Microsporidial Keratoconjunctivitis

II-1. Association between climatic/meteorological factors and onset

The occurrence of this disease has been quantitatively shown — particularly by studies from India — to be strongly associated with hot, rainy climatic and meteorological conditions. Reddy et al. (2011), asking "Is microsporidial keratitis a seasonal infection in India?", reported that of 30 cases, 20 occurred during the monsoon (June–September), 6 in winter (October–January) and 4 in summer (February–May), with significantly more during the monsoon than in summer (66.3% vs 13.3%, p = 0.0004)^[23]. The skew toward the monsoon has been attributed in part to contamination of water (ditch water, standing water) by rainfall and to the increase in insect populations during the rainy season.

Das and Basu (2021) analysed more than 180,000 people in Hyderabad (2016–2019) and, for 84 cases of acute MKC, showed a clear temporal pattern: onset rose from the monsoon's start in June, peaked in September, and declined with the arrival of winter. Increases in humidity and wind speed, and above all in rainfall, contributed to a higher year-round prevalence, whereas rising surface ozone concentrations were, if anything, protective against infection^[24]. In a separate three-year cohort in southern India (2013–2015), the mean monthly prevalence was 0.05%, peaking in July–October (highest at 0.12% in September), with a very strong correlation with rainfall (r² = 0.87, P < 0.0001) and a strong correlation with humidity. A review (Sharma et al., 2011) likewise concluded that, although reliable prevalence data are scarce, prevalence is higher in the rainy season and is prominent in India and countries with similar climates^[3].

The mechanisms inferred from these findings are: (1) contamination of ditch water, standing water and soil with spores due to rainfall and flooding; (2) prolonged survival of environmental spores under high humidity; (3) increased opportunities for contact with mud and contaminated water, with injection of spores into the corneal epithelium via minor trauma; and (4) increased insect populations during the rainy season. In short, it is understood that the main route is not "heat and rain themselves" but the contamination of water and soil and the increased exposure opportunities that heavy rainfall brings.

II-2. Reports in Japan

2.1　Reporting status to date

In Japan, microsporidial infection has traditionally been rare; only sporadic cases of MSK in immunocompromised patients were reported in 2014^[25] and 2019^[26], and the 2022 case series is considered the first of the superficial form (MKC). In other words, clustering in healthy individuals is a phenomenon that has become apparent only very recently.

2.2　Two outbreaks in Nagasaki

Uematsu et al. (2023, BMC Infect Dis) reported a cluster in September 2022 among five healthy men (aged 28–36) on the same football team as the first outbreak in Japan, identifying Vittaforma corneae by PCR of corneal scrapings (with a sequence matching the Singapore outbreak strain)^[27].

Building on this, Mohamed, Uematsu et al. (2026, Microorganisms 14(3):587) reported a study integrating clinical, molecular and environmental analyses of a total of 16 people (healthy men, aged 17–36) across two outbreaks in Nagasaki (2022 and 2023)^[28]. A major feature was that, in addition to patients' ocular specimens, 16 soil samples and 11 water samples were collected from the relevant areas and analysed together. Both outbreaks occurred in summer, immediately preceded by heavy rain that had left the playing fields wet. PCR of the soil on which the players had trained detected the same V. corneae as in the corneal scrapings, providing direct molecular evidence linking the environmental reservoir (soil and water) to human infection. Patients presented with reduced best-corrected visual acuity, redness, discharge, pain, itching and foreign-body sensation. The study further found that both outbreaks occurred after a month that met (or exceeded) "a mean monthly temperature of 23°C, relative humidity of 70% and monthly precipitation of 200 mm," similar to the meteorological conditions of MKC onset in India^{[17, 29]}.

2.3　Outbreak in the Kanto region

Furthermore, at Japan Cornea Conference 2025, Kakisu et al. reported an MKC cluster within a single sports team in the Kanto region (8 patients, 8 eyes; seen July–September 2024)^[30]. Seven eyes showed conjunctival hyperemia with diffuse, scattered granular infiltrates in the corneal epithelium, and one eye showed multiple stromal infiltrates; PCR of corneal scrapings was performed in six cases and detected microsporidial DNA in all six. All cases improved within four weeks with corneal debridement and fluoroquinolone antibacterial eye drops, with no two-line loss of visual acuity. Although no environmental survey of soil or water was reported, the occurrence of a cluster among healthy athletes in Kanto — following Nagasaki (Kyushu) — supports the domestic geographical spread of the disease.

