A 4-Day Incubation Period of Plasmodium falciparum Infection in a Nonimmune Patient in Ghana: A Case Report

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Open Forum Infect Dis. 2019 Jan; 6(1): ofy169.

Published online 2019 Jan 17. doi: 10.1093/ofid/ofy169

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Plasmodium falciparum can cause severe infection and has the shortest incubation period compared with all the other Plasmodium species. Incubation periods of 9–14 days for the immune and 6–14 days for the nonimmune have been reported for P. falciparum. However, an incubation period of less than 5 days has not been reported, as of yet. This report presents a case of a 23-year-old nonimmune female who presented with signs and symptoms 4 days after being bitten by mosquitoes while visiting Ghana. The patient was successfully treated with a 1-day course of parenteral artesunate, followed by a 3-day course of oral artemisinin combination therapy.

Keywords: artesunate, Ghana, incubation period, Malaria, nonimmune, Plasmodium falciparum, West Africa

Plasmodium falciparum is one of the prominent Plasmodium species, transmitted by malaria-causing vectors, in Ghana [1, 2]. This Plasmodium species is responsible for the majority of the uncomplicated and severe malaria cases that are reported in clinics and hospitals throughout Ghana [3]. Among the 5 species of Plasmodium that cause human infection, P. falciparum causes the most severe form of malaria [4]. Like the other species, P. falciparum is transmitted by the bite of an infected female Anopheles mosquito; however, it has a relatively shorter incubation period than the others [5]. The incubation period for P. falciparum is 9–14 days, whereas those of P. vivax and P. malariae are 12–17 days and 18–40 days, respectively [5]. Though a shorter incubation period of 6 days for P. falciparum has been reported, especially in the nonimmune [4], an incubation period of less than 5 days has not been reported in literature. Presented here is a case of a 4-day incubation period of P. falciparum infection in a nonimmune patient in Ghana.

A 23-year-old female medical student from the United Kingdom presented to a local hospital 5 days after arriving in Ghana, with a 24-hour history of fever, chills, bodily pains, vomiting, and diarrhea. She reported a recent incident of several mosquito bites while she was sitting outside the first night she arrived in the country. The patient had never visited Africa before this trip. She had been taking 250 mg of mefloquine once a week for malaria prophylaxis but admitted to not being compliant with her medication. The patient admitted to being a cigarette smoker and to smoking about 3 packs per week. Since the onset of her symptoms, she had vomited twice and passed loose, nonbloody stool 4 times. Upon examination, the patient exhibited several insect bite marks bilaterally on the legs and a temperature of 37.8°C; she was not dehydrated, pale, or in respiratory distress. She had a flat abdomen but reported mild epigastric tenderness. Breath sounds were clear bilaterally; in addition, heart sounds were clear, with no rubs, murmurs, or gallops. The patient was conscious and oriented to time, place, and person. Her full blood count investigation revealed a hemoglobin level (Hb) of 12.3 g/dL; white blood cell count (WBC) of 8.2 × 10⁹ µL with differentials (neutrophils 50%, lymphocytes 30%, monocytes 20%, and basophils 0%) and platelets of 158 × 10⁹ uL. A rapid diagnostic test (RDT) was positive for malaria parasites, and malaria parasites were also seen on blood film microscopy, with a parasitemia level of 2+. Urine pregnancy test was negative, and urinalysis showed no signs of infection. The patient was diagnosed with malaria and was immediately started on artesunate injection, 160 mg Q12H. The patient was also placed on 500 mL 5% dextrose normal saline infusion, alternating with 500 mL ringers lactate infusion, for 24 hours. The patient’s fever, vomiting, and diarrhea subsided 24 hours after commencing treatment. The patient was subsequently placed on oral, adult-course artemether lumefantrine (80/480 mg, repeated every 8 hours for the first day, then twice daily for the next 2 days) and paracetamol (acetaminophen) 1 g every 8 hours for 3 days. The patient’s condition improved, and she was discharged 3 days after. The patient was re-examined a week later and found to be recovering well, with resolution of her symptoms. Before leaving Ghana, 6 weeks post–hospital admission, there was no parasite observed in her blood film microscopy, and RDT was negative.

Our patient had not visited Africa or any other malaria-endemic region of the world. Therefore, she had no form of immunity against malaria. She manifested febrile symptoms 4 days after the mosquito bites, which infected her with the malaria parasite, as evidenced by the positive P. falciparum–specific RDT.

