Non-price rationing and the choice of medical care providers in rural Cote d'Ivoire

This paper investigates the role of travel time in rationing medical care services in a developing country where monetary prices are zero. A nested multinomial logit model of provider choice is estimated using 1985 data from rural Côte d'Ivoire. Unlike previous studies of health care demand in developing countries, our results indicate that travel time plays an important role in rationing health care, and that medical care demand for poorer individuals is substantially more travel time elastic than for richer individuals.     

Contraceptive efficacy of antimicrobial peptide Nisin: in vitro and in vivo studies

Sexually transmitted infections and unplanned pregnancies present a great risk to the reproductive health of women. Therefore, female-controlled vaginal products directed toward disease prevention and contraception are needed urgently. In the present study, efforts were made to evaluate the contraceptive potential of Nisin. The effect of Nisin on sperm motility was assessed under in vitro and in vivo conditions. The results showed that sperm motility was completely inhibited with Nisin. The minimum effective concentration of Nisin required to immobilize sperm (80-100 x 10(6)) in vitro within 20 s was found to be 50 microg in rat, 200 microg in rabbit and 300-400 microg in monkey and human. The effect on sperm motility was observed to be dose- and time-dependent. Intravaginal administration of Nisin (200 microg) before mating during proestrus-estrous transition phase caused complete arrest of sperm motility and blockage of conception. Subacute toxicity studies in rats indicated that, repetitive intravaginal application of Nisin at the dose of 200 microg for 14 consecutive days induced no abnormalities either in the length of estrous cycle or in the morphology of vaginal epithelial cells. No histopathological abnormalities in vaginal tissue or any change in blood and serum biochemical profiles were observed. Furthermore, no adverse effects were observed on subsequent reproductive performance, neonate survival and development of pups. It is suggested that Nisin, with its antibacterial and spermicidal activities, could be developed as a potent vaginal contraceptive for future use in humans.     

The comparative efficacy of chloroquine and sulfadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria in Kampala, Uganda

Chloroquine (CQ) remains the first-line treatment for uncomplicated malaria in much of Africa despite the growing problem of resistance to this drug. Sulfadoxine-pyrimethamine (SP) is often used after CQ treatment failure and has replaced CQ as the first-line treatment in parts of Africa. To compare the efficacy of these 2 regimens, we evaluated, in March-August 1999, clinical and parasitological responses over 28 days in 214 children and adults from Kampala, Uganda, with uncomplicated falciparum malaria. Compared to SP, significantly more patients treated with CQ developed early or late clinical failure (54% vs 11%, P < 0.001) and parasitological failure (72% vs 30%, P < 0.001) during 14 days of follow-up. The risk of treatment failure occurring after day 14 was similar between the 2 treatment groups. Among those treated with CQ, children aged < 5 years were at higher risk of clinical failure than older individuals (76% vs 28%, P < 0.001), an association not seen with SP (11% vs 10%, P = 0.91). Although early parasite clearance was significantly better in the SP group (P = 0.001), fever clearance at day 3 was the same (CQ 85%, SP 86%). These and other recent findings suggest that consideration be given to replacing CQ as the first-line therapy for uncomplicated malaria in Uganda, particularly in young children.     

Antimalarial efficacy of chloroquine, amodiaquine, sulfadoxine-pyrimethamine, and the combinations of amodiaquine + artesunate and sulfadoxine-pyrimethamine + artesunate in Huambo and Bie provinces, central Angola

