Fatal enhanced respiratory syncytial virus disease in toddlers.

In 1967, two toddlers immunized with a formalin-inactivated vaccine against respiratory syncytial virus (FIRSV) in the United States died from enhanced RSV disease (ERD), a severe form of illness resulting from aberrant priming of the antiviral immune response during vaccination. Up to 80% of immunized children subsequently exposed to wild-type virus were hospitalized. These events hampered RSV vaccine development for decades.

Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults.

Background: Therapies to interrupt the progression of early coronavirus disease 2019 (Covid-19) remain elusive. Among them, convalescent plasma administered to hospitalized patients has been unsuccessful, perhaps because antibodies should be administered earlier in the course of illness.

Methods: We conducted a randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adult patients within 72 hours after the onset of mild Covid-19 symptoms.

Short-course Benznidazole treatment to reduce Trypanosoma cruzi parasitic load in women of reproductive age (BETTY): a non-inferiority randomized controlled trial study protocol.

Background: Retrospective observational studies suggest that transmission of Trypanosoma cruzi does not occur in treated women when pregnant later in life. The level of parasitemia is a known risk factor for congenital transmission. Benznidazole (BZN) is the drug of choice for preconceptional treatment to reduce parasitic load.

Respiratory Failure and Death in Vulnerable Premature Children With Lower Respiratory Tract Illness.

Background: Efforts to better understand the risk factors associated with respiratory failure (RF) and fatal lower respiratory tract infection (LRTI) in premature children in developing countries are necessary to elaborate evidenced-based preventive interventions. We aim to characterize the burden of respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) LRTI in premature children and determine risk factors for RF and fatal illness in a vulnerable population.

Methods: This is a prospective, population-based, cross-sectional study.

Role for Maternal Asthma in Severe Human Metapneumovirus Lung Disease Susceptibility in Children.

Background: Severity of human metapneumovirus (hMPV) lower respiratory illness (LRTI) is considered similar to that observed for respiratory syncytial virus (RSV). However, differences in severity between these pathogens have been noted, suggesting the degree of illness may vary in different populations. Moreover, a potential association between hMPV and asthma also suggests that hMPV may preferentially affect asthmatic subjects.

A multifaceted intervention to improve syphilis screening and treatment in pregnant women in Kinshasa, Democratic Republic of the Congo and in Lusaka, Zambia: a cluster randomised controlled trial.

Background: Despite international recommendations, coverage of syphilis testing in pregnant women and treatment of those found seropositive remains limited in sub-Saharan Africa. We assessed whether combining the provision of supplies with a behavioural intervention was more effective than providing supplies only, to improve syphilis screening and treatment during antenatal care.

Methods: In this 18-month, cluster randomised controlled trial, we randomly assigned (1:1) 26 urban antenatal care clinics in Kinshasa, Democratic Republic of the Congo, and Lusaka, Zambia, to receive a behavioural intervention (opinion leader selection, academic detailing visits, reminders, audits and feedback, and supportive supervision) plus supplies for syphilis testing and treatment (intervention group) or to receive supplies only (control group).

Mortality Associated With Acute Respiratory Infections Among Children at Home.

Background: Numerous deaths in children aged <5 years in the developing world occur at home. Acute respiratory infections (ARIs) are thought to play an important role in these deaths. Risk factors and pathogens linked to fatal episodes remain unclear.

Syphilis screening and treatment in pregnant women in Kinshasa, Democratic Republic of the Congo and in Lusaka, Zambia: a cross-sectional study.

Congenital syphilis is associated with perinatal deaths, preterm births and congenital malformations. Low rates of syphilis screening during pregnancy and treatment of those found seropositive have been reported in the Democratic Republic of the Congo (DRC) and Zambia. We report the rates on antenatal syphilis screening, the seroprevalence of syphilis infection, and the frequency of antibiotic treatment in pregnant women screened positive for syphilis during their attendance at antenatal care (ANC) clinics in Kinshasa, DRC and Lusaka, Zambia.

Provision of medical supply kits to improve quality of antenatal care in Mozambique: a stepped-wedge cluster randomised trial.

Background: High levels of maternal and newborn mortality and morbidity remain a daunting reality in many low-income countries. Several interventions delivered during antenatal care have been shown to improve maternal and newborn outcomes, but stockouts of medical supplies at point of care can prevent implementation of these services. We aimed to evaluate whether a supply chain strategy based on the provision of kits could improve quality of care.

Effects of injectable progestogen contraception versus the copper intrauterine device on HIV acquisition: sub-study of a pragmatic randomised controlled trial.

Background: Evidence from observational studies suggests an increased risk of HIV acquisition among women using depot medroxyprogesterone acetate (DMPA) contraception.

Methods: Within the context of a South African programme to increase women's access to the intrauterine contraceptive device (IUD), we conducted a pragmatic, open-label, parallel-arm, randomised controlled trial (RCT) of the IUD versus injectable progestogen contraception (IPC) at two South African hospitals. The primary outcome was pregnancy; secondary outcomes included HIV acquisition.

Impact of a maternal immunization program against pertussis in a developing country.

Background: Pertussis disease is a growing concern for developing countries. In Argentina, rates of illness and death peaked in 2011. More than 50% of fatalities due to pertussis occurred in infants younger than two months of age, too young for vaccination.

