Immunization Status of under five Children suffering from cancer: a hospital Based Study.

 

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ORIGINAL ARTICLE

Immunization Status of under five Children suffering from cancer: a hospital Based Study.

 

Ghosh AK,¹ Saha SK,² Yasmin, F.³, Hossain B ⁴

1.Dr. Ashis Kumar Ghosh

2. Dr.Sanat Kumar Saha

3. Dr.Farida Yasmin

4. Dr.Billal Hossain

 

1. Assistant Professor

Department of Paediatric Haematology and Oncology

National Institute of Cancer Research and Hospital

 

2. Assistant Professor

Department of Neurosurgery

Sir Salimullah Medical College & Mitford Hospital.

 

3. Assistant Registrar

Department of Pediatric Hematology and Oncology

National Institute of Cancer Research and Hospital.

 

4. Research Assistant

Louisiana State University Health Sciences Center, New Orleans; USA

 

Correspondence to:

 

Dr. Ashis Kumar Ghosh

Email. ashiskumarghosh@gmail.com

 

(Bang Onc J.2019;14:31-37)

 

 

 

 

 

 

 

 

 

 

 

Immunization Status of under-five Children suffering from cancer                Ashis Kumar Ghosh et al

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Abstract

Background

Childhood vaccination in Bangladesh has improved, but there is still room for improvement i.e immunization of immunocompromised children. Nowadays re-vaccination following chemotherapy is an important issue for cancer patients and for re-immunization of cancer patients; knowledge about the base level of their immunization status is helpful for suggesting re-vaccine schedule.

 

Objectives: To determine the immunization status of under five (U₅) children suffering from cancer. To determine the vaccination coverage of individual vaccine of under five children. To determine the common cancers of under five children.

 

Methods: The study conducted from January 2018 to December 2018 at National Institute of Cancer Research and Hospital. Data are collected from under five patients admitted in the department of Pediatric Hematology and Oncology (PHO) of National Institute of Cancer Research and Hospital (NICRH) during the period of study. Readmitted cases and patients have not EPI card is excluded from study. The immunizations data were obtained from prime care taker and confirmed by immunization card (EPI Card) in every case.

Results: Most common cancer of  under five children are   Retinoblastoma(29.17%), Germ cell tumors (20%), Renal tumors(15.83%), Hematological Malignancy(14.17%),Soft tissue sarcoma (11.67%) and CNS and intraspinal neoplasms (3.33%).

Out of total 120 children, 33 (27.5%) were completely immunized, 81 cases (67.5 %) were partially immunized and 9 child (7.5%) were unimmunized. Fully immunized females were more than male (F:M=1.2:1).BCG vaccine had the highest completion of 111patients (92.5%), followed by pentavalent vaccine 84 (70%), OPV 88(73.33%), PCV 33 (27.50%) and MR 36(30 %). In this study IPV coverage was 27.5% (N=33).

Conclusions: Full immunization coverage of under-five children with cancer were very low. The damage to the immune system by cancer and cancer chemotherapy make them more immunocompromised and may be susceptible to vaccine preventable infections.

 

 

 

 

 

 

 

 

 

Immunization Status of under-five Children suffering from cancer                      Ashis Kumar Ghosh et al

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Introduction

Immunization is one of the most cost effective public health interventions which prevent the bulk of mortality in under-five (U₅) children. Complete vaccination of each and every child is the current need to reduce mortality and morbidity of U₅ in Bangladesh. A strong national commitment to childhood vaccination has contributed substantially to Bangladesh’s success in reaching Millennium Development Goal 4 to reduce childhood mortality. The death rate in Bangladeshi children under the age of 5 years declined from 133 per 1000 live births in 1993 to 46 per 1000 in 2014.¹

But it is not the end. Every day new challenge is coming in the field of immunization. So vaccination plans have been continuously updated during the last two decades due to either availability of new vaccines or the identification of new groups and age ranges in whom the use of vaccination results in an improvement of  health.²

Prevention of vaccine preventable diseases in children receiving chemotherapy or who have completed chemotherapy is a new challenge for the medical science. And Bangladesh is far behind to address this technology.

