Cost-effectiveness analysis of malaria chemoprophylaxis for travellers to West-Africa

Background  

The importation of malaria to non-endemic countries remains a major cause of travel-related morbidity and a leading cause of travel-related hospitalizations. Currently they are three priority medications for malaria prophylaxis to West Africa: mefloquine, atovaquone/proguanil and doxycycline. We investigate the cost effectiveness of a partial reimbursement of the cheapest effective malaria chemoprophylaxis (mefloquine) for travellers to high risk areas of malaria transmission compared with the current situation of no reimbursement.     

疟疾药物预防的现状与进展

近年来,疟疾的发病率已明显下降,但仍然是全球最重要的公共卫生负担。目前预防用药可以大大降低其发病率、病死率,控制传播,但长时间服药带来的不良反应及耐药等问题亟待解决,新的药物或组合方案应具有良好的耐受性、安全性和有效性。本文就疟疾预防用药的现状及进展作一综述。     

Tolerability of doxycycline monohydrate salt vs. chloroquine-proguanil in malaria chemoprophylaxis

The resistance of Plasmodium falciparum to the chloroquine-proguanil association (C/P) as antimalarial chemoprophylaxis is becoming increasingly common in Africa. Daily oral doxycycline hyclate 100 mg is effective as malaria prophylaxis. But the hyclate salt's adverse effects combined with the capsule's galenic form are incompatible with good chemoprophylaxis compliance. We conducted a randomized group study of 522 French soldiers deployed in Gabon and Chad for 4 months to determine the tolerability of short-term malaria chemoprophylaxis with a 100-mg daily tablet of a monohydrate doxycycline salt compared with a daily C/P capsule. At days 7 and 120, compliance was better in the doxycycline group [respectively 98.5%vs. 73.9% (P < 0.001) and 90.5%vs. 74% (P < 0.001)]. No major event (evacuation, hospitalization) was related to the medications. Epigastralgia, diarrhoea, urticaria, mouth ulcers, sun sensitization and desquamation were significantly more frequent in the C/P group (P < 0.05). There was no statistical difference for malaria incidence, vertigo, nausea and hair loss. These results suggest that doxycycline monohydrate may be safely used in short-term malaria chemoprophylaxis. With the same efficacy as a hyclate doxycycline, doxycycline monohydrate could be a good chemoprophylaxis for short-term travellers at particular risk of C/P resistant P. falciparum malaria.     

Leucopenia and abnormal liver function in travellers on malaria chemoprophylaxis

Of 2887 travellers between the years 1984-1985, 451 on prophylactic antimalarials were studied retrospectively for adverse haematological or hepatic drug reactions and compared to 296 drug non-users. Travellers using amodiaquine, chloroquine, or pyrimethamine for less than 10 weeks had significantly lower total leucocyte counts than non-users. This was due to diminution of lymphocytes, not neutrophils. Travellers using amodiaquine for less than 10 weeks also had significantly higher serum aspartate aminotransferase (SGPT) levels than non-users. Amodiaquine was associated with a 3.1-times increased risk (95% confidence limits 1.8-5.4) of abnormal SGPT values. We consider toxic products, including metabolites of amodiaquine, the most likely cause of amodiaquine-related hepatotoxicity in travellers.     

Pattern of osteoarthritis in a West African teaching hospital.

The study of the pattern of osteoarthritis in different populations may yield valuable aetiological clues and also allow subtypes to be defined. Over one year 252 osteoarthritic joints from 140 patients seen at a West African teaching hospital were prospectively reviewed. The knee was the joint most often affected. Hip and hand disease, as well as Heberden's nodes, were uncommon. Joint disease was predominantly monoarticular; no patient had three or more sites affected.     

Species prevalence of malaria in northern and southern Sudan, and control by mass chemoprophylaxis.

