What is the typical incubation period for Plasmodium vivax malaria. How can unexpectedly long incubation periods impact diagnosis and control efforts. Why do some P. vivax strains exhibit prolonged latency before symptoms appear. What factors influence the variability in malaria incubation periods.

The Intriguing Case of Extended Plasmodium vivax Incubation Periods

Malaria, a parasitic disease transmitted by Anopheles mosquitoes, continues to pose significant global health challenges. While Plasmodium falciparum often garners the most attention due to its severity, Plasmodium vivax presents unique complexities that warrant careful consideration. One particularly intriguing aspect of P. vivax malaria is its potential for extended incubation periods, which can have profound implications for diagnosis, treatment, and control efforts.

Typical Incubation Periods for Malaria Species

To understand the significance of extended P. vivax incubation periods, it’s crucial to first establish the typical timeframes for various malaria species:

• Plasmodium falciparum: 9-14 days
• Plasmodium vivax: 12-17 days
• Plasmodium malariae: 18-40 days

These ranges represent the average time between an infected mosquito bite and the onset of clinical symptoms. However, recent observations have challenged these established norms, particularly for P. vivax.

Unexpected Findings: Long-Latency P. vivax Cases in Brazil

A study conducted in Rio de Janeiro, Brazil, has shed light on cases of P. vivax malaria with remarkably extended incubation periods. Among 49 confirmed P. vivax infections, seven patients exhibited incubation periods ranging from three to 12 months. These individuals had primarily traveled to Brazilian Amazonian states, with one case linked to Indonesia.

Why is this finding significant? Rio de Janeiro is a non-endemic area for malaria, making it an ideal location to accurately assess incubation periods without the confounding factor of potential re-exposure.

Key Observations from the Brazilian Study

• 63% of confirmed malaria cases were caused by P. vivax
• 14% of P. vivax cases showed extended incubation periods
• None of the patients with prolonged incubation had taken antimalarial chemoprophylaxis

Historical Context: The Discovery of Long-Latency P. vivax Strains

The concept of P. vivax strains with extended incubation periods is not entirely new. Early 20th-century researchers laid the groundwork for understanding this phenomenon:

• 1901-1902: Korteweg in Holland first described delayed relapses and variations in incubation periods
• 1935: Nikolaev proposed two P. vivax strains with differing incubation periods
• 1946: Shute suggested a correlation between sporozoite inoculum and incubation length

These early observations sparked debates about the underlying mechanisms responsible for prolonged latency in P. vivax infections.

Theories Behind Extended P. vivax Incubation Periods

Several hypotheses have been proposed to explain the phenomenon of long-latency P. vivax strains:

1. Adaptive Evolution

Some researchers speculate that extended incubation periods may be an adaptive trait, allowing P. vivax to survive in regions with prolonged periods of vector absence. This theory suggests that the parasite has evolved to “hibernate” within the host, timing its emergence to coincide with the return of suitable mosquito populations.

2. Sporozoite Load

Early theories proposed an inverse relationship between the number of infective sporozoites and the length of the incubation period. However, subsequent research has challenged this notion, demonstrating that inherent properties of specific strains can determine latency regardless of inoculum size.

3. Parasite “Senility”

Some historical explanations attributed prolonged latency to the “senility” of sporozoites towards the end of the transmission season. This hypothesis suggested that older sporozoites might take longer to establish a productive infection.

4. Genetic Diversity

Modern genetic studies have revealed substantial diversity among P. vivax strains. This variability could account for differences in biological characteristics, including incubation periods.

Implications of Extended Incubation Periods for Malaria Control

The recognition of P. vivax strains with prolonged incubation periods has significant ramifications for malaria control efforts:

1. Diagnostic Challenges

Extended latency complicates the diagnosis of P. vivax malaria, especially in non-endemic areas. Healthcare providers may not consider malaria as a potential cause of fever in patients with distant travel history, leading to delayed or missed diagnoses.

2. Surveillance and Monitoring

Long incubation periods can obscure the true origin and timing of infections, making it difficult to accurately track malaria transmission patterns and implement targeted interventions.

