YAWS - Frambesia tropica Yaws is a long-term (chronic) infection that mainly affects the skin, bones, and joints.

Causes, incidence, and risk factors

Yaws is an infection caused by the spiral-shaped bacteria, Treponema pallidum, subspecies pertenue. It is closely related to the bacterium that causes syphilis, but this disease is not sexually transmitted. Yaws mainly affects children in rural, warm, tropical areas, such as the Caribbean Islands, Latin America, West Africa, India, and Southeast Asia. Yaws is transmitted by direct contact with the skin sores of infected people.

Symptoms
About 2 - 4 weeks after infection, the person develops a sore called a "mother yaw" where bacteria entered the skin. The sore is a growth that may be tan or reddish and looks like a raspberry. It is usually painless but does cause itching. These sores may last for months. More sores may appear shortly before or after the mother yaw heals as the person scratches or spreads the bacteria from the mother yaw to uninfected skin. Eventually the skin sores heal. Other symptoms include: Bone pain Scarring of the skin Swelling of the bones and fingers In the advanced stage, sores on the skin and bones can lead to severe disfigurement and disability. This occurs in up to 1 in 5 people who do not get antibiotic treatment.

Signs and tests

A sample from a skin sore is examined under a special type of microscope (darkfield examination). There is no blood test for yaws. However, the blood test for syphilis is usually positive in people with yaws because the bacteria that cause these two conditions are closely related.

Treatment
Treatment involves a single dose of one type of penicillin, or 3 weekly doses for later stage disease. It is rare for the disease to return. Anyone who lives in the same house with someone who is infected should be examined for yaws and treated if they are infected.

Expectations (prognosis)
If treated in its early stages, yaws can be cured. Skin lesions may take several months to heal. By its late stage, yaws may have already caused damage to the skin and bones. It may not be fully reversible, even with treatment.

Complications
Yaws may damage the skin and bones, affecting the appearance and ability to move. It can also cause deformities of the legs, nose, palate, and upper jaw.
Key facts Yaws is a neglected tropical disease that affects the skin, bone and cartilage. It is caused by a bacterium from the same group of organisms that cause venereal syphilis. However, the transmission of yaws is not sexually-related. Humans are the only reservoir of this bacterial infection. A recent discovery that a single-dose of azithromycin (given orally) can cure the disease has raised the prospects of eradicating yaws altogether. Yaws mainly affects children below 15 years of age and is endemic in at least 14 countries. India is the only country to completely interrupt transmission during the past 6 years. Mass treatment campaigns using injectable penicillin from 1952 to 1964 in 46 countries reduced the prevalence of yaws by 95% (from an estimated 50 million cases down to 2.5 million).

Yaws forms part of a group of chronic bacterial infections caused by treponemes which include endemic syphilis (bejel) and pinta and are commonly known as endemic treponematoses. Yaws is the most common of these infections.

It is also known as framboesia (German or Dutch) and pian (French) and affects the skin, bone and cartilage. Yaws is caused by T. Pallidum subspecies pertenue. This organism belongs to the same group of bacteria that cause venereal syphilis. It is found primarily in poor communities in warm, humid and tropical forest areas of Africa, Asia, Latin America and the Pacific. Yaws is transmitted through direct (person-to-person) non-sexual contact with the fluid from the lesion of an infected person. Most lesions occur on the limbs. The initial lesion of yaws is teemed with the bacteria. Contact with this fluid, especially among children who play together and sustain minor injuries, leads to transmission of infection. The incubation period is 990 days (average 21 days). About 75% of people affected are children under 15 years old (peak incidence occurs in children aged 610 years). Males and females are equally affected. Overcrowding and poor personal hygiene facilitate the spread of the yaws. Without treatment, infection can lead to chronic disfigurement and disability.
Signs and symptoms

There are two basic stages of yaws: early (infectious) and late (non-infectious).
In early yaws, an initial papilloma (a circular, solid, swelling on the skin, with no visible fluid) develops at the site of entry of the causative organism. This papilloma is full of the organisms and may persist for 3-6 months followed by natural healing. Without treatment, this is followed by disseminated skin lesions over the body. Papules (solid elevation of skin with no visible fluid up to a centimetre large) and macules (a discoloured flat skin patch without any sensory loss, e.g freckles) also occur in early yaws. Thickening and darkening of palms of the hand and soles of the feet characterize the early stage of yaws. Bone pain and bone lesions may also occur in the early stage. Late yaws appears after five years of the initial infection and is characterized by disfigurement of the nose and bones, and palmar/plantar hyperkeratosis (thickening of the palms of the hand and the soles of the feet). These complications on the soles of the feet make it difficult for patients to walk.

A person (75% are children below 15 years) who lives in an endemic area is assumed to have yaws if he/she presents with:

painless ulcer with scab; papilloma (benign tumour on skin); papules and macules; and thickening and darkening of palms of the hand and soles of the feet.

In the field, diagnosis is primarily based on clinical and epidemiological findings. WHO has recently published a pictorial guide to help health and community health workers in the field recognize the disease.
Complications

Without treatment, about 10% of affected individuals develop disfiguring and disabling complications deformities of the legs and nose - after five years. The disease and its complications cause school absenteeism and prevent adults from farming activities.
Treatment

Two antibiotics may be used to treat yaws. 1. A recent study1 published in the Lancet in 2012 has shown that a single oral dose of azithromycin is as effective as benzathine penicillin. The dose for the treatment of yaws is 30 mg/kg (maximum 2g). Because of the ease of using an oral medicine, non-health workers such as village health workers, volunteers and community drug distributors can be trained to administer the treatment during large-scale treatment programmes. Azithromycin is now the preferred first line treatment of yaws. 2. Benzathine penicillin had been the mainstay of yaws treatment until 2012 when a study showed that a single-dose oral azithromycin is also effective. The recommended dosage is 1.2 million units (adults) and 600 000 units (children). However, the fact that it is administered by injection, means that it requires adequately trained health staff and adherence to sterile protocols, making it not conducive for large-scale treatment. Benzathine penicillin is still used wherever azithromycin is unavailable or when the patient cannot be treated with azithromycin.
Prevention

There is no vaccine for yaws. Prevention is based on the interruption of transmission through early diagnosis and mass or targeted treatment of affected populations or communities. Health education and improvement in personal hygiene are essential components of prevention.

