There seems to be no biological sex difference regarding vulnerability to Ebola virus disease, yet many sociocultural and health-care-related factors increase the risks for women in the Ebola ...outbreak in west Africa.
...the south of Mozambique has historically experienced unsuccessful malaria control and elimination attempts using mainly IRS in the 1960s during the Global Malaria Eradication Program, and in the ...2000s in the context of the Lubombo Spatial Development Initiative (LSDI) that aimed to eliminate malaria in South Africa and Eswatini 6. IPTp, intermittent preventive treatment for pregnant women; IRS, indoor residual spraying; LLIN, long-lasting insecticidal net; MDA, mass drug administration; NMCP, National Malaria Control Program; rfMDA, reactive focal mass drug administration. https://doi.org/10.1371/journal.pmed.1003227.g001 Interventions and study procedures Programmatic interventions: Malaria case management in Magude consisted of the standard of care provided by the national health system, which relied on passive detection and testing with a histidine-rich protein 2 (HRP2)-based rapid diagnostic test (RDT) of all patients presenting with a fever (axillary temperature ≥37.5°C or reported fever in the previous 24 hours) at the HFs or to CHWs (or “Agente Polivalente Elemental,” APE in Portuguese), and on treating the confirmed positives with artemether-lumefantrine. The data submitted weekly included total number of outpatient visits, RDTs performed or slides read using microscopy, positive slides or RDTs, and cases treated, stratified by <5 and ≥5 years old (including malaria cases among pregnant women tested in the outpatient ward).
There is an urgent need to identify tools able to provide reliable information on the cause of death in low-income regions, since current methods (verbal autopsy, clinical records, and complete ...autopsies) are either inaccurate, not feasible, or poorly accepted. We aimed to compare the performance of a standardized minimally invasive autopsy (MIA) approach with that of the gold standard, the complete diagnostic autopsy (CDA), in a series of adults who died at Maputo Central Hospital in Mozambique.
In this observational study, coupled MIAs and CDAs were performed in 112 deceased patients. The MIA analyses were done blindly, without knowledge of the clinical data or the results of the CDA. We compared the MIA diagnosis with the CDA diagnosis of cause of death. CDA diagnoses comprised infectious diseases (80; 71.4%), malignant tumors (16; 14.3%), and other diseases, including non-infectious cardiovascular, gastrointestinal, kidney, and lung diseases (16; 14.3%). A MIA diagnosis was obtained in 100/112 (89.2%) cases. The overall concordance between the MIA diagnosis and CDA diagnosis was 75.9% (85/112). The concordance was higher for infectious diseases and malignant tumors (63/80 78.8% and 13/16 81.3%, respectively) than for other diseases (9/16; 56.2%). The specific microorganisms causing death were identified in the MIA in 62/74 (83.8%) of the infectious disease deaths with a recognized cause. The main limitation of the analysis is that both the MIA and the CDA include some degree of expert subjective interpretation.
A simple MIA procedure can identify the cause of death in many adult deaths in Mozambique. This tool could have a major role in improving the understanding and surveillance of causes of death in areas where infectious diseases are a common cause of mortality.
Plasmodium falciparum immature gametocytes are not observed in peripheral blood. However, gametocyte stages in organs such as bone marrow have never been assessed by molecular techniques, which are ...more sensitive than optical microscopy. We quantified P falciparum sexual stages in bone marrow (n = 174) and peripheral blood (n = 70) of Mozambican anemic children by quantitative polymerase chain reaction targeting transcripts specific for early (PF14_0748; PHISTa), intermediate (PF13_0247; Pfs48/45), and mature (PF10_0303; Pfs25) gametocytes. Among children positive for the P falciparum housekeeping gene (PF08_0085; ubiquitin-conjugating enzyme gene) in bone marrow (n = 136) and peripheral blood (n = 25), prevalence of immature gametocytes was higher in bone marrow than peripheral blood (early: 95% vs 20%, P < .001; intermediate: 80% vs 16%; P < .001), as were transcript levels (P < .001 for both stages). In contrast, mature gametocytes were more prevalent (100% vs 51%, P < .001) and abundant (P < .001) in peripheral blood than in the bone marrow. Severe anemia (3.57, 95% confidence interval 1.49-8.53) and dyserythropoiesis (6.21, 95% confidence interval 2.24-17.25) were independently associated with a higher prevalence of mature gametocytes in bone marrow. Our results highlight the high prevalence and abundance of early sexual stages in bone marrow, as well as the relationship between hematological disturbances and gametocyte development in this tissue.
