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ORIGINAL ARTICLE  
Year : 2017  |  Volume : 42  |  Issue : 3  |  Page : 167-169
 

The bone pain crisis of sickle cell disease and malaria: Observations from Gujarat, India


1 Chairman, Vision Medical Foundation for Rural Health and Research, Shishudeep Hospital, Bardoli, Gujarat, India
2 Secretary, Vision Medical Foundation for Rural Health and Research, Shishudeep Hospital, Bardoli, Gujarat, India
3 Sickle Cell Trust, Kingston, Jamaica, West Indies

Date of Submission26-Sep-2016
Date of Acceptance25-Apr-2017
Date of Web Publication3-Aug-2017

Correspondence Address:
Graham R Serjeant
Sickle Cell Trust (Jamaica), 14 Milverton Crescent, Kingston 6, Jamaica
West Indies
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijcm.IJCM_334_16

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   Abstract 

Background: Sickle cell disease is a common problem across central India, but its clinical features may differ from that in African populations. There is a need to define the features of sickle cell disease in India, and the current study addresses some features of the bone pain crisis. Objectives: The objective of the study was to describe the epidemiology of the bone pain crisis of sickle cell disease in Gujarat and explore the relationship with infection by Plasmodium vivax. Materials and Methods: This was a prospective review of all admissions in patients with sickle cell disease to a private pediatric institution in Bardoli, Gujarat, in the year 2015. Hemoglobin electrophoresis of all patients was consistent with homozygous sickle cell disease, but family studies indicated that at least seven cases had the severe sickle cell-beta + thalassemia presumed to be the common IVS1-5G>C mutation. Clinical, hematological, and parasitological features were recorded. Results: There were 914 admissions among 654 patients who had between one and seven admissions. The bone pain crisis accounted for 763 (83%) of admissions and increased between July and October coinciding with the monsoon period. Blood smears were examined for malarial parasites in 811 admissions and were positive for P. vivax in 73% patients. There was no evidence that P. vivax infections varied with the cause of admission or increased during the monsoon period. Conclusions: There was a high prevalence of P. vivax infection in hospital admissions of sickle cell patients, but the data did not support an etiological role in the bone pain crisis. A trial of malarial prophylaxis might determine its effect on the clinical features and outcome of sickle cell disease.


Keywords: Bone pain crisis, monsoon, Plasmodium vivax infection, sickle cell disease


How to cite this article:
Patel J, Patel B, Serjeant GR. The bone pain crisis of sickle cell disease and malaria: Observations from Gujarat, India. Indian J Community Med 2017;42:167-9

How to cite this URL:
Patel J, Patel B, Serjeant GR. The bone pain crisis of sickle cell disease and malaria: Observations from Gujarat, India. Indian J Community Med [serial online] 2017 [cited 2019 Dec 16];42:167-9. Available from: http://www.ijcm.org.in/text.asp?2017/42/3/167/212064



   Introduction Top


The sickle cell (HbS) gene is widespread in central India affecting peoples in eastern Gujarat, Madhya Pradesh, Maharashtra, Chhattisgarh, and Western Odisha with a smaller focus in the north of Tamil Nadu and Kerala.[1],[2] The mutation in HbS affects the beta globin gene, but the DNA sequence flanking this gene differs from that in populations of African ancestry, and it is believed to represent a separate occurrence of the HbS mutation, known as the Asian haplotype.[3] The distribution of the HbS gene in India coincides with that of the scheduled tribes, but it is also widespread among the “other backward classes” and the scheduled castes occurring throughout Hindu caste society.[4] Inheritance of the HbS gene from both parents results in homozygous sickle cell (SS) disease which, in Indian peoples, is often associated with alpha thalassemia and high levels of fetal hemoglobin. Both factors inhibit sickling, and there may be important differences in clinical features between Indian patients and those of African ancestry.[5] Splenomegaly persists for longer in Indian patients and persistence of splenic function is suggested by the lack of reports of pneumococcal septicemia in contrast to African forms of the disease. Leg ulceration and priapism appear much less frequent in Indian patients, but the bone pain crisis persists as a major clinical feature in both Indian and African forms of the disease. There is a need for better clinical documentation of the features of Indian disease,[6] and the current paper addresses the bone pain crisis and explores the relationship with infection by Plasmodium Vivax.


