Diagnostic performance of an ultra-sensitive RDT and a conventional RDT in malaria mass testing, treatment and tracking interventions in southern Ghana.

BACKGROUND: Application of numerous malaria control interventions has led to reduction in clinical malaria cases and deaths but also the realisation that asymptomatic parasite carriers play a key role in sustaining transmission. This study assessed the effectiveness of using the Ultra-sensitive NxTek eliminate RDT (uRDT) and conventional SD Bioline HRP2 RDT (cRDT) in diagnosing asymptomatic parasitaemia while measuring the impact of mass testing, treatment and tracking (MTTT) on the prevalence of asymptomatic malaria over a 1-year period in Ghana. METHODS: A total of 4000 targeted participants from two towns, Obom and Kofi Kwei, with their surrounding villages, were tested for asymptomatic malaria four times over the study period using uRDT (intervention) and the cRDT (control) respectively. Participants carrying malaria parasites were followed by home visit and phone calls for compliance to treatment, and filter paper blood blots collected from participants were used to determine true parasite carriage by PET-PCR. A mathematical model of the study site was developed and used to test the impact of test sensitivity and mass migration on the effect of MTTT. RESULTS: The start and end point sensitivities of the cRDT were 48.8% and 41.7% and those for the uRDT were 52.9% and 59.9% respectively. After a year of MTTTs, asymptomatic parasite prevalence, as determined by PCR, did not differ statistically in the control site (40.6% to 40.1%, P = 0.730) but decreased at the intervention site (55.9% to 46.4%, P < 0.0001). Parasite prevalence by RDT, however, indicated statistical reduction in the control site (25.3% to 22.3%, P = 0.017) and no change in the intervention site (35.1% to 36.0%, P = 0.614). The model predicted a mild effect of both diagnostic sensitivity and human movement in diminishing the impact of MTTT in the study sites. CONCLUSIONS: Asymptomatic parasite prevalence at the molecular level reduced significantly in the site where the uRDT was used but not where the cRDT was used. Overall, the uRDT exhibited higher sensitivity relative to the cRDT. Highly sensitive molecular techniques such as PET-PCR should be included in parasite prevalence estimation during MTTT exercises.

Multiple myeloma and Chagas disease: qPCR as a marker for preemptive antiparasitic therapy: a case reports series and review.

Multiple myeloma (MM) associated with Chagas disease is rarely described. This disease and its therapy suppress T cell and macrophage functions and increase regulatory T cell function, allowing the increase of parasitemia and the risk of Chagas Disease Reactivation (CDR). We aimed to analyze the role of conventional (cPCR) and quantitative Polymerase Chain Reaction (qPCR) for prospective monitoring of T. cruzi parasitemia, searching for markers of preemptive antiparasitic therapy in MM patients with Chagas disease. Moreover, we investigated the incidence and management of hematological diseases and CDR both inside and outside the transplant setting in the MEDLINE database. We found 293 studies and included 31 of them. Around 1.9-2.0% of patients with Chagas disease were reported in patients undergoing Stem Cell Transplantation. One case of CDR was described in eight cases of MM and Chagas disease. We monitored nine MM and Chagas disease patients, seven under Autologous Stem Cell Transplantation (ASCT), during 44.56±32.10 months (mean±SD) using parasitological methods, cPCR, and qPCR. From these patients, three had parasitemia. In the first, up to 256 par Eq/mL were detected, starting from 28 months after ASCT. The second patient dropped out and died soon after the detection of 161.0 par Eq/mL. The third patient had a positive blood culture. Benznidazole induced fast negativity in two cases; followed by notably lower levels in one of them. Increased T. cruzi parasitemia was related to the severity of the underlying disease. We recommend parasitemia monitoring by qPCR for early introduction of preemptive antiparasitic therapy to avoid CDR.

Haematological parameters and their correlation with the degree of malaria parasitaemia among outpatients attending a polyclinic.

BACKGROUND: Malaria is a parasitic disease caused by various species of the blood parasite Plasmodium; of all the parasitic diseases, malaria has the highest prevalence and mortality with an estimated 247 million cases and 619,000 deaths recorded worldwide as of 2021. Malaria causes febrile illness with several changes in blood cell parameters. Some of these changes include leucopenia, thrombocytopenia, and anaemia. If these changes could be correlated with the degree of parasitaemia, it can serve as a guide to physicians when treating malaria. This study was therefore aimed at correlating haematological parameters with levels of parasitaemia during malaria infection. METHODS: The study was a cross-sectional study involving 89 malaria positive patients. About 5 ml of blood was collected from each participant who gave his or her informed consent to partake in the study. A full blood count was performed on their samples to determine their haematological parameters using a haematology auto-analyzer. A parasite count was also performed via microscopy to determine the degree of parasitaemia. The data obtained from the study was entered into a database and statistically analysed using Statistical Package for Social Sciences (SPSS) version 23 and Microsoft Excel 2016. RESULTS: The study comprised of 89 participants out of which 35 were males and 54 were females with the mean age of 26.15 years. Secondary education participants were the highest with quaternary education the lowest. The highest parasite count recorded was 398,174 parasites/µl of blood, lowest count was 101 with the average being 32,942.32584. There was also a significant positive Pearson's correlation between total WBC and parasitaemia and with the WBC differentials, neutrophils, lymphocytes and monocytes had positive correlations while eosinophils and basophils had negative correlations. Furthermore, platelets, total RBC's, haemoglobin, MCH, MCHC and Hct all showed negative correlations. Linear regression also showed a linear relationship between parasite density and the various haematological parameters. CONCLUSION: The linear relationship (correlation) between WBC and MCH were the only significant ones at 95% and 99% confidence interval, respectively based on a two-tail t-test. Also, based on the regression analysis, the changes caused by WBC and PLT were the only significant changes at 95% confidence level in a two-tailed t-test.

