Skip to main content
Parasites & Vectors logoLink to Parasites & Vectors
. 2012 Jul 30;5:154. doi: 10.1186/1756-3305-5-154

Severe Plasmodium vivax malaria among sudanese children at New Halfa Hospital, Eastern Sudan

Hyder Mahgoub 1, Gasim I Gasim 2, Imad R Musa 3, Ishag Adam 4,
PMCID: PMC3464670  PMID: 22846165

Abstract

Background

There are few published reports on severe Plasmodium vivax malaria in Africa.

Methods

Clinical pattern/manifestations of severe P. vivax were described in children admitted at New Halfa Hospital in Sudan between September 2009-December 2011.

Results

Eighteen children were admitted at the hospital during the study period with different manifestations of severe P. vivax malaria namely: severe anaemia (6, 33.3%), jaundice (5, 27.8%), thrombocytopenia (4, 22.2%), hypotension (3, 16.7%), cerebral malaria (2, 11.1%), epistaxis (2, 11.1%), renal impairment (1, 5.5%), hypogylcaemia and more than one manifestation (5, 27.8%).

By day 2, all patients were asymptomatic, a parasitaemic and had started oral quinine and primaquine. There was no death among these patients

Conclusion

Severe P. vivax malaria is an existing entity in eastern Sudan. Further studies are required to understand emergence of severe P. vivax malaria.

Background

Malaria remains one of the most important parasitic infections in the world, with almost 225 million cases of infection and 0.78 million deaths in 2009, mainly in Africa, Asia and South America [1]. Plasmodium vivax is the second most common cause of malaria in the world after Plasmodium falciparum, moreover, P. vivax has a wider geographical distribution, where more people are at risk of infection (2.85 billion) [2], and it is more difficult to control because of the hypnozoite forms of the parasite [3,4]. Recent reports on P. vivax infections suggest that this parasite may be evolving and adapting to new epidemiological contexts, becoming not only more virulent but also more frequent in countries where the incidence has traditionally been low [3,5,6]. Furthermore, it has been shown that P. vivax is able to infect even Duffy-negative African patients [7].

This previous old paradigm of P. vivax as “benign tertian malaria” has been challenged recently by recent reports and documentation of severe P. vivax disease, and even deaths due to P vivax mono-infections [8-12]. Interestingly, in one of these studies, P. vivax malaria was confirmed by polymerase chain reaction (PCR) [12]. The vast majority of these reports on severe P. vivax malaria are from south East Asia and India, there are few published data on severe P. vivax from Africa [13]. The current study was conducted at New Halfa hospital in the eastern Sudan during the period of September 2009-December 2011 to investigate manifestations of severe P. vivax among children so as to add to the previous studies on severe malaria and its treatment in Sudan [14-17]. Such data is of paramount importance for the care givers, health planners and for controlling the disease e.g. by using an effective drug and eradicating this species. P. falciparum (95%) was the main species in the area and P. vivax was rare and constituted only 3% of the species in the area [18].

Methods

Children with symptoms and signs of malaria including: fever, chills, malaise, headache, vomiting or other systemic complaints were included in this study after informed consent was obtained from the parents/adolescent themselves. Then the details of the medical history were gathered for each patient (age, sex, axillary temperature, weight, fever history) using questionnaires. Children with one or more of the manifestations of severe malaria according to the World Health Organization [19] criteria, which include cerebral malaria (unarousable coma), convulsion (more than two per 24 hours), hypotension (systolic blood pressure < 80 mmHg with cold extremities), severe anaemia (haemoglobin < 5 gm/dl), jaundice (detected clinically or bilirubin > 3 mg/dl), hypoglycaemia (blood glucose < 40 mg/dl), hyperparasitaemia (parasite count > 100,000 asexual forms/μl) and severe thrombocytopenia (<50,000/μL) were managed according to the WHO guidelines, and the rest were considered as uncomplicated cases [19].