We studied three antimalarial treatments in Caala and Kuito, Angola, in 2002 and 2003. We tested chloroquine (CQ), amodiaquine (AQ) and sulfadoxine-pyrimethamine (SP) in Caala, and AQ, SP and the combinations AQ+artesunate (AQ+AS) and SP+artesunate (SP+AS) in Kuito. A total of 619 children (240 in Caala, 379 in Kuito) with uncomplicated Plasmodium falciparum malaria were followed-up for 28 days, with PCR genotyping to distinguish recrudescence from reinfection. PCR-corrected failure proportions at day 28 were very high in the CQ group (83.5%, 95% CI 74.1-90.5), high in the SP groups (Caala: 25.3%, 95% CI 16.7-35.8; Kuito: 38.8%, 95% CI 28.4-50.0), around 20% in the AQ groups (Caala: 17.3%, 95% CI 10.0-27.2; Kuito: 21.6%, 95% CI 14.3-30.6) and very low in the artemisinin-based combination groups (1.2%, 95% CI 0.0-6.4 for each combination AQ+AS and SP+AS). These results show that CQ and SP are no longer efficacious in Caala and Kuito and that the moderate efficacy of AQ is likely to be compromised in the short term if used as monotherapy. We recommend the use of AQ with AS, though this combination might not have a long useful therapeutic life because of AQ resistance.     

High Plasmodium falciparum resistance to chloroquine and sulfadoxine-pyrimethamine in Harper,Liberia: results in vivo and analysis of point mutations

In Liberia, little information is available on the efficacy of antimalarials against Plasmodium falciparum malaria. We measured parasitological resistance to chloroquine and sulfadoxine-pyrimethamine (SP) in Harper, south-west Liberia in a 28-d study in vivo. A total of 50 patients completed follow-up in the chloroquine group, and 66 in the SP group. The chloroquine failure rate was 74.0% (95% confidence interval [95% CI] 59.7-85.4%) after 14 d of follow-up and 84.0% (95% CI 70.9-92.8%) after 28 d (no polymerase chain reaction [PCR] analysis was performed to detect reinfections in this group). In the SP group, the failure rate was 48.5% (95% CI 36.2-61.0%) after 14 d and 69.7% (95% CI 57.1-80.4%) after 28 d, readjusted to 51.5% (95% CI 38.9-64.0%) after taking into account reinfections detected by PCR. Genomic analysis of parasite isolates was also performed to look for point mutations associated with resistance. Genotyping of parasite isolates revealed that all carried chloroquine-resistant K-76T mutations at gene pfcrt, whereas the triple mutation (S108N, N511, C59R) at dhfr and the A437G mutation at dhps, both associated with resistance to SP, were present in 84% and 79% of pretreatment isolates respectively. These results seriously question the continued use of chloroquine and SP in Harper and highlight the urgency of making alternative antimalarial therapies available. Our study confirms that resistance to chloroquine may be high in Liberia and yields hitherto missing information on SP.     

Clinical efficacy of chloroquine or sulfadoxine-pyrimethamine in children under five from south-western Uganda with uncomplicated falciparum malaria

We conducted a 14-day study (during March-May 1998) to assess the efficacy of chloroquine and sulfadoxine-pyrimethamine (SP) for treating uncomplicated Plasmodium falciparum malaria in Uganda. Overall treatment failure rates were 43 (81.1%) of 53 chloroquine recipients and 16 (25.0%) of 64 SP patients. Strategies to improve the life-span of standard and affordable anti-malarial drugs are needed.     

Efficacy of combined chloroquine and sulfadoxine-pyrimethamine in uncomplicated Plasmodium falciparum malaria in Bangladesh

A study of the therapeutic efficacy of combined chloroquine and sulfadoxine-pyrimethamine (SP) for the treatment of uncomplicated Plasmodium falciparum malaria was carried out from June to November 2002, using the standard protocol recommended by the WHO for a low-to-moderate transmission area, in two sentinel sites in Bangladesh: Alikadam Upazilla in Bandarban district and Matiranga Upazilla in Khagrachari district. A total of 133 patients was followed-up to 28 d. Total failure rates were 25.9 and 30.7% in Alikadam and Matiranga, respectively. No severe side effects due to the drugs were encountered during the study period. Chloroquine and SP is not a suitable combination for the first-line treatment of P. falciparum in Bangladesh.     