•In P falciparum–infected anemic children, immature gametocytes are more prevalent and abundant in bone marrow than in peripheral blood.•P falciparum–infected anemic children are gametocyte carriers that can potentially contribute to malaria transmission.
Adolescent substance abuse is a problem worldwide. This book provides a comprehensive overview of this issue with a special focus on alcohol abuse. Chapters discuss the biological, social, and ...environmental risk factors of substance abuse in adolescents, behavioral and pharmacological interventions to prevent or reduce the negative effects of substance abuse, psychological disorders associated with drug abuse, and much more.
Complete diagnostic autopsies (CDA) remain the gold standard in the determination of cause of death (CoD). However, performing CDAs in developing countries is challenging due to limited facilities ...and human resources, and poor acceptability. We aimed to develop and test a simplified minimally invasive autopsy (MIA) procedure involving organ-directed sampling with microbiology and pathology analyses implementable by trained technicians in low- income settings.
A standardized scheme for the MIA has been developed and tested in a series of 30 autopsies performed at the Maputo Central Hospital, Mozambique. The procedure involves the collection of 20 mL of blood and cerebrospinal fluid (CSF) and puncture of liver, lungs, heart, spleen, kidneys, bone marrow and brain in all cases plus uterus in women of childbearing age, using biopsy needles.
The sampling success ranged from 67% for the kidney to 100% for blood, CSF, lung, liver and brain. The amount of tissue obtained in the procedure varied from less than 10 mm2 for the lung, spleen and kidney, to over 35 mm2 for the liver and brain. A CoD was identified in the histological and/or the microbiological analysis in 83% of the MIAs.
A simplified MIA technique allows obtaining adequate material from body fluids and major organs leading to accurate diagnoses. This procedure could improve the determination of CoD in developing countries.
Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended by WHO to prevent malaria in African pregnant women. The spread of SP parasite resistance has ...raised concerns regarding long-term use for IPT. Mefloquine (MQ) is the most promising of available alternatives to SP based on safety profile, long half-life, and high efficacy in Africa. We evaluated the safety and efficacy of MQ for IPTp compared to those of SP in HIV-negative women.
A total of 4,749 pregnant women were enrolled in an open-label randomized clinical trial conducted in Benin, Gabon, Mozambique, and Tanzania comparing two-dose MQ or SP for IPTp and MQ tolerability of two different regimens. The study arms were: (1) SP, (2) single dose MQ (15 mg/kg), and (3) split-dose MQ in the context of long lasting insecticide treated nets. There was no difference on low birth weight prevalence (primary study outcome) between groups (360/2,778 13.0%) for MQ group and 177/1,398 (12.7%) for SP group; risk ratio RR, 1.02 (95% CI 0.86-1.22; p=0.80 in the ITT analysis). Women receiving MQ had reduced risks of parasitemia (63/1,372 4.6% in the SP group and 88/2,737 3.2% in the MQ group; RR, 0.70 95% CI 0.51-0.96; p=0.03) and anemia at delivery (609/1,380 44.1% in the SP group and 1,110/2743 40.5% in the MQ group; RR, 0.92 95% CI 0.85-0.99; p=0.03), and reduced incidence of clinical malaria (96/551.8 malaria episodes person/year PYAR in the SP group and 130/1,103.2 episodes PYAR in the MQ group; RR, 0.67 95% CI 0.52-0.88; p=0.004) and all-cause outpatient attendances during pregnancy (850/557.8 outpatients visits PYAR in the SP group and 1,480/1,110.1 visits PYAR in the MQ group; RR, 0.86 0.78-0.95; p=0.003). There were no differences in the prevalence of placental infection and adverse pregnancy outcomes between groups. Tolerability was poorer in the two MQ groups compared to SP. The most frequently reported related adverse events were dizziness (ranging from 33.9% to 35.5% after dose 1; and 16.0% to 20.8% after dose 2) and vomiting (30.2% to 31.7%, after dose 1 and 15.3% to 17.4% after dose 2) with similar proportions in the full and split MQ arms. The open-label design is a limitation of the study that affects mainly the safety assessment.
