The Malumfashi Project—an epidemiological, clinical and laboratory study

24

TRANSACTIONS OFTHEROYALSOCIETY OFTROPICAL MEDICINE ANDHYGIENE, VOL.77,No. 1,24-31(1983)

The Malumfashi

Project-an

epidemiological, study

clinical

and laboratory

H. M. GILLES, B. M. GREENWOOD, A. M. GREENWOOD, A. K. BRADLEY,I. BLAKEBROIJGH, R. N. H. PUGH, B. MUSA, U. SHEHU, M. TAYO AND J. JEWSBURY Liverpool School of Tropical Medicine; Department of Medicine and Institute of Health, Ahmadu Belle University, Zaria, Nigeria and Medical Research Council of Nigeria Introduction

The initial plan of study was to monitor the changing pattern of diseasein the Malumfashi district (Fig. 1) resulting from the ecological changeslikely to occur as a result of building one hundred low-earth dams in the area coupled with a change in agricultural policy from subsistence farming to mechanization. The gestation period of the project was rather long. The original submission to the Tropical Medicine Research Board was sent in 1970: a oilot survev was carried out in 1971; the proposal Gas approvkd in 1973and it was not until towards the end of 1974that the first member of the team arrived in Nigeria. This was Dr. Andew Bradley who was to be in charge of the demography. It became perfectly clear by 1975 that the build& of dams-the maior factor that was likely to changi the ecological environment-was going to be delayed considerably, and it was therefore thought wise to change the original plan completely.

Fig. 1. A map of Nigeria

showing the location of Malumfashi.

We were indeed proved to be right becausethe first dam was not built until 1977, one year before the five-year M.R.C. grant was due to expire. The change of plan involved the study of four main themes (I) the demography of the area, (II) the pattern of schistosomiasis before and after the building of the first dam, (III) the epidemiology of meningococcal meningitis in the area, and (IV) the possible immunosuppression effect of malaria in children under two years of age. Methods The various methods and techniques usedfor the above

investigations have been described elsewhere-demography (BRADLEYet al., 1982a and b) schistosomiasis (PUGH & GILLES, 1978, 1979aand b; PUGHet al., 1979); meningitis (GREENWOOD et al., 1980; BLAKEBROUGH et aZ., 1982) and malaria (BRADLEY-MOOREet al., 1983a and b).

(I) Demography This involved detailed mapping of the area, the enumera-

l-l. M. GILLES et aI.

25

70-

il

6050-

2

Males

40-

E 2 30$ a

.Ruwan area Masarl Dankwaro area

10for Malumfashi

village

20‘b

Fig, 2. Age-sex pyramid

Sanyi

village

area

hamlet

1977. 1

0

tion of 42,493 persons (1974-77)and registraton of a sub-set of the enumerated population numbering 26,100 who were visited once a month for a period of one year (1977-78). The age-sexpyramid derived from the enumeration data is given in Fig. 2. It is typical of that seen in many rural areas of the tropics with a broad base and tapering at the top-in keeping with the fact that only 3% of the population are 65 years or over. Registration involved a long period of training for the locally recruited enumerators who were individuals who had only- received seven years of primary education. The highlights of the retrospective enumeration data and prospective registration data were as follows: (a) 45% of the population were under 15 years of age (enumeration); (b) Crude birth rate 55%o(enumeration);48%o(registration); (c) Total fertility rate 6.8 (enumeration); 6.5 (registration); (d) Infant mortality rate 170?410 (enumeration); 88% (registration); (e) Child mortality rate 182%0(enumeration); 116%0(registration); (f) Crude ::$I rate 26% (enumeration); 16% (registra3 (g) Crude rate of natural increase 2.9% (enumeration). Various analysesof prospective registration data indicated under-reporting and reliance is placed on the estimates derived from the application of indirect techniques to the retrospective enumeration data (BRADLEYet al., 1982, a and

b.1

The relatively high crude rate of natural increase for Malumfashi indicates that considerable population growth will be experienced in the area in the future. At the monthly registration, an attempt was made to determine the main symptom or symptoms present before death. The analysis of 126children aged 0 to 4 years showed that 30 died from measles; 37 had diarrhoea as the main symptom and 59 had pyrexia. Of 37 children who died of diarrhoea, 24 died between May and August, while of 59 who died with pyrexia, 42 died between May and October. In this context it is worth noting that the peak months for malaria transmission in the Malumfashi area are May to October, and that in young children malaria can present as fever and/or diarrhoea. (II) Schistosomiasis

haematobia

The objectives of the investigation were as follows: (a) to identify the magnitude of the schistosomiasis haematobia problem in the Malumfashi area and to record any changes

