Humoral immune response to tetanus-diphtheria vaccine given during extended use of chloroquine or primaquine malaria chemoprophylaxis

Immune suppression resulting from prolonged chemoprophylaxis and potential drug-vaccine interaction were investigated within the context of a randomized placebo-controlled trial that compared daily primaquine or weekly chloroquine administration for malaria prevention. After 11 months of prophylaxis, adult male subjects received a tetanus-diphtheria (Td) vaccination. Prophylaxis continued 4 weeks longer. Anti-tetanus and anti-diphtheria antibody levels were measured by ELISA at baseline and at 1, 3, 7, and 14 months after Td vaccination. All groups were comparable at baseline. Immunization triggered significant increases in anti-tetanus and anti-diphtheria IgG levels over each group's pre-Td baseline levels and those of an unvaccinated control group. Geometric mean anti-tetanus titers (GMTs) in the primaquine group were significantly higher than those of the placebo group at 1, 3, and 14 months. Anti-tetanus GMTs in placebo and chloroquine groups declined over 14 months to levels comparable to those of unvaccinated controls, but levels in the primaquine group remained significantly higher than in controls.     

Intestinal parasite infections after extended use of chloroquine or primaquine for malaria prevention

Comparative results of baseline and endpoint screening for intestinal parasites are reported from Javanese men enrolled in a year-long, placebo-controlled malaria prophylaxis trial in Irian Jaya. The objective was to detect nontarget qualitative changes that may have resulted from prolonged chloroquine (300 mg base weekly) or primaquine (0.5 mg base/kg daily) prophylaxis. Fresh fecal specimens were examined (blinded trial) for parasites and ova using a modified Kato-Katz thick smear method. More than 88% (94/106) of the baseline population was infected by 1 or more parasite species of which hookworm and Blastocystis hominis were dominant. Paired comparison between baseline and endpoint revealed no significant changes within the primaquine or chloroquine groups with regard to the variety of species found, the mean number of species or ova/subject, the relative proportion of infections caused by these species, or the occurrence of parasite-free, single, and multiple infections. Relative to placebo, there was a significantly greater proportion of infections by Entamoeba histolytica/dispar and a lower mean hookworm egg count in the chloroquine group. The endpoint proportion of new or increased infections in the primaquine group was significantly lower than that of the chloroquine group but comparable to that of the placebo. Despite the dosage employed, the frequency and duration of use, and excretion primarily through the bowels as the active parent compound, primaquine appeared to have little or no significant effect against a variety of common intestinal parasites. These largely negative results lend support for the safety and acceptability of primaquine as a daily malaria prophylactic in a population frequently at risk of intestinal helminth infections.     

Single - dose immunization of human subjects against tetanus

A study was performed on human subjects to assess the effectiveness of single-dose immunization with 20 CU (1 ml) of adsorbed tetanus toxoid followed by revaccination with 10 CU (0.5 ml) 1 year later. Out of 1187 students, only those were selected for observation whose blood serum did not contain tetanus antitoxin (titre less than 0.001 IU/ml); this group counted 283 students. After administering the 20 CU (1 ml) of toxoid the antitoxin titre was repeatedly checked on days 10--15 and persons whose titre had risen to over 0.01 IU/ml were excluded from observation. The remaining 109 persons were tested for the antitoxin level 1 year later and revaccinated with 10 CU of tetanus toxoid. After 10--15 days their postrevaccination titre was determined. The single-dose immunization with 20 CU of tetanus toxoid in human subjects not given tetanus antigen previously was accompanied by a gradul rise in the antitoxin titre up to the protective level and its maintenance for 1 year (observation time) until revaccination. Revaccination with 10 CU of toxoid provided in 10--15 days a multiple (100--197fold) increase of the antitoxin titre, many times exceeding the protective level. The usefulness of transition to the shortened immunization scheme for tetanus prophylaxis of the adult population is discussed.     

Serological response to tetanus toxoid: a field study in Pondicherry, India

To study the serological response to various doses of tetanus toxoid given to pregnant women, 320 samples of blood obtained from 173 pregnant women were analysed using the indirect haemagglutination technique. Two doses of toxoid were necessary to achieve protective titres in women who were previously unimmunized. The antibody levels appeared to persist for up to 4 years. During a subsequent pregnancy, a single booster dose of toxoid was sufficient to raise the titres adequately for protection. These findings are in accordance with the immunization programme followed for prophylaxis against tetanus among pregnant women.     

