Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-30 (of 52 Records) |
Query Trace: Alonso L[original query] |
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Genomic characterization of the rotavirus G3P[8] strain in vaccinated children, reveals possible reassortment events between human and animal strains in Manhia District, Mozambique
Manjate F , João ED , Mwangi P , Chirinda P , Mogotsi M , Messa A Jr , Garrine M , Vubil D , Nobela N , Nhampossa T , Acácio S , Tate JE , Parashar U , Weldegebriel G , Mwenda JM , Alonso PL , Cunha C , Nyaga M , Mandomando I . Front Microbiol 2023 14 1193094 Mozambique introduced the rotavirus vaccine (Rotarix®; GlaxoSmithKline Biologicals, Rixensart, Belgium) in 2015, and since then, the Centro de Investigação em Saúde de Manhiça has been monitoring its impact on rotavirus-associated diarrhea and the trend of circulating strains, where G3P[8] was reported as the predominant strain after the vaccine introduction. Genotype G3 is among the most commonly detected Rotavirus strains in humans and animals, and herein, we report on the whole genome constellation of G3P[8] detected in two children (aged 18 months old) hospitalized with moderate-to-severe diarrhea at the Manhiça District Hospital. The two strains had a typical Wa-like genome constellation (I1-R1-C1-M1-A1-N1-T1-E1-H1) and shared 100% nucleotide (nt) and amino acid (aa) identities in 10 gene segments, except for VP6. Phylogenetic analysis demonstrated that genome segments encoding VP7, VP6, VP1, NSP3, and NSP4 of the two strains clustered most closely with porcine, bovine, and equine strains with identities ranging from 86.9-99.9% nt and 97.2-100% aa. Moreover, they consistently formed distinct clusters with some G1P[8], G3P[8], G9P[8], G12P[6], and G12P[8] strains circulating from 2012 to 2019 in Africa (Mozambique, Kenya, Rwanda, and Malawi) and Asia (Japan, China, and India) in genome segments encoding six proteins (VP2, VP3, NSP1-NSP2, NSP5/6). The identification of segments exhibiting the closest relationships with animal strains shows significant diversity of rotavirus and suggests the possible occurrence of reassortment events between human and animal strains. This demonstrates the importance of applying next-generation sequencing to monitor and understand the evolutionary changes of strains and evaluate the impact of vaccines on strain diversity. |
Targeted and whole-genome sequencing reveal a north-south divide in P. falciparum drug resistance markers and genetic structure in Mozambique
da Silva C , Boene S , Datta D , Rovira-Vallbona E , Aranda-Díaz A , Cisteró P , Hathaway N , Tessema S , Chidimatembue A , Matambisso G , Nhama A , Macete E , Pujol A , Nhamussua L , Galatas B , Guinovart C , Enosse S , De Carvalho E , Rogier E , Plucinski MM , Colborn J , Zulliger R , Saifodine A , Alonso PL , Candrinho B , Greenhouse B , Aide P , Saute F , Mayor A . Commun Biol 2023 6 (1) 619 Mozambique is one of the four African countries which account for over half of all malaria deaths worldwide, yet little is known about the parasite genetic structure in that country. We performed P. falciparum amplicon and whole genome sequencing on 2251 malaria-infected blood samples collected in 2015 and 2018 in seven provinces of Mozambique to genotype antimalarial resistance markers and interrogate parasite population structure using genome-wide microhaplotyes. Here we show that the only resistance-associated markers observed at frequencies above 5% were pfmdr1-184F (59%), pfdhfr-51I/59 R/108 N (99%) and pfdhps-437G/540E (89%). The frequency of pfdhfr/pfdhps quintuple mutants associated with sulfadoxine-pyrimethamine resistance increased from 80% in 2015 to 89% in 2018 (p < 0.001), with a lower expected heterozygosity and higher relatedness of microhaplotypes surrounding pfdhps mutants than wild-type parasites suggestive of recent selection. pfdhfr/pfdhps quintuple mutants also increased from 72% in the north to 95% in the south (2018; p < 0.001). This resistance gradient was accompanied by a concentration of mutations at pfdhps-436 (17%) in the north, a south-to-north increase in the genetic complexity of P. falciparum infections (p = 0.001) and a microhaplotype signature of regional differentiation. The parasite population structure identified here offers insights to guide antimalarial interventions and epidemiological surveys. |
Dengue vaccine acceptability before and after the availability of COVID-19 vaccines in Puerto Rico
Rodriguez DM , Major CG , Sánchez-González L , Jones E , Delorey MJ , Alonso C , Rivera-Amill V , Paz-Bailey G , Adams LE . Vaccine 2023 Dengue is a growing public health threat, causing approximately 400 million infections annually. In June 2021, the Advisory Committee on Immunization Practices recommended the first dengue vaccine (CYD-TDV) for children aged 9-16 years with a previous dengue infection, living in endemic areas, such as Puerto Rico (PR). As the COVID-19 pandemic affected vaccine intention worldwide, we assessed dengue vaccine intention before (pre-COVID) and after (post-COVID) COVID-19 vaccine availability among participants enrolled in the Communities Organized to Prevent Arboviruses (COPA) cohort to prepare for dengue vaccine implementation in PR. We used logistic regression models to evaluate changes in dengue vaccine intention by interview timing and participant characteristics. Among 2,513 participants pre-COVID, 2,512 answered the dengue vaccine intention question for themselves, and 1,564 answered relative to their children. Post-COVID, dengue vaccine intention in adults increased for themselves from 73.4% to 84.5% (adjusted odds ratio (aOR) = 2.27, 95%CI: 1.90-2.71) and relative to their children from 75.6% to 85.5% (aOR = 2.21, 95%CI: 1.75-2.78). Among all participants, groups with higher dengue vaccine intention included those who reported previous year influenza vaccine uptake and those who reported being frequently bitten by mosquitos, compared to those who did not. Adult males were also more likely to intend to vaccinate themselves than females. Respondents who were employed or in school were less likely to intend to vaccinate compared to those who were not working. The primary reasons for vaccine hesitancy were concerns with side effects and not believing in vaccines, which should be considered during educational strategies prior to dengue vaccine implementation. In general, dengue vaccine intention is high in PR and has increased after COVID-19 vaccine availability, potentially due to increased awareness of vaccine importance during the COVID-19 pandemic. |
Reply to Alonso et al. "Bangladesh and Rwanda: Cases of high burden of influenza in tropical countries?"