3. Chemoprophylaxis Strategies

Current antimalarial prophylaxis regimens may need reevaluation to account for the possibility of delayed P. vivax emergence. This could impact recommendations for travelers to endemic areas.

4. Elimination Efforts

In regions approaching malaria elimination, long-latency P. vivax infections could serve as hidden reservoirs, potentially reigniting transmission after prolonged periods of apparent absence.

Potential Advantages of Extended Incubation for P. vivax

While prolonged latency presents challenges for malaria control, it may confer certain advantages to the parasite:

• Improved survival in seasonal transmission settings
• Evasion of host immune responses
• Increased chances of transmission to new hosts
• Ability to persist in areas with intermittent vector presence

Understanding these potential benefits could provide insights into the evolutionary pressures shaping P. vivax biology.

Future Research Directions and Unanswered Questions

The discovery of P. vivax cases with unexpectedly long incubation periods raises several important questions for future research:

1. Are new P. vivax strains emerging in endemic regions?
2. Have existing strains undergone changes in their biological cycles?
3. What molecular mechanisms underlie extended latency?
4. How prevalent are long-latency P. vivax infections globally?
5. What are the implications for current diagnostic, treatment, and prevention strategies?

Addressing these questions will require a multidisciplinary approach, combining epidemiological studies, molecular genetics, and clinical research.

Recommendations for Healthcare Providers and Travelers

In light of the potential for extended P. vivax incubation periods, several recommendations emerge:

For Healthcare Providers:

• Maintain a high index of suspicion for malaria in patients with fever, regardless of the time elapsed since travel to endemic areas
• Consider malaria testing even in cases of prolonged or atypical presentations
• Educate patients about the possibility of delayed symptom onset and the importance of seeking prompt medical attention

For Travelers:

• Adhere to recommended chemoprophylaxis regimens, including post-travel continuation
• Use personal protective measures against mosquito bites, even in areas with seasonal transmission
• Remain vigilant for symptoms of malaria for an extended period after returning from endemic regions

By implementing these recommendations, we can improve the detection and management of P. vivax infections with atypical incubation periods.

The Global Impact of Long-Latency P. vivax Malaria

While the Brazilian study provides valuable insights into extended P. vivax incubation periods, it’s essential to consider the global implications of this phenomenon:

Geographical Distribution

Long-latency P. vivax strains have been historically associated with temperate regions, but their presence in tropical areas like the Amazon raises questions about their true distribution. Are these strains more widespread than previously thought?

Impact on Elimination Strategies

As countries progress towards malaria elimination, the persistence of long-latency P. vivax infections could pose significant challenges. How can elimination programs account for the potential resurgence of cases after prolonged periods of apparent absence?

Cross-Border Transmission

Extended incubation periods complicate efforts to track and prevent cross-border malaria transmission. How can neighboring countries collaborate to address this issue, particularly in regions with high population mobility?

Economic Considerations

The need for prolonged surveillance and potential changes to chemoprophylaxis recommendations could have economic implications for both healthcare systems and travelers. How can we balance the cost of extended monitoring with the benefits of improved detection and prevention?

Molecular Insights into P. vivax Latency

To fully understand the phenomenon of extended P. vivax incubation periods, we must delve into the molecular mechanisms at play:

Hypnozoites: The Key to Latency

P. vivax’s ability to form dormant liver stages, known as hypnozoites, is central to its capacity for delayed activation. What factors trigger hypnozoite reactivation, and how do they relate to extended incubation periods?

Genetic Markers

Identifying genetic markers associated with long-latency strains could revolutionize our approach to P. vivax surveillance and treatment. Are there specific genomic signatures that predict a strain’s propensity for extended incubation?

Epigenetic Regulation

Recent research has highlighted the role of epigenetic mechanisms in controlling P. vivax gene expression. How might epigenetic factors contribute to the timing of parasite activation and the duration of latency?