   Materials and Methods Top


This was a prospective study of all cases with sickle cell disease will acute illness deemed to be of sufficient severity to warrant hospital admission in 2015. The study was sited in a private pediatric institution with a long history of interest in sickle cell disease located in Bardoli, central Gujarat.

Laboratory methods

The genotype diagnosis was based on a single heavy band in the position of HbS on alkali hemoglobin electrophoresis supported by a positive solubility test. Family studies were not routinely performed, but in 7 (1.2%), a parent had an AA phenotype consistent with sickle cell-beta + thalassemia and the remaining 647 patients were assumed to have SS disease. Although not confirmed by structural studies, the cases of sickle cell-beta + thalassemia were likely to have the IVS1-5G>C mutation common in this population[7] and associated with very low levels of HbA; the genotypes have been combined for the present report. A venipuncture sample was collected in ethylenediaminetetraacetic acid (EDTA) for daily complete blood counts or more often if a fall in hemoglobin is suspected. Red cell indices were measured electronically (KX 21 hematology analyzer, Sysmex, Japan). Thin and thick blood smears were made directly from a blood drop from the syringe before the rest of the sample was collected into EDTA, stained by Giemsa stain and examined for malaria parasites under a high power oil immersion lens by the same observer (B.P.).

Clinical definitions

The bone pain crisis was based on the typical distribution and characteristics of bone pain without any history of trauma or other pathology. The clinical diagnosis of malaria was based on fever, rigors, and nonspecific symptoms and was easily overlooked in conjunction with the bone pain crisis. The acute chest syndrome was based on clinical signs in the chest and was not always confirmed radiologically.


   Results Top


There were 914 admissions in 654 patients (single admissions in 490, two admissions in 116, three in 34, four in 13, five in 5, six in 1, and seven admissions in one). Ages ranged from 1 to 59 years (mean 18 years and median 17 years), and among the 490 single admissions, there were 297 (60.6%) males. All patients except three were of the scheduled castes and admissions were seen by a single physician who allocated the clinical diagnosis. Mean and median duration of admission was 4.3 days (range 0–37 days). Hemoglobin levels were available in 772 admissions and did not differ between those negative for vivax (n = 208, mean 8.38, median 8.70, and range 2.4–12.4) and those with positive films (n = 564, mean 8.43, median 8.70, and range 2.1–13.5 g/dl).

Admission diagnosis

Bone pain crises accounted for 763 (83%) admissions (bone pain alone, 644 and bone pain associated with other features, 119) and diagnoses are summarized in [Table 1].
Table 1: Clinical diagnoses in admitted patients

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Secular changes in admissions

Admissions peaked from July to October, most of this excess being attributed to bone pain crisis alone or with associated clinical features [Figure 1].
Figure 1: Monthly distribution of admissions (Adm) for bone pain only (BP only), bone pain with other features (All BP) and percentage positive for Plasmodium Vivax (Vivax + ve)

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Secular changes in malarial parasite detection

Of the 914 admissions, blood films were examined in 811 (89%) admissions, were negative in 218 admissions and positive in 593 (73%) admissions. Parasite detection by month varied from 56% to 88% but did not differ during the 4 months at the peak of the monsoon (72%, positive) from the other 8 months (73%, positive). Furthermore, the proportion of positive samples for P. vivax did not differ between causes of admission and were not more common in bone pain crises. All parasites had the characteristics of P. vivax and no cases of P falciparum were detected.


   Discussion Top


P. vivax is the dominant malarial species throughout India[8],[9] although Plasmodium falciparum occurs in some forested areas of Odisha, this pattern may be changing.[10] Diagnosis of infection may be performed by rapid diagnosis tests detecting antigen or polymerase chain reaction detecting plasmodial DNA, but the gold standard is still microscopic examination by a skilled observer. Data in the current study are based on microscopy with the same experienced observer who found parasites in 73% of blood films. Interpretation of this finding is hampered by the lack of suitable control data in the general population or in steady state patients with SS disease. Attempts to use admission data in patients without bone pain crises were limited by the very small number of patients who did not have either bone pain crises or a clinical diagnosis of malaria.

