Active case detection and treatment of malaria in pregnancy using LAMP technology (LAMPREG): a pragmatic randomised diagnostic outcomes trial-study protocol.

INTRODUCTION: Malaria is one of the major public health problems in sub-Saharan Africa. It contributes significantly to maternal and fetal morbidity and mortality in affected countries. This study aims to evaluate the impact of enhanced case detection using molecular testing called loop-mediated isothermal amplification (LAMP) on birth outcomes in a prospective study design. METHODS AND ANALYSIS: A pragmatic randomised diagnostic outcomes trial will be conducted in several health institutes in different Ethiopian regions. Women (n=2583) in their first and second trimesters of pregnancy will be included in the study and individually randomised to the standard of care or enhanced case detection arms, and followed until delivery. Enrolment will encompass the malaria peak transmission seasons. In the standard of care arm, a venous blood sample will be collected for malaria diagnosis only in symptomatic patients. In contrast, in the intervention arm, mothers will be tested by a commercially available Conformité Européene (CE)-approved LAMP malaria test, microscopy and rapid diagnostic test for malaria regardless of their symptoms at each antenatal care visit. The primary outcome of the study is to measure birth weight. ETHICS AND DISSEMINATION: The study was approved by the following ethical research boards: Armauer Hansen Research Institute/ALERT Ethics Review Committee (FORM AF-10-015.1, Protocol number PO/05/20), the Ethiopia Ministry of Science and Higher Education National Research Ethics Review Committee (approval SRA/11.7/7115/20), the Ethiopia Food and Drug Administration (approval 02/25/33/I), UCalgary Conjoint Health Research Ethics Board (REB21-0234). The study results will be shared with the institutions and stakeholders such as the Ethiopia Ministry of Health, the Foundation for Innovative Diagnostics, WHO's Multilateral initiative on Malaria - Tropical Diseases Research (TDR-MIM), Roll Back Malaria and the Malaria in Pregnancy Consortium. The study results will also be published in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: NCT03754322.

Chagas Congenital Screening in Switzerland: Processes of Recognition and Knowledge-Sharing.

Disparities in control mechanisms to prevent the spread of Chagas disease in Switzerland raise questions about the process of its recognition as a public health problem, particularly as it concerns migrant populations. With a focus on congenital screening practices, I explore the way in which health care providers experience, problematize and respond to the disease, acting as key agents not only in the provision of care but also in the recognition of Chagas disease as a problem that needs to be addressed. Such an approach contributes to the understanding of processes of public health agenda creation around neglected tropical diseases in non-endemic countries.

Malaria in Pregnancy and Adverse Birth Outcomes: New Mechanisms and Therapeutic Opportunities.

Malaria infection during pregnancy is associated with adverse birth outcomes but underlying mechanisms are poorly understood. Here, we discuss the impact of malaria in pregnancy on three pathways that are important regulators of healthy pregnancy outcomes: L-arginine-nitric oxide biogenesis, complement activation, and the heme axis. These pathways are not mutually exclusive, and they collectively create a proinflammatory, antiangiogenic milieu at the maternal-fetal interface that interferes with placental function and development. We hypothesize that targeting these host-response pathways would mitigate the burden of adverse birth outcomes attributable to malaria in pregnancy.

Toxoplasmosis in pregnancy: a neglected bane but a serious threat in Nigeria.

Toxoplasmosis is a global health threat in which occurrence in pregnant women poses grave consequences to fetal wellbeing. Studies on prenatal Toxoplasma gondii infection are generally limited in sub-Saharan African countries, including Nigeria. The risk of transmission of toxoplasmosis is very high in Nigeria due to the favourable climatic conditions and prevailing behavioural and socio-economic factors that could aid transmission. Currently, there are no systematic and organized procedures for diagnosis and treatment of maternal toxoplasmosis in Nigeria. These conditions forecast possible unabated transmission in many areas and exponential impact on associated adverse events of the disease during pregnancy. This paper highlights the importance of early diagnosis and treatment during pregnancy which may forestall subsequent development of infection in children delivered by infected mothers. Inclusion of toxoplasmosis control policy in the routine antenatal care of pregnant women is therefore strongly recommended.

Chyluria in pregnancy: Etiology, diagnosis, and management perspective.

Chyluria is clinically described as passage of milky urine. Chyle is absorbed by intestinal lacteals and is composed of emulsified fats, few proteins, and fibrin in varying proportions. Parasitic chyluria is caused mainly by Wuchereria bancrofti infection. The incidence of chyluria in pregnancy is not uncommon in endemic regions. The literature pertaining tomedical management of chyluria in pregnancy is scant. The antifilarial drugs have potential teratogenic risk and are not recommended in pregnant patients. Hence, there is a management dilemma for managing patients with chyluria during pregnancy. In this review, we have tried to highlight the evidence-based diagnosis and management of chyluria in pregnancy.

Evaluation and Management of Congenital Chagas Disease in the United States.

