a narrative review of literature, accomplishments, and perspectives

Funding Information: We would like to thank the Calouste Gulbenkian Foundation and the Flandres Government (Building Institutional Capacity at the Mozambique INS – BICMINS) from where M. Cassocera has a PhD scholarship; Fundo Nacional de Investigação-Moçambique and German Research Foundation (DFG) from where A. Chissaque has scholarship. Sousa Ribe and Orvalho Augusto for the inputs and clarifications regarding the Expanded Program on Immunization. Publisher Copyright: © 2020 Fundacao Oswaldo Cruz. All rights reserved.In Mozambique, the Expanded Program on Immunization (EPI) was implemented in 1979 with the objective of reducing child mortality and morbidity through the provision of immunization services. This study aims to describe the characteristics of the EPI and review the available information related to immunization service in Mozambique, its accomplishments and perspectives. A narrative review of the literature was carried out and the electronic databases accessed were VHL, Google Scholar, and PubMed between 1979 and 2019, using descriptors related to the theme. A total of 28 articles and other relevant sources have been consulted for the review. The national immunization coverage in Mozambique between 1997 (47%) and 2015 (66%) improved 19 percentual points; also immunization coverage of children under 12 months has increased from 44.3% (1997) to 57% (2015). The 2015 survey showed that out of the 11 provinces, only the southern and Cabo Delgado province could reach the 80% recommended goal at the provincial level. Zambézia, Nampula, and Tete provinces have been reporting low coverage over the years and Cabo Delgado presents coverage oscillation. The BCG, DPT3, Polio 3, and measles have reached 80% of coverage goal from 1997 to 2015. Our analysis have shown important improvements in national immunization, characterized by an overall increase in the national and provincial coverage and a decrease in the number of children that did not receive any vaccine. Despite these improvements, some provinces have lower coverages than expected and it is necessary to understand the determinants of dropout in children to retain them and provide timely and full immunization.publishersversionpublishe

Wasting, stunting, and anemia in angolan children after deworming with albendazole or a test-and-treat approach for intestinal parasites: binary longitudinal models with temporal structure in a four-arm randomized trial

Undernutrition, anemia, and intestinal parasitic infections are public health problems in Angola, especially in pre-school children. We analyzed binary data from a longitudinal four-arm randomized parallel trial conducted in Bengo Province, northern Angola, over the course of two years, with seven follow-up assessments to explore the effects of four interventions (deworming and a test-and-treat approach for intestinal parasites, at both the individual and household levels) on wasting and stunting, and to understand their indirect benefits for anemia, malaria, diarrhea, and vomiting. A total of 121 children with intestinal parasitic infections received baseline treatment, and were allocated to the four arms (1:1:1:1). Using continuous outcome variables of height-for-age (HAZ) and weight-for-height (WHZ) statistical approaches did not reveal a clear benefit of any particular arm (Pathogens 2021, 10, 309). Next, HAZ and WHZ were transformed into binary variables of stunting and wasting, respectively, considering their mild-to-severe (Z-score bild, fitted models revealed the potential benefit of a test-and-treat approach at the individual level for wasting compared with annual albendazole at the individual level, especially considering mild-to-severe forms (ORadj = 0.27; p = 0.007). All arms showed similar effects on stunting, compared with annual albendazole, at a 5% significance level. Time and age at baseline presented favorable effects in the percentage of stunting using both severity degrees. Results showed a decreased chance of having anemia and diarrhea over time, although with no significant differences between arms. Data from longitudinal studies are essential to study the direct and indirect effects of interventions, such as deworming, and to explore additional approaches aiming at better understanding the temporal structure of nutrition and health outcomes in children.info:eu-repo/semantics/publishedVersio

Intestinal parasites in children up to 14 years old hospitalized with diarrhea in Mozambique, 2014–2019