Associations of maternal iron deficiency with malaria infection in a cohort of pregnant Papua New Guinean women.

BACKGROUND: Iron deficiency (ID) is common in malaria-endemic settings. Intermittent preventative treatment of malaria in pregnancy (IPTp) and iron supplementation are core components of antenatal care in endemic regions to prevent adverse pregnancy outcomes. ID has been associated with reduced risk of malaria infection, and correspondingly, iron supplementation with increased risk of malaria infection, in some studies. METHODS: A secondary analysis was conducted amongst 1888 pregnant women enrolled in a malaria prevention trial in Papua New Guinea. Maternal ID was defined as inflammation-corrected plasma ferritin levels < 15 µg/L at antenatal enrolment. Malaria burden (Plasmodium falciparum, Plasmodium vivax) was determined by light microscopy, polymerase chain reaction, and placental histology. Multiple logistic and linear regression analyses explored the relationship of ID or ferritin levels with indicators of malaria infection. Models were fitted with interaction terms to assess for modification of iron-malaria relationships by gravidity or treatment arm. RESULTS: Two-thirds (n = 1226) and 13.7% (n = 258) of women had ID and peripheral parasitaemia, respectively, at antenatal enrolment (median gestational age: 22 weeks), and 18.7% (120/1,356) had evidence of malaria infection on placental histology. Overall, ID was associated with reduced odds of peripheral parasitaemia at enrolment (adjusted odds ratio [aOR] 0.50; 95% confidence interval [95% CI] 0.38, 0.66, P < 0.001); peripheral parasitaemia at delivery (aOR 0.68, 95% CI 0.46, 1.00; P = 0.050); and past placental infection (aOR 0.35, 95% CI 0.24, 0.50; P < 0.001). Corresponding increases in the odds of infection were observed with two-fold increases in ferritin levels. There was effect modification of iron-malaria relationships by gravidity. At delivery, ID was associated with reduced odds of peripheral parasitaemia amongst primigravid (AOR 0.44, 95% CI 0.25, 0.76; P = 0.003), but not multigravid women (AOR 1.12, 95% CI 0.61, 2.05; P = 0.720). A two-fold increase in ferritin associated with increased odds of placental blood infection (1.44, 95% CI 1.06, 1.96; P = 0.019) and active placental infection on histology amongst primigravid women only (1.24, 95% CI 1.00, 1.54; P = 0.052). CONCLUSIONS: Low maternal ferritin at first antenatal visit was associated with a lower risk of malaria infection during pregnancy, most notably in primigravid women. The mechanisms by which maternal iron stores influence susceptibility to infection with Plasmodium species require further investigation.

A novel murine model of post-implantation malaria-induced preterm birth.

Despite major advances made in malaria treatment and control over recent decades, the development of new models for studying disease pathogenesis remains a vital part of malaria research efforts. The study of malaria infection during pregnancy is particularly reliant on mouse models, as a means of circumventing many challenges and costs associated with pregnancy studies in endemic human populations. Here, we introduce a novel murine model that will further our understanding of how malaria infection affects pregnancy outcome. When C57BL/6J (B6) mice are infected with Plasmodium chabaudi chabaudi AS on either embryonic day (E) 6.5, 8.5, or 10.5, preterm birth occurs in all animals by E16.5, E17.5, or E18.5 respectively, with no evidence of intrauterine growth restriction. Despite having the same outcome, we found that the time to delivery, placental inflammatory and antioxidant transcript upregulation, and the relationships between parasitemia and transcript expression prior to preterm birth differed based on the embryonic day of infection. On the day before preterm delivery, E6.5 infected mice did not experience significant upregulation of the inflammatory or antioxidant gene transcripts examined; however, peripheral and placental parasitemia correlated positively with Il1ß, Cox1, Cat, and Hmox1 placental transcript abundance. E8.5 infected mice had elevated transcripts for Ifnγ, Tnf, Il10, Cox1, Cox2, Sod1, Sod2, Cat, and Nrf2, while Sod3 was the only transcript that correlated with parasitemia. Finally, E10.5 infected mice had elevated transcripts for Ifnγ only, with a tendency for Tnf transcripts to correlate with peripheral parasitemia. Tumor necrosis factor deficient (TNF-/-) and TNF receptor 1 deficient (TNFR1-/-) mice infected on E8.5 experienced preterm birth at the same time as B6 controls. Further characterization of this model is necessary to discover the mechanism(s) and/or trigger(s) responsible for malaria-driven preterm birth caused by maternal infection during early pregnancy.