Duration of protective immunity conferred by maternal tetanus toxoid immunization: further evidence from Matlab, Bangladesh

OBJECTIVES: Although maternal tetanus immunization has been shown to be highly effective in the prevention of neonatal tetanus, unresolved questions remain concerning the required minimum number of doses and the resulting duration of effective immunity. This study examined the duration of effective immunity against neonatal tetanus provided by maternal tetanus immunization. METHODS: A randomized, double-blind cholera vaccine trial of 41,571 children and nonpregnant adult women carried out in 1974 in the Matlab comparison area of rural Bangladesh provided a unique opportunity to address dose and immunity issues. RESULTS: Children of women who received either 1 or 2 injections of tetanus toxoid experienced 4- to 14-day mortality levels consistently lower than those of children of unimmunized mothers. Analysis of neonatal-tetanus-related mortality showed that 2 injections of tetanus toxoid provided significant protection for subsequent durations of up to 12 or 13 years. CONCLUSIONS: The data demonstrate that a limited-dose regimen of maternal tetanus toxoid provides significant and extended protection against the risk of neonatal tetanus death.     

Involvement of nitric oxide and cGMP in the protective effect of neurotensin on hepatocytes

STUDY OBJECTIVE: Tetanus antibody levels have been shown to be inadequate in 50% of patients older than 65 years. Although immunization recommendations have been made for this age group, the efficacy of this intervention has not been well documented. We sought to determine the difference in tetanus antibody levels after the administration of one tetanus toxoid immunization to geriatric patients without adequate titers. METHODS: Thirty-five patients older than 65 years at a large urban comprehensive care geriatric center who were documented to have inadequate tetanus antibody titers were each given one tetanus toxoid immunization. Repeat titers were obtained at least 2 months after the immunization with the use of enzyme-linked immunosorbent assay (Bindazyme kit; the Binding Site Corporation, Birmingham, England). We considered tetanus antibody levels greater than .17 IU/mL protective. RESULTS: The mean age was 79.4 years; 30 of 35 (86%) were female. Repeat tetanus antibody titers were obtained an average of 123 days (range, 63 to 204 days) after immunization with tetanus toxoid. The mean preimmunization antibody titer was .1 IU/mL (range, .04 to .16 IU/mL). After immunization, antibody titers increased a mean of .61 IU/mL (range, -.01 to 2.23 IU/mL; 95% confidence interval, .35 to .87 IU/mL). Thirty of the 35 patients who received a single injection of tetanus toxoid (86%) developed protective titers. We found no relationship between seroconversion and age, sex, or medical history; nor did we find a relationship between antibody level and time elapsed since immunization when repeat titers were obtained. CONCLUSION: Administration of one tetanus toxoid injection affords protective immunity in many geriatric patients.     

Tetanus immunization and its association to hepatitis B vaccination in patients with chronic renal failure

A defect in the immune response of patients with chronic renal failure leads to low response rates and insufficient antibody concentrations following a number of highly recommended vaccinations. This has been shown before for immunization against hepatitis B and influenza. Few data are available concerning the efficacy of vaccination with tetanus toxoid in these patients. In a prospective, controlled study we vaccinated seronegative patients with chronic renal failure not on dialysis, patients on chronic intermittent hemodialysis, and patients after kidney transplantation with tetanus toxoid. The results were compared with those of a control group consisting of 13 age-matched patients with mild essential hypertension and normal kidney function. Only 11 of 20 (55%) patients in the chronic renal failure group and 16 of 23 (69%) in the dialysis group had a protective antibody response after triple vaccination. In contrast, all the patients in the control group and six of seven transplant patients seroconverted. The response to tetanus toxoid was highly associated with the response to a previously administered vaccination against hepatitis B. Responders to this vaccination also had a better response rate to tetanus toxoid. The antibody concentrations after vaccination were lower in all patient groups compared with the controls; the lowest titers were found in the transplant patients. Therefore, renal patients will need revaccination much earlier, and tetanus toxoid antibody levels should be checked if a patient is injured and potentially requires vaccination.     

