23. Tropical Diseases Lacking Adequate Control Measures: Dengue, Leishmaniasis, and African Trypanosomiasis

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Management and Control Strategies

 

Dengue


 

Patient Management and Treatment


Classic dengue fever is generally self-limiting. No specific treatment is available, but supportive treatment must be given, including fluid replacement when necessary. Early recognition of DHF cases—indicated by intense, continuous abdominal pain; persistent vomiting; and restlessness or lethargy—and early supportive treatment are of utmost importance to reduce case-fatality rates (Martinez 1992). For differential diagnosis, a wide spectrum of viral and bacterial infections should be considered, especially leptospirosis, malaria, yellow fever, chikungunya virus, rubella, and influenza.

 

Vector Control


Although good patient management can be effective for individual cases, currently no alternative to vector control is available for the prevention of dengue. Most endemic countries have a vector control component in their programs; however, the application of vector control measures is frequently insufficient, ineffective, or both and is currently failing to reduce the public health burden to an acceptable level.

Most Aedes control programs rely on the application of larvicides and adulticidal insecticide space sprays (Zaim and Jambulingham 2004). Because Ae. aegypti characteristically breeds in water that does not contain high levels of organic pollutants, control measures typically must be applied to water stored for household purposes, including drinking water. WHO currently approves five insecticides for application to potable water (FAO 1999; WHO 1991). Since the early 1970s, the organophosphate temephos has been the most widely used, but increasing levels of resistance to this insecticide are reducing the duration of effectiveness of treatments in some countries (Brengues and others 2003; Lima and others 2003; Rodriguez and others 2001). An additional challenge is the growing objection among householders, particularly in Latin America, to the application of chemicals to drinking water.

Biological control agents, including larvivorous fish and copepods, have had a demonstrable role in integrated control of Ae. aegypti, but operational difficulties—particularly a lack of facilities and of expertise in mass rearing and the need for repeated introduction of these agents into some container habitats—have largely precluded their widespread use. One encouraging exception is Vietnam, where indigenous species of predatory copepods are increasingly used to control semipermanent larval habitats of Ae. aegypti (Kay and others 2002; Nam and others 2000). However, some communities have strong cultural objections to the introduction of live animals into household water storage containers—for example, in Thailand, where bathing with water that contains small fish or other creatures is widely regarded as unacceptable.

Environmental management is generally considered the core component of dengue prevention and control, including cleanup campaigns, regular emptying and cleaning of containers, installation of water supply systems, solid waste management, and urban planning. However, huge investments in infrastructure are needed to increase access to safe and reliable water supplies, to provide solid waste management services, and to dispose of liquid waste. In addition to overall health gains, such provision would have a major effect on vector ecology, although the relationship is not invariably an inverse one. Cost-recovery mechanisms, such as the introduction of metered water, may encourage household collection and storage of roof catchment rainwater that can be harvested at no cost. Although unproven, the installation of community water services in rural townships and villages may be contributing to the rural spread of dengue in Southeast Asia and elsewhere.

At the household and community levels, where most vector control efforts are centered, increasing attention is given to such activities as covering or frequently cleaning water storage vessels, removing discarded food and beverage containers, and storing or disposing of used tires in such a way that they do not collect rainwater. Such tasks would seem to be simple and well suited to engagement by communities, but with a few exceptions, achievements to date have been unspectacular. Nevertheless, such community-based interventions are widely seen as the most promising way of achieving sustainable control through behavior change (Parks and Lloyd 2004).

 

Leishmaniasis


Leishmaniasis control is based primarily on finding and treating cases, combined where feasible with vector control and, in some zoonotic foci, control of animal reservoirs.

 

Diagnosis and Treatment


For VL, serological diagnosis is usually based on the enzyme-linked immunosorbent assay (ELISA), indirect fluorescent antibody tests, and direct agglutination tests, including a new direct agglutination test kit using lyophilized antigen, which avoids the need for refrigeration (Schallig and others 2001). A dipstick test based on a highly specific recombinant antigen is also available, together with a latex agglutination test that can be used to detect antigens in urine (Attar and others 2001; Sundar and others 1998). Parasitological diagnosis relies on microscopy of aspirates of the spleen, bone marrow, and lymph nodes.

Specific treatment includes the first-line drugs, which are pentavalent antimonials (sodium stibogluconate and meglumine antimoniate), and the second-line drugs, which are amphotericin B and AmBisome (amphotericin B in liposomes). Miltefosine for VL was registered in India in 2002, and aminosidine (paromomycin) has just completed phase 3 clinical trials and follow-up. For CL, parasitological diagnosis is made from skin smears followed by treatment with pentavalent antimonials. Treatment is given locally if lesions are few and relatively small, or systemically if lesions are more numerous. For mucocutaneous leishmaniasis, diagnosis relies on serology because patients generally develop a strong humoral response.

