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1.
J. infect ; 82(4): 45-57, abr. 2021.
Article in English | AIM (Africa), RSDM | ID: biblio-1526514

ABSTRACT

Maternal Plasmodium falciparum-specific antibodies may contribute to protect infants against severe malaria. Our main objective was to evaluate the impact of maternal HIV infection and placental malaria on the cord blood levels and efficiency of placental transfer of IgG and IgG subclasses. Methods: In a cohort of 341 delivering HIV-negative and HIV-positive mothers from southern Mozambique, we measured total IgG and IgG subclasses in maternal and cord blood pairs by quantitative suspension array technology against eight P. falciparum antigens: Duffy-binding like domains 3-4 of VAR2CSA from the erythrocyte membrane protein 1, erythrocyte-binding antigen 140, exported protein 1 (EXP1), merozoite surface proteins 1, 2 and 5, and reticulocyte-binding-homologue-4.2 (Rh4.2). We performed univariable and multivariable regression models to assess the association of maternal HIV infection, placental malaria, maternal variables and pregnancy outcomes on cord antibody levels and antibody transplacental transfer. Results: Maternal antibody levels were the main determinants of cord antibody levels. HIV infection and placental malaria reduced the transfer and cord levels of IgG and IgG1, and this was antigen-dependent. Low birth weight was associated with an increase of IgG2 in cord against EXP1 and Rh4.2. Conclusions: We found lower maternally transferred antibodies in HIV-exposed infants and those born from mothers with placental malaria, which may underlie increased susceptibility to malaria in these children.


Subject(s)
Humans , HIV , Fetal Blood , Schools, Nursery , Immunoglobulin G , Malaria
2.
Front Immunol ; 12: 614246, 2021.
Article in English | MEDLINE | ID: mdl-33746958

ABSTRACT

Transplacental transfer of antibodies is essential for conferring protection in newborns against infectious diseases. We assessed the impact of different factors, including gestational age and maternal infections such as HIV and malaria, on the efficiency of cord blood levels and placental transfer of IgG subclasses. We measured total IgG and IgG subclasses by quantitative suspension array technology against 14 pathogens and vaccine antigens, including targets of maternal immunization, in 341 delivering HIV-uninfected and HIV-infected mother-infant pairs from southern Mozambique. We analyzed the association of maternal HIV infection, Plasmodium falciparum exposure, maternal variables and pregnancy outcomes on cord antibody levels and transplacental transfer. Our results show that maternal antibody levels were the main determinant of cord antibody levels. Univariable and multivariable analysis showed that HIV reduced the placental transfer and cord levels of IgG and IgG1 principally, but also IgG2 to half of the antigens tested. P. falciparum exposure and prematurity were negatively associated with cord antibody levels and placental transfer, but this was antigen-subclass dependent. Our findings suggest that lower maternally transferred antibodies may underlie increased susceptibility to infections of HIV-exposed infants. This could affect efficacy of maternal vaccination, especially in sub-Saharan Africa, where there is a high prevalence of HIV, malaria and unfavorable environmental factors.


Subject(s)
Antibodies/immunology , HIV Infections/epidemiology , HIV Infections/immunology , Maternal-Fetal Exchange/immunology , Placenta/immunology , Adult , Antigens/immunology , Antiretroviral Therapy, Highly Active , Female , Fetal Blood/immunology , HIV Infections/drug therapy , HIV Infections/virology , Humans , Immunity, Maternally-Acquired , Immunoglobulin G/immunology , Mozambique , Placenta/metabolism , Pregnancy , Protein Transport , Sex Factors , Vaccines/immunology , Young Adult
3.
Front. immunol ; 12: 1-18, mar 3, 2021. ilus, graf
Article in English | RSDM | ID: biblio-1526527

ABSTRACT

Transplacental transfer of antibodies is essential for conferring protection in newborns against infectious diseases. We assessed the impact of different factors, including gestational age and maternal infections such as HIV and malaria, on the efficiency of cord blood levels and placental transfer of IgG subclasses. We measured total IgG and IgG subclasses by quantitative suspension array technology against 14 pathogens and vaccine antigens, including targets of maternal immunization, in 341 delivering HIV-uninfected and HIV-infected mother-infant pairs from southern Mozambique. We analyzed the association of maternal HIV infection, Plasmodium falciparum exposure, maternal variables and pregnancy outcomes on cord antibody levels and transplacental transfer. Our results show that maternal antibody levels were the main determinant of cord antibody levels. Univariable and multivariable analysis showed that HIV reduced the placental transfer and cord levels of IgG and IgG1 principally, but also IgG2 to half of the antigens tested. P. falciparum exposure and prematurity were negatively associated with cord antibody levels and placental transfer, but this was antigen-subclass dependent. Our findings suggest that lower maternally transferred antibodies may underlie increased susceptibility to infections of HIV-exposed infants. This could affect efficacy of maternal vaccination, especially in sub-Saharan Africa, where there is a high prevalence of HIV, malaria and unfavorable environmental factors