Past eradication efforts

In 1949, the second World Health Assembly passed resolution WHA2.36 recognizing the public health importance of endemic treponematoses (yaws and bejel). Between 1952 and 1964, WHO and UNICEF led a worldwide campaign to control and eventually eradicate these diseases in 46 countries. Mass campaigns using mobile teams in 46 countries examined over 300 million people and treated 50 million. By 1964, the prevalence of these diseases had decreased by 95% (2.5 million). This achievement is considered to be one of the success stories in public health. Premature integration of yaws and other endemic treponematoses activities into weak health systems and the dismantling of the vertical eradication programmes after 1964 led to the failure to finish with the remaining 5% of cases. By the late 1970s, the diseases had begun to creep back, resulting in a World Health Assembly Resolution WHA 31.58 in 1978.
WHOs response: new eradication push

A growing interest in neglected tropical diseases (NTDs), the publication in January 2012 of the WHO roadmap, the absence of transmission of yaws in India for the past six years, and the discovery that a singledose of oral azithromycin can completely cure yaws have raised the optimism that yaws can now be eradicated. Experts developed an eradication strategy for yaws during a meeting convened by WHO in Morges, Switzerland in March 2012. The two, new recommended policies that were developed in the meeting are:

Total Community Treatment (TCT) treatment of an entire endemic community, irrespective of the number of active clinical cases. Total Targeted Treatment (TTT) treatment of all active clinical cases and their contacts (household, school and playmates).

As a first step in implementing the new eradication strategy, WHO plans to initiate large-scale treatment campaigns in selected endemic districts of six countries (Cameroon, Ghana, Indonesia, Papua New Guinea, the Solomon Islands, and Vanuatu).

HYDATIDOSIS

Background
Cystic echinococcosis (CE) is the larval cystic stage (called echinococcal cysts) of a small taeniid-type tapeworm (Echinococcus granulosus) that may cause illness in intermediate hosts, generally herbivorous animals and people who are infected accidentally. Ultrasonographic appearance of echinococcal cysts is seen in the image below.

WHO Informal Working Group on Echinococcosis standardized ultrasound classification of echinococcal cysts. Image courtesy of World Health Organization (WHO).

Three other species are recognized within the genus Echinococcus, and they may also develop in the human host and cause various forms of echinococcosis (hydatidosis). E granulosus is discussed separately from the other 3 species, notably Echinococcus multilocularis, which causes alveolar echinococcosis, because of marked differences in epidemiology, clinical features, diagnosis, and treatment. In the normal life cycle of Echinococcus species, adult tapeworms (3-6 mm long) inhabit the small intestine of carnivorous definitive hosts, such as dogs, coyotes, or wolves, and echinococcal cyst stages occur in herbivorous intermediate hosts, such as sheep, cattle, and goats. A number of other suitable intermediate hosts, such as camels, pigs, and horses, are involved in the life cycle in many parts of the world. In the typical dog-sheep cycle, tapeworm eggs are passed in the feces of an infected dog and may subsequently be ingested by grazing sheep; they hatch into embryos in the intestine, penetrate the intestinal lining, and are then picked up and carried by blood throughout the body to major filtering organs (mainly liver and/or lungs). After the developing embryos localize in a specific organ or site, they transform and develop into larval echinococcal cysts in which numerous tiny tapeworm heads (called protoscolices) are produced via asexual reproduction. These protoscolices are infective to dogs that may ingest viscera containing echinococcal cysts (with protoscolices inside), mainly because of the habit in endemic countries of feeding dogs viscera of homeslaughtered sheep or other livestock. Protoscolices attach to the dog's intestinal lining and, in approximately 40-50 days, grow and develop into mature adult tapeworms, once again capable of producing infective eggs to be passed to the outside environment with the dog's feces. Because humans play the same role of intermediate hosts in the tapeworm life cycle as sheep, humans also become infected by ingesting tapeworm eggs passed from an infected carnivore. This occurs most frequently when individuals handle or contact infected dogs or other infected carnivores or inadvertently ingest food or drink contaminated with fecal material containing tapeworm eggs.

Pathophysiology
In primary echinococcosis, metacestodes develop from oncospheres after peroral infection with E granulosus eggs. In secondary echinococcosis, larval tissue proliferates after being spread from the primary site of the metacestode. This can occur by spontaneous trauma such as induced rupture or during medical interventions. In primary echinococcosis, larval cysts may develop in every organ. Most patients (as many as 80%) have single-organ involvement and harbor a solitary cyst. Approximately two thirds of patients experience liver echinococcosis. The second most common organ involved is the lung. In each anatomic site, cysts are surrounded by the periparasitic host tissue (pericyst), which encompasses the endocyst of larval origin. Inside the laminated layer, or hyaline membrane, the cyst is covered by a multipotential germinal layer, giving rise to the production of brood capsules and protoscolices. The central cavities of cysts of E granulosus are filled with clear fluid, numerous brood capsules, and protoscolices. In addition, daughter cysts of variable size are often detected. The growth rate of cysts is highly variable and may depend on strain differences. Estimates of the average increase of cyst diameter vary (approximately 11.5 cm/y). The clinical features of cystic echinococcosis are highly variable. The spectrum of symptoms depends on the following:

Involved organs

Size of cysts and their sites within the affected organ or organs Interaction between the expanding cysts and adjacent organ structures, particularly bile ducts and the vascular system of the liver Complications caused by rupture of cysts Bacterial infection of cysts and spread of protoscolices and larval material into bile ducts or blood vessels Immunologic reactions such as asthma, anaphylaxis, or membranous nephropathy secondary to release of antigenic material

Epidemiology
Frequency United States

Unfortunately, realistic national or international figures do not exist for total numbers of cases of cystic echinococcosis. The problem is that, until recently, the only basis for diagnosis was surgery, and few countries systematically reported cases. When they did report cases, uneven reporting occurred in different regions of countries. The groups most at risk of cystic echinococcosis are usually underserved by medical services. However, the increasing use of mass screenings with ultrasonography in endemic countries is generating important epidemiological data. As different cyst stages have been classified according to their sonographic appearance, attempts are being made to match the cyst morphology with the natural history of the cyst. This is evident with the World Health Organization (WHO) standardized classification (see Imaging). At a community level, the relative proportions of cyst types can provide epidemiological information on disease transmission and help design effective control programs.[1] In the United States, transmission of E granulosus in the dog-sheep cycle is known to occur most frequently in several western states, including California, Arizona, New Mexico, and Utah. In Arizona and New Mexico, cystic echinococcosis is known to occur in American Indians belonging to the Zuni, Navajo, and Santo Domingo tribes, whose members live in close proximity to their animals, kill many of their own animals each year, and generally have limited knowledge concerning the life cycle and transmissibility of the parasite. In the United States, Utah has had the highest number of surgical cases of those states involved, with approximately 45 cases from 1944-1994.
International

