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Indian Journal of Community Medicine

Effect of Immunity on Falciparum Gametocyte with Increasing Age and its Impact on Transmission in an Endemic Area

Author(s): Gyan Chand, V. Soan, R.S. Tiwary

Vol. 25, No. 2 (2000-04 - 2000-06)

Regional Medical Research Centre for Tribals (Indian Council of Medical Research), Nagpur Road, Jabalpur-482003

Abstract:

Research question: Does the adult age group with increasing immunity contribute to transmission of malaria in the endemic area.

Objective: To study the effect of increasing age and immunity on P. falciparum gametocyte and transmission.

Study designs: Longitudinal study over a period of two years. Mass blood survey covering 3 seasons each year. Incidence of malaria and production of gametocyte restricted during peak transmission season among adult age group by chloroquine chemoprophylaxis and over10 weeks covering peak transmission period.

Participants: Gond tribe of Jabalpur (M.P.).

Study variables: Slide positivity rate and slide falciparum rate were compared among 2-14 years and 14+ year age group before and after intervention.

Statistical analysis: Normal statistical test.

Results: There was significant reduction in slide positivity and slide falciparum rates in both the age groups during and after intervention (i.e. chemoprophylaxis). Reduction in indices among younger group was achieved because of less production of gametocytaemia in adults i.e. semi-immune population.

Conclusions: Immunity acquired with the repeated exposure does not have any role in modulating the infectiousness of gametocyte and on transmission in the present study.

Keywords: Plasmodium falciparum, Gametocyte, Chemoprophylaxis, Immunity, Gond tribe

Introduction:

It is well known that the population particularly the adults living in an endemic area naturally acquire immunity with the repeated attacks and exposure to malaria infection. Such adult population carries silent parasite and remains potential source of infection. Immunity acquired with the increasing age and exposure to repeated attacks of infection modulate the density of asexual parasitaemia and thereby, gametocytaemia and its infectivity and in turn malaria transmission. This aspect has been studied by estimation of anti-gametocyte antibodies and its influence on the production of sporozoites and its influence on the production of sporozoites in the vector1. Few studies have been carried out to quantify the P. falciparum gametocyte density and its logivity in different age groups2. Studies in Indian environment are rare. The present study attempts to answer the query - does the adult age group with increasing immunity contribute to transmission of Malaria in an endemic area?

Material and Methods:

The study was carried out in a village of Kundam block of Jabalpur district - a known malaria endemic area3,4. The block consisted of 193 villages with a population of about 1,00,000. More than 70% of its population is tribal. Gond is the predominant tribe of the area. The area has rocky hills and undulating terrain with thick forests of teak. Study village was located near stream and nallah as these are the main source of water for drinking (during hot season) and other household work during most part of the year.

Villages of the area remain cut off during the rains. Houses are kutcha, made up of bamboo walls with mud plaster. Ventillation is poor. Population is dependent for livelihood on forest produce and labour work under IRDP and other poverty alleviation programmes. The people of this block keep on migrating temporarily for few days ranging from a week to about 20 days within the range of 40-60 Kms during crop season.

Since the effect of immunity with increasing age on transmission was to be assessed in adult population, therefore, the incidence of malaria and production of gametocytaemia was checked during the peak transmission period in the population aged 14 years and above because this group is supposed to have different immune status from the younger age group. For this purpose, complete census of the village was carried out and all the households of the village were enumerated. For-calculation and interpretation of results the population was divided in two age groups below 14 years and above 14 years. Three mass blood surveys for each year at definite interval in the month of July (beginning of transmission), November (peak transmission) and February (end of transmission) were carried out for two consecutive year during 1993 and 94. Fortnightly active fever surveys were conducted to determine the peak transmission season for chemoprophylaxis. Slides were prepared by finger prick method, numbered and stained with giemsa stain. History of fever, age, sex and head of household were recorded. Presumptive treatment with 600 mg chloroquine per adult was given to all the febrile cases.

