Pregnancy outcomes in women with imported malaria in mainland France: A retrospective study from 2004 to 2014.

OBJECTIVES: There is little data on pregnant women with imported malaria in high-income countries, especially regarding offspring outcomes. We wanted to determine pregnancy outcomes of imported malaria in pregnant women in mainland France. PATIENTS AND METHODS: We conducted a retrospective, descriptive study of outcomes in pregnant women hospitalized with malaria from 2004 to 2014 in two regions of mainland France. An adverse outcome was defined as a miscarriage, stillbirth, preterm birth (<35 weeks of gestation), low birth weight (LBW) defined as less than 2500 g, or congenital malaria. RESULTS: Of 60 pregnancies, 5 were excluded because of elective abortions; 55 were investigated, of which 11 were primigravidae and 44 multigravidae. Pregnancies were singleton (n = 51) or twin (n = 4). Mean age was 30.4 years (range:19-45 y). Among the 55 cases, 9 ended in a miscarriage (8 singletons and 1 twin pregnancy) and 1 had a stillbirth at 21 weeks of gestation, all immediately after the malarial episode. 45 gave birth (29 vaginal deliveries and 16 caesarean sections) to 48 (42 singletons and 6 twins) newborns. Amongst these, 30 were healthy full-term newborns, 10 had LBW, and 8 were preterm. Overall, 26 of 55 (47.3%) pregnancies, and 29 of 59 (49.2%) offsprings had adverse outcomes. Compared to singleton pregnancies, twin pregnancies were associated with adverse outcomes (p = 0.0438). CONCLUSIONS: Imported malaria has a severe impact on pregnancy outcomes. Prevention and management of imported malaria in pregnancy should be optimized.

Changes in malaria epidemiology in France and worldwide, 2000-2015.

In 2015, 212 million new cases of malaria were reported, causing 429,000 deaths. The World Health Organization (WHO) estimated a 41% decrease in the number of new cases worldwide between 2000 and 2015. The number of deaths from malaria fell by 62% worldwide and by 71% in Africa. In mainland France, malaria is mainly imported by travelers or migrants from endemic areas, in particular sub-Saharan Africa (95%). In France, the number of imported malaria cases, mainly due to Plasmodium falciparum (85%), was estimated at about 82,000 for the period 2000-2015. Over the same period, 6,468 cases of malaria were reported in the French armed forces, of which 2,430 cases (37.6%) were considered as imported because occurring outside of endemic areas. The number of malaria cases also fell between 2000 and 2015 in Mayotte and French Guiana, a malaria transmission zone. Mayotte has entered the elimination of malaria with less than 15 cases per year. In French Guiana, between 300 and 500 cases have been reported annually in recent years. The decline in morbidity and mortality is usually attributed to vector control measures and improved access to effective treatments. However, the Anopheles mosquitoes that transmit the disease have developed resistance against most insecticides. Similarly, malaria parasites have developed resistance against most of the antimalarial drugs used as prevention or treatment, even the latest marketed combinations such as artemisinin-based combination therapies.

Management and prevention of imported malaria in children. Update of the French guidelines.

Since the 2007 French guidelines on imported Falciparum malaria, the epidemiology, treatment, and prevention of malaria have changed considerably requiring guidelines for all Plasmodium species to be updated. Over the past decade, the incidence of imported malaria has decreased in all age groups, reflecting the decrease in the incidence of malaria in endemic areas. The rates of severe pediatric cases have increased as in adults, but fatalities are rare. The parasitological diagnosis requires a thick blood smear (or a rapid immunochromatographic test) and a thin blood film. Alternatively, a rapid antigen detection test can be paired with a thin blood film. Thrombocytopenia in children presenting with fever is highly predictive of malaria following travel to a malaria-endemic area and, when detected, malaria should be strongly considered. The first-line treatment of uncomplicated P. falciparum malaria is now an artemisinin-based combination therapy (ACT), either artemether-lumefantrine or artenimol-piperaquine, as recommended by the World Health Organization in endemic areas. Uncomplicated presentations of non-falciparum malaria should be treated either with chloroquine or ACT. The first-line treatment of severe malaria is now intravenous artesunate which is more effective than quinine in endemic areas. Quinine is restricted to cases where artesunate is contraindicated or unavailable. Prevention of malaria in pediatric travelers consists of nocturnal personal protection against mosquitoes (especially insecticide-treated nets) combined with chemoprophylaxis according to the risk level.

Distinction of Plasmodium ovale wallikeri and Plasmodium ovale curtisi using quantitative Polymerase Chain Reaction with High Resolution Melting revelation.

