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Crimean-Congo haemorrhagic fever.

Crimean-Congo haemorrhagic fever (CCHF) is an often fatal viral infection described in about 30 countries, and it has the most extensive geographic distribution of the medically important tickborne viral diseases, closely approximating the known global distribution of Hyalomma spp ticks. Human beings become infected through tick bites, by crushing infected ticks, after contact with a patient with CCHF during the acute phase of infection, or by contact with blood or tissues from viraemic livestock. Clinical features commonly show a dramatic progression characterised by haemorrhage, myalgia, and fever. The levels of liver enzymes, creatinine phosphokinase, and lactate dehydrogenase are raised, and bleeding markers are prolonged. Infection of the endothelium has a major pathogenic role. Besides direct infection of the endothelium, indirect damage by viral factors or virus-mediated host-derived soluble factors that cause endothelial activations and dysfunction are thought to occur. In diagnosis, enzyme-linked immunoassay and real-time reverse transcriptase PCR are used. Early diagnosis is critical for patient therapy and prevention of potential nosocomial infections. Supportive therapy is the most essential part of case management. Recent studies suggest that ribavirin is effective against CCHF, although definitive studies are not available. Health-care workers have a serious risk of infection, particularly during care of patients with haemorrhages from the nose, mouth, gums, vagina, and injection sites. Simple barrier precautions have been reported to be effective.

Africa↗

Research and product development for Crimean-Congo haemorrhagic fever: priorities for 2024-30.

Crimean-Congo haemorrhagic fever (CCHF) is a widely distributed and potentially fatal tick-borne viral disease with no licensed specific treatments or vaccines. In 2019, WHO published an advanced draft of a research and development roadmap for CCHF that prioritised the development and deployment of the medical countermeasures most needed by CCHF-affected countries. This Personal View presents updated CCHF research and development priorities and is the product of broad consultation with a working group of 20 leading experts in 2023-24. The strategic goals, milestones, and timelines have been revised and expanded to reflect scientific advances since 2019, including the identification of antibodies with therapeutic potential and the progression of four vaccine candidates through phase 1 clinical trials. This update emphasises the need for a One Health approach to manage CCHF, from integrated cross-sectoral surveillance to novel interventions that target ticks and their vertebrate hosts to reduce CCHF virus transmission to humans. The overarching vision for rapid diagnostics and specific therapeutics by 2028, followed by options to limit CCHF virus transmission and control disease by 2030, is deliberately ambitious and will only be achieved through coordinated international action from affected countries, funders, scientists, product developers, manufacturers, regulators, national authorities, and policy makers.

Hemorrhagic Fever, Crimean↗

Determination of sodium 3,4-diaminonaphthalene-1-sulfonate, a Congo Red derivative, in plasma and brain of hamsters by high-performance liquid chromatography after solid-phase extraction and ultraviolet absorbance.

In the search for compounds with similar or greater activity than Congo Red (CR) in protecting normal prion protein from being converted into the pathological form, we have synthesized various compounds which derive from CR. One of these is the sodium 3,4-diaminonaphthalene-1-sulfonate (RCA) which has an activity similar to CR in preliminary experiments. This study describes a method to determine RCA in plasma and in brain tissue by high-performance liquid chromatography (HPLC), using a solid-phase extraction and UV detection. RCA is an amphoteric molecule difficult to separate from biological matrices. Extraction was achieved by solid-phase extraction (ENV+ columns) together with the use of a counter ion. The resulting solid-phase extraction is efficient and rapid. RCA was separated on a Symmetry C18 250 x 4.6 mm I.D. 5 lm column at 1 ml/min using a 50 mM NaSO4 in 5 mM tetra-n-butylammoniumiodide (TEBA) in water-methanol (82:18, v/v) mobile phase. Retention times of RCA and I.S. were 21 and 24 min. The UV detector was set at 210 nm. The limit of quantitation was 0.5 microg/ml. The method has intra-assay and inter-assay accuracies higher than 95%, coefficients of variation ranging between 2.8 and 8.6%, and recovery rates between 74.3 and 80.1% in plasma and in brain tissue. A linear response to quantities of RCA from 0.5 to 100 microg/ml or 10 microg/g in plasma or brain was obtained. The present method allows the study of the pharmacokinetics of RCA in plasma after i.p. administration, and the distribution of the compound into the brain at the peak time.