E granulosus is a cosmopolitan parasite, and endemic regions exist in each continent. Considerable public health problems occur in many areas, including countries of Central America and South America, Western and Southern/Southeastern Europe, the Middle East and North Africa, some sub-Saharan countries, Russia and adjacent countries, and China. Annual incidence rates of diagnosed human cases per 100,000 inhabitants vary widely, from less than 1 case per 100,000 to high levels. For example, rates in the indicated regions are as follows:

Greece - 13 cases per 100,000 persons Rural regions of Uruguay - 75 cases per 100,000 persons Rural regions of Argentina - 143 cases per 100,000 persons in Rio Negro province Parts of Xinjiang province of China - 197 cases per 100,000 persons Parts of the Turkana district of Kenya - 220 cases per 100,000 persons

Cystic echinococcosis causes not only illness but also productivity losses in human and agricultural animal population, and it can have large societal impacts on endemic areas. Research is being conducted to evaluate the burden of disease, including nonmonetary costs.
Mortality/Morbidity

Cystic echinococcosis is rarely fatal. Occasionally, deaths occur because of anaphylactic shock or cardiac tamponade in heart echinococcosis.[2] Rare locations of the cyst (muscle, bone, brain, orbit) can cause dramatic and disabling symptoms (blindness, paralysis).[3, 4, 5, 6, 7, 8, 9, 10]
Race

No racial predilection exists.

Sex

In some endemic countries, females are affected more than males because their lifestyle habits and practices bring them into contact with the parasite.

Age

Individuals of all ages are affected. In some endemic countries, children have higher infection rates because they are most likely to play with dogs.

History

Months or years may pass before an individual exhibits any signs or symptoms of infection with the cystic larval stages. During the natural course of infection, the fate of E granulosus cysts is variable. o Some cysts may grow to a certain size and then persist without noticeable change for many years. o Other cysts may rupture spontaneously or collapse and completely disappear. Spontaneous or traumatic cyst rupture and spillage of viable parasitic tissue during interventional procedures may result in secondary echinococcosis. Cysts may rupture into the peritoneal or pleural cavity, the pericardium, the bile ducts, the gastrointestinal tract, or even blood vessels, leading to extraordinary manifestations and severe complications. Spontaneous cure of cystic echinococcosis is possible. After a variable incubation period, infections may become symptomatic if cysts are growing and exerting pressure on adjacent tissue and inducing other pathologic findings. Sudden symptomatology is usually due to spontaneous or traumatic cyst rupture. Usually, cysts do not induce clinical symptoms before they have reached a size sufficient to exert pressure on adjacent organs.

Physical
The presentation of human echinococcosis is protean. Patients come to the clinician's attention for different reasons, such as when a large cyst has some mechanical effect on organ function or rupture of a cyst causes acute hypersensitivity reactions. The cyst may also be discovered accidentally during radiographic examination, body scanning, surgery, or for other clinical reasons.[11] Common chief symptoms are upper abdominal discomfort and pain, poor appetite, and a self-diagnosed mass in the abdomen. Physical findings are hepatomegaly, a palpable mass if on the surface of the liver or other organs, and abdominal distention. If cysts in the lung rupture into the bronchi, intense cough may develop, followed by vomiting of hydatid material and cystic membranes.[12] Liver o Hepatomegaly o Inferior vena cava compression or o Jaundice thrombosis o Budd-Chiari syndrome o Biliary coliclike symptoms o Cyst rupture, peritoneal spread, and o Cholangitis peritonitis o Pancreatitis o Hemobilia o Liver abscess o Biliary fistula to skin, bronchial o Portal hypertension system, or gastrointestinal tract o Ascites Lungs o Tumor of chest o Eosinophilic pneumonitis o Chest pain o Pleural effusion o Chronic cough, expectoration, and o Parasitic lung embolism dyspnea o Hemoptysis o Pneumothorax o Biliptysis Heart o Tumor o Pericardial effusion o Embolism Breast - Masses that must be differentiated from neoplasms[11] Spine - Mass with neurologic symptoms Brain - Mass with neurologic symptoms

Causes

See Background for a brief discussion of infection routes.

Susceptibility of humans to infection varies, presumably because of individual differences in nutritional, immunologic, and genetic factors. Adrenal Adenoma Amebic Hepatic Abscesses Breast Cancer, Ultrasonography Breast, Benign Calcifications Cholangiocarcinoma Cysticercosis, CNS Hepatic Adenoma Hepatic Carcinoma, Primary Hepatic Cysts

Differential Diagnoses

Lung Cancer, Non-Small Cell Lung Cancer, Small Cell Lung, Metastases Metastatic Cancer, Unknown Primary Site Pseudocyst, Pancreatic Pyogenic Hepatic Abscesses Pyonephrosis Renal Cancer Splenic Abscess

Laboratory Studies
Generally, routine laboratory tests do not show specific results. o In patients with rupture of the cyst in the biliary tree, marked and transient elevation of cholestatic enzyme levels occurs, often in association with hyperamylasemia and eosinophilia (up to 60%). o In most cases, eosinophilia is limited (< 15%) or absent. Cystic echinococcosis is one of the few parasitic infections in which the basis for laboratory diagnosis is primarily serology.[13] o Indirect hemagglutination test and enzyme-linked immunosorbent assay are the most widely used methods for detection of anti-Echinococcus antibodies (immunoglobulin G [IgG]). o Depending on the test system used and other parameters, approximately 10% of patients with hepatic cysts and 40% with pulmonary cysts do not produce detectable serum IgG antibodies and exhibit false-negative results. o Cysts of the brain or eye and calcified cysts often induce no or low antibody titers. o Children aged 3-15 years may produce minimal serologic reactions. No standard, highly sensitive, and specific serologic test exists for cystic echinococcosis antibody detection. In specialized laboratories, the arc 5 test or detection of cestode-specific antibodies can be used to exclude cross-reactions caused by noncestode parasites. Radiographic examination is useful for cysts in the lungs, bone, and muscle and for detecting calcified cysts. Ultrasonography is the procedure of choice when making the diagnosis of asymptomatic cystic echinococcosis because it is safe, noninvasive, and relatively inexpensive. Ultrasonography is an imaging technique that uses the reflection of ultrasound waves emitted by a probe on the bodily organs to build images of the organs explored. o Any abnormality can be viewed using ultrasonography from an infinite number of angles and positions. Cysts in every part of the abdomen and in muscles can be imaged with ultrasonography. o Ultrasonography is useful in longitudinal studies, such as monitoring the response of cysts to treatment and recording cyst growth rate.[14] o Ultrasonography has also been used extensively in endemic areas for mass screening, often using portable machines that can work without an electrical distribution system by running on batteries or on a generator. o Many authors consider ultrasonographic mass surveys to be the best way to assess prevalence. Various classifications exist of the ultrasonographic picture in cystic echinococcosis, the most widely used still being the one proposed by Gharbi in the early 1980s.[15] In 2003, the World Health Organization Informal Working Group on Echinococcosis (WHO-IWGE) proposed a standardized ultrasound classification based on the active-transitional-inactive status of the cyst as suggested by its sonographic appearance.[16] The standardized classification scheme is intended to promote uniform standards of diagnosis and treatment and may be applied to the clinical treatment of patients as well as to field diagnostic

