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Albendazole chemotherapy for treatment of diarrhoea in patients with AIDS in Zambia: a randomised double blind controlled trial

^a University Teaching Hospital, Lusaka, Zambia, ^b Ndola Central Hospital AIDS Home Care Service, Ndola, Zambia, ^c Kara Counselling and Training Trust, Lusaka, ^d Digestive Diseases Research Centre, Medical College of St Bartholomew's Hospital, London EC1M 6BQ

Correspondence to: Dr P Kelly, Digestive Diseases Research Centre, Medical College of St Bartholomew's Hospital, London EC1M 6BQ.

Abstract

Objective: To determine the value of short course, high dose albendazole chemotherapy in the treatment of persistent diarrhoea related to HIV in unselected patients in urban Zambia.
Design: A randomised double blind placebo controlled trial of albendazole 800 mg twice daily for two weeks. Patients were monitored intensively for one month and followed for up to six months.
Setting: Home care AIDS services in Lusaka and Ndola.
Patients: 174 HIV seropositive patients with persistent diarrhoea (defined as loose but not bloody stools three or more times a day for three weeks or longer). No investigations were undertaken except HIV testing after counselling.
Main outcome measures: Proportion of time periods during which diarrhoea was experienced after completion of treatment; proportion of patients with full remission after completion of treatment; mortality.
Results: The patients taking albendazole had diarrhoea on 29% fewer days than those taking placebo (P<0.0001) in the two weeks after treatment. The benefit of albendazole was maintained over six months. In patients with a Karnofsky score of 50 to 70 (needing help with activities of daily living and unable to work, but not needing admission to hospital) diarrhoea was reduced by 50%. Remission was obtained in 26% of all patients who received albendazole (P=0.004 against 9% receiving placebo), and this difference was maintained over six months (log rank test, P=0.003). Albendazole had no effect on mortality. Minimal adverse effects were noted.
Conclusions: For HIV infected Zambians with diarrhoea of more than three weeks' duration albendazole offers substantial relief from symptoms and may be used empirically, without prior investigation.

Introduction

The HIV pandemic continues to have a major impact on public health in sub-Saharan Africa.^{1 2 3} Many health care institutions are overwhelmed by the burden of disease, and the morbidity and mortality of AIDS is having social and economic consequences throughout the region.^{4 5} A major contributor to this morbidity and mortality is diarrhoeal disease; in studies from Zaire, Uganda, and Tanzania the lifetime occurrence of diarrhoea in AIDS patients varied from 40% to 75%.⁶ HIV prevalence in antenatal clinics in Lusaka has recently been estimated at 36%.⁷ A study conducted in a district hospital in southern Zambia showed that 11% of all adult inpatient days (including medical, surgical, and gynaecological admissions) were for treatment of diarrhoea, and 89% of these admissions were related to HIV (S Foster, personal communication, 1991).

The approach to AIDS related diarrhoea in industrialised countries follows a strategy of investigation to determine, when possible, the nature of the infecting opportunist, with treatment aimed at its eradication.⁸ In sub-Saharan Africa this is often not possible owing to constraints of technology and time. We recently carried out an intensive parasitological survey of 75 inpatients at the University Teaching Hospital in Lusaka and found infections in 81% of cases.⁹ The most common potential pathogens were microsporidia (23-35%), Isospora belli (28%), and Cryptosporidium parvum (25%).^{9 10} The microsporidia species, when identified, were Enterocytozoon bieneusi and Septata intestinalis in a ratio of 5:2. Strongyloides stercoralis and Giardia intestinalis were present in 5% and 1% of cases respectively. Geohelminth infections and schistosomes were each found in 3% of cases. Conlon et al, however, found microsporidia in only 2% of Zambian patients with AIDS and chronic diarrhoea using a Brown-Brenn Gram stain.¹¹ Given the intensive investigations needed to establish diagnosis in AIDS related diarrhoea and the frequency of multiple infections, treatments designed on an empirical basis for the population in question and given to all comers may be more logical than investigating each patient, certainly in many parts of Africa.