10 Age

20

30

(years)

3. Focaltransmissionof S. hayatobium infectionin Mahunfashi area.

Fig.

resulting from the building of the low earth dam at Ruwan Sanyi; (b) to formulate a plan of action which would miniinixe the risk of spread of the diseasein the area as well as in other parts of Northern Nigeria where similar dam building schemes were being contemplated. The over-all prevalence of Schistosoma haematobium in the Ruwan Sanyi area was 14.7% (4382 persons examined) and, as one might expect, there was a very marked focal transmission of the diseasewith prevalence rates as high as 70% in one village and as low as 20% in another. The peak age specific prevalence was, however, fairly constant being highest in the age groups 10 to 20 in all villages (Fig. 3). Renal function tests were carried out on about 58 boys aged 6 to 17 years with egg counts of 250 per 10 ml or over. Serum urea and serum creatinine were normal and the serum B2 microglobulin, which is considered to be a reasonable index of the glomerular filtration rate, was normal in 38 children, raised in 13 and very high in 7. No evidence of bacteriuria was found in any of the 1628 males tested, whether they were infected with S. haematobium or not. In females (1469 tested) the rate of bacteriuria was higher but there was no correlation between bacteriuria and the presenceof haematobium infection. We also looked for Salmonella typhi in 246 individuals and in none was S. cyphi isolated. This is in marked contrast with the findings in Egypt where there was evidence of a significantly higher urinary carrier rate of S. &phi in Schistosoma haematobiuminfected individuals as opposed to controls (LEHMANet al., 1973).

Using two urine analysis reagent strips-one for haematuria and one for proteinuria-we found a very close correlation between the combined crizerion,namely, a trace or more of haematuria and 30 mg or more of protemuria, and the intensity of infection (Table I). The results were similar to those of WILKINS et al., 1979. This simple test enablesone to identify, without the use of microscopy, individuals in any population with a moderate to high infection. The technique is thus eminently suited to the principles of targetted population chemotherapy aimed at treating only individuals with moderate to high intensity S. haematobium infection. Renography was carried out in 69 individuals aged 7 to 17 and in 32% there were abnormal pyelographic appearances