Imaging Studies

surveys. This classification has important implications for clinical decision-making ad prognosis.[17, 18, 13] CE1 and CE2 are active cysts containing viable protoscolices. CE3 has been subdivided into CE3a (detached endocyst) and CE3b (predominantly solid with daughter cysts). This subdivision is supported by a recent work that used high-field 1 H magnetic resonance spectroscopy to evaluate ex vivo the metabolic profiles of cyst contents.[19] Another paper has shown that, contrary to what previously assumed, calcifications are not limited to CE5 cysts, but are present to a various extent in all cystic stages.[20] Whatever the classification used, general consensus exists about the following: o Simple cysts with well-defined borders and uniform anechoic contents are not pathognomonic for echinococcal cysts (nonparasitic cysts have the same appearance). o Cysts with a visible split wall inside (floating membrane or water lily sign) are pathognomonic. o Septated cysts, or cysts with a honeycomb pattern, are likely to be echinococcal. o A solid heterogeneous mass is difficult to differentiate from granulomas or tumors, although calcification suggests echinococcal cyst. Echocardiography may be used to detect cardiac lesions. CT scanning has the advantage of inspecting any organ (lungs cannot be explored with ultrasonography), detecting smaller cysts when located outside the liver, locating cysts precisely, and sometimes differentiating parasitic from nonparasitic cysts. Measurement of cyst density appears to be an additional tool to differentiate parasitic from nonparasitic cysts and for follow-up studies during chemotherapy. However, the cost of CT scanning is prohibitive in several endemic countries. MRI may have some advantages over CT scanning in the evaluation of postsurgical residual lesions, recurrences, and selected extrahepatic infections, such as cardiac infections.[21] It is also superior in identifying changes of the intrahepatic and extrahepatic venous system and in identifying cystobiliary fistulas.[22] Endoscopic retrograde cholangiopancreatography may be indicated in patients with cholestatic jaundice. This technique may also be a therapeutic intervention when cysts communicating with the biliary tree can be basketed out. Fine-needle aspiration biopsy of the cyst performed under ultrasonographic guidance, by the transhepatic approach, and under anthelmintic coverage is generally safe and diagnostically useful for differentiation of cystic echinococcosis, malignancy, and abscesses.[23] It may be particularly helpful in cases with no detectable anti-Echinococcus serum antibodies and inconclusive imaging appearance. The hooks are usually numerous and can be found even in bacteriologically infected

Other Tests

Procedures

and/or degenerating cysts. Rostellar hooklets are seen in the image below. scolices (note rostellar hooklets).

Viable

Medical Care

Two benzimidazolic drugs, mebendazole and albendazole, are the only anthelmintics effective against cystic echinococcosis. Albendazole and mebendazole are well tolerated but show different efficacy. o Albendazole is significantly more effective than mebendazole in the treatment of liver cysts. Benzimidazole treatment alone requires prolonged administration over many weeks, with an unpredictable outcome in terms of response rates in individuals.[24] o Treatment with albendazole in E granulosus infection can result in an apparent cure in as many as 30% of patients, with a further 40-50% of patients showing objective evidence of response when observed short term. Patients who do not

show obvious initial evidence of response may be found to be cured when observed over several years. Duration of therapy and doses are also important. Albendazole efficacy increases with courses of up to 3 months in the more common cyst sites. Patients once received these drugs in cycles of 4 weeks separated by 1-2 weeks without drugs. This regimen is no longer advocated given the parasitostatic activity of benzimidazoles and their safety as shown by cumulative data from several retrospective studies. Continuous treatment is preferred and has been administered for periods of up to 2 years without significant side effects.[25, 13] The safety profile shows that liver function abnormalities are common, although they rarely limit treatment, while occasional hematologic changes affecting white cells may be more serious. The safety data supply the rationale for monitoring patients during treatment. Overall, albendazole has been demonstrated to be a useful advance in the management of cystic echinococcosis when used as sole treatment or as an adjunct to surgery or other treatments. Praziquantel has recently been suggested, administered additionally once per week in a dose of 40 mg/kg during treatment with albendazole. However, available data are limited.[26]

Surgical Care
Surgery was the only treatment available before the introduction of anthelmintic drugs. It is considered the first choice of treatment for echinococcosis but is associated with considerable mortality (up to 2% in some series, increasing with second and further operations), morbidity,[27] and recurrence rates (2-25%). Given the more frequent detection of early and asymptomatic E granulosus liver lesions, a widened indication for chemotherapy exists. Several procedures have been described for the treatment of hepatic echinococcal cysts, ranging from simple puncture to liver resection and transplantation, although the most commonly used technique is total or partial cystopericystectomy. Usually, radical surgery (total pericystectomy or partial hepatectomy) is indicated for liver cysts. Conservative surgery (open endocystectomy with or without omentoplasty) or palliative surgery (simple tube drainage of infected cysts or communicating cysts) is also an option. More radical interventions have higher intraoperative risks but less numerous relapses. With the inclusion of chemotherapy prior to or after surgery, lessaggressive surgery may be possible. Surgery for pulmonary cysts includes extrusion of cysts using Barrett technique (intact endocystectomy without preliminary aspiration), pericystectomy, and lobectomy.[28] Peripheral and unilobar echinococcal cysts, regardless of how complicated they are, can also be treated with laparoscopic surgery using partial cystopericystectomy and drainage. When surgery cannot be avoided, presurgical use of albendazole reduces risk of recurrence and facilitates surgery by reducing intracystic pressure. Percutaneous treatment

Minimally invasive treatment involves the following:

The puncture of echinococcal cysts has long been discouraged because of risks of anaphylactic shock and spillage of the fluid; however, as experience with ultrasonography-guided interventional techniques has increased since the early 1980s, an increasing number of articles have reported its effectiveness and safety in treating abdominal, especially liver, echinococcal cysts. A recent systematic review of the literature found that the overall fatality rate due to lethal anaphylaxis from puncture of echinococcal cysts is 0.03% (2 in 5943 procedures) for procedures and 0.04% (2 in 5517 cysts) for cysts respectively[23] . One study of 446 patients who were treated surgically for cystic echinococcosis (CE) found an increased incidence in anaphylatic shock in younger patients (P < 0.001) and in patients with pulmonary cysts. The authors suggest taking precautions such as reducing intracystic pressure, preventing antigen from contacting other tissues where it might trigger anaphylaxis, and resecting the cyst completely when feasible.[29] Under albendazole coverage, cysts are punctured under ultrasonographic or CT guidance either with a needle or with a catheter according to their size. The presence of an anesthesiologist who intervenes in case of allergic manifestations or anaphylactic shock is mandatory. Usually, a small quantity of fluid is first aspirated and examined by

light microscope to observe for the presence of viable protoscolices. If they are present, the cyst is aspirated completely. At this point, exclude possible connections of the cyst with the biliary tree by means of injection of contrast medium in the cavity. If no connections are evident, a scolecoidal agent, usually hypertonic sodium chloride solution or ethanol, is injected and left for a variable period (usually 5-30 min) and then reaspirated. The destruction of protoscolices can be observed in fluid sample aspirated after the injection of a scolecoidal agent. This sequence is termed PAIR (puncture, aspiration, injection, reaspiration). As happens with drug therapy, positive responses include both a decrease in cyst size and a progressive change in echo pattern (generally solidification).[30, 31, 32] From a diagnostic standpoint, PAIR is the only method that helps provide a direct diagnosis of the parasitic nature of the cysts. Neither imaging modalities nor serology is sufficient to exclude the diagnosis. PAIR is also an effective alternative to chemotherapy alone because it has a higher efficacy and avoids the problem of drug resistance. It also shortens the time of treatment and final recovery. PAIR is a valuable alternative to surgery in terms of cost containment and hospitalization time.[33, 34, 35, 36, 37, 38] In types I and II (Gharbi classification), CE1 and CE3a (WHO-IWGE classification) echinococcal cysts with no or incomplete response to therapy, PAIR is an effective therapeutic tool in the management of human cystic echinococcosis. Increasing evidence shows that CE2 cysts (multivesiculated, type I in Gharbi classification) and CE3b (predominantly solid with daughter cysts)[13] tend to relapse after PAIR,[39] so other percutaneous treatments should be adopted, if indicated, for this type of cyst. Reserve PAIR for use in highly specialized centers where teams are well prepared to deal with possible complications. Consult a surgeon to discuss the opportunity of surgical intervention. Consult a radiologist for injection of contrast medium in the cyst after fluid aspiration if PAIR is scheduled. Contrast injection in the cyst allows the physician to exclude connections of the cyst with the biliary tree. Contact of scolecoidal agents, such as alcohol and hypertonic sodium chloride solution, with the biliary epithelium may lead to cholangitis. Attempts to inject albendazole directly into the cysts have yielded interesting results in animal studies but are still methodologically weak in human studies. Most recently, a glucose solution as a scolecoidal agent has been used with good results in vitro.[40] Studies in vivo should confirm the safety of this approach before it can be applied to humans. Consult an anesthesiologist for assistance in case of anaphylactic shock or anaphylactoid reactions if PAIR is scheduled.

Consultations

Medication Summary
Albendazole and mebendazole are the only anthelmintics effective against cystic echinococcosis. Albendazole is the drug of choice against this disease because its degree of systemic absorption and penetration into hydatid cysts is superior to that of mebendazole. Albendazole in combination with percutaneous aspiration or PAIR therapy can lead to a reduction in cyst size, and, in one study, it improved efficacy over albendazole alone against hepatic hydatid cysts.[33] When surgery cannot be avoided, presurgical use of albendazole in echinococcus infestations reduced risk of recurrence and/or facilitated surgery by reducing intracystic pressure. Treatment of echinococcosis for patients weighing more than 60 kg is albendazole administered PO with meals in a dose of 400 mg twice daily for 28 days. A dose of 15 mg/kg of body weight daily in 2 divided doses (not to exceed total daily dose of 800 mg) has been suggested for patients weighing less than 60 kg. For cystic echinococcosis, the 28-day course may be repeated after 14 days without treatment to a total of 3 treatment cycles.

Anthelmintics
Class Summary

Parasite biochemical pathways are sufficiently different from the human host to allow selective interference by chemotherapeutic agents in relatively small doses.

Albendazole (Albenza)

Decreases ATP production in worm, causing energy depletion, immobilization, and, finally, death. To avoid inflammatory response in CNS, patient must also take anticonvulsants and high-dose glucocorticoids.
Mebendazole (Vermox) Causes worm death by selectively and irreversibly blocking uptake of glucose and other nutrients in susceptible adult intestine where helminths dwell.

TULAREMIA Tularemia is an acute, febrile, granulomatous, infectious zoonosis caused by the aerobic gram-negative pleomorphic bacillus Francisella tularensis. Although tularemia has likely existed since ancient times,[1] the disease was first described in Japan in 1837. In 1911, a plaguelike disease in ground squirrels was described in Tulare County, California (tulare is an Aztec word for the tule reed, a marsh plant commonly found in that area), and was later found to be caused by the bacterium now known as F tularensis. Edward Francis studied the causative organism further, named the disease, and, in 1928, described his experience.[2] Worldwide, more than 100 species of animals, birds, amphibians, and arthropods host F tularensis. The bacillus may also be found in mud and water. F tularensis produces acute infectious illness in humans. The mode of transmission and factors related to the host and organism influence the clinical presentation (ulceroglandular, glandular, oculoglandular, oropharyngeal, pneumonic, typhoidal).

Pathophysiology
Humans become infected with F tularensis after introduction of the bacillus by inhalation, intradermal injection, or oral ingestion. The clinical form of tularemia reflects the mode of transmission. Some authors classify the disease as typhoidal (predominance of systemic symptoms), pneumonic (pulmonary findings), or ulceroglandular (regional symptoms). To cause tularemia in humans via intradermal injection or inhalation, 10-50 bacilli are required. To transmit the disease orally, 100 million organisms are required. Ulceroglandular tularemia (80% of reported cases) usually occurs after F tularensis enters through the skin. Reportedly, bacilli can penetrate intact skin, but an abrasion (which may be clinically inapparent), a tick bite, or an insect bite is more likely to allow entry. Inoculation of the oral mucosa or conjunctiva may follow (1) contact with hands or fingers contaminated with tissue fluids or (2) contact with infectious aerosols. Following an incubation period of 3-5 days (range, 1-14 d), a papule develops. In 2-4 more days, the papule may ulcerate, usually accompanied by fever and regional lymphadenopathy. Humans are probably bacteremic during this phase. The bacilli become entrapped in the reticuloendothelial system, where they may survive for a prolonged period. Caseating granulomata, with or without multinucleated giant cells, may develop. Many animals and arthropods may carry F tularensis; however, ticks (especially Dermatocentor and Amblyomma species) and rabbits are the most common vectors implicated in cases of human tularemia. Domestic cats are increasingly recognized as associated with human tularemia. The deer fly is also a classic vector, although a less commonly reported one. Inhalation of F tularensis may lead to pulmonic tularemia, while oral ingestion may cause oropharyngeal tularemia. Conjunctival inoculation may follow contact with contaminated tissue fluids. The portal of entry is unknown in most cases of typhoidal tularemia.

