Malaria, Plasmodium Vivax

Tropical
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Diagnosis and reasoning

The febrile patient with a recent history of travel to a developing nation presents a unique diagnostic challenge for physicians in developed countries, as they may need to consider diseases which they are not necessarily familiar with. This problem is exacerbated by the fact that many of these patients present with vague and non-specific symptoms, which could potentially be caused by any one of a myriad of different infectious diseases. However, a careful and detailed history is often capable of making sense out of chaos, and pointing one towards a probable diagnosis. First and foremost, it should be appreciated that each geographic location has its own set of local infections; the “Travelers’ Health” section of the Centers for Disease Control and Prevention (CDC) website is an excellent resource in this regard. This reveals the presence of a broad range of bacterial, viral, protozoal and helminthic diseases endemic to Equador; these include Hepatitis A and B, Malaria, Yellow Fever, Trypanosomiasis, Dengue, Bartonellosis, and Amoebiasis. Note that the above infections are transmitted via several different modes: ingestion, vector transmission and direct contact. Thus, analysis of the type of travel engaged in may provide some additional clues. Unfortunately, adventure travellers (such as this patient) have ample opportunity to be exposed to all of the above pathogens. The next most important point in the history is the date of departure from the foreign country, as this gives an idea about the incubation period of the disease. In this patient, the long duration before manifestation of symptoms indicates a condition with a prolonged incubation period; this narrows down the list of possibilities significantly. Other important points in the history of this patient include the lack of progression of symptoms and presence of an intermittent fever. Note that the absence of localizing symptoms or physical findings makes a focal process (such as an abscess) clinically less likely. However, an intra-abdominal abscess (such as an amoebic liver abscess) may yet present in this manner. The next steps in the evaluation should be hematological and biochemical investigations. A full blood count is essential; this reveals a mild anemia, thrombocytopenia and a slightly elevated white cell count. The liver profile reveals mild elevation of all liver enzymes and serum bilirubin. Considering all of the above, we are left with a handful of possible differential diagnoses. Amoebiasis is a possibility. The white cell count and elevated liver functions are in favor of this, but the absence of abdominal tenderness and presence of thrombocytopenia make this unlikely. Bartonellosis (which is acquired via the bite of the sandfly in certain South American regions) is another possibility; while in most patients, the infection tends to take a fulminant course with fever, malaise, jaundice, hepatomegaly and generalized lymphadenopathy, atypical presentations are possible. Given the geographical location, prolonged incubation period and nonspecific symptoms, Malaria is not only a possible diagnosis but also a probable one. It is important to remember that the “classical” 48 to 72 hour fever cycles are seen only in patients with established disease, and may be absent altogether if the patient has been taking antipyretics. The diagnosis of Malaria is relatively straight forward. Inspection of thick and thin peripheral blood smears under direct microscopy can confirm the diagnosis and identify the species of Plasmodium causing the disease. In this case, the smear showed parasites within enlarged red cells, a characteristic feature of P. vivax but not P. falciparum. Once the diagnosis of malaria is established, and the type of Plasmodium identified, treatment should be started immediately. Uncomplicated cases of malaria such as this one can be treated with oral medication alone. The WHO recommends use of Chloroquine in treatment of P. vivax Malaria contracted in South America, combined with Primaquine to eliminate the liver forms of the parasite. Clindamycin is recommended by the WHO in the treatment of Malaria during pregnancy, and is not indicated in this patient. Contact screening is unnecessary, as Malaria is a vector-borne infection and is not spread by direct person to person contact.