Host-Parasite Interactions

The interplay between P. vivax and the human host’s immune system likely influences the length of the incubation period. What host factors might contribute to prolonged latency, and how can this knowledge inform new therapeutic approaches?

Innovative Approaches to Addressing Long-Latency P. vivax

As our understanding of extended P. vivax incubation periods grows, novel strategies for detection, prevention, and treatment emerge:

Advanced Diagnostics

Developing highly sensitive diagnostic tools capable of detecting low-level parasitemia during the extended incubation phase could revolutionize early intervention efforts. What biomarkers or molecular signatures might serve as indicators of latent P. vivax infection?

Tailored Chemoprophylaxis Regimens

Customizing preventive medication schedules based on the risk of exposure to long-latency strains could enhance protection for travelers and residents in endemic areas. How can we balance the need for extended prophylaxis with concerns about drug resistance and adherence?

Targeted Hypnozoite Elimination

Developing drugs specifically designed to eliminate hypnozoites could prevent both relapses and extended incubation periods. What novel compounds or treatment strategies show promise in targeting this elusive parasite stage?

Predictive Modeling

Integrating data on P. vivax strain genetics, environmental factors, and host characteristics could lead to more accurate predictions of incubation periods and transmission risks. How can machine learning and artificial intelligence contribute to these modeling efforts?

The Role of Climate Change in P. vivax Epidemiology

As global temperatures rise and weather patterns shift, the epidemiology of P. vivax malaria is likely to evolve:

Expanding Vector Ranges

Climate change may allow Anopheles mosquitoes to colonize new regions, potentially introducing P. vivax to areas previously considered non-endemic. How might this impact the global distribution of long-latency strains?

Seasonal Transmission Patterns

Altered seasonal rhythms could affect the timing of P. vivax transmission and the selective pressures on parasite latency. Will climate change favor the spread of long-latency strains or promote the evolution of new transmission strategies?

Human Migration and Displacement

Climate-driven population movements may facilitate the spread of P. vivax between regions, potentially introducing long-latency strains to new areas. How can health systems prepare for these changing patterns of human mobility and disease transmission?

Ethical Considerations in Long-Latency P. vivax Research

As we pursue a deeper understanding of extended P. vivax incubation periods, several ethical considerations come to the forefront:

Informed Consent for Long-Term Monitoring

Given the potential for delayed symptom onset, how can researchers ethically design studies to monitor participants over extended periods? What information should be provided to study volunteers regarding the risk of late-emerging infections?

Access to Prevention and Treatment

As our understanding of long-latency P. vivax evolves, ensuring equitable access to updated preventive measures and treatments becomes crucial. How can we address potential disparities in access to new interventions, particularly in resource-limited settings?

Balancing Individual and Public Health Interests

In some cases, the interests of individuals (e.g., avoiding prolonged medication regimens) may conflict with public health goals (e.g., preventing transmission of long-latency infections). How can policymakers and healthcare providers navigate these competing priorities?

Data Privacy and Long-Term Surveillance

Effective monitoring of long-latency P. vivax cases may require extensive data collection and analysis. How can we balance the need for comprehensive surveillance with individuals’ rights to privacy and data protection?

By addressing these ethical considerations proactively, we can ensure that research into extended P. vivax incubation periods proceeds responsibly and equitably, maximizing benefits while minimizing potential harms.

Unexpectedly long incubation period of Plasmodium vivax malaria, in the absence of chemoprophylaxis, in patients diagnosed outside the transmission area in Brazil

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• Malar J
• v.10; 2011
• PMC3120730

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Malar J. 2011; 10: 122.

Published online 2011 May 14. doi: 10.1186/1475-2875-10-122

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Background

In 2010, Brazil recorded 3343,599 cases of malaria, with 99. 6% of them concentrated in the Amazon region. Plasmodium vivax accounts for 86% of the cases circulating in the country. The extra-Amazonian region, where transmission does not occur, recorded about 566 cases imported from the Amazonian area in Brazil and South America, from Central America, Asia and African countries. Prolonged incubation periods have been described for P. vivax malaria in temperate climates. The diversity in essential biological characteristics is traditionally considered as one possible explanation to the emergence of relapse in malaria and to the differences in the duration of the incubation period, which can also be explained by the use of chemoprophylaxis. Studying the reported cases of P. vivax malaria in Rio de Janeiro, where there is no vector transmission, has made it possible to evaluate the extension of the incubation period and to notice that it may be extended in some cases.

