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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WHO: Malaria is a deadly threat to pregnant women and babies

Pregnancy reduces a woman’s immune system and her resistance to infection. In this regard, women during this period are more vulnerable to the disease, which in this case often leads to anemia and death. Moreover, malaria interferes with the healthy development of the fetus – children of infected mothers are more likely to be born prematurely and with low birth weight, which leads to an increase in infant mortality.

“Malaria has a significant impact on maternal and child health,” says Pedro Alonso, Director of the WHO Global Malaria Programme. “This year, for the first time, we devoted our annual report to this issue and we hope to draw the attention of states to this problem, the solution of which should be a priority.”

In general, according to the authors of the report, preventive measures to protect pregnant women and children from malaria are bearing fruit. Despite the fact that the incidence rates among these populations remain unacceptably high, they have decreased compared to the previous period. However, the overall statistics for countries that are most susceptible to the spread of infection remained almost unchanged between 2014 and 2018. Last year, 228 million people fell ill with malaria, 405 thousand of them died from the disease. The vast majority of those infected are in sub-Saharan Africa.

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Malaria continues to pose a threat to Brazilians, especially in the north of the country.

“We need more money to successfully fight the disease,” says Alonso. According to him, this first of all requires the political will of the leadership of countries where malaria poses the greatest threat to the population. In addition, according to WHO, it is necessary to improve the coordination of efforts between the various partners involved in the fight against infection, as well as improve the methods of collecting and processing information. Funding challenges remain, with only $2.7 billion of the $5 billion requested for malaria control last year.

The report highlights individual successes. In 49 countries out of 100 endemic for malaria, less than ten thousand cases of infection have been registered. Also this year, Argentina and Algeria have been officially declared malaria-free nations. Last year, we recall, Uzbekistan and Paraguay added to this list.

“This is a great public health achievement,” said the WHO representative. Iran, El Salvador and China also report no malaria. According to Pedro Alonso, these states can receive a WHO certificate of complete victory over the disease as early as next year. Other notables include India and Uganda, which have managed to significantly reduce the number of transmission cases.

Malaria vaccine

Malaria, remember, is a life-threatening disease caused by parasites. It is transmitted to humans by the bites of infected female Anopheles mosquitoes. The first symptoms—fever, headache, and chills—may be mild, making malaria difficult to detect.

Prevention is mainly through vector control. The most effective methods are insecticide-treated mosquito nets and indoor spraying of insecticides. Now doctors have another tool at their disposal.

“For almost a hundred years, mankind has been trying to develop a vaccine against malaria, and this is the first time such a vaccine has gone through the full development cycle and is being reviewed by the relevant authorities,” the WHO spokesman said. According to him, in the next five years, 300,000 children at risk will be vaccinated annually.

The malaria vaccine is not perfect – it only provides 40% protection and is recommended as a supplement to basic vector control methods. The WHO calls this vaccine “the first step” and hopes that it will be improved over time.

WHO report shows growing numbers of pregnant women and children with malaria prevention, but more action and funding needed to accelerate global response to malaria

More pregnant women and children reach malaria prevention, says WHO report, but more action and funding needed to accelerate global response to malaria

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• A growing number of pregnant women and children are receiving malaria prevention supplies, according to a WHO report, but more action and funding is needed to accelerate global action against the disease

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According to the 2019 World Health Organization Malaria Report, sub-Saharan Africa has seen a significant increase in the number of pregnant women and children provided with insecticide-treated mosquito repellents in recent years.
nets and malaria prophylaxis.

However, progress in reducing morbidity and mortality from malaria in countries with the highest prevalence of the disease has slowed down and needs to be accelerated. Last year, mainly in sub-Saharan Africa, malaria was estimated
228 million fell ill and 405,000 died.

Pregnancy reduces women’s immunity to malaria, making them more susceptible to infection and at greater risk of illness, severe anemia and death. Malaria during pregnancy also interferes with fetal development,
which increases the risk of preterm birth and low birth weight, one of the main causes of infant mortality.

“Pregnant women and children are most at risk of malaria, and we will not make progress against this disease without prioritizing action on these two groups,” said WHO Director-General Dr Tedros Adhanom Ghebreyesus.
“There are some positive results, but the amount of suffering and death associated with malaria remains unacceptable because in most cases it is all preventable. Lack of results in reducing morbidity and mortality
against malaria is of the deepest concern.”

In 2018, 11 million pregnant women were infected with malaria in moderate and high malaria areas in sub-Saharan Africa. As a result, almost 900,000 babies were born underweight.

Despite some encouraging results in the delivery of malaria prevention services to pregnant women and children, between 2014 and 2018 countries most affected by malaria showed no improvement in overall performance
morbidity.