Monitoring the chemoresistance of Plasmodium falciparum malaria in Yopougon (Abidjan): in vivo study of chloroquine sensitivity and evaluation of pyrimethamine resistance following the analysis of point mutation in the dihydrofolate reductase gene

A major endemic in C?te d'Ivoire, malaria is the first cause of hospital admissions and mortality in tropical Africa. The decrease of morbidity and mortality depends on early diagnosis and relevant treatment. This situation is hampered by an emerging resistance of P. falciparum to usual drugs such as chloroquine and sulfadoxine-pyrimethamine. In recognition of this problem, we established a monitoring system in the north of Abidjan (Yopougon) in order to better analyse P. falciparum resistance. The molecular basis of P. falciparum resistance to pyrimethamine is associated with point mutations in the dihydrofolate reductase (dhfr) gene. The presence of a wild-type codon 108-ser is defined by the presence of an Alu1 restriction site. A single base change resulting in the change of amino acid from 108-Ser to 108-Asn or 108-Thr results in the appearance of a Bsr1 or a Scrf1 restriction site respectively. In response to these needs, 42 children aged 6 to 59 months were enrolled in the study by using tests of therapeutic efficacy of chloroquine (14-day in vivo test of WHO). Before treatment, infected blood samples were stored at 20 C until P. falciparum DNA extraction. The results of the in vivo sensitivity of chloroquine showed 84.3% of plasmodic rate, 97.7 % of P. falciparum against 2.3% of P. malariae. However, 78.6% of adequate clinical response (ACR) was obtained and 21.4% of early therapeutic failure (ETF). At the end of the study, clearance of parasitemia and fever was obtained but the gametocytic rate was 4.8%. More, RFLP studies of amplified DNA fragment revealed that P. falciparum from 12 children (44.5%) had point mutation in the codon 108 of the dhfr gene. The mutation of these isolates was based on the change of amino-acid from 108-Ser to 108-Asn. Moreover, 51.8% of isolates were of the wild type. In conclusion, our results showed that chloroquine resistance is a reality in Abidjan just like anywhere else in West Africa. However, the number of isolates which had point mutation in the dhfr gene suggested that the future approach must be the study of possible correlation between the in vivo sulfadoxine-pyrimethamine test and point mutations in the dihydrofolate reductase and in the dihydropteroate synthase gene of P. falciparum from C?te d'Ivoire.     

Microfinance and HIV mitigation among people living with HIV in the era of anti-retroviral therapy: emerging lessons from Cote d'Ivoire

The effects of HIV/AIDS have been far-reaching in Africa. Beyond adverse health outcomes and the tremendous toll on life, AIDS has serious economic impacts on households, increasing livelihood insecurity while simultaneously depleting socio-economic resources. Although microfinance is believed to have the potential to mitigate the economic impacts of HIV by helping affected households and communities better prepare for and cope with HIV-related economic shocks, little empirical research exists on this subject. This qualitative study examines the socio-economic impacts of economic strengthening activities on people living with HIV (PLHIV) in the era of increased access to anti-retroviral therapy to determine if savings-led, community-managed microfinance is a justified activity for HIV programmes. Findings from a village savings and loan programme, implemented by CARE International in Cote d'Ivoire, revealed that when appropriate medical treatment is available PLHIV are capable of participating in and benefit from microfinance activities, which increased HIV-positive clients' access to money and economic self-sufficiency. By bringing individuals with similar experiences together, savings and loan groups also acted as self-support groups providing psychosocial support while reducing stigmatisation and increasing members' sense of dignity and self-worth.     

Treatment of uncomplicated malaria in children in Guinea-Bissau with chloroquine,quinine, and sulfadoxine-pyrimethamine

With the increasing resistance to commonly used antimalarial drugs, different untested 'local' treatment regimens for malaria will arise. We compared commonly used treatment regimens for children in Guinea-Bissau. Symptomatic children with Plasmodium falciparum mono-infection were allocated at random to one of 4 treatments: 15 mg/kg quinine twice a day for 3 d (group 1); 10 mg/kg quinine twice a day for 3 d followed by a total dose of 25 mg chloroquine base given over 3 d (group 2); a total dose of 50 mg/kg chloroquine base given in 2 daily doses for 3 d (group 3), or sulfadoxine-pyrimethamine (group 4). On day 28 more children from group 1 (33%; relative risk [RR] = 2.9, 95% confidence interval [CI] 1.5-5.7) and group 2 (26%; RR = 2.1, CI 1.0-4.3) had had parasitaemia than in group 4 (12%), whereas no significant difference was found between group 3 (17%; RR = 1.3, CI 0.6-2.2) and group 4. No severe adverse reaction was observed in any of the groups. Chloroquine is still effective in Guinea-Bissau at an increased dose of 50 mg/kg, which appears safe when given orally in 2 daily doses for 3 d. Sulfadoxine-pyrimethamine could serve as an efficient, cheap and easy to administer second-line drug, leaving quinine to be used for third-line treatment. Quinine should not be used in short courses, nor does the combination of quinine and chloroquine have any advantage.     