Plasmodium ovale curtisi (Poc) and Plasmodium ovale wallikeri (Pow) have been described as two distinct species, only distinguishable by molecular methods such as PCR. Because of no well-defined endemic area and a variable clinical presentation as higher thrombocytopenia and nausea associated with Pow infection and asymptomatic forms of the pathology with Poc infection, rapid and specific identification of Plasmodium ovale curtisi and Plasmodium ovale wallikeri are needed. The aim of the study was to evaluate a new quantitative real-time PCR coupled with high resolution melting revelation (qPCR-HRM) for identification of both species. Results were compared with a nested-PCR, considered as a gold standard for Pow and Poc distinction. 356 samples including all human Plasmodium species at various parasitaemia were tested. The qPCR-HRM assay allowed Poc and Pow discrimination in 66 samples tested with a limit of detection evaluated at 1 parasite/µL. All these results were concordant with nested-PCR. Cross-reaction was absent with others blood parasites. The qPCR-HRM is a rapid and convenient technique to Poc and Pow distinction.

Preferential expression of domain cassettes 4, 8 and 13 of Plasmodium falciparum erythrocyte membrane protein 1 in severe malaria imported in France.

OBJECTIVES: Severe Plasmodium falciparum malaria (SM) involves cytoadhesion of parasitized red blood cells, mediated by P. falciparum erythrocyte membrane protein 1, which is encoded by var genes. Expression of var gene group A and B or encoding domain cassettes DC4, DC5, DC8 and DC13 has been implicated in SM in African children, but no data exist in the context of imported malaria. The aim of this study was to investigate var gene expression linked to clinical presentation and host factors in SM imported into France. METHODS: Expression level of var gene groups A, B, C, var1, var2csa, var3 and var genes encoding DC4, DC5, DC8 and DC13 was measured by quantitative RT-PCR and expressed in transcript units. Seventy SM and 48 uncomplicated malaria (UM) P. falciparum cases were analysed according to disease severity, epidemiological characteristics (migrants or travellers) and anti-P. falciparum antibodies. Cluster analysis was performed to identify gene expression profiles. RESULTS: Var1 and B/C expression were higher in UM than SM (0.66 (0-1.1) and 1.88 (1.3-2.4); p <0.04, respectively). Group C expression differed between migrants and travellers (0.21 (0-0.75) versus 0 (0-0); p 0.002). Group A differed in naive and pre-exposed patients (1.1 (0.7-1.5) versus 0.4 (0-1.1); p 0.01). Population clusters revealed increased expression from group A and B var genes, and DC4, DC8 and DC13 in SM. CONCLUSIONS: These results corroborate the implication of DC4, DC8 and DC13 in severe imported malaria cases as African children, and their expression depends of host factors.

Decrease of microscopic Plasmodium falciparum infection prevalence during pregnancy following IPTp-SP implementation in urban cities of Gabon.

BACKGROUND: Six years after the implementation of intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) in Gabon, its impact on placental malaria and pregnancy outcomes remains unknown. METHODS: Age, gestational data, use of IPTp-SP and birth weight were recorded during a hospital-based cross-sectional survey performed in 2011 in 387 women at the end of pregnancy. RESULTS: Malaria prevalence was 6.7 and 5.3% in peripheral and placental blood respectively. Overall, 59.0% women took at least two IPTp-SP doses which was associated with 50% reduction of Plasmodium; (P.) falciparum infection in primigravidae. Previous malaria treatment was a risk factor for peripheral P. falciparum infection, while uptake of IPTp-SP was associated with reduced parasitaemia. Anaemia prevalence was 38.0%, low birth weight and prematurity rates were 6.0 and 12.0% respectively. Young age was associated with a higher frequency of malaria, anaemia, low birth weight and preterm delivery (p<0.01). Birth weight significantly rose with increasing age (p<0.01), parity (p=0.03) and number of SP doses (p=0.03). A birth weight reduction of 230 g in case of peripheral parasitaemia (p=0.02) and of 210 g with placental parasitaemia (p=0.13) was observed. CONCLUSIONS: Microscopic P. falciparum prevalence during pregnancy significantly declined between 2005 and 2011, following IPTp-SP implementation in Gabon. Young women and paucigravidae remain the most susceptible to malaria and associated outcomes.

The relationship between microfilaraemic and amicrofilaraemic loiasis involving co-infection with Mansonella perstans and clinical symptoms in an exposed population from Gabon.

