Cholera: Causes, Transmission and Prevention | 霍乱的病因、传播与防治

📚 Cholera: Causes, Transmission and Prevention | 霍乱的病因、传播与防治

Cholera is an acute watery diarrhoeal infection caused by the bacterium Vibrio cholerae. Despite being easily treatable, it remains a major global health threat where water and sanitation systems are inadequate.

霍乱是由霍乱弧菌引起的一种急性水样腹泻性感染。尽管这种病容易治疗，但在水和卫生系统不完善的地区，它仍然是全球主要的健康威胁。

1. Pathogen: Vibrio cholerae | 病原体：霍乱弧菌

Vibrio cholerae is a Gram-negative, comma-shaped bacterium that possesses a single polar flagellum, making it extremely motile. It can survive in both freshwater and marine environments, as well as in the human small intestine.

霍乱弧菌是一种革兰氏阴性、逗号状细菌，具有一根极生鞭毛，运动能力极强。它既能在淡水和海洋环境中生存，也能在人体小肠中存活。

The pathogen produces a powerful protein exotoxin called cholera toxin (CT). This toxin is the central molecular weapon that transforms a mild colonising bacterium into a cause of potentially fatal diarrhoea.

该病原体产生一种强效的蛋白质外毒素，称为霍乱毒素（CT）。这种毒素是将一种轻微定植的细菌转变为潜在致命性腹泻“元凶”的核心分子武器。

Among the many serogroups of V. cholerae, only O1 and O139 are known to cause epidemic or pandemic cholera. O1 strains are further classified into the classical and El Tor biotypes, with El Tor currently being the dominant biotype worldwide.

在霍乱弧菌的众多血清群中，只有O1和O139已知会引起流行性或大流行性霍乱。O1株进一步分为古典生物型和埃尔托生物型，目前埃尔托生物型在全球占主导地位。

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2. Mechanism of Infection | 感染机制

When a person ingests contaminated water or food, V. cholerae must first survive the acidic environment of the stomach. A high infective dose (around 10⁸ cells) or reduced gastric acidity significantly increases the probability that bacteria will pass into the small intestine.

当人摄入受污染的水或食物时，霍乱弧菌首先必须抵抗胃内的酸性环境。高感染剂量（约10⁸个细菌）或胃酸减少会显著提高细菌进入小肠的概率。

In the small intestine, V. cholerae uses its flagellum and specialised adhesins, particularly toxin-coregulated pili (TCP), to attach tightly to the microvilli of intestinal epithelial cells. The bacteria do not invade the tissue; they remain on the mucosal surface and multiply there.

在小肠中，霍乱弧菌利用鞭毛和特化的粘附素，尤其是毒素共调菌毛（TCP），紧密附着于肠上皮细胞的微绒毛上。细菌并不侵入组织，而是停留在黏膜表面并在那里繁殖。

Once a sufficient population has established, the bacteria secrete cholera toxin. The toxin is an AB₅-type protein toxin: five B (binding) subunits form a ring that binds to the GM1 ganglioside receptor on the host cell membrane; the single A (active) subunit is then translocated into the host cell.

一旦细菌达到足够数量，便会分泌霍乱毒素。该毒素为AB₅型蛋白毒素：五个B（结合）亚基形成一个环，与宿主细胞膜上的GM1神经节苷脂受体结合；单个A（活性）亚基随后被转运进入宿主细胞。

Inside the intestinal epithelial cell, the A subunit catalyses the transfer of ADP-ribose from NAD⁺ to the regulatory G protein Gsα. This ADP-ribosylation permanently activates Gsα, which in turn continuously stimulates the enzyme adenylate cyclase.

在肠上皮细胞内，A亚基催化NAD⁺上的ADP-核糖转移至调节性G蛋白Gsα。这种ADP-核糖基化使Gsα永久性激活，后者又持续刺激腺苷酸环化酶。

The result is a dramatic increase in intracellular cyclic AMP (cAMP) levels. High cAMP activates protein kinase A (PKA), which phosphorylates the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel on the apical membrane of the cell.