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Diarrhea remains a public health problem in Mozambique, even with control strategies being implemented. This analysis aimed to determine the proportion and factors associated with intestinal parasitic infection (IPI) in children up to 14 years old with diarrheal disease, in the southern, central and northern regions of Mozambique. A single diarrheal sample of 1424 children was collected in hospitals and examined using the formol-ether concentration and modified Ziehl-Neelsen techniques to identify intestinal parasites using optical microscopy. Sociodemographic characteristics were obtained by questionnaires. Descriptive statistics and cross-tabulation were performed, and p-values <0.05 were considered statistically significant. A single IPI was detected in 19.2% (273/1424) of the children. Cryptosporidium spp. was the most common parasite (8.1%; 115/1424). Polyparasitism was seen in 26.0% (71/273), with the co-infection of Ascaris lumbricoides and Trichuris trichiura (26.8%; 19/71) being the most common. Age and province were related to IPI (p-value < 0.05). The highest occurrence of IPI was observed in the wet period (October to March), with 21.9% (140/640), compared to the dry period (April to September), with 16.9% (131/776) (p-value = 0.017). Cryptosporidium spp. and the combination of A. lumbricoides/T. trichiura were the main intestinal parasites observed in children hospitalized with diarrhea in Mozambique.This work was supported by funds from the European Foundation Initiative for African Research into Neglected Tropical Diseases (EFINTD, grant number 98539), the World Health Organization, Deutsche Forschungsgemeinschaft (DFG, grant number JO369/5-1) and The Global Vaccine Alliance Initiative through Health System Strengthening. O.N., PhD, is supported by Camões—Instituto da Cooperação e da Língua.info:eu-repo/semantics/publishedVersio

A cross-sectional study in four provinces of Mozambique: Diarrheagenic Escherichia coli in Mozambique

Funding Information: The National Surveillance of Diarrhea was supported by a Senior Fellowship awarded to Nilsa de Deus by the European Foundations Initiative for African Research into Neglected Tropical Diseases (EFINTD, grant number 98539), the World Health Organization, a Master Fellowship funded by the Italian Agency for Development Cooperation (AICS) project AID10524, Deutsche Forschungsgemeinschaft (DFG, grant number JO369/5–1)—where Adilson Fernando Loforte Bauhofer and Assucênio Chissaque are fellows, GAVI (Global Alliance for Vaccines and Immunization) through Health System Strengthening (HSS), and Fundo Nacional de Investigação (FNI). The protocol was approved by the National Bioethics Committee for Health of Mozambique (IRB00002657, reference number: 348/CNBS/13), and each caregiver gave written informed consent to authorize their child's participation. The authors want to thank the parents or guardians who consented to their children's enrollment in the surveillance program. The authors acknowledge Dr. Octávio Jossai, the National Reference Laboratory of Microbiology team, all the focal points, and the provincial field teams who helped to conduct this study. Funding Information: The National Surveillance of Diarrhea was supported by a Senior Fellowship awarded to Nilsa de Deus by the European Foundations Initiative for African Research into Neglected Tropical Diseases (EFINTD, grant number 98539), the World Health Organization, a Master Fellowship funded by the Italian Agency for Development Cooperation (AICS) project AID10524, Deutsche Forschungsgemeinschaft (DFG, grant number JO369/5–1)—where Adilson Fernando Loforte Bauhofer and Assucênio Chissaque are fellows, GAVI (Global Alliance for Vaccines and Immunization) through Health System Strengthening (HSS), and Fundo Nacional de Investigação (FNI). Publisher Copyright: © 2022Objectives: Analyze the frequency of diarrheagenic Escherichia coli (DEC) pathotypes and their antimicrobial resistance profiles among children aged <15 years with diarrhea in four Mozambican provinces. Methods: A cross-sectional hospital-based surveillance program of diarrhea was implemented in Maputo, Sofala, Zambézia, and Nampula. A single stool sample was collected from each child from May 2014 to May 2017. Culture methods and biochemical characterization were performed to detect E. coli strains. DEC pathotypes were determined by conventional polymerase chain reaction targeting specific virulence genes. Antimicrobial susceptibility was assessed by the Kirby–Bauer method. Results: From 723 specimens analyzed by culture, 262 were positive for E. coli. A total of 208 samples were tested by polymerase chain reaction for DEC identification, of which 101 (48.6%) were positive for a DEC pathotype. The predominant pathotypes were enteroaggregative (66.3%, 67/101), enteropathogenic (15.8%, 16/101), enterotoxigenic (13.9%, 14/101), and enteroinvasive E. coli (4.0%, 4/101). No Shiga toxin–producing E. coli was identified. Regardless of the province, the most frequent pathotype was enteroaggregative E. coli. Isolated DEC presented high frequency of resistance to ampicillin (97.8%), tetracycline (68.3%), chloramphenicol (28.4%), nalidixic acid (19.5%), and gentamicin (14.4%). Conclusion: Children with diarrhea in Mozambique had DEC and higher resistance to ampicillin and tetracycline.publishersversionpublishe

