Pappataci Fever

PAPPATACI FEVER (synonyms: three-day fever, phlebotomus fever, summer fever, climatic fever, mosquito fever, sandfly fever, summer flu, malarial influenza, Bukhara influenza, sartian fever, Trebizond "hava", dog disease, endemic gastroenteritis, climatic gastroenteritis, gastric catarrh, Pick's disease) is an acute infectious disease that appears in certain countries only during the hot season, accompanied by a short-term (about three days) fever, causing severe general malaise, but always having a benign character. The as-yet-unknown pathogen—a filterable microbe—is transmitted by the sandfly (see) Phlebotomus papatasii; the name of the disease is derived from this vector (pappataci comes from the Italian words pappa—bites, tace—silently)—this is what they called the sandfly Phlebotomus papatasii, which usually "bites silently." History. Pappataci fever has been known for a long time under various names. In 1804, Pym (Ruth) described a "three-day fever" on the Mediterranean coast. In 1874–75, Cicoli described a "summer fever" in Pola (Istria), clinically similar to pappataci fever. In 1886, A. Pick in Herzegovina was the first to recognize pappataci fever as an independent infectious disease with characteristic clinical manifestations. In 1904, Taussig noted the coincidence of the disease with the appearance of sandflies (Phl. papatasii), which are found in hot months in low-lying areas and are absent in highlands; he was the first to consider sandflies the spreaders of this disease. In 1908, a special commission consisting of Doerr (bacteriologist, experimental part), Franz (clinical part), and Taussig (epidemiology and spread of the disease) specifically studied the etiology, clinical picture, and epidemiology of the three-day fever common in Herzegovina and Dalmatia and for the first time introduced the name "pappataci fever" into scientific medical literature. In 1908–09, Doerr first succeeded in experimentally transmitting the infection from patients to healthy individuals by injecting blood or filtered blood serum taken from patients. He was also the first to succeed in transmitting the infection via the phlebotomus. These experiments made it possible to establish the etiological character and epidemiological features of pappataci fever. Etiology. The pathogen of pappataci fever is unknown. Spirochetes (Whittingham) or rickettsia-like organisms found in the intestine of the female phlebotomus (Schilling) were described as the pathogen, but these findings were not confirmed. Work on searching for the pathogen in feces, urine, sputum, and vomitus yielded negative results. The pathogen is found in the circulating blood in the first 24 hours from the onset of the disease. 40 hours after the onset of the fever, the blood (serum) permanently loses its virulence. After passing through Berkefeld, Reichel, and Chamberland filters (but not through a Pasteur-Chamberland candle), the serum of patients retains its virulence and, when administered subcutaneously to healthy susceptible people, causes a typical disease in them after an incubation period of about 5 days. To cause the disease via subcutaneous injection, 0.001 cm³ of fresh virulent serum is sufficient; larger amounts of blood and serum (1–3 cm³) do not increase the severity of the disease (Doerr). According to Lepine, virulent serum completely loses its virulence after heating at 55° for 10 minutes; according to Doerr, at room temperature, the serum retains infectivity for up to 3.5 days. Injection of virulent blood or serum into various laboratory animals (guinea pig, rabbit, rats, dog) remains ineffective (Birt, Doerr, and others); it is also impossible to cause the disease in animals via sandflies (Lepine). Some authors still assume that animals contract pappataci fever and can be carriers of the virus (Brack). There are immune bodies in the blood of a recovering patient. Doerr and Russ mixed 1 cm³ of immune serum with the virulent serum of a patient (0.5 cm³) and, after leaving it for 4 hours, injected it into a healthy susceptible person; the serum was found to have lost its virulence. Since phlebotomi die in the autumn, and relapses of the disease in winter and spring before the appearance of phlebotomi are not observed, it is not clear where and how the virus is preserved during the time free from sandflies. Doerr and Russ assumed that the virus passes from the infected female through the egg to the larva, hibernates in it, and is then transmitted to the adult insect during further development. Whittingham and Rook took infected phlebotomi from Malta to London, where they obtained eggs and the full development of the