Chagas disease is underappreciated as a health concern in the United States. Approximately 40 000 women of childbearing age living in the United States have chronic Chagas disease. Most of them are unaware that they have an infection that is transmissible to their offspring. The estimated US maternal-to-infant transmission rate of Trypanosoma cruzi is 1% to 5%. Ten percent to 40% of neonates with congenital T cruzi infection have clinical signs consistent with a congenital infection but no findings are unique to Chagas disease. If left untreated, 20% to 40% of infants with Chagas disease will later develop potentially fatal cardiac manifestations. Molecular testing can confirm the diagnosis in neonates. Treatment is well tolerated in infancy and usually results in cure. Screening of at-risk women during pregnancy can identify maternal infection and allow early assessment and treatment for congenital T cruzi infection.

The treatment with selenium increases placental parasitismin pregnant Wistar rats infected with the Y strain of Trypanosoma cruzi.

Selenium (Se) is an essential micronutrient in the diet of mammals and has an important role in the immune function. Selenium is a key element in selenoproteins involved in the in the maintenance of the antioxidant defense. Diet with selenium is beneficial for the treatment of diseases correlated with high levels of oxidative stress, also observed in the Chagas disease. Chagas disease is a neglected disease caused by the protozoan Trypanosoma cruzi and several research groups are focused on the illness treatment. Immunomodulation of the infection using microelements is an important tool to avoid deleterious effects of the Chagas disease. Therefore, our objective was to evaluate the effects of selenium supplementation on pregnant Wistar rats infected with T. cruzi. Selenium treatment stimulated the weight and length of fetuses and placentas allied to the decrease of blood parasitemia. However, selenium demonstrated a low influence on T cells, diminishing the B cell population (CD45RA+). Moreover, the production of pro-inflammatory cytokines was downregulated under selenium administration. Low pro-inflammatory cytokines levels probably are related to the increase in the number of amastigote nests in infected and treated animals. Thus, selenium supplementation during pregnancy could impair the local placental immune response. Further studies are necessary to assess the interaction between selenium and the acute Chagas' disease during pregnancy, which will base future supplementation strategies.

Case Report: Acanthamoeba Keratitis Management in a First-trimester Pregnant Patient.

SIGNIFICANCE: Lacrimal punctal plugs may prevent the teratogenicity of the treatment used in infectious keratitis. Its use should be strongly considered in these cases. PURPOSE: We present the case of a 7-week pregnant patient with Acanthamoeba keratitis. CASE REPORT: The patient was a contact lens user with photophobia, redness, and intense pain in the right eye that started 2 weeks earlier. Corrected visual acuity was 20/63 (0.5 logMAR). Biomicroscopy revealed a ciliary injection, perineural infiltrates, and corneal edema. Confocal microscopy and culture confirmed the diagnosis of Acanthamoeba keratitis. Prior to treatment with amebicidal eye drops, plugs were implanted in the lacrimal puncta to reduce the risk of drugs' teratogenicity. Three months after initiating amebicidal treatment, a melting ulcer of immunological etiology developed, which was treated with ReGeneraTing Agent eye drops, carboxymethyl glucose polysulfate (Cacicol; Théa, Clermont-Ferrand, France). CONCLUSIONS: Lacrimal occlusion with punctal plugs is one of the available options available in cases of pregnant patients to reduce the risk of teratogenicity.

When Epidemiology Is the Clue to a Positive Outcome: A Case of Malaria During Pregnancy.

BACKGROUND Malaria infection during pregnancy is associated with increased perinatal and maternal morbidity and mortality. CASE REPORT A 29-year-old primigravida at 37 weeks of gestation, with no significant medical history, presented complaining of fever, chills, and generalized body aches. She had been living in Malawi for 1 year and was on atovaquone/proguanil prophylaxis until she was found to be pregnant. Prophylaxis was changed to mefloquine and discontinued upon her return to the US. Six weeks prior to presentation, she traveled to Malawi for 1 month when she was off prophylaxis. On admission, vital signs and physical exam results were normal. Given epidemiologic findings, a malaria smear was performed and showed 4% parasitemia. She was treated with mefloquine and discharged. Two days after discharge, she again presented with fever, chills, and body aches. A malaria smear showed <0.01% parasitemia, with 2 ring forms. Serologies for dengue, chikungunya, leptospira, and blood cultures were negative. These symptoms were deemed secondary to early recrudescence. The species was later identified as P. falciparum. The patient was treated with quinine sulfate and clindamycin. She delivered at full term without complication. CONCLUSIONS Pregnant women are more susceptible to severe forms of malaria, such as P. falciparum. A high index of suspicion and early identification of malaria are vital to prevent deleterious outcomes.

