Reemergence of Human Rabies in an Endemic Peruvian Amazon Region

ABSTRACT.

We report the case of two girls from a rural community in the Peruvian Amazon who were exposed to the rabies virus, with fatal outcomes in both cases. The reemergence of rabies in this endemic area after more than 11 years of successful control through massive immunization policies is highlighted in this report. In these cases, exposure occurred through contact with a domestic cat, although bat bites remain the most common source of rabies transmission in the region. Adopting a One Health approach and reinforcing periodic mass immunization campaigns are essential to prevent further outbreaks in endemic rabies zones.

INTRODUCTION

Rabies is a zoonotic viral disease caused by the rabies virus, a Lyssavirus of the family Rhabdoviridae. It is endemic in specific areas worldwide where infected wild mammals act as reservoirs and sources of transmission.^1,2 Peru has reported outbreaks of urban and sylvatic rabies in specific regions during the last decade. In the Amazonas region, sylvatic rabies outbreaks have mainly been reported in indigenous rural communities and are primarily associated with bat bites; however, no human rabies cases had been reported since 2013.^3,4 This absence of cases was likely related to the implementation of a rabies pre-exposure vaccination policy targeting indigenous communities that has been in place since 2011.^5,6 Despite this vaccination policy, epizootics have been reported in the region during subsequent years.⁷ In this report, we describe a recent human rabies outbreak in the Amazonas region after more than 11 years without reported cases in an area with endemic reservoirs (including vampire and non-vampire bats)⁸ and ongoing epizootics.

CASE REPORTS

Case 1.

An 8-year-old girl from the “Nueva Esperanza” hamlet in the Nieva District, Condorcanqui Province, Amazonas (Peruvian Amazon region; Figure 1), presented with a bite from a domestic cat on her right hand, with significant local signs of pain, erythema, and edema. Four days later, the patient experienced mild myalgia in her lower limbs, headache, fever, vomiting, and photophobia, which developed 12 days after the bite. By day 15, her symptoms had worsened, including altered mental status, visual hallucinations, sialorrha, and asthenia, prompting admission to a regional hospital in Bagua, Amazonas. She was treated for acute meningoencephalitis with ceftriaxone, vancomycin, and dexamethasone but deteriorated neurologically, leading to her referral to a hospital in Lima. During the transfer, she required intubation because of a significant decrease in her Glasgow Coma Scale (GCS) score. At admission (18 days post-bite), she was placed on mechanical ventilation and sedation (Figure 2).

Figure 1.

Distribution of human rabies cases in the Amazonas region from 2000 to 2024. Outbreaks of human rabies in Peru are primarily concentrated in the tropical regions of the jungle, where poverty, inadequate hygiene, and insufficient sanitation services intersect.

Figure 2.

History of reemergent rabies cases in Amazonas, Peru, in 2024. Comparative chronology of clinical events: Cases 1 and 2 exhibited incubation periods of ∼2 and 3 weeks, respectively, before the onset of neurological symptoms.

The patient’s clinical status showed a trend toward hypotension (blood pressure: 80/60 millimeters of mercury; heart rate: 103 beats per minute; respiratory rate: 25 breaths per minute; oxygen saturation: 97%; and GCS: 10/15), with meningeal signs (nuchal rigidity and Brudzinski’s sign).

Upon admission, laboratory tests revealed a marked elevation in liver enzymes, with an aspartate aminotransferase level of 382 U/L (reference range: 10–50 U/L) and an alanine aminotransferase level of 458 U/L (reference range: 10–40 U/L), both nearly 10 times the upper limit. A hematological analysis revealed a hemoglobin level of 11.24 g/dL (reference range: 11.5–14.5 g/dL) and a leukocyte count of 16,150 cells/µL (reference range: 5,000–13,000 cells/µL), with notable lymphopenia (484 cells/µL, reference range: 1,500–7,000 cells/µL). The international normalized ratio was 1.23 (reference range: 0.8–1.2). Renal function remained within normal limits, with a serum creatinine level of 0.67 mg/dL (reference range: 0.3–0.7 mg/dL). Serological test results for Treponema pallidum, hepatitis B virus, hepatitis C virus, HIV, and human T-lymphotropic virus types 1 and 2 were negative.