Systemic and mucosal immune responses of mice to aluminium-adsorbed or aluminium-non-adsorbed tetanus toxoid administered intranasally with recombinant cholera toxin B subunit

For the purpose of changing the immunization procedure of tetanus toxoid from intramuscular or subcutaneous injection, which has been in practice for a long time, to intranasal administration, we examined systemic and mucosal immune responses of mice to aluminium-adsorbed tetanus toxoid (aTT) and aluminium-non-adsorbed tetanus toxoid (nTT) inoculated intranasally with recombinant cholera toxin B subunit (rCTB). Intranasal immunization with aTT induced, at a concentration of 0.5 Lf, high levels of TT-specific serum IgG antibody titres and moderate levels of TT-specific serum IgA antibody titres in the presence and absence of rCTB. Induction of high or moderate levels of mucosal TT-specific IgA antibody responses was observed with and without rCTB in the lung, the nasal cavity, the small and large intestines and the vagina. Generally speaking, the co-administration of aTT and rCTB showed higher mucosal TT-specific IgA antibody titres when compared with the administration of aTT alone. In case of intranasal administration of nTT, the dose of 5 Lf was necessary and stimulated, only in the presence of rCTB (10 micrograms), high levels of tetanus toxoid (TT)-specific serum IgG antibody responses in all mice examined and moderate or slight levels of TT-specific IgA antibody responses in the nasal, pulmonary and small and large intestinal lavages of a few mice. All mice intranasally immunized with aTT alone or nTT and rCTB escaped onset of tetanus. This is the first report concerned with the mucosal adjuvant activity of an aluminium compound. Judging from these results, intranasal administration of aTT with and without rCTB or nTT with rCTB appears to be a very useful means for a vaccination against tetanus with respect to ease, safety, certainty, low cost and no need for an injection needle.     

Effect of hemoglobin status on humoral immune response of weanling pigs differing in coping styles

The effects of hemoglobin (Hb) status and coping style of pigs on performance and humoral immune response were studied. Twenty-four, 4-wk-old crossbred barrows were assigned to groups of three pigs based on weight and litter origin. Groups were allotted according to a 2 x 2 factorial treatment arrangement: two blood Hb concentration classes (low vs high) and two immunization procedures (control vs immunized). Immunized pigs received an antigen cocktail containing keyhole limpet hemocyanin (KLH), ovalbumin (OA), and tetanus toxoid (TT) at weaning. Additionally, pigs were stratified according to behavioral coping style in response to exposure to a stressor. During 41 d after weaning (approximate time of immunization), blood Hb concentration, ADG, and ADFI were measured weekly and serum antibody titers to KLH, OA, and TT twice weekly. Average Hb concentration differed between low and high Hb pigs (P < .001; 10.0 vs 12.0 g/dL), but this difference declined with time after weaning. Neither immunization procedure nor coping style affected Hb concentrations. In addition, ADG and ADFI were unaffected by any of the treatments. However, ADG was slightly greater in high Hb status pigs (586 vs 633 g/d) and was paralleled by a slightly greater ADFI in high Hb status pigs (812 vs 899 g/d). Antibody responses were negatively or not related to Hb status at weaning. Antibody responses (depending on isotype and antigen) were or tended to be lower in pigs with high blood Hb concentrations. Behavioral coping style strongly affected humoral immune responsiveness; enhanced or accelerated antibody responses were found in pigs that had a passive coping style.     

Comparison of multiple immunization schedules for Haemophilus influenzae type b-conjugate and tetanus toxoid vaccines following bone marrow transplantation

Antibody concentrations to vaccine-preventable diseases decline following BMT and an optimal schedule for vaccination after transplant has not been established. We examined antibody responses to tetanus toxoid (TT) and Haemophilus influenzae type b-conjugate (HIB) vaccines of BMT patients immunized at 6, 12 and 24 months (6 month group, n = 21) and compared them to those previously reported for patients immunized at 3, 6, 12 and 24 months (3 month group, n = 74) or at 12 and 24 months (12 month group, n = 17) following transplantation. Geometric mean total anti-HIB and IgG anti-TT concentrations were significantly higher after the 12 month dose in the 3 and 6 month immunization groups compared to the group who received their first dose at 12 months. Although HIB antibody concentrations were higher in the 3 month and 6 month groups 12 to 24 months after BMT, the proportion of patients with protective levels was not significantly different from the proportion protected in the 12 month group. Following the 24 month immunizations, geometric mean antibody concentrations to HIB and TT were similar for all three immunization groups. The proportion of patients in each group with protective levels of HIB antibody after the 24 month dose was > or = 80%. A two dose schedule of HIB and TT vaccines at 12 and 24 months after BMT should afford protection.     

