Surveillance of HIV Drug Resistance in Children Receiving Antiretroviral Therapy: A Pilot Study of the World Health Organization's Generic Protocol in Maputo, Mozambique

Between 2007 and 2008, the Mozambique Ministry of Health conducted an assessment of human immunodeficiency virus drug resistance (HIVDR) using World Health Organization (WHO) methods in a cohort of children initiating antiretroviral therapy (ART) at the main pediatric ART referral center in Mozambique. It was shown that prior to ART initiation 5.4% of children had HIVDR that was associated with nevirapine perinatal exposure (P < .001). Twelve months after ART initiation, 77% had viral load suppression (<1000 copies/mL), exceeding the WHO target of ≥70%; 10.3% had HIVDR at 12 months. Baseline HIVDR (P = .04), maternal prevention of mother-to-child transmission (P = .02), and estimated days of missed medication (P = .03) predicted HIVDR at 12 months. As efforts to eliminate pediatric AIDS are intensified, implementation of ritonavir-boosted protease inhibitor regimens in children with prevention of mother-to-child transmission exposure may reduce risk of virological failure in our settin

Epidemiology and clinical presentation of community-acquired Staphylococcus aureus bacteraemia in children under 5 years of age admitted to the Manhica District Hospital, Mozambique, 2001-2019

Staphylococcus aureus bacteraemia (SAB) is one of the most common bloodstream infections globally. Data on the burden and epidemiology of community-acquired SAB in low-income countries are scarce but needed to defne preventive and management strategies. Blood samples were collected from children<5 years of age with fever or severe disease admitted to the Manhiça District Hospital for bacterial isolation, including S. aureus. Between 2001 and 2019, 7.6% (3,197/41,891) of children had bacteraemia, of which 12.3% corresponded to SAB. The overall incidence of SAB was 56.1 episodes/100,000 children-years at risk (CYAR), being highest among neonates (589.8 episodes/100,000 CYAR). SAB declined signifcantly between 2001 and 2019 (322.1 to 12.5 episodes/100,000 CYAR). In-hospital mortality by SAB was 9.3% (31/332), and signifcantly associated with infections by multidrugresistant (MDR) strains (14.7%, 11/75 vs. 6.9%, 14/204 among non-MDR, p=0.043) and methicillin-resistant S. aureus (33.3%, 5/15 vs. 7.6%, 20/264 among methicillin-susceptible S. aureus, p=0.006). Despite the declining rates of SAB, this disease remains an important cause of death among children admitted to MDH, possibly in relation to the resistance to the frst line of empirical treatment in use in our setting, suggesting an urgent need to review current policy recommendationspublishersversionpublishe

Molecular Epidemiology of Rotavirus Strains in Symptomatic and Asymptomatic Children in Manhiça District, Southern Mozambique 2008–2019

..870-15 SC; the United States Agency for International Development (USAID), grant number AID-656-F-16-00002 and Fundo Nacional de Investiga??o (FNI), Mo?ambique, grant number 245-INV, within the context of diarrhoeal disease surveillance platform implementation. F.M PhD is supported by Calouste Gulbenkian Foundation, grant number 234066. The authors convey many thanks to all the caregivers who consented to their children?s participation in both studies (GEMS and the diarrhoeal disease platform). They would also like to thank all the professionals in the hospitals and those on field recruitment for their full dedication and effort in children enrolment and collection of data and samples whenever possible. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.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 geno-types circulating among symptomatic and asymptomatic children in Manhiça District, Mozambique, pre-and post-vaccine introduction. Stool was collected from enrolled children and screened for ro-tavirus 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.publishersversionpublishe

Impact of rotavirus vaccination on diarrheal hospitalizations in children younger than 5 years of age in a rural southern Mozambique