2.4　Global spread

Similar trends have been observed worldwide. In Israel, a multi-year outbreak due to V. corneae was reported around the Sea of Galilee in 2022–2024^[14], and in March 2026 an outbreak affecting more than 100 athletes was reported in Darwin, Australia (both due to V. corneae)^[31]. These suggest that water- and climate-related outbreaks of this disease are spreading geographically from the tropics and subtropics into the temperate zone.

II-3. Future Projections under Climate Change Scenarios — Analysis of JMA Data

The occurrence of this disease is strongly associated with heat, humidity, heavy rain and muddy conditions. Drawing on published data from the JMA and MEXT ("Climate Change Monitoring Report," "Climate Change in Japan 2025")^{[32, 33]}, we examine Japan's climate trends and the regions where outbreak risk may expand.

3.1　Japan's climate trends in JMA data (observed facts)

For temperature, Japan's annual mean temperature has been rising over the long term at a rate of about 1.4–1.44°C per century (the deviation from the 2025 baseline is +1.23°C), exceeding the global-mean rate of increase. Hot years have appeared frequently since the 1990s, with the record's highest rankings concentrated in the past decade or so. The annual numbers of extremely hot days (maximum ≥35°C) and tropical nights (minimum ≥25°C) have also increased, with tropical nights rising at roughly 18 days per century. Sea-surface temperatures in the seas around Japan have also risen at about 1.33–1.36°C per century, more than twice the global-mean rate^[33].

For precipitation, although there is no clear long-term trend in annual precipitation itself, the "way it rains" has become more extreme. The frequency of intense rainfall — hourly precipitation ≥80 mm, 3-hour precipitation ≥150 mm, daily precipitation ≥300 mm — has roughly doubled compared with around 1980, with higher rates of increase for heavier rain. The numbers of days with daily precipitation ≥100 mm and ≥200 mm have both increased, while the number of days with daily precipitation ≥1 mm has decreased, indicating a growing polarization ("more extreme when it rains, and more days without rain"). The annual maximum daily precipitation also shows an increasing trend. Furthermore, event-attribution analyses have shown that global warming raised the probability and intensity of heavy rain in events such as the July 2018 heavy rainfall, and that in the Setouchi region the probability of a "once in 50 years" 3-day precipitation event had become about 3.3 times higher^[33].

3.2　Future projections (2°C / 4°C scenarios, end of the 21st century)

"Climate Change in Japan 2025" makes projections under two scenarios: about 2°C warming above pre-industrial levels (RCP2.6) and about 4°C warming (RCP8.5). Japan's annual mean temperature is projected to rise by about 1.4–4.5°C by the end of this century, with the magnitude of increase not uniform across the country but larger at higher latitudes such as Hokkaido. Extremely hot days are projected to increase by up to about 18 days per year, and tropical nights by up to about 38 days. For precipitation, the frequency of short-duration heavy rain of ≥50 mm/hour is projected to increase by up to about 3.0-fold and the annual maximum daily precipitation by up to about 27%, while the number of days without rain also increases. Under the 4°C scenario, the frequency of heavy rain with daily precipitation ≥200 mm and ≥50 mm/hour increases in all regions and seasons of the country, reaching more than twice the level of the end of the 20th century on a national average, and more than 1.5 times even under the 2°C scenario. The early-summer (June) baiu rain band is projected to strengthen^[32].

3.3　Implications for MKC and region-level risk projection

This disease tends to occur when, in hot and humid summers, heavy rain and flooding leave playing fields muddy and waterlogged, people are exposed to soil and water through outdoor sports and the like, and V. corneae is present in the environment; the more these conditions overlap, the higher the risk^[28]. As JMA data show, the meteorological factors among these (heat and heavy rain) are intensifying nationwide, raising the underlying conditions for outbreaks across Japan as a whole. Taking regional differences into account, the following distribution is envisaged.