Cluster-randomized controlled trial of intermittent preventive treatment in infancy using sulfadoxine-pyrimethamine (SP-IPTi): a pilot study in Nigeria.

BACKGROUND: Malaria kills a child in sub-Saharan Africa every 2 min despite widely available interventions including intermittent preventive treatment in infants (IPTi). Since 2010, when World Health Organization (WHO) recommended IPTi, no country has implemented it. To our knowledge, no IPTi study has been conducted in Nigeria. Considering severity of malaria in infancy and urgency to improve malaria prevention, we proposed a study to investigate the efficacy of this intervention in reducing malarial morbidity and mortality. OBJECTIVE(S): The aim of this was to determine the safety and efficacy of SP-IPTi in reducing the prevalence of asymptomatic malaria parasitemia and malarial-associated hospital admissions. METHODS: We performed a cluster-randomized controlled trial in 1379 infants. SP was administered alongside routine vaccinations in immunization centers randomized to intervention groups. Infants in control groups received only routine vaccines. Malarial 'morbidity and adverse events were monitored through passive case-detection and cross-sectional surveys'. RESULTS: SP-IPTi was safe. There was no statistically significant difference in terms of risks of asymptomatic parasitemia at 9 months, fever or hospitalization between our control and intervention groups. CONCLUSIONS: Our study demonstrated that SP-IPTi had no benefit but was well tolerated. WHO and some researchers have also reported declining efficacy of SP, due to increasing drug resistance.

The epidemiology of Plasmodium vivax among adults in the Democratic Republic of the Congo.

Reports of P. vivax infections among Duffy-negative hosts have accumulated throughout sub-Saharan Africa. Despite this growing body of evidence, no nationally representative epidemiological surveys of P. vivax in sub-Saharan Africa have been performed. To overcome this gap in knowledge, we screened over 17,000 adults in the Democratic Republic of the Congo (DRC) for P. vivax using samples from the 2013-2014 Demographic Health Survey. Overall, we found a 2.97% (95% CI: 2.28%, 3.65%) prevalence of P. vivax infections across the DRC. Infections were associated with few risk-factors and demonstrated a relatively flat distribution of prevalence across space with focal regions of relatively higher prevalence in the north and northeast. Mitochondrial genomes suggested that DRC P. vivax were distinct from circulating non-human ape strains and an ancestral European P. vivax strain, and instead may be part of a separate contemporary clade. Our findings suggest P. vivax is diffusely spread across the DRC at a low prevalence, which may be associated with long-term carriage of low parasitemia, frequent relapses, or a general pool of infections with limited forward propagation.

Peripheral Plasmodium falciparum Infection in Early Pregnancy Is Associated With Increased Maternal Microchimerism in the Offspring.

BACKGROUND: Placental malaria has been associated with increased cord blood maternal microchimerism (MMc), which in turn may affect susceptibility to malaria in the offspring. We sought to determine the impact of maternal peripheral Plasmodium falciparum parasitemia during pregnancy on MMc and to determine whether maternal cells expand during primary parasitemia in the offspring. METHODS: We conducted a nested cohort study of maternal-infant pairs from a prior pregnancy malaria chemoprevention study. Maternal microchimerism was measured by quantitative polymerase chain reaction targeting a maternal-specific marker in genomic DNA from cord blood, first P falciparum parasitemia, and preparasitemia. Logistic and negative binomial regression were used to assess the impact of maternal peripheral parasitemia, symptomatic malaria, and placental malaria on cord blood MMc. Generalized estimating equations were used to assess predictors of MMc during infancy. RESULTS: Early maternal parasitemia was associated with increased detection of cord blood MMc (adjusted odds ratio = 3.91, P = .03), whereas late parasitemia, symptomatic malaria, and placental malaria were not. The first parasitemia episode in the infant was not associated with increased MMc relative to preparasitemia. CONCLUSIONS: Maternal parasitemia early in pregnancy may increase the amount of MMc acquired by the fetus. Future work should investigate the impact of this MMc on immune responses in the offspring.

Prevalence of asymptomatic malaria parasitaemia following mass testing and treatment in Pakro sub-district of Ghana.