Prophylactic chemotherapy with chloroquine in an initial dose of 10 mg per kg body weight5 followed by weekly dose of 5mg per Kg body weight for 10 consecutive weeks covering the peak transmission season i.e. first week of September 94 to mid November 94 were administered to all the available persons of all the households. To ensure the drug compliance the staff of R.M.R.C. Jabalpur themselves administered the doses personally. Individuals who missed chemotherapy for two consecutive or more weeks were dropped from the study. During intervention period all the individuals undergoing drug therapy were monitored for any side effect and adverse reactions of chloroquine. The incidence, recovery and conversion rates were calculated by using method of Beksey et al6. The effect of semi-immune population on transmission was assessed comparing value of each mass blood survey of intervention year against the value of corresponding baseline mass blood survey. Normal statistial test was applied to test the difference in mean and variation from season to season wherever necessary.

Results and Discussion:

Table I: Age and sex composition of the population.

Age (Yrs.) Male Female Total
0-2 22 33 55
2-9 54 55 109
9-14 40 46 86
14+ 245 270 515
Total 361 404 765

Age and sex structure of the study population is given in Table I. Of the 765 subjects 515 belonged to 14+ age group representing about 67% of the population of the village, eligible for chemoprophylexis. Out of these 320%(62%) completed 10 weeks course of chemoprophylaxis. Rest of them either refused to take the drug or missed for 2 consecutive weeks in between, because of absence or the other reasons.

Fortnightly fever survey and seasonal pattern:

Baseline data collected for the year 1993-94 showed a rise in malaria incidence from July onwards and attained peak in October and November and thereafter graph moved southwards from December till June. In the beginning P.vivaz predominated and with the progress of time P.vivaz was replaced by P. falciparum from September '93 to February '94. Thus indicating the peak transmission season of P. falciparum from September to November. The trend was similar as observe earlier in this area3 Similar trend was observed during the intervention year but the indices were low as compared to baseline observation. In the comparison village peak transmission rate i.e. slide positivity rate was higher than village A during intervention period. P. falciparum was the predominant species throughout the study period and in both the villages. Plasmodium vivax more frequently occurred during the intervention period the incidence of P. vivax was itself less and its incidence almost diminished during the period in both the age groups. Comparing the incidence of malaria and P. falciparum during peak transmission period it has been revealed that overall morbidity was reduced during the intervention period (Table II). The slide positivity rate and slide falciparum rate also reduced significantly among both the age group. Reduction in incidence of P. falciparum infection in adult age group exhibited the effect of chemoprophylaxis which had significant impact on the incidence of P. falciparum and malaria infection in younger age group.

Table II: Epidemiological situation of malaria during peak transmission period (September-November) year 1993-94.

Incides 1993 1994*
T <14 yrs 14+yrs T <14 yrs 14+ yrs
Blood slides collected 154 62 92 69 27 42
+ve 84 42 42 19 11 8
Pv 40 21 19 2 2 0
Pf 44 21 23 17 9 8
SPR 54.5 67.7 45.6 27.5 40.7 19.0
SFR 28.6 33.8 25.0 24.6 33.3 19.0
PF% 52.3 50.0 54.7 89.5 81.8 100.0

*Chemoprophylaxis began from Ist week of September for 10 weeks.

Mass blood survey:

Observations on mass blood surveys of both the years have been summarised in Table III. Results have indicated lowest slide positivity rate during the months of July in both the years and accounts 2% in 1993. In July 1993 not a single case of P. falciparum has been found, also not a single smeare was found positive for P. vivax too among younger age group. While in November (peak transmission) very high slide positivity rate was recorded. P. falciparum dominated over P. vivax (SPR - 34.7, SFR - 23.55). The observations at a glance reveal on out break of P. falciparum infection. Looking at the fortnightly fever survey it was revealed that the incidence of P. falciparum had increased gradually over the last 4 months. Absence of P. falciparum infection during July was either due to lack of exposure to infection or a result of protective immunity. Probably latent parasitaemia at very low density might have occurred during July-August which could not be detected with the existing conventional method of slide examination. During February 1994 slide positivity was lower compared to the rate observed in November and P. falciparum dominated over P. vivax. The slide positivity was slighlty higher in younger age group than the adult age group, but the difference was not significant.

Table III: Results of mass blood survey of pre and post intervention period.

