Last data update: Sep 16, 2024. (Total: 47680 publications since 2009)
Records 1-30 (of 36 Records) |
Query Trace: Karim N [original query] |
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Brainstorm: A case of granulomatous encephalitis
Benoit Patrick , Wang Stephanie , Wang Catherine , Chakravarti Arpita , Villalba Julian A , Ali Ibne Karim M , Roy Shantanu , Sapp Sarah GH , Reagan-Steiner Sarah , Nelson Kristoff , Cayrol Romain , Luong Me-Linh , Grand'Maison Sophie , Desjardins Michaël . J Assoc Med Microbiol Infect Dis Can 2024 9 (2) 113-120 Background: Free-living amoebas (FLAs) can cause severe and fatal central nervous system infections that are difficult to diagnose. Methods: We present the case of a 74-year-old immunocompetent woman admitted for focal neurological symptoms with enhancing lesions in the right cerebellar hemisphere. A first cerebral biopsy showed granulomatous inflammation, but no microorganisms were identified. After transient clinical improvement, she eventually deteriorated 4 months after initial presentation, with an MRI confirming multiple new masses affecting all cerebral lobes. Results: A second brain biopsy revealed granulomatous and acute inflammation with organisms containing a large central nucleus with prominent karyosome, consistent with FLAs. Immunohistochemical and polymerase chain reaction assays performed at CDC were positive for Acanthamoeba spp, confirming the diagnosis of granulomatous amoebic encephalitis (GAE) caused by Acanthamoeba spp. The patient was treated with combination therapy recommended by CDC, but died a few days later. Upon histopathological rereview, amoebic cysts and trophozoites were identified by histochemical and immunohistochemical methods in the first cerebral biopsy. Conclusion: FLA infections can be challenging to diagnose because of the low incidence, non-specific clinical and radiological presentation, lack of accessible diagnostic tools, and clinicians' unfamiliarity. This case highlights the importance of recognizing FLA as a potential cause of granulomatous encephalitis, even in the absence of risk factors, as early treatment might be associated with favourable outcomes in case reports. When suspected, CDC laboratories offer tests to confirm the diagnosis promptly. | Historique : Les amibes libres peuvent causer des infections du système nerveux central graves et fatales qui sont difficiles à diagnostiquer. Méthodologie : Les auteurs présentent le cas d'une femme immunocompétente de 74 ans hospitalisée à cause de symptômes neurologiques focaux avec lésions rehaussantes dans l'hémisphère cérébelleux droit. Une première biopsie cérébrale a révélé une inflammation granulomateuse, mais aucun microorganisme n'a été décelé. Après une amélioration clinique transitoire, son état s'est détérioré quatre mois après la première consultation, et l'IRM a confirmé de multiples nouvelles masses touchant tous les lobes cérébraux. Résultats : Une deuxième biopsie cérébrale a révélé une inflammation granulomateuse aiguë par des organismes dont les gros noyaux centraux et les caryosomes volumineux étaient évocateurs d'amibes libres. L'immunohistochimie et l'amplification en chaîne par polymérase effectuées aux CDC se sont avérés positives pour Acanthamoeba spp, ce qui a confirmé un diagnostic d'encéphalite amibienne granulomateuse causée par Acanthamoeba spp. La patiente a reçu une polythérapie recommandée par les CDC, mais est malheureusement décédée quelques jours plus tard. À la reprise de l'analyse histopathologique, des kystes amibiens et des trophozoïtes ont été décelés dans la première biopsie cérébrale par des méthodes histochimiques et immunohistochimiques. Conclusion : Les infections par des amibes libres peuvent être difficiles à diagnostiquer en raison de leur faible incidence, de leur présentation clinique et radiologique non spécifique, de l'absence d'outils diagnostiques accessibles et de la méconnaissance des cliniciens. Ce cas renforce l'importance d'inclure les amibes libres dans les causes potentielles d'encéphalite granulomateuse, même en l'absence de facteurs de risque, car un traitement rapide a été associé à des résultats favorables dans certains rapports de cas. Lorsqu'on en soupçonne la présence, les laboratoires des CDC offrent des tests pour confirmer rapidement le diagnostic. |
Multilocus sequence typing of Enterocytozoon bieneusi in nonhuman primates in China.
Karim MR , Wang R , He X , Zhang L , Li J , Rume FI , Dong H , Qi M , Jian F , Zhang S , Sun M , Yang G , Zou F , Ning C , Xiao L . Vet Parasitol 2014 200 13-23 To infer population genetics of Enterocytozoon bieneusi in nonhuman primates (NHPs), 126 positive specimens in 839 fecal specimens from 23 NHP species in China based on ITS locus were used, belonging to genotypes Type IV, D, Peru8, Henan V, Peru11, PigEBITS7 and 3 novel ones (CM1, CM2 and CM3). Multilocus sequence typing employing four micro and minisatellites (MS1, MS3, MS4 and MS7) and ITS were used to analyze population structure of 85 isolates successfully amplified at all five loci, which yielded 59 multilocus genotypes. Linkage disequilibrium (LD) was measured using both multilocus sequences and allelic profile data. The observation of strong and significant LD with limited recombination in multilocus sequence analysis indicated the presence of overall clonal population structure of E. bieneusi, which was supported by allelic profile data analysis. Fu's selective neutrality test demonstrated the absence of neutral mutations and molecular selection. The population structure of common ITS genotypes (CM1, Type IV and D) was compared. Strong LD in multilocus sequence analysis versus insignificant LD and/or LE in allelic profile data analysis implied epidemic population in common ITS genotypes. No significant genetic isolation was evidenced by either phylogenetic or substructural analyses. The population genetics was also compared among the sub-population 1 (contained mainly genotype Type IV), sub-population 2 (contained mainly genotypes CM1 and D), sub-population 3 (contained mixed genotypes) and sub-population 4 (contained genotype Henan V). The presence of strong LD in multilocus data analysis with insignificant LD and/or LE in allele profile data analysis suggested the epidemic population in sub-populations. |
Epidemiology and risk factors of norovirus infections among diarrhea patients admitted to tertiary care hospitals in Bangladesh