Animals↗

Viraemic transmission of Crimean-Congo haemorrhagic fever virus to ticks.

In order to determine the way in which vertebrates infected with Crimean-Congo haemorrhagic fever (CCHF) virus and potential ixodid tick vectors interact in nature, immature and adult ticks of several species were fed on viraemic mammals and then assayed for virus content at varying times after feeding. CCHF virus was not isolated from ticks of six species tested after feeding as adults and immature forms on sheep with viraemia of 10(2.5-3.2) LD 50/ml, nor from larval ticks fed on guinea-pigs and white-tailed rats with viraemia of 10(1.9-2.7) LD 50/ml. In contrast, virus was isolated from 10 of 152 pools of engorged adult ticks of 5 species that fed on cattle with viraemia of 10(1.5-2.7) LD 50/ml and from 3 of 137 female ticks after oviposition. Infection was transmitted to larval and nymphal Hyalomma truncatum and H. marginatum rufipes, but not to Rhipicephalus evertsi evertsi, from a scrub hare with viraemia of 10(4.2) LD 50/ml but only nymphal H. truncatum and H. m. rufipes became infected from scrub hares with viraemia of 10(2.6-2.7) LD 50/ml. Infection was transmitted trans-stadially in H. m. rufipes and H. truncatum infected as nymphae, and adult H. m. rufipes transmitted infection to a sheep. No evidence of transovarial transmission was found in larval progeny of ticks exposed to CCHF virus as adults on sheep and cattle or as immatures on scrub hares.

Animals↗

Enzyme-linked immunosorbent assays for the detection of antibody to Crimean-Congo haemorrhagic fever virus in the sera of livestock and wild vertebrates.

IgM antibody response to Crimean-Congo haemorrhagic fever (CCHF) virus was monitored in experimentally infected sheep and cattle by an IgM capture enzyme-linked immunoassay (ELISA). Specific binding of antigen was detected by a rabbit anti-CCHF horseradish peroxidase conjugate or a sandwich technique with hyperimmune mouse anti-CCHF ascitic fluid and commercially available anti-mouse immunoglobulin peroxidase conjugate. The persistence of IgM antibody activity was found to be of shorter duration than in humans, and this may be a function of the relative lack of susceptibility of these animals to infection with CCHF virus. IgG antibody responses in the sheep could be monitored by sandwich ELISA using commercially available anti-sheep immunoglobulin peroxidase conjugates. Total antibody activity in the sera of experimentally infected sheep, cattle and small mammals could be monitored in a competitive ELISA (CELISA) using rabbit anti-CCHF peroxidase conjugate. The CELISA was applied to the sera of 960 wild vertebrates from a nature reserve in South Africa, and the prevalence of antibody was found to be greatest in large mammals such as rhinoceros, giraffe and buffalo, which are known to be the preferred hosts of the adult tick (Hyalomma) vectors of the virus.

Animals↗

Serodiagnosis of Crimean-Congo haemorrhagic fever.

