Post‑Measles Complications and Mortality in Children under Five Years in Low‑ and Middle‑Income Countries: A Narrative Review

Challenges in measles elimination

Measles, with a basic reproduction number (R₀) of 12–18 [20], requires ≥95% vaccination coverage for herd immunity [21, 22]. The Global Vaccine Action Plan (2011–2020) targeted measles elimination in five WHO regions by 2020 [23]. WHO strategies emphasize two‑dose measles‑containing vaccine (MCV) coverage ≥95%, strengthened surveillance, and supplementary immunization activities. Between 2000 and 2016, vaccination prevented an estimated 20.4 million deaths through the Measles & Rubella Initiative [24]. Post‑COVID, some countries, such as Colombia, have successfully addressed immunity gaps [25]. However, despite progress, elimination remains elusive in LMICs. The proportion of countries with measles incidence >5 cases per million rose from 38% (2000) to 70% (2016), but progress has since stalled [26]. Global MCV1 coverage has remained in the range of 83–86% since 2010, and MCV2 is approximately 76% [2]. Poor cold chains, delayed diagnosis, and inadequate case management continue to sustain transmission. Subnational coverage gaps create susceptible reservoirs [27]. Infants aged 6–12 months face the highest risk of measles infection due to waning maternally derived antibodies, with most infants lacking passive immunity by 9–12 months [28]. Cyclical epidemics occur every 2–5 years in high‑fertility LMICs [29, 30]. Countries including Albania, Cambodia, Venezuela, Germany, the United Kingdom, and Uzbekistan have lost elimination status due to population movements, civil unrest, declining coverage, or anti‑vaccine movements [31–34], demonstrating that sustained high coverage and surveillance are essential. Susceptible populations remain at elevated risk of PMCs, and this risk will persist until measles elimination is achieved.

Pockets of vulnerability and the maintenance of circulation

The drivers of measles vulnerability are closely associated with marginalized or disadvantaged populations. Poverty underlies multiple risk factors, including malnutrition, limited healthcare access, crowded living conditions, low vaccination rates, and low health literacy. Children from the poorest households face substantially elevated risks of both exposure to measles and severe outcomes when infected [35].

Geographic pockets of vulnerability frequently coincide with socioeconomic disadvantage, creating clusters where multiple risk factors converge. Migrant populations, internally displaced people, refugees, and marginalized ethnic or religious minorities frequently have reduced access to routine health services, including vaccination programs [36]. In December 2025, there were 239 million people who needed humanitarian assistance across the globe [7]. After this period, there was an increase in people facing war or a similar situation in early 2026, most of whom are from LMICs. Language barriers, discrimination, lack of documentation, and mistrust of health authorities further impede engagement with immunization services in these populations. MCV1 coverage in low‑income countries is as low as 66% [3]. Such risk factors interact synergistically to amplify vulnerability to measles and its outcomes, explaining persistent inequities in measles burden and the challenges of achieving elimination in many LMICs [37, 38].

Post‑measles complications: An understudied dimension

Current guidelines of most LMICs do not focus on PMCs or post‑measles care and follow‑up. While acute measles mortality has received substantial attention in public health discourse, the full spectrum of PMCs and their contribution to child morbidity and mortality warrants greater scrutiny. The prolonged immunosuppression following measles infection increases vulnerability to a wide range of pathogens for months to years after apparent recovery from acute infection [39, 40]. Table 1 summarizes most of the PMCs with their reported incidence rates along with the primary data references.

PMCs are defined here as clinical sequelae arising during or after acute measles that share a temporal and causal relationship with the infection. Acute complications (e.g., pneumonia, diarrhea, OM, and conjunctivitis) arise during or within 3 weeks of illness via direct viral cytopathic and early secondary bacterial superinfection. Subacute complications (e.g., ADEM) emerge after 3 weeks to 3 months after infection and commonly include immune‑mediated mechanisms. Finally, long‑term sequelae (notably SSPE and outcomes of immune amnesia) present after 3 months.

PMCs can affect up to 40% of patients, with particularly high rates among young children and those with malnutrition [51]. The occurrence of PMCs also depends on the pre‑existing health status of children and the strength of the public health system. Marked variability in complication frequencies across Table 1 stems from differences in cohort age structure, baseline nutritional status, healthcare access, study area, timelines, and clinical setting. Studies conducted in tertiary hospital settings are likely to over‑represent more severe presentations relative to community‑based estimates. Hence, these figures cannot be directly used to compare PMC incidence rates but give a broad understanding of their occurrence.

Measles‑associated mortality often occurs days to weeks after acute infection, mediated by secondary infections and nutritional deterioration rather than direct viral effects alone. This delayed mortality may be underestimated in surveillance systems that focus on deaths during the acute illness. Furthermore, long‑term sequelae, including impaired neurodevelopment and reduced educational attainment, may extend the societal impact of measles well beyond immediate health outcomes [52].