Satter SM , Abdullah Z , Fariha F , Karim Y , Rahman MM , Balachandran N , Ghosh PK , Hossain ME , Mirza SA , Hall AJ , Gastañaduy PA , Rahman M , Vinjé J , Parashar UD . J Infect Dis 2023 228 (7) 818-828 BACKGROUND: Norovirus is a major cause of endemic acute gastroenteritis (AGE) worldwide. We described the epidemiology, risk factors, and genotypic distribution of noroviruses among hospitalized patients of all ages in Bangladesh. METHODS: From March 2018 to October 2021, 1250 AGE case patients and controls (age, sex, season, and site matched) were enrolled at 10 hospitals. Demographic and clinical information was collected; real-time reverse-transcriptase polymerase chain reaction (RT-PCR) used to test stool specimens, and positive samples were genotyped. RESULTS: Norovirus was detected in 9% of cases (111 of 1250) and 15% (182 of 1250) of controls. Eighty-two percent of norovirus-positive cases were in children <5 years old. Norovirus-positive AGE hospitalizations occurred year-round, with peaks in April and October. Risk factors for norovirus included age <5 years (adjusted odds ratio, 3.1 [95% confidence interval, 1.9-5.2]) and exposure to a patient with AGE in the 10 days before enrollment (3.8 [1.9-7.2]). GII.3[P16] and GII.4 Sydney[P16] were the predominant genotypes. CONCLUSIONS: We highlight the burden of norovirus in hospital settings. Young age and recent exposure to a patient with AGE were risk factors for norovirus. A high prevalence of norovirus among controls might represent asymptomatic reinfections or prolonged shedding from a previous infection; carefully designed longitudinal studies are needed to improve our understanding of norovirus infections in Bangladesh. |
Perspectives of public health organizations partnering with refugee, immigrant, and migrant communities for comprehensive COVID-19 case investigation and contact tracing
Dawson-Hahn E , Fredkove W , Karim S , Mohamed F , Abudiab S , de Acosta D , Ebengho S , Garcia Y , Hoffman S , Keaveney M , Mann E , Thomas C , Yu K , Yun K . Front Public Health 2023 11 1218306 OBJECTIVES: To understand public health organizations' experiences providing comprehensive COVID-19 case investigation and contact tracing, and related promising practices with refugee, immigrant and migrant communities. METHODS: We interviewed public health professionals (September 2020 to February 2021) from local and state health departments using a geographically stratified, purposive sampling approach. A multidisciplinary team at the National Resource Center for Refugees, Immigrants and Migrants (NRC-RIM) conducted a thematic analysis of the data. RESULTS: Six themes were identified: understanding community and public health context, cultivating relationships, ensuring linguistic and cultural concordance, communicating intentionally, evolving response, and implementing equity. The interconnection of themes and promising practices is explored. CONCLUSION: As public health continues to learn from and build upon COVID-19 response experiences, the thematic findings and potential promising practices identified in this project may foster proactive, community-engaged solutions for public health, and other organizations working and partnering with refugee, immigrant, and migrant communities. Implementing these findings with COVID-19 into current and future public health crisis responses may improve public health, collaborations with refugee, immigrant, and migrant communities, and staff wellbeing. |
Interlaboratory performance and quantitative PCR data acceptance metrics for NIST SRM 2917
Sivaganesan M , Willis JR , Karim M , Babatola A , Catoe D , Boehm AB , Wilder M , Green H , Lobos A , Harwood VJ , Hertel S , Klepikow R , Howard MF , Laksanalamai P , Roundtree A , Mattioli M , Eytcheson S , Molina M , Lane M , Rediske R , Ronan A , D'Souza N , Rose JB , Shrestha A , Hoar C , Silverman AI , Faulkner W , Wickman K , Kralj JG , Servetas SL , Hunter ME , Jackson SA , Shanks OC . Water Res 2022 225 119162 Surface water quality quantitative polymerase chain reaction (qPCR) technologies are expanding from a subject of research to routine environmental and public health laboratory testing. Readily available, reliable reference material is needed to interpret qPCR measurements, particularly across laboratories. Standard Reference Material® 2917 (NIST SRM® 2917) is a DNA plasmid construct that functions with multiple water quality qPCR assays allowing for estimation of total fecal pollution and identification of key fecal sources. This study investigates SRM 2917 interlaboratory performance based on repeated measures of 12 qPCR assays by 14 laboratories (n = 1008 instrument runs). Using a Bayesian approach, single-instrument run data are combined to generate assay-specific global calibration models allowing for characterization of within- and between-lab variability. Comparable data sets generated by two additional laboratories are used to assess new SRM 2917 data acceptance metrics. SRM 2917 allows for reproducible single-instrument run calibration models across laboratories, regardless of qPCR assay. In addition, global models offer multiple data acceptance metric options that future users can employ to minimize variability, improve comparability of data across laboratories, and increase confidence in qPCR measurements. |
Child marriage among displaced populations - a 2019 study in Kurdistan Region of Iraq
Goers M , Hunersen K , Karim LS , Jeffery A , Zedan A , Robinson C , Metzler J . BMC Public Health 2022 22 (1) 796 BACKGROUND: Many of the factors that increase risk of child marriage are common among refugees and internally displaced persons (IDPs). We sought to address the gaps in knowledge surrounding child marriage in displaced and host populations in the Kurdistan Region of Iraq (KRI). METHODS: A multistage cluster sample design was employed collecting data of KRI host communities, Iraqi IDPs, and Syrian refugees. Interviews were conducted in eligible households, requiring at least one adult female and one female adolescent present, addressing views of marriage, demographics and socioeconomic factors. Household rosters were completed to assess WHO indicators, related to child marriage including completed child marriage in females 10-19 and completed risk of previously conducted child marriages in females 20-24. RESULTS: Interviews were completed in 617 hosts, 664 IDPs, and 580 refugee households, obtaining information on 10,281 household members and 1,970 adolescent females. Overall, 10.4% of girls age 10-19 were married. IDPs had the highest percentage of married 10-19-year-old females (12.9%), compared to the host community (9.8%) and refugees (8.1%). Heads of households with lower overall education had higher percentages of child marriage in their homes; this difference in prevalence was most notable in IDPs and refugees. When the head of the household was unemployed, 14.5% of households had child marriage present compared to 8.0% in those with employed heads of household. Refugees and IDPs had larger percentages of child marriage when heads of households were unemployed (refugees 13.1%, IDPs 16.9%) compared to hosts (11.9%). When asked about factors influencing marriage decisions, respondents predominately cited family tradition (52.5%), family honor (15.7%), money/resources (9.6%), or religion (8.0%). Over a third of those interviewed (38.9%) reported a change in influencing factors on marriage after displacement (or after the arrival of refugees in the area for hosts). CONCLUSIONS: Being an IDP in Iraq, unemployment and lower education were associated with an increase in risk for child marriage. Refugees had similar percentages of child marriage as hosts, though the risk of child marriage among refugees was higher in situations of low education and unemployment. Ultimately, child marriage remains a persistent practice worldwide, requiring continued efforts to understand and address sociocultural norms in low socioeconomic and humanitarian settings. |
Enhancing meningococcal genomic surveillance in the meningitis belt using high-resolution culture-free whole genome sequencing.