Zika virus infection in pregnant women in Honduras: study protocol.

Background: Although there is increasing evidence for a relationship between symptomatic Zika virus (ZIKV) maternal infection, and microcephaly, a firm causal relation has yet to be established by epidemiologic studies. Studies also need to be conducted in recently infected settings. Our objectives are to assess the frequency of ZIKV infection during pregnancy in Honduras and the association of microcephaly with ZIKV infection.

Mortality due to Respiratory Syncytial Virus. Burden and Risk Factors.

Rationale: Respiratory syncytial virus (RSV) is the most frequent cause of hospitalization and an important cause of death in infants in the developing world. The relative contribution of social, biologic, and clinical risk factors to RSV mortality in low-income regions is unclear.

Objectives: To determine the burden and risk factors for mortality due to RSV in a low-income population of 84,840 infants.

Effects of the copper intrauterine device versus injectable progestin contraception on pregnancy rates and method discontinuation among women attending termination of pregnancy services in South Africa: a pragmatic randomized controlled trial.

Background: The copper intrauterine device (IUD) is under-utilised in South Africa, where injectable progestin contraception (IPC) dominates contraception usage. There is a lack of robust comparative data on these contraceptive options to inform policy, programs, clinical counseling, and women's choices.

Methods: Within the context of a South African program to increase women's access to the IUD, we conducted a pragmatic, open-label, parallel-arm, randomised controlled trial of the IUD versus IPC at two South African hospitals.

The effect of calcium supplementation on blood pressure in non-pregnant women with previous pre-eclampsia: An exploratory, randomized placebo controlled study.

Background: Epidemiological findings suggest that the link between poverty and pre-eclampsia might be dietary calcium deficiency. Calcium supplementation has been associated with a modest reduction in pre-eclampsia, and also in blood pressure (BP).

Methods: This exploratory sub-study of the WHO Calcium and Pre-eclampsia (CAP) trial aims to determine the effect of 500mg/day elemental calcium on the blood pressure of non-pregnant women with previous pre-eclampsia.

Challenges and opportunities for implementing evidence-based antenatal care in Mozambique: a qualitative study.

Background: Maternal mortality remains a daunting problem in Mozambique and many other low-resource countries. High quality antenatal care (ANC) services can improve maternal and newborn health outcomes and increase the likelihood that women will seek skilled delivery care. This study explores the factors influencing provider uptake of the recommended package of ANC interventions in Mozambique.

A cluster randomized controlled trial of the non-pneumatic anti-shock garment for obstetric haemorrhage: sub-analysis of the Zimbabwean Arm.

Objectives: To determine whether earlier application of the Non-pneumatic Anti-Shock Garment (NASG) at clinic level compared to the referral hospital level reduces maternal morbidity and mortality and recovery time from shock due to severe Obstetric Haemorrhage (OH) and to determine the safety of the NASG when applied at clinic level.

Design: A cluster Randomized Controlled Trial (RCT)

Setting: Harare and Parirenyatwa Referral Hospitals (RH) in Harare and the twelve Harare City Council clinics that offer maternity care.

Subjects: Women who had suffered severe OH at clinic level and were being transferred to a Referral Hospital (RH).

Bed rest in singleton pregnancies for preventing preterm birth.

Background: Bed rest in hospital or at home is widely recommended for the prevention of preterm birth. This advice is based on the observation that hard work and hard physical activity during pregnancy could be associated with preterm birth and with the idea that bed rest could reduce uterine activity. However, bed rest may have some adverse effects on other outcomes.

TLR4 genotype and environmental LPS mediate RSV bronchiolitis through Th2 polarization.

While 30%-70% of RSV-infected infants develop bronchiolitis, 2% require hospitalization. It is not clear why disease severity differs among healthy, full-term infants; however, virus titers, inflammation, and Th2 bias are proposed explanations. While TLR4 is associated with these disease phenotypes, the role of this receptor in respiratory syncytial virus (RSV) pathogenesis is controversial.

Implementation of evidence-based antenatal care in Mozambique: a cluster randomized controlled trial: study protocol.

Background: Antenatal care (ANC) reduces maternal and perinatal morbidity and mortality directly through the detection and treatment of pregnancy-related illnesses, and indirectly through the detection of women at increased risk of delivery complications. The potential benefits of quality antenatal care services are most significant in low-resource countries where morbidity and mortality levels among women of reproductive age and neonates are higher.WHO developed an ANC model that recommended the delivery of services scientifically proven to improve maternal, perinatal and neonatal outcomes.

Per-protocol effect of earlier non-pneumatic anti-shock garment application for obstetric hemorrhage.

Earlier non-pneumatic anti-shock garment intervention was highly protective against maternal mortality and morbidity when analyzed to account for intervention fidelity; however, not all outcomes reached statistical significance.

Non-pneumatic anti-shock garment (NASG), a first-aid device to decrease maternal mortality from obstetric hemorrhage: a cluster randomized trial.

Background: Obstetric hemorrhage is the leading cause of maternal mortality. Using a cluster randomized design, we investigated whether application of the Non-pneumatic Anti-Shock Garment (NASG) before transport to referral hospitals (RHs) from primary health care centers (PHCs) decreased adverse outcomes among women with hypovolemic shock. We hypothesized the NASG group would have a 50% reduction in adverse outcomes.