Malaria Updates from CDC, December, 2006
Malaria Updates from CDC, December, 2006
Special Report
By Lin Chen, MD
Assistant Clinical Professor, Harvard Medical School; Director Travel Resource Center, Mount Auburn Hospital, Cambridge, MA
Dr. Lin H. Chen reports no financial relationship relevant to this field of study.
At the 55th annual meeting of the American Society of Tropical Medicine and Hygiene held in Atlanta, Georgia, November 12-16, 2006, Dr. Paul Arguin from the Centers for Disease Control and Prevention presented his Malaria Updates from the CDC. Dr. Arguin reviewed the recent malaria outbreak in Great Exuma, the Bahamas, discussed revised recommendations for malaria chemoprophylaxis in Mexico, previewed new malaria maps that are being developed by the CDC, and reported on the development of artemisinin derivatives for malaria treatment in the United States.
During May-June 2006, an outbreak of Plasmodium falciparum malaria occurred in Great Exuma, the Bahamas. The initial case of P. falciparum was identified in a U.S. resident from Virginia who had visited Great Exuma and stayed at a resort. Subsequently, the Bahamian Ministry of Health conducted epidemiologic and entomologic surveys, as well as heightened mosquito controls. The CDC temporarily recommended malaria chemoprophylaxis with chloroquine for travelers going to Great Exuma. During May and June 2006, a total of 19 malaria cases were identified (15 malaria cases in residents of Great Exuma and 4 cases in travelers from the United States, Canada, and Germany).1 The parasite was most probably introduced by immigrants from Haiti. After a 3-month period, when no further cases were identified, the CDC rescinded the recommendation for malaria chemoprophylaxis.1
Dr. Arguin then presented a detailed analysis of malaria in U.S. travelers returning from Mexico. The CDC analyzed data from the World Tourism Organization, International Trade Administration, Office of Travel and Tourism Industries in the U.S. Department of Commerce, North American Transportation Statistics, Health Styles (a population-based national mail survey of adults), and both the U.S. and Mexican governments' national malaria surveillance data. The "same day" land border crossings are unlikely to be associated with malaria risk. The majority of the "overnight" land border crossings are also likely to be risk free areas. Most cruise ships are in port during the day and go to major resort areas, where there is no risk. Also, 86% of the air travel is to areas with no risk. Finally, the majority of the destinations that were not recorded are probably also in risk free areas.
Dr. Arguin reported that the comparison of the rates of malaria in 2000 showed a rate of >1,100/100,000 imported among U.S. travelers returning from Nigeria vs 0.06/100,000 returning from Mexico. The CDC analysis concluded that: 1) large numbers of U.S. travelers go to Mexico; 2) 99.9% go to places where there is no risk of malaria; 3) there are currently about 10 cases of malaria per year acquired in Mexico among U.S. travelers, and these were largely P. vivax.
Based on these analyses, recommendations for Mexico will be revised to reflect the following: "Risk is limited to areas infrequently visited by travelers including small foci along the Guatemala and Belize borders in the states of Chiapas, Quintana Roo, and Tabasco; rural areas in the states of Nayarit, Oaxaca, Sinaloa; and in an area between 24°N and 28°N latitude, and 106°W and 110°W longitude, which lies in parts of Sonora, Chihuahua, and Durango. No malaria risk exists along the United States-Mexico border. No malaria risk exists in the major resorts along the Pacific and Gulf coasts. Risk is very limited; therefore, prophylaxis is not recommended for most travelers to Mexico. Travelers should use personal protection measures such as insect repellents for malaria prevention. Chloroquine is recommended for the rare traveler going to the risk areas."
Through more detailed analyses similar to that which was performed for Mexico, the CDC Malaria Branch would like to increase the number of people who take chemoprophylaxis when they should, decrease the amount of unnecessary chemoprophylaxis, and develop better ways of estimating malaria risk for travelers based on the volume of travelers to a country, destinations within countries, and detailed national surveillance data.
Dr. Arguin described a new web-based malaria map being developed by the CDC that illustrates geographic risk areas. The map contains malaria risk assessment information that is reflected in Health Information for International Travel (the Yellow Book). The map will list information regarding malaria risk for specific cities within each country that users can type in or locate by searching a list. The map will have scheduled revisions every 2 years (concurrent with the revisions for the Yellow Book), but will have some unscheduled updates, new risk assessments, and outbreaks.
