Exploring the Distinctive Traits and Medical Implications of Gram-Unfavorable Cocci: A Complete Research

Exploring the Distinctive Traits and Medical Implications of Gram-Unfavorable Cocci: A Complete Research

 

NEISSERIA

Illnesses

The genus Neisseria accommodates two essential human pathogens:

Neisseria meningitidis and Neisseria gonorrhoeae. Neisseria

meningitidis primarily causes meningitis and meningococcemia

(Determine 16–1). In the USA, it’s the main explanation for

dying from an infection in youngsters. Neisseria gonorrhoeae causes

gonorrhea (Determine 16–2), the second most typical notifiable

bacterial illness in the USA (Tables 16–1 and 16–2).

It additionally causes neonatal conjunctivitis (ophthalmia neonatorum)

(Determine 16–3) and pelvic inflammatory illness (PID). Be aware that

N. meningitidis is also called the meningococcus (plural,

meningococci), and N. gonorrhoeae is also called the gono-

coccus (plural, gonococci).

Extra info relating to the medical elements of

infections attributable to the organisms on this chapter is supplied

in Half IX entitled Infectious Illnesses starting on web page 589.

Essential Properties

Neisseriae are gram-negative cocci that resemble paired kidney

beans (Determine 16–4).

(1) Neisseria meningitidis (meningococcus) has a outstanding

polysaccharide capsule that enhances virulence by its anti-

phagocytic motion. The capsule is also the immunogen within the

vaccine that induces protecting antibodies (Desk 16–3). Menin-

gococci are divided into a minimum of 13 serologic teams on the premise

of the antigenicity of their capsular polysaccharides. 5 sero-

sorts trigger most instances of meningitis and meningococcemia: A,

B, C, Y, and W-135. Serotype A is the main explanation for epidemic

meningitis worldwide. Serotype B accounts for many illness in

the USA. It’s because the group B polysaccharide

isn’t immunogenic in people and due to this fact isn’t a part of the

vaccines that include the capsular polysaccharide of the opposite

4 teams. In 2014, a vaccine towards group B meningococci

containing issue H binding protein because the immunogen was

authorized.

(2) Neisseria gonorrhoeae (gonococcus) has no polysaccharide

capsule however has a number of serotypes based mostly on the antigenicity of its

pilus protein. There’s marked antigenic variation within the gono-

coccal pili on account of chromosomal rearrangement; greater than

100 serotypes are recognized. Gonococci have three outer membrane

proteins (proteins I, II, and III). Protein II performs a job in attach-

ment of the organism to cells and varies antigenically as effectively.

Neisseriae are gram-negative micro organism and include endotoxin

of their outer membrane. Be aware that the endotoxin of neisseriae

encompass lipooligo saccharide (LOS), in distinction to the lipopoly

saccharide (LPS) present in enteric gram-negative rods. Each LPS

and LOS include lipid A, however the oligosaccharide a part of LOS

accommodates few sugars, whereas the polysaccharide a part of LPS

accommodates a protracted repeating sugar facet chain.

The expansion of each organisms is inhibited by poisonous hint

metals and fatty acids present in sure tradition media (e.g.,

blood agar plates). They’re due to this fact cultured on “chocolate”

agar containing blood heated to 80°C, which inactivates the

inhibitors. Neisseriae are oxidase-positive (Determine 16–5) (i.e.,

they possess the enzyme cytochrome c). This is a crucial

laboratory diagnostic check during which colonies uncovered to phenyl-

enediamine flip purple or black on account of oxidation of the

reagent by the enzyme (see Determine 16–2).

The genus Neisseria is certainly one of a number of within the household Neisseria-

ceae. A separate genus accommodates the organism Moraxella catarrhalis,

which is a part of the conventional throat flora however may cause such

respiratory tract infections as sinusitis, otitis media, bronchitis,

and pneumonia. Moraxella catarrhalis and members of different

genera, resembling Branhamella, Kingella, and Acinetobacter, are

described in Chapter 27. (Moraxella catarrhalis is the brand new identify

for Branhamella catarrhalis.)