A survey in northern and southern Sudan showed that Plasmodium falciparum is the predominant species in malaria cases, occurring in 91% and 87%, respectively of the positive cases in these two regions. P. ovale was extremely rare in southern Sudan and was absent in the north. The survey, which was carried out during the transmission season in northern Sudan, showed that malaria is common, occurring in 62% of those tested in some villages. A trial of mass chemoprophylaxis resulted in a marked decline in prevalence after 1 year, demonstrating the importance of chloroquine and establishing that malarial parasites in Sudan are highly sensitive to the drug.     

Effectiveness of chemoprophylaxis and other determinants of malaria in travellers to Kenya

Summary objective  To investigate the effectiveness of chemoprophylaxis and the determinants of malaria importation from Kenya.
method  In a population-based case-control study, 51 travellers from Bavaria diagnosed with falciparum malaria imported from Kenya (cases) and a sample of 383 healthy Bavarian travellers returning from Kenya (controls) were interviewed. Data were analysed by multiple logistic regression.
results  Mefloquine (OR = 0.055; 95% Cl 0.019-0.16) and chloroquine combined with proguanil (OR = 0.128; 95% CI 0.039-0.419) were highly protective against P. falciparum malaria, whereas other drugs were ineffective (OR = 1.225; 95% CI 0.536-2.803). Ineffective prophylaxis (10.4%) and non-prophylaxis (11.2%) were the main reasons for malaria importation. Travelling alone or with friends, male sex, and travel duration over 4 weeks could be identified as additional risk factors. The main reason for inadequate chemoprophylaxis was inappropriate medical advice (87.5%). Prophylaxis refusal occurred frequently despite correct advice (58.1%). Diagnosis was often delayed unnecessarily (27.5%).
conclusion  Malaria importation from Kenya could be reduced substantially (34%) by eliminating inappropriate medical advice.     

The association between protein-energy malnutrition,malaria morbidity and all-cause mortality in West African children

Both malaria and protein-energy malnutrition (PEM) are highly prevalent in young children of sub-Saharan Africa, and the association between PEM and malaria continues to be discussed controversially. We analysed the association between PEM, malaria morbidity and all-cause mortality in a cohort of 709 children aged 6-30 months in a malaria holoendemic rural area of Burkina Faso. Study children were followed over the main malaria transmission period (June-December) in 1999 through longitudinal malaria surveillance complemented by three cross-sectional clinical surveys. There was no association between PEM and malaria morbidity, but malnourished children had a more than two-fold higher risk of dying than non-malnourished children.     

HIV infection among youth in a South African mining town is associated with herpes simplex virus-2 seropositivity and sexual behaviour

OBJECTIVES: To determine the seroprevalence of HIV and herpes simplex virus-2 (HSV-2) by age and gender among young people aged 14--24 years in a South African town and to identify risk factors for HIV infection. DESIGN: A community-based, cross-sectional study was conducted on a random sample of men (n = 723) and women (n = 784) living in a township in the Carletonville district of South Africa. METHODS: Potential demographic and behavioural risk factors associated with HIV were recorded by questionnaire and biological tests were performed on serum and urine. Data analysis was performed using multivariate logistic regression. RESULTS: Among men and women the prevalence of HIV infection was 9.4 and 34.4%, respectively, and of positive HSV-2 serology was 17.0 and 53.3%, respectively. Among 24-year-old women the prevalence of HIV was 66.7% [95% confidence interval (CI), 54.6--77.3%]. HSV-2 seropositivity was a strong independent risk factor for HIV infection with odds ratios of 5.3 (95% CI, 2.7--10.3) for men and 8.4 (95% CI, 4.9--14.2) for women. There was no independent effect of age at first sex or serological markers of other sexually transmitted infections on HIV infection. CONCLUSIONS: HIV infection among young women increases rapidly after the onset of sexual activity and reaches extremely high levels by 24 years of age. These findings suggest that rates of HIV transmission from men to women are high and that HSV-2 plays a major role in the spread of HIV in this population.     