BACKGROUND: Global efforts to scale-up malaria control interventions are gaining steam. These include the use of Long-Lasting Insecticide Nets, Indoor Residual Spraying, Intermittent Preventive Treatment and Test, Treat and Track. Despite these, the drive for malaria elimination is far from being realistic in endemic communities in Africa. This is partly due to the fact that asymptomatic parasite carriage, not specifically targeted by most interventions, remains the bedrock that fuels transmission. This has led to mass testing, treatment and tracking (MTTT) as an alternative strategy to target asymptomatic individuals. We report the impact of MTTT on the prevalence of asymptomatic malaria parasitaemia over a one-year period in Ghana, hypothesizing that implementing MTTT could reduce the rate of asymptomatic parasitaemia. METHODS: A population of about 5000 individuals in seven communities in the Pakro sub-district of Ghana participated in this study. A register was developed for each community following a census. MTTT engaged trained community-based health volunteers who conducted house-to-house testing using RDTs every 4 months and treated positive cases with Artemisinin-based Combination Therapy. Between interventions, community-based management of malaria was implemented for symptomatic cases. RESULTS: MTTT Coverage was 98.8% in July 2017 and 79.3% in July 2018. Of those tested, asymptomatic infection with malaria parasites reduced from 36.3% (1795/4941) in July 2017 to 32.9% (1303/3966) in July 2018 (p = 0.001). Prevalence of asymptomatic parasitaemia among children under 15 years declined from 52.6% (1043/1984) in July 2017 to 47.5% (820/1728) in July 2018 (p = 0.002). Implementing MTTT significantly reduced asymptomatic parasitaemia by 24% from July 2017 to July 2018 after adjusting for age, ITN use and axillary temperature (OR = 0.76, CI = 0.67, 0.85 p ≤ 0.001). CONCLUSION: This study has demonstrated that implementing MTTT is feasible and could reduce the prevalence of asymptomatic malaria parasitaemia in children under 15 years of age. Furthermore, the use of community-based health volunteers could ensure high coverage at lower cost of implementation. TRIAL REGISTRATION: NCT04167566, Date 14/11/2019. Retrospective registration.

Seroprevalencia y detección molecular de Toxoplasma gondii en donantes de un banco de sangre de Cúcuta, Colombia / Seroprevalence and molecular detection of Toxoplasma gondii among donors in a blood bank in Cúcuta, Colombia

Resumen Introducción. La infección por Toxoplasma gondii puede presentarse en los humanos con un amplio rango de manifestaciones que van desde el estado asintomático hasta la enfermedad grave, según el estado inmunológico del individuo. Los mecanismos de transmisión incluyen la transfusión sanguínea, pero poco se sabe sobre la frecuencia del parásito en los bancos de sangre de Colombia. Objetivo. Determinar la prevalencia de la infección con T. gondii en donantes de un banco de sangre de Cúcuta mediante técnicas de diagnóstico serológico y molecular. Materiales y métodos. Se determinaron los anticuerpos IgG e IgM contra T. gondii mediante un inmunoensayo en suero en 348 donantes. Se determinó la frecuencia de ADN de T. gondii utilizando la reacción en cadena de la polimerasa (PCR) en sangre total de donantes seropositivos y se analizaron las variables de interés con base en la información obtenida durante la selección de donantes. Resultados. De los 348 donantes participantes, 134 (38,5 %) presentaron anticuerpos IgG contra T. gondii; dos (0,6 %) de ellos presentaron tanto IgG como IgM y, en dos (1,5 %), se detectó ADN del parásito en la sangre. Un análisis bivariado evidenció una asociación entre la seropositividad para T. gondii y tener más de 26 años de edad (p=0,020). Conclusiones. La prevalencia de la infección con T. gondii encontrada en los donantes de sangre sugiere una exposición significativa al agente, la cual adquiere relevancia al detectarse la parasitemia.

Abstract Introduction: Toxoplasma gondii infection manifests differently in humans according to their immunity ranging from asymptomatic profiles to severe disease. There are multiple transmission mechanisms including blood transfusions, but little is known about the frequency of T. gondii infection in Colombia's blood banks. Objective: To determine the prevalence of T. gondii infection in blood donors of a blood bank in the city of Cúcuta by serological and molecular diagnostic techniques. Materials and methods: We identified IgG and IgM antibodies against T. gondii by immunoassay in serum from 348 donors. The frequency of T. gondii DNA was determined by polymerase chain reaction (PCR) in whole blood from seropositive donors and relevant variables were analyzed based on the information obtained from surveys during blood donor selection. Results: Out of the 348 enrolled donors, 134 (38.5%) showed IgG antibodies against T. gondii; two of them (0.6%) had both IgG and IgM, and in two of them (1.5%), parasite DNA was detected in blood samples. A bivariate analysis indicated an association between seropositivity to T. gondii and being over 26 years of age (p=0.020). Conclusions: The prevalence of T. gondii infection found in the blood donors of this study suggests a significant exposure to the infectious agent that becomes relevant when parasitemia is detected.

Intermittent preventive treatment with dihydroartemisinin-piperaquine and risk of malaria following cessation in young Ugandan children: a double-blind, randomised, controlled trial.