Effects of diets with graded levels of naturally deoxynivalenol-contaminated oats on immune response in growing pigs

A trial was conducted to evaluate the effect of including different levels of deoxynivalenol (DON)-contaminated oats in the complete diets of growing pigs on immune response and performance. The diets contained 0.6, 1.8 and 4.7 mg DON/kg, and both restricted and ad libitum feeding were used. Performance was recorded as weight gain, feed intake, efficiency of feed utilization and carcass quality. Immune response parameters recorded included primary and secondary antibody titres after injections of five different antigens: Human serum albumin (HSA), sheep red blood cells (SRBC), paratuberculosis vaccine (MPT), tetanus toxoid (TT) and diphteria toxoid (DT). A johnin test was also performed. Lymphocyte stimulation response was measured with three different mitogens (PWM, ConA and PHA). A significant, DON dose-dependent reduction in secondary antibody response to tetanus toxoid was observed. A slightly higher mitogen response after PHA stimulation in lymphocytes from the medium and high DON groups compared to the low DON group after 9 weeks was considered inconclusive. No other indication of dose-dependent immune response inhibition or stimulation was found. Significantly reduced feed intake with increased levels of DON was observed in groups fed restricted rations according to weight, but not in animals fed ad libitum.     

Tolerability of prophylactic Lariam regimens

Three hundred and fifty-nine US Marines participated in a randomized double-blind clinical trial to assess tolerance of two prophylactic mefloquine regimens [250 mg salt weekly (n = 157) or 250 mg daily for 3 days followed by 250 mg weekly (n = 46)] compared with 300 mg weekly chloroquine (n = 156) over a 12-week period. The study participants were seen daily for four days, then weekly for 11 weeks. On each visit, the subject answered two computerized questionnaires (a review of body systems and an evaluation of mood states), participated in a physician interview, and was administered medications under supervision. A random sample of each group was assigned to either pharmacokinetic sampling or two wear a wrist watch size computerized sleep monitor (actigraph). The frequencies of intercurrent illness and other concomitant medications were tabulated. End study mefloquine plasma levels were obtained on all study participants. The results obtained showed no compromise in function due to dizziness or incoordination in the mefloquine groups. Overall, both weekly mefloquine and loading dose mefloquine were well tolerated. Sleep disturbance and increased dream activity were detected in the mefloquine groups. Depressive feelings were noted in two to three times more individuals in the mefloquine groups than in the chloroquine group early in the course of the study, and resolved in the majority of subjects as tolerance developed. Steady state mefloquine plasma levels were attained rapidly with the loading dose regimen in four days versus seven weeks with weekly mefloquine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Enhanced antibody response in Venezuelan infants immunized with Haemophilus influenzae type b-tetanus toxoid conjugate vaccine

The safety and immunogenicity of primary immunization at 2, 4 and 6 months of age with Haemophilus influenzae type b capsular polysaccharide conjugated to tetanus toxoid (PRP-T; Act-HIB) were evaluated in infants in Valencia, Venezuela. In order better to assess reactions to PRP-T, subjects received their initial PRP-T vaccine a mean of 6.5 days after their initial diphtheria-tetanus-pertussis (DTP) vaccine. The PRP-T vaccine was well tolerated. Serum was obtained at ages 2 and 7 months (before the first and 1 month after the third PRP-T dose). Antibody responses were compared with those from Nashville infants who had received PRP-T and DTP simultaneously in a previous trial. The preimmunization titers in the Venezuelan and Nashville infants did not differ. The geometric mean postimmunization titer in the Venezuelan infants was 37.9 micrograms/ml, as compared with 3.63 micrograms/ml in the Nashville infants (P < 0.00001). Possible explanations for the exceptional antibody response of these Venezuelan infants to PRP-T include carrier priming caused by prior DTP immunization, synergy associated with the specific DTP vaccine used, preimmunization immunologic experience that differed from their United States counterparts and genetic differences that altered response to the vaccines. Further studies are proposed to evaluate these possibilities.     