Finally, Dr. Arguin discussed the development of artemisinin derivatives for treatment of severe malaria in the United States. Approximately 1,200 cases of malaria occur in the United States annually, with 120 cases of complicated malaria requiring parenteral treatment for malaria. A total of 41 deaths from severe malaria occurred between 1999 and 2004, and the only parenteral drug available for treatment of severe malaria in the United States is quinidine. Quinidine is a class 1A antiarrhythmic with anti-malarial activity, but its use requires continuous cardiac monitoring; it can be associated with cardiac-conduction abnormalities and hypoglycemia. The development and preference for newer and better antiarrhythmics have decreased both the demand and, therefore, the availability of the drug.
Artemisinins are derived from sweet wormwood, and several have antimalarial properties: dihydroartemisinin, artemether, arteether, and artesunate. Artemisinin derivatives are recommended worldwide as first-line and essential malaria treatments,2-5 but none are currently FDA approved for use in the United States. Artesunate has demonstrated efficacy in vitro, and in experimental animal models. Many studies have shown that artesunate is at least as effective as quinine, and sometimes more effective.4
Artesunate rapidly clears malaria parasitemia, but is associated with high rates of recrudescence. It is not effective for monotherapy, but is highly effective when combined with other antimalarials. The CDC is planning to establish supplies of artesunate under an investigational drug protocol, and make the medication available through the quarantine stations. This will be welcomed in view of the supply problems clinicians have experienced with quinidine. However, clinicians who anticipate using artesunate may need to obtain an institutional review board approval in order to be able to use it when the occasion arises.
Dr. Lin H. Chen would like to thank Dr. Paul Arguin for his slides and notes in preparation for this update, and for reviewing the previous report.
References:
- CDC. Malaria — Great Exuma, Bahamas, May-June 2006. MMWR. 2006;55(37):1013-1016.
- Bukirwa H, et al. Artemisinin combination therapies for treatment of uncomplicated malaria in Uganda. PLoS Clin Trials. 2006;May;1(1):e7.
- Campbell P, et al. A randomized trial comparing the efficacy of 4 treatment regimens for uncomplicated falciparum malaria in Assam state, India. Trans R Soc Trop Med Hyg. 2006;Feb;100(2):108-118. Epub 2005; Nov 14.
- Dondorp A, et al. Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial. Lancet. 2005;Aug 27-Sep 2;366(9487):717-725.
- Ramharter M, et al. Artesunate-clindamycin versus quinine-clindamycin in the treatment of Plasmodium falciparum malaria: a randomized controlled trial. Clin Infect Dis. 2005;Jun 15;40(12):1777-1784.
Abstracts of Interest
#7. Zollner GE, et al. Evaluation of novel long-lasting, insecticide-impregnated materials to control adult sand flies in Iraq, Kenya and Egypt.
Field studies compared deltamethrin- or permethrin-treated materials to untreated materials in controlling sand flies. Sand flies were collected by light traps. Light traps inside treated nets or barriers caught fewer sand flies, whereas treated floorings did not reduce numbers. Treating nets or barriers with insecticide appears to be an effective control measure against sand flies.
#8. Lengeler C, et al. Malaria vector control in Sub-Saharan Africa: insecticide-treated nets vs indoor residual spraying.
The 2 interventions are compared in 2 Cochrane systematic reviews regarding impact on mortality and key morbidity indicators. Both are highly effective. Insecticide-treated nets reduce child mortality by 18% and also reduce the clinical episodes by 50%. Indoor residual spraying has a great deal of historical evidence. Therefore both insecticide-treated nets and indoor residual spraying are considered to be highly effective for malaria prevention.
#58. Senn N, Genton B. Acute hepatitis A in a young returning traveler from Kenya despite immunization before departure.
A 25-year-old man received hepatitis A vaccine (Havrix, 1440 units) 11 days before traveling to Kenya from January 18 - February 2, 2004. He presented with fever, myalgia, mild headache 14 days after return, and was subsequently diagnosed with acute hepatitis A. This case report is a reminder that while hepatitis A vaccine is highly protective, infections can sometimes occur in spite of immunization, especially if immunized close to departure for highly endemic countries.
#244. Hiwat H, Mitro S. Biting behavior of Anopheles darlingi in the southern Amerindian region of Suriname.
Investigators collected mosquitoes both indoors and by peridomestic human bait and analyzed the timing of bites. For bite, > 42% occurred indoors, and 95% occurred in the second half of the night, peaking between 4-6am (63%). The biting time contrasts with some other reports that found peak biting time of Anopheles darlingi to be in the early evening. Other studies have found peak biting time of Anopheles darlingi to be in the early evening, and clarification of these differences is needed to best advise travelers.
#311. Newton PN, et al. Counterfeit artesunate and malaria in Asia and Africa.