26

THE

MALUMFASHI

Fig. 4. Location of Ruwan Sanyi Dam. The first of 100 similar “low earth dams” proposed in the area.

~~~tio~-Schistosomiasis

haematobia-relationship

5367

No. of subjects % with combined urinalysis criterion

Table

118 Sahelian droufgh;

III-Prevalence

No. examined Prevalence %

of S. haenwtobium

1971 199 59.3

pfeifjeti.

of combined

Urinalysis

Criterion*

to intensity

Ova/10 ml 30-250 250-2000

4437

604

264

57

21%

50%

80%

of

>2000 5 100%

Labstix Urinalysis Reagent Strips

infection in Ruwan Sanyi boys (8-15 years) before and after Sahelian

No. examined 1971 1973 1976

Biotnphalaria

l-30

7%

of S. haematobium

in children with 250 eggs or over per 10 ml; there were also abnormal pyelographic appearancesin three of 23 adults who were examined. Follow-up one year after treatment in 18 of 22 boys who had had abnormal urograms showed complete resolution in four, improvement in nine and no change in five. The effect of the Sahelian drought on the intensity of infection in Ruwan Sanyi is shown in Table II. The results show very clearly that in areas like Ruwan Sanyi where transmission essentially occurs in pools during the dry season, a period of drought which abolishes manwater contact, substantially alters the epidemiological pattern of infection. The dam, the first one of the projected one hundred, was built in 1977between Ruwan Sanyi and Kuringafa (Fig. 4). Table III shows the prevalence of infection before and after the Sahelian drought and two years after the completion of the dam. It can be noted that although a rise in prevalence was already occurring two years after the drought (presumably because the dry seasonpools of water were now once again available to the community) a further and much sharper rise occurred in 197ethe prevalence of infection approximating that of 1973. Furthermore, a remarkable change in snail species also occurred subsequent to the dam being built. In 1976 the streams on which the dam was built was infested predominantly with Biomphalaria pfeifferi. After completion of the dam there was an almost total dominance of Bulinus globosus, the population of which rose to 95% with only 4%

Neg.

*Combined Criterion = Trace or more haematuria + 30 mg or more proteinuria

Table II-Intensity drought

PROJECT

No. with ova count 250/10 ml of urine

No. with ova count 1020/10ml of urine

57 (48.3%)

16 (13.5%)

18 (6.9%)

3 (1.2%)

in Ruwan Sanyi School before and after building

1973

Sahelian Drought

1975 190 33.8

1976 194 41.2

1977

Dam Built

of Dam

1979 217 55.8

H.

M.

et al.

GILLES

27

In Table V we present the incidence of carriage of meningococcal speciesby age. It can be noted that the carrier rate is highest in the age groups one to 14 years and that the longest interval between first detection and the last positive swab in any individual was four months. The epidemic provided us with the opportunity to study the meningococcal carrier rate in family contacts and the rest of the community. As expected (Table VI) the carrier rate in contacts sleeping in the same room as the index cases of meningococcal diseasewas significantly higher than in other family contacts or in the unrelated population of the village. The effects of chemoprophylaxis on the carrier rate is shown in Table VII. A marked reduction of the carrier rate occurred after treatment with rifampicin while sulphadimidine had no effect ‘whatsoever, confirming our laboratory in vitro findings that 90% of the strains isolated were resistant to sulphadiazine, a most unfortunate state of affairs considering the usefulness and low cost of these drugs in controlling epidemics of meningococcal disease in the past. People prematurely advocating the widespread use of Fansidar for malaria prophylaxis in Africa may well bear this in mind in relation to other diseasesstill susceptible to the sulphonamides. (b) Antibody levels in the communiry before and after an epidemic Two epidemics of Group A meningococcal diseasein 1977 and 1978gave us the opportunity to study antibody l:vels h, various age groups of the community at ‘Yar Talata before and after an euidemic. As can be seen in Table VIII, mean titres of group A meningococcal antibody were h&her in 1978 than in 1976 in all age groups except those under the age of four years. (c) Antibody response to meningococcal vaccines and rate of