1. Neisseria meningitidis

Pathogenesis & Epidemiology

People are the one pure hosts for meningococci. The

organisms are transmitted by airborne droplets; they colonize

the membranes of the nasopharynx and turn into a part of the

transient flora of the higher respiratory tract. Carriers are usu-

ally asymptomatic. From the nasopharynx, the organism can

enter the bloodstream and unfold to particular websites, such because the

meninges or joints, or be disseminated all through the physique

(meningococcemia).

About 5% of individuals turn into continual carriers and function a

supply of an infection for others. The carriage fee might be as excessive as

35% in individuals who dwell in shut quarters (e.g., navy recruits);

this explains the excessive frequency of outbreaks of meningitis in

the armed forces previous to using the vaccine. The carriage

fee can also be excessive in shut (household) contacts of sufferers. Outbreaks

of meningococcal illness even have occurred in school college students

dwelling in dormitories.

Two organisms trigger greater than 80% of instances of bacterial

meningitis in infants older than 2 months of age: Streptococcus

pneumoniae and N. meningitidis. Of those organisms, meningo-

cocci, particularly these in group A, are more than likely to trigger epi-

demics of meningitis. Group B meningococci trigger many instances

of meningitis in developed nations as a result of they aren’t pres-

ent within the capsular polysaccharide vaccine (see “Prevention,”

later). Total, N. meningitidis ranks second to S. pneumoniae as

a explanation for meningitis however is the commonest trigger in individuals

between the ages of two and 18 years.

Meningococci have 4 essential virulence components:

(1) A polysaccharide capsule that permits the organism to

resist phagocytosis by polymorphonuclear leukocytes (PMNs).

The capsule is the immunogen in a number of generally used vac-

cines towards meningococci.

(2) Endotoxin, which causes fever, shock, and different patho-

physiologic modifications (in purified type, endotoxin can reproduce

most of the medical manifestations of meningococcemia).

(3) An immunoglobulin A (IgA) protease that helps the

micro organism connect to the membranes of the higher respiratory tract

by cleaving secretory IgA.

(4) Issue H binding protein (FHBP) on meningococci,

which binds Issue H, an inhibitor of complement issue C3b.

The presence of Issue H on the floor of meningococci

reduces the opsonizing exercise of C3b and reduces the quantity

of membrane assault advanced produced (see complement motion

in Chapter 63). FHBP is the immunogen within the vaccine towards

group B meningococci.

Resistance to illness correlates with the presence of antibody

to the capsular polysaccharide. Most carriers develop protecting

antibody titers inside 2 weeks of colonization. As a result of immu-

nity is group-specific, it’s potential to have protecting antibodies

to 1 group of organisms but be vulnerable to an infection by

organisms of the opposite teams.

Complement is a crucial characteristic of the host defenses,

as a result of folks with complement deficiencies, notably in

the late-acting complement elements (C6–C9), have an

elevated incidence of meningococcal bacteremia. Sufferers

receiving eculizumab, a terminal complement inhibitor utilized in

the therapy of paroxysmal nocturnal hemoglobinuria, have a

1000-fold improve in meningococcal illness.

Medical Findings

The 2 most essential manifestations of illness are menin-

gococcemia (see Determine 16–1) and meningitis. Probably the most

extreme type of meningococcemia is the life-threatening

Waterhouse–Friderichsen syndrome, which is characterised by

excessive fever, shock, widespread purpura, disseminated intravas-

cular coagulation, thrombocytopenia, and adrenal insufficiency.

Bacteremia can lead to the seeding of many organs, particularly

the meninges. The signs of meningococcal meningitis are

these of typical bacterial meningitis, specifically, fever, headache,

stiff neck, and an elevated stage of PMNs within the spinal fluid.