The virulence of P. falciparum is seen in the severity of the disease [4, 6]. It has also been reported to have a short incubation period and life cycle [4, 6]. The life cycle begins with the bite from an infected female Anopheles mosquito. The sporozoites’ journey through the liver to the red blood cells which is marked by 2 important periods in the life cycle: the prepatent period (from sporozoite entry to parasite detection in the blood) and the incubation period (sporozoites to the manifestation of symptoms) [4]. The duration of these periods, especially the incubation period, is usually influenced by the level of immunity of the infected patient, antimalarial prophylaxis, and previous malaria treatment [4, 7]. The nonimmune state of our patient would have been responsible for the unusually short incubation period noted in this case [4]. Though she was on mefloquine prophylaxis, which is specific to P. falciparum [8], she was not consistent in taking the course. Though the patient had a short incubation period, her symptoms were not severe, probably because she reported to the hospital as soon as the symptoms began. She presented with the typical malarial symptoms of fever, chills, vomiting, and diarrhea [9]. The physical findings were also not remarkable, which is not uncommon, even in nonimmune patients [4]. The laboratory results also reflect the unremarkable nature of this infection, as all blood cells (leukocytes, red cells, and platelets) were within normal reference range. Usually, more severe infections, especially in the nonimmune, present with thrombocytopenia, anemia, and neutrophilia with band formation [10]. RDT was used as a diagnostic tool to diagnose malaria in this patient, and the positive RDT was confirmed with microscopy, which is indeed the best practice in laboratory diagnosis of malaria [11–13]. Though the patient did not present with severe malaria and, as per the World Health Organization guidelines, being nonimmune is not a criterion for treatment with intravenous artesunate [14], the decision to start the patient on parenteral antimalarial was because of the vomiting, as she might not have been able to tolerate oral medication. Artesunate was the parenteral antimalarial drug of choice for this patient. It is a very efficacious drug, whose rapid parasite clearance, lack of or minimal clinical side effects, and an easy administration made it a better option than quinine [15, 16].

P. falciparum malaria typically manifests within 2 months of exposure to mosquito bites and generally presents clinically in travelers after their return from an endemic region [17]. Unlike the typical incubation period, this case highlights the successful management of P. falciparum infection occurring in a nonimmune patient 4 days after being bitten by mosquitoes. The patient was successfully treated with a 1-day course of parenteral artesunate, followed by a 3-day course of oral antimalarial artemisinin combination therapy.

Potential conflicts of interest. All authors: no reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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Malaria – Symptoms & causes

Overview

Malaria is a disease caused by a parasite. The parasite is spread to humans through the bites of infected mosquitoes. People who have malaria usually feel very sick with a high fever and shaking chills.

While the disease is uncommon in temperate climates, malaria is still common in tropical and subtropical countries. Each year nearly 290 million people are infected with malaria, and more than 400,000 people die of the disease.

To reduce malaria infections, world health programs distribute preventive drugs and insecticide-treated bed nets to protect people from mosquito bites. The World Health Organization has recommended a malaria vaccine for use in children who live in countries with high numbers of malaria cases.

Protective clothing, bed nets and insecticides can protect you while traveling. You also can take preventive medicine before, during and after a trip to a high-risk area. Many malaria parasites have developed resistance to common drugs used to treat the disease.

Products & Services

Symptoms

Signs and symptoms of malaria may include:

• Fever
• Chills
• General feeling of discomfort
• Headache
• Nausea and vomiting
• Diarrhea
• Abdominal pain
• Muscle or joint pain
• Fatigue
• Rapid breathing
• Rapid heart rate
• Cough

Some people who have malaria experience cycles of malaria “attacks. ” An attack usually starts with shivering and chills, followed by a high fever, followed by sweating and a return to normal temperature.

Malaria signs and symptoms typically begin within a few weeks after being bitten by an infected mosquito. However, some types of malaria parasites can lie dormant in your body for up to a year.

When to see a doctor

Talk to your doctor if you experience a fever while living in or after traveling to a high-risk malaria region. If you have severe symptoms, seek emergency medical attention.

Causes

Malaria is caused by a single-celled parasite of the genus plasmodium. The parasite is transmitted to humans most commonly through mosquito bites.

Mosquito transmission cycle

Malaria transmission cycle

Malaria spreads when a mosquito becomes infected with the disease after biting an infected person, and the infected mosquito then bites a noninfected person. The malaria parasites enter that person’s bloodstream and travel to the liver. When the parasites mature, they leave the liver and infect red blood cells.