Between July 1977 and May 1978water contact activities were studied at the dam site. 455 observation hours revealed the following information: (i) males were responsible for 98% of activity involving contamination and exposure, (ii) the peak water contact activity occurred between noon and 15.00 hours. (ii) peak output of eggs in the urine occurs during this period, (iv) peak shedding of cercariae from the snail hosts also occurs between 12 noon and 15.00 hours. Thus a close correlation was established between man/water contact and the other factors responsible for transmission. In order to minimize the risk of further spread of infection in this area and as guidelines for other parts of Northern Nigeria where similar dam building schemes were being contemplated, we proposed the following plan of action: (1) Identification within the age group 5-20 years of individuals with moderate to heavy infections using the instant urinanalysis reagent strip method; (2) Selective targetted chemotherapy of these individuals with a single oral combined dose of metrifonate and niridazole*, or three doses of metrifonate at fortnightly intervals; (3) Selective dry season focal mollusciciding. (III) Meningococcal Meningitis Meningococcal disease is a major health problem in Northern Nigeria with sizeable epidemics occurring at regular intervals during the dry season(February-May). In the Malumfashi area we set out to try and answer three basic questions: (i) does the carrier rate of meningococci in the community parallel the seasonalpattern of the disease?i.e.., can one predict an epidemic by demonstrating an increase m the carrier rate in the community? (ii) what are the antibody levels in a village community before and after an epidemic of Group A meningococcal disease?, and (iii) what antibody response results from the meningococcal polysaccharide vaccines (A and C) in a Northern Nigeria rural community and what is the rate of antibody level decay?

&cay

The antibody responseto Group A and C meningococcal polysaccharide vaccine in Mahuta Village two weeks after vaccination was highly satisfactory but two years later the antibody evels were not significantly higher than those of carefully matched controls (Table IX), implying a rate of decay considerably faster than that recorded in Europe and in America. Whether these findings were due to environmental or technical factors remains to be fully determined. In conclusion, our studies on meningitis gave the following results-(i) there was no increase in carrier rate immediately before an epidemic of meningococcal diseasein the Malumfashi area, (ii) rifiampicin reduces the carrier rate but sulphodiamidine does not and 90% of isolated strains are resistant to sulphadiazine, (iii) the initial antibody response to meningococcal vaccine A and C is highly satisfactory but the rate of decay of antibody level is accelerated. In the light of the above findings, we would recommend massvaccination supplemented by rifampicin for household

(a) Carrier rate of meningococci in the communify The carrier rate of meningococci was studied at ‘Yar Talata Village (Pop. 530) on four occasionsat three-monthly intervals between October 1976 and July 1977. The results are presented in Table IV. It can be seen that the over-all carrier rates are similar before and after the epidemic of Group A meningococcal disease that occurred between January and April 1977. Moreover, no Group A carriers were isolated in January 1977just before the epidemic broke out. Clearly at community level one cannot predict the onset of an epidemic by a rise in the carrier rate of meningococci. The carriage rate of group A meningococci, however, increased significantly after the epidemic. *Large stocks of niridazole are available in Nigeria and it would be a waste to discard them.

Table IV-Carrier rates of meningococci at four times of year in ‘Yar Talata village: (Population 530): (by kind permission of the Journal of Infectious Diseases) Group i ii x 29E

Oct. 1976

Jan. 1977

-

April

1977 1

a

T 4

r

3 2

?1

July 1977 -

9

i

I

: 1

3 1

Non-groupable No. Swabbed

: 518

5:

5;1

5:

Total %

3.6

3.8

3.6

34

Epidemic-Group

t . A memngococcal disease

28

THE

MALUMFASHI

PROJECT

Table V-Incidence of carriage of meningococci species by age in ‘Yar Talata (February 77-June 78) (by kind permission of the Journd of Infectious Diseases)

Age (years)


l-4

5-9

10-14

15-19

20+

0

14

14

11

4

8

Meningococcal Carrier Rate (%)

Duration of carriage (Mean time between 1st and last +ve swab) = 3 months

Table VI-Group A meningococcal carriage in family contacts of patients with group A meningococcal disease (by kind permission of the Journal of Infectious Diseases)

Carrier rate in contacts sleeping in same room Carrier rate in family contacts not sleeping in same room Carrier rate in unrelated population *x2 = 5.09; 0*05> p>O*Ol

Table VII-Effects Diseases)

of prophylaxis

Sulphadimidine Rifampicin

on meningococcal

21.5%*

n = 209

13.7% 3.2%

n = 220 n = 501

carriage (by kind permission of the Journal of Infictious %