The bone pain crisis of sickle cell disease is usually attributable to bone marrow necrosis which is most prominent in the juxta-articular areas of the long bones, spine, ribs, and sternum. It is episodic in nature, and most events have clear precipitating factors such as skin cooling, infection, dehydration, and stress. The relationship with skin cooling although well recognized[11],[12] is not yet clearly understood.[13] The striking increase in bone pain crisis between July and October in the current study coinciding with the monsoon is consistent with these observations. In the current study, there was no evidence that P. vivax infection contributed to the increased bone pain crisis during the monsoon period from July to October. Furthermore, although control figures are not available, the presence of P. vivax parasites in 73% admissions draws attention to the potential importance of this infection in patients with sickle cell disease.

Sickle cell disease in India is a major public health problem with its dominance in rural areas with limited medical resources. Although much is known about the clinical features and management of sickle cell disease in peoples of African origin, Indian sickle cell disease remains to be properly documented, and with this lack of knowledge, physicians in India may have to use models of care derived for African disease which may be inappropriate and wasteful of scarce resources. Although some clinical differences are clear, the bone pain crisis remains a major feature of both African and Indian disease, and the current study is consistent with skin cooling being an important precipitating factor. Patient education on the importance of avoiding skin cooling and dressing warmly, especially, during the monsoon period may prevent bone pain crises. Since both P. vivax infection and sickle cell disease are common in central India, it would be interesting to study the effect of malarial prophylaxis in this population.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Rao VR. Genetics and epidemiology of sickle cell anemia in India. Icmr Bull 1988;9:87-90.  Back to cited text no. 1
    
2.
Colah R, Mukherjee M, Ghosh K. Sickle cell disease in India. Curr Opin Hematol 2014;21:215-23.  Back to cited text no. 2
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3.
Kulozik AE, Wainscoat JS, Serjeant GR, Kar BC, Al-Awamy B, Essan GJ, et al. Geographical survey of beta S-globin gene haplotypes: Evidence for an independent Asian origin of the sickle-cell mutation. Am J Hum Genet 1986;39:239-44.  Back to cited text no. 3
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4.
Kar BC. Sickle cell disease in India. J Assoc Physicians India 1991;39:954-60.  Back to cited text no. 4
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5.
Kar BC, Satapathy RK, Kulozik AE, Kulozik M, Sirr S, Serjeant BE, et al. Sickle cell disease in Orissa state, India. Lancet 1986;2:1198-201.  Back to cited text no. 5
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6.
Serjeant GR. Evolving locally appropriate models of care for Indian sickle cell disease. Indian J Med Res 2016;143:405-13.  Back to cited text no. 6
[PUBMED]  [Full text]  
7.
Colah R, Gorakshakar A, Nadkarni A, Phanasgaonkar S, Surve R, Sawant P, et al. Regional heterogeneity of beta-thalassemia mutations in the multi ethnic Indian population. Blood Cells Mol Dis 2009;42:241-6.  Back to cited text no. 7
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8.
Joshi H, Prajapati SK, Verma A, Kang'a S, Carlton JM. Plasmodium vivax in India. Trends Parasitol 2008;24:228-35.  Back to cited text no. 8
    
9.
Das A, Anvikar AR, Cator LJ, Dhiman RC, Eapen A, Mishra N, et al. Malaria in India: The center for the study of complex malaria in India. Acta Trop 2012;121:267-73.  Back to cited text no. 9
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10.
Singh N, Nagpal AC, Saxena A, Singh MP. Changing scenario of malaria in central India, the replacement of Plasmodium vivax by Plasmodium falciparum (1986-2000). Trop Med Int Health 2004;9:364-71.  Back to cited text no. 10
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11.
Redwood AM, Williams EM, Desal P, Serjeant GR. Climate and painful crisis of sickle-cell disease in Jamaica. Br Med J 1976;1:66-8.  Back to cited text no. 11
[PUBMED]    
12.
Resar LM, Oski FA. Cold water exposure and vaso-occlusive crises in sickle cell anemia. J Pediatr 1991;118:407-9.  Back to cited text no. 12
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13.
Mohan J, Marshall JM, Reid HL, Thomas PW, Hambleton I, Serjeant GR. Peripheral vascular response to mild indirect cooling in patients with homozygous sickle cell (SS) disease and the frequency of painful crisis. Clin Sci (Lond) 1998;94:111-20.  Back to cited text no. 13
[PUBMED]    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1]



 

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