• Uninfected mosquito. A mosquito becomes infected by feeding on a person who has malaria.
• Transmission of parasite. If this mosquito bites you in the future, it can transmit malaria parasites to you.
• In the liver. Once the parasites enter your body, they travel to your liver — where some types can lie dormant for as long as a year.
• Into the bloodstream. When the parasites mature, they leave the liver and infect your red blood cells. This is when people typically develop malaria symptoms.
• On to the next person. If an uninfected mosquito bites you at this point in the cycle, it will become infected with your malaria parasites and can spread them to the other people it bites.

Other modes of transmission

Because the parasites that cause malaria affect red blood cells, people can also catch malaria from exposure to infected blood, including:

• From mother to unborn child
• Through blood transfusions
• By sharing needles used to inject drugs

Risk factors

The greatest risk factor for developing malaria is to live in or to visit areas where the disease is common. These include the tropical and subtropical regions of:

• Sub-Saharan Africa
• South and Southeast Asia
• Pacific Islands
• Central America and northern South America

The degree of risk depends on local malaria control, seasonal changes in malaria rates and the precautions you take to prevent mosquito bites.

Risks of more-severe disease

People at increased risk of serious disease include:

• Young children and infants
• Older adults
• Travelers coming from areas with no malaria
• Pregnant women and their unborn children

In many countries with high malaria rates, the problem is worsened by lack of access to preventive measures, medical care and information.

Immunity can wane

Residents of a malaria region may be exposed to the disease enough to acquire a partial immunity, which can lessen the severity of malaria symptoms. However, this partial immunity can disappear if you move to a place where you’re no longer frequently exposed to the parasite.

Complications

Malaria can be fatal, particularly when caused by the plasmodium species common in Africa. The World Health Organization estimates that about 94% of all malaria deaths occur in Africa — most commonly in children under the age of 5.

Malaria deaths are usually related to one or more serious complications, including:

• Cerebral malaria. If parasite-filled blood cells block small blood vessels to your brain (cerebral malaria), swelling of your brain or brain damage may occur. Cerebral malaria may cause seizures and coma.
• Breathing problems. Accumulated fluid in your lungs (pulmonary edema) can make it difficult to breathe.
• Organ failure. Malaria can damage the kidneys or liver or cause the spleen to rupture. Any of these conditions can be life-threatening.
• Anemia. Malaria may result in not having enough red blood cells for an adequate supply of oxygen to your body’s tissues (anemia).
• Low blood sugar. Severe forms of malaria can cause low blood sugar (hypoglycemia), as can quinine — a common medication used to combat malaria. Very low blood sugar can result in coma or death.

Malaria may recur

Some varieties of the malaria parasite, which typically cause milder forms of the disease, can persist for years and cause relapses.

Prevention

If you live in or are traveling to an area where malaria is common, take steps to avoid mosquito bites. Mosquitoes are most active between dusk and dawn. To protect yourself from mosquito bites, you should:

• Cover your skin. Wear pants and long-sleeved shirts. Tuck in your shirt, and tuck pant legs into socks.
• Apply insect repellent to skin. Use an insect repellent registered with the Environmental Protection Agency on any exposed skin. These include repellents that contain DEET, picaridin, IR3535, oil of lemon eucalyptus (OLE), para-menthane-3,8-diol (PMD) or 2-undecanone. Do not use a spray directly on your face. Do not use products with oil of lemon eucalyptus (OLE) or p-Menthane-3,8-diol (PMD) on children under age 3.
• Apply repellent to clothing. Sprays containing permethrin are safe to apply to clothing.
• Sleep under a net. Bed nets, particularly those treated with insecticides, such as permethrin, help prevent mosquito bites while you are sleeping.

Preventive medicine

If you’ll be traveling to a location where malaria is common, talk to your doctor a few months ahead of time about whether you should take drugs before, during and after your trip to help protect you from malaria parasites.

In general, the drugs taken to prevent malaria are the same drugs used to treat the disease. What drug you take depends on where and how long you are traveling and your own health.

Vaccine

The World Health Organization has recommended a malaria vaccine for use in children who live in countries with high numbers of malaria cases.

Researchers are continuing to develop and study malaria vaccines to prevent infection.

What you need to know about malaria

Ministry of Health of the Astrakhan Region

Center for Medical Prevention

Memo for the population.

WHAT YOU NEED TO KNOW ABOUT MALARIA!