Laboratory Prognosis

The principal laboratory procedures are smear and tradition of

blood and spinal fluid samples. A presumptive prognosis of

meningococcal meningitis might be made if gram-negative cocci

are seen in a smear of spinal fluid (see Determine 16–4). The organ-

ism grows greatest on chocolate agar incubated at 37°C in a 5% CO2

environment. A presumptive prognosis of Neisseria might be made

if oxidase-positive colonies of gram-negative diplococci are discovered

(see Determine 16–5). The differentiation between N. meningitidis

and N. gonorrhoeae is made on the premise of sugar fermenta-

tion: meningococci ferment maltose, whereas gonococci don’t

(each organisms ferment glucose). Immunofluorescence can

even be used to establish these species. Assessments for serum antibodies

should not helpful for medical prognosis. Nonetheless, a process that

can help within the fast prognosis of meningococcal meningitis is

the latex agglutination check, which detects capsular polysaccha-

journey within the spinal fluid.

Therapy

Both ceftriaxone or penicillin G is the drug of selection for

meningococcal infections. Strains proof against penicillin have

hardly ever emerged, however sulfonamide resistance is widespread.

Prevention

Chemoprophylaxis and immunization are each used to stop

meningococcal illness. Both rifampin or ciprofloxacin can

be used for prophylaxis in individuals who have had shut contact

with the index case. These medication are most popular as a result of they’re

effectively secreted into the saliva, in distinction to penicillin G.

The meningococcal vaccines are described in Desk 16–4.

The vaccines towards teams A, C, Y, and W-135 meningococci

include the polysaccharide capsule because the immunogen. The vac-

cine towards group B meningococci accommodates FHBP as the primary

immunogen.

In the USA, the vaccines towards teams A, C, Y, and

W-135 meningococci are conjugate vaccines, that’s, the capsu-

lar polysaccharide is conjugated to a provider protein.

There are three types of the polysaccharide vaccine to be used

in the USA: (1) Menactra accommodates the 4 polysac-

charides conjugated to diphtheria toxoid because the provider protein;

(2) Menveo accommodates the 4 polysaccharides conjugated to a

unhazardous mutant of diphtheria toxin because the provider protein; and

(3) MenHibrix accommodates two polysaccharides (C and Y) plus the

capsular polysaccharide of Haemophilus influenzae, all conju-

gated to tetanus toxoid.

Menomune, the unconjugated vaccine, accommodates solely the

4 polysaccharides (not conjugated to a provider protein). It’s

not obtainable in the USA however is utilized in different nations.

One other vaccine created to be used within the meningitis belt of Africa,

known as MenAfriVac, is a conjugate vaccine that accommodates solely the

group A polysaccharide.

The conjugate vaccines induce larger titers of antibodies

in youngsters than does the unconjugated vaccine. The vaccines

induce related antibody titers in adults. Be aware that none of those

vaccines include the group B polysaccharide as a result of it’s not

immunogenic in people. The conjugate vaccine is recom-

mended for kids on the age of 11 to 12 years, which can

cut back the incidence of meningococcal illness in youngsters

and younger adults. The conjugate vaccine can also be beneficial

for kids youthful than 11 years with high-risk circumstances,

resembling asplenia and HIV an infection. Vacationers to areas the place an

epidemic of meningococcal illness is going on ought to obtain

the conjugate vaccine. School college students dwelling in dormitories are

inspired to obtain the conjugate vaccine.

The vaccine towards group B meningococci accommodates FHBP

because the immunogen. It induces antibody towards the binding

protein, thereby inhibiting the power of the micro organism to bind

Issue H on its floor. This enhances the motion of comple-

ment, an essential host protection, as a result of Issue H blocks

complement element C3b from binding to the bacterial sur-

face. Acknowledged one other approach, if Issue H can not bind to the floor

of the micro organism, that enables C3b, an essential opsonizer, to bind.