Subject(s)
Humans , Placenta/immunology , Placenta/metabolism , Immunoglobulin G , HIV , Antibodies, Monoclonal , Schools, Nursery , Pregnancy , HIV Infections/virology , Blood-Borne Pathogens , Malaria
4.
J Infect ; 82(4): 45-57, 2021 04.
Article in English | MEDLINE | ID: mdl-33636218

ABSTRACT

OBJECTIVES: Maternal Plasmodium falciparum-specific antibodies may contribute to protect infants against severe malaria. Our main objective was to evaluate the impact of maternal HIV infection and placental malaria on the cord blood levels and efficiency of placental transfer of IgG and IgG subclasses. METHODS: In a cohort of 341 delivering HIV-negative and HIV-positive mothers from southern Mozambique, we measured total IgG and IgG subclasses in maternal and cord blood pairs by quantitative suspension array technology against eight P. falciparum antigens: Duffy-binding like domains 3-4 of VAR2CSA from the erythrocyte membrane protein 1, erythrocyte-binding antigen 140, exported protein 1 (EXP1), merozoite surface proteins 1, 2 and 5, and reticulocyte-binding-homologue-4.2 (Rh4.2). We performed univariable and multivariable regression models to assess the association of maternal HIV infection, placental malaria, maternal variables and pregnancy outcomes on cord antibody levels and antibody transplacental transfer. RESULTS: Maternal antibody levels were the main determinants of cord antibody levels. HIV infection and placental malaria reduced the transfer and cord levels of IgG and IgG1, and this was antigen-dependent. Low birth weight was associated with an increase of IgG2 in cord against EXP1 and Rh4.2. CONCLUSIONS: We found lower maternally transferred antibodies in HIV-exposed infants and those born from mothers with placental malaria, which may underlie increased susceptibility to malaria in these children.


Subject(s)
Antimalarials , HIV Infections , Malaria, Falciparum , Malaria , Antibodies, Protozoan , Child , Female , Humans , Infant , Malaria, Falciparum/epidemiology , Plasmodium falciparum , Pregnancy
5.
Pediatr Pulmonol ; 56(2): 551-560, 2021 02.
Article in English | MEDLINE | ID: mdl-33205892

ABSTRACT

INTRODUCTION: Improved pneumonia diagnostics are needed in low-resource settings (LRS); lung ultrasound (LUS) is a promising diagnostic technology for pneumonia. The objective was to compare LUS versus chest radiograph (CXR), and among LUS interpreters, to compare expert versus limited training with respect to interrater reliability. METHODS: We conducted a prospective, observational study among children with World Health Organization (WHO) Integrated Management of Childhood Illness (IMCI) chest-indrawing pneumonia at two district hospitals in Mozambique and Pakistan, and assessed LUS and CXR examinations. The primary endpoint was interrater reliability between LUS and CXR interpreters for pneumonia diagnosis among children with WHO IMCI chest-indrawing pneumonia. RESULTS: Interrater reliability was excellent for expert LUS interpreters, but poor to moderate for expert CXR interpreters and onsite LUS interpreters with limited training. CONCLUSIONS: Among children with WHO IMCI chest-indrawing pneumonia, expert interpreters may achieve substantially higher interrater reliability for LUS compared to CXR, and LUS showed potential as a preferred reference standard. For point-of-care LUS to be successfully implemented for the diagnosis and management of pneumonia in LRS, the clinical environment and amount of appropriate user training will need to be understood and addressed.