BACKGROUND: Intermittent preventive treatment (IPT) of malaria with dihydroartemisinin-piperaquine is a promising strategy for malaria prevention in young African children. However, the optimal dosing strategy is unclear and conflicting evidence exists regarding the risk of malaria after cessation of chemoprevention. We aimed to compare two dosing strategies of IPT with dihydroartemisinin-piperaquine in young Ugandan children, and to evaluate the risk of malaria after cessation of IPT. METHODS: In this double-blind, randomised controlled phase 2 trial, women and their unborn children were recruited at Tororo District Hospital (Tororo, Uganda). Eligible participants were HIV-negative women aged 16 years or older with a viable pregnancy (gestational age 12-20 weeks). Women and their unborn children were randomly assigned (1:1:1:1) to one of four treatment groups, all receiving dihydroartemisinin-piperaquine, on the basis of the IPT intervention received by the woman during pregnancy: women every 8 weeks, children every 4 weeks; women every 4 weeks, children every 4 weeks; women every 8 weeks, children every 12 weeks; and women every 4 weeks, children every 12 weeks. Block randomisation was done by an independent investigator using a computer-generated randomisation list (permuted block sizes of six and 12). We analysed children on the basis of their random assignment to receive dihydroartemisinin-piperaquine (20 mg/160 mg tablets) once daily for 3 consecutive days every 4 weeks or 12 weeks. Children received study drugs from age 8 weeks to 24 months and were followed-up to age 36 months. Participants and investigators were masked to treatment allocation. The primary outcome was the incidence of symptomatic malaria during the intervention and following cessation of the intervention, adjusted for potential confounders. The primary outcome and safety were assessed in the modified intention-to-treat population, which included all children who reached 8 weeks of age and received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT02163447. FINDINGS: Between Oct 21, 2014, and May 18, 2015, 191 children were born, of whom 183 reached 8 weeks of age and received at least one dose of study drug and thus were included in the primary analysis (96 children in the 4-week group and 87 in the 12-week group). During the intervention, the incidence of symptomatic malaria was significantly lower among children treated every 4 weeks than children treated every 12 weeks; three episodes occurred among children treated every 4 weeks (incidence 0·018 episodes per person-year) compared with 61 episodes among children treated every 12 weeks (incidence 0·39 episodes per person-year; adjusted incidence rate ratio [aIRR] 0·041, 95% CI 0·012-0·150, p<0·0001). After cessation of IPT, children who had previously received dihydroartemisinin-piperaquine every 4 weeks had a lower incidence of symptomatic malaria than children who were treated every 12 weeks; 62 episodes occurred among children previously treated every 4 weeks (incidence 0·73 episodes per person-year) compared with 83 episodes among children treated every 12 weeks (incidence 1·1 episodes per person-year; aIRR 0·62, 0·40-0·95, p=0·028). In the 4-week group, 94 (98%) of 96 children had adverse events versus 87 (100%) of 87 children in the 12-week group. The most commonly reported adverse event was cough in both treatment groups (94 [98%] in the 4-week group vs 87 [100%] in the 12-week group). 16 children had severe adverse events (seven [7%] children in the 4-week group vs nine [10%] children in the 12-week group). No severe adverse events were thought to be related to study drug administration. One death occurred during the intervention (age 8 weeks to 24 months), which was due to respiratory failure unrelated to malaria. INTERPRETATION: IPT with dihydroartemisinin-piperaquine given every 4 weeks was superior to treatment every 12 weeks for the prevention of malaria during childhood, and this protection was extended for up to 1 year after cessation of IPT. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Challenges and perceptions of implementing mass testing, treatment and tracking in malaria control: a qualitative study in Pakro sub-district of Ghana.

BACKGROUND: Malaria remains endemic in Ghana despite several interventions. Studies have demonstrated very high levels of asymptomatic malaria parasitaemia in both under-five and school-age children. Mass testing, treatment and tracking (MTTT) of malaria in communities is being proposed for implementation with the argument that it can reduce parasite load, amplify gains from the other control interventions and consequently lead to elimination. However, challenges associated with implementing MTTT such as feasibility, levels of coverage to be achieved for effectiveness, community perceptions and cost implications need to be clearly understood. This qualitative study was therefore conducted in an area with on-going MTTT to assess community and health workers' perceptions about feasibility of scale-up and effectiveness to guide scale-up decisions. METHODS: This qualitative study employed purposive sampling to select the study participants. Ten focus group discussions (FGDs) were conducted in seven communities; eight with community members (n = 80) and two with health workers (n = 14). In addition, two in-depth interviews (IDI) were conducted, one with a Physician Assistant and another with a Laboratory Technician at the health facility. All interviews were recorded, transcribed, translated and analyzed using QSR NVivo 12. RESULTS: Both health workers and community members expressed positive perceptions about the feasibility of implementation and effectiveness of MTTT as an intervention that could reduce the burden of malaria in the community. MTTT implementation was perceived to have increased sensitisation about malaria, reduced the incidence of malaria, reduced household expenditure on malaria and alleviated the need to travel long distances for healthcare. Key challenges to implementation were doubts about the expertise of trained Community-Based Health Volunteers (CBHVs) to diagnose and treat malaria appropriately, side effects of Artemisinin-based Combination Therapies (ACTs) and misconceptions that CBHVs could infect children with epilepsy. CONCLUSION: The study demonstrated that MTTT was perceived to be effective in reducing malaria incidence and related hospital visits in participating communities. MTTT was deemed useful in breaking financial and geographical barriers to accessing healthcare. The interventions were feasible and acceptable to community members, despite observed challenges to implementation such as concerns about CBHVs' knowledge and skills and reduced revenue from internally generated funds (IGF) of the health facility.