There are 13 to 15 lakh cancer patients in Bangladesh, with about 2 lakh patients newly diagnosed with cancer each year.³ And expected about 13000 new childhood cancer cases/year ⁴ in Bangladesh.

 

Children treated with chemotherapy for malignancy and/or who undergo hematopoietic stem cell transplant (HSCT) for malignant or non-malignant conditions appear to have a persistent deficit in their immune function lasting months to years after chemotherapy or HSCT. ^5,6 These children are at high risk of complications from vaccine-preventable infections such as pneumococcal infection,^7,8which underscores the importance of immunization in these populations. Although re-immunization consensus criteria exist for children but there are no universally approved re-vaccination guidelines for non-transplanted childhood cancer survivors.^9,10,11 Most of the experts consider the previous immunization status of the child. As Fioredda F at al reported that younger patients, especially who had not completed the primary schedule, are less protected against vaccine antigens than the older ones.¹²  Esposito S et al Suggested  schedules for children with cancer according to Patients who have completed the vaccination schedule at the time of cancer diagnosis and who did not. ¹³

Other developed nations have started re-immunization of pediatric patients who underwent chemotherapy or radiotherapy or both. No doubt we have to start it. But for cost-effective re-immunization of these children with cancer, their previous immunization history and status will be helpful for the pediatric oncologist. The objective of this study was to estimate the extent of A

Immunization Status of under-five Children suffering from cancer                   Ashis Kumar Ghosh et al

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timely full immunization coverage and to investigate the coverage of different types of EPI vaccines of cancer patients.

Methods & materials

This was a hospital-based study conducted from January 2018 to December 2018. Data are collected from U₅ patients admitted in Pediatric Hematology and Oncology (PHO) ward during the period of study. Patients, who were neonates (i.e. age less than 28 days) and have not got scope to go for immunization, were also included in this study. Patients age 5 years or above were excluded from the study. Lack of reliable immunization history and readmitted cases were excluded from our study. The required information was collected from the prime caretaker after obtaining verbal consent. The accuracy and validity of the information were confirmed by immunization card in every case ( except those, who have not totally gone for vaccination) and inspection for the BCG scar. But pulse polio and Vitamin-A immunization was not included in this study. All information was recorded in a pre-formed questionnaire. Parental knowledge and attitude about immunization were recorded. Children were classified according to WHO guide line, as fully immunized [who received one BCG ; three doses of Pentavalent ; at least three doses of polio ; and one dose of measles vaccine ¹⁴ ,in proper doses and frequency as per Expanded program on Immunization( EPI.Table-1) up to the age], partially immunized (received some vaccine as per EPI but not completely immunized) and not immunized (a child who had not yet received any vaccine appropriate for the age). Statistical analysis of data was done by using SPSS software.

Table 1. Bangladesh immunization schedule, 2015. ^15,16

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 Vaccine                                     Age at administration

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BCG                                        At birth

Pentavalent ^a               6 weeks, 10 weeks, 14 weeks

OPV                                        6 weeks, 10 weeks, 14 weeks, 38 weeks

 PCV                                       6 weeks, 10 weeks, 14 weeks

IPV ^b                                      14 weeks

MR ^c                                        38 weeks

Measles                                   15 months

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BCG, bacillus Calmette–Guérin;   OPV, oral polio vaccine; PCV, pneumococcal conjugate vaccine ;

IPV, injectable polio vaccine;  MR, measles–rubella vaccine.

a Pentavalent includes DTP–Hib–Hep B (diphtheria–tetanus–pertussis, Haemo-  philus influenzae type b,

    and   hepatitis B virus).

 b Introduced into the Expanded Programme on Immunization in 2015. Used in conjunction with OPV.

 c MR introduced into the Expanded Programme on Immunization in 2012.