insects. By the bites of the new generation obtained there, they caused the disease. On the question of the overwintering of the virus in the larva and transmission to offspring, however, there is still much that is unclear and controversial. According to Newstead, in addition to Phl. papatasii, other species of phlebotomi can be carriers of pappataci fever, primarily Phl. perniciosus. Phl. minutus, Phl. molestus, Phl. nigerrimus, Phl. rostrans, and Phl. malabaricus are also blamed. Distribution. The spread of pappataci fever coincides with the place of distribution and the time of appearance of phlebotomi, predominantly Phlebotomus papatasii Scopoli. Pappataci fever is common in countries with tropical and subtropical, as well as temperate climates; endemic foci are lowlands and river valleys and sea coasts. Taussig in Dalmatia and Herzegovina notes affected places up to 420 m above sea level; according to the author's data, endemic places usually do not exceed 450 m. Other authors note even higher areas affected by pappataci fever: Jerusalem (780 m), Angora (1,000 m), etc. In the USSR, Kandelaki noted the spread of pappataci fever at an altitude of 800 m (Borjomi in the Georgian SSR). It is not always the case that where there are phlebotomi, pappataci fever is common; there are places "with phlebotomi without phlebotomus fever" (Phlebotomen ohne Phlebotomenfieber). Obviously, there is a whole range of unknown local factors on which the spread of pappataci fever depends. Phlebotomi appear in the summer months; depending on local meteorological and other conditions, the period of their distribution lasts in subtropical countries and in countries with a temperate climate from May or June to September or October. In hot countries (India, Egypt, etc.), phlebotomi appear earlier (April) and disappear later. At the same time, the appearance of phlebotomi always precedes the appearance of pappataci fever. In the USSR, the time of distribution of phlebotomi and pappataci fever is noted: for Transcaucasia—from June to September, for Central Asia—from May to September, for Crimea—from June to October. In Persia, an epidemic of pappataci fever appears from May. During the World War in 1917 in Trebizond (Turkey), an epidemic of pappataci fever appeared in the first half of June, gradually increased, reached its peak in July–August, and disappeared in October. In the same locality, the time of appearance and disappearance of the pappataci fever epidemic fluctuates depending on local meteorological and other external conditions; hot days contribute to the early appearance of the epidemic; cold, rainy, windy days push back the time of the epidemic's appearance, weaken it, and even interrupt it. In Tiflis, during a cold and rainy spring, the appearance of the phlebotomus and pappataci fever is delayed by several weeks. At the beginning of the epidemic, the clinical course of pappataci fever is usually milder, abortive, then by the height of the epidemic it becomes more severe. In the same locality, the pappataci fever epidemic does not proceed with the same intensity every year; there are years with a strong epidemic and, conversely, years when the pappataci fever epidemic proceeds quietly, imperceptibly, or is almost absent. In endemic places, the intensity of the spread of pappataci fever is associated with specific districts, sections, streets, houses, and even rooms. Residents of the lower floors of houses are more affected than those of the upper floors. Such selective spread of pappataci fever largely depends on the biological characteristics of the sandflies (proximity of breeding sites for sandflies, sanitary condition of houses and surrounding areas, ventilation of rooms), as well as on the susceptibility of the population. Everyone contracts pappataci fever, regardless of age, sex, and racial affiliation. Only a small percentage of natural immunity is observed. In endemic places, almost exclusively newcomers and children get sick. The local population, having been ill in childhood, has immunity. During the World War on the Caucasian Front, arriving military units and newcomers in general fell ill, while the local population remained healthy. For the army, pappataci fever deserves special attention. Although the disease does not last long and ends well, having a severe course, it leaves general weakness and inability to work for weeks. A large number of people fall ill at once, and up to 20–25% of the personnel are out of action for several weeks. Once contracted, the disease leaves immunity. A repeated illness in the same year or in a subsequent one is an exception. Geographic distribution of pappataci fever.