What is the Link between Malaria Prevention in Pregnancy and Neonatal Survival in Nigeria?

Neonatal mortality has been recognized as a global public health challenge and Nigeria has the highest prevalence in Africa. Malaria during pregnancy jeopardizes neonatal survival through placental parasitaemia, maternal anaemia, and low birth weight. This study investigated association between the malaria prevention in pregnancy and neonatal survival using a nationally representative data - Nigeria Demographic Health Survey 2013. Child recode data was used and the outcome variable was neonatal death. The main independent variables were the use of at least 2 doses of intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine (IPT-SP) and proportion of pregnant women who reported Insecticide Treated Net (ITN) use the night before the survey. Data were analyzed using Pearson Chi-square (x 2 ) test of association and survival analysis techniques. Total neonatal mortality rate was 38 per1000 live births. Cox proportional hazard model showed that low birth weight (HR 1.49, 95% CI (1.15 - 1.93 p=0.003) and adequate number of ANC visits (≥ 4 visits) (HR 0.68, 95% CI (0.53 - 0.93) were associated with neonatal survival. The use of at least 2 doses of IPT-SP was not an independent factor for neonatal survival (HR 0.72, 95% CI (0.53 - 1.15). Malaria prevention in pregnancy is crucial for neonatal survival through the prevention of low birth weight.

Safety and effectiveness of antimalarial therapy in sickle cell disease: a systematic review and network meta-analysis.

BACKGROUND: About 80% of all reported sickle cell disease (SCD) cases in children anually are recorded in Africa. Although malaria is considered a major cause of death in SCD children, there is limited data on the safety and effectiveness of the available antimalarial drugs used for prophylaxis. Also, previous systematic reviews have not provided quantitative measures of preventive effectiveness. The purpose of this research was to conduct a systematic review and meta-analysis of the available literature to determine the safety and effectiveness of antimalarial chemoprophylaxis used in SCD patients. METHODS: We searched in PubMed, Medline, CINAHL, POPLine and Cochrane library, for the period spanning January 1990 to April 2018. We considered randomized or quasi-randomized controlled trials comparing any antimalarial chemoprophylaxis to, 1) other antimalarial chemoprophylaxis, 2) placebo or 3) no intervention, in SCD patients. Studies comparing at least two treatment arms, for a minimum duration of three months, with no restriction on the number of patients per arm were reviewed. The data were extracted and expressed as odds ratios. Direct pairwise comparisons were performed using fixed effect models and the heterogeneity assessed using the I-square. RESULTS: Six qualified studies that highlighted the importance of antimalarial chemoprophylaxis in SCD children were identified. In total, seven different interventions (Chloroquine, Mefloquine, Mefloquine artesunate, Proguanil, Pyrimethamine, Sulfadoxine-pyrimethamine, Sulfadoxine-pyrimethamine amodiaquine) were evaluated in 912 children with SCD. Overall, the meta-analysis showed that antimalarial chemoprophylaxis provided protection against parasitemia and clinical malaria episodes in children with SCD. Nevertheless, the risk of hospitalization (OR = 0.72, 95% CI = 0.267-1.959; I2 = 0.0%), blood transfusion (OR = 0.83, 95% CI = 0.542-1.280; I2 = 29.733%), vaso-occlusive crisis (OR = 19, 95% CI = 1.713-2.792; I2 = 93.637%), and mortality (OR = 0.511, 95% CI = 0.189-1.384; I2 = 0.0%) did not differ between the intervention and placebo groups. CONCLUSION: The data shows that antimalarial prophylaxis reduces the incidence of clinical malaria in children with SCD. However, there was no difference between the occurrence of adverse events in children who received placebo and those who received prophylaxis. This creates an urgent need to assess the efficacy of new antimalarial drug regimens as potential prophylactic agents in SCD patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42016052514).

Efficacy of intermittent preventive treatment and insecticide treated nets on malaria parasitaemia in pregnancy among Igbo women in southeastern Nigeria.