In Zambia much attention has been paid to developing services to enable patients with AIDS to receive care at home.¹² Several models of delivery have evolved, but all health care staff realise that the number of cases is too great for the hospitals and that the delivery of acceptable care to this group of patients has to be at primary health care level.

We therefore designed and carried out a randomised double blind placebo controlled study to determine the extent to which diarrhoea as a symptom of AIDS can be treated or suppressed by a chemotherapeutic agent that can be given in the community setting without prior investigation. We chose albendazole as this agent acts against microsporidia,¹³ S stercoralis,¹⁴ and G intestinalis,¹⁵ although whether albendazole acts against I belli is not known.

Patients and study design SETTING

The trial was conducted in three centres in urban Zambia where primary AIDS care is delivered. The home care service of the University Teaching Hospital in Lusaka deals mainly with patients referred from the clinics and wards of that hospital. The patients of this service are transported to their homes on discharge from hospital and visited at home regularly. The second study centre (with a similar service) was at Ndola Central Hospital in the north, in Zambia's second most populated city. The third centre was at the Kara Counselling and Training Trust in central Lusaka--the Kara HIV Counselling and Testing project provides a drop in advice and primary care service. The trust also runs several other prevention, training, and counselling projects.

PATIENTS

We recruited patients consecutively. Patients were eligible for enrolment if they were aged over 18 years, were HIV seropositive by enzyme linked immunosorbent assay (ELISA) (Wellcozyme HIV 1 and 2), and had had persistent diarrhoea--loose but not bloody stools three or more times a day for three weeks or longer. We excluded patients if they were pregnant, unable to give informed consent, had received antibiotics in the preceding week, or were deteriorating clinically (Karnofsky score of 20 or less¹⁶ (see box). Patients in all three centres had already been counselled and tested for serum antibodies to HIV as part of their care. Consent was sought in the patient's own language by the counsellor or nurse, and a written explanation of the study was provided. We gave each patient a Karnofsky score as a measure of overall severity of illness at the time of entry into the study. The only generally available anthelminthic drug, mebendazole, is not used widely among adults, and none was prescribed to the patients during the study.

  Karnofsky scores16

  100   Normal (no complaint or evidence of disease)
   90   Able to carry on normal activity; minor signs of
        disease
   80   Normal activity with effort; some signs or symptoms
        of disease
   70   Cares for self; unable to carry on normal activity or
        do active work
   60   Needs occasional help and some medical care
   50   Needs considerable help and frequent medical care
   40   Disabled; needs special care and help
   30   Severely disabled; admission to hospital indicated,
        although death not imminent
   20   Very sick; admission to hospital and active support
        treatment necessary
   10   Moribund; fatal process progressing rapidly
    0   Dead

RANDOMISATION

After the study objectives had been explained and consent obtained the patients were randomised by allocation of a study pack containing either albendazole or placebo, which had been prepared in London according to a randomisation code. The code (constructed so that the numbers of patients randomised to albendazole and placebo balanced every 20 patients) was kept in London during the study; it was broken during the study only for individual cases when we were concerned about adverse drug reactions. Each pack contained 112 tablets of albendazole or placebo, which were indistinguishable.

STUDY PROTOCOL

Albendazole was administered in a dose of 800 mg twice daily for 14 days. Patients were allowed to receive codeine phosphate (which was supplied if the nurse thought it necessary) or loperamide as required, but the administration of such drugs was recorded. We provided all patients with oral rehydration salts (Unicef formula) and folic acid 5 mg daily. As well as the treatment pack we gave each patient a card on which to record the number of loose stools during each 24 hour period. The patients kept this record for the first month, after which we collected the cards, and the home care staff recorded for the next five months whether diarrhoea occurred in each two week period. The study was terminated after a total of six months of follow up. We asked patients not to take antibiotics for the diarrhoea, but if antibiotics were used for any other indication during the first month of follow up this was recorded. Any potential adverse effects were notified by the home care staff. If there was a potentially serious event the drug was withdrawn, the code broken in London, and the team advised if any further action was needed. Deaths were all notified, together with an assessment of the circumstances to allow assessment of whether death was due to the underlying disease or to an unexpected event.

