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Spatial clustering and transmission networks of multidrug-resistant tuberculosis in Rwanda: a national retrospective genomic and spatial epidemiological study.

BACKGROUND: Approximately 96% of rifampicin resistance/multidrug-resistant tuberculosis (RR/MDR-TB) cases in Rwanda result from direct transmission rather than acquired resistance. However, the nationwide spatial distribution and transmission dynamics of RR/MDR-TB remain poorly characterised. This study aims to analyse spatial patterns of RR/MDR-TB in Rwanda and explore relationships between spatial proximity and RR/MDR-TB strains' genetic relatedness. METHODS: We conducted a retrospective analysis of 249 confirmed RR-TB cases across Rwanda from 2017 to 2024, using the known geolocations of patients' residences. Spatial and space-time clustering was assessed using Kulldorff's scan statistics. Demographic and socioeconomic determinants were evaluated using multivariable regression. For 201 cases with whole-genome sequencing data, we performed transmission analysis using a 5-SNP threshold to define recent transmission clusters and investigated spatial relationships within genetically related strains. RESULTS: Significant spatial clustering of RR/MDR-TB was identified in 21 sectors, mainly in Nyarugenge, southern Gasabo and western Kicukiro (relative risk: 10.06; p<0.001). Our multivariable analysis showed that population density is positively associated with case notification rates. Molecular analysis revealed 88.5% of cases belonged to genotype clusters defined using a 12-SNP threshold, with 73.6% forming clusters at a strict 5-SNP threshold. Spatial K-function analysis of the six major clusters revealed heterogeneous transmission patterns, characterised by both tightly clustered outbreaks and regional transmission networks that spanned administrative boundaries. Most clusters (5/6) extended beyond Kigali, indicating that transmission networks operate across administrative divides. CONCLUSION: RR/MDR-TB in Rwanda shows significant spatial clustering with transmission occurring through both localised and regional networks. Integrating genomic and spatial data reveals transmission patterns that extend beyond household contacts and administrative boundaries. These findings underscore the need to implement geographically targeted interventions that address community-level transmission to control RR/MDR-TB in Rwanda effectively.

Rwanda

Exposure of Ankole and crossbred cattle to theileriosis in Rwanda.

Susceptible Ankole (Sanga: Bos indicus/Bos taurus) and crossbred Ankole x Jersey (B. taurus) and Ankole x Sahiwal (B. indicus) cattle derived from a farm in Rwanda with no recent history of theileriosis, were infected with Theileria parva stocks from Rwanda either by feeding infected Rhipicephalus appendiculatus ticks on the ears, inoculation of tick derived stabilate or natural exposure to tick challenge. The Ankole cattle originated from local stock born and bred in East Coast fever (ECF) endemic areas of Rwanda. Disease, followed by spontaneous recovery, was observed in 49 of the 72 Ankole cattle after infection with T. parva (68%); the other 23 animals (32%) died of ECF. In contrast 21 of the 33 infected crossbred cattle (64%) died of ECF. It is concluded that the partial Theileria tolerance of the Ankole is, to a great extent, genetic. The basis of this partial tolerance seems to be their ability to limit the explosive multiplication of macroschizonts during the acute phase of the disease.

Animals

Public awareness of AIDS in Rwanda.

AIDS is a rapidly growing epidemic in Kigali, Rwanda. To understand the level of public awareness of AIDS in that city, 33 informants (15 men and 18 women) were interviewed during September, 1985. Most (66.7%) said that they first heard of the disease only within the previous eight months. About half (46.9%) could not mention one or more AIDS symptoms. Younger informants and women reported less knowledge of AIDS symptoms. While nearly everyone recognized AIDS as a stigmatized disease, most informants apparently did not know why it is stigmatized. Only about one-third of the informants (34.4%) could correctly state the mode of AIDS transmission. People who are at greatest risk for the disease, unmarried men and women, were least likely to know how it is transmitted. Half (50.0%) of those informants who responded to the question of the origins of AIDS said that it began in 'America.' While many informants are frightened by the disease, no one has yet changed their sexual behavior as a response to the epidemic. All informants agreed that more information about AIDS should be made available in Rwanda. Preventive measures against the spread of AIDS are urgently needed in central Africa.