BACKGROUND & OBJECTIVES: Prevention of malaria in pregnancy is a key intervention for reducing maternal mortality and morbidity in the tropical region of Africa. The present study was aimed to determine whether the administration of two doses of intermittent preventive treatment (IPT) with sulphadoxine-pyrimethamine (IPT-SP) and use of insecticide treated nets (ITNs) is correlated with reduced incidence of malaria in pregnancy or not. METHODS: In total 270 pregnant women were randomly divided into three groups; A, B and C depending on the use of IPT and ITN, and were tested for malaria in pregnancy. RESULTS: The overall prevalence of malaria parasitaemia was found to be 57.8%. The prevalence rate was 56.7% for group A (IPT alone); 45.6% for group B (IPT and ITN) and 71.1% for group C (None). The difference between group A and C was statistically significant (χ2 = 4.07, OR = 1.88, p < 0.04). Also, women in group A were one and half times more susceptible to malaria than women in group B (χ2 = 2.22, OR = 1.56, p < 0.14). INTERPRETATION & CONCLUSION: The use of IPT-SP and ITN was found to be significantly associated with reduced malarial infestation during pregnancy in the study area. There is a need to scale up both the strategies in order to reduce the high burden of malaria in pregnant women.

Asymptomatic and sub-microscopic malaria infection in Kayah State, eastern Myanmar.

BACKGROUND: Myanmar has the heaviest burden of malaria in the Greater Mekong Sub-region. Asymptomatic Plasmodium spp. infections are common in this region and may represent an important reservoir of transmission that must be targeted for malaria elimination. METHODS: A mass blood survey was conducted among 485 individuals from six villages in Kayah State, an area of endemic but low transmission malaria in eastern Myanmar. Malaria infection was screened by rapid diagnostic test (RDT), light microscopy and real-time polymerase chain reaction (PCR), and its association with demographic factors was explored. RESULTS: The prevalence of asymptomatic Plasmodium spp. infection was 2.3% (11/485) by real-time PCR. Plasmodium vivax accounted for 72.7% (8/11) and Plasmodium falciparum for 27.3% (3/11) of infections. Men were at greater risk of infection by Plasmodium spp. than women. Individuals who worked as farmers or wood and bamboo cutters had an increased risk of infection. CONCLUSION: A combination of RDT, light microscopy and PCR diagnostics were used to identify asymptomatic malaria infection, providing additional information on asymptomatic cases in addition to the routine statistics on symptomatic cases, so as to determine the true burden of disease in the area. Such information and risk factors can improve malaria risk stratification and guide decision-makers towards better design and delivery of targeted interventions in small villages, representative of Kayah State.

Efficacy and safety of intermittent preventive treatment in schoolchildren with sulfadoxine/pyrimethamine (SP) and SP plus piperaquine in Democratic Republic of the Congo: a randomised controlled trial.

In endemic areas, malaria and its adverse effects in schoolchildren may be prevented by intermittent preventive treatment (IPTsc). However, the most appropriate drug regimen for IPTsc remains to be identified. A randomised controlled trial was conducted in Kinshasa, DRC. Enrolled schoolchildren were assigned to a passive control arm (n = 212), sulfadoxine/pyrimethamine (SP) (n = 202) or SP plus piperaquine (SP/PQ) (n = 202). The primary endpoint was haemoglobin (Hb) change. Secondary endpoints were anaemia, parasitaemia prevalence and clinical malaria incidence. Data were analysed by modified intention-to-treat (mITT) and per-protocol. A linear mixed mode was used due to repeated measurements. Of 616 enrolled children, 410 (66.6%) were eligible for mITT analysis. The control arm was used as reference. After 12 months, the Hb level increased by 0.20 g/dL (95% CI -0.61 to 0.47; P = 0.168) and 0.39 g/dL (0.12-0.66; P <0.01) in the SP and SP/PQ arms, respectively. SP treatment reduced anaemia, malaria parasitaemia and clinical malaria by 10% (0-20%; P = 0.06), 19% (2-33%; P = 0.042) and 25% (-32 to 57%; P = 0.37), respectively. The corresponding values for SP/PQ were 28% (19-37%; P <0.001), 40% (26-52%; P <0.001) and 58% (17-79%; P <0.01). No deaths or severe adverse events (SAEs) were observed. SP/PQ offered substantial protection against anaemia, malaria parasitaemia and clinical malaria and showed no SAEs. SP/PQ, a combination of two long-acting non-artemisinin-based antimalarials, may be a valuable option for IPTsc in Africa.

Effect of a short course of iron polymaltose on acquisition of malarial parasitaemia in anaemic Indonesian schoolchildren: a randomized trial.