Risk factors, genotypes distribution by vaccination status and age of children in Nampula Province, Northern Mozambique (2015-2019)

Publisher Copyright: © 2021 Chissaque et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Mozambique introduced the monovalent rotavirus vaccine (Rotarix®, GSK Biologicals, Rixensart, Belgium) in September 2015. Previous analysis, showed that Nampula province continues reporting a high frequency of Rotavirus A (RVA) infection and the emergence of G9P[6], G9P[4] and G3P[4] genotypes. This analysis aimed to determine the RVA frequency; risk factors; genotype distribution by vaccination status and age between pre- and post-vaccine periods in children under-five years old with diarrhea in Nampula. A cross-sectional, hospital-based surveillance study was conducted in the Hospital Central de Nampula in Mozambique. Socio-demographic and clinical data were collected to assess factors related to RVA infection in both periods. Stool specimens were screened to detect RVA by ELISA, and positive samples were genotyped. Between 2015 (pre-vaccine period) and 2016-2019 (post-vaccine period), 614 stool specimens were collected and tested for RVA in which 34.9% (67/192) were positive in pre-vaccine period and 21.8% (92/422) in post-vaccine (p = 0.001). In the post-vaccine period, age, year, and contact with different animal species (chicken, duck, or multiple animals) were associated with RVA infection. RVA infection was higher in children partially vaccinated (40.7%, 11/27) followed by the fully vaccinated (29.3%, 56/191) and the unvaccinated (15.3%, 21/137) (p = 0.002). G1P[8] and G9P[4] were common in vaccinated children less than 12 months. The present analysis showed that RVA infection reduced slightly in the post-vaccine period, with a high proportion of infection and genotype diversity in children, under 12 months of age, vaccinated. Further research on factors associated with RVA infection on vaccinated compared to unvaccinated children and vaccination optimization should be done.publishersversionpublishe

Immunogenicity of Reduced-Dose Monovalent Type 2 Oral Poliovirus Vaccine in Mocuba, Mozambique

Funding Information: This work was supported by Rotary International, through a grant from the World Health Organization (grant 2019/889177-2). Publisher Copyright: © The Author(s) 2020.Background. The monovalent type 2 oral poliovirus vaccine (mOPV2) stockpile is low. One potential strategy to stretch the existing mOPV2 supply is to administer a reduced dose: 1 drop instead of 2. Methods. We conducted a randomized, controlled, open-label, noninferiority trial (10% margin) to compared immunogenicity after administration of 1 versus 2 drops of mOPV2. We enrolled 9–22-month-old infants from Mocuba district of Mozambique. Poliovirus neutralizing antibodies were measured in serum samples collected before and 1 month after mOPV2 administration. Immune response was defined as seroconversion from seronegative (<1:8) at baseline to seropositive (≥1:8) after vaccination or boosting titers by ≥4-fold for those with titers between 1:8 and 1:362 at baseline. The trial was registered at anzctr.org.au (no. ACTRN12619000184178p). Results. We enrolled 378 children, and 262 (69%) completed per-protocol requirements. The immune response of mOPV2 was 53.6% (95% confidence interval, 44.9%–62.1%) and 60.6% (52.2%–68.4%) in 1-drop and 2-drop recipients, respectively. The noninferiority margin of the 10% was not reached (difference, 7.0%; 95% confidence interval, −5.0% to 19.0%). Conclusion. A small loss of immunogenicity of reduced mOPV2 was observed. Although the noninferiority target was not achieved, the Strategic Advisory Group of Experts on Immunization recommended the 1-drop strategy as a dose-sparing measure if mOPV2 supplies deteriorate further.publishersversionpublishe

emergence of genotypes G3P[4] and G3P[8]