Although counterfeit artesunate has been identified in southeast Asia for many years, counterfeit artemisinin derivatives have only recently been discovered in Africa. Some counterfeits can be identified through the packaging and fake holograms. Chemical analyses have identified the counterfeits and classified them into different groups: 1) contain no active ingredient, 2) contain small amount of artesunate, or 3) contain other drugs (erythromycin, chloramphenicol, sulfa drug, etc.). Ineffective therapy for malaria can lead to deaths, and low levels of artesunate can contribute to the development of drug resistance. Furthermore, unexpected ingredients contained in the counterfeits can lead to drug reactions, possibly life-threatening.
#374. Noedl H, et al. Artemisinin resistance along the Thai-Cambodian border?
Artesunate-mefloquine combination therapy failures along Thai-Cambodian border were evaluated. The 50% inhibitory concentrations (IC50) for dihydroartemisinin in isolates from patients who failed therapy were nearly twice those from of patients without recrudescence. Reduced artemisinin parasite sensitivity correlates with clinical failures. This is suggestive of possible reduced artemisinin sensitivity among malaria parasites in some areas along the southeastern border with Cambodia.
#416. Fukuda MM, et al. Mucosal leishmaniasis in a Central American immigrant diagnosed with real-time PCR: case report and review of diagnostic and treatment issues.
An immigrant from Honduras residing in the Washington, DC, area for 13 years had resection of a nasal polyp. Postoperative cellulitis did not respond to multiple antibiotics for 6 months, and RT-PCR confirmed mucosal leishmaniasis (ML). A 20-day regiment of amphotericin B led to the healing of the lesion. The case is a reminder that: 1) ML is possible in immigrants who have long residence away from endemic areas; 2) ML may occur more frequently in the United States; 3) RT-PCR and conventional PCR support the diagnosis of leishmaniasis in a timely fashion.
#454. Aristizabal LO, et al. Ticks infected with Rickettsia in Villeta, Cundinamarca, Colombia.
Investigators collected 679 ticks in the area where fatal RMSF had been reported recently. Four species of ticks were identified: Rhipicephalus sanguineus, Anocentor nitens (formerly Dermacentor nitens), Amblyomma cajennense, and Boophilus microplus. PCR amplification of rickettsial genes in search of the infection found infected ticks: 0.37% of R. sanguineus, 4.54% of A. cajennense, and 1.13% of B. microplus. The study confirms the presence of the vector for RMSF as well as presence of rickettsial infection in these ticks obtained in Colombia.
#608. Moore S, et al. Developing a low-cost repellent to reduce malaria in the Americas — results of 2 field trials in Guatemala and Peru.
Investigators noted that combining an active repellent with oil-based fillers and fixatives may extend the effective period and lower the cost. The study used a human-landing design and compared a combination of p-menthane diol (PMD, oil of lemon eucalyptus) and lemongrass oil to DEET on the Pacific coast of Guatemala and in the Peruvian Amazon. The PMD+LG repellents provided > 98% protection for 5 hours, whereas 15% DEET provided 94% protection in Guatemala. The PMD+LG repellent provided > 96% protection for 6 hours whereas 20% DEET provided 64% protection in Peruvian Amazon. The findings support the efficacy of PMD+LG in protection against Anopheles mosquitoes.
#693. Lenhart A, et al. Insecticide-treated bednets for the control of dengue vectors in Haiti.
Effect of insecticide-treated bednets (ITNs) on dengue mosquito vectors was assessed. Insecticide- treated nets reduced peridomestic dengue vector breeding. Furthermore, serosurveillance found that dengue IgM seroconversion rates declined from 33.7% to 18.5% in 12 months. In addition to the prevention of malaria, this study suggests that ITNs should also be effective in controlling dengue infections.
#929. Solorzano N, et al. Effects of house spraying with 3rd generation pyrethroids in populations of Lutzomyia verrucarum, Huaylas Province, Ancash, Peru.
Investigators evaluated the effect of pyrethroids on Lutzomyia verrucarum, the vector of leishmaniasis and bartonellosis in Peru. Vectors were collected with light traps. Baseline Night Traps Collection Indexes (NTCI) were 50-300. After the first spaying, the NTCI declined to between 30-100. This declined to 25-80 after the second spraying, and further to < 10 after the 3rd spraying. Spraying houses with pyrethroids reduced the populations of L. verrucarum. This study demonstrates the efficacy of pyrethroid spraying in controlling sand flies.
At the 55th annual meeting of the American Society of Tropical Medicine and Hygiene held in Atlanta, Georgia, November 12-16, 2006, Dr. Paul Arguin from the Centers for Disease Control and Prevention presented his Malaria Updates from the CDC.Subscribe Now for Access
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