Methods

Descriptive study of every malaria patients who visited the clinic in the last five years. The mean, standard deviation, median, minimum and maximum of all incubation periods were analysed.

Results

From the total of 80 patients seen in the clinic during the study time, with confirmed diagnosis of malaria, 49 (63%) were infected with P. vivax. Between those, seven had an estimated incubation period varying from three to 12 months and were returned travellers from Brazilian Amazonian states (6) and Indonesia (1). None of them had taken malarial chemoprophylaxis.

Conclusions

The authors emphasize that considering malaria as a possible cause of febrile syndrome should be a post-travel routine, independent of the time elapsed after exposure in the transmission area, even in the absence of malaria chemoprophylaxis. They speculate that, since there is no current and detailed information about the biological cycle of human malaria plasmodia’s in Brazil, it is possible that new strains are circulating in endemic regions or a change in cycle of preexisting strains is occurring. Considering that a prolonged incubation period may confer advantages on the survival of the parasite, difficulties in malaria control might arise.

The malaria incubation period is defined as the time elapsed between exposure to the infectious agent (through the bite of the Anopheles mosquito) and the manifestation of the first clinical sign or symptom. Usually, these periods vary depending on the species of Plasmodium causing malaria. The average incubation period is 9-14 days for Plasmodium falciparum, 12-17 days for infections by Plasmodium vivax and 18-40 days for infections caused by Plasmodium malariae [1].

The relapse patterns and variations in the length of the incubation period, including a delay of four months or longer, was first described by Korteweg in Holland between 1901 and 1902 (cited by Swellengrebel and De Buck [2]). Later, in 1935, Nikolaev proposed that there were two strains of P. vivax (cited by Tiburskaya [3]) with different incubation periods and gave the sub-specific taxonomic name of P. vivax hibernans to the variety with the longest incubation period. It was suggested that this sub-species had adapted to more northern latitudes where the anopheles vector was absent for much of the year. Shute (1946) [4] proposed that the sporozoite infective inoculum would be inversely related to the prepatent and incubation period. However, in Moscow, Tiburskaya [3] demonstrated situations in which the length of the incubation period did not depend on the number of inoculated sporozoites, but instead was determined by the inherent properties of the strains. It was also believed that strains with prolonged latency could be attributed either to the “senility” of the sporozoite towards the end of the season or to the low number of sporozoites in the infective bite [5].

According to Shute [5], the differences between the P. vivax strains could be explained by the assumption that, in varying proportions, all strains of P. vivax produce two types of sporozoites: one eliciting short prepatent periods (Type I) and the other lying dormant or developing slowly to give rise to long prepatent periods (Type II). In this model, the latter type would greatly predominate in “temperate strains”, but not in tropical ones. It was thought that relapses of P. vivax could in reality correspond to a delayed parasitaemia arising from Type II sporozoites. In the same year, Garnham stated that the length of the incubation period was considered the major biological difference between Dutch, Madagascar, and USSR strains, and although there was no evidence of specifically dormant forms, it was believed that if certain sporozoites failed to develop in the normal time, they could be reactivated by an unknown factor one year or more after inoculation [6].

In 1980, Warwick [7] proposed that the ambient winter temperatures could extend the incubation period of P. vivax in humans, based on the concept that temperatures persistently above a minimum of 23.9°C were required for sporozoite maturation [8], thereby limiting vector transmission in cold areas. Finally, in 2007, Nishiura et al in Korea [9] suggested that the incubation periods would likely reflect adaptation to the behaviour of the principal vector of the region, which hibernates during the winter season. Currently, several reports associate the extension of the incubation period to malaria prophylaxis among travellers [10,11].