Several methods for demonstrating antibody to Crimean-Congo haemorrhagic fever virus were compared on serum samples taken from 101 patients during the acute stage of illness and at intervals for up to 59 months thereafter, with emphasis on early detection of the immune response. The deaths of 23 patients on days 5-14 of illness were ascribed to the effects of the disease; two patients died later from other causes. Very few of the patients who died from the acute illness mounted an antibody response detectable by the methods tested. Four patients who died and 18 who recovered were treated with immune plasma collected from recovered patients. Treated patients acquired IgG antibody from the plasma, but it was possible to discern the onset of an endogenous IgM response in those individuals who survived the disease by all of the methods tested. Indirect immunofluorescence (IF) tests detected IgM and/or IgG antibodies at the earliest on day 4 of illness in about 10% of patients who survived the disease, and by day 9 all survivors had antibodies demonstrable by IF. A biotin-streptavidin IF technique offered no advantage over the standard IF test for the early detection of IgG antibody, but demonstrated higher antibody titres and detected IgM antibody earlier in about a quarter of the patients tested. An IgM-capture enzyme-linked immunoassay (ELISA) and an IgG sandwich ELISA demonstrated higher antibody titres than did IF tests, and detected antibody responses at an earlier stage of infection than did IF tests in about one-fifth of patients, but the reverse was true in a similar proportion of instances. A competition ELISA, which detected total antibody activity, produced lower titres than did the IgM and IgG ELISAs, but yielded results which were in close agreement with the findings in IF tests. It was concluded that the IF tests were most convenient for use in making a rapid serodiagnosis of the disease.

Antibodies, Viral↗

Molecular epidemiology of African and Asian Crimean-Congo haemorrhagic fever isolates.

Phylogenetic relationships were examined for 70 Crimean-Congo haemorrhagic fever (CCHF) isolates from southern, central and West Africa, the Middle East and Greece using sequence data determined for a region of the S segment of the genome. Analysis revealed up to 18% genetic differences. Tree topology supports previous evidence for the existence of three groups of genetically related isolates, A, B and C. Within group A there are two clades: an African clade and a predominantly Asian clade comprising isolates from Pakistan, China, Iran, Russia and Madagascar. Group B includes isolates from southern and West Africa and Iran, and group C includes a single isolate from Greece. Despite the potential which exists for dispersal of the virus between Africa and Eurasia, it appears that circulation of the virus is largely compartmentalized within the two land masses, and the inference is that the geographic distribution of phylogenetic groups is related to the distribution and dispersal of tick vectors of the virus.

Animals↗

Experimental infection of ostriches with Crimean-Congo haemorrhagic fever virus.

Following the occurrence of an outbreak of Crimean-Congo haemorrhagic fever (CCHF) among workers at an ostrich abattoir in South Africa in 1996, 9 susceptible young ostriches were infected subcutaneously with the virus in order to study the nature of the infection which they undergo. The ostriches developed viraemia which was demonstrable on days 1-4 following infection, with a maximum intensity of 4.0 log10 mouse intracerebral LD50/ml being recorded on day 2 in 1 of the birds. Virus was detectable in visceral organs such as spleen, liver and kidney up to day 5 post-inoculation, 1 day after it could no longer be found in blood. No infective virus was detected in samples of muscle, but viral nucleic acid was detected by reverse transcription-polymerase chain reaction in muscle from a bird sacrificed on day 3 following infection. It was concluded that the occurrence of infection in ostriches at abattoirs could be prevented by keeping the birds free of ticks for 14 days before slaughter.

Abattoirs↗

Synthesis of analogues of Congo red and evaluation of their anti-prion activity.

No cure as of yet exists for any of the transmissible spongiform encephalopathies. In this paper, we describe the synthesis of analogues of Congo red and evaluation against a cellular model of infection, the SMB (scrapie mouse brain) persistently infected cell line, for their ability to inhibit the infectivity of the abnormal form of prion protein (PrP-res). The compounds have also been tested for their ability to inhibit the polymerization of PrPC by PrP-res. A number of analogues showed inhibition of PrP-res infectivity at nanomolar concentrations. Several analogues show promise; the most active compound, 2a, inhibits the formation of PrP-res in SMB cells with an EC50 of 25-50 nM.

Animals↗

Deciphering the etiology of the 2024 outbreak of undiagnosed febrile illness in Panzi, Democratic Republic of the Congo.