The FHBP used within the vaccine is made by recombinant DNA

strategies in Escherichia coli. The vaccine is authorized to be used in

folks age 10 to 25 years. In 2015, a second vaccine towards group B

meningococci containing 4 floor proteins (fHbp, NadA

[neisserial adhesin A], NHBA [neisserial heparin binding anti-

gen], and OMV [outer membrane vesicle; PorA]) was authorized.

2. Neisseria gonorrhoeae

Pathogenesis & Epidemiology

Gonococci, like meningococci, trigger illness solely in people.

The organism is normally transmitted sexually; newborns might be

contaminated throughout start. As a result of gonococcus is sort of delicate to

dehydration and funky circumstances, sexual transmission favors its

survival. Gonorrhea is normally symptomatic in males however usually

asymptomatic in girls. Genital tract infections are essentially the most

widespread supply of the organism, however anorectal and pharyngeal

infections are essential sources as effectively.

Pili represent some of the essential virulence components,

as a result of they mediate attachment to mucosal cell surfaces and

are antiphagocytic. Piliated gonococci are normally virulent,

whereas nonpiliated strains are avirulent. Two virulence components

within the cell wall are endotoxin (lipooligosaccharide, LOS) and

the outer membrane proteins. The organism’s IgA protease

can hydrolyze secretory IgA, which may in any other case block

attachment to the mucosa. Gonococci haven’t any capsules.

The primary host defenses towards gonococci are antibodies (IgA

and IgG), complement, and neutrophils. Antibody-mediated

opsonization and killing inside phagocytes happen, however repeated

gonococcal infections are widespread, primarily on account of anti-

genic modifications of pili and the outer membrane proteins.

Gonococci infect primarily the mucosal surfaces (e.g., the

urethra and vagina), however dissemination happens. Sure strains

of gonococci trigger disseminated infections extra ceaselessly than

others. A very powerful characteristic of those strains is their resis-

tance to being killed by antibodies and complement. The mecha-

nism of this “serum resistance” is unsure, however the presence of a

porin protein (porin A) within the cell wall, which inactivates the C3b

element of complement, seems to play an essential function.

The incidence of a disseminated an infection is a perform not

solely of the pressure of gonococcus but in addition of the effectiveness of the

host defenses. Individuals with a deficiency of the late-acting comple-

ment elements (C6–C9) are in danger for disseminated infec-

tions, as are girls throughout menses and being pregnant. Disseminated

infections normally come up from asymptomatic infections, indicating

that native irritation could deter dissemination.

Medical Findings

Gonococci trigger each localized infections, normally within the geni-

tal tract, and disseminated infections with seeding of assorted

organs. Gonococci attain these organs by way of the bloodstream

(gonococcal bacteremia).

Gonorrhea in males is characterised primarily by urethritis

accompanied by dysuria and a purulent discharge (see Determine

16–2). Epididymitis can happen.

In girls, an infection is positioned primarily within the endocervix,

inflicting a purulent vaginal discharge and intermenstrual bleed-

ing (cervicitis). Probably the most frequent complication in girls is

an ascending an infection of the uterine tubes (salpingitis, PID),

which may end up in sterility or ectopic being pregnant on account of

scarring of the tubes.

Disseminated gonococcal infections (DGIs) generally

manifest as arthritis, tenosynovitis, or pustules within the pores and skin.

Disseminated an infection is the commonest explanation for septic

arthritis in sexually lively adults. The medical prognosis of DGI

is usually troublesome to substantiate utilizing laboratory exams as a result of the

organism isn’t cultured in additional than 50% of instances.