BACKGROUND: Concern exists about the safety of iron supplementation given to individuals in malarious areas. The possible unfavourable impact of iron supplementation on malaria might be less when slow-release iron compounds are used instead of ferrous salts, because no toxic non-transferrin bound iron is formed. The aim of this study was to determine the effect of iron supplementation using the slow-release iron compound iron polymaltose (IPM) on the acquisition of malarial parasitaemia. METHODS: A randomized, placebo-controlled trial was performed in schoolchildren aged 5-18 years with mild or moderate anaemia on the Indonesian island Flores. Microscopic malaria-negative children were randomized to receive 8 weeks of IPM (6 mg elemental iron/kg/day) or placebo . The primary outcomes were the occurrence of microscopically detectable malarial parasitaemia at week 4, 8, 12 and 16 after start of treatment and the proportion of participants with real-time (RT) PCR positive malarial parasitaemia at week 16. RESULTS: 294 Children were assigned to the IPM group and 297 to the placebo group. Whereas IPM supplementation failed to increased haemoglobin or ferritin concentrations, the IPM group had a significantly higher rate of occurrence of microscopically detectable parasitaemia [hazard ratio 2.2, 95% C.I. 1.2-4.0; P = 0.01]. This higher rate was confined to iron-replete children. At the end of the study, 89% of the children in the IPM group had remained free from microscopically detectable parasitaemia vs 95% of children in the placebo group. The proportion of plasmodial RT-PCR positive children was similar in both groups at week 16 (IPM group 16.6% vs placebo group 14.3%; P = 0.47). When analysis was restricted to iron-replete children (serum ferritin ≥30 µg/l), there was a trend for a higher proportion being RT-PCR positive at week 16 in the IPM group compared with the placebo group (20 vs 13.3%; P = 0.07). Erythrocyte microcytosis was an independent risk factor for microscopically detectable malarial parasitaemia. CONCLUSIONS: A short course of IPM should be used cautiously in anaemic children in malaria endemic areas, as it has limited efficacy in treating iron deficiency, while it increases the rate of microscopic malarial parasitaemia in those with replete iron stores. Trial registration ISRCTN 83091970. Registered 16 May 2012 (retrospectively registered).

Molecular detection of Sarcocystis aucheniae in the blood of llamas from Argentina.

Sarcocystis aucheniae are apicomplexan protozoa that infect South American camelids (SACs), giving rise to macroscopic cysts similar to rice grains in skeletal muscles. Visual detection of macrocysts in slaughtered animals hampers commercialization of SAC meat, a highly relevant economic exploitation for Andean rural families. Importantly, the consumption of undercooked S. aucheniae-infested meat causes gastroenteritis. A carnivore definitive host, possibly the dog, acquires the parasite when feeding on infected SAC meat, and later eliminates infective oocysts in its feces. The parasite cycle is completed when SACs ingest contaminated water or pastures. We hypothesized that parasite DNA can be detected in SAC blood using molecular methods. In order to test this hypothesis, a seminested PCR format was specifically designed to target the hypervariable 18S rRNA gene region of S. aucheniae. PCR conditions were optimized using genomic DNA extracted from macrocyst bradyzoites. A detection limit of up to 1 parasite in 10µl of llama blood was established based on DNA samples extracted from aliquots of S. aucheniae bradyzoite-spiked non-infected llama blood. The seminested PCR allowed to detect natural infections of S. aucheniae in llama blood samples originating in the Andean flatlands of Argentina. Specific amplification of S. aucheniae DNA was corroborated by amplicon sequencing. This is the first report of S. aucheniae detection in llama blood, which provides a valuable diagnostic tool for epidemiological studies and for the evaluation of the efficacy of control measures for this parasitosis.

Effect of HIV-1 Serostatus on the Prevalence of Asymptomatic Plasmodium falciparum Parasitemia Among Children Less Than 5 Years of Age in Benin City, Nigeria.

BACKGROUND: Human immunodeficiency virus (HIV) infection and Plasmodium falciparum malaria are 2 of the gravest health threats in sub-Saharan Africa. Multiple repeat infections with the malaria parasite as seen in endemic areas are necessary to develop specific malaria immunity. HIV is an immunosuppressive virus and in children aged <5 years, development of malaria-specific immunity may be impaired and malaria parasite clearance in theory will be delayed; hence the predisposition to increased incidence of asymptomatic malaria or severe malaria. This cross-sectional study was carried out to examine associations between immunosuppression and asymptomatic malaria parasitemia (ASMP) in HIV-infected children aged <5 years in Benin City. METHODS: One hundred seventy-nine asymptomatic HIV-1-positive and 179 age- and sex-matched HIV-1-negative children aged <5 years were recruited. The malaria parasite was determined by Giemsa-stained blood film by certified microscopy while concomitant CD4(+) count was estimated in the HIV-infected children. RESULTS: The prevalence of ASMP in those who were HIV-infected of 34.1% was significantly higher than 17.3% in the HIV uninfected (P = .001). The prevalence of ASMP was highest (59.3%) among subjects who were severely immunosuppressed (CDC immunologic category 3). The prevalence of ASMP significantly increased with advanced immune disease in the subjects (P = .011). Severe (World Health Organization) clinical staging was also significantly associated with increased prevalence of ASMP (P = .031). The prevalence of ASMP is significantly higher among subjects not receiving cotrimoxazole, associated with threefold risk of having ASMP (P = .003: odds ratio = 3.5). CONCLUSIONS: ASMP is more common in HIV-positive children aged <5 years and is significantly associated with declining CD4(+) T-cell count and severe clinical disease. There is a need for integration of HIV- and malaria-control programs for stronger case management. Malaria-control programs may consider malaria prevention interventions and cotrimoxazole prophylaxis for preschool children who are HIV-infected and living in malaria-endemic regions.