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Village-wide antibiotic prophylaxis reduces meningitis cases in epidemic
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During a recent epidemic of meningococcal meningitis in the heart of Africa’s meningitis belt, researchers found that village-wide distribution of ciprofloxacin reduced the overall attack rate by 60%, suggesting that antibiotic chemoprophylaxis — not currently recommended during epidemics — may be beneficial in this setting.
The researchers conducted a three-arm study during an outbreak of Neisseria meningitidis serogroup C (NmC) in rural southern Niger, comparing the effect of ciprofloxacin chemoprophylaxis given to household contacts or entire villages with the standard of care, which is no preventive antibiotics.
According to Matthew E. Coldiron, MD, MPH, medical epidemiologist at Epicentre, a Doctors Without Borders epidemiology program, and colleagues, chemoprophylaxis of close contacts of meningitis cases has long been standard care in high-resource settings. WHO recommends it for household contacts during nonepidemic periods but not during epidemics, saying there is a lack of evidence that it works.
Writing in PLoS Medicine, Coldiron and colleagues said epidemiologic features of the meningitis belt mean that “focusing only on households might not change the course of an epidemic.”
“After the emergence of NmC, and in the presence of an insufficient quantity of vaccine against this serogroup, a WHO expert panel recommended a trial of antibiotic prophylaxis with ciprofloxacin for household contacts of meningitis cases during an outbreak in the meningitis belt,” they wrote. “The objective of our study was thus to evaluate the effect of ciprofloxacin prophylaxis on overall meningitis attack rates (ARs).”
Coldiron and colleagues assigned three villages that reported a suspected case of meningitis to no antibiotic prophylaxis (control), single-dose oral ciprofloxacin for household contacts within 24 hours of case notification or village-wide distribution of ciprofloxacin within 72 hours of first case notification.
Between April 22 and May 18, 2017, the researchers said they enrolled 49 villages in the study — 17 in the control arm, 17 in the household prophylaxis arm and 15 where village-wide prophylaxis was given. They recorded a total of 297 meningitis cases among the villages, including 49 index cases and 248 subsequent infections.
According to Coldiron and colleagues, the adjusted AR ratio between the household prophylaxis arm and the control arm was 0.94 (95% CI, 0.52-1.73; P = .85) — showing no statistical difference in the methods, they said. But the adjusted AR ratio between the village-wide prophylaxis arm and control was 0.40 (95% CI, 0.19-0.87; P = .022).
“These results suggest that chemoprophylaxis is a promising epidemic response strategy, particularly given the shortage of available vaccines in the foreseeable future and the delays and logistical burden inherent with reactive vaccination campaigns,” Coldiron and colleagues wrote.
The results mirrored recently published findings from a study showing that mass dosing with azithromycin reduced child mortality in three sub-Saharan countries. In that study, the greatest effect was seen in Niger, which has one of the highest child mortality rates in the world.
There are questions about the impact that such strategies will have on antibiotic resistance. In a perspective commenting on the findings by Coldiron and colleagues, two experts from the Bill & Melinda Gates Foundation noted the benefit of mass prophylaxis in both studies but said the results “must be balanced against the impact on resistance.”
“These two trials of village-wide antibiotic prophylaxis suggest a major role for targeted mass single-dose antibiotic prophylaxis programs, at least in the short term,” Keith P. Klugman, MD, PhD, director of the foundation’s pneumonia program, and Rasa Izadnegahdar, MD, MPH, deputy director of the global health program, wrote. “Such a strategy would be beneficial in high-mortality, high-disease-burden settings such as Niger until a multivalent conjugate vaccine that is protective beyond serogroup A meningitis is available and [the annual reduction in mortality rate for children aged younger than 5 years] is reduced to lower than 90 deaths per 1,000 live births.
"Single-dose antimicrobial prophylaxis may have profound effects in the meningitis belt, which includes some of the poorest countries in sub-Saharan Africa — the long-term cost-to-benefit ratio in these communities should determine the way the antimicrobials are used.” – by Gerard Gallagher
Disclosures: Coldiron, Izadnegahdar and Klugman report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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