No. in sample

carrying before prophylaxis

244 235

it

%

%

carrying 2 weeks later

carrying 6 weeks later

14 5

10 3

*

*90% of strains isolated were resistant to 50 pg/ml of sulphadiazine in vitro Dosage of Rifampicin O-l years 75 mg.b.d. years 5-14 years 300 mg.b.d. for 2 days 15 years + 600 2-4 150 mg.b.d. I

Table VIII-Age Diseases)

distribution

Age (years) Mean A titre

of antibody levels in ‘Yar Talata (by kind permission of the JournaE of Infectious

1<2 0.4

log2)

Mean C titre

0.7

2-4

5-9

20+

Year

1.5 1.1 ;:;

:.:.

;:;

;::

;.;

::;

1.4 1.4

;:;

;:;

1976 1978 1976 1978

log2)

10-14

15-19

(N (N (N (N

= = = =

380) 112) 394) 110)

Group A epidemics in 1977 and 1978

Table IX-Meningococcal antibody levels before, 2 weeks and 2 years after immunization with group A and C meningococcal polysaccharide vaccine (50 pg) in Mahuta village (by kind permission of theJournal of Infectious Diseases)

n = 118 Mean A titre (log2) Mean C titre (log2) Controls (n = 140)

Prevaccination 2.9 + 1.4 1.2 * 1.3

2 weeks postvaccination 5.1 f 2.8 6.0 f 3.1

2 years postvaccination 2.7 f 1.2 2.4 f 1.6 A 2.4 + 1.2 C 1.8 f 1.2

H. M. GILLES et al.

Table X-Malarial

29

rates during wet and dry seasons in Gamzago village (Population 10,900) 1977 Crude Parasite Rate %

Sample size 230 100 320 500

Age

End of wet season (October)

End of dry season (April)

4 months-l year >l-4 years S-9 years Adults

68% 72% 93% 25%

54% 60% 76% 15%

Table XI-Relative prevalence of species of malaria parasites in Ganuago village area. 1977

P. falciparum P. malariae P. ovale

Wet Season

Dry Season

89% 31% 0.3%

69% 8.5% 1.9%

contacts as the most efficient means of controlling an epidemic in the Malumfashi area, but the cost of such a regimen would be high. (IV)

Malaria

and Immunosuppression

Studies in man have shown that acute malaria is immunosuppressive (GREENWOODet al., 1972; WILLIAMSON & GREENWOOD, 1978). In 1962, MCGREGOR& BARRshowed that children who had been frequently exposed to malaria over a period of four years had a lower antibody responseto tetanus toxoid than children protected from malaria with chloroquine. The main objective of our study was to investigate whether asymptomatic (“chronic”) parasitaemia in the first two years of life affects the immune response of Nigerian children to the routine vaccinations that are usually given during this period and especially those given during the first year of life. We felt that such an investigation was particularly pertinent at a time when the World Health Organization was actively encouraging an expanded programme of immunization of infants in the developing countries and in many of which malaria is endemic. The immune response of 199 young Nigerian children protected against malaria by chemoprophylaxis with weekly chloroquine shortly after birth was compared with the immune responseof 186age-matchedcontrol children, both groups receiving the following vaccinations: triple vaccine (D.P.T.); poliomyelitis; measles; typhoid; meningococcal vaccine A and C; and BCG. (a) Prevalence of malaria in the area of St&y The study was carried out in and around the village of Gamzago near Malumfashi. The dry season lasts from September until early May and the wet season from May until September. The parasite rates determined at the end of the wet and dry season clearly indicate that this was a holoendemic area of malaria with Plasmodium falciparum as the predominant species of parasite (Table X and XI). (b) Immune response of children on malaria chemoprophylanis and controls

Chloroquine was given weekly in the dosage of 100 mg base to children under the age of one year and in the dosage of 200 mg base to children one to two years old. Placebo tablets (vitamin C) were given to the controls. All children with a confirmed diagnosis of malaria were treated with a full

therapeutic course of chloroquine regardless of the nature of the study group to which they belonged. The vaccination schedule employed was as follows: Four months-First injection of triple vaccine (diphtheria, tetanus, pertussis) -First dose of oral poliomyelitis vaccine Five months-2nd injection of triple vaccine -2nd dose of oral poliomyelitis vaccine Six months-3rd injection of triple vaccine -3rd dose of oral poliomyelitis vaccine Seven months-Measles vaccine One year or two years-Meningococcal Vaccine (Group A + Group C) -Salmonella typhi vaccine Although chloroquine was given by a team of field workers who were expecially employed and trained for this purpose, complete protection from malaria was not achieved. Routine blood films (711) showed P. fulciparum asexual parasites in 8.9% and gametocytesin 3.9%. The corresponding figures for the control children (630 blood films) were 41.3% and 17.1% respectively. Both the differences are statistically significant (IYO.001). Humoral Immuniry