Ahmed M , Roguski K , Tempia S , Iuliano AD . Influenza Other Respir Viruses 2018 12 (5) 669-671 We thank Dr. Alonso et al for their commentary1 on our articles, “Estimates of Seasonal Influenza‐Associated Mortality in Bangladesh, 2010‐2012”2 and “The National Burden of Influenza‐Associated Severe Acute Respiratory Illness Hospitalization in Rwanda, 2012‐2014.”3 In their commentary, they described three assumptions that we would like to address: (1) their use of “substantial” burden compared to “high” burden, (2) the comparability of influenza burden in tropical climate countries, and (3) the impact of the influenza A(H1N1)pdm09 virus on mortality. In addition, they describe three concerns about our estimates, which we would also like to clarify, specifically: (4) a mismatch in the timing of respiratory deaths and the influenza virus circulation period, (5) mortality attribution, and (6) the comparison with Institute of Health Metrics and Evaluation (IHME) estimates. We will address each of these comments or concerns in this brief response. |
Correction: Comparative outcomes for mature T and NK/T-cell lymphomas in people with and without HIV and to AIDS-defining lymphomas
Koh MJ , Merrill MH , Koh MJ , Stuver R , Alonso CD , Foss FM , Mayor AM , Gill J , Epeldegui M , Cachay E , Thorne JE , Silverberg MJ , Horberg MA , Atlhoff KN , Nijhawan AE , McGinnis KA , Lee JS , Rabkin CS , Napravnik S , Li J , Castilho JL , Shen C , Jain S . Blood Adv 2022 6 (15) 4436 An author's name was misspelled in the byline on page 1420. “Keri N. Atlhoff” should read “Keri N. Althoff.” The error has been corrected in the published article. |
Impact of rotavirus vaccination on diarrheal hospitalizations in children younger than 5years of age in a rural southern Mozambique
Manjate F , Quintó L , Chirinda P , Acácio S , Garrine M , Vubil D , Nhampossa T , João ED , Nhacolo A , Cossa A , Massora S , Bambo G , Bassat Q , Kotloff K , Levine M , Alonso PL , Tate JE , Parashar U , Mwenda JM , Mandomando I . Vaccine 2022 40 (44) 6422-6430 BACKGROUND: Rotavirus vaccine(Rotarix®) was introduced in Mozambique through its Expanded Program of Immunization in September 2015. We assessed the impact of rotavirus vaccination on childhood gastroenteritis-associated hospitalizations post-vaccine introduction in a high HIV prevalence rural setting of southern Mozambique. METHODS: We reviewed and compared the trend of hospitalizations (prevalence) and incidence rates of acute gastroenteritis (AGE), and rotavirus associated-diarrhea (laboratory confirmed rotavirus) in pre- (January 2008-August 2015) and post-rotavirus vaccine introduction periods (September 2015-December 2020), among children <5 years of age admitted to Manhiça District Hospital. RESULTS: From January 2008 to December 2020, rotavirus vaccination was found to contribute to the decline of the prevalence of AGE from 19% (95% CI: 18.14-20.44) prior to the vaccine introduction to 10% (95% CI: 8.89-11.48) in the post-introduction period, preventing 40% (95 % IE: 38-42) and 84% (95 % IE: 80-87) of the expected AGE and laboratory confirmed rotavirus cases, respectively, among infants. Similarly, the overall incidence of rotavirus was 11.8-fold lower in the post-vaccine introduction period (0.4/1000 child-years-at-risk [CYAR]; 95% CI: 0.3-0.6) compared with the pre-vaccination period (4.7/1000 CYAR; 95% CI: 4.2-5.1) with the highest reduction being observed among infants (16.8-fold lower from the 15.1/1000 CYAR in the pre-vaccine to 0.9/1000 CYAR in the post-vaccine eras). CONCLUSIONS: We documented a significant reduction in all-cause diarrhea hospitalizations and rotavirus positivity after vaccine introduction demonstrating the beneficial impact of rotavirus vaccination in a highly vulnerable population. |
Emergence of a multidrug-resistant and virulent Streptococcus pneumoniae lineage mediates serotype replacement after PCV13: an international whole-genome sequencing study.
Lo SW , Mellor K , Cohen R , Alonso AR , Belman S , Kumar N , Hawkins PA , Gladstone RA , von Gottberg A , Veeraraghavan B , Ravikumar KL , Kandasamy R , Pollard SAJ , Saha SK , Bigogo G , Antonio M , Kwambana-Adams B , Mirza S , Shakoor S , Nisar I , Cornick JE , Lehmann D , Ford RL , Sigauque B , Turner P , Moïsi J , Obaro SK , Dagan R , Diawara I , Skoczyńska A , Wang H , Carter PE , Klugman KP , Rodgers G , Breiman RF , McGee L , Bentley SD , Almagro CM , Varon E . Lancet Microbe 2022 3 (10) e735-e743 BACKGROUND: Serotype 24F is one of the emerging pneumococcal serotypes after the introduction of pneumococcal conjugate vaccine (PCV). We aimed to identify lineages driving the increase of serotype 24F in France and place these findings into a global context. METHODS: Whole-genome sequencing was performed on a collection of serotype 24F pneumococci from asymptomatic colonisation (n=229) and invasive disease (n=190) isolates among individuals younger than 18 years in France, from 2003 to 2018. To provide a global context, we included an additional collection of 24F isolates in the Global Pneumococcal Sequencing (GPS) project database for analysis. A Global Pneumococcal Sequence Cluster (GPSC) and a clonal complex (CC) were assigned to each genome. Phylogenetic, evolutionary, and spatiotemporal analysis were conducted using the same 24F collection and supplemented with a global collection of genomes belonging to the lineage of interest from the GPS project database (n=25 590). FINDINGS: Serotype 24F was identified in numerous countries mainly due to the clonal spread of three lineages: GPSC10 (CC230), GPSC16 (CC156), and GPSC206 (CC7701). GPSC10 was the only multidrug-resistant lineage. GPSC10 drove the increase in 24F in France and had high invasive disease potential. The international dataset of GPSC10 (n=888) revealed that this lineage expressed 16 other serotypes, with only six included in 13-valent PCV (PCV13). All serotype 24F isolates were clustered in a single clade within the GPSC10 phylogeny and long-range transmissions were detected from Europe to other continents. Spatiotemporal analysis showed GPSC10-24F took 3-5 years to spread across France and a rapid change of serotype composition from PCV13 serotype 19A to 24F during the introduction of PCV13 was observed in neighbouring country Spain. INTERPRETATION: Our work reveals that GPSC10 alone is a challenge for serotype-based vaccine strategy. More systematic investigation to identify lineages like GPSC10 will better inform and improve next-generation preventive strategies against pneumococcal diseases. FUNDING: Bill & Melinda Gates Foundation, Wellcome Sanger Institute, and the US Centers for Disease Control and Prevention. |
Assessment of country implementation of the WHO Global Health Sector Strategy on Sexually Transmitted Infections (2016-2021)