结果是细胞内环磷酸腺苷（cAMP）水平急剧升高。高浓度的cAMP激活蛋白激酶A（PKA），PKA磷酸化细胞顶膜上的囊性纤维化跨膜传导调节因子（CFTR）氯离子通道。

Phosphorylated CFTR pumps chloride ions (Cl⁻) into the gut lumen. Sodium ions (Na⁺) follow through paracellular pathways to maintain electrical neutrality, and water moves out by osmosis. The net effect is massive secretion of isotonic fluid into the intestinal lumen.

磷酸化的CFTR将氯离子（Cl⁻）泵入肠腔。钠离子（Na⁺）通过细胞旁途径跟随以保持电中性，水则通过渗透作用流出。净效应是大量等渗液分泌到肠腔中。

In severe cholera, fluid loss can exceed 1 litre per hour. This explains the rapid onset of dehydration and electrolyte imbalance that can be fatal within hours if untreated.

在重症霍乱中，体液丢失每小时可超过1升。这解释了脱水和电解质紊乱为何会迅速发生，若不治疗可在数小时内致命。

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3. Transmission Routes | 传播途径

Cholera is transmitted primarily through the faecal-oral route. Infected individuals shed large numbers of V. cholerae in their faeces, and these bacteria can survive in water and on food surfaces for several days.

霍乱主要通过粪-口途径传播。感染者粪便中排出大量霍乱弧菌，这些细菌能在水中和食物表面存活数天。

• Contaminated drinking water: The most common vehicle in outbreaks. In communities without treated piped water or with broken sanitation, rivers, wells and water storage containers become contaminated.

  受污染饮用水：疫情期间最常见的传播媒介。在没有经过处理的自来水或卫生设施受损的社区，河水、井水和储水容器会被污染。

• Contaminated food: Eating raw or undercooked seafood, especially shellfish harvested from contaminated coastal waters, is a major risk. Vegetables and fruits washed with polluted water can also transmit the bacterium.

  受污染食物：食用生的或未煮熟的海鲜，尤其是来自受污染近海水域的贝类，是主要风险。用污染的水洗涤的蔬菜和水果也可能传播该菌。

• Person-to-person transmission: Direct faecal-oral spread can occur when hand hygiene is poor, such as among household contacts or in crowded camps. However, this route is less efficient than waterborne spread.

  人际传播：在卫生条件差的情况下，如家庭接触者之间或拥挤的营地中，直接粪-口传播可能发生。但这一途径不如水源传播有效。

The incubation period ranges from 12 hours to 5 days, which allows the disease to expand quickly within a community before the first cases are recognised.

潜伏期从12小时到5天不等，这使得疾病在社区内被识别之前就能迅速扩散。

Asymptomatic carriers and individuals with mild illness can also shed the bacteria, making outbreak control challenging.

无症状携带者和轻症患者也会排出细菌，使得疫情控制变得困难。

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4. Symptoms and Pathophysiology | 症状与病理生理

The hallmark of severe cholera is the painless, profuse ‘rice-water stool’: a pale, turbid fluid containing mucus flecks and intestinal epithelial cells, with no blood or pus. This stool resembles water in which rice has been washed.

重症霍乱的典型表现是无痛、大量的“米泔水样便”：一种淡黄色浑浊液体，含黏液片和肠上皮细胞，无血或脓。这种粪便像淘米水一样。

Rapid fluid loss leads to severe dehydration with characteristic signs: sunken eyes, wrinkled fingers, dry mucous membranes, poor skin turgor, intense thirst, low blood pressure and tachycardia.

快速体液丢失导致严重脱水，具有特征性体征：眼窝凹陷、手指起皱、黏膜干燥、皮肤弹性差、极度口渴、低血压和心动过速。

Electrolyte losses include Na⁺ (sodium), K⁺ (potassium), Cl⁻ (chloride) and HCO₃⁻ (bicarbonate). Hypokalaemia can cause muscle cramps, cardiac arrhythmias and paralytic ileus.

