To find out more, the scientists studied mice infected with the malaria parasite Plasmodium chabaudi. They discovered a significant reduction in numbers of cells called bone marrow lineage-negative cells, which include haematopoietic stem cells and early progenitor cells, during infection with Plasmodium chabaudi.
The scientists went on to show that the loss of early myeloid progenitors from the bone marrow was a key feature of malaria infection.
Furthermore, they found that mobilisation of these cells from the bone marrow resulted in myeloid cell production in the spleen. Crucially, the increase in myeloid cells in the spleen contributed to the clearance of parasite-infected red blood cells. The authors said: "Our study defined the molecular signals and interaction of various cell types that lead to the establishment of splenic myelopoiesis, which actively contributes to the effective initial control of the parasite by the mouse's immune system.
They added that further increasing understanding of these processes may lead to new cell-based methods to treat the disease. At this moment, due to a suspicion of spleen rupture and patient instability, a portable ultrasound scan was performed. This revealed a layer of free fluid in the splenorenal space and in the pelvis.
The patient was referred to a surgery hospital Hospital Pronto Socorro 28 de Agosto, also in Manaus , where he underwent an emergency splenectomy. Ten days after surgery, the patient had a positive blood smear 0. A negative blood smear was obtained 14 days after abdominal pain appeared. It was only a month after the splenectomy that blood parameters began to ameliorate, and primaquine was re-started at this point to attempt clearing of hypnozoites.
Two months after the beginning of the symptoms and 1 month after reintroducing primaquine, the patient had another malaria episode.
He presented with fever, headache and myalgia for 1 day, and parasitaemia was 0. Seven days later, the patient was asymptomatic and the blood smear negative.
The dose of primaquine was the same as the previous time, although treatment was not supervised. However, 2 months after the latest episode, the patient suffered another malaria attack 1. No features of severe malaria were present in either of the two episodes. Patient follow-up after the last episode was not possible as he moved out of Manaus.
The patient gave consent to analyse the removed spleen at the time of splenectomy. Upon visual inspection, the spleen appeared enlarged and displayed multiple lacerations. After being immersed in a fixative solution, examination of the ruptured spleen showed areas of different coloration and consistency Fig. Very solid brownish areas, some more liquid reddish ones and an almost black, large subcapsular haematoma could be distinguished. Splenic sections were embedded in OCT Optimal Cutting Temperature compound and frozen for histopathology analysis 6 months later.
Spleen rupture analysis and diagnostics. Plasmodium vivax is the most widely distributed human malaria parasite with an at-risk population of 2. In it caused approximately 8. Contrary to what was believed some years ago, molecular diagnosis techniques, and ruling out other infections or chronic diseases, have demonstrated that the P.
Plasmodium vivax infection can cause severe anaemia, hepatic dysfunction and jaundice, acute lung injury, acute respiratory distress syndrome and pulmonary oedema, shock, acute renal failure, severe thrombocytopaenia and splenic rupture [ 7 , 8 ].
It is still unclear if cerebral malaria is also among clinical manifestations [ 9 ]. Patients with no or low immunity to malaria have the highest risk of spleen rupture [ 10 ].
Therefore, patients with acute malaria should avoid activities with risk of abdominal trauma during several weeks after recovering from the acute disease [ 10 ]. In the present case, the patient had recurrent parasitaemia before and after the surgery, and suffered two more malaria attacks after the spleen rupture.
Unfortunately, at present there are no reliable biomarkers capable of differentiating malaria episodes originating from recrudescence, reinfection or relapse. Yet, it is likely that the recurrences in this case are indeed due to relapses, since the patient remained within the urban area of Manaus during the study period. Because treatment was not supervised and since reports of malaria resistant to primaquine are generally related to deficient supervision [ 11 ], inadequate primaquine dosing could be a plausible explanation for the recurrences observed in this patient.
Of note, this patient presented increasing parasitaemia at each attack, supporting the important role that the spleen plays in malaria [ 3 , 13 , 14 ]. The spleen could be a niche for P. Supporting this hypothesis, a spleen rupture previously reported from Manaus in a non-immune patient with P.
Unfortunately, all attempts to detect intact parasites in the current spleen by immunofluorescence analysis were unsuccessful. Yet, histopathological analysis showed equivalent findings, and PCR demonstrated the presence of P. There are several unknowns on splenic rupture yet to be clarified. The underlying pathophysiology of the spleen rupture has not been fully unveiled.
However, two mechanisms, both occurring in acute malaria, have been involved in the process. The first is an effect of activated lymphatic tissue of the spleen and marked stasis in its sinuses produced by deformed infected red blood cells with altered surface characteristics [ 10 ]. The second mechanism is a consequence of spleen compression by abdominal musculature during physiological activities such as sneezing, coughing, defecation and sitting up or turning in bed [ 2 ].
Another matter to be emphasized is about splenic rupture occurring in acute versus chronic malaria. In acute malaria, the spleen is soft and its capsule is thin and tightly stretched. Rupture may, therefore, occur with minor trauma or spontaneously, and is primarily single staged, with haematoma formation and rupture nearly occurring at the same time. In contrast, splenic rupture in chronic malaria is infrequent, and when it occurs, the spleen normally ruptures in two stages: an initial subcapsular haematoma progresses, which later ruptures through the capsule days to weeks later.