Taylor MM , Wi T , Gerbase A , Thwin SS , Gottlieb S , Babovic MT , Low-Beer D , Alonso M , Mello MB , Ishikawa N , Brink A , Hermez J , Sabry A , Sanni S , Ouedraogo L , Rewari B , Sharma M , Seguy N , Vovc E , Askew I , Doherty M , Broutet N . PLoS One 2022 17 (5) e0263550 BACKGROUND: In 2016, WHO launched the Global Health Sector Strategy on STIs, 2016-2021 (GHSS) to provide guidance and benchmarks for country achievement by 2020 and four global targets for achievement by 2030. METHODS: A country survey jointly developed by experienced technical personnel at WHO Headquarters (HQ) and WHO regional offices was reviewed and distributed by WHO regional advisors to 194 WHO Member States in September-March 2020. The survey sought to assess implementation and prioritization of STI policy, surveillance, service delivery, commodity availability, and surveillance based on targets of the GHSS. RESULTS: A majority (58%, 112/194) of countries returned a completed survey reflecting current (2019) STI activities. The regions with the highest survey completion rates were South-East Asia Region (91%, 10/11), Region of the Americas (71%, 25/35) and Western Pacific Region (67%, 18/27). Having a national STI strategy was reported by 64% (72/112) and performing STI surveillance activities by 88% (97/110) of reporting countries. Availability of STI services within primary health clinics was reported by 88% of countries (99/112); within HIV clinics by 92% (103/112), and within reproductive health services by 85% (95/112). Existence of a national strategy to eliminate mother-to-child transmission of HIV and syphilis (EMTCT) was reported by 70% of countries (78/112). Antimicrobial resistance (AMR) monitoring for gonococcal infection (gonorrhoea) was reported by 64% (57/89) of reporting countries with this laboratory capacity. Inclusion of HPV vaccine for young women in the national immunization schedule was reported by 59% (65/110) and availability of cervical cancer screening was reported by 91% (95/104). Stockouts of STI medicines, primarily benzathine penicillin, within the prior four years were reported by 34% (37/110) of countries. CONCLUSIONS: Mechanisms to support improvements to STI service delivery through national-level policy, commitment, programming and surveillance are needed to operationalize, accelerate and monitor progress towards achievement of the 2030 global STI strategy targets. |
WHO method for estimating congenital syphilis to inform surveillance and service provision, Paraguay
Heath K , Alonso M , Aguilar G , Samudio T , Korenromp E , Rowley J , Suleiman A , Shwe YY , Htin KCW , Ishikawa N , Owiredu MN , Taylor M . Bull World Health Organ 2022 100 (3) 231-236 PROBLEM: In Paraguay, incomplete surveillance data resulted in the burden of congenital syphilis being underestimated, which, in turn, led to missed opportunities for infant diagnosis and treatment. APPROACH: The prevalence of congenital syphilis, as defined by the World Health Organization (WHO), was estimated for Paraguay using the WHO congenital syphilis estimation tool. This tool was also used to monitor progress towards the elimination of mother-to-child transmission of syphilis. LOCAL SETTING: The burden of syphilis in Paraguay has historically been high: its prevalence in pregnant women was estimated to be 3% in 2018. RELEVANT CHANGES: The incidence rate of congenital syphilis estimated using the WHO tool was around nine times the reported prevalence. Subsequently, Paraguay: (i) provided training to improve diagnosis and case reporting; (ii) strengthened information systems for case monitoring and reporting; and (iii) procured additional rapid dual HIV-syphilis and rapid plasma reagin tests to increase syphilis testing capacity. In addition, the Ministry of Health prepared a new national plan for eliminating mother-to-child transmission of syphilis, with clear monitoring milestones. LESSONS LEARNT: Health-care providers' reporting and surveillance procedures for congenital syphilis may not adequately reflect national and international case definitions. Use of the WHO congenital syphilis estimation tool in Paraguay drew attention to congenital syphilis as a national public health problem and highlighted the importance of comprehensive national surveillance systems and accurate data. Ongoing use of the WHO tool can track progress towards the elimination of mother-to-child transmission of syphilis by helping improve syphilis service coverage and national surveillance. |
Molecular Epidemiology of Rotavirus Strains in Symptomatic and Asymptomatic Children in Manhiça District, Southern Mozambique 2008-2019.
Manjate F , João ED , Chirinda P , Garrine M , Vubil D , Nobela N , Kotloff K , Nataro JP , Nhampossa T , Acácio S , Tate JE , Parashar U , Mwenda JM , Alonso PL , Nyaga M , Cunha C , Mandomando I . Viruses 2022 14 (1) Group A rotaviruses remain the leading cause of diarrhoea in children aged <5 years. Mozambique introduced rotavirus vaccine (Rotarix(®)) in September 2015. We report rotavirus genotypes circulating among symptomatic and asymptomatic children in Manhiça District, Mozambique, pre- and post-vaccine introduction. Stool was collected from enrolled children and screened for rotavirus by enzyme-immuno-sorbent assay. Positive specimens were genotyped for VP7 (G genotypes) and VP4 (P genotypes) by the conventional reverse transcriptase polymerase chain reaction. The combination G12P[8] was more frequently observed in pre-vaccine than in post-vaccine introduction, in moderate to severe diarrhoea (34%, 61/177 vs. 0, p < 0.0001) and controls (23%, 26/113 vs. 0, p = 0.0013) and mixed genotypes (36%, 24/67 vs. 7% 4/58, p = 0.0003) in less severe diarrhoea. We observed changes in post-vaccine compared to pre-vaccine introduction, where G3P[4] and G3P[8] were prevalent in moderate to severe diarrhoea (10%, 5/49 vs. 0, p = 0.0002; and 14%, 7/49 vs. 1%, 1/177, p < 0.0001; respectively), and in less severe diarrhoea (21%, 12/58 vs. 0, p = 0.003; and 24%, 14/58 vs. 0, p < 0.0001; respectively). Our surveillance demonstrated the circulation of similar genotypes contemporaneously among cases and controls, as well as switching from pre- to post-vaccine introduction. Continuous surveillance is needed to evaluate the dynamics of the changes in genotypes following vaccine introduction. |
Comparative outcomes for mature T and NK/T-cell lymphomas in people with and without HIV and to AIDS-defining lymphomas
Koh MJ , Merrill MH , Koh MJ , Stuver R , Alonso CD , Foss FM , Mayor AM , Gill J , Epeldegui M , Cachay E , Thorne JE , Silverberg MJ , Horberg MA , Atlhoff KN , Nijhawan AE , McGinnis KA , Lee JS , Rabkin CS , Napravnik S , Li J , Castilho JL , Shen C , Jain S . Blood Adv 2022 6 (5) 1420-1431 There are no studies comparing the prognosis for mature T-cell lymphoma (TCL) in people with human immunodeficiency virus (PWH) to people without HIV (PWoH) and to AIDS-defining B-cell lymphomas (A-BCL) in the modern antiretroviral therapy (ART) era. NA-ACCORD and COMPLETE are cohorts that enroll patients diagnosed with HIV and TCL, respectively. In our study 52, 64, 101, 500 and 246 PWH with histological confirmation of TCL, primary CNS, Burkitt's, diffuse large B-cell lymphoma (DLBCL) and Hodgkin's lymphoma (HL) respectively and 450 TCL without HIV were eligible for analysis. At the time of TCL diagnosis, Anaplastic large-cell lymphoma (ALCL) was the most common TCL subtype within PWH. While PWH with TCL diagnosed between 1996-2009, experienced a low 5-year survival probability at 0.23 (95% CI: 0.13, 0.41), we observed a marked improvement in their survival when diagnosed between 2010-2016 (0.69; 95% CI: 0.48, 1; p=0.04) in contrast to TCL among PWoH (0.45; 95% CI: 0.41, 0.51; p=0.53). Similarly, PWH with ALCL diagnosed between 1996-2009 were associated with a conspicuously inferior 5-year survival probability (0.17; 95% CI: 0.07, 0.42) and consistently lagged behind A-BCL subtypes such as Burkitt's (0.43; 95% CI:0.33, 0.57; p=0.09) and DLBCL (0.17; 95% CI: 0.06, 0.46; p=0.11) and behind HL (0.57; 95% CI: 0.50, 0.65; p <0.0001). Despite a small number, those diagnosed between 2010-2016, experienced a remarkable improvement in survival (0.67; 95% CI: 0.3, 1) in comparison to PWoH (0.76; 95% CI: 0.66, 0.87; p=0.58). Thus, our analysis confirms improved overall survival for aggressive B and T-cell malignancies among PWH in the last decade. |
Evolutionary history of orangutan plasmodia revealed by phylogenetic analysis of complete mtDNA genomes and new biogeographical divergence dating calibration models.