In late 2024, an outbreak of over 400 cases of undiagnosed febrile illness, predominantly presenting as fever and cough, was reported in Panzi Health Zone, southwestern Democratic Republic of the Congo. Here we conducted an epidemiological and laboratory investigation to determine the etiology of the outbreak. Clinical data and specimens were prospectively collected from 108 individuals, of whom 59/108 (54.6%) were female. Children aged <5&#x2009;years were the most affected (47/108, 43.5%); 14/32 (43.7%) were malnourished. Oro/nasopharyngeal swabs from 96/108 individuals were PCR tested; 26 blood samples were sequenced. Plasmodium falciparum was detected in 56/108 (51.8%) individuals. Co-infections were also detected, with influenza A(H1N1)pdm09 virus in 16/56 (28.6%) and severe acute respiratory syndrome coronavirus 2 in 10/56 (17.9%) individuals. No novel pathogens were detected via metagenomics. Our findings suggest that the outbreak was primarily associated with a surge in malaria cases, with concurrent viral respiratory infections. Increasing decentralized laboratory capacity and strengthening broader health systems remain crucial for faster outbreak detection and investigation.

Disease Outbreaks↗

Dietary composition and ovarian function among Lese horticulturalist women of the Ituri Forest, Democratic Republic of Congo.

OBJECTIVE: To assess dietary composition in relation to energetic status and ovarian function. DESIGN: An eight-month prospective study undertaken in 1989. SETTING: Ituri Forest, northeast Democratic Republic of Congo. SUBJECTS: Sixty-four female volunteers of reproductive age (16-45), with a subsample of 30 for nutritional focal follows, 39 for analysis of salivary progesterone levels, and 18 for analysis of salivary oestradiol. INTERVENTIONS: Regular anthropometric measurements of heights, weights, and mid-triceps skinfolds, 204 h of nutritional focal follows when all foods prepared and consumed were recorded and weighed, analysis of dietary composition using African food tables, collection of saliva samples every-other day for radioimmunoassay of salivary oestradiol and progesterone. RESULTS: The primary staple in the Lese diet is manioc, consumed at nearly every meal, but the diet is subject to seasonal fluctuations. Important seasonal crops are groundnuts and rice. Carbohydrates comprise 64% of the diet, protein 14% and fat 22%, but seasonal fluctuations in food items create significant differences in protein content (P = 0.007). Energy intake falls by 25% in the hunger season. Lese energy balance reflects this lack with women losing a mean 7% of total body weight. The mean BMI for Lese women at the beginning of the study was 22.8 but, during the hunger season, the BMI for 20% of women fell to < 18.5, indicative of chronic energy shortage. Mean levels of Lese salivary oestradiol and progesterone are chronically and significantly lower than healthy, Western controls (P = 0.0001 for progesterone; P = 0.03 for follicular values of oestradiol, P = 0.0001 for mid-cycle values, and P = 0.0002 for luteal values). Mean salivary progesterone levels were significantly lower for those Lese women losing weight (P = 0.03), and significantly lower for weight-loss women when comparing levels at the beginning and end of the hunger season (P = 0.03). DISCUSSION: The relatively low-fat, high-fibre diet of the Lese appears healthy, but there are occasional seasonal deficiencies in protein-energy and micronutrient content, especially for pregnant and lactating women. Dietary composition may affect Lese levels of reproductive steroids, partly explaining the chronically low salivary oestradiol profile of this population.

Adolescent↗

Sexual isolation of genetically differentiated sympatric populations of Drosophila melanogaster in Brazzaville, Congo: the first step towards speciation?

Two sympatric populations of Drosophila melanogaster were collected in the Brazzaville area in Congo, one from the suburban countryside and the other from a brewery located in the city. They were compared for several genetically determined traits including morphology, allozymes, microsatellites, cuticular hydrocarbons, and sexual behaviour. The two populations were similar to other African populations for morphological traits, but differed significantly from each other for all other characters. The countryside population resembled other African populations, whereas the urban population was consistently similar to European populations. Mating choice experiments showed incipient reproductive separation between the populations. In agreement with the hypothesis that D. melanogaster originated in Africa and spread to the rest of the world by invading human-modified habitats, we suggest that man-adapted fruit fly populations have returned 'back to Africa', and remained partially isolated from older native stocks.