STATISTICAL EVALUATION

We evaluated efficacy by estimating (a) the proportion of days (in the first month) or fortnights (for the rest of the follow up) during which diarrhoea was experienced; (b) the proportion of patients in remission two weeks after completing treatment and their progress over follow up; and (c) mortality. The presence or absence of diarrhoea was evaluated daily during the first month and then over periods of two weeks during the next five months of follow up. We also assessed the frequency of adverse events. We compared these outcomes by determining the relative risk (and 95% confidence intervals) of experiencing diarrhoea during a day or fortnight conferred by treatment with albendazole. Significance was evaluated with two approaches--firstly, with Fisher's exact test, which assumes independence of the periods during which symptoms were recorded as being present or absent, and, secondly, by calculating the probability of experiencing diarrhoea during each period of follow up of each patient and by carrying out a Mann-Whitney non-parametric comparison. This does not make the independence assumption except in as much as the individual patients are assumed to be independent, but is insensitive during the later periods of follow up as many patients are given the same rank. For this reason, in one case the last five months of follow up were grouped together. Mortality and the probability of relapse after remission were compared with Kaplan-Meier analysis and the log rank statistic. Calculations were carried out with EPI-INFO, version 6 (Centers for Disease Control, Atlanta) and STATA, version 4.0 (Stata, Texas).

Approval for the study was obtained from the national AIDS research ethics committee of Zambia.

Results

In all, 174 patients were randomised. Six enrolment errors occurred during randomisation: in four patients diarrhoea had been present for less than three weeks, and two patients were inadvertently enrolled by both the University Teaching Hospital's team and the Kara Trust's team and therefore received two treatment packs. In 30 cases (16 in the group taking albendazole and 14 in the group taking placebo) the records were lost before any data were retrieved. These losses occurred because of patients moving house, natural catastrophes (for example, domestic fire, roof collapse), or unexplained factors. Records that for at least the first month were complete and could be evaluated were available for 138 patients (69 patients taking albendazole, 69 placebo).

Of the 138 correctly randomised patients with adequate records for the first month, four patients (two taking albendazole, two placebo) failed to complete the treatment course, as determined by inspection of the treatment pack. Eight patients withdrew from the study (five taking albendazole, three placebo); withdrawal was attributed to worsening diarrhoea or vomiting in (five patients) and to adverse effects (three patients receiving albendazole). Twenty one patients died (10 taking albendazole, 11 placebo) during the first 14 days of the trial and therefore did not complete treatment.

Table 1 shows the demographic and clinical data for the 174 patients according to treatment centre and treatment. No differences existed in the entry characteristics or in the recorded consumption of codeine or antibiotics between the patients allocated to albendazole and those allocated to placebo.

Table 1--Demographic and clinical characteristics of patients at randomisation, according
to centre and to treatment
----------------------------------------------------------------------------------------
                                        Centre                       Treatment
------------------------------------------------------------------------------------------
                            University                Kara
                        Teaching Hospital,  Ndola     Trust,
                             Lusaka        Hospital  Lusaka   Albendazole  Placebo
------------------------------------------------------------------------------------------
No                              58             74       42          87        87
Age (years)                     34.1           31.9     30.1        31.9      32.5
Sex (male:female)            29:29          38:36    30:12       45:42     52:35
Mean duration of
 diarrhoea (months)              9.7            7.1      6.3         7.8       7.4
Mean frequency of
 diarrhoea (per 24 h)            7.1            6.0      5.6         6.7       6.0
Mean Karnofsky score*           66             61       77          67        65
Receiving treatment for
 tuberculosis                   10              5        4           8        11
Oral candidiasis                 2             24        2          11        17
Fever                            4             46        5          26        29
Receiving antibiotics            2              0        1           0         3
Receiving codeine               12             34        0          23        23
------------------------------------------------------------------------------------------
*See box for meaning of scores.