Reid MJC , Switzer WM , Alonso SK , Lowenberger CA , Schillaci MA . Am J Primatol 2021 84 e23298 During the past 15 years, researchers have shown a renewed interest in the study of the Plasmodium parasites that infect orangutans. Most recently, studies examined the phylogenetic relationships and divergence dates of these parasites in orangutans using complete mitochondrial DNA genomes. Questions regarding the dating of these parasites, however, remain. In the present study, we provide a new calibration model for dating the origins of Plasmodium parasites in orangutans using a modified date range for the origin of macaques in Asia. Our Bayesian phylogenetic analyses of complete Plasmodium sp. mitochondrial DNA genomes inferred two clades of plasmodia in orangutans (Pongo 1 and Pongo 2), and that these clades likely represent the previously identified species Plasmodium pitheci and Plasmodium silvaticum. However, we cannot identify which Pongo clade is representative of the morphologically described species. The most recent common ancestor of both Pongo sp. plasmodia, Plasmodium. hylobati, and Plasmodium. inui dates to 3-3.16 million years ago (mya) (95% highest posterior density [HPD]: 2.09-4.08 mya). The Pongo 1 parasite diversified 0.33-0.36 mya (95% HPD: 0.12-0.63), while the Pongo 2 parasite diversified 1.15-1.22 mya (95% HPD: 0.63-1.82 mya). It now seems likely that the monkey Plasmodium (P. inui) is the result of a host switch event from the Pongo 2 parasite to sympatric monkeys, or P. hylobati. Our new estimates for the divergence of orangutan malaria parasites, and subsequent diversification, are all several hundred thousand years later than previous Bayesian estimates. |
Cost and cost-effectiveness of indoor residual spraying with pirimiphos-methyl in a high malaria transmission district of Mozambique with high access to standard insecticide-treated nets
Alonso S , Chaccour CJ , Wagman J , Candrinho B , Muthoni R , Saifodine A , Saute F , Robertson M , Zulliger R . Malar J 2021 20 (1) 143 BACKGROUND: As malaria cases increase in some of the highest burden countries, more strategic deployment of new and proven interventions must be evaluated to meet global malaria reduction goals. METHODS: The cost and cost-effectiveness of indoor residual spraying (IRS) with pirimiphos-methyl (Actellic®300 CS) were assessed in a high transmission district (Mopeia) with high access to pyrethroid insecticide-treated nets (ITNs), compared to ITNs alone. The major mosquito vectors in the area were susceptible to primiphos-methyl, but resistant to pyrethoids. A decision analysis approach was followed to conduct deterministic and probabilistic sensitivity analyses in a theoretical cohort of 10,000 children under five years of age (U5) and 10,000 individuals of all ages, separately. Model parameters and distributions were based on prospectively collected cost and epidemiological data from a cluster-randomized control trial and a literature review. The primary analysis used health facility-malaria incidence, while community cohort incidence and cross-sectional prevalence rates were used in sensitivity analyses. Lifetime costs, malaria cases, deaths and disability-adjusted life-years (DALYs) were calculated to determine the incremental costs per DALY averted through IRS. RESULTS: The average IRS cost per person protected was US$8.26 and 51% of the cost was insecticide. IRS averted 46,609 (95% CI 46,570-46,646) uncomplicated and 242 (95% CI 241-243) severe lifetime cases in a theoretical children U5 cohort, yielding an incremental cost-effectiveness ratio (ICER) of US$400 (95% CI 399-402) per DALY averted. In the all-age cohort, the ICER was higher: US$1,860 (95% CI 1,852-1,868) per DALY averted. Deterministic and probabilistic results were consistent. When adding the community protective effect of IRS, the cost per person protected decreased (US$7.06) and IRS was highly cost-effective in children U5 (ICER = US$312) and cost-effective in individuals of all ages (ICER = US$1,431), compared to ITNs alone. CONCLUSION: This study provides robust evidence that IRS with pirimiphos-methyl can be cost-effective in high transmission regions with high pyrethroid ITN coverage where the major vector is susceptible to pirimiphos-methyl but resistant to pyrethroids. The finding that insecticide cost is the main driver of IRS costs highlights the need to reduce the insecticide price without jeopardizing effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02910934 (Registered 22 September 2016). https://clinicaltrials.gov/ct2/show/NCT02910934?term=NCT02910934&draw=2&rank=1. |
Characteristics of Salmonella recovered from stools of children enrolled in the Global Enteric Multicenter Study.
Kasumba IN , Pulford CV , Perez-Sepulveda BM , Sen S , Sayed N , Permala-Booth J , Livio S , Heavens D , Low R , Hall N , Roose A , Powell H , Farag T , Panchalingham S , Berkeley L , Nasrin D , Blackwelder WC , Wu Y , Tamboura B , Sanogo D , Onwuchekwa U , Sow SO , Ochieng JB , Omore R , Oundo JO , Breiman RF , Mintz ED , O'Reilly CE , Antonio M , Saha D , Hossain MJ , Mandomando I , Bassat Q , Alonso PL , Ramamurthy T , Sur D , Qureshi S , Zaidi AKM , Hossain A , Faruque ASG , Nataro JP , Kotloff KL , Levine MM , Hinton JCD , Tennant SM . Clin Infect Dis 2021 73 (4) 631-641 BACKGROUND: The Global Enteric Multicenter Study (GEMS) determined the etiologic agents of moderate-to-severe diarrhea (MSD) in children under 5 years old in Africa and Asia. Here, we describe the prevalence and antimicrobial susceptibility of non-typhoidal Salmonella (NTS) serovars in GEMS and examine the phylogenetics of Salmonella Typhimurium ST313 isolates. METHODS: Salmonella isolated from children with MSD or diarrhea-free controls were identified by classical clinical microbiology and serotyped using antisera and/or whole genome sequence data. We evaluated antimicrobial susceptibility using the Kirby-Bauer disk diffusion method. Salmonella Typhimurium sequence types were determined using multi-locus sequence typing and whole genome sequencing was performed to assess the phylogeny of ST313. RESULTS: Out of 370 Salmonella-positive individuals, 190 (51.4%) were MSD cases and 180 (48.6%) were diarrhea-free controls. The most frequent Salmonella serovars identified were Salmonella Typhimurium, serogroup O:8 (C2-C3), serogroup O:6,7 (C1), Salmonella Paratyphi B Java and serogroup O:4 (B). The prevalence of NTS was low but similar across sites, regardless of age, and was similar amongst both cases and controls except in Kenya, where Salmonella Typhimurium was more commonly associated with cases than controls. Phylogenetic analysis showed that these Salmonella Typhimurium isolates, all ST313, were highly genetically related to isolates from controls. Generally, Salmonella isolates from Asia were resistant to ciprofloxacin and ceftriaxone but African isolates were susceptible to these antibiotics. CONCLUSION: Our data confirms that NTS is prevalent, albeit at low levels, in Africa and South Asia. Our findings provide further evidence that multi-drug resistant Salmonella Typhimurium ST313 can be carried asymptomatically by humans in sub-Saharan Africa. |
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. |
Diarrhoeal disease and subsequent risk of death in infants and children residing in low-income and middle-income countries: analysis of the GEMS case-control study and 12-month GEMS-1A follow-on study