Immunization Status of under-five Children suffering from cancer                  Ashis Kumar Ghosh et al

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Results

A total patients (age 0 to <18 years) enrolled in PHO in National Institute of Cancer Research and Hospital (NICRH) during January 2018 to December 2018 were 636. Among them under five patients were 182 (28.62%). But only 120 under five children were fulfilled the including criteria and included in this study. The male to female ratio was 1.45:1(71:49). Average age of our patients was 26.27 months and range 9 days - 55 months.  Only 15 (12.5%) cases were from Town and the remaining ones were from the village. None of them was slam dweller except a girl of Rohiga (Myanmar). Most of the patients belong to Low income group (N=108) rest of the cases are from medium income group (N-12.10%), there was no child from high income group. Majority of the parents of children 95% (N-114) were aware about the need of immunization but nine babies (7.5%) were found unimmunized due to various causes (Table-2). One baby of six years from Mayanma have no belief on vaccination.

Table-2           

Sl.	Name	Age	Sex	Diseases	Cause of immunization failure
1.	Asma	6 years	female	Retinoblastoma	She is from Mayanmar. Family don’t  believe vaccine
2.	Saidul	3 Months	Male	Infantile Fibrosarcoma	Early start of symptoms
3.	Baby of  Shamim	25 Days	Female	Sacrococcygeal teratoma	Too early start of symptom
4.	Naznin	9 Days	Female	Nephroblastomatosis	Too early start of symptom
5.	Nazim          PNET	3 Months	Male	PNET	Too early start of symptom
6.	Mymuna	15 Months	Female	Retinoblastoma	Early start of symptom but she was late to came to hospital
7.	Alif	4 Months	Male	Rhabdomyosarcoma	Early start of symptom
8.	Sadia himu	36 months	Female	Neuroblastoma	Early start of symptom
9.	Adil.	11 Months	Male	Germinoma of pineal gland	Early start of symptom

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To evaluate the trends in cancer incidence in children under 5 years of age, cancers were classification according to International Classification of Childhood Cancer (ICCC). In this series most common cancers (Table-3) were Retinoblastoma (29.17 %, N-35);followed by Germ cell tumors (20%, N-24),  Renal tumors (15.83%,N-19),; Hematological Malignancies(14.17%,

Immunization Status of under-five Children suffering from cancer                 Ashis Kumar Ghosh et al

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N-17), Soft tissue sarcomas (11.67%, N-14), CNS and intraspinal neoplasms (3.33%,N-4) Neuroblastoma (2.5%, N-3); Malignant bone tumors(2.5%, N-3). Hepatic tumors (0.83%, N-1); There was no carcinoma. Average age of development of signs and symptoms were 11 months.

 

Table-3

­­­Sl.	Name of Diseases	Number of Cases	%  of cases
1	Retinoblastoma	35	29.17
2	Germ cell tumors	24	20­­
3	Renal tumors	19	15.83
4	Hematological Malignancy	17	14.17
5	Soft tissue sarcomas	14	11.67
6	CNS and intraspinal neoplasms	4	3.33
7	Neuroblastoma	3	2.5
8	Malignant bone tumors	3	2.5
9	Hepatic tumors	1	0.83

                                                          

Out of total 120 children, 27.5% (N-33) were completely immunized, 65% (N- 78) were partially immunized and 7.5% (N-9) were unimmunized (Table-4). Fully immunized females patients were more than males (F: M=1.2:1).

The average age of completely immunized children was 32 months.

 

BCG had the highest completion 92.5% (N-111), followed by pentavalent vaccine 70% (N-84) OPV 73.33% (N-88), PCV 33 (27.5%) and MR 30% (N-36). In this study, IPV coverage was 27.50% (N-33). Regarding causes of failure of immunization, 40% (N-48) parents clearly told of diseases, the rest of the parents could not answer specifically. One parent from Mayanmar has no belief in vaccination. Fifty-five percent (N-66) of children (completely or partially immunized) were regular during their vaccination. 

