Severity markers in severe leptospirosis: a cohort study.

We aimed to evaluate parameters for their value as severity markers in hospitalized leptospirosis patients. We recruited 47 informed adult consenting patients and assessed a number of clinical, hematological, biochemical, and biological variables. Patients were sorted according to severity based on fatality or the requirement of mechanical ventilation or dialysis; the parameters studied were compared between groups on inclusion and the next day. Beside septic shock presentation or a high severity score (Simplified Acute Physiology Score; SAPS II), increased lactate, total bilirubin, lipase, and AST/ALT ratio or a decreased cytokines IL-10/TNF-α ratio were all significantly associated with severity. The gene expression of the IL-1 receptor antagonist IL-1ra, IL-1α, and the long pentraxin PTX-3 were also transcribed at higher levels in most severe cases. Patients could rapidly improve or deteriorate, highlighting the need for a new assessment the next day. Our results add to the limited body of knowledge about severity markers in leptospirosis. They also suggest that patients should be reassessed the next day before being possibly discharged from the hospital. Further studies are needed in order to confirm relevant and reliable prognostic parameters in leptospirosis that would be helpful for the purpose of triage.

Geographic and ecological distribution of the dengue and chikungunya virus vectors Aedes aegypti and Aedes albopictus in three major Cameroonian towns.

Aedes albopictus (Diptera: Culicidae) was first reported in Central Africa in 2000, together with the indigenous mosquito species Aedes aegypti (Diptera: Culicidae). Because Ae. albopictus can also transmit arboviruses, its introduction is a public health concern. We undertook a comparative study in three Cameroonian towns (Sahelian domain: Garoua; equatorial domain: Douala and Yaoundé) in order to document infestation by the two species and their ecological preferences. High and variable levels of pre-imaginal Ae. aegypti and Ae. albopictus infestation were detected. Only Ae. aegypti was encountered in Garoua, whereas both species were found in Douala and Yaoundé, albeit with significant differences in their relative prevalence. Peridomestic water containers were the most strongly colonized and productive larval habitats for both species. No major differences in types of larval habitat were found, but Ae. albopictus preferentially bred in containers containing plant debris or surrounded by vegetation, whereas Ae. aegypti tended to breed in containers located in environments with a high density of buildings. These findings may have important implications for vector control strategies.

Field evaluation of rapid diagnostic tests for meningococcal meningitis in Niger.

OBJECTIVE: To evaluate dipstick rapid diagnostic tests (RDTs) for meningococcal meningitis in basic health facilities. METHODS: Health facility staff received a one-day training. During the meningitis season, they performed RDTs on cerebrospinal fluid (CSF) specimens from suspected cases of meningitis. A frozen aliquot of CSF was later tested using polymerase chain reaction (PCR) to establish the reference diagnosis. RDTs used in health facilities were archived to allow checking the concordance between reported diagnosis and observed results. Reported diagnosis was also compared to PCR diagnosis. A second RDT was performed on each CSF specimen at the reference laboratory. RESULTS: Using RDTs, health facilities reported 382 negative results (73.9%), 114 NmA (22.1%), 12 NmW135 (2.3%) and nine uninterpretable results (1.7%), the latter corresponding to the misuse of a reagent by three agents. The agreement between reported diagnosis and archived dipsticks was excellent (kappa = 0.98). The agreement between PCR diagnosis and reported RDTs results was strong (kappa = 0.82). In health facilities, the sensitivity of RDTs for N. meningitidis A was Se = 0.91. The kappa coefficient measuring the agreement between RDTs operated in the reference laboratory and RDTs operated in health facilities was kappa = 0.78. CONCLUSION: We confirmed that dipstick RDTs to identify N. meningitidis serogroups A, C, W135 and Y can be reliably operated by non-specialized staff in basic health facilities. RDTs proved very useful to recommend vaccination in NmA epidemics, and also to avoid vaccination in epidemics due to serogroups not included in vaccines (NmX).

Present and future schistosomiasis control activities with support from the Schistosomiasis Control Initiative in West Africa.