• Relatively high risk in the short-to-medium term: Kyushu, Okinawa and Amami (subtropical to warm-humid; frequent heavy rain from the baiu, typhoons and linear precipitation bands; large increases in sea-surface temperature); Shikoku and Setouchi (high temperatures and rising probability of "once in 50 years" heavy rain); and the Pacific side of Kinki, Tokai, the Kii Peninsula and Kanto. These combine heat and humidity, heavy rain and active outdoor sports.
• Northward and outward expansion of risk: Because the magnitude of warming is larger at higher latitudes and heavy rain increases nationwide, opportunities to meet the "hot summer + heavy rain" condition will increase in Kanto, Hokuriku, Koshin, Tohoku and even Hokkaido, and suitable areas for outbreaks are projected to spread northward and eastward over time. The possibility of cluster outbreaks rises even in regions previously regarded as "non-endemic."
• Localized urban risk: In major cities (Tokyo, Osaka, Nagoya, Fukuoka, etc.), the combination of heat-island warming and standing water during heavy rain may raise risk locally.

Currently relatively high High to rising Gradually rising Rising over the longer term

II-4. Discussion and Future Challenges

Reviewing the reports and research to date, the positioning of microsporidial keratoconjunctivitis is shifting from a "rare disease" to a "common differential that should be recognized," and in recent years its character as a "climate-sensitive infection," closely linked to climatic and meteorological conditions, has become clear^{[24, 28]}. The remaining challenges are as follows.

• Surveillance: In Japan and elsewhere, a monitoring system and case definitions are needed to grasp the disease's occurrence. Early detection of clusters after outdoor sports is key.
• Environmental surveys: The distribution and persistence conditions of V. corneae in the environment (soil, water, turf) and their relationship to meteorological factors (rainfall, temperature, humidity) need to be clarified.
• Diagnosis and treatment: Standardization of rapid, highly sensitive diagnosis (PCR, mNGS, non-invasive methods) and the establishment of treatment evidence through high-quality randomized controlled trials are required.
• Prevention and adaptation: Preventive education linked to climate-change adaptation is important — avoiding competition on muddy grounds after heavy rain, eye-rinsing and hygiene guidance, eye protection such as goggles, ground drainage and maintenance, and appropriate contact-lens use.

III-1. Analytical Framework — The Meteorological Threshold for Onset and Two Modes of Transmission

1.1　The meteorological threshold

As introduced in Part II (Chapter 2), the study analysing the two Nagasaki outbreaks (16 healthy athletes in total, 2022 and 2023) showed that outbreaks "tend to occur after a month in which the conditions of 23°C temperature, 70% humidity and 200 mm precipitation are met or exceeded."^[28] The authors note that heat, high humidity and heavy rain may promote the proliferation of microsporidia in soil and surface water, and state that there is a time lag between the meteorological event and detection of onset, arising from delayed exposure, the incubation period and the stepwise progression of case recognition. A month meeting these three conditions (mean monthly temperature ≥23°C, relative humidity ≥70%, monthly precipitation ≥200 mm) is termed a "high-suitability month" for that region.

1.2　Two modes of transmission (which govern the geographical spread)

Taking the reports as a whole, there are broadly two modes of transmission, and these determine the breadth of the geographical spread.

• The "wet field" type (wet field eye): A route via the soil and surface water of playing fields turned muddy by heavy rain. Typical of tropical-to-subtropical monsoon regions where heat, high humidity and heavy rain coincide, and of temperate-zone summers. The meteorological threshold above applies directly.
• The "water body" type: A route via specific contaminated water bodies such as hot springs, swimming pools, lakes, ponds and rivers (Taiwan's hot springs and pools, Israel's Sea of Galilee, etc.)^{[12, 13, 14]}. Because this type can occur wherever a warm, contaminated water body exists — even if the region's monthly precipitation does not reach the threshold — it extends risk to regions such as Mediterranean climates where "summers are hot but dry."

III-2. Global Climate Change Trends (Key Points from IPCC AR6)

The IPCC Sixth Assessment Report (AR6) states that heavy precipitation increases in frequency and intensity as warming progresses, and that in a 4°C-warmer world, rare heavy-rain events will become more frequent and intense than in the past across all continents and all AR6 regions (virtually certain)^[34]. In particular, monsoon precipitation is projected to increase globally over the medium-to-long term, most notably in South and Southeast Asia, East Asia and West Africa^{[34, 35]}. In South Asia, large increases in extreme precipitation are expected in southern India, Myanmar, Thailand, Malaysia and elsewhere^[35]. Humid heat (sultry conditions with high wet-bulb temperatures) is also assessed to become stronger and more frequent throughout the 21st century. In short, the heat, humidity and heavy rain that are the conditions for the "wet field" type of this disease are set both to intensify in existing endemic areas and to expand toward their (temperate-side) margins.