Funding Information: We thank the participants in this study and their parents for allowing the collection of samples and data. The authors would also like to thank all Centro de Investigação em Saúde de Manhiça (CISM) staff particularly those supporting Diarrheal Disease Research Area and Manhiça District Hospital. Core funding for CISM is provided by the Spanish Agency for International Cooperation and Development (AECID). ISGlobal receives support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. The GEMS study was supported by the Bill & Melinda Gates Foundation (Project OPP 38874). The impact of rotavirus study was supported by GAVI funds through Centers for Disease Control and Prevention Foundation (CDCF), Atlanta & World Health Organization, Regional Offices for Africa (WHO AFRO). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The findings and conclusions of this report are those of the authors and do not necessarily represent the official position of the US Centers for Disease Control and Prevention and World Health Organization. The authors declare no conflict of interest. Funding Information: We thank the participants in this study and their parents for allowing the collection of samples and data. The authors would also like to thank all Centro de Investigação em Saúde de Manhiça (CISM) staff particularly those supporting Diarrheal Disease Research Area and Manhiça District Hospital. Core funding for CISM is provided by the Spanish Agency for International Cooperation and Development (AECID). ISGlobal receives support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. The GEMS study was supported by the Bill & Melinda Gates Foundation (Project OPP 38874). The impact of rotavirus study was supported by GAVI funds through Centers for Disease Control and Prevention Foundation (CDCF), Atlanta & World Health Organization, Regional Offices for Africa (WHO AFRO). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2022Background: 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.publishersversionpublishe

Genetic Characterization of Human T-Cell Lymphotropic Virus Type 1 in Mozambique: Transcontinental Lineages Drive the HTLV-1 Endemic

Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of Adult T-Cell Leukemia/Lymphoma (ATL), the Tropical Spastic Paraparesis/HTLV-1-associated Myelopathy (TSP/HAM) and other inflammatory diseases, including dermatitis, uveitis, and myositis. It is estimated that 2–8% of the infected persons will develop a HTLV-1-associated disease during their lifetimes, frequently TSP/HAM. Thus far, there is not a specific treatment to this progressive and chronic disease. HTLV-1 has means of three transmission: (i) from mother to child during prolonged breastfeeding, (ii) between sexual partners and (iii) through blood transfusion. HTLV-1 has been characterized in 7 subtypes and the geographical distribution and the clinical impact of this infection is not well known, mainly in African population. HTLV-1 is endemic in sub-Saharan Africa. Mozambique is a country of southeastern Africa where TSP/HAM cases were reported. Recently, our group estimated the HTLV prevalence among Mozambican blood donors as 0.9%. In this work we performed a genetic analysis of HTLV-1 in blood donors and HIV/HTLV co-infected patients from Maputo, Mozambique. Our results showed the presence of three HTLV-1 clusters within the Cosmopolitan/Transcontinental subtype/subgroup. The differential rates of HIV-1/HTLV-1 co-infection in the three HTLV-1 clusters demonstrated the dynamic of the two viruses and the need for implementation of control measures focusing on both retroviruses

Genomic characterization of the rotavirus G3P[8] strain in vaccinated children, reveals possible reassortment events between human and animal strains in Manhiça District, Mozambique

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

Genetic Diversity and Transmitted Drug Resistance of HIV-1 Subtypes in Blood Donors Candidates in Northern Mozambique

Submitted by Sandra Infurna ([email protected]) on 2017-03-02T18:17:22Z No. of bitstreams: 1 mg_morgado_etal_IOC_2016.pdf: 1302980 bytes, checksum: ffaa424446478129e87d76756bd8c531 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2017-03-02T18:26:12Z (GMT) No. of bitstreams: 1 mg_morgado_etal_IOC_2016.pdf: 1302980 bytes, checksum: ffaa424446478129e87d76756bd8c531 (MD5)Made available in DSpace on 2017-03-02T18:26:12Z (GMT). No. of bitstreams: 1 mg_morgado_etal_IOC_2016.pdf: 1302980 bytes, checksum: ffaa424446478129e87d76756bd8c531 (MD5) Previous issue date: 2016Instituto Nacional de Saúde. Maputo, Mozambique.Instituto Nacional de Saúde. Maputo, Mozambique.Instituto Nacional de Saúde. Maputo, Mozambique.Instituto Nacional de Saúde. Maputo, Mozambique.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS and Imunologia Molecular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS and Imunologia Molecular. Rio de Janeiro, RJ, Brasil.In order to evaluate the genetic diversity of HIV-1 subtypes and transmitted drug resistance (TDR) mutations in northern Mozambique, we analyzed 120 plasma specimens obtained from drug naive blood donors candidates, who tested positive during routine HIV screening in three blood banks in that region. The genotyping for HIV-1 resistance was performed using Trugene Genotyping SystemTM. HIV-1 genetic subtypes were defined based on entire PR and partial RT gene regions, using REGA HIV-1 Subtyping Tool version 3.0 algorithm and confirmed by phylogenetic inference, using NJ algorithm. The majority of genotyped samples were classified as HIV-1 subtype C (80.0%), followed by subtype A1 (10.5%), subtype D (3.2%) and subtype G (2.1%). The inter-subtype recombinant forms (A1/C, A1/D and C/D) were identified in four participants (4.2%). TDR mutations associated with nucleoside and nonnucleoside reverse transcriptase inhibitors (K219E, G190A, K101E and K103N) were observed in five (5.3%) subjects. Although a large proportion of HIV-1 subtype C was observed, non-C and recombinant forms together correspond to 20% in this study, which is different from what was described in central and southern regions, where subtype C was almost 100%. However, the profile mutations from this study correlate with the ARVs used both for first line schemes and PMTCT in Mozambique. This data reinforces the necessity of continuous surveillance of HIV-1 diversity, TDR and routes of spread, through inner cities of Mozambique to understand better the dynamics of the HIV-1 epidemic and support national public health policies in the country