Itsko M , Topaz N , Ousmane S , Popoola M , Ouedraogo R , Gamougam K , Sadji AY , Abdul-Karim A , Lascols C , Wang X . J Infect Dis 2022 226 (4) 729-737 Rollout of meningococcal serogroup A conjugate vaccine in Africa started in 2010, aiming to eliminate meningitis outbreaks, in meningitis belt countries. Since then, studies have been conducted, primarily using isolates, to assess the vaccine impact on the distribution of meningococcal strains in the region. Here, we implemented an innovative, culture-free whole genome sequencing approach on almost 400 clinical specimens collected between 2017-2019 from meningococcal meningitis cases in 6 African countries. About 50% of specimens provided high-quality whole genome sequence data for comprehensive molecular profiling of the meningococcal pathogen. Three major clonal complexes were identified: CC11 associated with serogroup W, CC181 associated with serogroup X and CC10217 associated with serogroup C, which continues to rise as a predominant clonal complex in the region. Genomic surveillance for meningococcal meningitis can be significantly improved using culture-free methods to increase data representativeness and monitor changes in epidemiological landscape, especially for countries with low culture rate. |
Genital immune cell activation and tenofovir gel efficacy: a case-control study
Liebenberg LJP , Passmore JS , Osman F , Jewanraj J , Mtshali A , Garcia-Lerma JG , Heneine W , Holder A , Archary D , Ngcapu S , Sivro A , Mansoor LE , Abdool Karim Q , Abdool Karim SS , McKinnon LR . Clin Infect Dis 2022 75 (6) 1088-1091 Genital inflammation (GI) undermines topical HIV pre-exposure prophylaxis (PrEP) efficacy through unknown mechanisms. Here, associations between activated endocervical CD4+ T cell numbers and higher deoxyadenosine triphosphate (dATP) concentrations suggest that competition for intracellular metabolites within HIV target cells may reduce the efficacy of antiretroviral-based PrEP in women with GI. |
Estimating the economic burden of pneumococcal meningitis and pneumonia in northern Ghana in the African meningitis belt post-PCV13 introduction
Kobayashi M , Abdul-Karim A , Milucky JL , Zakariah A , Leidner AJ , Asiedu-Bekoe F , Opare D , Eleeza JB , Ofosu W , Walker C , Whitney CG , Lessa FC . Vaccine 2021 39 (33) 4685-4699 BACKGROUND: Ghana introduced 13-valent pneumococcal conjugate vaccine (PCV13) into the routine infant immunization program in 2012, using a three-dose primary series without a booster. Despite ≥ 88% reported three-dose vaccination coverage since 2013, PCV13-type pneumococcal meningitis outbreaks have occurred. We estimated the ongoing economic burden of PCV13-type pneumococcal meningitis and pneumonia in northern Ghana, an area within the African meningitis belt with seasonal increases of pneumococcal meningitis post-PCV13 introduction, to inform PCV13 vaccination policy. METHODS: We performed a cross-sectional survey among patients with pneumonia or meningitis at three hospitals in northern Ghana to determine patient-level costs (direct medical and nonmedical, indirect patient and caregiver costs) incurred in household, outpatient, and inpatient settings. Pneumonia burden was estimated using 2017-2018 administrative records. Pneumococcal meningitis burden was estimated using 2017-2018 case-based surveillance data. Economic burden was reported in 2019 U.S. dollars ($) from the societal perspective. RESULTS: For an area with a total population of 5,068,521, our model estimated 6,441 PCV13-type pneumonia cases and 286 PCV13-type meningitis cases occurred in a typical year post-PCV13. In the base case scenario, the total economic burden was $5,230,035 per year ($777 per case). By age group, cost per PCV13-type pneumonia case was $423 (<5 years), $911 (5-14 years), and $784 (≥15 years); cost per PCV13-type meningitis case was $2,128 (<5 years), $3,247 (5-14 years), and $2,883 (≥15 years). Most (78.0-93.4%) of the total societal cost was due to indirect costs related to deaths from PCV13-type diseases. CONCLUSIONS: The estimated economic burden of PCV13-type disease in northern Ghana remains substantial, especially in older children and adults who were expected to have benefited from indirect effects from infant immunization. Additional interventions such as changes in the infant immunization schedule, reactive vaccination, or catch-up PCV13 vaccination may be needed to control remaining vaccine-type disease. |
COVID-19 Outbreak Associated with a SARS-CoV-2 R.1 Lineage Variant in a Skilled Nursing Facility After Vaccination Program - Kentucky, March 2021.
Cavanaugh AM , Fortier S , Lewis P , Arora V , Johnson M , George K , Tobias J , Lunn S , Miller T , Thoroughman D , Spicer KB . MMWR Morb Mortal Wkly Rep 2021 70 (17) 639-643 Although COVID-19 mRNA vaccines demonstrated high efficacy in clinical trials (1), they were not 100% efficacious. Thus, some infections postvaccination are expected. Limited data are available on effectiveness in skilled nursing facilities (SNFs) and against emerging variants. The Kentucky Department for Public Health (KDPH) and a local health department investigated a COVID-19 outbreak in a SNF that occurred after all residents and health care personnel (HCP) had been offered vaccination. Among 83 residents and 116 HCP, 75 (90.4%) and 61 (52.6%), respectively, received 2 vaccine doses. Twenty-six residents and 20 HCP received positive test results for SARS-CoV-2, the virus that causes COVID-19, including 18 residents and four HCP who had received their second vaccine dose >14 days before the outbreak began. An R.1 lineage variant was detected with whole genome sequencing (WGS). Although the R.1 variant has multiple spike protein mutations, vaccinated residents and HCP were 87% less likely to have symptomatic COVID-19 compared with those who were unvaccinated. Vaccination of SNF populations, including HCP, is critical to reduce the risk for SARS-CoV-2 introduction, transmission, and severe outcomes in SNFs. An ongoing focus on infection prevention and control practices is also essential. |
Draft Chromosome Sequences of a Clinical Isolate of the Free-Living Ameba Naegleria fowleri.
Ali IKM , Kelley A , Joseph SJ , Park S , Roy S , Jackson J , Cope JR , Rowe LA , Burroughs M , Sheth M , Batra D , Loparev V . Microbiol Resour Announc 2021 10 (15) We present the chromosome sequences of a Naegleria fowleri isolate from a human primary amebic meningoencephalitis (PAM) case. The genome sequences were assembled from Illumina HiSeq and PacBio sequencing data and verified with the optical mapping data. This led to the identification of 37 contigs representing 37 chromosomes in N. fowleri. |
Entamoeba sp. infection in a bearded dragon (Pogona vitticeps)
Diana S , Karim AMI , Shantanu R , Lisa PM , Brandy K , David E . Vet Glas 2019 74 (1) 77-84 A 3-year-old, male intact, pet inland bearded dragon (Pogona vitticeps) presented with a history of diarrhea, progressive inappetence and weight loss. A palpable cranial celomic mass was identified on physical examination and confirmed to be hepatic in origin by celomic ultrasonography. Hematologic and biochemical abnormalities were mild and consistent with inflammation, regenerative anemia, and hepatocellular injury. Fine needle aspiration of the liver masses was suggestive of amoebiasis and the patient was humanely euthanized. PCR and Sanger DNA sequencing of liver aspirates were supportive of Entamoeba infection, although definitive speciation was not possible. Pathogenic amoebiasis due to infection by E. invadens has been reported in a wide range of reptiles and is an important cause of morbidity and mortality in these species. |
A real-time PCR assay for simultaneous detection and differentiation of four common Entamoeba species that infect humans.