Immune compromise and post‑measles infections

The measles virus exhibits a strong tropism for immune cells that express the receptor SLAM/CD150, including memory T and B‑lymphocytes, dendritic cells, and subsets of monocytes/macrophages [53–55]. After initial replication in the respiratory epithelium and regional lymphoid tissue, infected lymphocytes disseminate the virus systemically, seeding lymphoid organs. During the acute rash phase, lymphocyte depletion can be profound, falling to as low as one‑seventh to one‑tenth of normal values [53, 55]. Studies also indicate that there is immune‑mediated clearance of MV‑infected CD45RA (‑) memory T‑lymphocytes and follicular B‑lymphocytes, causing immune amnesia [56]. Also, there may be a compromised function of dendritic cells and T‑helper 1 cell responses [57]. This systemic lymphopenia affects both naive and memory compartments and is accompanied by functional impairment of surviving T cells and antigen‑presenting cells, which together drive the characteristic immunosuppression of acute measles [58].

Beyond this transient lymphopenia, measles causes a deeper and longer‑lasting disruption of immunological memory that has been described as “immune amnesia” [59, 60]. Studies show that measles infection depletes pre‑existing memory B cells and contracts the diversity of the antibody repertoire directed against previously encountered pathogens, effectively erasing established humoral memory [61]. Measles can eliminate 11–73% of the host’s pre‑existing functional antibody repertoire, confirming that it directly depletes immunological memory rather than merely causing transient dysfunction [59]. Reconstitution of the B‑cell pool after recovery occurs primarily through new naïve B‑cell responses, meaning that the host must re‑establish immune protection against pathogens to which it was already immunologically primed [59, 61].

Transient immunosuppression and immune amnesia are distinct immunological consequences of measles virus tropism for Signaling Lymphocytic Activation Molecule SLAM‑expressing cells [53]. While peripheral lymphocyte counts typically normalize within a week, functional immunosuppression endures for weeks to months, driving immediate vulnerability to secondary bacterial complications like pneumonia and OM [53, 58]. In contrast, immune amnesia erodes pre‑existing humoral and cellular memory for 2–3 years [59, 60]. This prolonged deficit leaves children vulnerable to a wide array of previously encountered pathogens long after the resolution of acute lymphopenia [59, 61].

Epidemiological data show that excess mortality from infectious diseases remains elevated for 2–3 years after measles outbreaks, consistent with long‑term impairment of immunological memory [59, 60]. This state creates a permissive environment for bacterial invasion through several synergistic mechanisms. First, depletion and functional impairment of CD4+ and CD8+ T cells compromise macrophage activation, cytokine signaling, and cytotoxic responses, weakening control of both intracellular and extracellular bacterial pathogens [62]. Second, loss of antigen‑specific memory B cells and erosion of pre‑existing antibody repertoires reduce opsonizing and neutralizing antibodies against common bacterial agents, impairing clearance of common but serious pathogens that frequently cause post‑measles pneumonia, OM, and sepsis [53, 63]. Third, direct measles‑mediated damage to respiratory epithelium and mucosal barriers facilitates bacterial colonization, overgrowth, and translocation [47, 59]. Together, these immunological effects explain how measles infection chronically predisposes children to severe secondary bacterial infections and associated complications [53, 59–61].

Malnutrition and nutritional deficiencies

Measles and malnutrition have a lethal reciprocal interaction that results in a vicious cycle of illness and nutritional decline [63]. This bidirectional relationship is well‑documented: malnutrition predisposes children to severe measles, while measles infection is itself a significant contributor to the development and exacerbation of malnutrition [67].

Due to impaired T‑cell activity and mucosal immunity, malnourished children are particularly vulnerable to severe measles infection. Severe protein malnutrition causes thymic atrophy with reduced cell numbers and subsequently underdeveloped peripheral lymphoid organs, leading to long‑lasting immune defects characterized by leukopenia, a decreased CD4:CD8 ratio, and increased numbers of immature T cells [68]. These immunological impairments render malnourished children significantly more susceptible to measles and its complications. Malnutrition is a primary contributor to death in 45% of fatal measles cases [69].

Measles worsens malnutrition through multiple pathophysiological mechanisms [63]:

1. Decreased food intake (anorexia): Anorexia, nausea, and vomiting may be associated with electrolyte loss, imbalance, and dehydration during measles infection, directly compromising nutritional status during the acute phase of illness.

2. Malabsorption and gastrointestinal dysfunction: Acute measles infection causes significant gut malabsorption, particularly in the proximal small intestine. The measles virus can directly damage the intestinal lining, impair nutrient absorption, and cause substantial protein loss. Children who are undernourished and develop measles are especially at risk of severe malnutrition, including kwashiorkor, due to higher protein and energy needs during illness, reduced food intake, and ongoing gut losses [4]. Protein‑losing enteropathy is typically more severe and prolonged after measles, particularly when complicated by co‑infections such as Shigella and enterotoxigenic Escherichia coli [70].

3. Elevated metabolic demands: The febrile response and immune activation during measles significantly increase metabolic requirements [67]. A study in Nigeria found that severe metabolic demands during acute measles further deteriorated the condition of malnourished children, leading to weight loss, wasting, and reduced serum levels of essential amino acids [66].