Assessment of the safety of antimalarial drug use during early pregnancy (ASAP): protocol for a multicenter prospective cohort study in Burkina Faso, Kenya and Mozambique

Background: A major unresolved safety concern for malaria case management is the use of artemisinin combination therapies (ACTs) in the first trimester of pregnancy. There is a need for human data to inform policy makers and treatment guidelines on the safety of artemisinin combination therapies (ACT) when used during early pregnancy. Methods: The overall goal of this paper is to describe the methods and implementation of a study aimed at developing surveillance systems for identifying exposures to antimalarials during early pregnancy and for monitoring pregnancy outcomes using health and demographic surveillance platforms. This was a multi-center prospective observational cohort study involving women at health and demographic surveillance sites in three countries in Africa: Burkina Faso, Kenya and Mozambique [(ClinicalTrials.gov Identifier: NCT01232530)]. The study was designed to identify pregnant women with artemisinin exposure in the first trimester and compare them to: 1) pregnant women without malaria, 2) pregnant women treated for malaria, but exposed to other antimalarials, and 3) pregnant women with malaria and treated with artemisinins in the 2nd or 3rd trimesters from the same settings. Pregnant women were recruited through community-based surveys and attendance at health facilities, including antenatal care clinics and followed until delivery. Data from the three sites will be pooled for analysis at the end of the study. Results are forthcoming. Discussion: Despite few limitations, the methods described here are relevant to the development of sustainable pharmacovigilance systems for drugs used by pregnant women in the tropics using health and demographic surveillance sites to prospectively ascertain drug safety in early pregnancy.

Recommended management of Toxoplasma gondii infection in pregnant women and their children.

Aforesaid recommendations for the management of T.gondii infection, elaborated by the group of experts, are intended for physicians of various specialties in order to standardize and facilitate diagnostic and therapeutic management. Early diagnosis of congenital toxoplasmosis, both symptomatic and asymptomatic, in neonatal period, initiation of adequate treatment and long-term, multispecialist monitoring, including multi-organ rehabilitation of children may prevent or reduce the complications of congenital toxoplasmosis. Health education, whose role is often underestimated, should be targeted mainly on girls and women at reproductive age as to prevent from infection during pregnancy.

A case of cutaneous larva migrans presenting in a pregnant patient.

Cutaneous larva migrans (CLM) is a pruritic dermatitis caused by migration of animal hookworm larvae into the skin. We present a case of CLM in a 31-year-old pregnant woman. The treatment of CLM relies on antihelminthic agents, such as thiabendazole, albendazole, and ivermectin. This case was interesting in that the standard treatment options previously mentioned were contraindicated owing to the patient's pregnancy. Cryotherapy with liquid nitrogen resulted in complete resolution of her lesion and symptoms.

[Toxoplasmosis: Epidemiology, Diagnosis, Treatment].

The up-to-date literature and original data on the epidemiology, diagnosis and treatment of toxoplasmosis are presented. Particular attention is paid to the parasite infection during pregnancy. Spiramycin is the drug of choice for acute toxoplasmosis in pregnant women.

Adoptive transfer of Treg cells counters adverse effects of Toxoplasma gondii infection on pregnancy.

Acute infection with Toxoplasma gondii (T. gondii) during pregnancy is associated with adverse outcomes. The mechanisms that cause this phenomenon are not clear. Regulatory T cells (Tregs) are involved in maternal tolerance, and here we observed a decrease in the absolute numbers of CTLA-4(+) Tregs and PD-1(+) Tregs in spleen and at the fetal-maternal interface in T. gondii-infected mice. Our results suggest that T. gondii induces apoptosis of Tregs. Additionally, we found that the expression of CTLA-4 and PD-1 on Tregs at fetal-maternal interface were higher than on spleen cells from normal pregnant mice. Therefore, we adoptively transferred Tregs from fetal-maternal interface or from spleens of normal pregnant mice into infected pregnant mice. Pregnancy outcomes were improved when Tregs were transferred from the fetal-maternal interface but not from the spleen. The mechanism appears to be through up-regulation of the number of CTLA-4(+) Tregs and PD-1(+) Tregs and correction of the imbalance between tolerant cytokines (IL-10, TGF-ß) and inflammatory cytokines (IFN-γ). Our data indicate that Tregs at fetal-maternal interface express high levels of inhibitory molecules that play a vital immuno-protective role during pregnancy.

Oligohydramnios in a pregnant Pakistani woman with Plasmodium vivax malaria.

In the Western world, the diagnosis and management of Plasmodium vivax malaria in pregnant women can be challenging, and the pathogenesis of adverse outcomes for both the mother and the foetus is still poorly known. The authors describe the case of a 29-year-old Pakistani woman at the 29th week of her second pregnancy, who was admitted to the Hospital following the abrupt onset of fever. At the time of admission, she had been living in Italy without travelling to any malaria-endemic areas for eight months. She was diagnosed with vivax malaria after a thin blood smear revealed the presence of plasmodial trophozoites and gametocytes and treated accordingly. Due to the onset of oligohydramnios, she underwent caesarian section at the 31st week of pregnancy with no further complications. Histological examination of the placenta showed no evidence of plasmodial infection, but was inconclusive. It is unclear whether oligohydramnios is a complication of pregnancy-related Plasmodium vivax malaria. Given the long latency of hypnozoites, every febrile pregnant patient with a previous stay in an endemic area should be screened for malaria with a thick and a thin blood smear.