The opportunity to study some cases of P. vivax malaria in Rio de Janeiro, where there is no vector transmission, has made it possible to detect and to evaluate certain peculiar aspects of the natural evolution of the disease in human beings. One main aspect was the extension of time required for the parasites to progress through liver schizogony and produce symptoms by their propagation in the bloodstream.

Plasmodium vivax infections with prolonged periods of incubation and no association with malaria prophylaxis in patients from the Amazon region in Brazil and in one patient from Indonesia are presented.

In addition to demonstrating an interesting clinical situation and the need for clinicians to consider the diagnosis of malaria in a patient presenting symptoms a long time after exposure, even in the absence of chemoprophylaxis, our cases raise questions regarding the understanding of the biology of the host/P. vivax interactions.

Design and study location

This is a descriptive study conducted at the Acute Febrile Disease Outpatient Clinics of IPEC, Fiocruz, a specialized post-travel care clinic located in Rio de Janeiro, from January, 2005, to February, 2010.

Selection of patients

All malaria patients presenting clinical signs or symptoms of malaria and positive thick blood smears were enrolled in the study. The following variables of interest were recorded: estimated incubation period, place and year of infection, date of diagnosis, previous malaria history and year of the first malarial infection. No patients had malaria prophylaxis, had not received blood transfusions nor had close contact with a person with malaria after departure from the endemic area. No patients had haemoglobinopathies. Because it was not possible to determine the date of exposure to the infective mosquito bites, the minimum incubation period was estimated based on literature (9 days for P. falciparum and 12 days for P. vivax) [1]. The maximum was estimated by the interval between the day of the return from the malaria transmission area until the first day of symptoms. The mean, standard deviation, median, minimum and maximum of all incubation periods are shown in Table . Each patient gave fully informed consent. Children were not included.

Table 1

Time between the day of the return from the malaria transmission area and the first day of onset of symptoms of malaria cases diagnosed in the Acute Febrile Diseases Clinic, Rio de Janeiro (2005 until January 2010)

Open in a separate window

d = days; h = hours

The project was submitted and approved by the Ethical Committee in Research of the Instituto de Pesquisa Clínica Evandro Chagas (IPEC), Fiocruz (number 0020. 0.009.000-07), maintaining strict secrecy and confidentiality of the information obtained.

Detection and quantification of malaria parasites

Thin and thick blood smears were stained with Giemsa and analysed by light microscopy using an immersion oil lens (X100 objective magnification) to identify the parasite species and determine the density of Plasmodium asexual and sexual stages, according to standard procedures [12]. Each smear was evaluated separately by two expert microscopists who had been blinded to the clinical status of the patients.

Data analysis

All information was recorded on a standardised form for study and subsequently entered into a database using Statistical Package for Social Sciences (SPSS). SPSS-WIN 16.0 was also used for data analysis.

During the study period, 80 malarious patients were diagnosed and treated. Of them, 50 (62.5%) presented with P. vivax malaria, 20 (25%) with P. falciparum malaria, eight (10%) with mixed (P. vivax/P. falciparum) infection and two (2.5%) with P. malariae. All patients were travellers, most of them (51) from the Amazon region, in Brazil; 17 travelled from Africa, 11 were from South and Central America, and one was from Indonesia.

Time between the day of return from the malaria transmission area and the first day of onset of symptoms recorded for all patients diagnosed in the Acute Febrile Diseases Clinic Rio de Janeiro (2005 until January 2010) was four times longer for P.vivax than for Plasmodium falciparum and is illustrated in Table . The estimated mean incubation period for all cases was 31 days (SD 51 days), with a median of 12 days and extreme values of 9 and 360 days.

An estimated incubation period longer than 90 days was observed in seven (14%) of the patients with P. vivax malaria (Figure ). The average incubation period (147 days) among this group was about twelve times longer than the classical period described in the literature (12 days). Malaria was contracted during visits to the Amazonian region (in six cases) and Indonesia (in one). Their details are described in Table . There were no differences in clinical presentation between individuals with P. vivax infection with different incubation periods. No patient had undergone malaria chemoprophylaxis or had taken any pharmacological drug that could inhibit the parasite’s development.