III-3. Global Regional / Country-level Outbreak Projections

Combining the fit to the meteorological threshold, opportunities for outdoor-sport and water exposure, and IPCC AR6 future trends, regions and countries are shown in three categories (relative priorities, not probabilities of occurrence).

High (endemic / suitable / meets threshold) Expanding / on alert / conditional Local / rising in future (water-body mode) Low (below threshold, within resolved countries)

III-4. Seasonality of Outbreaks (Monthly Risk Calendar)

For principal regions, relative outbreak risk is shown by month, based on the meteorological threshold (23°C, 70%, 200 mm)^[28] and known seasonality. Northern-Hemisphere regions rise in summer/rainy season (roughly June–September), while northern Australia (★) in the Southern Hemisphere peaks about half a year offset, in January–March. Because there is a lag between meteorological conditions and onset, actual cases may become apparent several weeks after each peak month.

Low / off-season Medium High Peak

III-5. Positioning the Darwin (Australia) Outbreak

The March 2026 cluster in Darwin is consistent with the framework of this report^[31]. The wet season in northern Australia (the Top End) is roughly November–April, and March falls at the end of the wet season — a time when the three conditions of heat, high humidity and heavy rain coincide. Australian-rules football, an outdoor sport on soil and turf, is thought to have generated exposure on the muddied ground. Similar conditions are common to the "high" category above (monsoon Asia, tropical Oceania), and outbreaks of the same kind may recur in these regions. Moreover, the Darwin case shows that the disease also emerges in the Southern-Hemisphere tropics, corroborating the expansion of suitable areas in both north and south directions under climate change.

III-6. Important Caveats for the Projection (Limitations)

III-7. Recommendations (Public Health and Clinical)

• Surveillance: In high-risk regions and periods (especially 4–8 weeks after heavy-rain events), establish systems to detect keratoconjunctivitis clusters in outdoor-sport groups early. Include this disease in the differential for keratoconjunctivitis that is culture-negative and unresponsive to standard treatment.
• Environmental surveys: In both endemic and emerging areas, investigate the presence of V. corneae in playing-field soil and surface water and in recreational warm water bodies (lakes, ponds, hot springs, pools), and its relationship to meteorological factors.
• Prevention and adaptation: In tandem with climate-change adaptation, promote avoiding competition on muddy grounds after heavy rain, eye-rinsing and hygiene after play, eye protection such as goggles, improved ground drainage, appropriate disinfection of pools and hot springs, and appropriate contact-lens use.
• Awareness: Use plain-language terms such as "wet field eye" to raise awareness among players, coaches, the public and clinicians.

III-8. Conclusion

Once regarded as a rare opportunistic infection centred on AIDS patients, microsporidial keratoconjunctivitis has, since the 2000s, been reported with rapidly increasing frequency as a cause of keratoconjunctivitis in immunocompetent individuals, centred on Asia, and its occurrence has been quantitatively shown to be strongly associated with heat and heavy rain. In Japan, two outbreaks were reported in Nagasaki in 2022 and 2023, and the same Vittaforma corneae was detected in patients' corneal specimens and in soil from the playing fields, demonstrating a direct link between the environmental reservoir and human infection^{[27, 28]}. According to JMA data, rising temperatures and increasing frequency and intensity of heavy rain are observed and projected in Japan, and the underlying conditions for this disease are being raised nationwide. By region, risk is relatively high in areas that are hot and humid with frequent heavy rain — Kyushu, Okinawa, Shikoku, Setouchi and Tokai — and, as warming progresses, suitable areas are expected to expand into Kanto, Tohoku and Hokkaido. However, this is a qualitative projection based on limited data, and strengthening of surveillance and environmental surveys is essential. In ophthalmic practice, an attitude of including this disease in the differential is required for keratoconjunctivitis/keratitis that is culture-negative and unresponsive to standard treatment, especially in cases with a history of outdoor sports after heavy rain.

Internationally as well, using the meteorological threshold identified by the Nagasaki study (mean monthly temperature 23°C, relative humidity 70%, monthly precipitation 200 mm)^[28] to gauge suitable areas, the monsoon belts of South and Southeast Asia and tropical Oceania are already high-risk, while in the United States the Southeast and Gulf Coast are the top priority. Climate change expands both the regions and the periods that meet this threshold, and is expected to spread outbreaks even into temperate areas previously regarded as "non-endemic." This disease merits cross-disciplinary attention — not only as an ophthalmic condition but as a "climate-sensitive infection" to be monitored under climate change.

III-9. References