Subject(s)
Lung/diagnostic imaging , Pneumonia/diagnostic imaging , Female , Humans , Infant , Male , Mozambique , Pakistan , Radiography, Thoracic , Reproducibility of Results , Ultrasonography
6.
Front. immunol ; 12: 1-18, 2021. tab, fig
Article in English | RSDM | ID: biblio-1561692

ABSTRACT

Transplacental transfer of antibodies is essential for conferring protection in newborns against infectious diseases. We assessed the impact of different factors, including gestational age and maternal infections such as HIV and malaria, on the efficiency of cord blood levels and placental transfer of IgG subclasses. We measured total IgG and IgG subclasses by quantitative suspension array technology against 14 pathogens and vaccine antigens, including targets of maternal immunization, in 341 delivering HIV-uninfected and HIV-infected mother-infant pairs from southern Mozambique. We analyzed the association of maternal HIV infection, Plasmodium falciparum exposure, maternal variables and pregnancy outcomes on cord antibody levels and transplacental transfer. Our results show that maternal antibody levels were the main determinant of cord antibody levels. Univariable and multivariable analysis showed that HIV reduced the placental transfer and cord levels of IgG and IgG1 principally, but also IgG2 to half of the antigens tested. P. falciparum exposure and prematurity were negatively associated with cord antibody levels and placental transfer, but this was antigen-subclass dependent. Our findings suggest that lower maternally transferred antibodies may underlie increased susceptibility to infections of HIV-exposed infants. This could affect efficacy of maternal vaccination, especially in sub-Saharan Africa, where there is a high prevalence of HIV, malaria and unfavorable environmental factors.


Subject(s)
Humans , Male , Female , Pregnancy , Adolescent , Adult , HIV Infections/immunology , HIV Infections/epidemiology , Maternal-Fetal Exchange/immunology , Antibodies/immunology , Placenta/metabolism , Immunoglobulin G/immunology , Pregnancy , Vaccines/immunology , Carrier Proteins , HIV Infections/therapy , HIV Infections/virology , Sex Factors , Antiretroviral Therapy, Highly Active , Fetal Blood/immunology , Immunity, Maternally-Acquired , Antigens/immunology
7.
Front Microbiol ; 11: 1452, 2020.
Article in English | MEDLINE | ID: mdl-32765436

ABSTRACT

Maternal factors and exposure to pathogens have an impact on infant health. For instance, HIV exposed but uninfected infants have higher morbidity and mortality than HIV unexposed infants. Innate responses are the first line of defense and orchestrate the subsequent adaptive immune response and are especially relevant in newborns. To determine the association of maternal HIV infection with maternal and newborn innate immunity we analyzed the cytokine responses upon pattern recognition receptor (PRR) stimulations in the triad of maternal peripheral and placental blood as well as in cord blood in a cohort of mother-infant pairs from southern Mozambique. A total of 48 women (35 HIV-uninfected and 13 HIV-infected) were included. Women and infant innate responses positively correlated with each other. Age, gravidity and sex of the fetus had some associations with spontaneous production of cytokines in the maternal peripheral blood. HIV-infected women not receiving antiretroviral therapy (ART) before pregnancy showed decreased IL-8 and IL-6 PRR responses in peripheral blood compared to those HIV-uninfected, and PRR hyporesponsiveness for IL-8 was also found in the corresponding infant's cord blood. HIV infection had a greater impact on placental blood responses, with significantly increased pro-inflammatory, T H 1 and T H 17 PRR responses in HIV-infected women not receiving ART before pregnancy compared to HIV-uninfected women. In conclusion, innate response of the mother and her newborn was altered by HIV infection in the women who did not receive ART before pregnancy. As these responses could be related to birth outcomes, targeted innate immune modulation could improve maternal and newborn health.

8.
PLoS One ; 12(9): e0184762, 2017.
Article in English | MEDLINE | ID: mdl-28910402

ABSTRACT

BACKGROUND: Current diagnostic methods for detection of Streptococcus pneumoniae in children with suspected invasive pneumococcal disease have limitations of accuracy, timeliness, and patient convenience. This study aimed to determine the performance of pneumococcal load quantified with a real-time polymerase-chain reaction in nasopharyngeal samples to diagnose invasive pneumococcal disease in children. METHODS: Matched case-control study of patients <5 years of age with invasive pneumococcal disease admitted to the Manhiça District Hospital (Mozambique) and asymptomatic controls recruited in different periods between 2006 and 2014. Cases were confirmed by a positive bacterial culture for S. pneumoniae in blood or cerebrospinal fluid. Nasopharyngeal aspirates were collected from cases and controls and pneumococcal density was quantified by lytA real-time polymerase-chain reaction. RESULTS: Thirty cases (median age 12.8 months) and sixty controls (median age 11.7 months) were enrolled and 70% of them were male. Nasopharyngeal pneumococcal carriage was high in both groups: 28/30 (93.3%) for cases vs. 53/60 (88.3%) for controls (p = 0.71). Mean nasopharyngeal pneumococcal load was identified as a marker for invasive pneumococcal disease (7.0 log10 copies/mL in cases vs. 5.8 log10 copies/mL in controls, p<0.001) and showed good discriminatory power (AUC-ROC: 82.1%, 95% CI 72.5%-91.8%). A colonization density of 6.5 log10 copies/mL was determined as the optimal cut-off value to distinguish cases from controls (sensitivity 75.0%, specificity 73.6%). CONCLUSION: Use of non-invasive nasopharyngeal aspirates coupled with rapid and accurate quantification of pneumococcal load by real-time polymerase chain reaction has the potential to become a useful surrogate marker for early diagnosis of invasive pneumococcal disease in children.