电解质丢失包括Na⁺、K⁺、Cl⁻和HCO₃⁻。低钾血症可导致肌肉痉挛、心律失常和麻痹性肠梗阻。

Loss of bicarbonate causes metabolic acidosis, which can lead to deep breathing as the body tries to compensate. Untreated hypovolaemic shock and acidosis soon result in renal failure and death.

碳酸氢盐丢失引起代谢性酸中毒，机体可通过深呼吸代偿。未治疗的低血容量性休克和酸中毒很快导致肾衰竭和死亡。

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5. Diagnosis and Detection | 诊断与检测

During a known outbreak, a clinical diagnosis based on severe watery diarrhoea and dehydration is usually sufficient. However, laboratory confirmation is needed to identify the exact serogroup and to monitor antimicrobial resistance.

在已知疫情期间，根据严重水样腹泻和脱水进行临床诊断通常足够。但需要实验室确认以确定精确的血清群并监测耐药性。

Stool samples can be examined by dark-field microscopy, where the characteristic darting movement of V. cholerae is visible. For culture, samples are plated on thiosulphate-citrate-bile salts-sucrose (TCBS) agar; V. cholerae produces yellow colonies because it ferments sucrose.

粪便样本可用暗视野显微镜检查，可看到霍乱弧菌特有的穿梭运动。进行培养时，样本接种于硫代硫酸盐-柠檬酸盐-胆盐-蔗糖（TCBS）琼脂上；霍乱弧菌因发酵蔗糖而呈现黄色菌落。

Rapid diagnostic tests (RDTs) based on immunochromatographic detection are available and useful in field settings, but they are not substitutes for PCR identification. PCR can detect toxin genes, while serotyping uses specific antisera to distinguish O1 and O139.

基于免疫层析的快速诊断测试可在现场使用，但不能替代PCR鉴定。PCR可检测毒素基因，而血清分型使用特异性抗血清区分O1和O139。

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6. Prevention and Control | 预防与控制

The cornerstone of cholera prevention is improving water, sanitation and hygiene (WASH). Safe disposal of faeces prevents environmental contamination, and treating water before consumption breaks the faecal-oral route.

预防霍乱的基石是改善水、卫生设施和个人卫生（WASH）。安全处置粪便可防止环境污染，饮用水在使用前处理可阻断粪-口途径。

Water treatment methods include boiling, chlorination, flocculation, filtration and exposure to sunlight in bottles. In emergencies, simple chlorine tablets can be highly effective.

水处理方法包括煮沸、加氯、絮凝、过滤以及用瓶子在阳光下暴晒。在紧急情况下，简单的氯片非常有效。

Hygiene practices such as thorough handwashing with soap after defecation and before handling food are essential and need to be promoted through community education.

个人卫生习惯如便后和接触食物前用肥皂彻底洗手至关重要，需要通过社区教育加以推广。

Food safety includes cooking fish and shellfish thoroughly, avoiding raw products in endemic areas, washing and peeling fruit and vegetables, and protecting food from flies.

食品安全包括彻底煮熟鱼类和贝类、避免在流行区食用生食、清洗并去皮果蔬以及防止食物被苍蝇接触。

Oral cholera vaccines (OCV) provide additional short-term protection. Dukoral (B subunit + killed whole cells), Shanchol and Euvichol (killed whole-cell vaccines) are prequalified by WHO and used in high-risk areas or reactive campaigns.

口服霍乱疫苗（OCV）可提供额外短期保护。Dukoral（B亚基+灭活全菌体）、Shanchol和Euvichol（灭活全菌体疫苗）均已获WHO预认证，用于高风险地区或反应性疫苗接种运动。

Vaccination is not a substitute for water and sanitation improvements, but it can reduce disease while infrastructure is being developed.

