balish A , Haider N , Islam A , Chowdhury S , Rahman MZ , Haque A , Hosseini P , Gurley ES , Luby SP , Wentworth DE , Donis RO , Sturm-Ramirez K , Davis CT . PLoS One 2016 11 (3) e0152131 Influenza virus surveillance, poultry outbreak investigations and genomic sequencing were assessed to understand the ecology and evolution of low pathogenicity avian influenza (LPAI) A viruses in Bangladesh from 2007 to 2013. We analyzed 506 avian specimens collected from poultry in live bird markets and backyard flocks to identify influenza A viruses. Virus isolation-positive specimens (n = 50) were subtyped and their coding-complete genomes were sequenced. The most frequently identified subtypes among LPAI isolates were H9N2, H11N3, H4N6, and H1N1. Less frequently detected subtypes included H1N3, H2N4, H3N2, H3N6, H3N8, H4N2, H5N2, H6N1, H6N7, and H7N9. Gene sequences were compared to publicly available sequences using phylogenetic inference approaches. Among the 14 subtypes identified, the majority of viral gene segments were most closely related to poultry or wild bird viruses commonly found in Southeast Asia, Europe, and/or northern Africa. LPAI subtypes were distributed over several geographic locations in Bangladesh, and surface and internal protein gene segments clustered phylogenetically with a diverse number of viral subtypes suggesting extensive reassortment among these LPAI viruses. H9N2 subtype viruses differed from other LPAI subtypes because genes from these viruses consistently clustered together, indicating this subtype is enzootic in Bangladesh. The H9N2 strains identified in Bangladesh were phylogenetically and antigenically related to previous human-derived H9N2 viruses detected in Bangladesh representing a potential source for human infection. In contrast, the circulating LPAI H5N2 and H7N9 viruses were both phylogenetically and antigenically unrelated to H5 viruses identified previously in humans in Bangladesh and H7N9 strains isolated from humans in China. In Bangladesh, domestic poultry sold in live bird markets carried a wide range of LPAI virus subtypes and a high diversity of genotypes. These findings, combined with the seven year timeframe of sampling, indicate a continuous circulation of these viruses in the country. |
Effect of substituting IPV for tOPV on immunity to poliovirus in Bangladeshi infants: An open-label randomized controlled trial
Mychaleckyj JC , Haque R , Carmolli M , Zhang D , Colgate ER , Nayak U , Taniuchi M , Dickson D , Weldon WC , Oberste MS , Zaman K , Houpt ER , Alam M , Kirkpatrick BD , Petri WA Jr . Vaccine 2015 34 (3) 358-66 BACKGROUND: The Polio Endgame strategy includes phased withdrawal of oral poliovirus vaccines (OPV) coordinated with introduction of inactivated poliovirus vaccine (IPV) to ensure population immunity. The impact of IPV introduction into a primary OPV series of immunizations in a developing country is uncertain. METHODS: Between May 2011 and November 2012, we enrolled 700 Bangladeshi infant-mother dyads from Dhaka slums into an open-label randomized controlled trial to test whether substituting an injected IPV dose for the standard Expanded Program on Immunization (EPI) fourth tOPV dose at infant age 39 weeks would reduce fecal shedding and enhance systemic immunity. The primary endpoint was mucosal immunity to poliovirus at age one year, measured by fecal excretion of any Sabin virus at five time points up to 25 days post-52 week tOPV challenge, analyzed by the intention to treat principle. FINDINGS: We randomized 350 families to the tOPV and IPV vaccination arms. Neither study arm resulted in superior intestinal protection at 52 weeks measured by the prevalence of infants shedding any of three poliovirus serotypes, but the IPV dose induced significantly higher seroprevalence and seroconversion rates. This result was identical for poliovirus detection by cell culture or RT-qPCR. The non-significant estimated culture-based shedding risk difference was -3% favoring IPV, and the two vaccination schedules were inferred to be equivalent within a 95% confidence margin of -10% to +4%. Results for shedding analyses stratified by poliovirus type were similar. CONCLUSIONS: Neither of the vaccination regimens is superior to the other in enhancing intestinal immunity as measured by poliovirus shedding at 52 weeks of age and the IPV regimen provides similar intestinal immunity to the four tOPV series, although the IPV regimen strongly enhances humoral immunity. The IPV-modified regimen may be considered for vaccination programs without loss of intestinal protection. |
Environmental enteropathy, oral vaccine failure and growth faltering in infants in Bangladesh