 

 

 

 

 

Immunization Status of under-five Children suffering from cancer               Ashis Kumar Ghosh et al

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Table-4

Vaccine name	National data of vaccine Coverage	Vaccine coverage of Children suffering from cancer
Fully vaccinated	83% a	27.5% (N-33)
Not vaccinated	-	7.5% (N-9)
Partialy vaccinated	-	65 % (N-78)
BCG	98%b	92.5% (N-111 )
Pentavalent	94%b	70% (N-84)
OPV	94%b	73.33% (N-88)
PCV	88%b	27.50% (N-33)
IPV	Not available	27.50% (N-33)
MR	>95%c	30% (N-36)

 

^a. Matthew L. et al. Socioeconomic factors associated with full childhood vaccination in Bangladesh, 2014. International Journal Of Infectious Diseases 2018;69:35–40

^b UNICEF. Bangladesh: WHO and UNICEF estimates of immunization coverage 2015 revision July. 2015 (July):1–17.

^C Sudhir K, Rajendra B, Stephen C, Mohammad S, James L. Progress toward measles elimination-Bangladesh, 2000–2016. Morb Mortal Wkly Rep 2017; 66(28):753–7

 

Discussion

Total 636 children ( 0 to <18years) with cancer were enrolled in our department in 2018. Among them under five children were 185 (29%). Generally under five children in Bangladesh are 24% of pediatric group¹⁷. So in this study revealed that 5% U₅ children were more affected by cancer than healthy U₅ children and a pervious study of our institute (NICRH) by Jabeen S et al reported the  same  result of  30.96%  . ¹⁸

 Only 120 under five children were fulfilled the including criteria and included in this study. The male to female ratio was 1.45:1(M:F=71:49), which is not much different from national data (M:F-1.08:1) of this respective age.¹⁷ Average age of our patients was 26.27 months and range 9 days - 55 months.  Only 15 (12.5%) cases were from urban and the remaining ones were from the village. None of them was slam dweller except a girl from Rohiga (Myanmar).But in Bangladesh urban population percentage is 36.63%,¹⁹ which indicate that the rural U₅ children suffered from cancer more than urban population. Jabeen S et al found pediatric cancer percentage of rural and urban is 66.64% and 33.36% respectively,¹⁸  which was far from the percentage of U₅ cancer patients of our study. Most of the patient’s family were poor (N=107) rest of the cases are from medium income group (N-12, 10%), there was no child from a rich family. One baby of six years from Rohiga camp of  Chittagong hill tracts. Majority of the

Immunization Status of under-five Children suffering from cancer                   Ashis Kumar Ghosh et al

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parents of children (95%, N-114) were aware of the need for immunization, which correlate with the first dose (92.5%) of  BCG vaccination.

Generally concentration on the 0- to 4-year-old age range captures the peak of the acute lymphoblastic leukemia (ALL) and embryonal tumor incidence curves.¹⁹ So most common childhood cancer are Leukemia, Brain and spinal cord tumors, Neuroblastoma, Wilms tumor, Rhabdomyosarcoma. But incidence of diseases of U5 children in our department (PHO) were different. Most common cancer of our study was Retinoblastoma (29.17 %), then Germ cell tumors (20%) and Renal tumors (15.83%). Hematological malignancies (14.17%,N-17), Soft tissue sarcomas(11.67%, N-14), CNS and intraspinal neoplasms (3.33%,N-4) Neuroblastoma (2.5%, N-3), Malignant bone tumors (2.5%, N-3) and Hepatic tumors(0.83%, N-1). There was no carcinoma. Average age of development of signs and symptoms were 11 months. Basically our department (PHO) was not fully appropriate for the treatment of pediatric hematological malignancy, so this finding ( more solid tumors than hematological tumors)  if quite expected and relevant. In a hospital based study on pediatric cancer in India Hazarika M et al found in the sub group of < 5 year’s retinoblastoma was commonest²⁰ tumor of children, which correlate our findings.