Higher gametocyte prevalence following failure of treatment of Plasmodium falciparum malaria with sulfadoxine-pyrimethamine and the combination of chloroquine plus sulfadoxine-pyrimethamine: implications for progression of anti-folate resistance

Chloroquine (CQ) treatment of CQ-resistant Plasmodium falciparum is associated with a significantly higher prevalence of post-treatment gametocytaemia which has been linked to the preferential transmission of CQ-resistant parasites. It is not known whether treatment failure (TF) with sulfadoxine-pyrimethamine (SP) is associated with the same higher prevalence of gametocytaemia as that seen with CQ TF. Using 1997 WHO in-vivo drug efficacy protocols for malaria, we therefore compared (in a study in 1999) the frequency of gametocytaemia in those with TF to the frequency seen in those with an adequate clinical and parasitological response (ACPR) following treatment with one of 3 regimens in Papua, Indonesia: SP monotherapy (n = 87; TF 20.7%), CQ monotherapy (n = 48; TF 83.3%), and the combination of CQ plus SP (n = 34; TF 38.2%). Following SP, day 7 prevalence was significantly higher in those with TF (67%) than with ACPR (38%, P = 0.03). Following combination treatment with CQ + SP, the day 14 gametocyte prevalence was significantly higher in those with TF (100% vs 38%, P = 0.016). The higher prevalence of SP TF-associated gametocytaemia may contribute to increased transmission of antifolate-resistant strains, and further cautions against the use of SP as monotherapy. Adding SP to CQ, after significant resistance has emerged to both drugs, may not prevent enhanced transmission of dual-resistant strains and progression of anti-folate resistance.     

Antenatal chloroquine chemoprophylaxis in Malawi: chloroquine resistance, compliance, protective efficacy and cost

The roles of Plasmodium falciparum resistance to chloroquine and compliance in the protective efficacy of the antenatal chloroquine prophylaxis programme in Malawi were evaluated by interviewing pregnant women attending antenatal clinics and examining them for P. falciparum parasites in thick smears and chloroquine metabolites in urine. 36% of 642 women had urine chloroquine metabolite levels compatible with regular compliance to the weekly chloroquine dosage schedule. Among a subgroup of 288 pregnant women who were provided weekly prophylaxis under supervision for 4 consecutive weeks, P. falciparum infection rates were 37%, representing the failure of chloroquine to eliminate P. falciparum in Malawi. Among pregnant women not taking prophylaxis, the P. falciparum infection rate was 48%. Based on the P. falciparum infection rates among these 2 groups of women, the protective efficacy of CQ chloroquine was estimated as 23%. If the 36% of pregnant women who had chloroquine in their urines accurately estimates the proportion of women who comply with the prophylaxis programme in Malawi, the actual protective efficacy of the programme would be 8%. The cost of preventing one P. falciparum infection among pregnant women in the Malawi programme is estimated at US$ 10.87. This is an unacceptably high cost in much of Africa, and research is required to define more cost-effective interventions, including more effective drugs, and health education programmes to improve compliance among pregnant women.     

A randomized comparison of oral chloroquine and sulfadoxine-pyrimethamine for the treatment of uncomplicated Plasmodium falciparum malaria in Laos

Between June and October 2000 we conducted the first randomized trial in Laos comparing chloroquine (CQ) with sulfadoxine-pyrimethamine (SP) in the treatment of uncomplicated Plasmodium falciparum malaria (n = 29, 42-d follow-up, age > 5 years). The proportion of patients with treatment failure was high (CQ = 78%, RIII 46%; SP = 36%, RIII 15%). The treatment policy for uncomplicated P. falciparum malaria in Laos needs to be reviewed urgently.     

