Haemophilus
Haemophilus is a genus of gram-negative, nonmotile, and pleiomorphic coccobacilli bacteria, often referred to as "blood lovers" due to their requirement for hemin and NAD, which are found in blood. These bacteria are primarily found in the upper respiratory and urogenital tracts of humans and animals, where they can exist as normal flora. However, certain species, particularly Haemophilus influenzae and Haemophilus ducreyi, are recognized as opportunistic pathogens. H. influenzae is notable for causing a range of serious infections, such as meningitis and pneumonia, especially in children, and has seen a significant decline in incidence due to vaccination efforts. In contrast, H. ducreyi is associated with chancroid, a sexually transmitted infection prevalent in certain regions, notably sub-Saharan Africa.
Most Haemophilus species require enriched culture media for growth, and they exhibit varied pathogenicity, with encapsulated strains showing higher virulence. Treatment options for infections caused by these bacteria include ampicillin and other antibiotics, although resistance is increasingly common. Additionally, the dynamics of Haemophilus infections have been influenced by public health measures during the COVID-19 pandemic, illustrating the complex interplay between infectious diseases and societal behavior. Overall, while many Haemophilus species are benign, their pathogenic relatives pose significant health challenges, particularly in specific populations.
Haemophilus
- TRANSMISSION ROUTE: Direct contact, inhalation
Definition
Haemophilus is a gram-negative, nonmotile, non-spore-forming, pleiomorphic coccobacillus. Its name is derived from the Greek and means “blood lover.” Most strains of Haemophilus require hemin (factor X) and NAD (factor V), both of which are naturally found in blood. Strains may be aerobes or facultative anaerobes. Many Haemophilus spp. are normal flora in the upper respiratory and urogenital tracts of humans and other animals.
Natural Habitat and Features
Although Haemophilus spp. are usually classified as coccobacilli, they are quite pleiomorphic and can take on various shapes in culture. Most are cultured on chocolate agar, a nutrient-dense agar with added denatured hemoglobin. Additional NAD is usually added to this agar when culturing Haemophilus spp. Incubation is best at 98.6° Fahrenheit (37° Celsius), and growth is enhanced in an incubator enriched with carbon dioxide. Most species are commensal in the upper respiratory tract and are opportunistic pathogens with relatively limited host ranges. The major pathogenic species in humans are H. influenzae and H. ducreyi.
Pathogenicity and Clinical Significance
H. influenzae was named when it was isolated in the 1890s from persons suffering from influenza. It was later shown to be a secondary bacterial infection and not the causative agent of that disease. It is similar to many other members of this genus. H. aegyptius, which causes conjunctivitis and Brazilian purpuric fever, has been reclassified as a subtype of H. influenzae rather than a separate species. Natural infections occur only in humans, although infection can be artificially induced in a few animal species.
Both encapsulated and nonencapsulated strains exist. The encapsulated strains show higher degrees of pathogenicity, most likely because the capsule offers some protection against the host’s immune system and possibly increases the bacteria’s virulence. Encapsulated strains are divided into six serotypes (a-f), with H. influenzae serotype B (Hib) being the most common pathogenic group. Before the widespread use of the Hib vaccine, approximately 95 percent of all invasive Haemophilus infections in children, including 75 percent of meningitis cases and 50 percent of Haemophilus infections in adults, were caused by Hib. Hib commonly causes meningitis, pneumonia, bacteremia, cellulitis, epiglottitis, and septic arthritis. It also can cause osteomyelitis and endocarditis. In developed countries, Hib infections in children have markedly decreased since the early 1990s, when the Hib vaccine became widely used. In the United States, for example, Hib infections in children decreased 99 percent between 1990 and 2000.
The percentage of infections caused by nonencapsulated H. influenzae (NTHi) has risen markedly since the introduction of the Hib vaccine. NTHi strains are present in the nasopharynx of 80 percent of the adult population. Because the strains lack capsules, they are not affected by the vaccines that target capsular antigens. Migration of the NTHi bacteria from the nasopharynx can lead to otitis media (middle-ear infection), sinusitis, bronchitis, and pneumonia. Many of these infections are self-limiting because the immune system recognizes nonencapsulated strains more readily than those that are encapsulated. NTHi can also lead, more rarely, to disseminated systemic disease. Smoking, viral infections, chronic lung disease, and immunodeficiency can make NTHi infections much more likely. In the mid-2020s, NTHi accounted for the majority of H. influenzae infections in the United States.
Ampicillin has been the drug of choice for treating H. influenzae, but many strains have developed resistance to the penicillin family of antibiotics. Chloramphenicol has also been used, but chloramphenicol resistance is also on the rise. Second—and third-generation cephalosporins, fluoroquinolones, and clarithromycin are good alternatives. In severe cases, the cyclosporine cefotaxime and ceftriaxone can be administered intravenously.
The COVID-19 pandemic of the early 2020s had a complex impact on H. influenzae infections that was subsequently studied by the medical community. While initially, and most likely due to public health measures that encouraged social isolation and reduced transmission, H. influenzae infections experienced a significant decline during the early years of the pandemic. Then, there was a large increase in H. influenzae once restrictions were lifted and in the subsequent years. The situation provided valuable insight into public health directives, social behavior, and infectious diseases.
H. ducreyi was first isolated in 1899. It is most commonly isolated from the urogenital mucosa of humans, the bacterium’s only natural host. Like most members of its genus, H. ducreyi is a fastidious bacterium that requires enriched chocolate agar for growth. Genetic testing of H. ducreyi has shown it to be genetically related (albeit distantly) to other Haemophilus spp. and even to other members of Pasteurellaceae, although it has nutritional requirements similar to other members of this family. Some bacteriologists have suggested that H. ducreyi be placed as a monotypic genus in its own family.
H. ducreyi infection leads to chancroid (soft chancre), a common sexually transmitted disease in less developed countries in tropical and subtropical regions. The disease causes ulceration of the genitalia and is endemic to sub-Saharan Africa, especially among men who have sex with sex workers, who are often reservoirs for H. ducreyi. H. ducreyi infection increases the likelihood of human immunodeficiency virus (HIV) transmission ten to one hundred times. Chancroid is uncommon in the United States, with the last major outbreak in the 1980s. Azithromycin is the drug of choice for treating H. ducreyi infections. Erythromycin, ciprofloxacin, and in severe cases, ceftriaxone are also used.
Other Haemophilus spp. that are commensal in humans only rarely cause opportunistic infections. H. haemolyticus, H. parahaemolyticus, and H. parainfluenzae are commonly found in the nasopharynx and oral cavities but are seen associated only with pharyngitis and other conditions in debilitated persons. It has been suggested that H. avium and H. agni be placed within other genera in the Pasteurellaceae family because they are genetically distant from all other Haemophilus spp. Other species, such as H. paracuniculus and H. parasuis, are somewhat genetically closer to the Haemophilus spp. that affect humans, but their taxonomy is under scientific review.
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