 

Vector and Reservoir Control


In foci of peridomestic or intradomestic transmission, vector control can be carried out by indoor residual spraying using pyrethroid insecticides. Individual protection using pyrethroid-impregnated bednets is also used in some areas. In zoonotic foci of VL, control has also included culling stray dogs—and pet dogs if found to be infected—although this practice is often poorly accepted by communities and is probably of limited effectiveness. Trials with insecticide-treated dog collars are showing some promise as an alternative way to reduce the peridomestic reservoir of infection (Mazloumi Gavgani and others 2002). For zoonotic CL, rodent reservoirs can be controlled using poisoned bait and environmental management, including physical destruction of rodents' burrows.

 

African Trypanosomiasis


For human trypanosomiasis, control consists primarily of active and passive case finding and treatment, occasionally associated with vector control operations. Dissemination of sleeping sickness can be prevented by regular surveillance of the population at risk, including diagnosis and treatment; control of the tsetse-fly population can affect the transmission of sleeping sickness as well as of animal trypanosomiasis. In T.b. rhodesiense foci, where cattle are reservoirs of the disease, treating cattle with trypanocides is being investigated as an additional approach to controlling outbreaks.

 

Case Finding and Treatment


No single clinical sign is regarded as pathognomonic for sleeping sickness. Tests have been developed to detect antibodies, circulating antigens, or trypanosomal DNA, but all require parasitological confirmation. For mass screening, infection can be confirmed by the card agglutination trypanosomiasis test, which is easy to perform and relatively inexpensive. Parasitological confirmation is by microscopy of lymph node aspirates and of thin or thick blood films. Concentration methods increase sensitivity. The most sensitive is the miniature anion exchange centrifugation technique. The capillary tube centrifugation technique is less sensitive but is commonly used in the field because of its ease and rapidity of use and its low cost.

Determining the stage of disease is essential, because early-and late-stage infections require different treatments. The criteria for late-stage infection are based on cerebrospinal fluid analysis.

Sleeping sickness is fatal if untreated. No vaccination exists. Specific drugs are currently available free through WHO. Pentamidine is used to treat early-stage T.b. gambiense infection, and suramine is used for early-stage T.b. rhodesiense. The organoarsenical compound melarsoprol (Arsobal) is used for the late stages of both. Eflornithine has been introduced to treat late-stage T.b. gambiense but is difficult to administer. Nifurtimox, although not yet registered for the treatment of sleeping sickness, has been used on compassionate grounds to treat patients unresponsive to melarsoprol.

 

Vector Control


A wide range of techniques for tsetse control is available (Maudlin, Holmes, and Miles 2004). Most current approaches exploit the acute susceptibility of tsetse flies to biodegradable pyrethroid insecticides. Spraying can be applied from the ground to known fly resting sites or at ultra-low volume from the air. Spraying is carried out sequentially to kill all flies initially present and thereafter to kill each generation of newly emerging flies. The sequential aerosol technique uses extremely low levels of insecticide and has been effective in Botswana, Somalia, South Africa, and Zambia. It is also useful against epidemic outbreaks of sleeping sickness, where a rapid cessation in contact between humans and tsetse flies is needed.

Tsetse flies can also be controlled using traps and targets. Targets are combinations of cloth and netting baited with an odor attractant and impregnated with a pyrethroid insecticide. Traps work on the same principle, but the fly is encouraged to enter a net or plastic chamber where it remains trapped. Live bait techniques are also used. Cattle are treated with a veterinary formulation of pyrethroid insecticides applied as sprays or pourons, which kill both tsetse flies and ticks. This technique has been successfully used in Burkina Faso, Ethiopia, Kenya, Tanzania, Zambia, and Zimbabwe (Kuzoe and Schofield 2005).

The sterile insect technique involves mass release of sterilized male tsetse flies, which compete with local males to mate with females. Because female tsetse flies generally mate only once, the result is infertile offspring and a decline of the wild tsetse population. This technique is expensive, because it requires large-scale rearing of flies, and it is only recommended for use once the wild tsetse population has been suppressed to low levels using other techniques. A combination of insecticide spraying and trap deployment followed by the sterile insect technique has been successfully used to eliminate G. austeni from Zanzibar (Vreysen and others 2000).

Degrees of resistance to trypanosome infection are found in the N'dama, Dwarf, and Savannah Shorthorn breeds in West Africa and, to a lesser extent, in some Orma Boran breeds in East Africa. However, even though these cattle show tolerance, can control parasitemia, and resist development of anemia, they can ultimately succumb to the disease.