Levine MM , Nasrin D , Acacio S , Bassat Q , Powell H , Tennant SM , Sow SO , Sur D , Zaidi AKM , Faruque ASG , Hossain MJ , Alonso PL , Breiman RF , O'Reilly CE , Mintz ED , Omore R , Ochieng JB , Oundo JO , Tamboura B , Sanogo D , Onwuchekwa U , Manna B , Ramamurthy T , Kanungo S , Ahmed S , Qureshi S , Quadri F , Hossain A , Das SK , Antonio M , Saha D , Mandomando I , Blackwelder WC , Farag T , Wu Y , Houpt ER , Verweiij JJ , Sommerfelt H , Nataro JP , Robins-Browne RM , Kotloff KL . Lancet Glob Health 2019 8 (2) e204-e214 BACKGROUND: The Global Enteric Multicenter Study (GEMS) was a 3-year case-control study that measured the burden, aetiology, and consequences of moderate-to-severe diarrhoea (MSD) in children aged 0-59 months. GEMS-1A, a 12-month follow-on study, comprised two parallel case-control studies, one assessing MSD and the other less-severe diarrhoea (LSD). In this report, we analyse the risk of death with each diarrhoea type and the specific pathogens associated with fatal outcomes. METHODS: GEMS was a prospective, age-stratified, matched case-control study done at seven sites in Africa and Asia. Children aged 0-59 months with MSD seeking care at sentinel health centres were recruited along with one to three randomly selected matched community control children without diarrhoea. In the 12-month GEMS-1A follow-on study, children with LSD and matched controls, in addition to children with MSD and matched controls, were recruited at six of the seven sites; only cases of MSD and controls were enrolled at the seventh site. We compared risk of death during the period between enrolment and one follow-up household visit done about 60 days later (range 50-90 days) in children with MSD and LSD and in their respective controls. Approximately 50 pathogens were detected using, as appropriate, classic bacteriology, immunoassays, gel-based PCR and reverse transcriptase PCR, and quantitative real-time PCR (qPCR). Specimens from a subset of GEMS cases and controls were also tested by a TaqMan Array Card that compartmentalised probe-based qPCR for 32 enteropathogens. FINDINGS: 223 (2.0%) of 11 108 children with MSD and 43 (0.3%) of 16 369 matched controls died between study enrolment and the follow-up visit at about 60 days (hazard ratio [HR] 8.16, 95% CI 5.69-11.68, p<0.0001). 12 (0.4%) of 2962 children with LSD and seven (0.2%) of 4074 matched controls died during the follow-up period (HR 2.78, 95% CI 0.95-8.11, p=0.061). Risk of death was lower in children with dysenteric MSD than in children with non-dysenteric MSD (HR 0.20, 95% CI 0.05-0.87, p=0.032), and lower in children with LSD than in those with non-dysenteric MSD (HR 0.29, 0.14-0.59, p=0.0006). In children younger than 24 months with MSD, infection with typical enteropathogenic Escherichia coli, enterotoxigenic E coli encoding heat-stable toxin, enteroaggregative E coli, Shigella spp (non-dysentery cases), Aeromonas spp, Cryptosporidium spp, and Entamoeba histolytica increased risk of death. Of 61 deaths in children aged 12-59 months with non-dysenteric MSD, 31 occurred among 942 children qPCR-positive for Shigella spp and 30 deaths occurred in 1384 qPCR-negative children (HR 2.2, 95% CI 1.2-3.9, p=0.0090), showing that Shigella was strongly associated with increased risk of death. INTERPRETATION: Risk of death is increased following MSD and, to a lesser extent, LSD. Considering there are approximately three times more cases of LSD than MSD in the population, more deaths are expected among children with LSD than in those with MSD. Because the major attributable LSD-associated and MSD-associated pathogens are the same, implementing vaccines and rapid diagnosis and treatment interventions against these major pathogens are rational investments. FUNDING: Bill & Melinda Gates Foundation. |
Determinants of linear growth faltering among children with moderate-to-severe diarrhea in the Global Enteric Multicenter Study
Brander RL , Pavlinac PB , Walson JL , John-Stewart GC , Weaver MR , Faruque ASG , Zaidi AKM , Sur D , Sow SO , Hossain MJ , Alonso PL , Breiman RF , Nasrin D , Nataro JP , Levine MM , Kotloff KL . BMC Med 2019 17 (1) 214 BACKGROUND: Moderate-to-severe diarrhea (MSD) in the first 2 years of life can impair linear growth. We sought to determine risk factors for linear growth faltering and to build a clinical prediction tool to identify children most likely to experience growth faltering following an episode of MSD. METHODS: Using data from the Global Enteric Multicenter Study of children 0-23 months old presenting with MSD in Africa and Asia, we performed log-binomial regression to determine clinical and sociodemographic factors associated with severe linear growth faltering (loss of >/= 0.5 length-for-age z-score [LAZ]). Linear regression was used to estimate associations with DeltaLAZ. A clinical prediction tool was developed using backward elimination of potential variables, and Akaike Information Criterion to select the best fit model. RESULTS: Of the 5902 included children, mean age was 10 months and 43.2% were female. Over the 50-90-day follow-up period, 24.2% of children had severe linear growth faltering and the mean DeltaLAZ over follow-up was - 0.17 (standard deviation [SD] 0.54). After adjustment for age, baseline LAZ, and site, several factors were associated with decline in LAZ: young age, acute malnutrition, hospitalization at presentation, non-dysenteric diarrhea, unimproved sanitation, lower wealth, fever, co-morbidity, or an IMCI danger sign. Compared to children 12-23 months old, those 0-6 months were more likely to experience severe linear growth faltering (adjusted prevalence ratio [aPR] 1.97 [95% CI 1.70, 2.28]), as were children 6-12 months of age (aPR 1.72 [95% CI 1.51, 1.95]). A prediction model that included age, wasting, stunting, presentation with fever, and presentation with an IMCI danger sign had an area under the ROC (AUC) of 0.67 (95% CI 0.64, 0.69). Risk scores ranged from 0 to 37, and a cut-off of 21 maximized sensitivity (60.7%) and specificity (63.5%). CONCLUSION: Younger age, acute malnutrition, MSD severity, and sociodemographic factors were associated with short-term linear growth deterioration following MSD. Data routinely obtained at MSD may be useful to predict children at risk for growth deterioration who would benefit from interventions. |
The economic burden of malaria on households and the health system in a high transmission district of Mozambique
Alonso S , Chaccour CJ , Elobolobo E , Nacima A , Candrinho B , Saifodine A , Saute F , Robertson M , Zulliger R . Malar J 2019 18 (1) 360 BACKGROUND: Malaria remains a leading cause of morbidity and mortality in Mozambique. Increased investments in malaria control have reduced the burden, but few studies have estimated the costs of malaria in the country. This paper estimates the economic costs associated with malaria care to households and to the health system in the high burden district of Mopeia in central Mozambique. METHODS: Malaria care-seeking and morbidity costs were routinely collected among 1373 households with at least one child enrolled in an active case detection (ACD) cohort in Mopeia, and through cross-sectional surveys with 824 families in 2017 and 805 families in 2018. Household costs included direct medical expenses, transportation and opportunity costs of the time lost due to illness. Structured questionnaires were used to estimate the health system costs associated with malaria care in all 13 district health facilities. Cost estimations followed an ingredient-based approach with a top-down allocation approach for health system expenses. RESULTS: Among participants in cross-sectional studies, households sought care for nine severe malaria cases requiring hospital admission and for 679 uncomplicated malaria cases. Median