A brain computed tomography scan revealed generalized brain edema without structural or focal abnormalities. A cerebrospinal fluid (CSF) analysis revealed pleocytosis (70 white blood cells [WBC]; 97% lymphomononuclear), hyperproteinorrachia (185 mg/dL), and normal glucose levels. BioFire FilmArray Meningitis/Encephalitis panel (BioFire Diagnostics, Salt Lake City, UT) and Xpert MTB/RIF Ultra assay (Cepheid, Sunnyvale, CA) results were negative.

The patient was treated with antimicrobial therapy for acute meningitis using meropenem, vancomycin, ampicillin and doxycycline. On the fourth day of admission, she received human rabies immunoglobulin (4 mL) and a rabies vaccine. Despite these interventions, she experienced clinical deterioration, including multiple-organ failure (cardiogenic shock and renal, hepatic, and neurological impairment), requiring inotropic support with dobutamine. She died on the ninth day of admission. A postmortem brain analysis confirmed the rabies diagnosis through direct fluorescence antibody (DFA) testing, with histopathological findings including Babes nodules, edema, necrosis, perivascular cuffing, and Negri bodies in infected neurons (Figure 3).

Figure 3.

Histopathological findings in hematoxylin and eosin-stained CNS tissue from the necropsy of Case 1. (A) Brain tissue with edema and necrosis with perivascular cuffing or inflammation around a blood vessel and perivascular inflammatory cell infiltrates (200× magnification). (B) Babes nodules (red circles; aggregates of glial cells; 400× magnification). (C–F) Negri bodies in infected neurons of different areas of the brain (red arrows; 1,000× magnification). (C) Hippocampal sulcus in the temporal extension of the lateral ventricle (Ammon’s horn). (D) Medulla oblongata. (E and F) Cerebellum.

Case 2.

The second patient was a 9-year-old girl from the same community as the patient in Case 1. She was bitten on the knee by the same domestic cat. Her symptoms began 21 days post-bite, with general malaise, vomiting, epigastric pain, headache, fever, and seizures. On day 23, she was admitted to a regional hospital (Nieva) and treated for presumptive typhoid fever. After discharge, her symptoms worsened, including neurological symptoms such as severe headache, dizziness, aerophobia, lower limb weakness, a confused state, and death on day 28 post-bite. Saliva, hair follicle, and CSF samples tested positive for rabies via DFA testing.

The cat responsible for the bites was reported as a wild feline with proximity to human dwellings that died the same week. Both patients lacked a history of previous rabies immunization.

DISCUSSION

The reemergence of human rabies in the Amazonas region after 11 years is concerning. Between 2000 and 2013, 74 cases were reported in this region, 28 of which occurred in the Nieva District, with the remainder occurring in nearby localities (Figure 1).^3,4 Both patients presented with features of encephalitis, preceded by prodromal symptoms, such as myalgia and headache. Rapid neurological deterioration, including decreased GCS scores, and eventual death were observed in both cases. Clinical manifestations in pediatric cases typically include acute and fatal meningoencephalitis (furious rabies), with rapid progression to multiple-organ failure in some cases.^9–11

The absence of human rabies cases after 2013 was likely due to a successful mass immunization strategy initiated in 2011, which provided high coverage and population protection.^5,6 However, rabies epizootics persisted in the region, where the lifetime risk of bat bites among indigenous populations ranges from 41% to 88%.⁵ Rabies control efforts in South America have historically been focused on urban rabies through canine vaccination campaigns initiated in 1983, resulting in most of the continent being declared canine rabies-free, except for regions in Bolivia, Peru, and Brazil.¹² The control of sylvatic rabies has been less effective because of the complexity of wildlife reservoirs, although pre-exposure rabies prophylaxis has shown promise.^2,5

In Brazilian Amazon areas, the emergence of sylvatic rabies has been attributed to weakened prevention resources during the coronavirus disease 2019 pandemic, a pattern mirrored in Arequipa, Peru, where urban rabies cases increased.^13–15 Maintaining pre-exposure prophylaxis in high-risk areas like the Amazonas region is crucial to preventing outbreaks, particularly in regions where animal reservoirs are difficult to control. In both reported cases, the absence of pre-exposure rabies immunization, coupled with diminished immunization efforts, likely facilitated the reemergence of human rabies.

CONCLUSION

This outbreak underscores the importance of sustained rabies immunization coverage in endemic regions, as well as the need for the vigilant surveillance and reporting of febrile neurological syndromes to facilitate early detection and intervention in rabies cases.