Epidemiology
Frequency United States

A few hundred cases of tularemia are reported annually. Many cases are probably undiagnosed, misdiagnosed, or unreported. Tularemia has been reported in all states except Hawaii. Most reported cases occur in Arkansas, Tennessee, Texas, Oklahoma, Kansas, Utah, and Missouri. In the past, tularemia infections reportedly occurred more frequently during the cold-weather months (eg, rabbit-associated disease); however, recently, tularemia has been reported more frequently during warmweather months (eg, tick-associated disease).
International

Tularemia occurs throughout the Northern Hemisphere, except for in the United Kingdom. Cases have been reported in the United States, the former Soviet Union, Japan, Canada, Mexico, and Europe.[3, 4, 5] Tularemia has not been reported in Africa and South America.
Mortality/Morbidity

Overall, untreated tularemia carries a mortality rate of approximately 8%. The mortality rate of untreated typhoidal tularemia is 2-3 times higher. With early diagnosis and appropriate treatment, the mortality rate is less than 1%.
Race

All races are equally susceptible to tularemia.

Sex

Both sexes are equally susceptible to tularemia; however, societal activities common to young men may predispose them to F tularensis exposure.
Age

People of all ages are susceptible to the tularemia; however, young-to-middle-aged people are more likely to participate in activities that predispose them to exposure.

History
Most patients with tularemia experience an abrupt onset of fever, chills, malaise, and fatigue and develop 1 of 6 well-recognized clinical forms: ulceroglandular tularemia, glandular tularemia, oculoglandular tularemia, oropharyngeal tularemia, pneumonic tularemia, and typhoidal (septicemic) tularemia. Ulceroglandular tularemia o This form accounts for approximately 80% of tularemia cases. o F tularensis usually gains entry into the body via a scratch or abrasion and then spreads lymphatically, usually causing painful regional lymphadenopathy and an ulcerated skin lesion. Rarely, lymphangitis or nodular sporotrichoid lesions develop proximal to the ulcer. o In rabbit-associated disease, the ulcer is located on a finger or hand in more than 90% of

patients. See the image below. Eschar on thumb and under thumbnail at the site of a rabbit bite in a patient with tularemia. o In tick-borne tularemia, the ulcer is found on a lower extremity or the perineal area in 50% of patients, the trunk in 30%, and the head in 5-10%. Glandular tularemia o This form is similar to ulceroglandular tularemia except for the absence of the characteristic skin lesion. o F tularensis is presumed to enter via an inapparent abrasion and then to spread lymphatically

or via the bloodstream. See the image below. Axillary bubo in a patient with tularemia. Oculoglandular tularemia o In this form (1-2% of patients), F tularensis enters via the conjunctivae after inoculation from either splashing of blood or rubbing of eyes after contact with contaminated tissue fluids. o Clinical manifestations are usually unilateral. o Painful purulent conjunctivitis with preauricular or cervical lymphadenopathy may develop. Some patients experience chemosis, periorbital edema, and small nodular or ulcerative lesions of the palpebral conjunctivae. Oropharyngeal tularemia o This is a rare form that may occur after consumption of poorly cooked meat of an infected rabbit. o Patients with oropharyngeal tularemia usually report a sore throat, abdominal pain (due to mesenteric lymphadenopathy), nausea, vomiting, diarrhea, and, occasionally, frank gastrointestinal bleeding (caused by intestinal ulcerations). Pneumonic tularemia o Primary tularemia pneumonia is uncommon and occurs after inhalation of the F tularensis.[6] o Rarely acquired naturally, pneumonic tularemia may develop in laboratory workers.

Pneumonia develops after hematogenous spread in 10-15% of patients with ulceroglandular tularemia and in 30-80% of those with typhoidal tularemia. o Patients with this form of tularemia usually report a dry cough, dyspnea, and pleuritic-type chest pain. o Chest radiography may reveal patchy ill-defined infiltrates in one or more lobes. Frank lobar pneumonia may also develop. Bilateral hilar adenopathy may be present. Bloody pleural effusions are characteristic and demonstrate a mononuclear cellular response. o Adult respiratory distress syndrome (ARDS) develops in some patients. Typhoidal (septicemic) tularemia o This form accounts for 10-15% of tularemia cases. o It is more severe and probably represents F tularensis bacteremia. o Patients with this form of tularemia present with fever, chills, myalgias, malaise, and weight loss. They often have pneumonia. o Diagnosis is difficult because ulcers and lymphadenopathy are usually absent. Clinical symptoms o Clinical symptoms correspond to the type of tularemia. o As many as 20% of patients with tularemia have a blotchy, macular, maculopapular, or pustular rash. o Erythema nodosum and erythema multiforme are rare. Other forms o Rare manifestations of tularemia include osteomyelitis, pericarditis, peritonitis, endocarditis, and nervous system abnormalities, including meningitis, abscesses,[7] and optic neuritis.[8] o Other possible manifestations include acute renal failure, hepatomegaly, abnormal liver function, and rhabdomyolysis.
o

Physical
Physical findings of tularemia vary based on the clinical form disease presentation. Patients have fever and possibly tender hepatosplenomegaly. Ulceroglandular tularemia o This form is characterized by an ulcer at the site of F tularensis entry through the skin. The ulcer varies with the vector. It usually begins as a tender papule that eventually ulcerates and has a sharply demarcated border with a yellowish exudate. Initially, the base of the ulcer also has a yellowish exudate that turns to black. o Regional lymphadenopathy develops. The lymph nodes are usually edematous and tender. They can become fluctuant and may drain spontaneously. Oculoglandular tularemia o Ocular findings are usually unilateral. o Painful conjunctivitis with purulent exudate may be present. o Nodules or ulcerations may develop on the palpebral conjunctivae. o Submandibular, preauricular, and cervical adenopathy are common. o Corneal ulcerations may develop. Oropharyngeal tularemia: Exudative or membranous pharyngotonsillitis with regional adenopathy may be observed. Pneumonic tularemia: Chest examination findings may be normal in tularemic pneumonia, or rales may be present in the affected lung fields. Clinical symptoms: As many as 20% of patients with tularemia have a rash that may begin as blotchy, macular, or maculopapular and that may progress to pustular lesions. Erythema nodosum and erythema multiforme rarely occur. Less-common clinical forms of tularemia: In these forms of the disease (eg, meningitis, pericarditis, peritonitis, osteomyelitis), physical findings are the same as those commonly found in the clinical forms described above.