Pregnane derivatives as pregnancy interceptive agents: efficacy determination on growing trophoblasts (in vitro) and in pregnant hamsters (in vivo).

An in vitro test system was standardized to study potentiality of five hormonally inert pregnane derivatives on growing trophoblasts isolated from ectoplacental cone (EPC) of day 8 hamster embryo. Cells were incubated with different concentrations of respective compounds in surface droplets. The response was determined by analyzing the sequence of changes in cell morphology like attachment, growth, proliferation, differentiation and/or degeneration within 24 or 48 h following seeding. The in vivo efficacy of these compounds was determined in hamster during peri- and immediate post-implantation periods (days 3-8 post coitum). Two compounds 88/583 and 88/585 were found to inhibit not only growth and proliferation of the cells but caused total degeneration within 24 h. The same compounds induced partial to complete resorption of the foetuses in treated animals. Whereas, the other three compounds 88/506, 88/594 and 89/43 that showed lack of comparable potentiality in vitro were found to be equally ineffective in vivo. The results indicate a positive correlationship between in vitro and in vivo activity.     

In vivo and in vitro susceptibility to chloroquine of Plasmodium falciparum in Kinshasa and Mbuji-Mayi, Zaire

From April to June 1983, combined in vivo and in vitro studies were conducted to assess the response to chloroquine of Plasmodium falciparum in Kinshasa and Mbuji-Mayi, Zaire. A total of 109 patients were treated with chloroquine, either as a single dose of 10 mg/kg or as a full dose of 25 mg/kg. All patients rapidly cleared their asexual parasitaemia, no recurrence being noted during the subsequent 3 weeks of follow-up. In the fourth week, recurrences were noted in 3 out of 66 patients treated with the full dose of chloroquine and in 10 out of 43 patients treated with the single dose. A total of 101 in vitro tests (30 macro tests, 39 micro tests, and 32 48-hour tests) were successfully performed with blood samples collected from 51 of these patients. Full sensitivity to chloroquine was demonstrated in all but 3 of the successful in vitro tests, the results from these 3 tests being contradicted either by alternative in vitro tests or by the corresponding in vivo findings. These investigations thus failed to detect chloroquine resistance at the level reported in East Africa or eastern Zaire (in Kivu).     

Development of an in vitro microtest for determining the susceptibility of Plasmodium falciparum to sulfadoxine-pyrimethamine: laboratory investigations and field studies in Port-au-Prince, Haiti

An in vitro microtest for assessing the susceptibility of Plasmodium falciparum to sulfadoxine—pyrimethamine (S—P) was developed following WHO guidelines. Paraaminobenzoic acid and folic acid were depleted in the culture medium used, the test wells were predosed with sulfadoxine and pyrimethamine at a constant ratio of 80:1, and the parasites were incubated for 48 hours. Optimum parasite multiplication was obtained with a 2% erythrocyte suspension in medium supplemented with 12% serum. During in vitro studies with laboratory-adapted isolates, response patterns were obtained which distinguished 3 isolates with documented in vivo sensitivity to S—P from 2 isolates with documented in vivo resistance to S—P. In addition, among the three S—P-sensitive isolates, one isolate that was pyrimethamine-resistant in vitro had a higher S—P inhibitory endpoint than 2 isolates that were pyrimethamine-sensitive in vitro. The S—P microtest was further evaluated in combined in vivo and in vitro studies in Port-au-Prince, Haiti. Twenty-six patients infected with P. falciparum were treated with standard doses of S—P, resulting in prompt clearance of parasitaemia, with no recurrence in the 24 patients who completed a 28-day follow-up period. Parallel in vitro tests with pyrimethamine alone showed 3 pyrimethamine-resistant isolates out of 22 successful tests on the patients'' blood samples. In 23 successful S—P tests, the known in vivo S—P-sensitive parasites were inhibited at S—P concentrations that were generally lower for in vitro pyrimethamine-sensitive isolates than for in vitro pyrimethamine-resistant ones.