Different response to Plasmodium falciparum malaria in West African sympatric ethnic groups

The comparison of malaria indicators among populations that have different genetic backgrounds and are uniformly exposed to the same parasite strains is one approach to the study of human heterogeneities in the response to the infection. We report the results of comparative surveys on three sympatric West African ethnic groups, Fulani, Mossi, and Rimaibé, living in the same conditions of hyperendemic transmission in a Sudan savanna area northeast of Ouagadougou, Burkina Faso. The Mossi and Rimaibé are Sudanese negroid populations with a long tradition of sedentary farming, while the Fulani are nomadic pastoralists, partly settled and characterized by non-negroid features of possible caucasoid origin. Parasitological, clinical, and immunological investigations showed consistent interethnic differences in Plasmodium falciparum infection rates, malaria morbidity, and prevalence and levels of antibodies to various P. falciparum antigens. The data point to a remarkably similar response to malaria in the Mossi and Rimaibé, while the Fulani are clearly less parasitized, less affected by the disease, and more responsive to all antigens tested. No difference in the use of malaria protective measures was demonstrated that could account for these findings, and sociocultural or environmental factors do not seem to be involved. Known genetic factors of resistance to malaria did not show higher frequencies in the Fulani. The differences in the immune response were not explained by the entomological observations, which indicated substantially uniform exposure to infective bites. The available data support the existence of unknown genetic factors, possibly related to humoral immune responses, determining interethnic differences in the susceptibility to malaria.     

Compliance with malaria chemoprophylaxis and preventative measures against mosquito bites among Dutch travellers.

Summary Self-reported compliance with a malaria chemoprophylaxis regimen of proguanil (PG) plus chloroquine (CQ) was assessed in a cohort of 547 Dutch travellers who visited a single travel clinic when travelling to various areas endemic for falciparum malaria. 503 (92%) had taken PG/CQ prophylaxis, but only 326 (60%) reported regular and uninterrupted use throughout the journey and 4 weeks afterwards. Compliance differed by travel destination and was 45% in South America, 52% in West Africa, 53% in South-east Asia, 60% in the Indian Subcontinent and 78% in East Africa. Parasitologically confirmed falciparum malaria occurred in 5 travellers (0.9%), including 3 of 24 non-compliant travellers to West Africa (12.5%). Apart from destination, independent risk factors for non-compliance were young age, extensive travel experience and adventurous travel. Compliance with protection against mosquito bites was 80% for wearing long-sleeved shirts and long-legged trousers after sunset, 73% for use of repellents, 56% for sleeping under bednets and 37% for keeping the sleeping quarters free of mosquitoes. Although 440 travellers (80%) reported to have taken two or more of these measures at least once, only 88 (16%) had done so on a daily basis. Daily use of bednets was reported more frequently among subjects who were non-compliant with chemoprophylaxis. Compliance regarding malaria chemoprophylaxis should be improved, particularly in high-risk areas such as Sub-saharan Africa, with extra attention to young, adventurous travellers. More emphasis should be placed on prevention of Anopheles bites.     

Urban farming and malaria risk factors in a medium-sized town in Cote d'Ivoire

Urbanization occurs at a rapid pace across Africa and Asia and affects people's health and well-being. A typical feature in urban settings of Africa is the maintenance of traditional livelihoods, including agriculture. The purpose of this study was to investigate malaria risk factors in urban farming communities in a medium-sized town in C?te d'Ivoire. Two cross-sectional surveys were carried out among 112 households from six agricultural zones. First, the heads of households were interviewed on agricultural land use, farming practices, water storage, sanitation facilities, and socioeconomic status. Second, a finger prick blood sample was taken from all household members and examined for the occurrence and density of Plasmodia. Geographic coordinates of houses, farming plots, and potential mosquito breeding sites were recorded and integrated into a geographic information system. Predictors of Plasmodium falciparum parasitemia were assessed using non-random and random effects Bayesian regression models. The overall prevalence of P. falciparum was 32.1%. In children < 15 years of age, risk factors for a P. falciparum infection included living in a specific agricultural zone, close proximity to permanent ponds and fish ponds, periodic stays overnight in temporary farm huts, and low socioeconomic status. Our findings indicate that specific crop systems and specific agricultural practices may increase the risk of malaria in urban settings of tropical Africa.     