Open in a separate window

Estimated incubation period in days for each P. vivax infected patient.

Table 2

Patients with P. vivax infection and estimated incubation period ≥ 90 days

Open in a separate window

NA = non aplicable

This is the second report of prolonged incubation period of malaria in patients without chemoprophylaxis coming from an endemic area in Brazil. A recent paper by one of the authors of this report (Tauil PL) described three cases of vivax malaria originating from the Amazon region and diagnosed in Brasilia, Federal District, six months after departure from the endemic region in 2008 [13]. Two of those patients were infected in the same town (São Gabriel da Cachoeira, Amazonas State, Brazil), as one of the patients in the present study. Some of the cases in this study were detected in 2005 and 2006, prior to the cases detected in Brasilia and reported by Tauil et al [13]. All possible current explanations for these prolonged periods (use of malaria prophylaxis or other pharmacological drugs that would inhibit the Plasmodium development; blood transfusions; close contact with a person with malaria after departure from the endemic area or haemoglobinopathies) were eliminated. The observation of a longer incubation period (≥90 days) in 14% of the P. vivax malaria patients seen at IPEC, in Rio de Janeiro, may indicate the importance of monitoring these characteristics worldwide, as it may represent an evolutionary change in P. vivax behaviour. The average incubation period of P. vivax malaria presented here was approximately twelve times longer than the classical period described in the literature. In this study, the extended incubation time occurred in both prime-infected (130 days) and non-prime-infected (131 days) patients, so the possibility of relapse among non-prime-infected patients cannot be ruled out. However, in two patients previously infected with malaria, the period between the last infection and the current clinical manifestation was five and six years, by far exceeding the maximum period of relapse reported for P. vivax (three years) [14]. Cities such as Rio de Janeiro, as well as areas in the northern hemisphere without disease transmission may be considered strategic places for monitoring incubation period, clinical cures and treatment failure in cases of malaria, facilitating the identification of the above features without misinterpreting variations as the result of new infections.

During the five years of surveillance (2005-2010) no seasonal differences in the prevalence of clinical P. vivax malaria diagnosed outside the endemic area were observed between these cases with prolonged incubation periods. Regardless, the postulate that extended incubation periods may represent an adaptation of the species to overcome cold temperatures, thereby conferring advantages for the survival of the parasite, does not seem to fit the reality of tropical areas, where the temperature is rarely below 10°C. Although the role of strain-specific variation in prolonged incubation periods has been questioned by some authors [9], it is possible that new strains of Plasmodium are circulating in tropical areas, especially in the Amazon, which is a region frequently visited by foreigners and which has seen the movements of troops.

Fever is one of the most common clinical signs in returning travellers [15-20]. The incubation periods of potential pathogens should be considered when formulating differential diagnoses. The geographic location(s) visited, the traveller’s activities and the frequency of specific diseases in the region are usually taken into account. According to the observations reported here, malaria should be considered among the diseases with longer incubation periods (weeks to months after return), even in patients without malaria chemoprophylaxis.

It is classically considered that the co-existence of short and long-term incubation periods may imply that prolongation of this phase is either a genetically regulated feature of parasites or is controlled within Anopheles spp. by mechanisms yet to be defined. Therefore, new molecular tools need to be used for investigation of biological characteristics and origin of the Plasmodium strains that presents a prolonged incubation time in Brazilian patients that have never visited the temperate zone.

Plasmodium vivax, responsible for 86% of malaria cases in Brazil [21], has long been neglected and mistakenly [22]. The change in incubation period reported here is particularly important in theory, because it raises the possibility of changes in the biology and evolution of this organism, entering into strategic debates taking place on malaria epidemiology and control; and in practice because malaria is one of the most important infectious diseases among travellers and a long incubation period is one of the causes of missing early malaria diagnosis.

The authors declare that they have no competing interests.