Discussion

Malaria is a protozoan disease caused by one of four species of the genus Plasmodium: Plasmodium falciparum, P. vivax, P. ovale, or P. malariae. All species are transmitted by the bite of an infective female Anopheles mosquito. Rarely, transmission can occurs via processes such as blood transfusion and needle sharing. Malaria is a major international public health problem, causing over 200 million infections worldwide and over 600,000 deaths annually. Despite major efforts to reduce the global prevalence of malaria, many regions remain malaria endemic, especially in the developing world. Combined with inadequate preventive measures taken by most travelers, this explains the increased incidence of Malaria infections among travelers in the past couple of years. Malaria transmission occurs in large areas of Africa, Central and South America, Caribbean, Asia, Eastern Europe, and the South Pacific. The risk for acquiring malaria differs substantially from region to region. For example, it is estimated to be highest in West Africa and Oceania and much lower in South America and parts of Asia. The clinical presentation is usually nonspecific, with fever and influenza-like symptoms, including chills, headache, myalgias, and malaise. These symptoms can occur at intervals. There may be associated anemia and jaundice. In severe disease (usually with P. falciparum Malaria), seizures, mental confusion, kidney failure, acute respiratory distress syndrome, coma, and death may occur. Although the usual incubation period is around 2 weeks, symptoms can develop as early as 7 days after initial exposure and as late as several months or more after departure. Smear microscopy is the accepted gold standard for malaria diagnosis. It has the added advantage of being able to determine the species of malaria parasite and quantify the parasitemia - both of which are essential pieces of information for providing the most appropriate treatment. Microscopy results are usually available within a few hours. Various test kits are also available to detect antigens derived from malaria parasites. Such immunologic tests offer a useful alternative in situations where reliable microscopic diagnosis is not immediately available. Malaria can be a severe, potentially fatal disease (especially when caused by P. falciparum) and treatment should be initiated as soon as possible. Patients who have severe P. falciparum malaria or who cannot take oral medications should be given the treatment by continuous intravenous infusion. Most drugs used in treatment are active against the parasite forms in the blood (the form that causes disease) and include: chloroquine, atovaquone-proguanil (Malarone®), artemether-lumefantrine (Coartem®) and mefloquine (Lariam®). In addition, primaquine is active against the dormant parasite liver forms (hypnozoites) and prevents relapses. It is indicated in all cases of P. vivax and P. ovale malaria. Primaquine should not be taken by pregnant women or by people who are deficient in G6PD. The combination of drugs used for treatment of malaria depend on several factors, including; - The species of parasite - The area where the infection was acquired - Drug-resistance status - Status of the patient - Pregnancy - Drug allergies, other medications etc The WHO World Malaria Report provides detailed information regarding the prefered drug combinations for specific geographic locations. It is always advisable to consult with an expert in travel medicine or contact a specialized treatment center prior to starting the treatment. Malaria prevention consists of a combination of mosquito avoidance measures and chemoprophylaxis. All travelers are advised to use an effective mosquito repellent. All recommended primary chemoprophylaxis regimens involve taking a medicine before, during, and after travel to an area with malaria. Beginning the drug before travel allows the antimalarial agent to be in the blood before the traveler is exposed to malaria parasites. Some drug combinations that can be used as chemoprophylaxis include: Atovaquone-proguanil, Chloroquine phosphate or hydroxychloroquine sulfate, Doxycycline and Mefloquine. Again, it is advisable to consult an expert on the specific geographic area regarding the most suitable prophylaxis regimen. Malaria infection in pregnant women pose a special problem, as it can be more severe and the risk for adverse pregnancy outcomes is higher. Therefore women who are pregnant or likely to become pregnant should be advised to avoid travel to areas with malaria transmission if possible If travel to a malarious area cannot be avoided, use of an effective chemoprophylaxis regimen is essential.


Take home messages

  1. Travelers with fever present a unique diagnostic challenge.
  2. The geographic location, type of travel, and dates of travel are key towards arriving at a good differential diagnosis.
  3. The treatment of Malaria should be started as soon as possible following diagnosis.
  4. The treatment regimen depends on several factors including the species of parasite, geographical location and the status of the patient.
  5. It is always advisable to consult an expert or a specialized center in travel medicine prior to starting treatment for Malaria.

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  1. Leder K, Black J, O’Brien D, Greenwood Z, Kain KC, Schwartz E, et al. Malaria in travelers: a review of the GeoSentinel surveillance network. Clin Infect Dis. 2004 Oct 15;39(8):1104–12.
  2. Paul M. Arguin, Kathrine R. Tan, Malaria. Travelers’ Health, CDC. 2013.
  3. Steinhardt LC, Magill AJ, Arguin PM. Review: Malaria chemoprophylaxis for travelers to Latin America. Am J Trop Med Hyg. 2011 Dec;85(6):1015–24.
  4. Thrombocytopenia in malaria and its correlation with different types of malariaManmeet K Gill, Manisha Makkar, Sachan Bhat, Tanveer Kaur, Kalpana Jain, Geetika DhirAnnals of Tropical Medicine and Public Health, Year 2013, Volume 6, Issue 2 [p. 197-200]
  5. Treatment of Malaria (Guidelines For Clinicians) , CDC, July 2013
  6. World Health Organization. World malaria report 2012. Geneva: World Health Organization; 2012