Ali IKM , Roy S . J Clin Microbiol 2020 59 (1) There are over forty species within the genus Entamoeba, eight of which infect humans. Of these, four species (Entamoeba histolytica, E. dispar, E. moshkovskii, and E. bangladeshi) are morphologically indistinguishable from each other, yet differentiation is important for appropriate treatment decisions. Here, we developed a hydrolysis probe-based tetraplex real-time PCR assay that can simultaneously detect and differentiate these four species in clinical samples. In this assay, multi-copy SSU rDNA sequences were used as targets. We determined that the tetraplex real-time PCR can detect amebic DNA corresponding to as few as 0.1 trophozoite-equivalent of any of these species. We also determined that this assay can detect E. histolytica DNA in the presence of 10-fold more DNA from another Entamoeba species in the mixed infection scenarios. With a panel of more than 100 well-characterized clinical samples diagnosed and confirmed using a previously published duplex real-time PCR (capable of detecting E. histolytica and E. dispar), our tetraplex real-time PCR assay demonstrated comparable sensitivity and specificity with that of the duplex real-time PCR assay. The advantage of our assay over the duplex assay is that it can specifically detect two additional Entamoeba species and can be used in conventional PCR format. This newly-developed assay will allow further characterization of the epidemiology and pathogenicity of the four morphologically-identical Entamoeba species especially in low resource settings. |
HMG-CoA Reductase Inhibitors as Drug Leads against Naegleria fowleri .
Hahn HJ , Abagyan R , Podust LM , Roy S , Ali IKM , Debnath A . ACS Chem Neurosci 2020 11 (19) 3089-3096 Primary amebic meningoencephalitis (PAM), caused by the free-living ameba Naegleria fowleri, has a fatality rate of over 97%. Treatment of PAM relies on amphotericin B in combination with other drugs, but few patients have survived with the existing drug treatment regimens. Therefore, development of effective drugs is a critical unmet need to avert deaths from PAM. Since ergosterol is one of the major sterols in the membrane of N. fowleri, disruption of isoprenoid and sterol biosynthesis by small-molecule inhibitors may be an effective intervention strategy against N. fowleri. The genome of N. fowleri contains a gene encoding HMG-CoA reductase (HMGR); the catalytic domains of human and N. fowleri HMGR share <60% sequence identity with only two amino acid substitutions in the active site of the enzyme. Considering the similarity of human and N. fowleri HMGR, we tested well-tolerated and widely used HMGR inhibitors, known as cholesterol-lowering statins, against N. fowleri. We identified blood-brain-barrier-permeable pitavastatin as a potent amebicidal agent against the U.S., Australian, and European strains of N. fowleri. Pitavastatin was equipotent to amphotericin B against the European strain of N. fowleri; it killed about 80% of trophozoites within 16 h of drug exposure. Pretreatment of trophozoites with mevalonate, the product of HMGR, rescued N. fowleri from inhibitory effects of statins, demonstrating that HMGR of N. fowleri is the target of statins. Because of the good safety profile and availability for both adult and pediatric uses, consideration should be given to repurposing the fast-acting pitavastatin for the treatment of PAM. |
Modeling the potential impact of administering vaccines against Clostridioides difficile infection to individuals in healthcare facilities.
Toth DJA , Keegan LT , Samore MH , Khader K , O'Hagan JJ , Yu H , Quintana A , Swerdlow DL . Vaccine 2020 38 (37) 5927-5932 BACKGROUND: A vaccine against Clostridioides difficile infection (CDI) is in development. While the vaccine has potential to both directly protect those vaccinated and mitigate transmission by reducing environmental contamination, the impact of the vaccine on C. difficile colonization remains unclear. Consequently, the transmission-reduction effect of the vaccine depends on the contribution of symptomatic CDI to overall transmission of C. difficile. METHODS: We designed a simulation model of CDI among patients in a network of 10 hospitals and nursing homes and calibrated the model using estimates of transmissibility from whole genome sequencing studies that estimated the fraction of CDI attributable to transmission from other CDI patients. We assumed the vaccine reduced the rate of progression to CDI among carriers by 25-95% after completion of a 3-dose vaccine course administered to randomly chosen patients at facility discharge. We simulated the administration of this vaccination campaign and tallied effects over 5 years. RESULTS: We estimated 30 times higher infectivity of CDI patients compared to other carriers. Simulations of the vaccination campaign produced an average reduction of 3-16 CDI cases per 1000 vaccinated patients, with 2-11 of those cases prevented among those vaccinated and 1-5 prevented among unvaccinated patients. CONCLUSIONS: Our findings demonstrate potential for a vaccine against CDI to reduce transmissions in healthcare facilities, even with no direct effect on carriage susceptibility. The vaccine's population impact will increase if received by individuals at risk for CDI onset in high-transmission settings. |
Rapid, Noninvasive Diagnosis of Balamuthia mandrillaris Encephalitis by a Plasma-Based Next-Generation Sequencing Test.
Kalyatanda G , Rand K , Lindner MS , Hong DK , Sait Albayram M , Gregory J , Kresak J , Ibne KMA , Cope JR , Roy S , Gary JM , Reddy V , Ahmed AA . Open Forum Infect Dis 2020 7 (7) ofaa189 Granulomatous amoebic encephalitis (GAE) caused by Balamuthia mandrillaris is a rare subacute infection with exceptionally high mortality. Diagnosis is typically made by brain biopsy or at autopsy. Detection of Balamuthia mandrillaris cell-free DNA by next-generation sequencing of plasma enabled rapid, noninvasive diagnosis in a case of amoebic encephalitis. |
Occurrence and molecular characterization of Giardia duodenalis in lambs in Djelfa, the central steppe of Algeria.
Benhassine S , Baroudi D , Hakem A , Thomas M , Laatamna A , Belkessa S , Feng Y , Roellig D , Chen X , Adjou KT , Xiao L . Parasitol Res 2020 119 (9) 2965-2973 Little is known of the prevalence and genetic identity of Giardia duodenalis in sheep in Algeria. The present study aimed at characterizing G. duodenalis in lambs up to 6 months of age in Djelfa, Algeria. A total of 346 fecal specimens were collected from 28 farms and screened for G. duodenalis cysts by zinc sulfate flotation microscopy, and positive specimens were confirmed using a direct immunofluorescence assay. Microscopy-positive specimens were analyzed by PCR and sequence analysis of the triosephosphate isomerase and glutamate dehydrogenase genes to determine G. duodenalis assemblages. Coprological examination indicated that the overall infection rate was 7.0% (24/346). Lambs under 3 months of age had higher infection rate (18/197, 9.0%) than older (6/149, 4.0%) animals, and animals with diarrhea (7/44, 16.0%) had higher infection rate than animals without diarrhea (17/302, 5.6%). PCR sequence analyses of the 15 G. duodenalis isolates revealed the presence of assemblages A in 6 isolates, assemblage E in 7 isolates, and both in 2 isolates. Assemblage A was only found in pre-weaned lambs with diarrhea, while assemblage E was mostly found in post-weaned lambs without diarrhea. The assemblage E isolates from sheep were genetically related to those from cattle in Algeria, while assemblage A isolates were from a well-known subtype prevalent in humans. Data generated from the study improve our understanding of the transmission of G. duodenalis in Algeria. |
Moderate-to-High Levels of Pretreatment HIV Drug Resistance in KwaZulu-Natal Province, South Africa.