Naylor C , Lu M , Haque R , Mondal D , Buonomo E , Nayak U , Mychaleckyj JC , Kirkpatrick B , Colgate R , Carmolli M , Dickson D , van der Klis F , Weldon W , Oberste SM , Ma JZ , Petri WA . EBioMedicine 2015 2 (11) 1759-66 Background: Environmental enteropathy (EE) is a subclinical enteric condition found in low-income countries that is characterized by intestinal inflammation, reduced intestinal absorption, and gut barrier dysfunction. We aimed to assess if EE impairs the success of oral polio and rotavirus vaccines in infants in Bangladesh. Methods: We conducted a prospective observational study of 700 infants from an urban slum of Dhaka, Bangladesh from May 2011 to November 2014. Infants were enrolled in the first week of life and followed to age one year through biweekly home visits with EPI vaccines administered and growth monitored. EE was operationally defied as enteric inflammation measured by any one of the fecal biomarkers reg1B, alpha-1-antitrypsin, MPO, calprotectin, or neopterin. Oral polio vaccine success was evaluated by immunogenicity, and rotavirus vaccine response was evaluated by immunogenicity and protection from disease. This study is registered with ClinicalTrials.gov, number NCT01375647. Findings: EE was present in greater than 80% of infants by 12. weeks of age. Oral poliovirus and rotavirus vaccines failed in 20.2% and 68.5% of the infants respectively, and 28.6% were malnourished (HAZ. <. -2) at one year of age. In contrast, 0%, 9.0%, 7.9% and 3.8% of infants lacked protective levels of antibody from tetanus, Haemophilus influenzae type b, diphtheria and measles vaccines respectively. EE was negatively associated with oral polio and rotavirus response but not parenteral vaccine immunogenicity. Biomarkers of systemic inflammation and measures of maternal health were additionally predictive of both oral vaccine failure and malnutrition. The selected biomarkers from multivariable analysis accounted for 46.3% variation in delta HAZ. 24% of Rotarix® IgA positive individuals can be attributed to the selected biomarkers. Interpretation: EE as well as systemic inflammation and poor maternal health were associated with oral but not parenteral vaccine underperformance and risk for future growth faltering. These results offer a potential explanation for the burden of these problems in low-income problems, allow early identification of infants at risk, and suggest pathways for intervention. Funding: The Bill and Melinda Gates Foundation (OPP1017093). © 2015 The Authors. |
An outbreak of hepatitis E in an urban area of Bangladesh
Haque F , Banu SS , Ara K , Chowdhury IA , Chowdhury SA , Kamili S , Rahman M , Luby SP . J Viral Hepat 2015 22 (11) 948-56 We investigated an outbreak of jaundice in urban Bangladesh in 2010 to examine the cause and risk factors and assess the diagnostic utility of commercial assays. We classified municipal residents reporting jaundice during the preceding 4 weeks as probable hepatitis E cases and their neighbours without jaundice in the previous 6 months as probable controls. We tested the sera collected from probable cases and probable controls for IgM anti-hepatitis E virus (HEV), and the IgM-negative sera for IgG anti-HEV using a commercial assay locally. We retested the IgM-positive sera for both IgM and IgG anti-HEV using another assay at the Centre for Disease Control and Prevention (CDC), USA. Probable cases positive for IgM anti-HEV were confirmed cases; probable controls negative for both IgM and IgG anti-HEV were confirmed controls. We explored the local water supply and sanitation infrastructure and tested for bacterial concentration of water samples. Probable cases were more likely than probable controls to drink tap water (adjusted odds ratio: 3.4; 95% CI: 1.2-9.2). Fifty-eight percentage (36/62) of the case sera were IgM anti-HEV positive; and 75% of the IgM-positive samples were confirmed positive on retesting with another assay at CDC. Compared to confirmed controls, cases confirmed using either or both assays also identified drinking tap water as the risk factor. Two tap water samples had detectable thermotolerant coliforms. Research exploring decentralized water treatment technologies for sustainable safe water might prevent HEV transmission in resource-poor cities. Detection of serological markers in a majority of probable cases implied that available diagnostic assays could adequately identify HEV infection during outbreaks. |
Effect of maternal multiple micronutrient vs iron-folic acid supplementation on infant mortality and adverse birth outcomes in rural Bangladesh: the JiVitA-3 randomized trial
West KP Jr , Shamim AA , Mehra S , Labrique AB , Ali H , Shaikh S , Klemm RD , Wu LS , Mitra M , Haque R , Hanif AA , Massie AB , Merrill RD , Schulze KJ , Christian P . JAMA 2014 312 (24) 2649-58 IMPORTANCE: Maternal micronutrient deficiencies may adversely affect fetal and infant health, yet there is insufficient evidence of effects on these outcomes to guide antenatal micronutrient supplementation in South Asia. OBJECTIVE: To assess effects of antenatal multiple micronutrient vs iron-folic acid supplementation on 6-month infant mortality and adverse birth outcomes. DESIGN, SETTING, AND PARTICIPANTS: Cluster randomized, double-masked trial in Bangladesh, with pregnancy surveillance starting December 4, 2007, and recruitment on January 11, 2008. Six-month infant follow-up ended August 30, 2012. Surveillance included 127,282 women; 44,567 became pregnant and were included in the analysis and delivered 28,516 live-born infants. Median gestation at enrollment was 9 weeks (interquartile range, 7-12). INTERVENTIONS: Women were provided