A 5-day course of oral antibiotics followed by faecal transplantation to eradicate carriage of multidrug-resistant Enterobacteriaceae: a randomized clinical trial.

OBJECTIVES: Intestinal carriage with extended spectrum ß-lactamase Enterobacteriaceae (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE) can persist for months. We aimed to evaluate whether oral antibiotics followed by faecal microbiota transplantation (FMT) can eradicate intestinal carriage with ESBL-E/CPE. METHODS: Randomized, open-label, superiority trial in four tertiary-care centres (Geneva (G), Paris (P), Utrecht (U), Tel Aviv (T)). Non-immunocompromised adult patients were randomized 1: 1 to either no intervention (control) or a 5-day course of oral antibiotics (colistin sulphate 2 × 106 IU 4×/day; neomycin sulphate 500 mg 4×/day) followed by frozen FMT obtained from unrelated healthy donors. The primary outcome was detectable intestinal carriage of ESBL-E/CPE by stool culture 35-48 days after randomization (V4). ClinicalTrials.govNCT02472600. The trial was funded by the European Commission (FP7). RESULTS: Thirty-nine patients (G = 14; P = 16; U = 7; T = 2) colonized by ESBL-E (n = 36) and/or CPE (n = 11) were enrolled between February 2016 and June 2017. In the intention-to-treat analysis 9/22 (41%) patients assigned to the intervention arm were negative for ESBL-E/CPE at V4 (1/22 not receiving the intervention imputed as positive) whereas in the control arm 5/17 (29%) patients were negative (one lost to follow up imputed as negative) resulting in an OR for decolonization success of 1.7 (95% CI 0.4-6.4). Study drugs were well tolerated overall but three patients in the intervention group prematurely stopped the study antibiotics because of diarrhoea (all received FMT). CONCLUSIONS: Non-absorbable antibiotics followed by FMT slightly decreased ESBL-E/CPE carriage compared with controls; this difference was not statistically significant, potentially due to early trial termination. Further clinical investigations seem warranted.

Seasonality, malaria, and impact of prophylaxis in a West African village I. Effect of anemia in pregnancy.

The importance of malaria as a cause of anemia in pregnancy in endemic areas remains controversial. The prevalence of anemia in pregnant women following the dry (May) and the rainy (November) seasons was compared in two successive years in Bougoula village (region of Sikasso, Mali). Phase I (1992) was observational and included 172 pregnant women and 208 controls. In Phase II (1993, 174 pregnant women and 206 controls), malaria prophylaxis with proguanil (200 mg/day) and chloroquine (300 mg/week) was offered to pregnant women. A strong seasonal variation in the prevalence of moderate to severe anemia in pregnant women (hematocrit < 30%) occurred in Phase I (dry season = 8.7%, rainy season = 41.2%). This variation was present only in women of parity lower than five, and paralleled variation in parasitemia. In Phase II, the seasonal variation of anemia was suppressed in women under malaria prophylaxis (presence of antimalarial metabolites in urine), and the overall prevalence of moderate to severe anemia in pregnancy decreased by 55.5% (22.8-74.3%). We conclude that malaria is the major cause of anemia in pregnancy in this region. A high priority should be given to prevention of malaria in pregnancy.

Seasonality, malaria, and impact of prophylaxis in a West African village. II. Effect on birthweight.

The impact of malaria on low birthweight was investigated in Bougoula village (Sikasso region, Mali). In two successive years, pregnant women were followed until delivery. Phase I (1992) was observational, with 135 complete observations. Phase II (1993) included 126 participants, who were offered malaria prophylaxis with proguanil (200 mg/day) and chloroquine (300 mg/week). The results show that 1) infants of first and second pregnancies had lower birth weights (-382.7 +/- 62.6 g; P < 0.0001) compared with higher rank pregnancies; 2) strong seasonal variation in birthweight was observed in Phase I, with an annual cycle, a nadir in January, and an amplitude of 372.4 g (P = 0.0002); 3) parasitemia measured during pregnancy was associated with lower birthweight in infants from first and second pregnancies, but not from higher parity mothers; and 4) malaria prophylaxis taken for 20 weeks or more in Phase II suppressed the seasonal variation of birthweight and the effect of low parity (+423.4 +/- 118.8 g; P = 0.0004). We conclude that malaria in pregnancy has an important negative impact on birthweight in first and second pregnancies. Prophylaxis with proguanil and chloroquine is an effective prophylaxis when taken for 20 weeks or more.

Proteinuria screening using sulfosalicylic acid: advantages of the method for the monitoring of prenatal consultations in West Africa.

Screening for proteinuria is widely recommended in the monitoring of pregnancy in order to detect preeclampsia. The method often used in primary health care centers (urine heated with acetic acid) has often attained results of over 50% positive cases. This result indicates a considerable lack of specificity outside highly endemic, for urinary schistosomiasis areas. The sulfosalicylic acid test (SSA) represents a simple, reliable and inexpensive alternative. In order to validade this procedure in the conditions of a primary mother and child health (MCH) center, results of the SSA method were compared with standard commercial strip tests a. in a well equipped Swiss laboratory, b. in a school setting in Northern Cameroon. The proportion of agreement between the two methods was 82% (CI 66-98) and 90% (CI 83-96) respectively. The relatively easy implementation of the SSA test in a MCH center in an urban area in Southern Mali lead to results more compatible with what was expected epidemiologically (less than 5% from positive to highly positive results). This experiment confirms that the SSA technique is a simple method, easy to demonstrate and implement, as well as inexpensive. Consequences for monitoring of pregnancies in such conditions are finally discussed.

External quality control of direct antigen tests to detect group A streptococcal antigen.