In the present study, the percentage of fully immunized children was 27.5% (N-33), whereas the national coverage rate was 83% in Bangladesh.¹⁵ Fully immunized female patients were more than male (F:M=1.2:1). But in most of the studies of the subcontinent reported differently that fully-immunized children were predominantly male.²¹ and got full immunization among children 12-23 months old in rural Bangladesh.²² In our study the average age of completion of immunization re 32 months. It is quite relevant for cancer patients who have to postpone immunization for several times due to nonspecific illnesses.

 

In case of children with cancer, this full immunization coverage rate (27.5%) was a quite new experience for public health. According to WHO, for full immunization one BCG; three doses of  Pentavalent ; at least three doses of polio; and one dose of measles vaccine is needed.¹⁴ First dose of measles vaccine is given at 38 weeks of age.  So according to EPI schedule for full immunization, children have to remain healthy/ symptomless up to minimum 38 weeks from birth.

But children with cancer develop nonspecific fever, irritability, pain, and vomiting before many months of a cancer diagnosis. The rarity and nonspecific clinical presentation of symptoms influenced parent’s delay in seeking medical advice.^23,24 During this period parents did not take their kids for vaccination and health workers also refused to give vaccines during that illness. Children with cancer started to discontinue vaccination after getting the first dose of BCG, Pentavalent, Polio, and PCV and from then vaccination coverage fall suddenly. One of our

Immunization Status of under-five Children suffering from cancer                   Ashis Kumar Ghosh et al

---------------------------------------------------------------------------------------------------------------------------------------patients diagnosed as neuroblastoma at the age of 36 months but did not start EPI vaccination due to nonspecific illness from the age of 2 months.

In this study BCG coverage was 92.5%, which correlates with national coverage rate (98%). But the slight low coverage rate is due to early (< 6 weeks) diagnosis of cancer or start of nonspecific syndromes before diagnosis. Pentavalent and OPV coverage were 70% and 73.33% respectively, where the national coverage rate of both vaccine were 94%. Immunization coverage of ill children showed dropout during Pentavalent and OPV schedule, it is a normal picture of immunization of Bangladesh. Even in normal population there was decreasing trend of immunization as the age progressed.²⁵ and In our national immunization coverage partially and unimmunized children are 14%, and 2% respectively.²⁶

In fact MCV (Measles containing vaccine ) had the lowest coverage of any of the EPI immunization, whereas BCG, administered at birth, had a highest ,with OPV and pentavalent vaccine administered at 5,10,14 weeks falling somewhere in between.¹⁵ But in our study the findings are different. Our study has reported that PCV and IPV both coverage was 27.5%, whereas MR coverage rate was 30%, more than PCV and IPV. Last dose of both of the vaccine (PCV and IPV) were given in week-14 with 3^rd dose of Pentavalent and OPV but coverage rate is low than Pentavalent and OPV. The causes of low percentage of PCV and IPV were two, first children age and secondly unavailability of vaccines. Basically these two vaccines started in EPI in March 2015. Some of our study child enrolled in EPI before 2015 without PCV and IPV and at the early period (March to December 2015) of introduction vaccinations were not available in all EPI centers. So some children did not have PCV and IPV at that time. But later on, they got the MR vaccine.  For this reason MR coverage rate was more than PCV and IPV.

Limitation of this study was that the study was done only considering the appearance of cancer related illness and availability of EPI vaccine but there are other factors that influence the coverage of childhood vaccination like – wealth of parents, a region the child lives, maternal access to care and autonomy in healthcare decision making with peoples adherence to the vaccination schedule in Bangladesh.

Conclution:    The number of patients with cancer or immunosuppressed states is increasing. Furthermore, every day new immunosuppressive agents are being introduced. And Bangladesh possesses a large number of new pediatric cancer cases per year and every year fewer than four thousand U₅ children are entering these patient load. Among them 72.5% of these children enter in CT or RT without full immunization and due to cancer and chemotherapy they suffer more immunodeficiency. So no doubt their mortality morbidity due to vaccine preventable diseases should be increase than vaccinated cancer child. So this study will help to open another window of national immunization program and help the oncologist for planning in ensuing re-vaccination program of   cancer patients.

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