MALARIA is a severe parasitic disease widespread in countries with a tropical and subtropical climate (Asia Minor and Southeast, Africa, South America) and neighboring countries (Azerbaijan, Armenia, Uzbekistan, Tajikistan, Georgia). Malaria is characterized by attacks of fever (fever), anemia, enlargement of the liver and spleen .

Infection occurs when bitten by malarial mosquitoes. There are 4 types of malaria: tropical, three-day, four-day and oval malaria. The most severe is the tropical form, common in African countries.

According to the World Health Organization, currently 82 countries of the world are highly endemic for malaria and are in the process of combating it, and only 16 countries have achieved the elimination of malaria in their territories through anti-epidemic (preventive) measures, and 27 countries have received the status of “malaria-free”, confirmed by the WHO certificate. Russia is represented in the group of countries directing efforts to prevent local transmission of malaria.

Malaria is transmitted from a sick person to a healthy person through the bites of female mosquitoes. In addition, there are two more ways of infection – through blood transfusion and intrauterine, when a woman with malaria infects her unborn child. Entered into the human body during the bite of malarial mosquitoes, the parasites circulate in the blood, and then are carried to the liver, in the cells of which they begin their development.

The incubation period (the period from the moment of infection to the onset of the first clinical symptoms) ranges from 7 days to 1 month (in case of a tropical form of malaria, the incubation period can last up to 3 years).

Signs of the disease – the disease begins acutely: weakness, severe headache, chills appear. Then recurring attacks of fever begin, in which the body temperature rises to 40 ° and above, and lasts for several hours. The fever is accompanied by severe chills; at the end of the attack marked sweating. Attacks are repeated regularly – after a certain time (every other day, two or three days later). When such attacks occur, you should immediately seek medical help.

Tropical malaria the most severe form of malaria. The incubation period most often ranges from 8 to 16 days. Headache, fatigue, nausea, loss of appetite may occur 3-4 days before the development of the first clinical signs. The initial stages of the disease are characterized by severe chills, a feeling of heat, severe headache. In the absence of timely treatment, a fatal outcome occurs. Recovery depends on the correct selection of antimalarial drugs and the equipment of the clinic.

Malaria parasites are found in the blood of a sick person and can only be detected by examining the blood under a microscope. Treatment of this dangerous disease is carried out taking into account the type of pathogen and its sensitivity to chemotherapy drugs.

Prevention of malaria.

All travelers to tropical countries in Africa, Southeast Asia, Central and South America are recommended to carry out specific prophylaxis of malaria by taking antimalarial chemicals. More detailed advice on dosages and regimens for taking antimalarial drugs can be obtained from the offices of infectious diseases in polyclinics at the place of residence.

It must be remembered that during a stay in a malaria-prone country and within 3 years after returning home, in case of any increase in temperature, you should immediately contact a medical institution, informing the doctor about the fact of staying in tropical countries endemic for malaria.

In addition to taking antimalarial drugs, it is necessary to remember about personal non-specific prevention of malaria: the use of repellents (mosquito repellents), in the absence of air conditioning in places of accommodation, windows and doors should be blocked, electric fumigators should be used to kill mosquitoes.
People living in areas endemic for malaria should observe the following recommendations during their stay in the outbreak:

• dress in tight, as close as possible, light-colored clothing when leaving the house after sunset;
• apply repellents to exposed areas of the body;
• sleep in rooms that exclude the penetration of blood-sucking insects;
• before going to bed, treat the room with an insecticidal spray or use fumigators;
• in the presence of a large number of mosquitoes and the impossibility of screening the windows, organize sleep under a canopy made of gauze and treated with insecticide.

Remember! Only early detection of malaria patients will help them recover and prevent the spread of infection among the surrounding population!

Follow all the rules for malaria prevention! Take care of yourself!

The material was prepared by
editorial and publishing department
GBUZ JSC “Center for Medical Prevention”
2015.

414024, Astrakhan,
sq. Freedom / st. Kotovskogo, d.2/6,
Tel. (fax) 8 (8512) 51-24-77,
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Malaria and its prevention | Federal Budgetary Institution “Rostov Research Institute of Microbiology and Parasitology” of Rospotrebnadzor

Malaria and its prevention

Malaria (swamp fever, intermittent fever) is an acute infectious disease, which is characterized by the defeat of red blood cells by protozoan intracellular parasites of the genus Plasmodium (malarial plasmodium). It is transmitted through the bites of malarial mosquitoes of the genus Anopheles, through blood transfusions, or from mother to fetus during pregnancy. One bite of an infected mosquito is enough for a portion of sporozoites (spores) of the causative agent of malaria to enter the human blood or lymph along with its saliva. Next comes the complex life cycle of the malaria pathogen in the human body, the result of which is the manifestation of malaria in humans. At the same time, the blood of a person who has malaria becomes dangerous. A blood transfusion can cause infection in other people, or another mosquito can become infected when bitten.