Causes

Tularemia is caused by infection with the bacterium F tularensis.

Differential Diagnoses

Psittacosis Q Fever Routine laboratory testing is generally not helpful in tularemia, except to aid in excluding other diseases from the differential diagnoses. Hematologic values are usually within the reference range. The WBC count may be slightly elevated. Occasionally, the WBC differential demonstrates lymphocytosis. In 20-30% of patients with tularemia, urinalysis reveals sterile pyuria. Liver function is usually normal. An elevated creatine phosphokinase (CPK) level may be associated with rhabdomyolysis and is a poor prognostic sign. High CPK values are more common in the typhoidal form of tularemia. Examination of spinal fluid may demonstrate a slightly elevated protein value or a few WBCs; however, this is nonspecific. Routine blood culture results are usually negative for tularemia. Successful cultivation requires media that contains cysteine for growth. Cultivation in the laboratory poses a hazard for workers; thus, laboratory personnel should always be advised if tularemia is suspected so that they may take appropriate precautions. A Gram stain of sputum from a patient with pneumonic tularemia usually does not demonstrate F tularensis. Obtain chest radiography to evaluate for pneumonia. As many as 30% of patients with tularemic pneumonia have no physical findings or respiratory tract symptoms. The diagnosis of tularemia is usually based on serology results. Tularemia tube agglutination testing is the most commonly used serological test.[9] o Diagnosis is confirmed by a 4-fold increase in titer. o An acute-phase titer of 1:160 is suggestive, but such titers seldom develop until 11-21 days after onset of illness. o Titers of 1:10-80 occur in 1% of the American population, especially those with long-term exposure to rabbits. A titer result may be positive in absence of clinical disease. o Tularemia serologic tests may cross-react with Salmonella, Brucella, Yersinia, and Legionella species. Skin testing may reveal a cellular immune response and is both sensitive and specific; however, skin test antigens are not commercially available. Lymph node biopsy is generally not needed for diagnosis. Polymerase chain reaction on material from wounds is being studied in some centers and appears promising as a means of earlier and easier diagnosis.[10] This diagnostic modality is also being evaluated for potential use on other body substances.

Laboratory Studies

Imaging Studies

Other Tests

Histologic Findings
Early tularemic lesions may demonstrate areas of focal necrosis surrounded by neutrophils and macrophages. Later, the necrotic areas become surrounded by epithelioid cells and lymphocytes. Caseating granulomata with or without multinucleated giant cells may develop in some lesions.

Medical Care

Medical care in tularemia is directed primarily toward antibiotic eradication of F tularensis. Provide symptomatic and supportive care for accompanying conditions (eg, osteomyelitis, pericarditis, peritonitis) as clinically indicated. Streptomycin is considered the drug of choice (DOC). Less experience has been reported with other aminoglycosides, but gentamicin and amikacin are also effective. Chloramphenicol and tetracycline are clinically useful; however, relapse rates of up to 50% are reported when these agents are used. Case reports indicate a potential role for erythromycin or fluoroquinolones (ciprofloxacin, levofloxacin); however, clinical experience and in vitro data supporting their use are limited.

In vitro susceptibility data support the possible role of third-generation cephalosporins (cefotaxime, ceftriaxone) and rifampin. However, failures occur with attempted third-generation therapy, and these agents should not be used for known or suspected tularemia. F tularensis is naturally resistant to penicillins and first-generation cephalosporins. Surgical care is not needed in tularemia management unless an ulcerative lesion develops a superinfection and requires debridement or a lymph node requires drainage. Consider consultation with an infectious diseases specialist to help determine the diagnosis and treatment plan. In patients with pneumonia or ARDS, assistance from a pulmonologist may be necessary. No special diet is required in patients with tularemia. Activity should not be restricted in patients with tularemia.

Surgical Care Consultations

Diet

Activity Medication Summary

Medical therapy in tularemia is directed at antibiotic eradication of the bacterium F tularensis.

Antibiotics
Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.
Streptomycin

Aminoglycoside antibiotic traditionally considered as DOC for tularemia. Has been administered safely IV but usually administered IM.
Gentamicin (Gentacidin, Garamycin)

Aminoglycoside that may be used as an alternative to streptomycin. Less clinical experience with gentamicin than streptomycin in treatment of tularemia. May be administered IV/IM. Many dosing schedules based on CrCl, volume of distribution, site of infection, and type of infection. Monitor serum levels after steady state is reached (usually after 3-4 doses). Trough levels are usually obtained 0.5 h before dose; peak levels are usually obtained 1 h after dose is infused.
Doxycycline (Bio-Tab, Doryx, Vibramycin)

Preferred therapy. Also may eradicate other tick-related copathogens. Should be used for a full 14 d to avoid risk of relapse.
View full drug information Chloramphenicol (Chloromycetin)

Use only if tetracyclines or aminoglycosides cannot be used. Use if meningeal involvement is possible. Binds to 50S bacterial-ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. Effective against gram-negative and gram-positive bacteria.

Further Inpatient Care

Care in patients with tularemia primarily involves supportive and general medical care for manifestations that require hospitalization (eg, ARDS, pneumonia, lung abscess, renal insufficiency). Observe patients for resolution of clinical manifestations and potential toxicities of antibiotics. Relapses of tularemia are common and may be retreated with the same medication because recurrence is usually due to incomplete treatment rather than antimicrobial resistance. Administer antibiotics for 7-14 days to complete a course of treatment (see Medication). Transfer patients if complications require therapeutic options (eg, ventilator management, cerebrospinal fluid examination, hemodialysis) unavailable at the initial facility.