1993-94 1994-95
Month Age group SPR SFR %PFG SPR SFR %PFG Z value
SPR SFR
July 0-2 3.7 0 0 10.0 0 0
2-14 0 0 0 16.3 (+100) 3.5 (+100) 40
14+ 3.4 0 0 6.63 (51.3) 1.24 (100) 33.3
T 2.0 0 0 10.2 (+80) 2.0 (+100) 37.5 4.81* 2.86
Nov. 0-2 7.7 7.7 0 0 0 0
2-14 37.11 22.7 63.6 13.9 (-64) 13.9 (-39) 60
14+ 35.6 25.8 73.5 4.6 (-87) 4.6 (-82) 53.3
T 34.7 23.55 68.4 7.3 (-79) 7.3 (-69) 57.1 8.33* 3.47
Feb. 0-2 0 0 0 4.5 4.5 100
2-14 8.1 8.1 70.7 4.1 (-50) 3.4 (-55.35)
14+ 6.8 5.6 80.0 3.4 (-50) 3.1 (-44.6) 88.8
T 7.0 6.4 75.0 3.7 (-47) 3.0 (-53) 71.4 1.96 -2.08
Z value for
change from
Nov. to Feb.
2-14 5.1 3.06 2.94 3.19
14+ 6.5 5.0 0.75 0.99
T 8.18 5.61 2.45 2.98

Comparison of baseline data with intervention year and the post-intervention period revealed higher slide positivity rate during pre-monsoon period of intervention year and increase in SPR was 80% over baseline year (Z=4.8, p<0.05) indicating higher transmission in 1994-95. Incidence of P. falciparum malaria was also more. Presence of P. falciparum infection in younger age group is an indication of indigenous transmission in the village which was not seen during baseline year (Z=2.86, p<0.05). Majority of the P. falciparum infection did not have any sign of illness in all the mass blood surveys. It is reported that in malaria endemic areas probably more than one strain of P. falciparum exist which differ in their virulent effect7.

The overall slide positivity rate during intervention year in peak transmission period was reduced as compared to year 1993 (base line) observations. The reduction in slide positivity rate was more in adult age and highly significant (80%, Z=8.872, p<0.05) than the slide positivity rate in younger age group (64%, Z=3.99, p<0.05). The reduction in SPR was mainly because of the complete disappearance of P. vivax during post-intervention month. The reduction in slide falciparum rate was markedly less in younger age group (39%, Z=1.74, p<0.05). In adults reduction was sharp (82%, Z=6.57, p<0.05).

Comparing the reduction attributed from Nov. to Frb. before and after intervention, it is revealed that indices were reduced much more in pre-intervention period (79.8%, Z=8.18, p<0.05) than post-intervention period (49.7%, Z=2.45, p<0.05). Lesser reduction in post-intervention period is interpreted by the fact that during intervention period transmission (In peak season) has come down to very low level because of chemoprophylaxis and the persistent transmission reported in this area4.

The reduction in SPR was more in both the age groups during pre-intervention year. Reduction in slide falciparum rate was also more during pre-transmission period. The reduction was more in adult age group during pre-intervention period which was obvious because of drug load in adults. The reduction in younger age group in term of rate was almost similar during both the periods, but the incidence of infection was definitely less compared to base line period. Reduction in indices particularly in younger age group during intervention and post-intervention period inspite of higher transmission during intervention period shows that altered immunity with increasing age might not have any impact on transmission. If the immunity had any role in altering or modulating the infectiousness of gametocyte, the reduction in the incidence of infection during post-intervention would not have been achieved.

Malaria conversion rate in the present study could not be calculated because of the limitation of the method. However , incidence rate and recovery rate of P. falciparum malaria was calculated for intervention and post-intervention period, which is summarised in Table IV. As a evident from the table lesser incidence rate and higher recovery rate among the adults was observed from July to November as compared to the individuals belonging to younger age group which was expected because of chemoprophylaxis. The trend was reversed from November to February after intervention. This happened probably due to the altered situation, because of the involvement of adult population in transmission after the withdrawal of chemoprophylaxis.

Table IV: Incidence and recovery rate of Malaria (July '94 to Nov '94 & Nov '94 to Feb. '95).