household costs associated with uncomplicated malaria among individuals of all ages were US$ 3.46 (IQR US$ 0.07-22.41) and US$ 81.08 (IQR US$ 39.34-88.38) per severe case. Median household costs were lower among children under five (ACD cohort): US$ 1.63 (IQR US$ 0.00-7.79) per uncomplicated case and US$ 64.90 (IQR US$ 49.76-80.96) per severe case. Opportunity costs were the main source of household costs. Median health system costs associated with malaria among patients of all ages were US$ 4.34 (IQR US$ 4.32-4.35) per uncomplicated case and US$ 26.56 (IQR US$ 18.03-44.09) per severe case. Considering household and health system costs, the overall cost of malaria care to society was US$ 7.80 per uncomplicated case and US$ 107.64 per severe case, representing an economic malaria burden of US$ 332,286.24 (IQR US$ 186,355.84-1,091,212.90) per year only in Mopeia. CONCLUSIONS: Despite the provision of free malaria services, households in Mopeia incur significant direct and indirect costs associated with the disease. Furthermore, the high malaria cost on the Mozambican health system underscores the need to strengthen malaria prevention to reduce the high burden and improve productivity in the region. |
Obesity and diabetes in the Winnebago Tribe of Nebraska: From community engagement to action, 2014-2019
Alonso L , Decora L , Bauer UE . Prev Chronic Dis 2019 16 E103 The Winnebago Tribe of Nebraska implemented interventions to promote the health of their people, focusing on community-selected and culturally adapted policies, systems, and environmental (PSE) improvements to reduce the prevalence of obesity and type 2 diabetes. The interventions were implemented as part of the Centers for Disease Control and Prevention's (CDC's) 2014-2019 Good Health and Wellness in Indian Country program. The Winnebago Tribe used CDC's CHANGE community health assessment tool to prioritize and direct their interventions. They integrated findings from a community health assessment tool with observations from tribal working groups and implemented 6 new evidence-based PSE interventions. Their successful approaches - selected by the Winnebago community, culturally relevant, and driven by scientific assessment -demonstrate the value of flexibility in CDC grant programs. |
GENOTYPES AND POPULATION GENETICS OF CRYPTOCOCCUS NEOFORMANS AND CRYPTOCOCCUS GATTII SPECIES COMPLEXES IN EUROPE AND THE MEDITERRANEAN AREA.
Cogliati M , Desnos-Ollivier M , McCormick-Smith I , Rickerts V , Ferreira-Paim K , Meyer W , Boekhout T , Hagen F , Theelen B , Inacio J , Alonso B , Colom MF , Trilles L , Teresa Montagna M , De Donno A , Susever S , Ergin C , Velegraki A , Ellabib MS , Nardoni S , Macci C , Trovato L , Dipineto L , Akcaglar S , Mlinaric-Missoni E , Bertout S , Venca ACF , Sampaio AC , Criseo G , Ranque S , Cerikcioglu N , Marchese A , Vezzulli L , Ilkit M , Pasquale V , Polacheck I , Lockhart SR . Fungal Genet Biol 2019 129 16-29 A total of 476 European isolates (310 Cryptococcus neoformans var. grubii, 150 C. neoformans var. neoformans, and 16 C. gattii species complex) from both clinical and environmental sources were analyzed by multi-locus sequence typing. Phylogenetic and population genetic analyses were performed. Sequence analysis identified 74 sequence types among C. neoformans var. neoformans (VNIV), 65 among C. neoformans var. grubii (56 VNI, 8 VNII, 1 VNB), and 5 among the C. gattii species complex (4 VGI and 1 VGIV) isolates. ST23 was the most frequent genotype (22%) among VNI isolates which were mostly grouped in a large clonal cluster including 50% of isolates. Among VNIV isolates, a predominant genotype was not identified. A high percentage of autochthonous STs were identified in both VNI (71%) and VNIV (96%) group of isolates. The 16 European C. gattii species complex isolates analyzed in the present study originated all from the environment and all belonged to a large cluster endemic in the Mediterranean area. Population genetic analysis confirmed that VNI group of isolates were characterized by low variability and clonal expansion while VNIV by a higher variability and a number of recombination events. However, when VNI and VNIV environmental isolates were compared, they showed a similar population structure with a high percentage of shared mutations and the absence of fixed mutations. Also linkage disequilibrium analysis reveals differences between clinical and environmental isolates showing a key role of PLB1 allele combinations in host infection as well as the key role of LAC1 allele combinations for survival of the fungus in the environment. The present study shows that genetic comparison of clinical and environmental isolates represents a first step to understand the genetic characteristics that cause the shift of some genotypes from a saprophytic to a parasitic life style. |
Global burden of maternal and congenital syphilis and associated adverse birth outcomes-Estimates for 2016 and progress since 2012
Korenromp EL , Rowley J , Alonso M , Mello MB , Wijesooriya NS , Mahiane SG , Ishikawa N , Le LV , Newman-Owiredu M , Nagelkerke N , Newman L , Kamb M , Broutet N , Taylor MM . PLoS One 2019 14 (2) e0211720 BACKGROUND: In 2007 the World Health Organization (WHO) launched the global initiative to eliminate mother-to-child transmission of syphilis (congenital syphilis, or CS). To assess progress towards the goal of <50 CS cases per 100,000 live births, we generated regional and global estimates of maternal and congenital syphilis for 2016 and updated the 2012 estimates. METHODS: Maternal syphilis estimates were generated using the Spectrum-STI model, fitted to sentinel surveys and routine testing of pregnant women during antenatal care (ANC) and other representative population data. Global and regional estimates of CS used the same approach as previous WHO estimates. RESULTS: The estimated global maternal syphilis prevalence in 2016 was 0.69% (95% confidence interval: 0.57-0.81%) resulting in a global CS rate of 473 (385-561) per 100,000 live births and 661,000 (538,000-784,000) total CS cases, including 355,000 (290,000-419,000) adverse birth outcomes (ABO) and 306,000 (249,000-363,000) non-clinical CS cases (infants without clinical signs born to un-treated mothers). The ABOs included 143,000 early fetal deaths and stillbirths, 61,000 neonatal deaths, 41,000 preterm or low-birth weight births, and 109,000 infants with clinical CS. Of these ABOs- 203,000 (57%) occurred in pregnant women attending ANC but not screened for syphilis; 74,000 (21%) in mothers not enrolled in ANC, 55,000 (16%) in mothers screened but not treated, and 23,000 (6%) in mothers enrolled, screened and treated. The revised 2012 estimates were 0.70% (95% CI: 0.63-0.77%) maternal prevalence, and 748,000 CS cases (539 per 100,000 live births) including 397,000 (361,000-432,000) ABOs. The estimated decrease in CS case rates between 2012 and 2016 reflected increased access to ANC and to syphilis screening and treatment. CONCLUSIONS: Congenital syphilis decreased worldwide between 2012 and 2016, although maternal prevalence was stable. Achieving global CS elimination, however, will require improving access to early syphilis screening and treatment in ANC, clinically monitoring all women diagnosed with syphilis and their infants, improving partner management, and reducing syphilis prevalence in the general population by expanding testing, treatment and partner referral beyond ANC. |
Colonization factors among enterotoxigenic Escherichia coli isolates from children with moderate-to-severe diarrhea and from matched controls in the Global Enteric Multicenter Study (GEMS).