Increase of birth weight following chloroquine chemoprophylaxis during the first pregnancy: results of a randomized trial in Cameroon

A randomized trial was carried out from 1991 to 1993 among women attending an antenatal clinic in Ebolowa, Cameroon where malaria is hyperendemic and transmission occurs at a high level all year round. All pregnant women attending the clinic for their first prenatal visit between October 1991 and November 1992 were alternately assigned to chloroquine (CQ) or control (CT) groups. Chloroquine was given under observation at a weekly oral dose of 300 mg. At delivery, smears from maternal, cord, and placental blood were made and stained with Giemsa for parasites. An in vivo chloroquine sensitivity investigation was carried out on women attending the postnatal consultation to evaluate the level of chloroquine resistance in the target population. The efficacy of chloroquine was moderate in placental infection (39.2% infected in the CQ group versus 57.8% in the CT group: P = 0.05), probably because of a resistance to chloroquine estimated to be 10.9%. In the CQ group, the mean birth weight was significantly higher (P = 0.02) and the proportion of low birth weight newborns was lower (10.5% versus 27.7%; P = 0.02). A strong correlation between placental infection and birth weight was observed: the mean birth weight difference between infected and noninfected placentae was 359 g (P < 0.0001) and the proportion of low birth weight new born babies was 35.6% versus 5.9% (P = 0.0001). In Cameroon, in spite of a moderate resistance to chloroquine, this drug proved to be highly effective in increasing birth weight when administered to primigravidae. We therefore think such a prophylaxis should be recommended only to primigravidae in high transmission areas.     

Tetanus toxoid stimulation of the hypothalamic-pituitary-adrenal axis correlates inversely with the increase in tetanus toxoid antibody titers

In humans, endotoxin activates the hypothalamic-pituitary-adrenal (HPA) axis, and the resulting increase in cortisol modulates the immune response. There is little information on the HPA axis response to other antigens. We examined the effect of the protein antigen tetanus toxoid on HPA axis activity in 10 healthy, premenopausal women (aged 28.6 +/- 2.6 yr). Subjects received im injections of placebo and tetanus toxoid at 1600 h on consecutive days. Blood samples for ACTH and cortisol were obtained every half-hour from--1 to 6 h and at 8, 12, and 16 h after each injection. Compared to placebo, tetanus toxoid administration stimulated significant increases in plasma ACTH and serum cortisol, with the maximum cortisol increase of 1.6-fold occurring 4.5 h after drug administration. Urinary free cortisol increased 1.8-fold in the 8 h after tetanus toxoid administration compared to that after placebo administration. Additionally, there was a significant inverse correlation (r = 0.87; P < 0.005) between the tetanus toxoid-induced increase in serum cortisol and the increase in tetanus antibody levels measured 1 month postvaccination. Thus, administration of the protein antigen tetanus toxoid activated the HPA axis in healthy, premenopausal women. This activation of the HPA axis correlated inversely with the antibody response to tetanus toxoid.     

Measles, polio and tetanus toxoid antibody levels in Gambian children aged 3 to 4 years following routine vaccination

A nation-wide cross-sectional survey of 816 children 3-4 years old was carried out in The Gambia between September 1990 and July 1991 to assess the seroprevalence of antibodies against 3 diseases included in the expanded programme on immunization: measles, poliomyelitis and tetanus. Among 689 children whose records were available, 94.5% were fully immunized. Measles vaccine was administered to 97% of the children and 91% of these had detectable antibodies at the time of the survey. Antibodies against type 1 and type 3 polioviruses, after up to 6 doses of oral polio vaccine, were present in 88.1% and 89.3% of the children respectively. Ninety-seven percent of the children who had received 4 doses of diphtheria-pertussis-tetanus vaccine (DPT) and 91% of those who received 3 doses had detectable tetanus toxoid antibodies at the age of 3-4 years. This study shows that serological responses to EPI vaccines given in infancy persist at very satisfactory levels throughout early childhood.     

Primary sinonasal mucosal melanoma: three different therapeutic approaches to inoperable local disease or recurrence and a review of the literature

Neonatal tetanus is still an important public health problem in both urban and rural Bangladesh, with an estimated 41,000 cases occurring annually. This article analyses the coverage of tetanus toxoid (TT) immunizations among women of reproductive age in Zone 3 of Dhaka City in 1995. Although 85% of women with a child under 1 year of age had received two TT immunizations, only 11% of women of reproductive age had obtained the complete series of five TT immunizations and only 52% of women of reproductive age had received one or more TT immunizations. Access to TT immunization, as defined by having had at least one such immunization, was lower among women aged over 30 years and also among those aged under 20 years, especially those who were not yet married or who had not yet become pregnant. Characteristics associated with TT immunization status included the following: educational level of the woman, distance from the nearest immunization centre, and level of contact with family planning field workers. Additional characteristics that influenced women's TT immunization status included age, marital and working status, recency of migration from rural to urban area, and number of children. The relationships were complex and varied depending on the number of TT immunizations received (one or two) and on the type of analysis being carried out (bivariate or multivariate). The findings point to the need for a broad-based campaign to promote access to TT immunization as well as to promote the completion of all five TT doses in Bangladesh. Reducing missed opportunities for promotion of immunization as well as targeting home visitation of women in need of additional immunizations constitute further approaches to improving coverage. Although TT coverage rates were only marginally lower among women in slum households, such women were more likely than those in non-slum households to be pregnant and hence more likely to bear a baby at risk of neonatal tetanus. Furthermore, the environment of slum households, where deliveries normally take place, is more conducive to the development of neonatal tetanus among unprotected neonates; a strategy of focusing on slum households is therefore also needed.     