Acquired Immunodeficiency Syndrome

Condoms and cosmology: the 'fractal' person and sexual risk in Rwanda.

While condoms are readily available in the urban centers of Rwanda, where the AIDS epidemic has ranged most intensely, researchers report that women are reluctant to have their partners use them. When asked to explain their reluctance, these women express the fear (along with other misgivings) that the condom might remain lodged in the vagina after intercourse. This behavior flies in the face of the biomedical assessment of risk. Rwandans, however, perceive risk in a manner which is consistent with their views concerning the social construction of the moral person. Of prime importance in this process is the body's perceived aptitude to engage in meaningful exchange and fertile sexuality. Moreover, these notions take root within a coherent cosmological matrix which emphasizes the socially ordered flow of fertility fluids. Only when these issues are considered in light of the concept of the 'fractal person' does the meaning of risk--as it relates to sexual behavior and AIDS in Rwanda--become clear.

Acquired Immunodeficiency Syndrome

Estimating the incubation period of paediatric AIDS in Rwanda.

OBJECTIVE: To estimate the distribution of the incubation period of paediatric AIDS in Rwanda. DESIGN: Data were collected between February 1984 and December 1990 at the Centre Hospitalier de Kigali (CHK), the capital city of Rwanda, Central Africa. PATIENTS: We used a sample of 685 AIDS cases registered consecutively in the Department of Paediatrics of the CHK, in which the proportion of perinatally acquired HIV-1 infection was estimated to be 98.6%. METHODS: We performed both non-parametric and parametric analyses. The methods of estimation were adapted to truncated data, using essentially the same methods as Auger et al. in their analysis of data from the New York City and the New York State AIDS case registries in 1988. RESULTS: We found that a double Weibull model fitted the data very well and that the risk of developing AIDS was high for subjects under 18 months of age, but lower for older subjects. CONCLUSIONS: Our results were qualitatively similar to those of Auger et al.. There were quantitative differences between the two studies, but it was not possible to compare median survival periods. Parameters such as median or mean survival times cannot be validly estimated using only data from registers because these data exclude infected subjects who have not yet developed AIDS.

Acquired Immunodeficiency Syndrome

Characterization, in vitro susceptibility, and clinical significance of CDC group HB-5 from Rwanda.

From June 1984 until July 1988, CDC group HB-5 isolates were recovered from the exudates of genital ulcers in 25 of 675 (3.6%) patients (204 women, 471 men) in Kigali, Rwanda. Among a group of 145 men presenting with urethritis but without genital ulcers, a positive culture for HB-5 of a specimen from the coronal groove of the penis of only 1 man (0.7%) was found. During the same period, the organism was not obtained in cultures of vaginal specimens from 838 women without genital ulcer disease. The main biochemical characteristics of the isolated microorganisms included weak oxidase positivity, catalase negativity, indole positivity, reduction of nitrate to nitrite, acid production from D-glucose and fructose, and H2S production. A total of 75% of the organisms were susceptible to penicillin G. beta-Lactamase production was detected by the chromogenic cephalosporin test in a quarter of the strains. This study confirms that HB-5 can be found in the genital tract. HB-5 was associated with genital ulcer disease in Rwanda. However, its etiologic role in patients with this condition remains unclear.

Drug Resistance, Microbial

Strategies for mitigating emerging artemisinin-based antimalarial drug resistance in Rwanda: a promising approach for managing therapies in malaria-endemic countries.