PB – responsible for conception and design of the work, interpretation of data and drafting the manuscript.

APC – analyzed data, made the literature review and helped drafting the manuscript.

RSP – helped analyzing the data and reviewed the text.

CSB – responsible for the production of data and helped reviewing the text.

SS – carried out the parasitological examinations and helped in the literature review.

PLT – helped in interpretation of data, literature review and reviewing the manuscript.

CTDR – helped in the design of the work and reviewed the text up to the final version to be published.

All authors read and approved the final manuscript.

This work was supported by CGLAB from the Secretaria de Vigilância em Saúde to the Centro de Pesquisa Diagnóstico e Treinamento em Malária (CPD-Mal), Fiocruz, Ministério da Saúde, Brazil.

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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
• PMC6335624

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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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25 April is World Malaria Day

April 25, 2023

Every year April 25 is World Malaria Day

Malaria is an anthroponotic transmissible protozoal disease caused by protozoan parasites of the genus Plasmodium. Most often, malaria is transmitted from a sick person to a healthy person through the blood-sucking of female mosquitoes. There are two more ways of infection – through blood transfusion and intrauterine, when a woman with malaria infects her unborn child. Parasites that enter the human body circulate in the blood, and then are carried to the liver, in the cells of which they develop.

4 types of pathogen parasitize in humans: P. vivax, P.ovale, P.malariae and P.falciparum. The latter causes the most severe and frequently encountered form – tropical. The incubation period for tropical malaria is usually 8 to 16 days. In other forms, the incubation period is different and can be 2 years or more.

The disease is characterized by damage to erythrocytes, recurrent cyclic course, anemia and periodic febrile attacks (body temperature rises to 40 degrees and above, accompanied by chills and severe sweating at the end of the attack), alternating with fever-free periods, the pattern of occurrence of which corresponds to the development cycle of the pathogen. Therefore, if there is a clear recurrence of fever attacks after a certain time, one should think about a possible disease with malaria.

Tropical malaria can take a “malignant course” if diagnosed late and treated more than 6 days after onset. Mortality in the malignant course of tropical malaria can reach 100% and largely depends on the time of initiation of treatment, the correct selection of antimalarial drugs and the equipment of the clinic. Children, pregnant women, and non-immune adults are more likely to develop severe tropical malaria.

In order to prevent malaria, it is necessary to start taking antimalarial drugs a week before leaving for malaria-endemic countries in Africa, Southeast Asia, and South America. It is necessary to continue taking the drugs for the entire period of stay and for another 4-6 weeks after returning. It is also necessary to remember about protecting the premises from the penetration of mosquitoes (nets on windows and doors) and protecting the body from mosquito bites with the help of special repellents.

Over the past 10 years in the Clinical Infectious Diseases Hospital. S.P. Botkin, 139 patients with malaria were hospitalized, two cases were fatal in 2016 and 2019. In 2020, 8 patients were treated for malaria in the hospital, in 2021 – 12, in 2022 – 13. This year, 2 cases of malaria have already been recorded.

Be aware of symptoms after returning from a malaria-prone region. If you suddenly develop a fever, headache, or muscle pain, seek immediate medical attention. Do not forget that in rare cases, the incubation period for the development of malaria is 3 years!

December 08, 2020

About the work of medical staff at the Mariinsky Hospital

October 17, 2017

Petersburgers actively vote for their favorite doctors on the site of the Our Favorite Doctor contest

Beware of malaria: prevention and treatment of an infectious disease

With the onset of summer, the flow of tourists to countries with a tropical climate increases.

In order not to spoil your vacation abroad with illness, you should be aware of preventive measures for the most common exotic diseases. With the primary symptoms of the disease, they should be recognized in time. Let’s talk about malaria.