Group A rotavirus (RVA) remains the most important etiological agent associated with severe acute diarrhea in children. Rotarix® monovalent vaccine was introduced into Mozambique’s Expanded Program on Immunization in September 2015. In the present study, we report the diversity and prevalence of rotavirus genotypes, pre-(2012–2015) and post-vaccine (2016–2019) introduction in Mozambique, among diarrheic children less than five years of age. Genotyping data were analyzed for five sentinel sites for the periods indicated. The primary sentinel site, Mavalane General Hospital (HGM), was analyzed for the period 2012–2019, and for all five sites (country-wide analyses), 2015–2019. During the pre-vaccine period, G9P[8] was the most predominant genotype for both HGM (28.5%) and the country-wide analysis (46.0%). However, in the post-vaccine period, G9P[8] was significantly reduced. Instead, G3P[8] was the most common genotype at HGM, while G1P[8] predominated country-wide. Genotypes G9P[4] and G9P[6] were detected for the first time, and the emergence of G3P[8] and G3P[4] genotypes were observed during the post-vaccine period. The distribution and prevalence of rotavirus genotypes were distinct in pre-and post-vaccination periods, while uncommon genotypes were also detected in the post-vaccine period. These observations support the need for continued country-wide surveillance to monitor changes in strain diversity, due to possible vaccine pressure, and consequently, the effect on vaccine effectiveness.publishersversionpublishe

A Hospital Based Cross-Sectional Study, 2015–2019

792. The Global Alliance for Vaccine and Immunization through the Health System Strengthening (HSS) project. The Flandres Government, BICMINS project. The Calouste Gulbenkian Foundation from where J?lia Sambo, Marta Cassocera and Assuc?nio Chissaque have a PhD fellowship. Acknowledgments: We would like to thank the parents or guardians who consented for their children to be enrolled in the surveillance and all ViNaDia team for their dedication and effort with recruitment, data collection and shipment of specimens to the central laboratory in Maputo: Miguel Bambo, Carlos Guilamba, Celina Nhamuave, M?rcia Nhaca, Judite Sal?ncia, Herm?nio Cossa, F?lix Gundane, Aun?sia Marurele, Angelina Pereira, Mulaja Kabeya ?tienne, Celso Gabriel, Titos Maulate, Julieta Ernesto, Siasa Mendes, H?rcio Simbine, Susete de Carvalho, Marcos Joaquim, Elvira Sarguene, Fernando Vilanculos, Felicidade Martins, Dulce Gra?a, Edma Samuel, Vivaldo Pedro, L?cia Matabel, Aida Junta, Gilda Maria Safrina, Nat?rcia Abreu, Vanessa da Silva, Nazareth Mabutana, Delcio Muteto, Benilde Munlela and Carolina Conjo. A special thank you also to Timothy Kellogg for all the guidance during the initial data analysis process. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Diarrhoea is associated with undernutrition and this association is related to increased morbidity and mortality in children under-five. In this analysis we aimed to assess the frequency and associated factors of undernutrition in children under-five with diarrhoea. A hospital-based cross-sectional study was conducted from January 2015 to December 2019 through a surveillance system in five sentinel hospitals in Mozambique. Sociodemographic and clinical information was collected, including anthropometry. A total of 963 children were analysed. The overall undernutrition frequency was 54.1% (95% CI: 50.9–57.2), with 32.5% (95% CI: 29.6–35.5) stunting, 26.6% (95% CI: 23.9–29.6) wasting and 24.7% (95% CI: 22.1–27.5) underweight. Children from Nampula province had 4.7 (p = 0.016) higher odds for stunting compared with children from Maputo and Zambézia. Children whose mother was illiterate had higher odds of being underweight 5.4 (p < 0.001). Children born under 2500 g of weight had 2.85 (p = 0.001), 2.97 (p < 0.001) and 2.19 (p = 0.013) higher odds for being underweighted, wasted and stunted, respectively. The HIV positive status of the children was associated with higher odds of being underweight 2.88 (p = 0.005), wasted 2.24 (p = 0.025), and stunted 2.89 (p = 0.004). The province, caregiver education level, child’s birthweight and HIV status were factors associated with undernutrition in children with diarrhoea. These findings emphasise the need for additional caregiver’s education on the child’s nutrition and associated infectious diseases. More studies are needed to better understand the social context in which a child with diarrhoea and undernutrition is inserted.publishersversionpublishe