Malaria treatment failures associated with reduced efficacy of chloroquine (CQ) and amodiaquine (AQ) antimalarial drugs emerged in Rwanda during the 1980s, prompting the policy shift towards adopting artemisinin-based combination therapies in 2006 as an alternative. However, recent findings from malaria surveillance and therapeutic efficacy studies have revealed a countrywide increase in antimalarial drug resistance. Particularly, artemether-lumefantrine (AL) efficacy has significantly decreased, probably due to the emergence of Plasmodium falciparum (Pf) genomic mutations. To mitigate the current drug resistance, Rwanda has adopted targeted multiple first-line therapies. Through the national malaria control program, antimalarial drugs were deployed in accordance with the reported resistance profile. A significant rise in Pfkelch13 mutations, particularly A675V associated with AL resistance, was mainly reported in the western region; therefore, artesunate-pyronaridine was recommended. Dihydroartemisinin-piperaquine was considered in eastern and central regions, where R561H mutations were predominant. On the contrary, AL was maintained in the southern region, where the prevalence of the R561H mutation was low. Insights from this data-driven model will inform its extension to other malaria-endemic countries facing emerging Pf genetic diversity.

Antimalarials

[Seroepidemiology of toxoplasmosis in 2 communities of Rwanda (Central Africa)].

We collected dry blood specimens from two rural areas in Rwanda, that were tested for antibodies to Toxoplasma gondii through the Direct Agglutination technique. 50% of the adults in both communities had antibodies to T. gondii. The Ngenda (NGD) population apparently acquired antibodies at a later stage of its life (only 12% were positive at 14 years of age). The Nyarutovu (NVU) population already showed a 31% positivity at the same age. We would like to point out the pathogenic role played by toxoplasmosis during pregnancy and the need of new studies about the epidemiology of the disease as well as the transmission mechanism in Rwanda.

Adolescent

Human immunodeficiency virus infection in urban Rwanda. Demographic and behavioral correlates in a representative sample of childbearing women.

OBJECTIVE: --To determine behavioral and demographic risk factors for human immunodeficiency virus (HIV) infection in central Africa. DESIGN: --Cross-sectional survey. SETTING: --Kigali, Rwanda. PARTICIPANTS: --A representative sample of 1458 childbearing women aged 19 to 37 years who were recruited from outpatient prenatal and pediatric clinics at the only community hospital in the city. MAIN OUTCOME MEASURE: --Antibodies to HIV assessed by enzyme immunoassay and confirmed by Western blot or indirect immunofluorescence. RESULTS: --The HIV seroprevalence was 32% overall. Infection rates were higher in women who were single, in those in steady relationships that began after 1981, and in the 33% of women reporting more than one lifetime sexual partner. Women in legal marriages or monogamous partnerships had lower rates of infection, but even low-risk women had prevalences on the order of 20%. History of venereal disease in the past 5 years, although the strongest risk factor in a multiple logistic analysis (odds ratio, 2.7; 95% confidence interval, 2.0 to 3.7), was reported by only 30% of those infected. Having a male sexual partner who drank alcohol or who had higher income were significant risk factors for HIV infection in the multivariate analysis, but use of oral contraceptives and having an uncircumcised partner were not. CONCLUSIONS: --The epidemic of the acquired immunodeficiency syndrome in Rwanda has spread beyond high-risk groups to the general population of women without known risk factors. For most of these women, a steady male partner is the source of their HIV risk and therefore a vital target for intervention efforts.

Adult

BCG vaccination and pediatric HIV infection--Rwanda, 1988-1990.

In Africa, tuberculosis (TB) is one of the most common severe diseases associated with human immunodeficiency virus (HIV) infection. For infants in Rwanda and other countries where the risk for TB infection is high, the World Health Organization (WHO) recommends vaccination against TB at birth with bacille Calmette-Guérin (BCG) vaccine (1). This report summarizes a study of the occurrence of immune responses and adverse reactions following BCG vaccination among a cohort of infants born to HIV-seropositive and HIV-seronegative mothers in Kigali, Rwanda, where the prevalence of HIV infection among women of childbearing age is approximately 30% (2).