Besides Herzegovina and Dalmatia, where Pappataci fever was first described under this name, its distribution has been noted in many places adjacent to the Mediterranean Sea; it is found in Spain, Portugal, southern France and Italy, on the islands of Malta, Corsica, Sicily and Sardinia, in Greece, Bulgaria, Turkey, Persia, Syria, Mesopotamia, the East Indies, Egypt, India, on the island of Ceylon, in China, and in some parts of America and Australia. In the USSR, Pappataci fever is widespread in Transcaucasia, Crimea, and Central Asia. In the USSR, Pappataci fever first attracted special attention since the time of the World War, when on the Caucasian front in many garrisons, military units fell ill almost entirely with three-day fever, the identity of which with Pappataci fever was proven by Kandelaki and Martsinovsky. Among the military units of the Caucasian front, Pappataci fever proved to be widespread along the shores of the Black Sea (Trebizond, Platana), the Caspian Sea (Enzeli), as well as in Shakhtakhty, Kermanshah, and others (Martsinovsky, Kandelaki, Isaakyan, Patrick, and others). In Georgia, Pappataci fever is especially widespread in the Kura River valley. Its endemic foci exist in some parts of Tiflis. Pappataci fever is further widespread in various regions of Azerbaijan (the valley of the Kura and Aras rivers, the Caspian coast, etc.), and is also strongly prevalent in Armenia; in the latter, the city of Erivan is the most affected. Pappataci fever is quite widely distributed in Crimea, where it had long been known under various names (summer flu, three-day fever, etc.). In Central Asia, Pappataci fever began to be correctly recognized from 1924 by military doctors among military units, as well as among the civilian population in Eastern Bukhara, Tashkent, Tajikistan, and Turkmenistan. Here, the vectors of Pappataci fever—phlebotomus—were also carefully studied. Pathological anatomy. There are no deaths directly from Pappataci fever. According to available data, no specific pathological-anatomical changes characteristic of Pappataci fever are noted in the internal organs. Course of the disease and symptomatology. The incubation period lasts from 3 to 7 days. A prodromal period is usually absent. Mild prodromal phenomena, if present, are expressed in the form of general malaise, a feeling of fatigue, minor headaches, and lack of appetite, which appear a few hours before the onset of the disease. For the most part, the disease begins suddenly: sometimes during work, on guard duty, or during sleep. Without chills or with slight shivering, the temperature reaches 39-40° or 41° within a few hours (approx. 6 hours). At this height, the temperature holds for 24 hours, then begins to gradually decrease, and on the third day, it falls to normal. Usually, the fever ends in three days, which is why it is also called three-day fever (Fig. 1). In mild or atypical cases, the temperature may fall earlier—after 48 or even 24 hours (abortive form); the temperature may also hold longer—up to 4-5 and even up to 7 days. Sometimes the temperature, having fallen to normal, may rise again on the third day or earlier. Relapses can occur a few days or 1-2 weeks after the temperature falls (Fig. 2). Depending on the individual, manifestations from the nervous system are diverse; in general, they give a picture characteristic of Pappataci fever. The patient feels agonizing headache, especially in the area of the temples, forehead, and eye sockets. In addition to a feeling of fatigue, heaviness in the joints, severe weakness, and dizziness, apathy, mental depression, insomnia, and sometimes an excited state, delirium, and convulsions are noted. Fainting and sometimes apoplexy-like states are observed. The patient feels pulling and tearing pains in the nerves and muscles. Severe muscle pain is present especially at the beginning of the disease; these pains intensify during active movements. They are especially strong in the back, lower back, intercostal spaces, and calf muscles. The joints are usually not affected. The eyeballs are very painful, especially during movement and pressure. The eye muscles are also very painful. Figure 1. If the skin of the lowered upper eyelid is lifted with two fingers, the patient feels extreme pain ("Eye symptom"—Taussig). The conjunctiva of the sclera is strongly injected, especially at the outer corner of the eye, where there is redness in the form of stripes or a triangle with the apex facing the cornea (Pick's symptom). The oral mucosa is often strongly red. Hyperemia and edema of the soft palate are noted; punctate hemorrhages of the mucosa in various places of the oral cavity and nose, and nosebleeds occur. There are no catarrhal phenomena from the respiratory tract. Appetite is reduced. The tongue is covered with a white or yellowish-brown coating, slightly moist, and in severe cases, dry. Vomiting is not uncommon. In the beginning, constipation is mostly noted, subsequently—diarrhea. Liquid stool with an admixture of mucus and blood is observed, sometimes cholera-like stool. In some cases, disorders of the digestive tract in Pappataci fever are especially sharp. The spleen and liver are not enlarged. No changes are noted in the urogenital organs. Only in rare cases during high temperature can traces of protein be found in the urine, which quickly disappears. The circulatory