Norovirus Genetic Diversity in Children under Five Years Old with Acute Diarrhea in Mozambique (2014–2015)

Funding Information: This study was supported by the European Initiative for Research in Neglected Tropical Diseases (EFINTD), World Health Organization (WHO), The Global Alliance for Vaccines and Immunizations—Health System Strengthening (GAVI—HSS), Fundo Nacional de Investigação (FNI) and the National Research Foundation, South Africa (M.B.T., Grant specific reference number (UID 85799). Any opinion, finding, conclusion or recommendation expressed in this material is that of the author(s), and the NRF does not accept any liability in this regard. Publisher Copyright: © 2022 by the authors.Norovirus (NoV) is the second most important cause of viral diarrheal disease in children worldwide after rotavirus and is estimated to be responsible for 17% of acute diarrhea in low-income countries. This study aimed to identify and report NoV genotypes in Mozambican children under the age of five years with acute diarrhea. Between May 2014 and December 2015, stool specimens were collected within the Mozambique Diarrhea National Surveillance (ViNaDia) and tested for NoV genogroups I (GI) and II (GII) using conventional reverse transcriptase-polymerase chain reaction (RT-PCR). Partial capsid and RNA-dependent RNA polymerase (RdRp) nucleotide sequences were aligned using the Muscle tool, and phylogenetic analyses were performed using MEGA X. A total of 204 stool specimens were tested for NoV. The detection rate of NoV was 14.2% (29/204). The presence of NoV was confirmed, by real-time RT-PCR (RT-qPCR), in 24/29 (82.8%) specimens, and NoV GII predominated (70.8%; 17/24). NoV GII.4 Sydney 2012[P31] was the predominant genotype/P-type combination detected (30.4%; 7/23). This is the first study which highlights the high genetic diversity of NoV in Mozambican children and the need to establish a continuous NoV surveillance system.publishersversionpublishe

Enterovirus detection in stool samples from Mozambican children with acute gastroenteritis

Funding Information: Diocreciano Bero, Ph.D. was supported by Brazilian National Council for Scientific and Technological Development and the Academy of Sciences for the Developing World (CNPq/TWAS, grant number 190,897/2015–5). The ViNaDia was sponsored by Gavi, the Vaccine Alliance through Centers for Disease Control and Prevention (CDC) , Atlanta and World Health Organization, Regional Office for Africa (WHO/AFRO), Deutsche Forschungsgemeinschaft (DFG, grant number JO369/5–1). Nilsa de Deus was fellowship of the European Foundation Initiative into African Research in Neglected Tropical Diseases (EFINTD, grant number 89,539). Publisher Copyright: © 2022Enteroviruses (EV) are predominantly enteric viruses, present in all parts of the world causing disease in humans with a broad spectrum of clinical presentations. The purpose of this study was to identify non-polio enteroviruses (NPEV) in stool samples collected from children with acute gastroenteritis (AGE) symptoms of unknown etiology in four provinces (Maputo, Nampula, Sofala and Zambézia) of Mozambique. From June 2014 to March 2018, 327 stool samples were collected from children hospitalized with AGE in health care units. NPEVs were detected in 52 samples (52/327; 15.9%) and were more frequent in children under 5 years of age. The age group from 12 to 23 months was the most affected and showed more severity of disease. We also identified 26 different EV-types with the following detection pattern EV-B>EV-C>EV-A. The major EV-types were EV-A119 (9/52; 17.3%) and EV-C99 (8/52; 15.4%), accounting for 32.7% of the total. In addition to EV-A119, other uncommon EV-types were also identified, such as EV-B75, EV-B97 and EV-C113. The current study shows a high heterogeneity of EV types circulating in children with AGE in Mozambique as well as the identification of rarely described enteroviruses.publishersversionpublishe