Thin and Thick blood films were prepared and stained with 10% Giemsa, and 100 oil immersion fields were examined. The parasite density was evaluated by counting the number of asexual parasites for every 200 leukocytes, assuming a leukocyte count of 8000 leukocytes/μl. All slides were double-checked in a blinded manner and only considered negative if no parasites were detected in 100 oil immersion fields. Blood glucose was measured at baseline before quinine infusion, two hours after quinine infusion and if there was clinical suspicion of hypoglycaemia using the bedside device Accu-Chek™ Multiclix (Roche diagnostics, Mannheim Germany). The Accu-Chek™ machine was calibrated weekly and every time a new box of test strips was opened. Blood indices were performed by hematology analyzer.

Resuscitation and supportive management were given according to the WHO guidelines [19]; i.e. quinine infusion at 10 mg/kg three times a day over 2–3 hours changed to oral quinine tablets when the patient could tolerate them, correction of hypoglycaemia with 10% glucose, termination of convulsions with intravenous diazepam if this persisted for more than three minutes. Paracetamol was given every 6 hours until defervescence. Those with severe anaemia (haemoglobin < 5 g/dl) and respiratory distress were transfused with blood screened for hepatitis and HIV. Vital signs were measured every 15 minutes for the first hour, then every 2 hours until 24 hours, and thereafter every 6 hours until the discharge from the hospital. Baseline investigations were performed for every patient on admission and repeated when clinically indicated. These included levels of haemoglobin, serum urea, serum creatinine, and serum bilirubin as well as the white blood cell count. Patients were discharged home on oral quinine tablets (10 mg/kg every eight hours till day 7) and primaquine tablets for 15 days.

Ethics

The study received ethical clearance from the Research Board of the Faculty of Medicine, University of Khartoum, Sudan.

Results

Among 298 children diagnosed with malaria at the paediatric ward, 79 (18.0%) fulfilled one or more of the WHO criteria for severe malaria [19]. Out of these 79 children with severe malaria, 61 (77.2%) were severe P. falciparum malaria and 18 (22.8%) [10, 55.6% were male] had various manifestations of severe P. vivax malaria namely: severe anaemia (6, 33.3%), jaundice (5, 27.8%), thrombocytopenia (4, 22.2%), hypotension (3, 16.7%), repeated convulsions (3, 16.7%), cerebral malaria (2, 11.1%), epistaxis (2, 11.1%), renal impairment (1, 5.5%), hypogylcaemia and more than one manifestation (5, 27.8%). There was no death among these patients.

Three patients with severe anaemia received blood transfusion. Out of the six patients with severe anaemia; two patients had jaundice, one patient had hypotension and thrombocytopenia. Two patients had an enlarged spleen. All children were febrile. Different symptoms such as nausea (14, 77.8%), vomiting (9, 50%), aches (8, 44.4%), sweating (7; 39.0%), headache (7; 39.0%), and diarrhoea (3; 16.7%) were observed among these children. All of these cases were P. vivax mono-infections.

The admission characteristics of these children are shown in Table 1. None of the patients developed hypoglycaemia during quinine treatment. By day 2, comatose patients were fully conscious and all patients were symptom free and a parasitaemic. All patients started oral quinine and primaquine tablets within two days.

Table 1.

The admission variables of the Sudanese children with severe P. vivax malaria ( n = 18) at New Halfa Hospital, Eastern Sudan

Variable Mean (standard deviation)
Age, years
4.9 (2.4)
Duration of illness, days
2.8(1.6)
Weight, Kg
13.2(4.4)
Height, cm
96.1(19.7)
Temperature, C
38.3(1.1)
Haemoglobin, g/dl
7.8(2.6)
White blood cells
5.6(2.1)
Parasitaemia, geometric mean parasite/μ/l
14280
Blood glucose, mg/dl
102(38.1)
Urea, mg/dl
40.6(16.8)
Creatinine, mg/dl
0.9(0.3)
Bilirubin 1.9(1.4)

Discussion

The current study documented the severe manifestations of P. vivax malaria (anaemia, jaundice, hypotension, thrombocytopenia, repeated convulsions, cerebral malaria, epistaxis, renal impairment and hypogylcaemia) in an area characterized by P. falciparum malaria [18]. We have previously observed the same manifestations of severity that were due to P. falciparum malaria in the same pediatric ward as well as in the different regions of Sudan [14-17]. Only 3% of malaria cases (99/1539 blood films from 190 individuals) in the same setting were P. vivax while 95% were P. falciparum malaria giving the rate of P. vivax/P. falciparum malaria of 0.03 [18]. Perhaps there is an increase in the P. vivax malaria due to influx of Ethiopian and Eritrean populations through the border following the peace and construction of Asphalt roads between these countries and Sudan. Recent reports showed that most of the malaria infections in Ethiopia were P. vivax infections and even with reported treatment failure [20-22]. Our data therefore confirmed the findings of some authors, who also believe that P. vivax in not a rare disease in Africa and might use receptors other than Duffy to invade erythrocytes [20-24].

