In vitro susceptibility to quinine and microsatellite variations of the Plasmodium falciparum Na+/H+ exchanger (Pfnhe-1) gene: the absence of association in clinical isolates from the Republic of Congo.

BACKGROUND: Quinine is still recommended as an effective therapy for severe cases of Plasmodium falciparum malaria, but the parasite has developed resistance to the drug in some cases. Investigations into the genetic basis for quinine resistance (QNR) suggest that QNR is complex and involves several genes, with either an additive or a pairwise effect. The results obtained when assessing one of these genes, the plasmodial Na+/H+ exchanger, Pfnhe-1, were found to depend upon the geographic origin of the parasite strain. Most of the associations identified have been made in Asian strains; in contrast, in African strains, the influence of Pfnhe on QNR is not apparent. However, a recent study carried out in Kenya did show a significant association between a Pfnhe polymorphism and QNR. As genetic differences may exist across the African continent, more field data are needed to determine if this association exists in other African regions. In the present study, association between Pfnhe and QNR is investigated in a series of isolates from central Africa. METHODS: The sequence analysis of the polymorphisms at the Pfnhe-1 ms4760 microsatellite and the evaluation of in vitro quinine susceptibility (by isotopic assay) were conducted in 74 P. falciparum isolates from the Republic of Congo. RESULTS: Polymorphisms in the number of DNNND or NHNDNHNNDDD repeats in the Pfnhe-1 ms4760 microsatellite were not associated with quinine susceptibility. CONCLUSIONS: The polymorphism in the microsatellite ms4760 in Pfnhe-1 that cannot be used to monitor quinine response in the regions of the Republic of Congo, where the isolates came from. This finding suggests that there exists a genetic background associated with geographic area for the association that will prevent the use of Pfnhe as a molecular marker for QNR. The contribution of Pfnhe to the in vitro response to quinine remains to be assessed in other regions, including in countries with different levels of drug pressure.

A 62-year-old man with stridor and dyspnoea.

Stridor is a sign of vital emergency that immediately orientates towards a laryngeal or tracheal obstruction. This case report focuses on the management of stridor, which comprises emergency securing of airways and parallel aetiological investigations. https://bit.ly/39CTjOg.

Screening for comorbidities in COPD.

Due to growing recognition of comorbidities, COPD is no longer considered a disease affecting only the respiratory system. Its management now entails the early diagnosis and treatment of comorbidities. However, although many studies have examined the impact of comorbidities on the evolution of COPD and patients' quality of life, very few have explored the means to systematically identify and manage them. The aims of this article are to summarise the state of current knowledge about comorbidities associated with COPD and to propose a possible screening protocol in the outpatient setting, emphasising the areas needing further research.

A 44-Year-Old Man With Acute Chest Pain.

CASE PRESENTATION: A 44-year-old man consulted in April 2020 for a 1-week persistent left lateral chest pain, increased with deep breathing and change of position. He had left lower limb pain without redness or swelling 2 weeks before presentation. He did not complain of shortness of breath, cough, hemoptysis, syncope, fever, nor general status alteration.

What pulmonologists need to know about extrapulmonary tuberculosis.

Extrapulmonary tuberculosis (EPT) can affect all organs. Its diagnosis is often challenging, especially when the lung is not involved. Some EPT locations, such as when the central nervous system is involved, are a medical emergency, and some have implications for treatment options and length. This review describes clinical features of EPT, diagnostic tests and treatment regimens.

Multinormal in vitro distribution model suitable for the distribution of Plasmodium falciparum chemosusceptibility to doxycycline.

The distribution and range of 50% inhibitory concentrations (IC(50)s) of doxycycline were determined for 747 isolates obtained between 1997 and 2006 from patients living in Senegal, Republic of the Congo, and Gabon and patients hospitalized in France for imported malaria. The statistical analysis was designed to answer the specific question of whether Plasmodium falciparum has different phenotypes of susceptibility to doxycycline. A triple normal distribution was fitted to the data using a Bayesian mixture modeling approach. The IC(50) geometric mean ranged from 6.2 microM to 11.1 microM according to the geographical origin, with a mean of 9.3 microM for all 747 parasites. The values for all 747 isolates were classified into three components: component A, with an IC(50) mean of 4.9 microM (+/-2.1 microM [standard deviation]); component B, with an IC(50) mean of 7.7 microM (+/-1.2 microM); and component C, with an IC(50) mean of 17.9 microM (+/-1.4 microM). According to the origin of the P. falciparum isolates, the triple normal distribution was found in each subgroup. However, the proportion of isolates predicted to belong to component B was most important in isolates from Gabon and Congo and in isolates imported from Africa (from 46 to 56%). In Senegal, 55% of the P. falciparum isolates were predicted to be classified as component C. The cutoff of reduced susceptibility to doxycycline in vitro was estimated to be 35 microM.

Severe imported malaria: clinical presentation at the time of hospital admission and outcome in 42 cases diagnosed from 1996 to 2002.

The objectives of this retrospective study were to describe initial clinical profiles and subsequent outcome of adult patients in France who were diagnosed with severe imported malaria, as defined by the World Health Organization (WHO). Forty-two patients diagnosed from 1996 to 2002 were included (median age: 30 years, men: 78%, non-immune persons: 74%, return from Africa: 100%, inappropriate antimalarial chemoprophylaxis: 95%). At the time of hospital admission, jaundice (62%), hyperparasitemia (56%), and prostration (52%) were the most frequent findings, followed by acute renal failure (31%). Other findings, as described by the WHO criteria, were less common. Twenty-three patients presented only with jaundice, hyperparasitemia, or prostration in isolation, or in combination. Of these 23, five non-immune persons subsequently developed coma, shock, acute respiratory distress syndrome or acute renal failure; this led to death in 2 of these cases. This suggests that non-immune persons with imported malaria who present with jaundice, hyperparasitemia, or prostration should be admitted to the intensive care unit for close monitoring.

Prevalence of in vitro resistance to eleven standard or new antimalarial drugs among Plasmodium falciparum isolates from Pointe-Noire, Republic of the Congo.

We determined the level of in vitro resistance of Plasmodium falciparum parasites to standard antimalarial drugs, such as chloroquine, quinine, amodiaquine, halofantrine, mefloquine, cycloguanil, and pyrimethamine, and to new compounds, such as dihydroartemisinin, doxycycline, atovaquone, and lumefantrine. The in vitro resistance to chloroquine reached 75.5%. Twenty-eight percent of the isolates were intermediate or had reduced susceptibility to quinine. Seventy-six percent and 96% of the tested isolates showed in vitro resistance or intermediate susceptibilities to cycloguanil and pyrimethamine, respectively. Only 2% of the parasites demonstrated in vitro resistance to monodesethylamodiaquine. No resistance was shown with halofantrine, lumefantrine, dihydroartemisinin, or atovaquone. Halofantrine, mefloquine, and lumefantrine demonstrated high correlation. No cross-resistance was identified between responses to monodesethyl-amodiaquine, dihydroartemisinin, atovaquone, and cycloguanil. Since the level of chloroquine resistance in vitro exceed an unacceptable upper limit, high rates of in vitro resistance to pyrimethamine and cycloguanil and diminution of the susceptibility to quinine, antimalarial drugs used in combination, such as amodiaquine, artemisinin derivatives, mefloquine, lumefantrine, or atovaquone, seem to be appropriate alternatives for the first line of treatment of acute, uncomplicated P. falciparum malaria.