Beware of the blood-sucking

Malaria is a parasitic disease with an acute and sometimes protracted course, characterized by febrile attacks, enlargement of the liver, spleen, and development of anemia. The causative agents of malaria belong to the genus Plasmodium. P. vivax. The causative agent of three-day malaria is widespread in Asia, Oceania, South and Central America. P.ovale (oval-malaria) – the causative agent of three-day malaria; its range is mainly limited to Equatorial Africa, isolated cases have been reported on the islands of Oceania and in Thailand. P.malariae – the causative agent of four-day malaria and P.falciparum – the causative agent of tropical malaria are widespread in offshore Africa, as well as in some countries of Asia, Oceania, South and Central America.

Malaria is transmitted when a human is bitten by an Anopheles mosquito that carries the pathogen. The mosquito itself becomes infected by feeding on the blood of a malaria patient or a carrier of sexual forms of the malarial plasmodium.

Tremendous chills

Malaria is characterized by a period of acute attacks of fever (primary attack) followed by a fever-free period. In some untreated or undertreated patients, fever resumes after 7-14 days or more within 2-3 months after the cessation of the primary attack (early relapses). After an incubation period of varying duration (from 1 to 6 weeks, depending on the type of pathogen), non-immune patients experience characteristic chilling, headache, low-grade fever, malaise, muscle pain, and sometimes diarrhea (with tropical malaria).

An attack of malaria (paroxysm) proceeds with a change of phases: tremendous chills, fever, sweat. In the chill phase, the skin is pale, cold, rough (“goose-like”) with a cyanotic tint. The chill lasts from 10-15 minutes to 2-3 hours and is accompanied by a very rapid rise in temperature (up to 39-40°C and above). After a few hours, the heat is replaced by profuse sweating. In general, malarial paroxysm lasts 6-12 hours, and with tropical malaria – up to a day or more. After the attack, there is a period of normalization of temperature. It lasts 48 hours for three days of malaria and 72 hours for four days.

Patients are treated in an infectious diseases hospital with special antimalarial drugs. The success of malaria treatment is largely determined by the timeliness and correct choice of the drug.

Prevention

When staying in areas where malaria is prevalent, the following precautions should be taken:

– sleep in rooms where windows and doors are covered with netting or net curtains, preferably impregnated with insecticide;

– from dusk to dawn, dress in such a way as not to leave arms and legs open;

– Treat open areas of the body with repellent, especially staying outdoors in the evening and at night;

– prophylactic administration of antimalarial drugs is recommended for people traveling to foci of medium and high endemicity.

Malaria is a parasitic tropical disease characterized by bouts of fever, anemia and enlargement of the spleen. There are 4 types of malaria: tropical, three-day, four-day and oval malaria. The heaviest is tropical. Malaria is transmitted from a sick person to a healthy person through the blood-sucking of female mosquitoes. 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 develop.

The incubation (hidden) period of development of parasites ranges from seven days to three years. This amplitude depends on the type of malaria; in tropical malaria, the incubation period is short. The disease begins with symptoms of general intoxication (weakness, weakness, severe headache, chills). Then come repeated attacks of fever, the body temperature rises to 40 degrees and above, lasts for several hours and is accompanied by chills and heavy sweating at the end of the attack. If there is a clear recurrence of such attacks after a certain time – daily (every other day or two days later), you should think about a possible illness with malaria and immediately seek medical help.

Tropical malaria is the most severe form of malaria. The incubation period ranges from 8 to 16 days. Headache, fatigue, nausea, loss of appetite may occur 3-4 days before the development of clinical symptoms. The initial manifestations are characterized by severe chills, a feeling of heat, severe headache. In some cases, malaria attacks occur without chills. Fever at the onset of the disease can be constant without pronounced attacks, which makes diagnosis difficult. With late diagnosis and delay in treatment of tropical malaria, take a “malignant course”.

The risk of developing “malignant” malaria is especially increased if treatment is delayed more than 6 days from the onset of the disease. Mortality in tropical malaria ranges from 10 to 40%, depending on the time of initiation of treatment, the correct selection of antimalarial drugs and the equipment of the clinic. Children, pregnant women, and non-immune adults are more likely to develop severe tropical malaria. Cerebral malaria is the most common complication of tropical malaria, characterized by convulsions, rigidity, and retinal hemorrhages.