Different contaminated websites embody the anorectal space, throat, and

eyes. Anorectal infections happen mainly in girls and homo-

sexual males. They’re ceaselessly asymptomatic, however a bloody or

purulent discharge (proctitis) can happen. Within the throat, pharyn-

gitis happens, however many sufferers are asymptomatic. In new child

infants, purulent conjunctivitis (ophthalmia neonatorum)

(see Determine 16–3) is the results of gonococcal an infection acquired

from the mom throughout passage via the start canal. The

incidence of gonococcal ophthalmia has declined vastly in

current years due to the widespread use of prophylactic

erythromycin eye ointment (or silver nitrate) utilized shortly

after start. Gonococcal conjunctivitis additionally happens in adults as a

results of the switch of organisms from the genitals to the attention.

Different sexually transmitted infections (e.g., syphilis and non-

gonococcal urethritis attributable to Chlamydia trachomatis) can

coexist with gonorrhea; due to this fact, acceptable diagnostic and

therapeutic measures should be taken.

Laboratory Prognosis

The prognosis of urogenital infections depends upon Gram stain-

ing and tradition of the discharge (see Determine 16–4). Nonetheless,

nucleic acid amplification exams are broadly used as screening

exams (see later).

In males, the discovering of gram-negative diplococci inside

PMNs in a urethral discharge specimen is ample for diag-

nosis (see Determine 16–4). In girls, using the Gram stain

alone might be troublesome to interpret; due to this fact, cultures ought to be

performed. Gram stains on cervical specimens might be falsely optimistic

due to the presence of gram-negative diplococci within the nor-

mal flora and might be falsely detrimental due to the lack to

see small numbers of gonococci when utilizing the oil immersion

lens. Cultures should even be utilized in diagnosing suspected phar-

yngitis or anorectal infections.

Specimens from mucosal websites, such because the urethra and

cervix, are cultured on Thayer-Martin medium, which is a

chocolate agar containing antibiotics (vancomycin, colistin,

trimethoprim, and nystatin) to suppress the conventional flora. The

discovering of an oxidase-positive colony (see Determine 16–5) com-

posed of gram-negative diplococci is ample to establish the

isolate as a member of the genus Neisseria. Particular identifica-

tion of the gonococcus might be made both by its fermentation

of glucose (however not maltose) or by fluorescent antibody staining.

Be aware that specimens from sterile websites, resembling blood or joint

fluid, might be cultured on chocolate agar with out antibiotics

as a result of there isn’t a competing regular flora.

Nucleic acid amplification exams, usually abbreviated NAAT,

detect the presence of gonococcal nucleic acids in affected person

specimens. These exams are broadly used for screening functions,

produce outcomes quickly, and are extremely delicate and particular.

They can be utilized on urine samples, obviating the necessity for

extra invasive assortment strategies. Be aware that serologic exams to

decide the presence of antibody to gonococci within the affected person’s

serum should not helpful for prognosis.

Therapy

Ceftriaxone is the therapy of selection in uncomplicated gono-

coccal infections. If the affected person is allergic to penicillins or

cephalosporins, a routine resembling gentamicin plus azithromycin

can be utilized.

As a result of blended infections with C. trachomatis are widespread,

azithromycin or doxycycline ought to be prescribed as well as

to ceftriaxone. A follow-up tradition ought to be carried out 1 week

after completion of therapy to find out whether or not gonococci

are nonetheless current. Therapy of difficult gonococcal infec-

tions, resembling PID, usually requires hospitalization. Therapy

regimens are advanced and past the scope of this e-book.

Previous to the mid-Nineteen Fifties, all gonococci have been extremely delicate to

penicillin. Subsequently, isolates emerged with low-level resis-

tance to penicillin and to different antibiotics resembling tetracycline

and chloramphenicol. One of these resistance is encoded by the

bacterial chromosome and is because of decreased uptake of the drug

or to altered binding websites slightly than to enzymatic degradation

of the drug.

Then, in 1976, penicillinase-producing (PPNG) strains

that exhibited high-level resistance have been remoted from sufferers.

