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The seventh cholera pandemic has heavily affected Africa, although the origin and continental spread of the disease remain undefined. We used genomic data from 1070 Vibrio cholerae O1 isolates, across 45 African countries and over a 49-year period, to show that past epidemics were attributable to a single expanded lineage. This lineage was introduced at least 11 times since 1970, into two main regions, West Africa and East/Southern Africa, causing epidemics that lasted up to 28 years. The last five introductions into Africa, all from Asia, involved multidrug-resistant sublineages that replaced antibiotic-susceptible sublineages after 2000. This phylogenetic framework describes the periodicity of lineage introduction and the stable routes of cholera spread, which should inform the rational design of control measures for cholera in Africa., (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

In 1993, after 6 years of absence, cholera re-emerged in the Horn of Africa. Following its introduction to Djibouti, the disease spread to the central and southern areas of Ethiopia reaching Somalia in 1994. Cholera outbreaks persisted in Ethiopia with a recrudescence of cases in 1998. Twenty-two Vibrio cholerae O1 strains, selected to represent the 1998 history of cholera in Ethiopia, were characterized by random amplified polymorphic DNA patterns, BglI ribotyping and antimicrobial susceptibility. All isolates showed a unique amplified DNA pattern and a prevalent ribotype B8a. All strains were multidrug-resistant and harboured an IncC plasmid which conferred resistance to ampicillin, chloramphenicol, streptomycin, sulfamethoxazole and trimethoprim. These findings indicate that a group of closely related V. cholerae O1 strains was responsible for the cholera epidemic in Ethiopia in 1998.

One hundred and three Vibrio cholerae O1 strains, selected to represent the cholera outbreaks which occurred in Somalia in 1998-1999, were characterized by random amplified polymorphic DNA patterns, ribotyping, and antimicrobial susceptibility. All strains showed a unique amplified DNA pattern and 2 closely related ribotypes (B5a and B8a), among which B5a was the more frequently identified. Ninety-one strains were resistant to ampicillin, chloramphenicol, spectinomycin, streptomycin, sulfamethoxazole, and trimethoprim, conferred, except for spectinomycin, by a conjugative plasmid IncC. These findings indicated that the group of strains active in Somalia in the late 1990s had a clonal origin.

Objectives: The objective of this study was to investigate the extent of resistance patterns and associated mobile genetic elements in epidemic V. cholerae O1 El Tor strains isolated from Eastern Africa in the late 1990s., Methods: Self-transmissible genetic elements and associated clusters of genes encoding resistance were detected by conjugation experiments. Detection of SXT-related integrating conjugative elements (ICEs) and associated antibiotic resistance genes was performed by PCR to amplify the SXT element-integrase gene (int), right SXT element-chromosome junction (attP-prfC) and genes conferring resistance to chloramphenicol (floR), sulfamethoxazole (sulII), streptomycin (strA) and trimethoprim (dfrA1). Genomic relatedness was established by random amplified polymorphic DNA patterns., Results: Of 224 strains analysed, 200 isolates exhibited resistance to four or more antimicrobials. An IncC plasmid, encoding resistance to ampicillin, chloramphenicol, streptomycin, sulfamethoxazole and trimethoprim, conferred multidrug resistance to 113 strains isolated from Somalia and Ethiopia, whereas an SXT-related ICE, encoding resistance to chloramphenicol, streptomycin, sulfamethoxazole and trimethoprim, conferred multidrug resistance to 74 strains isolated from Sudan, Kenya and Tanzania., Conclusions: This study has shown the spread of SXT-related ICEs among V. cholerae O1 African isolates. It has also highlighted the role of two distinct genetic elements in conferring multiple resistance to the two distinct groups of V. cholerae O1 strains that, in the late 1990s, spread through Eastern Africa, a critical geographic region for the persistence and transmission of cholera to the entire continent.

Eighty Vibrio cholerae O1 strains selected to represent the 1998-to-1999 history of the largest cholera epidemic in Kenya were characterized by ribotyping, antimicrobial susceptibility, and random amplified polymorphic DNA patterns. Except for 19 strains from 4 local outbreaks in North Eastern Province along the Somalia border, the other 61 strains from 25 outbreaks occurring in districts scattered around the country were all ribotype B27 and resistant to chloramphenicol, spectinomycin, streptomycin, sulfamethoxazole, and trimethoprim. The 61 strains showed similar and specific amplified DNA patterns. These findings indicate that the predominant strains that caused the Kenyan epidemic had a clonal origin and suggest that ribotype B27 strains, which first appeared in West Africa in 1994, have had a rapid spread to eastern Africa.

In 1994 a cholera epidemic occurred in Italy and Albania after more than a decade of case absence. To investigate genotypic characteristics and the origin of the epidemic strains, 110 Vibrio cholerae O1 El Tor isolates from Italy and Albania were studied by randomly amplified polymorphic DNA analysis (RAPD), BglI ribotyping, and pulsed-field gel electrophoresis (PFGE) of genomic DNA. The Italian and Albanian strains were all ribotype 6 and their RAPD and PFGE patterns were identical as well. These findings indicated that the 1994 isolates belonged to the same clone and that the clone was part of the larger global spread of epidemic ribotype 6 strains, which started in southern Asia in 1990.

The prevalence of Vibrio cholerae O1 and non-O1 has been investigated in numerous Somali regions of the Horn of Africa from 1983 to 1990. From January 1983 to January 1985 and between December 1986 and December 1990, no strains of V. cholerae O1 and 226 strains (5.3%) of V. cholerae non-O1 were isolated from 4,295 diarrhea cases. During a cholera epidemic in 1985 and 1986, the overall case-fatality rate was 13% and the attack rate was 3-3.5 per 1,000 population. Matched case-control studies identified a waterborne route of transmission. A drug-susceptible Ogawa strain from Ethiopia caused the introduction of the disease into northern Somalia. There were two major resistant derivatives of the original strain, and the one resistant to ampicillin, kanamycin, streptomycin, sulfonamide, and tetracycline (TC) predominated in the spreading disease. In 1986, susceptible Ogawa strains quickly displaced this resistant strain. The two incompatibility group C plasmids responsible for the resistance patterns had complex and scattered differences in their structures. Physical analysis of the plasmid DNA region coding for TC resistance demonstrated its genetic amplification in highly resistant variants of Ogawa strains.