Chimukangara B , Kharsany ABM , Lessells RJ , Naidoo K , Rhee SY , Manasa J , Graf T , Lewis L , Cawood C , Khanyile D , Diallo K , Ayalew KA , Shafer RW , Hunt G , Pillay D , Abdool SK , de Oliveira T . AIDS Res Hum Retroviruses 2019 35 (2) 129-138 There is evidence of increasing levels of pretreatment HIV drug resistance (PDR) in Southern Africa. We used data from two large population-based HIV surveillance studies to estimate prevalence of PDR in KwaZulu-Natal, the province with the highest HIV prevalence in South Africa. Sanger sequencing was performed on samples obtained from a longitudinal HIV surveillance program (study A, 2013-2014) and the HIV Incidence Provincial Surveillance System (study B, 2014-2015). Sequences were included for adult HIV positive participants (age >/=15 years for study A, age 15-49 years for study B) with no documented prior exposure to antiretroviral therapy (ART). Overall and drug class-specific PDR was estimated using the World Health Organization 2009 surveillance drug resistance mutation (SDRM) list, and phylogenetic analysis was performed to establish evidence of drug resistance transmission linkage. A total of 1,845 sequences were analyzed (611 study A; 1,234 study B). An overall PDR prevalence of 9.2% [95% confidence interval (CI) 7.0-11.7] was observed for study A and 11.0% (95% CI 8.9-13.2) for study B. In study B, the prevalence of non-nucleoside reverse-transcriptase inhibitor (NNRTI) PDR exceeded 10% for sequences collected in 2014 (10.2%, 95% CI 7.5-12.9). The most prevalent SDRMs were K103NS (7.5%), M184VI (2.4%), and V106AM (1.4%). There was no evidence of large transmission chains of drug-resistant virus. High level NNRTI PDR (>10%) suggests a need to modify the standard first-line ART regimen and to focus attention on improving the quality of HIV prevention, treatment, and care. |
Trends in HIV prevention, treatment, and incidence in a hyperendemic area of KwaZulu-Natal, South Africa
Kharsany ABM , Cawood C , Lewis L , Yende-Zuma N , Khanyile D , Puren A , Madurai S , Baxter C , George G , Govender K , Beckett S , Samsunder N , Toledo C , Ayalew KA , Diallo K , Glenshaw M , Herman-Roloff A , Wilkinson E , de Oliveira T , Abdool Karim SS , Abdool Karim Q . JAMA Netw Open 2019 2 (11) e1914378 Importance: In Africa, the persistently high HIV incidence rate among young women is the major obstacle to achieving the goal of epidemic control. Objective: To determine trends in coverage of HIV prevention and treatment programs and HIV incidence. Design, Setting, and Participants: This cohort study consisted of 2 sequential, community-based longitudinal studies performed in the Vulindlela and Greater Edendale area in KwaZulu-Natal, South Africa. Participants enrolled from June 11, 2014, to June 22, 2015 (2014 survey), with a single follow-up visit from June 24, 2016, to April 3, 2017 (2016 cohort), or enrolled from July 8, 2015, to June 7, 2016 (2015 survey), with a single follow-up visit from November 7, 2016, to August 30, 2017 (2017 cohort). Men and women aged 15 to 49 years were enrolled in the 2014 and 2015 surveys, and HIV-seronegative participants aged 15 to 35 years were followed up in the 2016 and 2017 cohorts. Analysis was conducted from January 1 through December 31, 2018. Exposures: HIV prevention and treatment programs in a real-world, nontrial setting. Main Outcomes and Measures: Trends in sex- and age-specific HIV incidence rates, condom use, voluntary medical male circumcision, knowledge of HIV-seropositive status, uptake of antiretroviral therapy, and viral suppression. Results: A total of 9812 participants (6265 women [63.9%]; median age, 27 years [interquartile range, 20-36 years]) from 11 289 households were enrolled in the 2014 survey, and 10 236 participants (6341 women [61.9%]; median age, 27 years [interquartile range, 20-36 years]) from 12 247 households were enrolled in the 2015 survey. Of these, 3536 of 4539 (annual retention rate of 86.7%) completed follow-up in the 2016 cohort, and 3907 of 5307 (annual retention rate of 81.4%) completed follow-up in the 2017 cohort. From 2014 to 2015, condom use with last sex partner decreased by 10% from 24.0% (n = 644 of 3547) to 21.6% (n = 728 of 3895; P = .12) in men and by 17% from 19.6% (n = 1039 of 6265) to 16.2% (n = 871 of 6341; P = .002) in women. Voluntary medical male circumcision increased by 13% from 31.9% (1102 of 3547) to 36.1% (n = 1472 of 3895); P = .007) in men, and the proportion of women reporting that their partner was circumcised increased by 35% from 35.7% (n = 1695 of 4766) to 48.2% (n = 2519 of 5207; P < .001). Knowledge of HIV-seropositive status increased by 21% from 51.8% (n = 504 of 3547) to 62.9% (n = 570 of 3895; P < .001) in men and by 14% from 64.6% (n = 1833 of 6265) to 73.4% (n = 2182 of 6341; P < .001) in women. Use of antiretroviral therapy increased by 32% from 36.7% (n = 341 of 3547) to 48.6% (n = 432 of 3895; P < .001) in men and by 29% from 45.6% (n = 1251 of 6265) to 58.8% (n = 1743 of 6341; P < .001) in women; HIV viral suppression increased by 20% from 41.9% (n = 401 of 3547) to 50.3% (n = 456 of 3895; P = .005) in men and by 13% from 54.8% (n = 1547 of 6265) to 61.9% (n = 1828 of 6341; P < .001) in women. Incidence of HIV declined in women aged 15 to 19 years from 4.63 (95% CI, 3.29-6.52) to 2.74 (95% CI, 1.84-4.09) per 100 person-years (P = .04) but declined marginally or remained unchanged among men and women in other age groups. Conclusions and Relevance: This study showed a significant decline in HIV incidence in young women; however, to further reduce HIV incidence, HIV prevention and treatment program coverage must be intensified and scaled up. |
Trends in Pretreatment HIV-1 Drug Resistance in Antiretroviral Therapy-naive Adults in South Africa, 2000-2016: A Pooled Sequence Analysis.