The manifestations of severe P. vivax malaria in this setting are similar to the severe manifestations of P. vivax malaria that has been reported from India [10,12,25-28], Brazil [29], Papua New Guinea [8,30] and Indonesia [31] both in adults and children.

Generally, according to the WHO guidelines, cerebral malaria, severe anaemia, severe thrombocytopenia and pancytopenia, jaundice, splenic rupture, acute renal failure and acute respiratory distress syndrome are the expected manifestations of severe P. vivax malaria [32]. Severe anaemia and acute pulmonary oedema are not uncommon. The underlying mechanisms of severe manifestations are not fully understood. It worth mentioning that there are no specific manifestations/treatment of severe P. vivax malaria, but according the WHO guidelines, prompt and effective treatment and case management should be the same as for severe and complicated P. falciparum malaria [32].

In the current study patients were asymptomatic within two days following the treatment with quinine. According to the WHO new guidelines intravenous artesunate is superior to quinine in the treatment of severe malaria [32]. Compared to quinine, intravenous artesunate has a lower risk of hypoglycaemia, significantly reduces the risk of death from severe malaria, and does not require rate controlled infusion/cardiac monitoring [33]. Yet, intravenous artesunate is not registered and available in Sudan. Primaquine is currently the only drug available for radical cure of P. vivax and can be safely used in children 1 to 10 years of age [34].

Conclusion

Severe P. vivax malaria is an existing entity in eastern Sudan. Further studies involving clinical and molecular research are required to understand emergence of severe P. vivax malaria.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

HM and IA designed the study. GIG and ER carried out the study and participated in the procedures. All the authors read and approved the final version.

Contributor Information

Hyder Mahgoub, Email: hdrmahgoub@yahoo.com.

Gasim I Gasim, Email: gasimgsm@yahoo.com.

Imad R Musa, Email: irthesudanese@hotmail.com.

Ishag Adam, Email: ishagadam@hotmail.com.