Penicillinase is plasmid-encoded. PPNG strains are actually com-

mon in lots of areas of the world, together with a number of city areas

in the USA, the place roughly 10% of isolates are

resistant. Isolates proof against fluoroquinolones, resembling cipro-

floxacin, have turn into a big downside, and fluoroqui-

nolones should not beneficial as therapy. Isolates resistant

to sulfonamides and tetracyclines have additionally been recovered.

In 2017, the World Well being Group (WHO) reported that

a number of strains of gonococci proof against all recognized antibiotics

have been remoted.

Prevention

The prevention of gonorrhea entails using condoms and

the immediate therapy of symptomatic sufferers and their intercourse

companions. Circumstances of gonorrhea should be reported to the general public

well being division to make sure correct follow-up and get in touch with trac-

ing. A significant downside is the detection of asymptomatic carriers.

Gonococcal conjunctivitis in newborns is prevented most frequently

by means of erythromycin ointment. Silver nitrate drops are

utilized in some nations. No vaccine is obtainable.

SELF-ASSESSMENT QUESTIONS

1. Relating to the variations between N. meningitidis (meningo-

cocci) and N. gonorrhoeae (gonococci), which one of many follow-

ing is essentially the most correct assertion?

(A) Meningococci are oxidase-positive, whereas gonococci should not.

(B) Meningococci have a thick polysaccharide capsule, whereas

gonococci don’t.

(C) Meningococci have lipid A, whereas gonococci don’t.

(D) Meningococci produce penicillinase, whereas gonococci don’t.

(E) Meningococci synthesize IgA protease, whereas gonococci do

2. Your affected person is a 14-year-old lady who was despatched house from faculty

as a result of she had a fever of 102°C and a extreme headache and was

falling asleep at school. When her fever rose to 104°C, her mom

took her to the emergency room, the place a blood strain of

60/20 mm Hg and several other petechial hemorrhages have been discovered.

Gram-negative diplococci have been seen in a Gram stain of the spinal

fluid. Which one of many following is more than likely to trigger the fever,

hypotension, and petechial hemorrhages?

(A) Endotoxin

(B) IgA protease

(C) Oxidase

(D) Pilus protein

(E) Superantigen

3. Relating to the affected person in Query 2, which one of many following is

one of the best antibiotic to deal with the an infection?

(A) Azithromycin

(B) Doxycycline

(C) Penicillin G

(D) Rifampin

(E) Trimethoprim-sulfamethoxazole

4. Relating to the variations between N. meningitidis (meningo-

cocci) and N. gonorrhoeae (gonococci), which one of many follow-

ing is essentially the most correct assertion?

(A) People are the reservoir for each organisms.

(B) Many medical isolates of meningococci produce β-lactamase,

however medical isolates of gonococci don’t.

(C) Meningococci have a number of antigenic sorts, however gonococci

have just one antigenic sort.

(D) The conjugate vaccine towards gonorrhea accommodates seven sorts

of the pilus protein because the immunogen.

(E) The primary mode of transmission for each organisms is respira-

tory droplets.

5. Your affected person is a 20-year-old man with a urethral exudate. You do

a Gram stain of the pus and see gram-negative diplococci with

neutrophils. Which one of many following is one of the best antibiotic to

deal with the an infection?

(A) Ceftriaxone

(B) Gentamicin

(C) Penicillin G

(D) Trimethoprim-sulfamethoxazole

(E) Vancomycin

ANSWERS

(1) (B)

(2) (A)

(3) (C)

(4) (A)

(5) (A)

SUMMARIES OF ORGANISMS

Transient summaries of the organisms described on this chapter

start on web page 653. Please seek the advice of these summaries for a fast

evaluation of the important materials.

PRACTICE QUESTIONS: USMLE &

COURSE EXAMINATIONS

Questions on the matters mentioned on this chapter might be discovered

within the Medical Bacteriology part of Half XIII: USMLE

(Nationwide Board) Follow Questions beginning on web page 715. Additionally

see Half XIV: USMLE (Nationwide Board) Follow Examination

beginning on web page 753.