REDUCTION IN DIARRHOEA

Diarrhoea was less common in the group taking albendazole than in the group taking placebo during the entire six month period of follow up; this was significant at all time points except during weeks 5 to 8. Table 2 shows the relative risk of experiencing diarrhoea conferred by albendazole (0.71 in weeks 3-4 (a reduction in the proportion of days with diarrhoea of 29%) and 0.58 to 0.83 over the rest of follow up).

Table 2--Proportion of time periods with and without diarrhoea in groups receiving
albendazole or placebo over six months of follow up
---------------------------------------------------------------------------------------------------------
                                                        Weeks of follow up
---------------------------------------------------------------------------------------------------------
                              1-2*            3-4*           5-8+             9-16+            17-24+
---------------------------------------------------------------------------------------------------------
Albendazole (n=52):
  With diarrhoea              530             291             34                35               21
  Without diarrhoea           279             439             55               102               74
Placebo (n=53):
  With diarrhoea              563             409             40                55               33
  Without diarrhoea           228             318             47                70               55
Relative risk (95%            0.92            0.71           0.83             0.58              0.59
  confidence interval)    (0.86 to 0.98)  (0.63 to 0.79)  (0.59 to 1.18)   (0.41 to 0.82)  (0.37 to 0.94)
P (Fisher's exact test)       0.016          <0.0001         0.36               0.002           0.02
P (Mann-Whitney rank
  test)++                                     0.028                             0.011
---------------------------------------------------------------------------------------------------------
*No of patient days.
+Number of two weekly periods.
++Probability of experiencing diarrhoea during weeks 3-4 and 5-24 (see methods).

Table 3 shows the proportions of patients who were in remission after completion of treatment (26% in the group taking albendazole, 9% in that taking placebo), and their progress over follow up. A significant difference between the two groups was seen at each time point and when the whole period of follow up was compared with a Kaplan-Meier analysis and log rank test (P=0.003). The proportion of patients lost to follow up over the six months was similar in both groups (albendazole, 23/69; placebo, 19/69).

Table 3--Number of patients who achieved remission of diarrhoea after completion of
treatment*
---------------------------------------------------------------------------------------------------------
                                                    Weeks of follow up
---------------------------------------------------------------------------------------------------------
                                  3-4             5-8             9-16              17-24
---------------------------------------------------------------------------------------------------------
Albendazole (n=69)                 18              15              13                 10
Placebo (n=69)                      6               5               5                  1
Relative risk (95%
  confidence interval)      3.0 (1.3 to 7.1) 3.0 (1.2 to 7.8) 2.6 (1.0 to 6.9) 10.0 (1.4 to 82.0)
P (Fisher's exact
  test)+                          0.008           0.017            0.048             0.005
---------------------------------------------------------------------------------------------------------
*Analysis includes non-compliers, those lost to follow up, deaths, and withdrawals, but not those incorrectly
randomised or those whose records were lost before any data were retrieved. Remission was defined as
having no more than one day of diarrhoea in the two weeks after treatment; any further diarrhoea at all was
regarded as relapse.
+Kaplan-Meier analysis and log rank test confirmed overall significance (P=0.003).

The reduction in diarrhoea was seen in all treatment centres, but the magnitude and significance of the benefit varied. In weeks 3 to 4--that is, after completion of treatment--the patients at the Kara Trust who could be evaluated (n=29) achieved a 31% reduction (P=0.004), those in Ndola (n=57) a 41% reduction (P<0.0001), but those at University Teaching Hospital (n=18) only a 10% reduction (not significant).

The outcome was found to be poor in those few patients who had been given a score of 40 or less at the time of randomisation; at one month eight out of 12 patients in this group had died--no meaningful conclusions could be drawn. The other patients were divided into those with scores of 80 or 90 (able to work) and those with scores of 50 to 70 (needing help with activities of daily living and unable to work, but not needing admission to hospital). Table 4 shows that the benefit of albendazole is conferred on patients with Karnofsky scores of 50 to 70.