Tables XII, XIII and XIV show the mean rise in antibody titre (post-vaccination titre minus pre-vaccination titre) observed following immunization with triple vaccine, measles, poliomyelitis and typhoid vaccines in the children who had received malaria chemoprophylaxis and in the control children, The percentage of children who seroconverted in the two groups is also given. It can be seenthat an excellent responseto tetanus toxoid, diphtheria toxoid and to measles vaccine was obtained in both the malaria-protected ,and control children. The responseto oral poliomyelitis vaccine was poor as previously recorded in many developing countries. For meningococcal polysaccharide vaccine Group C, both the mean rise in antibody titre and percentage sero-conversions were significantly lower in the control group. Seroconversionrates were not significantly affected by the presenceor absenceof parasitaemia at the time of immunisation; but the mean rise in antibody level for tetanus toxoid was significantly lower in the parasitaemic children (P
No. of children Mean rise in antibody level

Parasitaemia present

Parasitaemia absent

41

200

1.12 f 0.33

1.32 f 0.26

For all the other immunizations the presenceor absenceof parasitaemia did not significantly affect the mean rise in antibody levels (post-vaccination titre-pre-vaccination titre).

30

THE

MALUMFASHI

PROJECT

Table XII-The mean rise in antibody (post-vaccination titre-pre-vaccination titre) in children who received malaria chemoprophylaxis and in control children one month after vaccination as well as the percentage of children who sero-converted in the two groups* Antibody

% Conv.

Mean titre Diphtheria

Control Children

Protected Children

1.45 + 0.24 (1;;)

(123)

(1;;) ($)

1.31 + 0.25

Measles

5.15 + 2.81

% Conv.

1.45 & 0.25

(121)

Tetanus

Mean titre

(118)

(121)

(1;:)

1.25 ? 0.31 (119) 5.57 k 2.36

(129:)

(116)

(E)

*Notes for Tables XII, XIII and XIV 1. Post-vaccination diphtheria, tetanus and poliomyelitis antibodies were measured one month after the administration of the last 3 doses of vaccine. 2. For tetanus and diphtheria antibody levels are expressed as an absorbance and sero-version defined as a change of absorbance from <0*2 before vaccination to >0*2 after vaccination; for measles, meningococcal and S. typhi antibodies as a reciprocal of the log 2 titre and sero-conversion defined as the appearance of antibody after vaccination at a titre of 1:8 or more and for poZiomyeZitisantibodies, as a reciprocal of the neutralizing antibody titre and sero-conversion defined as the appearance of antibody after vaccination at a titre of 32 or greater. 3. For mean rise in antibody titre all children have been included irrespective as to whether they had antibodies at the time of vaccination or not. 4. For sero-conversion only children without antibody at the time of vaccination are included. 5. Figures in brackets indicate the number of observations made. Table XIII-The mean rise in antibody titre (post-vaccination titre-pre-vaccination conversion in malaria protected and unprotected children one month after vaccination Antibody

Protected Children Mean titre

Unprotected

% Conversion

Polio type 1

379 + 609 (29) Polio type 2 134 + 217 (29) Polio type 3 210 + 363 (29) **Includes 2 samples with very high. values

cl;) (ZZ) (&

Mean titre

titre)

and sero-

Children % Conversion

1344**? 2320 (19) 145 * 193 (19) 190 rt 311 (19)

(Z) ($)

Table XIV-The mean rise in antibody titre (post-vaccination titre-pre-vaccination titre) conversion in malaria protected and unprotected children one month after vaccination* Antibody

Protected Children Mean titre

Meningococcal Group A Meningococcal Group C S. typhi * P-=0.02 ** P
Unprotected

% Conversion

Mean titre

1.08 rt 1.42

0.77 + 1.60

*l 71(?)1 92

*O-97 zk 1.60

016d:)1‘77 (70) *

Cellular Immunity The response of protected and of control children to natural immunization with Candida albicans and Mycobacterium tuberculosis as assessed by skin tests carried out at the age

of one and two years showed no differences between the two groups of children.

and sero-

Children % Conversion

633)

w (3)

0.73!?)1 36 (67) ’

Yi2 (3)

Conclusions 1. Asymptomatic malaria parasitaemia does not significantly affect the immune response of infants to “routine” immunization but it may depress the immune response to polysaccharide vaccines.

H.

hi.

GILLES