Since 2004 the West African countries of Burkina Faso, Mali and Niger have implemented national schistosomiasis and soil-transmitted helminthiasis control programmes with financial and technical support from the Schistosomiasis Control Initiative (SCI). In the first three years of the control programmes, nearly 13.5 million doses of praziquantel and albendazole have been administered against schistosomiasis and soil-transmitted helminthiasis with coverage rates varying between 67.0% and 93.9%. These treatments have resulted in a reduction of the prevalence and intensity of Schistosoma infection in the sentinel cohorts that were set up to monitor and evaluate the national control programmes. The challenges currently faced by these national control programmes are the ability to maintain the reduction in morbidity achieved thus far due to the mass treatment campaigns and ensuring sustainability. For reinforcement of surveillance, the establishment of a geographical information system is suggested in order to contribute towards enhanced sustainability of these programmes. Our new working hypothesis is that targeted control accompanied by periodic mass treatment campaigns (every two to three years) can contribute to maintaining the low levels of morbidity achieved thus far. The implementation of integrated neglected tropical disease control programmes in these countries will provide means to ensure the financial sustainability of control activities for the years to come.

[Illicit drug trade on the markets of Yaounde (Cameroon) and Niamey (Niger): characteristics of salesmen and quality of drugs]. / Le circuit informel des médicaments à Yaoundé et à Niamey: étude de la population des vendeurs et de la qualité des médicaments distribués.

This study characterizes salesmen and evaluates the drugs offer and quality of the drugs in the illicit selling network in Yaoundé (Cameroon) and Niamey (Niger). A sample of 75 and 124 drug salesmen working in these cities was questioned using a standardized questionnaire. The prescription of drugs and the advices provided by these poorly trained salesmen could have an important impact in term of public health: 32% and 67% of the salesmen in Yaoundé give systematically or occasionally advices regarding the prescription. The active substances are always present in the 153 drugs of our analysed sample, except for chloroquine-based drugs, among which 5/30 samples did not contain active substance. However, the rate of nonconformity is approximately 50% in the two cities. Complementary studies are needed to explore the origin of these nonconformities, between counterfeiting, low quality of the products provided by the factories, defects of conservation or instability of the formulations.

Evaluation of the Pastorex meningitis kit for the rapid identification of Neisseria meningitidis serogroups A and W135.

The recent emergence of Neisseria meningitidis W135 as a cause of epidemic bacterial meningitis and the availability of a trivalent ACW135 vaccine have created a need for accurate and timely meningococcal serogroup determination for organization of epidemic vaccine response. The sensitivity and specificity of the Pastorex meningitis kit (Bio-Rad) to identify serogroups A and W135 in the African meningitis belt was assessed using PCR testing as the gold standard. The sensitivity and specificity for serogroups A and W135 were 87 and 85%, respectively, while the specificities were 93 and 97%. The positive and negative likelihood ratios for A were 12 and 0.14 and for W135 were 33 and 0.16. The positive and negative predictive values, computed to simulate an epidemic of meningococcal meningitis with an estimated 70% prevalence of N. meningitidis among suspected cases, were 97% and 75% for A and 99% and 73% for W135. In remote locations of the African meningitis belt, latex agglutination is the only currently available test that can rapidly determine meningococcal serogroup. This study showed that latex agglutination performs well and could be used during the epidemic season to determine appropriate vaccine response.

[Prevalence of tuberculous meningitis in Niamey's Hospital, Niger]. / Prevalence de la méningite tuberculeuse a l'hôpital de Niamey, Niger.

Tuberculosis is hyperendemic in Niger. In Niamey between June 2002 and May 2004, 996 cerebro-spinal fluids (CSF) collected from meningitis suspected patients have been analysed by PCR for the detection of Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae: the aetiologic diagnosis was obtained for 208 cases (20.9%). The Mycobacterium tuberculosis PCR assay performed on the negative samples was positive for 4 CSF: 0.4% prevalence among suspected cases of meningitis or 1.9% among confirmed bacterial meningitis.

Current epidemiology of human plague in Madagascar.

From 1996 to 1998, 5,965 patients with suspected plague were identified in 38 districts of Madagascar (40% of the total population are exposed). Using standard bacteriology, 917 of them were confirmed or presumptive (C + P) cases. However, more than 2,000 plague cases could be estimated using F1 antigen assay. Two out of the 711 Yersinia pestis isolates tested were resistant to chloramphenicol and to ampicillin (both isolates found in the harbour of Mahajanga). Urban plague (Mahajanga harbour and Antananarivo city) accounted for 37.4% of the C + P cases. Bubonic plague represented 97.2% of the cases, and the lethality rate was still high (20%). In comparing the exposed population, plague was more prevalent in males (M:F sex ratio 1.3:1) and patients under 20 years (2.7% babies under two years). Buboes were mainly localised in the inguinal/femoral regions (55.8%). The epidemiological risk factors are discussed.

Relationship between parasite density and fever risk in a community exposed to a low level of malaria transmission in Madagascar highlands.