Table 4--Reduction in diarrhoea, expressed as relative risk (95% confidence interval) of
experiencing diarrhoea in group taking albendazole compared with group taking
placebo, with respect to Karnofsky score*
----------------------------------------------------------------------------------------------------------
                                                       Weeks of follow up
----------------------------------------------------------------------------------------------------------
                                1-2             3-4             5-8             9-16            17-24
----------------------------------------------------------------------------------------------------------
Karnofsky score 50-70:         0.83            0.55            0.59            0.38            0.52
                          (0.75 to 0.92)  (0.47 to 0.63)  (0.39 to 0.89)  (0.23 to 0.61)  (0.27 to 1.01)
  No of patients                65              65              59              41              31
  P (Fisher's exact test)     <0.001          <0.001          0.019           <0.001           0.06
  P (rank test)                0.19           <0.001           0.02           0.007            0.12
Karnofsky score 80-90:         1.0             1.05            1.22            0.89            0.81
                                                          (0.64 to 2.34)  (0.55 to 1.45)  (0.41 to 1.59)
  No of patients               38               38              34              32              23
----------------------------------------------------------------------------------------------------------
No assessment of efficacy could be made in the group with Karnofsky scores of 40 or below as the mortal-
ity in this small group was very high. Effect of albendazole was not significant at any time during follow up
with either test for group of patients with score of 80-90.
*See box for meaning of scores.

DEATH

Death was known to have occurred in 49 patients (in 22 patients taking albendazole and 27 placebo). Log rank analysis showed that albendazole had no significant effect on mortality at any time during follow up (P=0.55).

ADVERSE EVENTS

Adverse events were recorded in 10 patients (in seven taking albendazole and three taking placebo). Five patients had an exacerbation of diarrhoea, together with vomiting. One patient (taking albendazole) had a cutaneous reaction; this was a transient morbilliform rash that resolved within one week of discontinuing the drug. Four other patients taking albendazole complained of dizziness (1), headache (1), cough (1), and difficulty swallowing (1), but these symptoms are indistinguishable from symptoms due to the underlying illness.

Discussion

EFFICACY OF ALBENDAZOLE

This trial has shown that albendazole reduces the proportion of time that patients with AIDS in urban Zambia have diarrhoea. Remission was achieved in 26% of patients (compared with 9% of those taking placebo), but this proportion rose to 35% (18/52) if the analysis excluded deaths and withdrawals from treatment. The empirical approach adopted in this study shows that patients can expect benefit from treatment without having undergone a search for specific pathogens. The therapeutic benefits were obtained in a setting that applies to many African patients with AIDS and may have been underestimated in our study, as we allowed, for ethical reasons, the concomitant use of codeine phosphate and similar agents. If codeine, antibiotics, or traditional herbal medicines were used more freely than was admitted to, this might lead to a further reduction in apparent efficacy, and we know that the use of herbal remedies is common.

We cannot comment on the value of albendazole in seriously ill patients as in our patients the mortality was high, but we have clear evidence that it is beneficial in patients who cannot work and need help with activities of daily living. In these patients albendazole confers a protection against experiencing diarrhoea at any one time of about 50% over six months. Some of the patients who were given Karnofsky scores of 50 to 70 at randomisation would already have shown improvement after treatment with oral rehydration and codeine in hospital and may have been more seriously ill even a few days previously. Patients with persistent diarrhoea--that is, nonresponders--would have probably been more likely to be lost to follow up, and this may partly explain the improvement in symptoms in both groups over time (table 2). This effect would not explain, however, the difference between the group taking albendazole and that taking placebo.

