Low Prevalence of Pneumocystis pneumonia (PCP) but High Prevalence of Pneumocystis dihydropteroate synthase (dhps) Gene Mutations in HIV-Infected Persons in Uganda

ABSTRACT Mutations in the dihydropteroate synthase (DHPS) gene of Pneumocystis jirovecii are associated with the failure of sulfa prophylaxis. They can develop by selection in patients receiving sulfa drugs or be acquired via person-to-person transmission. DHPS mutations raise concern about the decreasing efficacy of sulfa drugs, the main available therapeutic tool for Pneumocystis pneumonia (PCP). The prevalence of Pneumocystis DHPS mutations was examined in Pneumocystis isolates from 56 sulfa-prophylaxis-naive adults with a first episode of PCP from 2002 to 2010 in Santiago, Chile. Their clinical history was reviewed to analyze the effect of these mutations on response to trimethoprim-sulfamethoxazole (TMP-SMX) therapy and outcome. Mutant genotypes occurred in 22 (48%) of 46 HIV-infected patients and in 5 (50%) of 10 HIV-uninfected patients. Compared to patients with a wild-type genotype, those with mutant genotypes were more likely to experience sulfa treatment-limiting adverse reactions and to have a twice-longer duration of mechanical ventilation if mechanically ventilated. Specific genotypes did not associate with death, which occurred in none of the HIV-infected patients and in 50% of the non-HIV-infected patients. Chile has a high prevalence of DHPS mutations, which were presumably acquired through interhuman transmission because patients were not on sulfa prophylaxis. These results contrast with the low prevalence observed in other Latin American countries with similar usage of sulfa drugs, suggesting that additional sources of resistant genotypes may be possible. The twice-longer duration of mechanical ventilation in patients with mutant DHPS genotypes suggests a decreased efficacy of TMP-SMX and warrants collaborative studies to assess the relevance of DHPS mutations and further research to increase therapeutic options for PCP.

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Pneumocystis jirovecii dihydropteroate synthase gene mutations in a group of HIV-negative immunocompromised patients with Pneumocystis pneumonia

Experimental and Therapeutic Medicine ◽

10.3892/etm.2014.2002 ◽

2014 ◽

Vol 8 (6) ◽

pp. 1825-1830 ◽

Cited By ~ 5

Author(s):

YINGJIAO LONG ◽

CHENG ZHANG ◽

LI SU ◽

CHENGLI QUE

Keyword(s):

Gene Mutations ◽

Pneumocystis Pneumonia ◽

Pneumocystis Jirovecii ◽

Immunocompromised Patients ◽

Dihydropteroate Synthase ◽

Hiv Negative

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Pneumocystis jirovecii Dihydropteroate Synthase Gene Mutations and Human Immunodeficiency Virus-Associated Pneumocystis Pneumonia

Journal of Eukaryotic Microbiology ◽

10.1111/j.1550-7408.2006.00195.x ◽

2006 ◽

Vol 53 (s1) ◽

pp. S114-S116 ◽

Cited By ~ 6

Author(s):

LAURENCE HUANG ◽

DAVID A. WELSH ◽

ROBERT F. MILLER ◽

C. BEN BEARD ◽

GENA G. LAWRENCE ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Gene Mutations ◽

Pneumocystis Pneumonia ◽

Pneumocystis Jirovecii ◽

Dihydropteroate Synthase ◽

Immunodeficiency Virus

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Dihydropteroate Synthase (DHPS) Gene Mutations in Human Pneumocystosis

10.33696/aids.3.015 ◽

2021 ◽

Vol 3 (1) ◽

Keyword(s):

Gene Mutations ◽

Dihydropteroate Synthase ◽

Dhps Gene

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Changes in contraception use among Brazilian women after childbirth, 2006-2013

European Journal of Public Health ◽

10.1093/eurpub/ckaa166.981 ◽

2020 ◽

Vol 30 (Supplement_5) ◽

Author(s):