Epidemiology and molecular characterization of multidrug-resistant Escherichia coli isolates harboring blaCTX-M group 1 extended-spectrum &beta;-lactamases causing bacteremia and urinary tract infection in Manhi&ccedil;a, Mozambique

Elisabet Guiral,1 Maria Jes&uacute;s Pons,1 Delfino Vubil,2 Marta Mar&iacute;-Almirall,1 Betuel Siga&uacute;que,2,3 Sara Maria Soto,1 Pedro Lu&iacute;s Alonso,1,2 Joaquim Ruiz,1 Jordi Vila,1,4 In&aacute;cio Mandomando2,3 1Barcelona Institute for Global Health (ISGlobal), Hospital Cl&iacute;nic-Universitat de Barcelona, Barcelona, Spain; 2Centro de Investiga&ccedil;&atilde;o em Sa&uacute;de de Manhi&ccedil;a (CISM), Maputo, Mozambique; 3Instituto Nacional de Sa&uacute;de (INS), Minist&eacute;rio da Sa&uacute;de, Maputo, Mozambique; 4Microbiology Department, Hospital Cl&iacute;nic, School of Medicine, University of Barcelona, Barcelona, Spain Background: The emergence and spread of extended-spectrum &beta;-lactamases (ESBLs), especially CTX-M, is an important public health problem with serious implications for low-income countries where second-line treatment is often unavailable. Knowledge of the local prevalence of ESBL is critical to define appropriate empirical therapeutic strategies for multidrug-resistant (MDR) organisms. This study aimed to assess and characterize the presence of ESBL and especially CTX-M-producing Escherichia coli MDR isolates from patients with urinary tract infections (UTIs) and bacteremia in a rural hospital in Mozambique. Materials and methods: One hundred and fifty-one E. coli isolates from bacteremia and UTI in children were screened for CTX-M, TEM, SHV and OXA &beta;-lactamases by polymerase chain reaction and sequencing. Isolates carrying CTX-M group 1 &beta;-lactamases were further studied. The resistance to other antibiotic families was determined by phenotypic and genotypic methods, the location of the blaCTX-M gene and the epidemiology of the isolates were studied, and extensive plasmid characterization was performed. Results: Approximately 11% (17/151) of E. coli isolates causing bacteremia and UTI were ESBL producers. CTX-M-15 was the most frequently detected ESBL, accounting for 75% of the total isolates characterized. The blaCTX-M gene is located in different plasmids belonging to different incompatibility groups and can be found in non-epidemiologically related isolates, indicating the high capacity of this resistance determinant to spread widely. Conclusion: Our data suggest the presence of a co-selection of third-generation cephalosporin-resistant determinants in the study area despite limited access to these antibiotics. This highlights the importance of continuous surveillance of antimicrobial resistance of both genetic elements of resistance and resistant isolates in order to monitor the emergence and trends of ESBL-producing isolates to promote adequate therapeutic strategies for the management of MDR bacterial infections. Keywords: CTX-M-15, multidrug-resistance, Enterobacteriaceae, resistance determinant locatio