References

  1. WHO Global Malaria Programme. World Malaria Report Geneva. Geneva: World Health Organization; 2010. [Google Scholar]
  2. Guerra CA, Howes RE, Patil AP, Gething PW, Van Boeckel TP, Temperley WH, Kabaria CW, Tatem AJ, Manh BH, Elyazar IR, Baird JK, Snow RW, Hay SI. The international limits and population at risk of Plasmodium vivax transmission in 2009. PLoS Negl Trop Dis. 2010;4(8):e774. doi: 10.1371/journal.pntd.0000774. 3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baird JK. Resistance to therapies for infection by Plasmodium vivax. Clin Microbiol Rev. 2009;22:508–534. doi: 10.1128/CMR.00008-09. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Sattabongkot J, Tsuboi T, Zollner GE, Sirichaisinthop J, Cui L. Plasmodium vivax transmission: chances for control? Trends Parasitol. 2004;20:192–198. doi: 10.1016/j.pt.2004.02.001. [DOI] [PubMed] [Google Scholar]
  5. Galinski MR, Barnwell JW. Plasmodium vivax: who cares? Malaria J. 2008;7(Suppl 1):S9. doi: 10.1186/1475-2875-7-S1-S9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Mueller I, Galinski MR, Baird JK, Carlton JM, Kochar DK, Alonso PL, del Portillo HA. Key gaps in the knowledge of Plasmodium vivax, a neglected human malaria parasite. Lancet Infect Dis. 2009;9:555–566. doi: 10.1016/S1473-3099(09)70177-X. [DOI] [PubMed] [Google Scholar]
  7. Wurtz N, Mint Lekweiry K, Bogreau H. Vivax malaria in Mauritania includes infection of a Duffy-negative individual. Malaria J. 2011;10:336. doi: 10.1186/1475-2875-10-336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Manning L, Laman M, Law I, Bona C, Aipit S, Teine D, Warrell J, Rosanas-Urgell A, Lin E, Kiniboro B, Vince J, Hwaiwhanje I, Karunajeewa H, Michon P, Siba P, Mueller I, Davis TM. Features and prognosis of severe malaria caused by Plasmodium falciparum, Plasmodium vivax and mixed Plasmodium species in Papua New Guinean children. PLoS One. 2011;6(12):e29203. doi: 10.1371/journal.pone.0029203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gogia A, Kakar A, Byotra SP. Is benign tertian malaria actually benign? Trop Doct. 2012;42:92–93. doi: 10.1258/td.2011.110295. [DOI] [PubMed] [Google Scholar]
  10. Naha K, Dasari S, Prabhu M. Spectrum of complications associated with Plasmodium vivax infection in a tertiary hospital in South-Western India. Asian Pac J Trop Med. 2012;5:79–82. doi: 10.1016/S1995-7645(11)60251-4. [DOI] [PubMed] [Google Scholar]
  11. Singh H, Parakh A, Basu S, Rath B. Plasmodium vivax malaria: is it actually benign? J Infect Public Health. 2011;4:91–95. doi: 10.1016/j.jiph.2011.03.002. [DOI] [PubMed] [Google Scholar]
  12. Tanwar GS, Khatri PC, Sengar GS, Kochar A, Kochar SK, Middha S, Tanwar G, Khatri N, Pakalapati D, Garg S, Das A, Kochar DK. Clinical profiles of 13 children with Plasmodium vivax cerebral malaria. Ann Trop Paediatr. 2011;31:351–356. doi: 10.1179/1465328111Y.0000000040. [DOI] [PubMed] [Google Scholar]
  13. Roder H, Vietze G. Plasmodium vivax infection with brain symptoms. Dtsch Gesundheitsw. 1968;23:1328–1331. [PubMed] [Google Scholar]
  14. Adam I, Idris HM, Mohamed-Ali AA, Aelbasit IA, Elbashir MI. Comparison of intramuscular artemether and intravenous quinine in the treatment of Sudanese children with severe falciparum malaria. East Afr Med J. 2002;79:621–625. doi: 10.4314/eamj.v79i12.8668. [DOI] [PubMed] [Google Scholar]
  15. Ali AA, Elhassan EM, Magzoub MM, Elbashir MI, Adam I. Hypoglycaemia and severe Plasmodium falciparum malaria among pregnant Sudanese women in an area characterized by unstable malaria transmission. Parasit Vectors. 2011;23(4):88. doi: 10.1186/1756-3305-4-88. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Eltahir HG, Omer AA, Mohamed AA, Adam I. Comparison of artesunate and quinine in the treatment of Sudanese children with severe Plasmodium falciparum malaria. Trans R Soc Trop Med Hyg. 2010;104:684–686. doi: 10.1016/j.trstmh.2010.05.009. [DOI] [PubMed] [Google Scholar]
  17. Mirghani HA, Eltahir HG, A-Elgadir TM, Mirghani YA, Elbashir MI, Adam I. Cytokine profiles in children with severe Plasmodium falciparum malaria in an area of unstable malaria transmission in central Sudan. J Trop Pediatr. 2011;57:392–395. doi: 10.1093/tropej/fmq109. [DOI] [PubMed] [Google Scholar]
  18. Himeidan YE, Elbashir MI, El-Rayah E-A, Adam I. Epidemiology of malaria in New Halfa, an irrigated area in eastern Sudan. East Mediterr Health J. 2005;11:499–504. [PubMed] [Google Scholar]
