In the city of São Paulo, Brazil, two children, one a 7-month-old boy and one a 6-year-old boy, were hospitalized with invasive meningococcal disease (IMD) caused by the rare bacteria Neisseria meningitidis serogroup X (MenX). The unconnected cases occurred in November 2021 and January 2022 and were described in a research letter published in Emerging Infectious Diseases, the journal of the US Centers for Disease Control and Prevention (CDC), in September. There is currently no licensed vaccine against serogroup X.
"Serogroup X is rare outside of Africa. In Brazil, only six cases had been reported in the last 15 years. Now, we have two cases in 2 months," Ana Paula S. Lemos, MD, PhD, told Medscape Medical News. She is a medical microbiology researcher specializing in the epidemiologic study of bacterial meningitides at the Adolfo Lutz Institute, and she is one of the letter's authors.
"Meningococcal disease is peculiar because, although rare, it is unpredictable and occurs suddenly, causing great panic when it does emerge. It most often occurs in previously healthy individuals, the majority of whom are children," Marco Aurélio Sáfadi, MD, PhD, professor of pediatrics and infectious diseases at the São Paulo Holy House Hospital School of Medical Sciences, explained. He was not one of the letter's authors.
Sáfadi believes that cases of MenX are cause for concern. However, he doesn't believe there is cause to worry specifically about serogroup X right now. "The concern is with the other [serogroups], which are more common. Serogroup X is just another player that may become the cause of potential disease among us."
Lemos, on the other hand, believes this is the time to pay attention to these cases and that we need to be aware of and closely monitor them "like we do for the ongoing cases, we have to launch a preventive intervention."
Serogroup X is extremely rare outside of Africa. Even in Africa, there were few recorded cases of the disease caused by this serogroup until the 1980s. Since 1990, MenX has been associated with outbreaks and epidemics in Burkina Faso, Togo, Niger, Kenya, and Uganda. In 2006 and 2007, some African countries experienced an explosion of serogroup X cases.
Cases of MenX infection have also been reported in Europe. "It is so rare that if you search for it in literature, you will find two studies describing just a few cases, and these are always connected with isolated cases in Africa," said Lemos.
In Brazil, there had been six cases in the previous 15 years. Therefore, the emergence of two cases within such a short period deserves follow-up. "It may be that these are just two isolated cases, and that's it," Lemos stated. "But we must be alert, because different serogroups behave distinctly. We have to keep an eye on it," she added.
The team at the Adolfo Lutz Institute quickly sought to unearth the history of serogroup X in Brazil. The researchers reevaluated a set of isolated cases with samples from the past 30 years using new gene analysis technologies. The research group identified seven isolated cases of N meningitidis serogroup X. Their results have not yet been published.
"In the retrospective study, it was observed that this lineage had been in circulation since at least 2013. This is important. So, we can tell that these were not the first cases. [Subgroup X] was already in circulation," said the researcher.
Vaccines are extremely effective in preventing meningococcal disease, but no vaccine covers all meningococcal serogroups. In general, vaccines provide protection against the specific serogroup included in the immunization agent.
A pentavalent vaccine that includes serogroup X (NmCV-5) is under development, but the study is still in phase 2. According to Lemos, studies that included 376 children aged 12 to 16 months showed there was a good response against serogroup X.
"Even if we had a serogroup X vaccine today, the epidemiological situation would not justify its use on a national level," she added.
Lemos pointed out that a study assessed whether the serogroup B vaccine could be effective against serogroup X. "It was a directed study. However, a study must be conducted using the lineage in circulation [now] to see if [the immunization agent used against serogroup B] would be beneficial or not," she explained.
The Brazilian National Immunization Program has offered a meningococcal C vaccine since 2010. This immunization program resulted in a significant reduction in the number of cases attributed to meningococcal C among children. Currently, "the cases basically occur in adults or children who are too young to get vaccinated," said Sáfadi.
The vaccine for serogroups ACWY, which provides protection against additional meningococcal serogroups, is offered through the Brazilian public health system to the adolescent population. Nevertheless, Sáfadi emphasized that the serogroup that circulates significantly in Brazil and is the leading cause of meningococcal disease in the country is serogroup B. The vaccine for this serogroup is only available through the private healthcare system.
More Cases Coming?
There is no way to know whether new cases will emerge. However, given the fact the COVID-19 pandemic has caused an interruption in the mandatory use of masks and other nonpharmacologic measures to control SARS-CoV-2 transmission, a resurgence in cases of IMD is likely.
"In Brazil, we went from recording approximately 1000 cases of meningococcal disease in 2019 to only 200 cases in 2021. This was a global phenomenon," Lemos stated. She was involved in a study that included Brazil and 25 other countries, the results of which revealed a drop in IMD rates caused by Streptococcus pneumoniae, Haemophilus influenzae, and N meningitidis during the pandemic.
"We can assume we will now see a resurgence of the disease, as it is transmitted person to person via the respiratory route," Sáfadi predicted. He also pointed out an exacerbating factor: the decrease in vaccine coverage rates in general, and of the meningococcal vaccine in particular. "Our [vaccination] rates among adolescents are very low."
Moreover, an immunologic window was created among the population. This refers to the population's lack of exposure to these meningococcal strains that used to remain in the throat and induce antibodies, which helped to prevent meningococcal disease. "With this lack of circulation during the COVID-19 pandemic, we accumulated a larger population of people susceptible to these diseases," said Sáfadi.
The mortality rate of IMD is between 10% and 20%. There is no difference in the clinical profiles associated with infection caused by the different serogroups except serogroup W, for which the mortality rate is 25%. Approximately 1 in 5 patients with IMD die, even after receiving appropriate treatment. Among those who survive, a significant percentage experience neurologic sequelae or limb amputation.
According to the authors of the research letter published in Emerging Infectious Diseases, ongoing surveillance of IMD, as well as new surveillance initiatives in some regions, are needed to ensure a successful public health response in terms of both prevention and control.
Sáfadi and Lemos have disclosed no relevant financial relationships.
Roxana Tabakman is a biologist, freelance reporter, and writer who resides in São Paulo, Brazil. She is the author of the books A Saúde na Mídia, Medicina para Jornalistas, Jornalismo para Médicos (in Portuguese), and Biovigilados (in Spanish). Follow her on Twitter: @roxanatabakman.
This article was translated from the Medscape Portuguese edition.
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Cite this: Brazil Records Two Cases of Invasive Meningococcal X Disease - Medscape - Oct 03, 2022.