Animals↗

Polarization confocal microscopy and congo red fluorescence: a simple and rapid method to determine the mean cellulose fibril orientation in plants.

The mean or net preferential orientation of cellulose fibrils in plant cell walls is detected with polarization confocal laser scanning microscopy using the fluorescence dichroism of Congo Red. Single cells, arrays of cells in a tissue, or the epidermis of whole organs can be assayed in vivo. Aerial parts require an extra pectinase treatment because of the cuticle, which is impermeable to aqueous solutions. Peeling off the epidermis can be an elegant alternative, especially for leaves. With this method the net preferential fibril orientation can be related to the symmetry axis of the cell in quantitative terms. Data issuing from this approach are useful in current research on plant biomechanics.

Cell Wall↗

Voluntary health insurance in Bwamanda, Democratic Republic of Congo. An exploration of its meanings to the community.

An insurance scheme covering hospital care in the rural district of Bwamanda in the North-west of the Democratic Republic of Congo, which locally is called the mutuelle, was conceived and developed in 1986 on the initiative of Belgian doctors working in the district under the arrangements for bilateral Belgian aid. After more than 10 years of operation the Bwamanda scheme has achieved a high rate of coverage, contributed to a significant improvement in access to hospital-based in-patient care, and constitutes a stable source of revenue for the operation of the hospital. We present an investigation conducted through focus groups in 1996 of the population's social perceptions of this risk-sharing scheme to identify ways to improve it. The findings pertain to the reasons for people to subscribe to the scheme; to the perception of its redistribution effects; to people's frustrations and questions; and finally to the relationships between the insurance scheme and traditional mutual aid arrangements. The difference between a hospital insurance scheme (a logic of contract) and the traditional systems of mutual aid (a logic of alliance) is highlighted, and the impact of the hospital insurance scheme on social inequalities is discussed. The implications of this study on the management of the Bwamanda health insurance scheme are reviewed, and this study may be useful to health managers working in similar contexts.

Democratic Republic of the Congo↗

Survey among survivors of the 1995 Ebola epidemic in Kikwit, Democratic Republic of Congo: their feelings and experiences.

This study describes experiences of the survivors of the 1995 Ebola epidemic in Kikwit, Democratic Republic of Congo. Most of the survivors in our sample had cared for a sick family member before becoming ill themselves, and most had never heard of Ebola before they developed symptoms and therefore did not suspect that they were infected by the virus. Fear, denial and shame were their principal initial feelings. After release from hospital, survivors were abandoned by family or friends more often than they had expected. Belief in god was an important aid to all of them. Their most negative experiences were witnessing other people dying in the isolation ward of the Kikwit General Hospital, and the reluctance of hospital personnel to treat them. During Ebola outbreaks more attention should be given to the psychosocial implications of such an epidemic. Information campaigns should include antidiscrimination messages and more psychosocial support should be given to patients and their families.

Democratic Republic of the Congo↗

Crimean-congo haemorrhagic fever: a seroepidemiological and tick survey in the Sultanate of Oman.

In 1995 and 1996, 4 persons from the Sultanate of Oman were confirmed with clinical Crimean-Congo haemorrhagic fever (CCHF). To assess the prevalence of CCHF virus infection in Oman, a convenience sample of imported and domestic animals from farms, abattoirs and livestock markets was examined by enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G (IgG) antibodies to CCHF virus. Ticks were collected from selected animals, identified, pooled by species, host and location and tested for evidence of infection with CCHF virus by antigen-capture ELISA. Serum samples from individuals working in animal and nonanimal contact-related jobs were also tested for CCHF antibodies. Serological evidence of infection was noted in 108 (22%) of 489 animals. Most of the ticks collected (618 of 912) from all species of sampled livestock were Hyalomma anatolicum anatolicum, a competent vector and reservoir of CCHF virus. 243 tick pools were tested for CCHF antigen, and 19 pools were positive. Of the individuals working in animal contact-related jobs, 73 (30.3%) of 241 non-Omani citizens and only 1 (2.4%) of 41 Omani citizens were CCHF antibody-positive. Butchers were more likely to have CCHF antibody than persons in other job categories. The presence of clinical disease and the serological results for animals and humans and infected Hyalomma ticks provide ample evidence of the presence of CCHF virus in yet another country in the Arabian Peninsula.