  19. WHO Severe and complicated malaria Trans R Soc Trop Med Hyg 200094Suppl 11–90.10748883 [Google Scholar]
  20. Woyessa A, Deressa W, Ali A, Lindtjorn B. Prevalence of malaria infection in Butajira area, south-central Ethiopia. Malaria J. 2012;11:84. doi: 10.1186/1475-2875-11-84. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Alemu A, Abebe G, Tsegaye W, Golassa L. Climatic variables and malaria transmission dynamics in Jimma town, South West Ethiopia. Parasites Vectors. 2011;4:30. doi: 10.1186/1756-3305-4-30. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ketema T, Getahun K, Bacha K. Therapeutic efficacy of chloroquine for treatment of Plasmodium vivax malaria cases in Halaba district, South Ethiopia. Parasites Vectors. 2011;4:46. doi: 10.1186/1756-3305-4-46. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ménard D, Barnadas C, Bouchier C, Henry-Halldin C, Gray LR, Ratsimbasoa A, Thonier V, Carod JF, Domarle O, Colin Y, Bertrand O, Picot J, King CL, Grimberg BT, Mercereau-Puijalon O, Zimmerman PA. Plasmodium vivax clinical malaria is commonly observed in Duffy-negative Malagasy people. Proc Natl Acad Sci USA. 2010;107:5967–5971. doi: 10.1073/pnas.0912496107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Mendes C, Dias F, Figueiredo J, Mora VG, Cano J, De Sousa B, Do Rosário VE, Benito A, Berzosa P, Arez AP. Duffy Negative Antigen Is No Longer a Barrier to Plasmodium vivax - Molecular Evidences from the African West Coast (Angola and Equatorial Guinea) PLoS Negl Trop Dis. 2011;5:e1192. doi: 10.1371/journal.pntd.0001192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kaushik JS, Gomber S, Dewan P. Clinical and epidemiological profiles of severe malaria in children from Delhi, India. J Health Popul Nutr. 2012;30:113–116. doi: 10.3329/jhpn.v30i1.11291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Bammigatti C, Shetty S, Shetty S, Kumar A. Benign tertian malaria–a misnomer? Trop Doct. 2011;41:168–169. doi: 10.1258/td.2011.110025. [DOI] [PubMed] [Google Scholar]
  27. Kochar DK, Das A, Kochar SK, Saxena V, Sirohi P, Garg S, Kochar A, Khatri MP, Gupta V. Severe Plasmodium vivax malaria: a report on serial cases from Bikaner in northwestern India. AmJTrop Med Hyg. 2009;80:194–198. [PubMed] [Google Scholar]
  28. Yadav D, Chandra J, Aneja S, Kumar V, Kumar P, Dutta AK. Changing profile of severe malaria in north Indian children. Indian J Pediatr. 2012;79:483–487. doi: 10.1007/s12098-011-0603-x. [DOI] [PubMed] [Google Scholar]
  29. Lança EF, Magalhães BM, Vitor-Silva S, Siqueira AM, Benzecry SG, Alexandre MA, O'Brien C, Bassat Q, Lacerda MV. Risk factors and characterization of Plasmodium vivax-associated admissions to pediatric intensive care units in the Brazilian Amazon. PLoS One. 2012;7(4):e35406. doi: 10.1371/journal.pone.0035406. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Genton B, D'Acremont V, Rare L, Baea K, Reeder JC, Alpers MP, Müller I. Plasmodium vivax and mixed infections are associated with severe malaria in children: a prospective cohort study from Papua New Guinea. PLoS Med. 2008;5(6):e127. doi: 10.1371/journal.pmed.0050127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Tjitra E, Anstey NM, Sugiarto P, Warikar N, Kenangalem E, Karyana M, Lampah DA, Price RN. Multidrug-resistant Plasmodium vivax associated with severe and fatal malaria: a prospective study in Papua. Indonesia PLoS Med. 2008;5(6):e128. doi: 10.1371/journal.pmed.0050128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. WHO | Guidelines for the treatment of malaria, second edition Publication date. Languages. 2010. English ISBN: 9789241547925 www.who.int/malaria/publications/atoz/9789241547925.
  33. Sinclair D, Donegan S, Lalloo DG. Artesunate versus quinine for treating severe malaria. Cochrane Database Syst Rev. 2011;3:CD005967. doi: 10.1002/14651858.CD005967.pub3. [DOI] [PubMed] [Google Scholar]
  34. Betuela I, Bassat Q, Kiniboro B, Robinson LJ, Rosanas-Urgell A, Stanisic D, Siba PM, Alonso PL, Mueller I. Tolerability and safety of primaquine in Papua New Guinean children 1 to 10 years of age. Antimicrob Agents Chemother. 2012;56:2146–2149. doi: 10.1128/AAC.05566-11. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Parasites & Vectors are provided here courtesy of BMC

RESOURCES