Female

HIV antibodies in a remote rural area in Rwanda, Central Africa: an analysis of potential risk factors for HIV seropositivity.

Detection of HIV antibodies by means of an immunoenzymatic assay, an indirect immunofluorescence technique and Western blot was attempted on 375 serum samples collected in the Murunda area, a remote rural area situated in Rwanda, central Africa. Two out of 147 (1.4%) adults from a strict rural area, five out of 59 (8.5%) adults from an adjacent market place, and 49 out of 169 (30%) STD clinic attenders from the same area were HIV seropositive. In the first two groups, HIV seropositivity was associated with a history of sexually transmitted disease (STD) in the previous 2 years (P less than 0.001) and with a history of travel to a Rwandese urban centre in the previous 5 years (P less than 0.05). This study suggests that HIV seroprevalence is low in rural central Africa compared with urban centres. Risk factors for HIV seropositivity are similar in rural and urban-based adults in Rwanda, i.e. heterosexual promiscuity and STDs. Many HIV seropositive rural subjects from this study are likely to have acquired HIV infection through sexual contacts in Rwandese cities.

Acquired Immunodeficiency Syndrome

[3-year study of shigellosis epidemic in Rwanda, Central Africa. Problems of public health and bacteriological aspects].

Since 1979, the Lakes region (Kivu in Zaïre, Western Uganda, Rwanda, Burundi) has been stricken by a bacillary dysentery epidemic at S. dysenteriae type 1. Supposed to be extinct since the 1950s., this bacillus has revealed a very noticeable virulence as well by the number of registered cases (524/100.000 in 1983 at Ruhengeri-Rwanda) as its fast break through. Demographic density (from 400 to 600/km2) has played an important role and has facilitated the transition toward epidemicity. Systematic bacteriological exams on the spot has allowed prompt identification of the involved germ, antibiotics to be used, and resistance variations during the period under consideration. The role of a regional laboratory to monitor diarrheal diseases has been demonstrated as of prime importance to set up a fighting strategy at regional level.

Anti-Bacterial Agents

Nutrition studies of Ugandan refugees in Sudan and Rwanda. A report on surveys using the mid-upper arm circumference method.

Nutritional surveys were undertaken in refugee camps in southern Sudan and Rwanda. Nutrition status was assessed using the mid-upper arm circumference method. A high level of malnutrition was found in the main transit camp for refugees from Uganda into southern Sudan. Nutrition status in refugee settlements was adequate in the Rwanda camps, where refugees had only been displaced for a short period of time; there was only a limited degree of malnutrition. The findings correlate with the time period of displacement of the refugees.

Arm

Safety and immunogenicity of high-dose Edmonston-Zagreb measles vaccine in children with HIV-1 infection. A cohort study in Kigali, Rwanda.

OBJECTIVE: To compare the reactogenicity and immunogenicity of high-dose Edmonston-Zagreb (EZ) measles vaccine in children with and without human immunodeficiency virus, type 1 (HIV-1), infection. DESIGN: Prospective cohort study. SETTING: General pediatric clinic and home visits in Kigali, the capital of Rwanda. PARTICIPANTS: Infants born to HIV-1-seropositive and -seronegative mothers were vaccinated with a 10(5.0) 50% tissue culture infective dose of EZ measles vaccine at 6 months of age. Control visits were made 10 and 14 days later to monitor local and general reactions. Measles serum antibodies were measured by an enzyme-linked immunosorbent assay technique at birth and at 6 and 9 months of age. Three groups were compared: infected children (n = 43), uninfected children born to seropositive mothers (n = 135), and uninfected children born to seronegative mothers (n = 194). RESULTS: Three hundred twenty-three children (86.8%) were available for the reactogenicity study. No statistically significant difference between the three groups was found in the occurrence of minor adverse reactions. No severe adverse reaction was observed. One hundred ninety children (51.1%) were available for the immunogenicity study. The percentage of infants negative for measles antibody at 6 months was significantly higher (P = .021) in HIV-infected children (85%) and in uninfected children born to seropositive mothers (90%) than in uninfected children born to seronegative mothers (75%). The overall seroconversion rate at 9 months was 90% (95% confidence interval, 85.7% to 94.3%), without any statistically significant difference between the three groups. CONCLUSION: High-dose EZ vaccine administered at 6 months of age is safe and highly immunogenic in both HIV-infected and uninfected children.