Women taking MQ IPTp (15 mg/kg) in the context of long lasting insecticide treated nets had similar prevalence rates of low birth weight as those taking SP IPTp. MQ recipients had less clinical malaria than SP recipients, and the pregnancy outcomes and safety profile were similar. MQ had poorer tolerability even when splitting the dose over two days. These results do not support a change in the current IPTp policy.
ClinicalTrials.gov NCT 00811421; Pan African Clinical Trials Registry PACTR 2010020001429343 Please see later in the article for the Editors' Summary.
About 3·7 billion doses of ivermectin have been distributed in mass drug administration (MDA) campaigns globally over the past 30 years. At 10–100 times higher than current human doses, ivermectin is ...a known teratogen in mammals. During these campaigns with recommended doses, pregnant women might be inadvertently exposed. We therefore aimed to evaluate the existing evidence for serious and non-serious adverse events after ivermectin exposure in pregnant women.
For this systematic review and meta-analysis, we searched relevant databases and trial registry platforms on July 15, 2018, for randomised controlled trials (RCTs) and observational studies that reported adverse events in pregnant women. We did not use language or date restrictions. Outcomes of interest were spontaneous abortions, stillbirths, congenital anomalies, and neonatal death (serious adverse events), as well as maternal morbidity, preterm births, and low birthweight (adverse events). The risk of bias was assessed using the Newcastle-Ottawa Scale for observational studies and the Cochrane Risk of Bias Tool for RCTs. We did the meta-analysis of observational studies and RCTs separately. The quality of evidence was assessed using the GRADE approach. The study protocol is registered with PROSPERO, protocol CRD42016046914.
We identified 147 records, of which only five observational studies and one RCT were included for quantitative analysis; these studies were published between 1990 and 2008, and were done in six African countries. 893 women with 899 pregancy outcomes were included, of whom 496 pregnant women (500 pregnancy outcomes) received ivermectin inadvertently during MDA campaigns in the observational studies and 397 pregnant women (399 pregnancy outcomes) purposely received ivermectin as part of the open-label RCT. No study reported neonatal deaths, maternal morbidity, preterm births, or low birthweight. It is unclear whether exposure to ivermectin during pregnancy increases the risk of spontaneous abortions and stillbirths (odds ratio OR 1·15 95% CI 0·75–1·78 with very low certainty of evidence for the four observational studies and 0·62 0·18–2·14 with very low certainty of evidence for the RCT) or congenital anomalies (OR 1·69 95% CI 0·83–3·41 with very low certainty of evidence for the five observational studies and 1·10 0·07–17·65 with very low certainty of evidence for the RCT).
There is insufficient evidence to conclude on the safety profile of ivermectin during pregnancy. Treatment campaigns should focus additional efforts on preventing inadvertent treatment of pregnant women.
Unitaid.
The minimally invasive autopsy (MIA) is being investigated as an alternative to complete diagnostic autopsies for cause of death (CoD) investigation. Before potential implementation of the MIA in ...settings where post-mortem procedures are unusual, a thorough assessment of its feasibility and acceptability is essential.