M Felisbino-Mendes ◽

B Barrozo Siqueira

Keyword(s):

Health System ◽

Secondary Data ◽

Reproductive Age ◽

Cross Sectional ◽

Regional Inequalities ◽

Unified Health System ◽

Contraception Use ◽

High Prevalence ◽

Modern Methods ◽

Low Prevalence

Abstract Introduction There are gaps in knowledge regarding the neglected and vulnerable subgroups of FP actions in Brazil, such as postpartum women and women in general, regardless of their marital status. Objective To assess changes in the prevalence of use and in the contraceptive pattern of Brazilian women up to two years after pregnancy, between 2006 and 2013. Methods Cross-sectional, descriptive and analytical study which used secondary data from national surveys. We studied Brazilian women with up to 2 years postpartum, of reproductive age, sexually active, non-pregnant and menstruating, and compared them with all the other women. We estimated the prevalence of use, contraception pattern of contraception and ranking of modern methods. Percentual change in indicators between the years was evaluated by calculating the difference between estimates. Results 85% of Brazilian women used CM, remaining stable in 2006 and 2013, with a high prevalence of modern methods use. An increase in the use of CM was observed among those with up to six months postpartum (71.0% to 89.0%). Pills and condoms accounted for about 60% of modern methods used in the postpartum period in both surveys. There was an increase in dual protection (2.9% to 10.1%) and contraceptive insecurity (1.6% to 5.7%) and a reduction in sterilization (16.2% to 13.4%) and traditional methods (2.1% to 1.4%). Conclusions Even with the maintenance of a high prevalence of use of CM and with the increase in contraception among women with up to six months postpartum, regional inequalities in access to CM and low prevalence of the use of other methods made available by the Unified Health System (SUS) persist, pointing out the maintenance of the insufficient care, failures in the means to regulate fertility and that public policies still hinder to guarantee the sexual and reproductive rights of the most vulnerable population. Key messages Regional inequalities in access to contraceptive methods and low prevalence of other methods made available by the Unified Health System (SUS) persist. There was an increase in contraception use among women with up to six months postpartum in Brazil.

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Molecular Basis of In Vivo Resistance to Sulfadoxine-Pyrimethamine in African Adult Patients Infected withPlasmodium falciparum Malaria Parasites

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.42.7.1811 ◽

1998 ◽

Vol 42 (7) ◽

pp. 1811-1814 ◽

Cited By ~ 45

Author(s):

Leonardo K. Basco ◽

Rachida Tahar ◽

Pascal Ringwald

Keyword(s):

Dihydrofolate Reductase ◽

Point Mutations ◽

Gene Mutations ◽

Adult Patients ◽

Wild Type ◽

Dihydropteroate Synthase ◽

Reductase Gene ◽

Parasite Populations

ABSTRACT In vitro sulfadoxine and pyrimethamine resistance has been associated with point mutations in the dihydropteroate synthase and dihydrofolate reductase domains, respectively, but the in vivo relevance of these point mutations has not been well established. To analyze the correlation between genotype and phenotype, 10 Cameroonian adult patients were treated with sulfadoxine-pyrimethamine and followed up for 28 days. After losses to follow-up (n = 1) or elimination of DNA samples due to mixed parasite populations with pyrimethamine-sensitive and pyrimethamine-resistant profiles (n = 3), parasite genomic DNA from day 0 blood samples of six patients were analyzed by DNA sequencing. Three patients who were cured had isolates characterized by a wild-type or mutant dihydrofolate reductase gene (with one or two mutations) and a wild-type dihydropteroate synthase gene. Three other patients who failed to respond to sulfadoxine-pyrimethamine treatment carried isolates with triple dihydrofolate reductase gene mutations and either a wild-type or a mutant dihydropteroate synthase gene. Three dihydrofolate reductase gene codons (51, 59, and 108) may be reliable genetic markers that can accurately predict the clinical outcome of sulfadoxine-pyrimethamine treatment in Africa.

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