Further Outpatient Care

Inpatient & Outpatient Medications

Transfer

Consider transfer if evaluation by a subspecialist (eg, infectious diseases specialist, pulmonologist, nephrologist) is needed and those subspecialists are not available at the initial facility. Avoid tick bites, if possible, by avoiding tick-infested areas, wearing trousers and long-sleeved shirts, using tick repellants, and by frequently inspecting clothing and bodies for evidence of ticks. Remove ticks promptly by grasping the tick near the mouthparts and pulling upward, taking care to not squeeze the body because tick secretions may be infectious. Avoid exposure to dead or wild mammals, if possible. When exposure is necessary (eg, skinning or eviscerating a rabbit carcass), gloves should be worn, especially if abrasions are on the hands. Frequent and thorough hand washing is also advised. A live attenuated vaccine is available. Although it does not provide complete protection against development of tularemia, it reduces the severity of disease in vaccinated people. Consider it only in people who may have repeated exposure because of vocation (eg, laboratory workers, wild-animal veterinarians, taxidermists). Pneumonia Lung abscess Respiratory failure, including possible ARDS Rhabdomyolysis Renal failure with possible hemodialysis Hemoptysis Meningitis Endocarditis Untreated tularemia carries a mortality rate of 5-15%. Treated tularemia carries a mortality rate of 1-3%. The mortality rate is 2-3 times higher in patients with typhoidal tularemia than in those with other forms. See Deterrence/Prevention. For excellent patient education resources, see eMedicineHealth's patient education article Ticks.

Deterrence/Prevention

Complications

Prognosis

Patient Education

CHIKUNGUNYA

Key facts Chikungunya is a viral disease that is spread by mosquitoes. It causes fever and severe joint pain. Other symptoms include muscle pain, headache, nausea, fatigue and rash. The disease shares some clinical signs with dengue, and can be misdiagnosed in areas where dengue is common. There is no cure for the disease. Treatment is focused on relieving the symptoms. The proximity of mosquito breeding sites to human habitation is a significant risk factor for chikungunya. The disease occurs in Africa, Asia and the Indian subcontinent. In recent decades mosquito vectors of chikungunya have spread to Europe and the Americas. In 2007, disease transmission was reported for the first time in Europe, in a localized outbreak in north-eastern Italy.

Chikungunya is a mosquito-borne viral disease first described during an outbreak in southern Tanzania in 1952. It is an alphavirus of the family Togaviridae. The name chikungunya derives from a root verb in the Kimakonde language, meaning "to become contorted" and describes the stooped appearance of sufferers with joint pain.
Signs and symptoms

Chikungunya is characterized by an abrupt onset of fever frequently accompanied by joint pain. Other common signs and symptoms include muscle pain, headache, nausea, fatigue and rash. The joint pain is often very debilitating, but usually ends within a few days or weeks. Most patients recover fully, but in some cases joint pain may persist for several months, or even years. Occasional cases of eye, neurological and heart complications have been reported, as well as gastrointestinal complaints. Serious complications are not common, but in older people, the disease can contribute to the cause of death. Often symptoms in infected individuals are mild and the infection may go unrecognized, or be misdiagnosed in areas where dengue occurs.
Transmission

The virus is transmitted from human to human by the bites of infected female mosquitoes. Most commonly, the mosquitoes involved are Aedes aegypti and Aedes albopictus, two species which can also transmit other mosquito-borne viruses, including dengue. These mosquitoes can be found biting throughout daylight hours, although there may be peaks of activity in the early morning and late afternoon. Both species are found biting outdoors, but Ae. aegypti will also readily feed indoors. After the bite of an infected mosquito, onset of illness occurs usually between four and eight days but can range from two to 12 days.
Diagnosis

Several methods can be used for diagnosis. Serological tests, such as enzyme-linked immunosorbent assays (ELISA), may confirm the presence of IgM and IgG anti-chikungunya antibodies. IgM antibody levels are highest three to five weeks after the onset of illness and persist for about two months. The virus may be isolated from the blood during the first few days of infection. Various reverse transcriptasepolymerase chain reaction (RTPCR) methods are available but are of variable sensitivity. Some are suited to clinical diagnosis. RTPCR products from clinical samples may also be used for genotyping of the virus, allowing comparisons with virus samples from various geographical sources.
Treatment

There are no specific drugs to cure the disease. Treatment is directed primarily at relieving the symptoms, including the joint pain. There is no commercial chikungunya vaccine.
Prevention and control

The proximity of mosquito vector breeding sites to human habitation is a significant risk factor for chikungunya as well as for other diseases that these species transmit. Prevention and control relies heavily on reducing the number of natural and artificial water-filled container habitats that support breeding of the mosquitoes. This requires mobilization of affected communities. During outbreaks, insecticides may be sprayed to kill flying mosquitoes, applied to surfaces in and around containers where the mosquitoes land, and used to treat water in containers to kill the immature larvae. For protection during outbreaks of chikungunya, clothing which minimizes skin exposure to the day-biting vectors is advised. Repellents can be applied to exposed skin or to clothing in strict accordance with product label instructions. Repellents should contain DEET (N, N-diethyl-3-methylbenzamide), IR3535 (3-[N-

acetyl-N-butyl]-aminopropionic acid ethyl ester) or icaridin (1-piperidinecarboxylic acid, 2-(2hydroxyethyl)-1-methylpropylester). For those who sleep during the daytime, particularly young children, or sick or older people, insecticide treated mosquito nets afford good protection. Mosquito coils or other insecticide vaporizers may also reduce indoor biting.
Disease outbreaks

Chikungunya occurs in Africa, Asia and the Indian subcontinent. Human infections in Africa have been at relatively low levels for a number of years, but in 1999-2000 there was a large outbreak in the Democratic Republic of the Congo, and in 2007 there was an outbreak in Gabon. Starting in February 2005, a major outbreak of chikungunya occurred in islands of the Indian Ocean. A large number of imported cases in Europe were associated with this outbreak, mostly in 2006 when the Indian Ocean epidemic was at its peak. A large outbreak of chikungunya in India occurred in 2006 and 2007. Several other countries in South-East Asia were also affected. In 2007 transmission was reported for the first time in Europe, in a localized outbreak in north-eastern Italy.
More about disease vectors

Both Ae. aegypti and Ae. albopictus have been implicated in large outbreaks of chikungunya. Whereas Ae. aegypti is confined within the tropics and sub-tropics, Ae. albopictus also occurs in temperate and even cold temperate regions. In recent decades Ae. albopictus has spread from Asia to become established in areas of Africa, Europe and the Americas. The species Ae. albopictus thrives in a wider range of water-filled breeding sites than Ae. aegypti, including coconut husks, cocoa pods, bamboo stumps, tree holes and rock pools, in addition to artificial containers such as vehicle tyres and saucers beneath plant pots. This diversity of habitats explains the abundance of Ae. albopictus in rural as well as peri-urban areas and shady city parks. Ae. aegypti is more closely associated with human habitation and uses indoor breeding sites, including flower vases, water storage vessels and concrete water tanks in bathrooms, as well as the same artificial outdoor habitats as Ae. albopictus. In Africa several other mosquito vectors have been implicated in disease transmission, including species of the A. furcifer-taylori group and A. luteocephalus. There is evidence that some animals, including nonprimates, may act as reservoirs.