We conducted a socio-behavioural study at the community level to understand local attitudes and perceptions related to death and the hypothetical feasibility and acceptability of conducting MIAs in six distinct settings in Gabon, Kenya, Mali, Mozambique, and Pakistan. A total of 504 interviews (135 key informants, 175 health providers including formal health professionals and traditional or informal health providers, and 194 relatives of deceased people) were conducted. The constructs "willingness to know the CoD" and "hypothetical acceptability of MIAs" were quantified and analysed using the framework analysis approach to compare the occurrence of themes related to acceptability across participants. Overall, 75% (379/504) of the participants would be willing to know the CoD of a relative. The overall hypothetical acceptability of MIA on a relative was 73% (366/504). The idea of the MIA was acceptable because of its perceived simplicity and rapidity and particularly for not "mutilating" the body. Further, MIAs were believed to help prevent infectious diseases, address hereditary diseases, clarify the CoD, and avoid witchcraft accusations and conflicts within families. The main concerns regarding the procedure included the potential breach of confidentiality on the CoD, the misperception of organ removal, and the incompatibility with some religious beliefs. Formal health professionals were concerned about possible contradictions between the MIA findings and the clinical pre-mortem diagnoses. Acceptability of the MIA was equally high among Christian and Islamic communities. However, in the two predominantly Muslim countries, MIA acceptability was higher in Mali than in Pakistan. While the results of the study are encouraging for the potential use of the MIA for CoD investigation in low-income settings, they remain hypothetical, with a need for confirmation with real-life MIA implementation and in populations beyond Health and Demographic Surveillance System areas.
This study showed a high level of interest in knowing the CoD of a relative and a high hypothetical acceptability of MIAs as a tool for CoD investigation across six distinct settings. These findings anticipate potential barriers and facilitators, both at the health facility and community level, essential for local tailoring of recommendations for future MIA implementation.
Animal embryotoxicity data, and the scarcity of safety data in human pregnancies, have prevented artemisinin derivatives from being recommended for malaria treatment in the first trimester except in ...lifesaving circumstances. We conducted a meta-analysis of prospective observational studies comparing the risk of miscarriage, stillbirth, and major congenital anomaly (primary outcomes) among first-trimester pregnancies treated with artemisinin derivatives versus quinine or no antimalarial treatment.
Electronic databases including Medline, Embase, and Malaria in Pregnancy Library were searched, and investigators contacted. Five studies involving 30,618 pregnancies were included; four from sub-Saharan Africa (n = 6,666 pregnancies, six sites) and one from Thailand (n = 23,952). Antimalarial exposures were ascertained by self-report or active detection and confirmed by prescriptions, clinic cards, and outpatient registers. Cox proportional hazards models, accounting for time under observation and gestational age at enrollment, were used to calculate hazard ratios. Individual participant data (IPD) meta-analysis was used to combine the African studies, and the results were then combined with those from Thailand using aggregated data meta-analysis with a random effects model. There was no difference in the risk of miscarriage associated with the use of artemisinins anytime during the first trimester (n = 37/671) compared with quinine (n = 96/945; adjusted hazard ratio aHR = 0.73 95% CI 0.44, 1.21, I2 = 0%, p = 0.228), in the risk of stillbirth (artemisinins, n = 10/654; quinine, n = 11/615; aHR = 0.29 95% CI 0.08-1.02, p = 0.053), or in the risk of miscarriage and stillbirth combined (pregnancy loss) (aHR = 0.58 95% CI 0.36-1.02, p = 0.099). The corresponding risks of miscarriage, stillbirth, and pregnancy loss in a sensitivity analysis restricted to artemisinin exposures during the embryo sensitive period (6-12 wk gestation) were as follows: aHR = 1.04 (95% CI 0.54-2.01), I2 = 0%, p = 0.910; aHR = 0.73 (95% CI 0.26-2.06), p = 0.551; and aHR = 0.98 (95% CI 0.52-2.04), p = 0.603. The prevalence of major congenital anomalies was similar for first-trimester artemisinin (1.5% 95% CI 0.6%-3.5%) and quinine exposures (1.2% 95% CI 0.6%-2.4%). Key limitations of the study include the inability to control for confounding by indication in the African studies, the paucity of data on potential confounders, the limited statistical power to detect differences in congenital anomalies, and the lack of assessment of cardiovascular defects in newborns.
Compared to quinine, artemisinin treatment in the first trimester was not associated with an increased risk of miscarriage or stillbirth. While the data are limited, they indicate no difference in the prevalence of major congenital anomalies between treatment groups. The benefits of 3-d artemisinin combination therapy regimens to treat malaria in early pregnancy are likely to outweigh the adverse outcomes of partially treated malaria, which can occur with oral quinine because of the known poor adherence to 7-d regimens.
PROSPERO CRD42015032371.
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