To establish a simple definition of a malaria attack based on blood parasite density and other explanatory covariates, a cohort study was conducted from 1993 to 1996 in the Madagascar highlands undergoing a low seasonal transmission of falciparum malaria. Using logistic regression, the explanatory variables found to be significantly related to the risk of fever are parasite density, age, season, and year. However, and in contrast with other studies, we found no evidence of a clear cutoff in parasite density values consistent with the concept of "pyrogenic threshold" despite a gradual increase of the risk of fever with increasing parasite density. Furthermore, the model evidenced an individual-dependent relationship at a given age. This point was in accordance with the immunological data recorded from the participants. The investigators conclude that the parasite density to distinguish malaria attacks from other causes of fever is not reliable in a context of low falciparum transmission.

Relationships between several markers of extracellular matrix turn-over and ultrasonography in human Schistosomiasis mansoni.

We measured the concentrations of several serum and urinary fibrosis markers, which are metabolites of extracellular matrix, in schistosomiasis patients to investigate their relationship with the ultrasonographic scoring system and with parasitologic data. This study was conducted in patients with various stages of the disease evaluated by ultrasonography (intestinal disease with no organ involvement, with minor hepatosplenic involvement and with severe disease) and in endemic controls. The level of hyaluronan, which were increased in infected patients compared with controls (P < 0.01), was the only fibrosis marker that correlated with the ultrasonographic score (P = 0.003) and is thus a potential serum marker of schistosomiasis-associated morbidity. Urinary free pyridinoline levels were lower (P < 0.001) in infected patients with fibrosis (score > or = 1) than in nonfibrotic patients. A two-year follow-up of the patients treated with praziquantel showed that type I collagen and hyaluronan decreased during the first year post-treatment, whereas free pyridinolines peaked after 12 months and decreased thereafter.

Replacement of streptomycin by ethambutol in the intensive phase of tuberculosis treatment: no effect on compliance.

SETTING: Seven tuberculosis clinics in the National Tuberculosis Programme of Madagascar. OBJECTIVE: To compare the treatment efficacy and tolerance of regimens including either streptomycin or ethambutol for patient compliance during initial treatment of smear-positive tuberculosis. DESIGN: The 1023 patients included in the study were randomly divided into two treatment groups-one to receive streptomycin (S), isoniazid (H), rifampicin (R) and pyrazinamide (Z) (SHRZ), and the other to receive EHRZ, where streptomycin was replaced by ethambutol (E). During the 2-month intensive phase, drug delivery was completely supervised. The same 6-month continuation regimen was then given in both groups. Follow-up consisted of a clinical and bacteriological examination at the end of the second, fifth and eighth months. RESULTS: There was no significant difference between the two regimens as regards compliance with treatment, the number of patients lost or who died, or for bacteriological response during the intensive phase. EHRZ was better tolerated. During the continuation phase, the results of the two groups remained comparable, but treatment failures occurred earlier in the patients who had received streptomycin. CONCLUSION: Patient compliance was not better with streptomycin. The ethambutol-containing regimen was as efficient as the other, and better tolerated. There is no argument for preferring streptomycin in the intensive phase of treatment of smear-positive tuberculosis.

Anti-tuberculosis drug resistance in Madagascar in 1994-1995.

SETTING: A new tuberculosis control programme has been implemented in Madagascar since 1991. A survey on Mycobacterium tuberculosis resistance to the major drugs was conducted between August 1994 and December 1995. OBJECTIVE: To determine primary and acquired resistance in pulmonary tuberculosis patients in four main cities. DESIGN: Were included 401 randomly sampled new smear positive patients (36.2% of declared new patients) and 137 recurrent cases (72.9% of declared cases) from 8 centres. Drug susceptibility testing was performed on Löwenstein Jensen medium according to the proportion method. RESULTS: The male to female ratio was 1.35:1 in new patients (age range 11-74 years) and 1.98:1 in recurrent patients (age range 16-76 years). The primary resistance rate to any drug was 20% (95% Confidence Interval [CI] 16-23) and the acquired resistance rate 40% (95% CI 32-48, P < 2.10(-7). Primary resistance to one drug was 18% (95% CI 15-22), mainly attributable to streptomycin resistance (14.5%). Multidrug resistance (MDR) to isoniazid and rifampicin was 0.25% (95% CI 0-0.7) for primary resistance and 5% (95% CI 2.6-10.6) for secondary resistance. No difference was observed between sexes or ages. CONCLUSION: This survey conducted in big cities gives a very negative picture of resistance in Madagascar.

Ultrasonographical assessment of morbidity in schistosomiasis mansoni in Madagascar: a community-based study in a rural population.