Adolescent↗

Pregnancy and HIV-1 incidence in 178 married couples with discordant HIV-1 serostatus: additional experience at an HIV-1 counselling centre in the Democratic Republic of the Congo.

To determine the effect of an HIV-1 counselling programme on rates of HIV-1 infection and pregnancy in a large group of married couples in Kinshasa, DRC with discordant HIV-1 infection status, we conducted a baseline cross-sectional HIV-1 seroprevalence study in two large Kinshasa businesses. We identified 178 married couples (mean duration of marriage = 12.3 years) with discordant HIV-1 serostatus (92 M+F-/86 M-F+). Seroincidence and pregnancy rates were observed during 310 person-years of follow-up (PYFU). The 92 M+F- couples had an HIV-1 incidence of 3.7/100 PYFU and a pregnancy rate of 8.6/100. The 86 M-F+ couples had a pregnancy rate of 6.8/100 PYFU and an HIV-1 incidence of 6.8/100 PYFU. Couples seeking to have children but minimize their HIV-1 transmission risk frequently had unprotected sex only during the woman's perceived monthly fertility period. This strategy resulted in the birth of 24 live-born children and only one (4%; 95% CL = 0.0-21.6%) new HIV infection in couples having a child. Only 1 of 6 women who developed HIV-1 infection (16. 7%; 95 C.L. = 0-40.4%) became pregnant. While seronegative men had more extramarital sex once their wives' positive HIV-1 infection status became known, most of these episodes involved safe sex. Divorce was rare. This study provides additional information concerning issues of safe sex in married couples with discordant HIV-1 infection status, the dynamics of HIV transmission within couples and the effect of serostatus notification on the marriage and on intramarital and extramarital sexual behaviour in Kinshasa, Congo.

Adult↗

[The behavioral determinants for health centers in health districts of urban Africa: results of a survey of households in Kinshasa, Congo].

This study analyses the choice determinants of the population for health centres through a survey of the behaviour of families in a representative sample of 1,000 households in the health districts of Kinshasa, Congo in 1997. For the most recent episode of illness, the respondents turned to seven types of care: the health centre (37%), private dispensaries (26.5%), self-medication through a pharmacy (23.9%), traditional practitioner (21%), traditional self-medication (16.9%), private outpatients' clinic (16.7%) and a reference hospital (10.4%). Past logistics have shown that patients resort to a health centre rather than another type of care structure (P = 0.05) when looking for quality care, reasonable prices and the availability of varied services. On the other hand, concern about the geographical proximity in relation to the family's residence calls for using the private dispensary. When looking for a doctor or the existence of a 'convention', families are more inclined to choose a private officially recognized outpatients' clinic. Those who had been looking for a solution to a special type of illness opted primarily for a traditional practitioner. In conclusion, the results of this study show that if people choose the care offered by health centres, it is because they judge it to be of good quality. The integrated care offered by the same technician, with a required training, is a major asset in the acceptability of the first line of primary health care in Kinshasa. This study suggests that it would no doubt be beneficial to integrate non-official private care structures into the primary health care system, as far as it is possible for them to achieve a level of quality comparable to that of the health centres. In order that the traditional practitioner might play an important complementary role in the realization of primary health care, even in urban areas, the possibility of promoting sites of communication should be studied. Moreover, considering the weak buying power of the city's inhabitants and the previous existence of tontines out of solidarity, the 'conventions' providing relief of health care costs, under the leadership of the local communities, should be integrated into the organization of the urban health system.

Adult↗