疫苗接种不能替代水和卫生设施的改善，但在基础设施发展期间可减少疾病发生。

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7. Treatment and Management | 治疗与管理

Rapid and correct rehydration is the most important lifesaving intervention. For mild and moderate dehydration, oral rehydration solution (ORS) containing glucose, sodium chloride, potassium chloride and trisodium citrate is recommended.

快速、正确的补液是最重要的救命措施。对于轻度和中度脱水，推荐使用含葡萄糖、氯化钠、氯化钾和枸橼酸三钠的口服补液盐（ORS）。

ORS works because glucose molecules and sodium ions are co-transported into the intestinal epithelial cell by the sodium-glucose cotransporter SGLT1. This transport remains functional even when cholera toxin is present, because it does not depend on CFTR.

ORS起作用的原因是葡萄糖分子和钠离子通过钠-葡萄糖共转运体SGLT1被共同转运进入肠上皮细胞。即使霍乱毒素存在时这种转运仍保持功能，因为它不依赖CFTR。

As sodium and glucose are absorbed into the cell, an osmotic gradient is established, allowing water to be reabsorbed from the gut lumen; chloride follows paracellularly to maintain charge and osmotic balance.

随着钠和葡萄糖被吸收进入细胞，形成渗透梯度，使水得以从肠腔重吸收；氯离子通过细胞旁途径跟随以维持电荷和渗透平衡。

Severe dehydration requires rapid intravenous replacement of fluids with Ringer’s lactate or normal saline. Total deficit may equal 10–15% of body weight in adults and needs to be replaced within 2–4 hours.

严重脱水需要快速静脉输注乳酸林格液或生理盐水。成人总丢失量可达体重的10–15%，需要在2–4小时内补充。

Antibiotics such as doxycycline or azithromycin reduce diarrhoea duration and bacterial shedding. They are indicated in severe cases but are never a substitute for rehydration. Zinc supplements (10–20 mg/day) reduce duration and severity in children.

多西环素或阿奇霉素等抗生素可缩短腹泻持续时间和减少排菌。它们适用于重症病例，但绝不能替代补液。儿童补充锌（每天10–20 mg）可缩短腹泻持续时间和减轻严重程度。

With proper treatment, the case fatality rate is below 1%, highlighting the importance of early access to care.

经过恰当治疗，病死率低于1%，凸显了早期获得医疗的重要性。

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8. Immunity and Vaccination | 免疫与疫苗

Infection with V. cholerae induces local mucosal immunity in the intestine, primarily secretory immunoglobulin A (sIgA) against the O-antigen lipopolysaccharide and cholera toxin. However, immunity is short-lived and reinfection can occur after several years.

感染霍乱弧菌可诱导肠道局部黏膜免疫，主要是针对O抗原脂多糖和霍乱毒素的分泌型免疫球蛋白A（sIgA）。然而，免疫持续时间短，数年后可再次感染。

Killed whole-cell vaccines elicit local sIgA responses without causing disease. They require two or three oral doses for high protection and provide immunity for about 2–3 years.

灭活全菌体疫苗可诱导局部sIgA反应而不引起疾病。它们需要2–3剂口服才能提供高保护力，免疫保护期约2–3年。

Live attenuated vaccines (e.g. CVD 103-HgR, marketed as Vaxchora) are also available in some countries. They mimic natural infection more closely and require only a single dose, but are not recommended for pregnant women or severely immunocompromised people.

减毒活疫苗（如CVD 103-HgR，市售名为Vaxchora）在一些国家也可使用。它们更接近自然感染，只需要单剂，但不建议孕妇或严重免疫低下者使用。

Vaccines are most effective when used as part of a comprehensive package: treating cases, improving sanitation, and promoting hygiene behaviour change.

疫苗作为综合措施的一部分使用效果最佳：包括病例治疗、改善卫生设施和推广卫生行为改变。

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9. Epidemiology and Global Burden | 流行病学与全球负担

Cholera remains endemic in over 50 countries, especially in sub-Saharan Africa, South Asia and the Caribbean. The World Health Organization reports that up to 4 million cases and 143

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