Subject(s)
Bacterial Proteins/genetics , Nasopharynx/microbiology , Pneumococcal Infections/diagnosis , Real-Time Polymerase Chain Reaction/methods , Streptococcus pneumoniae/isolation & purification , Bacterial Load , Case-Control Studies , Child, Preschool , Female , Humans , Infant , Male , Mozambique , Prospective Studies , Sensitivity and Specificity , Streptococcus pneumoniae/physiology
9.
Acta trop. ; 146Sept. 2015. mapas, tab
Article in English | RSDM, Sec. Est. Saúde SP | ID: biblio-1525760

ABSTRACT

Vaccines are an effective public health measure. Vaccination coverage has improved in Africa in the last decades but has still not reached WHO/UNICEF target of at least 90% first-dose coverage for vaccines in the Expanded Programme on Immunization (EPI) implemented in Mozambique in 1979. There are concerns about reliability of vaccination coverage official data from low-income countries, and inequities in vaccine administration. We randomly sampled 266 under-five years children from Taninga, a poor rural area in Southern Mozambique under a Demographic surveillance system and collected data directly from the individual national health cards when available (BCG, DTP/HepB/Hib, Polio, Measles). We also collected data on socio-economic variables through an interview. Overall, only 5% of the participants did not receive all the doses of the vaccines included in the EPI in a timely manner (overall vaccination coverage 95%, 95% CI: 93.5-95.5%). The socio-economic status was homogenously low and no differences were found between vaccinated and unvaccinated children. Vaccination coverage in Taninga was very high, despite the low socio-economic status of the population. The high performance of the EPI in Taninga is an encouraging experience for achieving high vaccination coverage in low-income rural settings.


Subject(s)
Humans , Male , Female , Child, Preschool , Child , Adolescent , Virus Diseases/prevention & control , BCG Vaccine/therapeutic use , Immunization Programs , Diphtheria/prevention & control , Rural Population , Poliovirus Vaccine, Oral , Diphtheria-Tetanus-Pertussis Vaccine , Mass Vaccination , Hepatitis B Vaccines , Tuberculosis Vaccines , Haemophilus Infections , Mozambique
10.
Acta Trop ; 149: 262-6, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26095045

ABSTRACT

Vaccines are an effective public health measure. Vaccination coverage has improved in Africa in the last decades but has still not reached WHO/UNICEF target of at least 90% first-dose coverage for vaccines in the Expanded Programme on Immunization (EPI) implemented in Mozambique in 1979. There are concerns about reliability of vaccination coverage official data from low-income countries, and inequities in vaccine administration. We randomly sampled 266 under-five years children from Taninga, a poor rural area in Southern Mozambique under a Demographic surveillance system and collected data directly from the individual national health cards when available (BCG, DTP/HepB/Hib, Polio, Measles). We also collected data on socio-economic variables through an interview. Overall, only 5% of the participants did not receive all the doses of the vaccines included in the EPI in a timely manner (overall vaccination coverage 95%, 95% CI: 93.5-95.5%). The socio-economic status was homogenously low and no differences were found between vaccinated and unvaccinated children. Vaccination coverage in Taninga was very high, despite the low socio-economic status of the population. The high performance of the EPI in Taninga is an encouraging experience for achieving high vaccination coverage in low-income rural settings.


Subject(s)
Bacterial Infections/prevention & control , Immunization Programs , Patient Compliance/statistics & numerical data , Vaccines/therapeutic use , Virus Diseases/prevention & control , BCG Vaccine/therapeutic use , Child, Preschool , Data Collection , Diphtheria/prevention & control , Diphtheria-Tetanus-Pertussis Vaccine/therapeutic use , Female , Haemophilus Infections/prevention & control , Haemophilus Vaccines/therapeutic use , Hepatitis B/prevention & control , Hepatitis B Vaccines/therapeutic use , Humans , Infant , Male , Mozambique , Poliomyelitis/prevention & control , Poliovirus Vaccine, Oral/therapeutic use , Poverty , Rural Population , Social Class , Tetanus/prevention & control , Tuberculosis/prevention & control , Whooping Cough/prevention & control
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