MORTALITY

Albendazole had no effect on mortality. Perhaps this is not surprising as early deaths are likely to have been determined before enrolment, whether by nutritional deficiency, systemic infection, or the severity of immunosuppression. Albendazole may have an effect on late (after the first two months) mortality, but our study may not have had sufficient power to detect it in that some of the patients who were lost to follow up would have died. Local customs dictate that seriously ill people are taken back to their ancestral home to die, and at death many of their personal belongings are destroyed. This suggests that deaths would be overrepresented in the group whose record cards were not returned despite the efforts of the home care staff to trace their whereabouts. This was a particular problem in the patients attending University Teaching Hospital in Lusaka, which has a high proportion of residents who consider themselves to have a true domicile elsewhere. Patients at the Kara Trust centre were less unwell, and follow up was more successful. Another possible explanation for the lack of effect on mortality could be infection with other pathogens: Lucas et al in Abidjan found unsuspected advanced tuberculosis to be responsible for much mortality in patients with slim disease,¹⁷ and septicaemic complications are almost certainly responsible for many deaths.¹⁸ Unexpectedly, five of the 21 early deaths occurred in patients with Karnofsky scores of 60 or more.

IMPLICATIONS OF FINDINGS

We surmise that much of the effectiveness of albendazole in the patients in our study was due to its effect in eardicating or suppressing infection with microsporidia. S intestinalis is sensitive to albendazole,^{19 20} and we have previously reported the presence of this organism in Zambia.¹⁰ Infections with other parasites (G intestinalis and S stercoralis) also respond to albendazole, but these infections are less common in patients with AIDS in Zambia. We do not know the response of C parvum or I belli to albendazole. The regimen that we used could probably be improved further with the addition of other chemotherapeutic agents, but antibiotic resistance is very common among isolates of enteric bacteria in Lusaka at the moment.

We know of no other placebo controlled studies that have shown efficacy of a treatment for diarrhoea in patients with AIDS in Africa. Current practice in many areas is to give co-trimoxazole and metronidazole in standard doses, with or without loperamide. In a previous study a substantial response to placebo showed considerable variability in the natural course of the diarrhoea,²¹ and so the use of a placebo in a blinded study was important and fully justified.²² If the results of our study (including the apparent safety of high dose albendazole) are confirmed, the following recommendations would seem reasonable. On presentation, patients with salt and water depletion should have fluid and electrolyte replacement, usually with an oral glucose electrolyte solution containing potassium. If the diarrhoea has been present for over three weeks then albendazole 800 mg twice daily may be given. If the patient is moribund or if the diarrhoea is of less than three weeks' duration then codeine phosphate should be used to try to control the diarrhoea, as in these situations we have no direct evidence of benefit. In the light of our findings patients with Karnofsky scores of 80 or more should probably be treated in the same way.

Albendazole chemotherapy for AIDS in Africa seems to be beneficial, with minimal adverse reactions, and is effective in empirical use in a community setting. Individuals infected with HIV, and their families, often spend much of their resources on treatments,²³ many of which are of doubtful value. We believe that treatment with albendazole, which is effective over six months, is likely to have a high benefit:cost ratio in this devastating disease. Further work is urgently needed to corroborate these findings, to compare albendazole with cheaper antibiotic regimens, and to improve the regimen by addition of other agents.

We acknowledge the dedicated work of the following nursing and counselling staff of the home care services for their careful monitoring of the patients: Mrs N Chiselo, Mrs J Chimoto, Mr J Daka, Mrs G Goma, Mrs A Kapaya, Mrs P Kapembwa, Mrs V Kunda, Mr R Makulele, Mrs Q Moyowanyambe, Mrs S Phiri, Mrs R Sakala, Mr S Silomba, Mrs M Tonha, and Mrs R Zulu. We thank Mr John Young for valuable help with packaging and pharmaceutical quality control, Dr Joan Morris for statistical guidance, and our patients for their willingness and cooperation.

Funding: SmithKline Beecham for financial support and provision of drugs.

Conflict of interest: None.