One of the main difficulties remains the lack of funding. In 2018, the total financial resources allocated to malaria control and elimination activities reached about US$ 2.7 billion, well short of the target
in the global strategy funding target of $5 billion.

Heavy Burden of Disease Demands Effective Action

Last year, WHO and the WBO Malaria Partnership launched the High Burden of Disease Demands Effective Action initiative to reduce malaria cases and deaths
countries with the highest rates of morbidity and mortality. The initiative is being implemented by 11 countries, which accounted for about 70% of the global malaria burden in 2017. By November 2019d. the activities envisaged by this initiative were
initiated in nine of these countries. Two of them registered a significant decrease in the number of malaria cases in 2018 compared to the previous year (India (down 2.6 million cases) and Uganda (down 1.5 million cases)).

Prevention of malaria in women and children

An estimated 61% of pregnant women and children were provided with insecticide-treated mosquito nets in sub-Saharan Africa in 2018, compared with only 26% in 2010.

Preventive treatment coverage for malaria during pregnancy (3 or more doses of intermittent chemoprophylaxis as recommended) in antenatal care facilities increased from 22% in 2017 to 31% in 2018.

To protect pregnant women and children from malaria, WHO recommends use of effective malaria vector control agents (insecticide-treated bed nets or indoor residual spraying).
The key to successfully achieving the goals of the Global Technical Strategy for Malaria Control 2016–2030 is to build a strong health service delivery system that provides improved access to the above
and other proven malaria control tools, including prompt diagnosis and treatment.

Yet far too many women still do not receive the recommended number of doses of intermittent preventive therapy or do not have access to it at all. Some women do not have access to prenatal care. Those who are able to apply
in an antenatal care facility, do not receive preventive treatment for malaria due to lack of necessary drugs or prescription from a doctor.

For children under 5 years of age in the Sahel subregion of Africa, WHO recommends seasonal malaria chemoprophylaxis (SCM) during the rainy season, a period of high incidence. In 2018, malaria preventive treatment received
72% of children with relevant indications.

Another recommended intervention is intermittent preventive therapy for infants, which consists of prescribing antimalarial drugs to infants as part of the national immunization system.
This activity is currently being piloted in Sierra Leone.

“Intermittent chemoprophylaxis is an excellent way to save the life and health of infants,” said Dr Pedro Alonso, Director of the WHO Global Malaria Programme. WHO welcomes new initiative
UNITAID, which was announced today, aims to accelerate the process of introducing and scaling up intermittent chemoprophylaxis for infants in other malaria-endemic countries in sub-Saharan Africa.”

Prompt diagnosis and treatment are vital. However, many parents do not see a doctor when their child has a fever. According to a recent study in sub-Saharan Africa, 36% of children
with fever do not receive any medical care.

Comprehensive community-based service delivery for malaria, pneumonia and diarrhea can close a gap in health care for people in hard-to-reach communities. Although this approach is implemented in 30 countries, most
Sub-Saharan Africa is having difficulty implementing it, mainly due to a lack of funding.

Note to editors

Country progress towards malaria elimination

Despite slow progress towards malaria elimination in many high-burden countries, more and more low-burden malaria countries are confident
moving towards elimination of the disease. In 2018, 27 countries reported fewer than 100 cases of malaria. In 2017, only 17 countries managed to achieve such indicators. At least 10 countries where it is implemented
the WHO Elimination 2020 initiative, are well on their way to the global strategy target for malaria elimination by 2020. Latest progress report on the Elimination 2020 strategy
available at: https://www.who.int/malaria/publications/atoz/e-2020-progress-report-2019/en/.

Free worldwide
from malaria received 38 countries. WHO announces this status if a country can prove that the local chain of malaria transmission has been interrupted and has not recovered for at least three years. With a complete list of such countries
available at: https://www. who.int/malaria/areas/elimination/malaria-free-countries/en/.

Progress in the Greater Mekong Subregion

The six countries of the Greater Mekong Subregion also made good progress. Between 2010 and 2018 the subregion achieved a 76% reduction in malaria cases and a 9% reduction in malaria deaths5%. In particular,
the report notes a sharp decline in the number of cases of P. falciparum malaria, which is a major concern due to the ongoing threat of resistance to antimalarial drugs in this pathogen.

WHO Malaria Elimination Strategic Advisory Group

The WHO Malaria Elimination Strategic Advisory Group has identified the establishment of a new agenda for research and development areas. The advisory group believes that successful malaria eradication also requires universal access to affordable and people-centred health services, the establishment of reliable, rapid and accurate surveillance and response systems, and the development of national and subnational strategies adapted to local conditions.