It is usually preceded by an obvious trauma. Regarding this observation, a thick splenic capsule detected in patients with chronic malaria and schistosomiasis may delay rupture of the subcapsular haematoma [ 4 ].
Related to this topic, patients with low immunity or no immunity to malaria have the highest risk of rupture. Thus, an abnormal immunological response during the acute stage causes a rapid growth of the spleen, which drives to a higher incidence of splenic rupture.
Therefore, all patients with acute malaria should be advised to avoid activities with increased risk of abdominal trauma for several weeks after curing acute disease [ 10 ]. Concerning the diagnosis, and from the clinical point of view, it is important to note that the longer the symptoms of malaria attacks persist, the higher the risk for splenic rupture, with early diagnosis becoming of utmost importance for prevention [ 3 ].
In that sense, splenic rupture should always be suspected in a patient from an endemic region displaying a rapid onset of hypotension and left hypochondrial pain [ 2 ]. Confirmation of the splenic rupture in a haemodynamically stable patient can be obtained by ultrasonography, computerized tomography scanning, and arteriography.
Computerized tomography has replaced angiography as the preferred diagnostic tool, and is useful in diagnosis and monitoring a patient in whom conservative management of splenic rupture is considered [ 2 ].
Yet, in many endemic regions, computerized tomography is not economically feasible and often not available.
By contrast, ultrasound technology can be more easily available economically and geographically. Portable ultrasound devices are widely used in medicine, as operation of ultrasounds is non-invasive, inexpensive and not associated with radiation exposure [ 16 ]. Although they are primarily used for diagnostic purposes, they are also used for therapeutic intentions e. They have shown utility in limited resource settings and in remote areas where treatment may be improved by transmitting images to central sites [ 17 ].
Most of the medical staff in the emergency department are clinicians general practitioners, pediatricians, infectiologists, and dermatologists. There is also a radiology department, although radiologists are not present 24 h a day. Minor interventions of elective surgery can be performed in the hospital. However, when this patient arrived, there was no radiologist nor surgeon in the hospital. The clinician did the ultrasonography and, after that, the patient was referred to the general hospital.
There, another portable ultrasound scanner was used and surgery started in a short period. A selection bias cannot be excluded either and some patients, especially of the first years, may have been missed. The potential problems of the case definition have been discussed above. PCR for malaria is not used at CTD for routine diagnosis, therefore this information is lacking for our patients.
It is possible that some of the cases with negative blood films and QBC would have been found positive by the more sensitive PCR.
It has recently been suggested by McGregor et al. In their series of seven patients, only three subjects that did not respond to therapy had negative blood films and PCR, seemingly indicating that the syndrome requires the presence of Plasmodium in blood. So the Authors suggest that a negative PCR predicts a treatment failure. The hyper-reactive malarial splenomegaly HMS is the most severe form of chronic malaria, and not a different disease.
However, reinfection must be prevented or immediately treated. As a lifelong prophylaxis does not appear to be feasible in malaria-endemic countries, considering the high number of chronic malaria carriers and patients with splenomegaly, research is needed in order to evaluate the efficacy of intermittent treatment as well as its best periodicity.
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Intermittent preventive treatment of malaria in pregnancy using sulfadoxine—pyrimethamine. Download references. ZB conceived of the study, gave a major contribution to its design and coordination and drafted the first version of the manuscript.
SL participated in the design of the study and performed the first data analysis. CL and FEE participated in the design of the study and collaborated to data analysis. DB gave a major contribution to the study design and coordination, to data analysis and drafted the final version of the manuscript. All authors read and approved the final manuscript. This retrospective work did not receive any external funding. You can also search for this author in PubMed Google Scholar.
Correspondence to Zeno Bisoffi. Reprints and Permissions. Bisoffi, Z. Chronic malaria and hyper-reactive malarial splenomegaly: a retrospective study on the largest series observed in a non-endemic country. Malar J 15, Download citation. Received : 04 February Accepted : 03 April Published : 21 April Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative.
Skip to main content. Search all BMC articles Search. Download PDF. Abstract Background Chronic malaria is usually defined as a long-term malarial infection in semi-immune subjects, usually without fever or other acute symptoms. Methods A retrospective, longitudinal study, describing all patients with HMS diagnosed at the Centre for Tropical Diseases of Negrar, Verona, took place over a year period. Results Forty-four subjects with HMS were retrieved.
Conclusion HMS is the most severe form of chronic malaria. Background Chronic malaria is a long-term infection in semi-immune subjects. Methods Study design Retrospective-longitudinal study The clinical records of patients were retrieved as described previously [ 8 ], covering the period from 1 January, to 3 September, date of the last follow-up visit of the last patient.
Final outcome was assessed on the basis of the last follow up visit. Data entry and data elaboration Data were exported to a pre-structured Excel file, including the main epidemiological, clinical and laboratory findings as well as the results of an ultrasound scan, as available at baseline T1 , short-term follow-up T2 and long-term follow-up T3 [ 8 ]. Treatment and prophylaxis All patients were treated with a single anti-malarial, as for an acute malaria, once the diagnosis was established.
Ethical issues Data were entered anonymously in the database. Results The study population Figure 1 shows the patient flow.
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