1. Piot P, Kapita BM, Were JBO, Laga M, Colebunders RL. AIDS in Africa: the first decade and challenges for the 1990s. AIDS 1991;5(suppl 1):S1-5.
2. Gilks C. The clinical challenge of the HIV epidemic in the developing world. Lancet 1993;342:1037-9. [Medline]
3. Mulder DW, Nunn AJ, Kamali A, Nakiyingi J, Wagner H-U, Kengeya-Kayondo JF. Two year HIV-1 associated mortality in a Ugandan rural population. Lancet 1994;343:1021-3. [Medline]
4. Foster S. Maize production, drought and AIDS in Monze district, Zambia. Health Policy and Planning 1993;8:247-54. [Abstract/Free Full Text]
5. Garnett GP, Anderson RM. No reason for complacency about the potential demographic impact of AIDS in Africa. Trans R Soc Trop Med Hyg 1993;87(suppl 1):19-22.
6. Colebunders RL, Latif AS. Natural history and clinical presentation of HIV-1 infection in adults. AIDS 1991;5(suppl 1):S103-12.
7. Fylkesnes K, Brunborg H, Msiska R. The socio-economic impact of AIDS; background paper I: Zambia; the current HIV/AIDS situation and future demographic impact. Lusaka: Ministry of Health, 1994.
8. Gazzard BG, Blanshard C. Diarrhoea in AIDS and other immunodeficiency states. Baillieres Clin Gastroenterol 1993;7:387-419. [Medline]
9. Kelly P, Baboo KS, Wolff M, Ngwenya B, Luo NP, Farthing MJG. The prevalence and aetiology of persistent diarrhoea in adults in urban Zambia. Acta Tropica (in press).
10. Drobniewski F, Kelly P, Carew A, Ngwenya B, Luo N, Pankhurst C, et al. Human microsporidiosis in African AIDS patients with chronic diarrhea. J Infect Dis 1995;171:515-6. [Medline]
11. Conlon C, Pinching AP, Perera CU, Moody A, Luo NP, Lucas SB. HIV related enteropathy in Zambia: a clinical, microbiological and histological study. Am J Trop Med Hyg 1990;42:83-8.
12. Chela CM, Siankanga ZC. Home and community care: the Zambia experience. AIDS 1991;5(suppl 1):S157-61.
13. Blanshard C, Ellis DS, Tovey DG, Dowell S, Gazzard BG. Treatment of intestinal microsporidiosis with albendazole in patients with AIDS. AIDS 1992;6;311.
14. Archibald LK, Beeching NJ, Gill GV, Bailey JW, Bell DR. Albendazole is effective treatment for chronic strongyloidiasis. Q J Med 1993;86:191-5. [Abstract/Free Full Text]
15. Meloni BP, Thompson RCA, Reynoldson JA, Seville P. Albendazole: a more effective antigiardial agent in vitro than metronidazole or tinidazole. Trans R Soc Trop Med Hyg 1990;84:375-9. [Medline]
16. Karnofsky DA, Abelmann WH, Craver LF, Burchenal JH. The use of the nitrogen mustards in the palliative treatment of carcinoma. Cancer 1948;1:634-56.
17. Lucas SB, De Cock KM, Hounnou A, Peacock C, Diomande M, Honde M, et al. Contribution of tuberculosis to slim disease in Africa. BMJ 1994;308:1531-3. [Abstract/Free Full Text]
18. Shanson DC. Septicaemia in patients with AIDS. Trans R Soc Med Hyg 1990;84(suppl 1):14-6.
19. Cali A, Kotler DP, Orenstein JM. Septata intestinalis ng, nsp, an intestinal microsporidian associated with chronic diarrhoea and dissemination in AIDS patients. J Eukaryot Microbiol 1993;40:101-12. [Medline]
20. Molina JM, Oksenhendler E, Beauvais B, Sarfati C, Jaccard A, Derouin F, et al. Disseminated microsporidiosis due to Septata intestinalis in patients with AIDS: clinical features and response to albendazole therapy. J Infect Dis 1995;171:245-9. [Medline]
21. Kelly P, Buve A. Chemotherapy of African AIDS diarrhoea: a preliminary study. AIDS 1993;7:91-3. [Medline]
22. Byar DP, Schoenfeld DA, Green SB, Amato DA, Davis R, De Gruttola V, et al. Design considerations for AIDS trials. N Engl J Med 1990;323:1343-7. [Medline]
23. Foster SD. Affordable clinical care for HIV related illness in developing countries. Tropical Diseases Bulletin 1990;87:R1-9.

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