How does malaria manifest itself?

Depending on the type of malaria pathogen, a person becomes infected with one of 4 forms of malaria – three-day malaria, four-day malaria, tropical and oval malaria. The most dangerous, which can lead to severe complications and death, is tropical malaria. The incubation period (from the moment of the bite to the first signs of the disease) – with tropical malaria is from 7 to 30 days, with other forms up to 14 months. After this, acute attacks of fever (primary attack) appear, which are replaced by a fever-free period. The number of attacks in primary malaria reaches 8-12. Then, in some cases, recovery occurs, but more often the disease again makes itself felt.

A malarial attack consists of two phases – chills and sweating. The chill phase can last from several minutes to several hours, the body temperature during this period reaches 39-40 ° C and above, the skin acquires a pale or pale blue color, becomes cold, covered with pimples. During this phase, the patient suffers from a severe headache, increasing muscle pain, vomiting, thirst, and sometimes confusion and delirium. The growing heat causes a sharp reddening of the skin of the face, an accelerated heartbeat. After the end of this phase, there is a sharp sweating, while the body temperature drops below normal. The patient’s condition improves, only weakness remains. After a while, the attacks are repeated.

Immunity after malaria is formed slowly and almost does not protect against re-infection. However, with re-infection, the disease is less severe.

The diagnosis is made on the basis of laboratory tests and the detection of typical signs.

Epidemiology of malaria

As a result of the huge complex work, by 1960 malaria was practically eliminated in the USSR, but in the 70-80s, due to the expansion of interstate ties with the countries of Africa, Southeast Asia, and Latin America, a tendency towards an increase in the incidence of imported malaria began to be observed. There is a real threat of resumption of the transmission of this infection in the south of Russia, in the Volga region and other regions. The potential for malaria to spread is determined by the length of the mosquito transmission season.

Malaria occurs seasonally: in a temperate climate for 1.5-3 months, in subtropical regions -5-8 months, in the tropics – all year round.

How real is the threat of malaria within our country? Indeed, we do not seem to have typical malarial conditions – heat and tropical swamps. But recent active human movements from north to south and back, tourist visits to the countries of Asia, Africa, Latin America can open a new chapter in the history of Russian malaria, especially since the climatic conditions in Russia do not prevent mosquitoes from living in our open spaces – anopheles carriers of malaria pathogens.

Malaria prevention

There are currently no vaccines against malaria. The main preventive measure is protection from mosquito bites. Therefore, the fight against malaria requires the active participation of each person. You need to make sure that open water does not stagnate near the house, protect your home by netting door and window openings with mosquito nets, preferably with special repellent impregnation (chemicals that repel mosquitoes). In areas dangerous for malaria (southern regions), it is better to be dressed and shod in light clothes at night. Clothing should be spacious with long sleeves, instead of shorts – trousers, instead of sandals – sneakers with socks.

The following repellents are used to protect against mosquitoes: Komarex, Biban, DEFI-plus, Evital, Taiga, Defizol, Arodet, Komarant, Defizol-2, etc.

Electrofumigators, mosquito coils, sprayers (aerosols) are used to treat the interior. Folk remedies that repel mosquitoes: the smells of cloves, eucalyptus, basil, anise – are used in the form of oils for application to the skin or adding a drop of oil to a fire source (fireplace, stove, fire, frying pan). In addition, you can use chamomile bouquets that will repel mosquitoes for 5-7 days. In a tablespoon of any cologne, you can add 8-10 drops of these oils and wipe the exposed areas of the body. To relieve itching after mosquito bites, you can use crushed leaves of bird cherry, mint, parsley, plantain, garlic clove, dandelion juice, green onion, soda solution (1 teaspoon of baking soda or ammonia in a glass of water), Vietnamese Asterisk balm.

Need to know!

• – Everyone traveling to countries with a tropical and subtropical climate is obliged to consult with a local doctor about the danger of contracting malaria, the need to take antimalarial drugs and the absence of contraindications to this group of drugs.
• – The use of drugs should be started one to two weeks before the onset of the possibility of infection, continue the entire period of risk and 4 weeks after its termination.
• – If you have malaria, you must follow all the doctor’s prescriptions.