Antibodies, Viral

Metastatic focal infections due to multiresistant Salmonella typhimurium in children: a 34 month experience in Rwanda.

Nineteen out of 139 children with severe systemic disease due to multiresistant Salmonella typhimurium observed during a 34-month period in an in-patient department in Rwanda had focal metastatic infections. More than 80% of the invasive Salmonella infections were acquired in the hospital. Focal metastatic infections occurred after longer hospital stays than bacteremia (29.1 +/- 17.4 days as against 13.5 +/- 9.0 days, p less than 0.01) and were diagnosed more time after the first sign of infection (3.28 +/- 1.41 days as against 1.86 +/- 1.10 days, p less than 0.01). Bacteremia was documented in 13 of the 17 children with focal infection from whom blood cultures were obtained. Seven of 12 had positive stool cultures. The sites of metastatic focal infection were meninges (7 cases), soft tissue (5 cases), joint or bone (4 cases), pleura (2 cases), eye (1 case). The clinical course of meningitis was fulminant and 6/7 patients died before receiving adequate antimicrobial therapy. One child with meningitis and 9 patients with focal infections at other sites were treated with cefotaxime and were cured or improved.

Child

Composition of the essential oil of Ocimum canum grown in Rwanda.

The essential oil from leaves and flowers of Ocimum canum Sims, growing wild in Rwanda, was investigated by LSC, GLC and GC-MS. All samples were characterized by a high content of linalool (60-90%). Neither camphor nor citral and methyl cinnamate, compounds reported to be characteristic for different types of O. canum, could be detected. All monoterpene hydrocarbons were present in minor amounts (less than 1.5%). The oil samples with the lowest linalool content consisted of relatively large amounts of sesquiterpene hydrocarbons such as bergamotene (about 10%) and beta-caryophyllene (about 5%). Oct-1-en-3-ol and 3-octanol were the only oxygen-containing components, besides linalool, that amounted to more than 1% in most of the oil samples.

Chemical Phenomena

Productivity of the small East African goat and its crosses with the Anglo-Nubian and the Alpine in Rwanda.

Data from a research station in the central African country of Rwanda relating to purebred Small East African (SEA) goats, Anglo-Nubian x SEA and Alpine x SEA goats were analysed. Both SEA (598 days) and Alpine crosses (557 days) were younger at first kidding than the Anglo-Nubian crosses (766 days). There were no differences among genotypes in kidding interval which averaged 343 days nor did they differ in litter size (1.75). Mortality to 150 days (17.8%) was significantly higher in the Anglo-Nubian crosses than in Alpine crosses with the SEA being intermediate and not differing from either. Birth weights of individual kids were significantly lighter for purebred SEA (2.35 kg) than for Anglo-Nubians (2.68 kg) which were significantly lighter than the Alpine crosses (2.89 kg). Total litter weight at 150 days was significantly lower for SEA (14.5 kg) than for Alpine (18.8 kg), the Anglo-Nubian (16.9 kg) not differing significantly from either. Female postpartum weights differed significantly among genotypes, SEA being lightest (37.5 kg), Alpine crosses (42.1 kg) intermediate and Anglo-Nubian crosses (51.4 kg) heaviest. Productivity indices (total weight of live young at 150 days per kg of dam per year) averaged 442 g and did not differ among genotypes.

Age Factors