Lung asbestos content in long-term residents of a chrysotile mining town

The effects of long-term exposure to very small amounts of chrysotile asbestos are controversial. To examine this problem, the lung asbestos content from 7 long-term (25 yr and greater) residents of Thetford Mines, Quebec, who were never employed in the chrysotile mining and milling industry, was analyzed. Thetford Mines is a chrysotile mining town with a demonstrated ambient atmospheric concentration of chrysotile asbestos approximately 200 to 500 times that in urban areas of North America. Data on the residents' lungs were compared with those obtained from 20 long-term (25 yr and greater) chrysotile industry workers from Thetford Mines and 20 members of the general population of Vancouver. The median concentrations of chrysotile and tremolite in the Thetford residents were only about one fiftieth of those of the chrysotile workers, but about 10 times that of the population of Vancouver. Because long fibers of asbestos are generally thought to be more dangerous than short ones are, the sizes of fibers from these 3 groups were also examined. The fiber size distribution of the asbestos from the Thetford residents was significantly longer than that of the Vancouver population, and resembled that of the chrysotile workers. Because epidemiologic studies have consistently failed to find an increased respiratory disease incidence in lifelong residents of Quebec chrysotile mining towns who were never employed in the chrysotile industry, these findings imply that even asbestos burdens much higher, and fiber size distributions much longer, than those of the general population of most North American cities, are not associated with demonstrable pathologic effects.     

Environmental pleural plaques in residents of a Quebec chrysotile mining town

We report four cases of pleural plaques found at autopsy in individuals who resided in or near the chrysotile mining town of Thetford Mines, Quebec, and who had never been employed in the chrysotile mining and milling industry. Three of these patients were farmers, and one was a road construction worker. Lung asbestos content of these cases was compared with that of a group of nine persons living in the same vicinity who did not have pleural plaques. The plaque group was found to have an equal chrysotile content but about a fourfold elevation in median tremolite content, a statistically significant increase. Fiber sizes were the same in both groups. Also, one plaque case had an elevated level of relatively long titanium oxide fibers. These observations suggest that environmental pleural plaques in this region of Quebec are probably caused by exposure to tremolite derived from local soil and rock and that other types of mineral fibers such as titanium oxide may occasionally also be the cause of such lesions.     

Lassa fever in West African sub-region: an overview

Lassa fever is an acute viral zoonotic illness caused by Lassa virus, an arenavirus known to be responsible for a severe haemorrhagic fever characterised by fever, muscle aches, sore throat, nausea, vomiting and, chest and abdominal pain. The virus exhibits persistent, asymptomatic infection with profuse urinary virus excretion in the ubiquitous rodent vector, Mastomys natalensis. Lassa fever is endemic in West Africa and has been reported from Sierra Leone, Guinea, Liberia, and Nigeria. Some studies indicate that 300,000 to 500,000 cases of Lassa fever and 5000 deaths occur yearly across West Africa. Studies reported in English, that investigated Lassa fever with reference to West Africa were identified using the Medline Entrez-PubMed search and were used for this review. The scarcity of resources available for health care delivery system and the political instability that characterise the West African countries would continue to impede efforts for the control of Lassa fever in the sub-region. There is need for adequate training of health care workers regarding diagnostics, intensive care of patients under isolation, contact tracing, adequate precautionary measures in handling infectious laboratory specimens, control of the vector as well as care and disposal of infectious waste.     

Sigmoid volvulus in a West African population

The incidence, clinical presentation, etiology, and treatment of sigmoid volvulus in a West African population are described. This retrospective study, based on 146 cases in eight years, shows that the incidence of the disorder of 12 new cases per 100,000 population per year is extremely high in the area described. It also shows that good results can be obtained in the treatment of sigmoid volvulus even in suboptimal conditions in rural hospitals when adhering to sound surgical principles.