Between June and November 1993, a parasitological, clinical and ultrasonographical survey was carried out in the mid west of Madagascar, among the whole population of a village where Schistosoma mansoni was endemic. S. mansoni eggs were found in the stools of 61.8% of the 544 individuals examined; the highest prevalence of infection (85.7%) was observed in the 15-19 years old age group. The most intense infections were recorded in the 10-14 years age group, in which the geometric mean egg count was 265 eggs/g of faeces and 34.3% of the individuals excreted more than 400 eggs/g. The egg count decreased steadily from the age of 15 years. Ultrasonographical examination was performed in 482 inhabitants older than 2 years: 29% of them presented definite schistosome associated liver alterations according to the proposals for staging S. mansoni infection made by the World Health Organization Cairo working group. Stage 3 was never observed in subjects under 30 years old. This is consistent with the need for a long-standing infection before serious lesions occur. A significant relationship between egg count and degree of liver alterations was found only in the 20-29 years age group.

Schistosoma haematobium infection in western Madagascar: morbidity determined by ultrasonography.

To assess the morbidity related to Schistosoma haematobium infection in western Madagascar, an ultrasonographic examination was performed of 574 inhabitants > 5 years old in a village in an old-established endemic area where no prior systematic antischistosomal treatment had been given. The overall prevalence of infection was 75.9% and the geometric mean egg count of positive individuals was 36 eggs/10 mL of urine. Recent haematuria had been experienced by 31.8% of individuals. Echographic abnormalities of the urinary tract were present in 50.5% of individuals: they were more frequent in males. Bladder wall lesions were observed in 93.1% of individuals with ultrasonographic changes, irregularities of the inner surface being the most common finding. Congestive changes were noted in 8.4% of kidneys, but we observed only 4 severe congestions. Bladder lesions and congestive changes in kidneys predominated in youth; their presence and severity were significantly correlated with egg excretion. In 12 inhabitants, grade 1 periportal fibrosis was observed, but no significant association was found with S. haematobium infection. In a control village, where the prevalence of S. haematobium infection was 7%, moderate congestion of kidneys was observed in 2% of examined inhabitants, and bladder changes in 6%, with a significant relationship with S. haematobium infection.

Reversibility of Schistosoma mansoni-associated morbidity after yearly mass praziquantel therapy: ultrasonographic assessment.

A parasitological, clinical and ultrasonographic longitudinal study was undertaken in 1993 in a focus hyperendemic for Schistosoma mansoni infection in the central highlands of Madagascar. All the inhabitants were systematically treated with praziquantel. A complete examination and treatment were repeated each year. Among the 289 villagers who underwent the complete 3 years' follow up, 65.9% excreted eggs at the initial survey and the mean egg count of infected individuals was 202 eggs/g. In 1996, the prevalence of infection was 19.3% with a mean egg count of 27 eggs/g and, among inhabitants aged > 44 years, only one was found to be infected. The proportion of individuals complaining of bloody stool decreased from 24.9% in 1993 to 8.4% in 1996. Compared to the initial clinical examination, the age-adjusted prevalence of splenomegaly was significantly lower in 1996, but remained high: 62% in the 10-14 years age group and 59% in individuals aged > 24 years. Ultrasonographic examination after 3 years of praziquantel therapy showed a marked decrease of the overall prevalence of schistosomal hepatic fibrosis, from 28% in 1993 to 10.3% in 1996. This improvement had already been achieved during the second year of follow-up for most subjects. Usually, the reversal of morbidity affected individuals classified as stage 1 at the beginning of the study. Stage 3 was not observed in the last 2 surveys. One patient's ascites disappeared during the follow-up, associated with a significant reversal of periportal fibrosis. Our results indicate that repeated praziquantel therapy can lead to improvement of liver morbidity and the prevention of the development of schistosomal hepatic fibrosis, even in an old-established hyperendemic focus.

Validity of Lot Quality Assurance Sampling to optimize falciparum malaria surveys in low-transmission areas.

To control the reappearance of malaria in the Madagascan highlands, indoor house-spraying of DDT was conducted from 1993 until 1998. Before the end of the insecticide-spraying programme, a surveillance system was set up to allow rapid identification of new malaria epidemics. When the number of suspected clinical malaria cases notified to the surveillance system exceeds a predetermined threshold, a parasitological survey is carried out in the community to confirm whether or not transmission of falciparum malaria is increasing. Owing to the low specificity of the surveillance system, this confirmation stage is essential to guide the activities of the control programme. For this purpose, Lot Quality Assurance Sampling (LQAS), which usually requires smaller sample sizes, seemed to be a valuable alternative to conventional survey methods. In parallel to a conventional study of Plasmodium falciparum prevalence carried out in 1998, we investigated the ability of LQAS to rapidly classify zones according to a predetermined prevalence level. Two prevalence thresholds (5% and 15%) were tested using various sampling plans. A plan (36, 2), meaning that at least 2 individuals found to be positive among a random sample of 36, enabled us to classify a community correctly with a sensitivity of 100% and a specificity of 94%. LQAS is an effective tool for rapid assessment of falciparum malaria prevalence when monitoring malaria transmission.