The relationship between the frequency of loiasis objective symptoms and microfilaraemic or amicrofilaraemic infection was assessed in 1148 exposed patients also infected, or not, with Mansonella perstans. Filarial infections were detected by direct microscopy, leucoconcentration and serology, with prevalence values of 39.5% Loa loa, 5.6% M. perstans and 3.4% co-infection with both filarial species. Amicrofilaraemic or occult loiasis (OL) predominated among L. loa-infected individuals, with a prevalence of 58.2%. Hypermicrofilaraemia (>8000 microfilariae (mf)/ml) was found in 18.4% of L. loa microfilaraemic patients, with 25.7% of them harbouring more than 30,000 mf/ml. Up to 34% of patients with OL showed evidence of Calabar swelling, compared with 26.3% of microfilaraemic patients (P= 0.03). Overall 5.3% of patients presented with adult worm migration across the eye, representing 16.3% of microfilaraemic individuals and 11.4% of amicrofilaraemic patients (P= 0.13). This symptom was similarly found in patients with more than 30,000 mf/ml (22%), those with microfilaraemia between 8 and 30,000 mf/ml (15.4%) and also in individuals with low or without microfilaraemia (16.1%) (P= 0.7). Five (14.3%) hypermicrofilaraemic patients did not present any L. loa-specific objective symptoms, as well as all the patients with single M. perstans infection. The presence of adult eye worm migration as a strong predictor of high microfilaraemia density would obscure the real burden of L. loa hypermicrofilaraemia in exposed individuals. For epidemiological purposes and control strategies, the mapping of L. loa in endemic areas should also take into account the group of patients with occult loiasis.

Travelers with cutaneous leishmaniasis cured without systemic therapy.

BACKGROUND: Cutaneous leishmaniasis (CL) is a disfiguring but not life-threatening disease. Because antileishmanial drugs are potentially toxic, the World Health Organization (WHO) recommends simple wound care or local therapy as first-line treatment, followed or replaced by systemic therapy if local therapy fails or cannot be performed. METHODS: To determine the feasibility and impact of the recommended approach, we analyzed the results of a centralized referral treatment program in 135 patients with parasitologically proven CL. RESULTS: Infections involved 10 Leishmania species and were contracted in 29 different countries. Eighty-four of 135 patients (62%) were initially treated without systemic therapy. Of 109 patients with evaluable charts, 23 of 25 (92%) treated with simple wound care and 37 of 47 (79%) treated with local antileishmanial therapy were cured by days 42-60. In 37 patients with large or complex lesions, or preexisting morbidities, or who had not been cured with local therapy, the cure rate with systemic antileishmanial agents was 60%. Systemic adverse events were observed in 15 patients, all receiving systemic therapy. CONCLUSIONS: In this population of CL patients displaying variable degrees of complexity and severity, almost two-thirds of patients could be initially managed without systemic therapy. Of these, 60 were cured before day 60. The WHO-recommended stepwise approach favoring initial local therapy therefore resulted in at least 44% of all patients being cured without exposure to the risk of systemic adverse events. Efforts are needed to further simplify local therapy of CL and to improve the management of patients with complex lesions and/or preexisting comorbidities.

[Malaria in France: Mainland and territories]. / Le paludisme en France : métropole et outre-mer.

Malaria, which was eliminated first from Metropolitan France (mainland and Corsica), then in the French West Indies and the Reunion Island during the 20(th) century, remains endemic in two French territories: French Guiana and the Indian Ocean Mayotte island. Despite differences in the dominating plasmodial species and epidemiological patterns, these two territories have achieved marked quantitative improvements (in the reported number of cases and severe cases) thanks to efforts undertaken over the past decade. The situation, however, remains a concern from a qualitative standpoint with the emergence of resistance to antimalarial drugs and logistical and administrative issues which hinder access to treatment. Although malaria was eradicated in Metropolitan France half a century ago, competent vectors remain present in part or all of these territories and can give rise to limited outbreaks.

[HIV seroprevalence among tuberculosis patients in Nkembo Hospital, Libreville, Gabon. Short note]. / Séroprévalence du VIH au sein des tuberculeux de l'hôpital de Nkembo à Libreville, Gabon.

There are nearly 31,000 HIV infected patients in Gabon. In Libreville, the capital, the prevalence is estimated at 7.7%. About 2627 tuberculosis patients, all types included, have been notified in 2001 to the World Health Organization of which 43% of smear positive new cases. The co-infection HIV-TB worsens the overall prognosis of our patients. The objective of our study is to determine the HIV seroprevalence among our tuberculosis patients. It is a cross-sectional study conducted between June 25th and August 31th 2001. All patients are new or relapse tuberculosis cases. There is no difference between the types of tuberculosis. The diagnosis was clinical, radiological and based on smear AFB sputum (according to the Ziehl Neelsen method). The patients agreed orally for HIV testing. We made two tests: a rapid one followed by Elisa if positive. 358 patients were examined among them 141 women and 217 men. The M/F sex ratio was 1.53 and the average age 32 years. Proportion of new patients reached 61%. Ninety seven per cent of patients suffered from a pulmonary tuberculosis, 58% smear positive and 26% were HIV-1 positive. According to this status, no statistical difference was notified towards sex, types of disease or patients and the smear sputum results.