Age group Period Time span Incidence rate Recovery rate
2-14 July 94 136 days 0.00200 0.1750
14+ Nov. 94 0.00110 0.0210
2-14 Nov. 94 91 days 0.00015 0.0347
14+ Feb. 95 0.00071 0.0161

The observations of this study and earlier studies showed that the area is endemic for P. falciparum. Variation from season to season and year to year in indices are the peculiarity of the unstable malaria. Under Such situations some proportion of adult population has altered immune status which is said to influence the infectiousness of P. falciparum gametocyte.

The observations are not in consistence with the conclusion of study carried out elsewhere, where it was stated that population of 14+ year age which constituted about 65% contributed equal amount of transmission to that contributed by 1-5 year age which constituted 12% of population and hence semi-immune population carried more frequently non-infectious gametocytes8,9.

A more accurate method to assess the infectiousness of gametocyte in population is through feeding of mosquitoes on such individuals. In the present study, indirect method of examining its infectiousness was employed by suppressing gametocyte conversion from asexual parasitaemia. It may be noted that in this study only 62% of the total eligible population took part in chloroquine prophylexis and significant reduction in incidence was observed. If incidence and conversion of asexual parasitaemia to sexual form would have been restricted in entire eligible population the impact on transmission and incidence would have been much higher in younger age group. Further, poor response of chloroquine against P. falciparum has been reported in this area10. Therefore, it is more likely that some individuals may not have responded to chloroquine prophylaxis.

Since, the incidence of malaria was reduced significantly among the younger age group after the suppression on incidence of malaria and the formation of gametocyte by chemoprophylaxis to adults (14+ years age group) it can said that the immunity acquired with age in adults has not altered or reduced the infectiousness of gametocytes, otherwise the impact on values in younger age group would not be visible. Further, entomological studies are needed to confirm the findings of this study.

Acknowledgement:

The authors thankfully acknowledge the help and assistance of Dr. P.Govardhini during planning and execution of the study. Sincere field work carried out by the staff of Vector Biology Division of RMRC is also acknowledged.

References :

  1. Smalley & Sindon: Plasmodium falciparum gametocyte longivity and infectivity. Parasitology 1977; 74: 1-8.
  2. Muirhead & Thompson: The malaria infectivity of an African population to mosquito (Anopheles gambiae) A random Xenodiagnostic Survey. Am. J. Trop Med. Hyg. 1957; 6: 971-9.
  3. Singh N, Sharma VP, Shukla MM, Chand G: Malaria outbreak in Kundam Block, Jabalpur (M.P.). Indian J. Malariol 1988; 25: 41-9.
  4. Singh N, Sharma VP: Persistant Malaria Transmission in Kundam Block, District Jabalpur (M.P.). Indian J. Malariol. 1989; 28: 1-7.
  5. Nicholas J. White: Loading dose of antimalarial prophylaxis. Trans Roy. Soc. Trop. Med. Hyg. 1988; 79 (correspondence).
  6. Bekessy A, Molineeaux L, Storey J: Estimation of incidence and recovery rate of Plasmodium falciparum parasitaemia from logitudinal data. Bull. W.H.O. 1976; 54: 658-93.
  7. Ibrahim M. Elhasson, Lass Huiid, Jacksen PL et al: High proportion of subclinical plasmodium falciparum infection in an area of seasonal and unstable malaria in Sudan. Am. J. Trop. Med. Hyg. 1995; 53(1): 78-83.
  8. Carter R, Miller LH: A method for study of gametocytogenesis by plasmodium falciparum in culture: Evidence for environmental modulation of gametocytogenesis. Bull. W.H.O. 1979; 57 (Suppl.) 1: 38-67.
  9. Mc. Carthy VC et al: Plasmodium falciparum: Responses of a semi-immune individual to homologous and heterologous challenges and non infectiously of gametocytes in Anopheles stephensi. Am. J. Trop. Med. Hyg. 1978; 27: 6-8.
  10. Singh N, Shukla MM, Sharma VP, Saxena BN: A focus of high degree of chloroquine resistant P. falciparum in Mandla district (M.P.). Indian J. Malariol. 1989; 45-51.
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