4. Diarrheal disease: Measles‑associated diarrhea contributes significantly to malnutrition through reduction in food intake, decreased nutrient absorption, and increased catabolism of nutrient reserves. Studies measuring fecal α‑1 antitrypsin found that 87% of patients with shigellosis, 63% with enterotoxigenic E. coli, and 42% with rotavirus diarrhea experienced significant protein loss [71].

Neurological complications, including encephalitis

ADEM, occurring in approximately 1 in 1000 measles cases, is the most common neurological consequence linked to measles infection [44]. ADEM is an autoimmune disorder in which the immune system inadvertently targets the central nervous system’s (CNS) myelin sheath, causing acute demyelination [17]. Onset typically occurs 1–2 weeks after the acute rash and may present with encephalopathy, focal neurological deficits, seizures, and ataxia. In ADEM, no single confirmatory biomarker exists; diagnosis rests on a monophasic clinical presentation of acute encephalopathy with polyfocal neurological deficits, supported by MRI evidence of widespread, asymmetric, poorly demarcated white matter lesions on T2/FLAIR sequences. Cerebrospinal fluid (CSF) findings—mild pleocytosis and elevated protein—are non‑specific and must be interpreted alongside neuroimaging, as normal CSF does not exclude the diagnosis [75, 76]. Management is primarily supportive, with corticosteroids used in severe cases, although outcomes are variable [72].

SSPE is a rare but universally fatal late complication of measles, caused by persistent CNS infection with a defective, mutated measles virus [77]. Following acute measles, viral particles harboring mutations in the matrix (M) protein accumulate in neurons and glial cells, evading immune clearance and establishing a slowly progressive, destructive encephalitis [45]. Spread within the CNS occurs trans‑synaptically rather than via the bloodstream, explaining the insidious onset and the characteristically absent measles virus in CSF on standard testing.

SSPE progresses through four recognizable clinical stages: (I) subtle behavioral changes, personality alteration, and cognitive decline; (II) myoclonic jerks, deteriorating intellectual function, and characteristic periodic EEG complexes (Radermecker complexes); (III) rigidity, autonomic instability, and loss of purposeful movement; and (IV) a persistent vegetative state preceding death. The median latency from primary measles infection to clinical onset is 5–10 years, meaning that children infected in infancy may not present until school age or early adolescence [78]. Median survival from symptom onset is 1–3 years. Because standard CSF analysis does not detect measles virus, diagnosis relies on markedly elevated CSF measles antibody titers and characteristic EEG findings [45].

The risk of SSPE is strongly age‑dependent, with estimates in LMICs reaching 27.9 per 100,000 measles cases among children infected before the age of two [45]—far exceeding historical population‑level estimates of 1 per 100,000.

Ocular complications

Measles‑associated conjunctivitis is a prodromal phase symptom characterized by red, watery eyes, weeping, and mild photophobia [79]. It affects nearly all measles patients and is often a minor, self‑limiting inflammation that fades as the systemic infection progresses [80]. It serves as an important early diagnostic signal alongside coryza and cough [79]. Although the primary inflammation is viral, subsequent bacterial superinfection is possible, necessitating watchful eye care in children—particularly in high‑risk groups [81].

Keratitis, or corneal inflammation, is a more dangerous ocular consequence that can cause permanent vision impairment [80]. Measles keratitis can progress from superficial punctate erosions to profound corneal ulcers through direct viral destruction and secondary bacterial invasion [81]. Malnutrition, particularly vitamin A deficiency, significantly increases risk, predisposing to severe keratomalacia (corneal melting) [82]. Prompt diagnosis and high‑dose vitamin A supplementation are critical to prevent corneal scarring and blindness.

Measles remains a leading cause of childhood blindness, accounting for an estimated 15,000–60,000 new cases each year, the vast majority in low‑income countries. Visual loss is frequently caused by severe keratitis and corneal scarring (adherent leucoma) [82]. The combination of measles infection with pre‑existing vitamin A deficiency has a synergistic and destructive effect, accelerating corneal damage [77, 82]. In Tanzania, 37% of corneal ulcers in a hospital cohort of children were associated with recent measles infection [47]; in Nigeria, at least 42% of corneal scars in a pediatric survey were attributed to post‑measles ulceration [48].

Measles retinopathy—direct inflammation or injury to retinal tissue—can cause temporary or permanent vision loss, sometimes years after the initial infection [81]. Optic neuritis presents with acute eye pain and significant, usually transient, color blindness, and visual acuity impairment [80, 81]. Both conditions are rare but serious, necessitating prompt specialist evaluation.

Other rare complications

Beyond the common PMCs described above, several rare manifestations have been documented. Gastrointestinal involvement includes hepatitis with elevated transaminases and appendicitis with characteristic measles giant cells on histopathology. Neurological complications extend beyond ADEM to include viral meningitis and post‑infectious encephalomyelitis with immune‑mediated demyelination. The pantropic nature of the measles virus enables multisystem involvement, particularly among young children, adults over 20 years, pregnant women, and immunocompromised individuals [83].