Chimukangara B , Lessells RJ , Rhee SY , Giandhari J , Kharsany ABM , Naidoo K , Lewis L , Cawood C , Khanyile D , Ayalew KA , Diallo K , Samuel R , Hunt G , Vandormael A , Stray-Pedersen B , Gordon M , Makadzange T , Kiepiela P , Ramjee G , Ledwaba J , Kalimashe M , Morris L , Parikh UM , Mellors JW , Shafer RW , Katzenstein D , Moodley P , Gupta RK , Pillay D , Abdool Karim SS , de Oliveira T . EClinicalMedicine 2019 9 26-34 Background: South Africa has the largest public antiretroviral therapy (ART) programme in the world. We assessed temporal trends in pretreatment HIV-1 drug resistance (PDR) in ART-naïve adults from South Africa. Methods: We included datasets from studies conducted between 2000 and 2016, with HIV-1 pol sequences from more than ten ART-naïve adults. We analysed sequences for the presence of 101 drug resistance mutations. We pooled sequences by sampling year and performed a sequence-level analysis using a generalized linear mixed model, including the dataset as a random effect. Findings: We identified 38 datasets, and retrieved 6880 HIV-1 pol sequences for analysis. The pooled annual prevalence of PDR remained below 5% until 2009, then increased to a peak of 11·9% (95% confidence interval (CI) 9·2-15·0) in 2015. The pooled annual prevalence of non-nucleoside reverse-transcriptase inhibitor (NNRTI) PDR remained below 5% until 2011, then increased to 10.0% (95% CI 8.4–11.8) by 2014. Between 2000 and 2016, there was a 1.18-fold (95% CI 1.13–1.23) annual increase in NNRTI PDR (p < 0.001), and a 1.10-fold (95% CI 1.05–1.16) annual increase in nucleoside reverse-transcriptase inhibitor PDR (p = 0.001). Interpretation: Increasing PDR in South Africa presents a threat to the efforts to end the HIV/AIDS epidemic. These findings support the recent decision to modify the standard first-line ART regimen, but also highlights the need for broader public health action to prevent the further emergence and transmission of drug-resistant HIV. Source of Funding: This research project was funded by the South African Medical Research Council (MRC) with funds from National Treasury under its Economic Competitiveness and Support Package. Disclaimer: The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of CDC. |
Continued occurrence of serotype 1 pneumococcal meningitis in two regions located in the meningitis belt in Ghana five years after introduction of 13-valent pneumococcal conjugate vaccine
Bozio CH , Abdul-Karim A , Abenyeri J , Abubakari B , Ofosu W , Zoya J , Ouattara M , Srinivasan V , Vuong JT , Opare D , Asiedu-Bekoe F , Lessa FC . PLoS One 2018 13 (9) e0203205 BACKGROUND: Increases in pneumococcal meningitis were reported from Ghanaian regions that lie in the meningitis belt in 2016-2017, despite introduction of 13-valent pneumococcal conjugate vaccine (PCV13) in 2012 using a 3-dose schedule (6, 10, and 14 weeks). We describe pneumococcal meningitis epidemiology in the Ghanaian Northern and Upper West regions across two meningitis seasons. METHODS: Suspected meningitis cases were identified using World Health Organization standard definitions. Pneumococcal meningitis was confirmed if pneumococcus was the sole pathogen detected by polymerase chain reaction, culture, or latex agglutination in cerebrospinal fluid collected from a person with suspected meningitis during December 2015-March 2017. Pneumococcal serotyping was done using PCR. Annual age-specific pneumococcal meningitis incidence (cases per 100,000 population) was calculated, adjusting for suspected meningitis cases lacking confirmatory testing. FINDINGS: Among 153 pneumococcal meningitis cases, 137 (89.5%) were serotyped; 100 (73.0%) were PCV13-type, including 85 (62.0%) that were serotype 1, a PCV13-targeted serotype. Persons aged >/=5 years accounted for 96.7% (148/153) of cases. Comparing 2015-2016 and 2016-2017 seasons, the proportion of non-serotype 1 PCV13-type cases decreased from 20.0% (9/45) to 4.1% (3/74) (p = 0.008), whereas the proportion that was serotype 1 was stable (71.1% (32/45) vs. 58.1% (43/74); p = 0.16). Estimated adjusted pneumococcal meningitis incidence was 1.8 in children aged <5 years and ranged from 6.8-10.5 in older children and adults. CONCLUSIONS: High pneumococcal meningitis incidence with a large proportion of serotype 1 disease in older children and adults suggests infant PCV13 vaccination has not induced herd protection with this schedule in this high-transmission setting. |
The tick endosymbiont Candidatus Midichloria mitochondrii and selenoproteins are essential for the growth of Rickettsia parkeri in the Gulf Coast tick vector
Budachetri K , Kumar D , Crispell G , Beck C , Dasch G , Karim S . Microbiome 2018 6 (1) 141 BACKGROUND: Pathogen colonization inside tick tissues is a significant aspect of the overall competence of a vector. Amblyomma maculatum is a competent vector of the spotted fever group rickettsiae, Rickettsia parkeri. When R. parkeri colonizes its tick host, it has the opportunity to dynamically interact with not just its host but with the endosymbionts living within it, and this enables it to modulate the tick's defenses by regulating tick gene expression. The microbiome in A. maculatum is dominated by two endosymbiont microbes: a Francisella-like endosymbiont (FLE) and Candidatus Midichloria mitochondrii (CMM). A range of selenium-containing proteins (selenoproteins) in A. maculatum ticks protects them from oxidative stress during blood feeding and pathogen infections. Here, we investigated rickettsial multiplication in the presence of tick endosymbionts and characterized the functional significance of selenoproteins during R. parkeri replication in the tick. RESULTS: FLE and CMM were quantified throughout the tick life stages by quantitative PCR in R. parkeri-infected and uninfected ticks. R. parkeri infection was found to decrease the FLE numbers but CMM thrived across the tick life cycle. Our qRT-PCR analysis indicated that the transcripts of genes with functions related to redox (selenogenes) were upregulated in ticks infected with R. parkeri. Three differentially expressed proteins, selenoprotein M, selenoprotein O, and selenoprotein S were silenced to examine their functional significance during rickettsial replication within the tick tissues. Gene silencing of the target genes was found to impair R. parkeri colonization in the tick vector. Knockdown of the selenogenes triggered a compensatory response from other selenogenes, as observed by changes in gene expression, but oxidative stress levels and endoplasmic reticulum stress inside the ticks were also found to have heightened. CONCLUSIONS: This study illustrates the potential of this new research model for augmenting our understanding of the pathogen interactions occurring within tick hosts and the important roles that symbionts and various tick factors play in regulating pathogen growth. |
Molecular xenomonitoring for Wuchereria bancrofti in Culex quinquefasciatus in two districts in Bangladesh supports transmission assessment survey findings.