Vidal RM , Muhsen K , Tennant SM , Svennerholm AM , Sow SO , Sur D , Zaidi AKM , Faruque ASG , Saha D , Adegbola R , Hossain MJ , Alonso PL , Breiman RF , Bassat Q , Tamboura B , Sanogo D , Onwuchekwa U , Manna B , Ramamurthy T , Kanungo S , Ahmed S , Qureshi S , Quadri F , Hossain A , Das SK , Antonio M , Mandomando I , Nhampossa T , Acacio S , Omore R , Ochieng JB , Oundo JO , Mintz ED , O'Reilly CE , Berkeley LY , Livio S , Panchalingam S , Nasrin D , Farag TH , Wu Y , Sommerfelt H , Robins-Browne RM , Del Canto F , Hazen TH , Rasko DA , Kotloff KL , Nataro JP , Levine MM . PLoS Negl Trop Dis 2019 13 (1) e0007037 BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) encoding heat-stable enterotoxin (ST) alone or with heat-labile enterotoxin (LT) cause moderate-to-severe diarrhea (MSD) in developing country children. The Global Enteric Multicenter Study (GEMS) identified ETEC encoding ST among the top four enteropathogens. Since the GEMS objective was to provide evidence to guide development and implementation of enteric vaccines and other interventions to diminish diarrheal disease morbidity and mortality, we examined colonization factor (CF) prevalence among ETEC isolates from children age <5 years with MSD and from matched controls in four African and three Asian sites. We also assessed strength of association of specific CFs with MSD. METHODOLOGY/PRINCIPAL FINDINGS: MSD cases enrolled at healthcare facilities over three years and matched controls were tested in a standardized manner for many enteropathogens. To identify ETEC, three E. coli colonies per child were tested by polymerase chain reaction (PCR) to detect genes encoding LT, ST; confirmed ETEC were examined by PCR for major CFs (Colonization Factor Antigen I [CFA/I] or Coli Surface [CS] antigens CS1-CS6) and minor CFs (CS7, CS12, CS13, CS14, CS17, CS18, CS19, CS20, CS21, CS30). ETEC from 806 cases had a single toxin/CF profile in three tested strains per child. Major CFs, components of multiple ETEC vaccine candidates, were detected in 66.0% of LT/ST and ST-only cases and were associated with MSD versus matched controls by conditional logistic regression (p</=0.006); major CFs detected in only 25.0% of LT-only cases weren't associated with MSD. ETEC encoding exclusively CS14, identified among 19.9% of 291 ST-only and 1.5% of 259 LT/ST strains, were associated with MSD (p = 0.0011). No other minor CF exhibited prevalence >/=5% and significant association with MSD. CONCLUSIONS/SIGNIFICANCE: Major CF-based efficacious ETEC vaccines could potentially prevent up to 66% of pediatric MSD cases due to ST-encoding ETEC in developing countries; adding CS14 extends coverage to ~77%. |
Combination of indoor residual spraying with long-lasting insecticide-treated nets for malaria control in Zambezia, Mozambique: a cluster randomised trial and cost-effectiveness study protocol
Chaccour CJ , Alonso S , Zulliger R , Wagman J , Saifodine A , Candrinho B , Macete E , Brew J , Fornadel C , Kassim H , Loch L , Sacoor C , Varela K , Carty CL , Robertson M , Saute F . BMJ Glob Health 2018 3 (1) e000610 Background: Most of the reduction in malaria prevalence seen in Africa since 2000 has been attributed to vector control interventions. Yet increases in the distribution and intensity of insecticide resistance and higher costs of newer insecticides pose a challenge to sustaining these gains. Thus, endemic countries face challenging decisions regarding the choice of vector control interventions. Methods: A cluster randomised trial is being carried out in Mopeia District in the Zambezia Province of Mozambique, where malaria prevalence in children under 5 is high (68% in 2015), despite continuous and campaign distribution of long-lasting insecticide-treated nets (LLINs). Study arm 1 will continue to use the standard, LLIN-based National Malaria Control Programme vector control strategy (LLINs only), while study arm 2 will receive indoor residual spraying (IRS) once a year for 2 years with a microencapsulated formulation of pirimiphos-methyl (Actellic 300 CS), in addition to the standard LLIN strategy (LLINs+IRS). Prior to the 2016 IRS implementation (the first of two IRS campaigns in this study), 146 clusters were defined and stratified per number of households. Clusters were then randomised 1:1 into the two study arms. The public health impact and cost-effectiveness of IRS intervention will be evaluated over 2 years using multiple methods: (1) monthly active malaria case detection in a cohort of 1548 total children aged 6-59 months; (2) enhanced passive surveillance at health facilities and with community health workers; (3) annual cross-sectional surveys; and (4) entomological surveillance. Prospective microcosting of the intervention and provider and societal costs will be conducted. Insecticide resistance status pattern and changes in local Anopheline populations will be included as important supportive outcomes. Discussion: By evaluating the public health impact and cost-effectiveness of IRS with a non-pyrethroid insecticide in a high-transmission setting with high LLIN ownership, it is expected that this study will provide programmatic and policy-relevant data to guide national and global vector control strategies. Trial registration number: NCT02910934. |
Burden of invasive pneumococcal disease among children in rural Mozambique: 2001-2012
Sigauque B , Verani JR , Massora S , Vubil D , Quinto L , Acacio S , Mandomando I , Bassat Q , Nhampossa T , Pimenta F , Sacoor C , Carvalho MDG , Macete E , Alonso PL . PLoS One 2018 13 (1) e0190687 BACKGROUND: Invasive pneumococcal disease (IPD) is a major cause of illness and death among children worldwide. 10-valent pneumococcal conjugate vaccine (PCV10) was introduced as part of the Mozambican routine immunization program in April 2013. We characterized the IPD burden in a rural area of Mozambique before PCV introduction and estimated the potential impact of this intervention. METHODS: We conducted population-based surveillance for IPD, defined as S. pneumoniae isolated from blood or cerebrospinal fluid, among children <5 years old admitted to Manhica District Hospital, a referral hospital in a rural area with high prevalence of human immunodiciency virus infection. S. pneumoniae was identified using standard microbiologic methods and serotyped using sequential multiplex PCR or Quellung. IPD incidence was calculated among cases from a defined catchment area. RESULTS: From January 2001 through December 2012, we isolated 768 cases of IPD, 498 (65%) of which were bacteraemic pneumonia episodes. A total of 391 (51%) were from the catchment area, yielding IPD incidence rates of 479, 390 and 107 episodes per 100,000 children-years at risk among children <12, 12-23 and 24-<60 months old, respectively. The overall IPD incidence fluctuated and showed a downward trend over time. In these same age groups, in-hospital death occurred in 48 (17%), 26 (12%), and 21 (13%) of all IPD cases, respectively. Overall 90% (543/603) of IPD isolates were available for serotyping; of those, 65% were covered by PCV10 and 83% by PCV13. Among 77 hospital deaths associated with serotyped IPD, 49% and 69% were caused by isolates included in the PCV10 and PCV13, respectively. CONCLUSIONS: We describe very high rates of IPD among children in rural Mozambique that were declining before PCV introduction. Children <1 year old have the greatest incidence and case fatality; although the rates remain high among older groups as well. Most IPD episodes and many deaths among children <5 years old will likely be prevented through PCV10 introduction in Mozambique. |