Presented here are the results of an external quality control survey organized by the Swiss Center for Quality Control (CSCQ) to evaluate the performance of direct antigen tests (DATs) widely used in Swiss medical practices and laboratories for the diagnosis of group A streptococcal pharyngitis. Twice yearly over a 4-year period, just over 100 participants were requested to analyze positive, weakly positive and negative samples provided to them by the CSCQ with their routinely used DATs and to send the results to the CSCQ. For 1,620 samples distributed, the CSCQ received 1,484 (91.6%) results obtained with 17 different DATs. The specificity of all DATs for negative samples was >91%. For samples containing abundant group A streptococcal antigen, sensitivities ranged from 59.1% to 95.5%; however, for samples containing low levels of antigen, the sensitivity was much lower for all DATs, ranging from 8.7% to 69.8%. Therefore, negative DAT results should be verified with well-performed cultures in order to assure the optimal care of patients with pharyngitis.

What does a single determination of malaria parasite density mean? A longitudinal survey in Mali.

Temporal variations of blood parasite density were evaluated in a longitudinal study of young, asymptomatic men in a village with endemic malaria in Mali (West Africa). Our main intention was to challenge the value of a single measure of parasite density for the diagnosis of malaria, and to define the level of endemicity in any given area. Parasitaemia and body temperature were recorded three times a day in the wet season (in 39 subjects on 12 days) and in the dry season (in 41 subjects on 13 days). Two thousand nine hundred and fifty seven blood smears (98.5% of the expected number) were examined for malaria parasites. We often found 100-fold or greater variations in parasite density within a 6-hour period during individual follow-up. All infected subjects had frequent negative smears. Although fever was most likely to occur in subjects with a maximum parasite density exceeding 10000 parasites/mm3 (P = 0.009), there was no clear relationship between the timing of these two events. Examples of individual profiles for parasite density and fever are presented. These variations (probably due to a 'sequestration-release' mechanism, which remains to be elucidated) lead us to expect a substantial impact on measurements of endemicity when only a single sample is taken. In this study, the percentage of infected individuals varied between 28.9% and 57.9% during the dry season and between 27.5% and 70.7% during the wet season. The highest rates were observed at midday, and there were significant differences between days. Thus, high parasite density sometimes associated with fever can no longer be considered as the gold standard in the diagnosis of malaria. Other approaches, such as decision-making processes involving clinical, biological and ecological variables must be developed, especially in highly endemic areas where Plasmodium infection is the rule rather than the exception and the possible causes of fever are numerous.

Seasonality and malaria in a west African village: does high parasite density predict fever incidence?

In this cohort study, the authors studied the effect of blood malaria parasite density on fever incidence in children in an endemic area with 9 days' follow-up of 1- to 12-year-old children during two time periods: the end of the dry season (May 1993: n = 783) and the end of the rainy season (October 1993: n = 841) in Bougoula, West Africa (region of Sikasso, Mali). The cumulative incidence of fever (temperature > 38.0 degrees C) was 2.0% in the dry season and 8.2% in the rainy season (p < 0.0001). In the rainy season, the risk of fever was increased in children of ages 1-3 years (relative risk (RR) = 2.5, 95% confidence interval (CI) 1.6-4.1); in those with an initial parasitemia > 15,000/microliter (RR = 2.7, 95% CI 1.4-5.4); in children with an enlarged spleen (RR = 2.0, 95% CI 1.2-3.3); or in those with anemia (hematocrit < 30%: RR = 1.8, 95% CI 1.1-2.9). In the dry season, anemia was the only predictor of fever incidence. In the rainy season, the best predictors of fever were, in order, age (< 4 years), enlarged spleen, and high parasite density. Even in the higher risk groups, the cumulative incidence was < 20%. The authors conclude that most children with high parasite density do not develop fever subsequently. The association between parasite density and fever varies according to age and season. Since even high levels of parasite density do not reliably predict fever incidence, parasite density should be considered as just one of a group of indicators that increase the probability of a fever of malarial origin.

PIP: In a cohort study, the effect of blood malaria parasite density on fever incidence in children was studied in an endemic area with 9 days' follow-up of children aged 1-12 years during two time periods: the end of the dry season (May 1993: n = 783) and the end of the rainy season (October 1993: n = 841) in Bougoula, West Africa (region of Sikasso, Mali). The number of registered children was 928 in the dry season and 998 in the rainy season. Complete follow-up and information were available for 835 children in the dry season and for 964 children in the rainy season. The 9-day cumulative fever incidence (body temperature above 38.0 degrees Celsius) increased from 2.0% in the dry season to 8.2% in the rainy season (p 0.0001). In the rainy season, the risk of fever increased in children aged 1-3 years (relative risk [RR] = 2.5; 95% confidence interval [CI], 1.6-4.1); in those with an initial parasitemia greater than 15,000/mcl (RR = 2.7; 95% CI, 1.4-5.4); in those with an enlarged spleen (RR = 2.0; 95% CI, 1.2-3.3); or in those with anemia (hematocrit 30%: RR = 1.8; 95% CI, 1.1-2.9). In the dry season, anemia (hematocrit 30%) was the only predictor of fever incidence with a cumulative incidence of 10.0%. In nonanemic children, a parasite count of 2000/mcl was the next best predictor. In the rainy season, the best predictors of fever were age (4 years), enlarged spleen, and high parasite density (1/mcl). Even in the higher risk groups, the cumulative incidence was 20%. Most children with high parasite density do not develop fever subsequently. The association between parasite density and fever varies according to age and season. Since even high levels of parasite density do not reliably predict fever incidence, parasite density should be considered not so much a direct marker of an ongoing attack but as just one indicator of the likelihood of a current or imminent attack or even one just passed.