Irish SR , Al-Amin HM , Paulin HN , Mahmood Asms , Khan RK , Muraduzzaman AKM , Worrell CM , Flora MS , Karim MJ , Shirin T , Shamsuzzaman AKM , Tahmina S , Lenhart A , Dubray C . PLoS Negl Trop Dis 2018 12 (7) e0006574 BACKGROUND: Careful monitoring for recrudescence of Wuchereria bancrofti infection is necessary in communities where mass drug administration (MDA) for the elimination of lymphatic filariasis (LF) as a public health problem has been stopped. During the post-MDA period, transmission assessment surveys (TAS) are recommended by the World Health Organization to monitor the presence of the parasite in humans. Molecular xenomonitoring (MX), a method by which parasite infection in the mosquito population is monitored, has also been proposed as a sensitive method to determine whether the parasite is still present in the human population. The aim of this study was to conduct an MX evaluation in two areas of Bangladesh, one previously endemic district that had stopped MDA (Panchagarh), and part of a non-endemic district (Gaibandha) that borders the district where transmission was most recently recorded. METHODOLOGY/PRINCIPAL FINDINGS: Mosquitoes were systematically collected from 180 trap sites per district and mosquito pools were tested for W. bancrofti using real-time PCR. A total of 23,436 intact mosquitoes, representing 31 species, were collected from the two districts, of which 10,344 (41%) were Culex quinquefasciatus, the vector of W. bancrofti in Bangladesh. All of the 594 pools of Cx. quinquefasciatus tested by real-time PCR were negative for the presence of W. bancrofti DNA. CONCLUSIONS/SIGNIFICANCE: This study suggested the absence of W. bancrofti in these districts. MX could be a sensitive tool to confirm interruption of LF transmission in areas considered at higher risk of recrudescence, particularly in countries like Bangladesh where entomological and laboratory capacity to perform MX is available. |
Community-based HIV prevalence in KwaZulu-Natal, South Africa: results of a cross-sectional household survey
Kharsany ABM , Cawood C , Khanyile D , Lewis L , Grobler A , Puren A , Govender K , George G , Beckett S , Samsunder N , Madurai S , Toledo C , Chipeta Z , Glenshaw M , Hersey S , Abdool Karim Q . Lancet HIV 2018 5 (8) e427-e437 BACKGROUND: In high HIV burden settings, maximising the coverage of prevention strategies is crucial to achieving epidemic control. However, little is known about the reach and effect of these strategies in some communities. METHODS: We did a cross-sectional community survey in the adjacent Greater Edendale and Vulindlela areas in the uMgungundlovu district, KwaZulu-Natal, South Africa. Using a multistage cluster sampling method, we randomly selected enumeration areas, households, and individuals. One household member (aged 15-49 years) selected at random was invited for survey participation. After obtaining consent, questionnaires were administered to obtain sociodemographic, psychosocial, and behavioural information, and exposure to HIV prevention and treatment programmes. Clinical samples were collected for laboratory measurements. Statistical analyses were done accounting for multilevel sampling and weighted to represent the population. A multivariable logistic regression model assessed factors associated with HIV infection. FINDINGS: Between June 11, 2014, and June 22, 2015, we enrolled 9812 individuals. The population-weighted HIV prevalence was 36.3% (95% CI 34.8-37.8, 3969 of 9812); 44.1% (42.3-45.9, 2955 of 6265) in women and 28.0% (25.9-30.1, 1014 of 3547) in men (p<0.0001). HIV prevalence in women aged 15-24 years was 22.3% (20.2-24.4, 567 of 2224) compared with 7.6% (6.0-9.3, 124 of 1472; p<0.0001) in men of the same age. Prevalence peaked at 66.4% (61.7-71.2, 517 of 760) in women aged 35-39 years and 59.6% (53.0-66.3, 183 of 320) in men aged 40-44 years. Consistent condom use in the last 12 months was 26.5% (24.1-28.8, 593 of 2356) in men and 22.7% (20.9-24.4, 994 of 4350) in women (p=0.0033); 35.7% (33.4-37.9, 1695 of 5447) of women's male partners and 31.9% (29.5-34.3, 1102 of 3547) of men were medically circumcised (p<0.0001), and 45.6% (42.9-48.2, 1251 of 2955) of women and 36.7% (32.3-41.2, 341 of 1014) of men reported antiretroviral therapy (ART) use (p=0.0003). HIV viral suppression was achieved in 54.8% (52.0-57.5, 1574 of 2955) of women and 41.9% (37.1-46.7, 401 of 1014) of men (p<0.0001), and 87.2% (84.6-89.8, 1086 of 1251) of women and 83.9% (78.5-89.3, 284 of 341; p=0.3670) of men on ART. Age, incomplete secondary schooling, being single, having more than one lifetime sex partner (women), sexually transmitted infections, and not being medically circumcised were associated with HIV-positive status. INTERPRETATION: The HIV burden in specific age groups, the suboptimal differential coverage, and uptake of HIV prevention strategies justifies a location-based approach to surveillance with finer disaggregation by age and sex. Intensified and customised approaches to seek, identify, and link individuals to HIV services are crucial to achieving epidemic control in this community. FUNDING: The President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention. |
Genital inflammation undermines the effectiveness of tenofovir gel in preventing HIV acquisition in women
McKinnon LR , Liebenberg LJ , Yende-Zuma N , Archary D , Ngcapu S , Sivro A , Nagelkerke N , Garcia Lerma JG , Kashuba AD , Masson L , Mansoor LE , Karim QA , Karim SSA , Passmore JS . Nat Med 2018 24 (4) 491-496 Several clinical trials have demonstrated that antiretroviral (ARV) drugs taken as pre-exposure prophylaxis (PrEP) can prevent HIV infection, with the magnitude of protection ranging from -49 to 86% (refs. ). Although these divergent outcomes are thought to be due primarily to differences in product adherence, biological factors likely contribute. Despite selective recruitment of higher-risk participants for prevention trials, HIV risk is heterogeneous even within higher-risk groups. To determine whether this heterogeneity could influence patient outcomes following PrEP, we undertook a post hoc prospective analysis of results from the CAPRISA 004 trial for 1% tenofovir gel (n = 774 patients), one of the first trials to demonstrate protection against HIV infection. Concentrations of nine proinflammatory cytokines were measured in cervicovaginal lavages at >2,000 visits, and a graduated cytokine score was used to define genital inflammation. In women without genital inflammation, tenofovir was 57% protective against HIV (95% confidence interval (CI): 7-80%) but was 3% protective (95% CI: -104-54%) if genital inflammation was present. Among women who highly adhered to the gel, tenofovir protection was 75% (95% CI: 25-92%) in women without inflammation compared to -10% (95% CI: -184-57%) in women with inflammation. Immunological predictors of HIV risk may modify the effectiveness of tools for HIV prevention; reducing genital inflammation in women may augment HIV prevention efforts. |
Meningitis outbreak caused by vaccine-preventable bacterial pathogens - northern Ghana, 2016
Aku FY , Lessa FC , Asiedu-Bekoe F , Balagumyetime P , Ofosu W , Farrar J , Ouattara M , Vuong JT , Issah K , Opare J , Ohene SA , Okot C , Kenu E , Ameme DK , Opare D , Abdul-Karim A . MMWR Morb Mortal Wkly Rep 2017 66 (30) 806-810 Bacterial meningitis is a severe, acute infection of the fluid surrounding the brain and spinal cord that can rapidly lead to death. Even with recommended antibiotic treatment, up to 25% of infected persons in Africa might experience neurologic sequelae.. Three regions in northern Ghana (Upper East, Northern, and Upper West), located in the sub-Saharan "meningitis belt" that extends from Senegal to Ethiopia, experienced periodic outbreaks of meningitis before introduction of serogroup A meningococcal conjugate vaccine (MenAfriVac) in 2012 . During December 9, 2015-February 16, 2016, a total of 432 suspected meningitis cases were reported to health authorities in these three regions. The Ghana Ministry of Health, with assistance from CDC and other partners, tested cerebrospinal fluid (CSF) specimens from 286 patients. In the first 4 weeks of the outbreak, a high percentage of cases were caused by Streptococcus pneumoniae; followed by an increase in cases caused by Neisseria meningitidis, predominantly serogroup W. These data facilitated Ghana's request to the International Coordinating Group* for meningococcal polysaccharide ACW vaccine, which was delivered to persons in the most affected districts. Rapid identification of the etiologic agent causing meningitis outbreaks is critical to inform targeted public health and clinical interventions, including vaccination, clinical management, and contact precautions. |