organs react strongly to the infection and show characteristic changes. The pulse does not correspond to the temperature; bradycardia is observed. A slight slowing of the pulse rate is noted from the very first day, but as a rule, it is expressed from the second and third day. The pulse rate slows down to 60, and sometimes even to 40 per minute. Bradycardia can last from one to two weeks. Blood pressure during the febrile stage corresponds to the norm, and in the recovery period, it decreases slightly (Taussig and Franz). The blood picture shows strongly expressed leukopenia, which is noted from the very first day of the disease (2,400-4,450). At the same time, lymphocytosis, monocytosis, aneosinophilia, and an increase in band neutrophils are noted (Schilling, Gaglazov, and others). There are no characteristic changes in the skin; skin exanthema is absent. During the febrile state, hyperemia of the skin (vasomotor redness) is noted. Often, one can notice on the skin only traces of mosquito bites on certain parts of the body, mostly on the legs and arms (see separate table for the article Pellagra, figure 1). Traces of bites vary depending on the sensitivity and reaction of the patient; fresh bites have the appearance of tiny red spots, resembling bedbug bites. These spots, upon disappearing, leave nodules; the picture can change from scratching due to itching. In sharply reacting patients, infiltration appears at the site of the bites, and then small, gradually increasing vesicles with light yellow fluid. The vesicles burst, dry out, and form a crust with irregular jagged edges. Sometimes, as a secondary infection, purulent vesicles are observed (Derr). Diagnosis. During an epidemic outbreak in the summer, in endemic places where phlebotomus are distributed, recognizing the disease is not difficult. It is necessary to differentiate it from certain febrile diseases (malaria, dengue, influenza, Malta fever, typhoid, and paratyphoid). In malaria, a blood test resolves the issue. For dengue, unlike Pappataci fever, tachycardia at high temperature, exanthema, a relapsing type of fever, and joint pain (in Pappataci fever, pain is predominantly in the muscles) are characteristic; the Pappataci fever epidemic begins in the spring, while the dengue epidemic occurs in the autumn. Unlike influenza, in Pappataci fever, there is leukopenia and an absence of catarrhal phenomena from the respiratory tract. Serological and bacteriological reactions serve to distinguish it from Malta fever, typhoid, and paratyphoid. Prognosis is always favorable. Recovery is often delayed for weeks. Treatment. There are no specific remedies. Treatment is symptomatic. To relieve pain, aspirin and pyramidon are given; the state of the gastrointestinal tract is regulated. A comfortable bed, mouth rinsing. Prevention. When carrying out preventive measures, it is necessary to keep in mind 1) the source of infection (a sick person at the beginning of the disease); 2) the vector of infection (phlebotomus); 3) the susceptible person. Fighting the source of infection is a very difficult task. Theoretically, patients should be isolated on the very first day of the disease in a separate room protected from phlebotomus. But in practice, this is difficult to implement. The fight against phlebotomus must be conducted in two directions: against winged insects and against their breeding grounds. Since phlebotomus attacks humans at night, especially during sleep, it is necessary to protect rooms (bedrooms) from them. With open windows, light attracts a large number of phlebotomus into the room. Mechanical protection—screens on windows—is the best means, but the diameter of the screen holes should not exceed 0.75 mm, as phlebotomus easily crawl through wider holes.

On the other hand, netting restricts air, which makes it of little use on sultry summer nights. A room must be checked daily for the presence of Phlebotomus; they are easier to find early in the morning: having gorged themselves on blood, they sit on the walls, in corners, and under the ceiling. The ceiling and walls of the room should be well whitewashed, as then the Phlebotomus are more easily seen. It is necessary to thoroughly clean the walls, corners, and ceilings with a brush and spray them with insecticidal liquids. Newstead recommends a 1% solution of formalin; fumigation can be used periodically. It is recommended to create drafts or artificial (electric) ventilation near the bed, since Phlebotomus cannot tolerate air movement. For personal prophylaxis, the best remedy is a canopy over the bed. Various recommended aromatic substances (Ol. Anisi, Ol. Eucalypti, Ol. Terebinth., etc.) are of little effect. Natural enemies of Phlebotomus (birds, spiders, etc.) also have no practical significance. Combating the breeding grounds of Phlebotomus is also difficult, since these places have not yet been sufficiently studied. One should not allow the accumulation of refuse, both organic and inorganic. It is necessary to demolish ruins and any unnecessary outbuildings; latrines, storerooms, sheds, and animal enclosures should be kept clean and aired out frequently. Public measures should aim at improving the general hygienic and sanitary conditions of endemic areas. When on campaigns, it is recommended to avoid overnight stays in known endemic areas and to choose higher, Phlebotomus-free locations.