2. Conversion rates for diphtheria, tetanus and measlesin the first year of life are excellent although the mean rise in antibody level is lowered in the case of tetanus. 3. Within the context of the WI-IO Expanded Programme of Immunization, our results indicated that malaria chemoprophylaxis is not necessaryin the first year of life in order to achieve the desired infant protection against diphtheria, tetanus and measles. 4. These over-all conclusions should be temuered by the following considerations-(a) the exposure to malaria in our control children was relatively short at the time of “routine” immunization (four to eight months), (b) children with malarious parasitaemia at the time of the first dose of tetanus toxoid had a lower mean rise in antibody level than those free of parasites on the day, even though the rise was probably still high enough to be associatedwith protective immunity, (c) in holoendemic areas of malaria it may be prudent to complement tetanus toxoid booster doses (at primary school entry) and meningococcal vaccination when required with a concomitant single dose of antimalarials . General

Comments

A multipurpose study such as the above is a complex undertaking fraught with unexpected financial, political and other hazards. Anyone undertaking long-term community studies must be fully aware that they are far from easy to plan, difficult to implement and relatively costly. In many parts of the tropics community participation is becoming increasingly difficult especially if serial venous blood studies are required-even serial finger prick collection for microtechniques meetswith increasing opposition especially if pre-school children are involved. Despite all these constrains community based studies are very worthwhile since the results obtained often have immediate and wide practical application.

et al.

31

Bradley, A. K., Macfarlane, S. B. J., Moody, J. B., Gilles, H. M., Blacker, J. G. C. & Musa, B. D (1982b). Malumfashi Endemic Diseases Research Project, XX. Demographic findings: mortality. Annals of Tropical Medicine and Parasitology,

76, 393-404.

Bradley-Moore, A. M., Greenwood,B. M., Bradley,A. K., Bartlett, A., Bidwell, D. E., Voller, A., Croske, J:, Kirkwood, W. & Gilles, H. M. (1983a). Malarra chemoprophylaxis with chloroquine in young Nigerian children. Its effect on the immune response to vaccination. Annals of Tropical Medicine ana’ Parasitology (in press). Bradley-Moore, A. M., Greenwood, B. M., Bradley, A. K., Bartlett, A., Bidwell, D. E., Voller, A., Croske, J., Kirkwood? E. & Gilles, H. M. (1983b). Malaria chemoprophylaxis in young Nigerian children. Its effect on nutrition. Annals of Tropical Medicine and Parasitology, 77. (in mess).

Gre&v&; B. k., Bradley, A. K., Blakebrough,I. S., Wittle, H. C., Marshall, T. F. de C. & Gilles, H. M. (1980). The immune responseto a meningococcal polysaccharide vaccine in an African village. Transactions of the Royal Society of Tropical Medicine and Hygiene, 74, 340-346. Greenwood, B. M. & Whittle, H. C. (1981). Zmmunologyof Medicine in the Trooics. London: Edward Arnold.

Greenwood, B. M., Bradley-Moore, A. M., Palet,. A. & Bryceson, A. D. M. (1972). Immunosuppressron in children with malaria. Lancer, i, 169-172. Lehman, J. C., Farid, Z., Smith, J. H., Bassily, S. & El-Masry? N. A. (1973). Urinary schistosomtasis in Egypt: chnical, radiological, bacteriological and parasitological correlations. Transactions of the Royal Society of Tropical Medicine and Hygiene, 67, 384-399.

McGregor, I. A. & Barr, M. (1962). Antibody response to tetanus toxoid inoculation in malarious and nonmalarious Gambian children. Transactions of the Royal So&v

of Tropical Medicine and Hygiene, 56, 364-

Pugh, R. N. H. & Gilles, H. M. (1978). Malumfashi

Endemic DiseasesResearchProject, III. Urinary schistosomiasis: a longitudinal study. Annals of Tropical Medicine and Parasitology, 72, 471-482. Pugh, R. N. H. & Gllles, H. M. (1979a). Malumfashi Endemic Diseases Research Project, X. Schiswsoma haemawbium and bacteriuria in the Malumfashi area. Annals of Tropical Medicine and Parasitology, 72, 471482.

Acknowledgements The work was financially supported by the following: The Tropical Medicine Research Board, M.R.C., England; The Edna McConnell Clark Foundation, U.S.A.; The Medical Research Council of Nigeria; Ahmadu Bello University, Zaria, Nigeria; and The Barmg Foundation, England. References Blakebrough, I. A., Greenwood, B. M., Whittle, H. C., Bradley, A. K. & Gilles, H. M. (1982). Journal of Infectious Diseases, 146, 292. Bradley, A. K., Macfarlane, S. B. J., Moody, J. B., Gilles, H. M., Blacker, J. G. C. & Musa, B. D. (1982a). Malumfashi Endemic Diseases Research Project, XIX. Demographic findings: population structure and fertili3tii-3Ab;nals of Trqptcal Medicme and Parasitology,

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