Strengthening HIV surveillance in the antiretroviral therapy era: rationale and design of a longitudinal study to monitor HIV prevalence and incidence in the uMgungundlovu district, KwaZulu-Natal, South Africa
Kharsany AB , Cawood C , Khanyile D , Grobler A , McKinnon LR , Samsunder N , Frohlich JA , Abdool Karim Q , Puren A , Welte A , George G , Govender K , Toledo C , Chipeta Z , Zembe L , Glenshaw MT , Madurai L , Deyde V M , Bere A . BMC Public Health 2015 15 (1) 1149 BACKGROUND: South Africa has over 6,000,000 HIV infected individuals and the province of KwaZulu-Natal (KZN) is the most severely affected. As public health initiatives to better control the HIV epidemic are implemented, timely, detailed and robust surveillance data are needed to monitor, evaluate and inform the programmatic interventions and policies over time. We describe the rationale and design of the HIV Incidence Provincial Surveillance System (HIPSS) to monitor HIV prevalence and incidence. METHODS/DESIGN: The household-based survey will include a sample of men and women from two sub-districts of the uMgungundlovu municipality (Vulindlela and the Greater Edendale) of KZN, South Africa. The study is designed as two sequential cross-sectional surveys of 10,000 randomly selected individuals aged 15-49 years to be conducted one year apart. From the cross sectional surveys, two sequential cohorts of HIV negative individuals aged 15-35 years will be followed-up one year later to measure the primary outcome of HIV incidence. Secondary outcomes include the laboratory measurements for pulmonary tuberculosis, sexually transmitted infections and evaluating tests for estimating population-level HIV incidence. Antiretroviral therapy (ART) access, HIV-1 RNA viral load, and CD4 cell counts in HIV positive individuals will assess the effectiveness of the HIV treatment cascade. Household and individual-level socio-demographic characteristics, exposure to HIV programmatic interventions and risk behaviours will be assessed as predictors of HIV incidence. The incidence rate ratio of the two cohorts will be calculated to quantify the change in HIV incidence between consecutive samples. In anticipation of better availability of population-level HIV prevention and treatment programmes leading to decreases in HIV incidence, the sample size provides 84 % power to detect a reduction of 30 % in the HIV incidence rate between surveys. DISCUSSION: The results from HIPSS will provide critical data regarding HIV prevalence and incidence in this community and will establish whether HIV prevention and treatment efforts in a "real world", non-trial setting have an impact on HIV incidence at a population level. Importantly, the study design and methods will inform future methods for HIV surveillance. |
Re-evaluation of an Acanthamoeba Molecular Diagnostic Algorithm following an Atypical Case of Amoebic Keratitis.
Lau R , Cunanan M , Jackson J , Ali IK , Chong-Kit A , Gasgas J , Tian J , Ralevski F , Boggild AK . J Clin Microbiol 2015 BACKGROUND: Amoebic keratitis (AK) is a potentially blinding infection, the prompt diagnosis of which is essential to limiting ocular morbidity. We undertook a quality improvement initiative around the molecular detection of Acanthamoebae in our laboratory due to an unusual case of discordance. METHODS: Nine ATCC strains of Acanthamoeba and 40 delinked, biobanked surplus corneal scrapings were retrieved and analyzed for the presence of Acanthamoebae by 4 separate real time PCR assays. The assay used by the Free Living and Intestinal Amebas laboratory of the CDC was considered the reference standard, and performance characteristics of each individual assay, and pairs of assays were calculated. Outcome measures were sensitivity, specificity, and positive predictive value (PPV) and negative (NPV) predictive value. RESULTS: Of 49 included specimens, 14 (28.6%) were positive by the gold standard assay, and 35 (71.4%) were negative. Sensitivity of the individual test assays ranged from 64.3% to 92.9% compared to the gold standard, while specificity ranged from 88.6% to 91.4%. PPV and NPV ranged from 69.2% to 78.6%, and 86.1% to 96.9%, respectively. Combinations of assay pairs led to improved performance with sensitivities ranging from 92.9% to 100%, and specificity from 97.1% to 100%. ATCC and clinical strains of Acanthamoeba that failed detection by certain individual assays included A. castellani, A. culbertsoni, and A. lenticulata. In 3 clinical specimens, false negativity of the gold standard assay could not be excluded. CONCLUSIONS: Molecular diagnostic approaches, especially combinations of both highly sensitive and specific assays, offer a reasonably performing, operator independent, and rapid strategy for the detection of Acanthamoebae from clinical specimens, and are likely more practical than either culture or direct microscopic detection. |
Intestinal Amebae.
Ali IK . Clin Lab Med 2015 35 (2) 393-422 Among the Entamoeba species that infect humans, Entamoeba histolytica causes diseases, Entamoeba dispar is a harmless commensal, Entamoeba moshkovskii seems to be a pathogen, and the pathogenicity of Entamoeba bangladeshi remains to be investigated. Species-specific detection needed for treatment decisions and for understanding the epidemiology and pathogenicity of these amebae. Antigen-based detection methods are needed for E dispar, E moshkovskii, and E bangladeshi; and molecular diagnostic test capable of detecting E histolytica, E dispar, E moshkovskii, and E bangladeshi simultaneously in clinical samples. Next-generation sequencing of DNA from stool is needed to identify novel species of Entamoeba. |
Multi-locus analysis of Giardia duodenalis from nonhuman primates kept in zoos in China: geographical segregation and host-adaptation of assemblage B isolates.
Karim MR , Wang R , Yu F , Li T , Dong H , Li D , Zhang L , Li J , Jian F , Zhang S , Rume FI , Ning C , Xiao L . Infect Genet Evol 2014 30 82-88 Only a few studies based on single locus characterization have been conducted on the molecular epidemiology of Giardia duodenalis in nonhuman primates (NHPs). The present study was conducted to examine the occurrence and genotype identity of G. duodenalis in NHPs based on multi-locus analysis of the small-subunit ribosomal RNA (SSU rRNA), triose phosphate isomerase (tpi), glutamate dehydrogenase (gdh), and beta-giardin (bg) genes. Fecal specimens were collected from 496 animals of 36 NHP species kept in seven zoos in China and screened for G. duodenalis by tpi-based PCR. G. duodenalis was detected in 92 (18.6%) specimens from 18 NHP species, belonging to assemblage A (n=4) and B (n=88). In positive NHP species, the infection rates ranged from 4.8% to 100%. In tpi sequence analysis, the assemblage A included subtypes A1, A2 and one novel subtype. Multi-locus analysis of the tpi, gdh, and bg genes detected 11 (8 known and 3 new), 6 (3 known and 3 new) and 9 (2 known and 7 new) subtypes in 88, 47 and 35 isolates in assemblage B, respectively. Thirty-two assemblage B isolates with data at all three loci yielded 15 multi-locus genotypes (MLGs), including 2 known and 13 new MLGs. Phylogenetic analysis of concatenated sequences of assemblage B showed that MLGs found here were genetically different from those of humans, NHPs, rabbit and guinea pig in Italy and Sweden. It further indicated that assemblage B isolates in ring-tailed lemurs and squirrel monkeys might be genetically different from those in other NHPs. These data suggest that NHPs are mainly infected with G. duodenalis assemblage B and there might be geographical segregation and host-adaptation in assemblage B in NHPs. |
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