supplements containing 15 micronutrients or iron-folic acid alone, taken daily from early pregnancy to 12 weeks postpartum. MAIN OUTCOMES AND MEASURES: The primary outcome was all-cause infant mortality through 6 months (180 days). Prespecified secondary outcomes in this analysis included stillbirth, preterm birth (<37 weeks), and low birth weight (<2500 g). To maintain overall significance of alpha = .05, a Bonferroni-corrected alpha = .01 was calculated to evaluate statistical significance of primary and 4 secondary risk outcomes (.05/5). RESULTS: Among the 22,405 pregnancies in the multiple micronutrient group and the 22,162 pregnancies in the iron-folic acid group, there were 14,374 and 14,142 live-born infants, respectively, included in the analysis. At 6 months, multiple micronutrients did not significantly reduce infant mortality; there were 764 deaths (54.0 per 1000 live births) in the iron-folic acid group and 741 deaths (51.6 per 1000 live births) in the multiple micronutrient group (relative risk [RR], 0.95; 95% CI, 0.86-1.06). Multiple micronutrient supplementation resulted in a non-statistically significant reduction in stillbirths (43.1 vs 48.2 per 1000 births; RR, 0.89; 95% CI, 0.81-0.99; P = .02) and significant reductions in preterm births (18.6 vs 21.8 per 100 live births; RR, 0.85; 95% CI, 0.80-0.91; P < .001) and low birth weight (40.2 vs 45.7 per 100 live births; RR, 0.88; 95% CI, 0.85-0.91; P < .001). CONCLUSIONS AND RELEVANCE: In Bangladesh, antenatal multiple micronutrient compared with iron-folic acid supplementation did not reduce all-cause infant mortality to age 6 months but resulted in a non-statistically significant reduction in stillbirths and significant reductions in preterm births and low birth weight. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00860470. |
Molecular genotyping and quantitation assay for rotavirus surveillance.
Liu J , Lurain K , Sobuz SU , Begum S , Kumburu H , Gratz J , Kibiki G , Toney D , Gautam R , Bowen MD , Petri WA Jr , Haque R , Houpt ER . J Virol Methods 2014 213 157-63 Rotavirus genotyping is useful for surveillance purposes especially in areas where rotavirus vaccination has been or will be implemented. RT-PCR based molecular methods have been applied widely, but quantitative assays targeting a broad spectrum of genotypes have not been developed. Three real time RT-PCR panels were designed to identify G1, G2, G9, G12 (panel GI), G3, G4, G8, G10 (panel GII), and P[4], P[6], P[8], P[10], P[11] (panel P), respectively. An assay targeting NSP3 was included in both G panels as an internal control. The cognate assays were also formulated as one RT-PCR-Luminex panel for simultaneous detection of all the genotypes listed above plus P[9]. The assays were evaluated with various rotavirus isolates and 89 clinical samples from Virginia, Bangladesh and Tanzania, and exhibited 95% (81/85) sensitivity compared with the conventional RT-PCR-Gel-electrophoresis method, and 100% concordance with sequencing. Real time assays identified a significantly higher rate of mixed genotypes in Bangladeshi samples than the conventional gel-electrophoresis-based RT-PCR assay (32.5% versus 12.5%, P<0.05). In these mixed infections, the relative abundance of the rotavirus types could be estimated by Cq values. These typing assays detect and discriminate a broad range of G/P types circulating in different geographic regions with high sensitivity and specificity and can be used for rotavirus surveillance. |
Impact of neighborhood biomass cooking patterns on episodic high indoor particulate matter concentrations in clean fuel homes in Dhaka, Bangladesh
Salje H , Gurley ES , Homaira N , Ram PK , Haque R , Petri W , Moss WJ , Luby SP , Breysse P , Azziz-Baumgartner E . Indoor Air 2014 24 (2) 213-20 Exposure to particulate matter (PM2.5 ) from the burning of biomass is associated with increased risk of respiratory disease. In Dhaka, Bangladesh, households that do not burn biomass often still experience high concentrations of PM2.5 , but the sources remain unexplained. We characterized the diurnal variation in the concentrations of PM2.5 in 257 households and compared the risk of experiencing high PM2.5 concentrations in biomass and non-biomass users. Indoor PM2.5 concentrations were estimated every minute over 24 h once a month from April 2009 through April 2010. We found that households that used gas or electricity experienced PM2.5 concentrations exceeding 1000 mug/m(3) for a mean of 35 min within a 24-h period compared with 66 min in biomass-burning households. In both households that used biomass and those that had no obvious source of particulate matter, the probability of PM2.5 exceeding 1000 mug/m(3) were highest during distinct morning, afternoon, and evening periods. In such densely populated settings, indoor pollution in clean fuel households may be determined by biomass used by neighbors, with the highest risk of exposure occurring during cooking periods. Community interventions to reduce biomass use may reduce exposure to high concentrations of PM2.5 in both biomass and non-biomass using households. |
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