美国佐治亚州埃默里大学医学院Monica M. Farley小组近日取得一项新成果。他们对2008-2018年佐治亚州亚特兰大市艾滋病毒成年感染者中侵袭性不可分型流感嗜血杆菌感染的情况进行了分析。2019年12月24日出版的《美国医学会杂志》发表了这项成果。

成人中侵袭性不可分型流感嗜血杆菌（NTHi）感染通常与细菌性肺炎有关。不可分型流感病毒的基因多样性和感染集群很罕见。

为了评估2017-2018年佐治亚州亚特兰大市男同性恋HIV感染者中侵袭性NTHi感染的增长情况，2008年1月1日至2018年12月31日，研究组采用队列亚研究和描述性流行病学分析，对成人侵袭性NTHi感染进行监测。

共有553例成人患侵袭性NTHi感染，中位年龄为66岁，男性占52%，黑人占38%，HIV感染者60例。2017-2018年HIV感染者的侵袭性NTHi感染率为每10万人41.7例，明显高于2008-2016年的HIV感染者（每10万人9.6例）和2008-2018年的非HIV感染者（每10万人1.1例）。

2017-2018年18-55岁患有侵袭性NTHi感染的179例成人中，HIV感染者为31人，与2008-2018年间未感染HIV的成人相比，这些HIV感染者中男性、黑人、患有化脓性关节炎的比率较高。对这179例NTHi感染者中的174例取样进行脉冲场凝胶电泳，确定了2个基因不同的克隆群，其中C1有24例，C2有23例。

全基因组测序证实了这两个NTHi感染的克隆谱系，并显示所有的C1分离株携带IS1016，即一种与流感病毒包膜基因相关的插入序列。2017-2018年间的HIV感染者患C1或C2侵袭性NTHi感染的发病率为90%，显著高于2008-2016年的HIV感染者（42%）和2008-2018年的非HIV感染者（8%）。

在C1或C2侵袭性NTHi感染者中，HIV感染者有38例，中位年龄为34.5岁，均为男性黑人，82%为同性恋。其中32人居住在亚特兰大市的两个县，与未感染C1或C2侵袭性NTHi者相比，这32人呈现明显的地区聚集性。

总之，在亚特兰大的HIV感染者中，与2008-2016年相比，2017-2018年间侵袭性NTHi感染的发病率显著增加。研究组鉴定出两个独特且与遗传相关的克隆菌株，该菌株与同区居住的黑人男同性恋中感染性关节炎密切相关。

附：英文原文

Title: Invasive Nontypeable Haemophilus influenzae Infection Among Adults With HIV in Metropolitan Atlanta, Georgia, 2008-2018

Author: Lauren F. Collins, Fiona P. Havers, Amy Tunali, Stephanie Thomas, Julie A. Clennon, Zanthia Wiley, Melissa Tobin-D’Angelo, Tonia Parrott, Timothy D. Read, Sarah W. Satola, Robert A. Petit, Monica M. Farley

Issue&Volume: 2019/12/24

Abstract: 

Importance  Invasive nontypeable Haemophilus influenzae (NTHi) infection among adults is typically associated with bacteremic pneumonia. Nontypeable H influenzae is genetically diverse and clusters of infection are uncommon.

Objective  To evaluate an increase in invasive NTHi infection from 2017-2018 among HIV-infected men who have sex with men in metropolitan Atlanta, Georgia.

Design, Setting, and Participants  A population-based surveillance study with a cohort substudy and descriptive epidemiological analysis identified adults aged 18 years or older with invasive NTHi infection (isolation of NTHi from a normally sterile site) between January 1, 2008, and December 31, 2018 (final date of follow-up).

Exposures  Time period, HIV status, and genetic relatedness (ie, cluster status) of available NTHi isolates.

Main Outcomes and Measures  The primary outcome was incidence of invasive NTHi infection (from 2008-2016 and 2017-2018) among persons with HIV and compared with NTHi infection from 2008-2018 among those without HIV. The secondary outcomes were assessed among those aged 18 to 55 years with invasive NTHi infection and included epidemiological, clinical, and geographic comparisons by cluster status.

Results  Among 553 adults with invasive NTHi infection (median age, 66 years [Q1-Q3, 48-78 years]; 52% male; and 38% black), 60 cases occurred among persons with HIV. Incidence of invasive NTHi infection from 2017-2018 among persons with HIV (41.7 cases per 100?000) was significantly greater than from 2008-2016 among those with HIV (9.6 per 100?000; P < .001) and from 2008-2018 among those without HIV (1.1 per 100?000; P < .001). Among adults aged 18 to 55 years with invasive NTHi infections from 2017-2018 (n = 179), persons with HIV (n = 31) were significantly more likely than those from 2008-2018 without HIV (n = 124) to be male (94% vs 49%, respectively; P < .001), black (100% vs 53%; P < .001), and have septic arthritis (35% vs 1%; P < .001). Persons with HIV who had invasive NTHi infection from 2017-2018 (n = 31) were more likely than persons with HIV who had invasive NTHi infection from 2008-2016 (n = 24) to have septic arthritis (35% vs 4%, respectively; P = .01). Pulsed-field gel electrophoresis of 174 of 179 NTHi isolates from 18- to 55-year-olds identified 2 genetically distinct clonal groups: cluster 1 (C1; n = 24) and cluster 2 (C2; n = 23). Whole-genome sequencing confirmed 2 clonal lineages of NTHi infection and revealed all C1 isolates (but none of the C2 isolates) carried IS1016 (an insertion sequence associated with H influenzae capsule genes). Persons with HIV were significantly more likely to have C1 or C2 invasive NTHi infection from 2017-2018 (28/31 [90%]) compared with from 2008-2016 among persons with HIV (10/24 [42%]; P < .001) and compared with from 2008-2018 among those without HIV (9/119 [8%]; P < .001). Among persons with C1 or C2 invasive NTHi infection who had HIV (n = 38) (median age, 34.5 years; 100% male; 100% black; 82% men who have sex with men), 32 (84%) lived in 2 urban counties and an area of significant spatial aggregation was identified compared with those without C1 or C2 invasive NTHi infection.

Conclusions and Relevance  Among persons with HIV in Atlanta, the incidence of invasive nontypeable H influenzae infection increased significantly from 2017-2018 compared with 2008-2016. Two unique but genetically related clonal strains were identified and were associated with septic arthritis among black men who have sex with men and who lived in geographic proximity.

DOI: 10.1001/jama.2019.18800

Source: https://jamanetwork.com/journals/jama/article-abstract/2757815