World Health Organization global health sector strategy on sexually transmitted infections: An evidence-to-action summary for Colombia
Taylor M , Alonso-Gonzalez M , Gomez B , Korenromp E , Broutet N . Rev Colomb Obstet Ginecol 2017 68 (3) 193-201 Curable and incurable sexually transmitted infections (STI) are acquired by hundreds of millions of people worldwide each year. Undiagnosed and untreated STIs cause a range of negative health outcomes including adverse birth outcomes, infertility and other long term sequelae such as cervical cancer. In 2016, the World Health Organization (WHO) launched the Global STI Strategy (2016- 2021). The WHO Global STI Strategy's public health approach focuses on three causative organisms of STIs that need immediate action and for which cost-effective interventions exist: (a) Neisseria gonorrhoeae as a cause of infertility, a risk factor for coinfection with other STIs and because of increasing bacterial resistance to antibiotic treatment, (b) Treponema pallidum given the contribution of syphilis to adverse birth outcomes including stillbirth and neonatal death and (c) Human papillomavirus due to its link to cervical cancer. The range of actions recommended for countries includes: (a) strengthening surveillance, with program monitoring and progress evaluation, (b) STI prevention, (c) early diagnosis of STIs, (d) patient and partner management, and (e) approaches to reach the most vulnerable populations. This summary describes the WHO Global STI Strategy alongside findings from a STI surveillance workshop held in Colombia in May of 2017. Observations related to the Global STI Strategy and findings from the STI estimation workshop are described here for stakeholders in Colombia to consider as they identify opportunities to improve STI services and surveillance. |
Health Promotion and Diabetes Prevention in American Indian and Alaska Native Communities--Traditional Foods Project, 2008-2014
Satterfield D , DeBruyn L , Santos M , Alonso L , Frank M . MMWR Suppl 2016 65 (1) 4-10 Type 2 diabetes was probably uncommon in American Indian and Alaska Native (AI/AN) populations before the 1940s. During 2010-2012, AI/AN adults were approximately 2.1 times as likely to have diabetes diagnosed as non-Hispanic white adults. Although type 2 diabetes in youth is still uncommon, AI/AN youth (aged 15-19 years) experienced a 68% increase in diagnosed diabetes from 1994 to 2004. Health disparities are related to biological, environmental, sociological, and historical factors. This report highlights observations from the Traditional Foods Project (2008-2014) that illustrate tribally driven solutions, built on traditional ecological knowledge, to reclaim foods systems for health promotion and prevention of chronic illnesses, including diabetes. |
Erratum: Environmental distribution of Cryptococcus neoformans and C. gattii around the Mediterranean basin
Cogliati M , D'Amicis R , Zani A , Montagna MT , Caggiano G , De Giglio O , Balbino S , De Donno A , Serio F , Susever S , Ergin C , Velegraki A , Ellabib MS , Nardoni S , Macci C , Oliveri S , Trovato L , Dipineto L , Rickerts V , McCormick-Smith I , Akcaglar S , Tore O , Mlinaric-Missoni E , Bertout S , Mallié M , Martins MD , Vencà AC , Vieira ML , Sampaio AC , Pereira C , Criseo G , Romeo O , Ranque S , Al-Yasiri MH , Kaya M , Cerikcioglu N , Marchese A , Vezzulli L , Ilkit M , Desnos-Ollivier M , Pasquale V , Korem M , Polacheck I , Scopa A , Meyer W , Ferreira-Paim K , Hagen F , Theelen B , Boekhout T , Lockhart SR , Tintelnot K , Tortorano AM , Dromer F , Varma A , Kwon-Chung KJ , Inácio J , Alonso B , Colom MF . FEMS Yeast Res 2016 16 (7) This paper has been updated to correct a spelling error concerning an author name. It previously showed as Giuseppe Griseo, however the correct spelling is Giuseppe Criseo. |
Cuba validated as the first country to eliminate mother-to-child transmission of human immunodeficiency virus and congenital syphilis: Lessons learned from the implementation of the global validation methodology
Caffe S , Perez F , Kamb ML , Gomez Ponce de Leon R , Alonso M , Midy R , Newman L , Hayashi C , Ghidinelli M . Sex Transm Dis 2016 43 (12) 733-736 The World Health Organization (WHO) estimates that each year 150,000 [110,000–190,000] infants are born with human immunodeficiency virus (HIV)1 and 350,000 perinatal deaths are caused by untreated maternal syphilis at the global level.2 Results from HIV clinical trials demonstrated effectiveness of antiretroviral therapy for prevention of HIV transmission from mother to child.3,4 However, the goal of elimination of mother-to-child transmission (EMTCT) of HIV remained largely aspirational until the adoption of the HIV elimination target by the Americas region in 20105 and the launch of the Global Plan for EMTCT of HIV in 2011.6 | An effective intervention against congenital syphilis—early serologic detection of infection in women before or during pregnancy, and treatment of syphilis-infected women with parenteral penicillin—has been available for 70 years.7 However, until recently, syphilis testing in antenatal care (ANC) remained limited in countries with constrained laboratory capacity. In 2007, WHO launched a strategy for the elimination of congenital syphilis as a public health problem.8 Congenital syphilis elimination had already been established as a priority in the Americas a decade before the launch of the global strategy.9 |
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. |
Aeromonas-associated diarrhea in children under 5 years: The GEMS experience
Qamar FN , Nisar MI , Quadri F , Shakoor S , Sow SO , Nasrin D , Blackwelder WC , Wu Y , Farag T , Panchalingham S , Sur D , Qureshi S , Faruque AS , Saha D , Alonso PL , Breiman RF , Bassat Q , Tamboura B , Ramamurthy T , Kanungo S , Ahmed S , Hossain A , Das SK , Antonio M , Hossain MJ , Mandomando I , Mintz ED , Tennant SM , Kotloff KL , Levine MM , Zaidi AK . Am J Trop Med Hyg 2016 95 (4) 774-780 We report the clinical findings, epidemiology, and risk factors for moderate-to-severe diarrhea (MSD) associated with Aeromonas species in children 0-59 months of age, from the Global Enteric Multicenter Study, conducted at three sites in south Asia and four sites in sub-Saharan Africa. Children with MSD were enrolled along with controls matched for age, gender, and neighborhood. Pooled, age-stratified conditional logistic regression models were applied to evaluate the association of Aeromonas infection controlling for coinfecting pathogens and sociodemographic variables. A pooled, age-stratified, multivariate logistic regression analysis was done to identify risk factors associated with Aeromonas positivity in MSD cases. A total of 12,110 cases and 17,291 matched controls were enrolled over a period of 48 months. Aeromonas was identified as a significant pathogen in 736 cases of MSD in Pakistan and Bangladesh (22.2%). Aeromonas remained a significant pathogen even after adjustment for the presence of other pathogens and sociodemographic factors. Odds ratio (OR) for Aeromonas were higher in the presence of Shigella (matched OR: 6.2, 95% confidence interval [CI]: 1.9-20.2). Cases of Aeromonas were likely to present with dysentery, particularly in the 0-11 months (OR: 1.4, 95% CI 1.0-2.0) and 12-23 months (OR: 1.8, 95% CI: 1.3-2.5) age group. The odds of Aeromonas increased with increasing degree of stunting, being highest for severe stunting (OR: 10.1, 95% CI: 3.6-28.9). Aeromonas is a significant pathogen for MSD in Pakistan and Bangladesh. Presence of dysentery and co-occurrence with other pathogens, notably Shigella spp. are significant features of Aeromonas-associated diarrhea. |
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