Impaired human responses to tetanus toxoid in vitamin A-deficient SCID mice reconstituted with human peripheral blood lymphocytes

Vitamin A deficiency is associated with increased childhood morbidity and mortality from respiratory and diarrheal diseases. In order to evaluate the effect of vitamin A on human antibody responses, we developed a vitamin A-deficient severe combined immunodeficient (SCID) mouse model. Vitamin A-deficient mice were produced by depriving them of vitamin A at day 7 of gestation. Mice were reconstituted with human peripheral blood lymphocytes (huPBL) from tetanus toxoid immune donors at 6 weeks of age and immunized with tetanus toxoid at 6 and 8 weeks of age. Secondary human antibody responses were determined 10 days later. The geometric mean human anti-tetanus toxoid immunoglobulin G concentrations were 3.75 micrograms/ml for the deficient mice and 148 micrograms/ml for controls (P = 0.0005). Vitamin A-deficient mice had only a 2.9-fold increase in human anti-tetanus toxoid antibody compared with a 74-fold increase in controls (P < 0.01). Supplementation with vitamin A prior to reconstitution restored human antibody responses to normal. These data suggest that vitamin A deficiency impairs human antibody responses. We speculate that impaired responses could increase susceptibility to certain infections. Furthermore, we propose that effects of other nutritional deficiencies on the human immune system could be evaluated in the SCID-huPBL model.     

Vaginal mucosal immunization for recurrent urinary tract infection: phase II clinical trial

PURPOSE: Decreased local immunity to uropathogenic bacteria may be a factor predisposing women to recurrent urinary tract infections. Our phase I study demonstrated the safety of a multi-strain vaccine administered as a vaginal suppository. A phase II study was conducted to determine vaccine efficacy. MATERIALS AND METHODS: A total of 91 women susceptible to recurrent urinary tract infections was entered into the study and the courses were analyzed in a randomized, double-blind, placebo controlled trial of vaginal mucosal immunization. Subjects received 3 vaginal suppositories at weekly intervals. Depending on the treatment group each suppository contained 1 of 2 vaccine doses or suppository material only. Each patient was followed for 5 months to record infection episodes, and obtain urine, vaginal irrigates and serum to measure immunological responses. RESULTS: Immunogen treated women who were off antibiotic prophylaxis throughout the study had a significant delay in interval to reinfection during the first 8 weeks compared to women receiving placebo. Mean interval until reinfection was delayed from 8.7 weeks for placebo treated to 13 weeks for vaccine treated women. Immunological responses in serum, urine and vaginal fluid were variable. No serious adverse effects were observed. CONCLUSIONS: These data demonstrate that vaginal mucosal immunization can enhance resistance to urinary tract infections in susceptible patients.     

Compliance with and tolerance of mefloquine and chloroquine + proguanil malaria chemoprophylaxis in French short-term travellers to sub-Saharan Africa

To compare the compliance with and tolerance of mefloquine (MQ) and chloroquine + proguanil (CQ-PRO) chemoprophylaxis, we conducted a study using a self-reported questionnaire in 2 groups of native French adult visitors to Senegal or Kenya. CQ (100 mg daily) + PRO (200 mg daily) prophylaxis was prescribed for all patients travelling to Senegal and for those going to Kenya when MQ was contraindicated; MQ (250 mg weekly) was prescribed for the other subjects. There were no significant differences in age, sex, exposition and measures of protection against mosquito bites, concomitant drug use or mean duration of chemoprophylaxis between the 2 groups, and compliance during travel was excellent in both. Chemoprophylaxis was more frequently interrupted prematurely in the MQ group. The rates of overall side-effects attributed to malaria chemoprophylaxis were 16% for MQ against 12% CQ-PRO (not significant). However, nonserious neuropsychiatric adverse events are more frequent with MQ: 11.5% compared to 2% with CQ-PRO. MQ should be used with caution.