Malaria in the highlands of Madagascar after five years of indoor house spraying of DDT.

The central region of Madagascar is a vast area of highlands (altitude 700-2000 m). Malaria transmission has re-established itself here since the last epidemic of 1985-90 and has caused the deaths of 40,000 persons according to the Minister of Health. To combat the main malaria vector in the region, Anopheles funestus, annual programmes of indoor house spraying of DDT were carried out between December 1993 and January 1998 in most rural areas at altitude 1000-1500 m. A parasitological and serological study was then conducted in the highland schools to evaluate the impact of the programme and set up a database on the region. Using a cluster-sampling method 2 independent selections were conducted (one of 130 sites, the other of 40 sites). During the study, 13,462 schoolchildren were examined, 71% living in sprayed villages. Parasite prevalence among schoolchildren declined as altitude increases, from 11% at 700-900 m to 0.4% at > 1500 m. Below 1500 m, the impact of the spraying on the prevalence of the parasite was very clear (an average decrease of from 20% to 2.7% below 1000 m and of from 4.5% without spraying to 0.8% at 1000-1500 m). Geographical analysis of the data showed that the marginal regions remained the most affected by malaria (especially outside spraying zones), and persistence of 'pockets of transmission' at 1000-1500 m, essentially in areas where spraying has never been used. In 9 schools, anti-Plasmodium antibodies were sought by indirect immunofluorescence on thick smears of parasitized red blood cells. The seroprevalence ranged from 22% to 63%, which suggests that the parasite is still circulating in the region. Even though our data show that vector control continues to be very successful in the Madagascan highlands, rapid reinfection could occur and must be monitored following spraying. To this end, the Minister for Health, with the support of the Italian Co-operation, has placed the region under epidemiological surveillance since 1997. An alert system for the timely detection of the sources of epidemics and the targeting of the antivectoral campaign is also in operation. Our study suggests that this strategy should be reinforced by the spraying of DDT in the marginal zones in order to consolidate the results obtained at higher altitudes.

Fatal mass poisoning in Madagascar following ingestion of a shark (Carcharhinus leucas): clinical and epidemiological aspects and isolation of toxins.

In November 1993, 188 people were admitted to hospital after eating the meat from a single shark (Carcharhinus leucas) in Manakara, a medium-sized town on the south-east coast of Madagascar. This shark and its meat had no unusual characteristics. The attack rate was about 100%. The first clinical signs appeared within 5-10 hr after ingestion. The patients presented with neurological symptoms almost exclusively, the most prominent being a constant, severe ataxia. Gastrointestinal troubles, like diarrhoea and vomiting, were rare. The overall case mortality ratio was close to 30% among the 200 poisoned inhabitants. There were no reports of previous similar poisonings in this area, and fishermen in Manakara usually eat this kind of shark without problems. Bacteriological and chemical causes were eliminated. Two liposoluble toxins were isolated from the liver and tentatively named carchatoxin-A and -B, respectively. They were distinct from ciguatoxin in their chromatographic properties.

Validity of intradermal tuberculin testing for the screening of bovine tuberculosis in Madagascar.

A sample survey with the objective of determining the prevalence of bovine tuberculosis by means of an intradermal tuberculin test was conducted in Madagascar and it was found that the prevalence rate varied from 0-30% by veterinary district. In order to estimate the true prevalence, the validity of the test was investigated by assessing its sensitivity and specificity in two groups of animals from two different regions, which were destined for slaughter. In the first group where the probability of non-infected animals should have been the highest, sensitivity was estimated at 0.52 (n = 21) and specificity at 0.99 (n = 79). In the second group selected on the basis of apparent ill health of the animals in a high-prevalence bovine tuberculosis area, sensitivity was estimated at 0.8 (n = 10) and specificity at 1 (n = 12). The results obtained from both groups of cattle were not combined for statistical purposes because the sensitivity of the skin test seemed to fluctuate in relation to the chronicity of the disease. These fluctuations are discussed. However, since the first group of zebu cattle was more representative of the cattle population across the country as a whole, its results were retained as operational parameters for further screening.